Congenital Vascular Malformations Research Articles

Controversy on the management of patients carrying RET p.V804M mutation.

RET p.V804M is classified as a moderate risk mutation for familial medullary thyroid cancer (FMTC). There is a significant controversy on the management of patients carrying this mutation. We describe a family incidentally discovered to have this mutation and review the literature on RET p.V804M mutation. The proband was born to first-degree relative parents. He was noticed to have hypertrophy of some parts of the body and vascular skin changes. Whole-exome sequencing of DNA extracted from a skin biopsy showed a mutation in the PIK3CA (c.3132T>G, p.ASN1044LYS). This variant was not found in DNA extracted from blood. This confirmed the diagnosis of CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi and Scoliosis, skeletal or spinal anomalies). Another incidentally found mutation in the skin biopsy and blood sample was RET p.V804M. Although there was no family history of MTC or MEN 2 syndromes, family screening revealed RET p.V804M mutation and FMTC in the proband's father, paternal grandmother, one sister, and one aunt. There was significant interfamilial heterogeneity in the age of presentation and pathology. A review of literature showed that RET p.V804M mutation is a moderate risk mutation associated with late-onset FMTC, usually at middle to old age. Despite the controversy and the heterogeneous presentation of patients with RET p.V804M mutation, our study and review of the literature suggest that this seemingly "low" risk mutation is associated with late-onset but potentially aggressive MTC. This indicates the need for follow-up and timely intervention based on calcitonin level elevation.

Clinical presentation of simple and combined or syndromic arteriovenous malformations

ObjectiveArteriovenous malformations of the lower extremities (AVMLE) can present as simple or complex combined or syndromic forms (eg, Parkes Weber Syndrome). We aimed to characterize the differences in clinical presentation and natural history of these potentially life- and limb-threatening congenital vascular malformations. MethodsWe conducted a retrospective analysis of a consecutive series of patients with AVMLE who presented to a tertiary referral center in Switzerland between 2008 and 2018. Clinical baseline characteristics, D-dimer level, and course were summarized and differences between simple, non-syndromic and combined or syndromic AVMLE determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. ResultsOverall, 506 patients were prospectively enrolled in the Bernese Congenital Vascular Malformation Registry, 31 (6%) with AVMLE. There were 16 women and 15 men, with a mean age of 18 years at first diagnosis (range, 1 month to 72 years). Simple AVMLE was present in 22 (71%) and combined or syndromic AVMLE with limb overgrowth in 9 patients (29%), respectively. Common symptoms and signs were pain (n = 25; 81%), swelling (n = 21; 68%), and soft tissue hypertrophy (n = 13; 42%). Among combined or syndromic patients, three patients died from wound infection with sepsis or disseminated intravascular coagulation with bleeding complications (intracranial hemorrhage and bleeding from extensive leg ulcers). Combined or syndromic patients presented more often with bleeding (67% vs 5%; P < .001), malformation-related infection (44% vs 5%; P = .017) and leg length difference (56% vs 14%; P = .049). D-dimer levels were elevated (mean, 17,256 μg/L; range, 1557-80,000 μg/L) and angiographic appearance showed complex, mixed type of AVMs, including interstitial type IV, in all patients with combined or syndromic AVMLE. ConclusionsPatients with congenital simple AVMLE most often present with benign clinical features and rarely with complications related to hemodynamic changes. Patients with combined or syndromic AVMLE often face serious outcomes dominated by complications other than direct high-flow-related heart failure.

Venous malformations.

The often inexorable growth and expansion of congenital vascular malformations can result in substantial morbidity and, in some cases, premature death of these patients. Despite this, patients suffering from such lesions are often erroneously diagnosed and/or inadequately treated, due to a lack of expertise among primary care practitioners as well as specialists. Venous malformations are the most common type of congenital vascular malformations. Over the last two decades management of these lesions has significantly improved, predominantly due to the introduction and implementation of multidisciplinary team concept as well as improvement in diagnostic and treatment modalities. Relatively recently genetic studies are providing more insights into underlying pathophysiological mechanisms responsible for the development and progression of venous malformations and pharmacotherapy is becoming extensively evaluated for safety and efficacy in the treatment of these often challenging vascular lesions.

Ruptured Spinal Arteriovenous Malformation (AVM) Results in Paraplegia During Pregnancy

A 21-year-old pregnant woman at 34-weeks’ gestation presented to the emergency room with sudden lower extremity weakness and discovered a devastating diagnosis. A magnetic resonance imaging report described a neoplasm versus spinal arteriovenous malformation (AVM). Diagnostic angiogram indicated an AVM involving thoracic spinal levels 8–12, a rare condition that results in rapidly progressive paraplegia. Undiagnosed congenital vascular malformation developmental defects of the arterial and venous vasculature may become symptomatic due to physiological changes in pregnancy.

Abstract P168: Promising Diagnostic Biomarkers For Congenital Vascular Malformations

Background: Congenital vascular malformations (CVMs) are vascular lesions that result from developmental errors during embryogenesis. They can occur anywhere in the body, causing pain, bleeding, ulcers, disfiguration, organ failure or limb loss. Depending on intralesional blood flow dynamics, CVMs can be broadly classified into low-flow (LF), which involve veins, lymphatics, capillaries or a mixture, and high-flow (HF), which involve arteries and veins. Accurate diagnosis and monitoring of LF and HF CVMs remains challenging and requires a wide range of imaging modalities. Aim: We sought to identify potential diagnostic serum biomarkers, particularly those pertaining to the processes of inflammation and angiogenesis. Methods: Sera were isolated from the peripheral bloods of consented healthy controls ( n = 10) and patients diagnosed as having either LF ( n = 10) or HF ( n = 10) CVMs. Various mediators of inflammation and angiogenesis were analysed in the sera using the Inflammation 20-Plex and Angiogenesis 18-Plex Human ProcartaPlex™ Panels. The levels of these mediators in patients with LF or HF CVMs were compared with those in healthy controls using the Kruskall-Wallis test and correlated with lesion volumes and visual analogue scores for pain using the Spearman rank correlation test. Results: Compared to healthy controls, the inflammatory mediators E-selectin, IFNα, IFNγ, IL1β, IL4, IL12, IL17, MIP1α, MIP1β and TNFα were elevated in the sera of LF CVM patients, whereas only MIP1α was raised in the sera of HF CVM patients. None of the angiogenic mediators were altered in the sera of patients with LF or HF CVMs. Serum IFNα, IFNγ, IL4, IL12, TNFα, VEGFA, VEGFD and syndecan correlated positively with pain scores in patients with LF CVMs, whereas only IP10 did in patients with HF CVMs. Serum Ang1 and leptin correlated negatively with lesion volumes in patients with LF or HF CVMs, respectively. Conclusion: Serum inflammatory mediators could be used as biomarkers to distinguish LF from HF CVMs and their expression seemed to be associated with pain severity in patients with LF CVMs. The angiogenic mediators Ang1 and leptin were associated with lesion volumes in patients with LF or HF CVMs, respectively.

Sturge-Weber syndrome: Clinico-neuroradiological features and treatment profile

Introduction: Sturge Weber syndrome (SWS) is a rare, nonhereditary genetic disorder. SWS belongs to a diverse group of Neurocutaneous disorders. A somatic mutation in the early development of cells in SWS patients causes the formation of a congenital capillary vascular malformation. SWS is characterized by nevus flammeus on the face (also called Port-Wine Birthmark), brain (leptomeningeal angioma), and eyes (glaucoma). Methods and Materials: We present three patients diagnosed with Sturge Weber syndrome who attended a teaching hospital between 2013 to 2016. The clinical, neuroradiological features and treatment of SWS patients were reviewed retrospectively from medical records. Results: Two males and females with SWS were reviewed. The facial nevus flammeus was unilateral in one patient and bilateral in two patients. The extensive nevus flammeus including the face, trunk, and upper limb was found in one patient. Epilepsy, neurodevelopmental delay, and intellectual disability were the most common presentation in the series. Episodic hemiparesis was manifested in one patient. Levetiracetam and oxcarbazepine, either single or combined, were used in every SWS patient (n=3). Six months seizure-free was obtained in a patient with SWS with combined anticonvulsant therapy. Conclusion: Drug-refractory and early-age epilepsy is associated with lower intelligence level that consequently affects poor social skill and quality of life in the patients with SWS. Sudden or gradual loss of vision is also a threat for SWS patients. Diagnosis at birth or during early age, multidisciplinary intervention, and follow-up is a must to improve absolute outcomes in the patients with SWS.

A case report of a spontaneous sternocleidomastoid hematoma: a challenging diagnosis in infantile neck swellings

BackgroundPediatric neck masses are a common complaint in children. The most common etiologies include congenital lesions, lymphadenopathy, vascular malformations, inflammatory, and malignant lesions. Spontaneous sternocleidomastoid hematoma is exceptional in infant.Case presentationWe describe a case of spontaneous cervical hematoma diagnosed in a 4-month-old child. Past history did not reveal a neck trauma, a history of difficult labor, a bleeding disorder or a pertinent family history. The diagnosis was suspected based on the imaging features and confirmed after surgical removal.ConclusionsSternocleidomastoid swelling is commonly encountered in infancy.Ultrasound still remains the initial modality of choice. The management modalities are controversial.

B-IN02-04 TRANSHEPATIC ACCESS TO FACILITATE LEAD EXTRACTION IN A PATIENT WITH INTERRUPTED INFERIOR VENA CAVA

Unconventional approaches to achieve transvenous pacing may be required in patients with congenital vascular anomalies and vascular occlusion. We report a case of a patient with congenital interruption of the IVC and multiple venous occlusions requiring transhepatic access for dual chamber pacing system extraction and re-implantation. N/A A 21 year old female with congenital heart disease and a right axillary transvenous pacemaker implanted at age 11 for complete heart block presented with lead fracture. Her history was notable for coarctation repair, bicuspid aortic valve and closure of a large VSD. Vascular access to the heart was limited by a right subclavian vein occlusion extending to the SVC associated with indwelling leads, congenital interruption of the IVC, bilateral IJ occlusions, contralateral L subclavian occlusion and R iliac vein occlusion. A plan was made for lead extraction and placement of new leads. Temporary pacing was achieved with a deflectable decapolar catheter via the left femoral vein to the azygous vein to the SVC. During extraction lead dislodgement occurred before the mechanical extraction sheath could be advanced across the subclavian occlusion. Transhepatic access was obtained to snare the lead tip and apply traction for sheath advancement. With vascular access to the heart achieved, new RA and RV leads were positioned. The transhepatic venotomy was closed with a vascular plug. The patient was discharged without complication. Transhepatic venous access is a safe and effective alternative to more conventional approaches to lead extraction when limited by congenital vascular malformations or occlusion.

Incidental Finding of a Persistent Stapedial Artery in a Patient Presenting With Conductive Hearing Loss.

A persistent stapedial artery is a congenital vascular malformation that can cause tinnitus and/or conductive hearing loss. Although rare, this case highlights the importance of recognizing aberrant anatomy as a potential cause of patients' symptoms. It also demonstrates how to recognize and treat patients with a symptomatic persistent stapedial artery.

Case Reports of an Innovative Technique for Columellar Reconstruction in Children Using a Custom-Made Composite Graft from the Back of the Ear

The columella is unique as a nasal subunit. The nasalcolumella has traditionally been a difficult subunit to repairbecause of its unique contours, tenuous vascularity, and limitedavailability of adjacent skin. Columellar defects can significantlyimpair aesthetic appearance. Columellar damage canbe caused by congenital loss, ischemic injuries, trauma, tumorresection, and vascular malformations. Columella reconstructioncan be very challenging for plastic surgeons.Defects of the nasal columella can be repaired usingvarious methods including composite free grafts from the ear(1,2), nasolabial flaps (3), nasofacial sulcus flaps (4), foreheadflaps (5), extended Abbe flaps (6), and free flaps (7).Auricular chondrocutaneous composite grafts have beenreported in the literature. The main advantage of these graftsare avoidance of facial scars and provision of tip support.However, risk of composite graft loss was reported as a maincomplication.Herein, we report two cases of columellar defect reconstructionsin children using a custom-made columella froma conchal composite graft with the tongue-in-groove principle.The main advantages of this technique are that it is a onestagemethod; the custom-made columella depends on thedimensions of the defect, so it can be tailored according tothe dimension of the columellar defect; the use of the tonguein-groove principle increases the contact surface between thegraft and recipient, therefore, increase the possibility ofsurvival of the reconstructed columella; with minimal donorsite morbidity.

Relationship between a Tracheal and Left Pulmonary Artery Stenosis Index and the Prognosis of Pulmonary Artery Sling with Tracheal Stenosis.

Pulmonary artery sling is a rare congenital pulmonary vascular malformation, often associated with tracheal or bronchial stenosis. Surgical treatment of pulmonary artery sling with tracheal stenosis (T) has a high risk of death and a relatively poor prognosis. This study explored the relationship between the T and left pulmonary artery stenosis (P) ratio and the effects of surgery for pulmonary artery sling with tracheal stenosis. Patients undergoing surgery for pulmonary artery sling in our center from January 2010 to December 2018 were retrospectively analyzed. Routine cardiac-enhanced computed tomography (CT) was performed preoperatively, and the P and T diameters were measured on the CT image. The T/P ratio was then calculated and analyzed. Thirty cases of pulmonary artery sling combined with tracheal stenosis were operated under cardiopulmonary bypass. The mean age at operation was 13.8 ± 13.6months (1.2-57.1months, Q1-Q3: 5-17months), and the mean body weight was 8.8 ± 3.5kg (3.8-17.3kg, Q1-Q3: 5.8-11.5kg). Twenty-three patients survived, and seven died, with an overall survival rate of 76.7%. Twenty-four patients underwent left pulmonary artery re-implantation, six patients underwent simultaneous left pulmonary artery re-implantation and slide tracheoplasty, and patients with intracardiac malformations (ventricular septal defect (n = 6) and atrial septal defect (n = 4)) underwent concurrent repair of the intracardiac defect. All cases had different degrees of tracheal stenosis, and the most narrowed trachea occurred with compression by the left pulmonary artery sling. The T/P ratio in the tracheoplasty group was significantly higher than that in the non-tracheoplasty group. The mortality rate in the T/P ≤ 1.15 group was significantly lower than that in the T/P > 1.15 group. Pulmonary artery sling treatment has a high risk of death. Left pulmonary artery re-implantation is an effective and safe surgical method for treating pulmonary artery sling, and slide tracheoplasty is an effective surgical method to correct tracheal stenosis. Children with T > 78.4% should receive active intervention for the tracheal stenosis, and these children have a considerable postoperative survival rate. The T/P ratio can be used to compare the relative superiority of the two compressions. A T/P ratio > 1.15 can be used as a reference index for intervention in tracheal stenosis and is a risk factor for postoperative death.

Patients with Congenital Low-Flow Vascular Malformation Treated with Low Dose Sirolimus

IntroductionPatients with congenital vascular malformations often suffer from an impaired quality of life (QoL) because of pain and functional disabilities. Previous studies have shown that the mTOR inhibitor sirolimus can reduce complaints and improve QoL in some patients. High target levels of sirolimus of 10–15 ng/ml were well tolerated; however, in a relative high percentage of patients sirolimus caused serious adverse events (AEs).MethodsA case series of 12 patients with therapy-resistant low-flow vascular malformations was treated with sirolimus, using low target levels of 4–10 ng/ml. Efficacy of sirolimus was evaluated in regard to pain symptoms using the visual analogue scale/numeric rating scale and patients reported QoL. To rule out a placebo effect of sirolimus, sirolimus was stopped after a certain time point and reintroduced as soon as complaints returned. Adverse events were closely monitored and graded using the Common Terminology Criteria for Adverse Events (CTCAE) grading.ResultsAn improvement in symptoms was seen in 92% (n = 11/12) of patients. In nine patients pain complaints returned. Seven out of nine of them (78%) again experienced a reduction of symptoms after restarting sirolimus treatment. Despite low target levels, these response rates are comparable to those found in the literature using higher target levels of sirolimus. However, significantly less serious AEs were observed with low dose sirolimus, suggesting low dose sirolimus might be safer. Unfortunately, young adolescent female patients developed serious menstrual disturbances during treatment with low dose sirolimus. We describe this adverse event for the first time in patients with congenital vascular malformations and this might be specifically related to low dose sirolimus.ConclusionsLow dose sirolimus showed a high efficacy in patients with therapy-resistant and low-flow malformation, with a lower incidence of serious adverse events. At the same time a new adverse event, namely menstrual cycle disturbance, was observed in young adolescents, indicating the need for caution when sirolimus is given. This is extremely relevant to patients with low-flow vascular malformation, who are likely to require lifelong treatment for their condition.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01758-y.

Nigel Standfield: vascular surgeon who trained generations worldwide

Nigel Standfield was born in Wuppertal, Germany, to John Standfield, who had served in the British and Indian armies during the second world war and then in British intelligence, and...

Case Reports of An Innovative Technique for Columellar Reconstruction in Children Using a Custom-Made Composite Graft from the Back of the Ear

AbstractThe columella is unique as a nasal subunit. The nasal columella has traditionally been a difficult subunit to repair because of its unique contours, tenuous vascularity, and limited availability of adjacent skin. Columellar defects can significantly impair aesthetic appearance. Columellar damage can be caused by congenital loss, ischemic injuries, trauma, tumor resection, and vascular malformations. Columella reconstruction can be very challenging for plastic surgeons.Defects of the nasal columella can be repaired using various methods including composite free grafts from the ear (1,2), nasolabial flaps (3), nasofacial sulcus flaps (4), forehead flaps (5), extended Abbe flaps (6), and free flaps (7).Auricular chondrocutaneous composite grafts have been reported in the literature. The main advantages of these grafts are avoidance of facial scars and provision of tip support. However, risk of composite graft loss was reported as a main complication.Herein, we report two cases of columellar defect reconstructions in children using a custom-made columella from conchal composite graft with the tongue-in-groove principle. The main advantage of this technique is that it is one-stage method; the custom-made columella depends on the dimensions of the defect, so it can be tailored according to the dimension of the columellar defect; the use of the tongue-in-groove principle increases the contact surface between the graft and recipient. Therefore, increase the possibility of survival of the reconstructed columella with minimal donor site morbidity.

Treatment Update of Port-Wine Stain: A Narrative Review.

Port-wine stain (PWS) is a congenital vascular malformation affecting 0.3&ndash;0.5% of normal population. These characteristic lesions arise due to the interplay of vascular, neural, and genetic factors. Treatment options include lasers, cosmetic tattooing, electrotherapy, cryosurgery, derma-abrasion, and skin grafting; however, none of these treatment alternatives appears to be satisfactory and is unable to provide consistent, satisfactory responses or even complete cures. Currently, laser is the treatment of choice, as it is comparatively safe and more effective than other procedures. The most commonly used modality is pulsed dye laser (PDL). The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) to January 2020 and reference lists of respective articles. Only articles published in English language were included. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5005.

Closure of Challenging Pediatric Scalp Wounds by a Tension-Relief System.

Pediatric scalp defects may be challenging, due to their variant tension level and specific etiologies. Tissue characteristics and pre- and post-management considerations may pose difficulties to reconstruction in the pediatric patient. Primary closure is the preferred surgical technique but is not always possible. Various techniques have been described for facilitating primary wound closure, by reducing tension from the skin wound margins. The authors use a tension-relief system in some challenging scalp wounds when simple primary closure cannot be achieved. This enables primary closure without tension on the surgical margins, and may thus preclude the need for other closure techniques such as tissue-expanders, grafts, and flaps. The authors describe our use of a tension-relief system in 21 pediatric patients treated during 2017-2020, for congenital deformities, vascular malformations and other skin lesions, traumatic wounds, burn scars, and complicated surgical wounds with and without hardware exposure. A tension-relief system is a prompt, simple-to-use, safe, and low-cost surgical solution that offers several advantages over other techniques when tension-free primary intention closure is not possible. These benefits include less extensive surgery, fewer surgeries and associated anesthesia, shorter treatment period and hospitalization, better scarring, lower distress and burden to patients and their families, better pain-control, the absence of donor-site with its comorbidities, and less bleeding and risk of damaging adjacent structures. Based on our experience and the system characteristics detailed, the authors recommend using the described technique, which is convenient, accessible, and reliable, to close challenging scalp wounds in pediatric patients.

Diode laser for the treatment of a high flow lip vascular malformation.

About 50% of vascular malformations are located at the head and neck region where they can usually be associated with functional and/or aesthetic limitations. Laser treatment has proven to be effective in treatment of small low-flow vascular malformations, but little is known about the use of this therapy for high-flow larger arteriovenous malformations (AVMs). A congenital high-flow vascular malformation of the upper lip had to be treated because it was causing functional impairment and deformity which were affecting the quality of life. The mainstay of treatment is surgical therapy after embolization of the lesion, but the treatment of high-flow lesions is difficult because of the high risk of mortality and morbidity. The lesion was then treated with transmucosal diode laser applications in multiple sessions. The lesion progressively reduced in dimension without any sign of recurrence after multiple sessions of transmucosal diode laser applications. The clinical examination and the ultrasound scan performed four years after the last treatment demonstrated that no complications or further recurrence occurred. Multiple sessions of diode laser application can be a safe, effective and minimally-invasive treatment for oral mucosa vascular malformations, even if characterized by high flow.

Epidemiology, Diagnostics, and Management of Vein of Galen Malformation

BackgroundVein of Galen malformation (VGM) is a rare congenital intracerebral vascular malformation. The aim of this study was to gain reliable data about epidemiology; clinical manifestations; and pre-, peri- and postinterventional treatment strategies in Germany. MethodsThis prospective epidemiologic study was conducted by Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland, a hospital-based German nationwide surveillance unit for rare pediatric diseases. Patients aged upto 18 years with a new diagnosis of VGM were prospectively included between January 1, 2014 and December 31, 2015. ResultsIn the two-year study period, 30 individuals with newly diagnosed VGM were identified, resulting in an estimated annual incidence rate of VGM in Germany of at least 1: 58,100 live births. The main symptoms were age dependent. Neonates presented with mainly cardiac manifestations of high output failure; infants and older children mainly suffered from neurological complications. Of the patients with endovascular treatment 95% survived, but only 41% of these patients were discharged home without any complications. The Bicêtre Neonatal Evaluation Score was a good predictor for poor outcome but could have led to palliative care in some patients with good outcome. ConclusionsThe incidence of VGM in Germany is estimated to be 1:58,100 live births. The majority of patients were eligible for endovascular treatment. Nevertheless, due to side effects and long-term sequelae in the majority of patients, further improvement in care of children with VGM is needed.

Influence of Port-wine Stains on Quality of Life of Children and Their Parents.

Port-wine stains are congenital vascular malformations that affect the quality of life of children and their parents. This study used the Family Dermatology Life Quality Index and Children’s Dermatology Life Quality Index to examine the effects of port-wine stains on the quality of life of children and their parents, including an in-depth, systematic analysis of the moderating effects of the children’s sex and port-wine stain classification. The study included 43 children (25 girls and 18 boys) and their parents. The presence of a port-wine stain had a significantly greater impact on the quality of life of mothers than on that of fathers (p < 0.001). Port-wine stains in girls had a greater effect on paternal quality of life than did port-wine stains in boys (girls p < 0.01; boys p = 0.542). Severe types of port-wine stains exerted a greater impact on maternal quality of life (pink-red type, dark-red type, and purple-dark type: p < 0.001, p = 0.948 and p = 0.086, respectively). Therefore, clinicians should consider familial relationships and differences when offering psychological support.

Giant venous malformation of the tongue with macroglossia: A hidden menace

Venous malformations (VMs) are congenital slow flow vascular malformations that are usually present at birth. They grow proportionate with the age and do not regress with time differentiating them from hemangiomas. VM presents as bluish discoloration of skin/mucosa or as soft subcutaneous masses. It may affect any organ, including viscera-like gastrointestinal tract or brain. VM is generally slowly progressive and asymptomatic as they grow slowly with age. We report the case of asymptomatic giant VM over the tongue for which the patient presented due to herpetic stomatitis.