Endovenous laser therapy vs. high ligation/stripping for varicosity of the great saphenous vein

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1 Original article 7 Endovenous laser therapy vs. high ligation/stripping for varicosity of the great saphenous vein Clinical and sonographic findings I. Flessenkämper 1 ; D. Stenger 2 ; M. Hartmann 3 ; S. Roll 4 1 HELIOS Klinikum Emil von Behring, Klinik für Gefäßmedizin, Berlin/Germany; 2 Venenzentrum Saarlois, Saarlois/Germany; 3 Venenzentrum Freiburg, Freiburg/Germany; 4 Institut für Sozialmedizin, Epidemiologie und Gesundheitsökonomie, Medizinisches Zentrum der Charité, Berlin/Germany Keywords EVLT, crossectomy, rct, side effects, ultrasound Summary Introduction: Varicosis therapy options include a combination of crossectomy/stripping and the endoluminal laser therapy, however, to date lacking statistically relevant data. Material and Methods: In an open multicentre, randomized 3-arm-trial sonographic and clinical parameters were compared perioperatively, and after 2 and between endoluminal venous laser therapy, high ligation, and invaginating stripping. (Laser: 980 nm Biolitec, Continous-Mode, 30 W). Data of 449 patients were available for the perioperative and examination. 388 patients were followed up until 6 We compare clinical recurrencies, sonographic reflux findings, and refluxive side branches in the inguinal region at the saphenofemoral junction. Results: We found significantly more refluxive side-branches in the laser groups, however, no statistically significant relation between clinical recurrencies and sonographic reflux. Over the time, there were no intraindividual constant refluxes. Regarding the Correspondenz to: Dr. Ingo Flessenkämper Klinik für Gefäßmedizin, Helios Klinikum E. v. Behring Walterhöferstr. 11, D Berlin, Germany Tel / , Fax / ingo.flessenkaemper@helios-kliniken.de further endpoints edema, lymphatic edema, local disturbancies of sensibility and irritations of the saphenous nerve, matting and postoperative restricitions, lymphatic edema, local disturbancies of sensibility and irritations of the saphenous nerve were significantly more present in the two laser groups. Discussion: In a long time follow-up we have to investigate the importance of refluxive sidebranches for the development of clinical recurrencies. According to the findings on side effects, the tested laser technique is not less harmful to the patients than open surgery. Schlüsselwörter EVLT, Crossektomie, Crosserezidiv, rct, Nebenwirkungen, Ultraschall Phlebologie 2013; 42: 7 11 DOI: /2128_1_2013 Received: December 9, 2012 Accepted: December 21, 2012 Zusammenfassung Einleitung: Zur Therapie der Stammvaricosis der Vena saphena magna stehen u.a. die Kombination Crossektomie/ Stripping und die endoluminale Lasertherapie zur Verfügung, jedoch bislang ohne statistisch belastbare Daten. Material und Methode: Perioperativ, nach 2 und 6 Monaten, wurden sonographische und klinische Parameter in einer prospektiven randomisierten dreiarmigen Multicenter-Studie zwischen der endoluminalen Lasertherapie, der invaginierend durchgeführten, modifizierten, offen operativen Therapie der Stammvarikosis der Vena saphena magna und der endoluminalen Lasertherapie (Laserprozedur mit 980 nm Laser (Biolitec), Continuous-Mode-Verfahren mit 30 Watt) verglichen. Initial und nach 2 Monaten wurden Daten von 449 Patienten, nach 6 Monaten von 388 Patienten erhoben. Zielparameter waren die sonographischen, inguinalen Refluxbefunde einschließlich durchströmter Seitenäste und deren Bezug zu klinischen Rezidiven. Ergebnisse: In den beiden Lasergruppen wurden signifikant mehr crossennahe Seitenäste gefunden als in der operativen Therapie. Es gab zu diesem Zeitpunkt keinen statistisch signifikanten Zusammenhang zwischen Refluxbefunden und klinischen Rezidiven. Die Refluxund Rezidivbefunde zeigten im zeitlichen Verlauf keine intraindividuelle Konstanz. Bezüglich der Endpunkte Ödeme, Lymphödeme, neurologische Sensibilitätsstörungen, Matting und postoperative Einschränkungen gab es signifikant mehr Lymphödeme, lokale Sensibilitätsstörungen und Saphenusschäden in den beiden Lasergruppen. Diskussion: Mit längerfristigen Nachuntersuchungen muss die Bedeutung der crossenahen Seitenäste für die Entwicklung klinischer Rezidive geklärt werden. Aufgrund des Nebenwirkungsprofils kann die verwendete Lasertechnik nicht als schonenderes Verfahren gegenüber der klassischen Operation bezeichnet werden.

2 8 I. Flessenkämper et al.: Endoluminal laser therapy vs crossectomy/stripping of the varicose great saphenous vein Introduction Besides other therapeutic options, the combination of crossectomy/stripping and endoluminal laser therapy are possible methods for treating the trunk varicosis of the great saphenous vein (GSV). As the only available data were statistically unreliable, the Deutschen Gesellschaft für Phlebologie (German Society of Phlebology) supported a prospective randomised trial to compare these methods. The short-term clinical findings and ultrasound results with respect to reflux in the inguinal region have already been reported (1). In the presentation of peri- and post-operative end points in the current article, it is necessary to describe medium term results, whereby the perioperative results are considered in relation to the findings after six In addition, it reports on the clinical and ultrasound findings in the region of the saphenofemoral junction (SFJ), as these may be relevant to long-term developments. Methods Patients 449 patients with trunk varicose veins (320 women, 129 men; mean age 48.7 years) were enrolled in the study at three centres (Berlin, Freiburg, Saarlouis; Germany). 159 patients Crossectomy with invagination stripping (C/S) 159 patients after > 550 patients screened 449 patients randomised 142 patients Laser 142 patients after The patients were randomised into one of three intervention groups (central randomisation): Laser therapy (Laser, n=142), Crossectomy and stripping (C/S, n=159) Crossectomy with laser therapy (C/Laser, n=148). Patients aged with trunk varicose veins in Hach stage II-IV had to be anatomically suitable for surgery as well as for laser therapy. The diameter of the vein could not exceed 16 mm at a point 5 cm distal to the SFJ. One specific exclusion criterion was previous surgery on the great saphenous vein (GSV). Interventions In the C/Laser and C/S groups, the GSV was ligatured at the same level with nonabsorbable suture thread. An invaginative surgical technique was used for stripping in all cases. This was carried out from proximal to distal, whereby the procedure was tailored in each case to the respective stage of the disease. A 980 nm laser (Biolitec) was used for the laser treatment. After distal puncture and placement of an introducer sheath, tumescence was obtained with ml solution. 30 Watts were 148 patients C/Laser 148 patients after then applied in continuous mode on withdrawal of the fibre. In the C/Laser group, the crossectomy was performed first. The laser probe was then inserted, starting from the transected GSV, and passed distally as far as the most distal point of incompetence. The same procedure as for the laser group was then followed. In all three groups, branch vein exeresis was performed by mini-phlebectomy. All surgical procedures were carried out under general anaesthetic. Data collection Standardised data on duplex ultrasonography, CEAP classification, clinical score, on the impairment score for venous diseases and on the neurological status of the leg were collected at follow-up visits after two and six Ethics The study was approved by the Ethics Committee of the Berlin Medical Association. End points The primary end point of the main study was the determination of inguinal recurrence at the SFJ after two years. The evaluation presented here aims to correlate clinical and ultrasound findings and also to detect branch veins sited distal to the SFJ with retrograde flow. It was postulated that clinical recurrence could arise from these vessels in the long term. Further study end points aimed to determine the situation with regard to local pain, oedema, the occurrence of matting or telangiectasia and neurological damage in the form of local sensory deficits or saphenous nerve injury in the treated leg. The limitation of the findings with regard to the patient s ability to work were also determined. Follow-up visits Fig patients after Patient flow chart 127 patients after 133 patients after In accordance with the study protocol, patients were examined preoperatively, after two months, and after six Duplex ultrasonography of the great saphenous vein was performed to look for inguinal re- Phlebologie 1/2013 Schattauer 2013

3 I. Flessenkämper et al.: Endoluminal laser therapy vs crossectomy/stripping of the varicose great saphenous vein 9 flux. The treated vein segment was monitored for the entire duration. Statistics The three groups were compared for each of the categorical end points with the chisquare test, using SAS Version 9.2 (SAS Institute Inc., Cary, NC, USA). The level of significance was set at No adjustment was made for multiple testing. Results The follow-up rate was 100 % after two months and 86 % after six months ( Fig. 1). After randomisation, stages C2 and C3 of the CEAP classification were more or less the same in each group: 81 % in the C/S group, 82 % in the Laser group and 85 % in the C/Laser group. Inguinal recurrence in the region of the SFJ and the clinical presence of varicose convolutions in the flow region of the treated great saphenous vein were specifically looked for as primary end points of the main study. Table 1 presents the results after two and six months, both separately and in relation to each other. At this juncture, it was also checked, whether clinical recurrence occurs after two and six Thereby, twenty patients stood out, who had a clinical recurrence after two months, which was, however, no longer apparent after six Fourteen patients had an ultrasonically demonstrated recurrence after two months, which likewise could no longer be detected after six Ultrasound scanning for branch veins distal to the SFJ showed that these could be found at a distance of up to 2 cm in the immediate postoperative period. Branches could also be demonstrated further away after two months and six months, but with no increase seen between these two points in time ( Fig. 2). Table 2 shows the secondary end points of telangiectasia, local pigmentation, oedema, local neurological deficits and saphenous nerve injury at the two- and sixmonth study visits. Tab. 1 Clinical and ultrasound recurrence after two and six End point Clinical recurrence Ultrasound recurrence Clinical or ultrasound recurrence Clinical and ultrasound recurrence Ultrasound recurrence, but no clinical recurrence Clinical recurrence, but no ultrasound recurrence Follow up C/S: crossectomy and stripping; C/Laser: crossectomy with laser therapy With respect to pain, a clear reduction can be seen after two months in comparison with the postoperative period, with marked group-specific differences (p=0.006). The distribution in the groups showed a sustained, but not significant trend to the disadvantage of the laser group (p=0.361). This trend persisted at six The number of patients with pain was greater in the two laser groups than the surgery-only group throughout the study, but the difference was no longer significant after the postoperative period (p=0.388) ( Fig. 3). According to the visual circle scale (VCS), compared with the preoperative state, there was marked improvement after Fig. 2 Distance from the SFJ in cm of branch veins found on ultrasound scanning: postoperatively, and after two and six C/S (%) Laser (%) two months in all groups with respect to the limitations imposed by venous disease. After six months, almost none of the most severe limitations remained. Only in the mixed group was there a discrete increase in symptomatic patients in comparison with the laser group and the open surgery group ( Fig. 4). Discussion C/Laser (%) This study has shown that three invasive therapeutic strategies with very different approaches give very good early results both clinically and on ultrasonography. % Postoperative 35 5 cm 4 cm 3 cm 2 cm 1 cm p

4 10 I. Flessenkämper et al.: Endoluminal laser therapy vs crossectomy/stripping of the varicose great saphenous vein Tab. 2 End point Telangiectasia Secondary end points after two and six Local pigmentation Oedema Local neurological deficit Saphenous nerve injury Follow up C/S (%) C/S: crossectomy and stripping; C/Laser: crossectomy with laser therapy % Postoperative % 80% 60% 40% 20% 0% severe, with Analgetica mild, no Analgetica Präoperative Laser (%) C/Laser (%) p Fig. 3 Mild or severe pain requiring analgesics, postoperatively, after two and after six Level 4: unable to work with compression Level 3: 8 hrs. working only possible with compression Level 2: symptomatic, working ability with compression Level 1: asymptomatic Fig. 4 Limitation of working ability due to venous disease preoperatively and after two and six With respect to the development of clinical recurrence, which is of relevance to the patient, no definite conclusions can be drawn at this time. Regarding the demonstration of patent branch veins extending from the proximal great saphenous vein, the relevance of the significantly different ultrasonography findings between the groups can only be determined over a longer period of time. It can be expected that this trend will continue in the long term and that clinical recurrence will occur over these reflux segments and branch veins, as described by Darwood and Disselhoff in their studies (2, 3). But there is no evidence of this after only six At this point in time, there is no direct relationship between clinical recurrence and that found on ultrasonography. The two variants appear independently of each other. The expectation that reflux seen on ultrasonography would be the cause of visible clinical recurrence was met in only a very few patients in each group ( %). The long-term results must definitely be awaited. It was also surprising that intraindividually there was no unidirectional consistency with respect to the findings on reflux and recurrence. Findings of reflux after two months could no longer be demonstrated after six months, something that might be important in the future, when advising patients affected by reflux at an early stage. Darwood (3) reported similar findings, describing reflux after three months that was no longer detectable after one year. In the present study, the strategy of combined crossectomy/laser is not convincing with respect to end points such as pain and postoperative limitations. This, in turn, agrees with the findings of Lurie (4), who also reported increased pain. In addition, even though considerably less reflux and fewer patent branch veins were reported in comparison with pure laser therapy (as also found by Disselhoff), this author also considers that even more neovascular development has to be reckoned with (5). On consideration of the end points, the results concerning pain stand out. Although it was surprising that the laser groups had a significantly higher perioper- Phlebologie 1/2013 Schattauer 2013

5 I. Flessenkämper et al.: Endoluminal laser therapy vs crossectomy/stripping of the varicose great saphenous vein 11 ative pain score than those undergoing open operations (1), it was even more surprising that this trend persisted through the two-month results and up to the sixmonth visit. This was not the case for Rasmussen (6). He found that the pain level was considerably higher, even though he worked with the same wavelength (980 nm) as in this study and, at 73.5 J/cm, the linear endovenous energy density (LEED) was in a comparable range. There is no clear explanation for the high level of pain persisting over six months in the laser groups. It is possible that the symptoms are not caused by wound healing in the pull-through channel with resolving haematomas, as in classic operations, but are rather due to thermal effects and their typical pattern of healing, with considerably more aggravated pain. This would also explain the increased swelling seen in the laser groups. The visual results are reflected in the development of pigmentation. After two months, there seems to be a negative trend for the laser procedure, although this disadvantage disappears completely after six About 10 % of patients are affected, irrespective of the procedure carried out. Since a tendency to regression has been demonstrated, it will be of interest to see whether this trend is maintained at subsequent follow-up visits. This may also be an important consideration when advising future patients, especially women. Telangiectasia occurred with a similar frequency for all three methods and gives no grounds for deciding between them. Results on irritation of the saphenous nerve and local sensory deficits were also unexpected. In planning, the latter was actually viewed as a parameter for damage caused by the mini-phlebectomies. But, highly significantly, both neurological abnormalities were more common in the two laser groups, so that it has to be assumed that a relationship to the method does exist. After six months, there was still a highly significant difference to the disadvantage of the laser groups. The same applies to the occurrence of oedema. For both parameters, the question remains open whether the damage is due to the energy applied per se or is possibly even due to the tumescence intended to provide a protective effect. The results of the different procedures clearly show, however, that endoluminal therapy cannot be called a more gentle method (1). Conflict of interest The study was sponsored by the Deutschen Gesellschaft für Phlebologie (DGP). None of the authors has any conflict of interest. References 1. Flessenkamper I, Hartmann M, Stenger D, Roll S. Endovenous laser ablation with and without high ligation compared with high ligation and stripping in the treatment of great saphenous varicose veins: initial results of a multicentre randomized controlled trial. Phlebology 2012 Mar Disselhoff BC, der Kinderen DJ, Kelder JC, Moll FL. Randomized clinical trial comparing endovenous laser with cryostripping for great saphenous varicose veins. Br J Surg 2008; 95(10): Darwood RJ, Theivacumar N, Dellagrammaticas D, Mavor AI, Gough MJ. Randomized clinical trial comparing endovenous laser ablation with surgery for the treatment of primary great saphenous varicose veins. Br J Surg 2008; 95(3): Lurie F, Creton D, Eklof B, Kabnick LS, Kistner RL, Pichot O, et al. Prospective randomised study of endovenous radiofrequency obliteration (closure) versus ligation and vein stripping (EVOLVeS): two-year follow-up. Eur J Vasc Endovasc Surg 2005; 29(1): Disselhoff BC, der Kinderen DJ, Kelder JC, Moll FL. Randomized clinical trial comparing endovenous laser ablation of the great Saphenous vein with and without ligation of the sapheno-femoral junction: 2-year results. Eur J Vasc Endovasc Surg 2008; 36(6): Rasmussen LH, Bjoern L, Lawaetz M, Blemings A, Lawaetz B, Eklof B. Randomized trial comparing endovenous laser ablation of the great saphenous vein with high ligation and stripping in patients with varicose veins: short-term results. J Vasc Surg 2007; 46(2): The translation of this article was made possible by courtesy of: Covidien Germany GmbH Bauerfeind AG Medi Germany Sigvaris Germany Bayer GmbH Ofa Bamberg Biolitec AG