Sirolimus vascular malformation

CASE: A 24-year-old man with Klippel-Trenaunay syndrome (KTS) presented with severe knee osteoarthritis unresponsive to conservative measures. Owing to end-stage, debilitating arthritic symptoms, surgery was pursued. Careful preoperative, multidisciplinary planning/treatment included magnetic resonance imaging to characterize the venous malformations throughout the right lower extremity, preoperative sclerotherapy, sirolimus, and robotic-assisted cementless total knee arthroplasty (TKA)...

AIM: Sirolimus, a mammalian target of rapamycin inhibitor, inhibits cell growth and proliferation by controlling ribosome biogenesis and protein synthesis in vascular anomalies and cancers. However, most sirolimus studies on vascular anomalies were conducted in the pediatric population, with limited data in adults. In this study, we assessed the effectiveness and safety of sirolimus in adult patients with vascular malformation, a subtype of vascular anomaly. METHODS: We conducted a retrospective analysis of adult vascular malformation patients aged over 16, treated at Hacettepe University Cancer Institute from January 2013 to September 2022...

The Kasabach-Merrit syndrome is characterized as the association of a vascular tumor, typically a caposiform hemangioendothelioma and rarely a tufted hemangioma, and a severe consumptive coagulopathy with potentially life-threatening thrombocytopenia. The severe coagulopathy with increased bleeding tendency must be considered before invasive procedures and often requires repeated platelet concentrate substitutions. We present a case of a mature male neonate with Kasabach-Merritt- Syndrome as well as VACTERL association...

Venous malformations (VMs) are the most common vascular malformations. TEK and PIK3CA are the causal genes of VMs, and may be involved in the PI3K/AKT pathway. However, the downstream mechanisms underlying the TEK or PIK3CA mutations in VMs are not completely understood. This study aimed to identify a possible association between genetic mutations and clinicopathological features. A retrospective clinical, pathological, and genetic study of 114 patients with VMs was performed. TEK, PIK3CA, and combined TEK/PIK3CA mutations were identified in 49 (43%), 13 (11...

Port-wine stains (PWS) are capillary vascular anomalies that are often treated with pulsed-dye laser (PDL). Revascularization limits persistent clearance; however, the anti-angiogenic effects of sirolimus (SIRO) may inhibit revascularization. This review aims to determine differences in PWS outcomes when treated with PDL monotherapy or in combination with SIRO. A systematic review was conducted using PubMed, Cochrane, and Embase databases. The following search terms were used: 'port wine stain PDL SIRO', 'port wine stain PDL', and 'port wine stain PDL and topical treatment' with (MeSH) and (Title/Abstract) limits...

OBJECTIVES: The management of vascular malformations is complex and challenging. This study aimed to explore efficacy, plasma trough concentrations of sirolimus, post-withdrawal conditions, and adverse reactions of sirolimus in treating complex vascular malformations. METHODS: In our center, we analyzed vascular malformations treated with sirolimus (and corticosteroid) from August 2017 to June 2021. Meanwhile, we reviewed the medical records, the efficacy, side effects, and laboratory tests...

BACKGROUND: Vascular anomalies often result in aesthetic flaws, pain, and impair the quality of life. They require challenging treatments that frequently do not provide the desired results. The mammalian target of rapamycin (mTOR) is directly involved in the development of these malformations. However, the exact mechanism behind mTOR dysregulation has not been unambiguously defined. The purpose of this study is to investigate the activation of selected substrates of mTOR to partially assess its involvement in the disease process...

BACKGROUND AND OBJECTIVES: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first-line therapy in the absence of available prospective clinical trials. METHODS: Patients from 17 institutions diagnosed with KHE/TA between 2005 and 2020 with more than 6 months of follow-up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months...

BACKGROUND: Managing complex vascular anomalies in pediatric care requires comprehensive approaches. Sirolimus, an mTOR inhibitor with immunosuppressive and anti-angiogenic properties, offers promise. We evaluated sirolimus's effectiveness and safety in pediatric patients with complex vascular anomalies at a tertiary children's hospital. METHODS: Our study included 20 patients, aged 1 month to 19 years, with diverse vascular anomalies resistant to conventional therapies or located in high-risk areas precluding surgery...

Discovery of inherited and somatic genetic mutations, along with advancements in clinical and scientific research, has improved understanding of vascular anomalies and changed the treatment paradigm. With aim of minimizing need for invasive procedures and improving disease outcomes, molecularly targeted medications and anti-angiogenesis agents have become important as both adjuncts to surgery, and increasingly, as the primary treatment of vascular anomalies. This article highlights the commonly used and emerging therapeutic medications for non-malignant vascular tumors and vascular malformations in addition to medical management of associated hematologic abnormalities...

BACKGROUNDSlow-flow vascular malformations frequently harbor activating mutations in the PI3K/AKT/mTOR cascade. Phase II trials pinpointed sirolimus effectiveness as a drug therapy. Efficacy and safety of sirolimus thus need to be evaluated in large prospective phase III trials.METHODSThe Vascular Anomaly-Sirolimus-Europe (VASE) trial, initiated in 2016, is a large multicentric prospective phase III trial (EudraCT 2015-001703-32), which evaluates efficacy and safety of sirolimus for 2 years in pediatric and adult patients with symptomatic slow-flow vascular malformations...

BACKGROUND: The diagnosis and treatment of fibro-adipose vascular anomaly (FAVA) of the limb remains challenging since this entity is rare and complex. This paper is aimed to describe the clinical and imaging features, staging and management of this underrecognized disease of the limb. MATERIAL AND METHOD: Patients diagnosed with FAVA and managed between September 2019 and May 2022 in department of pediatric surgery & vascular anomalies of Xi'an international medical center hospital were retrospectively reviewed...

BACKGROUND AND OBJECTIVES: Initially developed as immunosuppressive agents, mammalian target of rapamycin (mTOR) inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition. METHODS: This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus...

Vascular anomalies, broadly classified as nonmalignant tumors and malformations, consist of a multitude of disorders that have a wide range of symptoms and complications as well as overlapping clinical, radiologic, and histologic findings. Although usually difficult, distinguishing between nonmalignant vascular tumors and malformations, as well as the precise diagnosis within these distinctions, is critical because prognosis, therapy, and chronicity of care vary greatly. In contrast to normal endothelial turnover in vascular malformations, vascular tumors are characterized by the abnormal proliferation of endothelial cells and aberrant blood vessels...

The discovery of inherited and somatic genetic mutations, along with advancements in clinical and scientific research, has improved the understanding of vascular anomalies and changed the treatment paradigm. With the aim of minimizing the need for invasive procedures and improving disease outcomes, molecularly targeted medications and anti-angiogenesis agents have become important as both adjuncts to surgery, and increasingly, as the primary treatment of vascular anomalies. This article highlights the commonly used and emerging therapeutic medications for nonmalignant vascular tumors and vascular malformations...

The treatment of hemangiomas and vascular malformations should be individualized, based upon the size of the lesion(s), morphology, location, presence or possibility of complications, the potential for scarring or disfigurement, the age of the patient, and the rate of growth or involution at the time of evaluation. The major challenge is the location in a head and neck can lead to unsightly scars if approached improperly, or with inadequate approaches can lead to intraoperative and postoperative morbidity with neurovascular damage and inadequate lesion excision...

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular malformations that frequently cause stroke. CCMs arise due to loss of function in one of the genes that encode the CCM complex, a negative regulator of MEKK3-KLF2/4 signaling in vascular endothelial cells. Gain-of-function mutations in PIK3CA (encoding the enzymatic subunit of the PI3K (phosphoinositide 3-kinase) pathway associated with cell growth) synergize with CCM gene loss-of-function to generate rapidly growing lesions...

INTRODUCTION: Lymphatic malformations (LMs) are rare vascular anomalies predominantly affecting infants, which can be debilitating or life-threatening when complicated with intralesional bleeding or infection. Effective and safe management strategies are essential in such cases. CASE PRESENTATION: We report a case series involving four Chinese neonates with life-threatening LMs, initially treated with oral sirolimus. All patients achieved rapid relief and sustained remission, using a lower sirolimus dosage than previously recommended...

BACKGROUND: Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations. METHODS: A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms "venous malformation," "lymphatic malformation," "lymphaticovenous malformation," "genetic variant," "genetic mutation," "endothelial cells," and "animal model...

Numerous clinical trials of sirolimus, an inhibitor of mechanistic/mammalian target of rapamycin complex 1, for the treatment of vascular malformations have been conducted. However, aside from lymphatic malformations, the efficacy of sirolimus for venous and capillary malformations has not been established. Moreover, no generalized venous or capillary malformations have been treated with topical sirolimus. To evaluate the safety and efficacy of topical sirolimus for venous and capillary malformations and to compare the efficacy of topical and systemic sirolimus therapy, an open-label single-arm pilot study with 0...