Keywords venous malformation - embolization -
n -butyl cyanoacrylate
Introduction
Venous malformations (VMs), with a prevalence of 1 to 4%, represent the most common
type of congenital vascular anomaly.[1 ]
[2 ]
[3 ] These are slow-flow lesions consisting of dysplastic venous channels or sacs that
lack normal connections to the systemic venous network. VMs are typically soft and
compressible, often becoming engorged during exercise, when in a dependent position,
or during Valsalva's maneuver. Sluggish or stagnant flow promotes intralesional thrombus.
Pain is overwhelmingly the most common presenting symptom, though patients may also
have swelling, fullness, bleeding, and limited range of motion when the lesion extends
across a joint.
While conservative measures such as compression garments or nonsteroidal anti-inflammatory
agents such as aspirin (which reduces thrombus formation) can be helpful, invasive
therapy is required for patients with severe symptoms. For decades, surgical excision
was the primary treatment, despite the challenges of poorly defined lesion margins
and often high-volume intraoperative blood loss. Sclerotherapy has emerged as a minimally
invasive alternative,[1 ]
[4 ]
[5 ]
[6 ]
[7 ]
[8 ] but repeated treatments are frequently necessary due to recurrent or persistent
symptoms, increasing costs, anesthetic risks, and radiation exposure.
A new single-stage, combined surgical and interventional radiology treatment approach
for head and neck VMs was described in 2013 by investigators at Seattle Children's
Hospital.[9 ] Patients underwent single-stage preoperative n -butyl cyanoacrylate (n -BCA) glue embolization of their VMs followed immediately by surgical excision. Patients
enjoyed excellent symptom relief, and the challenges of surgical excision were reduced.
Early experience redemonstrated efficacy when applied to truncal and extremity VMs.[10 ] While embolization of cavitary VMs resulted in expanded, solid masses and gratifying
procedures for both the interventionalist and surgeon, the technique performed well
across a variety of venous malformations including infiltrative and dysplastic morphologies.
Technique
Cyanoacrylates
The basic monomer structure of a cyanoacrylate features two carbon groups with a relatively
positive methylene group (=CH2 ) bound to a carbonyl group. Interaction of an anion, such as the various compounds
found in blood, with the positive methylene group forms a stable but reactive carbanion.
The induced negativity in the carbonyl group attacks and strongly binds to the methylene
group of the next cyanoacrylate monomer, and the polymerization cascade continues.
Long, strong polymer chains are formed. Various hydrocarbons attached to the carbonyl
group determine the name and properties of the cyanoacrylate, ranging from commercially
available ethyl-2-cyanoacrylate (Krazy Glue, Elmer's Products) to the medical adhesives
n -BCA and 2-hexyl cyanoacrylate.
Histoacryl (B. Braun) and Trufill (Codman) are both n- BCAs widely available in the Unites States with approval by the Food and Drug Administration
(FDA) for wound closure and arteriovenous malformation embolization, respectively.
Unadulterated n -BCA is a low-viscosity, clear, radiolucent liquid. Although a variety of powdered
metals and iodized solutions may be added to n -BCA for radiopacity and manipulation of the polymerization rate, the authors exclusively
use ethiodized oil for these purposes. Lipiodol (Guerbet USA) provides radiopacity
([Fig. 1 ]) and a near linear relationship of dilution to polymerization rate for commonly
used formulations.[11 ]
[12 ] Though glue-to-oil ratios varying from 1:1 to 1:4 are commonly used for arteriovenous
malformations, the slower flow of VMs affords greater dilution for longer polymerization
times and more thorough lesion filling. The authors plan a default mixture of 1:4
for typical untreated VMs ([Fig. 2 ]). More dilute formulations (1:5–1:6) promote penetration into fine channels of lesions
previously treated with sclerotherapy ([Fig. 3 ]). Rarely, a more concentrated mixture is made if the accessed channel of the malformation
exhibits a short or broad connection to a normal conducting vein ([Fig. 4 ]).
Fig. 1 Fluoroscopic image of unopened radiolucent n-butyl cyanoacrylate (n -BCA) glue (left) (Trufill; Codman) and radiopaque ethiodized oil (right) (Lipiodol;
Guerbet USA).
Fig. 2 A 17-year old boy with a painful upper extremity venous malformation. Unsubtracted
(a) and subtracted angiographic (b) images demonstrate a typical lesional appearance with drainage to basilic and brachial
veins.
Fig. 3 A 5-year old girl with painful popliteal fossa malformation post multiple previous
sclerotherapy treatments. Digital subtraction angiogram image demonstrates fine, irregular
channels typical of prior sclerotherapy. Embolization was performed with 1:6 dilution
n -BCA:ethiodol.
Fig. 4 A 16-year old girl with painful popliteal fossa venous malformation. Initial unsubtracted
(a ) and subtracted (b ) angiogram images demonstrate a broad connection to the popliteal vein. The outflow
segment was carefully embolized with 1:2 dilution n -BCA:ethiodol (c ) allowing subsequent embolization without egress into the popliteal vein (d ). Three-dimensional surface rendering images from a completion cone beam CT (e ) were created for surgical guidance.
Equipment Preparation
Cyanoacrylate polymerization begins whether contact with an ionic solution was intentional
or unintentional. Preservation of the “ion-free” environment should receive the same
meticulous attention as preservation of the sterile field. A separate small table
serves this purpose. Interventionalists or technologists handling items from this
area must replace their gloves if they have previously touched items from the main
table or procedural field. With sufficient personnel available, a dedicated “ion-free”
assistant adds efficiency while minimizing costly and frustrating embolic contamination.
The authors’ standard glue table organization is depicted ([Fig. 5 ]). Nonheparinized 5% dextrose in water (D5W) serves as the nonionic flush solution.
Several hundred milliliters are maintained in a large basin and used to replenish
3-mL D5W flush syringes and a larger (20 mL) D5W “overwash” syringe. Ethiodized oil,
n -BCA, and potentially contaminated glue “leftovers” are to be maintained in three
labeled shot glasses. A small volume of D5W may be used to rinse the shot glasses
of any potential contaminants prior to glue preparation. Ethiodized oil and n -NBCA are typically combined in the predetermined ratio, although some interventionalists
will wait and use the first venogram for glue ratio determination in the case of previously
treated malformations. Inadequate mixing results in layering of n -BCA and ethiodol. Failure to recognize this phenomenon can lead to unexpectedly concentrated
or dilute formulations and potential complications. Layering is obvious with blue
tinted Histoacryl ([Fig. 6 ]) but obscure when using colorless Trufill. The selected ratios of n -BCA and ethiodol are combined within a shot glass. Thorough stirring with an 18-gauge
needle at the time of mixture and immediately before drawing for embolization is recommended
regardless of grossly apparent homogeneity. Given the propensity for degradation of
plastics by ethiodized oil, the glue mixture should be maintained in glass until immediately
before embolization. Polycarbonate syringes are more resistant (but not impervious)
to this effect and are readied to serve in embolic delivery with 18-gauge needles
to draw the glue mixture. Floating polymerized glue “icebergs” are the first sign
of ionic contamination ([Fig. 7 ]).
Fig. 5 Glue table. Nonheparinized 5% dextrose in water (D5W) serves as the nonionic flush
solution, maintained in a large basin and used to replenish 3 mL D5W flush syringes
and a larger (20 mL) D5W “overwash” syringe. Ethiodized oil, n -BCA, and potentially contaminated glue “leftovers” are maintained in three labeled
shot glasses. Polycarbonate 3-mL syringes are used to delivery glue, drawn up after
mixing with an 18-gauge needle.
Fig. 6 Layering of ethiodized oil and glue. Inadequately mixed glue made evident by blue-tinted
n -BCA glue (Histoacryl; B. Braun) layering atop ethiodized oil (Lipiodol; Guerbet USA).
Fig. 7 Contaminated glue mixture. Polymerized glue “icebergs” indicate contamination with
ionic solutions.
A standard procedural table serves the access and angiography aspects of the procedure
and is organized in the usual fashion. Winged (butterfly) 23-gauge needles suffice
for superficial lesion channel access and have attached tubing. The authors use 21-gauge
micropuncture access needles for deeper lesion channels, attaching short Luer-Slip
tubing. Tubing and needles are preloaded with either saline flush or iodinated contrast
media, and then sealed with either tube clamps or 1-mL syringes ([Fig. 8 ]).
Fig. 8 Access needle and syringe. A 1-mL syringe and tubing attached to a 21-gauge access
needle maintains air-free access. The syringe is removed to check for backbleeding
after lesion channel access.
Access and Angiography
Prior cross-sectional imaging is reviewed. Reference imaging on the fluoroscopy monitor
can supplement the lesion shape stored in the mind's eye. Preprocedure ultrasound
mapping is performed to map the lesion as well as adjacent macroscopic neurovascular
structures. Patients are anesthetized and remain sedated through both the embolization
and surgical resection. Tourniquets create nonphysiologic conditions and high intralesional
pressure, resulting in unpredictable behavior during embolizations; they are not routinely
used by the authors.
After sterile preparation and draping, fluoroscopic views are optimized. Saving of
table position and image intensifier configuration allows adjustments for more ergonomic
ultrasound access but rapid return to positions suited for angiography. Deep or difficult
channels are targeted first, anticipating artifactual degradation of the ultrasound
images as the embolization proceeds. Selecting a slightly longer-than-necessary access
path increases needle stability. The access needle is advanced into the target channel
under continuous ultrasound visualization. After sonographic confirmation of lesion
entry, the tubing seal is released. Blood return is indicative of malformation (or
at least vascular) access. Gentle injection of iodinated contrast media confirms position
and grossly highlights both channel capacity and early drainage to conducting veins.
Once lesion entry is confirmed, digital subtraction angiography is acquired and then
the tubing is again sealed. Images are studied for flow patterns including drainage
to normal conducting veins, particularly those leading to the deep venous system.
An image best delineating drainage is displayed for reference during the subsequent
embolization.
Embolization
Image subtraction fluoroscopy “negative roadmap” technique is selected with a paired
unsubtracted dual fluoroscopy image panel ([Fig. 9 ]). The assistant or technologist readies the D5W flush, D5W overwash, and glue syringes.
Glue is once more stirred with the 18-gauge needle before being drawn up into a 3-mL
polycarbonate syringe. Drawing only slightly more than the predicted amount needed
will conserve glue as the case progresses and minimize procedural costs. Needle access
tubing is flushed with a small volume of D5W before connecting the glue syringe. The
assistant or technologist uses the overwash D5W syringe to rinse the proceduralist's
hands and the catheter hub before and during syringe exchanges, taking care not to
make contact and contaminate the syringe or his/her hands. Preparation and communication
are essential. Clumsy syringe exchanges allow back bleeding into the access needle
tubing, obviating the purpose of the D5W flush and potentiating premature polymerization
in the tubing.
Fig. 9 A 18-year-old woman with a disfiguring venous malformation of upper lip. Screen capture
images from the fluoroscopic monitor demonstrate parallel observation of embolic delivery
with negative roadmap (a ) and reference dual fluoroscopy (b ) imaging.
Glue is slowly introduced with fluoroscopic imaging commencing as the glue reaches
the needle hub. The embolization is as much an art as a science from this stage onward,
and a balance must be struck between overzealous (risking extravasation and nontarget
embolization) and apprehensive (resulting in premature polymerization and access loss)
injections. Maintaining momentum with gentle accelerations and deceleration as indicated
is ideal in most circumstances. Constant attention must be paid to known as well as
potential previously undocumented draining veins to avoid deep venous thrombosis or
central embolization. The accessed lesion channel fills first. With sufficient pressure,
glue “bursts” into an adjacent channel of the malformation and the pattern continues,
frequently filling large aspects of a malformation from a single access point.
Extension into a draining vein is managed with a slowing or ceasing of the injection
but continued observation. Extrinsic compression may be attempted for runaway glue,
but vigilant observation should identify nontarget embolization when it is still easily
managed with subtle injection pressure adjustments. A 30- to 45-second pause is usually
sufficient for polymerization in the draining vein while maintaining a partially liquid
state in the malformation. Cautious subsequent increases in the injection pressure
often allow ongoing lesion embolization without further expansion into the draining
vein.
Periodic resetting of the fluoroscopic subtraction enables subtle detection of changes
as the embolization proceeds. A “cap” on embolic within a draining vein after device
reset indicates central expansion ([Fig. 10 ]), and embolization should be slowed or stopped. A black boundary or “India ink”
appearance after device reset suggests a lesion channel expanding under pressure ([Fig. 11 ]), which may be desirable as the proceduralist cautiously attempts to push glue into
adjacent compartments of the lesion. Caution must be exercised as supraphysiologic
pressures created may result in surprising egress into previously unseen outflow channels
([Fig. 12 ]). When maximal embolization is achieved, the needle tubing is again clamped. If
a significant volume of glue remains in the syringe, this may be potentially salvaged
later by directly injecting into the dedicated shot glass for used (potentially contaminated)
glue. The glue syringe and D5W flush syringe are discarded to avoid inadvertent return
to the “ion-free” glue table.
Fig. 10 A 4-year old girl with a painful lower extremity malformation. Negative roadmap imaging
following device reset with subtraction of the initial glue installation and propagation
into a draining vein (a) . A negative roadmap “cap” on the draining vein embolic (b ) indicates central expansion, and embolization should be slowed or stopped.
Fig. 11 An 8-year old boy with a painful lower extremity venous malformation. Negative roadmap
imaging following device reset with subtraction of the initial glue installation.
An “India ink” appearance forms as additional glue causes lesion distension (a ) followed by egress into a separate channel as lesional pressure increased (b ).
Fig. 12 A 13-year old girl with a painful supraclavicular venous malformation. Preembolization
angiogram (a ) demonstrated no central drainage and embolization commenced. Increased intralesional
pressure resulted in egress of glue from the inferior medial aspects of the malformation
into the brachiocephalic vein. Ipsilateral jugular access was successful in snaring
and partially removing the nontarget glue (b ). However, axial images from a completion cone beam CT (c ) demonstrated clinically silent pulmonary embolization of several small fragments.
Attention is then turned to the remaining channels of the malformation that will be
accessed, imaged, and embolized in the same fashion. In the minutes after one region
of treatment is performed, tissue manipulations such as ultrasound scanning should
be performed gently to avoid massaging still-liquid glue unpredictably out of the
embolized channels. Needles should remain in place for a minimum of 10 minutes to
minimize glue extravasation after needle removal. Occasionally, the easily accessible
channels of a malformation will contain thrombus or phlebolith. Though this limits
backbleeding confirmation of lesion entry, access followed by gentle hydrodissection
or thrombus fracture will enable imaging and embolization. Rarely, residual patent
channels will be sonographically obscure but obvious by a photopenic defect in the
fluoroscopic appearance of the lesion. If the region is known to be void of critical
structures, this aspect can be targeted with computed tomography (CT) or fluoroscopic
guidance alone ([Fig. 13 ]). Embolization procedure times vary widely from 30 minutes for previously untreated
focal, cavitary subtypes to 2 hours for infiltrating lesions with complex architecture
or lesions with small isolated channels as a result of prior sclerotherapy.
Fig. 13 A 22-year-old woman with a venous malformation of the knee complicated by pain and
hemarthrosis. Post embolization three-dimensional surface rendering cone beam CT image
(a ) demonstrates a photopenic defect at the inferomedial aspect of the malformation.
This aspect of the malformation was sonographically obscure but known to be present
by STIR sequence images of the preprocedure MR (b ). The residual malformation was targeted fluoroscopically, imaged (c ), and embolized (d ) to complete the procedure.
Completion Imaging
Fluoroscopic imaging after each embolization stage tracks progression until the glue
cast grossly resembles the entirety of the lesion targeted for excision. Although
channel distension commonly results in minor geometric distortion, an excellent spatial
match to previous imaging should be sought. After a complete fluoroscopic appearance
is achieved, the authors acquire a cone beam CT of the region of interest. Multiplanar
reformations compared side by side to fluid sensitive sequences of previous magnetic
resonance studies provide confident confirmation of total embolization. Three-dimensional
surface renderings, particularly for lesions interdigitating between unresectable
anatomy, made available before surgical excision are helpful to the surgical colleagues,
particularly intraoperatively ([Fig. 4 ]). At embolization completion, the patient is transferred under anesthesia to the
operating room.
Conclusion
Venous malformations may be treated with surgical excision or sclerotherapy. Though
these options can provide symptomatic relief, multiple treatment rounds are often
required for full therapeutic benefit. Each procedure brings addi tional costs, risks,
and a protracted treatment schedule. Preoperative glue embolization of VMs followed
immediately by surgical excision provides definitive treatment in a single session.
This single-stage procedure requires extensive communication and coordination between
multiple teams, namely interventional radiology, surgery, and anesthesia, which may
not be feasible at every institution. Because of diffuse disease or comorbidities,
some patients will not be good candidates for preoperative glue embolization. Still
others may decide they would prefer multiple rounds of sclerotherapy rather than undergoing
surgery and having a scar. Nonetheless, this procedure offers an appealing alternative
to sclerotherapy or surgery alone. In experienced hands, it is safe and has a high
technical success rate. It limits rounds of treatment and therefore radiation exposure.
Additionally, this technique dramatically reduces intraoperative blood loss and makes
exc ision less technically challenging by defining lesion margins.
