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Endovenous laser ablation of great and small saphenous vein incompetence with a 1470-nm laser and radial fiber
Endovenous laser ablation of great and small saphenous vein incompetence with a 1470-nm laser and radial fiber Giorgio Spreafico, MD,a Andrea Piccioli, MD,a Enrico Bernardi, MD, PhD,b Enzo Giraldi, MD,a Patrizia Pavei, MD,a Riccardo Borgoni, PhD,c Attilio Nosadini, MD,a and Ugo Baccaglini, MD,a Padua, Pieve di Soligo, and Milan, Italy Objective: Endovenous laser ablation (EVLA) of great (GSV) and small saphenous vein (SSV) chronic insufficiency with 1470-nm diode laser and radial fiber yields good short-term results. The aim of this study was to assess its efficacy after at least 12 months of follow-up. Methods: We performed a prospective interventional cohort study in an ambulatory care/day surgery setting. Consecutive patients with chronic, symptomatic GSV or SSV insufficiency were treated by EVLA with a 1470-nm diode laser and a radial fiberoptic. Patients were recruited between 2008 and 2011, and the follow-up was completed in 2012. All patients underwent clinical and echo color Doppler evaluations during follow-up. The primary outcome was the incidence of echo color Dopplerconfirmed failures during follow-up. We also investigated potential associations between failures and patients’ characteristics, echo color Doppler findings, or surgical
features. The secondary outcome was the postoperative pain course. Results: The planned 12-month follow-up was completed in 372 patients. Echo color Doppler-confirmed failures occurred in 37 (12%) of 310 patients with GSV insufficiency, whereas none of 62 patients with SSV insufficiency experienced a failure. Multiple Cox proportional hazards regression analysis showed a significant association of failures with a Clinical, Etiologic, Anatomic, and Pathologic class C $4 and a mean confluence of the superficial inguinal veins diameter $9 mm in patients with GSV insufficiency. Postoperative pain course was favorable. More than two thirds of the patients were asymptomatic at 7 days. Conclusions: EVLA with 1470-nm diode laser and radial fiberoptic is effective for treatment of GSV and especially SSV insufficiency and is well tolerated by the patients. (J Vasc Surg: Venous and Lym Dis 2014;2:403-10.)
After the publication of the paper by Navarro et al in 2001, commonly regarded as the beginning of the endovenous laser ablation (EVLA) era, several laser wavelengths (810, 940, 980, 1320, 1470, and 1500 nm) and fiberoptics (bare, no-touch, radial) have been tested, aiming at improving the efficacy of the technique and the patients’ quality of life.1-9 The aim of this study was to assess the outcome of patients with great saphenous vein (GSV) and small saphenous vein (SSV) incompetence treated with a 1470-nm diode laser and a radial fiberoptic.
laser and radial fiber for treatment of GSV and SSV insufficiency. Patients were recruited between May 2008 and December 2011 at the Multidisciplinary Centre for Day Surgery, University Hospital of Padua, Italy. The follow-up phase ended in December 2012. The study protocol was approved by our institution’s review board (No. 2671P).
METHODS Design and setting We undertook a prospective interventional cohort study to assess the efficacy of EVLA by use of a 1470-nm diode From the Multidisciplinary Centre for Day Surgery, University Hospital of Padua, Paduaa; the Emergency Department ULSS7, Pieve di Soligob; and the Department of Statistics, University of Milano-Bicocca, Milan.c Author conflict of interest: none. Reprint requests: Giorgio Spreafico, MD, Multidisciplinary Centre for Day Surgery, University Hospital of Padua, Ospedale Giustinianeo, via Giustiniani 2, 35128 Padua, Italy (e-mail: giorgio.spreafi[email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 2213-333X/$36.00 Copyright Ó 2014 by the Society for Vascular Surgery. http://dx.doi.org/10.1016/j.jvsv.2014.04.012
Participants All consecutive patients with suspected GSV and SSV insufficiency referred for evaluation to our center during the study period were considered for inclusion. Patients were excluded if they were pregnant or breast-feeding, if they had an American Society of Anesthesiologists physical status classification score >3, if they were not eligible for ambulatory treatment, or if they were technically unsuitable for EVLA.10 To evaluate this last issue, all patients underwent echo color Doppler (ECD) examination to assess for the presence of the following EVLA feasibility criteria: a saphenous vein reflux due to saphenous-femoral junction (SFJ) or saphenous-popliteal junction (SPJ) incompetence (ie, reverse venous flow lasting more than 0.5 second after Valsalva maneuver, augmentation maneuvers, or both); a navigable (ie, patent and straight) saphenous vein trunk; and a saphenous vein diameter >4 mm at the puncture site, measured in the standing position. The presence of venous dilations along the saphenous trunk or near the confluence of the superficial inguinal veins (CSIV) or popliteal veins (CSPV), irrespective of their size, did not 403
404 Spreafico et al
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constitute an exclusion criterion for the study. At the same visit, patients were interviewed with a standardized questionnaire detailing all other necessary information, including age, sex, body mass index (BMI), and leg signs and symptoms according to class C of the Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification. All patients also underwent a baseline Venous Clinical Severity Score (VCSS) assessment. Patients without exclusion criteria were informed about the study purposes and were asked to participate in the study. Only those who formally agreed to undergo EVLA and to attend the planned follow-up visits were included in the study. To be included, patients were required to sign a preprinted informed consent form. Surgical procedures. All EVLA procedures were performed by three trained surgeons (U.B., G.S., P.P.) in an ambulatory setting at our day surgery unit with tumescent ECD-guided perivenous anesthesia, according to a standardized protocol.4 All patients were offered a light sedation with diazepam 5 mg sublingually; some were also given an intravenous bolus of midazolam 2.5 mg in case of persisting restlessness or fentanyl 0.05 mg intravenously if they were undergoing more than five stab vein avulsions. A 1470-nm diode laser (Ceralas E; Biolitec AG, Wien, Germany) and a commercial kit (ELVeS Radial kit; Biolitec AG) containing all the equipment for the procedure (19-gauge needle for percutaneous introduction, J guidewire 0.035-inch, 6F/11 cm introducer catheter, 600 mm radial fiberoptic) were used in all patients. The laser was set in the continuous mode, with a power of 5 to 6 W. The linear endovenous energy density (LEED) to be delivered to the saphenous trunk was calculated on the basis of the “times 10” rule, that is, LEED (J/cm) ¼ mean trunk diameter (mm) 10. The first 5 cm from the junction was always treated with 100 to 300 J/cm. The fiberoptic was introduced in the most distal part of the vein where reflux could be detected, except in the lower third of the calf, where EVLA was never attempted. If the fiberoptic could not be forwarded from the access point toward the junction, several percutaneous accesses were performed to treat the whole refluxing saphenous trunk. The most prominent varices were treated with stab vein avulsion directly at the end of the EVLA procedure, according to the Muller technique.11 Patients with residual (ie, still clearly visible, despite successful EVLA) varicose veins were offered postoperative sclerotherapy, usually scheduled at 12 weeks after surgery. Low-molecular-weight heparin prophylaxis, unless contraindicated, was initiated preoperatively and continued for 6 days postoperatively in all patients with moderate risk factors for venous thromboembolism at the dose suggested for moderate-risk surgery according to the 2008 American College of Chest Physicians guidelines.12 Furthermore, all patients wore a 35 mm Hg elastic compression stocking (Struva 35; Medi, Bayreuth, Germany) for 24 hours a day during the first week after EVLA and then switched to a second-class graduated elastic compression stocking for another 4 weeks during the daytime. Postoperative pain evaluation and management. All patients were managed according to the institution’s pain
management protocol. Pain intensity was evaluated by a verbal numeric scale (0-10) or word scale (none, mild, moderate, severe) by trained nurses, according to patients’ preferences. Patients with a pain intensity <4 (or none to mild) were discharged without analgesic prescription but were allowed to use their favorite over-the-counter medications for pain relief. A nurse recorded pain intensity, along with the type and amount of analgesics used, at discharge (day 0), at day 1 by telephone interview, and at day 2 and day 7 postoperatively during the planned ambulatory visits on a convenience sample of 111 consecutive patients. At the day 2 and day 7 visits, patients complaining of pain or who had been taking analgesics for any reason were further interviewed by a physician to assess the precise location of pain, the reason for taking pain medications, the impact of pain on common daily activities, and the time to return to work. Follow-up. Patients were scheduled for clinical and ECD assessments at 2, 7, 90, and 270 days after EVLA and thereafter once yearly for up to 4 years. To be considered for the analysis, all patients had to complete at least 12 months of follow-up. All examinations were carried out by five experienced vascular physicians (G.S., A.P., P.P., E.G., A.N.). The clinical course of symptoms or signs affecting the patients before the procedure was evaluated by reassessing the VCSS at the 90-day follow-up visit. At the end of each follow-up visit, patients with newly detected ECD-confirmed EVLA failures (ECEFs) were offered sclerotherapy on the basis of the ECD pattern and the presence of visible varices. Ultrasound-guided sclerotherapy was performed with the intention to treat both the ECEF and the varicosities with sodium tetradecyl sulfate foam 1% to 3%. The procedure was always performed according to the patient’s preferences. Outcomes The primary study outcome was the incidence of ECEF during follow-up. Associations between failures and patients’ characteristics (age, sex, BMI, C class of CEAP classification), presurgical ultrasonographic findings (SFJ and SPJ competence, aspect, and diameter; saphenous trunk mean and largest diameters), and surgical features (length of the treated trunk, energy delivered, and power) were investigated by multiple Cox proportional hazards regression analysis. The secondary study outcome was the postoperative pain course. ECEF classification. ECEFs were categorized according to a previously published classification, as follows: type 1, venous reflux limited to the junction or the residual saphenous stump or a collateral of the junction, for a maximum length of 5 cm from the junction; type 2, reflux at the junction or in the treated trunk or in a collateral vein of the junction for more than 5 cm from the junction, without clinically evident recurrent varices; or type 3, reflux at the junction site, or into the treated trunk, or on a
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collateral to the junction for a length of more than 5 cm from the junction, with clinically evident recurrent varices, either symptomatic or asymptomatic.13 ECD technique. ECD examinations were performed with a Technos or MyLab ultrasound machines (Esaote, Italy) equipped with a 4.0 to 13.0 MHz linear probe. Testing was carried out in the orthostatic position, following a standardized protocol. First, the saphenous junction competence, defined as absence of venous reflux or presence of venous reflux lasting for $1 second after Valsalva or augmentation (ie, muscle squeezing) maneuvers, was assessed. Of note, we chose a longer time cutoff than that used for the preoperative assessment (ie, reflux lasting >0.5 second) to account for the normal pseudoreflux limited to the venous stump that may be occasionally detected after EVLA. In the presence of a refluxing junction, the investigators always tried to individuate its outflow. Second, the saphenous trunk patency was assessed by compression and color Doppler sampling. If the trunk was patent, its diameter was recorded, and venous reflux, if present, was evaluated with the Valsalva and augmentation maneuvers. Finally, varicose veins were evaluated to distinguish between residual and recurrent varicosities, the latter defined as refluxing varices fed by an unsuccessfully treated venous segment. As stated before, we sought to investigate whether presurgical ultrasonographic findings (SFJ and SPJ competence, aspect, and diameter; saphenous trunk mean and largest diameters) were associated with ECEF. To this purpose, we standardized in advance several ultrasonographic variables, as follows. The CSIV or CSPV was defined as the proximal part of the saphenous vein, starting from the SFJ or SPJ and extending distally through the trunk for a maximum of 5 cm. The CSIV or CSPV diameter was measured with a longitudinal scan at a distance of 2 cm from the junction and also at the point of maximal dilation within 5 cm from the junction, with the patient standing. The CSIV or CSPV was defined as “competent” if no venous reflux could be recorded with color and pulsed Doppler mode. The CSIV or CSPV was labeled “enlarged” when its diameter was >10 mm and “atypical” if the SFJ or SPJ was more than 2 cm deep from the skin surface, if the CSIV or CSPV featured an eccentric aneurysmatic dilation or was kinked on transverse or longitudinal scans, or if venous reflux toward the collaterals was recorded. We measured the SFJ and SPJ depth starting from the skin, with the patient supine. Three morphologic aspects of the CSIV were considered, according to the literature: funnel, cylindrical, and bulbous.14 Finally, the saphenous trunk diameter was defined as the average diameter of non-locally enlarged segments of the vein, measured every 10 cm from the junction to the puncture site, with transverse scans in the standing patient. We also recorded the point of maximal dilation of the saphenous trunk. Statistical analysis Descriptive statistics were calculated for all variables. The probability of experiencing a failure was determined
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by the Kaplan-Meier method. The hazard ratio (HR) and 95% confidence interval (CI) based on the Cox proportional hazards model were estimated to test the association between the risk of failure and factors such as age, gender, BMI, C class of the CEAP classification, CSIV and CSPV diameters, and trunk diameters. Continuous covariates were treated both as continuous and as categorized. The selection of the cutoff value for the continuous variables, such as age, CSIV and CSPV diameters, and trunk diameters, corresponded to the most significant difference in time to failure between groups.15 The assumption of proportional risk was evaluated by the Schoenfeld residuals test. Multiple Cox proportional hazards regression analysis was used to determine the adjusted association between clinical and ECD covariates and the risk of failure. Covariates were removed by backward elimination according to a selection stay criterion of .05. Data analyses were performed with the SAS statistical package (release 9.1; SAS, Cary, NC). RESULTS Between May 2008 and December 2011, 381 consecutive patients underwent EVLA at our institution (Fig 1). The mean procedure time was 32 minutes (standard deviation, 13 minutes). Two patients with GSV incompetence did not complete EVLA because of technical reasons (ie, failure to catheterize the saphenous trunk or the SFJ due to local spasm of the vein) and were excluded from the analysis. Of 379 patients who successfully completed EVLA, 317 underwent the procedure because of GSV insufficiency and 62 (16%) because of SSV insufficiency. Six patients (2%), all with GSV incompetence, were lost to follow-up, either because they could not be contacted (n ¼ 2) or because they declined further examinations (n ¼ 4). Another patient in the GSV group unexpectedly died of cancer 5 months after EVLA and was thus excluded from the analysis. Hence, 372 patients completed the planned 12-month follow-up. The mean follow-up time was 22 6 12 months. No symptomatic episodes of pulmonary embolism or deep venous thrombosis were detected during the follow-up period. Demographic, anatomic, and surgical features of the patients who completed the planned follow-up observation are reported in Table I. Primary outcome SSV insufficiency. The ECEF rate in patients with SSV insufficiency was 0%; that is, all had both a competent junction and a persistently occluded trunk by the end of follow-up. Therefore, no further analysis was performed in this group of patients. GSV insufficiency. Of 310 patients treated for GSV insufficiency, 37 patients (12%; 95% CI, 8.5%-17%) were found to have an ECEF. Interestingly, all patients had a persistently occluded saphenous trunk by the end of follow-up; thus, ECEFs were observed only at the junction level. Of these 37 patients, 24 (8%) had a type 1 ECEF; 10 (3%) had a type 2 ECEF, nine at the anterior and one at the posterior accessory saphenous vein; and three (1%) had a type 3 ECEF, all at the anterior accessory
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EVLA performed, n = 381
EVLA not completed, n = 2 (failure to catheterize the saphenous trunk or the SFJ)
EVLA completed, n = 379
EVLA performed for GSV insufficiency, n = 317 (84%)
EVLA performed for SSV insufficiency, n = 62 (16%)
Lost to follow-up, n = 6 (2%) Dead at <1 year n =1
Lost to follow-up, n=0
1-year follow-up completed, n = 310
1-year follow-up completed, n = 62
ECD-confirmed EVLA failures, n = 37 (12%)
ECD-confirmed EVLA failures, n=0
Fig 1. Consort diagram of the study. ECD, Echo color Doppler; EVLA, endovenous laser ablation; GSV, great saphenous vein; SFJ, saphenous-femoral junction; SSV, small saphenous vein.
saphenous vein. Of all ECEFs, 26 (70%) were diagnosed during the first year of follow-up, including six type 2 and two type 3 (at 1 and 6 months); 11 (30%) were recorded during the second year of follow-up, including four type 2 and one type 3. The following clinical and ECD variables were significantly associated with ECEF: a BMI $30 (HR, 2.5; 95% CI, 1.2-5.2; P ¼ .0102); the presence of a CEAP C class $4 (HR, 3.1; 95% CI, 1.5-6.2; P ¼ .0019); an atypical CSIV (HR, 2.0; 95% CI, 1.0-3.7; P ¼ .0436); a mean CSIV diameter $9 mm (HR, 2.5; 95% CI, 1.2-5.2; P ¼ .0134) in the standing position; and a mean trunk diameter $8 mm (HR, 2.1; 95% CI, 1.1-4.0; P ¼ .0288). After adjustment for covariates that had been selected from the univariate analysis on the basis of a 0.25 significance criterion, ECEF was significantly associated only with the presence of a CEAP C class $4 (HR, 2.8; 95% CI, 1.4-5.6; P ¼ .0049) and a mean CSIV diameter $9 mm in the standing position (HR, 2.2; 95% CI, 1.05-4.5; P ¼ .0321). Secondary outcome Postoperative pain course. At 2 and 7 days postoperatively, more than two thirds of the patients had no pain at all (Table II). In the remaining patients, pain was rated mild or moderate, and no patient reported severe pain.
Analgesic use was recorded in one third of patients at 2 days and in 15% at 7 days postoperatively. Interestingly, only nine patients related pain to the site of EVLA, and this often was due to thrombosis of a dilated venous segment or to treatment of very superficial veins. Conversely, in the remaining 25 patients, pain was related to the site of stab vein avulsion (n ¼ 18) or to the use of elastic stockings (n ¼ 7). Both undergoing more than four phlebectomies (HR, 3.5; 95% CI, 1.1-12.7) and having phlebectomy performed at the thigh and at the calf in the same session (HR, 2.96; 95% CI, 1.1-8.5) were independently associated with the development of moderate pain. Pain was identified as the main cause for not resuming work in only five patients. Finally, 11 patients reported use of analgesics, which was either not related to EVLA (eg, headache, back pain) or intended as “prophylaxis” in the absence of any pain. Additional findings. During the EVLA session, 311 patients (82%) underwent stab vein avulsions (median number, five per patient; range, 1-14). Another 11 patients (3%) with residual varicose veins received sclerotherapy within 12 weeks from the procedure. One patient, after the conclusion of EVLA, was hospitalized because of the intraoperative onset of atrial fibrillation. Five patients (1%) with GSV incompetence had an asymptomatic type 2 heat-induced thrombosis at the SFJ,
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Table I. Demographic and preoperative characteristics of patients undergoing endovenous laser ablation (EVLA) for great saphenous vein (GSV) (n ¼ 317) and small saphenous vein (SSV) (n ¼ 62) insufficiency GSV Age Mean (SD) Median (IQR) Sex Male Female BMI Normal weight (18.5-24.9) Overweight (25-29.9) Obesity ($30) CEAP C Varicose veins (C2) Edema without skin changes (C3) Skin changes: pigmentation, eczema (C4a) Skin changes: lipodermatosclerosis, white atrophy (C4b) Skin changes with healed ulceration (C5) Skin changes with active ulceration (C6) CSIV and CSPV Morphology Aneurysmal Funnel Bulbous Cylindrical Other Depth (from skin surface) #2 cm >2 cm Diameter, cm (measured at 2 cm from the SFJ and SPJ) Mean (SD) Median (IQR) Diameter, cm, maximal Mean (SD) Median (IQR) LEED, J/cm Mean (SD) Median (IQR) Trunk Diameter, cm Mean (SD) Median (IQR) Diameter, cm, maximal Mean (SD) Median (IQR) LEED, J/cm Mean (SD) Median (IQR) Length of treated saphenous trunk, cm Mean (SD) Median (IQR)
52.2 (13.5) 52 (42-62)
SSV 56.1 (10.6) 56 (51-63)
109 (34) 208 (66)
14 (22) 48 (77)
140 (44) 112 (35) 65 (20)
41 (66) 14 (23) 7 (11)
118 52 95 25 24 3
(37) (16) (30) (8) (8) (1)
23 19 14 5 1
(37) (31) (23) (8) (2) d
19 102 70 122 4
(6) (32) (22) (38) (1)
9 24 10 12 7
(14) (39) (16) (19) (11)
233 (73) 84 (26)
51 (82) 11 (18)
9 (2) 9 (8-10)
8 (1) 8 (7-8)
12 (4) 11 (9-13)
10 (3) 9 (8-11)
218 (49) 218 (200-241) 7 (1) 7 (7-8)
213 (52) 206 (197-238) 7 (1) 7 (7-8)
11 (4) 9 (8-12)
8 (2) 8 (7-8.5)
83 (25) 78 (68-91)
91 (31) 84 (71-104)
37 (10) 39 (31-44)
19 (5) 20 (16-22)
BMI, Body mass index; CEAP, Clinical, Etiologic, Anatomic, and Pathologic; CSIV, confluence of the superficial inguinal veins; CSPV, confluence of the superficial popliteal veins; IQR, interquartile range; LEED, linear endovenous energy density; SD, standard deviation; SFJ, saphenous-femoral junction; SPJ, saphenous-popliteal junction. Except where otherwise stated, numbers in parentheses represent percentages.
diagnosed by routine ECD control at 2 days or 7 days postoperatively. Twelve patients (3%) had lower limb paresthesias; four of them (1%), all with GSV incompetence, had hypoesthesia (n ¼ 3) or hyperesthesia (n ¼ 1) persisting for $12 months.16 The mean baseline VCSS was 6.3 (standard deviation, 2.8); that recorded at the 90-day visit was 2.4 (standard deviation, 1.7). The VCSS variation was due to active ulcer
size (100%), active ulcer duration (100%), active ulcer number (100%), varicose veins (83%), inflammation (76%), pain and other discomfort (61%), venous edema (49%), use of compression therapy (43%), induration (12%), and skin pigmentation (5%). During an average period of 2 years from EVLA, no patients progressed from type 1 to type 2 ECEF or from type 2 to type 3 ECEF. Ultrasound-guided
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Table II. Postoperative pain course and use of analgesics, evaluated on a convenience sample of 111 patients
DISCUSSION
patients. These observations are in line with other reports from the literature, although our study patients were followed up for a longer time.20 Conversely, some 12% of the patients treated for GSV insufficiency had a stable venous reflux limited to the junction, not associated with clinical events or with ECD-detectable neovascularization, that was never treated. In summary, only 2% of the patients underwent a second intervention in the same venous segment during the 22month mean follow-up period. The finding of reflux limited to the SFJ had already been reported in the literature; in our previous study, we observed that patients with isolated SFJ reflux remained stable, asymptomatic, and without recurrent varices and never underwent a second intervention after a 6-year follow-up. Of course, it may well be that after longer follow-up periods (up to 10 years or more), isolated SFJ reflux may eventually result in a failure, such as those observed after high ligation.13 Time to event analysis shows that all ECEFs are identified within 2 years from EVLA (Fig 2), confirming previous findings.13 Accordingly, we suggest performance of an ECD evaluation at 1 to 2 years from intervention to identify those patients with suboptimal EVLA results who might benefit from further follow-up or even sclerotherapy. Our results confirm the promising data on radial fibers coming from previous studies, although the present study had a longer follow-up period (2 years vs 6 months) and different laser settings.17-21 Our results were obtained with 5 to 6 W of continuous power and a LEED proportional to the mean diameter of the treated vein according to the “times 10” rule. Indeed, in our experience, the use of a continuous power higher than 9 W may cause the carbonization of the fiberoptic and possibly jeopardize the ablation rates. We recently published a study in which patients undergoing EVLA for GSV insufficiency were followed up for 6 years.13 The methodology, the investigators, and the data array were the same as in the present study; however,
The present study shows a high efficiency of the 1470-nm laser and radial fiber EVLA technique, evaluated by technology standard assessment, in patients observed for up to 4 years. Indeed, no recanalization of saphenous trunks with a diameter ranging from 5 to 27 mm was observed. Hence, primary ablation was obtained in 100% of cases. These observations are in line with other reports from the literature, although patients were followed up for a longer time in our study.17-20 We believe these results not only are due to the type of laser and fiber employed but also depend on the fact that the amount of energy delivered was always targeted to the diameter of the saphenous trunk to be treated, albeit a higher amount of energy was delivered in the first 5 cm from the junction. Neither trunk recanalization nor residual stump reflux was observed in patients undergoing EVLA for SSV insufficiency; therefore, no ECEFs were recorded in these
Fig 2. Time to event analysis of patients with great saphenous vein (GSV) insufficiency.
Pain Absent Mild Moderate Severe Analgesics use No Yes
Day 0, %
Day 1, %
Day 2, %
Day 7, %
29 71 0.0 0.0
68 30 3 0.0
68 14 18 0.0
70 13 16 0.0
88 12
67 33
85 15
d d
foam sclerotherapy of varices was performed in eight patients with either type 2 ECEF (n ¼ 5) or type 3 ECEF (n ¼ 3), on average for 1.9 sessions per patient. Interestingly, all patients were asymptomatic at the moment of sclerotherapy. Finally, no patients with EVLA failure underwent high ligation or saphenous vein stripping. Of 24 patients with type 1 ECEF, the site of outflow was identified in 17 as being directed toward the centrilobular lymph node veins (n ¼ 10); or due to a mouse-tail recanalization within the first 5 cm of the trunk (n ¼ 3); or due to incompetence of the branches of the CSIV (n ¼ 4), in particular, the superficial epigastric and the external pudendal. In all cases of type 1 ECEF, reflux was elicited by Valsalva maneuver, being of low intensity at pulsed Doppler in 19 patients. In the 10 patients with a type 2 ECEF, the site of outflow was in the anterior accessory saphenous vein in nine and in the posterior accessory saphenous vein in one. In all three patients with type 3 ECEF, the site of outflow was a large vessel because of neovascularization originating below the refluxing stump and draining into an accessory anterior saphenous vein and then into thigh varicosities.
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in the former study, we used a 980-nm diode laser and bare fiber, whereas in the present study, we employed a 1470-nm diode laser and radial fiber. Although no formal comparisons are feasible, no trunk recanalization was observed in the present study, but in our previous study, the corresponding figure was 11%. Similarly, the occurrence of reflux at the anterior accessory saphenous vein and isolated at the SFJ was almost halved. In this respect, it is also important to note that the present cohort displayed on average a more severe clinical profile, including a higher CEAP class, a larger diameter of the treated veins, a higher incidence of comorbidities, and a greater number of obese (BMI >30) subjects. The use of 1470-nm radial fibers appears to have a favorable effect also on postoperative pain because the majority (85%) of patients reported either no or mild pain by day 7, and a similar proportion (85%) did not take analgesics. Furthermore, most of the patients (18%) reporting moderate pain, when specifically asked, actually related it to the site of stab vein avulsion, rather than to the EVLA site, or to the use of elastic stockings. Similar data were reported in previous studies dealing with the 1470-nm diode laser and radial fibers.17,18 A randomized study comparing EVLA performed with 810- or 980-nm laser and bare fibers with radiofrequency ClosureFAST ablation reported a higher incidence of postoperative pain in patients treated with EVLA.22,23 Lacking direct comparisons, we believe the low incidence of postoperative pain and ecchymosis observed in our study may be due to the use of radial fibers because they cause neither contact lesions nor perforation of the vessel wall.24 According to the multiple Cox proportional hazards regression analysis, only a CEAP C class $4 and a CSIV diameter $9 mm measured in the standing position were associated with the development of ECEF. These findings confirm our previous observation with use of a 980-nm diode laser and bare fiber. Being that these two variables are simple and convenient to record, it would be desirable for them to be confirmed as reliable predictors of ECEF in future studies.13 We encourage other researchers to gather this information prospectively. CONCLUSIONS In the future, the availability of new products belonging to the radial fiber family (slim, dual-ring) is likely to allow expansion of the current indications for EVLA to smaller veins, such as the perforating or the accessory veins (slim), and to narrow (slim) or large (dual-ring) saphenous trunks that cannot be addressed with the standard radial fibers. Dual-ring fibers, because of the double-irradiation feature, should also warrant a more complete and accurate vessel wall damage and a faster pullback time. AUTHOR CONTRIBUTIONS Conception and design: GS Analysis and interpretation: GS, AP, EB, RB Data collection: GS, AP, EB, PP, AN, UB
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Writing the article: GS, AP, EB Critical revision of the article: GS, AP, EB, EG, PP, RB, AN, UB Final approval of the article: GS, AP, EB, EG, PP, RB, AN, UB Statistical analysis: EB, RB Obtained funding: Not applicable Overall responsibility: GS
REFERENCES 1. Navarro L, Min RJ, Bone C. Endovenous laser: a new minimally invasive method of treatment for varicose veins: preliminary observations using an 810 nm diode laser. Dermatol Surg 2001;27:117-22. 2. Min RJ, Khilnani N, Zimmet SE. Endovenous laser treatment of saphenous vein reflux: long-term results. J Vasc Interv Radiol 2003;14: 991-6. 3. Proebstle T, Gul D, Kargl A, Knop J. Endovenous laser treatment of the greater saphenous vein with a 940 nm diode laser: thrombotic occlusion after endoluminal thermal damage by laser-generated steam bubbles. J Vasc Surg 2002;35:729-36. 4. Agus GB, Mancini S, Magi G, IEWG. The first 1000 cases of Italian Endovenous-laser Working Group (IEWG). Rationale and long-term outcomes for the 1999-2003 period. Int Angiol 2006;25:209-15. 5. Goldman MP, Mauricio M, Rao J. Intravascular 1320-nm laser closure of the great saphenous vein: a 6- to 12-month follow-up study. Dermatol Surg 2004;30:1380-5. 6. Pannier F, Rabe E, Maurins U. First results with a new 1470-nm diode laser for endovenous ablation of incompetent saphenous veins. Phlebology 2009;24:26-30. 7. Vuylsteke ME, Vandekerckhove PJ, De Bo T, Moons P, Mordon S. Use of a new endovenous laser device: results of the 1,500 nm laser. Ann Vasc Surg 2010;24:205-11. 8. Kabnick LS, Caruso JA. No-wall touch laser fiber vs bare-tip laser fiber for endothermal venous ablation of great saphenous vein: are the results the same? In: Gerard JL, editor. Controversies and updates in vascular surgery. Edizioni Panminerva Medica: Torino; 2008. p. 401-2. 9. Sroka R, Weick K, da Conta A. Investigations on the acute effects of circumferential laser light energy application for endovenous laser treatment. In: Becquemin JP, Alimi YS, Gerard JL, editors. Controversies and updates in vascular surgery. Edizioni Minerva Medica: Torino; 2009. p. 442-6. 10. Sakland M. Grading of patients for surgical procedures. Anesthesiology 1941;2:281-4. 11. Muller R. Treatment of varicose veins by ambulatory phlebectomy. Phlebologie 1966;19:277-9. 12. Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(Suppl):381S-453S. 13. Spreafico G, Piccioli A, Bernardi E, Giraldi E, Pavei P, Borgoni R, et al. Six-year follow-up of endovenous laser ablation for great saphenous vein incompetence. J Vasc Surg 2013;1:20-5. 14. Creton D, Pichot O, Sessa C, Proebstle TM. ClosureFast Europe Group. Radiofrequency-powered segmental thermal obliteration carried out with the ClosureFast procedure: results at 1 year. Ann Vasc Surg 2010;24:360-6. 15. Contal C, O’Quigley J. An application of change point methods in studying the effect of age on survival in breast cancer. Comput Stat Data Anal 1999;30:253-70. 16. Dexter D, Kabnick L, Berland T, Jacobowitz G, Lamparello P, Maldonado T, et al. Complications of endovenous lasers. Phlebology 2012;27(Suppl 1):40-5. 17. Doganci S, Demirkilic U. Comparison of 980 nm laser and bare-tip fibre with 1470 nm laser and radial fibre in the treatment of great saphenous vein varicosities: a prospective randomised clinical trial. Eur J Vasc Endovasc Surg 2010;40:254-9.
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18. Schwarz T, Hodenberg E, Furtwängler C, Rastan A, Zeller T, Neumann FJ. Endovenous laser ablation of varicose veins with the 1470-nm diode laser. J Vasc Surg 2010;51:1474-8. 19. Pannier F, Rabe E, Rits J, Kadiss A, Maurins U. Endovenous laser ablation of great saphenous veins using a 1470 nm diode laser and the radial fibredfollow-up after six months. Phlebology 2011;26:35-9. 20. Doganci S, Yildirim V, Demirkilic U. Does puncture site affect the rate of nerve injuries following endovenous laser ablation of the small saphenous vein? Eur J Vasc Endovasc Surg 2011;41:400-5. 21. Arnez A, Kiser R, Lakhanpal S, Nguyen K. Letter regarding: F Pannier, E Rabe, J Rits, A Kadiss, U Maurins. Endovenous laser ablation of great saphenous veins using a 1470 nm diode laser and the radial fibredfollow-up after six months. Phlebology 2011;26:35-9. Phlebology 2012;27:101.
22. Gale SS, Lee JN, Walsh ME, Wojnarowski DL, Comerota AJ. A randomized, controlled trial of endovenous thermal ablation using the 810-nm wavelength laser and the ClosurePLUS radiofrequency ablation methods for superficial venous insufficiency of the great saphenous vein. J Vasc Surg 2010;52:645-50. 23. Shepherd AC, Gohel MS, Brown LC, Metcalfe MJ, Hamish M, Davies AH. Randomized clinical trial of VNUS ClosureFAST radiofrequency ablation versus laser for varicose veins. Br J Surg 2010;97:810-8. 24. Spreafico G, Giordano R, Piccioli A, Iaderosa G, Pavei P, Giraldi E, et al. Histological damage of saphenous venous wall treated in vivo with radial fiber and 1470 nm diode laser. Italian J Vasc Endovasc Surg 2011;18:241-7. Submitted Dec 11, 2013; accepted Apr 27, 2014.
features. The secondary outcome was the postoperative pain course. Results: The planned 12-month follow-up was completed in 372 patients. Echo color Doppler-confirmed failures occurred in 37 (12%) of 310 patients with GSV insufficiency, whereas none of 62 patients with SSV insufficiency experienced a failure. Multiple Cox proportional hazards regression analysis showed a significant association of failures with a Clinical, Etiologic, Anatomic, and Pathologic class C $4 and a mean confluence of the superficial inguinal veins diameter $9 mm in patients with GSV insufficiency. Postoperative pain course was favorable. More than two thirds of the patients were asymptomatic at 7 days. Conclusions: EVLA with 1470-nm diode laser and radial fiberoptic is effective for treatment of GSV and especially SSV insufficiency and is well tolerated by the patients. (J Vasc Surg: Venous and Lym Dis 2014;2:403-10.)
After the publication of the paper by Navarro et al in 2001, commonly regarded as the beginning of the endovenous laser ablation (EVLA) era, several laser wavelengths (810, 940, 980, 1320, 1470, and 1500 nm) and fiberoptics (bare, no-touch, radial) have been tested, aiming at improving the efficacy of the technique and the patients’ quality of life.1-9 The aim of this study was to assess the outcome of patients with great saphenous vein (GSV) and small saphenous vein (SSV) incompetence treated with a 1470-nm diode laser and a radial fiberoptic.
laser and radial fiber for treatment of GSV and SSV insufficiency. Patients were recruited between May 2008 and December 2011 at the Multidisciplinary Centre for Day Surgery, University Hospital of Padua, Italy. The follow-up phase ended in December 2012. The study protocol was approved by our institution’s review board (No. 2671P).
METHODS Design and setting We undertook a prospective interventional cohort study to assess the efficacy of EVLA by use of a 1470-nm diode From the Multidisciplinary Centre for Day Surgery, University Hospital of Padua, Paduaa; the Emergency Department ULSS7, Pieve di Soligob; and the Department of Statistics, University of Milano-Bicocca, Milan.c Author conflict of interest: none. Reprint requests: Giorgio Spreafico, MD, Multidisciplinary Centre for Day Surgery, University Hospital of Padua, Ospedale Giustinianeo, via Giustiniani 2, 35128 Padua, Italy (e-mail: giorgio.spreafi[email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 2213-333X/$36.00 Copyright Ó 2014 by the Society for Vascular Surgery. http://dx.doi.org/10.1016/j.jvsv.2014.04.012
Participants All consecutive patients with suspected GSV and SSV insufficiency referred for evaluation to our center during the study period were considered for inclusion. Patients were excluded if they were pregnant or breast-feeding, if they had an American Society of Anesthesiologists physical status classification score >3, if they were not eligible for ambulatory treatment, or if they were technically unsuitable for EVLA.10 To evaluate this last issue, all patients underwent echo color Doppler (ECD) examination to assess for the presence of the following EVLA feasibility criteria: a saphenous vein reflux due to saphenous-femoral junction (SFJ) or saphenous-popliteal junction (SPJ) incompetence (ie, reverse venous flow lasting more than 0.5 second after Valsalva maneuver, augmentation maneuvers, or both); a navigable (ie, patent and straight) saphenous vein trunk; and a saphenous vein diameter >4 mm at the puncture site, measured in the standing position. The presence of venous dilations along the saphenous trunk or near the confluence of the superficial inguinal veins (CSIV) or popliteal veins (CSPV), irrespective of their size, did not 403
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constitute an exclusion criterion for the study. At the same visit, patients were interviewed with a standardized questionnaire detailing all other necessary information, including age, sex, body mass index (BMI), and leg signs and symptoms according to class C of the Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification. All patients also underwent a baseline Venous Clinical Severity Score (VCSS) assessment. Patients without exclusion criteria were informed about the study purposes and were asked to participate in the study. Only those who formally agreed to undergo EVLA and to attend the planned follow-up visits were included in the study. To be included, patients were required to sign a preprinted informed consent form. Surgical procedures. All EVLA procedures were performed by three trained surgeons (U.B., G.S., P.P.) in an ambulatory setting at our day surgery unit with tumescent ECD-guided perivenous anesthesia, according to a standardized protocol.4 All patients were offered a light sedation with diazepam 5 mg sublingually; some were also given an intravenous bolus of midazolam 2.5 mg in case of persisting restlessness or fentanyl 0.05 mg intravenously if they were undergoing more than five stab vein avulsions. A 1470-nm diode laser (Ceralas E; Biolitec AG, Wien, Germany) and a commercial kit (ELVeS Radial kit; Biolitec AG) containing all the equipment for the procedure (19-gauge needle for percutaneous introduction, J guidewire 0.035-inch, 6F/11 cm introducer catheter, 600 mm radial fiberoptic) were used in all patients. The laser was set in the continuous mode, with a power of 5 to 6 W. The linear endovenous energy density (LEED) to be delivered to the saphenous trunk was calculated on the basis of the “times 10” rule, that is, LEED (J/cm) ¼ mean trunk diameter (mm) 10. The first 5 cm from the junction was always treated with 100 to 300 J/cm. The fiberoptic was introduced in the most distal part of the vein where reflux could be detected, except in the lower third of the calf, where EVLA was never attempted. If the fiberoptic could not be forwarded from the access point toward the junction, several percutaneous accesses were performed to treat the whole refluxing saphenous trunk. The most prominent varices were treated with stab vein avulsion directly at the end of the EVLA procedure, according to the Muller technique.11 Patients with residual (ie, still clearly visible, despite successful EVLA) varicose veins were offered postoperative sclerotherapy, usually scheduled at 12 weeks after surgery. Low-molecular-weight heparin prophylaxis, unless contraindicated, was initiated preoperatively and continued for 6 days postoperatively in all patients with moderate risk factors for venous thromboembolism at the dose suggested for moderate-risk surgery according to the 2008 American College of Chest Physicians guidelines.12 Furthermore, all patients wore a 35 mm Hg elastic compression stocking (Struva 35; Medi, Bayreuth, Germany) for 24 hours a day during the first week after EVLA and then switched to a second-class graduated elastic compression stocking for another 4 weeks during the daytime. Postoperative pain evaluation and management. All patients were managed according to the institution’s pain
management protocol. Pain intensity was evaluated by a verbal numeric scale (0-10) or word scale (none, mild, moderate, severe) by trained nurses, according to patients’ preferences. Patients with a pain intensity <4 (or none to mild) were discharged without analgesic prescription but were allowed to use their favorite over-the-counter medications for pain relief. A nurse recorded pain intensity, along with the type and amount of analgesics used, at discharge (day 0), at day 1 by telephone interview, and at day 2 and day 7 postoperatively during the planned ambulatory visits on a convenience sample of 111 consecutive patients. At the day 2 and day 7 visits, patients complaining of pain or who had been taking analgesics for any reason were further interviewed by a physician to assess the precise location of pain, the reason for taking pain medications, the impact of pain on common daily activities, and the time to return to work. Follow-up. Patients were scheduled for clinical and ECD assessments at 2, 7, 90, and 270 days after EVLA and thereafter once yearly for up to 4 years. To be considered for the analysis, all patients had to complete at least 12 months of follow-up. All examinations were carried out by five experienced vascular physicians (G.S., A.P., P.P., E.G., A.N.). The clinical course of symptoms or signs affecting the patients before the procedure was evaluated by reassessing the VCSS at the 90-day follow-up visit. At the end of each follow-up visit, patients with newly detected ECD-confirmed EVLA failures (ECEFs) were offered sclerotherapy on the basis of the ECD pattern and the presence of visible varices. Ultrasound-guided sclerotherapy was performed with the intention to treat both the ECEF and the varicosities with sodium tetradecyl sulfate foam 1% to 3%. The procedure was always performed according to the patient’s preferences. Outcomes The primary study outcome was the incidence of ECEF during follow-up. Associations between failures and patients’ characteristics (age, sex, BMI, C class of CEAP classification), presurgical ultrasonographic findings (SFJ and SPJ competence, aspect, and diameter; saphenous trunk mean and largest diameters), and surgical features (length of the treated trunk, energy delivered, and power) were investigated by multiple Cox proportional hazards regression analysis. The secondary study outcome was the postoperative pain course. ECEF classification. ECEFs were categorized according to a previously published classification, as follows: type 1, venous reflux limited to the junction or the residual saphenous stump or a collateral of the junction, for a maximum length of 5 cm from the junction; type 2, reflux at the junction or in the treated trunk or in a collateral vein of the junction for more than 5 cm from the junction, without clinically evident recurrent varices; or type 3, reflux at the junction site, or into the treated trunk, or on a
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collateral to the junction for a length of more than 5 cm from the junction, with clinically evident recurrent varices, either symptomatic or asymptomatic.13 ECD technique. ECD examinations were performed with a Technos or MyLab ultrasound machines (Esaote, Italy) equipped with a 4.0 to 13.0 MHz linear probe. Testing was carried out in the orthostatic position, following a standardized protocol. First, the saphenous junction competence, defined as absence of venous reflux or presence of venous reflux lasting for $1 second after Valsalva or augmentation (ie, muscle squeezing) maneuvers, was assessed. Of note, we chose a longer time cutoff than that used for the preoperative assessment (ie, reflux lasting >0.5 second) to account for the normal pseudoreflux limited to the venous stump that may be occasionally detected after EVLA. In the presence of a refluxing junction, the investigators always tried to individuate its outflow. Second, the saphenous trunk patency was assessed by compression and color Doppler sampling. If the trunk was patent, its diameter was recorded, and venous reflux, if present, was evaluated with the Valsalva and augmentation maneuvers. Finally, varicose veins were evaluated to distinguish between residual and recurrent varicosities, the latter defined as refluxing varices fed by an unsuccessfully treated venous segment. As stated before, we sought to investigate whether presurgical ultrasonographic findings (SFJ and SPJ competence, aspect, and diameter; saphenous trunk mean and largest diameters) were associated with ECEF. To this purpose, we standardized in advance several ultrasonographic variables, as follows. The CSIV or CSPV was defined as the proximal part of the saphenous vein, starting from the SFJ or SPJ and extending distally through the trunk for a maximum of 5 cm. The CSIV or CSPV diameter was measured with a longitudinal scan at a distance of 2 cm from the junction and also at the point of maximal dilation within 5 cm from the junction, with the patient standing. The CSIV or CSPV was defined as “competent” if no venous reflux could be recorded with color and pulsed Doppler mode. The CSIV or CSPV was labeled “enlarged” when its diameter was >10 mm and “atypical” if the SFJ or SPJ was more than 2 cm deep from the skin surface, if the CSIV or CSPV featured an eccentric aneurysmatic dilation or was kinked on transverse or longitudinal scans, or if venous reflux toward the collaterals was recorded. We measured the SFJ and SPJ depth starting from the skin, with the patient supine. Three morphologic aspects of the CSIV were considered, according to the literature: funnel, cylindrical, and bulbous.14 Finally, the saphenous trunk diameter was defined as the average diameter of non-locally enlarged segments of the vein, measured every 10 cm from the junction to the puncture site, with transverse scans in the standing patient. We also recorded the point of maximal dilation of the saphenous trunk. Statistical analysis Descriptive statistics were calculated for all variables. The probability of experiencing a failure was determined
Spreafico et al 405
by the Kaplan-Meier method. The hazard ratio (HR) and 95% confidence interval (CI) based on the Cox proportional hazards model were estimated to test the association between the risk of failure and factors such as age, gender, BMI, C class of the CEAP classification, CSIV and CSPV diameters, and trunk diameters. Continuous covariates were treated both as continuous and as categorized. The selection of the cutoff value for the continuous variables, such as age, CSIV and CSPV diameters, and trunk diameters, corresponded to the most significant difference in time to failure between groups.15 The assumption of proportional risk was evaluated by the Schoenfeld residuals test. Multiple Cox proportional hazards regression analysis was used to determine the adjusted association between clinical and ECD covariates and the risk of failure. Covariates were removed by backward elimination according to a selection stay criterion of .05. Data analyses were performed with the SAS statistical package (release 9.1; SAS, Cary, NC). RESULTS Between May 2008 and December 2011, 381 consecutive patients underwent EVLA at our institution (Fig 1). The mean procedure time was 32 minutes (standard deviation, 13 minutes). Two patients with GSV incompetence did not complete EVLA because of technical reasons (ie, failure to catheterize the saphenous trunk or the SFJ due to local spasm of the vein) and were excluded from the analysis. Of 379 patients who successfully completed EVLA, 317 underwent the procedure because of GSV insufficiency and 62 (16%) because of SSV insufficiency. Six patients (2%), all with GSV incompetence, were lost to follow-up, either because they could not be contacted (n ¼ 2) or because they declined further examinations (n ¼ 4). Another patient in the GSV group unexpectedly died of cancer 5 months after EVLA and was thus excluded from the analysis. Hence, 372 patients completed the planned 12-month follow-up. The mean follow-up time was 22 6 12 months. No symptomatic episodes of pulmonary embolism or deep venous thrombosis were detected during the follow-up period. Demographic, anatomic, and surgical features of the patients who completed the planned follow-up observation are reported in Table I. Primary outcome SSV insufficiency. The ECEF rate in patients with SSV insufficiency was 0%; that is, all had both a competent junction and a persistently occluded trunk by the end of follow-up. Therefore, no further analysis was performed in this group of patients. GSV insufficiency. Of 310 patients treated for GSV insufficiency, 37 patients (12%; 95% CI, 8.5%-17%) were found to have an ECEF. Interestingly, all patients had a persistently occluded saphenous trunk by the end of follow-up; thus, ECEFs were observed only at the junction level. Of these 37 patients, 24 (8%) had a type 1 ECEF; 10 (3%) had a type 2 ECEF, nine at the anterior and one at the posterior accessory saphenous vein; and three (1%) had a type 3 ECEF, all at the anterior accessory
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EVLA performed, n = 381
EVLA not completed, n = 2 (failure to catheterize the saphenous trunk or the SFJ)
EVLA completed, n = 379
EVLA performed for GSV insufficiency, n = 317 (84%)
EVLA performed for SSV insufficiency, n = 62 (16%)
Lost to follow-up, n = 6 (2%) Dead at <1 year n =1
Lost to follow-up, n=0
1-year follow-up completed, n = 310
1-year follow-up completed, n = 62
ECD-confirmed EVLA failures, n = 37 (12%)
ECD-confirmed EVLA failures, n=0
Fig 1. Consort diagram of the study. ECD, Echo color Doppler; EVLA, endovenous laser ablation; GSV, great saphenous vein; SFJ, saphenous-femoral junction; SSV, small saphenous vein.
saphenous vein. Of all ECEFs, 26 (70%) were diagnosed during the first year of follow-up, including six type 2 and two type 3 (at 1 and 6 months); 11 (30%) were recorded during the second year of follow-up, including four type 2 and one type 3. The following clinical and ECD variables were significantly associated with ECEF: a BMI $30 (HR, 2.5; 95% CI, 1.2-5.2; P ¼ .0102); the presence of a CEAP C class $4 (HR, 3.1; 95% CI, 1.5-6.2; P ¼ .0019); an atypical CSIV (HR, 2.0; 95% CI, 1.0-3.7; P ¼ .0436); a mean CSIV diameter $9 mm (HR, 2.5; 95% CI, 1.2-5.2; P ¼ .0134) in the standing position; and a mean trunk diameter $8 mm (HR, 2.1; 95% CI, 1.1-4.0; P ¼ .0288). After adjustment for covariates that had been selected from the univariate analysis on the basis of a 0.25 significance criterion, ECEF was significantly associated only with the presence of a CEAP C class $4 (HR, 2.8; 95% CI, 1.4-5.6; P ¼ .0049) and a mean CSIV diameter $9 mm in the standing position (HR, 2.2; 95% CI, 1.05-4.5; P ¼ .0321). Secondary outcome Postoperative pain course. At 2 and 7 days postoperatively, more than two thirds of the patients had no pain at all (Table II). In the remaining patients, pain was rated mild or moderate, and no patient reported severe pain.
Analgesic use was recorded in one third of patients at 2 days and in 15% at 7 days postoperatively. Interestingly, only nine patients related pain to the site of EVLA, and this often was due to thrombosis of a dilated venous segment or to treatment of very superficial veins. Conversely, in the remaining 25 patients, pain was related to the site of stab vein avulsion (n ¼ 18) or to the use of elastic stockings (n ¼ 7). Both undergoing more than four phlebectomies (HR, 3.5; 95% CI, 1.1-12.7) and having phlebectomy performed at the thigh and at the calf in the same session (HR, 2.96; 95% CI, 1.1-8.5) were independently associated with the development of moderate pain. Pain was identified as the main cause for not resuming work in only five patients. Finally, 11 patients reported use of analgesics, which was either not related to EVLA (eg, headache, back pain) or intended as “prophylaxis” in the absence of any pain. Additional findings. During the EVLA session, 311 patients (82%) underwent stab vein avulsions (median number, five per patient; range, 1-14). Another 11 patients (3%) with residual varicose veins received sclerotherapy within 12 weeks from the procedure. One patient, after the conclusion of EVLA, was hospitalized because of the intraoperative onset of atrial fibrillation. Five patients (1%) with GSV incompetence had an asymptomatic type 2 heat-induced thrombosis at the SFJ,
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Table I. Demographic and preoperative characteristics of patients undergoing endovenous laser ablation (EVLA) for great saphenous vein (GSV) (n ¼ 317) and small saphenous vein (SSV) (n ¼ 62) insufficiency GSV Age Mean (SD) Median (IQR) Sex Male Female BMI Normal weight (18.5-24.9) Overweight (25-29.9) Obesity ($30) CEAP C Varicose veins (C2) Edema without skin changes (C3) Skin changes: pigmentation, eczema (C4a) Skin changes: lipodermatosclerosis, white atrophy (C4b) Skin changes with healed ulceration (C5) Skin changes with active ulceration (C6) CSIV and CSPV Morphology Aneurysmal Funnel Bulbous Cylindrical Other Depth (from skin surface) #2 cm >2 cm Diameter, cm (measured at 2 cm from the SFJ and SPJ) Mean (SD) Median (IQR) Diameter, cm, maximal Mean (SD) Median (IQR) LEED, J/cm Mean (SD) Median (IQR) Trunk Diameter, cm Mean (SD) Median (IQR) Diameter, cm, maximal Mean (SD) Median (IQR) LEED, J/cm Mean (SD) Median (IQR) Length of treated saphenous trunk, cm Mean (SD) Median (IQR)
52.2 (13.5) 52 (42-62)
SSV 56.1 (10.6) 56 (51-63)
109 (34) 208 (66)
14 (22) 48 (77)
140 (44) 112 (35) 65 (20)
41 (66) 14 (23) 7 (11)
118 52 95 25 24 3
(37) (16) (30) (8) (8) (1)
23 19 14 5 1
(37) (31) (23) (8) (2) d
19 102 70 122 4
(6) (32) (22) (38) (1)
9 24 10 12 7
(14) (39) (16) (19) (11)
233 (73) 84 (26)
51 (82) 11 (18)
9 (2) 9 (8-10)
8 (1) 8 (7-8)
12 (4) 11 (9-13)
10 (3) 9 (8-11)
218 (49) 218 (200-241) 7 (1) 7 (7-8)
213 (52) 206 (197-238) 7 (1) 7 (7-8)
11 (4) 9 (8-12)
8 (2) 8 (7-8.5)
83 (25) 78 (68-91)
91 (31) 84 (71-104)
37 (10) 39 (31-44)
19 (5) 20 (16-22)
BMI, Body mass index; CEAP, Clinical, Etiologic, Anatomic, and Pathologic; CSIV, confluence of the superficial inguinal veins; CSPV, confluence of the superficial popliteal veins; IQR, interquartile range; LEED, linear endovenous energy density; SD, standard deviation; SFJ, saphenous-femoral junction; SPJ, saphenous-popliteal junction. Except where otherwise stated, numbers in parentheses represent percentages.
diagnosed by routine ECD control at 2 days or 7 days postoperatively. Twelve patients (3%) had lower limb paresthesias; four of them (1%), all with GSV incompetence, had hypoesthesia (n ¼ 3) or hyperesthesia (n ¼ 1) persisting for $12 months.16 The mean baseline VCSS was 6.3 (standard deviation, 2.8); that recorded at the 90-day visit was 2.4 (standard deviation, 1.7). The VCSS variation was due to active ulcer
size (100%), active ulcer duration (100%), active ulcer number (100%), varicose veins (83%), inflammation (76%), pain and other discomfort (61%), venous edema (49%), use of compression therapy (43%), induration (12%), and skin pigmentation (5%). During an average period of 2 years from EVLA, no patients progressed from type 1 to type 2 ECEF or from type 2 to type 3 ECEF. Ultrasound-guided
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Table II. Postoperative pain course and use of analgesics, evaluated on a convenience sample of 111 patients
DISCUSSION
patients. These observations are in line with other reports from the literature, although our study patients were followed up for a longer time.20 Conversely, some 12% of the patients treated for GSV insufficiency had a stable venous reflux limited to the junction, not associated with clinical events or with ECD-detectable neovascularization, that was never treated. In summary, only 2% of the patients underwent a second intervention in the same venous segment during the 22month mean follow-up period. The finding of reflux limited to the SFJ had already been reported in the literature; in our previous study, we observed that patients with isolated SFJ reflux remained stable, asymptomatic, and without recurrent varices and never underwent a second intervention after a 6-year follow-up. Of course, it may well be that after longer follow-up periods (up to 10 years or more), isolated SFJ reflux may eventually result in a failure, such as those observed after high ligation.13 Time to event analysis shows that all ECEFs are identified within 2 years from EVLA (Fig 2), confirming previous findings.13 Accordingly, we suggest performance of an ECD evaluation at 1 to 2 years from intervention to identify those patients with suboptimal EVLA results who might benefit from further follow-up or even sclerotherapy. Our results confirm the promising data on radial fibers coming from previous studies, although the present study had a longer follow-up period (2 years vs 6 months) and different laser settings.17-21 Our results were obtained with 5 to 6 W of continuous power and a LEED proportional to the mean diameter of the treated vein according to the “times 10” rule. Indeed, in our experience, the use of a continuous power higher than 9 W may cause the carbonization of the fiberoptic and possibly jeopardize the ablation rates. We recently published a study in which patients undergoing EVLA for GSV insufficiency were followed up for 6 years.13 The methodology, the investigators, and the data array were the same as in the present study; however,
The present study shows a high efficiency of the 1470-nm laser and radial fiber EVLA technique, evaluated by technology standard assessment, in patients observed for up to 4 years. Indeed, no recanalization of saphenous trunks with a diameter ranging from 5 to 27 mm was observed. Hence, primary ablation was obtained in 100% of cases. These observations are in line with other reports from the literature, although patients were followed up for a longer time in our study.17-20 We believe these results not only are due to the type of laser and fiber employed but also depend on the fact that the amount of energy delivered was always targeted to the diameter of the saphenous trunk to be treated, albeit a higher amount of energy was delivered in the first 5 cm from the junction. Neither trunk recanalization nor residual stump reflux was observed in patients undergoing EVLA for SSV insufficiency; therefore, no ECEFs were recorded in these
Fig 2. Time to event analysis of patients with great saphenous vein (GSV) insufficiency.
Pain Absent Mild Moderate Severe Analgesics use No Yes
Day 0, %
Day 1, %
Day 2, %
Day 7, %
29 71 0.0 0.0
68 30 3 0.0
68 14 18 0.0
70 13 16 0.0
88 12
67 33
85 15
d d
foam sclerotherapy of varices was performed in eight patients with either type 2 ECEF (n ¼ 5) or type 3 ECEF (n ¼ 3), on average for 1.9 sessions per patient. Interestingly, all patients were asymptomatic at the moment of sclerotherapy. Finally, no patients with EVLA failure underwent high ligation or saphenous vein stripping. Of 24 patients with type 1 ECEF, the site of outflow was identified in 17 as being directed toward the centrilobular lymph node veins (n ¼ 10); or due to a mouse-tail recanalization within the first 5 cm of the trunk (n ¼ 3); or due to incompetence of the branches of the CSIV (n ¼ 4), in particular, the superficial epigastric and the external pudendal. In all cases of type 1 ECEF, reflux was elicited by Valsalva maneuver, being of low intensity at pulsed Doppler in 19 patients. In the 10 patients with a type 2 ECEF, the site of outflow was in the anterior accessory saphenous vein in nine and in the posterior accessory saphenous vein in one. In all three patients with type 3 ECEF, the site of outflow was a large vessel because of neovascularization originating below the refluxing stump and draining into an accessory anterior saphenous vein and then into thigh varicosities.
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in the former study, we used a 980-nm diode laser and bare fiber, whereas in the present study, we employed a 1470-nm diode laser and radial fiber. Although no formal comparisons are feasible, no trunk recanalization was observed in the present study, but in our previous study, the corresponding figure was 11%. Similarly, the occurrence of reflux at the anterior accessory saphenous vein and isolated at the SFJ was almost halved. In this respect, it is also important to note that the present cohort displayed on average a more severe clinical profile, including a higher CEAP class, a larger diameter of the treated veins, a higher incidence of comorbidities, and a greater number of obese (BMI >30) subjects. The use of 1470-nm radial fibers appears to have a favorable effect also on postoperative pain because the majority (85%) of patients reported either no or mild pain by day 7, and a similar proportion (85%) did not take analgesics. Furthermore, most of the patients (18%) reporting moderate pain, when specifically asked, actually related it to the site of stab vein avulsion, rather than to the EVLA site, or to the use of elastic stockings. Similar data were reported in previous studies dealing with the 1470-nm diode laser and radial fibers.17,18 A randomized study comparing EVLA performed with 810- or 980-nm laser and bare fibers with radiofrequency ClosureFAST ablation reported a higher incidence of postoperative pain in patients treated with EVLA.22,23 Lacking direct comparisons, we believe the low incidence of postoperative pain and ecchymosis observed in our study may be due to the use of radial fibers because they cause neither contact lesions nor perforation of the vessel wall.24 According to the multiple Cox proportional hazards regression analysis, only a CEAP C class $4 and a CSIV diameter $9 mm measured in the standing position were associated with the development of ECEF. These findings confirm our previous observation with use of a 980-nm diode laser and bare fiber. Being that these two variables are simple and convenient to record, it would be desirable for them to be confirmed as reliable predictors of ECEF in future studies.13 We encourage other researchers to gather this information prospectively. CONCLUSIONS In the future, the availability of new products belonging to the radial fiber family (slim, dual-ring) is likely to allow expansion of the current indications for EVLA to smaller veins, such as the perforating or the accessory veins (slim), and to narrow (slim) or large (dual-ring) saphenous trunks that cannot be addressed with the standard radial fibers. Dual-ring fibers, because of the double-irradiation feature, should also warrant a more complete and accurate vessel wall damage and a faster pullback time. AUTHOR CONTRIBUTIONS Conception and design: GS Analysis and interpretation: GS, AP, EB, RB Data collection: GS, AP, EB, PP, AN, UB
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Writing the article: GS, AP, EB Critical revision of the article: GS, AP, EB, EG, PP, RB, AN, UB Final approval of the article: GS, AP, EB, EG, PP, RB, AN, UB Statistical analysis: EB, RB Obtained funding: Not applicable Overall responsibility: GS
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