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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3869_Библиотеки_им_академика_М_И_Перельмана.pdf
26 D. Tuite and K. O’Regan
• The AVP is released by anticlockwise rotation of the delivery wire, which
unscrews the plug from t he wire.
Amplatz vascular obstruction device (Amplatz spider) (Cook Medical
Inc., Bloomington, IN, USA)
• This creates a s tainless steel scaffold system onto which a nest of coils can be
built up. The device prevents distal embolization of coils. It is available in a
range of sizes between 9 and 20 mm and is delivered through a 5Fr introducer
sheath.
Associated Complications and Strategies for Minimizing These
Unable to obtain selective catheter position: The use of guide catheters, hydrophilic
wires, and microcatheters can all be employed at this stage. Guide catheters provide
support; hydrophilic wires and microcatheters improve the chances of accessing a difficult vessel. Often the use of different microwires can prove helpful. If
optimal position cannot be obtained, then consideration can be given to more proximal embolization; however, this will increase the potential for collateral tissue
damage.
Unable to obtain stable catheter position: Initially a guiding catheter should be
used. Ensure that the shape of the catheter and guide catheter is optimized. If this
does not work, then an approach from a different access point should be considered,
i.e., brachial approach vs femoral approach.
Misplaced coil: Misplaced coils occur as a result of oversized coils, undersized
coils, or unstable catheter position. They can be removed using a snare but this can
cause additional problems and may even dislodge the coil nest! If the coil is not
likely to cause a problem, then leave it alone.
Catheter is pushed back during deployment: Gentle forward pressure is necessary
as is the support from your base catheter. It may be necessary to enlist assistance
from a second operator to stabilize the catheter system during coil deployment.
Coil occludes the catheter: This is a result of coil–catheter mismatch, when there
is a kink or tight bend in the catheter or when the inner lumen of the catheter has
been damaged by particulate matter or coils.
• First determine the site of obstruction with fluoroscopy.
• Attempt disimpacting the coil using a saline flush.
• If there is a kink in the delivery catheter, provide gentle forward pressure on the
pusher wire while the deployment catheter is withdrawn slightly. The back (stiff)
end of the pusher wire can also be tried.
• If the coil is impacted in the catheter outside of the patient, then the catheter can
be cut distal to the coil, a wire passed, and the catheter replaced.
• If the coil i s impacted in the catheter within the patient, then the catheter must be
removed and position re-established with a new catheter.
2 Coils, Occluders, and Plugs 27
Other Problems
Coagulopathic patients. Thrombus formation is essential for coil embolization to be
successful. In the coagulopathic patient this will not occur.
• One strategy for dealing with this is to deploy a nest of coils, then gelfoam pled-
gets, and then pack with coils again, thus creating a gelfoam sandwich. The
coils prevent the gelfoam from embolizing distally and the gelfoam provides
mechanical occlusion of the vessel.
• Remember to use non-heparinized saline for flushing.
Keypoints
• Plan, plan, and plan again.
• Obtain good angiographic images that detail the anatomy and pathology.
• Choose site of embolization.
• Ensure stable catheter position.
• Select appropriate coils and appropriate deployment method.
• Check completion angiogram.
Suggested Further Reading
Kessel D, Robertson I. Interventional Radiology: A survival Guide. 2nd edition, Elsevier,
Amsterdam 2005 ISBN 0-4431-0044-6.
Berenstein A, Lasjaunias P, Ter Brugge KG. Surgical Neuroangiography: Clinical and
Endovascular Treatment Aspects in Adults vol. 2, Springer-Verlag Berlin and Heidelberg GmbH
& Co. K; 2Rev Ed. 2004 ISBN-10: 3540416684.
Schmutz F, McAuliffe W, Anderson DM, Elliott JP, Eskridge JM, Winn HR.
Embolization of cerebral arteriovenous malformations with silk: histopathologic changes and
hemorrhagic complications. AJNR Am J Neuroradiol. 1997 Aug;18(7):1233–7.
Osuga K, Mikami K, Higashihara H, Maeda N, Tsuboyama T, Kuwabara M, Onishi H, Hori M,
Kim T, Tomoda K, Murakami T, Nakamura H. Principles and techniques of transcatheter
embolotherapy for peripheral vascular lesions. Radiat Med. 2006 May;24(4):309–14. Review.
Chapter 3
Permanent Particulate Agents
Audrey Fohlen and Jean-Pierre Pelage
Introduction
Embolization materials can be classified according to their physical and biological
characteristics. They are chosen according to the following:
• Characteristics of the target vessels: size, flow, and type of vessel (artery or
vein).
• Permanent particulate agents are not resorbed and are intended to provide durable
occlusion (Fig. 3.1).
• The level of arterial occlusion obtained with particulate agents varies from
proximal to distal according to the chosen agent.
• Recanalization can occur due to expulsion, distal migration, fragmen-
tation of the embolization material, and formation of a new vessel
lumen.
• Occlusion can be purely mechanical or may be a conjunction of different
mechanisms with vessel wall destruction by inflammation or sclerosis.
Fig. 3.1 500–700 μm
Tris-acryl microspheres
Embosphere (Biosphere
Medical, Louvres, France)
located in the perifibroid
arterial plexus in a patient
treated with
pre-myomectomy
embolization
Transcatheter Embolization and Therapy,
Techniques in Interventional Radiology, DOI 10.1007/978-1-84800-897-7_3,
C
Springer-Verlag London Limited 2010
29
30 A. Fohlen and J.-P. Pelage
This chapter outlines the different permanent particulate embolization agents
available, their characteristics, and how to choose and use them.
Not all particles are equal; they differ in physical and biological properties.
Particle Physical Properties
• Size: all particles come in a range of sizes. The diameter of vessel that will be
occluded depends on this and other properties (including compressibility and
elastic recovery).
• Uniformity: some particles are very uniform in size (calibrated). Others are
variable and described according to mean particle size (Fig. 3.2).
• Compressibility: some particles (mainly microspheres) compress during deploy-
ment which makes delivery of large sizes through microcatheters easy but may
block vessels smaller than the nominal particle diameter if the elastic recovery
is slow.
• Aggregation: some particles tend to clump which will affect the level of
embolization (Fig. 3.3).
• Visibility:
◦ Most particles are suspended in 50% contrast to allow visualization during
injection (Fig. 3.2).
◦ Some particles are intended to be visible on computed tomography (CT) or
magnetic resonance (MR) follow-up.
a
Fig. 3.2 Bronchial artery embolization for hemoptysis. (a) Superselective catheterization
of the bronchial artery shows abnormal lung vascularity. (b) Targeted devascularization is
obtained using 700–900 μm tris-acryl microspheres seen as uniform filling defects in the
arterial lumen
b
3 Permanent Particulate Agents 31
Fig. 3.3 Conventional
polyvinyl alcohol particles
are of irregular shape
Mechanism of Action
• Simple mechanical occlusion
• Active agents: drug eluting, radioactive
Commonly Used Agents
Polyvinyl Alcohol Particles (PVA)
PVA is an inert plastic which has been used as an embolic agent for 20 years and
has a long-track record of safety and efficacy in embolization procedures.
Non-spherical Polyvinyl Alcohol Particles
• Non-spherical PVA particles do not completely occlude the lumen of the
occluded arteries. Occlusion is completed by thrombus formation within the
interstices of the particles.
• Non-spherical PVA particles cause moderate perivascular inflammatory change.
• Recanalization can occur after several months or years due to the following:
◦ Distal migration, fragmentation or extravascular migration of PVA particles
◦ Resorption of thrombus
◦ Calcification of PVA particles has been reported but is of uncertain
significance
• The irregular shape of the material is associated with a larger granulometric range
of the particles than advertised (Fig. 3.3). Some of the particles are smaller than
the advertised size. Small fragments of PVA may cause non-target embolization
of normal tissue (e.g., the ovaries during uterine artery embolization).
• Aggregation of PVA particles can lead to obstruction of the delivery catheter
and potentially to uncontrolled level of arterial occlusion. With non-spherical
particles, clumping of the embolic material may result in a false angiographic
end-point at the conclusion of the embolization.
32 A. Fohlen and J.-P. Pelage
PVA Microspheres
• PVA spheres have been recently introduced (Contour SE, Boston Scientific,
Nattick, MA, USA and Bead Block, Biocompatibles, Farnham, UK).
• PVA microspheres are easily visible because of their white (Contour SE) or blue
(Bead Block) coloration (Figs. 3.4 and 3.5).
Fig. 3.4 Polyvinyl alcohol
microspheres Contour SE
(Boston Scientific, Nattick,
MA, USA)
Fig. 3.5 Acrylamido
polyvinyl alcohol
microspheres Bead Block
(Biocompatibles, Farnham,
UK)
3 Permanent Particulate Agents 33
• The following size ranges are currently available: 100–300, 500–700, 700–900,
and 900–1200 μm.
• Even large PVA microspheres are easy to inject through microcatheters and tend
to travel more distally than the irregular PVA particles or tris-acryl microspheres
of theoretical same diameter.
Tris-Acryl Microspheres
• Tris-acryl microspheres are made from precisely calibrated microporous cross-
linked acrylic beads embedded with gelatin (Embosphere, Biosphere Medical,
Roissy, France).
• The following size ranges are currently available: 40–120, 100–300, 500–700,
700–900, and 900–1200 μm. The diameter of occluded arteries correlates well
with the microsphere size.
• The spheres are compressible, which allow easy passage through a microcatheter
with a luminal diameter smaller than that of the microspheres.
• Angiographically, apparent clumping may occur with microspheres. The
embolic material redistributes depending on the infusion rate and the
concentration.
• In the long-term, there is no chronic inflammatory reaction and no degradation of
the polymer (Fig. 3.1).
Hydrogel–Polyzene F Microspheres
• Calibrated microspheres consisting of a hydrogel core of polymethylmethacry-
late with a thin coating that may reduce inflammation for better biocompatibility
(Embozene, Celonova, Newnan, GA, USA).
• The following sizes are currently available: 40, 100, 250, 400, 500, 700, 900, and
1100 μm.
• As opposed to the other types of microspheres, a tight size distribution exists;
this means that each vial or syringe contains microspheres that are consistently
the same size.
• Particles are color-coded by particle size (Fig. 3.6). This is useful to avoid inap-
propriate mixing, contamination of saline and contrast syringes, and confirmation
that optimal suspension is reached before embolization.
Fig. 3.6 Hydrogel–polyzene
F microspheres Embozene
(Celonova, Newnan, GA,
USA)
34 A. Fohlen and J.-P. Pelage
Novel Agents
Bio-active Particles
These embolic agents combine vascular occlusion with other local effects such as
drug delivery or irradiation. The embolic property causes particles to lodge in a
specific location, they then act a as platform to deliver high-intensity therapy in a
selected location.
Drug-Eluting Microspheres
The theoretical advantages of drug-loaded particles are numerous, including a
higher local drug concentration and a lower total dose of drug compared to a
systemic administration and the potential to use drugs that are potentially toxic
using the systemic route. Several such agents are under investigation including the
following.
• Anti-tumor drugs: doxorubicin and irinotecan-loaded microspheres are being
currently investigated in pre-clinical evaluations and clinical studies.
• Analgesic agents: ibuprofen-loaded microspheres (Biocompatibles, Farnham,
UK) are being assessed to evaluate the clinical effects on post-embolization pain
following UAE.
Other possibilities include
• Agents that enhance or prolong the duration of arterial occlusion: vasoactive
drug, such as prothrombotic agents and anti-angiogenic factors.
• Agents that prevent local tumor regrowth such as hormones, growth factor
inhibitors, or anti-mitotic agents.
Two Types of Drug-Eluting Microspheres are Available
• Those that behave “like sponges” able to osmotically absorb large amounts
of drug in solution (Hepasphere/Quadrasphere, Biosphere Medical, Roissy,
France). These can be considered as a ready-to-load platform for any type
of water-soluble drugs, but elution of the agent can occur before and during
injection.
• Those produced from polymers able to adsorb a given drug which reaches high
concentration inside the biomaterial (DC Beads, Biocompatibles, Farnham, UK)
(Fig. 3.7). Drug release is more controlled and allows long-term delivery, but only
selected drugs can be successfully loaded and released.
3 Permanent Particulate Agents 35
Fig. 3.7 Doxorubicin-eluting
microspheres DC-Beads
(Biocompatibles, Farnham,
UK)
Several Factors May Influence the Ability to Deliver
Drugs in Practice
• The diffusion area is composed of the vessel wall and the perivascular space,
which comprises veins, lymphatic ducts, and interstitial tissue.
• Within a few hours, a foreign body reaction develops around the microsphere.
• This inflammatory response may modify the drug release by creating a bar-
rier that reduces the diffusion of the drug or by eliminating the drug in the
process.
For these reasons the drug release is very promising strategy, but its efficiency
needs to be demonstrated experimentally first in animals and second in patients. In
animals, the following has to be proven:
• The systemic level of the drug is null or much lower than after a systemic
administration.
• The microsphere can release the loaded drug in significant amounts
• There are proven signs of the biological action of the drug
• No adverse local or general event or side effect occurs
• Finally the primary effect of the microspheres is not changed by the loaded drug.
Therefore, it remains to be proven in large cohort of patients that chemotherapyloaded microspheres are safe and effective in terms of symptoms or prevention of
tumor recurrence.
36 A. Fohlen and J.-P. Pelage
Radioactive Microspheres
Radioembolization consists of intra-arterial delivery of carrier spheres onto which
radioactive particles are attached. There are two types of currently available radioactive microspheres that can be used in the treatment of primary and metastatic liver
diseases. They both contain Yttrium-90 (
type of carrier particle. Average activity per sphere is known allowing the delivered
90
dose to be calculated.
age tissue penetration of 10 mm.
Y is predominantly a beta-particle emitter with an aver-
90
radioembolization. The indications, patient selection, preparation, and technique are
identical for both preparations.
90
Y glass microspheres (TheraSphere, MDS Nordion, Canada) are glass spheres
•
with a diameter of 25 ± 10 μm impregnated with
the arteriole level.
90
Y resin-based microspheres (SIR-spheres, Sirtex Medical, Australia) with a
•
diameter of 29–35 μm.
• SIR-spheres have a much lower specific activity per bead, meaning that many
more beads must be injected to achieve the same radiation dose when compared
to TheraSpheres. This leads to a much greater “embolic effect” when using SIRspheres as compared to TheraSpheres.
90
Y) as the active element but differ in the
Y becomes inactive approximately 10 days after
90
Y. Theraspheres embolize at
Considerations Relating to90Y Microspheres
Radioactive microspheres have been used to treat liver tumors and metastases.
Experience has been limited because of very restrictive conditions of use, strict
patient selection, and costs. As in the case for transarterial chemoembolization,
radioembolization takes advantage of the preferential hepatic arterial supply of hepatocellular carcinoma (HCC) or vascular metastases to deliver targeted therapy to
the tumor, relatively sparing the normal liver parenchyma, that is mostly supported
by the portal venous system.
• The total dose to be delivered depends on the tumor burden and the liver volume
based on imaging evaluation (CT or MRI).
• A total dose of 120–150 Gy is considered to be optimal.
• The degree of shunting between the hepatic artery and hepatic vein needs to
be precisely assessed by performing a perfusion study of the liver with
m macroaggregated albumin (MAA) particles. The MAA particles are injected
through a catheter located in the arterial branch that will be used for radioembolization. The patient is then taken to the nuclear medicine department and
planar images of the liver and lungs are obtained [14, 15]. Normal lungs can
tolerate a total dose of 30 Gy. If the calculated liver dose is 120 Gy, the shunt
fraction should then be less than 25%.
99
T-