Ethanol sclerotherapy of peripheral venous malformations

European Journal of Radiology 52 (2004) 283–287

Ethanol sclerotherapy of peripheral venous malformations U. Rimon a,∗ , A. Garniek a , Y. Galili b , G. Golan a , P. Bensaid a , B. Morag a a

Department of Diagnostic Imaging, Interventional Radiology Sectionm Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel b Department of Vascular Surgery, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel Received 15 July 2003; received in revised form 15 September 2003; accepted 17 September 2003

Abstract Background: venous malformations are congenital lesions that can cause pain, decreased range of movement, compression on adjacent structures, bleeding, consumptive coagulopathy and cosmetic deformity. Sclerotherapy alone or combined with surgical excision is the accepted treatment in symptomatic malformations after failed treatment attempts with tailored compression garments. Objectives: to report our experience with percutaneous sclerotherapy of peripheral venous malformations with ethanol 96%. Patients and methods: 41 sclerotherapy sessions were performed on 21 patients, aged 4–46 years, 15 females and 6 males. Fourteen patients were treated for painful extremity lesions, while five others with face and neck lesions and two with giant chest malformations had treatment for esthetic reasons. All patients had a pre-procedure magnetic resonance imaging (MRI) study. In all patients, 96% ethanol was used as the sclerosant by direct injection using general anesthesia. A minimum of 1-year clinical follow-up was performed. Follow-up imaging studies were performed if clinically indicated. Results: 17 patients showed complete or partial symptomatic improvement after one to nine therapeutic sessions. Four patients with lower extremity lesions continue to suffer from pain and they are considered as a treatment failure. Complications were encountered in five patients, including acute pulmonary hypertension with cardiovascular collapse, pulmonary embolus, skin ulcers (two) and skin blisters. All patients fully recovered. Conclusion: sclerotherapy with 96% ethanol for venous malformations was found to be effective for symptomatic improvement, but serious complications can occur. © 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Venous malformations; Sclerotherapy; Ethanol

1. Introduction Venous malformations are a sub-class of the vascular malformations classified in 1982 by Mulliken [1]. This biologic classification separates true hemangiomas (neoplasms) from vascular malformations, based on cellular growth and physical examination. The modified Hamburg classification presented in 1993 is now the accepted anatomopathological classification of congenital vascular defects [2]. This classification divides these defects into five types according to their predominantly malformed vessels (arterial, venous, lymphatic, A–V shunting and combined/mixed) and their anatomopathological form (truncular or extratruncular). The truncular form is characterized by dysplasia of differentiated vascular trunks. The extratruncular forms are derived from primitive capillary network. The truncular forms can appear as obstructed or dilated vessels, and deep or superficial in ∗

Corresponding author. Tel.: +972-3-5302-673; fax: 972-3-5305-146. E-mail address: [email protected] (U. Rimon).

location. The extratruncular form can appear as infiltrating (diffuse) or limited (localized) [2]. The clinical history and physical examination can usually differentiate between hemangiomas and malformations as well as between the different kinds of malformations. Regarding imaging of the venous malformations, phleboliths visualized on a plain X-ray film are pathognomonic for this condition [3]. Cross sectional imaging (US, US Doppler, MRI) is performed in uncertain diagnostic situations, and when intervention is considered [4–6]. A tailored compression garment, if anatomically possible, is the first line treatment for symptomatic slow-flow malformations in the extremities. The second-line treatment for these lesions is sclerotherapy, either alone or combined with surgical excision. Ethibloc, 1% sodium tetra-decylsulfate and ethanol 100% are some of the sclerosing agents that have been used [5,7–9], with ethanol being the most often used due to its wide availability, low cost and the lowest recurrence rate [5,8]. Absolute ethanol induces thrombosis by denaturating blood proteins, denuding the vascular wall

0720-048X/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2003.09.010

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of endothelial cells while precipitating their protoplasm and fracturing the vascular wall to the level of the internal elastic lamina [8]. First-line surgical resection is not indicated owing to a large amount of blood loss, incomplete resection with risk of recurrence and usually poor cosmetic results [7,10]. We report our experience in treating symptomatic peripheral venous malformations.

2. Patients and methods Between January 1997 and July 2002, 41 sclerotherapy sessions were performed in 21 patients (15 females aged four to 40 years, mean 19.7 years, and six males aged 32–46 years, mean 37.5 years) with extratruncular limited (n=14) or infiltrating (n=7) predominantly venous defects (venous malformations) according to the Hamburg modified classification [2]. Fourteen patients with upper (n=6) and lower (n=8) extremity lesions were treated for pain, five for facial or neck lesions and two for large chest wall malformations causing esthetic asymmetry (Fig. 1). One of the two patients with a chest wall malformation had had an episode of acute uncontrolled bleeding which necessitated urgent intervention for bleeding control. Six patients had undergone at least one attempt in the past to remove the lesion surgically. Five of these six had an upper extremity and one a lower extremity lesion. These patients were looking for a different treatment modality, when their symptoms recurred a few months after excisional surgery (Fig. 2). Nine of the 21 patients had phleboliths on the plain X-ray film. All patient had had MRI before sclerotherapy to investigate the depth of the malformation and tissue involvement. Regarding treatment, all the patients with an extremity lesion were treated first with a tailored compression garment, but symptoms continued despite this treatment. Thirteen of the 21 patients had one sclerotherapy (seven lower extremities, four facial and two upper extremities). Three patients had two sessions (two upper extremities and one neck lesion). Three had three sclerotherapy sessions (one upper extremity, one lower extremity and one chest malformation). One patient with a hand lesion had five sclerotherapy sessions and one patient with a chest wall lesion had eight sessions as a continuing treatment. All procedures were performed under general anesthesia in the angiography suite. Forty procedures were performed under fluoroscopic guidance and one with MR guidance as fluoroscopy gave incomplete visualization of the malformation. A venous pressure tourniquet was applied if anatomically possible. After a sterile field was gained, direct puncture was performed via normal skin with a 21-g IV cannula. Once venous blood returned, contrast material was injected to opacify the malformation and to determine the amount of alcohol to be injected (Fig. 1c). Alcohol 96% was the sole sclerosant agent used and amounts of 2–55cc were injected.

Follow-up was performed with clinic visits and telephone interviews. Follow-up imaging studies were performed only when symptoms recurred, to evaluate for further sclerotherapy.

3. Results Forty sclerotherapy sessions were technically successful, meaning the lesion could be punctured and ethanol delivered into the malformation. A summary of the treatment results is shown in Table 1. Three of the eight patients with lower extremity lesions had complete resolution of their pain after one sclerotherapy for a minimum of 1 year and a maximum of 4 years follow-up, one of them with an infiltrating thigh lesion and two with limited heel lesions. Three other patients with infiltrating lesions did not have symptomatic improvement and preferred not to repeat the sclerotherapy. One patient with an infiltrating malformation in the popliteal region had only partial resolution of pain within 2 years of follow-up (Table 1). The last patient had a diffuse foot lesion after four incomplete treatments (one at another institution and two at our center). This patient continues to suffer from disabling foot pain, despite significant reduction in the size of the lesion according to MRI. Regarding the upper extremity lesions, four patients became asymptomatic up to 4 years after treatment. Three of them have limited malformations and one an infiltrating lesion. The other two patients with infiltrating hand lesions have had temporary relief of their symptoms, and returned to treatment when symptoms recurred (one had three sessions and the other had five). All five patients with limited facial and neck lesions had esthetic improvement regarding asymmetry. The two patients with infiltrating chest-wall lesions are under observation during their expected long-term treatment. Both subjective and objective esthetic improvement occurred in one patient who has had 8 treatments up till now. The other patient had successful sclerotherapy to control an acute bleeding event. She has not yet shown any cosmetic improvement. We had two major and three minor complications. In one patient acute pulmonary hypertension appeared with cardiovascular collapse probably due to the large amount of ethanol injected (1 cc/kg), which necessitated resuscitation and 24 h stay in the intensive care unit. This patient was discharged home three days after the procedure and has had four treatments since then without complications. One patient had a pulmonary embolus two days after sclerotherapy for a malformation in the right calf. A hypercoagulability state was diagnosed, and recovery was complete with no sequelae. Two patients had skin ulceration due to skin ischemia with full recovery after 4–6 months. One patient had skin blistering, which resolved spontaneously.

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Fig. 1. Giant chest wall venous malformation. (a) A photograph of a 7-year-old girl with disfiguring giant venous malformation of the right chest and arm. (b) Right upper extremity venography of a different patient with same lesion. There is no direct venous connection to the malformation. Note extrinsic venous compression. (c) Direct puncture with partially opacified malformation. Also note multiple phleboliths (arrows). Table 1 Location, lesion typea and outcome after treatment in 21 patients (15 females, 6 males) with symptomatic venous malformations Limited Infiltrating Total a

UEb 3 3 6

LEc 2 6 8

Face and neck 5 – 5

Chest wall – 2 2

Based on Hamburg modified classification (1993). All are extratruncular lesions. Upper extremity. c Lower Extremity. b

Complete 10 2 12

Outcome partial – 5 5

Failed – 4 4

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Fig. 2. Recurrence of pain and malformation in the arm after two surgical procedures in a 15-year-old girl. (a) Large annoying scar. (b) Axial T2 MRI 2 years post last surgery shows diffuse venous malformation (arrows). This was a recurrence.

4. Discussion Diagnosis of venous malformations can usually be made based on the clinical history and physical examination. Imaging should be performed in uncertain diagnostic situations and before invasive treatment is considered [6,7]. Plain X-rays showing phleboliths (Fig. 1c) in a lesion are pathognomonic for a venous malformation, but unfortunately this

finding is seen only in a minority of these patients. US (gray-scale and Doppler) and MRI are useful for diagnosis, with the latter being superior due to its excellent ability to show the lesion and the surrounding tissues [4–6] and is used prior to interventional treatment [5,6]. Arteriography shows small venous lakes at the late phase of the examination and is not needed as a diagnostic tool, but combined with embolization for high-flow malformations and to rule out an arterial component in combined low-flow malformations [7]. Venography, as well, is not needed for diagnosis. It does not demonstrate the malformation but can show extrinsic compression of the mass in large lesions (Fig. 1b). The best treatment results are achieved in centers with a dedicated team of specialists, who review all aspects of the malformation regarding treatment options, complications and long-term follow-up and rehabilitation. This team should include interventional radiologists, vascular, orthopedic, pediatric, plastic surgeons, as well as pediatric, anesthesiologic, dermatologic, rehabilitation specialists, and social workers [5,7,10]. Other specialists can cooperate on a case-to-case basis. Asymptomatic patients should be observed only. A tailored compression garment, if anatomically possible is the first line of treatment for symptomatic lesions. Percutaneous sclerotherapy for venous malformations is the treatment of choice for symptomatic lesions that do not respond to a tailored compression garment or for lesions, in which compression cannot be applied anatomically [4,5,7,10]. The treatment aim is not cure but palliation. Achieving long-term palliation is satisfactory for both patient and physician, while maintaining a low rate of morbidity and complications. Conventional surgical excision is indicated only for very localized, but symptomatic, lesions [10]; these were not seen in our series. Complete extirpation of more complex malformations is impossible [10]. Six of our patients had undergone at least one attempt at surgical removal (and three had three attempts each) with recurrence within a few months and an annoying scar (Fig. 2). Combined surgical excision and sclerotherapy is another option, when sclerosed lesions become smaller and easier to excise completely. But if after sclerotherapy the lesion is asymptomatic usually no further treatment is warranted. Reported successful results are 74–91% [4,5,7,10]. In our small series we achieved partial or complete symptomatic relief in 16 of 21 patients (76.2%). The better results were obtained with the localized type where in most of them palliation was achieved after one treatment only. Patients with diffuse lesions had to have repeat sessions with temporary relief of symptoms. We performed clinical follow-up to evaluate whether the sclerotherapy caused improvement or disappearance of the symptoms, which is our treatment goal. We used imaging studies only when symptoms recurred and more sclerotherapy attempts were considered. The major disadvantage of this treatment is that severe complications can occur [12]. Five of our patients suffered

U. Rimon et al. / European Journal of Radiology 52 (2004) 283–287

from complications, which is within the reported range of 7.5–26.7% [8–12]. The most common complication is skin ischemia causing blistering and ulcers due to ethanol leakage to the skin. Skin blisters are self-limited, but skin ulcers can take a long time (months) to heal. To avoid leakage from the needle hole to the skin, it is suggested to embolize the needle tract with Avitene (Alcon Laboratories, Ft. Worth, TX) or gel-foam [12]. If the malformation involves the skin itself the patient and family should have it clearly explained to them that such a complication might occur. We had a very rare but documented complication of acute pulmonary hypertension due to direct ethanol induced vasospasm of the pulmonary microvasculature, which can lead to right heart failure and cardio-pulmonary collapse [11,12], as was the case in our patient. To avoid such a catastrophic situation, it is suggested to inject the ethanol slowly, over a period of several minutes and not exceeding 1 cc/kg of body weight while monitoring the pulmonary artery pressure [8,12]. Other complications of ethanol sclerotherapy are motor or sensory nerve injury (usually reversible), consumptive coagulopathy (this phenomenon can happen with large venous malformations without any treatment), pulmonary embolism, deep vein thrombosis, and hemoglobinuria, which can cause reversible acute renal failure [7,8,10,11]. In conclusion, ethanol sclerotherapy for venous malformations can achieve palliation in most symptomatic patients. Severe complications can occur but are rare. Self-limited complications are more often seen. A specialists’ team for diagnosis, evaluation and treatment of a vascular malformation center is the best way to treat these confusing, disfiguring and complicated cases.

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