Sirolimus vascular anomalies

Vascular anomalies represent a diverse group of disorders classified broadly as malformations or tumors and include the second most common hereditary bleeding disorder worldwide, hereditary hemorrhagic telangiectasia (HHT). Patients with HHT and other vascular anomalies suffer morbid consequences of these diseases, including bleeding, thrombosis, anemia, localized intravascular coagulation, tissue overgrowth, infections, and other complications. The International Society for the Study of Vascular Anomalies (ISSVA) has developed a standard classification of these disorders, creating a uniform approach to their diagnosis, and the treatments for vascular anomalies are rapidly evolving...

BACKGROUND: Fibro-adipose vascular anomaly (FAVA) is a rare and new entity of vascular anomaly. Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene were identified at a frequency of 62.5% in FAVA cases. The PIK3CA mutations excessively activate mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis, implying that PIK3CA mutations may act as drivers of FAVAs. This study investigated the correlations between PIK3CA mutational status, clinicopathological features and immunohistochemical expression of the mTOR pathway in a series of FAVA...

Objectives: Experimental data indicate that activating mutations in the mTOR (mammalian target of rapamycin) pathway may lead to abnormal arterial wall structure. Vascular anomalies like arterial stenoses are reported in pediatric patients with tuberous sclerosis complex (TSC). In addition, large renal lesions (angiomyolipoma-AML and cysts) are risk factors for arterial hypertension in adult patients with TSC. This study aimed to assess blood pressure, including central blood pressure and arterial damage (early vascular aging-EVA) in children with TSC...

BACKGROUND: Chylothorax can be a presenting symptom of complex lymphatic anomaly in children and is associated with significant respiratory morbidity. Historically, the traditional pharmacological treatment has been octreotide. There are several treatments that have been utilized in the past few years including sirolimus; however, data regarding their efficacy and outcomes is limited. Furthermore, sirolimus has proven efficacy in complex vascular malformations, and hence, its utility/efficacy in infantile primary chylous effusions warrants further investigation...

Extensive lymphatic malformations (LMs) of the head and neck region may require tracheostomy to secure the airway. Treatment of these life-threatening LMs is usually multimodal and includes sclerotherapy and surgery, among others. Recently, systemic therapy with sirolimus has been introduced as an effective treatment for venous and lymphatic malformations; its efficacy and safety profile in patients with extensive LM requiring tracheostomy are, however, as yet not fully known. We performed a retrospective, multicenter review and identified 13 patients with an extensive LM of the head and neck region, who previously underwent placement of tracheostomy and subsequently received sirolimus treatment with the aim to improve the local respiratory situation and remove the tracheostomy...

Blue rubber bleb nevus syndrome (BRBNS) is a rare multifocal venous malformation (VM) that may affect any tissue or organ but mainly affects the skin, subcutaneous tissue and gastrointestinal (GI) tract. Patients present with serious anemia, treated with lifelong iron supplements and frequent blood transfusion secondary to chronic GI bleeding. Variable therapeutic modalities were used in the management of BRBNS; sirolimus (SRL), a mammalian target of rapamycin (mTOR) inhibitor, is found to be a promising therapy for vascular anomalies...

IMPORTANCE: Sirolimus is increasingly being used to treat various vascular anomalies, although evidence of its efficacy is lacking. OBJECTIVE: To assess the efficacy and safety of sirolimus for children with slow-flow vascular malformations to better delineate the indications for treatment. DESIGN, SETTING AND PARTICIPANTS: This multicenter, open-label, observational-phase randomized clinical trial included 59 children aged 6 to 18 years with a slow-flow vascular malformation who were recruited between September 28, 2015, and March 22, 2018, in 11 French tertiary hospital centers...

We present a series of four newborns diagnosed with complicated congenital vascular anomalies, with different localization: Congenital lymphatic malformation (CLM) on the left hemithorax extending on the left upper limb; congenital hepatic hemangioma (CHH) with important complications in the first 7 weeks of life; Kaposiform hemangioendothelioma (KHE) of the left lower limb complicated with Kasabach Merritt phenomenon (KMM) and most probable diffuse capillary malformation with overgrowth (DCMO). All patients were treated with combined antiproliferative therapy with sirolimus and propranolol...

Klippel-Trenaunay syndrome (KTS) is a congenital vascular disorder characterized by the triad of cutaneous capillary malformation, lymphatic and venous anomalies, and soft tissue and bone overgrowth. Sirolimus is a mechanistic target of rapamycin inhibitor used as an immunosuppressive drug. It has also been used to improve and treat vascular malformations that can predispose to intravascular coagulopathy. We have described the case of a patient with KTS receiving a therapeutic anticoagulation dose, for whom sirolimus was initiated, and who had presented with an extensive venous thromboembolism...

BACKGROUND AND OBJECTIVES: Vascular malformations (VM) are a complex pathology with few treatment options. In previously published studies, oral sirolimus has shown promising results in the treatment of low-flow VM, while its usefulness in high-flow VM is controversial. The aim was to evaluate the efficacy and safety of sirolimus for the treatment of high-flow VM in real-life practice. MATERIAL AND METHODS: In a unit specialized in vascular anomalies, patients treated with oral sirolimus for a high-flow VM were located by consulting the drugs dispensations...

Vascular and lymphatic malformations represent a challenge for clinicians. The identification of inherited and somatic mutations in important signaling pathways, including the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin), RAS (rat sarcoma)/RAF (rapidly accelerated fibrosarcoma)/MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinases), HGF (hepatocyte growth factor)/c-Met (hepatocyte growth factor receptor), and VEGF (vascular endothelial growth factor) A/VEGFR (vascular endothelial growth factor receptor) 2 cascades has led to the evaluation of tailored strategies with preexisting cancer drugs that interfere with these signaling pathways...

BACKGROUND: Theragnostic management, treatment according to precise pathological molecular targets, requests to unravel patients' genotypes. We used targeted next-generation sequencing (NGS) or digital droplet polymerase chain reaction (ddPCR) to screen for somatic PIK3CA mutations on DNA extracted from resected lesional tissue or lymphatic endothelial cells (LECs) isolated from lesions. Our cohort (n = 143) was composed of unrelated patients suffering from a common lymphatic malformation (LM), a combined lymphatic malformation [lymphatico-venous malformation (LVM), capillaro-lymphatic malformation (CLM), capillaro-lymphatico-venous malformation (CLVM)], or a syndrome [CLVM with hypertrophy (Klippel-Trenaunay-Weber syndrome, KTS), congenital lipomatous overgrowth-vascular malformations-epidermal nevi -syndrome (CLOVES), unclassified PIK3CA-related overgrowth syndrome (PROS) or unclassified vascular (lymphatic) anomaly syndrome (UVA)]...

Objective: Difficulties encountered in the diagnosis and treatment of vascular anomalies located in the extremities of the children. The most common vascular lesions are hemangiomas and venous malformations. The complex malformations, such as, Klippel-Trenaunay Syndrome are much less commonly encountered lesions. Treatment of vascular malformations are variable based on the etiology of the lesion and clinical presentation. In this study, we aimed to share our experience on the clinical features of vascular lesions in the extremities of the children...

BACKGROUND: Kaposiform lymphangiomatosis (KLA), which is a new subtype of generalized lymphatic anomaly, is a rare disease with a poor prognosis. Currently, there is no standard treatment due to the poor understanding of KLA. Sirolimus, which is an inhibitor of mammalian target of rapamycin, has been shown to have promising potential in the treatment of complicated vascular anomalies. The aim of this study was to introduce the use of sirolimus for the treatment of KLA and to highlight the challenges of managing this refractory disease...

OBJECTIVE: Complicated vascular anomalies (VAs) can be intractable and uncontrollable using conventional treatment and can result in lethal outcomes. We undertook a prospective, multicenter phase II trial to evaluate the efficacy and safety of sirolimus in pediatric patients with complicated VAs. METHODS: Eligible patients were required to be aged 0 to 14 years and to have a complicated VA. The patients were treated with daily oral sirolimus for 12 months...

Topical sirolimus has become a crucial treatment option for many dermatologic disorders. Because an FDA-approved topical formulation is not commercially available, sirolimus creams, ointments, and gels are professionally prepared by compounding pharmacies. Also, the topical use of a commercially available sirolimus solution approved for oral administration is described regularly. To better guide providers in their decision-making when topical sirolimus is being considered, this article highlights the substantial pharmaceutical and clinical differences between commercial oral solution and compounded preparations specifically designed for topical therapy...

BACKGROUND/PURPOSE: Cervicofacial lymphatic malformations (CFLM) are rare, potentially life-threatening vascular anomalies, yet reports on multidisciplinary treatment strategies are lacking. We evaluated outcomes for CFLMs following sclerotherapy, surgical resection, and/or medical management. METHODS: We identified children with a CFLM at a vascular anomalies center from 2004 to 2019. EXCLUSION CRITERIA: retro-orbital malformations, untreated malformations, patients without follow-up...

Complex lymphatic anomalies (CLA) are congenital diseases of the lymphatic circulation system that are associated with significant morbidity and early mortality. While guidelines for the comprehensive evaluation of the CLA were recently published, the diagnostic approach and medical management are not standardized. This article presents the clinical features of four CLA: Gorham-Stout disease, generalized lymphatic anomaly, kaposiform lymphangiomatosis, and central collecting lymphatic anomaly. We also offer three cases from the authors' practice and our views on diagnostic testing and disease management including supportive care, medical therapies, and other interventions...

OBJECTIVE: Recently, sirolimus has emerged as a safe and effective treatment modality for unresectable vascular lesions. In the present study, we investigated the effectiveness and safety of sirolimus from our early experience with patients with unresectable vascular anomalies. METHODS: The medical records and radiologic images of all patients with unresectable vascular anomalies treated with sirolimus at our center from January 2018 to November 2019 were retrospectively reviewed...

OBJECTIVE: Vascular malformations arise from defects in the morphologic development of the vascular system and can have an impact on quality of life and/or lead to severe complications. To date, vascular malformations are frequently managed by invasive techniques, after which recurrence is common. Sirolimus, a downstream inhibitor of the phosphatidylinositol 3 kinase/AKT pathway and best known for its immunosuppressive effect, has been used off-label for lesions for which approved therapies were associated with unsatisfactory results or recurrence...