Low-flow Vascular Malformations Research Articles

In-Human Clinical Experience with Direct Stick Embolization of Low-Flow Vascular Malformations Using an mTOR Inhibitor

BackgroundWhile direct stick embolization (DSE) of low-flow vascular malformations (LFVMs) with off-label embolotherapeutic compounds is the current mainstay of therapy, systemic oral mTOR inhibition has evolved into an important adjunctive therapy that is associated with frequent blood draws, systemic toxicity, and rebound signs/symptoms upon cessation. We, herein, report our experience with in-human DSE of LFVMs with an mTOR inhibitor for direct, intralesional targeting of the culprit mutated pathway without repeated systemic exposure. MethodsSince 2020, 33 procedures involving DSE were performed in 25 patients with LFVMs using a patented formulation and technique involving the intravenously compatible mTOR inhibitor Yale-OCR7737, used as a liquid compound in a collagen matrix emulsion for added viscosity and intralesional residence. Data was prospectively maintained and retrospectively reviewed for technical success (successful catheterization of the lesion and intralesional delivery of compound); clinical success (improvement in signs/symptoms with radiologically documented reduction in flow and/or volume of treated lesion); complications; side effects; and re-interventions. ResultsFrom 2020 to 2023, 33 procedures involving DSE were performed using Yale-OCR7737 in 25 patients (10[40%] men; 15[60%] women; mean age: 28 years [range 1 -70 years]) with LFMVs involving the head/neck (48%) and limbs (40%); 88% were non-syndromic while 12% had Klippel-Trenaunay Syndrome; 68% exhibited venous malformations, while 32% had lymphatic malformations. Technical and clinical success were 100%. Mean DSE sessions per patient was 1.4 (range 1 to 5). Localized intravascular coagulopathy was present after 16 (49%) DSE procedures; D-dimer improved post-DSE in 7 cases. No perioperative or delayed complications occurred. Side-effects were 7 (21%) cases of self-limited, transient oral aphthous ulcers. ConclusionsOur findings suggest that DSE of LFVMs with mTOR inhibitors (Yale-OCR7737) may be safe and effective. This may represent the new embolotherapeutic frontier in the endovascular treatment of LFMVs.

Atypical presentation of periorbital rhinosporidiosis: A rare case report

Periorbital rhinosporidiosis (PR) is an aquatic protistan parasitic infection that commonly affects mucous membranes of the nasal cavity. This report presents a case of PR mimicking a low-flow vascular malformation (VM) that was later diagnosed as an atypical case of PR. A 48-year-old male presented with a painless mass medially below the right eye’s lower lid, which progressively increased in size. Initial examination suggested a low-flow VM. However, histopathological analysis of the biopsy specimen confirmed the presence of rhinosporidiosis with features such as arteriovenous malformation. There is a need for a multidisciplinary approach to manage such cases.

Venous malformations in children: comparison between magnetic resonance imaging and histopathological findings.

Among low-flow vascular malformations, venous malformations are relatively frequent. The pathological patterns vary in severity and are generally characterized by dilated vessels and low-flow blood that over time can organize into phleboliths. Sometimes small capillary and/or lymphatic vessels may be associated, micro- and/or macro-shunts may form alone or in different combinations, and finally adipose tissue may be interposed between the malformed vessels. Magnetic resonance imaging (MRI) is a crucial examination for confirming venous malformations because it can accurately identify different features of the lesions. The aim of our study was to compare MRI and histopathological findings of venous malformations in childrento assess thepossibilities and limitationsof MRI. In a retrospective study, two observers independently evaluated the contrast-enhanced MRI of 26 children with venous malformations. Several radiological parameters were considered and compared with histopathological findings. The agreement between the interobserver radiological evaluation and between histopathological and radiological diagnosis was verified using Cohen's kappa. MRI interobserver agreement was excellent for micro-shunts and good for the remaining findings. The radiological-pathological agreement was perfect for the presence/absence of phleboliths and of macro-shunts and almost perfect for the presence of intralesional adipose tissue, lymphatic component, and micro-shunts. MRI in venous malformations can detect the presence of phleboliths, adipose tissue, and lymphatic components with excellent accuracyand good to excellent interobserver agreement. Furthermore, MR angiography can detect micro-shunts in simple and combined venous malformations with substantial agreement with histopathological findings.

Classification, diagnosis, and treatment of low-flow congenital vascular malformations

Classification, diagnosis, and treatment of low-flow congenital vascular malformations

Comparison between Bleomycin Foam and Liquid Injection in Treatment of Maxillofacial Low Flow Vascular Malformations

Comparison between Bleomycin Foam and Liquid Injection in Treatment of Maxillofacial Low Flow Vascular Malformations

Cerebrofacial Venous Metameric Syndrome Mimicking Vein of Galen Aneurysmal Malformation

Cerebrofacial venous metameric syndrome (CVMS) is a complex low-flow vascular malformation affecting bone and soft tissues including brain, dura mater, and eye. We show images of CVMS in an 18-month-old boy presenting facial venous malformations, developmental venous anomalies, dural sinus malformations, and dilated great cerebral vein, suggesting a vein of Galen aneurysmal malformation. Although Sturge-Weber syndrome is the most known form of CVMS, its presentations are variable and include several venous malformations. Recognizing the various manifestations of CVMS is necessary for adequate screening, treatment, and follow-up.

Deep learning-based differentiation of peripheral high-flow and low-flow vascular malformations in T2-weighted short tau inversion recovery MRI.

Differentiation of high-flow from low-flow vascular malformations (VMs) is crucial for therapeutic management of this orphan disease. A convolutional neural network (CNN) was evaluated for differentiation of peripheral vascular malformations (VMs) on T2-weighted short tau inversion recovery (STIR) MRI. 527 MRIs (386 low-flow and 141 high-flow VMs) were randomly divided into training, validation and test set for this single-center study. 1) Results of the CNN's diagnostic performance were compared with that of two expert and four junior radiologists. 2) The influence of CNN's prediction on the radiologists' performance and diagnostic certainty was evaluated. 3) Junior radiologists' performance after self-training was compared with that of the CNN. Compared with the expert radiologists the CNN achieved similar accuracy (92% vs. 97%, p = 0.11), sensitivity (80% vs. 93%, p = 0.16) and specificity (97% vs. 100%, p = 0.50). In comparison to the junior radiologists, the CNN had a higher specificity and accuracy (97% vs. 80%, p < 0.001; 92% vs. 77%, p < 0.001). CNN assistance had no significant influence on their diagnostic performance and certainty. After self-training, the junior radiologists' specificity and accuracy improved and were comparable to that of the CNN. Diagnostic performance of the CNN for differentiating high-flow from low-flow VM was comparable to that of expert radiologists. CNN did not significantly improve the simulated daily practice of junior radiologists, self-training was more effective.

Phleboliths, not Sialoliths: a submandibular gland venous malformation: case report and literature review

Although venous malformations occurring in the submandibular gland are extremely rare, most have been diagnosed as "hemangiomas". Based on the literature review very few cases of submandibular gland venous malformation were reported for the last 55 years. We provide one of this rare cases; A 62-year-old female patient presented with swelling in the left submandibular area for 6 months with no complaints of xerostomia nor suppuration from the salivary ducts. Ultrasound Sonography test of the neck and CT scan revealed an heterogenous lesion in left submandibular area with multiple calcifications. The mass was surgically excised, the histopathological examination reported a submandibular gland venous malformation with phleboliths. Low-flow vascular malformations of the head and neck region can develop phleboliths that may be mistaken for sialoliths given the similar calcified nature and location specially in salivary gland area. Appropriate history, clinical examination and investigation leads to the correct diagnosis and treatment.

Combination of lauromacrogol and bleomycin in the treatment of low-flow vascular malformations: a web-based meta-analysis.

Combination of lauromacrogol and bleomycin in the treatment of low-flow vascular malformations: a web-based meta-analysis.

Magnetic resonance - guided treatment of low-flow vascular malformations and the technologies to potentiate adoption.

Vascular malformations are congenital, non-neoplastic lesions that arise secondary to defects in angiogenesis. Vascular malformations are divided into high-flow (arteriovenous malformation) and low-flow (venous malformations and lymphatic malformations). Magnetic resonance imaging (MRI) is the standard for pre-and post-intervention assessments, while ultrasound (US), X-ray fluoroscopy and computed tomography (CT) are used for intra-procedural guidance. Sclerotherapy, an image-guided therapy that involves the injection of a sclerosant directly into the malformation, is typically the first-line therapy for treating low-flow vascular malformations. Sclerotherapy induces endothelial damage and necrosis/fibrosis with eventual involution of the malformation. Image-guided thermal therapies involve freezing or heating target tissue to induce cell death and necrosis. MRI is an alternative for intra-procedural guidance and monitoring during the treatment of vascular malformations. MR can provide dynamic, multiplanar imaging that delineates surrounding critical structures such as nerves and vasculature. Multiple studies have demonstrated that MR-guided treatment of vascular malformations is safe and effective. This review will detail (1) the use of MR for the classification and diagnosis of vascular malformations, (2) the current literature surrounding MR-guided treatment of vascular malformations, (3) a series of cases of MR-guided sclerotherapy and thermal ablation for the treatment of vascular malformations, and (4) a discussion of technologies that may potentiate interventional MRI adoption including high intensity focused ultrasound and guided laser ablation.

Intralesional injection of bleomycin in the management of low flow vascular malformations: Results and factors affecting the outcome

ObjectiveEthanol has been a commonly used sclerosant for low-flow vascular malformations, but it carries a high risk of complications. Bleomycin has been recently introduced as a potentially effective treatment. The aim of this study was to evaluate the safety and efficacy of bleomycin intralesional injection for the treatment of low-flow vascular malformations and determine the different factors affecting the outcome. Patients and methodsA total of fifty patients with low-flow vascular malformations were enrolled in the study between April 2020 and March 2022. All patients underwent preoperative duplex ultrasound and magnetic resonance angiography. The procedure was performed under ultrasound and fluoroscopic guidance. All patients were assessed for the objective improvement, ultrasound assessment, and patient-reported outcome. ResultsThe overall rate of objective improvement was 79.53% (78.05% in venous and 87.5% in lymphatic malformations), whereas 81.25% of the patients showed a degree of size reduction or complete obliteration on postoperative ultrasound. The patient-reported outcome analysis showed a statistically significant improvement in the mean score for the pain, overall symptoms, and self-confidence. On regression analysis, the only factor associated with poor objective outcome was diffuse lesions (ill-defined or extending in more than one body region or one compartment). No major complications were recorded. ConclusionsBleomycin intralesional injection is a safe and effective treatment for low-flow vascular malformations.

Approach to the Management of Vascular Malformations of Head and Neck and Its Challenges: An Institutional Experience

Abstract Background: Vascular malformations (VMs) in the region of the head and neck are a complex group of lesions that present with serious challenges in diagnosis and management. We sought to study the efficacy and safety of a therapeutic algorithm emphasizing multimodal management in the treatment of head and neck VMs. Methodology: A retrospective study was conducted reviewing all the patient information from the database who were treated for VM of the head and neck at the institution. Patients who presented during the period between January 2012 and December 2022 were included in the study. Conservative care, sclerotherapy, embolization, surgical excision, or a combination of these techniques were among the management options based on the clinical profile of the patient as well as the characteristics of the lesion. Results: 91 VMs in the region of the head and neck included 45 (49%) males and 46 (51%) females, with an age range of between 4 years and 71 years (mean 23.9 ± 14.06 years). There were 53 low-flow vascular malformations (LFVMs), of which 6 (11.9%) were managed conservatively, 26 (49.05%) were treated with sclerotherapy, 20 (37.7%) underwent excision, and 1 (1.8%) was treated with combination therapy. Of the 38 high-flow vascular malformations (HFVMs), 12 (31.5%) were treated with arterial embolization, 13 (34.2%) were primarily resected, 2 (5.2%) with excision and reconstruction, 5 (13.1%) underwent embolization and excision, and 1 (2.6%) underwent emergency external carotid artery ligation. In the LFVM group, response to sclerotherapy led to improvements in 24 (92%) patients, while surgical resection led to improvements in 20 (100%) individuals. In the HFVM group, embolization therapy improved 9 (75%), combination therapy improved 5 (100%), and surgical resection improved 15 (100%) of the patients. Conclusions: In our experience, the implementation of a multimodal management algorithm has had favorable outcomes with an acceptable complication rate in head and neck VMs.

Baseline Quality of Life in Pediatric Patients With Low-flow Vascular Malformations.

The aim of this study was to quantify and describe baseline patient and parent-proxy health-related quality of life scores in patients with low-flow vascular malformations at a single, tertiary-care vascular anomalies clinic. This is a retrospective study of data collected on patients with low-flow vascular malformations between the ages of 2 to 25 who were seen at a single, tertiary-care center vascular anomalies clinic. A total of 266 patients are included in this study. Patients with lymphatic malformations report decreased quality of life scores as compared with venous malformations in the emotional, psychological, school, and social domains. Patients with lower extremity malformation report decreased quality of life scores as compared with head/neck, trunk, upper extremity, and multifocal malformations; most notably in the physical domain. Treatment of low-flow vascular malformations should aim to improve patient quality of life. The use of standardized health-related quality of life measures in this study quantifies baseline quality of life scores among patients with low-flow vascular malformations.

Influence of genetic variants on the pharmacokinetics and pharmacodynamics of sirolimus: a systematic review.

Sirolimus is an antiproliferative and immunosuppressive compound inhibiting the mTOR pathway, which is often activated in congenital low-flow vascular malformations. Studies have demonstrated the efficacy of sirolimus for this disease. Studies in kidney transplant patients suggest that genetic variants can influence these pharmacokinetic parameters. Therefore, a systematic literature search was performed to gain insight into pharmacogenetic studies with sirolimus. Most studies investigatedCYP3A4 and CYP3A5, with inconsistent results. No pharmacogenetic studies focusing on sirolimus have been performed for low-flow vascular malformations. We analyzed two common variants of CYP3A4 and CYP3A5 (CYP3A4*22 and CYP3A5*3, respectively) in patients (n=59) with congenital low-flow vascular malformations treated with sirolimus. No association with treatment outcome was identified in this small cohort of patients.

Cerebral cavernomatosis and epilepsy: treatment and serial imaging follow-up

Cerebral malformations, known as cavernomas, are low flow vascular malformations that have a multilobulated appearance. A large percent of cavernous malformations have seizures as initial symptoms. We report a case of a 48 years old patient presented in the neurological department for seizure work-up. We performed serial brain imaging to follow the evolution of bleeding cavernomas and electroencephalography to find epileptogenic cavernomas. Conservative management was decided and the evolution under antiepileptic drugs was good, but with some compliance issues further discussed.

Surgery for Port-Wine Stains: A Systematic Review.

Port-wine stains (PWS) are congenital low-flow vascular malformations of the skin. PWS tend to become thicker and darker with time. Laser therapy is the gold standard and the first-line therapy for treating PWS. However, some resistant PWS, or PWS that have tissue hypertrophy, do not respond to this therapy. Our aim is to evaluate the role of surgery in the treatment of PWS birthmarks. A literature search was performed in PubMed, Scopus, Web of Science (WOS) and Google Scholar for all papers dealing with surgery for port-wine stains, from January 2010 to December 2020 using the search strings: (capillary vascular malformation OR port-wine stains OR Sturge Weber Syndrome OR sws OR pws) AND (surgical OR surgery). Ten articles were identified and used for analysis. They were almost all case series with a short follow up period and lacked an objective-systematic score of evaluation. Delay in treatment of port wine stains may result in soft tissue and bone hypertrophy or nodules with disfiguring or destructive characteristics. The correction of PWS-related facial asymmetry often requires bone surgery followed by soft tissue corrections to achieve a more harmonious, predictable result.

Abstract No. 577 Mixed-Methods Assessment of the Patients-Reported Outcome Measure for Vascular Malformations Questionnaire (PROVAM) in Patients with Low-Flow Vascular Malformations: A Prospective Cohort Study

Abstract No. 577 Mixed-Methods Assessment of the Patients-Reported Outcome Measure for Vascular Malformations Questionnaire (PROVAM) in Patients with Low-Flow Vascular Malformations: A Prospective Cohort Study

Abstract No. 200 Comparison Between Patients-Reported Outcome Measure for Vascular Malformations Questionnaire (PROVAM) and Outcome Measures for VAscular Malformations (OVAMA) Responses in Patients with Low-Flow Vascular Malformations

Abstract No. 200 Comparison Between Patients-Reported Outcome Measure for Vascular Malformations Questionnaire (PROVAM) and Outcome Measures for VAscular Malformations (OVAMA) Responses in Patients with Low-Flow Vascular Malformations

Subcutaneous Granuloma Annulare vs. Subcutaneous Vascular Malformations in Children: A Diagnostic Challenge.

There are various subcutaneous lesions in children and often there is difficulty in obtaining an accurate diagnosis by non-invasive diagnostic procedures. Subcutaneous granuloma annulare (SGA) is a rare granulomatous disease that, even after imaging, is often mistaken for a low-flow subcutaneous vascular malformation (SVM). This study aimed to accurately identify clinical and imaging clues to distinguish SGA from low-flow SVM. We retrospectively analyzed complete hospital records of all children with a confirmed diagnosis of SGA and low-flow SVM who underwent MR imaging at our institution from January 2001 to December 2020. Their disease history, clinical and imaging findings, management, and outcome were evaluated. Among 57 patients with granuloma annulare, we identified 12 patients (nine girls) with a confirmed SGA diagnosis who underwent a preoperative MRI. Their median age was 3.25 years (range 2-5 years). Of 455 patients diagnosed with vascular malformations, 90 had malformations limited to the subcutaneous area. Among them only 47 patients with low-flow SVM were included in the study and further analyzed. Our SGA cohort had a female predilection (75%) and a short history of lump appearance of 1.5 months. SGA lesions were immobile and firm. Before MRI, patients underwent initial evaluation by ultrasound (100%) and X-ray (50%). Surgical tissue sampling was performed in all SGA patients to establish a diagnosis. All 47 patients with low-flow SVM were diagnosed correctly by MRI. A total of 45 patients (96%) underwent surgical resection of the SVM. A careful retrospective review of imaging findings of patients with SGA and SVM showed that SGA present as homogenous lesions in the shape of an epifascial cap with a typical broad fascial base extending towards the subdermal tissue in the middle of the lesion. In contrast, SVMs always present with variable-sized multicystic or tubular areas. Our study shows clear clinical and imaging differences between low-flow SVMs and SGA. SGA presents characteristically in the shape of a homogenous "epifascial cap," which distinguishes these lesions from multicystic heterogenous SVMs.

Evolving indications for pediatric neurointerventional radiology: A single institutional 25-year experience in infants less than one year of age and a brief historical review.

Pediatric neurointerventional radiology is an evolving subspecialty with growing indications and technological advancement such as miniaturization of devices and decreased radiation dose. The ability to perform these procedures is continuously balanced with necessity given the inherently higher risks of radiation and cerebrovascular injury in infants. The purpose of this study is to review our institution's neurointerventional experience in infants less than one year of age to elucidate trends in this patient population. We retrospectively identified 132 patients from a neurointerventional database spanning 25 years (1997-2022) who underwent 226 procedures. Treatment type, indication, and location as well as patient demographics were extracted from the medical record. Neurointerventional procedures were performed as early as day of life 0 in a patient with an arteriovenous shunting malformation. Average age of intervention in the first year of life is 5.9 months. Thirty-eight of 226 procedures were completed in neonates. Intra-arterial chemotherapy (IAC) for the treatment of retinoblastoma comprised 36% of neurointerventional procedures completed in infants less than one year of age followed by low flow vascular malformations (21.2%), vein of Galen malformations (11.5%), and dural arteriovenous fistulas (AVF) (9.3%). Less frequent indications include non-Galenic pial AVF (4.4%) and tumor embolization (3.0%). The total number of interventions has increased secondary to the onset of retinoblastoma treatment in 2010 at our institution. The introduction of IAC for the treatment of retinoblastoma in the last decade is the primary driver for the increased trend in neurointerventional procedures completed in infants from 1997 to 2022.