Sotorasib for Vascular Malformations Associated with KRAS G12C Mutation.

KRAS gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such KRAS-driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic Kras G12C mutation. We then administered sotorasib to two adult patients with severe KRAS G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with KRAS G12C-related vascular malformations. (Funded by the European Research Council and others.).

Malformação arteriovenosa uterina: um relato de caso / Uterine arteriovenous malformation: a case report

O presente estudo tem como objetivo relatar o caso de uma paciente com malformação arteriovenosa uterina, efetivamente tratada com embolização seletiva e com fertilidade preservada. A malformação arteriovenosa uterina é uma alteração vascular rara até então pouco descrita na literatura. A paciente do sexo feminino apresentou quadro de sangramento uterino anormal, com início 30 dias após um abortamento, sem realização de curetagem, de uma gestação resultante de fertilização in vitro. Foram, então, realizados exames de imagem, que levaram ao diagnóstico de malformação arteriovenosa uterina. O tratamento de escolha foi a embolização arterial seletiva, com resolução do caso. Após sete meses, nova fertilização in vitro foi realizada, encontrando-se na 36a semana de gestação. São necessários mais estudos sobre essa malformação a fim de que sejam estabelecidos os métodos mais eficazes para o manejo de casos futuros, especialmente quando há desejo de gestar.

The present study aims to report the case of a patient with uterine arteriovenous malformation, effectively treated with selective embolization and with preserved fertility. Uterine arteriovenous malformation is a rare vascular disorder that has so far been rarely described in the literature. Female patient presented with abnormal uterine bleeding, starting 30 days after an abortion without subsequent curettage, of a pregnancy resulting from in vitro fertilization. Imaging tests were then performed that led to the diagnosis of uterine arteriovenous malformation. The treatment of choice was selective arterial embolization, with successful results. After seven months, a new in vitro fertilization was performed, being in the 36th week of pregnancy. Further studies on this pathology are needed in order to establish the most effective methods for the management of future cases, especially when there is a desire to become pregnant.

Liquid Embolization of Peripheral Arteriovenous Malformations with Ethylene-Vinyl Alcohol Copolymer in Neonates and Infants.

In the postnatal period, extensive peripheral arteriovenous malformations (AVM) are associated with high morbidity, especially when localized in the liver. Their urgent treatment is always a challenging problem in neonates and infants. We analyzed four consecutive children aged three days to three years who underwent eight liquid embolization procedures with ethylene-vinyl alcohol copolymer. The AVM were situated on the thoracic wall, in the liver, and on the lower leg. In three cases, the malformations showed total regression. The tibial AVM degenerated widely. If impaired beforehand, cardiac or hepatic function normalized after the interventions. There were no embolization-associated complications such as nontarget embolization or tissue ischemia. We conclude that application of ethylene-vinyl alcohol copolymer seems to be a safe therapeutic option and can be used in neonates and infants with peripheral AVM in consideration of the agent's characteristics. Nevertheless, there are still hardly any data concerning young children.

Medical management of vascular anomalies of the head and neck.

Depending on impairment, treatment of vascular anomalies is decided on a case-by-case basis in pluridisciplinary consultations. Interventional treatments, especially surgery and sclerotherapy, are usually partially efficient and management of patients with vascular anomalies increasingly involves the use of medical drugs. The most common vascular tumor is infantile hemangioma where first-line medical treatment, when necessary, is propranolol. Kasabach-Merritt phenomenon is now largely treated with sirolimus whereas first-line treatment of coagulation disorders associated with venous malformations is based on low-molecular-weight heparins or direct anticoagulants. Sirolimus is the standard treatment for painful inflammatory manifestations of low-flow vascular malformations such capillary, venous, and lymphatic malformations that can occur singly or in combination but PIK3CA inhibitors, originally developed in oncology, have shown promising results in patients with PIK3CA-related overgrowth spectrum. Currently, medical treatments are poorly developed for high-flow malformations such as arteriovenous malformations. However, new research aimed at delineating the different arteriovenous malformations based on molecular findings has given new hope for future development of targeted therapies.

¿Neumonía redonda o hallazgo casual? / Round pneumonia or incidental finding?

El diagnóstico diferencial de las neumonías redondas es amplio y engloba enfermedades infecciosas, neoplásicas y congénitas. La paciente que se presenta a continuación fue diagnosticada de una neumonía redonda con una clínica e imagen radiológica compatible. Sin embargo, el diagnóstico definitivo fue una malformación vascular. Este caso permite reflexionar sobre la importancia de valorar distintitos diagnósticos ante una condensación redondeada y sobre la necesidad o no de realizar una radiografía de control en estos casos. Además, lo más original del caso radica en el tratamiento que recibió para la malformación vascular, que no estaba descrito previamente: el propranolol (AU)

The differential diagnosis of round pneumonia is broad and includes infectious, malignant, and congenital diseases. The patient presented below received a diagnosis of round pneumonia based on compatible clinical and radiological findings; however, the definitive diagnosis was a vascular malformation. This case allows us to reflect on the importance of considering alternative diagnoses in the presence of round opacities in the lung and when performance of a follow-up X-ray is or not required in such cases. In addition, the most original aspect of this case lies in the treatment provided for the vascular malformation, which has not been previously described: propranolol. (AU)

Successful management of an arteriovenous malformation with trametinib in a patient with capillary-malformation arteriovenous malformation syndrome and cardiac compromise.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant condition characterized by multifocal, noncontiguous pink patches on the skin that often have a surrounding pale halo. In some cases, an association with a fast flow, arteriovenous malformation (AVM) can be identified. Here, we describe a case report of a 16-year-old woman with CM-AVM syndrome and significant cardiac compromise successfully treated with trametinib, a mitogen-activated protein kinase (MEK) inhibitor.

Placental polyp with arteriovenous malformation treated with a gonadotoropin-releasing hormone antagonist.

A 35-year-old woman (gravida 1, para 0) underwent termination of pregnancy (ToP) at 12 weeks of gestation. One month after ToP, she experienced significant vaginal bleeding and the mass with blood flow was identified on imaging. The presence of a placental polyp with arteriovenous malformation (AVM) was suspected on transvaginal sonography and MRI. Since the bleeding had ceased when she visited our hospital, we decided to treat the placental polyp with AVM with gonadotropin-releasing hormone (GnRH) antagonist therapy instead of surgery. Two months after GnRH antagonist treatment, the mass and blood flow in the uterus disappeared. Menstruation resumed 1 month after the completion of treatment. In our case, we were able to successfully treat placental polyps with AVM using GnRH antagonist therapy.

Multiple Arterial Vascular Anomalies in the Periorbital, Paranasal, and Intracranial Spaces Treated With Systemic Bevacizumab.

ABSTRACT: Arteriovenous malformations of the orbit are rare congenital hamartomas defined by a direct connection between the arterial and venous systems without an intervening capillary bed. Treatment can be challenging, as these lesions are anatomically complex, often involve multiple locations, and have a tendency to recur. A multidisciplinary approach is typically required, involving endovascular and surgical teams. The authors present a case of a 33-year-old man with a complex, recurrent orbital arteriovenous malformations in the context of wider head and neck vascular anomaly syndrome involving the paranasal sinuses, deep facial tissues, and intracranial spaces. The complex and evolving clinical manifestations of this disease are presented with emphasis on the interdependence of the anomalies and biologic management strategies.

RhoA activation-mediated vascular permeability in capillary malformation-arteriovenous malformation syndrome: a hypothesis.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a class of capillary anomalies that are associated with arteriovenous malformations and arteriovenous fistulas, which carry a risk of hemorrhages. There are no broadly effective pharmacological therapies currently available. Most CM-AVMs are associated with a loss of RASA1, resulting in constitutive activation of RAS signaling. However, protein interaction analysis revealed that RASA1 forms a complex with Rho GTPase-activating protein (RhoGAP), a negative regulator of RhoA signaling. Herein, we propose that loss of RASA1 function results in constitutive activation of RhoA signaling in endothelial cells, resulting in enhanced vascular permeability. Therefore, strategies aimed at curtailing RhoA activity should be tested as an adjunctive therapeutic approach in cell culture studies and animal models of RASA1 deficiency.

Periocular steroids for macular edema associated with retinal arteriovenous malformation: A case report.

Retinal racemose hemangiomas (RRH) are vascular malformations comprising of direct arteriovenous communications in the retina. Exudation and neurosensory detachment are some of the complications which may cause decreased visual acuity. Herein, we describe a case of a 38-year-old male presenting with unilateral Group II RRH complicated with macular edema. Initial treatment with intravitreal bevacizumab yielded a poor therapeutic response. Subsequently, he was treated with a posterior sub-tenon injection of triamcinolone acetonide following which there was a prompt decrease in edema with simultaneous improvement in vision. The visual acuity was maintained and no recurrence was seen even after 6 months of successful treatment.

Cesarean scar pregnancy combined with arteriovenous malformation successfully treated with transvaginal fertility-sparing surgery: A case report and literature review.

INTRODUCTION: A cesarean scar pregnancy (CSP), when combined with an arteriovenous malformation (AVM), is a rare, but potentially life-threatening condition that may be associated with uncontrolled hemorrhage. Hysterectomy is indicated when conservative treatment fails. Preservation of fertility is challenging. PATIENT CONCERNS: We reported a 33-year-old woman with a CSP combined with an AVM who failed methotrexate administration as conservative treatment. DIAGNOSES: A CSP combined with an AVM was diagnosed via three-dimensional color Doppler angiogram and magnetic resonance imaging. INTERVENTIONS: Transvaginal removal of the ectopic gestation and repair of the uterine defect was performed without incident. OUTCOMES: The fertility of the patient was preserved and hysterectomy was avoided. CONCLUSION: Transvaginal fertility-sparing surgery may be successfully performed to prevent hysterectomy when conservative treatment fails in patients with a CSP combined with an AVM.

Monitoring Arteriovenous Malformation Response to Genotype-Targeted Therapy.

Arteriovenous malformations (AVMs) have recently been reported to have a high incidence of somatic KRAS mutations suggesting potential for treatment with mitogen-activated protein kinase inhibitors. In this case report, we describe genotype-targeted treatment of a KRAS mutant metameric AVM in a patient with Cobb syndrome using the mitogen-activated protein kinase inhibitor trametinib. Therapeutic response was monitored with phase-contrast magnetic resonance angiography to quantify AVM arterial inflow as an imaging biomarker. Treatment with trametinib resulted in a substantial decrease in blood flow to the AVM, with a >75% reduction in arterial inflow after 6 months of trametinib therapy.

Swyer-James-MacLeod syndrome and pulmonary arteriovenous malformations: a rare combination.

This case describes a female patient who presented with an acute on chronic deterioration in respiratory symptoms, on a background of chronic obstructive pulmonary disease and heavy cigarette smoking. Chest radiograph demonstrated long-standing hyperlucency of the right lower lobe, with further imaging later confirming the rare combination of Swyer-James-MacLeod syndrome and multiple pulmonary arteriovenous malformations within the affected lung.