Guidelines for the diagnosis and therapy of diseases of the veins and lymphatic vessels
Evidence-based report by the Italian College of Phlebology
INTERNATIONAL ANGIOLOGY vol. 20 - suppl.2 to issue 2 - JUNE 2001
G.B. Agus, C. Allegra, G. Arpaia, G. Botta, A Cataldi, V. Gasbarro, S. Mancini
in collaboration with:
M. Bartolo jr., G Belcaro, P. Bonadeo, S. Camilli, M. Georgiev, A. Orsini, F. Stillo, P. Zamboni
3. Classification and categories (CEAP)
4. Non-invasive diagnosis
5. Surgical treatment
8. Drug therapy
10. Mineral water therapy
11. Treatment of venous ulcers
12. Venous malformations
13. Quality of life (QOL)
GUIDELINES FOR THE PREVENTION AND TREATMENT OF THROMBOEMBOLIC DISEASE
Prophylaxis of venous thromboembolism.
Treatment of deep venous thrombosis (DVT): methods and recommendations
GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF THE LYMPHATIC DISEASE
Lymphatic vessel diseases
Malformations of the lymphatic vessels
Quality of life
PRESENTATION OF THE CLAUDIO ALLEGRA
President of the Italian College of Phlebology
I have real pleasure in writing this introduction to the Italian College of Phlebology’s guidelines on venous and lymphatic diseases planned and drafted at the start of my presidency. For those of us with a “Latin” culture, this is the answer to the equation ‘clinical approach/controlled feasibility checks’. It provides us with a means of sharing with our Colleagues the best, proven information available in the field today. It is not the “Gospel” for sure, but only a set of recommendations based on our own and international research.
While apparently ‘recommendations’ implies the positive aspects of evidence-based medicine, in reality it shows how much still remains unproven and subjective in the field of venous and lymphatic pathology. To this summary of the state of the art we must add the incentive for future rigorous, reliable and reproducible research.
A comparison of these guidelines and those drawn up by respected international groups shows that we are not too far from the proven opinions of our foreign Colleagues – so we are entitled to the satisfaction of being the professional authors of a universally agreed text.
However, what distinguishes these guidelines is the discussion of difficult subjects such as compression and sclerotherapy. Again, the “Latin” peoples have long traditions on these subjects, which are now set in an appropriate context using Anglo-Saxon methods which bring everything back to controlled evidence.
Intuition, tradition, trade, and craft, all characteristics of the Mediterranean peoples, become signposts along the path of diagnosis and treatment, obeying international regulations.
It is exciting that this summary comes from the Italian College of Phlebology which a few years ago recognised the need to unite the main Italian phlebology societies within the College.
Recommendation: What really holds scientific associations together is the cultural message borne in the seed of continuity beyond personal and group claims and ambitions.
METHODS AND DEFINITIONS OF THE RECOMMENDATIONS
In Spring 1998, the Italian College of Phlebology set up task forces to prepare guidelines for diagnosis and treatment in phlebology and lymphangiology. The basic method drew on evidence-based medicine (1-3), applying the rules of evidence to the medical literature to produce recommendations for clinical management. Particular consideration was given to the evidence set out in Consensus Statements in this field (4-11) and the meta-analyses and available randomised trials were used.
We set out to adapt the findings to the working methods and approach taken by the Italian National Health Service, taking account of the extensive experience of European phlebology, using recent Anglo- Saxon scientific models.
Therefore, the different levels of recommendations have been classified as A, B and C:
1. Sackett GL et al. Evidence-based medicine: how to practice and teach EBM. London: Churchill Livingstone, 1996.
2. Greenhalgh T. How to read a paper. The basics of evidence-based medicine. B. M. J. publishing group, 1997 (Ediz. Italiana; Infomedica. Pianezza – TO, 1998).
3. Liberati A. (Ed.), La medicina delle prove di efficacia. Potenzialità e limiti della evidence-based medicine. Roma: Il Pensiero Scientifico. Ed., 1997
4. Porter JM, Moneta GL and International Consensus Committee on Chronic Venous Disease: reporting standards in venous disease. J Vasc Surg 1995; 21: 635-45
5. Consensus paper on venous leg ulcers. Phlebology 1991: 7:48-58.
6. Sclerotherapy for varicose veins: practical guidelines and sclerotherapy procedures. Handbook of Venous Disorders. London: Chapman & Hall. 1996: 337-54
7. Consensus Conference on sclerotherapy on varicose veins of the lower limbs. Phlebology 1997;12: 2 -16.
8. Consensus statement - The investigation of chronic venous insufficiency. Circulation 2000.
9. International Task Force. The management of chronic venous disorders of the leg: an evidence-based report. Phlebology 1999; 14 (Supplement 1).
10. Consensus Statement. Prevention of venous thromboembolism. Int Angiol 1997 ; 16: 3-38.
11. Consensus Document. The diagnosis and treatment of peripheral lymphedema. Lymphology 1995: 28: 113-7.
Chronic venous insufficiency (CVI) is caused by inadequate function of the peripheral veins. The equilibrium between tissue requirements and the amount of blood returning to the heart is not guaranteed, either in an orthostatic position or lying down. However, CVI does not simply involve the patency of the veins and the condition of their walls and valves (vascular factor) but includes any other cause that might affect venous return, such as muscle pump action in the feet, calves and thighs or changes in joint mobility and connective tissue (extravascular factors). A distinction must also be made between insufficiency of the superficial venous system and insufficiency of the deep venous system, or of both.
The key to recognising the subjective and objective signs of CVI is local or diffuse venous hypertension with rheologic repercussions on the macrocirculation and microcirculation, leading to the characteristic edema. These signs are valid at both the physiopathological and clinical levels.
The acquired or congenital pathological process causing CVI (angiodysplasia, valvular insufficiency or agenesis) can be functional or organic, the latter being more common but usually less severe.
CVI is a serious clinical condition affecting large numbers of people, and is important both from an epidemiological point of view and on account of its socio-economic repercussions. In the western world the consequences of the high prevalence of CVI are well known, the costs of diagnostic procedures and treatment programmes, the significant amount of work hours lost and the repercussions on quality of life (1-3).
The current prevalence of CVI in the lower limbs is from 10-50% of the adult male population and 50-55% of the adult female population. Clinical signs of varicosis are present in 10-33% of women and 10-20% adult men (1, 4-6).
To give pure data on the incidence of these diseases, prospective epidemiological studies are most interesting from our point of view, although in actual fact very few of these focus solely on CVI. The most widely cited is the Framingham study, which found the incidence of varicose veins (new cases appearing in each unit of time) was 2.6% in women and 1.9% in men per year; at two years varicose veins affect 39/1000 men and 52/1000 women (7). The prevalence of varicose veins in epidemiological studies covering different geographical areas varies widely (6).
The correlation between the prevalence of varicose veins and age is almost linear: 7-35% and 20-60% respectively in men and women between the ages of 35 and 40 years up to 15-55% in men and 40-78% in women over the age of 60. Venous diseases and varicose veins are rarely seen in children and adolescents, although children with a family history of varicose veins can develop venous ectasia and incompetence in their teens (1, 6, 8).
It is still debated whether the transmission of venous disorders is hereditary. The incidence of varicose veins in people with or without transmissible hereditary factors varies between 44 and 65% in the presence of these factors as opposed to 27-53% when these factors are absent (6). Familial predisposition is found in 85% of people with varicose veins but only 22% of those with no family history (9). Although many studies demonstrate "vertical inheritance" none have yet shown a “horizontal inheritance” which could be attributed to a genetic model.
CVI mainly affects women in their fifties and sixties. After this age there is no real difference between the sexes. Overall, epidemiological studies give evidence of a male/female ratio of 1:2-3, although Widmer’s large Basel trial (10) found a ratio of 1:1. This is probably due to the different trial methods (6).
Numerous epidemiological studies correlate the incidence of varicose veins with pregnancies and with the number of births. This varies between 10 and 63% in women with children as opposed to 4-26% in nulliparous women. Women who have had 1-5 pregnancies have an incidence of venous disease of between 11 and 42%, the proportion rising linearly with the number of births. This correlation is even more striking if the woman already has venous disorders. However, there is no shortage of studies disagreeing with this conclusion, which find no relationship between the incidence of varicose veins and the number of births (6).
The relationship between varicose veins and body weight has been widely examined. People who are overweight, especially women living in developed countries, suffer more from CVI and varicose diseases than people of normal weight: from 25% to over 70% (both sexes) as opposed to 16-45% (6). Varicose veins appear in both legs in 39-76% of cases (6).
Hypertension, cigarette smoking and constipation have not been shown to be correlated to CVI nor to be statistically significant risk factors for CVI.
It is widely recognised that certain occupations, particularly those that involve standing for long periods, are associated with an increased prevalence of varicose veins; however, it is extremely difficult to demonstrate a statistical correlation (4,11). Studies have focused on the incidence of varicose veins among people in a variety of jobs, particularly industrial and several authors have confirmed the association between the upright posture and varicose veins (6,12). The temperature of the workplace also has an influence (11).
Edema and trophic lesions, eczema and hyperpigmentation, all expressions of CVI CEAP categories 4-6, are reported in 3-11% of the population. The development of new symptoms/year is about 1% for edema and 0.8% for mild skin disorders (1). Active venous ulcers (VU) are found in about 0.3% of the adult population in the West and the overall prevalence of active and healed ulcers has been put at 1%, rising to 3% in the over-70 age bracket.
VU seems to be less likely or slower to heal among patients in the middle-lower social classes. The prognosis for VU is anyway not good, as they take a long time to heal and recur easily; 50-75% take 4-6 months to heal while 20% are still open at 24 months and 8% at five years.
Among patients of working age 12.5% apply for early retirement (1,, 2, 13-15). CVI is thus not only a serious burden on the health care services but also a considerable cost to society (16,17).
The number of working hours lost through CVI each year in England and Wales is around 500,000, whilst in the United States (where 25,000,000 people have varicose veins, 2,500,000 suffer from CVI and 500,000 from active venous ulcers) it reaches 2,000,000. The Brazilian public health figures show that, of the fifty illnesses most often cited as the reason for absenteeism and normally acknowledged in compensation schemes, CVI is placed 14th as it is the 32nd most frequent cause of permanent invalidity (1).
The annual cost of CVI management – almost certainly underestimated - is put at GB£290 million, 14.7 billion French francs, 2,420 million German marks, 1,638 billion Italian lira and 17,240 million Spanish pesetas. In addition, the European Community allocates 1.5 – 2% of its entire health budget – 418-1135 million ECU in 1992 – for the principal countries in Europe, over and above the indirect costs due to disability (2,17).
The annual cost of treating VU in the UK reaches £400-600,000,000 (£40,000,000 for medications alone), more than one billion dollars in the United States ($300,000,000 for domiciliary treatment), 400,000,000 DM in Germany and 300,000,000 Swedish krona, whilst in France ulcer treatments cost an average of 240,000 francs a year (1). In Italy around 291,000 doctor’s visits/year are made for ulcers, with prescriptions in 95% of cases, giving a financial burden of 243 billion lira (18). In total, the direct and indirect cost of CVI is around one billion dollars for each European state for which recent figures are available (UK, France, Germany) (1).
3. CLASSIFICATION AND CATEGORIES (CEAP)
The CEAP classifications were drawn up by an international group of specialists in 1994, the aim being to produce a new, standard method for the evaluation of chronic venous diseases which encompassed all the signs and symptoms of the disease (19). At the World Conference of Phlebology, in London in 1996, these classifications were reviewed and validated internationally. Since then, they have been translated into a number of languages and the international literature offers many papers that use these classifications (20-26).
CO no signs of venous disease
C1 teleangectasia or reticular veins
C2 varicose veins
C3 edema without skin changes
C4 skin changes (pigmentation, venous eczema, lipodermatosclerosis)
C5 skin changes with healed ulceration
C6 skin changes with active ulceration
1) Cs2 – Ep – As4 – Pr
Patient with primary varicose veins of the small saphenous vein with reflux.
Anatomic scoring: 1
Disability scoring: 1
Clinical scoring: 2
2) Cs6 – Es – As2 – 3 – 5, p11-13, Pr,o
Patient with post-phlebitis syndrome with active trophic lesions and obstruction of the deep femoral circulation with incontinence along the whole great saphenous vein.
Anatomic scoring: 5
Disability scoring: 3
Clinical scoring: 7
C = clinical signs (C0-6)
a = asymptomatic
s = symptomatic
E = etiology (Ec, Ep, Es)
A = anatomic findings (As, d, p)
P = physiopathology (Pr, o)
Clinical classifications (C 0-6)
class 0: no visible or palpable clinical signs of venous disease
class 1: telangiectasia or reticular veins
class 2: varicose veins
class 3: edema
class 4: skin changes of venous origin (pigmentation, eczema, subcutaneous inflammation)
class 5: as class 4 with healed ulceration
class 6: as class 4 with active ulceration
Etiologic classifications (Ec, Ep, Es)
Ec = congenital (from birth)
Ep = primary (non-identifiable cause)
Es = secondary (post-thrombotic, post-traumatic, other)
Anatomic classifications (As,d,p)
As = involving the superficial veins
Ad = involving the deep veins
Ap = involving the perforating veins
Superficial veins: As
1) telangiectasias, reticular veins on the small vena saphena
2) above the knee
3) below the knee
4) small saphenous vein
5) non-saphenous venous districts
Deep veins: Ad
6) inferior vena cava/iliac vein
7) common iliac
8) internal iliac
9) external iliac
10) pelvic veins: gonadal, broad ligament, femoral vein, other
11) common femoral
12) deep femoral
13) superficial femoral
14) popliteal vein
15) crural, and leg veins: anterior and posterior tibial, peroneal
16) muscle veins: gastrocnemius, soleus, etc.
Scoring venous malfunction by severity
*anatomic scoring: number of parts affected: 1 point for each part affected
*clinical scoring: objective symptoms and signs
pain 0 none
1 moderate, not requiring treatment
2 severe, requiring pain killers
edema 0 none
1 moderate, not requiring treatment
venous claudication 0 none
1 moderate, not requiring treatment
pigmentation 0 none
subcutaneous 0 none
inflammation 1 localised
ulcer (size) 0 none
1 less than 2 cm
2 more than 2 cm
ulcer (duration) 0 none
1 less than 3 months
2 more than 3 months
ulcer (recurrences) 0 not recurrent
1 only one ulcer
2 recurs after healing
ulcer (number) 0 none
2 more than one
disability score 0 asymptomatic
1 symptoms, but can lead a normal life without support hose
2 able to work an eight-hour day only with support hose
3 unable to work even with support hose
4. NON-INVASIVE DIAGNOSIS
Non-invasive diagnostic methods for venous disease were developed for screening, for quantifying lesions, and for hemodynamic studies. Centers for non-invasive diagnosis have grown up mainly in the last few decades.
Both the general practitioner and the specialist must, with varying degrees of competence, know the significance of the various vascular tests, their indications and limitations, so they can avoid having to prescribe unnecessarily invasive and costly tests (27-29).
Venous disease is more difficult to evaluate than arterial disease and requires experience and closer evaluation. This means venous tests are much more operator- dependent and require specific clinical skills, particularly in the evaluation of CVI. CVI can be the result of obstruction to venous outflow or return, or to a combination of the two. Clinical examination and diagnostic techniques therefore aim to establish which conditions are present. The anatomical location of the alterations must be found and the reflux and/or obstruction must be identified.
There are many simple, rapid and efficient tests available which are cost-effective. Just three types of examinations give the basic information usually needed to evaluate and quantify venous problems:
- continuous-wave (CW) Doppler
- duplex scan/colour Doppler ultrasound
adding, as necessary:
- investigation of the microcirculation.
EVALUATION OF VENOUS REFLUX
Reflux is usually assessed with the patient standing, with the limb under examination relaxed and the knee slightly bent. After the clinical and physical examination the screening can be completed with a directional pocket Doppler scanner which gives information about the presence or absence of reverse flow at the sapheno-femoral and sapheno-popliteal junctions. Manual compression of the calf produces an upward flow in the limb and reverse flow can be seen when the pressure is released. Compression must be applied for at least three seconds, not more than 10-20 cm distally from the site of examination. If the reverse flow disappears on compressing the superficial vein distal to the junction it is limited to the superficial system.
The CW Doppler gives information on the presence or absence of reflux at the venous junctions in 50-90% of patients (Consensus). Anatomical anomalies in the popliteal cavity can cause various errors; for example, reverse flow in the gastrocnemius veins may be interpreted as incontinence of the popliteal vein. The CW Doppler is not useful for locating incompetent perforating veins.
Screening with the CW Doppler can be completed with a duplex/color flow map (CFM), giving information on the site of the reflux; for example, the femoral vein, the popliteal or the perforating veins can all be studied individually. Color testing (CFM) means a faster assessment can be made. Using a 7.5 MHz probe the vein under examination can be visualised with the patient upright. The compression test can then show whether there is reverse flow. A high-resolution probe serves to document the competence of the valve. CFM is particularly useful for locating reverse flow in patients with recurrent varicose veins after surgery or sclerotherapy, or with anatomical anomalies. CFM also confirms the competence of the deep venous system and the extent and the site of any deep reflux. Reverse flow in a single vein can be quantified but this takes longer.
Some plethysmographic techniques give accurate and reproducible results.
Venous plethysmography measures changes in venous blood volume in the legs, to evaluate overall venous function. Three plethysmography techniques are currently in use: photoplethysmography/light reflection rheography (PPG/LRR), strain gauge plethysmography (extensimetric, SGP), and air plethysmography (APG) (30, 1, 31).
PPG/LLR uses photo sensors attached to the skin to measure filling of the cutaneous vein network (27). SGP uses extensimetric sensors (elastic sensor straps) to measure changes in the circumference of the leg at the point where they are applied (28). The APG sensors are inflatable leg cuffs which measure changes in the total venous volume of the leg (29).
By taking measurements in various positions and during various maneuvres it is possible to evaluate the following:
- venous outflow (slowed if there is occlusion)
- total venous reflux (degree of valvular incontinence)
- the efficiency of the muscle pump in the calf (venous drainage during exercise and the speed of refilling after exercise).
These measurements can be done as baseline values, as a basis for assessing overall venous function or, using a tourniquet to exclude the superficial veins, to give separate evaluations of the superficial and deep veins.
Venous plethysmography has the following applications in clinical practice:
- to measure and document the degree of impairment of the various venous functions (obstruction, reverse flow) and follow them over time;
- to measure the involvement of the superficial and deep veins and predict the hemodynamic effects of superficial vein surgery;
- to study and document the hemodynamic effects of different surgical options and validate new technics.
METHODS FOR INVESTIGATING THE MICROCIRCULATION
- Interstitial pressure
- O2 and CO2 partial pressure
5. SURGICAL TREATMENT
Surgical treatment for superficial venous insufficiency
BACKGROUND AND INDICATIONS
Surgical treatment of varicose veins in the lower limbs started virtually a century ago, with the work of Mayo and Babcock (32, 33), and is still a current procedure. Many thousands of operations and studies have confirmed its value (34-36). Essentially, three relative innovations have improved the results of the standard surgical technique: the stripping technique itself has been improved, in the light of new anatomical and physiopathological knowledge; simplified surgical procedures are now used, such as microsurgical phlebectomy (37,38) and stripping by invagination (39); and pre-operative mapping is done using colour echo-Doppler tests (40-43).
Many new surgical approaches have been proposed, some only used by the proponent. These may give good clinical results, but controlled multicenter trials are needed to assess them. For the time being, therefore, they cannot be considered substitutes for the standard techniques; at best they can be considered alternatives.
The importance of varicose vein surgery in Western health services is shown by the frequency of demand. Generally, the requirements are calculated at 70 interventions per 100,000 inhabitants in the United Kingdom (44), 200 per 100,000 inhabitants in Finland (45), and a much larger number in France (more than 150,000/year (46) and Italy (more than 100,000/year in 1997 according to an estimate by the DGR, including - but probably underestimating - the private sector. Therefore, the surgical indications must be discussed in depth.
The aim of surgery is total removal of all varicose veins, and this itself must be viewed within the context of the underlying pathology - CVI - and the troublesome problem of varicose veins recurring and new ones appearing after surgery.
The main aim of treating patients with CVI is to cure or improve the symptoms and to prevent or treat complications. The standard treatment for varicose veins is elevation of the lower limb to a drainage position and elastic compression hosiery to control edema, with local medication for ulcers. However, this does not treat the underlying hemodynamic disorder causing the venous disease.
Significant progress has been made in the surgical treatment of severe forms of CVI which can now be diagnosed non-invasively with imaging and velocimetry methods. It is possible to distinguish between situations in which obstruction prevails, and others – either primary or secondary – in which reverse flow is dominant. The surgical strategy chosen will depend on the different clinical, anatomical and pathological presentations. A wide range of strategies is available, no longer restricted to extensive and indiscriminate ablation, but aimed at correcting, where possible, the venous and microcirculatory hemodynamic abnormalities in the limb (47,48).
Indications for surgery in CVI depend on the symptoms, and on the objective findings of varices or their complications. The symptoms and pathologies that motivate the surgical choices are:
- clinical presentation and appearance
- heaviness of the leg
- fatigue in the limb
- superficial venous thrombosis
- bleeding varices
- pigmentation at the ankle
- white atrophy
However, as the patient himself may not attribute several of these signs and symptoms to CVI, a thorough, specific case history should be taken. Fifty percent of patients with telangiectasia and varices suffer from some of the disorders listed and with suitable treatment these problems will be eliminated in 85% of cases (49).
Heaviness of the legs is the most common reason for an examination by a venous specialist, especially among younger women. Recent studies indicate that it may not be caused by a varicose state, nor is it necessarily a pre-varicose syndrome. It is more likely to be the result of a combination of constitutional venous stasis, venous hypertension and lipedema (50,51).
Numerous other diseases give the same symptoms of fatigue and easy functional exhaustion: joint, neurological and peripheral arterial diseases are the most frequently cited. Similarly, edema of the lower legs is not obligatorily correlated with CVI, and a differential diagnosis must be made taking account of congestive cardiopathy, blood dyscrasia, metabolic disorders, etc. Finally, patients who have an unhealthy lifestyle, are overweight, do little exercise, have bad posture and are excessively sedentary may also have CVI, or actually become predisposed to CVI because of these factors. In these cases, surgery may even be contraindicated, and corrective measures may be sufficient to obviate the need for surgical intervention. Recent studies suggest that many symptoms may not be caused by venous factors and the venous disorder is simply concomitant with the underlying problem; in cases such as these surgical intervention is unlikely to relieve the symptoms (52,53).
Surgery of the superficial venous system accounts for a substantial portion of the workload of a general and vascular surgical unit and is one of the main reasons why waiting lists tend to be long. There is also the suggestion that “inadequate” venous surgery is responsible for many cases of recurrent varicose veins, even if the surgical technique was error-free (54) although it is not clear what exactly was meant by adequate (or appropriate) or inadequate (or inappropriate) surgery (55).
SURGICAL TECHNIQUES FOR VARICOSE VEINS
Nowadays any surgical intervention for superficial venous insufficiency should be preceded by hemodynamic studies using colour echo-Doppler mapping of the area.
The surgical techniques can be classified in four main groups:
- ablative surgery
- symptomatic ablative surgery
- conservative surgery, without excision of the saphenous trunks
- endovascular treatment
This includes stripping along the whole length of the greater saphenous vein (from the sapheno-femoral junction to the medial malleolus), restricted stripping of the greater saphenous vein (from the sapheno-femoral junction as far as the upper third of the leg), stripping the small saphenous vein (from the saphenous-popliteal junction to the lateral malleolus or the mid-calf).
Ablation of the saphenous veins is usually completed by varicectomy and by section and ligature of the incompetent perforating veins so as to achieve the required hemodynamic result by excising the refluxing vessels.
This is the standard surgical treatment. It has been extensively studied over the years and comparative studies have been made with sclerotherapy and with crossectomy alone or combined with sclerotherapy, but there have been no comparative studies with the alternative surgical treatments. However, ablative surgery was more effective than the other two methods (34, 35, 56-62). Several techniques have been described: Babcock’s intravenous stripping; Mayo’s external stripping – and its derivations; stripping by invagination as done by Van der Strict, Ouvry, Oesch.
Symptomatic ablative surgery
Nowadays this is a phlebectomy with or without incisions, according to Muller, and may be either used to cure varicose veins or complementary to other techniques.
The Muller method is technically preferable as it gives less trauma and a better esthetic and functional result. An incision of few millimeters is made and the incompetent branches of the superficial circulation, with the exclusion of the saphenous junction, are removed through this incision using special instruments (37,38).
Another technique for treating the symptoms is to incise the thrombosed varicose branches to ablate them or, in the case of superficial venous thrombosis, simply squeeze out the thrombotic material.
Conservative surgery without excision of the saphenous trunk
The aim is to treat the varicose veins, maintaining the saphenous drainage but not the reflux. Saphenous flow can be directed physiologically (sapheno-femoral external valvuloplasty and first step of the CHIVA 2 strategy - see below) or reversed and directed towards the re-entering perforating vein (CHIVA 1).
These techniques can be complemented by phlebectomy but an echo-Doppler examination must be done beforehand.
Sapheno-femoral external valvuloplasty
The rationale for this treatment is based on the histological finding that in the initial stages the valve cusps are still healthy but are incompetent because of dilation of the vessels walls (63,64).
The aim of the intervention is to bring the valve leaflets back together, closing the dilated vessel walls. This can be done by either suturing the wall directly or by “banding” the vessel with some sort of external prosthetic belt. An ultrasound examination must be made to check that the valve is mobile and not atrophied at the terminal or subterminal level of the greater saphenous vein. Competence can be tested during the operation using the milking maneuver and/or a Doppler scan.
CHIVA type 1 hemodynamic correction
This is done when the perforating re-entry vein of a refluxing saphenous system is on the saphenous trunk. The sapheno-femoral vein is disconnected and the saphenous vein is freed of any incompetent branches, with or without a phlebectomy. The perforating re-entry vein should be treated by tying it off or sectioning the saphenous vein downstream of its entry point (terminalization) (40,65).
CHIVA type 2 hemodynamic correction
This is done when the penetrating re-entry vein of a refluxing saphenous system is on a tributary of the saphenous vein. The tributary/ies are disconnected flush from the saphenous wall by clipping and a phlebectomy may be carried out (66). In 60% of cases, after 18 months, this is the only intervention required. In the remaining cases the treatment will need to be completed by a CHIVA 1 hemodynamic correction or by repeating this procedure depending on the hemodynamic outcome.
Crossectomy with or without phlebectomy.
A simple crossectomy gives functional results in the treatment of varicose veins, but is less effective than stripping. (67,68). Crossectomy with phlebectomy gives results comparable to stripping only when it is based on thorough preoperative radiological or ultrasound examination (69-71).
This heading includes positioning Van Cleef type clips under radiological guidance, and treating the walls at the height of the terminal valves with a heat-transmitting radio probe.
SURGERY OF THE PERFORATING VEINS
The perforating veins supply blood through the muscular aponeurosis to the superficial and deep venous systems. These veins are numerous, from 80 to 140 per leg, the diameters not exceeding two millimeters. The valves are normally located in the sub-aponeurotic area.
Venous examination must assess the anatomical and morphological criteria in parallel with the hemodynamic criteria. A reflux is defined as pathological if it fulfils the following criteria:
- duration more than one second
- caliber of the perforating vein more than 2 mm, calculated from the ultrasound findings.
The severity of the CVI in relation to incontinent perforating veins is based on the number of perforating veins involved and, in particular, whether more than one system (superficial/deep/perforating) is involved (72,73); there may be a venous–venous shunt starting in the deep venous system and involving the saphenous vein, the perforating veins or even the pelvic veins, or a venous-venous shunt established in the superficial system (74).
However, there is some controversy over the identification of incontinent perforating veins in the leg. Doppler ultrasound appears to be the most reliable investigation, but there is still debate about the best method (75,76).
Elimination of the incontinent perforating veins in combination with drainage of the varicose veins and restoration of the saphenous return in patients with severe chronic venous insufficiency is one therapeutic approach for trophic disorders of the skin (77).
There are two main procedures for surgical treatment of perforating veins: the traditional method (of Linton, Cockett, Felder, De Palma) for the suprafascial and subfascial veins (78) or endoscopic treatment of the subfascial veins. Indications for traditional surgical and endoscopy are incompetent perforating veins of the leg and active or healed ulcers (CEAP classes C5- C6); this mainly involves post-thrombotic syndromes. Treatment of perforating veins due to superficial vein inadequacies is reserved for symptomatic cases. Some studies suggest the surgical approach for patients with symptomatic cutaneous dystrophy (CEAP class C4) (79,80).
The various traditional treatment methods give broadly similar results, with 9-16.7% of patients having recurring ulcers when followed up for 5-10 years (78, 81, 82). The percentage of recurring ulcers in patients with post-thrombotic syndrome is higher (>16%) with a five-year follow-up.
Some authors have combined these methods with venous bypass (83), valve grafts and endoscopy (78), but the outcomes cannot be compared.
Considerations: No substantial differences have been observed between the traditional techniques and there are as yet no multicenter trials to compare the results of the different traditional approaches alone or in association with other methods.
Endoscopy, a recent concept in this field, uses single access (one trocar) or double access (operating trocar and optic). A number of studies report recurrent ulcers at five-year follow-up in 0-10% of cases (80, 84-87).
Many authors have associated surgical endoscopic treatment with drainage of the incontinent superficial venous system, reporting similar proportions of recurrent ulcer at five years of follow-up. One multicenter trial, however, which compared endoscopic surgery alone with endoscopy plus drainage of the superficial system, found a smaller percentage of recurring ulcers in the second group at two years of follow-up (86).
Considerations – Multicenter trials are currently in progress to evaluate endoscopy compared with traditional treatment and whether it is appropriate to combine this with plastic surgery for the ulcers. Regardless of the methods used, the worst results have been seen in patients with post- thrombotic syndrome.
At present, endoscopic surgery is preferred to traditional techniques as it is less invasive, causes fewer post-operative complications and, under endoscopic guidance, it is possible to work at a distance from the site of ulceration.
RECURRENT VARICOSE VEINS
These are varicose veins that appear after surgical treatment, not the remains of the treated veins (88-92). Although surgery for varicose veins in the lower limbs appears to be a simple procedure, there are a number of traps. The high percentages of recurrences reported in the international literature confirm this (88-93). However, it is difficult to interpret these findings, as the patient populations differ and the diagnostic and therapeutic protocols vary.
The most frequent causes of recurrences are:
- errors in the diagnostic strategy and inappropriate treatment
- technical errors.
Errors of diagnostic strategy and treatment
The long-term results of surgical treatment of varicose veins depends on correct diagnosis. If the hemodynamic causes of the varicose veins are properly identified an appropriate treatment plan can be chosen (94). “Radical surgery”, defined as physical extraction of the saphenous vein with all its collaterals and all the enlarged varices, which has been the surgical procedure of choice for varicose veins for almost a century, is increasingly being replaced by “radical hemodynamics”, meaning elimination of all the hemodynamic defects which are at the root of the formation of the varices (the reflux).
Mapping was started a decade ago to ensure reproducibility over time (40). A sort of “geographical” map of the varicose veins and circulation defects of the lower limbs is used in both CHIVA interventions and “traditional” surgical procedures. Incorrect application of these concepts can leave the way open to recurrences.
Numerous papers have given incontrovertible evidence of a high number of errors, frequently serious, made during operation (93, 95-98).
Haeger in an autopsy study reported 158 (15.1%) residual saphenous veins in 837 lower limbs that had been operated on for varicose veins.
Crane described 57% crossectomy ligatures that were incorrectly executed.
Marques reported 54.5% of incorrect ligatures in cases of re-operations for recurring varicose veins.
Tong found 168 (68.9%).saphenous vein residues in 244 lower limbs studied
Of all the causes of error during surgery for varicose veins in the lower limbs, the main one is the wide range of anatomical variation at the junction of the saphenous-femoral veins which may cause the surgeon to leave some collaterals in place.
Surgery: The most suitable seems to be the lateral subfascial approach where the technical difficulty of dealing with cicatricial sclerosis is not encountered (99, 100); this is reserved for cases where there is a residual stump of the saphenous vein with collaterals. Where indicated, varicectomies using Muller micro-incisions and hemodynamic correction of the incompetent perforating veins is performed.
Pharmacological and compression treatment or sclerosing therapy: Used in all cases in which surgical treatment is not indicated or as an alternative.
Mixed: A combination of the two approaches.
NATIONAL HEALTH INSURANCE (ITALIAN) CLASSIFICATIONS
A proposal for regulations (101) has been made to cover clinical, organisational and administrative possibilities for surgical interventions, invasive and semi-invasive diagnostic and/or therapeutic procedures without hospital admission and without the need for post-operative observation; such procedures can be done in the consulting room, in out-patient or other supervised centers, using local and/or local-regional anesthetics. Three possible regimens for surgical treatment of varicose veins are given: walk-in, day surgery or standard admission.
Day surgery is probably suitable for the majority of surgical interventions for varicose veins as long as specific selection criteria are used:
- procedures carried out as day surgery should preferably last less than one hour
- patients scheduled for this treatment must be very carefully selected and should be informed prior to the procedure about the type of intervention and/or treatment. They should signed a personalised informed consent form;
- the lines between the interventions feasible under the various regimens are blurred. Therefore, the medical team will decide which type of regimen is best suited to each patient, after having carefully selected and informed them individually about the choice of regimens available;
- selection must take into account the patient’s general condition and any pertinent family and logistic factors;
- patients who are entered in walk-in and day surgery programmes must be in good general health. The ideal candidates are classified as ASA classes 1 and 2. Emergencies cannot be dealt with on this basis;
- age and weight selection criteria apply. With few exceptions, the upper age limit is 75 years. Obesity is a very important risk factor and must be very carefully evaluated.
- as regards logistics, the patient’s home should not be too far from the place where the operation will be done. The patient should be reachable in a short time, if necessary. Therefore the travelling time should be less than one hour. Another requirement is that phone contact with the center should be possible;
- patients must have a family member or reliable person with them during the recovery period, particularly during the first 24 hours after surgery. This person should be given detailed instructions and should be able to accompany the patient home and give any assistance the patient might require, particularly in the first 24 hours;
- the decision to enroll a patient in a particular regimen is the exclusive responsibility of the doctor, who, after obtaining the patient’s informed consent, must be at liberty to select the most suitable regimen, on the grounds of the sound scientific and ethical principles always underlying health care;
- the choice of the most suitable regimen will be guided by the patient’s clinical and psychological condition. Many of the pathologies that would normally lend themselves to treatment under a walk-in regimen should, if they are more extensive or complicated, be treated in the day surgery or actually in hospital.
- finally, even if a pathology or surgical procedure appears on the official list of services available in day surgery, this does not oblige a doctor necessarily to carry out the treatment under that regimen.
However, various difficulties are still encountered in Italy due to the very high demand for these procedures, and there is no obligation for a patient to be enrolled in any particular regimen without a specialist’s evaluation and without giving informed consent (102)
Certain clear observations justify hospital admission. In such cases, regardless of the doctor’s opinion whether day surgery is possible or not, the patient must agree to being operated in hospital. If a patient, for whatever logistic or psychological reason, does not want to be operated in day surgery but insists on hospital admission, this is a valid reason for the NHS covering the whole cost, provided it is clearly documented in the clinical records and on the informed consent form.
Logistic and family factors are particularly important in Italy and they can be justification for admitting a patient the day before the procedure, provided there are also valid health care reasons. The period after discharge must be carefully organised: the patient must be properly accompanied after discharge, s/he must be able to contact the center easily for advice or help and must be able to return there easily if complications arise. Any logistic situation which does not comply with these requirements must be described in the patient’s records and may justify a longer stay.
Current DRG data for varicose vein surgery (101) show an average stay in hospital of 3.7 days; 54.3% of these patients stay in hospital 2-3 days; under-use of day surgery is limited to 8.3% of cases.
Surgical treatment of deep venous reflux
Candidates for deep venous surgery suffer from severe CVI, with significant
venous reflux and ambulatory venous hypertension. Conservative therapy has
failed for these patients and the venous disease reduces their quality of life.
When the deep vein reflux is slight, stripping of the saphenous vein can bring
considerable benefit and eradicate the reflux in the femoral vein (103).
However, if there is severe, fast reflux, the deep venous system will require direct surgery, considering the high percentage of recurring ulcers after conservative treatment and the excellent, lasting results obtained in centers that opt for the direct approach.
Reconstructive valvular surgery includes direct methods, which aim to restore the competence of the valve, and indirect methods, which aim to improve the venous hemodynamics of the limb (104-107). Direct surgical methods are indicated in PPVI when the valve cusps are dilated or prolapsed but still present and functioning. In STP or valvular agenesis when the valves are damaged or absent an indirect technique is the better therapeutic choice.
CVI is a complex pathology as the venous circulation involves so many levels and systems. Rapid healing of stasis ulcers can be achieved by correcting all the points of reflux and maintaining or setting up venous return channels. Depending on the site and extent of the valvular lesion a variety of surgical techniques can be used.
In a review of 423 valve reconstructions Raju (108) listed the duration of success of the surgical methods, monitored with Doppler ultrasound, in the following order:
- internal valvoplasty;
-external valvoplasty with prosthetic cuff
- external valvoplasty with direct sutures;
- venous graft.
There were no significant differences in the recurrence of ulcers with these various methods.
The time is ripe for standardisation of pathology reports, clinical reports and hemodynamic parameters so that the different surgical techniques can be compared in randomised prospective trials.
Sclerotherapy is the chemical obliteration of varicose veins. The veins are injected with a histo-lesive substance (sclerosing liquid) which damages the endothelium, producing spasm, thrombosis and an inflammatory reaction which are intended to produce stenosis, fibrosis and the permanent obliteration of the vein (Table I).
Table I – The most widely used sclerosing substances: indications and concentrations
Sodium tetradecyl sulphate
Type of varices and recommended concentration
Large varicose veins
Saphenous vein segments
inserire i dati dalla tab.I, p.16, cambiando le virgole in punti!
The initial obliteration of the vein is obtained in more than 80% of cases; however, part of the sclerosed veins will subsequently open again.
INSTRUMENTAL STUDY OF INDIVIDUAL VEINS
In studies monitored using Doppler examination or ultrasound the greater saphenous vein was obliterated in 81-85% of cases (109, 110), but one year later between 17% and 35% of cases had opened again (111, 112), 33%, 60% and 80% of cases after two years (113, 114, 75) and 48% after three years (112).
Similar results have been obtained with the small saphenous vein, which was initially closed in 87% of cases (109) but after two years there was blood flowing again in 33% of cases (113), while after five years recanalisation was found in 27% when the popliteal vein was competent (primary varicose veins) and 77% when the popliteal vein was incompetent (secondary varicose veins) (115).
In the single trial covering collateral veins, at two years 26% were patent again (113).
From 1984 to 1996 four prospective randomised clinical trials with clinical monitoring were conducted. These showed that at the beginning sclerotherapy gave results comparable with those of surgical extirpation; but, over time, the recurrence of varicose veins was definitely more frequent after sclerotherapy.
In Doran's trial (116), after two years the results of sclerotherapy and surgery were the same. Chant and Beresford (118, 117) found that after three and five years recurrence with sclerotherapy was respectively 22% and 40%, in contrast to 14% and 24% with surgery. In Hobb’s trial (119), one, five and ten years after sclerotherapy recurrences were seen in 8%, 57% and 90% respectively, compared with 6%, 25% and 34% after surgery. Jacobson (58) found 63% of recurrences after three years, as opposed to 10% after surgery.
TRIALS WITH CLINICAL AND INSTRUMENTAL MONITORING
In Einarsson’s trial (120), after five years the recurrence rate was 74%, in contrast to 10% with surgery. In this trial the results were checked by measuring hemodynamic parameters (volumetric measurements of the feet), but even using these criteria the results of surgery were better.
Between 1973 and 1975 three unsigned editorials in the British Medical Journal and the Lancet (121-123), proposed that, as regards both the results and the cost/efficacy ratio, a combination of surgery at the sapheno-femoral junction and sclerotherapy for the remaining varicose veins was the best option. However, though combined therapy proved more effective than sclerotherapy alone, it was always less effective than surgical removal of the varicose veins.
Lofgren (124) already reported this in the Fifties, on the basis of a retrospective study: at five years, there was 70 % recurrence with combined therapy but only 30% with surgery. In Jacobson's prospective trial (58) recurrence at three years was 35% with combined therapy, 63% with sclerotherapy alone and 10 % with surgery alone.
In Neglén’s trial (125) after combined therapy 21% of patients had residual varices, while after five years the recurrence rate was 84%. Volumetric measurements of the feet, normal after treatment, had already deteriorated after one year and after five years had returned to the pre-treatment values.
In Rutger’s trial (61), after three years the recurrence rate was 61% with ligature and sclerotherapy and 39% with stripping and phlebectomy. Doppler scanning showed saphenous reflux in 46% of patients in the first group and 15% of the second. This is the only study in which there were more clinical failures with sclerotherapy (61%) than saphenous recanalisations detected on Doppler scanning (46%). In all the other studies, half the cases of recanalisation detected instrumentally showed clinical improvement. However, these objective failures with sclerotherapy were partially mitigated by the patients’ subjective evaluations which were invariably better than the surgeon’s.
EVALUATING THE EVIDENCE
Despite some criticisms, all the trials published so far – six prospective and randomised (116-120, 58, 61), one retrospective (124) and one prospective controlled (125) – have given unanimous results, definitively showing the superiority of surgical excision over sclerotherapy and combined therapy, at least for varicose veins with incompetence of the greater saphenous vein.
The high rates of recanalisation and recurrence mean that sclerotherapy is a secondary choice, not an alternative to surgery. It becomes the treatment of choice only in cases in which surgery is inadvisable (because it is difficult, with uncertain results or high risk), or is specifically requested by the patient, who must be fully informed of the likely results, complications, advantages and disadvantages of sclerotherapy in comparison with surgery.
Sclerotherapy was introduced in France in 1853, but the first attempts at producing guidelines were only made in 1996, by the International Consensus Conference (1996), the American Academy of Dermatology (126) and the American Venous Forum (74). However, only the American Venous Forum specifically formulated the indications for sclerotherapy, which are the same as the ones the Collegio Italiano di Flebologia is proposing here. These indications include:
2) small diameter varices (1-3 mm);
3) residual veins after surgery (purposely left by the surgeon)
4) varicose veins recurring after surgery (if originating from a perforating vein <4 mm diameter)
5) varices from venous malformations (Klippel-Trenaunay type) for which surgery is not advisable;
6) emergency treatment for bleeding ruptured varicose veins
7) perforating veins <4 mm diameter
8) varicose veins around an ulcer
As this list shows, sclerotherapy is an important and indispensable method for the optimal treatment of a wide range of varicose veins, from spider veins, which are not just anesthetic problem but can cause skin pathologies and even serious hemorrhage, to the serious, disabling forms of CVI such as lipodermatosclerosis, stasis ulcers and congenital venous malformations.
contraindications to sclerotherapy include allergy to the sclerosing solution,
serious decompensated systemic disease, recent DVT, local or systemic infection,
non-reducible edema of the lower limb, immobilisation and critical ischemia of
the lower limb. Caution is needed in patients with a history of recurring DVT, with confirmed thrombophilia, women taking estrogen/progestogen preparations, or who are pregnant.
Like any manual technique, sclerotherapy has to be learned. The various techniques currently in use are derived from three European schools, Tournay (127), Sigg (128) and Fegan (129), and are described in Italian in two publications (130,131).
The type and concentration of sclerosing fluid varies according to the type of varicose vein and is shown in Table 1. Injections are given in more than one sitting, a few days or a few weeks apart, depending on the individual technique. Better results are obtained, with fewer adverse effects, if the injected vein and the leg are immediately compressed with either adhesive or free bandages or with elastic-compression stockings (132). Compression is all the more important, and needs to be more prolonged (from three to six weeks or more) if the varicose veins are particularly large and diffuse. In some cases – e.g. large varicose veins or legs with a tendency to edema - compression is indispensable.
In the last few years injection of sclerosing fluids under ultrasound guidance (ultrasound sclerotherapy) has been introduced (109), but it has not yet been confirmed more efficient in the long term. Also requiring confirmation is the utility of injecting detergent-based sclerosing compounds (polydocanol or tetradecyl sodium sulphate) in microfoam form rather than liquid (133,134).
Compression is the pressure applied to a limb, using a variety of materials, elastic or firm, to prevent and treat diseases of the venous or lymphatic systems.
Elastic compression treatment has been used throughout the history of medicine. Traces of the use of bandages have been found among the Ancient Egyptians and the tribes living along the River Tigris. The prophet Isaiah in the 8th century B.C. wrote about the utility and purposes of bandaging the legs, as did Hippocrates and his school of medicine. The Roman legionnaires in 20 B.C. bandaged their legs tightly during long marches to prevent stiffness. Aurelio Cornelius Celso, a Roman author writing at the time of Tiberius, recommended occlusive and compressive linen bandages for treating ulcus cruris. And throughout the medieval period, influenced by Arabic medicine, compressive dressings were widely employed.
venous system, assisted by the lymph vessels, returns the blood from the tissues
to the heart. Every time the venous flow is slowed or impeded a sort of “traffic
jam” build up: ischemia occurs in the cells, as the stasis prevents oxygen and
nutrients leaving the arterial capillary wall to enter the interstitial space
and get to the cell walls where they are absorbed. This is because of an
inversion of the local pressure ratios; the slowing of the blood flow causes an
increase in interstitial pressure which counterbalances the residual arterial
The lack of flow leads to an increase in perivascular oncotic and osmotic pressures, causing water retention and edema, a self-sustaining cycle.
Compression therapy works by changing the venous hemodynamics; there is an increase in the flow speed (evaluated using plethysmography and venous occlusion), a reduction in the vessel dimensions, and valvular competence returns (confirmed by Duplex scan). Rheographic examination shows an increase in the refilling time after exercise, an indication of improved venous compliance. Overall, the reduction in pericellular edema limits tissue damage (135-137).
Physiological and technical rationale
In phlebolymphology the materials used to achieve compression are bandages, elastic and inelastic hose (138,139).
Bandages are generally used to protect the lower leg. The most important property of bandages is that they can stretch or expand. The expansion factors in relation to the initial size are:
- small expansion (<70%);
- medium expansion (70-140%);
- long expansion (>140%).
The inelastic or barely elastic bandage produces a considerable amount of “working” pressure when walking, as it prevents the increase in the circumference of the leg caused by contraction of the calf muscles, whilst the pressure at rest is minimal. In contrast, the elastic bandage exerts a moderate amount of "working" pressure and high "resting" pressure, the difference between the two being inversely proportional to the elasticity. An elastic bandage maintains continuous pressure on the superficial venous system which is relatively independent of muscular activity.
Elastic bandages made of fibers with a long expansion factor act in a similar way. Inelastic or barely elastic bandages can be worn day and night whereas bandages that stretch more than 70% and support stockings should be taken off at night, as they are not designed to be worn when the patient is lying down (140,141).
Taking into account the various types of bandage, the pressure exercised is always found by using the Laplace law:
P = t/r
modified as follows for a bandage:
P = tn/ra
where t is the tension, n the number of turns of the bandage, r the radius of the circumference of the compression, and a the width of the bandage. Compression can thus be “dosed” to meet treatment requirements.
The length of time the bandages are worn is not standardised. Some studies show equal efficacy with bandages worn for a few hours or for six weeks; there is a significant drop in the amount of compression exerted by a bandage 6-8 hours after application (142,143).
ELASTIC SUPPORT HOSE
Elastic support hose, for prevention or therapy (144-146) are manufactured in various sizes, either standard or to measure, and are classified according to their length as:
- knee-length socks
- mid-thigh stockings
- single leg tights
There are also “cuffs” for the arms.
When pressure on the ankle is less than 18 mm Hg the support is defined as preventive or resting. There is controversy over whether this is effective, just as debate continues on the utility of hosiery whose pressure is expressed in “deniers” (den).
When the pressure on the ankle is greater than 18 mm Hg the support is defined as therapeutic. Graduated, defined compression is achieved on the lower limb, decreasing from the bottom towards the top, being 100% at the ankle, 70% at the calf and 40% at the thigh. Depending on the compression at the ankle, expressed in mm Hg, therapeutic support hose are grouped in four classes, which differ according to whether the German standards or the French standards are followed.
Manufacturers of therapeutic elastic support stockings based on the German RAL GZ 387 standards give four classes of compression:
18.7 – 21.7
25.5 – 32.5
36.7 – 46.5
Based on the French NFG 30-102 B standards therapeutic elastic support stockings are also grouped into four compression classes but these have lower values:
16 - 20
21 – 36
Besides these support stockings for prevention and therapy there are also “antiembolism” support stockings for the prophylaxis of thromboembolism. These are different from the other models as they give a standard compression of 18 mm Hg at the ankle and 8 mm Hg at the thigh and can be worn comfortably even when resting.
The manufacturing standards for an elastic support stocking were drawn up at the request of the German authorities, as these appliances are eligible for national health system reimbursement, and appear in the official German drug formulary (CEN documents).
These standards comprise:
- a table establishing the four classes of compression to which all the support hose for compression treatment belong;
- a table showing the pressure distribution for the different classes, so the elastic support will guarantee the correct gradient along the length of the lower limb;
- specifications for the manufacture of the hosiery, with details of both the longitudinal and circumferential stretch;
- specific methods for the stitching, the seams, the heel, etc.
- the materials which must be used are given, with precise limits for the thickness of the yarn, so the product will be strong enough to ensure its properties remain constant over time;
- finally, there is a section on the inspection methods for the finished stocking.
The RAL-GZ 387 standards are entrusted to two authorities, one in Germany and the other in Switzerland. The preliminary tests (HOSY system) certify that the support hose complies with the technical specifications, with particular attention to the visual checks, tests for transverse and longitudinal elasticity, and analysis of the materials used. There is also a sophisticated test to measure the compression and how it decreases from the base of the stocking towards the top. This test is conducted using special equipment which can measure any type of elastic stocking and record its static and dynamic performance.
These very strict and restrictive standards have been used for thirty years to monitor the production and distribution of elastic support hose in Germany and are proposed as the model for European Union regulations.
Intermittent Pneumatic Compression
This is indicated for the prophylaxis of venous thromboembolism and the treatment of venous ulcers. Intermittent pneumatic compression (IPC) increases venous blood flow during periods of immobilisation. IPC devices are adjuvant measures for the treatment of lower limb edema, venous ulcers or both, and for the prevention of pulmonary thromboembolism.
IPC should be considered for patients with a high risk of hemorrhagic complications or in whom a minor bleed could have serious consequences. IPC is indicated for patients who have had neurosurgical surgery, major urological, eye, spinal and knee surgery. It is also indicated in patients with suspected or documented intracranial hemorrhage or after recent cerebral or spinal traumas.
IPC as coadjuvant therapy for venous ulcers.
IPC is indicated in the treatment of venous ulcers, giving a higher recovery rate, in a shorter time.
Compression is indicated for any chronic or acute venous insufficiency, either associated with other treatments or alone. The efficacy of compression for the symptomatic treatment of CVI or the prevention of complications is supported by clinical experience and by a substantial amount of scientific literature, particularly for the advanced stages of venous disease. However, only the most recent publications satisfy the extremely rigorous case/control comparison criteria, with adequate sample sizes.
The type of compression used, the method of application and length of time used will vary according to the clinical context and for each patient even in groups with the same pathologies. Therefore the choice of compression hose needs to be centered on individual requirements and the severity of the disease.
In order to unify the evaluation criteria for acute and chronic venous insufficiency, and its prophylaxis and treatment, generalised classification standards must be used. These are the CEAP international classification for CVI and the high/moderate/low risk classifications from the Consensus Statement on Prevention of Venous Thromboembolism.
Superficial thrombophlebitis is considered benign if there are no thrombophilic risk factors, and is one of the common complications of varicose veins. However, it may progress to pulmonary embolism and this can be fatal. In the majority of thrombophlebitis cases, with or without varicose veins, after drug therapy (anti-inflammatory drugs and heparin) elastic compression hose and mobilisation are the first line of defence for both treatment and prevention. (147).
Deep vein thrombosis
The graduated-pressure elastic stocking reduces the incidence of DVT after surgery, using an optimum pressure of 18 -20 mm Hg at the ankle and 8 mm Hg at the thigh (148,149).
Although evidence from controlled trials is still lacking, the current treatment for DVT remains based on heparin. Mobilisation and compression have long been recommended by some specialists, even in the acute phase of DVT (150,151). However, opinions still vary about the early mobilisation of patients with DVT or the preferred method of compression using inelastic, mobile or adhesive bandaging, or elastic stockings.
For the time being it is not possible to make recommendations.
PREVENTION OF POST-THROMBOTIC SYNDROME
Post-thrombotic syndrome (PTS) is an aftermath of DVT in between 10 and 100% of cases; it may cause moderate to painful disabling edema, and trophic cutaneous changes leading to ulceration. The use of elastic knee-socks with 40 mmHg compression at the ankle for at least two years has been endorsed by a randomised controlled trial where it halved the incidence of DVT when the stocking was used regularly (152).
COMPRESSION AFTER SURGERY OR SCLEROTHERAPY FOR VARICOSE VEINS
Compression after surgery is indicated for the prevention of venous thromboembolism, the prevention of hematoma, the treatment of postoperative problems and the prevention of recurring varicose veins (141,153,154).
a) Functional symptoms of mild venous
insufficiency (CEAP 0 = no visible signs of venous disease)
There is no reliable data on the efficacy of “resting” or “preventive” commercial support stockings (155).
b) Telangiectasias and spider veins (CEAP 1)
Venous ectasia accompanied by clinical symptoms of CVI are an indication to increase compression at the ankle and consequently on the calf and thigh (156).
c) Varicose veins (CEAP class 2)
Compression is considered fundamental in the clinical management of patients with varicose veins, as it reduces the feeling of heaviness and pain and acts on trophic changes in the tissues, either alone (117, 157, 71) or in combination with drug therapy (158). For a small group of 31 patients who had varices without complications, low- compression stockings, exerting 20 mm Hg at the ankle, were as effective clinically and hemodynamically as stockings giving 30 mm Hg compression, and compliance was better (159).
d) Edema (CEAP class 3)
Edema is a common complication of venous insufficiency even in early clinical stages. There is slight swelling around the ankles towards the end of the day in CVI, more marked in varicose diseases with skin disorders and stasis ulcers. It is caused by changes in the interstitial pressure ratios caused by venous hypertension (144).
e) Trophic changes of venous origin, pigmentation, eczema, subcutaneous inflammation, healed ulcers (CEAP classes 4 and 5).
Skin changes in chronic venous disease are indicators of serious tissue damage caused by hypoxia from chronic stasis. A review of the literature by Moffat (160), showed recurring ulcers in 2/3 patients without compression therapy.
f) Venous ulcers (CEAP class 6)
Venous ulcers can be effectively treated with compressive therapy after local surgical and/or pharmacological therapy. Elastic stockings, Unna bandages, multilayer bandages or IPC are useful. A review of the literature, published in the BMJ in 1997 (161), which considered all the available trials on the treatment of venous ulcers, concluded that compression improved the prognosis of this condition, preferably using high pressure. There does not seem to be any one system which is better than the others (multi-layer, short-stretch bandaging, Unna boot).
Table II – Venous physiopathological processes affected by drug therapy
- Reduced venous tone
- Depressed venous-arteriolar reflux
- Vasomotor disturbances
- Increase in capillary permeability
- Pericapillary fibrin cuff
- Reduced fibrinolysis
- Increase in plasma plasminogen
- Changes in leucocyte and erythrocyte rheology
- Leucocyte activation
- Capillary microthrombi
- Stasis of the microcirculation
8. DRUG THERAPY
Pharmacotherapy for CVI has greatly developed over the last 40 years. It is therefore surprising that there are no clinical or experimental trials to study the tone and contractility of the veins nor venous pressure in relation to treatment problems (162).
Drugs for the venous system were initially called phlebotonics as they were believed to act on venous tone. They are still largely used in the symptomatic treatment of CVI and to make patients more comfortable (163).
Phlebotrophic drugs in their modern form are aimed at a wide range of processes (Table II). They are naturally occurring, semi-natural and synthetic products, some of them combining two or more active principles to improve the efficacy. Most of these belong to the flavonoid family; 600- 800 of these substances have been identified and grouped by Geissman and Hinreiner under the name of flavonoids, plant polyphenols containing a flavone chemical structure, which in 1955 were given the name “bioflavonoids” by the New York Academy of Sciences (164). Their mechanisms of action vary, but their main property is activation of venous and lymph return.
Phlebotrophic drugs are the therapeutic strategy of choice for CVI patients who are unsuitable or not indicated for surgery, or for whom surgery is coadjuvated by drug therapy (165-170).
CO5 B Anti-varicose treatment
CO5 BA Preparations containing heparin for topical use
CO5 C Capillary protecting substances
CO5 CA Bioflavonoids
CO5 CX Other capillary protecting substances
Phlebotrophic drugs are widely prescribed and marketed in Italy, France, Germany and most of Europe but are less used in English-speaking and Scandinavian countries, presumably because of the scarcity of published data. With new research methods this should change.
The effects of phlebotrophic drugs on physiological parameters such as venous tone, venous hemodynamics, capillary permeability and lymph drainage can be evaluated with a range of diagnostic procedures, preferably non-invasive (1). However, the main tool for assessing the clinical effects of a phlebotrophic drug is a well-conducted clinical trial satisfactorily meeting clinical, scientific and ethical requirements (171). The trial must be randomised, possibly double-blind, and strong enough to at least attempt to answer firm questions regarding the patient’s state of health. Having the CEAP classification now means that the same scoring system can be used for the clinical picture before and after treatment. The symptoms, signs and quality of life should all be taken into consideration.
Efficacy on the different outcomes can be obtained using drugs with different chemical structures but the same clinical indications. The ATC classifications define phlebotrophic drugs as “vasoprotectors”, and makes a distinction between topical treatments for varicose veins and “capillary protective substances”, mainly bioflavonoids (Table III).
The clinical efficacy on the symptoms (feeling of heaviness, pain, paresthesia, heat and burning sensations, night cramps, etc.) has long been confirmed by Level III, IV and V evidence, but there are now Level I and II trials on specific drugs. For the bioflavonoids double-blind, randomised trials have used diosmin-hesperidin (172,173), troxerutin (174); rutoside (175); escin (176); bilberry anthocyanosides (164); and synthetic calcium deobesilate (177). Phlebotrophic action has been demonstrated in pharmaceutical classes other than the flavonoids, such as Ruscus aculeatus (178) and Centella asiatica (179).
Various protective agents have been shown to have clinical efficacy on the main sign, edema, acting on the microcirculation by lowering endothelial permeability, reducing the release of lysosomal enzymes and inflammatory substances, inhibiting free radicals and reducing white cell adhesion (158,180,181).
A surprising improvement in quality of life after a dose of 1g of micronised diosmin-hesperidin was observed in a study of 934 patients with CVI (182). This improvement was seen in all areas of life, physical, psychological and relational.
In the last ten years the relationship between macro- and microcirculation in the more severe types of CVI has become clearer; it was already clear that the relationship between reflux and venous hypertension was a factor in capillary damage (183,184). Much basic research, and some studies in man, have confirmed the effect of some phlebotrophic drugs, particularly micronised diosmin-hesperidin, on microcirculations that have been impaired by CVI. (170,182,185-187).
In the light of these findings a series of drugs have been introduced into clinical practice; however, their clinical usefulness has not always been confirmed in enough clinical trials of sufficient power. These drugs are used as coadjuvants in severe CVI (CEAP Stages 4/5/6) and are listed in the ATC classification as BO1, Anti-thrombotics, and in some cases as CO4/CO1E, Vasodilators, for their action on the altered endothelium and blood flow patterns, for their action on microthrombi and their oxygen barrier effect.
The effect of the fibrinolytic enzyme, urokinase, is documented in two papers (188,189); the glycosaminoglycans such as sulodexide have profibrinolytic activity (190) as does heparan sulphate (191), and defibrotide (192); but the utility of stanozolol is considered fairly limited (193,194).
Among the vasodilators, the effects of pentoxifyllin have been well documented (195,196) as has prostaglandin E1 (197) for the treatment of ulcers. The only indication for platelet anti-aggregation with aspirin is as coadjuvant treatment for healing ulcers in CVI (198).
Patients with chronic venous and lymphatic insufficiency should generally be advised on appropriate lifestyle habits (199). Nowadays, the press publishes a large amount of dietary and health advice, particularly as regards prevention. General practitioners and specialists should dedicate a part of the consultation to giving their patients advice on this subject, taking time to convince them. There is plenty of easily accessible explanatory literature and record forms, and the doctor can personalise these to motivate the patient, by underlining the important information or adding extra advice.
The correct amount of physical activities should be prescribed, with advice on good posture, and the contraindications outlined (200,201). Clinical and phlebodynamic testing, plethysmography, percutaneous oxygen pressure all demonstrate the advantageous effects of an exercise schedule on the macro- and micro-circulation (202).
Manual venous-lymphatic drainage (lymphodrainage)
One of the most widespread and popular massage treatment methods for all forms of venous and lymphatic stasis, manual lymphatic drainage, was introduced by E. Vodder in 1936 (203). Current usage was codified by Leduc (204) and the Vodder school (205). It is also indicated for CVI (206,207).
Vodder’s concept of mechanical action is based on the harmonic displacement of fluids and interstitial solutes through the lymphatic capillaries towards the ganglia or main drainage areas. The massage must be rhythmic and smooth and must not exceed the physiological drainage capacity of the tissues. It is important to evaluate the overall anatomical area as a basis for deciding the amount of strength and coordination during manual compression.
The patient should enjoy immediate relief of the symptoms if the technique is carried out properly; this will obviously depend on the experience and the manual skill of the person doing the massage. Results are shown by the immediate reduction in the circumference of the limb and can be checked using indirect lymphoscintigraphy.
In Germany physiotherapy for lymphedema based on lymphodrainage is termed KPE (Komplexe Physikalische Entstauungstherapie) which can be translated as “multi-factor decongesting physiotherapy treatment” (208).
10. MINERAL WATER THERAPY
The beneficial action of water on venous and lymphatic stasis in the limbs has been noticed and is used empirically by the patients themselves (209,210). However, the wide variety of forms of this treatment means that precise indications and “dosage” recommendations are needed to establish contraindications and avoid complications. In general, home, sea or spa treatments are based on the effects of hydrostatic pressure, and the temperature of the bath, while the “medicinal” effects are provided by the salts in the water (211). The therapeutic effect is achieved by two mechanisms:
1) aspecific or hydrotherapeutic action, given by the physical properties of the water:
- hydrostatic pressure
- active and/or passive movement
2) specific action, meaning the therapeutic action related to the chemico-physical characteristics of the water:
- mineral salts
- trace elements
Although from the physical viewpoint the use of any type of mineral water can be beneficial, chemically there are only certain types of water which are specifically indicated for treatment and rehabilitation in chronic venous and lymphatic insufficiency (Table IV)
Bromide salts Fluid removal from the edematous tissue
Ferruginous arsenicals Tonic, stimulant, anti-stress
Calcium sulphate Venous contractility stimulant
Radioactive Sedative, analgesic, antispasmodic
Patients can have mineral water treatments at any time during the year. If possible, they should have two cycles a year, preferably in autumn and spring, with at least three months’ interval. The treatment should last at least three weeks for the patient to gain the full effect, and less than two weeks is not worth while (212,213).
11. TREATMENT OF VENOUS ULCERS
Epidemiological studies done in the 1980’s showed that 1-2% of the adult population suffer from leg ulcers (10, 214). Although the etiological factors are fairly varied, most patients with leg ulcers have venous disease (215,216).
CVI, although it has received less attention than chronic arterial insufficiency (CAI), affects ten times as many adults (217). Consequently, its treatment is neglected or completely inadequate. Many patients walk around for months, or even years, with ulcers treated only with local medication, with no effort being made to cure the venous insufficiency causing them (13).
Appearance of venous ulcers
Venous ulcers of the leg usually present as an irregular area of loss of skin, the base covered with a yellow exudate, with well-defined margins, surrounded with erythematous, hyperpigmented or liposclerotic skin. The ulcers vary in size and site, but in patients with varicose veins they are usually seen in the medial region of the lower third of the leg (218). A venous ulcer in the lateral portion of the leg is often associated with small saphenous vein insufficiency (Bass, 1997). ref.no ???
Patients with venous ulcers may suffer intense pain even though there is no infection. The pain is worse when they are upright and relieved when the leg is elevated (219).
Venous ulcer treatment is based on an understanding of the physiopathological mechanisms involved in producing the ulcer. These mechanisms are not exclusively concerned with macrovascular hemodynamics, but involve the microcirculation and endothelium too (220, 1).
Since the venous ulcer is a manifestation of a chronic condition with slow repair and a tendency to recur, therapy must aim not only at curing the ulcer but, above all, at preventing it recurring (221). At the same time the patient’s mental attitude must be improved, either so as to convince them to enter and comply with a treatment program or to improve their quality of life (3).
Treatment of a venous ulcer can involve one or more of the following (13):
- basic treatment;
- pharmacological treatment;
- topical medication;
- other therapies;
- general measures.
The basic treatment must obey the general rule of considering the patient as a whole and not just focusing on treating the ulcer (222). Patients’ lifestyles are extremely important: their ability to walk, their work, whether they are obese, diabetic or have other concomitant diseases (13).
The main targets are venous tone, hemoconcentration, increased capillary permeability, edema, reduced fibrinolytic activity, increased plasma fibrinogen, anomalies in leucocyte function, pain relief, and management of superinfections and concomitant diseases. Fibrinolytic agents or substances that favor fibrinolysis, hydroxyrutosides (223,224, Wright, 1991 ref.no ?), micronised diosmin-hesperidin (225,226), prostaglandin E1 (Beitner, 1980; 197) and pentoxifyllin (227) are widely used.
As there have been few high-level clinical trials on support drug therapy in patients with venous ulcers, it is still debated how effective some of these drugs are for curing these lesions. However, the methodological limitations of the past have been overcome in recent trials, at least in trials of certain bioflavonoids in combination with elastocompression (225,226).
All patients with venous ulcers require compressive treatment. Whatever treatment is given for the venous ulcer must always be combined with compression. The patient must also be able to move about so as to obtain maximum benefit from the compression (228).
Compression stimulates the venous flow, reduces the pathological reflux when the patient is walking (Partsch, 1990 ref.no ?), improves the microcirculation and boosts lymphatic drainage (161). The chronic edema and the ulcer exudate are reduced and the lesion not only regresses sooner but is also less likely to recur.
Compressive therapy can be done with elastic bandages or stockings (219,229). In the acute phase, inelastic bandages, zinc oxide bandages, or multilayer bandaging are the most effective type of compression. A multilayer bandage can be left in place for at least a week, but at the start of treatment, until the exudate and the edema have subsided, it is advisable to remove and reapply the bandaging more often. Good healing has been reported using four-layer compressive bandaging (230,231) which seem to give effective compression even when applied by unskilled personnel (232). However, at the moment, there is no agreement on whether the multilayer system is more effective than two layers.
The bandage must give a resting pressure of at least 20-30 mm Hg at the ankle and the lower third of the leg with gradually less compression towards the upper third of the leg and thigh (144,13).
In patients with moderate occlusive arterial disease, with an ankle-brachial index (ABI) between 0.6 and 0.8, bandaging must be done very carefully. Inelastic material must be used, so as to exert low resting pressure. If the arterial insufficiency is very severe, with an ABI below 0.6, any type of bandaging is contraindicated (13).
Compression with elastic stockings helps maintain the results gained from treating the ulcers and to prevent recurrence. Generally, they are Class II compression stockings (30-40 mm Hg at the ankle) or Class III (40-50 mm Hg). Elderly patients or people with joint mobility problems may find it easier to put on two Class I stockings (20-30 mm Hg at the ankle), one on top of the other (229). For bed-ridden patients, or those who walk very little, anti-thrombus stockings should be considered. Intermittent pneumatic compression may be beneficial in selected cases (233).
Recurrence may occur after healing, in the short or longer term, in 20-70% of patients (234,14). Recurrence is linked to a variety of risk factors, but particularly to the persistence of the hemodynamic changes and inadequate or unacceptable compression (230,154). The success of compression also depends on how much the patient moves; patients must be encouraged to walk and take regular physical exercise and rehabilitation therapy (228,235).
When planning topical treatment for patients with venous ulcers it is important to take account of clinical observations such as the presence of dead tissue, exudates, infections and the state of the skin surrounding the ulcer (229).
Topical treatment for venous ulcers is designed to keep the lesion clean, to preserve the microenvironment, protect the lesion from infectious agents and stimulate cell repair mechanisms (219). Ideal medications should meet the following criteria:
- they should not adhere, and should leave no residues on the ulcer
- they should keep the surface of the ulcer moist
- they should be impermeable to liquids, but allow for gaseous exchange
- they should create a barrier against bacteria and fungi
- they should stimulate granulation tissue
- they should give some pain relief
- they should be affordable.
At the present time, despite the wide variety of medications available, none of them are ideal and it is not possible to draw up rigorous protocols valid for the treatment of all venous ulcers (222). Experience shows that any product may be effective initially, but the benefits will decrease over time and another product may eventually heal the ulcer. Consequently, the physician’s attitude must be dynamic, taking account of the different phases of natural healing: necrotic, fibrinous, exudative, infectious, cleansing, granulation, re-epithelialization.
In years past the only treatment was rigid compressive bandaging and local medication with a few cleansing and/or disinfecting products. Now, however, there are many treatments available with a variety of indications for the different stages of the disease. There are occlusive and semi-occlusive medications, absorbents, medications based on carboxymethyl cellulose, alginates, polyurethane, collagen, fibrin glue, chitosan; they come as pastes, granules, foams and gels. Local application of growth factor has been proposed (236) and can administered by infiltration (237).
The exudate from infected ulcers should be cultured and systemic antibiotics started. Topical antibodies are not generally indicated as they can facilitate the onset of contact dermatitis (238,239). A prospective trial showed that patients with venous ulcers treated with silver sulfadiazine emulsion combined with elastocompression healed sooner than the group treated with compression alone (240).
As healing progresses and there is little secretion and the ulcer becomes superficial, the medication can be changed to a so-called “biological” treatment: a thin cellulose or hyaluronic acid-based film, which protects the wound, stops the ulcer getting infected and gives good support for the migration and proliferation of basal epidermal cells while maintaining a good level of moisture so the lesion does not dry out. (219).
Surgery should not be considered as the only treatment or as an alternative treatment for venous ulcers, but as a complement to conservative therapy. Surgery for ulcers has two fundamental objectives:
- correcting the hemodynamic changes
- covering the ulcer with grafted skin to reduce the healing time.
This procedure must be preceded by detailed morphological and hemodynamic study of the superficial and deep venous systems and by the usual diagnostic procedures (31,241).
It is commonly considered that surgery of the superficial venous system in patients with varicose ulcers achieves the best results, reducing healing time and delaying recurrences, especially if there is no changes in the deep vein system (222). Surgery for post-thrombotic ulcers is less satisfactory (242).
Surgery on perforating veins in CVI has improved recently with the development of the endoscopic technique for tying the subfascial veins (36). Although the early results are excellent, the failure and recurrence rates are between 2.5 and 22% (86,243,244). One technical limitation is the difficulty of access to perimalleolar perforating veins. It has been observed that 50% of incompetent perforating veins within 10 cm of the ground, identified pre-operatively with Duplex scanning, cannot be treated with the endoscopic technique. (243).
Insufficiency in superficial and perforating veins must always be fully corrected before considering any interventions on the deep venous circulation.
Valvuloplasty, valves and venous grafts must be used as a last resort. These procedures are still in the development phase, and can only be considered in specialist centers and during controlled clinical trials (13).
Skin grafts are possible, using various methods:
- meshed split skin grafting (243)
- pinch grafting (246)
- allograft of human keratinocytes cultured in vitro (247)
- free flap grafts of venous sections with valves, preceded by ulcerectomy and ligature of the incompetent perforating veins (248).
- “shave therapy”, i.e. ulcerectomy, removal of the lipodermatosclerotic tissue and meshed grafts (249).
The meshed grafting technique gives the best results, whilst human keratinocyte allografts and human skin substitutes are under critical review, with no data as yet to show the effect on recurrence (250).
Sclerotherapy combined with compression treatment is indicated in selected patients with superficial venous system insufficiency, particularly if there are only short segments with reflux from incompetent perforating veins (251), even if there is an open ulcer (252). Sclerotherapy with ultrasound guidance was proposed in one study (109).
- hyperbaric oxygen;
- ozone therapy;
- vacuum therapy;
- polarised light;
- laser therapy.
These are experimental treatments with limited caselists, and as yet there is no full documentation for the results and follow-up.
Patients with venous ulcers must be advised to keep as close to their ideal body weight as possible. Regular walks on flat ground, 2-3 times a day for at least 30 minutes, should be encouraged. Patients should avoid standing for long periods. They should also position themselves occasionally during the day with their legs higher than the level of their heart, and sleep with their legs slightly raised.
Manual lymphatic drainage can be considered for patients with edema caused by CVI. Physiotherapy can improve joint mobility of the ankles.
Treatment for venous ulcers is a very old problem, much discussed but not resolved – as we have seen - because these lesions are slow to heal and quick to return.
Many clinical trials have been published but they are too selective to be representative of the general population. They usually only report short-term cure rates, without giving longer-term data on recurrences. To supply reliable clinical evidence and validate the techniques still under investigation more rigorous methods and investigation standards are needed.
The international literature calls for the establishment of special units dedicated to the study and cure of ulcers of the legs. These would be responsible for home care and rehabilitation services, with a view to improving the quality of the services offered, keeping down costs, and - last but not least – ensuring a better quality of life for the patient.
12. VENOUS MALFORMATIONS
Venous malformations (VM) are the most widespread vascular anomalies in the general population (253-256). These congenital malformations involve various morphological and functional alterations in the central or peripheral venous system.
The pathogenesis of VM appears to be linked to genetic anomalies in various biochemical mediators (e.g. angiopoietin) and the membrane receptors that regulate the interactions between endothelial and smooth muscle cells in the end stages of angiogenesis. The resulting maturation defect leads to the formation of anomalous veins with a monolayer of flat endothelial cells on the walls, but no real smooth muscular tunic.
VM mostly presents in the sporadic form in subjects with no family history, but there are also descriptions of hereditary and familial forms. In the majority of cases there is an isolated malformation, but multifocal and even systemic disseminated forms are also seen.
VM are usually located on the skin and mucous membranes, but they are often intramuscular or even intra-articular, and any organ may be involved. Distribution by site shows a marked prevalence of peripheral VM, particularly in the lower limbs, and cranio-facial VM, particularly in the temporo-masseteric, fronto-palpebral and lingual and labial regions. Other, less common, locations are the chest, abdomen and genitals.
VM can lead to multiple secondary effects or complications. The most striking are esthetic and psychological, though these are by far from the only ones, and certainly not the most important. VM in the cranio-facial area can cause serious functional disorders, with problems in swallowing, speech, respiration, sight or hearing); in peripheral regions they can cause problems disorders in grasping, posture and walking), sometimes with disabling effects.
Circulation complications take the form of venous stasis, peripheral forms leading to CVI, and loco-regional hypercoagulation with localised thrombosis and the possible depletion of coagulation factors (Table V).
Esthetic Superficial blemishes
Functional Motor deficiencies: swallowing
sensory disorders: sight
Hemodynamic Chronic venous stasis
Coagulation Localised thrombosis
The natural history of VM tends to vary. Generally, these malformations are evident from birth but sometimes they only become detectable later, during childhood or adolescence. In most cases, the maximum development is during puberty, with a marked increase in size, while later the malformation expands much more slowly, linked to the progressive slackening of surrounding tissues. The hemodynamic repercussions of the venous anomalies can become clinically evident and get progressively worse over the years, even if there is no real increase in the malformation.
Table VI gives a schematic classification of simple and complex VM, based on their anatomical and pathological criteria.
Simple VM Subcutaneous form
Complex VM Venous hypo/aplasia
Congenital valvular incompetence
SIMPLE VENOUS MALFORMATIONS
In simple forms the anomalous veins may be abnormally dilated, with very thin walls consisting of a single layer of endothelial cells, and a markedly hypoplastic smooth muscular coat (lacunar veins).
Subcutaneous VM are the most frequent and are usually lacunar or reticular veins in the subcutaneous adipose tissue, at variable depth but often over the fascial layer.
Intramuscular VM are more rare but are now being seen increasingly frequently. Generally these malformations look like lacunar veins; they may be large and extensive, and lie between the large muscle bundles, for instance in the quadriceps femoris muscle or the brachial biceps.
The intra-articular form is the least frequent and the hardest to diagnose clinically; large venous lacunae may be located inside a joint, causing gradual synovial erosion with degenerative lesions in the joint head as is typically observed in the femoral-tibial joint.
COMPLEX VENOUS MALFORMATIONS
Complex VM involve a combination of congenital venous anomalies such as hypoplasia or agenesis of the superficial and/or deep venous system, primary valvular incontinence, and persistence of embryonal trunk veins such as the marginal vein.
In the hypo/aplastic form there may be complete agenesis, or varying degrees of hypoplasia and reduction in caliber in one or more segments of the superficial and/or deep venous systems of a limb. One of the most frequent complex VM is agenesis of the poplito-femoral and/or the femoral-iliac tract, with compensatory hypertrophy of the greater saphenous vein which, in some cases, continues, typically in a large suprapubic vein cross-over confluent with the contralateral iliac axis.
In congenital valvular incontinence there is primary deep vein insufficiency, caused by complete atresia of the cusps of one of the venous valves or by dysplastic changes producing a mechanical defect in valve flap closure. These anomalies are mostly found in the superficial femoral vein, but can also involve the deep femoral vein, the common femoral vein and the internal iliac vein.
In the form with persisting embryonal veins there are anomalous, large-caliber venous trunks which develop in the early stages of vasculogenesis and normally regress during the later phase of modeling of the vascular tree. The most common embryonal veins are the sciatic and marginal veins. The sciatic vein presents as a large trunk continuous with the popliteal vein which runs posteriorly in the thigh and terminates in the pelvis, meeting the ipsilateral iliac. The marginal vein is a large-caliber venous collector originating in the external malleolar region and running along the lateral surface of the lower limb for varying distances, draining into various vessels in the deep venous system. This has been illustrated in a classification of the multiple variants of this vein’s course (Table VII).
Table VII Classification of the outlets of the marginal vein
- Superficial femoral vein
- Deep femoral vein
- Common femoral vein
- External iliac vein
- Inferior gluteal vein
- Internal iliac vein
- Common iliac vein
- Multiple confluences
The signs and symptoms of VM widely: differences are seen in the site, the depth, the extension and the extent of anatomical and hemodynamic changes. Malformed veins on the surface are visible as a subcutaneous swelling of variable size and form, soft and elastic in consistency, collapsing easily with pressure, covered with bluish or purple-colored skin of normal temperature. The veins do not have an intrinsic pulse but typically expand in the anti-gravity position; this sign is very useful for diagnosis and must be checked carefully. On palpation there are small hard nodules: these are “phleboliths” – venous stones - caused by local thrombosis.
Intramuscular or intra-articular VM are less evident on objective examination, particularly if they are small, as they are deep and are often covered by healthy skin. However, careful clinical observation will generally show a typical asymmetry of the anatomical region compared to the contralateral area. This is accentuated when the patient is lying down.
Embryonal veins present as twisted and irregular ectatic venous trunks which extend into the acral regions for varying distances in the direction of the root of the limb. In hypo/aplasia of the deep venous circulation or congenital valvular incontinence, there will be clinical signs of chronic venous hypertension: edema, secondary varicose veins, lipodermatosclerosis and stasis ulcers.
Skeletal and soft tissue changes, with hypertrophy or hypotrophy, are less frequent than with venous-arterial malformations, but may be present, particularly in the peripheral forms.
VM are frequently associated with anomalies in the lymph system, and signs of lymphostasis are frequent.
In the mixed venous-capillary form subcutaneous VM are often associated with flat superficial angiomas.
The triad of a complex peripheral VM, cutaneous capillary malformation and skeletal and soft tissue hypertrophy in a limb is known as the Klippel-Trenaunay syndrome. The Proteo syndrome has multifocal capillary-venous and lymph system malformations with anomalies of the muscles and skeleton and the peripheral nerves. It causes extreme hypertrophy and deformation of the affected limb.
Maffucci syndrome is the combination of a superficial VM and multiple enchondromatosis of the upper or lower extremities, leading to marked skeletal deformations with shortening of the limb and possible later chondrosarcoma. The presence of multiple subcutaneous VM may be an element in the rare Bean syndrome, characterised by the simultaneous presence of disseminated VM of the gastrointestinal tract.
Venous malformations are generally diagnosed by clinical examination.
Cranio-facial venous Cranial X-ray
malformations Colour echoDoppler
Direct phlebography Cranio-facial MR
Peripheral venous Comparative limb
However, every patient should also have a thorough preoperative clinical and instrumental diagnostic evaluation, as the treatment indications are closely correlated with the morphological and functional characteristics of the VM. The elements investigated will include the site and the anatomical relationships, the extent and dimensions, hemodynamic effects, patency and competence of the superficial and deep venous systems.
A rigorously standardised diagnostic protocol must be employed based on the following instrumental examinations: standard X-ray, colour echoDoppler, computerised tomography (CT), magnetic resonance imaging (MRI) and phlebography (Table VIII).
Standard X-rays show the indirect signs of VM such as phleboliths and any associated skeletal dysplasia and size abnormalities. Colour echoDoppler is the preliminary examination, for studying the extent of the VM, the patency and competence of the superficial and deep venous systems, the morphology and functional status of the venous valves and to exclude the presence of arterio-venous fistulas.
CT and MRI scans permit an accurate definition of the extent of the VM and their anatomical relationships with internal organs and the musculo-skeletal structures, particularly when the malformations are deep. The diagnosis will be completed with a phlebography examination. This is indispensable to obtain a complete morphological and hemodynamic picture of the malformations and the entire superficial and deep venous system. The examination should be done in the ascending and descending phases and with direct puncture of the malformation, as these all give complementary information.
The ascending phase explores the patency and conformation of the main venous axes, showing up any hypo/aplasia with great diagnostic accuracy. The descending phase gives a picture of valve competence, showing any primary venous insufficiency; the degree can be assessed on the basis of the retrograde opacity in the deep venous system.
These investigations are completed with a selective hemodynamic study by direct injection, which is vital for the examination of lacunar VM with low-velocity flow, or for embryonal veins which can be visualised throughout their length as far as the confluence.
By using tourniquets and hemostatic cuffs or other systems of selective compression, isolated parts of the venous circulation can be examined in all phlebography phases.
This procedure can even be done intraoperatively, so that the VM can be checked in real time during sceleroembolising treatment. It can also be used to give an immediate postoperative check on the results.
Treating VM poses serious problems for the vascular surgeon as these are often extremely complex malformations, appearing in babies or young children, with very serious hemodynamic, functional and esthetic implications. The aims of treatment are the partial or complete regression of the malformation, reduction or disappearance of the signs of venous insufficiency, functional rehabilitation of the limb, elimination or reduction of unattractive varices.
A complete preoperative diagnostic evaluation is absolutely vital before any treatment is decided; the instrumental findings must guide each individual therapeutic program so that surgical procedures and/or percutaneous treatments can be combined as most appropriate for each patient.
The indications and the strength of the recommendations for the various treatment options in the different forms of VM are summarized in Table IX.
Table IX – Therapeutic options for venous malformations (VM)
- Percutaneous sclerotherapy (++)
- Phlebo-guided sclerotherapy (++++)
- Surgery (+)
Simple subcutaneous peripheral VM
- Percutaneous sclerotherapy (+++)
- Phlebo-guided sclerotherapy (+++)
- Surgery (++)
Simple intramuscular peripheral VM
- Percutaneous sclerotherapy (+)
- Phlebo-guided sclerotherapy (++++)
Simple intra-articular peripheral VM
- Phlebo-guided sclerotherapy (++++)
Complex peripheral VM with hypo/aplasia
- Wait and see (+++)
- Surgery (+)
- Complex peripheral VM with valvular incontinence
- Surgery (++)
- Complex peripheral VM with embryonal vein
- Surgery (+++)
- Phlebo-guided sclerotherapy (++)
- Percutaneous sclerotherapy (+)
Direct percutaneous sclerotherapy can be done on isolated, superficial, small VM. If they are more extensive and deeper it is better to do the sclerotherapy under radioscopic guidance, using the direct injection phlebography technique. This allows close control of the injection site and the diffusion of the sclerosing mixture, giving immediate confirmation of the results.
Various sclerosing mixtures are used. The choice will depend on the morphological characteristics, anatomical site and extent of the malformation. For spider veins and/or small-caliber VM, particularly on the lips and tongue, a 2-3% polydocanol solution is recommended. For large-caliber, extensive VM (lacunar veins), which are frequently found in the temporo-mandibular area, a more powerful sclerosing agent is called for, such as 95% ethanol and Ethibloc.
The dosage of the sclerosing agent will be established in proportion to the size of the malformed veins, up to a maximum dose of 2 ml/kg body weight.
The sclerotherapy technique must obviously be extremely rigorous because accidental injection of the sclerosing mixture outside the vein can provoke many serious complications, such as thrombophlebitis, cutaneous necrosis, granuloma, neurological damage. A normal, reversible side effect is loco-regional inflammation/edema, varying in size which will disappear in a few weeks; it can be treated, if necessary, with a steroidal anti-inflammatory drug.
Surgery plays a fundamental role in the complex overall treatment strategy for VM. The most common surgical procedure is to strip lacunar or reticular malformed veins in the lower limbs; this should preferably be done by a micro-invasive technique, through micro-incisions in the skin and using special phlebectomy hooks.
For a persisting embryonal venous trunk the only therapeutic procedure is surgical removal. This must also be done with the least invasive technique possible. In the past large incisions were made along the outer surface of the limb, but nowadays only minimal skin incisions are needed, so the outcome is esthetically more acceptable. Detailed preoperative mapping must be done on the embryonal vein, and when feasible, mini-strippers can be used.
When dealing with congenital valvular incompetence, and preoperative ultrasound examination indicates the presence of dysplastic valvular flaps, the venous valves can be surgically reconstructed by external venoplasty with reinforced Dacron or PTFE prostheses. The correct positioning of the prosthetic band – of the right caliber – will restore valve competence by drawing the dysplastic flaps closer together, while maintaining the patency of the veins.
For segmentary hypoplasia of the deep venous circulation secondary to extrinsic compression from an abnormal fibrous muscle band, as is often seen in the popliteal cavity, a decompression procedure can be done to facilitate development of the hypoplastic venous structures.
In cases of deep vein agenesis with compensatory hypertrophy of superficial veins such as the greater saphenous vein and its collaterals, surgical removal of the malformed veins is obviously contra-indicated, as they serve as hemodynamic substitutes.
To conclude, therefore, the therapeutic strategy must be carefully thought out and planned for each patient on the basis of the clinical and instrumental findings, with particular reference to the site, the morphology and the extent of the VM, and taking account of the architecture and the hemodynamics of the loco-regional venous circulation.
The site of the malformation can be a major factor in choosing treatment. In the facial and genital areas sclerotherapy is preferred as it has fewer esthetic and functional implications, whereas surgery, being more radical, is used more for the peripheral forms.
The complexity and size of the VM will have a directly proportional effect on the choice of surgical approach. Simple or isolated VM are treated by elective intravascular percutaneous sclerotherapy under venographic guidance. Complex VM call for corrective and/or reconstructive surgery, depending on the anatomical and hemodynamic changes present.
In the majority of cases, combined therapy is the preferred option. Percutaneous and surgical treatment combined offers the best clinical, morphological and functional results. Ligature and stripping the malformed veins can be combined with preliminary or intraoperative sclerosing treatment, so that minimally invasive techniques can be employed to remove moderately sized dysplastic lacunar or spider veins.
Similarly, after stripping the main trunk of an embryonal vein the intervention can be completed by percutaneous sclerotherapy on the numerous collateral veins, particularly the terminal end near the confluence with the deep venous system.
In conclusion, surgery and percutaneous sclerotherapy should not be considered alternatives but can be usefully combined in the complex and delicate strategies for treating VM. An important point, particularly in cases of extensive VM, is that numerous sequential surgical operations or sclerotherapies may be necessary to obtain complete regression of the malformations.
13. QUALITY OF LIFE
There are many reasons for considering the Quality of Life (QoL) as part of the therapeutic outcome, in CVI like in other diseases (Garrat, 1993, 256, 1). The current method of generic measuring, considered the standard in the USA and in Europe, is the Medical Outcomes Study Short Form Health Survey – 36 (MOS SF36) (258,259).
Specific questionnaires for CVI (CVIQ1 and CVIQ2) have been used since 1992, with surprising results for a disease that has hitherto been so severely underestimated. CVI has a profoundly negative effect on the patient’s daily life and the results illustrate the impact of CVI on morbidity and the efficacy of drug therapy (260,261).
Evaluation of randomised controlled trials on surgery and its effect on QoL is more complicated (262). Trials are still in progress to assess recent surgical techniques for CVI such as subfascial endoscopic ligature of the perforating veins (SEPS) and valvuloplasty.
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