ORIGINAL ARTICLE ANZJSurg.com
Ethanol sclerotherapy for venous malformation Frederica Steiner,* Trevor FitzJohn† and Swee T. Tan*† *Gillies McIndoe Research Institute, Wellington, New Zealand and †Centre for the Study & Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand
Key words alcohol, complication, embolization, ethanol, sclerotherapy, treatment, venous malformation. Correspondence Professor Swee T. Tan, Gillies McIndoe Research Institute, PO Box 7184, Newtown, Wellington 6242, New Zealand. Email: [email protected] F. Steiner; T. FitzJohn MBBS, BMedSci, DMRD, FRCR, FRANZCR; S. T. Tan MBBS, FRACS, PhD. This paper was presented, in part, at the 81st Annual Scientific Congress of the Royal Australasian College of Surgeons, Kuala Lumpur, Malaysia, 6–11 May 2012 and the 19th International Society for the Study of Vascular Anomalies Workshop, Malmo, Sweden, 16–19 June 2012. Accepted for publication 28 July 2014. doi: 10.1111/ans.12833
Abstract Background: Ethanol sclerotherapy (ES) is the preferred treatment for venous malformation (VM) with surgery playing an adjunctive role. Results of ES, however, are not well documented in the literature. Methods: VM patients were identified from our vascular anomalies database from 1996 to 2011. After treatment completion, patients completed questionnaires evaluating symptoms and their severity and effect on appearance, function and overall quality of life (QoL), before and >6 months after treatment, using visual analogue scales of 0–10. Patients rated their overall satisfaction with ES using a scale of 0–10. Results: Fifty-four (23.9%) of the 226 VM patients underwent a total of 90 ES sessions (average 1.7 sessions per patient). Complications occurred in 12 (22.2%) patients in 12 (13.3%) ES sessions. Minor complications occurred in nine (16.7%) patients including transient paraesthesia (n = 3), transient weakness of facial nerve branch(es) (n = 3), skin blistering (n = 2) and spontaneously healing ulceration (n = 1). Major complications occurred in three (5.6%) patients in three (3.3%) ES sessions including skin necrosis (n = 1), Horner’s syndrome (n = 1) and finger paraesthesia with joint stiffness (n = 1). ES improved the severity of background pain, episodic pain, contour deformity and skin discoloration in 86.0%, 72.4%, 83.0% and 72.2% of patients respectively. It reduced the effect of VM on appearance, function and overall QoL in 69.8%, 73.0% and 64.3% of patients. Mean treatment satisfaction was 7.9 (range, 0–10). Conclusion: ES reduces pain, contour deformity and skin discoloration, and improves appearance, function and QoL. Our complication rates are consistent with the literature.
Introduction Vascular anomalies are categorized into vascular tumours and vascular malformations, according to the International Society for the Study of Vascular Anomalies classification system,1,2 based on the classification first proposed by Mulliken and Glowacki.3 Vascular malformation may affect arteries, veins, capillaries or lymphatics singly (simple malformations) or in combination (combined malformations). Vascular anomalies can also be categorized into high-flow or low-flow lesions according to their rheology.2,4 Venous malformation (VM), the most common vascular malformation, affects 1% of the population.5 It can be sporadic or familial, with the latter accounting for 1% of VMs.6 We have documented a 2.7% familial incidence among patients with VM in New Zealand (unpublished data). A mutation in the TIE-2 gene on the long arm of © 2014 Royal Australasian College of Surgeons
chromosome 9 has been identified in familial VM7 and up to 50% of sporadic cases.8 VMs are present at birth and enlarge proportionately with the child’s growth, although they may not be noticed until later in life.9 It may suddenly expand because of hormonal changes, trauma and incomplete surgical excision.9 In VM, the wall of the affected veins is deficient of smooth muscle cells and elastic tissue, leading to sequential ‘blow-outs’.10 Pooling of blood within these ectatic channels results in spontaneous thrombosis causing thrombophlebitis and pain. Dystrophic calcification within the organized thrombus results in formation of phleboliths within the lesions.11 VM affects different regions and tissues in the body, with variable symptoms including swelling/contour deformity, skin discoloration and pain. ANZ J Surg •• (2014) ••–••
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Imaging of VM includes plain radiography,12 Doppler ultrasonography,12 computed tomography12 and magnetic resonance imaging (MRI).13 In atypical or complex VM, direct venography may be useful.14 However, MRI with Gadolinium contrast remains the single most useful investigation to confirm the diagnosis, assess the size, flow characteristics and its anatomic position.15 Management of VM includes observation, elastic support,16 low dose aspirin,14 sclerotherapy,11 surgical excision4 or a combination of these treatments. Sclerotherapy is the preferred treatment for VM in the majority of patients,4,11 performed under fluoroscopy under general anaesthesia.17 Different sclerosants have been used for VM including polidocanol, ethanolamine and sodium tetradecyl sulfate, with ethanol being the most popular.18,19 Treatment directly targets the VM and the ethanol acts as a sclerosant by causing hypertonic dehydration of cells, protein denaturation, thrombosis and vessel occlusion.18,20 It produces an intense inflammatory response, leading to swelling and worsening symptoms lasting up to 4 weeks postoperatively.17 Complications of ethanol sclerotherapy (ES) include tissue necrosis, nerve damage, pain, swelling, deep vein thrombosis and cardiopulmonary failure.21
Methods Consecutive patients with VM were identified from the vascular anomalies database at our Vascular Anomalies Centre from 1996 to 2011. Information gathered was supplemented with the patients’ medical records. The diagnosis of VM was based on clinical features and confirmed on MRI. Clinically, most VMs are characterized by a bluish or purplish non-pulsatile, compressible soft tissue mass.14 Deep-seated VMs often present with pain and/or swelling and/or loss of function.22 VM appears hyper-intense on T2-weighted MRI and iso-intense on T1-weighted sequence11,23 with homogeneous Gadolinium enhancement. Hypodense areas on T2-weighted MRI may represent thrombosis, septation or phleboliths.11 Treatment options were discussed and offered to patients with symptomatic VM. Generally, ES was the preferred treatment method with surgery playing an important role.24 Before treatment, all patients were consented regarding treatment process, risks and benefits, including low likelihood of complete symptomatic relief and potential need for further ES. The amount of ethanol used depended on the size of the lesion, not exceeding the recommended 0.5 mL/kg per treatment session. Treatment was performed under fluoroscopy under general anaesthesia. Tourniquets were not used for limb VMs. All procedures were performed by the same interventional radiologist (TF) using 23G butterfly needles inserted directly into the VM. Once correct needle placement was confirmed, by observing blood flash-back, Omnipaque 300 (GE Healthcare, Auckland, New Zealand) was injected. If extravasation occurred, the needle was abandoned. The volume of ethanol required was estimated from the amount of contrast injected into the lesion before its ‘spillage’ into adjacent normal veins. One hundred per cent ethanol was injected in 1 mL or 2 mL aliquots into the VM under fluoroscopy, while observing the washout of the precedent contrast. This process was repeated until
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good coverage of the VM (as judged by clinical response and fluoroscopy) had been achieved. Post-operatively, the treated part was elevated to reduce swelling. High-dose dexamethasone was initiated at induction and tapered over 5 days. Broad-spectrum antibiotics were administered if the lesion was located around the aerodigestive or perineal areas. Elastic support was used immediately post-operatively for limb VMs and physiotherapy was commenced on the following day. Patients were routinely placed on intravenous fluids at twice-daily maintenance in addition to oral intake. The treated area was examined for complications before discharge on the following day. All patients were followed-up within 3 months of treatment and all complications were recorded. After treatment completion, patients completed a questionnaire to assess their symptoms and their severity before and >6 months after the treatment(s) using a visual analogue scale from 0 (no symptom) to 10 (maximal symptom severity). A similar visual analogue scale was used to assess the effect of VM on appearance, function/daily activities and overall quality of life (QoL), from 0 (no effect) to 10 (maximal effect). Patients who underwent more than one ES session rated their experience after all sessions were completed. They also rated their overall treatment satisfaction from 0 (complete dissatisfaction) to 10 (complete satisfaction). Non-responders to the questionnaire within 4 weeks were followed-up by telephone. Treatment outcome was stratified as complete abrogation of symptoms, partial reduction of symptoms by 1–49%, 50–74% and 75–99%, or treatment failure, defined as no effect or worsening of symptoms.
Results Of the 226 patients with VM identified, 54 (23.9%) underwent ES as a primary treatment. There were 33 females and 21 males, aged 9–61 (mean 29) years. The VM was located in the head and neck (n = 31), lower limb (n = 18), trunk (n = 6), upper limb (n = 3) and perineum (n = 1). Three patients were affected in two anatomic sites and one patient in three sites. VM affected the mucosa (n = 21), cutaneous/ subcutaneous tissue (n = 37), muscle (n = 15), parotid (n = 3), joint (n = 1) or bone (n = 1). VM affected two tissue types in 18 patients and three tissue types in three patients. The 54 patients underwent a total of 90 ES sessions (average 1.7 sessions per patient), with 31 patients receiving one, 15 receiving two, five receiving three, two receiving four and one receiving six treatments. An average of 10.5 mL (range, 2–30) of ethanol was used per patient per session, equating to 0.16 mL/kg (range, 0.03–0.4). Complications occurred in 12 (22.2%) patients in 12 (13.3%) ES sessions. These included major complications in three (5.6%) patients in three (3.3%) ES sessions, including necrosis of the upper lip requiring surgical debridement (n = 1), transient Horner’s syndrome (n = 1) and finger paraesthesia with reduced wrist supination (n = 1). Minor complications included transient sensory dysfunction (n = 3), transient weakness of the facial nerve branch(es) (n = 3), skin blistering (n = 2) and minor tongue ulceration that healed spontaneously (n = 1). Three patients underwent surgical excision following ES as an adjunctive procedure. © 2014 Royal Australasian College of Surgeons
Ethanol sclerotherapy for venous malformation
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Table 1 Types of symptoms and their mean severity scores before and after ethanol sclerotherapy in 49 patients with venous malformation Symptoms
Background pain Acute episodic pain Contour deformity Skin discoloration Bleeding Headaches Reduced motion Obstructive sleep apnoea Dizziness
Number of patients with symptoms before treatment (%)
Average rating† before treatment
Average rating† after treatment
Complete resolution of symptoms (%)
75–99% reduction (%)
Partial reduction of symptoms 50–74% reduction (%)
1–49% reduction (%)
43 (87.8) 29 (59.2) 47 (95.9) 36 (73.5) 6 (12.2) 1 (2.0) 6 (12.2) 1 (2.0) 1 (2.0)
5.4 8.1 6.9 6.5 5.2 4.5 6.8 8.0 7.0
2.6 4.1 3.2 3.6 1.5 1.0 3.2 3.0 0
14 (32.6) 8 (27.6) 10 (21.3) 7 (19.4) 4 (66.7) — 2 (33.3) — 1 (100)
4 (9.3) 1 (3.4) 6 (12.8) 1 (2.8) 1 (16.7) 1 (100) — — —
9 (20.9) 5 (17.2) 11 (23.4) 7 (19.4) — — 1 (16.7) 1 (100) —
10 (23.3) 7 (24.1) 12 (25.5) 11 (30.6) — — 1 (16.7) — —
Treatment failure (%)‡
6 (14.0) 8 (27.6) 8 (17.0) 10 (27.8) 1 (16.7) — 2 (33.3) — —
†Using a visual analogue scale of 0 (no symptom) to 10 (maximum severity). ‡Defined as no reduction or worsening of symptoms.
Table 2 Impact of venous malformation before and after ethanol sclerotherapy in 49 patients Effect of venous malformation on:
Appearance Function/daily activities Quality of life
Number of patients affected (%)
Average rating† before treatment
Average rating† after treatment
Complete resolution (%)
43 (87.8) 37 (75.5) 42 (85.7)
7.3 6.2 6.0
4.1 3.1 3.1
6 (14.0) 9 (24.3) 6 (14.3)
Partial resolution 75–99% reduction (%)
50–74% reduction (%)
1–49% reduction (%)
4 (9.3) 4 (10.8) 8 (19.0)
10 (23.2) 5 (13.5) 5 (11.9)
10 (23.2) 9 (24.3) 8 (19.0)
Treatment failure (%)‡
13 (30.2) 10 (27.0) 15 (35.7)
†Using a visual analogue scale of 0 (no effect) to 10 (maximum effect). ‡Defined as no reduction or worsening of symptoms.
Fig. 1. A 15-year-old female with a venous malformation (VM) affecting her left cheek and orbit (a). A T2 magnetic resonance imaging showing the VM within the left buccal space, extending into the temporal region, deep to the temporalis muscle (b). Ethanol sclerotherapy (ES) of the VM (c), which outlined dilated venous channels (d). Marked swelling following treatment (e). Improved facial symmetry after ES (f). The residual VM over the lateral canthus was debulked and remained unchanged over 2 years (g).
(a)
(d) (c)
(e)
The questionnaire was sent to all except five patients, whose whereabouts could not be traced. The remaining 49 patients responded. The mean follow-up was 5.4 years (range, 0.5–15). Types of symptoms and their mean severity scores before and after ES and the percentage reduction of symptoms after treatment are shown in Table 1. ES improved the severity of background pain, acute episodic pain, contour deformity and skin discoloration in © 2014 Royal Australasian College of Surgeons
(b)
(f)
(g)
86.0%, 72.4%, 83.0% and 72.2% of patients respectively. The effect of VM on the appearance, function and the overall QoL before and after treatment are shown in Table 2. ES reduced the effect of VM on the appearance, function and overall QoL in 69.8%, 73.0% and 64.3% of patients (Table 2). The mean overall patient satisfaction with treatment was 7.9 (range, 0–10). Representative cases are presented in Figures 1–4.
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(a)
(b)
(c)
(a)
(d)
(c)
(b)
(f) (d)
(e)
Discussion Sclerotherapy is the preferred treatment for VM, especially for diffuse lesions,4 which if treated surgically, would lead to significant functional impairment.25 In our Vascular Anomalies Centre, surgery is indicated as a primary treatment when ES is impossible for a particular anatomic site or the extent of the lesion, or as an alternative because of the patient’s preference, especially for localized lesions in which complete excision is feasible with low morbidity.24 Sometimes, combined treatments are required. Different sclerosants are available for treating VM including sodium tetradecyl, polidocanol, ethanolamine and ethanol.18,19 Sodium tetradecyl, available in liquid or foam,20 is regarded to be
Fig. 2. A 6-year-old girl with a venous malformation (VM) on the right cheek, upper neck and lower lip (a). A T2 magnetic resonance imaging showing the VM in the subcutaneous space of the cheek, the base of the tongue and lower lip (b,c). The patient underwent three ethanol sclerotherapy sessions, with marked improvement of facial symmetry (d).
Fig. 3. A 30-year-old woman with an extensive venous malformation (VM) (noticed soon after birth) on the right side of her neck, cheek (a), oral cavity and oropharynx (b). This expanded and caused discomfort when stooping or exercising. A T2 magnetic resonance imaging (MRI) showing involvement of the masseter muscle, oropharynx and larynx, which was significantly narrowed (c). A repeat T1 MRI following four ethanol sclerotherapy (ES) sessions (with elective tracheostomy for airway protection) showing significant VM reduction, with marked improvement of the airway (d). Two years later, flexible endoscopy showed airway narrowing by the expanded residual VM following a pregnancy (e). This was associated with severe obstructive sleep apnoea, confirmed on a sleep study. Two further ES treatments were performed, complicated by right-sided Horner’s syndrome. These symptoms had resolved when the patient was reviewed 8 months later. Subsequent surgical debulking of the residual fibrous residuum in the neck (f).
safer than ethanol. However, there is a lack of studies comparing the two agents.20 Polidocanol is effective for small VMs, as it often spares the normal adjacent veins, and its anaesthetic effect may reduce the need for general anaesthesia. Ethanolamine has decreased penetration of the vascular wall, reducing damage to the surrounding neurological and soft tissue structures.20 However, it can cause renal failure and therefore prophylactic albumin and haptoglobin may be required.12,18 Ethanol is regarded as the most potent, destructive and effective agent. All patients with VM undergoing sclerotherapy in our Centre are treated with ethanol. The use of a single agent, with which the interventional radiologist has experience in using, increases the safety of the procedure. © 2014 Royal Australasian College of Surgeons
Ethanol sclerotherapy for venous malformation
Fig. 4. A 32-year-old man with a 3 × 4cm venous malformation (VM) in the tongue (a,b), affecting swallowing and speech. A T2 magnetic resonance imaging showing an intramuscular VM within the tongue and the floor of the mouth (c). The lesion was treated with a single session of ethanol sclerotherapy. Postoperatively, the patient developed minor tongue ulceration which healed spontaneously (d,e). There was no clinical evidence of residual VM 6 months later.
(a)
(d)
All patients undergoing ES were administered high-dose dexamethasone at induction, tapering over the next 5 days. Dexamethasone is used routinely in sclerotherapy and head and neck surgical procedures to reduce post-operative swelling.26,27 Haemolysis, haemoglobinuria and oliguria are recognized complications of ES that can lead to renal injury.28,29 All patients were placed on intravenous fluids post-operatively with twice-daily maintenance, in addition to free oral intake, as recommended in other studies.28,29 The average dosage of alcohol used in our series was 0.16 mL/kg per session. Our complication rate for ES of 22.2% per patient (13.3% per session), including a major complication rate of 5.6% per patient (3.3% per session), is consistent with the reported 10–30% overall complication rates with one study showing a 25% early complication and 3% late complication rate per patient.30–33 Complications that occurred in our series included necrosis of the lip requiring surgery, transient Horner’s syndrome, finger paraesthesia and reduced wrist supination, transient weakness or sensory dysfunction, skin blistering and tongue ulceration. These are recognized complications of ES which also include deep vein thrombosis, pulmonary embolism, systemic alcohol contamination and cardiac arrest if the dose of 1 mL/kg per session is exceeded.12,18,20,21,34,35 Serial ES sessions are often required, especially for extensive VM.36 We have shown that ES reduces the severity of pain, improves swelling/contour deformity, skin discoloration and other symptoms such as bleeding in VM patients. ES improves the severity of background pain, acute episodic pain, contour deformity and skin discoloration in 86.0%, 72.4%, 83.0% and 72.2% of patients respectively. ES reduces the effect of VM on appearance, function and overall QoL in 69.8%, 73.0% and 64.3% of patients. © 2014 Royal Australasian College of Surgeons
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(b)
(c)
(e)
We report a mean overall treatment satisfaction of 7.9 (range, 0–10). As the majority of patients did not have full resolution of VM symptoms, this high rate of satisfaction may reflect our thorough consent process for ES. There are limitations in our study. Firstly, pretreatment data on symptoms, their severity and their effect were not collected prospectively, which would provide more accurate assessment of the effect of ES on VM. Secondly, a validated disease-specific tool to measure QoL was not used in this study. VMs are challenging problems and it is impossible to eradicate the lesions in most instances. Many patients require serial ES to control the symptoms. In some patients, surgery would be required to address the residuum. However, patient satisfaction can still be high if adequate consent prior to treatment is provided.
Acknowledgements Frederica Steiner was supported by a summer student scholarship of the Gillies McIndoe Research Institute. We thank Dr Francis Hall, formerly otolaryngologist at Hutt Hospital, and Dr Cathy Ferguson, otolaryngologist at Wellington Regional Hospital, for their assistance in the management of a patient (Case 3). We are grateful to Mrs Annette Wikeepa for her assistance with this study.
References 1. Enjolras O, Mulliken JB. Vascular tumors and vascular malformations. Adv. Dermatol. 1997; 13: 375–423. 2. Tan ST. Cellular and molecular basis of haemangioma. PhD Thesis, University of Otago, 2001.
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3. Mulliken JB, Glowacki J. Haemangiomas and vascular malformations in infants and children; a classification based on endothelial characteristics. Plast. Reconstr. Surg. 1982; 69: 412–20. 4. Jackson IT, Carreño R, Potparic Z, Hussain K. Hemangiomas, vascular malformations, and lymphovenous malformations: classification and methods of treatment. Plast. Reconstr. Surg. 1993; 91: 1216–30. 5. Mulliken JB. Diagnosis and natural history of hemangiomas. In: Mulliken JB, Young AE (eds). Vascular Birthmarks: Haemangioma and Vascular Malformations. Philadelphia: WB Saunders, 1988; 41–62. 6. Brouillard P, Vikkula M. Genetic causes of vascular malformations. Hum. Mol. Genet. 2007; 16: 140–9. 7. Boon LM, Mulliken JB, Vikkula M et al. Assignment of a locus for dominantly inherited venous malformations to chromosome 9p. Hum. Mol. Genet. 1994; 3: 1583–7. 8. Limaye N, Wouters V, Uebelhoer M, Tuominen M, Wirkkala R, Mulliken JB et al. Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations. Nat. Genet. 2009; 41: 118–24. 9. Mulliken JB, Fishman SJ, Burrows PE. Vascular anomalies. Curr. Probl. Surg. 2000; 37: 517–84. 10. Gallione CJ, Pasyk KA, Boon LM et al. A gene for familial venous malformations maps to chromosome 9p in a second large kindred. J. Med. Genet. 1995; 32: 197–9. 11. Mulliken JB, Fishman SJ, Burrows PE. Current problems in surgery. Vascular Anomalies 2000; 37: 43–9. 12. Hyodoh H, Hori M, Akiba H, Tamakawa M, Hyodoh K, Hareyama H. Peripheral vascular malformations: imaging, treatment approaches, and therapeutic issues. Radiographics 2005; 25: S159–71. 13. Fayad LM, Hazirolan T, Carrino JA, Bluemke DA, Mitchell S. Venous malformations: MR imaging features that predict skin burns after percutaneous alcohol embolization procedures. Skeletal Radiol. 2008; 37: 895–901. 14. Dubois J, Soulez G, Olivia VL, Berthiaume MJ, Lapierre C, Therasse E. Soft-tissue venous malformations in adult patients: imaging and therapeutic issues. Radiographics 2001; 21: 1519–31. 15. Moukaddam H, Pollak J, Haims AH. MRI characteristics and classification of peripheral vascular malformations and tumours. Skeletal Radiol. 2009; 38: 535–47. 16. Dompmartin A, Vikkula M, Boon LM. Venous malformation: update of aetiopathogenesis, diagnosis and management. Phlebology 2010; 25: 224–35. 17. Savador SJ, Trerotola SO. Diagnosis and management of venous malformations. In: Savader SJ, Trerotola SO (eds). Venous Interventional Radiology with Clinical Perspectives. New York: Thieme, 2000; 183–93. 18. Dubois J. Vascular embolotherapy. In: Golzarian J, Sun S, Sharafuddin MJ (eds). Predominantly Venous Malformations. Germany: SpringerVerlag, 2006; 26–9. 19. Cabrera J, Cabrera J Jr, Garcia-Olmedo MA, Redondo P. Treatment of venous malformations with sclerosant in microfoam form. Arch. Dermatol. 2003; 139: 1409–16.
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20. Albanese G, Kondo K. Pharmacology of sclerotherapy. Semin Intervent Radiol 2010; 27: 391–9. 21. Puig S, Aref H, Chigot V, Bonin B, Brunelle F, Classification of venous malformations in children and implications for sclerotherapy. Pediatr. Radiol. 2003; 33: 99–103. 22. Enjolras O, Ciabrini D, Mazoyer E, Laurian C, Herbreteau D. Extensive pure venous malformations in the upper or lower limb: a review of 27 cases. J. Am. Acad. Dermatol. 1997; 26: 219–25. 23. Dobson MJ, Hartley RWJ, Ashleigh R, Watson Y, Hawnaur JM. MR angiography and MR imaging of symptomatic vascular malformations. Clin. Radiol. 1997; 57: 595–602. 24. Steiner F, FitzJohn T, Tan ST. Surgical treatment for venous malformation. J Plast. Reconstr. Aesthet. Surg. 2013; 66: 1741–9. 25. Yakes WF. Diagnosis and management of low-flow veno-lymphatic vascular malformations. Ces. Radiol. 2008; 62: 131–45. 26. Johnson P, Eckard D, Brecheisen M, Girod D, Tsue T. Percutaneous ethanol sclerotherapy of venous malformations of the tongue. AJNR Am. J. Neuroradiol. 2002; 23: 779–82. 27. Filho J, Maurette P, Allais M, Cotinho M, Fernandes C. Clinical comparative study of the effectiveness of two dosages of dexamethasone to control postoperative swelling, trismus and pain after the surgical extraction of mandibular impacted third molars. Med. Oral Pathol. Oral Cir. Bucal. 2008; 13: 129–32. 28. Greene A, Alomari A. Management of venous malformations. Clin. Plast. Surg. 2011; 38: 83–93. 29. Zheng J, Mai H, Zhang L et al. Guidelines for the treatment of head and neck venous malformations. Int. J. Clin. Exp. Med. 2013; 6: 377–89. 30. Gloviczki P. Vascular malformations. In: Moore WS (ed.). Vascular and Endovascular Surgery: A Comprehensive Review, 7th edn. Philadelphia, PA: Saunders Elsevier, 2006; 198–213. 31. Lee B, Do Y, Byun H, Choo I, Kim D, Huh S. Advanced management of venous malformation with ethanol sclerotherapy: mid-term results. J. Vasc. Surg. 2003; 37: 533–8. 32. Lee H, Kim K, Jeon P et al. Ethanol sclerotherapy for the management of craniofacial venous malformations: the interim results. Korean J. Radiol. 2009; 10: 269–76. 33. Yakes WF, Luethke JM, Parker SH et al. Ethanol embolization of vascular malformations. Radiographics 1990; 10: 787–96. 34. Baek HJ, Hong JP, Suh DC. Direct percutaneous alcohol sclerotherapy for venous malformations of head and neck region without fluoroscopic guidance: technical consideration and outcome. Neurointervention 2011; 6: 84–8. 35. Hammer F, Boon L, Mathurin P, Vanwijck R. Ethanol sclerotherapy of venous malformations: evaluation of systemic ethanol contamination. J. Vasc. Interv Radiol 2001; 12: 595–600. 36. Yakes WF, Haas DK, Parker SH et al. Symptomatic vascular malformations: ethanol embolotherapy. Radiology 1989; 170: 1059–66.
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Ethanol sclerotherapy for venous malformation Frederica Steiner,* Trevor FitzJohn† and Swee T. Tan*† *Gillies McIndoe Research Institute, Wellington, New Zealand and †Centre for the Study & Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand
Key words alcohol, complication, embolization, ethanol, sclerotherapy, treatment, venous malformation. Correspondence Professor Swee T. Tan, Gillies McIndoe Research Institute, PO Box 7184, Newtown, Wellington 6242, New Zealand. Email: [email protected] F. Steiner; T. FitzJohn MBBS, BMedSci, DMRD, FRCR, FRANZCR; S. T. Tan MBBS, FRACS, PhD. This paper was presented, in part, at the 81st Annual Scientific Congress of the Royal Australasian College of Surgeons, Kuala Lumpur, Malaysia, 6–11 May 2012 and the 19th International Society for the Study of Vascular Anomalies Workshop, Malmo, Sweden, 16–19 June 2012. Accepted for publication 28 July 2014. doi: 10.1111/ans.12833
Abstract Background: Ethanol sclerotherapy (ES) is the preferred treatment for venous malformation (VM) with surgery playing an adjunctive role. Results of ES, however, are not well documented in the literature. Methods: VM patients were identified from our vascular anomalies database from 1996 to 2011. After treatment completion, patients completed questionnaires evaluating symptoms and their severity and effect on appearance, function and overall quality of life (QoL), before and >6 months after treatment, using visual analogue scales of 0–10. Patients rated their overall satisfaction with ES using a scale of 0–10. Results: Fifty-four (23.9%) of the 226 VM patients underwent a total of 90 ES sessions (average 1.7 sessions per patient). Complications occurred in 12 (22.2%) patients in 12 (13.3%) ES sessions. Minor complications occurred in nine (16.7%) patients including transient paraesthesia (n = 3), transient weakness of facial nerve branch(es) (n = 3), skin blistering (n = 2) and spontaneously healing ulceration (n = 1). Major complications occurred in three (5.6%) patients in three (3.3%) ES sessions including skin necrosis (n = 1), Horner’s syndrome (n = 1) and finger paraesthesia with joint stiffness (n = 1). ES improved the severity of background pain, episodic pain, contour deformity and skin discoloration in 86.0%, 72.4%, 83.0% and 72.2% of patients respectively. It reduced the effect of VM on appearance, function and overall QoL in 69.8%, 73.0% and 64.3% of patients. Mean treatment satisfaction was 7.9 (range, 0–10). Conclusion: ES reduces pain, contour deformity and skin discoloration, and improves appearance, function and QoL. Our complication rates are consistent with the literature.
Introduction Vascular anomalies are categorized into vascular tumours and vascular malformations, according to the International Society for the Study of Vascular Anomalies classification system,1,2 based on the classification first proposed by Mulliken and Glowacki.3 Vascular malformation may affect arteries, veins, capillaries or lymphatics singly (simple malformations) or in combination (combined malformations). Vascular anomalies can also be categorized into high-flow or low-flow lesions according to their rheology.2,4 Venous malformation (VM), the most common vascular malformation, affects 1% of the population.5 It can be sporadic or familial, with the latter accounting for 1% of VMs.6 We have documented a 2.7% familial incidence among patients with VM in New Zealand (unpublished data). A mutation in the TIE-2 gene on the long arm of © 2014 Royal Australasian College of Surgeons
chromosome 9 has been identified in familial VM7 and up to 50% of sporadic cases.8 VMs are present at birth and enlarge proportionately with the child’s growth, although they may not be noticed until later in life.9 It may suddenly expand because of hormonal changes, trauma and incomplete surgical excision.9 In VM, the wall of the affected veins is deficient of smooth muscle cells and elastic tissue, leading to sequential ‘blow-outs’.10 Pooling of blood within these ectatic channels results in spontaneous thrombosis causing thrombophlebitis and pain. Dystrophic calcification within the organized thrombus results in formation of phleboliths within the lesions.11 VM affects different regions and tissues in the body, with variable symptoms including swelling/contour deformity, skin discoloration and pain. ANZ J Surg •• (2014) ••–••
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Imaging of VM includes plain radiography,12 Doppler ultrasonography,12 computed tomography12 and magnetic resonance imaging (MRI).13 In atypical or complex VM, direct venography may be useful.14 However, MRI with Gadolinium contrast remains the single most useful investigation to confirm the diagnosis, assess the size, flow characteristics and its anatomic position.15 Management of VM includes observation, elastic support,16 low dose aspirin,14 sclerotherapy,11 surgical excision4 or a combination of these treatments. Sclerotherapy is the preferred treatment for VM in the majority of patients,4,11 performed under fluoroscopy under general anaesthesia.17 Different sclerosants have been used for VM including polidocanol, ethanolamine and sodium tetradecyl sulfate, with ethanol being the most popular.18,19 Treatment directly targets the VM and the ethanol acts as a sclerosant by causing hypertonic dehydration of cells, protein denaturation, thrombosis and vessel occlusion.18,20 It produces an intense inflammatory response, leading to swelling and worsening symptoms lasting up to 4 weeks postoperatively.17 Complications of ethanol sclerotherapy (ES) include tissue necrosis, nerve damage, pain, swelling, deep vein thrombosis and cardiopulmonary failure.21
Methods Consecutive patients with VM were identified from the vascular anomalies database at our Vascular Anomalies Centre from 1996 to 2011. Information gathered was supplemented with the patients’ medical records. The diagnosis of VM was based on clinical features and confirmed on MRI. Clinically, most VMs are characterized by a bluish or purplish non-pulsatile, compressible soft tissue mass.14 Deep-seated VMs often present with pain and/or swelling and/or loss of function.22 VM appears hyper-intense on T2-weighted MRI and iso-intense on T1-weighted sequence11,23 with homogeneous Gadolinium enhancement. Hypodense areas on T2-weighted MRI may represent thrombosis, septation or phleboliths.11 Treatment options were discussed and offered to patients with symptomatic VM. Generally, ES was the preferred treatment method with surgery playing an important role.24 Before treatment, all patients were consented regarding treatment process, risks and benefits, including low likelihood of complete symptomatic relief and potential need for further ES. The amount of ethanol used depended on the size of the lesion, not exceeding the recommended 0.5 mL/kg per treatment session. Treatment was performed under fluoroscopy under general anaesthesia. Tourniquets were not used for limb VMs. All procedures were performed by the same interventional radiologist (TF) using 23G butterfly needles inserted directly into the VM. Once correct needle placement was confirmed, by observing blood flash-back, Omnipaque 300 (GE Healthcare, Auckland, New Zealand) was injected. If extravasation occurred, the needle was abandoned. The volume of ethanol required was estimated from the amount of contrast injected into the lesion before its ‘spillage’ into adjacent normal veins. One hundred per cent ethanol was injected in 1 mL or 2 mL aliquots into the VM under fluoroscopy, while observing the washout of the precedent contrast. This process was repeated until
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good coverage of the VM (as judged by clinical response and fluoroscopy) had been achieved. Post-operatively, the treated part was elevated to reduce swelling. High-dose dexamethasone was initiated at induction and tapered over 5 days. Broad-spectrum antibiotics were administered if the lesion was located around the aerodigestive or perineal areas. Elastic support was used immediately post-operatively for limb VMs and physiotherapy was commenced on the following day. Patients were routinely placed on intravenous fluids at twice-daily maintenance in addition to oral intake. The treated area was examined for complications before discharge on the following day. All patients were followed-up within 3 months of treatment and all complications were recorded. After treatment completion, patients completed a questionnaire to assess their symptoms and their severity before and >6 months after the treatment(s) using a visual analogue scale from 0 (no symptom) to 10 (maximal symptom severity). A similar visual analogue scale was used to assess the effect of VM on appearance, function/daily activities and overall quality of life (QoL), from 0 (no effect) to 10 (maximal effect). Patients who underwent more than one ES session rated their experience after all sessions were completed. They also rated their overall treatment satisfaction from 0 (complete dissatisfaction) to 10 (complete satisfaction). Non-responders to the questionnaire within 4 weeks were followed-up by telephone. Treatment outcome was stratified as complete abrogation of symptoms, partial reduction of symptoms by 1–49%, 50–74% and 75–99%, or treatment failure, defined as no effect or worsening of symptoms.
Results Of the 226 patients with VM identified, 54 (23.9%) underwent ES as a primary treatment. There were 33 females and 21 males, aged 9–61 (mean 29) years. The VM was located in the head and neck (n = 31), lower limb (n = 18), trunk (n = 6), upper limb (n = 3) and perineum (n = 1). Three patients were affected in two anatomic sites and one patient in three sites. VM affected the mucosa (n = 21), cutaneous/ subcutaneous tissue (n = 37), muscle (n = 15), parotid (n = 3), joint (n = 1) or bone (n = 1). VM affected two tissue types in 18 patients and three tissue types in three patients. The 54 patients underwent a total of 90 ES sessions (average 1.7 sessions per patient), with 31 patients receiving one, 15 receiving two, five receiving three, two receiving four and one receiving six treatments. An average of 10.5 mL (range, 2–30) of ethanol was used per patient per session, equating to 0.16 mL/kg (range, 0.03–0.4). Complications occurred in 12 (22.2%) patients in 12 (13.3%) ES sessions. These included major complications in three (5.6%) patients in three (3.3%) ES sessions, including necrosis of the upper lip requiring surgical debridement (n = 1), transient Horner’s syndrome (n = 1) and finger paraesthesia with reduced wrist supination (n = 1). Minor complications included transient sensory dysfunction (n = 3), transient weakness of the facial nerve branch(es) (n = 3), skin blistering (n = 2) and minor tongue ulceration that healed spontaneously (n = 1). Three patients underwent surgical excision following ES as an adjunctive procedure. © 2014 Royal Australasian College of Surgeons
Ethanol sclerotherapy for venous malformation
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Table 1 Types of symptoms and their mean severity scores before and after ethanol sclerotherapy in 49 patients with venous malformation Symptoms
Background pain Acute episodic pain Contour deformity Skin discoloration Bleeding Headaches Reduced motion Obstructive sleep apnoea Dizziness
Number of patients with symptoms before treatment (%)
Average rating† before treatment
Average rating† after treatment
Complete resolution of symptoms (%)
75–99% reduction (%)
Partial reduction of symptoms 50–74% reduction (%)
1–49% reduction (%)
43 (87.8) 29 (59.2) 47 (95.9) 36 (73.5) 6 (12.2) 1 (2.0) 6 (12.2) 1 (2.0) 1 (2.0)
5.4 8.1 6.9 6.5 5.2 4.5 6.8 8.0 7.0
2.6 4.1 3.2 3.6 1.5 1.0 3.2 3.0 0
14 (32.6) 8 (27.6) 10 (21.3) 7 (19.4) 4 (66.7) — 2 (33.3) — 1 (100)
4 (9.3) 1 (3.4) 6 (12.8) 1 (2.8) 1 (16.7) 1 (100) — — —
9 (20.9) 5 (17.2) 11 (23.4) 7 (19.4) — — 1 (16.7) 1 (100) —
10 (23.3) 7 (24.1) 12 (25.5) 11 (30.6) — — 1 (16.7) — —
Treatment failure (%)‡
6 (14.0) 8 (27.6) 8 (17.0) 10 (27.8) 1 (16.7) — 2 (33.3) — —
†Using a visual analogue scale of 0 (no symptom) to 10 (maximum severity). ‡Defined as no reduction or worsening of symptoms.
Table 2 Impact of venous malformation before and after ethanol sclerotherapy in 49 patients Effect of venous malformation on:
Appearance Function/daily activities Quality of life
Number of patients affected (%)
Average rating† before treatment
Average rating† after treatment
Complete resolution (%)
43 (87.8) 37 (75.5) 42 (85.7)
7.3 6.2 6.0
4.1 3.1 3.1
6 (14.0) 9 (24.3) 6 (14.3)
Partial resolution 75–99% reduction (%)
50–74% reduction (%)
1–49% reduction (%)
4 (9.3) 4 (10.8) 8 (19.0)
10 (23.2) 5 (13.5) 5 (11.9)
10 (23.2) 9 (24.3) 8 (19.0)
Treatment failure (%)‡
13 (30.2) 10 (27.0) 15 (35.7)
†Using a visual analogue scale of 0 (no effect) to 10 (maximum effect). ‡Defined as no reduction or worsening of symptoms.
Fig. 1. A 15-year-old female with a venous malformation (VM) affecting her left cheek and orbit (a). A T2 magnetic resonance imaging showing the VM within the left buccal space, extending into the temporal region, deep to the temporalis muscle (b). Ethanol sclerotherapy (ES) of the VM (c), which outlined dilated venous channels (d). Marked swelling following treatment (e). Improved facial symmetry after ES (f). The residual VM over the lateral canthus was debulked and remained unchanged over 2 years (g).
(a)
(d) (c)
(e)
The questionnaire was sent to all except five patients, whose whereabouts could not be traced. The remaining 49 patients responded. The mean follow-up was 5.4 years (range, 0.5–15). Types of symptoms and their mean severity scores before and after ES and the percentage reduction of symptoms after treatment are shown in Table 1. ES improved the severity of background pain, acute episodic pain, contour deformity and skin discoloration in © 2014 Royal Australasian College of Surgeons
(b)
(f)
(g)
86.0%, 72.4%, 83.0% and 72.2% of patients respectively. The effect of VM on the appearance, function and the overall QoL before and after treatment are shown in Table 2. ES reduced the effect of VM on the appearance, function and overall QoL in 69.8%, 73.0% and 64.3% of patients (Table 2). The mean overall patient satisfaction with treatment was 7.9 (range, 0–10). Representative cases are presented in Figures 1–4.
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(a)
(b)
(c)
(a)
(d)
(c)
(b)
(f) (d)
(e)
Discussion Sclerotherapy is the preferred treatment for VM, especially for diffuse lesions,4 which if treated surgically, would lead to significant functional impairment.25 In our Vascular Anomalies Centre, surgery is indicated as a primary treatment when ES is impossible for a particular anatomic site or the extent of the lesion, or as an alternative because of the patient’s preference, especially for localized lesions in which complete excision is feasible with low morbidity.24 Sometimes, combined treatments are required. Different sclerosants are available for treating VM including sodium tetradecyl, polidocanol, ethanolamine and ethanol.18,19 Sodium tetradecyl, available in liquid or foam,20 is regarded to be
Fig. 2. A 6-year-old girl with a venous malformation (VM) on the right cheek, upper neck and lower lip (a). A T2 magnetic resonance imaging showing the VM in the subcutaneous space of the cheek, the base of the tongue and lower lip (b,c). The patient underwent three ethanol sclerotherapy sessions, with marked improvement of facial symmetry (d).
Fig. 3. A 30-year-old woman with an extensive venous malformation (VM) (noticed soon after birth) on the right side of her neck, cheek (a), oral cavity and oropharynx (b). This expanded and caused discomfort when stooping or exercising. A T2 magnetic resonance imaging (MRI) showing involvement of the masseter muscle, oropharynx and larynx, which was significantly narrowed (c). A repeat T1 MRI following four ethanol sclerotherapy (ES) sessions (with elective tracheostomy for airway protection) showing significant VM reduction, with marked improvement of the airway (d). Two years later, flexible endoscopy showed airway narrowing by the expanded residual VM following a pregnancy (e). This was associated with severe obstructive sleep apnoea, confirmed on a sleep study. Two further ES treatments were performed, complicated by right-sided Horner’s syndrome. These symptoms had resolved when the patient was reviewed 8 months later. Subsequent surgical debulking of the residual fibrous residuum in the neck (f).
safer than ethanol. However, there is a lack of studies comparing the two agents.20 Polidocanol is effective for small VMs, as it often spares the normal adjacent veins, and its anaesthetic effect may reduce the need for general anaesthesia. Ethanolamine has decreased penetration of the vascular wall, reducing damage to the surrounding neurological and soft tissue structures.20 However, it can cause renal failure and therefore prophylactic albumin and haptoglobin may be required.12,18 Ethanol is regarded as the most potent, destructive and effective agent. All patients with VM undergoing sclerotherapy in our Centre are treated with ethanol. The use of a single agent, with which the interventional radiologist has experience in using, increases the safety of the procedure. © 2014 Royal Australasian College of Surgeons
Ethanol sclerotherapy for venous malformation
Fig. 4. A 32-year-old man with a 3 × 4cm venous malformation (VM) in the tongue (a,b), affecting swallowing and speech. A T2 magnetic resonance imaging showing an intramuscular VM within the tongue and the floor of the mouth (c). The lesion was treated with a single session of ethanol sclerotherapy. Postoperatively, the patient developed minor tongue ulceration which healed spontaneously (d,e). There was no clinical evidence of residual VM 6 months later.
(a)
(d)
All patients undergoing ES were administered high-dose dexamethasone at induction, tapering over the next 5 days. Dexamethasone is used routinely in sclerotherapy and head and neck surgical procedures to reduce post-operative swelling.26,27 Haemolysis, haemoglobinuria and oliguria are recognized complications of ES that can lead to renal injury.28,29 All patients were placed on intravenous fluids post-operatively with twice-daily maintenance, in addition to free oral intake, as recommended in other studies.28,29 The average dosage of alcohol used in our series was 0.16 mL/kg per session. Our complication rate for ES of 22.2% per patient (13.3% per session), including a major complication rate of 5.6% per patient (3.3% per session), is consistent with the reported 10–30% overall complication rates with one study showing a 25% early complication and 3% late complication rate per patient.30–33 Complications that occurred in our series included necrosis of the lip requiring surgery, transient Horner’s syndrome, finger paraesthesia and reduced wrist supination, transient weakness or sensory dysfunction, skin blistering and tongue ulceration. These are recognized complications of ES which also include deep vein thrombosis, pulmonary embolism, systemic alcohol contamination and cardiac arrest if the dose of 1 mL/kg per session is exceeded.12,18,20,21,34,35 Serial ES sessions are often required, especially for extensive VM.36 We have shown that ES reduces the severity of pain, improves swelling/contour deformity, skin discoloration and other symptoms such as bleeding in VM patients. ES improves the severity of background pain, acute episodic pain, contour deformity and skin discoloration in 86.0%, 72.4%, 83.0% and 72.2% of patients respectively. ES reduces the effect of VM on appearance, function and overall QoL in 69.8%, 73.0% and 64.3% of patients. © 2014 Royal Australasian College of Surgeons
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(b)
(c)
(e)
We report a mean overall treatment satisfaction of 7.9 (range, 0–10). As the majority of patients did not have full resolution of VM symptoms, this high rate of satisfaction may reflect our thorough consent process for ES. There are limitations in our study. Firstly, pretreatment data on symptoms, their severity and their effect were not collected prospectively, which would provide more accurate assessment of the effect of ES on VM. Secondly, a validated disease-specific tool to measure QoL was not used in this study. VMs are challenging problems and it is impossible to eradicate the lesions in most instances. Many patients require serial ES to control the symptoms. In some patients, surgery would be required to address the residuum. However, patient satisfaction can still be high if adequate consent prior to treatment is provided.
Acknowledgements Frederica Steiner was supported by a summer student scholarship of the Gillies McIndoe Research Institute. We thank Dr Francis Hall, formerly otolaryngologist at Hutt Hospital, and Dr Cathy Ferguson, otolaryngologist at Wellington Regional Hospital, for their assistance in the management of a patient (Case 3). We are grateful to Mrs Annette Wikeepa for her assistance with this study.
References 1. Enjolras O, Mulliken JB. Vascular tumors and vascular malformations. Adv. Dermatol. 1997; 13: 375–423. 2. Tan ST. Cellular and molecular basis of haemangioma. PhD Thesis, University of Otago, 2001.
6
3. Mulliken JB, Glowacki J. Haemangiomas and vascular malformations in infants and children; a classification based on endothelial characteristics. Plast. Reconstr. Surg. 1982; 69: 412–20. 4. Jackson IT, Carreño R, Potparic Z, Hussain K. Hemangiomas, vascular malformations, and lymphovenous malformations: classification and methods of treatment. Plast. Reconstr. Surg. 1993; 91: 1216–30. 5. Mulliken JB. Diagnosis and natural history of hemangiomas. In: Mulliken JB, Young AE (eds). Vascular Birthmarks: Haemangioma and Vascular Malformations. Philadelphia: WB Saunders, 1988; 41–62. 6. Brouillard P, Vikkula M. Genetic causes of vascular malformations. Hum. Mol. Genet. 2007; 16: 140–9. 7. Boon LM, Mulliken JB, Vikkula M et al. Assignment of a locus for dominantly inherited venous malformations to chromosome 9p. Hum. Mol. Genet. 1994; 3: 1583–7. 8. Limaye N, Wouters V, Uebelhoer M, Tuominen M, Wirkkala R, Mulliken JB et al. Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations. Nat. Genet. 2009; 41: 118–24. 9. Mulliken JB, Fishman SJ, Burrows PE. Vascular anomalies. Curr. Probl. Surg. 2000; 37: 517–84. 10. Gallione CJ, Pasyk KA, Boon LM et al. A gene for familial venous malformations maps to chromosome 9p in a second large kindred. J. Med. Genet. 1995; 32: 197–9. 11. Mulliken JB, Fishman SJ, Burrows PE. Current problems in surgery. Vascular Anomalies 2000; 37: 43–9. 12. Hyodoh H, Hori M, Akiba H, Tamakawa M, Hyodoh K, Hareyama H. Peripheral vascular malformations: imaging, treatment approaches, and therapeutic issues. Radiographics 2005; 25: S159–71. 13. Fayad LM, Hazirolan T, Carrino JA, Bluemke DA, Mitchell S. Venous malformations: MR imaging features that predict skin burns after percutaneous alcohol embolization procedures. Skeletal Radiol. 2008; 37: 895–901. 14. Dubois J, Soulez G, Olivia VL, Berthiaume MJ, Lapierre C, Therasse E. Soft-tissue venous malformations in adult patients: imaging and therapeutic issues. Radiographics 2001; 21: 1519–31. 15. Moukaddam H, Pollak J, Haims AH. MRI characteristics and classification of peripheral vascular malformations and tumours. Skeletal Radiol. 2009; 38: 535–47. 16. Dompmartin A, Vikkula M, Boon LM. Venous malformation: update of aetiopathogenesis, diagnosis and management. Phlebology 2010; 25: 224–35. 17. Savador SJ, Trerotola SO. Diagnosis and management of venous malformations. In: Savader SJ, Trerotola SO (eds). Venous Interventional Radiology with Clinical Perspectives. New York: Thieme, 2000; 183–93. 18. Dubois J. Vascular embolotherapy. In: Golzarian J, Sun S, Sharafuddin MJ (eds). Predominantly Venous Malformations. Germany: SpringerVerlag, 2006; 26–9. 19. Cabrera J, Cabrera J Jr, Garcia-Olmedo MA, Redondo P. Treatment of venous malformations with sclerosant in microfoam form. Arch. Dermatol. 2003; 139: 1409–16.
Steiner et al.
20. Albanese G, Kondo K. Pharmacology of sclerotherapy. Semin Intervent Radiol 2010; 27: 391–9. 21. Puig S, Aref H, Chigot V, Bonin B, Brunelle F, Classification of venous malformations in children and implications for sclerotherapy. Pediatr. Radiol. 2003; 33: 99–103. 22. Enjolras O, Ciabrini D, Mazoyer E, Laurian C, Herbreteau D. Extensive pure venous malformations in the upper or lower limb: a review of 27 cases. J. Am. Acad. Dermatol. 1997; 26: 219–25. 23. Dobson MJ, Hartley RWJ, Ashleigh R, Watson Y, Hawnaur JM. MR angiography and MR imaging of symptomatic vascular malformations. Clin. Radiol. 1997; 57: 595–602. 24. Steiner F, FitzJohn T, Tan ST. Surgical treatment for venous malformation. J Plast. Reconstr. Aesthet. Surg. 2013; 66: 1741–9. 25. Yakes WF. Diagnosis and management of low-flow veno-lymphatic vascular malformations. Ces. Radiol. 2008; 62: 131–45. 26. Johnson P, Eckard D, Brecheisen M, Girod D, Tsue T. Percutaneous ethanol sclerotherapy of venous malformations of the tongue. AJNR Am. J. Neuroradiol. 2002; 23: 779–82. 27. Filho J, Maurette P, Allais M, Cotinho M, Fernandes C. Clinical comparative study of the effectiveness of two dosages of dexamethasone to control postoperative swelling, trismus and pain after the surgical extraction of mandibular impacted third molars. Med. Oral Pathol. Oral Cir. Bucal. 2008; 13: 129–32. 28. Greene A, Alomari A. Management of venous malformations. Clin. Plast. Surg. 2011; 38: 83–93. 29. Zheng J, Mai H, Zhang L et al. Guidelines for the treatment of head and neck venous malformations. Int. J. Clin. Exp. Med. 2013; 6: 377–89. 30. Gloviczki P. Vascular malformations. In: Moore WS (ed.). Vascular and Endovascular Surgery: A Comprehensive Review, 7th edn. Philadelphia, PA: Saunders Elsevier, 2006; 198–213. 31. Lee B, Do Y, Byun H, Choo I, Kim D, Huh S. Advanced management of venous malformation with ethanol sclerotherapy: mid-term results. J. Vasc. Surg. 2003; 37: 533–8. 32. Lee H, Kim K, Jeon P et al. Ethanol sclerotherapy for the management of craniofacial venous malformations: the interim results. Korean J. Radiol. 2009; 10: 269–76. 33. Yakes WF, Luethke JM, Parker SH et al. Ethanol embolization of vascular malformations. Radiographics 1990; 10: 787–96. 34. Baek HJ, Hong JP, Suh DC. Direct percutaneous alcohol sclerotherapy for venous malformations of head and neck region without fluoroscopic guidance: technical consideration and outcome. Neurointervention 2011; 6: 84–8. 35. Hammer F, Boon L, Mathurin P, Vanwijck R. Ethanol sclerotherapy of venous malformations: evaluation of systemic ethanol contamination. J. Vasc. Interv Radiol 2001; 12: 595–600. 36. Yakes WF, Haas DK, Parker SH et al. Symptomatic vascular malformations: ethanol embolotherapy. Radiology 1989; 170: 1059–66.
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