Effectiveness and safety of sirolimus in the treatment of venous malformations: A meta-analysis of prospective studies.

Objective ‒ to evaluate the results of treatment of patients with extra-trunk (diffuse) venous malformations (VM) and microfistulous arteriovenous malformations (AVM) of superficial localization, to whom the technique of sclerotherapy was applied, by direct puncture of the «node» of the malformation and a combination of endovascular embolization with sclerotherapy. Determine the criteria for using the sclerosation method as monotherapy or in combination with embolization.Materials and methods. In the period from 2017 to 2023, 47 patients (22 (46.8 %) men and 25 (53.2 %) women) with VM (n=27) and AVM (n=20) located superficially were examined and treated were treated for the malformation using sclerosation. The age of the patients ranged from 5 to 67 years, the average age ‒ (28.9 ± 7.4) years. Pathology localization: head and neck – 31, upper extremity – 6, lower extremity – 7, trunk – 3. In 17 patients, sclerotherapy was used as monotherapy, 30 patients underwent a combination of sclerotherapy with embolization The observation period ranged from 6 months to 8 years, the average observation period was (5.2 ± 0.98) years.Results. Out of 27 patients with VM, 17 (62.9 %) patients were diagnosed with a VM based on the results of diagnostic venography and arteriography. From 17 patients were treated with sclerotherapy as monotherapy with a satisfactory clinical result in 14 (82.3 %) patients. In 10 (37.1 %) 27 patients with VM, signs of arteriovenous shunt (AVS) were found in the structure of VM. A combination of endovascular embolization and sclerosation was used in the treatment of VM with signs of arteriovenous shunting in 10 patients. A positive effect was obtained in 7 (70.0 %) cases. AVM treatment using a combination of sclerosation and embolization was carried out in 20 patients. A satisfactory clinical result was obtained in 17 (85.0 %) patients. Treatment of 47 patients with VM and AVM was technically successful in all cases (100 %). Overall clinical improvement was obtained in 38 (81.0 %). A complication in the form of tissue necrosis in the malformation area occurred in 3 (6.4 %) patients. 43 (91.4 %) patients received 2 to 4 AVM embolization and 2 to 5 sclerotherapy sessions during the treatment period.Conclusions. According to the obtained results, sclerotherapy by direct puncture of the venous structures of malformations with the introduction of a sclerosing drug into the «node» is a safe and effective method of treating VM. In every third patient (37.1 %) with VM, signs of AVS were found in the structure of VM, which requires prior embolization of existing AVS. Preliminary embolization of the afferent arteries of AVM leads to a slowing down of the blood flow rate and enables the use of sclerotherapy techniques, maintaining the effective concentration of the drug in the «node» of the AVM. Evaluation of the results of the treatment of 47 patients with extra-trunk (diffuse) venous and microfistulous AVM of superficial localization using the methods of endovascular embolization and sclerotherapy proves that the combined use of these methods allows to improve the results and increase the effectiveness of the treatment of this complex pathology.

View Video S1

Background: Venous malformations (VMs) are the most common low-flow vascular malformations. Various sclerosants have been shown to be effective, but their relative effects are not well established. Methods We performed a Bayesian network meta-analysis (NMA) to assess the efficacy and adverse effects of different sclerosants for VMs. We searched PubMed, Embase, Cochrane Library, Scopus and Web of Science for randomized clinical trials up to April 1, 2021. We estimated odds ratios using pairwise and network meta-analysis with random effects. We also calculated the surface under the cumulative ranking curve for each treatment and carried out the cluster analysis. Findings: A total of 22 randomized clinical trials (1 805 patients) comparing 11 different therapeutic regimens were identified. Polidocanol foam and ethanol showed significant improvement in VMs compared with bleomycin and sodium morrhuate, while polidocanol foam and polidocanol combined with bleomycin were statistically significantly superior to ethanol and sodium morrhuate in safety. Bleomycin foam was ranked high as the most effective treatment, but the evidence stems from one small study and most comparative effect estimates were not statistically significant. Ethanol ranked second only to bleomycin foam in efficacy. SUCRA cluster analysis demonstrated that bleomycin, polidocanol, polidocanol foam, bleomycin combined with dexamethasone and polidocanol combined with bleomycin are the five treatments with higher SUCRA values for both outcomes compared with the second group of sodium morrhuate and sodium tetradecyl sulfate. Last cluster only included ethanol, characterized by the relatively good efficacy and obvious side effects. Interpretation: Polidocanol foam and ethanol are more effective than bleomycin and sodium morrhuate in VMs, while ethanol and sodium morrhuate are associated with severe adverse effects. Funding: None to declare. Declaration of Interest: None to declare.

Background:The pathophysiologic of vascular malformations is still unclear, and the treatment of vascular malformations is a challenge. With improvement in the understanding of pathogenesis of vascular malformations, sirolimus has been a promising and effective treatment. As so far, there is absent convincing evidence to confirm the efficacy of sirolimus for vascular malformations. The purpose of this study was to evaluate the effectiveness and safety of sirolimus in the treatment of vascular malformations.Methods:The literatures about the management of vascular malformations with sirolimus would be searched from databases of MEDLINE, EMBASE, PubMed, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine Database (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database. We will search each database from inception or 1995 to August 20, 2020. Two researchers worked independently on literature selection, data extraction and quality assessment. The efficacy and safety of sirolimus in the treatment of vascular malformations were the main outcomes. Adverse events after sirolimus were evaluated as the secondary outcomes. The included studies will be analyzed by Review Manager 5.3. If the results are applicable, meta-analysis would also be performed.Results:The study will evaluate the efficacy and safety of sirolimus in the treatment of vascular malformations based on current evidence.Conclusion:The conclusion of this study will provide more reliable, evidence-based data for the use of sirolimus in the treatment of vascular malformations.PROSPERO registration number:CRD42020167881.

Objective: To evaluate the clinical efficacy of sclerotherapy using absolute ethanol combined with 3% polidocanol injectable foam in treatment of venous malformation in maxillofacial region of children. Methods: Totally 68 patients with venous malformation were treated by sclerotherapy under general anesthesia from September 2015 to July 2016. All cases were classified as two types such as fast-flow and low-flow venous malformation according to local puncture angiography. 21 cases with fast-flow venous malformations were treated by sclerotherapy using absolute ethanol and 3% polidocanol injectable foam, 47 cases with low-flow venous malformations were treated by sclerotherapy using 3% polidocanol injectable foam or with absolute ethanol. They were followed up for 6 to 15 months with an average of 10 months. The therapeutic effects and side effects were observed. The clinical evaluations were divided into four categories: cured, basic cured, effective and ineffective. Results: 47 cases of low-flow venous malformation were treated successfully, 9 cases were cured, 23 cases were basically cured, 15 cases were effective, and the total effective rate was 100%. 21 cases of fast-flow venous malformation were treated successfully, 6 cases were basically cured, 14 cases were effective, 1 case was ineffective, and effective rate was 95.2% (20/21) . The total effective rate of two types was 98.5% (67/68) . Adverse reactions: postoperative complications included transient swelling in 189 cases, blisters formed in 33 cases and lower fever in 25 cases among 211 treatments, and the symptoms were relieved obviously after symptomatic treatment. Pulmonary arterial hypertension symptoms such as rapid decline in blood oxygen and heart rate decreased after injection of absolute ethanol in 2 cases, and the symptoms disappeared after positive treatment. Skin ulceration appeared in one case, and the skin was cured after special therapy for 2 months. There was not any case with allergic reaction, ectopic embolism or nerve injury. Conclusions: Sclerotherapy using absolute ethanol combined with 3% polidocanol injectable foam is an effective and safe method with few side effect for the treatment of venous malformations in children. Key words: Venous malformation; Children; Sclerotherapy; Polidocanol; Absolute ethanol

Treatment of congenital venous malformations poses a major clinical challenge. Surgery is difficult and frequently unsuccessful, radiological intervention with embolization has an ill-defined role, and conventional sclerotherapy has little to offer. To evaluate the efficacy and safety of sclerosant in microfoam form in treating congenital venous malformations. A retrospective study of medical records, pretreatment and posttreatment color photographs, echo-Doppler ultrasonographic results, and/or magnetic resonance imaging in patients with congenital vascular malformations of venous predominance. Follow-up ranged from 6 to 103 months (mean, 30 months). Private vascular surgery clinic in Granada, Spain, and dermatology department at a university hospital in Pamplona. Patients The study population comprised 50 patients, 19 with limited venous malformations, 16 with infiltrating venous malformations, and 15 with Klippel-Trénaunay syndrome.Intervention Percutaneous sclerotherapy by direct injection of 0.25% to 4% polidocanol microfoam under du-plex ultrasonographic guidance. The number of sessions varied between 1 and 46 (mean, 12 sessions). The primary efficacy end point was defined as a reduction in size after completion of the treatment. Sclerosis therapy with polidocanol microfoam was judged beneficial in 46 (92%) of the 50 patients. Among the 46 responders, 18 showed disappearance of treated malformations, 15 showed a reduction in malformation size of more than 50%, and 13 showed a reduction in malformation size of 50% or less. Of the 39 patients who presented with pain, the pain disappeared in 25 and was reduced in 14. No major adverse effects were reported by any patient. There were 4 cases of transient skin pigmentation and 3 cases of skin necrosis. Color echo-Doppler ultrasonography-guided sclerotherapy with polidocanol microfoam was effective in 46 (92%) of the patients. The technique is delivered on a strictly ambulatory basis and has proved simple and innocuous. The quality and durability of the outcome make this novel procedure the treatment of choice in the care of patients with congenital venous malformations.

Treatment of venous malformations in the orofacial region remains a challenge. Laser therapy is an alternative treatment in inoperable cases. To retrospectively evaluate the effectiveness and complications associated with neodymium-doped yttrium aluminium garnet (Nd:YAG) laser treatment of oral venous malformations. A total of 10 children (mean age: 7.3 years; range: 10 months-15 years) with oral venous malformation were treated with Nd:YAG laser during 2005 to 2013. Clinical improvement, including degree of color lightening and size reduction, and treatment complications, including dyspigmentation, textural change, and scarring were evaluated. Color clearing of 51% to 75% and >75% was seen in 25% and 45% of patients, respectively. Size reduction of 25% to 50%, 51% to 75%, and >75% was observed in 30%, 15%, and 45% of patients, respectively. Mild and moderate scarring was observed in 15% and 5% of cases, respectively. Nd:YAG laser is a promising alternative treatment in pediatric patients with inoperable venous malformations in the oral cavity. Mild to moderate scarring was the most common complication.

Traitement médical et chirurgical des malformations veineuses

Venous malformation (VM) originates from a congenital venous network disorder, configuring about 40% of the vascular anomalies that occur in the head and neck region. The usage of diode lasers in the treatment of VM is associated with various advantages, such as short operating time and few postoperative complications. Nevertheless, for larger and deeper VM treatment, it may require more than one session for the complete resolution of the lesion. Laser surgery for oral VM may induce heat accumulation due to excessive irradiation causing adverse events postoperatively, including pain and ulcer formation with scarring. In this clinical case, it was recommended to use the leopard technique (LT) to reduce the lesion size, evaluate the remaining unhealed lesion, and apply different laser techniques to obtain the complete resolution of the lesion.

Prospective randomized efficacy of ultrasound-guided foam sclerotherapy compared with ultrasound-guided liquid sclerotherapy in the treatment of symptomatic venous malformations

Introduction: Chronic rejection after transplantation and drug induced nephrotoxicity continue to be major clinical problems. Sirolimus is a potent immunosuppressant acting on the mTOR receptor with no adverse effects on renal function. AIM To evaluate the safety and efficacy of Sirolimus in intestinal transplantation (ITx) and liver (LTx) transplant recipients in children. Methods: Retrospective review from Jan ’01 to Dec ’02. 14 children (9M): renal toxicity (n=5);recurrent rejection/acute steroid resistant rejection after ITx and/or LTx (n=9) were included. Results: Median age at transplant (Tx): 34 months. Median time post Tx at starting Sirolimus: 41.8 months. Sirolimus treatment followed up for 100–500 days. Patients receiving Sirolimus due to nephrotoxicity showed an improvement in cGFR from 52 to 73 ml/ml/1.73m2. Liver function tests improved in those with recurrent rejection and small bowel allograft function. Table 1 summarises data on efficacy and safety of Sirolimus. Adverse events: Infection: pneumonia (7 episodes), adenovirus (1), Influenza (1), EBV viraemia (4) and staphylococcus (2). Two children developed mucosal lesions, buccal mucosal ulcer (1) and candidial oesophageal lesions (1). 3 patients developed high triglycerides not requiring treatment. 5 children experienced transient thrombocytopaenia. Sirolimus temporarily withheld for EBV viraemia (1) and discontinued(1)for protracted neutropenia. Two patients with intestinal graft died after 8m and 15m exposure to Sirolimus (bowel perforation and fungal endocardititis).Table 1Conclusion: Sirolimus as a concomitant immunosuppressant is effective in acute steroid resistant and chronic rejection for ITx/LTx recipients. We recommend caution in the long term use of Sirolimus in ITx recipients

Perivascular infiltration of tumescent anaesthesia (TA) is an essential element of endovenous thermal ablative procedures employed to treat superficial venous disease. In addition to anaesthesia, TA is administered to achieve vessel wall approximation and to protect surrounding structures from thermal damage. However, its role in the treatment of venous malformations (VMs) has not been established. To assess the safety and efficacy of tumescent-assisted thermal and chemical ablative methods in the treatment of VMs. Adult and paediatric patients presenting with VMs were treated using a combination of endovenous laser ablation, foam embolo-sclerotherapy and liquid embolisation using n-BCA. All procedures were ultrasound-guided. Treatment outcomes were assessed in early and late follow-ups. To assess the efficacy of TA in achieving vessel wall approximation, cross-sectional lesional diameters were measured by ultrasound, before and after the administration of TA during endovenous procedures. In a 12month period, 22 patients recruited in the study presented with 27 VMs which included 23 extra-truncular lesions (16 subcutaneous and seven intramuscular) and four truncular anomalies. On average the subcutaneous lesions measured 5.5mm (1.9-24.5mm) in diameter, intramuscular lesions measured 9.2mm (5.9-15.1mm) and truncular anomalies measured 4.9mm (1.2-12mm) in diameter. Perivascular infiltration of TA resulted in a significant reduction in vessel calibre (90% reduction on average). Intramuscular VMs were less compressible with TA (69.2% reduction) compared to subcutaneous lesions (98% reduction). Truncular anomalies such as the embryonic marginal vein achieved complete approximation (100% reduction). Procedures were safely tolerated with no major complications such as thromboembolism, stroke, nerve damage or tissue necrosis. Most patients had significant clinical as well as ultrasonographic improvement. Tumescent-assisted endovenous laser ablation and foam sclerotherapy provides safe and effective outcomes in patients with a variety of VMs.

Absolute ethanol is the most effective agent in the treatment of venous malformation (VM) although it is quite risky to use because of the danger of diffusion beyond the target. To reduce this risk, we have developed an alcoholic sclerosing solution that is less diffusible. The viscosity of absolute ethanol was enhanced with monographic ethyl-cellulose at a concentration of 5.88% ie 0.75 g in 15 ml of absolute ethanol 95%. 23 patients with VM located on the buttock (1), hand (2), leg (1) and face (19) were treated. A mean volume of 1.99 ml of the solution was injected directly into the VM. Each patient had an average of 2.8 procedures. Sixteen patients were done under general anaesthesia and seven with local anaesthesia. Evaluation was performed by the patient, the dermatologist of the treating multidisciplinary team and a dermatological group not involved in the treatment of the patients. Patients were evaluated after a mean delay of 24.52 months. Evaluation of the cosmetic result was made with a five point scale and the global result with a three point scale. VM pain was evaluated by the patients with a Visual Analogue Scale. The aesthetic results were graded as satisfactory (> 3) for the patient and the dermatologist of the multidisciplinary team. However the results were not as good with the independent dermatological group evaluation. The pain was significantly less important after the treatment (p << 0.001). Among the 23 patients, the local adverse events were nine necrosis with or without ethylcellulose fistula followed by only two surgical procedures. There were no systemic adverse events. Sclerotherapy of VM is usually performed with absolute ethanol or ethibloc. The main advantage of our sclerosing mixture is that it expands like a balloon when injected slowly in a aqueous media. Because of the important increase in viscosity the volume of injected solution is much lower than ethanol alone and the risk of systemic reactions is lower. Contrary to ethibloc, post-sclerosing surgery is not necessary because sub-cutaneous ethylcellulose disappears secondarily.

Venous malformations (VMs) are a type of vascular malformations that result in abnormal development of veins that become extensible over time due to an error in vascular morphogenesis. They usually appear in newborns or in early adulthood as a bluish, soft, swollen and eventually painful skin formation. Treatment includes conservative therapy, sclerotherapy and surgical excision. Aim of the paper is to evaluate the therapeutic effect of scleraotherapy in pediatric patients with venous malformations. Material and methods: In a three-year period, from 2019 to 2021, venous malformation was found in 33 patients aged 4 to 14 years (average age: 8 years). Pain as a symptom occurred in 8 patients. Two patients had lesions measuring up to 5 cm and 5 cm respectively, while in the remaining subjects the lesion was over 5 cm. Ultrasound was performed routinely in all subjects, and MRI in two patients. Conservative treatment was instituted in 13 patients with venous malformations of the extremities, surgical excision with local reconstruction was performed in 11 patients, and sclerotherapy with bleomycin under general anesthesia was performed in 8 patients. Combined treatment was used in one patient that presented with venous malformation of the upper arm that underwent partial sclerotherapy with subsequent operative excision due to a phlebolith. Follow-up examinations revealed regression of the change not only from functional but from aesthetic aspect as well. Conclusion: Sclerotherapy is the established golden standard, first-line treatment for venous malformations. Excellent results were achieved as the reduction of the lesions was below 50% of the initial size. However, the modality of treatment should be individualized to each patient as it can sometimes require a combination of more than one treatment option. Venous malformations are best treated early, but they usually recur over time. Treatment helps relieve symptoms and control the growth of vascular malformations.

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