Keywords
vascular malformations - head and neck - sclerotherapy
Introduction
Mulliken and Glowacki proposed the classification of vascular anomalies in 1982. Based
on clinical course and histologic characteristics, this classification divides vascular
anomalies into tumors and malformations.[1] Vascular malformations are subdivided depending on (1) the predominant type of vessels
involved (capillary, venous, arteriovenous, lymphatic, or combined) and (2) the flow
characteristics (low-flow, high-flow, and combined lesions).[2]
[3]
Venous and lymphatic malformations are low-flow vascular malformations. Majority of
them occur in the head and neck region and can infiltrate normal structures. They
can give rise to functional disabilities, including obstruction to airway and swallowing
difficulties. Also, they can cause visual or auditory disturbance and delayed speech
development. In addition, bleeding, pain, infection, skeletal deformity, and cosmetic
disfigurement may occur.
Clinical diagnosis is made by taking history details and physical examination. Radiological
investigations aim for confirming the diagnosis and define the anatomy of lesion in
relation to the surrounding structures, which are important for planning of sclerotherapy.
Ultrasonography (USG) with Doppler scan and intravenous contrast enhanced magnetic
resonance imaging (MRI) are commonly performed.
Unlike most hemangiomas that will involute before puberty, venous malformations will
grow with age, infiltrating normal structures. Most lymphatic malformations persist
and can be acutely enlarged because of bleeding and inflammation. Thus, active treatment
of venous and lymphatic malformations is indicated especially in head and neck region.
Surgery can cause damage to normal surrounding structures, resulting in significant
disfigurement and loss of function. Complete excision is often impossible for infiltrative
lesions. Image-guided sclerotherapy has gained popularity recently and become the
first-line treatment for low-flow vascular malformations in head and neck region.
The authors review the management protocol for this condition and evaluate the clinical
outcomes.[4]
[5]
[6]
[7]
Material and Methods
A retrospective review of all children below age 18 years with vascular malformations
undergoing image-guided sclerotherapy from 2010 to 2013 was done. Patients with low-flow
vascular malformations involving the head and neck region were included. Patient demographics,
presenting symptoms, clinical and radiological findings were collected. All patients
were assessed by pediatric surgeons and interventional radiologists in the multidisciplinary
vascular anomalies clinic. USG and intravenous contrast enhanced MRI were performed
preoperatively. Platelet count, clotting profile, and serum D-dimer level was checked
before sclerotherapy.
For large vascular malformations with potential airway involvement, the authors would
plan for staged sclerotherapy to control the postsclerotherapy edema and prevent sclerosant
overdose. Sclerotherapy was performed under general anesthesia. On induction, intravenous
mannitol 0.5 g/kg was infused to expand the intravascular volume, preventing thromboembolic
complications. A Foley catheter was inserted to monitor urine output and detect hematuria.
Endotracheal intubation was performed in all patients for airway protection. Intravenous
dexamethasone 0.2mg/kg together with esomeprazole was given intraoperatively to control
postsclerotherapy edema.
Sclerotherapy was performed with sonographic and fluoroscopic guidance. A 24-gauge
angiocatheter was inserted to the lesion under USG guidance. Presclerotherapy fluoroscopy
was performed by injecting 50% diluted Omnipaque300 (GE HealthCare Inc., Wauwatosa,
Wisconsin, United States) in normal saline to the lesion to define the anatomy of
vascular malformation. Also, it could minimize extravasation and spillage to sclerosant
during sclerotherapy.
Different types of sclerosants were used in the authors' series. STS foam or ethanolamine
was used as first-line sclerosant for venous malformations. STS foam was produced
by mixing 2 mL 3% STS, 0.5 mL Lipiodol (Guerbet Group, Villepinte, France) and 2.5
mL air. Doxycycline was the primary sclerosant for lymphatic malformations. For resistant
lesions, 98% ethanol was added as adjuvant sclerosant in selected cases of repeated
sclerotherapies. Sclerosant was deployed to the lesion under fluoroscopic guidance.
In venous malformation of lip, tongue, and palate, vascular (Cooley-Derra or Debakey)
clamp was applied to control the venous outflow and compartmentalize the injected
sclerosant.
If the vascular malformations had potential airway involvement, the patients would
be admitted to intensive care unit after sclerotherapy. They were deeply sedated with
airway protected by endotracheal intubation and mechanical ventilation. Intravenous
dexamethasone was continued 8 hourly for few days in decreasing dose according to
the extent of postsclerotherapy edema. Patients were closely observed and extubated
when the edema of lesion subsided. The patients would be transferred to general ward
after uneventful extubation. If they tolerated diet well and showed no postoperative
complications, they would be discharged home in 1 or 2 days. After discharge, they
were followed up in the multidisciplinary vascular anomalies clinic at 2 weeks, 3,
6, and 12 months. More frequent follow-up was offered if the patients had persistent
or recurrent lesion needing repeated sclerotherapies. USG was performed 6 months after
sclerotherapy to assess the size of malformations. MRI was reserved for those patients
with persistent lesions planned for repeated sclerotherapies.
The primary outcome measure was the size of vascular malformations after treatment.
Major size reduction was defined as more than 50% decrease in size of lesions. Secondary
outcome measures included the perioperative complications, status of obstruction symptoms,
and cosmetic results.
Obstruction was defined as swallowing symptoms including slow feeding, drooling of
saliva and choking; or upper airway symptoms such as stridor, noisy breathing, snoring,
and obstructive sleep apnoea.
Results
Overall 40 patients (21 girls and 19 boys) had low-flow vascular malformations with
sclerotherapy performed in the study period. Among them, 27 patients had vascular
malformations at trunk or limbs. Thirteen children (8 males and 5 females) had involvement
in head and neck region and they were recruited in this study. There were five venous
and eight lymphatic malformations. The sites of vascular malformations included eight
cervical (62%), one lingual (8%), one parotid (8%), one lip (8%), one facial (8%),
and one palatal (8%) lesions. The mean age at treatment was 25 months (range, 2 mo–11
y).
Overall 10 patients (77%) presented with a mass or swelling, 2 patients (15%) with
pain after bleeding, 1 patient (8%) with bluish discoloration of the overlying skin,
6 patients (46%) had obstructive upper airway symptoms, and 1 patient (8%) had feeding
difficulty.
All patients underwent sclerotherapy with a total of 25 sessions of sclerotherapy
done. Eight patients underwent one sclerotherapy session, two patients underwent two
sclerotherapy sessions. One patient underwent three sessions. He suffered from a 5
cm diameter left parotid venous malformation with stridor and sleep apnoea at the
age of 3 years. Sclerotherapy sessions were performed at 5 and 9 months interval.
One patient had four treatment sessions. She was born with congenital giant lymphatic
malformation involving left side of face extending into the pharyngeal spaces and
submandibular area across the midline. She had upper airway obstruction with tracheostomy
performed. Multistaged sclerotherapy was performed. One patient was born with congenital
giant lymphatic malformation involving right neck, extending through the right axilla,
chest, and lower abdomen. He underwent partial excision of the lesion, followed by
five percutaneous OK-432 sclerotherapy sessions in other centers. Doxycycline sclerotherapy
was performed at 6 years of age.
The median duration of follow-up was 1.5 years (range, 2 mo–3 y). Clinical significant
size reductions of more than 50% volume were achieved in all patients. From postoperative
imaging, complete resolution occurred in two patients (15%). All patients with obstructive
symptoms showed improvement.
There were no airway complications. One patient had mild hematuria after STS foam
sclerotherapy for venous malformation. The condition subsided after intravenous fluid
supplement. One patient with lymphatic malformation had postsclerotherapy bleeding
and one had recurrent swelling. USG-guided aspiration of lymphatic cysts was done.
Discussion
Vascular anomalies are broadly classified into vascular tumors and vascular malformations.
Infantile hemangioma is the most common vascular tumor characterized by an initial
proliferative phase followed by involution after 1 year of age. It is responsive to
propranolol and interventional treatment is often not required.[8] In contrast, vascular malformations do not involute and will persist. Bleeding or
infection of cysts could occur in lymphatic malformations, causing acute swelling
and pain. Enhanced infiltrative growth of venous malformations occur under hormonal
influence especially in puberty, steroid therapy, or pregnancy.[9] They can cause worsening symptoms with detrimental functional complications. Intervention
should be considered before adolescence.
Vascular malformations can be further differentiated according to the flow characteristic
and the type of vessel involved. The classification according to the hemodynamic properties
is of important clinical significance. High-flow vascular malformations, such as arteriovenous
fistulas and arteriovenous malformations, are treated by transarterial embolization,
whereas low-flow malformations can be treated with sclerotherapy.[10]
In this study, the authors focus on low-flow vascular malformations causing mechanical
symptoms to head and neck region. Venous malformations and lymphatic malformations
are the most common conditions. Venous malformations account for approximately 60%
of low-flow vascular malformations. A bluish discoloration of the overlying skin or
mucosa may occur. Doppler ultrasound will demonstrate a heterogeneous spongy-like
lesion with tortuous vessels. Other sonographic characteristics are expansion during
valsalva maneuvers, phleboliths, and absence of dilated feeding arteries and draining
veins.[1]
[4]
[11]
[12]
[13]
[14] Lymphatic malformations can be subclassified into macrocystic and microcystic, which
is of therapeutic importance. Macrocystic lymphatic malformations can be treated effectively
by sclerotherapy.[15] In microcystic lesions, treatment response to sclerotherapy is suboptimal and excision
is often required. More than two-third of lymphatic malformations are found in the
soft tissue of the neck and are often associated with inflammations and bleeding.[11] USG appearance of macrocystic lymphatic malformations are homogenous and hypoechoic.
After hemorrhage and infection, cysts with mixed echogenicity are revealed under USG.
The infiltrative and extensive nature of vascular malformations in the head and neck
region often makes resection impossible without sacrificing the vital structures.
Sclerotherapy, a minimal invasive treatment modality that involves injection of chemical
agent to cause inflammation of vascular endothelium, has become the first-line treatment.[4]
[5]
[16]
Vascular malformations in head and neck region are exceptionally challenging clinical
conditions that require multidisciplinary management. Commonly used sclerosants induce
endothelium inflammation and edema of surrounding tissue. In head and neck region
they can cause airway obstruction postoperatively. Extravasation of sclerosants can
cause skin or muscle necrosis and neuropathy. Spillage of excessive sclerosants to
cerebral and pulmonary circulations may result in detrimental complications such as
stroke and pulmonary embolism.[17] Thus, it is essential to have extra care when performing sclerotherapy for vascular
malformations in head and neck region. In the authors' series all patients were assessed
in the multidisciplinary vascular anomalies clinic preoperatively, with participation
of pediatric surgeons, interventional radiologists, anesthesiologists, pediatric intensivists,
and nurse specialists. USG and intravenous contrast enhanced MRI were performed. Before
sclerotherapy, thrombocytopenia and deranged clotting profile were excluded. Interestingly,
localized intravascular coagulopathy is common in venous malformations with increased
serum D-dimer level.[18] Depending on the volume and sites of vascular malformations, excessive sclerosant
injection may cause uncontrolled edema affecting airway or overdose toxicity. Five
patients in the authors' series had staged procedures. Repeated sclerotherapy is considered
not as a failure but rather a necessary strategy in management of large vascular malformations.
Several maneuvers are performed to control the postsclerotherapy edema. Intravenous
dexamethasone was given intraoperatively and continued for a few days after the procedure.
In every patient, sclerotherapy was done under general anesthesia with endotracheal
intubation. The endotracheal tube was kept after procedure and patient was transferred
to intensive care unit for mechanical ventilation if there was concern for postsclerotherapy
airway edema.
Systemic spillage and extravasation of sclerosants have been reported. They can lead
to skin necrosis, neuropathy, muscle atrophy and contracture, deep vein thrombosis,
pulmonary embolism, disseminated intravascular coagulation, and cardiopulmonary collapse.[19]
[20] Siniluoto et al reported one major complication of blindness following injection
into an ophthalmic vein.[21] Berenguer et al reported two transient facial weakness and one permanent unilateral
vocal cord paralysis.[10] In the study by Lee, eight patients developed deep venous thromboses and nine patients
developed peripheral nerve damage, in which two were permanent.[5] Birmingham study reported superficial skin necrosis that resolved conservatively.[22] To minimize these complications, all the authors' patients had fluoroscopy performed
before sclerotherapy by injecting water-soluble contrast to the targeted vascular
malformations. Intravenous mannitol was given to expand the intravascular volume to
prevent thromboembolism. Hemoglobinuria may occur and all their patients had Foley
catheter inserted during sclerotherapy. One patient in the authors' series developed
transient hematuria postoperatively. It was treated conservatively by rehydration.
In three patients with venous malformations at lip, tongue and palate, the authors
used vascular clamps were used to occlude the venous outflow and prevent sclerosant
spillage to ophthalmic vein and cavernous sinus.
Although only two patients in the authors' series had complete radiological resolution
of lesion, clinical significant volume reduction, and symptoms improvement occurred
in all patients. The principle of sclerotherapy treatment is to control the lesion
by size reduction. Eradication of vascular malformations is not possible in all modalities
of treatment including surgical resection.
No airway and thromboembolic complications were observed in this series. The authors'
treatment protocol aims to prevent airway and thromboembolic complications in the
management of vascular malformations of the head and neck in children. Comparing with
other series in the literature, their result showed an excellent response rate and
the complication rate is low, all being minor and transient. In the series from Tan
et al[23] 70% achieved a positive clinical response and there were no major complications.
There was a 75% positive clinical response rate observed by Berenguer et al. However,
there were 42 complications occurred and 14 of those were major.[10] Siniluoto et al reported a success rate of 82% and there was one major complication
of blindness.[21] Lee et al reported a 99% success rate and a complication rate of 51%.[5] In the Birmingham study, 84% of patients showed improvement, but 18% had complication,
with one being major.[22]
One limitation in this retrospective study is the lack of standardization of sclerosants
used. The choice of sclerosants was dependent on the supply and preference of interventional
radiologists. Also, the outcomes measurement may be biased as the observers may have
involved in the treatment protocol. A prospective study with independent observers
blinded to the treatment protocol is necessary to evaluate the long-term results in
future.
Conclusion
Sclerotherapy is a safe and effective treatment for head and neck vascular malformations
in children. Routine perioperative protocol is essential to reduce airway and thromboembolic
complications. Size reduction and functional improvement occurred in all patients
undergoing sclerotherapy.
