Primary Varicose Research Articles

Endocrine mechanisms in the pathogenesis of primary varicosis

SummaryIntroduction: Varicose veins affect up to 40 % of men and up to 51 % of women. The patho-physiology of primary varicosis (chronic venous insufficiency, CVI) is poorly understood. Here, the available data on possible endocrine mechanisms in healthy and varicose veins are reviewed.Methods: An extensive literature search was conducted in PubMed using the following key words: Chronic venous insufficiency, CVI, chronic venous disease, CVD, varicosis, saphenous vein, pathogenesis, hormone.Results: Several theories ranging from incompetence of the valves to functional, biological or morphologic changes in different layers of the vein wall have been proposed. However, an increasing body of evidence suggests that endocrine mechanisms might be involved in the pathogenesis of primary varicosis. In this respect a growing number of hormones (e.g. estrogen, progesterone, relaxin-2, and oxytocin) and their receptors have been linked to primary varicosis in experimental, pharmacological and histological studies.Conclusion: In summary, endocrine-based mechanisms seem to play a role in the pathogenesis of primary varicosis. This opens up the perspective for pharmacological treatments targeting the various described endocrine regulatory networks.

A Novel Role for Relaxin-2 in the Pathogenesis of Primary Varicosis

BackgroundVaricose veins affect up to 40% of men and up to 51% of women. The pathophysiology of primary varicosis is poorly understood. Theories ranging from incompetence of the venous valves to structural changes in the vein wall have been proposed.Methodology/Principal FindingsWe analyzed the functional state of the intramural smooth muscle cells (n = 14 pairs matched for age and gender) and the expression of relaxin-2 and its receptors RXFP1 and RXFP2 in samples of varicose and healthy great saphenous veins (GSV) (n = 21 healthy GSV; n = 46 varicose GSV). Relaxin-2 and RXFP1 contents were determined in tissue samples (n = 9 samples per group). Pharmacological analyses were performed in a perfusion chamber. Morphometric determination of the nuclear size of the smooth muscle compartment yielded no significant difference in varicose GSV in comparison with the healthy controls. Relaxin-2 and its receptors were expressed in the muscular layer, endothelial cells and in blood vessels contained in the vein wall. Immunohistochemical expression of relaxin-2, RXFP1 and RXFP2 was significantly decreased in varicose GSV. Relaxin-2 and RXFP1 measured by ELISA and Western Blot were decreased in varicose GSV (relaxin-2 ELISA healthy vs. varicose GSV: 12.49±0.66 pg/mg versus 9.12±3.39 pg/mg of total protein; p = 0.01; Student's T-test). Contractions of vein samples induced by cholinergic or adrenergic stimulation were antagonized by relaxin-2.Conclusions/SignificanceWe report that relaxin-2 and its receptors RXFP1 and RXFP2 are expressed in GSV and that their expression is significantly decreased in varicose GSV. Further, we were able to demonstrate a functional pharmacological relaxin-2 system in varicose GSV. Our results suggest a novel role for relaxin-2 in the pathogenesis of primary varicosis, rendering relaxin-2 a novel possible pharmacological agent for the treatment of this widely prevailing venous disease.

Aberrant expression of Tiel gene in venous valves in great saphenous varicose vein

Objective To investigate the aberrant expression of Tiel gene in venous valves in great saphenous varicose vein,and its role in pathogenesis of varicose vein of lower extremity.Methods Varicose veins group ( 15 samples) and normal control group ( 11 samples) were set up.By using immunohistochemistry staining,the expression of CD31 and Tiel in the first valves in great saphenous veins was detected.Western blotting was used to check the expression of Tiel protein in venous valves.Results In normal control group valves,there was no difference between proximal and distal sides endothelium in expressing CD31 (P ＞ 0.05 ).The proximal side endothelium expressed Tie1 stronger than distal side at the basal part (P ＜ 0.05 ),but this difference was not found at valve cusp (P ＞ 0.05 ).In varicose veins group,besides morphological changes of valves,the proximal side endothelia expressed CD31 weaker than diatal side endothelia ( P ＜ 0.05 ),and expressed Tiel much weaker than diatal side endothelia ( P ＜0.01 ).The expression of Tiel protein was undetectable in venous valves.Conclusion The decreased expression of Tiel in proximal side of venous valves may play a role in the pathogenesis of primary lower extremity varicose veins. Key words: Tiel gene; Venous valve; Varicose vein

Diagnose und Therapie der primären Varikose

This is the first of two articles on the diagnosis and treatment of varicose veins. Primary varicosis is a congenital degenerative disease of the peripheral venous system of the lower extremities. The realisation factors are age, female sex and pregnancy. Degeneration of the peripheral veins leads to dilatation of the lumen and insufficient closure of the valves resulting in a backflow of blood from deep to the superficial venous system. This leads to ambulatory hypertension in the superficial venous system and recirculation of noteworthy amounts of venous drainage blood in the affected leg. Without treatment this results in the long term in variable degrees of decompensation of the recirculation pathways and an increasing (volume-induced) secondary insufficiency of the deep venous system. The result corresponds to the clinical symptoms of chronic venous insufficiency (CVI). When treatment is started early enough the pathological course can be reduced or avoided. The various therapeutic measures will be described in the second article of this series.

Diagnostic procedures for venous problems

Venous diseases are a common worldwide problem. Numerous methods for the evaluation of the venous system are available. The major objectives include the diagnosis and medically relevant classification of varicose vein disease, as well as the identification and assessment of hemodynamic disturbances. In addition, it is necessary to characterize and classify disturbances of the deep venous system and to differentiate between primary and secondary varicose veins. The physician should also exclude or detect and classify concomitant peripheral arterial occlusive disease, and an accompanying disorder of lymphatic drainage. The diagnostic evaluation of venous disorders, depending on the severity of the disease, includes as standard the use of Doppler sonography. Light reflection rheography (LRR), photoplethysmography (PPG), venous occlusion plethysmography and phlebodynamometry (PD) complete the hemodynamic evaluation. The standard imaging technique now routinely used is duplex color scanning. More complex imaging studies include ascending and descending phlebography computed tomography or magnetic resonance imaging. In selected cases invasive investigations or serological tests may complement the diagnostic work-up.

Venenchirurgie zwischen gestern und heute

SummaryAfter World War II, all the vein operations at a Berlin Städtisches Krankenhaus der Maximalversorgung [Berlin Municpal Hospital for Maximum Care] were performed as they were when surgery began. The doctors relied completely on the clinical findings. There were no imaging techniques. With the introduction of ascending pressure phlebography in 1972, it became possible to diagnose the morphological and pathogenetic aspects of the clinical picture of primary varicosis and to elucidate new principles. Findings that are still considered important today include the division of superficial varicosis into several stages, and above all the development of secondary deep vein insufficiency in spontaneous courses. This resulted in a number of new surgical techniques.The history of medicine contains a number of different operations for chronic venous insufficiency. The concept of a venous fascial compression syndrome provided new findings pertinent to surgery for this serious clinical picture. It provides the basis for fasciotomy and fascia resection.Imaging diagnostics also had direct surgical ramifications with regard to deep venous and pelvic vein thrombosis.However, phlebology made the greatest advances in the field of social medicine. This unloved, ugly, and often incurable disease gave rise to a specialty in vascular surgery that today has finally achieved the scientific recognition it deserves. For the first time ever in the history of medicine, doctors can truly help hapless patients.

Veias linfonodais: uma causa pouco conhecida de varizes

As veias linfonodais fazem parte de uma rede venosa no triângulo de Scarpa, que liga em vários pontos o sistema venoso superficial às veias profundas, e podem tanto ser causa de incompetência do sistema venoso superficial quanto estar envolvidas na recorrência pós-safenectomia. Na rotina diária dos exames de Doppler venoso de membros inferiores, temos notado de maneira cada vez mais freqüente a associação das veias linfonodais com varizes primárias e recorrentes. A adequada caracterização dessas veias pode ajudar na compreensão do mecanismo fisiopatológico do aparecimento das varizes e permitir um controle e tratamento mais dirigidos. Este artigo lança luz sobre os aspectos anatômicos e fisiológicos das veias linfonodais, objetivando chamar a atenção dos profissionais envolvidos no diagnóstico de doenças venosas dos membros inferiores para uma causa pouco difundida de varizes.

Authors' reply: Randomized clinical trial comparing endovenous laser ablation with surgery for the treatment of primary great saphenous varicose veins (Br J Surg 2008; 95: 294–301)

Authors' reply: Randomized clinical trial comparing endovenous laser ablation with surgery for the treatment of primary great saphenous varicose veins (<i>Br J Surg</i> 2008; 95: 294–301)

Randomized clinical trial comparing endovenous laser ablation with surgery for the treatment of primary great saphenous varicose veins (Br J Surg 2008; 95: 294–301)

Randomized clinical trial comparing endovenous laser ablation with surgery for the treatment of primary great saphenous varicose veins (<i>Br J Surg</i> 2008; 95: 294–301)

Meta-Analysis of Endovenous Radiofrequency Obliteration of the Great Saphenous Vein in Primary Varicosis

To compare radiofrequency obliteration (RFO) and conventional surgery with respect to postoperative complications, effectiveness of treatment, and quality of life (QoL). Several healthcare databases were interrogated to identify all studies published between 1994 and 2007 comparing RFO in primary varicosis to conventional therapy with vein ligation and stripping. Of 65 articles identified, 8 studies representing 428 patients [224 (52%) endovenous RFO and 204 (48%) stripping] were eligible for the meta-analysis. Adverse events, effectiveness, and QoL outcomes were assessed at several time points up to 2 years. There were significant reductions in tenderness and ecchymosis at 1 week and significantly fewer hematomas at 72 hours, 1 week, and 3 weeks associated with RFO. There was no significant difference between the RFO and surgery in immediate or complete great saphenous vein (GSV) occlusion, incomplete GSV closure, freedom from reflux, recurrent varicose veins, recanalization, or neovascularization. QoL results significantly favoring RFO over surgery included return to normal activity and return to work. It seems that RFO benefits most patients in the short term, but rates of recanalization, re-treatment, occlusion, and reflux may alter with longer follow-up. The lack of such data demonstrates the need for further randomized clinical trials of RFO versus conventional surgery.

Ultrasound diagnosis in post-thrombotic syndrome. Comparative study with color duplex, cw-Doppler and B-image ultrasound

Comparison of colour-coded Doppler sonography, CW-Doppler and real time sonography in the diagnostics of the postthrombotic syndrome. Colour-coded Doppler sonography, CW-Doppler and real time sonography were studied in 40 legs with postthrombotic syndrome, confirmed by phlebography. In a further step deep veins of patients with primary varicosis (n = 40) and a group of normal veins (n = 40) where compared with the postthrombotic group (n = 40). The sensitivity of CW-Doppler was 71.2% and that of real time sonography 67.5%, their specificity 92.3% and 92.2%, respectively, while colour-coded Doppler sonography had a sensitivity of 90.9% and a specificity of 88.9%. In addition, colour-coded Doppler sonography in combination with measurement of the peak velocity of venous reflux in deep veins had the highest sensitivity with 92.8% and specificity with 95.4% of all ultrasound methods tested. By means of colour-coded Doppler sonography together with measurement of the peak velocity of venous reflux, healthy persons and patients with varicosis could be distinguished with high significance (p < 0.003) by a peak velocity of venous reflux of more than 10 cm/s. In comparison to real time sonography and CW-Doppler, quantitative analysis of reflux in the deep veins by means of colour-coded Doppler sonography is the most valid ultrasound method in the diagnosis of postthrombotic syndrome.

The Nature of Skin Pigmentations in Chronic Venous Insufficiency: A Preliminary Report

Chronic Venous Insufficiency (CVI) provokes skin pigmentation commonly seen in the gaiter region of the leg. The exact nature and pathogenesis of this are poorly understood. To evaluate the presence of melanin and haemosiderin in histological sections of the skin of limbs with primary varicose veins. Histological investigations were performed in 49 biopsies from pigmented and non-pigmented skin of limbs with varicose veins and control limbs. All samples from pigmented skin showed a higher content of melanin than controls. In contrast, haemosiderin was found in only a few biopsies taken from the more severely pigmented skin in areas of lipodermatosclerosis. Erythrocyte diapedesis was observed only where an intense inflammatory process was also present. Our findings suggest that in the initial phases of skin changes due to venous disease, pigmentation is attributable to melanin. Haemosiderin seems to play a role in the evolution of skin changes toward lipodermatosclerosis and ulceration. Erythrocyte diapedesis is likely to occur only during acute phases of the inflammatory process. Further investigations are needed to explain the cause and the exact cellular and molecular mechanisms responsible for hypermelanisation occurring in early phases of skin changes in CVI.

Conventional Versus Invaginated Stripping of the Great Saphenous Vein: A Randomized, Double‐Blind, Controlled Clinical Trial

BackgroundAn invaginated strip of the great saphenous vein (GSV) may be associated with diminished blood loss and less discomfort compared to conventional stripping in patients with unilateral primary GSV varicosis.MethodsNinety-two patients were randomized for conventional (CON) or invaginated (INVAG) stripping and were followed for 26 weeks postoperatively.ResultsBoth groups (n = 46) were well balanced for age, gender distribution, and body mass index. The CON group lost twice as much blood compared to the INVAG group (CON: 28 ± 4 g, INVAG: 15 ± 2 g, p < 0.001). Infragenual incision length following a conventional strip was twice as long (CON: 16 ± 1 mm, INVAG: 8 ± 1 mm, p < 0.001). Pain as measured with a visual analog scale (minimal 0, max 10) decreased in both groups in a similar fashion from 3.2 ± 0.3 preoperatively to 0.6 ± 0.2 after 26 weeks (p < 0.001). Saphenous nerve damage after one month was observed in four CON patients compared to no patients following invagination. Return to work was not different (CON: 13 ± 2 days, INVAG: 11 ± 2 days).ConclusionInvagination of the GSV in uncomplicated primary varicosis may be associated with less surgical trauma compared to a conventional stripping technique.

Primary varicosis

The classic varicose vein operation still represents the "gold standard" in the operative therapy of varicose veins. The results of this procedure in view of perioperative complications are very good, with the incidence of perioperative deep venous thrombosis varying between 0.05% and 0.1%. Recurrence rates between 6% and 60% are published. However, the true recurrence rate is unknown since an exact definition of recurrent varicosis is still lacking. In recurrent varices it is essential to distinguish between disease progression, including neorevascularisation, and technical errors. Endovascular procedures for elimination of the superficial venous system - radiofrequency obliteration and endovenous laser therapy - meanwhile have established themselves as alternative, minimally invasive procedures. The perioperative complication rate of endovenous procedures is very low and comparable to that of the classic operation. Good results, with occlusion rates of the treated vein around 87% to 93% up to 2 years postoperatively, have been published for both endovenous laser therapy and radiofrequency obliteration. For the latter, 5-year results were published, with occlusion of the treated vein in 87%. Results in the literature for radiofrequency are better documented than for endovenous laser treatment because there are now five prospective randomised trials for the former and most publications for endovenous laser treatment are single-center experiences. The advantage of endovenous procedures, especially radiofrequency obliteration, over the classic operation is the lower rate of perioperative pain and better quality of life. The spectrum of operative treatment methods of the superficial venous system has increased tremendously due to new technical developments. For the surgeon this implies the necessity of informing patients conscientiously about the pros and cons and available results of each procedure, and carefully weighing which methods are at the time best for the patient.

Transilluminated powered phlebectomy in the treatment of primary and recurrent varicose disease: six-month follow-up of 135 legs

Objective: Tumescent anaesthesia and transillumination can be used in removing varicose veins (VV) together with a specially designed rotating resector device and suction drain system (transilluminated powered phlebectomy, TIPP). The purpose of this study was to evaluate safety, short-term results and learning curve of this novel technique in the treatment of primary and recurrent VV. Methods: A total of 135 legs in a cohort of 96 patients received surgery for varicose disease in one private hospital during a 14-month period. All operations were performed by a single surgeon using TIPP alone or together with hook phlebectomy and stripping of great or short saphenous vein. This retrospective data included the following issues: preoperative evaluation (Doppler or duplex), perioperative details (duration of operation, number of incisions, used techniques) and postoperative examination two weeks and six months after surgery (complications, short-term results). Results: The mean age was 48 years and 92 patients (96%) were women. There were 39 (41%) bilateral procedures and 78 legs (58%) had a recurrent varicose disease. The distribution of clinical, aetiological, anatomical and pathophysiological clinical class was as follows: class C2 16%, class C3 79% and class C4 5%. TIPP was performed without other surgical procedures in 29 (21%) legs. Duration of operation (mean) was 81 min in primary legs, and 84 min in recurrent cases. The number of incisions was 3.2 in primary legs and 4.5 in recurrent ones. Complications were noted in 11 (8%) of the legs two weeks postoperatively. Pigmentation was noted in 10 (7%) legs (10.3% in recurrent legs and 4.0% in primary legs) and residual VV in 11 (8%) after a six-month follow-up. No major complications (deep infection, deep venous thrombosis, fat embolism, pulmonary embolism) were found during the six-month follow-up. When the beginning of the learning curve (31 legs) was compared with subsequently operated 104 legs, there were more skin lesions (6.5 versus 0%; P &lt; 0.05), and more residual VV in the follow-up (16 versus 8%; P &lt; 0.05) at the early stage of the learning curve. However, no difference was noted in the incidence of pigmentation, infection, haematomas or lymphatic disorders. Conclusions: Rate of complications after TIPP is low in patients undergoing day-case surgery for varicose disease. The number of incisions is low in both primary and recurrent legs. Late pigmentation is not frequent, but the incidence of pigmentation is higher in recurrent legs. Residual varicosis is rarely seen in six-month follow-up.

Prevalência do refluxo na veia safena parva em varizes primárias não complicadas dos membros inferiores pelo eco-Doppler colorido

OBJETIVO: Determinar a prevalência de refluxo venoso na veia safena parva em membros inferiores com varizes primárias não complicadas pelo eco-Doppler colorido. MÉTODO: No período de 18 meses, 1.953 pacientes foram submetidos ao eco-Doppler colorido de membros inferiores por doença venosa. Destes, 1.631 com varizes primárias não complicadas foram selecionados para esta análise, sendo que 1.383 eram do sexo feminino (84,79%) e 248 (15,21%) do sexo masculino. A média de idade dos pacientes foi de 42,89 (± 0,48) anos, variando de 13 a 85 anos. Dos 1.631 pacientes, 1.323 foram submetidos a exame bilateral e 308 a exame unilateral, totalizando 2.954 membros inferiores com varizes primárias não complicadas avaliados. Desse total, 1.461 eram membros inferiores direitos e 1.493, esquerdos. Todos os exames foram realizados seguindo o mesmo protocolo. RESULTADO: Dos 2.954 membros inferiores avaliados, 372 (12,59%) apresentaram refluxo em veia safena parva. A prevalência nos homens foi de 14,08% e, nas mulheres, de 12,35%. O refluxo da safena parva foi maior no membro inferior esquerdo (13.13%) do que no direito (12,05%). A prevalência do refluxo foi significativamente maior nos pacientes acima de 60 anos. CONCLUSÃO: O refluxo da veia safena parva é relativamente comum, e sua pesquisa deve ser sempre realizada em pacientes com varizes primárias de membros inferiores.

Recurrent varicose veins: assessment of the saphenofemoral junction.

Thirty-six consecutive unselected patients, who had apparently previously undergone saphenofemoral ligation for primary uncomplicated long saphenous varicosities and who had then re-presented with recurrent thigh varices emanating from the groin, underwent preoperative clinical assessment, hand-held Doppler and duplex ultrasonographic examination and varicography to establish the presence or absence of saphenofemoral incompetence as the cause of recurrence. All patients underwent reexploration of the saphenofemoral junction (SFJ) via a lateral approach. Twenty-six patients had an intact SFJ (type I recurrence) and ten had varices arising from either a thigh perforator, or from abdominal or perineal veins (type II recurrence). Clinical examination alone was poor at distinguishing type I from type II recurrence. Doppler ultrasonography was sensitive (88 per cent) but non-specific (40 per cent). In contrast, duplex scanning was insensitive (42 per cent) but extremely specific (100 per cent) and accurate, with a positive predictive value of 100 per cent. Varicography also had a specificity and positive predictive value of 100 per cent, a sensitivity of 73 per cent and in addition provided a precise anatomical 'road-map'. A combination of clinical examination and hand-held Doppler ultrasonography seems to be the most appropriate first-line method of preoperative assessment in these patients. Duplex ultrasonography, if available, will provide additional useful information about both the SFJ and the presence of thigh perforators. Contrast examination may be reserved for patients who have equivocal results on non-invasive investigations, who have had more than one previous groin operation or who have, in addition, deep venous disease.

Chronische venöse Insuffizienz mit Ulcus cruris bei einem 16-jährigen Mädchen

Hintergrund. Wir beschreiben eine 16-jahrige Patientin mit einer chronischen venosen Insuffizienz (CVI) und einem Ulcus cruris am linken Unterschenkel. Fallbericht. Wegen einer praduktalen Aortenisthmusstenose wurden in der 1. Lebenswoche und mit 11 Monaten je eine Herzkatheteruntersuchung uber die rechte und linke V. saphena durchgefuhrt. Bei keiner der Untersuchungen ergab sich unmittelbar danach der Hinweis auf eine venose Thrombose. Mit 15 Jahren wurde erstmals eine Varikose, mit 16 Jahren eine ausgepragte CVI Grad IV mit einem 3 cm×3 cm grosen Ulcus cruris am linken Unterschenkel beobachtet. Phlebographisch fand sich ein 3 cm langer vollstandiger Verschluss der V. femoralis links. Es gibt keinen Hinweis auf eine hereditare Thromboseneigung der Patientin, samtliche Gerinnungswerte waren im Normbereich, die Patientin hatte lediglich besenreiserartige Varizen im Rahmen einer geringen primaren Varikose im Bereich der Kniekehlen beider Beine. Diskussion. Unser Fall zeigt, dass eine asymptomatische Thrombose, die im Sauglingsalter nach einer Herzkatheteruntersuchung aufgetreten ist, nach mehr als 1 1/2 Jahrzehnten zu einer CVI mit Ulcus cruris fuhren kann.

The Quality of Local Anaesthesia Associated with Intravenous Administration of Ketoprofen in Radical Operations for Leg Varicose Veins

Objective: To evaluate the use of intravenous ketoprofen administration during varicose vein surgery undertaken under local anaesthesia. Setting: Regional general hospital in Poland. Patients: One hundred and six patients presenting with primary long saphenous varicose veins, including those with skin changes and leg ulceration. Interventions: Patients underwent sapheno-femoral ligation and long saphenous stripping under local anaesthesia including femoral nerve block, having first received an intravenous infusion of ketoprofen. Outcome measures: Patients recorded their level of discomfort or pain on a five-point scale. Blood pressure and pulse were also recorded. Results: One hundred and two patients found the level of analgesia produced by this technique to be acceptable, and 75 reported no discomfort at all. Conclusions: The combined use of intravenous ketoprofen and local anaesthesia allowed the treatment of all patients with superficial venous incompetence irrespective of their fitness for general anaesthesia.

Resistance to activated protein C due to factor V Leiden mutation: high prevalence in patients with post-thrombotic leg ulcers.

Activated protein C (APC) resistance is the most frequently diagnosed heritable thrombophilic defect predisposing to thrombosis. To determine the prevalence of APC resistance due to factor V Leiden mutation in patients with leg ulcers. Within a 2-year-period 100 consecutive patients with leg ulcers were examined for factor V Leiden mutation. APC resistance due to factor V Leiden mutation was detected in 19 of 53 patients (36%) with post-thrombotic leg ulcers and in three of 47 patients (6%) with ulcers caused by primary varicosis. In a healthy control group APC resistance due to factor V Leiden mutation was found in five of 96 (5%) volunteers. In view of this high prevalence of APC resistance of 36%, which has never previously been reported, patients with post-thrombotic leg ulcers should be investigated for APC resistance.