Interventions for varicose veins

Summary

Chronic venous disease is common and increases with age. In addition to the classically described complaints, it may also result in skin changes and venous ulcers. Chronic venous disease (CVD) has a great impact on patients’ health-related quality of life and is associated with considerable health care costs. Minimally invasive techniques, such as (ultrasound-guided foam) sclerotherapy, phlebectomies, and endovenous thermal ablation, are most frequently used for the treatment of (saphenous) varicose veins. Endovenous ablation techniques for saphenous veins have a high success rate, are associated with few complications and can be performed in an outpatient setting, avoiding hospitalisation.

Introduction

Varicose veins are tortuous and enlarged veins caused by a weakening in the vein’s wall or valves. They are a part of chronic venous disease (CVD), which may lead to serious complications, such as leg ulcers. The term chronic venous insufficiency is reserved for more serious stages of CVD when patients have edema and/or skin changes. The prevalence of varicose veins is high, especially in the western population, where it is approximately 30%.

Although many individuals will consult their physician for cosmetic reasons, others will have serious complaints and visible complications. Eighty percent of leg ulcers, whose incidence increases with age, are venous ulcers. Half of all venous leg ulcers are caused by varicose veins. The treatment of leg ulcers is extremely intensive and very expensive; therefore, treatment of superficial varicose veins in order to prevent the development of serious venous disease is recommended.

Unfortunately, there are no good clinical tests to predict which individual is at risk for developing serious complications of his/her varicose veins. Patients with clinical signs and symptoms of varicose veins that are not treated (e.g., when they do not want to be treated) are advised to be investigated every 3-5 years. As the severity of the disease will increase with age, their venous function should be re-evaluated and varicose veins should be treated to prevent serious complications.

Compression therapy is still the cornerstone of the treatment of venous disease. Many patients, however, do not comply with advice to wear bandages or compression hosieries. The current treatment options are compression therapy, surgery, sclerotherapy and endovascular thermal and non-thermal ablation techniques. Almost all treatments can be performed under tumescent anesthesia and have minimal complications. When adequate pre-operative duplex ultrasound examination has been performed, success rate is high. This chapter will describe the percutaneous interventions for varicose veins and not the surgical techniques (stripping, ligation, phlebectomies).

EPIDEMIOLOGY OF CHRONIC VENOUS DISEASE

Lower extremity venous disease is a common medical condition. Half of the adult population bear the stigmata of minor venous disease [11. Evans CJ, Fowkes FG, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study. J Epidemiol Community Health. 1999;53(3):149-53. ] and about 25% of the population has lower extremity varicose veins [22. Rabe E, Berboth G, Pannier F. [Epidemiology of chronic venous diseases] Epidemiologie der chronischen Venenkrankheiten. Wien Med Wochenschr. 2016;166(9-10):260-3. , 33. Rabe E, Guex JJ, Puskas A, Scuderi A, Fernandez Quesada F, Coordinators VCP. Epidemiology of chronic venous disorders in geographically diverse populations: results from the Vein Consult Program. Int Angiol. 2012;31(2):105-15. ]. More than 25% of people with varicose veins have insufficiency of the saphenous veins of the legs. A history of serious leg injury or phlebitis represent important risk factors resulting in a 2.4-fold and 25.7-fold increase in the risks for CVI, respectively [44. Scott TE, LaMorte WW, Gorin DR, Menzoian JO. Risk factors for chronic venous insufficiency: a dual case-control study. J Vasc Surg. 1995;22(5):622-8. ]. Since varicose veins increase with age in a linear manner, the prevalence of venous insufficiency will increase considerably. Venous ulcers (the end-stage of CVI) have a prevalence of 1% to 2% in people older than 65 years of age [55. Margolis DJ, Bilker W, Santanna J, Baumgarten M. Venous leg ulcer: incidence and prevalence in the elderly. J Am Acad Dermatol. 2002;46(3):381-6. ].

PATHOPHYSIOLOGY

Chronic venous disease can be divided into primary CVD, post thrombotic syndrome and congenital malformations. They all share a similar pathophysiology. Varicose veins have more distensibility of the connective tissue of the vein wall than control veins, suggesting a primary systemic basis for the anomaly [66. Zsoter T, Cronin RF. Venous distensibility in patients with varicose veins. Can Med Assoc J. 1966;94(25):1293-7. ]. The varicose vein wall is less resistant to the pressure that is generated in the upright position. Under normal circumstances, the pressure in the dorsal foot vein is approximately 80-100 mmHg in the upright position and only 5-10 mmHg in the supine position. Normal ambulatory venous pressure should be <40 mmHg.

Another pathophysiological mechanism of varicose veins is the malfunctioning of valves. When the valves that are present in the veins do not close sufficiently in the upright position, reflux is caused which results in high pressure. Insufficiency of valve functioning at the sapheno-femoral junction causes descending varicose veins. The mechanism of ascending insufficiency may be best illustrated in athletes. Ascending varicose veins occur when the superficial veins dilate due to a high increase in arterial and therefore venous flow. The transmural pressure of the vein wall increases with progressive dilatation of the vein and the valve ring, with resulting incompetence [77. Lane RJ, Cuzzilla ML. Aetiology of varicose veins: haemodynamics. ANZ J Surg. 2003;73(11):874-6. ]. The alterations in blood flow and swirling of the valvular cups lead to secondary inflammation of the endothelium.

In contrast to primary varicose veins, secondary varicose veins are the result of damage to the valves after deep vein thrombosis and recanalisation. Deep vein reflux can be due to previous thrombosis that leads to destruction of valves, or can be idiopathic. Without previous deep vein thrombosis, reflux can also be the result of floppy valve cups, valvular agenesis or aplasia [88. Morano JU, Raju S. Chronic venous insufficiency: assessment with descending venography. Radiology. 1990;174(2):441-4. , 99. Plate G, Brudin L, Eklof B, Jensen R, Ohlin P. Congenital vein valve aplasia. World J Surg. 1986;10(6):929-34. , 1010. Shami SK, Sarin S, Cheatle TR, Scurr JH, Smith PD. Venous ulcers and the superficial venous system. J Vasc Surg. 1993;17(3):487-90. ]. Dysfunctioning of the venous macrocirculation that is not fully compensated by the calf muscle pump action leads to changes in the venous microcirculation. This is a very complex mechanism. In brief, the interaction between endothelium and blood components on the one hand, and the interaction between the venous wall, the pericapillar halo and the extracellular matrix on the other hand play an important role in this mechanism. Changes in the skin microcirculation result in edema, pigmentation, eczema and ulceration. Such changes are dilation, elongation and tortuosity of capillaries that are associated with a high microvascular flow. In later stages, thrombosis in capillaries may impede good skin nutrition and oxygen levels, eventually leading to ulceration [1010. Shami SK, Sarin S, Cheatle TR, Scurr JH, Smith PD. Venous ulcers and the superficial venous system. J Vasc Surg. 1993;17(3):487-90. , 1111. Belcaro G, Laurora G, Cesarone MR, De Sanctis MT, Incandela L. Microcirculation in high perfusion microangiopathy. J Cardiovasc Surg (Torino). 1995;36(4):393-8. ].

CLINICAL CHARACTERISTICS OF CVD

Clinical characteristics of CVD are telangiectasias, reticular veins, varicose veins, edema, eczema, hyperpigmentation, lipodermatosclerosis, white atrophy, , and venous ulcers. ( Figure 1) Classic symptoms of CVD are discomfort, heaviness, aching, muscle cramps, restless legs and itching. Clinical characteristics of CVD appear when the compensating mechanism of insufficient venous return fails. The progression of CVD is characterised by signs and symptoms that increase almost linearly in time. Classically, progression of CVD is divided into three stages: from the adaptation stage to a compensating stage to a decompensating stage, finally leading to symptoms and later to complications. Chronic venous disease has a great impact on patients’ health-related quality of life, which is comparable to other common diseases, and is associated with considerable health care costs [1212. Kurz X, Kahn SR, Abenhaim L, Clement D, Norgren L, Baccaglini U, et al. Chronic venous disorders of the leg: epidemiology, outcomes, diagnosis and management. Summary of an evidence-based report of the VEINES task force. Venous Insufficiency Epidemiologic and Economic Studies. Int Angiol. 1999;18(2):83-102. ].

CLASSIFICATION

The CEAP classification [1313. Lurie F, Passman M, Meisner M, Dalsing M, Masuda E, Welch H, et al. The 2020 update of the CEAP classification system and reporting standards. J Vasc Surg Venous Lymphat Disord. 2020;8(3):342-52. , 1414. Porter JM, Moneta GL. Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg. 1995;21(4):635-45. ] ( Table 1 ) is used for the description of clinical signs, aetiology (congenital, primary or secondary), anatomy (divided in superficial, deep and perforating veins) and pathophysiological (reflux, obstruction or both). The CEAP classification [1313. Lurie F, Passman M, Meisner M, Dalsing M, Masuda E, Welch H, et al. The 2020 update of the CEAP classification system and reporting standards. J Vasc Surg Venous Lymphat Disord. 2020;8(3):342-52. , 1414. Porter JM, Moneta GL. Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg. 1995;21(4):635-45. ] for the description of CVD serves as a systematic guide in the daily clinical investigation of patients. It is an orderly documentation system and forms a synthesis of the phlebological status of a patient. Furthermore it helps in choosing the appropriate treatment. This classification made diagnosing CVD more precise, and served as a basis for more scientific analysis of management alternatives. The first CEAP consensus document was developed at the Sixth Annual Meeting of the American Venous Forum in 1994. Another scoring system is the Venous Clinical Severity Score (VCSS) ( Table 2 ) [1515. Vasquez MA, Rabe E, McLafferty RB, Shortell CK, Marston WA, Gillespie D, et al. Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group. J Vasc Surg. 2010;52(5):1387-96. ] that facilitates the follow-up of features of venous disease that change with treatment and is often used in clinical trials.

History

The ancient Greeks already recognised the importance of varicose veins and were able to treat them with ambulatory phlebectomies. The first illustration of a varicose vein, discovered at the foot of the Acropolis (Athens) dates back to the fourth century BC. It is a tablet that shows a massive leg with a tortuous swelling on its medial site, which has all the characteristics of a varicose vein.

Compression therapy has played a key role in the treatment of venous disease since ancient times. Sclerotherapy has been known in medicine since the 19th century. W. G. Fegan added compression to sclerotherapy in 1965 and since then, sclerotherapy is always combined with compression therapy for better results [1616. Fegan WG. Continuous compression technique of injecting varicose veins. Lancet. 1963;2(7299):109-12. , 1717. Fegan WG. Injection with compression as a treatment for varicose veins. Proc R Soc Med. 1965;58(11 Part 1):874-6. ]. Nowadays, liquid and ultrasound-guided foam sclerotherapy (UGFS) are still commonly used with aethoxysclerol and sodium tetradecyl sulfate as sclerosants. The surgical treatment (ligation plus stripping) of saphenous varicose veins is one of the very few medical treatments that has hardly changed since its invention more than one hundred years ago. In 1884, German surgeon Otto Wilhelm Madelung invented a radical operation to extirpate the great saphenous vein (GSV) and its perforators through one long skin incision from groin to ankle. In 1905, American surgeon William Keller introduced the stripping technique using a wire and multiple small incisions [1818. Keller W. A new method of extirpating the internal saphenous and similar veins in varicose conditions: a preliminary report. N Y Med J. 1905;82:385-6. ]. Since then, the long skin incision has been abandoned. William Babcock, also an American surgeon, invented the tools that form the basis for the current vein stripper [1919. Babcock W. A new operation for the extirpation of varicose vein of the leg. N Y Med J. 1907;86:153-6. ]. The last major revision was the introduction of the high ligation at the sapheno-femoral junction that was added to the standard procedure in 1916 by John Homans [2020. Homans J. The operative treatment of varicose veins and ulcer based on a classification of these lesions. Surg Gynecol Obestet. 1916;23:143. ]. Several variations were made on the basic principle, such as cryostripping, and different types of strippers, nowadays stripping is more and more performed under tumescent anesthesia. In the last few years, new attention has been focused on the surgical treatment of tributaries. Ambulatory conservative haemodynamic management of varicose veins (CHIVA) proved to be better than stripping regarding recurrence rates [2121. Carandina S, Mari C, De Palma M, Marcellino MG, Cisno C, Legnaro A, et al. Varicose vein stripping vs haemodynamic correction (CHIVA): a long term randomised trial. Eur J Vasc Endovasc Surg. 2008;35(2):230-7. , 2222. Pares JO, Juan J, Tellez R, Mata A, Moreno C, Quer FX, et al. Varicose vein surgery: stripping versus the CHIVA method: a randomized controlled trial. Ann Surg. 2010;251(4):624-31. ]. The latest idea is that tributaries have a great impact on the problem of varicose veins allowing for differentiating between ascending and descending varicose veins. This idea concerns the fact that treating superficial varicose veins can be divided into two concepts. First, treating insufficient tributaries of the insufficient saphenous vein may lead to abolition of the saphenous reflux, so the GSV need not be treated. The second concerns treating the insufficient saphenous vein together with the insufficient tributaries to avoid phlebitis of the saphenous vein. Several studies showed that patients who have both a refluxing GSV and a refluxing tributary can be treated with phlebectomy of the tributary only. Removing the tributary leads in approximately one third of these patients to a cured and competent GSV [2323. Biemans AA, van den Bos RR, Hollestein LM, Maessen-Visch MB, Vergouwe Y, Neumann HA, et al. The effect of single phlebectomies of a large varicose tributary on great saphenous vein reflux. J Vasc Surg Venous Lymphat Disord. 2014;2(2):179-87. , 2424. Pittaluga P. Méthode ASVAL (Ablation Sélective des Varices sous Anesthésie Locale): principes et résultats préliminaires. Phlebology. 2005;58:175-81. , 2525. Pittaluga P, Chastanet S, Locret T, Barbe R. The effect of isolated phlebectomy on reflux and diameter of the great saphenous vein: a prospective study. Eur J Vasc Endovasc Surg. 2010;40(1):122-8. This publication showed that insufficiency of the saphenous vein can be reduced or eliminated by performing phlebectomies only.
The results of this study led to renewed attention to the concept of ascending, instead of descending, varicose veins]. It has been hypothesized that patients with a small diameter of the GSV and/or large tributaries will benefit most from this approach [2525. Pittaluga P, Chastanet S, Locret T, Barbe R. The effect of isolated phlebectomy on reflux and diameter of the great saphenous vein: a prospective study. Eur J Vasc Endovasc Surg. 2010;40(1):122-8. This publication showed that insufficiency of the saphenous vein can be reduced or eliminated by performing phlebectomies only.
The results of this study led to renewed attention to the concept of ascending, instead of descending, varicose veins].

The demand of cosmetically superior, less invasive and successful treatment modalities has led to the introduction of minimally invasive techniques. The thermal ablation techniques were introduced around 2000 and radically changed the treatment of varicose veins. Endovenous laser ablation (EVLA), and radiofrequency ablation (RFA) are the most frequently used procedures. The essentials of these techniques are that they can be performed under tumescent anesthesia, so there is no need for spinal or general anaesthesia, and that the efficacy rate of these thermal techniques is high [2626. van den Bos R, Arends L, Kockaert M, Neumann M, Nijsten T. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg. 2009;49(1):230-9. ]. Endovenous steam ablation is another thermal technique but never became very popular due to reimbursement problems. [2727. van den Bos RR, Malskat WS, De Maeseneer MG, de Roos KP, Groeneweg DA, Kockaert MA, et al. Randomized clinical trial of endovenous laser ablation versus steam ablation (LAST trial) for great saphenous varicose veins. Br J Surg. 2014;101(9):1077-83. ] Another new development is obliteration of the varicose vein with cyanoacrylate, with high efficacy rates and the advantage that tumescent anesthesia is not needed. Due to the high price and the fact that there is less scientific evidence available for this technique, it is not very frequently used. [2828. Eroglu E, Yasim A. A Randomised Clinical Trial Comparing N-Butyl Cyanoacrylate, Radiofrequency Ablation and Endovenous Laser Ablation for the Treatment of Superficial Venous Incompetence: Two Year Follow up Results. Eur J Vasc Endovasc Surg. 2018;56(4):553-60. , 2929. Garcia-Carpintero E, Carmona M, Chalco-Orrego JP, Gonzalez-Enriquez J, Imaz-Iglesia I. Systematic review and meta-analysis of endovenous cyanoacrylate adhesive ablation for incompetent saphenous veins. J Vasc Surg Venous Lymphat Disord. 2020;8(2):287-96. ]

Ultrasound examination and anatomy

ULTRASOUND EXAMINATION

The gold standard of diagnosing varicose veins is ultrasound examination. Ideally, the ultrasound examination is performed in a warm room with the patient standing so that the anatomy and haemodynamics can be investigated optimally. Diameter as well as reflux time and obstruction can be measured accurately. The leg to be examined should be relaxed and slightly flexed. The superficial and deep venous systems of the legs are identified with linear transducers. The high frequency of the transducer is used for good resolution of superficial veins. Low frequency penetrates deeper and is therefore indicated to visualise deeper veins. A curvilinear probe is used for obese patients and for pelvic and abdominal veins. A system with both low and high frequency transducers is preferred to analyse different structures and different individuals. A high-frequency linear array transducer with a frequency between 5 and 12 MHz gives good quality images of superficial veins. The use of “low flow” settings is recommended to optimise the machine for low flow velocities encountered within veins. The Doppler range should be set to 5–10 cm/s with the wall filter at its lowest setting. The B-mode (brightness) should be used. Using B-mode, fluid (e.g., blood in the veins) is black and the surrounding tissues have a grey tone. In the colour-duplex setting, the Doppler sign is measured with the pulsed wave (PW) mode in the colour box. The colour, red or blue, indicates the direction of the blood flow in the vein. Usually, red is chosen for reflux and blue for flow during compression. Both transverse and longitudinal views of the veins should be used during duplex ultrasound scanning of the lower limbs. The transverse view is indicated to visualise the venous anatomy and thrombus formation during a manual compression manoeuvre. The longitudinal view is indicated to assess orthograde flow and venous reflux. The probe does not need to have an inclination in normal view, but in the colour mode, an inclination of 30 degrees is indicated. Reflux in the groin is demonstrated by the Valsalva manoeuvre and by flow augmentation after releasing manual pressure on the leg. Reflux duration in the superficial veins of >0.5 seconds is considered pathological.

In some cases, ultrasound examination alone is insufficient to visualise the anatomy or post-thrombotic changes. Also, venous malformations can be difficult to visualise on ultrasound examination. Probably the most important observation is that the deep veins, and especially partial thrombosis extending to pelvic veins, are difficult to assess entirely with ultrasound examination. In these cases, MRV, intravascular ultrasound (IVUS), phlebography or CT-angiography can be valuable as an additional investigation. Ambulatory venous pressure measurement can be added as diagnostic and prognostic tools for several reasons, such as assessing and understanding complex haemodynamics, venous hypertension, or when clinical signs of venous insufficiency are not compatible with ultrasound examination [1313. Lurie F, Passman M, Meisner M, Dalsing M, Masuda E, Welch H, et al. The 2020 update of the CEAP classification system and reporting standards. J Vasc Surg Venous Lymphat Disord. 2020;8(3):342-52. , 3030. Nicolaides AN, Cardiovascular Disease E, Research T, European Society of Vascular S, Organization TIASAC, International Union of A, et al. Investigation of chronic venous insufficiency: A consensus statement (France, March 5-9, 1997). Circulation. 2000;102(20):E126-63.
This consensus document provides an up-to-date account of the various methods available for the investigation of chronic venous insufficiency of the lower limbs, with an outline of their history, usefulness and limitations, 3131. Nicolaides AN, Zukowski AJ. The value of dynamic venous pressure measurements. World J Surg. 1986;10(6):919-24. ].

ANATOMY AND NOMENCLATURE

Saphenous veins

The GSV, the small saphenous vein (SSV), the anterior accessory saphenous vein (AASV) and the posterior accessory saphenous vein (PASV) belong to the saphenous veins. Typical of these veins is their localisation embedded between the hypodermic fascia and the muscular fascia. This compartment is called the saphenous compartment and it contains the saphenous vein. The appearance of the saphenous vein between the fascia blades is also called the “saphenous eye”, or “the Egyptian eye” ( Figure 2 ).

Ultrasound examination ideally starts at the saphenofemoral junction (SFJ). The femoral vein and femoral artery are visualised together with the GSV, this is called the “Mickey Mouse sign” ( Figure 3 ). Competence of the terminal valve is examined at the SFJ and competence of the pre-terminal valve is examined 2-5 cm distally from the SFJ in the GSV. The accessory saphenous veins are venous segments that ascend parallel to the saphenous veins, anterior, posterior or more superficial than the saphenous vein ( Figure 4 ). The AASV is located within the saphenous compartment next to the GSV for several centimetres before leaving the saphenous compartment. Typically, the AASV is located laterally from the GSV and is in line with the femoral artery and vein, called the “alignment sign” ( Figure 5A). At knee level, the zone between the fascia blades may not contain the GSV. This is called congenital hypoplasia or aplasia of the GSV. Side branches (tributaries) run parallel to the GSV outside the saphenous compartment. A true duplication of the GSV within the saphenous compartment is present in 1% of individuals.

The SSV arises at the lateral ankle, runs between the gastrocnemius muscles and usually terminates in the popliteal vein. The termination zone is called the saphenopopliteal junction (SPJ). Usually, the SPJ is localised 2-5 cm above the popliteal fossa, but a great inter-individual variation exists. Often, a thigh extension (TE) of the SSV is seen. The TE runs between the biceps femoris muscle and terminates in one or more superficial or perforating veins of the thigh or gluteal region. A cranial extension of the SSV can also communicate with the GSV ( Figure 5 ).

Perforating veins

Important perforating veins (PV) are the PVs of the foot, the ankle, the leg at knee-level, the tight and the gluteal muscles. Colour mode and Doppler mode are indicated to analyse their blood flow direction. PVs play a role as a re-entry point of the varicose veins into the deep venous system in primary varicose veins. In a normal situation, blood flows from the superficial to the deep venous system, except for the foot where it the other way around. Duplex examination showing blood flow in two directions indicates incompetence of a PV. The haemodynamic consequences of incompetent PVs are unclear and may not be of clinical relevance, except in those cases where re-entry and recirculation occurs and when they are located around a recurrent leg ulcer.

Deep veins

The veins of the deep venous system are divided in intermuscular and intramuscular veins. The intermuscular veins are the anterior and posterior tibial veins, the peroneal veins, the popliteal veins and the femoral veins at thigh-level. The intramuscular veins are the soleus and gastrocnemius veins. Blood flow, reflux, (thrombotic) occlusion and/ or post-thrombotic vein wall changes in the femoral vein can be visualised in the standing or supine position. When continuous flow is seen, one should suspect an occlusion proximally. Further examination of the iliac veins and the vena cava inferior is recommended. Reflux of the tibial veins is typical for patients with an history of deep venous thrombosis or insufficient PVs. Reflux of the peroneal and popliteal veins is frequently seen in (post)thrombotic patients [3232. Caggiati A, Bergan JJ, Gloviczki P, Jantet G, Wendell-Smith CP, Partsch H, et al. Nomenclature of the veins of the lower limbs: an international interdisciplinary consensus statement. J Vasc Surg. 2002;36(2):416-22.
This consensus document describes an agreement on anatomic terminology, which is important for a common language in phlebology and for an effective exchange of information, 3333. Coleridge-Smith P, Labropoulos N, Partsch H, Myers K, Nicolaides A, Cavezzi A. Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part I. Basic principles. Eur J Vasc Endovasc Surg. 2006;31(1):83-92.
This document represents a consensus on a methodology for the investigation of the lower limbs venous system by duplex ultrasonography, as well as the interpretation of images and measurements obtained].

Indications for different treatments

Each of the minimally invasive therapies can be performed in outpatient settings. EVLA, RFA and EVSA can be performed using local tumescent anaesthesia, and UGFS and cyanoacrylate ablation do not require anaesthesia. Each of the minimally invasive techniques requires US experience, preferably by the physician, but technicians can assist during the procedure. UGFS takes about 5 minutes, whereas the endovenous therapies may last 30 to 45 minutes. UGFS can be used to treat tortuous veins, previously treated varicose veins and recurrences after surgery (i.e., neovascularisation). Varicose veins with small and large diameters can be treated with UGFS, but saphenous veins with diameters of 10 mm or more may require multiple treatments and large volumes of foam (up to 3 sessions and 15 cc of foam) [2525. Pittaluga P, Chastanet S, Locret T, Barbe R. The effect of isolated phlebectomy on reflux and diameter of the great saphenous vein: a prospective study. Eur J Vasc Endovasc Surg. 2010;40(1):122-8. This publication showed that insufficiency of the saphenous vein can be reduced or eliminated by performing phlebectomies only.
The results of this study led to renewed attention to the concept of ascending, instead of descending, varicose veins]. UGFS can be used in patients with severe chronic venous disease and may enhance ulcer healing [2525. Pittaluga P, Chastanet S, Locret T, Barbe R. The effect of isolated phlebectomy on reflux and diameter of the great saphenous vein: a prospective study. Eur J Vasc Endovasc Surg. 2010;40(1):122-8. This publication showed that insufficiency of the saphenous vein can be reduced or eliminated by performing phlebectomies only.
The results of this study led to renewed attention to the concept of ascending, instead of descending, varicose veins]. This technique is also used to treat perforator veins and congenital venous malformations [2525. Pittaluga P, Chastanet S, Locret T, Barbe R. The effect of isolated phlebectomy on reflux and diameter of the great saphenous vein: a prospective study. Eur J Vasc Endovasc Surg. 2010;40(1):122-8. This publication showed that insufficiency of the saphenous vein can be reduced or eliminated by performing phlebectomies only.
The results of this study led to renewed attention to the concept of ascending, instead of descending, varicose veins]. UGFS is very promising for the treatment of saphenous recurrences after vein stripping because these veins are tortuous and often have a relatively small diameter, and the anatomical situation is altered. Ambulatory phlebectomies are preferred for tortuous veins that are well visible and palpable; this treatment leads to a very good cosmetic result. Endovenous thermal treatments are more effective than UGFS and are the treatment of choice for primary insufficiency of the GSV and SSV. Because of the rigidity and size of the disposables, linear primary saphenous veins with a diameter of 5 mm or more are ideal for endovenous thermal techniques. They can also be used for the accessory veins and perforator veins, although in these cases the procedure can be technically more difficult [2525. Pittaluga P, Chastanet S, Locret T, Barbe R. The effect of isolated phlebectomy on reflux and diameter of the great saphenous vein: a prospective study. Eur J Vasc Endovasc Surg. 2010;40(1):122-8. This publication showed that insufficiency of the saphenous vein can be reduced or eliminated by performing phlebectomies only.
The results of this study led to renewed attention to the concept of ascending, instead of descending, varicose veins]. One should be careful with treating recurrent or partly recanalised varicose veins, because introducing the laser or catheter may be difficult and there might be more risk of a vein perforation. Endovenous laser ablation is effective with several wavelengths (e.g., 940nm, 1470nm) and different fiber tip designs (bare fiber, radial fiber). The indications for RFA are comparable to EVLA. A 5 Fr (1.7 mm) catheter can be used for veins with a diameter of 2-8 mm, and an 8 Fr (2.7 mm) catheter can be used for veins of 12 mm or more.

Procedures and their mechanism of action

ULTRASOUND-GUIDED FOAM SCLEROTHERAPY

With UGFS, liquid sclerosing solution, which is used in classic sclerotherapy, is mixed with air to create foam. This foam of fine bubbles is injected intravenously with ultrasound (US) guidance. In classic sclerotherapy, the air block technique (in which an air bubble [3434. Wollmann JC. The history of sclerosing foams. Dermatol Surg. 2004;30(5):694-703; discussion. ] is injected before injecting the sclerosant) has been used to enhance the contact time with the venous wall and to reduce the “wash out” of the agent injected in the veins. With UGFS, a foam (e.g., 1 cc of aethoxysclerol/polidocanol or sodium tetradecyl sulphate 1% to 3% in Europe and the United States, respectively, mixed with 3 to 4 cc air) is created by connecting two syringes (Luer Lock) using a two- or three-way stopcock. One of the syringes is filled with the agent and the other with air [3535. Breu FX, Guggenbichler S, Wollmann JC. 2nd European Consensus Meeting on Foam Sclerotherapy 2006, Tegernsee, Germany. Vasa. 2008;37 Suppl 71:1-29. , 3636. Frullini A. New technique in producing sclerosing foam in a disposable syringe. Dermatol Surg. 2000;26(7):705-6. , 3737. Tessari L, Cavezzi A, Frullini A. Preliminary experience with a new sclerosing foam in the treatment of varicose veins. Dermatol Surg. 2001;27(1):58-60. ].

Because most of the foam moves in the direction of venous flow, it is usually injected at the (most) distal part of the saphenous varicose vein while the patient is in a horizontal position. However, in the Second European Consensus Meeting report, it was recommended to inject at the proximal thigh, 10 cm below the junction, to achieve optimal occlusion of the proximal part of the vein [3535. Breu FX, Guggenbichler S, Wollmann JC. 2nd European Consensus Meeting on Foam Sclerotherapy 2006, Tegernsee, Germany. Vasa. 2008;37 Suppl 71:1-29. ]. To guide access, the vein is visualised longitudinally by US. The foam can be injected directly, or through a cannula or butterfly needle [3838. Smith PC. Chronic venous disease treated by ultrasound guided foam sclerotherapy. Eur J Vasc Endovasc Surg. 2006;32(5):577-83. ]. The volume of foam depends on the length and diameter of the vessels. The volume may vary and is restricted by the increased risk of clinically relevant air emboli. There is no high level of evidence detailing the maximum volume of foam that can be used per treatment session. Recommendations vary widely, but the volume should not exceed 10 mL per session, based on the Second European Consensus opinion. For saphenous varicose veins, a 3% polidocanol foam appears to cause more adverse events, such as hyperpigmentation and phlebitis. After injection, patients remain horizontally or in the reverse Trendelenburg position to enhance contact for at least 5

minutes. After therapy, cotton wool or foam pads can be applied, and compression therapy (bandages, anti-thromboembolism stockings, and/or medical elastic compression stockings class II) are recommended for a period of 1 week..

ENDOVENOUS LASER ABLATION

Endovenous laser ablation can be performed under tumescent anaesthesia in an outpatient setting. Venous access is obtained by puncturing with a 16 or 18-gauge needle under US guidance, or with direct exposure through a phlebectomy incision. Usually, the incompetent GSV is entered at knee level because of ease of access (i.e., large diameter and linear course) and the smaller risk of nerve injury. If possible, identified causes of venous insufficiency, such as insufficient perforator veins (e.g., Boyd’s, Dodd’s, or May’s perforators) should be treated concurrently. After entrance to the varicose vein is established, a guidewire, or directly the laser fiber, is passed through the hollow needle into the vein until the junction. ( Figure 6) If the varicose vein is too tortuous, or has a small diameter (due to spasm), large side branches, or contains thrombotic or sclerotic fragments (after phlebitis or prior treatment, respectively), advancing the wire can be difficult, and caution is indicated because of the enhanced risk of perforation. After the guidewire is in place, the needle is removed, and a small cutaneous incision of 3 mm is made, an introducer sheath will pass over the guidewire and is positioned a few centimetres below the junction. Subsequently, the laser fibre (diameter ranges between 200 to 600 um) can be introduced after removing the guidewire. The most pivotal step in the EVLA procedure is positioning the echo-dense tip of the sheath 1 to 2 cm distally from the junction under longitudinal US visualisation. The laser wavelengths used with EVLA target deoxygenated haemoglobin and/or water and range between 810 and 1500 nm. About 250 to 500 mL (depending on the length of vein treated) of tumescent anaesthesia (5 mL epinephrine [5 mL bicarbonate] and 35 mL lidocaine 1% diluted in 500 mL saline solution or Ringer’s lactate) is administered into the perivenous space under US guidance using a syringe or mechanical infusion pump. Tumescent anaesthesia is warranted because it reduces pain, cools the perivenous tissue and decreases the venous diameter. After activation, the laser is pulled back continuously (about 3-5 mm/s, depending on the power and wavelength; with the 1320-nm laser, a pull-back speed of 1 mm/s is commonly used) [3939. 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(11):1380-5. ] or in a pulsed fashion with the objective to administer about 50 to 70 J/cm. Compressive bandages or medical elastic compression stockings class II are advised for 5-14 days after treatment.

ENDOVENOUS RADIOFREQUENCY ABLATION

The segmental radiofrequency catheter (VNUS Medical Technologies, Inc, Sunnyvale, CA, USA) [4040. VNUS website. http://www. vnus. com (last accessed 4 August 2008). ] is most frequently used. Access to the varicose vein is obtained with a 16-gauge needle under US guidance typically below knee level or distal to the point of reflux. The catheter is positioned 1 to 2 cm distally from the junction under longitudinal US visualisation. The catheter has a heating length of 7 cm and is in direct contact with the venous wall and omits high radiofrequency energy (regulated by power, impedance and time) that is generated by a radiofrequency generator (VNUS Medical Technologies, Inc). The catheter heats local tissue up to 120°C at the site of direct contact, with the heat conducted to deeper tissue planes, causing collagen shrinkage, denudation of endothelium and obliteration of the venous lumen [4141. Schmedt CG, Sroka R, Steckmeier S, Meissner OA, Babaryka G, Hunger K, et al. Investigation on radiofrequency and laser (980 nm) effects after endoluminal treatment of saphenous vein insufficiency in an ex-vivo model. Eur J Vasc Endovasc Surg. 2006;32(3):318-25. ]. A thermocouple monitors the temperature during treatment. Similar to EVLA, perivenous tumescent anaesthesia is applied to optimise contact surface and to decrease pain and risk of dysesthesia [4242. Weiss RA, Weiss MA. Controlled radiofrequency endovenous occlusion using a unique radiofrequency catheter under duplex guidance to eliminate saphenous varicose vein reflux: a 2-year follow-up. Dermatol Surg. 2002;28(1):38-42. ]. Also, manual compression is recommended during the treatment to enhance contact of the catheter with the vein wall. After 1 cycle of 20 seconds, the catheter is pulled back 7 cm to treat the following segment [4343. Zikorus AW, Mirizzi MS. Evaluation of setpoint temperature and pullback speed on vein adventitial temperature during endovenous radiofrequency energy delivery in an in-vitro model. Vasc Endovascular Surg. 2004;38(2):167-74. ]. Compressive bandages or medical elastic compression stockings class II are advised for 5-14 days after treatment. [4444. Proebstle TM, Alm BJ, Gockeritz O, Wenzel C, Noppeney T, Lebard C, et al. Five-year results from the prospective European multicentre cohort study on radiofrequency segmental thermal ablation for incompetent great saphenous veins. Br J Surg. 2015;102(3):212-8. , 4545. Proebstle TM, Vago B, Alm J, Gockeritz O, Lebard C, Pichot O. Treatment of the incompetent great saphenous vein by endovenous radiofrequency powered segmental thermal ablation: first clinical experience. J Vasc Surg. 2008;47(1):151-6.
This was the first publication of a study performed on a large group of patients showing very good results of segmental RFA]

CYANOACRYLATE ABLATION

Under US guidance, a 5F introducer sheath/catheter is advanced to the SFJ and positioned 5.0 cm caudal to the SFJ. Using US to compress the proximal GSV, two injections of approximately 0.10 mL cyanoacrylate are given 1 cm apart at this location, followed by a 3-minute period of local compression, and then repeated injections and 30-second ultrasound probe and hand compression sequences until the entire length of the target vein segment is treated. Also, compression stockings are advised for several days.[4646. Morrison N, Gibson K, McEnroe S, Goldman M, King T, Weiss R, et al. Randomized trial comparing cyanoacrylate embolization and radiofrequency ablation for incompetent great saphenous veins (VeClose). J Vasc Surg. 2015;61(4):985-94. ]

Efficacy of the different treatments

ULTRASOUND-GUIDED FOAM SCLEROTHERAPY

Compared to liquid sclerotherapy, foam sclerotherapy is about 4 times more effective, due to the increased contact time of the foam with the venous wall, and venous spasm that is induced [4747. Yamaki T, Nozaki M, Iwasaka S. Comparative study of duplex-guided foam sclerotherapy and duplex-guided liquid sclerotherapy for the treatment of superficial venous insufficiency. Dermatol Surg. 2004;30(5):718-22; discussion 22. ]. In several prospective studies with short follow-up, about two-thirds of the saphenous varicose veins were occluded after one UGFS session, and more than 90% of treatments were successful after two or three sessions [4848. Ceulen RP, Bullens-Goessens YI, Pi VANDEVSJ, Nelemans PJ, Veraart JC, Sommer A. Outcomes and side effects of duplex-guided sclerotherapy in the treatment of great saphenous veins with 1% versus 3% polidocanol foam: results of a randomized controlled trial with 1-year follow-up. Dermatol Surg. 2007;33(3):276-81.
This article is a well performed RCT on the efficacy and the complications of ultrasound-guided foam sclerotherapy, 4949. Darke SG, Baker SJ. Ultrasound-guided foam sclerotherapy for the treatment of varicose veins. Br J Surg. 2006;93(8):969-74. , 5050. Pascarella L, Bergan JJ, Mekenas LV. Severe chronic venous insufficiency treated by foamed sclerosant. Ann Vasc Surg. 2006;20(1):83-91. ]. Several randomized trials on the treatment of saphenous veins have shown that UGFS is less effective than surgery and endovenous ablation techniques [5151. Hamann SAS, Giang J, De Maeseneer MGR, Nijsten TEC, van den Bos RR. Editor’s Choice - Five Year Results of Great Saphenous Vein Treatment: A Meta-analysis. Eur J Vasc Endovasc Surg. 2017;54(6):760-70. , 5252. van der Velden SK, Biemans AA, De Maeseneer MG, Kockaert MA, Cuypers PW, Hollestein LM, 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;102(10):1184-94. ]. The study by van der Velden et al [5252. van der Velden SK, Biemans AA, De Maeseneer MG, Kockaert MA, Cuypers PW, Hollestein LM, 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;102(10):1184-94. ] showed that at 5 years follow-up, estimates of obliteration or absence of the GSV were 85, 77 and 23 per cent in the conventional surgery, EVLA and UGFS groups respectively. Also recurrence rates are higher after UGFS than after EVLA and RFA. UGFS was associated with higher recurrence rate compared with EVLA (68.6% vs 24.4% and at 5 years, recurrence rate was lower after RFA than UGFS (RR= 6.35 [95% CI, 2.60-15.54]; p<.0001) [5353. Kheirelseid EAH, Crowe G, Sehgal R, Liakopoulos D, Bela H, Mulkern E, et al. Systematic review and meta-analysis of randomized controlled trials evaluating long-term outcomes of endovenous management of lower extremity varicose veins. J Vasc Surg Venous Lymphat Disord. 2018;6(2):256-70. ]. Because of the low occlusion rates, UGFS may be considered when a swift treatment of the saphenous vein is preferred (e.g. in old or immobile patients, or patients who are not able to lay down for a longer time on an operating table), or for saphenous veins with small diameter (<6mm) [5454. Shadid N, Nelemans P, Lawson J, Sommer A. Predictors of recurrence of great saphenous vein reflux following treatment with ultrasound-guided foamsclerotherapy. Phlebology. 2015;30(3):194-9. ] , but UGFS is especially useful for tortuous veins (neovascularization) when it is impossible to introduce a catheter.

ENDOVENOUS LASER ABLATION

The first case series suggesting that EVLA might be successful for treating large varicose veins were published in 2001 [5555. Min RJ, Zimmet SE, Isaacs MN, Forrestal MD. Endovenous laser treatment of the incompetent greater saphenous vein. J Vasc Interv Radiol. 2001;12(10):1167-71. , 5656. 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(2):117-22. ]. Thereafter, multiple case series (number of treated limbs ranging from 6 to 1,250) have been presented, and systematic reviews and meta-analyses have been published [2626. van den Bos R, Arends L, Kockaert M, Neumann M, Nijsten T. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg. 2009;49(1):230-9. , 5353. Kheirelseid EAH, Crowe G, Sehgal R, Liakopoulos D, Bela H, Mulkern E, et al. Systematic review and meta-analysis of randomized controlled trials evaluating long-term outcomes of endovenous management of lower extremity varicose veins. J Vasc Surg Venous Lymphat Disord. 2018;6(2):256-70. , 5757. Mundy L, Merlin TL, Fitridge RA, Hiller JE. Systematic review of endovenous laser treatment for varicose veins. Br J Surg. 2005;92(10):1189-94. , 5858. Pannier F, Rabe E. Endovenous laser therapy and radiofrequency ablation of saphenous varicose veins. J Cardiovasc Surg (Torino). 2006;47(1):3-8. , 5959. Siribumrungwong B, Srikuea K, Orrapin S, Benyakorn T, Rerkasem K, Thakkinstian A. Endovenous ablation and surgery in great saphenous vein reflux: a systematic review and network meta-analysis of randomised controlled trials protocol. BMJ Open. 2019;9(1):e024813. ]. Although the success rate of EVLA decreases over time, it remains at least 90% in the majority of the studies. In a prospective study, 93% of 499 GSVs were occluded 2 years after therapy. An Italian workgroup reported a success rate of 97% in 1,000 patients with a follow-up of 3 years, and another large study with more than 1,250 limbs treated showed a success rate of approximately 95% [6060. 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(2):209-15. , 6161. Min RJ, Khilnani N, Zimmet SE. Endovenous laser treatment of saphenous vein reflux: long-term results. J Vasc Interv Radiol. 2003;14(8):991-6. , 6262. Ravi R, Rodriguez-Lopez JA, Trayler EA, Barrett DA, Ramaiah V, Diethrich EB. Endovenous ablation of incompetent saphenous veins: a large single-center experience. J Endovasc Ther. 2006;13(2):244-8. ]. A combined 4-year follow-up study of endovascular laser therapy combined with ambulatory phlebectomies for the treatment of superficial venous incompetence showed recurrence rates of 4.3% at 4 years, 3.6% at 2 years, and 5.9% at 1 year [6363. Sadick NS, Wasser S. Combined endovascular laser plus ambulatory phlebectomy for the treatment of superficial venous incompetence: a 4-year perspective. J Cosmet Laser Ther. 2007;9(1):9-13. ]. Three small, short-term studies compared EVLA and surgical stripping and suggested that they were equally effective, but patient-reported outcomes were in favour of EVLA [6464. de Medeiros CA, Luccas GC. Comparison of endovenous treatment with an 810 nm laser versus conventional stripping of the great saphenous vein in patients with primary varicose veins. Dermatol Surg. 2005;31(12):1685-94; discussion 94. , 6565. Mekako AI, Hatfield J, Bryce J, Lee D, McCollum PT, Chetter I. A nonrandomised controlled trial of endovenous laser therapy and surgery in the treatment of varicose veins. Ann Vasc Surg. 2006;20(4):451-7. , 6666. 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):308-15. ]. Several more recent RCTs with 5-year follow-up showed equal success rates of surgical stripping and EVLA, both higher than UGFS. [5252. van der Velden SK, Biemans AA, De Maeseneer MG, Kockaert MA, Cuypers PW, Hollestein LM, 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;102(10):1184-94. , 6767. Lawaetz M, Serup J, Lawaetz B, Bjoern L, Blemings A, Eklof B, et al. Comparison of endovenous ablation techniques, foam sclerotherapy and surgical stripping for great saphenous varicose veins. Extended 5-year follow-up of a RCT. Int Angiol. 2017;36(3):281-8. , 6868. Wallace T, El-Sheikha J, Nandhra S, Leung C, Mohamed A, Harwood A, et al. Long-term outcomes of endovenous laser ablation and conventional surgery for great saphenous varicose veins. Br J Surg. 2018;105(13):1759-67. ] Apart from recanalization, frequent sources of recurrent reflux after EVLA are neovascularization from the SFJ, reflux in tributaries of the SFJ, and reflux in accessory veins such as the AASV [6969. Rass K, Frings N, Glowacki P, Graber S, Tilgen W, Vogt T. Same Site Recurrence is More Frequent After Endovenous Laser Ablation Compared with High Ligation and Stripping of the Great Saphenous Vein: 5 year Results of a Randomized Clinical Trial (RELACS Study). Eur J Vasc Endovasc Surg. 2015;50(5):648-56. ].

ENDOVENOUS RADIOFREQUENCY ABLATION

Small, short-term comparative studies suggest that EVLA and RFA are equally effective compared to vein stripping, but are more appreciated by patients [7070. Puggioni A, Kalra M, Carmo M, Mozes G, Gloviczki P. Endovenous laser therapy and radiofrequency ablation of the great saphenous vein: analysis of early efficacy and complications. J Vasc Surg. 2005;42(3):488-93. ].Many prospective studies with short-term follow-up reported occlusion rates of >90%. Siribumrungwong’s meta-analysis [5959. Siribumrungwong B, Srikuea K, Orrapin S, Benyakorn T, Rerkasem K, Thakkinstian A. Endovenous ablation and surgery in great saphenous vein reflux: a systematic review and network meta-analysis of randomised controlled trials protocol. BMJ Open. 2019;9(1):e024813. ] that included 28 RCTs showed that there were no significant differences between EVLA and RFA vs high ligation plus stripping in primary failure and in clinical recurrences.

CYANOACRYLATE ABLATION

The first RCT in which cyanoacrylate ablation was compared to thermal ablation methods showed similar occlusion rates; 2-year occlusion rates were 92.6%, in the cyanoacrylate group, 90.9% in the RFA group, and 91.5% in the EVLA group, with no significant difference between groups [2828. Eroglu E, Yasim A. A Randomised Clinical Trial Comparing N-Butyl Cyanoacrylate, Radiofrequency Ablation and Endovenous Laser Ablation for the Treatment of Superficial Venous Incompetence: Two Year Follow up Results. Eur J Vasc Endovasc Surg. 2018;56(4):553-60. ]. Secondary outcomes seemed in favor to cyanoacrylate ablation; procedural pain was less and patients had a faster recovery after the procedure.

Complications

ULTRASOUND-GUIDED FOAM SCLEROTHERAPY

Extravenous injection of foam may cause local cutaneous side effects such as hyperpigmentation and, rarely, skin necrosis. Compared to classic liquid sclerotherapy, foam sclerotherapy is more likely to induce post-inflammatory hyperpigmentation, but less likely to induce skin necrosis because it has much higher sclerosing power at a 3- to 4-fold dilution. A few weeks after therapy, patients may experience a string-like, sometimes painful, induration of the injected vein due to venous obliteration. Most adverse adverse events are comparable to those after liquid sclerotherapy and include rare events such as migraine-like neurological symptoms and scotomas, especially in people with a patent foramen ovale. Although the sclerosing foam enters the systemic circulation and can be detected in the right ventricle of the heart a few seconds after administration, very few deep vein thromboses (DVTs) and pulmonary emboli have been reported. The likelihood of these serious side effects may depend on the volume of injected foam. Some authors recommend the use of low molecular-weight heparins (LMWHs) for 5 days to prevent DVTs, especially in patients with a high risk of thromboembolic complications.

ENDOVENOUS THERMAL ABLATION TREATMENTS

The high temperature that is caused by the laser energy, especially with bare fiber tips, induces multiple microperforations of the venous wall; this may cause pain (“pulling cord”) and ecchymosis. These common adverse events disappear spontaneously within 2 weeks and/or can be controlled by elastic stockings and analgesics. Using modern laser fibres (e.g., radial fibre or tulip fibre) or RFA leads to less damage of the vein wall and therefore post-operative pain.. Although minimally invasive thermal techniques may reduce side effects associated with surgery (e.g., wound infection and scarring), it may be associated with specific adverse events such as DVT and skin burns (if tumescent anaesthesia is not properly used). EVLA induces a symmetric and non-floating sclerosis. From this treatment-induced sclerosis, a thrombus may progress into the deep venous system creating a DVT, usually asymptomatic. However, the likelihood of DVT is less than 1% [6060. 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(2):209-15. , 6161. Min RJ, Khilnani N, Zimmet SE. Endovenous laser treatment of saphenous vein reflux: long-term results. J Vasc Interv Radiol. 2003;14(8):991-6. , 6262. Ravi R, Rodriguez-Lopez JA, Trayler EA, Barrett DA, Ramaiah V, Diethrich EB. Endovenous ablation of incompetent saphenous veins: a large single-center experience. J Endovasc Ther. 2006;13(2):244-8. ]. In addition to careful instructions to the patient, some authors advise performing US examination 1 week after EVLA to exclude DVT and others use LMWH for 5 to 7 days after the procedure to prevent the development of DVT [7070. Puggioni A, Kalra M, Carmo M, Mozes G, Gloviczki P. Endovenous laser therapy and radiofrequency ablation of the great saphenous vein: analysis of early efficacy and complications. J Vasc Surg. 2005;42(3):488-93. ]. Skin burns are also rare, and may occur when the administered energy is too high, when superficial veins are treated, and/or when the cooling effect of tumescent anaesthesia is insufficient. Caution is warranted for the extrafascial part (tributary) of the saphenous varicose veins and the cutaneous exit site of the laser fibre. Superficial thrombosis, dysaesthesia, haematoma, cellulitis and arteriovenous fistulae have been reported after EVLA [6060. 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(2):209-15. , 6161. Min RJ, Khilnani N, Zimmet SE. Endovenous laser treatment of saphenous vein reflux: long-term results. J Vasc Interv Radiol. 2003;14(8):991-6. , 6262. Ravi R, Rodriguez-Lopez JA, Trayler EA, Barrett DA, Ramaiah V, Diethrich EB. Endovenous ablation of incompetent saphenous veins: a large single-center experience. J Endovasc Ther. 2006;13(2):244-8. , 6363. Sadick NS, Wasser S. Combined endovascular laser plus ambulatory phlebectomy for the treatment of superficial venous incompetence: a 4-year perspective. J Cosmet Laser Ther. 2007;9(1):9-13. , 6464. de Medeiros CA, Luccas GC. Comparison of endovenous treatment with an 810 nm laser versus conventional stripping of the great saphenous vein in patients with primary varicose veins. Dermatol Surg. 2005;31(12):1685-94; discussion 94. , 6666. 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):308-15. , 7070. Puggioni A, Kalra M, Carmo M, Mozes G, Gloviczki P. Endovenous laser therapy and radiofrequency ablation of the great saphenous vein: analysis of early efficacy and complications. J Vasc Surg. 2005;42(3):488-93. , 7171. Allegra C, Antignani PL, Carlizza A. Recurrent varicose veins following surgical treatment: our experience with five years follow-up. Eur J Vasc Endovasc Surg. 2007;33(6):751-6. ].

CYANOACRYLATE ABLATION

Side-effects of cyanoacrylate ablation are mild, mainly phlebitis. Hypersensitivity reactions, DVT, induration and ecchymosis are rare. Results from 2 RCTs show that peri-procedural pain was significantly lower after cyanoacrylate than after 1470nm EVLA and RFA (p<.001), but there was no difference in post-operative pain. The occurrence of DVT, bleeding, and phlebitis were similar in all groups [2828. Eroglu E, Yasim A. A Randomised Clinical Trial Comparing N-Butyl Cyanoacrylate, Radiofrequency Ablation and Endovenous Laser Ablation for the Treatment of Superficial Venous Incompetence: Two Year Follow up Results. Eur J Vasc Endovasc Surg. 2018;56(4):553-60. , 7272. Calik ES, Arslan U, Erkut B. Ablation therapy with cyanoacrylate glue and laser for refluxing great saphenous veins - a prospective randomised study. Vasa. 2019;48(5):405-12. ]. Other complications include cyanoacrylate protrusion into theSFJ or endovenous glue induced thrombosis (1.4%- 5.8%) [7373. Vos CG, Unlu C, Bosma J, van Vlijmen CJ, de Nie AJ, Schreve MA. A systematic review and meta-analysis of two novel techniques of nonthermal endovenous ablation of the great saphenous vein. J Vasc Surg Venous Lymphat Disord. 2017;5(6):880-96. ].

COMPARISON OF COMPLICATIONS BETWEEN TREATMENTS

Because of the destruction and/or irritation of endothelial cells and the ensuing sclerosis (which is different from a thrombus because it is symmetrical and causes adherence of the venous walls with no free-floating component), the development of DVT is the main concern of each of theminimal invasive techniques. DVT and LE occur rarely, several studies report an incidence around 1% and it does not seem to differ between treatment modalities. However, symptomatic and asymptomatic thromboembolic events and methods of diagnosis should be differentiated when comparing thromboembolic outcomes in these treatments. Several preventive measures, such as hypercoagulability screen (for high-risk individuals selected by history and physical examination), preoperative and/or postoperative LMWH (about a week), US control of the junction following treatment after 1 week, localisation of the catheter distal from the inferior epigastric vein, ample administration of tumescent anaesthesia, avoidance of perforation, and for UGFS limb elevation, immobilisation and applying pressure on the junction after injecting the foam, have been suggested to reduce the risk of DVT.

Neurological damage is one of the most common serious side effects of saphenous stripping. Saphenous nerve damage occurs in about 7% in short stripping and 40% in long stripping of the GSV [7474. Holme JB, Skajaa K, Holme K. Incidence of lesions of the saphenous nerve after partial or complete stripping of the long saphenous vein. Acta Chir Scand. 1990;156(2):145-8. , 7575. Morrison C, Dalsing MC. Signs and symptoms of saphenous nerve injury after greater saphenous vein stripping: prevalence, severity, and relevance for modern practice. J Vasc Surg. 2003;38(5):886-90. ]. Paresthesias have been reported after UGFS, EVLA, RFA and cyanoacrylate but the incidence is significantly lower than with surgery. Similar to surgery, the likelihood of saphenous nerve damage may increase when the catheter-directed procedures of the GSV are started at the ankle. To avoid sural nerve damage, it is recommended to administer additional tumescent anaesthesia at the popliteal fossa before EVLA and RFA treatment of the SSV.

New developments

The developments in endovenous thermal treatments were rapid over the last 10 years. EVLA devices changed every year, the first fibres were bare and wavelengths were low (810nm, 940nm, 980nm). Later, other fibre tip designs were introduced, such as radial fibres, double radial fibres, tulip fibres and higher wavelengths were applicated (1320nm, 1470nm). These innovations were meant to result in lower painscores and less phlebitis. Radiofreqency ablation innovated into a segmental heating catheter that is nowadays commonly used. Endovenous steam ablation was introduced in 2011 and was a promising alternative for EVLA; a RCT showed lower pain scores and non-inferior efficacy. However, due to reimbursement problems steam never became very popular. A variation of sclerotherapy, mechanochemical ablation, a catheter-directed combination of mechanical damage delivered by a propeller and liquid sclerotherapy, was introduced as alternative to endovenous thermal therapies with the advantage that the procedure could be performed without tumescent anesthesia. However, efficacy rates were not as high as the thermal treatment. Therefore and because of the relative high price of the catheters this treatment modality also did not become a frequently used alternative [7676. Mohamed AH, Leung C, Wallace T, Smith G, Carradice D, Chetter I. A Randomized Controlled Trial of Endovenous Laser Ablation Versus Mechanochemical Ablation With ClariVein in the Management of Superficial Venous Incompetence (LAMA Trial). Ann Surg. 2021;273(6):e188-e95. , 7777. Vahaaho S, Halmesmaki K, Mahmoud O, Alback A, Noronen K, Venermo M. Three-year results of a randomized controlled trial comparing mechanochemical and thermal ablation in the treatment of insufficient great saphenous veins. J Vasc Surg Venous Lymphat Disord. 2021;9(3):652-9. ].

Cyanoacrylate for saphenous vein ablation was introduced in 2013. The advantage of this technique is that no tumescent anesthesia is needed in contrary to laser and radiofrequency ablation. This procedure is expensive in comparison with the thermal techniques and probably therefore not widely used, but is in some countries performed in private practices. The best technique for the future should be highly effective, swift, cheap and patient-friendly. As varicose veins are very common, cost-effectiveness is an important parameter.

Conclusion

Chronic venous disease, including varicose veins, has a great impact on patients’ health-related quality of life and is associated with considerable health care costs. There are several treatment options for varicose veins. The choice for a treatment depends on patient characteristics and duplex ultrasound findings, but also costs and the experience the practitioner and availability of the devices are guiding this decision. The treatment of side branches consists either of phlebectomies or (foam) sclerotherapy. Incompetent saphenous veins are nowadays best treated with endovenous methods, such as endovenous laser or radiofrequency ablation under tumescent anesthesia or with a method that is non thermal and does not need tumescent anesthesia such as cyanoacrylate ablation.

Personal perspective | Renate R. Van Den Bos

For more than 100 years, the “gold standard” for the treatment of insufficient saphenous veins has been ligation plus stripping. The introduction of endovenous thermal ablation (EVTA) techniques in the last twenty years and later non-thermal techniques such as cyanoacrylate, has changed this. With the introduction of these techniques, finally extremely effective treatments with very high success rates became available [7878. Whing J, Nandhra S, Nesbitt C, Stansby G. Interventions for great saphenous vein incompetence. Cochrane Database Syst Rev. 2021;8:CD005624. ]. The effectiveness of current endovenous treatments is excellent (>90%). Side effects are mild as well, and serious complications are rare [7979. Nijsten T, van den Bos RR, Goldman MP, Kockaert MA, Proebstle TM, Rabe E, et al. Minimally invasive techniques in the treatment of saphenous varicose veins. J Am Acad Dermatol. 2009;60(1):110-9.
This article describes the different minimally invasive endovenous treatments and compares their efficacy, indications and complications]. Usually, the practitioner’s experience, availability of a device and/or the reimbursement criteria dictate the choice for one of the treatment options. Several publications support the hypothesis of ascending or multifocal development of varicose disease starting from the distal superficial venous network. The surgical approach focusing on the treatment of the varicose reservoir by phlebectomies and meanwhile conservation of a refluxing saphenous vein is enjoying renewed attention. Treating insufficient tributaries of the insufficient saphenous vein may lead to abolition of the saphenous reflux, so the saphenous vein could be saved. This concept challenges the current approach to treatment of venous insufficiency, which usually focuses on the treatment of saphenous insufficiency. Choosing to treat tributaries first may become the preferential approach. One study in patients with both GSV and tributary insufficiency, showed that one year after phlebectomies of the tributary only, two third of patients were symptom free and only 30% needed additional GSV ablation. These data are used to design a RCT in which almost 500 patients with GSV or AASV insufficiency plus an insufficient tributary were studied. Patients were randomized into treatment with ablation plus phlebectomies or phlebectomies only. This large RCT confirmed the hypothesis that part of the patients can be offered a less invasive and less costly treatment approach. Only one third of the patients needed additional ablation one year after phlebectomies. Both groups were equally satisfied and experienced similar quality of life [8080. Scheerders ERY, van der Velden SK, Goossens LMA, Hamann SAS, de Maeseneer MGR, Malskat WSJ, et al. Single ambulatory phlebectomy versus saphenous thermal ablation with concomitant phlebectomy (SAPTAP Trial): results of a multicenter non-inferiority randomized clinical trial. 2022. ].

At a time of increasing health care costs, with procedure driven reimbursement, efficient treatment of patients with varicose veins is important. More targeted treatment may not only improve patient-centred health care but may also reduce the burden of treatment by means of fewer secondary procedures with subsequently less treatment-related complications and a faster postoperative recovery. Physicians should recognise these advantages and implement individualised care in clinical practice. Criteria for venous treatment should shift from presence of saphenous reflux only to a combination of patient characteristics, clinical and DUS findings. In the future, patient, anatomical, DUS and clinical characteristics may become predictors that could guide the choice for the best, minimal invasive and less costly treatment approach.