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Embolic
Agents:
Choice
of particles for uterine artery
embolization for leiomyomata
With
the emergence of uterine embolization for fibroids, there has been renewed
interest in the properties of embolic material (particles) used to block
the arteries. This page will review the theory behind the use of embolic
particles in UAE and describe the materials currently in use.
FDA
Approval Status
When
reviewing this material, it is important to realize that while both
PVA and Emboshperes® are approved for general embolization by the FDA,
neither is specifically approved by the FDA for the treatment of uterine
fibroids. To obtain this approval, multi-center studies are underway
with both products. The standard for this type of approval is high.
Not only must the material be shown to be safe and effective for treating
fibroids, but uterine embolization must be shown to be safe and effective
when compared to surgical treatment. So each study must compare the
results of UAE with surgery. The PVA study is using myomectomy as the
comparison; the Embospheres® study is comparing UAE to hysterectomy.
Embolization:
how much blockage of the artery is enough?
When UAE was first
performed, it was assumed that the artery had to be completely blocked
to successfully treat the fibroids. This has become the common practice
during uterine embolization.
Some experts in this field have theorized that the artery
may not need to blocked entirely, but only the vessels going to the
fibroids. This theory has been supported by research into a new particle,
called Embospheres® Microspheres. This particle is a clear acrylic flexible
sphere. Studies have shown that it is more likely than other types of
particles to block the fibroid vessels without closing the entire uterine
arteries. The particles appear to be equally effective to others in
use. It is not yet clear whether Emboshperes® are safer than other agents,
but their introduction has caused many interventionalists to reassess
the extent of embolization and many now attempt to leave the main uterine
artery open and try only to occlude the fibroid feeding vessels.
Both Emboshperes®
and PVA can be used in a similar way, leaving at least partial flow
in the uterine arteries. It is not yet known if one particle type is
superior to the other for UAE. At Georgetown, we are just beginning
a study to compare these 2 products, asking patients to allow us to
randomly assign to one or the other particle and then measuring the
outcome. This will allow us to determine is there is an advantage of
one product over the other.
Polyvinyl Alcohol Particles (PVA)
PVA is ground from
blocks of foam and then separated into different size groupings. The
commonest sizes used for uterine embolization are 355 to 500 micron
and 500 to 710 micron. A micron is one thousandth of a meter and so
these particles are about the size of grains of coarse sand.
PVA has a number
of desirable characteristics. It is a particulate material capable of
penetrating the fibroid blood supply and blocking it. PVA is relatively
inexpensive and easy to deliver. Most interventional radiologists have
extensive experience in its use and both animal studies and the published
experience in patients suggest that it is safe without any known long-term
side effects.
There are some potential
downsides. The particles swell after they mix with saline or contrast.
Once wet, they tend to aggregate and may clump within vessels after
injection. As a result, PVA may completely block the uterine artery.
As discussed above, there is not yet agreement among experts in this
area as to the extent to which the artery ought to be blocked. It is
fair to say that the majority of interventionalists completely block
the artery and that does effectively treat the fibroids. However, there
is an ongoing debate as to whether complete blockage of the artery is
needed and whether it might be safer to just block the blood supply
to the fibroids. At this time, PVA is in common use for embolization.
Gelfoam (gelatin sponge)
Gellfoam or gelatin sponge
is a dissolvable sponge-like material that has been used for many years
in surgery. It comes in small flat rectangular blocks about the size
of a matchbook. In this form, it can be applied to a minor area of bleeding
during an operation and helps a clot form. It has also been used for
embolization of fiboids as well, although the reported experience is
very limited. For embolization the sponge is compressed flat and then
cut into tiny squares (called pledgets) with a sterile scissors. Prior
to injection, many operators will load these pledgets into syringes
and mix them until they break down into a slurry. Whether used as a
slurry or as cut pledgets, gelatin sponge usually results in complete
occlusion of the uterine artery at the end of the embolization. Because
it generally behaves as a temporary agent in other vascular beds, it
has been assumed that the gelfoam will dissolve and the artery will
reopen in several days to a few weeks. This reopening of the uterine
artery has not been documented in any study to date and therefore it
is unclear whether this actually occurs. Its use has been suggested
for patients that may want to preserve their fertility because of the
perception that the artery will reopen, but further study is needed
to determine the long-term rate of reopening (called recanalization)
of the uterine arteries. To provide some perspective, reopening of the
main uterine arteries has been reported in over 80% of patients after
PVA embolization. This research by Dr. Razavi at Stanford suggests that
permanent occlusion of the uterine arteries is uncommon after a PVA
embolization.
Embosphere® Microspheres
Embosphere®
Microspheres are clear acrylic microspheres that were previously used
as a micro-carrier for cell culture, which helped confirm their biocompatibility.
They received FDA approval in May of 2000 for general use for embolization.
There are some attractive characteristics of this material. The spheres
are compressible and this allows easy passage through a micro-catheter
with a lumenal diameter smaller than that of the spheres. Studies by
Derdelyn and Pelage have shown that these spheres are more uniform in
size and the particle sizes do not changed in liquids. They have little
tendency to clump after injection and animal studies indicate that they
have less tissue reaction than is typically seen with PVA.
In
September of 2001, we reported the initial US results with Embospheres
from a three center study. The initial clinical experience with Embospheres®
is very promising. The symptom change following UAE was substantial,
resulting in a dramatic decrease in the impact of symptoms both during
menstrual periods and between periods. MRI 3 months after treatment
showed no evidence of injury to the normal uterine tissue and fibroid
reductions similar to those seen after PVA embolization. This study
confirmed that blockage of the main uterine artery is not necessary
to achieve successful treatment of the fibroids.
Summary
At this time there is not clear evidence if one
of the embolic agents in use is superior to others. Currently, most
physicians choose the material to fit the individual patient circumstances
and their preference. It is hoped that with additional study, the use
of products will be able to be tailored to the anatomy of a patient
to optimize the results. | 