The study evaluates a new technique called 'thrombization' during endovascular aneurysm repair (EVAR) which significantly reduces the risk of type II endoleaks compared to standard EVAR. Out of 404 patients, those undergoing EVAR with thrombization had a much lower endoleak incidence (2.2%) compared to those with standard EVAR (15.2%). The use of fibrin glue and microcoils for thrombization is shown to be a safe, effective, and cost-efficient method for stabilizing the aneurysm sac.

1. ¤CLINICAL INVESTIGATION ¤
Aneurysm Sac ‘‘Thrombization’’ and Stabilization
in EVAR: A Technique to Reduce the Risk of
Type II Endoleak
Salvatore Ronsivalle, MD1; Francesca Faresin, MD1; Francesca Franz, MD1;
Carlo Rettore, MD2; Mario Zanchetta, MD3; and Armando Olivieri, MD4
1Department of Cardiovascular Disease–Vascular and Endovascular Surgery and
Angiology,2Department of Radiology,3Division of Cardiology, and4Department of
Prevention–Epidemiology Unit, Cittadella Hospital, Cittadella, Italy.
¤ ¤
Purpose: To evaluate the reduction in type II endoleak risk after introducing a new
prevention method, ‘‘thrombization’’ or clotting of the aneurysm sac, during endovascular
aneurysm repair (EVAR) versus the standard EVAR technique.
Methods: From September 1999 to December 2008, 469 consecutive patients underwent
EVAR for AAA at our institution. In 2003, the injection of fibrin glue with or without microcoils
into the aneurysm sac was added to the EVAR treatment plan (‘‘thrombization’’ technique).
Patients who did not meet the inclusion criterion (at least 1-year follow-up imaging) were
censored at the end of 2007, leaving 404 patients eligible for the study: 224 patients (210 men;
mean age 71.968.5 years, range 25–88) undergoing EVAR alone from September 1999 to May
2003 (group 1) compared to 180 patients (161 men; mean age 72.668 years, range 46–89) who
underwent EVAR + thrombization from June 2003 to December 2006 (group 2).
Results: The 2 treatment groups were similar with regard to aneurysm morphology. No
allergic or anaphylactic reactions were encountered related to the fibrin glue. Over median
follow-up times of 72 months in group 1 and 26 months in group 2, there were 34 (15.2%)
endoleaks in group 1 versus 4 (2.2%) in group 2 (p,0.0001). The incidence of type II
endoleak was 0.25/100 person-months for group 1 versus 0.07/100 person-months for
group 2. The preventive sac thrombization technique was significantly associated with a
reduced risk of type II endoleak (HR 0.13, 95% CI 0.05 to 0.36; p,0.0001) regardless of the
type of stent-graft fixation (infrarenal versus suprarenal).
Conclusion: The preventive method of intrasac ‘‘thrombization‘‘ using fibrin glue injection
with or without the insertion of coils proves to be a simple, low cost, safe, and effective
technique to significantly reduce the risk of type II endoleaks irrespective of the endograft used.
J Endovasc Ther. 2010;17:517–524
Key words: abdominal aortic aneurysm, endovascular aneurysm repair, type II endoleak,
microcoils, fibrin glue, sac thrombosis
¤ ¤
Endovascular aneurysm repair (EVAR) is used
increasingly to treat abdominal aortic aneu-
rysm (AAA) in patients with suitable anatomy.
See commentary page 525
This less invasive technique has been estab-
lished as a safe and effective method of short-
term aneurysm exclusion, but the surveil-
lance program is still debated. Nevertheless,
unique mid- and long-term graft-specific
The authors have no commercial, proprietary, or financial interest in any products or companies described in this article.
Address for correspondence and reprints: Salvatore Ronsivalle, MD, Department of Cardiovascular Disease, Vascular
Surgery and Angiology, Cittadella Hospital, Via Riva dell’Ospedale, 35013 Cittadella, Padua, Italy. E-mail: vascolare_cit@
ulss15.pd.it
J ENDOVASC THER
2010;17:517–524 517
ß 2010 by the INTERNATIONAL SOCIETY OF ENDOVASCULAR SPECIALISTS Available at www.jevt.org

2. complications related to EVAR continue to
present management dilemmas for clinicians.
Principal among these adverse events is the
presence of a type II endoleak, which occurs
at some interval after EVAR in 20% to 30% of
patients.1,2
Type II endoleak, the most common se-
quelae of the EVAR procedure, is due to
partial or incomplete thrombosis of the
aneurysm sac after successful aneurysm
exclusion in conjunction with retrograde
perfusion from aortic collateral branches
(lumbar, inferior mesenteric, sacral, and renal
accessory arteries). The treatment approach-
es to types I and III endoleak are well
established, while the management of type
II is still a matter of debate. A conservative
approach is usually used when there is
gradual sac shrinkage, although its impact on
long-term outcome after EVAR is still un-
known.3–5
On the other hand, aneurysm sac
enlargement within 6 to 12 months calls for
more aggressive techniques, such as percuta-
neous transarterial or direct translumbar em-
bolization with microcoils or liquid embolic
agents, laparoscopic retroperitoneal branch
ligation, or endoscopic aneurysm sac fenes-
tration.6–16
These procedures seldom resolve
the problem, and the best results are achieved
with open surgery, which is therefore the most
appropriate choice in most cases.
The natural history of a type II endoleak led
us to believe that prevention is the best
strategy in managing this complication. In
2003, we began stimulating and accelerating
complete aneurysm sac thrombosis by intro-
ducing biocompatible materials during EVAR,
primarily fibrin glue.14,15
Several years later,
we introduced microcoils along with the
fibrin glue to stabilize the sac in a process
we now call ‘‘thrombization.’’ The aim of this
study was to evaluate the effect that thrombi-
zation of the aneurysm sac has on the risk of
type II endoleak compared to the standard
EVAR technique alone.
METHODS
Study Design
This observational retrospective study was
designed to encompass all consecutive pa-
tients who underwent EVAR for AAA at our
institution from September 1999 to December
2008 and had at least 1-year follow-up
imaging. A contrast-enhanced helical com-
puted tomography scan with 2.5-mm cuts
was used preoperatively to determine if a
patient met the radiological criteria for stent-
graft repair based on the manufacturer’s
Instructions for Use. Five different stent-graft
designs were used in the study period: Talent,
AneuRx, and Endurant (Medtronic CardioVas-
cular, Santa Rosa, CA, USA); Excluder (W.L.
Gore & Associates, Inc. Flagstaff, AZ, USA);
and Anaconda (Vascutek, a Terumo Compa-
ny, Inchinnan, Scotland, UK). The follow-up
protocol included a color duplex ultrasound
(CDU) scan at discharge; at 3, 6, and
12 months; and at 6-month intervals thereaf-
ter. Abdominal radiography was also per-
formed at discharge and a year later. A CT
scan was scheduled at 6 months.
At the end of the observation period, all
imaging tests were collected and separately
viewed in a double-blinded manner by 2
EVAR experts (a vascular surgeon and an
interventional cardiologist). The size of the
aneurysm sac and the presence and type of
endoleak were evaluated. In accordance with
current standard reports for EVAR,17
primary
clinical success was defined as absence of
aneurysm-related death, aneurysm rupture,
conversion to open surgery, and secondary
endovascular or surgical procedures. Assist-
ed primary and secondary clinical success
were applicable when success was achieved
with additional endovascular or surgical pro-
cedures, respectively.
Fibrin Sealant
Fibrin glue (Tisseel/Tissucol; Baxter-Hyland
Immuno AG, Vienna, Austria) is a fully
absorbable biological adhesive matrix with-
out cytotoxic effects made from a fibrinogen
solution containing plasma proteins and
factor XIII and a thrombin solution containing
calcium chloride and aprotinin. These com-
ponents are commercially prepared from
human plasma, except for aprotinin, which
is extracted from bovine lung. When mixed
together, the 2 solutions recreate the final
phase of the natural coagulation cascade
518 ANEURYSM SAC STABILIZATION IN EVAR
Ronsivalle et al.
J ENDOVASC THER
2010;17:517–524

3. forming a structured fibrin clot similar to the
physiological clot, susceptible to fibrinolytic
degradation by proteolytic enzymes such as
plasmin.18
Over the last 3 decades, fibrin glue
has been used extensively by surgeons.19,20
Fibrin glue does not interfere with magnetic
resonance imaging (MRI), CT, or CDU. The
required dose of sealant to cover 40 cm2
or
3.5 cm3
is about 5 mL; however, its use in
aneurysm sac embolization is an off-label
indication. In Italy, 5 mL of Tissucol costs 435
euros (,US$565).
Coils
MReye embolization coils (IMWCE 35-20-
20; Cook Medical, Bloomington, IN, USA) are
made of a radiopaque nickel and cobalt alloy
(inconel) that allows the use of MRI without
altering CT or CDU imaging. Most commonly
utilized in arterial and venous embolization,
these coils exert a greater radial strength than
platinum coils; they are introduced through
0.035- or 0.038-inch catheters. In Italy, one coil
costs 48 euros (,US$62).
Thrombization Technique
After deployment of the main stent-graft
component with its contralateral iliac exten-
sion, the angiographic pigtail catheter is
withdrawn, leaving a 180-cm-long 0.035-inch
standard J guidewire between the endograft
and the native aorta. A 23- to 35-cm-long 5-F
Brite Tip introducer (Cordis, a Johnson &
Johnson company, Miami Lakes, FL, USA) is
then fed through the standard guidewire
under fluoroscopic monitoring and released
into the desired position inside the aneurysm
sac. After the guidewire and 5-F cannula have
been removed, an aneurysmogram is per-
formed by manually injecting 10 mL of
contrast into the sac to identify the number
and site of lumbar and inferior mesenteric
arteries. One or more MReye embolization
coils are then advanced into the sac through
the 5-F dilator and released by advancing the
0.035-inch J guidewire inside the dilator
toward the end of the introducer sheath. A
25- to 35-cm-long Duplocath catheter (Baxter
International) inserted on a Duploject syringe
clip (Baxter International) is fed into the
introducer until it reaches the aneurysm sac.
Then a latex balloon is inflated into the distal
end of the iliac graft extension so as to
prevent distal embolization of the fibrin glue.
With the balloon inflated, 2.5 mL of each
fibrin glue solution are simultaneously inject-
ed into the sac through a 2-way catheter; a
second injection with the same amount can
be done if necessary. After the Duplocath
catheter is removed, an aneurysmogram is
performed to verify sac thrombization with
root occlusion of the lumbar and inferior
mesenteric arteries. The Brite Tip introducer
is then removed, and the completion angio-
gram is performed (Fig. 1).
Patient Sample
During the study period, 469 patients
underwent temporally sequential EVAR
techniques. From September 1999 to May
2003, 224 patients (210 men; mean age
71.968.5 years, range 25–88) had standard
EVAR. From June 2003 to December 2006, 124
patients (114 men; mean age 73.268 years,
range 51–89) underwent EVAR with preven-
tive fibrin glue intrasac thrombization. Finally,
from January 2007 to December 2008, 121
patients (110 men; mean age 71.767 years,
range 46–88) underwent EVAR with enhanced
preventive intrasac thrombization featuring
insertion of $1 microcoils followed by a fibrin
Figure 1 ¤(A) Control CT with visible inconel
(radiopaque nickel and cobalt alloy) coils and (B)
final aneurysmogram performed to verify sac
thrombization, with occlusion of lumbar and
inferior mesenteric arteries.
J ENDOVASC THER
2010;17:517–524
ANEURYSM SAC STABILIZATION IN EVAR 519
Ronsivalle et al.

4. glue injection to achieve better aneurysm sac
stabilization.
Patients who did not meet the criteria for
study inclusion were censored at the end of
2007, along with those who died or were lost
to follow-up. Thus, 65 patients were excluded
owing to lack of 1-year follow-up due to death
or loss to follow-up, leaving 404 patients
eligible for the study. For purposes of analy-
sis, the 224 patients undergoing EVAR alone
(Table 1) were compared to the 180-patient
cohort (161 men; mean age 72.668 years,
range 46–89) who had either form of throm-
bization.
Statistical Analysis
Continuous data are presented as the mean
6 standard deviation or the median for
nonparametric data; categorical data are
given as counts (percentages). Time to iden-
tification of a type II endoleak was the primary
outcome in the study: freedom from endoleak
was estimated with Kaplan-Meier analysis
from the date of surgery/intervention to the
date at which type II endoleak was diagnosed.
The log-rank test was used to compare the
outcomes in patients with and without sac
thrombization. Cox proportional hazard mod-
eling was used to examine the risk of type II
endoleak between the 2 groups after adjust-
ing for potential confounders [age, gender,
smoking habit, family history of AAA, chronic
renal failure, carotid artery disease, peripheral
artery disease, obesity (body mass index
.30 kg/m2
), hypertension, cardiac disease,
hyperlipidemia, stent-graft type, aneurysm
diameter, aneurysm length, neck diameter,
neck length, and number/size of patent lum-
bar and inferior mesenteric arteries]. Out-
comes of the model are given as the hazard
ratio (HR) and the 95% confidence intervals
(CI). Statistical analysis was performed with
Stata software (version 8.2; Stata Corpora-
tion, College Station, TX, USA).
RESULTS
Both groups were homogeneous for all
anatomical parameters assessed (Table 2;
sac and neck size, diameter of the iliac
arteries, and number of sacral and/or renal
accessory arteries). Mean AAA diameter was
58.1613.1 mm in the EVAR-only patients
(group 1) and 58.2614.1 mm in the EVAR +
thrombization patients (group 2). The patients
with suprarenal fixation of the main stent-
graft (Talent, Endurant) were homogeneous
for all anatomical parameters with patients
receiving infrarenally fixed stent-grafts (An-
euRx, Excluder, Anaconda; Table 3). Patients
had an average of 3 to 4 patent lumbar
arteries.
Endoleak Analysis
Over median follow-up times of 72 months
in group 1 and 26 months in group 2
(composite 19,065 months of follow-up after
surgery), there were 38 episodes of type II
endoleak: 34 (15.2%) in group 1 and 4 (2.2%)
in group 2. Half of the type II endoleaks in
group 1 arose within the first month of follow-
up. Among the 34 type II endoleaks detected,
16 (47%) resolved spontaneously, 3 (9%) were
treated with open surgery (complete conver-
sion) after failed transarterial embolization, 1
(3%) underwent surgical ligation of a lumbar
¤ ¤
TABLE 1
Baseline Characteristics of the Study Cohort
EVAR Alone
(n5224)
EVAR + Thrombi-
zation (n5180) p
Men 210 (93.7%) 161 (89.4%) 0.116
Age, y 71.968.5 72.668 0.385
Smoking 51 (22.7%) 19 (10.5%) 0.001
Family history of
AAA 2 (0.8%) 1 (0.5%) 0.695
Chronic renal
failure 54 (24.1%) 38 (21.1%) 0.475
Carotid artery
disease 88 (39.2%) 103 (57.2%) ,0.001
Peripheral artery
disease 80 (35.7%) 24 (13.3%) ,0.001
BMI .30 kg/m2
47 (20.9%) 41 (22.7%) 0.664
Hypertension 190 (84.8%) 172 (95.5%) ,0.001
Cardiac disease 125 (55.8%) 130 (72.2%) 0.001
Diabetes
mellitus 40 (17.8%) 26 (14.4%) 0.356
Hyperlipidemia 150 (66.9%) 158 (87.7%) ,0.001
¤ ¤
Continuous data are presented as means 6
standard deviation; categorical data are given as
counts (percentages).
EVAR: endovascular aneurysm repair, AAA: ab-
dominal aortic aneurysm, BMI: body mass index.
520 ANEURYSM SAC STABILIZATION IN EVAR
Ronsivalle et al.
J ENDOVASC THER
2010;17:517–524

5. artery (semi-conversion), 4 (12%) were un-
available for follow-up, and 10 (29%) were
stable at follow-up. All patients having been
treated with transarterial embolization of the
collateral aortic arteries with a negative
outcome underwent open surgery. Of the 4
type II endoleaks in the EVAR + thrombization
group (all occurring after 1 month), 1 resolved
spontaneously, 1 was unavailable for follow-
up, and 2 were stable. The reduction in sac
diameters averaged 5 mm in both groups
(p5NS).
The incidence of type II endoleak was 0.25/
100 person-months for the EVAR-alone group
and 0.07/100 person-months for the EVAR +
thrombization group. The Kaplan-Meier anal-
ysis (Fig. 2) showed significantly better
(p,0.0001) freedom from type II endoleak in
the EVAR + thrombization group. In the
hazard model, preventive sac thrombization
was shown to significantly reduce the risk of
type II endoleak (HR 0.13, 95% CI 0.05 to 0.36;
p,0.0001). Among the other factors analyzed,
only female gender (HR 0.32, 95% CI 0.14 to
0.74; p50.007) and obesity (HR 0.10, 95% CI
¤ ¤
TABLE 2
Anatomical Parameters for the EVAR Alone Versus
EVAR + Thrombization Groups
EVAR
Alone
EVAR +
Thrombization p
AAA
Diameter, mm 58.1613.1 58.2614.1 0.949
Length, mm 70.9625.1 69.0622.3 0.432
Neck
Diameter, mm 23.162.7 23.462.9 0.299
Length, mm 27.3610.9 27.7612.8 0.734
Right CIA 15.566.8 17.1610.6 0.089
Left CIA 17.1610.2 15.766.1 0.079
¤ ¤
Data are presented as means 6 standard devia-
tion.
EVAR: endovascular aneurysm repair, AAA: ab-
dominal aortic aneurysm, CIA: common iliac
artery.
¤ ¤
TABLE 3
Anatomical Parameters for the EVAR Alone Versus EVAR + Thrombization Groups
According to the Level of Stent-Graft Fixation
Suprarenal Fixation Infrarenal Fixation
EVAR Alone
EVAR +
Thrombization EVAR Alone
EVAR +
Thrombization
AAA
Diameter, mm 60.7612.6 59.1614.0 52.9612.5 55.4614.4
Length, mm 71.1626.4 69.6622.7 70.4622.5 67.2621.1
Neck
Diameter, mm 23.562.7 23.762.9 22.462.6 22.462.6
Length, mm 27.069.8 26.5612.4 28.0612.9 31.7613.3
Right CIA 15.466.4 17.3611.7 15.867.5 16.466.2
Left CIA 17.6610.9 15.665.8 16.268.6 15.867.0
¤ ¤
Data are presented as means 6 standard deviation.
EVAR: endovascular aneurysm repair, AAA: abdominal aortic aneurysm, CIA: common iliac artery.
Figure 2 ¤The Kaplan-Meier analysis comparing
the freedom from type II endoleak for the 2
treatment groups. Numbers under the curves
represent the patients at risk at each time interval.
Standard error #10% up to 113 months.
J ENDOVASC THER
2010;17:517–524
ANEURYSM SAC STABILIZATION IN EVAR 521
Ronsivalle et al.

6. 0.01 to 0.73; p50.023) were independently
associated with type II endoleak.
Late Complications
In group 1, 6 (2.6%) patients presented with
late type Ia endoleak. Five were treated with
surgical conversion and 1 had additional cuff
implantation. Six (2.6%) patients in this
subgroup developed type Ib endoleak and
received an iliac extension. One (0.4%) patient
had a type III endoleak that was treated with
additional cuff implantation. Three (1.3%)
patients developed a partial graft limb throm-
bosis that was treated with angioplasty
accompanied by stenting in 2 and by addi-
tional iliac cuff implantation in the third. Nine
(4%) patients had graft limb occlusion; 4
underwent femorofemoral bypass, 4 were
stable at regular follow-up, and the last
patient was not available for follow-up. One
(0.4%) patient developed acute renal failure
due to partial renal artery occlusion, which
was treated by stenting.
In group 2 patients, 2 (1.1%) type Ia
endoleaks were detected; 1 was treated with
open surgery and the other with an additional
cuff implantation. Four (2%) type Ib endoleaks
were resolved by iliac extension. There were 3
(1.6%) partial graft limb thromboses treated
with stent insertion in 2 and iliac cuff
implantation in the other. Three (1.6%) graft
limb occlusions required femorofemoral by-
pass crossover in 2 (the other is stable). Two
(1.1%) cases of acute renal failure due to
partial renal artery occlusion were identified;
1 was treated with stenting and the other
underwent surgical conversion. There was
also 1 (0.5%) case of colon ischemia that was
treated with partial colon resection.
There were no signs of allergic, anaphylac-
tic, or tissue reaction to the microcoils or
fibrin glue in any patient during the follow-up
period.
Survival Analysis
In group 1, 21 (9%) patients died of multiple
causes at a median follow-up of 24 months,
whereas 20 (9%) patients were lost to follow-
up at a median 12 months. In group 2, 20
(11%) patients died of multiple causes at a
median follow-up of 12 months and 14 (8%)
patients were lost at a mean follow-up of
11 months. There were no statistically signif-
icant differences (p.0.05) in the all-cause
mortality rates between group 1 (10.7%) and
group 2 (11.1%).
DISCUSSION
Type II endoleak represents the most frequent
form of endoleak after EVAR. Several treat-
ment options are available for the manage-
ment of type II endoleak. A few of these, for
example, transarterial chemical or coil embo-
lization, as well as translumbar sac emboliza-
tion, have been well described in the litera-
ture.6–11
Laparoscopic or open ligation of
feeding vessels has also been advocated as a
potential option.12
However, the success of
these techniques varies widely. Baum et al.10
compared transarterial coil embolization with
translumbar embolization: transarterial treat-
ment had an 80% failure rate, while 92% of
cases were treated successfully with translum-
bar embolization. Timaran et al.21
had similar
results in catheter-based treatment of persis-
tent endoleaks: a transfemoral approach
achieved only a 38% success rate, although a
71% success rate was noted with a translumbar
approach. Muthu et al.22
tried a branch vessel
management strategy consisting of routine
intraoperative embolization of all patent mes-
enteric arteries, but there were no significant
differences in the incidence of type II endoleak
rate between the pre-protocol group compared
with the post-protocol group. Evidently, inferi-
or mesenteric artery (IMA) embolization does
not avoid type II endoleak, which can develop
in the setting of chronic IMA occlusion.
Most of the treatment techniques that are
available for type II endoleak seldom solve
this problem once present; hence, we believe
that the best strategy is prevention. Our
experience indicates a 13% lower risk of type
II endoleak in patients who received intrasac
thrombization during EVAR either with fibrin
glue alone or with combined inconel coils and
fibrin glue compared to patients having
undergone standard EVAR alone.
In the thrombization technique, biomateri-
als used for intrasac embolization are inserted
between the main stent-graft and aneurysm
522 ANEURYSM SAC STABILIZATION IN EVAR
Ronsivalle et al.
J ENDOVASC THER
2010;17:517–524

7. wall as a means of forming a scaffold. The
addition of a fibrin sealant accelerates and
consolidates clot formation into a concretion,
resulting in a durable, long-lasting, sturdy
stabilization of the entire complex en bloc.
Centripetal backflow inside aortic collateral
branches reduces the risk of peripheral micro-
embolization during the procedure. In our
cohort, fibrin glue injections did not cause
any allergic or anaphylactic reactions nor
were there any intra- or perisac tissue reac-
tions when using fibrin glue. The addition of
preventive sac thrombization adds ,US$630
to the total cost of the EVAR procedure, which
is far less that the time and resources needed
to follow type II endoleaks and treat those that
persist.
In addition to documenting the type II
endoleak risk reduction potential of our
preventive strategy, Cox proportional hazard
modeling identified only gender and obesity
as factors associated with type II endoleak.
Indeed, more than a third (36%) of the women
in group 1 developed a type II endoleak and
11% in group 2. However, identification of
positive predictive factors for type II endoleak
was not an endpoint of this study. The
prognostic role of gender and obesity (as
well as other variables) might be considered
in future studies.
Limitations
This study was limited because it was
observational and nonrandomized; nonethe-
less, the results were positive. The EVAR
procedures without thrombization were all
performed before 2004, and although some
studies23,24
have indicated that the more
experienced the operator or center the better
the patient outcome, Shackley et al.23
docu-
mented an unchanged endoleak rate based
on patient volume in their review. Further, all
interventions in the study period (1999–2008)
were performed by the same primary surgeon
together with the same interventional cardi-
ologist; both had passed the EVAR learning
curve before the 1999 start date.
The EVAR procedures with thrombization
actually consisted of 2 groups of patients:
those who received only fibrin glue and those
who received fibrin glue and coils. Therefore,
it is unclear which technique resulted in
endoleak reduction.
Conclusion
The natural history of a type II endoleak
leads us to consider that prevention is the
best strategy to manage this complication.
Intrasac thrombization performed during
EVAR, with coil insertion followed by fibrin
glue injection, seems to be a quick, money-
saving, and safe technique, regardless of the
stent-graft used. It is effective in demonstrat-
ing a significant reduction of type II endoleak
incidence without complications, thereby in-
creasing EVAR success and reducing the need
of a close follow-up.
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