Search Results (41)

Objectives: This research aims to examine the impact of intracystic hemorrhage (ICH) on therapeutic outcomes in children with macro or mixed cystic lymphatic malformation (cLM). Methods: This retrospective study included macro/mixed cLM cases with or without ICH who underwent treatment between January 2019 and June 2024. All patients were diagnosed using preoperative imaging findings and intraoperative indocyanine green (ICG) lymphography. The baseline data of enrolled cases were retrospectively collected. The clinical characteristics were documented, including gender, age, histological typing, location, maximum diameter, and intracystic condition. Patients with or without ICH were divided into two groups. The dependent variables for predicting an excellent outcome were analyzed using multivariable logistic regression models after adjusting for potential factors using a univariable regression model. Postoperative variables, including duration of negative drainage, local infection, scar hyperplasia, and follow-up, were compared between the two groups. Results: A total of 83 cLM patients were included (ICH group: n = 36 and without ICH group: n = 47). A complete absence of afferent lymphatic vessels was demonstrated using intraoperative ICG lymphography, suggesting the isolated nature of ICH cases. ICH (p = 031; OR, 2.560; 95% CI, 1.089–6.020) was identified as the main predictor, and younger patients (p = 035; OR, 0.415; 95% CI, 0.183–0.940) had a lower potential for excellent outcomes. For the postoperative variables, the ICH group exhibited a shorter duration of negative drainage than the without ICH group (p < 0.001), while no significant differences were found regarding local infection (p = 0.693) and scar hypertrophy (p = 0.648). Conclusions: Although characterized by aggressive progression and compressive symptoms, ICH emerges as an independent favorable prognostic predictor in macro/mixed cLM management, potentially attributable to its isolated nature. Full article

Background: Klippel–Trenaunay syndrome (KTS) is a congenital vascular malformation syndrome characterized by low-flow vascular anomalies, including venous malformation (VM) and lymphatic involvement. These anomalies may lead to limb asymmetry due to soft tissue and/or bone overgrowth. Compression therapy using elastic garments is considered a conservative and minimally invasive first-line treatment option for KTS. However, the benefits of compression therapy for low-flow vascular malformations, particularly limb VMs, have not been sufficiently evaluated. This prospective, multi-center study assessed the efficacy and safety of compression therapy for KTS with VM. Methods: After measuring the affected limb, a custom-made elastic garment providing 30 mmHg of compression was manufactured (THUASNE, France). A total of 20 patients (7 male, 13 female; mean age: 10.9 years) underwent compression therapy for 26 weeks at four nationwide institutions in Japan. The primary outcome was the change in lower limb circumference. Secondary outcomes included pain, modified Rankin Scale (mRS) score, body water content, vital signs, changes in garment elasticity, and adverse events. Results: All 20 patients completed the study. At the study endpoint, the circumference ratio of the affected to unaffected limbs was significantly reduced at the superior end of the tibial tuberosity (p = 0.02) and the thinnest part of the ankle (p < 0.001). The elastic force of the garment declined by approximately 50% over 26 weeks. No serious adverse events related to the intervention were reported. Conclusions: Compression therapy using a custom-made elastic garment appears to be a safe and effective approach for managing limb overgrowth in patients with KTS and VM. To maintain the therapeutic effect, garment replacement is recommended at least every six months. Full article

Background/Objectives: This study aims to identify baseline imaging parameters, across various imaging modalities, that can predict the response to bleomycin sclerotherapy in patients with head and neck lymphatic–venous malformations (LVMs). Methods: A retrospective analysis of 80 patients (85 lesions) treated at a tertiary care center between January 2018 and December 2022 was conducted. Imaging modalities, including CT, MRI, ultrasonography, and dynamic digital radiographic images, were reviewed for lesion characteristics. Factors including lesion type, volume, morphology, location, and contrast opacification patterns were analyzed for their association with treatment response, defined as a >50% reduction in lesion size and symptom improvement. Univariable and multivariable logistic regression analyses were performed. Results: Of 85 lesions, 45 (52.9%) responded to treatment. Univariable analysis showed that pure lymphatic malformations (OR = 6.12, p = 0.004), macrocystic components (OR = 10, p = 0.016), cavitary morphology on dynamic digital radiographic images (OR = 8.90, p < 0.001), neck location (OR = 4, p = 0.03), and deep-seated lesions (OR = 3.69, p = 0.03) were significantly associated with better outcomes. Multivariable analysis identified cavitary morphology as the strongest predictor (p = 0.04). A combination of cavitary morphology, macrocystic components, and pure LM type yielded the highest predictive accuracy (AUC = 0.80, p = 0.03). Conclusions: The presence of lymphatic channels or large cystic venous spaces—such as macrocystic features on imaging or cavitary morphology—along with neck or deep-seated lesion location, predicts a favorable response to bleomycin sclerotherapy in head and neck LVMs. Full article

Background: Vascular malformations (VAMs) impose multifaceted burdens extending beyond physical impairments to psychosocial dysfunction. While prior studies predominantly utilized generic quality-of-life instruments, disease-specific tools are critical for addressing heterogeneous symptom profiles and sociocultural variability, particularly in understudied Asian populations. This study investigated psychosocial impacts across pediatric and adult VAM patients via validated, condition-specific measures. Methods: A prospective cohort of 233 hospitalized VAM patients (114 pediatric patients, 119 adult patients) completed the OVAMA questionnaire, and 114 adult, 68 pediatric patients, and 115 parent-proxies completed corresponding PROMIS questionnaires. The subtypes included arteriovenous malformations (AVMs), venous/lymphatic/lymphovenous malformations (VMs/LMs/LVMs), port-wine stains (PWSs), and other vascular malformations. Statistical analyses (Mann–Whitney U test, Kruskal–Wallis test, linear regression) were used to evaluate associations between demographics, clinical characteristics, and psychosocial outcomes. Results: Compared with children, adults reported significantly greater distress related to general (p = 0.004) and appearance (p = 0.003) problems. Compared with AVM (p = 0.01) and PWS (p = 0.041) patients, VM/LM/LVM patients presented elevated general problem scores. Pain and bleeding were related to general problems, whereas temporary enlargement was related togeneral and appearance problems. The PROMIS results revealed that 42.1% of adults had below-normal psychosocial-positive scores, whereas 33% demonstrated abnormal psychosocial-negative scores. Pediatric self-reports were associated with higher anxiety and depression rates than parent proxies were, with the VM/LM/LVM subgroups reporting poorer family relationships (p = 0.0062) and life purposes (p = 0.0075). Treatment frequency was correlated with increased psychological stress in children (p = 0.007). Conclusion: VAMs significantly impair psychosocial functioning across all ages, with adults experiencing heightened distress and social role deficits. Pediatric patients with low-flow malformations (VMs/LMs/LVMs) face compound depressive symptoms and familial strain. Disease-specific tools such as OVAMA and PROMIS are essential for comprehensive assessments, guiding tailored interventions to address both physical and psychosocial burdens. Full article

Background/Objectives: Bleomycin electrosclerotherapy (BEST), which combines intralesional bleomycin administration with electroporation, enhances drug uptake and has shown efficacy in treating vascular malformations resistant to conventional therapies. While BEST is increasingly used in various anatomical sites, its application in the upper aerodigestive tract remains underexplored. This study evaluates the safety and effectiveness of BEST in managing slow-flow vascular malformations of the oral cavity, tongue, larynx, and hypopharynx. Methods: In this retrospective, multicenter study, 20 patients with symptomatic slow-flow vascular malformations of the upper aerodigestive tract were treated with BEST. Clinical and radiological assessments were used to evaluate the treatment response, categorized as “significantly reduced”, “reduced”, “stable disease”, or “lesion growth”. Postprocedural complications and functional outcomes were systematically recorded. Results: A total of 29 BEST sessions were performed. Lesions of the tongue (n = 8) and combined oral cavity and tongue (n = 6) showed the highest response rates, with significant symptom reduction in five out of eight and five out of six patients, respectively. Among isolated oral cavity lesions (n = 4), one out of four demonstrated a significant reduction. In contrast, laryngeal and hypopharyngeal lesions (n = 2) had limited response, with one case showing partial reduction and the other remaining stable. Severe complications, including bleeding and dyspnea requiring tracheostomy, limited further treatment in these locations. No systemic adverse events, such as pulmonary toxicity, were observed. Conclusions: BEST is effective for treating vascular malformations of the upper aerodigestive tract, particularly in the tongue and oral cavity, but presents significant risks in laryngeal and hypopharyngeal lesions. A multidisciplinary approach is required to optimize treatment protocols for these challenging locations. Full article

Background/Objectives: This study aimed to investigate surgical resections of vascular malformations and haemangiomas of the upper extremity, pre- and postoperative symptoms, complications and recurrences. Methods: A total of 82 patients with vascular malformations and haemangiomas treated by surgical resection from 2010 to 2020 were included in this observational study. Pre- and postoperative symptoms, including pain and swelling, as well as complications and recurrence rates, were assessed. Descriptive statistics were provided for all reported data. Parametric and non-parametric tests were used for group comparisons. Alterations of reported pain were assessed. A two-sided alpha of 5% determined statistical significance. Results: A total of 88 procedures were performed in 82 patients. The most common vascular malformation was a venous malformation, followed by arterio-venous malformations. More than 50% of the patients reported pain prior to the surgery, while 14.6% of patients experienced pain postoperatively, which indicated significant improvement (p = 0.001). Minor postoperative complications occurred in 31.7% of patients. Overall, a recurrence rate of 17.1% was recorded during postoperative follow-up, mostly occurring in diffuse and infiltrating types of vascular malformations. Conclusions: Surgical resections of vascular anomalies of the upper extremity led to symptom improvement and are an important part of the multidisciplinary treatment algorithm. Full article

Background/Objectives: Vascular malformations form masses in subcutaneous and muscular tissues throughout the body and are occasionally misdiagnosed as subcutaneous nonvascular tumors. Understanding and differentiating their clinical and imaging features are crucial due to their different treatments and prognoses. This study aimed to report cases of nonvascular tumors that were initially misdiagnosed and treated as vascular malformations. Methods: In this retrospective observational study, we enrolled 14 (1.8%) patients with pathologically diagnosed nonvascular tumors from among 536 patients with 759 lesions of clinically diagnosed vascular malformations. Results: The average age at the initial visit was 41.9 years, with a male-to-female ratio of 3:11. Tumor locations included the lower limb in seven patients, the upper limb in five patients, and the trunk and head in one patient each. Ultrasound evaluation revealed 12 lesions of low-flow vascular malformations and two lesions of high-flow vascular malformations. These findings led to an initial diagnosis of venous or lymphatic malformations in 12 patients and arteriovenous malformations in two patients. Based on the clinical diagnosis, treatments administered before tumor resection included sclerotherapy in four patients and transcatheter arterial embolization in one patient. All patients underwent tumor resection. The final histopathological diagnoses included schwannoma in six patients, epidermal cyst and angiomyoma in two patients each, and other types of tumors in four patients. The average time from initial diagnosis to final histopathological diagnosis was 370 days. Conclusions: Multimodal diagnostic strategies, especially the use of ultrasound, enhance the differentiation between vascular malformations and nonvascular tumors. Full article

Lymphatic malformations (LMs) are benign, congenital vascular anomalies caused by abnormal lymphangiogenesis during embryology, often presenting as fluid-filled cystic lesions. Though LMs can affect any part of the body except the brain, they primarily manifest in the head and neck or axilla regions of children. With a prevalence of approximately 1 in 4000 births, LMs are commonly diagnosed by age two, with symptoms varying based on lesion location and size. This paper reviews the classification of LMs and discusses the de Serres staging system, which aids in assessing prognosis based on lesion site. Mutations in the (PIK3CA) gene are implicated in most cases, and LMs are also associated with syndromic conditions like Turner and Noonan syndromes. They are diagnosed by ultrasound (USS) or magnetic resonance imaging (MRI), while a histologic analysis can confirm lymphatic origin. Treatment options range from conservative approaches, such as observation, to sclerotherapy, pharmacotherapy, and surgery. Sclerotherapy, particularly with agents like OK-432, bleomycin, and doxycycline, has shown significant efficacy in reducing LM size and symptoms with minimal side effects. Pharmacological therapies, such as sirolimus, that target the mTOR pathway are also increasingly being used, with a good effect on the burden of disease. While surgical excision remains a choice for symptomatic or large lesions, minimally invasive approaches are often preferred due to lower morbidity. Emerging techniques include gravity-dependent sclerotherapy, electrosclerotherapy, alpelisib, everolimus, and Wnt/β-catenin pathway stimulators (e.g., tankyrase inhibitors, porcupine inhibitors). Computational atomistic molecular dynamics (MD) and density functional tight binding (DFTB) techniques may offer an experimental approach to future therapeutic targets. This paper highlights a multidisciplinary approach to LM management, emphasising individualised treatment based on lesion characteristics and patient needs. Full article

A number of standard molecules are used for the molecular and histological characterization of lymphatic endothelial cells (LECs), including lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), Podoplanin (D2-40), VEGFR3, Prospero homeobox protein 1 (PROX1), and CD31. The number of molecules whose mutations cause lymphatic malformations or primary congenital lymphedema is considerable, but the majority of these diseases have not yet been characterized at the molecular level. Therefore, there is still considerable scope for molecular and functional studies of the lymphatic vasculature. Using RNASeq, we have previously characterized lymphatic endothelial cells (LECs) under normoxic and hypoxic conditions. We used this information to compare it with immunohistochemical data. We carried out some of the immunohistology ourselves, and systematically studied the Human Protein Atlas, a cell and tissue database based in Sweden. Here we describe molecules that are expressed at RNA and protein levels in LECs, hoping to stimulate future functional studies of these molecules. Full article

RASopathies are a group of genetic syndromes caused by germline mutations in genes involved in the RAS/Mitogen-Activated Protein Kinase signaling pathway, which regulates cellular proliferation, differentiation, and angiogenesis. Despite their involvement at different levels of this pathway, RASopathies share overlapping clinical phenotypes. Noonan syndrome is the most prevalent RASopathy, with an estimated incidence of 1 in 2500 live births, and it is typically inherited in an autosomal dominant manner, with 50% of cases involving gain-of-function mutations in the PTPN11 gene. De novo mutations are common, accounting for 60% of cases. The phenotype of Noonan syndrome includes characteristic facial and physical features, congenital cardiac defects, lymphatic and cerebrovascular anomalies, renal malformations, hematological abnormalities, developmental issues, and an increased risk of cancer. Severe congenital cardiac defects and lymphatic abnormalities significantly impact prognosis, contributing to increased morbidity and mortality. Recent therapeutic advancements have introduced trametinib, an MEK1/2 inhibitor, for treating Noonan syndrome patients with severe cardiac and lymphatic complications. To assess its efficacy, here, we present a case of a newborn with Noonan syndrome who exhibited refractory chylothorax, ventricular hypertrophy, and pulmonary stenosis who was treated with trametinib. The patient demonstrated significant improvement in chylothorax and left ventricular hypertrophy, though pulmonary stenosis persisted. This case further confirms trametinib’s potential as a therapeutic option for severe Noonan syndrome complications, emphasizing the need for further clinical trials to optimize treatment protocols and evaluate long-term outcomes. Full article

This retrospective study was aimed at characterizing vascular malformations (VMFs) presenting for minimally invasive image-guided therapies (MIT) at a tertiary-care center and evaluating treatment regimens and image-based outcomes using MRI. We analyzed demographic, disease-related, and radiologic features of VMFs presenting to interventional radiology between May 2008 and August 2020 using compendium vascular anomaly (Compva) criteria. MIT and specific agents were evaluated, and treatment effects were assessed through volumetry and mean signal intensity (MSI) on multiparametric longitudinal MRI. The statistics included the paired t-test, ANOVA, and Fisher’s exact test. The cohort included 217 patients (mean age 30 ± 18.4 years; 134 female). Venous malformations were most common (47%). VMFs were frequently located in the head-neck region (23.5%), legs (23.04%), and arms (13.8%). Among 112 treatments, sclerotherapy was performed most frequently (63.9%), followed by embolization (19.3%). MRI showed a significant reduction in T2 MSI for venous (1107.95 vs. 465.26; p = 0.028) and decreased contrast media uptake for lymphatic malformations (557.33 vs. 285.33; p = 0.029) after sclerotherapy, while the lesion volumes did not change significantly (p = 0.8). These findings propose MRI-derived MSI as a potential non-invasive biomarker for assessing the response of VMF to MIT. By leveraging MRI, this study addresses challenges in managing rare diseases like VMFs, while advocating for standardized approaches and prospective studies to better link imaging findings with clinical outcomes. Full article

Congenital cervicofacial vascular anomalies are extremely rare and present many difficulties in diagnosis and treatment requiring a multidisciplinary approach. Firstly, there is little consensus on this subject among head and neck specialists. There are two main types of vascular anomalies: vascular tumors and vascular malformations. Vascular malformations are also divided into malformations with slow blood flow (veins, lymphatics, capillaries or combined) and malformations with a fast blood flow (arteriovenous malformations and fistula). Vascular tumors like hemangiomas are known for their spontaneous involution with aging, while vascular malformations grow in dimensions with age. It is very important to choose the correct differential diagnosis between cervicofacial hemangiomas and vascular malformations for proper therapy management. Anamnesis and clinical exams help in raising suspicions about the real nature of a cervico-vascular anomaly. Furthermore, imaging brings in-depth details of the anomaly, ranging from ultrasound and contrast CT to MRI scanning and minimally invasive angiography. Angiography with selective embolization is rarely a curative procedure for arteriovenous malformations, being more suitable as a preliminary step before attempted surgical removal. Surgery is clearly necessary when there are aesthetic and functional deficits. Slow-flow vascular malformations present a reduced morbidity, and in cases without involution, the surgical ablation is reserved for the cases with aesthetic dysfunctions or psychological trauma. Lymphatic malformations must undergo surgical ablation when they are associated with mass effects and compression of great vessels or aerial viscera. The prognosis after surgical removal is good, with a low rate of recurrence or morbidity. Fast-flow vascular malformations require a combined approach, with embolization and excision in the next 48 h for safety reasons. Removal may be followed by reconstructive surgery depending on the location and dimensions of the malformation, with a possible secondary recovery of the normal microscopic vessels. Some of the masses may hinder the normal airflow and swallowing. Pathology is the gold standard for confirming the clinical and imaging diagnosis. Full article

Congenital vascular malformations (CVMs) are the result of an aberrant development during embryogenesis. Although these lesions are present at birth, they are not always visible yet. Once symptomatic, patients suffer from pain, bleeding, ulcers, infections or lymphatic leakage, depending on the subtype of vessels involved. Treatment includes conservative management, surgery, sclerotherapy, embolization and pharmacological therapy. The clinical presentation varies widely and treatment can be challenging due to the rarity of the disease and potential difficulties of treatment. This review gives an overview of the historical developments in diagnosis and classification and exposes the key elements of innovations in the past decades on the identification of genetic mutations and personalized treatment. These advances in the field and a multidisciplinary approach are highly valuable in the optimization of clinical care aimed at both curing or stabilizing the CVM and pursuing physical and psychosocial wellbeing. Full article

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. Methods: We analyzed tissue samples collected from patients with vascular anomalies treated in our department. We included patients with histopathological diagnoses of lymphatic, venous, capillary malformations, mixed lesions, and a control group of healthy skin samples. We stained the samples using H and E and immunohistochemistry. We used primary antibodies against p70 S6 Kinase, 4EBP1, and p-4EBP1. We graded their color reactions. The statistical analyses were performed using the FactoMineR and factoextra R v.4.1 packages. p-values < 0.05 were considered statistically significant. Results: The analysis of 82 patients showed that healthy tissue vessels expressed lower levels of tested mTOR pathway substrates compared to high activation in vascular malformations. Elevated substrate expression in a comparison between sexes revealed higher P-4EBP1 expression in the female malformation group. We observed a decrease in mTOR substrate expression with age. Conclusion: The higher expression of mTOR substrates in vascular malformations compared to healthy tissue confirms their involvement in abnormal vascular development. Age-related changes in mTOR substrate expression highlight the need for timely intervention. Our study contributes to the understanding of the mTOR signaling pathway in vascular malformations and highlights its potential as a therapeutic target, contributing to personalized medicine. Full article

Klippel–Trenaunay syndrome (KTS) is a very rare vascular malformation syndrome also referred to as a capillary–lymphatic–venous malformation with unknown aetiology. The aim of our paper is to highlight interesting images, regarding a rare case of foetal Klippel–Trenaunay syndrome diagnosed prenatally in our department and confirmed postnatally with a favourable evolution during the gestation and neonatal periods. This case was diagnosed at 26 weeks gestation and characterised through ultrasound by the presence of superficial multiple cystic structures of different sizes spreading over the left leg with hemihypertrophy and reduced mobility. The cystic lesions were spreading to the left buttock and the pelvic area. The right leg and upper limbs had normal appearance with good mobility. There were no signs of hyperdynamic circulation or foetal anaemia, but mild polyhydramnios was associated. The ultrasound findings were confirmed postnatally, the left leg presented multiple cystic lesions and port wine stains, and there was hypertrophy and fixed position, with favourable evolution at 6 months of life, when the size of the lesions began to decrease and the mobility of the leg improved. Full article