Keywords
hepatic embolization - flow-directed catheters - antireflux catheters
Introduction
Transarterial chemoembolization (TACE) and selective internal radiation therapy (SIRT)
with Y resin and glass microspheres are established treatments for unresectable liver
cancers including primary hepatocellular carcinoma (HCC), liver-dominant metastasis,
and intrahepatic cholangiocarcinoma. Serious complications during transarterial embolization
of liver masses may occur as a result of unintended embolization to nontarget hepatic
and extrahepatic tissues. One potential complication is gastrointestinal ulceration
after nontarget embolization of hepatoenteric collaterals such as the gastroduodenal
artery (GDA), right gastric artery, and right gastroepiploic artery, leading to damage
of the gastric wall, duodenum, and pancreas.[1]
[2] Nontarget embolization of a patent falciform artery may lead to burning sensations
and pain in the umbilical and anterior abdominal wall region.[3] Additionally, radiation and chemotherapy induced cholecystitis has also been reported
from nontarget embolization after chemoembolization beads and Y treatment.[4] One way this may occur is anterograde blood flow through hepatofugal arteries forming
collaterals to nearby arteries and operators often have to navigate these variations
in foregut vascular anatomy to prevent nontarget embolization.[5]
This already difficult anatomy may become even more complex after liver resection
where small collateral vessel may develop and provide blood supply to small segments
of the liver or drain blood from the remaining liver artery into neighboring organs
such as the duodenum.
Also, refluxing embolic particles are a major source of nontarget embolization. Retrograde
blood flow during diastole can carry particles to nearby arterial branch points, allowing
embolization of unintended tissues ([Fig. 1]).[1] To prevent reflux, interventionalists have conventionally used coil embolization
in pretreatment planning before TACE and SIRT. Often, arteries involved in reflux
are too small to place coils into and on the day of treatment, the flow may have redistributed
in a different way compared with the day of embolization. This calls for alternative
ways to manage such situations, such as antireflux catheters. These catheters are
designed to increase the relative deposition of embolic material to the target with
temporary manipulation of the anatomy and physiology of the arterial system. At present,
there are two kinds of antireflux catheters available, one with expandable basket
catheter system and other with temporary occlusive balloon expandable micro catheters.
Fig. 1 Retrograde blood flow during diastole using a standard end-hole catheter to administer
embolic particles. Blood flow is seen refluxing into nontarget tissues creating a
potential source of complications.
The Surefire Infusion System (Surefire Medical Inc. now TriSalus Life Sciences, Westminster,
Colorado, United States) was developed as an antireflux alternative to the standard
end-hole catheter and coil embolization for infusing embolic particles during TACE
and SIRT. As seen in [Fig. 2], the Surefire catheter contains a flexible, cone-shaped self-expanding basket with
a hydrophilic coating that collapses to allow anterograde flow during systolic flow.
The antireflux basket will re-expand during diastolic retrograde blood flow that occludes
the vessel and traps embolic particles thus preventing reflux.[6]
[7]
Fig. 2 Mechanism of Surefire antireflux microcatheter. (A) Systolic blood pressure collapses the antireflux basket to allow anterograde blood
flow. (B) Diastolic blood pressure allows antireflux basket to expand and catch embolic particles,
preventing reflux to unintended tissue.
Temporary occlusion using balloon microcatheters has also been explored as a means
to prevent particle reflux ([Fig. 3]). Balloon occlusion results in decreased vascular blood pressure in the tumor-supplying
artery that reverses blood flow in adjacent hepatoenteric arteries. This mechanism
has been demonstrated by Rose et al, which showed increased deposition of microspheres
in target porcine hepatic arteries.[8] There have been a few recent studies investigating the feasibility and efficacy
of balloon catheter occlusion in preventing reflux, higher target bead packing and
enhancing target embolization. Balloon devices currently being studied include IsoFlow
(Vascular Designs Inc., San Jose, California, United States), Hyperform (Medtronic,
Minneapolis, Minnesota, United States), Occlusafe microcatheter (Terumo, Japan), and
Sniper (Embolx Inc., Sunnyvale, California, United States).
Fig. 3 Mechanism of balloon catheter occlusion. Inflation of balloon allows temporary arterial
occlusion and prevents reflux to unintended tissues.
We present cases showing the clinical uses of antireflux catheters in patients undergoing
hepatic artery chemoembolization and radio embolization. In addition, we review current
literature on preventing reflux and enhancing downstream embolization using the Surefire
microcatheter and balloon tip catheters.
Case #1: Surefire for Y 90 Therapy
A 62-year-old woman presented with recurrent cholangiocarcinoma status post right
hepatic lobectomy and chemoradiation therapy for her initial lesion. Surveillance
imaging revealed a new solitary lesion in the fourth hepatic segment ([Fig. 4]). Biopsy was consistent with recurrent cholangiocarcinoma. A multidisciplinary team
decided to treat this tumor with SIRT given that with her previous surgery, she was
unable to undergo further resection.
Fig. 4 A 62-year-old woman who presented with recurrent cholangiocarcinoma status post right
hepatic lobectomy and chemo-radiation therapy for her initial lesion. Surveillance
imaging revealed a new solitary lesion in the fourth hepatic segment (arrow). Patient
is status post right hepatectomy.
Pretreatment celiac angiogram revealed a replaced left hepatic artery that branches
off the proximal celiac artery and provides the major blood supply to the hypertrophied
left liver lobe ([Fig. 5]). The common hepatic artery branches off into GDA and two small parasitized collateral
branches supplying segment 4, which is the cut surface of the liver and bears the
tumor. These two arteries showed competitive flow from the left hepatic artery and
the GDA. On interrogation, the lateral of these branches supplies the tumor as shown
by DynaCT; however, on forceful injection of contrast, there is reflux via intrahepatic
collaterals into the medial segment 4 artery and retrograde flow into the GDA ([Fig. 6]). Attempts were made to engage these two small branches from the left hepatic artery;
however, this was unsuccessful. This would leave the possibility of a nonselective
injection of Y90 particles into the distal left hepatic artery with protective embolization
of the two parasitized collateral branches or the GDA itself. However, the excellent
opacification of the tumor after selective injection into the lateral collateral branch
favored treatment through this branch with protection against unintended reflux. During
treatment, a Surefire microcatheter was advanced into the lateral hypertrophied collateral
branch vasospasm occurred after filter deployment that responded to 60 mg of cardiac
lidocaine. Repeated contrast injections showed arterial patency and no further vasospasm
([Fig. 7]). In contrast to pretreatment angiography, after filter deployment no reflux was
seen. Subsequently, 90Y resin spheres were administered to the tumor through the Surefire microcatheter.
Intermittent angiograms were obtained during 90Y injection to assess persistent antegrade flow without reflux into the GDA to identify
a suitable end-point of radioembolization.
Fig. 5 A 62-year-old woman who presented with recurrent cholangiocarcinoma status post right
hepatic lobectomy and chemoradiation therapy for her initial lesion. Surveillance
imaging revealed a new solitary lesion in the fourth hepatic segment. Pretreatment
angiography of the celiac trunk. Large white arrow represents replaced left hepatic
artery. Large black arrow represents gastroduodenal artery. Black arrowhead represents
lateral branching posterior hepatic artery supplying blood to tumor. White arrowhead
represents medial branching posterior hepatic artery.
Fig. 6 A 62-year-old woman who presented with recurrent cholangiocarcinoma status post right
hepatic lobectomy and chemoradiation therapy for her initial lesion. Surveillance
imaging revealed a new solitary lesion in the fourth hepatic segment. Pretreatment
angiography of the lateral branching posterior hepatic artery that supplies the tumor.
Refluxing contrast is seen into gastroduodenal artery (arrow) via the medial branching
middle hepatic artery.
Fig. 7 A 62-year-old woman who presented with recurrent cholangiocarcinoma status post right
hepatic lobectomy and chemoradiation therapy for her initial lesion. Surveillance
imaging revealed a new solitary lesion in the fourth hepatic segment. Deployment of
the Surefire antireflux catheter tip during 90Y radioembolization. No evidence of reflux is seen in contrast to pretreatment angiography.
Postembolization Bremsstrahlung scan did not show any extrahepatic activity. The 3-month
follow-up scan showed extensive tumor necrosis. One year later, the patient developed
intrahepatic metastatic disease and underwent a repeat SIRT. This time, as metastases
were distributed throughout the entire left lobe; a nonselective treatment via the
left hepatic artery was performed after embolization of the remaining medial collateral
branch. The lateral collateral branch was completely occluded at the time of the repeat
treatment.
Case # 2: Surefire for Chemoembolization
A 59-year-old male presented with hepatitis C, treated briefly with Harvoni, underwent
ultrasound that showed a mass. Follow-up magnetic resonance imaging (MRI) in February
showed a 3.3 cm mass in the right lobe ([Fig. 8A]), with delayed washout consistent with HCC. The patient was evaluated for liver
transplant. As a bridge to liver transplant, chemoembolization of the liver was requested.
Angiogram showed the blood supply to the lesion from right hepatic artery. To minimize
the potential reflux of chemo beads, Surefire catheter was used ([Fig. 8B]) that minimized staining of the surrounding area with intense staining of the tumor.
Follow-up contrast-enhanced MRI showed no enhancement of the liver lesion with expected
peripheral rim enhancement as posttreatment changes. The patient went on to undergo
a successful orthotopic liver transplant.
Fig. 8 Surefire catheter for chemoembolization. (A) Axial post contrast magnetic resonance imaging (MRI) of the liver showing an enhancing
lesion in the right lobe (arrow). (B) Catheter angiogram using Surefire catheter (thick arrow) with intense staining of
liver lesion. (C) Follow-up axial contrast-enhanced MRI showing no residual enhancement of the treated
lesion (arrow).
Case # 3: Balloon Occlusion Catheter for Chemoembolization
A 61-year-old male, with hepatitis B virus-related cirrhosis, presented with right
upper quadrant pain and underwent cholecystectomy. Liver MRI was done showing liver
lesions. MRI was inconclusive for diagnosis ([Fig. 9A]). A biopsy was performed that proved it to be well differentiated HCC. Chemoembolization
was requested. The lesion in segment 6 was targeted; however, with the end-hole catheter,
there was significant reflux to the portal venous side via portal venous shunt. This
was treated with Sniper balloon occlusion catheter (Embolx Inc., Sunnyvale, California,
United States) with significant decrease in the portal venous shunting ([Fig. 9C]). The patient is under follow-up and slated to undergo imaging next month.
Fig. 9 A 61-year-old male with hepatitis B virus with incidentally found liver lesion and
biopsy-proven hepatocellular carcinoma. (A) Axial post contrast magnetic resonance imaging showing the liver lesion in right
lobe of liver (arrow). (B) Angiogram with regular end hole catheter showing significant shunting to the portal
vein (thin arrow). (C) Angiogram with sniper balloon occlusion catheter showing significant decrease in
the portal vein filling (thin arrow). The injection conditions of both end hole catheter
and sniper were unchanged.
Technical Note
The Surefire catheter and balloon embolization catheters are compatible with the present
sheaths commercially available. We used 6 French sheaths. This allows flushing of
the sheath using the side arm. The balloon occlusion catheters are compatible with
routinely available 5 French catheters. Surefire catheter requires specific catheters
that were provided by the same company, in the usual shapes (Cobra, Simmons). These
catheters have thinner walls, increasing the lumen size to accommodate the flow-directed
catheters.
The Surefire catheter is prepped per the company guidelines, which is targeted toward
avoiding any trapped air in the fabric of the device, thereby avoiding any distal
air embolization.
Discussion
In this review, we describe a patient undergoing SIRT for recurrent cholangiocarcinoma
with complex hepatoenteric anatomy. Pretreatment angiography showed reflux into GDA;
thus, a decision was made to use antireflux catheter (Surefire) for the treatment.
Of the available antireflux catheters, Surefire has been studied the most, which is
suggested by the number of publications involving it. The primary goals of antireflux
catheters are to avoid reflux and increase the percentage distribution of embolized
particles to the target versus nontarget tissues. However, whether this translates
into decreased number of treatments or increased survival is yet to be proven.
The ability of the Surefire antireflux microcatheter to help embolization when there
is complex hepatic anatomy has been previously documented; a case study by Saddekni
et al highlights the success in delivering chemoembolization particles to downstream
liver tumors despite a collateralizing variant retroportal artery with retrograde
flow providing a problematic course for nontarget embolization. By using the antireflux
catheter, the authors avoided obliteration of the flow through the collateral and
successfully treated the patient with multifocal HCC.[6]
As demonstrated in our case study, the Surefire microcatheter can avoid the need to
coil embolize as a means to prevent reflux and nontarget embolization. This is supported
in a case study by van den Hoven et al where the authors were unable to coil embolize
the right gastric artery yet successfully administered Y using the Surefire system
to prevent extrahepatic deposition.[9] Fischman et al verified these findings in a prospective trial comparing nontarget
embolization between coil embolization with an end-hole catheter and the Surefire
antireflux catheter alone during pretreatment angiography in patients undergoing Y
radioembolization. In this prospective trial, 30 patients with primary or metastatic
liver cancer underwent pretreatment angiography and SIRT. There was no nontarget distribution
of radiotracer seen in either group after planning angiography and macroaggregated
albumin (MAA) using single-photon emission computed tomography/computed tomography.
The authors assert that the antireflux catheter is equally as good as coil embolization
in reducing nontarget embolization with decreased procedure time, less radiation,
and less contrast use while maintaining patency of collaterals by avoiding embolization.[10] This was earlier proven in animal study, using a porcine renal artery model, by
Arepally et al who showed statistically significantly decreases in nontarget deposition
compared with the end-hole catheter using tantalum bead embolization. The authors
propose that the nontargeted kidney pole received more bead with the end-hole catheter
compared with the Surefire antireflux catheter as a result of more irregular particle
distribution pattern with the end-hole catheter.[11]
Beyond preventing nontarget embolization, there is evidence that antireflux catheter
enhances downstream particle delivery to liver tumors. Arepally et al describe deeper
penetration of tantalum microspheres in downstream kidney parenchyma of porcine kidneys
after infusion with an antireflux catheter compared with an end-hole catheter. The
antireflux catheter had a statistically significantly increase in embolization efficiency
(99.9%) compared with end-hole catheter (72%) in this in vivo model; and only 0.1%
of tantalum microspheres exhibited arterial reflux with the antireflux catheter compared
with 28% reflux to nontarget renal tissue with the end-hole catheter.[11] These findings were further supported by the work of Pasciak et al, who treated
unresectable liver cancer with same day MAA and Y90 treatments. They showed a significant
decrease in nontarget deposition by 24 to 89% and statistically significant relative
increase in tumor deposition by 33 to 90%.[12] These findings were also shown to be consistent in drug-eluting bead transarterial
chemoembolization (DEB-TACE) where larger particles are used for treatment, in comparison
to the Y90 therapy. The retrospective study by Kim et al found no evidence of nontarget
hepatotoxicity following DEB-TACE in all 22 patients using the Surefire Infusion System,
suggesting that this antireflux catheter is a suitable and safe alternative to the
end-hole catheter.[13]
The Surefire catheter has also been shown to change procedure parameters. According
to Morshedi et al, using a Surefire antireflux catheter alone results in a statistically
significant decrease in procedure time, fluoroscopy time, and contrast dose compared
with coil embolization and end-hole catheter for nontarget embolization protection
during pretreatment angiography before Y. However, there was no significant decrease
in radiation dose. A shorter procedure and fluoroscopy time increase efficiency and
can decrease overall cost. However, there was no statistically significant decrease
in radiation dose. In addition, a lower contrast dose could be beneficial for patients
with renal disease. These findings may be beneficial to the patient in reducing risk
and exposure to radiation, contrast material, and anesthesia.[14]
These findings are supported are by Fischman et al who found that the antireflux catheter
alone can significantly decrease procedure time, fluoroscopy time, contrast agent
dose, and radiation dose in pretreatment planning angiography for SIRT when compared
with coil embolization with an end-hole catheter.[10]
Mechanism of Action
The mechanism of action of the antireflux catheter is multifactorial and more complex
than simple expansion of basket to prevent particle reflux. Rose et al investigating
alterations in blood pressure in hepatoenteric arterial flow discovered that when
the antireflux tip expands during diastolic retrograde flow, it occludes the arterial
lumen and creates two separate vascular compartments—a lower pressure compartment
distal to the catheter tip and a higher pressured systemic arterial compartment. There
are significant decreases in systolic, diastolic, and mean arterial blood pressure
in the hepatic arterial system when the antireflux tip is expanded versus closed (mean
SBP decreased by 25; mean DBP decreased by 17; MAP decreased by 21). It has been suggested
that the Surefire catheter is most efficacious in decreasing distal pressure in arteries
with an internal diameter less than 4 mm.[7] The authors suggest that there is a decrease in downstream hepatic arterial blood
pressure when the antireflux catheter tip is expanded potentially causes hepatopedal
flow in hepatoenteric arteries, reducing nontarget embolization. This provides retrograde
protection through reflux prevention and anterograde protection through reversal of
hepatoenteric flow.[7] In theory, as the expandable tip collapses during systolic flow, the increased pressure
difference may enhance embolic particle distribution into more distal target arteries.
This was further supported by an in-vitro hepatic arterial model, by van den Hoven
et al showing differences in particle flow physics between end-hole catheters and
the Surefire antireflux catheter. The authors assert that because the end-hole catheter
results in more laminar particle outflow, and that normal arterial blood flow is laminar,
downstream particle distribution with an end-hole catheter is more reliant upon catheter
position within the arterial lumen. Therefore, distribution of embolization particles
is more heterogeneous, and downstream spread may be subjected error and “streamlined”
by pre-existing pathways of blood flow. Infusion with the antireflux catheter results
in turbulent flow that may cause lateralization of embolic particles and lead to a
more homogenous downstream particle distribution. The ability of the Surefire basket
to disrupt laminar flow may lead to improved target radioembolization.[15]
Limitations
Use of antireflux catheters has some limitations in transarterial embolization. Initially,
for the Surefire antireflux vessel diameter and access guiding catheters were limitation
since it needed a 6 French guiding catheter; however, with the advent of newer microcatheter
systems and Surefire-compatible guiding catheters, these have been circumvented. In
a study by Rose et al, 33% of the initial study candidates were excluded from participation
as the guide sheath could not fit due to aortoceliac or aorto-superior mesenteric
artery anatomy.[7] This may be related to the stiffness of the guide sheath.[14]
The use of the Surefire antireflux catheter also changes the definition of embolization
end-point.[6] Conventionally, operators use fluoroscopic reflux of contrast material during embolization
as an indication to stop infusion. Because the antireflux catheter prevents reflux,
it may be difficult to identify an end-point and this could lead to over embolization.[7] Kim et al have developed a method of optimizing embolization end points: routinely
retract the tip and perform angiograms to assess anterograde flow at intervals of
every one-half vial of infusion particles after two vials and stop infusion when contrast
reflux is seen despite tip expansion.[13] We used this same method in our case study that was satisfactory. This approach
is operator-dependent, so there is a need for quantifying and standardizing the embolization
end-points, especially to eliminate variation and bias when performing systematic
reviews.
Multiple studies have reported that the Surefire antireflux catheter is associated
with distal hepatic arterial vasospasm that has led to the use of nitroglycerin and
verapamil infusions during embolization.[9]
[10] In our study, a vasospasm was seen after deployment of the Surefire tip in which
we used cardiac lidocaine to abate. It is unclear what effect this may have on embolization
procedures and particle distribution, if any.
A significant issue is that, while there is clear evidence that the Surefire system
enhances downstream embolization and inhibits reflux, there is no data suggesting
survival benefit. While this catheter helped us treat the patient with difficult hepatic
arterial anatomy, her cancer unfortunately returned in the same location.
Further limitations to the literature presented here include problems with heterogeneous
patient populations. Many of the studies are small case studies, or retrospective
studies with variable demographics, making assessment difficult. In addition, it seems
that the antireflux catheter has a higher learning curve that may make standardization
of TACE and transarterial radioembolization studies and treatments harder to accomplish
at first, if using the Surefire catheter becomes more routine.[10]
There is concern that the antireflux catheters are more expensive compared with the
traditional end-hole catheter, coil embolization, and alternative techniques. However,
analysis from Morshedi et al suggests that the Surefire antireflux catheter leads
to a lower cost compared with procedures requiring coil embolization due to decreases
in procedure and fluoroscopy time.[14] This is difficult to quantify as the cost and supply of different equipment vary
from institution to institution and region to region around the world.
Recent research has determined that temporary occlusion using balloon microcatheters
is a safe and feasible means of preventing reflux and increasing downstream particle
distribution in TACE and SIRT.[8]
[16]
[17]
[18] While there is no data suggesting balloon catheters increase survival benefit in
embolization therapy, they have been shown to successfully navigate complex anatomy
and prevent reflux. For example, Hagspiel et al could temporarily occlude the cystic
artery during Y treatment.[18] While balloon microcatheters are expensive, they are significantly less costly than
the Surefire microcatheter. To summarize the limitations, the flow-directed catheters
are difficult to handle in tortuous anatomy, increase risk of spasm and dissection
especially in patients receiving antiangiogenetic therapies, and with long inflation
time can lead to parent vessel thrombosis.[19]
In summary, using the antireflux catheter is useful in avoiding reflux in patients
during liver-directed arterial therapies. We successfully treated patients with complex
hepatoenteric anatomy and minimized unintended reflux. While the antireflux systems
have been shown to prevent reflux, increase target embolization, and downstage certain
HCC patients for potential liver transplant, it has limitations that mainly include
cost and lack of a proven survival benefit. Temporary occlusion using balloon microcatheters
may prove to be a less expensive and effective means to avoid reflux and increase
downstream particle uptake in liver tumors. More research is needed to look at survival
benefit in patients with using nontraditional, antireflux devices, and compare them
for efficacy and ultimately survival benefit.
