Ablation of the great saphenous vein with nontumescentn-butyl cyanoacrylate versus endovenous laser therapy_
IsmailKoramaz, MD,a Helin El Kılıç, MD,a Fatih Gökalp, MD,a Macit Bitargil, MD,a Nilüfer Bektaş, MD,aErsoy Engin, MD,a Mehmet Taşkın Egici, MD,b and Ahmet Kürşat Bozkurt, MD,c Istanbul, Turkey

ABSTRACT
Objective: The endovenous application of n-butyl cyanoacrylate (NBCA) is a new nontumescent ablation technique forthe treatment of venous insufﬁciency. The aim of this study was to retrospectively compare an NBCA-based ablation
method with endovenous laser ablation (EVLA) for the management of incompetent great saphenous veins.
Methods: Between May 2013 and August 2014, there were 339 patients with incompetent varicose veins who were treatedwith either the endovenous application of NBCA (VariClose Vein Sealing System [VVSS]; Biolas, Ankara, Turkey) or EVLA.
The preprocedural, intraprocedural, postprocedural, and follow-up data of the patients were collected and retrospectively compared.
Results: The mean age was 45.09 6 12 years in the VVSS group and 47.08 6 11 years in the EVLA group (P ¼ .113). The averageablated vein length was 31.97 6 6.83 cm in the VVSS group and 31.65 6 6.25 cm in the EVLA group (P ¼ .97). The averagetumescent anesthesia use was 300 mL (range, 60-600 mL) in the EVLA group. The average procedure time was 7 minutes(range, 4-11 minutes) in the VVSS group and 18 minutes (range, 14-25 minutes) in the EVLA group (P < .01). On the basis ofultrasound examinations performed at the end of the procedure, all procedures in both groups were successful, and thetarget vein segments were fully occluded. The 12-month total occlusion rates in the VVSS and EVLA groups were 98.6% and97.3%, respectively (P ¼ .65). In both the VVSS and EVLA groups, the Venous Clinical Severity Score declined signiﬁcantlywith no difference between groups. There were fewer adverse events after VVSS treatment compared with EVLA treatment(pigmentation, P # .002; phlebitis, P # .015). There was no need for tumescent anesthesia in the VVSS group.
Conclusions: The NBCA-based vein sealing system is a fast and effective treatment option for the management ofincompetent saphenous veins that does not involve tumescent anesthesia, compression stockings, paresthesia, burnmarks, or pigmentation. Further large-scale studies with long-term outcomes are required to identify the optimaltreatment modalities for patients with saphenous vein insufﬁciency. (J Vasc Surg: Venous and Lym Dis 2017;5:210-5.)

Chronic venous insufﬁciency with the resultant varicose
veins is an important entity that is responsible for substantial morbidity. Lower limbs can manifest a range ofsigns that include edema, pigmentation, and venous
ulcers.1 The treatment of venous insufﬁciency haschanged dramatically during the past decade. Conventional methods have been replaced by interventionalmodern methods, and new technologies are being introduced every year. Conventional methods, such as ligationand stripping, are associated with complications,
including hematoma and paresthesia, and are perceived

From the Department of Cardiovascular Surgerya and Department of Family
Medicine,b Şişli Hamidiye Etfal Research and Training Hospital; and theDepartment of Cardiovascular Surgery, Cerrahpaşa Medical Faculty, Istanbul
University.c
Author conﬂict of interest: none.
Correspondence: Macit Bitargil, Department of Cardiovascular Surgery, Şişli
Hamidiye Etfal Research and Training Hospital, Istanbul 34371, Turkey(e-mail: mctbtr@hotmail.com).
The editors and reviewers of this article have no relevant ﬁnancial relationships todisclose per the Journal policy that requires reviewers to decline review of any
manuscript for which they may have a conﬂict of interest.
2213-333X
Copyright Ó 2016 The Authors. Published by Elsevier Inc. on behalf of the Society for Vascular Surgery. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
http://dx.doi.org/10.1016/j.jvsv.2016.09.007

210

as risky and disﬁguring.2 The long recovery times associated with conventional methods are decreasing the
popularity of these methods.3
Foam sclerotherapy is the most commonly used minimally invasive technique for the treatment of varicose
veins worldwide, but it is plagued with high recurrence
rates.4 Adverse effects, such as air embolism, headache,pulmonary embolism, and deep venous thrombosis(DVT), are substantial disadvantages of this treatment.4
Endovascular ablation techniques, such as laser andradiofrequency ablation, are widely used and proventreatments. The procedural techniques and methodologies differ between these two techniques, but the results
are fundamentally similar, and both achieve nearly 90%
long-term success rates.5,6 Although thermal ablation
represents a breakthrough that is associated with fewer
complications, the need for tumescent anesthesia andthe occurrence of adverse events such as burns, pigmentation. and paresthesia are unavoidable downsides.5-7
Although the current techniques are successful, thesearch for new innovative techniques is rapidly intensifying with the goals of increasing the success rate,
improving the patient’s quality of life, and reducing thepotential complications. A new technique for veinablation has recently been developed that involves
the endovenous application of n-butyl cyanoacrylate

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Volume 5, Number 2(NBCA) and does not require the use of tumescentanesthesia. Although approved in the European Union,
it is not approved for use in the United States. In addition, the results of a 2-year trial of the cyanoacrylate
embolization of incompetent great saphenous veins(GSVs) were published.8 During endovenous application, NBCA rapidly solidiﬁes and creates a rapid polymerization reaction. This reaction creates aninﬂammatory effect on the vein wall that induces anablative reaction. On injection into a vein, a compress
over the vein seals the vessel by polymerization.8-10
The aims of this study were to present our experience
with this new nontumescent ablation method, tocompare this experience with laser ablation, and topresent both anatomic and clinical results of our 12month follow-up.

METHODS
Study design
The study was a purely retrospective review of therecord. Here we present the results of 150 patientstreated with the endovenous application of NBCA
(VariClose Vein Sealing System [VVSS]; Biolas, Ankara,
Turkey) and 189 patients treated with 1470-nm endovenous laser ablation (EVLA; Evlas Circular Fiber, Biolas).
Between May 2013 and May 2014, there were 202
patients initially treated with EVLA; then between April
2014 and August 2014, there were 166 patients treatedwith VVSS. All patients who had full follow-up wereselected for comparison. The full follow-up groups consisted of 150 patients in the VVSS group and 189 patientsin the EVLA group. The follow-up interval was 1 year.
The primary indications for the procedures were a GSV
diameter >5.5 mm (2-3 cm distal to the saphenofemoral
junction [SFJ]) with venous reﬂux lasting for >0.5 second.
All patients were symptomatic. All patients were treatedwith either ablation of the GSV or endovenous application of NBCA. The remaining reﬂuxing tributaries weretreated with microphlebectomy at the same session.
There was no concurrent treatment of the small saphenous vein or anterior accessory saphenous vein. The
inclusion and exclusion criteria are listed in Table I. The
patients’ histories and physical examination ﬁndings
and color Doppler ultrasound (CDUS) results were notedin the primary evaluation. The preoperative clinicaldisease severity was graded according to the Clinical,
Etiology, Anatomy, and Pathophysiology (CEAP) classiﬁcation, and the clinical ﬁndings were assessed with the
Venous Clinical Severity Score (VCSS). As a retrospective
study, consent of the patients and Institutional Review
Board approval were waived by our institution.
Procedural protocols
Endovenous application of NBCA. The disposable
VVSS includes 3 mL of VariClose NBCA and the VariClose
Delivery System (VDS).The GSV was accessed with a 6F

ARTICLE HIGHLIGHTS
d

d

d

d

d

d

Signiﬁcance: Saphenous ablation using n-butyl
cyanoacrylate (NBCA) is a new, minimally invasive
intervention that does not require use of tumescentanesthesia or compression.
Type of Research: Retrospective nonrandomized
analytical study of 339 patients treated for varicose
veins.
Take Home Message: Great saphenous vein ablation
using NBCA was as effective as endovenous laser
therapy at achieving vein closure and improving
clinical outcome at 12 months.
Recommendation: The authors suggest thatsaphenous ablation with NBCA, without tumescentanesthesia, is as effective as endovenous laser
ablation at 1 year after intervention.
Strength of Recommendation: 2. Weak.
Level of Evidence: B. Low or very low.

introducer set with the assistance of CDUS. A 0.035inch  150-cm guidewire was sent through the 6F
introducer sheath to the SFJ. Once the guidewire was
conﬁrmed to be in the SFJ by CDUS, a 5F long introducer
sheath was advanced to the SFJ over the guidewire. After
conﬁrmation of the position of the long introducer
sheath at the beginning of the SFJ, the long introducer
sheath was pulled back from the SFJ by 6 cm. The sheath
was pulled back by 6 cm because the 4F delivery
catheter’s tip comes out of the long introducer sheath by
3 cm. Thus, the 4F delivery catheter had to be positioned
3 cm distal to the SFJ. Once the position of the 4F delivery catheter was conﬁrmed, the NBCA injection setup
was complete. A VDS gun and adaptor were connectedto each other, and 2 mL of the 3 mL of the NBCA wereaspirated into the injector. The injector was connected to
the gun adaptor and the end of the delivery catheter by
a spin lock mechanism.
After setup and positioning of the VDS were complete,
the procedure began. First, pressure over the SFJ wasapplied with CDUS, and closure of the SFJ was
conﬁrmed. Before the injection of NBCA inside the vein
lumen, the delivery catheter was primed. One trigger
push was applied for 1 second to prime the delivery catheter. After priming, the trigger was pushed again for
5 seconds, and this time, the delivery catheter was pulledback at 2 cm/s. The VDS was set up for the injection of
0.03 mL of NBCA per centimeter. Continuous pressure
was applied over the target vein segment simultaneouslywith the pulling back of the delivery catheter by the
CDUS probe without releasing the pressure from the
SFJ. Every 5 seconds or 10 cm, the trigger had to bepressed. This trigger-pressing and pressure application
routine was performed continuously until the target
vein segment was fully sealed. Once the entire vein

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Table I. Study eligibility criteria
Inclusion criteria
1.

Age $20 years and #70 years

2.

Vein diameter at the GSV $5.5 mm and #15 mm

3.

Reﬂux in GSV >0.5 second

4.

CEAP classiﬁcation between C2 and C5

5.

Patients attended the follow-up examinations

6.

Patients were sufﬁciently mentally healthy toconsent to the operation

Exclusion criteria
1.

Tortuous GSV

2.

Symptomatic peripheral arterial disease history
or an ABI <0.9

3.

History of DVT or PE

4.

Life expectancy <2 years

5.

Active thrombophlebitis in the deep orsuperﬁcial veins

6.

Signiﬁcant femoral or popliteal venous
insufﬁciency and perforator vein insufﬁciency

7.

Known sensitivity to cyanoacrylate adhesives

8.

Aneurysm >15 mm in the target vein

9.

Previously treated GSV

10.

Existence of malignant disease

11.

Pregnancy

12.

Immobilization

ABI, Ankle-brachial index; CEAP, Clinical, Etiology, Anatomy, andPathophysiology classiﬁcation; DVT, deep venous thrombosis; GSV,
great saphenous vein; PE, pulmonary embolism.

segment was injected with NBCA with the continued
application of pressure during the procedure, a ﬁnal
pressure was applied for 30 seconds over the entire
target vein segment.
EVLA. The suitability for EVLA was assessed in the preoperative evaluation. The disposable Biolas Evlas Circular
Fiber EVLA kit consisted of 600 mm of radially extending
ﬁber that functioned at a wavelength of 1470 nm withthe 6F introducer kit. The GSV access was achieved
with the 6F introducer kit under the assistance ofCDUS. The laser ﬁber was advanced through the sheath
to 0.5 cm distal to the superﬁcial epigastric vein. Conﬁrmation of the ﬁber’s position was achieved on the basisof both CDUS and the laser light beam. After conﬁrmation, tumescent anesthesia was applied around the tissue surrounding the GSV. Thermal laser energy wasapplied from the SFJ to the access point at 10 J/mm
(ie, 10 J of energy per millimeter of the diameter), andthe apparatus was slowly pulled back. During the pullback, pressure was applied over the vein to increase
the obliteration of the vein.
Deﬁnitions of adverse events
Patients with reddening of the skin area involving 20%
or more of the treated part or blistered skin involving
20% or less of the treated area were regarded as havingskin burn. Patients without pain and with tolerable pain
requiring no additional analgesics were regarded as having no pain, and those requiring additional analgesics or
topical cooling or those in whom pain affected their activities of daily life were regarded as having pain. Patientswith speciﬁc color or darker bruising involving 20% ormore of the treated area or those with markedly darkbruising involving 20% or less of the treated area wereregarded as having bruising. Patients with numbness ortingling sensation of the treated area were regarded ashaving paresthesia.
Postprocedural management
The NBCA patients were mobilized after the treatment
without any prescription of compression stockings. The
laser group patients were prescribed class II compression
stockings (thigh high) for 2 weeks after the treatment. All
patients underwent physical examinations and CDUS
control before and after the procedure and at the ﬁrst
week and 6 and 12 months after treatment. CDUS controls at 6 and 12 months after treatment were done by
the radiology department, whereas ﬁrst-week controls
were performed in our clinic with CDUS by surgeons
who had CDUS course certiﬁcation.
Procedural success was deﬁned as complete occlusionof the treated vein segment or a partial recanalizationof <5 cm.8 Clinical recovery was assessed by comparing
the VCSS values before and after the procedures.
Statistics
The analyses were performed using the SPSS Statistics
for Windows, version 22.0 (IBM Corp, Armonk, NY). The
continuous data are presented as the mean 6 standard
deviation and median (minimum-maximum) values.
The comparisons between groups were performed withc2 and Fisher exact tests for categorical variables. As
the results of the Shapiro-Wilk test for normality showedthat the continuous variables were not distributed normally, the Mann-Whitney U test was used to compare
the groups and Wilcoxon rank sum test was performed
for the comparison within the groups. The P value <.05 was considered statistically signiﬁcant.

RESULTS
There were 339 successfully performed ablation procedures for GSV insufﬁciency. There was no bilaterally
handled patient in the same session. The VVSS groupconsisted of 74 men and 76 women (150 patients in total),
and the EVLA group consisted of 95 men and 94 women(189 patients in total). The mean ages were 45.09 6 12
years in the VVSS group and 47.08 6 11 years in the
EVLA group (P ¼ .11). The average preprocedural GSV diameters were 6.88 6 1.80 mm (range, 5.5-15 mm) in theVVSS group and 7.15 6 1.77 mm (range, 5.5-14 mm) in
the EVLA group (P ¼ .06). All patients were symptomatic.
The preprocedural CEAP classiﬁcations and demographic
and baseline characteristics are illustrated in Table II.

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Volume 5, Number 2

Table II. Demographics and baseline characteristics

treatment compared with EVLA treatment (pigmentation, P # .002; phlebitis, P # .015). There was no needfor tumescent anesthesia in the VVSS group.

Group
VVSS (n ¼ 150)

EVLA (n ¼ 189)

P

Male

74 (49.3)

95 (50.3).865a

Female76 (50.7)

94 (49.7)

Anatomic success. On the basis of the ultrasoundexaminations performed at the end of the procedures,
all of the procedures in both groups were successful,and the target vein segments were fully occluded. In
the ﬁrst week, one patient in the VVSS group experienced a partial recanalization >5 cm at the SFJ level
because of the lack of experience with the use of thedispensing gun. (This patient was our second patient,so we thought that might be because of lack of experience or the learning curve at that time.) In the
EVLA group, two patients exhibited partial recanalizations >5 cm at the SFJ level. At 6 months, one patientin the VVSS group presented with partial recanalizationof >5 cm at the mid-GSV level, whereas two patients
presented with total recanalization and one patientpresented with partial recanalization >5 cm in the EVLA
group. No additional recanalizations were observed at
the 12-month follow-up. Thus, the total 12-month occlusion rates were 98.6% and 97.3% in the VVSS and EVLA
groups, respectively (P ¼ .65).

Sex

CEAP class (preprocedural)
.788a

C2

20 (13.3)

C3

66 (44.0)

93 (49.2)

C4

54 (36.0)

64 (33.9)

C5

10 (6.7)

10 (5.3)

Age, years

45.09 6 12
(43 [20-70])

47.08 6 11
(46 [20-86])

.113b

VCSS

7.53 6 1.03
(7 [7-13])

7.73 6 1.58
(7 [7-13]).493b

GSV diameter,mm

6.88 6 1.80
(range, 15-5.5)(6.05 [4.6-16.0])

22 (11.6)

7.15 6 1.77.065b(range, 14-5.5)(6.70 [4.5-14.0])

CEAP, Clinical, Etiology, Anatomy, and Pathophysiology classiﬁcation;
EVLA, endovenous laser ablation; GSV, great saphenous vein; VCSS,
Venous Clinical Severity Score; VVSS, VariClose Vein Sealing System.
Categorical variables are presented as number (%). Continuous variables are presented as mean 6 standard deviation (median [minimum-maximum]).
a 2
c test.
b
Mann-Whitney U test.

The average ablated vein lengths were 31.97 6 6.83 cm
in the VVSS group and 31. 65 6 6.25 cm in the EVLA
group. The average tumescent anesthesia use was
300 mL (range, 60-600 mL) in the EVLA group. The
average procedure times were 7 minutes (range, 4-11
minutes) in the VVSS group and 18 minutes (range,
14-25 minutes) in the EVLA group (P < .01). The procedural characteristics are summarized in Table III. There
were fewer adverse events (Table IV) after VVSS

VCSS. The VCSS values were recorded at each followup and compared with the baseline values. The VCSS
declined from 7.53 6 1.03 to 2.79 6 1.05 (P < .001) in theVVSS group and from 7.73 6 1.58 to 2.83 6 1.21 (P < .001) inthe EVLA group, but there was no difference between
groups (Table III).
Adverse events. Adverse events (Table IV) were lessfrequent after VVSS treatment compared with EVLA
treatment for pigmentation (P ¼ .002) and phlebitis(P ¼ .015). The most important adverse events were pain
and phlebitis in the VVSS group, which occurred at rates

Table III. Procedure characteristics

GSV diameter, mm
Length of the ablated GVS, cm
Amount of tumescent anesthesia, mL

VVSS

EVLA

Pa

6.88 6 1.80 (range, 15-5.5)(6.05 [4.6-16.0])

7.15 6 1.77 (range, 14-5.5)(6.70 [4.5-14.0]).065

31.97 6 6.84
(30 [23-70])

31.64 6 6.26
(30 [23-70])

.974

d

300 (range, 60-600)

7 (range, 4-11)

18 (range, 14-25)<.001

Occlusion rate

148 (98.6)

184 (97.3).659

Pretreatment VCSS

7.53 6 1.03
(7 [7-13])

7.73 6 1.58
(7 [7-13]).493

Post-treatment VCSS

2.79 6 1.05
(2 [1-6])

2.83 6 1.21
(2 [2-6])

.882

<.001

<.001

Procedure duration, minutes

Pb

EVLA, Endovenous laser ablation; GSV, great saphenous vein; VCSS, Venous Clinical Severity Score; VVSS, VariClose Vein Sealing System.
Categorical variables are presented as number (%). Continuous variables are presented as mean 6 standard deviation (median [minimummaximum]) unless otherwise indicated.
aMann-Whitney U test.
b
Wilcoxon signed rank test.

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Table IV. Adverse eventsGroup
VVSS (n ¼ 150)

EVLA (n ¼ 189)

P

7 (4.7)17 (9.0)

.123a

Burns

d

4 (2.1).133b

Pigmentationd

11 (5.9).002b

Bruisingd5 (2.6).069b

Paresthesiad3 (1.6).258b

Phlebitis

3 (2.1)15 (7.9).015bd

3 (1.6).258b

Pain (ﬁrst week)

DVT

DVT, Deep venous thrombosis; EVLA, endovenous laser ablation; VVSS,
VariClose Vein Sealing System.
Values are reported as number (%).
a 2
c test.
b
Fisher exact test.

of 4.67% and 2%, respectively. Postoperative pain wasobserved at the SFJ or entry levels during the ﬁrst 3 days
(1-3 days). The patients with phlebitis fully recovered afteran average of 4 days (3-5 days).
In the EVLA group, 8.99% of the patients experienced
pain in the ﬁrst week and 5 days (4-7), and 2.12%, 5.82%,
and 2.65% of the patients experienced burning, pigmentation, and bruising, respectively, but these conditions
resolved by the 6-month follow-up. In 1.59% of thepatients, paresthesia was observed and resolved within
6 months. Phlebitis was observed and treated with 14
days of antibiotic (sulbactam-ampicillin) and nonsteroidal anti-inﬂammatory medications in 7.94% of the patients. DVT was diagnosed on the patient’s visit to our
outpatient clinic and radiologic CDUS conﬁrmation.
DVT was treated with anticoagulant medication(low-molecular-weight heparin) in 1.59% of the patients.
These DVTs dissolved in an average of 10 days (7-15days). All of them were endovenous heat-induced
thrombosis class 1. The adverse events are summarizedin Table IV.

DISCUSSION
The intravascular use of NBCA has a history of >20 years
in arteriovenous malformations and venous applicationsin other parts of the body. Study results have revealed
that on contact with intravascular tissue, NBCA rapidly
undergoes a polymerization reaction and begins to solidify.11,12 This polymerization creates an inﬂammatory effectover the vein wall. This inﬂammatory effect creates animmediate tensile force that is the ﬁrst stage of the polymerization process. The second stage consists of a stabletensile force, and the third stage is the ﬁnal polymerization during which bonding to the endothelium
occurs.13,14
Recent studies have reported promising results associated with the use of NBCA for the treatment of venous
insufﬁciency.8 Our results also conﬁrm earlier ﬁndings
regarding the use of NBCA in chronic venous disease.7-9This study revealed that the rate of complications after
NBCA use was signiﬁcantly lower than that of EVLA,
which are summarized in Table IV (pigmentation, phlebitis; P # .05). EVLA complications are generally causedby thermal effects, which supports the use of NBCA
because of the lower frequency of complications associated with this procedure. The closure rate after NBCA use
was as high as that of EVLA. Recent studies compared
EVLA, ultrasound-guided foam sclerotherapy, and conventional surgery for great saphenous varicose veinsand found that after 1 year, the anatomic success rate
was highest after EVLA (88.5%), followed by conventional
surgery (88.2%) and ultrasound-guided foam sclerotherapy (72.2%).15 Rasmussen et al reported that 5-year
follow-up of a randomized controlled trial comparing
EVLA with open surgery in patients with GSV incompetence did not show any signiﬁcant difference between
the two groups in primary or secondary end points.
EVLA seems to be a valid alternative to open surgery.11
Both treatment methods showed good safety proﬁles.
In a European multicenter cohort study, Proebstle et alreported a 98.6% immediate success rate.9 In a randomized trial comparing NBCA and radiofrequency ablation,
the NBCA closure rate was reported to be 100%,10
whereas we observed a closure rate of 98.6% at 12
months of follow-up. In the former report, the application and type of NBCA differed from those used in ourpresent study. The differences between these studies
included viscosity, application type, and initial positioning 5 cm away from the junction. The product that
we used in this study was a low-viscosity NBCA thatprovided immediate polymerization and a sealing effectin <5 seconds. This polymerization enabled rapid
procedures (the mean NBCA application time was 20
seconds). Because the delivery of NBCA was continuous
and without any pulsations or stops, each millimeter ofthe venous lumen was injected with a thin layer ofNBCA. The combination of this application method andthe low viscosity of the NBCA signiﬁcantly increased
the success rate (98.6%) and decreased the phlebitis
rate (2%) compared with the results from earlier
NBCA studies.
The rapid closure and minimal procedural time prevented DVT and pulmonary embolism. Because the
NBCA polymerized so quickly, the SFJ portion of
the GSV was rapidly closed, and the application of thecorrect amount of pressure over the SFJ reduced
the risk of media ﬂow into the deep vein. Moreover, theabsence of heat ensured that burn marks, pigmentation,and paresthesia did not occur. The fact that tumescentanesthesia is not required largely accounts for the
improved procedure time for VVSS compared with
EVLA (7 minutes for VVSS and 18 minutes for EVLA
[P # .01] in our study) and the patient’s comfort after
the procedure.9 The postoperative pain was slightly
decreased compared with EVLA. Moreover, the absence

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Journal of Vascular Surgery: Venous and Lymphatic Disorders215

Volume 5, Number 2of a need for compression stocking use improved the patients’ quality of life.
Morrison et al reported that adverse events were similar
between these groups. No severe procedure- or
device-related adverse events occurred in either group.
Device-related adverse events with cyanoacrylate
embolization were mostly cases of phlebitis of thetreated GSV. The difference might reﬂect the mechanism of action of the adhesive.10
This study has several limitations, including the retrospective nature of the analysis of a single database, therelatively small number of patients, and the lack of objective measures for evaluating the postinterventional painand discomfort. We also failed to stratify the patientson the basis of objective measures of reported varicose
veins or the quality of life before and after the procedures. We did not record data regarding the disappearance rates of varicose veins after the procedures. We
focused only on the closure rates of the techniques. In
addition to these limitations, our follow-up period was
too short, and data regarding the long-term efﬁcacy of
NBCA use are currently lacking.
Thus, the long-term success compared with other treatment options, such as surgery, remains to be assessed by
future studies. Furthermore, our study has the limitationthat the patients undergoing EVLA and VVSS were nottreated concurrently. Therefore, it is possible that the differences noted between the procedures (or lack of difference) may be confounded by unmeasured changes intechnique or follow-up care as the result of an evolutionof our experience in treating chronic venous insufﬁciency. In addition, the study was not sufﬁciently powered to be classiﬁed as a noninferiority study. Thismeans that the nonsigniﬁcant differences between treatment groups cannot be interpreted to mean that thetreatments are equivalent.

CONCLUSIONS
Current minimally invasive methods of ablating
the saphenous vein involve the use of thermal energy
and require the use of tumescent anesthesia and postoperative compression stockings. The NBCA-basedvein-sealing system has been suggested to be a viable
alternative method that does not involve the use oftumescent anesthesia or require the postoperative useof compression stockings and has a shorter procedure
time. Vein ablation rates and complication rates arecomparable to those of EVLA.

AUTHOR CONTRIBUTIONS
Conception and design: IK, HE, FG, MB, NB, EE, AB
Analysis and interpretation: IK, HE, FG, MB, NB, EE, AB
Data collection: IK, HE, FG, MB, NB, EE, AB
Writing the article: IK, HE, FG, MB, NB, EE, AB
Critical revision of the article: IK, HE, FG, MB, NB, EE, AB
Final approval of the article: IK, HE, FG, MB, NB, EE, ME, AB

Statistical analysis: ME
Obtained funding: Not applicable
Overall responsibility: MB

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Submitted May 12, 2016; accepted Sep 24, 2016.