Recurrent hematuria involving urinary system with Klippel-Trenaunay syndrome: A case report.

RATIONALE: Klippel-Trenaunay syndrome (KTS) is a rare congenital venous malformation, it had been found to be caused by mutations of the phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Currently KTS is defined as a triad of skin wine pigmented spots, varicose veins and malformations of the lower extremities, and hypertrophy of bone and soft tissue, involving urinary system up to 6% to 30%. When the urinary system is involved, KTS is often presented as painless massive gross hematuria. PATIENT CONCERNS: This article describes a woman who was hospitalized with painless massive gross hematuria. Physical examination revealed significant hypertrophy of the right lower limb with varicose veins, port-wine stains in the skin, and right perineal hemangiomatous changes with swelling. The patient was admitted to hospital 4 times for repeated hematuria and infection. DIAGNOSES: By physical examination, CT urography, ureteroscopy and cystoscopy, the patient was diagnosed to have Klippel-Trenaunay syndrome, involving the urinary system. INTERVENTIONS: The patient hematuria improved after multiple indwelling D-J tubes and anti-inflammatory treatment. OUTCOMES: The final symptoms of hematuria improved significantly, follow-up so far has not recurred. LESSONS: This case presents the possibility of painless gross hematuria with KTS. Most of patients can be improved by conservative treatment. Cystoscopic laser therapy is the preferred treatment for poor bleeding control. Cystectomy and nephrectomy should be considered when life-threatening.

Percutaneous Sclerotherapy of Large Venous Malformations Using Consecutive Polidocanol and Bleomycin Foam: MR Imaging Volumetric and Quality-of-Life Assessment.

PURPOSE: To retrospectively evaluate sclerotherapy using consecutive polidocanol and bleomycin foam (CPBF) for large untreated venous malformations (VMs) and/or those resistant to prior treatment. MATERIALS AND METHODS: This retrospective study included all patients treated with CPBF for untreated VMs larger than 10 mL and/or refractory to treatment between May 2016 and October 2019. Baseline and follow-up VM volumes were measured on fat-suppressed T2-weighted magnetic resonance (MR) imaging. Outcome was evaluated on postprocedural MR imaging volumetry and by a retrospective survey assessing clinical response and adverse events. Imaging response was considered good for volume reduction from 50% to 70% and excellent for volume reduction ≥70%. Symptoms and quality-of-life (QoL) scores were compared before and after CPBF sclerotherapy. RESULTS: Forty-five patients (mean age, 16 years; range, 1-63 years; 25 males) with 57 VMs were analyzed and treated by 80 sclerotherapy. Sixty percent (27 of 45) of patients had undergone prior treatment for VM. Median VM volume was 36.7 mL (interquartile range, 84 mL) on pretherapy MR imaging. Good and excellent results after the last sclerotherapy were achieved in 36% (16 of 45) and 29% (13 of 45) of patients, respectively, corresponding to a decrease of >50% in 60% (34 of 57) of VMs. QoL score increased by at least 3 points, regardless of initial symptoms. Most patients did not desire additional sclerotherapy owing to near complete symptomatic relief, even for patients who did not achieve a good response. Swelling, pain, and motor impairment scores significantly improved after CPBF. Adverse events included fever (44%, 15 of 34) and nausea/vomiting (29%, 10 of 34). CONCLUSIONS: CPBF sclerotherapy represents an effective therapy for large and/or refractory VMs with minimal adverse events.

The risk of muscle involvement in focal venous malformations in children.

BACKGROUND: Venous malformations (VMs) are the most common vascular malformations, which can be classified as focal, multifocal, or diffuse types. But the risk of focal venous malformations with muscle involvement is not well defined. METHODS: This is a single-center, retrospective review of patients treated for focal VMs between February 2021 and February 2022. RESULTS: We assessed 26 patients focal VMs with 47 lesions; 18 (69%) were unifocal, 3 (12%) were dual-focal, and 5 (19%) were multifocal type VMs, and 29 (62%) were intramuscular VMs. The lower limbs intramuscular VMs had a significantly elevated risk of focal VMs (relative risk [RR],1.7; 95% confidence interval [CI], 1.148-2.394). CONCLUSION: Intramuscular involvement of the body should be considered in focal VMs. The lower limbs intramuscular VMs had a significantly elevated risk of focal VMs.

Clinical phenotype of adolescent and adult patients with extracranial vascular malformation.

OBJECTIVE: In recent years, genotypic characterization of congenital vascular malformations (CVMs) has gained attention; however, the spectrum of clinical phenotype remains difficult to attribute to a genetic cause and is rarely described in the adult population. The aim of this study is to describe a consecutive series of adolescent and adult patients in a tertiary center, where a multimodal phenotypic approach was used for diagnosis. METHODS: We analyzed clinical findings, imaging, and laboratory results at initial presentation, and set a diagnosis according to the International Society for the Study of Vascular Anomalies (ISSVA) classification for all consecutively registered patients older than 14 years of age who were referred to the Center for Vascular Malformations at the University Hospital of Bern between 2008 and 2021. RESULTS: A total of 457 patients were included for analysis (mean age, 35 years; females, 56%). Simple CVMs were the most common (n = 361; 79%), followed by CVMs associated with other anomalies (n = 70; 15%), and combined CVMs (n = 26; 6%). Venous malformations (n = 238) were the most common CVMs overall (52%), and the most common simple CVMs (66%). Pain was the most frequently reported symptom in all patients (simple, combined, and vascular malformation with other anomalies). Pain intensity was more pronounced in simple venous and arteriovenous malformations. Clinical problems were related to the type of CVM diagnosed, with bleeding and skin ulceration in arteriovenous malformations, localized intravascular coagulopathy in venous malformations, and infectious complications in lymphatic malformations. Limb length difference occurred more often in patients with CVMs associated with other anomalies as compared with simple or combined CVM (22.9 vs 2.3%; P < .001). Soft tissue overgrowth was seen in one-quarter of all patients independent of the ISSVA group. CONCLUSIONS: In our adult and adolescent population with peripheral vascular malformations, simple venous malformations predominated, with pain as the most common clinical symptom. In one-quarter of cases, patients with vascular malformations presented with associated anomalies on tissue growth. The differentiation of clinical presentation with or without accompanying growth abnormalities need to be added to the ISSVA classification. Phenotypic characterization considering vascular and non-vascular features remains the cornerstone of diagnosis in adult as well as pediatric patients.

Outcome after surgical treatment of venous malformations of the hand in childhood.

OBJECTIVE: Surgical treatment of venous malformations (VMs) of the hand is challenging. The hand's small functional units, dense innervation, and terminal vasculature can be easily compromised during invasive interventions like surgery or sclerotherapy, leading to an increased risk of functional impairment, cosmetic consequences, and negative psychological effects. METHODS: We have conducted a retrospective review of all surgically treated patients diagnosed with VMs of the hand between 2000 and 2019 and evaluated their symptoms, diagnostic investigations, complications, and recurrences. RESULTS: Twenty-nine patients (females, n = 15) with a median age of 9.9 years (range, 0.6-18 years) were included. Eleven patients presented with VMs involving at least one of the fingers. In 16 patients, the palm and/or dorsum of the hand was affected. Two children presented with multifocal lesions. All patients presented with swelling. Preoperative imaging was done in 26 patients and consisted of magnetic resonance imaging in nine patients, ultrasound in eight patients, and both modalities in nine patients. Three patients underwent surgical resection of the lesions without any imaging. Indications for surgery were pain and restriction of function (n = 16), and when lesions were preoperatively evaluated as completely resectable (n = 11). In 17 patients, a complete surgical resection of the VMs was performed, whereas in 12 children, an incomplete resection of VM was deemed due to nerve sheath infiltration. At a median follow-up of 135 months (interquartile range, 136.5 months; range, 36-253 months), recurrence occurred in 11 patients (37.9%) after a median time of 22 months (range, 2-36 months). Eight patients (27.6%) were reoperated because of pain, whereas three patients were treated conservatively. The rate of recurrences did not significantly differ between patients presenting with (n = 7 of 12) or without (n = 4 of 17) local nerve infiltration (P = .119). All surgically treated patients who were diagnosed without preoperative imaging developed a relapse. CONCLUSIONS: VMs in the region of the hand are difficult to treat, and surgery is associated with a high recurrence rate. Accurate diagnostic imaging and meticulous surgery may contribute to improve the outcome of the patients.

American society of pediatric otolaryngology vascular anomalies task force review of tongue venous malformations: Techniques, pearls, and pitfalls.

Management of tongue venous malformations can be challenging in the pediatric population due to their heterogeneity in presentation, extent of involvement and functional compromise. It is important to recognize the value of various treatment options in order to guide management of each patient in an individualized fashion. Here we describe a series of patients with tongue venous malformations that are managed using diverse modalities to illustrate the relative benefits and risks of each technique. The challenges of venous malformation treatment can be mitigated by tailoring the approach to each individual patient and malformation. This case series also emphasizes the need and importance of working in the setting of a multidisciplinary vascular anomalies team.

Combined sclerotherapy followed by surgical resection of a large extracranial venous malformation in a 14-month-old child: preoperative workup and technical note.

INTRODUCTION: Venous malformations affect around 2 per 10,000 newborn and are the most common type of congenital vascular malformation. They are always present at birth and are often misdiagnosed with hemangiomas. Accurate diagnosis and adequate targeted therapy through a multidisciplinary approach is advocated for a successful treatment, considering a combination of modalities in complex cases. We present here the workup and treatment of a venous malformation in a 14 month old child by combining a preoperative sclerotherapy with sodium tetradecyl sulfate (STS) followed by complete surgical excision respecting the calvarium. CASE PRESENTATION: A large right extracranial fronto-parietal venous malformation and scalloping of the underlying calvarium, attached to the pericranium, surgically excised after preoperative sclerotherapy with STS in a 14-month-old child. RESULTS: The patient had an uneventful postoperative course with complete resection of the lesion, satisfying cosmetic appearance and no complications. Histopathological examination confirmed a venous malformation. CONCLUSION: We demonstrated the workup and the rationale of the combined sclerotherapy followed by surgical resection of a large growing extracranial venous malformation. Preoperative direct contrast injection and sclerotherapy allowed to rule out significative extracranial to intracranial venous inflow and reduce blood loss for the surgical procedure, respectively. Complete removal of the malformation minimized the impact on future growth of the calvarium.

Surgical Resection Combined with Sclerotherapy Treating Maffucci Syndrome's Venous Malformation in Head and Neck Region.

PURPOSE: Here, we report our experience treating a patient with Maffucci syndrome and evaluate the outcomes resulting from surgical management combined with sclerotherapy in the treatment of head and neck venous malformations (VMs). A 19-years-old woman with multiple enchondromas and heterauxesis complained of masses in the oral cavity that had gradually increased in size and eventually affected her daily life. A tracheotomy was performed followed by traditional sclerotherapy to treat the oropharyngeal VMs. Next, we surgically excised the VMs of the oral cavity and maxillofacial skin. RESULTS: Magnetic resonance imaging indicated that the oral VMs were nearly eradicated and the oropharyngeal VMs had stabilized. The patient's appearance and normal maxillofacial region function were restored. CONCLUSION: In summary, local resection combined with sclerotherapy facilitated timely and efficient VMs removal from the head and neck region of a patient with Maffucci syndrome.

Polidocanol monotherapy for a superficial orbital venous malformation in a horse.

OBJECTIVE: To describe the use of 1% polidocanol as the sole treatment for a superficial orbital venous malformation in a horse. ANIMAL: A 23-year-old Welsh Cobb cross gelding with a distensible swelling affecting the left lower eyelid, and secondary palpebral margin abnormalities and superficial keratitis. PROCEDURE: Color flow Doppler ultrasonography revealed non-pulsatile blood flow within the tortuous vascular network most consistent with a superficial orbital venous malformation appearing to involve the lateral palpebral and transverse facial veins. An intravenous catheter was placed within the lateral aspect of the venous malformation, and agitated saline was slowly injected into the vessel while simultaneously ultrasound imaging the medial aspect in which the bubbles were observed coursing across, consistent with lateral to medial flow. Contrast venography confirmed a corkscrew vessel along the ventral aspect of the orbital rim. Under standing sedation, 1% polidocanol solution was administered slowly through the intravenous catheter while manual pressure was applied on the medial and lateral aspects of the venous malformation. RESULTS: Ultrasonography performed immediately after administration of polidocanol confirmed venous stasis, and formation of a thrombus. No adverse side effects were noted. The venous malformation and associated palpebral margin abnormalities and superficial keratitis resolved at the time of re-examination at 4 months. CONCLUSION AND CLINICAL RELEVANCE: Polidocanol as the sole treatment for a superficial orbital venous malformation in a horse was well tolerated and led to clinical resolution. Sclerosant monotherapy may be a safe treatment option for superficial orbital venous malformations.

Treatment Outcomes and Effects of Ethanol Sclerotherapy on Systemic Coagulation Profile of Patients with Venous Malformation.

BACKGROUND: Venous malformations (VMs) and sclerotherapy may disrupt the normal systemic coagulation profile in individuals. This study investigated a correlation between the clinical efficacy of sclerotherapy in the treatment of VMs and the changes in coagulation indexes to provide data that will inform the future application of this therapy. METHODS: From September 2019 to September 2020, 61 patients were enrolled in this study to receive sclerotherapy with absolute alcohol. The clinical outcomes and the coagulation profile were assessed. RESULTS: Sclerotherapy induced increasing fibrin (original) degradation products (FDP) and D-dimer (D-D) levels. The changes in FDP and D-D level pretreatment and posttreatment were positively correlated with treatment outcomes. Moreover, a repeated treatment with absolute alcohol may restore normal levels of FDP and D-D. CONCLUSIONS: Upregulation of FDP and D-D levels after sclerotherapy results in good therapeutic outcomes. Therefore, monitoring changes in FDP and D-D levels in patients with VMs undergoing sclerotherapy may reflect the effects of sclerotherapy.

Recurrence of Distensible Orbital Venous-dominant Venolymphatic Malformations After Sclerotherapy Versus Embolization With Excision.

PURPOSE: Treatment for orbital venolymphatic malformations (VLMs) commonly includes 3 major options: sclerotherapy, surgery, and embolization followed by surgical excision. Each has certain advantages, although it is not clear whether all are effective. The authors characterize the clinical course for a series of patients with distensible orbital venous-dominant VLM treated with sclerotherapy and/or embolization with excision. METHODS: In this cross-sectional cohort study, patients affected by distensible orbital venous-dominant VLM presenting to the orbital and ophthalmic plastic surgery service from 2014 to 2020 were identified. Patients were included if they presented with a moderate-flow, distensible venous-dominant malformation associated with Valsalva-related symptoms (e.g., pain, proptosis, and diplopia). RESULTS: Six cases were treated with sclerotherapy. Four underwent multiple treatments, with a mean ± SD of 3.5 ± 2.3 (range 1-7). All patients in this group failed to improve or experienced recurrence of symptoms after sclerotherapy. Twelve cases were treated with embolization and excision. Resolution of symptoms in all 12 cases was noted and maintained for a mean of 3.4 ± 2.1 years. There have been no cases of recurrence. Patients treated with sclerotherapy were more likely to experience recurrence of symptoms compared to those treated with embolization and excision (p < 0.001). CONCLUSIONS: Treatment of distensible venous-dominant moderate-flow orbital VLM with sclerotherapy may provide temporary improvement in some cases. However, in the medium to long term, recurrence was universal in this series. Embolization with excision appears to provide more definitive management, avoiding recurrence in all cases for a mean follow-up of 3 years.

Downregulation of microRNA-21 contributes to decreased collagen expression in venous malformations via transforming growth factor-ß/Smad3/microRNA-21 signaling feedback loop.

OBJECTIVE: Venous malformations (VMs) are the most frequent vascular malformations and are characterized by dilated and tortuous veins with a dysregulated vascular extracellular matrix. The purpose of the present study was to investigate the potential involvement of microRNA-21 (miR-21), a multifunctional microRNA tightly associated with extracellular matrix regulation, in the pathogenesis of VMs. METHODS: The expression of miR-21, collagen I, III, and IV, transforming growth factor-ß (TGF-ß), and Smad3 (mothers against decapentaplegic homolog 3) was evaluated in VMs and normal skin tissue using in situ hybridization, immunohistochemistry, Masson trichrome staining, and real-time polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used to explore the underlying mechanisms. RESULTS: miR-21 expression was markedly decreased in the VM specimens compared with normal skin, in parallel with downregulation of collagen I, III, and IV and the TGF-ß/Smad3 pathway in VMs. Moreover, our data demonstrated that miR-21 positively regulated the expression of collagens in HUVECs and showed a positive association with the TGF-ß/Smad3 pathway in the VM tissues. In addition, miR-21 was found to mediate TGF-ß-induced upregulation of collagens in HUVECs. Our data have indicated that miR-21 and the TGF-ß/Smad3 pathway could form a positive feedback loop to synergistically regulate endothelial collagen synthesis. In addition, TGF-ß/Smad3/miR-21 feedback loop signaling was upregulated in bleomycin-treated HUVECs and VM specimens, which was accompanied by increased collagen deposition. CONCLUSIONS: To the best of our knowledge, the present study has, for the first time, revealed downregulation of miR-21 in VMs, which might contribute to decreased collagen expression via the TGF-ß/Smad3/miR-21 signaling feedback loop. These findings provide new information on the pathogenesis of VMs and might facilitate the development of new therapies for VMs.

Persistent sciatic vein.

BACKGROUND: Venous anomalies of the lower extremity are a challenge when found as rare variations. Physicians should be aware of morphological variations in this region for correct diagnosis and management of diseases such as deep vein thrombosis. MATERIALS AND METHODS: During the routine dissection of the lower extremities of a Caucasian male cadaver, a case of persistent sciatic vein was found. RESULTS: A persistent sciatic vein originating from the saphenopopliteal junction coursed proximally and laterally to enter into the adductor magnus muscle, at the right side. Running through the fibres of the adductor magnus anteriorly, the variant vein drained into the deep femoral vein just medial to the vastus medialis muscle. CONCLUSIONS: As being a rare congenital vascular anomaly, the persistent sciatic vein should be correctly diagnosed and defined during the radiologic assessments, surgical interventions and blockades for better outcomes and lesser complications.

Characteristics, clinical presentation, and treatment outcomes of venous malformation in the extremities.

OBJECTIVE: The clinical presentation of venous malformations (VMs) is variable and not well documented. The present study was designed to determine the clinical characteristics and outcomes in association with the type and extent of VM in the extremities. METHODS: Patients with a diagnosis of a VM using ultrasound, computed tomography, or magnetic resonance imaging were included in the present study. The VM extent and tissue involvement, signs, and symptoms were retrospectively collected. Those with arteriovenous malformations, Klippel-Trenaunay syndrome, lymphedema, and symptoms from other unrelated diseases were excluded. The VMs were classified as extensive or localized according to whether different tissues or the entire compartment was involved. The clinical outcomes and imaging studies were obtained for both the treated patients and those who had chosen to not undergo any intervention. RESULTS: A total of 72 patients, of whom 26 were men, were included in the present study, with a median age of 30 years. The VM had extended into the subfascial space in 40 patients (55.6%). Patients with VM distributed on their leg had mostly experienced pain, which was more evident during physical activity (n = 40; 80.0%), with swelling worsening with prolonged standing (n = 35; 70.0%). For those with VMs in the upper extremities, the most prominent complaints were venous enlargement (n = 10; 45.5%), pain (n = 9; 40.9%), and swelling (n = 11; 50.0%). The symptoms were related to the extent of the lesion (odds ratio, 7.664; 95% confidence interval, 2.006-29.291; P = .003). Treatment was decided by the extent and depth of the lesions. Excision was performed in 15 patients (20.8%), sclerotherapy in 12 (16.7%), sclerotherapy with phlebectomy or coil embolization in 8 (11.1%), and stripping in 2 (2.8%). An excellent result was achieved with the treatment of localized VMs. For those with extensive VMs, the symptom intensity was reduced or controlled after multiple treatments. CONCLUSIONS: VMs of the extremities affect patients' quality of life significantly owing their appearance and the resulting pain. The VM extent was associated with symptom severity. The clinical outcomes have been excellent for localized VMs; however, extensive VMs will require multiple treatments to reduce the symptom intensity.

Cellular heterogeneity and immune microenvironment revealed by single-cell transcriptome in venous malformation and cavernous venous malformation.

Venous malformation (VM) and cavernous venous malformation (CVM) are two types of vascular malformations. Even if the two diseases are similar in appearance and imaging, the distinct cellular components and signaling pathways between them might help distinguish the two from a molecular perspective. Here, we performed single-cell profiling of 35,245 cells from two VM samples and three CVM samples, with a focus on endothelial cells (ECs), smooth muscle cells (SMCs) and immune microenvironment (IME). Clustering analysis based on differential gene expression unveiled 11 specific cell types, and determined CVM had more SMCs. Re-clustering of ECs and SMCs indicated CVM was dominated by arterial components, while VM is dominated by venous components. Gene set variation analysis suggested the activation of inflammation-related pathways in VM ECs, and upregulation of myogenesis pathway in CVM SMCs. In IME analysis, immune cells were identified to accounted for nearly 30% of the total cell number, including macrophages, monocytes, NK cells, T cells and B cells. Notably, more macrophages and monocytes were discovered in VM, indicating innate immune responses might be more closely related to VM pathogenesis. In addition, angiogenesis pathway was highlighted among the significant pathways of macrophages & monocytes between CVM and VM. In VM, VEGFA was highly expressed in macrophages & monocytes, while its receptors were all abundantly present in ECs. The close interaction of VEGFA on macrophages with its receptors on ECs was also predicted by CellPhoneDB analysis. Our results document cellular composition, significant pathways, and critical IME in CVM and VM development.

Leiomiosarcoma de vena cava / Vena cava leiomyosarcoma

Caso clínico: se presenta el caso de un varón de 64 años con sospecha de leiomiosarcoma de vena cava inferior (VCI) tratado con radioterapia neoadyuvante previa a resección quirúrgica en bloque tumoral y de VCI con reconstrucción mediante injerto de PTFE anillado, seguido de quimioterapia. Discusión: el leiomiosarcoma de VCI es una patología maligna muy infrecuente, de mal pronóstico y que requiere un manejo multidisciplinar. Representan la localización más frecuente de los leiomiosarcomas venosos, tienen predilección por el sexo femenino y una edad media de presentación entre 50 y 60 años. El síntoma más frecuente es el dolor abdominal, aunque muchos son asintomáticos. La prueba diagnóstica de elección es la RM y el tratamiento se basa en la resección quirúrgica, no estando aún claramente definido el papel de la radio y quimioterapia.(AU)

Case report: we present the case of a 64-year-old man with suspected inferior vena cava leiomyosarcoma (IVC) treated with neoadjuvant radiotherapy, tumor and IVC overall surgical resection with a ringshaped PTFE graft reconstruction, followed by chemotherapy. Discussion: IVC leiomyosarcoma is a very infrequent malignant disease, its prognosis is dark and requires multidisciplinary management. They represent the most frequent location of venous leiomyosarcomas, have a predilection for the female sex and a mean age of presentation between 50 and 60 years. The most frequent symptom is abdominal pain, although many are asymptomatic. The diagnostic test of choice is MRI and treatment is based on surgical resection, the role of radio and chemotherapy is not clearly defined yet.(AU)

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.