S.CAPURRO: Three-dimensional Regenerative Ambulatory Phlebotherapy (T.R.A.P.)- WWW.PHLEBOTHERAPY.COM- CAPURRO RESEARCH PUBLICATIONS (WWW.CRPUB.ORG) --EDIZIONI D’ARSONVAL ON LINE YEAR 2006 NUMBER 1 – GENOVA ITALY COPYRIGTH 2006

Three-dimensional Regenerative Ambulatory Phlebotherapy (T.R.A.P.)

A new curative treatment for varicose veins and spider veins

Sergio Capurro

Capurro Research Group
CapurroResearch Publications
Phlebotherapy
Phlebotherapy Forum
sergio.capurro@fastwebnet.it

Keywords: “curative” treatment of varicose veins, spider vein, non obliterative sclerotherapy, three-dimensional regenerative ambulatory phlebotherapy (T.R.A.P.) , physiopathology of lower limbs venous circulation

Abstract

The efficacy of traditional sclerotherapy is limited; it is unable to prevent the recurrence of varicose pathologies in the lower limbs, and frequently leads to complications. It acts on the clearly pathological superficial vessels, which represent merely the effect rather than the cause of the disorder.

Our aim is to permanently restore the entire perforating and superficial circulation in the lower limbs. The physiopathology of the circulation in the lower limbs reveals how this objective can be achieved by reducing the diameter of the vessels and strengthening the vessel walls, thereby reducing their excessive capacity and restoring valvular continence. Logically, this objective cannot be achieved by means of an obliterative or ablative procedure, but only a “regenerative” method. To this end, we have invented a new technique: three-dimensional regenerative ambulatory phlebotherapy (T.R.A.P.). T.R.A.P. is a “gentle”, non-obliterative form of “sclerotherapy” which extends to the entire superficial and perforating network. The phenomenon that we call “regeneration” involves fibrosis that is neither sclerotic nor obliterative. (according to Blakeston Gould’s Medical Dictionary, 1979, “regeneration” means “the repair of structures or tissues lost by disease or by injury). Histological examination reveals reduced calibre of the lumen and consolidated the connective structure of the treated vessels. T.R.A.P. is carried out by injecting a new “regenerating” solution, sodium salicylate 6% in an alkaline hydroglycerin vehicle, methodically in large total quantities (from 10.5 to 31.5 ml) into all visible vessels, including those visualised by means of transillumination. T.R.A.P. yields an aesthetic and functional result that cannot be achieved by means of any of the techniques previously used by us, including surgical procedures. The results obtained have proved to be stable after six years, thus demonstrating the functional effect of the method.

Introduction

The complications, recurrences and scant efficacy of sclerotherapy are, in our view, inherent in the obliterative concept on which the method is based. This concept has been called into question by the creation of three-dimensional regenerative ambulatory phlebotherapy (T.R.A.P.). T.R.A.P. constitutes a step forward from traditional sclerotherapy, which mainly treats the effect of valvular insufficiency, to a non-obliterative therapy that extends to the entire superficial and perforating circulation, thereby treating the cause of the disorder as well as its effect.

Figure 1. T.R.A.P. is the systematic three-dimensional injection of regenerative solution into all vessels visible even by means of transillumination.

T.R.A.P. uses a non-aggressive well-tolerated solution that exerts a constant action and can be injected in large quantities. In an extremely complex system of tubes, such as the venous circulation in the lower limbs, what could be more rational and less invasive than to apply the proper therapy through the tubes themselves?

Physiopathology and therapeutic strategy

The functional anatomy of the venous circulation in the lower limbs reveals that the valvular insufficiency of the perforating veins and the ectasia of the truncal veins, reticular veins, venules and telangiectasias are, except for rare cases (mechanical obstructions, traumas, arteriovenous fistulas, congenital angiopathies, excessive functional performance (1), prolonged exposure to heat or sun, cortisone application, radiodermatitis, inflammation, chronic skin disorders, etc) due to congenital miopragia of the vessel walls (1, 2, 3, 4, 5). This condition is manifested under the influence of hemodynamic pressure, age, hormones, posture, habits and numerous other pathogenic factors. Miopragia involves, albeit to different degrees, the entire superficial and perforating circulation. The progressive weakening of the walls of the vessels that connect the superficial circulation with the deep circulation causes the valves to become incontinent. The resulting anomalous pressure in the superficial circulation causes the vessels to dilate, an effect which is first manifested in those vessels whose anatomical structure is least resistant.
Valvular insufficiency is dynamic. Contraction of the so-called ‘peripheral heart’, which is constituted by the leg muscles, generates the highest venous pressure: up to 300 mm of mercury (6,7). This region, which is of strategic importance for the correct functioning of the venous circulation, contains about 100 perforating veins (8), as well as the origin of the small saphenous vein. By contrast, the valvular and ostial incontinence of the great saphenous vein is of marginal importance with regard to pressure, since the hydrostatic pressure at the ankle is 80/100 mm of mercury regardless of whether the valves are continent or not (9,10). The valvular incontinence of the largest superficial vein has a clinical significance only if it is associated to saphenopopliteal incompetence and/or valvular insufficiency of the perforating veins. Indeed, cases have been observed of subjects born without valves in the great saphenous vein who do not manifest any disorder, while efficient valves have been found in the external iliac vein of subjects suffering from varicose veins (11).

Variations in the expression of the disorder depend on blood pressure, on how close to the surface the incontinent perforating veins are located, and on how well the walls of the vessels affected by hypertension can withstand the increased pressure. Indeed, if the reticular veins in an area subjected to anomalous pressure easily become ectatic, then ectatic capillaries are less likely to form. If the walls of the reticular veins are able to withstand the increased pressure, a dense network of telangiectasias is more likely to form. Telangiectasias form when the ectatic reticular veins are no longer able to absorb the rapid pressure increases caused by muscular contraction. Telangiectasias may form even in the absence of visible reticular veins if the capillary network is directly connected to an incontinent perforating vein. Telangiectasias frequently form even after sclerotherapy and ablative or obliterative surgery on the large superficial veins (see Fig. 10). Venous insufficiency therefore displays multiple clinical manifestations, but what is evident is that the ectatic veins that can be seen with the naked eye and those that can be seen only by means of transillumination represent the quantity of blood that escapes from the deep circulation. The ectatic vessels therefore constitute escape valves for hemodynamic hypertension. If we reduce this venous network without treating the cause of the disorder, the pressure on the superficial circulation will increase and the initial unsightly conditions will soon be restored. The anatomical-physiological considerations outlined above, and the fact that phlebectasias very often recur after traditional obliterative sclerotherapy and ablative surgery, have prompted us to adopt a radically different approach. The obliteration and ablation of visible varicose areas does not work because it is conceptually wrong; it treats the effect of the disorder, and rarely the cause. Even if obliterative techniques are applied to perforating veins that appear incontinent on color-flow Doppler scanning, the problem will not be solved and the progression of the disorder will not be prevented. Indeed, hemodynamic alterations may be caused that give rise to new capillary (matting) and venular ectasias; following the obliteration of a perforating vein, the pressure on the superficial venous circulation determined by other incontinent perforating veins that cannot be revealed by means of the instrumental examinations available may increase and be manifested at the surface of the skin.

Traditional obliterative sclerotherapy and surgical ablation do not respect the anatomical and functional integrity of the circulation, nor do they correct miopragia. They act exclusively on the full-blown aspects of the alteration in venous circulation, while the disorder is sustained by perforating vessels which reveal their insufficiency only when the patient runs or walks. Clearly then, the insufficiency of even a small percentage of these vessels, which cannot be revealed by means of the instruments available, can thwart any traditional treatment and give the erroneous impression that ectatic veins can form without a hemodynamic cause, apart from the causes listed above. Saphenectomy is certainly three-dimensional. The improvement seen in patients following ablation of the great saphenous vein largely depends on the ligature of the major perforating veins and on the obliteration of the perforating veins that are connected to it. Surgical ablation of the saphenous vein, however, is an incomplete treatment which yields unpredictable results (12, 13, 14, 15, 16, 17, 18, 19) and, from our point of view, cannot be adopted as the therapy of choice for insufficiency of the venous circulation in the lower limbs, in the majority of cases. Saphenectomy yields long-lasting, good-quality results only in those patients in whom the residual perforating veins are continent. Even in such cases, however, the developmental aspects of the varicose disorder determined by the miopragia of the vessel walls cannot be avoided. While fine-tuning T.R.A.P., we have noticed that saphenectomy patients need more sessions of phlebotherapy in order to achieve optimum results. We may hypothesize that this is due to the anatomical-functional alterations caused by the operation itself.

With regard to ambulatory phlebectomy, until now this has been justified only by the absence of residual hyperpigmentation. Obviously, the availability of a solution that does not generate permanent post-sclerotherapy hyperpigmentation relegates this operation to the level of a second choice.
Since it is not conceptually possible to obliterate or remove the entire superficial circulation together with all the perforating veins, some authors have focused on treating the ectatic reticular veins; these, however, represent the effect rather than the cause of the disorder.
For all of the above-mentioned reasons, we have created a method that is not obliterative. Three-dimensional regenerative phlebotherapy. shifts the focus of the therapy from the superficial ectatic vessels and some of the major perforating vessels to the entire superficial and perforating circulation. Rather than obliterating the vessel, it aims at reducing the caliber of the lumen and thickening and strengthening the vessel walls. To describe these non-obliterative fibrotic effects on the vessel wall, we have adopted the term “regeneration”. This term has been chosen in order to highlight the fact that the vascular structure is restored to its pre-phlebectasia condition. The result is that normal vascular capacity is recovered and the circulation begins to function properly again. This is in stark contrast to the concept of obliterative sclerosis or ablative surgery endorsed by traditional therapy.

Given that the miopragia of the vessel walls involves the entire superficial and perforating circulation, all the visible vessels must be injected, including those visualized by means of transillumination. Moreover, the solution, which obviously must not be obliterative, will need to be forced into the underlying vessels.
On the basis of studies and experimentation on non-aggressive solutions, we adopted a 6% solution of sodium salicylate in an alkaline hydroglycerin vehicle (20). The 6% solution exerts a strengthening effect and can be injected without risk at high individual or total doses. In addition to the “regenerative” 6% solution, we also use a 10% solution, which is injected primarily in cases of hemodynamic matting.
The traditional injection technique that we adopted with this and other sclerosing solutions was not, however, capable of resolving severe and moderately severe cases of the disorder. Even in the most favorable cases, the result obtained was not sufficiently long-lasting. Six years ago, therefore, we changed our approach and created T.R.A.P. The principal concepts that we modified are outlined in Tab. 1

Tab.1

On the basis of the general concepts described above, it is clear that, in order to treat pathological circulation, all the vessels, truncal veins, reticular veins and telangiectasias need to be injected in order in the same session, with the aid of transillumination. Indeed, these vessels constitute the “gateway” through which the solution comes into contact with the walls of the non-visible (perforating and communicating) vessels.

Tab. 2 General concepts

• Why obliterate or remove the veins when they can be cured?
• Treating the effect and not the cause cannot "cure" the veins
• Two-dimensional techniques are not able to treat a three-dimensional disorder
• The size of the vessel is not important; the pressure is.
• A disorder that extends to the entire venous circulation in the lower limbs cannot be treated by acting only on a part of that circulation.
• To treat a complex circulation, what can be better than introducing the cure through the vessels themselves and letting it go where it has to go?
• It is more sensible to prevent the formation of varices than to cure them once they have formed.
• The great saphenous vein is blameless.
• Doppler is blind
• In the treatment of varicose veins, the most important diagnostic tool is the syringe
• The efficacy of phlebological procedures is judged by means of photographs taken “before and after”, and in terms of the persistence of the result obtained

“Regenerative” solution

The sodium salicylate in an alkaline hydroglycerin buffered vehicle solutions (********[1]) were formulated in 1992 and their formulae were published in 1993 (21). Sodium salicylate was chosen because it has both an anti-inflammatory and an anti-clotting effect. Its alkaline pH is useful in that it limits the absorption of the salicylate, neutralizes its metabolites and accelerates its excretion. The hydroglycerin vehicle slows down the flow of the solution in the vein, thereby allowing the sodium salicylate to remain in contact with the endothelium for a longer time. The viscosity of the solution, in addition to retarding its dilution, enables complete contact to be made with the intravascular surface, a feature that aqueous sclerosing solutions lack, unless air is added. The use of foam, however, is an extreme measure in obliterative sclerotherapy and is not suited to “regenerating” the circulation. The glycerol contained in ******** slows down the absorption of the sodium salicylate, further enhancing the safety of the solution. The fact that glycerol exerts a preservative and anti-bacterial effect means that, when it is used in association with sodium salicylate, there is no need to use benzyl alcohol, as other formulae do; allergic complications are therefore avoided (22).
The viscosity of the 6% solution is such that it facilitates injection into the reticular and truncal veins, while the less viscous 10% solution facilitates injection into the finest telangiectasias. In the case of reticular veins, the viscosity of the solution enables it to be injected into the vessel lumen safely and  without aspiration. Consequently, a lower concentration of the active ingredient is required to treat larger vessels, while a higher concentration is used to treat smaller vessels (matting).

From 1992 to 1997, we used these solutions in a traditional manner.
They were very well tolerated, both locally and generally, and did not give rise to any permanent hyperpigmentation, ulcers, marked or long-lasting edema or post-sclerotherapy pain. Even today, in patients who do not wish to undergo treatment of the circulation, we continue to use ******** in its three concentrations (the 8% solution is obtained by mixing the 6% and 10% solutions).
Comparison between 0.5% polydocanol and 8% sodium salicylate in an alkaline hydroglycerin buffered vehicle on both legs in 100 patients (23) revealed that, for the same efficacy, the latter exerted a more constant action, caused fewer side-effects and yielded a more rapid return to health.

[1] Experimental name

	The absence of marked inflammatory phenomena, and the very good tolerability are particularly important in that they enable large amounts of the solution to be injected.

The LD-50 of intravenous polydocanol in the dog is 50 mg/kg The LD-50 of intravenous sodium salicylate in the dog is 562 g/Kg. In humans, concentrations of salicylate greater than 200 mg/ml are regarded as toxic. In mice, the LD-50 of glycerol administered intravenously is 6.0 g/Kg. It should be stressed, however, that the alkalization of ******** makes the absorption of sodium salicylate at the systemic level practically nil.

“Regenerative” fibrosis

We do not claim that the vessel fibrosis caused by sodium salicylate in an alkaline hydroglycerin buffered vehicle is histologically different from that caused by other chemical solutions. A non-buffered solution of sodium salicylate and glycerol almost identical to 6% ******** has been tested on an ear vein of the rabbit, producing a clinical and histological effect equivalent to that of chromic glycerin (24). The author of that paper observed that this solution is excellent in the treatment of telangiectasias of less than 1 mm. In comparison with chromic glycerin, however, sodium salicylate in an alkaline hydroglycerin buffered vehicle solution has the advantage of not containing trivalent chromium, which is both irritative and allergenic (25), not least because it contains nickel, which is present as an impurity in chromium salt (21). Moreover, far higher doses of sodium salicylate in an alkaline hydroglycerin buffered vehicle can be injected without untoward effects.

The histological specimens taken from one of our patients show the structural effects exerted by 6% sodium salicylate in an alkaline hydroglycerin buffered vehicle on large-caliber veins, the walls of which display a fibro-elastic structure. The wall fibrosis induced by the endoluminal injection of the solution causes thickening without disorganization of the wall; indeed, the elastic fibers within the wall remain intact (Fig. 1).

Figure 1 (Left) Histological section of skin (fixed in 10% buffered formalin, paraffin embedded and routinely processed; Weigert stain; enlargement 20 X). Dermal venule of medium-large calibre. The structure of this type of venule is characterised by sparse elastic fibres – not organised into a true, continuous elastic lamina – in the context of fibrous connective tissue of the wall. The vessel (visible “in vivo” as a phlebectasia) has a large eccentric lumen. The wall displays a non-uniform thickness and disorganised layers at several sites, and is permeated by a scant inflammatory infiltrate consisting mainly of lymphoid and monocytoid cells. The endothelial lining lacks continuity. Sub-endothelial microvacuolation is also seen. (Right) Histological section of skin. The same patient, the same area and a vein of equal size, seen after treatment with 6% sodium salicylate in an alkaline hydroglycerin buffered vehicle solution. Weigert stain; enlargement 20 X. The wall is of regular thickness. The internal endothelial layer is continuous. The wall shows no inflammatory infiltrate. Sodium salicylate in an alkaline hydroglycerin buffered vehicle solution treatment has restored uniform wall thickness, reduced the calibre of the lumen and consolidated the connective structure of the vessel wall. We have summarised these effects with the term “regeneration”.

The ability to cause controlled, predictable fibrosis, which is a feature of sodium salicylate in an alkaline hydroglycerin buffered vehicle solution,, can be verified by observing the superficial vessels. If small amounts of 6% solution are injected into a vein, the caliber of the vein will be reduced within a week. Further injection into the same vein will result in a further reduction in caliber within another week, and so on until the vein is no longer visible. If, by contrast, we inject enough of the solution to “regenerate” the underlying vessels, the resulting reduction in hemodynamic pressure will allow the vein to shrink until it is no longer visible after only one treatment session. This does not mean that the vein has been obliterated. Obliteration is accompanied by evident inflammation and by sclerotic hardening of the vessel. The injection of ******** does not have such effects, even in large-diameter reticular veins. Intravascular blood accumulation may occasionally occur during T.R.A.P.. However, even in such cases, the vessel is not obliterated completely.

Indeed, if a vessel containing an accumulation of blood (and therefore already treated) is erroneously re-treated, it will still be able to take in a fair amount of solution, and the only indication that a vessel containing an accumulation has been injected will be the quality of the blood that seeps from the injection site. Intravascular accumulations of blood should be avoided as far as possible, though one or two are acceptable. They may occur in large superficial varicosities and in veins in which the blood flow is slow. They have never occurred, and we think it unlikely that they may occur, in vessels in which the blood flow is rapid, as in the perforating veins.

With regard to telangiectasias, it is irrelevant whether their disappearance is due to obliteration or to “regeneration”, as long as they disappear. This is not merely an esthetic consideration, as their disappearance indicates that hemodynamic continence has been correctly restored. For what concerns the ability to consistently induce efficacious fibrosis, we do not know whether this feature is exclusive to sodium salicylate in an alkaline hydroglycerin buffered vehicle solution or whether it can be achieved by means of other solutions. At present, we know that chromic glycerin is able to produce a similar degree of fibrosis, though we have never considered the possibility of injecting large amounts of this solution. With regard to exclusively water-based solutions, we believe that, if suitably diluted, they may be able to exert a “regenerative” effect. However, we do not know whether they are able to maintain this effect in depth, on starting from the superficial vessels, or whether they would immediately become diluted and therefore lose all efficacy.

Patient assessment

All patients undergo anamnestic and vascular examination. A history of thrombophilia warrants particular attention. In T.R.A.P., it is important to observe the skin and subcutaneous tissues carefully in order to pick out all the “gateways” to be injected. Of the 400 patients treated by us, solo il 10% had already undergone color-flow Doppler scanning examination. This examination is not important in the three-dimensional regenerative phlebotherapy. Indeed, in the case of an exquisitely dynamic disorder that is manifested when the patient is in movement, the diagnostic potential of color-flow Doppler scanning is modest. This assertion is supported by Fig 2.27 of the treatise Sclerotherapy by Mitchel P. Goldman (24), in which Doppler examination of a patient suffering from a severe venous disorder does not reveal any impairment of the sapheno-femoral or sapheno-popliteal junctions, nor any incompetence of the perforating veins. To our way of thinking, this is completely absurd, in that even the tiniest telangiectasia is the outward manifestation of the valvular incontinence of an underlying vessel (26), except for those rare cases already mentioned. If we consider that all the vessels that make up the venous network in the lower limbs are interconnected (27), it is fairly obvious that valvular insufficiency may be manifested in the superficial circulation. The permanent esthetic and functional results of T.R.A.P. are achieved through the non-obliterative fibrosis of the large and small incontinent perforators and the truncal veins, which may be thought of as special superficial-perforating veins. It should be borne in mind that most incontinent perforators are not visible on color-flow Doppler examination. In any case, color-flow Doppler scanning was performed in all patients presenting complex or painful disorders.

Patients were subdivided into five groups: A) isolated capillary ectasias; B) isolated capillary and venular ectasias; C) diffuse capillary ectasias; D) diffuse capillary and venular ectasias; E) diffuse capillary, venular and venous ectasias.

Technique

T.R.A.P. utilizes a 2.5 ml syringe, two or three 30 G ½ needles, the 6% ******** solution, 1% lidocaine chlorhydrate, cotton wool and disinfectant (benzalkonium chloride).
Both the syringe and the needle must be standardized, as they are diagnostic as well as therapeutic tools. Indeed, the operator is able to use the syringe to assess the degree of incontinence of the vessels under treatment. Consequently, the same syringe and needle are used to inject both truncal veins and telangiectasias. When the needle is no longer able to penetrate easily into the telangiectasias, it must be replaced. While a worn needle-tip is still able to penetrate a vein, it will tend to displace rather than penetrate telangiectasias.

The lower limb is subdivided into three functional regions: medial, posterior and lateral (Fig. 3).

Figure 3  The limb is divided into three functional regions: medial, posterior and lateral.

First, the medial region of the foot, lower leg and thigh is injected; a week later, the posterior region is treated, followed in the third week, by the lateral region. During the fourth week, the first region is treated again, and so on. If the disorder is mild, two regions, or even the entire limb, may be treated in the same session. Once the skin has been disinfected, the 6% solution, to which 0.5 or 1 ml of 1% lidocaine chlorhydrate without conserving agents has been added inside a 3 ml vial, is injected. The addition of lidocaine is useful on account of its analgesic, anti-inflammatory (28) and vasodilatory action (29, 30).

The operator begins by injecting the phlebectatic corona in the foot. In this area we add 1 ml of lidocaine to the 3 ml vial. Working upwards towards the root of the thigh, the operator injects, in order, all the vessels encountered. The operator begins by injecting the phlebectatic corona in the foot. In this area we add 1 ml of lidocaine to the 3 ml vial. Working upwards towards the root of the thigh, the operator injects, in order, all the vessels encountered.

Figure 4
(Above) Phlebectatic corona. (Center) Immediately after the second session of regenerative phlebotherapy.
(Below) Result after the third session.

Abb.5 Phlebektatische Krone vor und nach Phlebotherapie

This means that treatment begins in the area of the highest hemodynamic pressure and ends in the area where hemodynamic pressure is lowest. In the lateral region of the thigh, we now treat the veins first. This is in contrast with the other regions, in which the veins and telangiectasias are treated at the same time. Indeed, in the lateral region, injecting the telangiectasias has a two-dimensional effect that is not encountered in the other regions; the solution mainly spreads superficially rather than in depth. This engenders a risk of matting on the part of an untreated incontinent perforator. Hemodynamic matting is caused by incomplete treatment together with an excessive concentration of solution.
This highlights the need to inject the solution in a way which is both orderly and complete (all the “gateways”), from the regions of higher pressure to those of lower pressure.

Moreover, in order to ensure that ******** exerts a constant effect, it is also important to set the final concentration of the solution accurately within a narrow range (from 0,5ml to 1ml of lidocaine per 3 ml vial). The amount of solution to be injected and the area of surface whitening are not predetermined. If the plunger of the syringe encounters firm resistance, a small amount of solution is injected; if resistance is weak, the amount necessary to regenerate the communicating vessels will be injected, up to a maximum of 2 ml. The injected solution is swept along the vessels by firmly stroking the surface of the skin with cotton wool soaked in benzalkonium chloride so that it comes into contact with the largest possible area of the endothelial surface. The solution always follows the path of least resistance, which is usually the deep path. Normally, 0.5 ml of solution is enough to treat the perforating vessels in the leg (31). The way that the operator can be sure that the tip of the needle has penetrated the vessel is by gauging the resistance encountered by the plunger of the syringe. The recent adoption of transillumination has solved all our injection-related problems and has simplified the correct execution of the technique. In the first treatment sessions, there is no need for the telangiectasias to disappear.

Like the reticular veins, telangiectasias are merely "gateways" and remain visible until the hemodynamic pressure in the region is reduced. Obliterating the telangiectasias during the initial sessions does not constitute phlebological therapy. Given that such an approach treats only the effect and not the cause of the disorder, it must be regarded as purely cosmetic. Moreover, if we do adopt this approach, we will for some time be prevented from treating the incontinent perforating veins, which are the true cause of the disorder. The three-dimensional concept is clearly illustrated by the fact that 1 ml of 6% solution may be injected into an isolated telangiectasia 2 mm in length (21). This means that the pressure on the plunger of the syringe is low and that the telangiectasia is the superficial manifestation of the valvular incontinence of an underlying vein that is directly connected to it (32) and which flows into the deep circulation. The resistance felt on the plunger of the syringe is therefore not related to the size of the visible vessel injected, but to the size of the vessels connected with it. If the injection sites bleed, they are momentarily covered with a swab of cotton wool soaked in benzalkonium chloride. Within a few seconds, perivascular edema stops the bleeding. The operator must learn to evaluate the speed at which blood issues from the injection sites, as this is a valuable indication of the residual hypertension.

If this pressure is still high, treatment of the non-visible ectatic circulation will have to be completed by injecting all the reticular veins in the area involved, as well as the telangiectasias. Unlike traditional sclerotherapy, in which the concentration of the sclerosing solution is usually increased if the patient fails to respond well, T.R.A.P. deals with “difficult” patients by increasing the amount of the solution injected. The recommended limit of 31.5 ml of 5% solution is determined by the duration of the treatment session, which is about 30 minutes, and by the need to keep well within the safety margins: 31.5 ml of solution contains 27 ml of 6% sodium salicylate in an alkaline hydroglycerin buffered vehicle solution plus 4.5 ml of 1% lidocaine, which is sufficient to treat even the most severe cases. During experimentation of the method, we injected up to twice this amount of solution (therefore 9 ml of lidocaine) without any untoward effect. In that case, the amount of sodium salicylate injected was 3.15 g and therefore still within the 3.6 g limit of sodium salicylate used as a sclerosing solution (33, 34). The amount of lidocaine that can be injected as an intravenous bolus in cardiac pathology is 100 mg, which is the equivalent of 10 ml of 1% lidocaine. Small quantities of lidocaine diluted in a hydroglycerin vehicle and injected into different sites in the peripheral venous system are extremely well tolerated. The LD-50 of intravenous lidocaine in mice is 45.1 mg/kg.

During treatment, no sticking plasters are used. After treatment, the patient remains immobile on the table for 2 or 3 minutes in order to allow the solution to remain in contact with the vascular endothelium and to prevent rapid dispersion of the solution into the circulation. In patients in whom the disorder is severe, this period is extended to 5 or 10 minutes. This longer period of immobility is adopted only after the first course of treatment sessions carried out on the three regions of the same limb, and only after hemodynamic improvement has been ascertained.

The saphenous veins also have to be regenerated by means of direct injection, with the aid of transillumination or Doppler, and indirectly through their collateral vessels. Once all the veins, venules and several of the telangiectasias in one limb are no longer visible, the contralateral limb is treated. After treatment, an anti-inflammatory product is applied to the area. Before getting up, the patient puts on elastic stockings; in more severe cases, these should also be worn for the first night. This elastic compression is important, in that it prevents blood stasis, improves blood flow in the limb and facilitates ‘regeneration’. It must be maintained for a few weeks after completion of the treatment. All patients require anti-platelet therapy in order to limit the accumulation of intravascular blood and prevent venous thromboses. We administer 50 or 100 mg of acetylsalicylic acid or of a product of our own formulation, composed of several vegetable extracts, vitamins and lipoic acid, which exerts an anti-platelet, anti-homocysteine, chelating, anti-inflammatory, hemorrheological and anti-free radical action. The anti-platelet action of this preparation is achieved through the sub-active dosage of four extracts, which act at four different points in the platelet-aggregation cascade (Angiovein). Post-treatment edema lasts only a few hours, and ecchymoses generally no longer than two or three weeks. The rare small sites of intravascular blood stasis are pierced with the 30 G1/2 needle during the subsequent sessions.

If the patient has evident varicosity, bandages are used to compress the large varices, in order to prevent intravascular blood stasis; they are also used after injection of the evident phlebectatic corona in the foot. Intravascular blood stasis is infrequent, and can be reduced even further by reducing the concentration of the solution injected in patients with evident varicosity; this is achieved by adding 1 ml (instead of 0.5 ml) of 1% lidocaine, the same dilution used in the phlebectatic corona, to the 3 ml ampule of 6% ******** during the first three sessions of phlebotherapy. The slower blood flow and the stasis determined by the ectasias enhance the efficacy of the solution.

Results

The effect of T.R.A.P. is clearly visible on the surface of the skin (Fig.6-10).

Figure 6 Saphenectomised patient with evident phlebectatic corona and varices. Result after “regenerative“ treatment of the right leg.

Aesthetic results can be classified at three levels: 1) vessels are no longer visible when the limb is observed from a distance of 1.5 meters; 2) vessels are no longer visible when the limb is observed from a distance of 50 cm; 3) telangiectasias are no longer visible when the limb is observed under the magnifying glass. Our recent adoption of transillumination also enables us to verify the complete disappearance of the dilated reticular veins, which are not visible without transillumination. The fact that a vessel can no longer be seen does not mean that it has been obliterated. Rather, it indicates correct shrinkage of the vessel, provided that the inflammatory and thrombotic phenomena associated with obliteration are not manifested. The fact that the results obtained seem to be permanent is the most convincing proof that functional integrity has been restored. However, it must be borne in mind that the permanent disappearance of telangiectasias and varices achieved by means of T.R.A.P. depends on the reduction in hemodynamic pressure and the reactivity of the vessel wall.

Figure 7 Varicose veins before and after

Figure 8 (Left) Patient who had never undergone any therapy. (Center) Immediately after T.R.A.P. in the posterior region of the left leg, 28 ml of solution have been injected. (Right) Result after three sessions of regenerative phlebotherapy

Clearly then, if the capillaries are very fragile, complete disappearance of the telangiectasias cannot be guaranteed. From the point of view of T.R.A.P., “difficult” patients are not those with very evident ectatic veins and capillaries, much less those with one or two large varicose veins; rather, they are patients in whom the vessel walls in the whole venous tree, from the veins to the finest capillaries, display marked miopragia. Such patients present with a fine network of visible ectatic venules and capillaries that take on the appearance of red patches in which the anatomical structure of the capillaries can no longer be discerned, even under a magnifying glass. In such patients it is difficult to achieve a completely satisfactory esthetic result.

Figure 9 Patient under treatment with three-dimensional regenerative phlebotherapy. The telangiectasias must not be obliterated; they form if the reticular veins resist dilation. Regenerative treatment always begins with the vessels in the foot. The regenerative solution is injected into all the “gateways” that are visible either with the naked eye or by means of transillumination, in a single region of a single limb. It is not necessary for the telangiectasias to disappear during the first few sessions; they will disappear once the three-dimensional regenerative treatment has normalised the hypertension caused by the insufficiency of the non-visible veins. Restoring normal blood pressure will cause the telangiectasias to disappear even though the “regenerative” solution has no sclerosing action. The advantages of using a non-obliterating solution are obvious: the treatment is rapid, does not give rise to complications and does not cause the pain that typically follows sclerotherapy.

With regard to matting, we carefully treat the area with three-dimensional phlebotherapy and inject the telangiectasias with 10% ********. The most difficult cases of matting to treat are those with the highest pressure and those that arise even after modest pressure increases in a context of very marked miopragia. If the former cases were treated with a two-dimensional technique (laser and sclerotherapy), matting would inevitably recur. The cases of inflammatory matting resolve spontaneously and do not require treatment (inflammatory matting is clearly visible when timedsurgical de-epithelialisation at 1 Watt is performed on sites of recent hyperpigmentation, as this reveals the dilated capillary-papillary plexus).

Figure 10: Extensive matting in a patient who had undergone saphenectomy and subsequent obliterative sclerotherapy. This is the most difficult situation to deal with on account of the serious iatrogenic alterations to blood flow and the lack of “gateways” through which to regenerate the underlying vessels. After phlebotherapy. regeneration.

Figure 11 Injection of a small perforating vein visualised by means of transillumination. The syringe and the needle are perpendicular to the surface of the skin.

Discussion

The fact that only a very small percentage of the people affected by venous disorders currently undergo phlebological therapy is indicative of a widespread lack of confidence in the treatments proposed. This lack of confidence stems from the failure of traditional techniques to produce results that fulfill patients’ expectations. Before the creation of T.R.A.P., our results were very poor, even though for some years we believed that they were good. This was due to the fact that poorly efficacious techniques had become consolidated, without ever being subjected to a rational critique.

T.R.A.P. is a conservative technique for the functional and esthetic treatment of venous insufficiency. It is easy to carry out and its results are consistent and longer-lasting than those of any other technique that we have used. In our view, this is the best indicator of the efficacy of the method. After undergoing three-dimensional regenerative phlebotherapy, patients can immediately return to their normal activities, without any untoward effects.. The use of a non-obliterating solution considerably reduces the risks of the treatment. Over the six years of development of this technique, our utilization of the sodium salicylate in an alkaline hydroglycerin buffered vehicle solution has steadily improved. Cases of pigmentation are rare, limited to the injection sites and short-lived; from the esthetic point of view they are therefore irrelevant and, after the first session, are always avoidable. With regard to matting, we maintain that the most critical areas are the internal region of the knee and the lateral region of the thigh. Transillumination, which we have only been using for the past year, has proved very useful in completing the regenerative action in these areas and has enabled us to minimize this complication, which, moreover, normally resolves easily. T.R.A.P. acts on the entire superficial and perforating circulation; it therefore enables the source of the problem to be treated and proper venous capacity to be restored, thereby limiting recurrence of the disorder. Another advantage of using a non-obliterating solution is that the valves, which are the most resistant structures in the vessel (35), are not damaged. This contrasts starkly with what happens during obliterative sclerotherapy, in which re-canalization almost always gives rise to a valveless vessel. Owing to the characteristics of the solution used, standardization of the syringe, and, especially, the use of transillumination, injection of the poorly visible ectatic reticular veins, which is troublesome when traditional sclerosing solutions are used, becomes extremely easy. In our experience, the injection of large amounts of sodium salicylate solution in a 6% hydroglycerin vehicle supplemented with lidocaine has never caused any notable side-effects in patients. No post-therapy scotoma has ever been recorded and tests for micro-hematuria and hemoglobinuria have always proved negative. Moreover, pharmacokinetic testing has revealed that the solution is totally eliminated after 24 hours. Finally, the addition of lidocaine chlorhydrate has never caused patients any trouble. Another advantage of using a non-obliterative solution is that the phlebectatic corona, a region in which traditional sclerosing solutions are risky, can safely be injected. T.R.A.P. begins “regeneration” where the thrust begins that allows the blood to reach the right atrium. Moreover, it is interesting that sodium salicylate, which is considered to be only of historical curiosity (34), when indeed it is considered at all (36), should constitute a useful tool in the treatment of venous insufficiency. Indeed, sodium salicylate possesses an essential characteristic that is overlooked by most authors: it is not conducive to hyperpigmentation (37, 38).

The methodical injection of all the vessels, which we regard as “gateways” to the non-visible vessels, reduces the excessive capacity of the circulation, improves the patient’s symptoms, corrects hemodynamic alterations and hinders progression of the disorder. Today, transillumination enables us to pick out many “gateways”, such as the tiny, more superficial perforating vessels, which would otherwise be invisible . Moreover, it allows us to achieve even more rapid and complete results, and to inject a smaller amount of solution for each single injection. In T.R.A.P., short-term “recurrence” is not looked upon as failure, as it is in obliterative sclerotherapy. The “recurrence” is caused by hemodynamic factors and is a sign that the tributary vessels in the area have not yet achieved sufficient continence. The appearance of a reticular vein during regeneration is always useful, given that it constitutes a “gateway” through which the non-visible vessels that have not yet been treated can be reached. In such cases, the amount of solution injected is increased slightly. In young patients with a familial predisposition to venous insufficiency. T.R.A.P. can be used as a preventive measure. T.R.A.P. may also have an exclusively functional value, in that just a few sessions, prior to the application of bandages, are able to improve subjective symptoms in elderly patients.

We also feel that the results of T.R.A.P. may help to change the attitude of patients; we have already observed that patients are willing to undergo treatment with a technique that is efficacious, yields good esthetic results and is more respectful of the anatomy and functioning of the venous circulation in the lower limbs. Indeed, all our patients have enjoyed a marked improvement in their subjective symptoms as a result of the treatment. Moreover, echographic examination reveals that the caliber of the vessels treated is reduced. We believe that T.R.A.P. has the potential to be widely used. Indeed, alongside the rigorously obliterative approach, there exists an orientation towards a milder form of sclerotherapy that utilizes the minimal effective concentration of solution (MSC), even when associated to the minimum volume(36). Clearly, a form of sclerotherapy that is by definition obliterative cannot embrace our philosophy. Indeed, “obliterating” the entire superficial and perforating circulation is unthinkable; it can, however, be “regenerated”.
We commonly inject ******** solution even into the veins of the hands and forearm , periocular venules, telangiectasias of the face  (39), vascular neoformations and, in very small quantities (a few drops) into spider naevi. As the veins of the hands and forearm are less sensitive to the action of 6% ******** than those of the lower limbs, they can be reduced in caliber and reinforced in one treatment session or in two sessions a month apart. Facial telangiectasias, if they can be injected, are part of a three-dimensional disorder.

The reduction in the overall volume of the veins reduces the hemodynamic pressure on the capillary-papillary plexus, thereby enabling a more rapid and stable result to be achieved through subsequent treatment by physical means, which is always necessary in this region in order to eliminate the vessels completely. By contrast, complete elimination of telangiectasias of the lower limbs, in our experience, does not require the use of any physical technique. The solution injected into the vessels of the cheek mainly flows toward the mandible; only in the nasal and palpebral regions, therefore, do we apply compression during injection of the angular vein at the internal corner of the eyelid. Although the angular vein is normally valved, this maneuver is recommended on account of the possibility of anatomical alterations of the vessel.
For what concerns subcutaneous and submucosal venous angiomas, we first inject a large quantity of 6% sodium salicylate in an alkaline hydroglycerin buffered vehicle solution, followed by a powerful obliterative sclerosing solution, once the vessels have been reduced.

Conclusions

The limits to three-dimensional regenerative ambulatory phlebotherapy will only be established when the method is more widely used, more complex disorders are treated and the results are monitored over a long period. At present, however, the minimal invasiveness of the technique, its preservation of anatomical integrity, its ease of execution, the high quality and persistence of the results, the rapidity with which they are achieved, the absence of complications and the satisfaction of the patients treated indicate that, in terms of efficacy and safety, T.R.A.P. is far superior to any of the techniques that we previously used.

Our intentions regarding Phlebotherapy

We are convinced that the validation of any phlebological treatment must include photographic documentation of the patient before and after the procedure. Tables, figures, diagrams and vague procedural hypotheses are meaningless if no visual evidence of the result is provided. That this subterfuge of not showing any proof of results has become the established common practice during courses and congresses is, to say the least, alarming. Worse still, this criticism also applies to phlebology publications, even to those international journals such as Dermatologic Surgery (the official publication of the American College of Phlebology) and Phlébologie. Indeed, leafing through years of back-issues of these publications will not turn up a single verifiable result of the therapies proposed! As a plastic surgeon, I judge this behaviour to be highly questionable, at the very least. If, during our courses on Timedsurgery or Elasticum face-lifting, we were unable to show the tangible results of our operations, the participants would demand their money back, and rightly so. Since the problem of therapeutic efficacy also concerns three-dimensional regenerative phlebotherapy (T.R.A.P.), we intend to post on this site the results of the most recent study on the efficacy of this technique; the study terminated in July and the data are currently being analysed. This double-blind study shows photographic proof of the results achieved in 60 patients treated with a predetermined quantity of regenerative solution in two sessions of phlebotherapy. In 20 cases, the photographic results have been elaborated by means of pixel-count by the Faculty of Engineering of the University of Genoa.

Acknowledgements

 I wish to thank Silvia Perrella Segre, Bernard Patrick, Angela Sementa, Aberto Cavalchini, Giovanni Levrero and Ottavio Cancelli, for their contribution to this work

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