Intra-arterial bleomycin for treatment of labial arteriovenous malformations in children

Abstract

Labial arteriovenous malformations (AVMs) pose a great challenge due to their location, angiogenic potential, and recurrence rate. Emerging treatments include sclerotherapy, such as intra-arterial bleomycin, which has been proven safe and effective in adults; however, there is limited literature available for children. Here, we present two successful cases of intra-arterial bleomycin use for treating lip AVMs in children, resulting in complete cure and no recurrence after a two-year follow-up period. Our findings support the limited but growing body of literature that presents intra-arterial bleomycin as a safe and viable option for pediatric facial AVMs.

Background

Arteriovenous malformations (AVMs) are high-flow vascular malformations that account for about 5% of all congenital vascular malformations. Treatment of extracranial AVMs of the head and neck in children is especially difficult due to their location, angiogenic potential, and recurrence rate.^1,2 AVMs not only pose aesthetic issues but also can lead to serious outcomes if left untreated, such as ischemia, hemorrhage, tissue necrosis, or high-output heart failure. ³

Therapeutic strategies include embolization and/or sclerotherapy via endovascular or percutaneous techniques to obliterate the nidus, and/or surgical resection.^4,5 Current treatments are successful in dealing with the primary lesion, but recurrence and complication rates are high, including tissue necrosis and predisposing to stroke and cranial nerve palsies.^1,4,5

Intra-arterial bleomycin is a technique that has demonstrated high efficacy and safety for treating AVMs with low rates of recurrence in adults.^3,6 However, its role in the pediatric population is limited to a few reports, especially in infants and toddlers. Here, we describe the successful use of intra-arterial bleomycin, a sclerosing agent, to treat labial AVMs in two children.

Case presentation

Case A

A 2-year-old girl with a history of RASA-1 mutation and capillary malformation AVM syndrome presented with recurrent lip bleeding. Conventional angiography revealed a Yakes type II AVM with dominant supply from the inferior right labial artery (Figure 1). The right common femoral artery was accessed using a 4 Fr micropuncture catheter set under ultrasound and fluoroscopy guidance. Under roadmap and fluoroscopic guidance, the microcatheter was advanced over the microwire to select the right inferior labial artery. Once the microcatheter was advanced as distally as possible into the left lip AVM and wedged, 1.75 units of foamed bleomycin were slowly injected. The patient underwent a single session of intra-arterial bleomycin sclerotherapy, receiving 1.75 units of a bleomycin–albumin mixture, created by adding 5 units/1 mL of bleomycin and 4 mL 25% albumin, for a 1 : 1 solution. The injection, which was instilled slowly over 5 min, was performed with compression of the draining veins (performed by the first assist) to prevent the washout of the medication during and after the injection, as well as after catheter removal. No angiographic control run was performed to avoid the washout of the medicine within the AVM. The procedure was uncomplicated. Over the following weeks, bleeding decreased, and additional sclerotherapy was deferred. At two-year follow-up, the labial AVM had completely resolved on angiography (Figure 1), and there were no episodes of bleeding. No additional treatment sessions were performed.

Figure 1.

Lateral (a) and posteroanterior (b) angiogram of the proximal right external carotid artery shows a diffuse blush of the left inferior lip with early draining veins (black arrows). Posteroanterior (c) follow-up right ECA angiogram 2.5 years later after single embolization with bleomycin, shows complete resolution of the left inferior labial AVM.

ECA: external carotid artery; AVM: arteriovenous malformation.

Case B

A 12-year-old girl with a history of asthma and eczema presented to the neurointerventional radiology (NIR) service with a three-year history of progressive swelling and erythema of the right superior lip. Plastic surgery referred the patient for embolization before surgery. Initial magnetic resonance imaging showed classical findings of AVM in the lip (Figure 2).

Figure 2.

Axial T2 MRI (a) and post-gadolinium axial T1 MRI (b) depicting classic imaging findings of right superior lip AVM (white arrows).

MRI: magnetic resonance imaging; AVM: arteriovenous malformation.

At initial presentation, the lesion was non-tender, blue in color, and stable in size. The patient denied functional symptoms but expressed concern about her appearance as mask mandates were being lifted near the end of the COVID-19 pandemic. Angiography revealed a Yakes type II AVM with dominant supply from the right superior labial artery (Figure 3). The right common femoral artery was accessed using a 5 Fr micropuncture catheter set under ultrasound and fluoroscopy guidance for each session. The patient underwent five sessions of intra-arterial bleomycin sclerotherapy over 12 months (total dose: 21 units). Bleomycin (5 units/mL) was mixed in a 1 : 1 ratio with 25% albumin and administered via selective catheterization of the pedicle of the feeding parent artery and instilled over 15 min. Venous compression was applied to the draining veins during and after injection. No angiographic control run was performed. Every four weeks, the patient underwent follow-up ultrasonography, performed by the senior author in the NIR clinic, to determine flow within the AVM, and intra-arterial bleomycin was administered every 5–6 weeks. The treatment course was well tolerated. Minor swelling and groin bruising resolved spontaneously. A follow-up angiogram after 1.5 years showed complete resolution of the lesion (Figure 3). The patient underwent surgical contouring by plastic surgery and continues to demonstrate excellent cosmetic outcomes at follow-up. No additional treatment sessions were performed.

Figure 3.

Lateral (a) and posteroanterior (b) angiogram of the proximal right external carotid artery shows a diffuse blush of the right superior lip, with extension of the blush past midline, with early draining veins (white arrows). Lateral right ECA angiogram (c) after 8 months shows complete resolution of right superior lip AVM.

ECA: external carotid artery; AVM: arteriovenous malformation.

Discussion

AVMs of the lips are challenging to treat, with limitations on total resection to maintain cosmesis. The standard of care for lip AVMs is embolization with liquid embolic agents followed by resection, but approximately a quarter of patients experience recurrence, with recurrent lesions being more challenging to treat. ¹ In addition, embolization often leads to complications, including tissue necrosis, and poses other risk factors such as stroke and cranial nerve palsies. ⁴ This has led to the search for additional therapies with better efficiency and lower risk. This includes the use of sclerotherapy agents via endovascular and percutaneous routes. ⁷ We present two successful cases of the use of intra-arterial bleomycin to treat labial AVMs in symptomatic children, including one case in a toddler.

Only one study to date, to our knowledge, has evaluated the efficacy and safety of intra-arterial bleomycin to treat head and neck Yakes stage I and II extracranial AVMs. ³ A case series by Li and colleagues demonstrated that intra-arterial bleomycin offered partial improvement to total cure in patients aged 1.5 to 20 years old. ⁸ Of those patients, nine were children aged 3 to 18 years old. Of those, only one case had a complete response to intra-arterial bleomycin and was stable for almost 7.5 years. Six children initially showed a partial response, with one exhibiting slight progression after a 20-month follow-up. In our cohort, a complete response was observed, and lesions did not recur for up to two years after therapy.

Minor complications have been reported in patients undergoing intra-arterial bleomycin injection. Minor treatment-related complications included hyperpigmentation and cellulitis. ³ Outside of groin bruising, similarly, none of our patients suffered short- or long-term complications.

As opposed to direct percutaneous (intralesional) injection, intra-arterial, endovascular treatment involves selective catheterization of the parent artery just proximal to the nidus, as well as a more controlled bleomycin instillation rate, ultimately benefiting patients with complex angioarchitecture or those who present with deeper or anatomically challenging vascular lesions.

In conclusion, intra-arterial bleomycin can be a safe and effective treatment option for labial AVMs in children, resulting in symptom improvement, excellent cosmetic outcomes, and a decrease in recurrence rates. Further studies with larger cohorts are needed to validate and expand its routine use in the clinical setting.