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Factors influencing the success of endovenous laser ablation (EVLA)
Reviews in Vascular Medicine 3 (2015) 31–34
Contents lists available at ScienceDirect
Reviews in Vascular Medicine journal homepage: www.elsevier.com/locate/rvm
Review
Factors influencing the success of endovenous laser ablation (EVLA) Giorgio Spreafico a,n, Enrico Bernardi b, Patrizia Pavei a, Enzo Giraldi a a b
Multidisciplinary Centre for Day Surgery, University Hospital of Padua, Italy Emergency Department ULSS7, Pieve di Soligo, Italy
Contents 1. The success 2. Success and 3. Success and 4. Success and 5. Discussion . REFERENCES . . .
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Endovenous laser ablation (EVLA) celebrates its fourteenth birthday in 2015 [1]. The purpose of EVLA is to achieve a stable occlusion of the refluxing saphenous trunk through the thermal damage caused by the exposition to laser light with an 810– 1500 nm wavelength [2]. Saphenous trunk occlusion usually restores the competence of the residual, untreated junction. The EVLA technique is well standardized [3]; however, both the materials (laser, and fiberoptic) and several technical details have evolved over the years [4,5].
1. The success A technically/anatomically successful EVLA procedure is defined as a complete and stable occlusion of the saphenous trunk confirmed by echo-color-Doppler (ECD). This outcome has been extensively investigated in the literature, being a mandatory information for publications on the efficacy of EVLA. The “Recommended reporting standards for endovenous ablation for the treatment of venous insufficiency: joint statement of The American Venous Forum and The Society of Interventional Radiology” [6], when discussing the efficacy of treatment, emphasizes the importance of a correct ablation of the saphenous n Correspondence to: Multidisciplinary Centre for Day Surgery, University Hospital Giustinianeo, Via Giustiniani 2, 35121 Padua, Italy. E-mail address: spreafi[email protected] (G. Spreafico).
http://dx.doi.org/10.1016/j.rvm.2015.10.001 2212-0211/& 2015 Elsevier GmbH All rights reserved.
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trunk, while it does not stress the importance of regaining the junction competence; although it is well known that a persistent reflux at the junction level may result in neovascularization or reflux towards the residual branches of the junction, such as the accessory saphenous veins of the thigh. Objective confirmation of trunk occlusion is based on well defined and agreed criteria (non-compressible or non-visible vein, absence of intraluminal venous flow, assessed by ECD). To the contrary, difficulties arise whenever the clinical meaning or the classification of trunk partial recanalization are addressed, due to the different failure criteria adopted in published studies, such as the minimum length of patent segments, their caliper, the presence/absence of reflux, or their relationship with the junction, the collateral or the perforating veins. Unfortunately, there are no agreed standards in the literature to evaluate partial trunk recanalization, except for the landmark paper by De Maeseneer, et al. [7]. For instance, the minimum meaningful length for a patent vein segment was formerly estimated at 10 cm, while it is currently accepted also at 5 cm [8]; and the caliper of the patent segment is almost never reported, although a caliper lower than 2–3 mm probably does not have clinical relevance. The same holds true for patent and competent venous segments interposed between two correctly occluded segments. Accurate analysis of these treatment shortcomings is not useful in the short/medium-term, as they are infrequently associated with recurrent symptoms or varices; to the contrary, long-term follow-up would be desirable to establish their clinical
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G. Spreafico et al. / Reviews in Vascular Medicine 3 (2015) 31–34
course. For instance, 6-year follow-up of venous reflux limited to the saphenous junction following EVLA demonstrated a very mild impact on the incidence of clinically evident recurrence [9]. Similarly, in the sclerotherapy arm of the MAGNA study [10] a notably higher recanalization rate was observed, as compared with the EVLA arm. Interestingly, while no differences in terms of quality of life (QoL) were observed at the 1-year follow-up, a further increase both in the recanalization rate, and in the re-intervention rate, and a reduction of the QoL were recorded at the 5-year evaluation. The finding of an anatomically successful procedure should represent a mainstay to exclude that recurrent symptoms or varices are due to an EVLA failure. However, besides anatomical success, especially clinical efficacy should be considered when evaluating the efficacy of EVLA. Clinical efficacy is usually assessed by means of either general or disease-specific QoL questionnaires, and of standardized questionnaires (e.g.: the Venous Clinical Severity Score, or VCSS). For instance, the primary outcome in the CLASS study [8] was not the anatomical success but the improvement of QoL, evaluated by means of both the disease-specific AVVQ (Aberdeen Varicose Vein Questionnaire), and the general SF36 and EQ5D questionnaires. AVVQ improvements were observed at 6 weeks and at 6 months in the EVLA arm, the earlier being relevant, the latter being slight. Similar results, though to a lesser degree, were also recorded using the SF-36 and EQ5D questionnaires. Other secondary clinical outcomes were assessed with the VCSS questionnaire, and the discomfort associated with varices by means of a visual-analog scale. In both instances, a trend of improvement similar to that observed for the primary outcome was recorded in the EVLA arm. The need for long-term follow-up data to better evaluate the clinical course is stressed by the conclusions of the CLASS study, where the impact of the anatomical success on the QoL and the clinical picture at 6 months is labeled as “unclear”; though an anatomical failure could be predictive of clinical recurrence and of the need for retreatments in the longterm. We will hereafter refer to anatomical success only.
2. Success and laser-type At the beginnings of EVLA, Navarro et al. [1] employed an 810 nm laser diode, targeting hemoglobin, based on a “1-second activity/1-second pause” impulse sequence. In the course of time, laser wavelengths progressively increased (940, 980,1064, 1320,1470 nm) up to 1500 nm, targeting water, and energy is now mainly delivered in a continuous mode. The main reasons driving this evolution were the search for a less painful postoperative course, with a lower ecchymosis burden. As to efficacy, the only available study comparing delivered energies is that by Samuel et al. [11] in which, using an 810 nm laser, a power of 14 W in continuous mode was tested against a power of 12 W in pulsed mode. After a 5-year follow-up, a higher occlusion rate along with a lower recurrence rate was observed in the first treatment group (14 W, continuous mode). Several other small studies, focusing mainly on the quality of the postoperative course rather than on efficacy, and with significant biases, compared different laser wavelengths [12–14]. Furthermore, all studies employed bare fibers which carbonize rapidly once the laser is activated. A black film forms on the laser-tip which absorbs and converts into heat any wavelength, preventing further evaluation of the role of wavelengths on the success of EVLA. Water-targeted lasers are currently employed at a lower power than hemoglobin-targeted lasers; however, if one complies to the manufacturers’ indications about power settings, there are no data
suggesting that power changes may impact on efficacy. Most of lasers currently employed in EVLA procedures are diode-lasers, except for the Nd:YAG 1320 nm (CoolTouch CTEV) laser, employing a micro-pulsed, high power-peak technology. Of three available retrospective studies, with significant biases, two demonstrated a higher efficacy of the Nd:YAG as compared to an 810 nm diode-laser [15,16], and one reported a 99.7% occlusion rate at 1-year follow-up, although with a high number of patients lost-to-follow-up [17]. The peculiar method of energy delivery and the automated and standardized pull-back system of the fiber, makes it very difficult to evaluate the real impact of the 1320 nm wavelength.
3. Success and fiberoptic-type Initially, bare fibers were used to perform intravenous lasertreatments [1]. Such fibers rapidly carbonize, creating a small high-temperature zone (up to 1000 °C) on the fiber-tip, called “hot spot”. The hot spot may come into contact with the venous wall, causing a contact-lesion, ranging from a burn to a perforation of the vein itself. The damage caused to the wall is significant, though very localized, and appears to provoke the skin ecchymosis and the postoperative pain, potentially contributing to some anatomical failures. To solve these problems, a new fiberoptic generation has been developed specifically for EVLA. Some of these new-generation fiberoptics, though based on bare-fibers, either feature a tulipshaped device (tulip fiber) attached to the terminal part of the fiber [18], or a ceramic/metal cap (capped/jacked fiber) shielding the fiber-tip [2], to prevent the hot spot from coming into contact with the venous wall. In terms of efficacy, the 1-year tulip fibers occlusion rate reached 97%, quite similar to that observed for bare fibers [18]; while, for capped fibers, Prince et al. [19] reported a 6-month recanalization rate of 11%, as compared to 2% with bare fibers. A different fiber-type, called “radial”, emits laser-light laterally and circumferentially, with an angle close to 70° from the fiber-axis. Radial fibers, when used with recommended power settings, do not carbonize; thus, the 1470 nm laser-light can penetrate the venous wall, being absorbed by water, its cromophore. Based on in-vitro or in-vivo histological studies, the resulting thermal damage is uniform, deep, and circumferential, and without contactlesions [20–21], translating into occlusion rates of 99.6%, 100%, and 100% at 1, 2, and 3 years respectively, according to prospective observational studies [22–24]. In terms of efficacy, head to head comparisons of bare and radial fibers, using a 1470 nm laser, did not yield significant differences, either in the short-term, with occlusion rates of 100% for both fiber-types [25], or in the medium-term, with occlusion rates of 100% at 32 months with radial fibers, and 99.5% at 4 years with bare fibers [24]. Interestingly, the post-operative course (bruising and pain), was reported to be better in the radial fiber group, in both studies. The uniform, deep, and circumferential thermal damage caused by radial fibers may explain the high success-rate observed; while the absence of contact-lesions may in turn justify the lower ecchymosis burden and the modest post-operative pain observed with radial fibers. Furthermore, the absence of contact-lesions allows the operator to deliver high-energy shots, without negatively impacting on the early post-operative course. 4. Success and delivered energy Proebstle et al. [26] observed a correlation between high recanalization rates and low energy levels, the latter being expressed
G. Spreafico et al. / Reviews in Vascular Medicine 3 (2015) 31–34
as “fluence” (J/cm2). Afterwards, delivered-energy was simply expressed as LEED (Linear Endovenous Energy Delivered), corresponding to the amount of Joules delivered per cm treated. Timpermann et al., in an energy dose-finding study, did not report vein-recanalization for LEED over 80 J/cm [27]. The same author, in a subsequent prospective study, observed a 95% success-rate with a mean LEED of 95 J/cm [28]. Theivacumar et al. [29], analyzing potential influencing factors for EVLA efficacy, identified a LEED over 60 J/cm as the determinant of success. Elmore et al. [30], reported 98% and 99.7% success-rates using a LEED of 109 and 115 J/cm, respectively, in two consecutive patient-series. In all of these studies, the main goal was to identify a standard energy dose to be employed in most patients. Prince et al. [31], investigating the relationship between failures and energy levels, indicated the diameter of the vein to be treated as the determinant of failure. From this findings spread a new research line aimed at targeting the delivered-energy to the vein size. Indeed, in prospective studies which adjusted energy levels to the vein size, medium- and long-term occlusion rates approached 100% [23,32]. A simple rule of thumb is the “times-10” rule, which calculates the desired LEED multiplying the mean vein diameter by 10. For instance, if the mean vein diameter is 7 mm, the LEED is 70 J/cm. Following this rule to adjust the LEED for veins, with a diameter ranging from 4 to 33 mm, the observed occlusion rate was 100% after a mean follow-up of 22 months [23].
5. Discussion Firstly, published data on EVLA is generally of low, or even very-low level, as emphasized by the respective Cochrane and NICE reviews [33,34]. Furthermore, when speaking about EVLA one needs to take into account the various laser-types (with different wavelengths, and diverse modes of energy-delivery and power settings), various fiberoptic-type, various techniques (especially of energy-delivery), and treatment strategies. The literature evaluating different EVLA methods is usually of low quality, being also frequently dated, so that head to head comparisons of new materials or techniques are almost lacking. In view of the efficacy evaluation, patient data (mean saphenous vein diameter, class “C” of CEAP) are poorly reported or even lacking, as well as those referring to the duration and completeness of followup, and to the criteria adopted to assess efficacy. Hence, we chose anatomical success as indicator, because it appears to be the better suited to evaluate EVLA efficacy. The most important determinant of EVLA efficacy is the amount of energy delivered, measured as LEED. Initially, researchers focused on the standard amount of energy necessary to reduce the recanalization rate of the saphenous trunk. A relatively broad range, spanning from 60 to 100 J/cm was identified, albeit lower LEED have been reported to be equally efficacious [35]. High energy levels (around 100 J/cm), although very effective, are only rarely employed, especially with bare fibers, because they are associated with increased post-operative pain, ecchymosis and nervous damage. Subsequently, researchers focused on the relationship between energy levels and vein diameter. It is a well-known principle of sclerotherapy to increase the concentration or amount of drug according to the vein diameter. Similarly, “thermal sclerotherapy” should adjust energy levels based on the same principle, in order to avoid energy over- and, in particular, under-dosing; being very likely with fixed energy-levels. Observational studies by Desmittere et al. [32], and Spreafico et al. [23], though conducted with different lasers and fiberoptic, show that high medium- and longterm occlusion rates are to be expected if energy levels are adjusted to the vein diameter. In our experience, the “times-10” rule,
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to establish the LEED for the saphenous trunk is simple and very efficacious. Another similar issue, underemphasized by the literature, is the opportunity to use higher energy levels in the first centimeters near the junction. This is well standardized in the thermo-ablation procedure using the closure-fast radiofrequency catheter, where two cycles are delivered in the first segment near the junction. As to EVLA, there are currently no standards in this respect; although, according to the “times-10” rule, a higher energy amount must be delivered near the junction because its diameter is usually bigger, or quite larger, than that of the trunk. In our experience, higher amounts of energy delivered in the first 3–5 cm near the junction, according to a “times 20/30” rule, determine an occlusion that can be demonstrated intraoperatively, and seem to abolish neovascularization. No data support the relationship between efficacy and different wavelength. The current trend is to use laser wavelengths higher than 1000 nm, targeting water, in a continuous mode. Power varies according to laser-type and fiberoptic, according to the literature or the manufacturers’ indications. The only non-diode laser available (Nd:YAG CoolTouch CTEV 1320 nm), uses its own settings, and yielded interesting results in terms of efficacy, even though high-level evidence is lacking [15– 17]. Personally, we do not have any experience with the Nd:YAG CoolTouch CTEV 1320 nm. As to fiberoptic, the major part of the available literature concerns bare-fibers. Those were the first to be employed, but are troublesome as they rapidly carbonize abolishing potential advantages coming from the use of specific wavelengths; feature a hot-temperature spot on the tip that may cause contact-lesions; and specially, determine a restricted venous-wall damage, thus enhancing the recanalization rate. The available literature on no-touch fibers is limited, suggesting that tulip fibers are as affective as bare fibers [18], while capped fibers may be less efficacious [19]. Radial fibers at 1470 nm were only compared to bare fibers in one short-term study, showing a similar efficacy, approaching 100%, at 3-month; similarly, mid-term studies report occlusion rates up to 100% [22–24]. In conclusion, adjusting energy amounts on the vein mean diameter (for instance with the “times-10” rule), and using radial fibers with a 1470 nm laser seem to grant an anatomical success rate close to 100%.
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document, Eur. J. Vasc. Endovasc. Surg. 42 (1) (2011) 89–102. [8] J. Brittenden, S.C. Cotton, A. Elders, E. Tassie, G. Scotland, C.R. Ramsay, et al., Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial, Health Technol. Assess. 19 (27) (2015) 1–342. [9] G. Spreafico, A. Piccioli, E. Bernardi, E. Giraldi, P. Pavei, R. Borgoni, et al., Sixyear follow-up of endovenous laser ablation for great saphenous vein incompetence, J. Vasc. Surg.: Venous Lymphat. Dis. 1 (1) (2013) 20–25. [10] S.K. van der Velden, A.A. Biemans, M.G. De Maeseneer, M.A. Kockaert, P. W. Cuypers, L.M. Hollestein, et al., Five-year results of a randomized clinical trial of conventional surgery, endovenous laser ablation and ultrasound-guided foam sclerotherapy in patients with great saphenous varicose veins, Br. J. Surg. (2015), http://dx.doi.org/10.1002/bjs.9867 [Epub ahead of print]. [11] N. Samuel, T. Wallace, D. Carradice, F.A. Mazari, I.C. Chetter, Comparison of 12w versus 14-w endovenous laser ablation in the treatment of great saphenous varicose veins: 5-year outcomes from a randomized controlled trial, Vasc. Endovasc. Surg. 47 (5) (2013) 346–352. [12] L.S. Kabnick, Outcome of different endovenous laser wavelengths for great saphenous vein ablation, J. Vasc. Surg. 43 (1) (2006) 88–93. [13] D.Y. Yu, H.C. Chen, S.Y. Chang, Y.C. Hsiao, C.J. Chang, Comparing the effectiveness of 1064 vs. 810 nm wavelength endovascular laser for chronic venous insufficiency (Varicose Veins), Laser Ther. 22 (4) (2013) 247–253. [14] A. Cavallini, Endovenous laser treatment of saphenous veins: is there clinical difference using different endovenous laser wavelengths? Int. Angiol. 34 (1) (2015) 1–8. [15] R.A. Weiss, M.A. Weiss, S. Eimpunth, S. Wheeler, S. Udompunturak, K. L. Beasley, Comparative outcomes of different endovenous thermal ablation systems on great and small saphenous vein insufficiency: long-term results, Lasers Surg. Med. 47 (2) (2015) 156–160. [16] J.M. Lee, I.M. Jung, J.K. Chung, Clinical and duplex-sonographic outcomes of 1320 nm endovenous laser treatment for saphenous vein incompetence, Dermatol. Surg. 38 (10) (2012) 1704–1709. [17] D.K. Moul, L. Housman, S. Romine, H. Greenway, Endovenous laser ablation of the great and short saphenous veins with a 1320 nm neodymium:yttriumaluminum-garnet laser: retrospective case series of 1171 procedures, J. Am. Acad. Dermatol. 70 (2) (2014) 326–331. [18] M.E. Vuylsteke, S. Thomis, P. Mahieu, S. Mordon, I. Fourneau, Endovenous laser ablation of the great saphenous vein using a bare fibre versus a tulip fibre: a randomised clinical trial, Eur. J. Vasc. Endovasc. Surg. 44 (6) (2012) 587–592. [19] E.A. Prince, G.M. Soares, M. Silva, A. Taner, S. Ahn, G.J. Dubel, et al., Impact of laser fiber design on outcome of endovenous ablation of lower-extremity varicose veins: results from a single practice, Cardiovasc. Intervent. Radiol. 34 (3) (2011) 536–541. [20] G. Spreafico, R. Giordano, A. Piccioli, G. Iaderosa, P. Pavei, E. Giraldi, et al., Histological damage of saphenous venous wall treated in vivo with radial fiber and 1470 nm diode laser, Italian J. Vasc. Endovasc. Surg. 18.4 (2011) 241–247.
[21] T. Yamamoto, M. Sakata, Influence of fibers and wavelengths on the mechanism of action of endovenous laser ablation, J. Vasc. Surg.: Venous Lymphat. Dis. 2 (1) (2014) 61–69. [22] E. von Hodenberg, C. Zerweck, M. Knittel, T. Zeller, T. Schwarz, Endovenous laser ablation of varicose veins with the 1470 nm diode laser using a radial fiber – 1-year follow-up, Phlebology 30 (2) (2015) 86–90. [23] G. Spreafico, A. Piccioli, E. Bernardi, E. Giraldi, P. Pavei, R. Borgoni, et al., Endovenous laser ablation of great and small saphenous vein incompetence with a 1470 nm laser and radial fiber, J. Vasc. Surg.: Venous Lymphat. Dis. 2 (4) (2014) 403–410. [24] M. Hirokawa, N. Kurihara, Comparison of bare-tip and radial fiber in endovenous laser ablation with 1470 nm diode laser, Ann. Vasc. Dis. 7 (3) (2014) 239–245. [25] T. Schwarz, E. von Hodenberg, C. Furtwängler, A. Rastan, T. Zeller, F. J. Neumann, Endovenous laser ablation of varicose veins with the 1470 nm diode laser, J. Vasc. Surg. 51 (6) (2010) 1474–1478. [26] T.M. Proebstle, F. Krummenauer, D. Gül, J. Knop, Nonocclusion and early reopening of the great saphenous vein after endovenous laser treatment is fluence dependent, Dermatol. Surg. 30 (2 Pt 1) (2004) 174–178. [27] P.E. Timperman, M. Sichlau, R.K. Ryu, Greater energy delivery improves treatment success of endovenous laser treatment of incompetent saphenous veins, J. Vasc. Interv. Radiol. 15 (10) (2004) 1061–1063. [28] P.E. Timperman, Prospective evaluation of higher energy great saphenous vein endovenous laser treatment, J. Vasc. Interv. Radiol. 16 (6) (2005) 791–794. [29] N.S. Theivacumar, D. Dellagrammaticas, R.J. Beale, A.I. Mavor, M.J. Gough, Factors influencing the effectiveness of endovenous laser ablation (EVLA) in the treatment of great saphenous vein reflux, Eur. J. Vasc. Endovasc. Surg. 35 (1) (2008) 119–123. [30] F.A. Elmore, D. Lackey, Effectiveness of endovenous laser treatment in eliminating superficial venous reflux, Phlebology 23 (1) (2008) 21–31. [31] E.A. Prince, S.H. Ahn, G.J. Dubel, G.M. Soares, An investigation of the relationship between energy density and endovenous laser ablation success: does energy density matter? J. Vasc. Interv. Radiol. 19 (10) (2008) 1449–1453. [32] J. Desmyttère, C. Grard, B. Wassmer, S. Mordon, Endovenous 980 nm laser treatment of saphenous veins in a series of 500 patients, J. Vasc. Surg. 46 (6) (2007) 1242–1247. [33] C. Nesbitt, R. Bedenis, V. Bhattacharya, G. Stansby, Endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus open surgery for great saphenous vein varices, Cochrane Database Syst. Rev. 7 (2014) CD005624. [34] National Institute for Health and Care Excellence. Varicose veins in the legs— the diagnosis and management of varicose veins, (Clinical guideline 168.), 2013. 〈http://guidance.nice.org.uk/CG168〉. [35] H.S. Kim, I.J. Nwankwo, K. Hong, P.S. McElgunn, Lower energy endovenous laser ablation of the great saphenous vein with 980 nm diode laser in continuous mode, Cardiovasc. Interv. Radiol. 29 (1) (2006) 64–69.
Contents lists available at ScienceDirect
Reviews in Vascular Medicine journal homepage: www.elsevier.com/locate/rvm
Review
Factors influencing the success of endovenous laser ablation (EVLA) Giorgio Spreafico a,n, Enrico Bernardi b, Patrizia Pavei a, Enzo Giraldi a a b
Multidisciplinary Centre for Day Surgery, University Hospital of Padua, Italy Emergency Department ULSS7, Pieve di Soligo, Italy
Contents 1. The success 2. Success and 3. Success and 4. Success and 5. Discussion . REFERENCES . . .
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Endovenous laser ablation (EVLA) celebrates its fourteenth birthday in 2015 [1]. The purpose of EVLA is to achieve a stable occlusion of the refluxing saphenous trunk through the thermal damage caused by the exposition to laser light with an 810– 1500 nm wavelength [2]. Saphenous trunk occlusion usually restores the competence of the residual, untreated junction. The EVLA technique is well standardized [3]; however, both the materials (laser, and fiberoptic) and several technical details have evolved over the years [4,5].
1. The success A technically/anatomically successful EVLA procedure is defined as a complete and stable occlusion of the saphenous trunk confirmed by echo-color-Doppler (ECD). This outcome has been extensively investigated in the literature, being a mandatory information for publications on the efficacy of EVLA. The “Recommended reporting standards for endovenous ablation for the treatment of venous insufficiency: joint statement of The American Venous Forum and The Society of Interventional Radiology” [6], when discussing the efficacy of treatment, emphasizes the importance of a correct ablation of the saphenous n Correspondence to: Multidisciplinary Centre for Day Surgery, University Hospital Giustinianeo, Via Giustiniani 2, 35121 Padua, Italy. E-mail address: spreafi[email protected] (G. Spreafico).
http://dx.doi.org/10.1016/j.rvm.2015.10.001 2212-0211/& 2015 Elsevier GmbH All rights reserved.
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trunk, while it does not stress the importance of regaining the junction competence; although it is well known that a persistent reflux at the junction level may result in neovascularization or reflux towards the residual branches of the junction, such as the accessory saphenous veins of the thigh. Objective confirmation of trunk occlusion is based on well defined and agreed criteria (non-compressible or non-visible vein, absence of intraluminal venous flow, assessed by ECD). To the contrary, difficulties arise whenever the clinical meaning or the classification of trunk partial recanalization are addressed, due to the different failure criteria adopted in published studies, such as the minimum length of patent segments, their caliper, the presence/absence of reflux, or their relationship with the junction, the collateral or the perforating veins. Unfortunately, there are no agreed standards in the literature to evaluate partial trunk recanalization, except for the landmark paper by De Maeseneer, et al. [7]. For instance, the minimum meaningful length for a patent vein segment was formerly estimated at 10 cm, while it is currently accepted also at 5 cm [8]; and the caliper of the patent segment is almost never reported, although a caliper lower than 2–3 mm probably does not have clinical relevance. The same holds true for patent and competent venous segments interposed between two correctly occluded segments. Accurate analysis of these treatment shortcomings is not useful in the short/medium-term, as they are infrequently associated with recurrent symptoms or varices; to the contrary, long-term follow-up would be desirable to establish their clinical
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course. For instance, 6-year follow-up of venous reflux limited to the saphenous junction following EVLA demonstrated a very mild impact on the incidence of clinically evident recurrence [9]. Similarly, in the sclerotherapy arm of the MAGNA study [10] a notably higher recanalization rate was observed, as compared with the EVLA arm. Interestingly, while no differences in terms of quality of life (QoL) were observed at the 1-year follow-up, a further increase both in the recanalization rate, and in the re-intervention rate, and a reduction of the QoL were recorded at the 5-year evaluation. The finding of an anatomically successful procedure should represent a mainstay to exclude that recurrent symptoms or varices are due to an EVLA failure. However, besides anatomical success, especially clinical efficacy should be considered when evaluating the efficacy of EVLA. Clinical efficacy is usually assessed by means of either general or disease-specific QoL questionnaires, and of standardized questionnaires (e.g.: the Venous Clinical Severity Score, or VCSS). For instance, the primary outcome in the CLASS study [8] was not the anatomical success but the improvement of QoL, evaluated by means of both the disease-specific AVVQ (Aberdeen Varicose Vein Questionnaire), and the general SF36 and EQ5D questionnaires. AVVQ improvements were observed at 6 weeks and at 6 months in the EVLA arm, the earlier being relevant, the latter being slight. Similar results, though to a lesser degree, were also recorded using the SF-36 and EQ5D questionnaires. Other secondary clinical outcomes were assessed with the VCSS questionnaire, and the discomfort associated with varices by means of a visual-analog scale. In both instances, a trend of improvement similar to that observed for the primary outcome was recorded in the EVLA arm. The need for long-term follow-up data to better evaluate the clinical course is stressed by the conclusions of the CLASS study, where the impact of the anatomical success on the QoL and the clinical picture at 6 months is labeled as “unclear”; though an anatomical failure could be predictive of clinical recurrence and of the need for retreatments in the longterm. We will hereafter refer to anatomical success only.
2. Success and laser-type At the beginnings of EVLA, Navarro et al. [1] employed an 810 nm laser diode, targeting hemoglobin, based on a “1-second activity/1-second pause” impulse sequence. In the course of time, laser wavelengths progressively increased (940, 980,1064, 1320,1470 nm) up to 1500 nm, targeting water, and energy is now mainly delivered in a continuous mode. The main reasons driving this evolution were the search for a less painful postoperative course, with a lower ecchymosis burden. As to efficacy, the only available study comparing delivered energies is that by Samuel et al. [11] in which, using an 810 nm laser, a power of 14 W in continuous mode was tested against a power of 12 W in pulsed mode. After a 5-year follow-up, a higher occlusion rate along with a lower recurrence rate was observed in the first treatment group (14 W, continuous mode). Several other small studies, focusing mainly on the quality of the postoperative course rather than on efficacy, and with significant biases, compared different laser wavelengths [12–14]. Furthermore, all studies employed bare fibers which carbonize rapidly once the laser is activated. A black film forms on the laser-tip which absorbs and converts into heat any wavelength, preventing further evaluation of the role of wavelengths on the success of EVLA. Water-targeted lasers are currently employed at a lower power than hemoglobin-targeted lasers; however, if one complies to the manufacturers’ indications about power settings, there are no data
suggesting that power changes may impact on efficacy. Most of lasers currently employed in EVLA procedures are diode-lasers, except for the Nd:YAG 1320 nm (CoolTouch CTEV) laser, employing a micro-pulsed, high power-peak technology. Of three available retrospective studies, with significant biases, two demonstrated a higher efficacy of the Nd:YAG as compared to an 810 nm diode-laser [15,16], and one reported a 99.7% occlusion rate at 1-year follow-up, although with a high number of patients lost-to-follow-up [17]. The peculiar method of energy delivery and the automated and standardized pull-back system of the fiber, makes it very difficult to evaluate the real impact of the 1320 nm wavelength.
3. Success and fiberoptic-type Initially, bare fibers were used to perform intravenous lasertreatments [1]. Such fibers rapidly carbonize, creating a small high-temperature zone (up to 1000 °C) on the fiber-tip, called “hot spot”. The hot spot may come into contact with the venous wall, causing a contact-lesion, ranging from a burn to a perforation of the vein itself. The damage caused to the wall is significant, though very localized, and appears to provoke the skin ecchymosis and the postoperative pain, potentially contributing to some anatomical failures. To solve these problems, a new fiberoptic generation has been developed specifically for EVLA. Some of these new-generation fiberoptics, though based on bare-fibers, either feature a tulipshaped device (tulip fiber) attached to the terminal part of the fiber [18], or a ceramic/metal cap (capped/jacked fiber) shielding the fiber-tip [2], to prevent the hot spot from coming into contact with the venous wall. In terms of efficacy, the 1-year tulip fibers occlusion rate reached 97%, quite similar to that observed for bare fibers [18]; while, for capped fibers, Prince et al. [19] reported a 6-month recanalization rate of 11%, as compared to 2% with bare fibers. A different fiber-type, called “radial”, emits laser-light laterally and circumferentially, with an angle close to 70° from the fiber-axis. Radial fibers, when used with recommended power settings, do not carbonize; thus, the 1470 nm laser-light can penetrate the venous wall, being absorbed by water, its cromophore. Based on in-vitro or in-vivo histological studies, the resulting thermal damage is uniform, deep, and circumferential, and without contactlesions [20–21], translating into occlusion rates of 99.6%, 100%, and 100% at 1, 2, and 3 years respectively, according to prospective observational studies [22–24]. In terms of efficacy, head to head comparisons of bare and radial fibers, using a 1470 nm laser, did not yield significant differences, either in the short-term, with occlusion rates of 100% for both fiber-types [25], or in the medium-term, with occlusion rates of 100% at 32 months with radial fibers, and 99.5% at 4 years with bare fibers [24]. Interestingly, the post-operative course (bruising and pain), was reported to be better in the radial fiber group, in both studies. The uniform, deep, and circumferential thermal damage caused by radial fibers may explain the high success-rate observed; while the absence of contact-lesions may in turn justify the lower ecchymosis burden and the modest post-operative pain observed with radial fibers. Furthermore, the absence of contact-lesions allows the operator to deliver high-energy shots, without negatively impacting on the early post-operative course. 4. Success and delivered energy Proebstle et al. [26] observed a correlation between high recanalization rates and low energy levels, the latter being expressed
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as “fluence” (J/cm2). Afterwards, delivered-energy was simply expressed as LEED (Linear Endovenous Energy Delivered), corresponding to the amount of Joules delivered per cm treated. Timpermann et al., in an energy dose-finding study, did not report vein-recanalization for LEED over 80 J/cm [27]. The same author, in a subsequent prospective study, observed a 95% success-rate with a mean LEED of 95 J/cm [28]. Theivacumar et al. [29], analyzing potential influencing factors for EVLA efficacy, identified a LEED over 60 J/cm as the determinant of success. Elmore et al. [30], reported 98% and 99.7% success-rates using a LEED of 109 and 115 J/cm, respectively, in two consecutive patient-series. In all of these studies, the main goal was to identify a standard energy dose to be employed in most patients. Prince et al. [31], investigating the relationship between failures and energy levels, indicated the diameter of the vein to be treated as the determinant of failure. From this findings spread a new research line aimed at targeting the delivered-energy to the vein size. Indeed, in prospective studies which adjusted energy levels to the vein size, medium- and long-term occlusion rates approached 100% [23,32]. A simple rule of thumb is the “times-10” rule, which calculates the desired LEED multiplying the mean vein diameter by 10. For instance, if the mean vein diameter is 7 mm, the LEED is 70 J/cm. Following this rule to adjust the LEED for veins, with a diameter ranging from 4 to 33 mm, the observed occlusion rate was 100% after a mean follow-up of 22 months [23].
5. Discussion Firstly, published data on EVLA is generally of low, or even very-low level, as emphasized by the respective Cochrane and NICE reviews [33,34]. Furthermore, when speaking about EVLA one needs to take into account the various laser-types (with different wavelengths, and diverse modes of energy-delivery and power settings), various fiberoptic-type, various techniques (especially of energy-delivery), and treatment strategies. The literature evaluating different EVLA methods is usually of low quality, being also frequently dated, so that head to head comparisons of new materials or techniques are almost lacking. In view of the efficacy evaluation, patient data (mean saphenous vein diameter, class “C” of CEAP) are poorly reported or even lacking, as well as those referring to the duration and completeness of followup, and to the criteria adopted to assess efficacy. Hence, we chose anatomical success as indicator, because it appears to be the better suited to evaluate EVLA efficacy. The most important determinant of EVLA efficacy is the amount of energy delivered, measured as LEED. Initially, researchers focused on the standard amount of energy necessary to reduce the recanalization rate of the saphenous trunk. A relatively broad range, spanning from 60 to 100 J/cm was identified, albeit lower LEED have been reported to be equally efficacious [35]. High energy levels (around 100 J/cm), although very effective, are only rarely employed, especially with bare fibers, because they are associated with increased post-operative pain, ecchymosis and nervous damage. Subsequently, researchers focused on the relationship between energy levels and vein diameter. It is a well-known principle of sclerotherapy to increase the concentration or amount of drug according to the vein diameter. Similarly, “thermal sclerotherapy” should adjust energy levels based on the same principle, in order to avoid energy over- and, in particular, under-dosing; being very likely with fixed energy-levels. Observational studies by Desmittere et al. [32], and Spreafico et al. [23], though conducted with different lasers and fiberoptic, show that high medium- and longterm occlusion rates are to be expected if energy levels are adjusted to the vein diameter. In our experience, the “times-10” rule,
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to establish the LEED for the saphenous trunk is simple and very efficacious. Another similar issue, underemphasized by the literature, is the opportunity to use higher energy levels in the first centimeters near the junction. This is well standardized in the thermo-ablation procedure using the closure-fast radiofrequency catheter, where two cycles are delivered in the first segment near the junction. As to EVLA, there are currently no standards in this respect; although, according to the “times-10” rule, a higher energy amount must be delivered near the junction because its diameter is usually bigger, or quite larger, than that of the trunk. In our experience, higher amounts of energy delivered in the first 3–5 cm near the junction, according to a “times 20/30” rule, determine an occlusion that can be demonstrated intraoperatively, and seem to abolish neovascularization. No data support the relationship between efficacy and different wavelength. The current trend is to use laser wavelengths higher than 1000 nm, targeting water, in a continuous mode. Power varies according to laser-type and fiberoptic, according to the literature or the manufacturers’ indications. The only non-diode laser available (Nd:YAG CoolTouch CTEV 1320 nm), uses its own settings, and yielded interesting results in terms of efficacy, even though high-level evidence is lacking [15– 17]. Personally, we do not have any experience with the Nd:YAG CoolTouch CTEV 1320 nm. As to fiberoptic, the major part of the available literature concerns bare-fibers. Those were the first to be employed, but are troublesome as they rapidly carbonize abolishing potential advantages coming from the use of specific wavelengths; feature a hot-temperature spot on the tip that may cause contact-lesions; and specially, determine a restricted venous-wall damage, thus enhancing the recanalization rate. The available literature on no-touch fibers is limited, suggesting that tulip fibers are as affective as bare fibers [18], while capped fibers may be less efficacious [19]. Radial fibers at 1470 nm were only compared to bare fibers in one short-term study, showing a similar efficacy, approaching 100%, at 3-month; similarly, mid-term studies report occlusion rates up to 100% [22–24]. In conclusion, adjusting energy amounts on the vein mean diameter (for instance with the “times-10” rule), and using radial fibers with a 1470 nm laser seem to grant an anatomical success rate close to 100%.
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