Varicose Vein Formation Research Articles

Innovative Approaches and Future Directions in the Management and Understanding of Varicose Veins: A Systematic Review.

Varicose veins, a prevalent condition that primarily affects the lower limbs, present significant hurdles in diagnosis and treatment due to their diverse causes. This study dives into the complex hormonal, environmental, and molecular elements that influence varicose vein genesis, emphasizing the need for precise diagnostic methods and changing therapy approaches to improve patient outcomes. It investigates the epidemiology and demographic distribution of varicose veins, delves into their pathophysiology, and assesses diagnostic methods such as duplex ultrasonography and the CEAP classification system. In addition, the study discusses novel therapies such as sclerotherapy and endovenous thermal ablation, as well as the effectiveness of existing diagnostic methods in detecting chronic venous illnesses. By investigating venous wall remodeling and inflammatory pathways, it gives a thorough knowledge of varicose vein formation. The study calls for future research that focuses on patient-centered methods, bioengineering advances, digital health applications, and genetic and molecular studies to improve the accuracy and effectiveness of vascular therapy. As a result, a multidisciplinary literature analysis was done, drawing on insights from vascular medicine, epidemiology, genetics, and pharmacology, to consolidate existing knowledge and identify possibilities to enhance varicose vein diagnosis, treatment, and patient care outcomes.

Mechanoresponsive ETS1 causes endothelial dysfunction and arterialization in varicose veins via NOTCH4/DLL4 signaling

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies.

Factors influencing recurrent varicose vein formation after radiofrequency thermal ablation for truncal reflux performed in two high-volume venous centers

ObjectiveRecanalization of the saphenous vein trunk after endovenous radiofrequency ablation (RFA) is often associated with recurrent varicose veins (RVVs) or recanalization. This study aimed to assess the long-term results of RFA of the great saphenous vein (GSV) and identify the risk factors for GSV recanalization and RVVs during follow-up for patients presenting to dedicated outpatient vein centers. MethodsAll consecutive patients with incompetent GSVs who underwent RFA between 2009 and 2019 were retrospectively analyzed. The primary study end points were freedom from GSV recanalization and the RVV rate during follow-up. The secondary study end points were the postoperative complication rate and the risk factors for GSV recanalization and RVVs. Univariate and multivariate analyses were performed to identify the potential risk factors for GSV recanalization and RVVs. ResultsDuring the study period, 1568 limbs were treated in 1300 consecutive patients (mean age, 53.5 ± 12.9 years; 71.9% women; CEAP [clinical, etiology, anatomy, pathophysiology] C2-C6; venous clinical severity score >5). Technical success was achieved in 99.7% of cases. At a mean follow-up of 57.2 ± 25.4 months, the GSV occlusion and freedom from reintervention rates were 100% and 100% within 1 week, 97% and 95.7% at 1 year, 95.2% and 93.1% at 3 years, and 92.4% and 92.8% at 5 years, respectively. The recurrence rate was 10% (n = 158) during the follow-up period. On multivariate analysis, a direct confluence of the accessory saphenous vein into the saphenofemoral junction (odds ratio [OR], 1.561; 95% confidence interval [CI], 1.0-7.04; P = .032), a history of pregnancy >2 (OR, 3.68; 95% CI, 1.19-11.36; P = .023), C4 (OR, 6.41; 95% CI, 1.36-30.28; P = .019), and preoperative GSV diameter >10 mm (OR, 1.82; 95% CI, 1.65-4.03; P = .043) were risk factors for GSV recanalization. Moreover, age >70 years (OR, 1.04; 95% CI, 1.01-1.06; P = .014) and incompetent perforator veins (OR, 1.17; 95% CI, 0.65-2.03; P = .018) were also risk factors for RVVs. ConclusionsRFA is a safe technique to ablate the GSV with a low complication rate and durability during 5 years of follow-up. However, patients with a high clinical score and those with direct confluence of the accessory saphenous vein into the saphenofemoral junction experienced higher long-term GSV recanalization and RVV rates.

Pregnancy conditions and complications associated with the development of varicose veins

BackgroundPregnancy is a known risk factor for developing varicose veins (VV). However, pregnancy is often considered a homogeneous entity and few studies have examined if specific characteristics and complications of pregnancy may influence VV formation. This study sought to identify which pregnancy-specific factors are associated with the development of VV. MethodsAll women who gave birth (live or still) between 1998 and 2020 within a multicenter health care system were identified retrospectively and followed through all hospital encounters (inpatient and outpatient). The primary outcome was VV, defined as any encounter with a primary diagnosis code for VV or a procedure for VV. The study period for each woman was the time from the first to last encounter. Extended Cox regression modeling evaluated the association between VV and pregnancy-related factors as a time-varying covariates while controlling for patient comorbidities. ResultsThere were 156,622 women with a median follow-up of 8.3 years (interquartile range, 2.7-16.6 years) included. During this time, 225,758 deliveries occurred. The 10- and 20-year freedom from VV was 97.0% (95% CI, 96.8%-97.1%) and 92.7% (95% CI, 92.4%-93.0%), respectively, from the estimated start of first pregnancy. Overall, 4028 patients (2.57%) developed VV during the follow-up period and 1594 (1.02%) underwent a procedure for VV. After risk adjustment, increasing parity was significantly associated with VV, with each subsequent pregnancy increasing hazard of developing VV (parity = 1: hazard ratio [HR], 1.78; 95% CI, 1.55-1.99; P < .001; parity ≥6: HR, 4.83; 95% CI, 2.15-1.99-10.9; P < .001), Other significant pregnancy factors included excessive weight gain in pregnancy (HR, 1.44; 95% CI, 1.09-1.91; P = .011), post-term pregnancy (HR, 1.12; 95% CI, 1.02-1.21; P = .021), pre-eclampsia (HR, 0.79; 95% CI, 0.70-0.90; P < .001), and postpartum transfusion of platelets, plasma, or cryoprecipitate (HR, 2.05; 95% CI, 1.19-3.53; P = .001). ConclusionsIncreasing parity, excessive weight gain in pregnancy, post-term pregnancy, and pre-eclampsia affect the development of VV after pregnancy. Although VV after pregnancy are likely underreported and true incidence is unknown, women should be counseled about the impact of these factors on VV development after pregnancy.

Pregnancy-Related Factors and the Development of Varicose Veins

Pregnancy is a known risk factor for developing varicose veins (VVs). However, prior studies lacked sufficient size and follow-up to determine the specific characteristics of pregnancy that might influence VV formation. We sought to identify which pregnancy-specific factors are associated with the development of VVs.

Increased CRP/albumin ratio is associated with superficial venous reflux disease and varicose vein formation

Kontext: Nedávno byl publikován názor, že kromě zvýšeného žilního tlaku může vznik a progresi křečových žil ovlivňovat i zánět. Poměr C-reaktivního proteinu (CRP) a albuminu (CRP/albumin ratio, CAR) představuje nový marker zánětu spojený s nepříznivou prognózou u různých skupin pacientů. Cílem naší studie bylo zjistit vztah mezi průměrem varikózní velké safény (varicose greater saphenous vein, VSM) a parametrem CAR. Metody: Do studie bylo zařazeno celkem 150 pacientů s nedostatečností VSM (skupina 1, n = 114) a nepostiženými VSM (n = 36). Průměr VSM se měřil B-mode ultrazvukem a reflux se kvantifikoval délkou uzavírání chlopně měřenou spektrální dopplerovskou křivkou. Krevní vzorky se odebíraly při zařazování pacientů do studie. Hodnota CAR se stanovuje vydělením hodnoty CRP hodnotou albuminu v séru. Výsledky: Skupinu 1 tvořilo 21 (18,4 %) mužů a 93 (81,5 %) žen; ve skupině 2 bylo 7 mužů a 29 žen. Průměrný věk pacientů v obou skupinách byl podobný (48,02 &#177; 12,20 roku ve skupině 1 vs. 44,9 &#177; 8,92 roku ve skupině 2; p = 0,44). Průměrná hodnota indexu tělesné hmotnosti (BMI) pacientů se významně nelišila (skupina 1: 26,4 &#177; 3,7 kg/m2 vs. skupina 2: 25,7 &#177; 4,2 kg/m2; p = 0,13). Průměrné hodnoty průměru VSM byly 5,70 &#177; 0,29 mm ve skupině 1 a 3,21 &#177; 0,34 mm ve skupině 2 (p = 0,0023). Průměrné hodnoty CRP a albuminu ve skupině 1 byly 6,18 &#177; 4,99 mg/l, resp. 4,45 &#177; 0,27 g/dl; ve skupině 2 to bylo 4,25 &#177; 2,46 mg/l, resp. 6,18 &#177; 1,14 g/dl (hodnota p pro CRP = 0,049, hodnota p pro albumin = 0,074). Poměr CRP/albumin ve skupině 1 činil 1,28 &#177; 1,34; ve skupině 2 byla naměřena hodnota 1,11 &#177; 1,21, tedy statisticky nevýznamný rozdíl (p = 0,58). Byla nalezena středně těsná korelace mezi průměrem VSM a poměrem CRP/albumin i refluxem povrchových žil (r: 0,48). Závěr: Zvýšený poměr CRP/albumin je spojen se zvýšenou incidencí varixů a větším průměrem velké safény, a tedy i vyšší incidencí refluxu povrchových žil. Zjištění podporují hypotézu, že ve vzniku křečových žil může hrát jistou úlohu systémový zánět. &#169; 2021, ČKS.

MicroRNA‑199a‑5p regulates FOXC2 to control human vascular smooth muscle cell phenotypic switch.

Varicose veins are among the most common disorders of the vascular system; however, the pathogenesis of varicose veins remains unclear. The present study aimed to investigate the roles of microRNA (miR)-199a-5p in varicose veins and in the phenotypic transition of vascular smooth muscle cells (VSMCs). Bioinformatics analysis confirmed that miR-199a-5p had target sites on the forkhead box C2 (FOXC2) 3′-untranslated region. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to detect the expression levels of miR-199a-5p and FOXC2 in varicose vein and normal great saphenous vein tissues. Cell Counting Kit-8 and Transwell migration assays were performed to validate the effects of miR-199a-5p on VSMCs. Contractile markers, such as smooth muscle 22α, calponin, smooth muscle actin and myosin heavy chain 11 were used to detect phenotypic transition. RT-qPCR revealed that miR-199a-5p was downregulated in varicose veins compared with expression in normal great saphenous veins, whereas FOXC2 was upregulated in varicose veins. In addition, biomarkers of the VSMC contractile phenotype were downregulated in varicose veins. Overexpression of miR-199a-5p by mimics suppressed VSMC proliferation and migration, whereas depletion of miR-199a-5p enhanced VSMC proliferation and migration. Notably, the effects caused by miR-199a-5p could be reversed by FOXC2 overexpression. Dual luciferase reporter analysis confirmed that FOXC2 was a target of miR-199a-5p. In conclusion, miR-199a-5p may be a novel regulator of phenotypic switching in VSMCs by targeting FOXC2 during varicose vein formation.

VenaSeal for vertical veno-venous reflux elimination in patients with chronic venous disease

Introduction. Chronic venous disease significantly reduces quality of life and often leads to complications. The only way to eliminate hemodynamically significant blood flow disorders is the surgical method, incl. its latest modification is the VenaSeal.Objective of the study. To study the immediate and long-term results of the use of VenaSeal adhesive technology to obliterate the incompetent major saphenous veins, as well as the potential benefits in special groups of patients based on three-year experience in using VenaSeal Glue Procedure.Materials and methods. Over a 3-year period, we have treated 104 patients with VenaSeal. The average age was 59.6 ± 14.97 years, the CEAP class was 3.2 ± 1.09. 101 patients had varicose veins, in three cases - post-thrombotic. The intervention was performed on 117 incompetent main veins: GSV – 107, SSV – 10.Results and discussion. Clinical evaluation and ultrasound imaging of veins immediately after the intervention of vein occlusion throughout the intervention. There was no pronounced pain syndrome after surgery. Complications occurred in 3 patients in the form of chemical phlebitis. Long-term results up to 3 years were studied clinically and using ultrasound in 72 patients (76 veins): recanalization was noted in 2 GSV (2.6%), which in one case was accompanied by the formation of a recurrent varicose veins. To study the effect of VenaSeal on the quality of life in a comparative aspect, a non-randomized, single-center, open-label study was carried out; it included patients, incl. with GSV occlusion using RFA and EVLT. In the group of patients after VenaSeal, the quality of life indicators were better values. In addition, the absence of the need for elastic compression made the surgical treatment of patients with chronic venous disease and concomitant lesions of the peripheral arterial bed. In groups of elderly and senile patients, patients with weeping eczema, with obesity, additional advantages were found in the form of a decrease in the invasiveness of the intervention and the possibility of correcting reflux as a hemodynamic basis for the development of trophic disorders with the aim of their faster and more effective relief.Conclusions. Non-thermal obliteration of incompetent major saphenous veins using VenaSeal in varicose veins and post-thrombotic disease is highly effective: the immediate results assessed with clinical methods and using ultrasound duplex scanning confirmed the occlusion of the target vein in all cases. The study of long-term results revealed recanalization of two veins out of 76, which accounted for 2.6%.

Sinistral Portal Hypertension Prediction During Pancreatoduodenectomy With Splenic Vein Resection

BackgroundPancreaticoduodenectomy with porto-mesenterico-splenic confluence resection can cause sinistral portal hypertension (SPH), which may lead to gastrointestinal bleeding. Nevertheless, it remains difficult to predict SPH development during surgery. The aim of this study is to assess the feasibility of measuring splenic vein (SV) pressure to predict SPH. MethodsThe patients who underwent pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection between January 2016 and December 2017 were included in this study. SV pressure was measured before SV clamping (SVP1) and after SV clamping (SVP2). SPH was defined as varicose vein formation detected by follow-up computed tomography. Incidence of SPH was assessed in patients who had no SV drainage after surgery. ResultsSV pressure was measured in 41 patients. Among them, 24 had no SV drainage (13 patients had occluded SV reconstruction, and 11 had SV ligation without an attempt at reconstruction) and were included for the analysis. SPH was observed in 16 of 24 patients (67%). The median ΔSVP (SPV2-SVP1) in patients with SPH was higher than that in patients without SPH (13.5 mmHg versus 7.5 mmHg, P = 0.0237). Most patients with SVP2 >20 mmHg (12/14 [86%]) or ΔSVP >10 mmHg (10/11 [91%]) developed SPH. ConclusionsFor the patients with SV resection, high SV pressure after clamping (≥20 mmHg) and a large SV pressure difference (≥10 mmHg) before and after clamping are feasible indication criteria for SV reconstruction to prevent SPH.

On the Opportunities of Using the Indices of Lipid Peroxidation – Antioxidant Defense System in the Diagnostics of Varicose Veins of Small Pelvis in Women

Background: The prevalence of varicose veins of small pelvic veins in women of reproductive age varies widely – from 5.4 to 80 %, due to the low specificity and low sensitivity of clinical diagnostic techniques, and the absence of biomarkers that can be used to identify the formation and progression of varicose veins of small pelvic veins in women.Aims: To identify changes in the levels of parameters of the system “lipid peroxidation – antioxidant protection” with the development of varicose veins of the pelvis in women, as well as the possibility of their diagnostic use.Materials and methods: We examined 200 women with clinical signs of varicose veins of small pelvis. Control group included 30 women without any pathology of venous system. Treatment group included 137 women with varicose veins of small pelvis: with mild degree of severity – 39 women, with moderate degree of severity – 65 women, with severe degree of severity – 33 women. We performed comparative analysis of lipid peroxidation – antioxidant defense system in women with and without varicose veins of small pelvis taking into account the severity degrees of pathological process.Results: We obtained the most informative indices for lipid peroxidation – antioxidant defense processes in blood of women with varicose veins of small pelvis: concentration of diene conjugate (DC) for the mild degree of severity of pathological process, lipid hydroperoxide (LHP), DC and malonic dialdehyde (MDA) – for the moderate and severe degree of severity, and also changes in the activity of antioxidant enzymes with increase of the severity of the disease. Assessment of the level of catalase (Cat) and glutathione peroxidase (GP) showed their highest informative value at the mild degree of severity. Concentrations of glutathione reductase (GR), glutathione S-transferase (GST) and reduced glutathione (GSH) are more statistically significant markers for severe forms of pathological process.Conclusions: Our research showed the relevance and advisability of the studying the levels of lipid peroxidation – antioxidant defense indices in women with varicose veins of small pelvis. We registered the highest diagnostic value of DC, Cat and GP in the beginning of the disease and of LHP, DC, MDA, GR, GST and GSH – at severe forms of the pathological process. We obtained reference values for DC, MDA, Cat, SOD and GP concentration that can be considered as the predictors of the development of varicose veins of small pelvis.

Anterior accessory saphenous vein confluence anatomy at the sapheno-femoral junction as risk factor for varicose veins recurrence after great saphenous vein radiofrequency thermal ablation.

Varicose veins recurrence rate remained almost unchanged despite the constant technological advancement in its treatment. The aim of this study is to evaluate the variable accessory saphenous vein (ASV) anatomy at the sapheno-femoral junction (SFJ) as a possible risk factor for recurrent varicose vein (RVV) after great saphenous vein (GSV) radiofrequency thermal ablation (RTA). Two-hundred consecutive patients affected by chronic venous disease (mean age 52.4±10.3 years; 187 women; CEAP C2-C6; 25.2±1.4), underwent to RTA from 2014 to 2016, at our Institute. Preoperatively all patients underwent duplex-ultrasound scanning, reporting the anatomical site, extension of reflux and the ASV anatomy at the SFJ. Duplex ultrasound and physical examination was performed postoperatively at 1, 6 and 12 months, and yearly thereafter. Patients were divided in two groups based on the anatomical site of reflux: group A (N.=187) including GSV and SFJ, group B (N.=82) including SFJ reflux. There was no preoperative statistical difference between the two groups. At a mean follow-up of 29.7±2.4 months, a freedom from recurrent varicose vein and GSV recanalization was: 100% and 100% at 1 month, 95.9% and 99.1% at 1 year, 93.7% and 96.7% at 3 years, respectively. A higher rate of RVV was documented for patients in group A at 3-year of follow-up (P=0.042). Cox regression analysis found, among five potential predictors of outcome, that direct confluence of ASV in SFJ (HR=1.561; 95% CI: 1.0-7.04; P=0.032) was a negative predictors of 1-year RVV. Sapheno-femoral junction morphology may affect recurrent varicose veins formation. In particular, a concomitant incompetence of the accessory saphenous vein or its directly confluence into the SFJ could represent an indication to simultaneous treatment by non-surgical techniques (RTA or laser) and avoid surgical ligation.

Varis etiyopatogenezinde lökosit aktivasyonu ile apopitozisin ilişkisi

Aim: Varicose veins are the most common disorders of the lower extremities. The purpose of this study is to investigate the effect of leukocyte activation in the vein wall and apoptosis in the etiopathogenesis of varicose veins.Material and Methods:Forty-six patients with varicose veins were included in the study. High ligation with stripping with or without additional individual ligation and excision was performed for symptoms, complications or cosmetic needs. ELISA was used to measure the serum concentration of caspase-8 and caspase-9.Results: There was a statistically significant difference between the cephalic vein and saphenous vein groups (p=0.04 and p&amp;lt;0.0001 respectively). Conclusion: As a conclusion, the complex pathophysiology underlying varicose veins has yet to be fully defined. It is suggested that both leukocyte activation and dysregulation of apoptosis are associated with susceptibility for varicose vein formation however this argument needs further research.

Clinical characteristics of women with infertility and ovaricovaricocele

Despite numerous studies devoted to the etiological factors and pathogenetic aspects of infertility, the lack of a comprehensive analysis of the causes of ovarian dysfunction and the exact diagnosis leads to the polypharmacy of hormonal drugs and their low effectiveness. One of the less well known and poorly studied factors is pelvic venous complications, including varicose veins of the ovaries. Violation of venous circulation in the pelvic organs plays a significant role in the structure of gynecological pathology, particularly in the development of ovarian dysfunction. The purpose of our study was to analyze the clinical characteristics of women with functional infertility and ovaricovaricocele, namely the features of anamnesis of life, gynecological and somatic anamnesis, the study of which allows to assess and determine the risk factors, possible causes of ovarian dysfunction and the formation of varicose veins. To solve the goals and objectives, were prospectively examined and divided into 2 groups for the comparative analysis 117 pregnant women of reproductive age (21–44 years old) with functional infertility: the main group was 62 women with infertility and varicose veins in the ovaries; comparison group has 55 women with infertility without varicose veins. Patients were examined by a specially designed questionnaire, which included the results of gynecological and somatic anamnesis, anamnesis of life. In the main group of women there is an increased proportion of women with intellectual differentiation of labor and psycho-emotional and physical activity, which may be the basis for the formation of maladaptation syndrome with the subsequent occurrence of functional disorders of the reproductive system. In addition, conditions of work with considerable physical activity can indirectly have a negative effect on venous hemodynamics in the small pelvis. Women with functional infertility and ovaricovaricocele had a high incidence of infectious diseases in childhood — 83.9%. It is precisely at the stage of formation of reproductive function that the action of an infectious factor can be significant in the occurrence of violations of complete oogenesis in the subsequent reproductive life of patients. Attention is drawn to the large number of inflammatory diseases of the internal organs in women as the main group and the comparison group in the study of the somatic anamnesis: from the otolaryngologic organs — 48.3%, respiratory organs – 54.7%, genitourinary system — 43.5% and in the structure of gynecological diseases: inflammation of ovaries — 43.5%, vagina and cervix — 25.8%, suggesting that factors of violations of folliculogenesis in active reproductive age may be inflammatory diseases of the genitals. There is a significant percentage of dyshormonal abnormalities in the form of abnormal uterine bleeding in the structure of gynecological pathology in women with functional infertility and ovaricovaricocele (30.6%) against patients with infertility without structural changes in ovarian veins. Patients with infertility are more likely to point out dysgharmony of sexual life (58.1%), which in patients with varicose veins in the pelvic organs was accompanied by dyspareunia (32.2%), suggesting the role of chronic stress as a risk factor for ovarian dysfunction, which is also exacerbated by the presence pain of syndrome in the lower abdomen in women of the main group (77,4%). The more significant percentage of gynecological pathology of endocrine genesis in women with functional infertility and ovaricovaricocele and the presence of certain extragenital pathology, which affects the formation of pelvic pelvic flooring in comparison with patients with infertility without structural changes in ovarian veins, is established during the analysis of the clinical characteristics of the significant percentage of venous hemodynamics in the functional properties of the ovary and induces further investigation of the role of varicose veins of the pelvic reservoirs, in particular ovariсovariсocele, in the pathogenesis of ovarian dysfunction in order to further develop the methods of therapeutic correction.

Varicose veins in women with Pelvic Congestion Syndrome: the hypothesis of the hormonal pathogenesis

Pelvic veins incompetence may cause varicose veins formation in the lower extremity due to leak points of the pelvic circulation. This observation is particularly frequent in recurrence cases especially in multi parity. The cause of pelvic vein dilatation is still not clear. Traditional mechanism for varicose veins formation referred to leg varices cannot be transferred to pelvic circulation where a strong efficient pumping mechanism and a high hydrostatic column is missing. An alternative explanation is possible if hormonal factors are considered to contribute to vasodilatation (estrogen is a potent vasodilator), and pelvic veins are naturally exposed to high doses of ovarian hormones. Pelvic veins dilatation/hypertension , rich in estrogens, may be directed through leak points to leg veins where estrogens effect of vasodilation is maintained. Then, at every Valsalva like action, some blood rich in estrogens passes in the leg network giving rise, among others, to perineal veins dilatation, recurrence after groin dissection for SFJ high ligation, intermittent leg pain/discomfort. Estrogens sampling studies could confirm this hypothesis and guide alternative treatments.

Oxidative Stress And Prolidase Enzyme Activity In The Pathogenesis Of Primary Varicose Veins.

Objectives Vascular endothelial dysfunction leads to the emerging of free oxygen radicals, deficiency of antioxidant system, forming of oxidative stress, inflammatory processes and release of proinflammatory cytokines. These things play big role in the development of primary varicose veins. Prolidase has been reported as an indicator of oxidative stress in diabetes, diabetic neuropathy, non-ulcerous dyspepsia, osteoporosis, polycystic over syndrome and many other diseases. The aim of this study is to evaluate the oxidative stress at venous insufficiency and to provide preliminary knowledge about the role of prolidase enzyme in varicose vein formation. Methods Ninety patients aged between 22 and 80 (47.35 ± 17.69) were included in the study and divided into 3 groups. Group1(n:30)(Serum control group): Patients without venous insufficiency. Group 2(n:30)(Tissue control group(healthy vein group): Patients underwent coronary artery bypass surgery (the remaining portion of great saphenous vein used as coronary artery bypass graft used as normal tissue) . Group 3(n:30)(Varicose vein group): Patients underwent varicose vein surgery (varicose vein and serum of these patients were used for study). Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI) and Prolidase enzyme levels were detected in tissue and serum samples. Results No significant changes were detected between three groups' serum samples in oxidative stress parameters and in the prolidase enzyme activity. The tissue TOS and OSI were higher in varicose vein group according to normal vein group and this was found statistically significant. And TAC levels in varicose vein group were significantly lower than normal vein group. Prolidase enzyme activity in varicose vein group was found higher according to normal vein group. Conclusion Oxidative stress plays a role at the development of primary varicose veins at biochemical level. Prolidase enzyme related with oxidative stress may play an important role in the pathogenesis of primary varicose veins.

CLINIC OF ATYPICAL FORMS OF PROGRESSIVE VARICOSE VEINS IN PREGNANT WOMEN (VARICOSE VEINS OF THE INGUINAL CANAL)

Based on Public Facility Regional Perinatal Center of Rivne Regional Council since the beginning of 2013 to 2016 inclusively 14,093 patients gave birth. 825 (5.85%) of them were diagnosed with progressive primary varicose veins of the lower extremities C2-4s, Ep, As, p, Pr (clinical class according to CEAP classification: C-2 – in 250 pregnant women, C-3 – in 566 patients, C-4 – in 9 pregnant women), perineum, external genitalia and inguinal canal and in their combination. By duplex scanning during pregnancy attempts were made to study the formation of varicose veins of the inguinal canal. The attention was paid through which and from which venous pools there is abnormal venous reflex (AVR) in the vein of the inguinal canal. The clinical manifestations of disease depending on the form of varicose veins of inguinal canal were considered. Varicose veins of the inguinal canal were found in 11.2% of examined persons, ie in 86 patients; 24 (27.9%) patients were diagnosed with isolated varicose veins, which did not extend beyond the inguinal canal (19 of them gave birth for the first time), in 38 (44.2%) patients varicose veins of the inguinal canal were within the inguinal canal through the external inguinal ring and formed varicose veins of the external genitalia (32 of them had two or more births), in 24 (27.9%) cases it was combined with varicose veins of the lower extremities and two of them formed a recurrence of varicose veins of the lower extremity. Mostly (72.09%) there was met unilateral veins lesions of the inguinal canal and, preferably, in 56 (65.1%) patients, changes were experienced in the left inguinal region. In 16 (25.8%) cases there was bilateral lesion. Often the source of their formation were combined venous branches, which were through the internal inguinal ring from the uterus and ovary, in 28 (41.8%) of pregnant women, at least – only from ovary in 20 (29.4%) cases, or from the angle of the uterus – 18 (26.5%) examined persons and much less from the external iliac vein – in 10 (16.7%) examined persons.

Pathophysiology of venous ulceration.

Our understanding of the pathophysiologic process of venous ulceration has dramatically increased during the past two decades because of dedicated, venous-specific basic science research. Currently, the mechanisms regulating venous ulceration are a combination of macroscopic and microscopic pathologic processes. Macroscopic alterations refer to pathologic processes related to varicose vein formation, vein wall architecture, and cellular abnormalities that impair venous function. These processes are primarily caused by genetic factors that lead to the destruction of normal vein wall architecture and venous hypertension. Venous hypertension causes a chronic inflammatory response that over time can cause venous ulceration. The inciting inflammatory injury is chronic extravasation of macromolecules and red blood cell degradation products and iron overload. Chronic inflammation causes white blood cell extravasation into the dermis with secretion of numerous proinflammatory cytokines. These cytokines transform the phenotype of fibroblasts to a contractile phenotype that increases tension in the dermis. In addition, iron overload keeps macrophages in an M1 phenotype, which leads to tissue destruction instead of dermal repair. Current surgical and medical therapies are primarily directed at eliminating venous hypertension and promoting venous ulcer wound healing. Despite advances in our understanding of venous ulcer formation and healing, ulcers still take an average of 6months to heal, and ulcer recurrence rates at 5years are >58%. To improve the care of patients with venous ulcers, we need to further our understanding of the underlying pathologic events that lead to ulcer formation, prevent healing, and decrease ulcer-free recurrence intervals.

Clinico-histopathological study of varicose vein and role of matrix metalloproteinases-1, matrix metalloproteinases-9 and tissue inhibitor of matrix metalloproteinase-1 in varicose vein formation.

Varicose vein (VV) is an important cause of morbidity in the young and elderly population. Many studies of the Western country suggest that matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs have a crucial role in the pathogenesis of VV, but limited work has been done in Indian population. The aim of this study is to study detailed histology of VV and to see the expression of MMP-1, MMP-9 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). A total of 63 cases of VV and 10 control leg veins were included in this prospective study. Paraffin sections of VV were prepared. Hematoxylin and eosin (H and E), Masson trichrome and Verhoeff's staining were performed. Immunohistochemistry of VV was done with MMP-1, MMP-9, and TIMP-1 antibodies. Cytoplasmic expression of MMP-1, MMP-9 and TIMP-1 were graded as intense positive (++), weak/slight positive (+), and absent (-). Focal intimal thickening (47.6%), increased medial thickening (73%) and fragmentation of elastin fibers (84.1%) were the major histological changes noted in H and E and special stained sections. MMP-1 expression increased in all layers of VV in 58 cases (92.1%) as compared to control veins. As compared to the control veins, intimal and adventitial expression of MMP-9 were increased in 31 (49.2%) and 40 (63.5%) cases, respectively. Expression of TIMP-1 was absent in both the varicose and the control veins. Increased expression of MMP-1 and MMP-9 suggests they have an important role in the pathogenesis of VV.

Rat Model of Parkes Weber Syndrome.

The Parkes Weber syndrome is a congenital vascular malformation, characterized by varicose veins, arterio-venous fistulas and overgrown limbs. No broadly accepted animal model of Parkes Weber syndrome has been described. We created side-to-side arterio-venous fistula between common femoral vessels with proximal non-absorbable ligature on common femoral vein limiting the enlargement of the vein diameter in Wistar rats. Contralateral limb was sham operated. Invasive blood pressure measurements in both iliac and inferior cava veins were performed in rats 30 days after fistula creation. Tight circumference and femoral bone length were measured. Histopathology and morphology of soleus muscle, extensor digitorum longus muscle, and the common femoral vessel were analyzed. 30 days following arterio-venous fistula creation, a statistically significant elevation of blood pressure in common iliac vein and limb overgrowth was observed. Limb enlargement was caused by muscle overgrowth, varicose veins formation and bone elongation. Arterio-venous fistula with proximal outflow limitation led to significant increase of femoral vein circumference and venous wall thickness. Our study indicates that the described rat model mimics major clinical features characteristic for the human Parkes Weber syndrome: presence of arterio-venous fistula, venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy. We reveal that limb overgrowth is caused by bone elongation, muscle hypertrophy, and venous dilatation. The newly established model will permit detailed studies on the mechanisms underlying the disease and on the efficacy of novel therapeutic strategies for the Parkes Weber syndrome treatment.

Vitamin K: The missing link to prostate health

Though age-related prostate enlargement is very common in Western societies, and the causes of benign prostate hyperplasia, BPH, have been diligently sought after, there is no biological, mechanistic explanation dealing with the root causes and progression of this very common disorder among men. All treatments to date are based on symptomatic relief, not a fundamental understanding of the cause of the disease. However, recent advances have shown that even subclinical varicoceles, which are more common than generally realized, cause retrograde blood flow from the testes past the prostate gland causing over a 130-fold increase in free testosterone in the veins near the prostate. By treating the varicoceles via embolization of the internal spermatic vein and its communicating and connected vessels the prostate enlargement can be reversed with corresponding symptomatic relief. So, varicose veins in the pampiniform venous plexus, varicoceles, are the direct cause of BPH. But what causes varicoceles?Recent research has uncovered the role of vitamin K in the calcification of varicose veins as well as a role in the proliferation of smooth muscle cells in the media layer of the vein wall. Vitamin K is intimately involved in the formation of varicose veins. The hypothesis is that poor prostate health is essentially a vitamin K insufficiency disorder. By providing vitamin K in the right form and quantity, along with other supporting nutrients and phytochemicals, it is likely that excellent prostate health can be extended much longer, and perhaps poor prostate health can be reversed. A protective role for vitamin K with respect to advanced prostate cancer was already found in the Heidelberg cohort of the EPIC study. This hypothesis can be further evaluated in studies examining the connection between vitamin K and varicoceles, and also by examining the connection between varicoceles and benign prostate hyperplasia. If this hypothesis is found to be true, management of prostate health will be radically altered. Rather than focusing on prostate health as a hormonal imbalance, prostate enlargement will be seen as a result of poor health of the veins in general and the internal spermatic veins in particular. Factors which promote the health of the veins will become a greater focus of research, including the role of vitamin K. Finally, the emerging understanding of the cause of BPH will empower men to take care of their bodies so they can enjoy much better health through their entire lifespan.