Key words
Varicose vein surgery - recurrent varicose veins - neoangiogenesis - barrier techniques - remodelling hypothesis
Introduction
Recurrent varicose veins following surgical treatment present a huge problem to both patients and doctors. Operations on recurrences are more difficult, more time-consuming, and more expensive than primary interventions. Postoperative complications are more frequent than after primary interventions and may be serious [1], [2], [3], [4], [5], [6].
In the literature, the frequency of recurrent saphenofemoral incompetence after surgery without any protection against neovascularisation is given as between 33 % [7] and 60 % [8]. For some time, therefore, efforts have been made to reduce the incidence of postoperative varicose vein recurrence.
Based on data in the literature and our own experience, this review will look at the current hypotheses on the development of varicose veins, analyse the various types of recurrence, present the possibilities of preventing recurrences and define today’s cutting-edge approach to high ligation of the saphenous vein. Given the phenomenon of neovascularisation (NV) and the remodelling hypothesis for the development of varicose veins associated with various inflammatory processes [9], [10] the question arises as to whether comprehensive prophylaxis against recurrent saphenofemoral incompetence is possible with surgical measures alone, or whether non-surgical measures have also to be included.
In addition, we will try to identify patient populations with a low or high risk of recurrent saphenofemoral incompetence and determine the patient group in which prevention of recurrence is not a main goal of varicose vein surgery.
For many years, it was thought that reflux through incompetent valves was pivotal in the development of varicose veins. More recently, however, there is evidence that valve dysfunction is not the actual cause of chronic venous insufficiency (CVI) and its progression, but rather remodelling of the vein wall with subsequent valve incompetence. Remodelling, triggered by physical flow characteristics and biochemical processes, is stimulated by unfavourable lifestyle factors such as sitting or standing for long periods, lack of exercise, and overweight [9], [10], [11], [12].
If remodelling of the vein wall is the crucial pathophysiological cause and valve incompetence is a secondary effect of this remodelling, the suspicion rapidly arises that surgical procedures on defective valves with stripping/exeresis of varicose veins cannot sustainably prevent recurrent saphenofemoral incompetence with any degree of certainty.
Classification of postoperative recurrence according to avoidability and site
Classification of postoperative recurrence according to avoidability and site
Despite these limitations, for systematic didactic reasons we should first look at recurrence in terms of avoidability and unavoidability, as well as the site of recurrence in the groin and leg.
Avoidable recurrence:
This recurrence group is known to follow inadequacies in the diagnosis, determination of the indication, or surgical treatment. Such shortcomings include overlooking saphenofemoral incompetence during exclusive phlebectomy, incorrect high saphenous ligation, and leaving behind a duplicate main trunk vein or incompetent perforator.
Unavoidable recurrence:
If recurrent saphenofemoral incompetence or varicose veins in the leg appear – even many years later – after a high saphenous ligation that has been performed correctly, it has to be viewed as unavoidable. Apart from the remodelling process in the vein wall, recurrent saphenofemoral incompetence is also due to genetic factors [13], [14], other factors associated as shown in [
Table 1
], and especially to neovascularisation.
Table 1
Factors that are associated with neovascularisation and which secrete biochemical inflammatory and growth factors [9], [10], [15], [23], [24], [25].
|
Constellations that promote neovascularisation
|
|
|
Today, the existence of neovascularisation is generally accepted [1], [7], [8], [16], [17], [18], [19], [20], [21], [22], and various authors have tried to define it on the basis of macroscopic and histological criteria [17], [18], [19], [20], [22].
Endothelial hypoxia occurring in the stump left after saphenofemoral ligation seems to be of key importance in the pathogenesis of neovascularisation. It leads to activation of endothelial cells and increased release of inflammatory mediators. Molecular biological processes and a platelet/endothelium interaction are the key aspects [7], [23], [24], [25], [26], [27] ([
Table 2
]).
Table 2
Molecular biology and platelet/endothelium interaction. All cell reactions are regulated by molecular biological processes or by platelet/endothelium interactions [7], [23], [24], [25], [26], [27].
|
Stimulation of neovascularisation by molecular biological processes
|
-
VEGF (vascular endothelial growth factor)
-
IGF (insulin light growth factor)
-
NGF (nerve-growth factor) etc.
-
Cytokines (more than 30)
-
TGF (transforming growth factor)
-
FGF (fibroblast growth factor)
-
Prostaglandins
-
Cyclo-oxygenase I and II
|
A clear reason why neovascularisation occurs only in some patients has not yet been found. In short, we can only agree with Reinhard Fischer’s summary of the phenomenon: No stump – no stump-related neovascularisation [25].
Recurrence prophylaxis
Avoidable recurrences
In comparison with other types, this group of recurrences is the easiest to prevent – at least in theory – by a well-trained vascular surgeon and the correct diagnostic investigation, indication for treatment, and surgical technique.
Saphenofemoral and saphenopopliteal junctions
Surgical errors at the saphenofemoral junction (SFJ) are a significant cause of recurrent varicose veins. There is a general agreement that ligation of the great saphenous vein flush with the femoral vein together with ligation of all the regional GSV tributaries together with ligation of the femoral vein tributaries can reduce the frequency of recurrent saphenofemoral incompetence [1], [3], [6], [20], [21], [25], [28].
Prophylaxis is disparately more difficult in the case of the small saphenous vein (SSV) ligation, possibly because of aneurysmal gastrocnemius veins that may grow in close proximity to the saphenopopliteal junction. Operating with the patient lying prone is the preferred position for preventing recurrence. Even so, the surgical procedure sometimes has to be limited and the possibility of junctional recurrence has to be accepted, in order to avoid any serious bleeding or nerve damage when dissecting out the tissues (Reinhard Fischer, personal communication).
Varicose veins of the leg
When all the relevant tributaries and incompetent perforators have been dealt with surgically or by occlusion, everything therapeutically possible has been done to prevent recurrence.
Unavoidable recurrence
Unfortunately, recurrence cannot be completely prevented even with the correct saphenous ligation or therapeutic technique.
Saphenofemoral junction
Neovascularisation is the most important pathogenetic factor for the surgeon with respect to recurrent saphenofemoral incompetence.
Apart from a precise high ligation, various surgical and barrier techniques able to reduce the rate of postoperative reflux have been published as prophylactic measures ([
Table 3
]).
Table 3
Studies on neovascularisation prevention – primary surgical procedure [1], [3], [4], [16], [29], [30], [31], [32], [38].
|
Lead author
|
Technique
|
Legs
(n)
|
Follow-up
(months)
|
Recurrence
|
|
Glass 1998 [29]
|
Cribriform fascia, mersilene patch
|
127
|
> 48
|
3,0 %
|
|
Jaeschock 1996 [30]
|
Stump excision
|
100
|
3
|
0 %
|
|
Earnshaw 1998 [1]
|
PTFE patch
|
51
|
12
|
14,0 %
|
|
De Maeseneer 2002 [16]
|
Silicone patch and cribriform fascia
|
210
|
12
|
6,0 %
|
|
Frings 2004 [31]
|
Long stump
|
65
|
9
|
5,0 %
|
|
Frings 2004 [3]
|
Endothelial suture
|
70
|
24
|
3,0 %
|
|
Frings 2010 [4]
|
Extended SFJ ligation
|
100
|
24
|
1,5 %
|
|
Papapostolou 2013 [32]
|
Electrocoagulation and cribriform fascia
|
668
|
12
|
2,2 %
|
|
Rass 2015 [38]
|
Extended SFJ ligation
|
129
|
60
|
1,6 %
|
The definitive preventative approach consists of ensuring that widely gaping free endothelium is covered or eliminated following saphenous vein ligation:
Long stump ([
Fig. 1
]), overstitching of the junction ([
Fig. 2
]), extensive high saphenous ligation and overstitching of the SV stump ([
Fig. 3
]), electrocoagulation with lamina cribrosa suture ([
Fig. 4
]), diverse patches ([
Fig. 5
]) and stump excision ([
Fig. 6
]).
Fig. 1 Long SV stump (b) with adhesion of the free stump endothelium. A = femoral vein, B = SV stump [31]
Fig. 2 Continuous prolene overstitching of the SV stump, so that no free stump endothelium can come into contact with the surrounding tissues. A = femoral vein, B = SV stump [3]
Fig. 3 Extensive saphenofemoral ligation with overstitching of the SV stump (1) as well as stripping of the tributary vessels (shown in red) well into the periphery (2) [4]
Fig. 4 Electrocoagulation of the SV stump with lamina cribrosa suture (LaVaCro study). Left: A = femoral vein, B = SV stump. Right: A = femoral vein; B = suture of the lamina cribrosa [32]
Fig. 5 Covering the saphenous vein endothelium with various patches, aiming to prevent contact of the stump endothelium with the subcutaneous tissues. A = femoral vein, B = patch over the saphenous vein endothelium [1], [16], [29]
Fig. 6 Excision of the SV stump from the femoral vein with suture closure. With this technique there is no residual stump endothelium. A = femoral vein, B = closure of the femoral vein where the saphenous vein has been excised [30]
The simplest surgical techniques are those which do not involve a patch or stump excision ([
Fig.
1
] to [
Fig. 6
]).
These NV-prevention techniques used in primary interventions give results between 0 % (stump excision with a follow-up period of only three months) and 14 % (PTFE patch, follow-up 12 months). Taking only studies with follow-up periods of 2–5 years into consideration, the recurrence rates lie between 1.5 % and 3 % [1], [3], [4], [16], [29], [30], [31], [32], [38] ([
Table 3
]).
Even for surgery on recurrences, various barrier techniques can still be employed, including pectineal fascia occlusion, silicone patches, PTFE patches, and overstitching the stump with more extensive ligation. The postoperative recurrence rate in these cases lies between 2.4 % and 65 % [33], [34], [35], [36], [37] ([
Table 4
]).
Table 4
Studies on neovascularisation prevention – revision (‘redo’) surgery [33], [34], [35], [36], [37].
|
Lead author
|
Year
|
Technique
|
Legs
(n)
|
Follow-up
(months)
|
Recurrence
|
|
Gibbs [33]
|
1999
|
Pectineal fascia
|
34
|
> 18
|
65 %
|
|
De Maeseneer [34]
|
2004
|
Silicone patch
|
34
|
60
|
9 %
|
|
Winterborn [35]
|
2007
|
PTFE
|
16
|
24
|
31 %
|
|
Freis [36]
|
2016
|
PTFE
|
85
|
12
|
2,4 %
|
|
Gerontopoulou (in press) [37]
|
2018
|
Overstitching,
extended redo FJ ligation
|
100
|
16
|
5 %
|
Varicose veins of the leg
This type of recurrence, which – as mentioned above – is caused either by genetic factors or an unfavourable lifestyle (lack of exercise, overweight) with subsequent remodelling of the vein wall, is less easy to prevent than recurrence in the groin.
Indications for varicose vein surgery
Indications for varicose vein surgery
As recurrent saphenofemoral incompetence may unfortunately still occur even decades later, the intelligent indication for surgery in younger patients (possibly < 30 years) should err on the conservative side. If treatment is essential, endovascular techniques should be employed, allowing subsequent saphenous ligation to be carried out more easily than after primary high ligation.
Symptomatic indications
A curative indication with freedom from recurrence is not, however, the primary therapeutic goal for every patient. Elderly patients with very painful varicose veins, recurrent phlebitis or bleeding from ruptured varicose veins and people with medical risk factors should have their varicose veins eliminated quickly, safely and without risk – always remembering that minimally invasive techniques are not worthwhile. This population also includes obese patients with painful lipolymphoedema who are planning to have joint replacement for painful osteoarthritis of the hip or knee. With this particular constellation, recommendations for gait training and weight reduction are not constructive. Here, too, primary treatment consists of reliable, safe elimination of the varicose veins so that orthopaedic surgery can be performed. Physical measures of drainage, gait training, and weight reduction can only be introduced once the joint pain has been reduced. Any possible later groin or leg vein recurrence requiring treatment can then be dealt with by open surgery or minimally invasive techniques under much more favourable circumstances.
Identifying patients at low or high risk of recurrent saphenofemoral incompetence
In our experience, slender or moderately overweight patients with little adhesive tissue found in the groin at operation – that is to say, those who have not had any previous inflammatory processes in the leg, catheter investigations, extensive prior treatment with sclerotherapy or phlebectomy, or any tattoos affecting the inguinal lymph nodes – have the lowest risk of recurrent saphenofemoral incompetence. After surgery, the patients themselves can reinforce this low risk by introducing or continuing to follow a lifestyle that is beneficial to the veins. This includes maintaining a normal weight or being only moderately overweight, avoiding standing or sitting for long periods, possibly wearing compression stockings if their work involves strain on the legs, and taking regular endurance exercise.
If surgical repair of the SFJ valve is carried out with an extraluminal valvuloplasty where the SV stump is not divided, endothelium-induced neovascularisation cannot by definition occur.
Discussion
The sobering results of varicose vein surgery without recurrence prophylaxis place an obligation on the surgeon to implement barrier techniques into the spectrum of treatment. As surgical measures alone cannot achieve freedom from groin recurrence over many years, due to neovascularisation and remodelling of the vein wall in association with various biochemical and inflammatory processes, non-surgical measures should also be incorporated into the therapeutic options.
Remodelling with progression of the varicose veins cannot be stopped or reversed with complete regression of the changes in the vein walls (reverse remodelling). On the contrary, pathogenic biochemical changes take place not only in the obvious varicose veins but also in segments of vein in which no macroscopic wall changes can be seen. These veins are ‘potentially varicose’ [9].
Nevertheless, we consider a correct high saphenous ligation to be merely the minimum treatment programme for recurrence prophylaxis. Cutting-edge medicine today demands the inclusion of a barrier technique: endothelial coagulation of the SV stump with lamina cribrosa suture [32] and extended SFJ ligation with overstitching of the stump [4] represent the most straightforward of these techniques. Unfortunately, even such refined procedures cannot completely prevent recurrent saphenofemoral incompetence in the long term. The best results show 1.5 % to 3 % groin recurrence after 2–5 years under study conditions, while the rates of reflux found in routine clinical practice are certainly higher. Unfortunately, there are no reliable ultrasound-controlled studies over a period of much more than 10 years. Rass has found evidence that local tumescence anaesthesia also has a protective effect against neovascularisation [38].
Optimal recurrence prophylaxis therefore does not have to involve surgical procedures. The most important approach is to persuade the patient to introduce and maintain changes in lifestyle that have an anti-inflammatory effect, such as weight reduction and intensive endurance exercise.
Although the varicose veins and valve incompetence basically have to be viewed as irreversible changes, they can be partially compensated by compression therapy and active use of the muscle and joint pump. Increasing venous tone with medication may also help [9]. We can assume that meaningful measures in patients with lipoedema, such as an anti-inflammatory low carbohydrate (ketogenic) diet and reduction of visceral fat with diminished production of numerous hormones and neovascularisation-promoting cytokines are also worth recommending for the prevention of recurrent varicose veins (an in-depth discussion can be found elsewhere [39]). Complications of any recurrent varicose veins can be minimised if the patient attends regularly for follow-up: the recurrence can be dealt with at an early stage with sclerotherapy or another minimally invasive technique.
Ideally, patients should be informed about non-surgical preventative measures before they undergo surgery.
Most patients are then highly motivated and ask about what they can do themselves. In the preoperative briefing sessions, key aspects include emphasising the importance of a lifestyle beneficial to the veins and paying attention to the weight factor. Additionally, an anti-inflammatory diet can be suggested to obese patients with lipoedema [39]. As it is well known that health education alone has little effect, it is advantageous to let patients develop a positive relationship to their bodies and legs through endurance training. This approach is hardly possible in an outpatient or day-care varicose vein surgery setting, but patients who have been admitted to hospital for longer periods can participate in power walking and vein exercises in group sessions. In many cases, patients do actually follow our recommendation to continue this programme after discharge as their motivation is high.
There are no prospective studies on the efficacy of these theoretically meaningful non-surgical prophylactic measures and, indeed, such studies would be difficult to carry out, as they would require long-term follow-up. We can only hope that comprehensive recurrence prophylaxis will reduce the healthcare costs, but we cannot make any firm predictions at the present time.
At least theoretical future therapeutic approaches include the use of neovascularisation-inhibiting substances such as aspirin, and even eliminating the genetic factors responsible for recurrence [40], [41].
Correctly performed high ligation is the minimum requirement for the prevention of saphenofemoral recurrence. Cutting-edge medicine today demands the additional use of a barrier technique. Optimal recurrence prophylaxis can, however, only be achieved by the addition of non-surgical anti-inflammatory measures. Factors that are associated with recurrent saphenofemoral incompetence – in particular lack of exercise and abdominal obesity – have to be mentioned here. Taking the remodelling hypothesis into account, analysis of data from the literature supports this approach to treatment even though no prospective studies are available.
