Phlebology: The Journal of Venous Disease

We report a retrospective analysis of venous malformation patients treated with percutaneous sclerotherapy, describing their clinical manifestations, therapeutic outcomes and procedural complications.

We reviewed our Vascular Anomalies database for all patients who underwent percutaneous sclerotherapy for venous malformation between January 2005 and July 2011 and retrieved 186 patients, out of which 116 were included in the final analysis. The majority of patients were treated using 100% alcohol (72%) and the rest were treated with <100% alcohol, Sodium Tetradecyl Sulfate or combination of these therapies. The most common location was the lower extremity in 67 patients (58%), followed by the head and neck in 27 (23%) and the upper extremity in 11 (9%). Retrospective review of medical records was performed. Outcomes were classified on an improvement scale based on clinical therapeutic effects.

Two-hundred and forty-five sclerotherapy procedures were performed in 116 patients, of which 52 patients (45%) underwent a single procedure, 32 (28%) had two procedures and 32 (28%) underwent ≥3 procedures. Median follow-up period from the last procedure was 2.5 months (interquartile range of 2.0 to 6.75 months). Significant improvement was seen in 37 patients (32%), moderate improvement in 31 (27%), mild improvement in 20 (17%), no improvement in 21 (18%) and worse than before in 7 (6%) patients. Major post-procedural complications were nerve injuries in 6 patients (5%), deep vein thrombosis in 5 (4%), muscle contracture in 2 (2%), infection in 3 (3%), skin necrosis in 4 (3%) and other complications in 3 (3%).

Our study demonstrated that 76% of our patients with venous malformation had some level of improvement in symptoms with majority (72%) undergoing only one or two percutaneous sclerotherapy procedure/s. Although major complications occurred in 20% of the patients, majority (74%) of the complications either resolved spontaneously or were successfully treated.

Although varicose veins are a common cause of morbidity, the UK National Health Service and private medical insurers have previously sought to ration their treatment in a non-evidence based manner in order to limit health-care expenditure and reimbursement. In July 2013, the UK National Institute for Health and Care Excellence published new national Clinical Guidelines (CG168) to promote evidence-based commissioning and management of varicose veins. The aim of this study was to evaluate the impact of CG168 on the referral and management of varicose veins at the Heart of England NHS Foundation Trust, Birmingham, UK.

Interrogation of a prospectively gathered database, provided by the Heart of England NHS Foundation Trust Performance Unit, of patients undergoing interventions for varicose veins since 1 January 2012. Patients treated before (group 1) and after (group 2) publication of CG168 were compared.

There were 253 patients, 286 legs (48% male, mean (range) age 54 (20–91) years) treated in group 1, and 417 patients, 452 legs, (46% male, mean (range) age 54 (14–90) years) treated in group 2, an increase of 65%. CG168 was associated with a significant reduction in the use of surgery (131 patients (52%) group 1 vs. 127 patients (30%) group 2, p = 0.0003, χ²), no change in endothermal ablation (30 patients (12%) group 1 vs. 45 patients (11%) group 2), a significant increase in ultrasound-guided foam sclerotherapy (92 patients (36%) group 1 and 245 patients (59%) group 2, p = 0.0001, χ²) and an increase in treatment for C2/3 disease (53% group 1 and 65.2% group 2, p = 0.0022, χ²).

Publication of National Institute for Health and Care Excellence CG168 has been associated with a significant increase (65%) in the number of patients treated, referral at an earlier (CEAP C) stage and increased use of endovenous treatment. CG 168 has been highly effective in improving access to, and quality of care, for varicose veins at Heart of England NHS Foundation Trust.

Patients with painful varicose veins and venous insufficiency can be treated by eliminating axial reflux only or by eliminating axial reflux plus phlebectomy with transilluminated powered phlebectomy. This study was undertaken with the aim of determining and improving signs and symptoms of venous disease (measured by venous clinical severity score) and complications (by routine surveillance ultrasound and long-term post-operative follow up) for each treatment strategy.

We performed a retrospective evaluation of prospectively collected data from 979 limbs undergoing procedures for significant varicose veins and venous insufficiency from March 2008 until June 2014 performed at a single tertiary referral hospital. Patient demographics, Clinical Etiology Anatomy and Pathophysiology classification, venous clinical severity scores pre- and post-procedure, treatment chosen, and peri-operative complications were collected; descriptive statistics were calculated and unadjusted surgical outcomes for patients stratified by the procedure performed. Multivariable logistic regression was used to evaluate the relationship between procedure type and thrombotic complications after adjusting for patient characteristics, severity of disease, pre-operative anticoagulation, and post-operative compression.

Venous clinical severity scores improved more with radiofrequency ablation + transilluminated powered phlebectomy as compared to radiofrequency ablation alone (3.8 ± 3.4 vs. 3.2 ± 3.1, p = 0.018). Regarding deep venous thrombosis, there was no significant difference between radiofrequency ablation + transilluminated powered phlebectomy vs. radiofrequency ablation alone. There was no statistical difference in asymptomatic endovenous heat-induced thrombosis or infection, although there were slightly more hematomas and cases of asymptomatic superficial thrombophlebitis with combined therapy. On multivariable analysis, only procedure type predicted thrombotic complications.

Ablation of axial reflux plus transilluminated powered phlebectomy produces improved outcomes as measured by venous clinical severity score, with slight increases in minor post-operative complications and should be strongly considered as initial therapy when patients present with significant symptomatic varicose veins and superficial venous insufficiency. Implementation of a standardized thromboprophylaxis protocol with individual risk assessment results in few significant thrombotic complications amongst high-risk patients, thus potentially obviating the need for routine post-operative duplex.

Venous thromboembolism is a common complex disorder, being the resultant of gene–gene and gene–environment interactions. Tumor necrosis factor-alpha is a proinflammatory cytokine which has been implicated in venous thromboembolism risk. A promoter 308G/A polymorphism in the tumor necrosis factor-alpha gene has been suggested to modulate the risk for venous thromboembolism. However, the published findings remain inconsistent.

In this study, we conducted a meta-analysis of all available data regarding this issue. Eligible studies were identified through search of Pubmed, EBSCO Medline, Web of Science, and China National Knowledge Infrastructure (CNKI, Chinese) databases up to June 2014. Pooled Odd ratios (ORs) with 95% confidence intervals were applied to estimating the strength of the genetic association in the random-effects model or fixed-effects model.

A total of 10 studies involving 1999 venous thromboembolism cases and 2166 controls were included in this meta-analysis to evaluate the association between tumor necrosis factor-alpha-308G/A polymorphism and venous thromboembolism risk. Overall, no significantly increased risk venous thromboembolism was observed in all comparison models when all studies were pooled into the meta-analysis. However, in stratified analyses by ethnicity, there was a pronounced association with venous thromboembolism risk among West Asians in three genetic models (A vs. G: OR = 1.82, 95%CI = 1.13–2.94; GA vs. GG: OR = 1.82, 95%CI = 1.08–3.06; AA/GA vs. GG: OR = 1.88, 95%CI = 1.12–3.16). When stratifying by source of controls, no significant result was detected in all genetic models.

This meta-analysis demonstrates that tumor necrosis factor-alpha 308G/A polymorphism may contribute to susceptibility to venous thromboembolism among West Asians. Studies are needed to ascertain these findings in larger samples and different racial groups.

Disordered programmed cell death may play a role in the development of superficial venous incompetence. We have determined the number of cells undergoing apoptosis and the alterations in the apoptotic level in the wall of different segments of the great saphenous varicose vein.

Twenty-one varicose great saphenous veins (VGSVs) (varicose group) and 12 normal great saphenous veins (GSVs) (control group) were collected, and the apoptosis level in the upper, middle, and lower segments were immunohistochemically stained with antibodies (anti-Bax and anti-Bcl-xl). Apoptosis was evaluated by the TUNEL assay and immunofluorescence staining. The morphology of apoptotic cells was observed with an electron microscope.

Quantitative analysis showed that the apoptotic ratios in venous walls (intima and media) of the varicose group were significantly lower than the corresponding regions in the control group (all P < 0.05). A significantly higher apoptotic rates of the venous walls was observed in control group within the upper compared with the lower segment (P < 0.05). Significantly higher positive proteins expression rates of Bcl-xl/Bax were also detected in the VGSVs compared with the GSVs within the three segments, respectively (P < 0.01). Electron microscopic observations confirmed that endothelial and smooth muscle cells in varicose and normal vein walls exhibited apoptotic morphologic features, such as fuzzy mitochondrial cristae, medullary changes, and margination of the nuclear chromatin.

VGSV walls were found to have a significant decrease in apoptotic rate compared with that of GSVs. The rate of apoptosis in the intima and media within the upper segment was increased more than the middle and lower segments in the GSVs. Our findings confirm that programmed cell death is down-regulated in primary varicose veins.

To investigate the association of polymorphisms located near the FOXC2 gene with the risk of varicose veins in ethnic Russians.

Allele, genotype, and haplotype frequencies were determined in the sample of 474 patients with primary varicose veins and in the control group of 478 individuals without a history of chronic venous disease.

Polymorphisms rs7189489, rs4633732, and rs1035550 showed the association with the increased risk of varicose veins, but none of the observed associations remained significant after correction for multiple testing. Haplotype analysis revealed the association of haplotype rs7189489 C–rs4633732 T–rs34221221 C–rs1035550 C–rs34152738 T–rs12711457 G with the increased risk of varicose veins (OR = 2.67, P = 0.01).

Our results provide evidence that the studied polymorphisms do not play a major role in susceptibility to varicose veins development in the Russian population.

To investigate venous histopathology of chronic venous insufficiency and varicose patients (C2).

Retrospective review of venous histopathology of 52 patients (13, 8, 2, and 28 were C2, C4, C5 and C6).

The intimal thickness, intimal fibrosis, total thickness and intimal/total thickness ratio were highest in venous clinical severity score 0, 1 chronic venous insufficiency (no or minimal varicosity) follow by Venous Clinical Severity Score 2,3 chronic venous insufficiency (trunkal varice) and C2 veins (mean intimal thickness 62, 36, 26 µm, mean intimal fibrosis 74%, 72%, 65%, mean total thickness 184, 159, 133 µm, mean intimal/total thickness ratio 0.32, 0.20, 0.21). The statistical significances were found when comparing intimal thickness, intimal fibrosis, intimal/total thickness ratio and total thickness of Venous Clinical Severity Score 0, 1 chronic venous insufficiency veins and C2 veins. The medial changes are relatively constant among groups.

Compared with C2 vein, the intimal changes in chronic venous insufficiency venous wall differ, particularly in the VCSS 0, 1 chronic venous insufficiency.

To prospectively compare disease severity in subjects with anterior accessory saphenous vein versus great saphenous vein incompetence with an incompetent saphenofemoral junction.

Data were^ collected from 241 subjects and 290 limbs over a six-month period. These subjects were categorized into three groups with primary venous reflux disease, namely anterior accessory saphenous vein, great saphenous vein, and control. Statistical methods including descriptive statistics, student t-tests, and log linear modeling were employed to compare groups and determine predictive features out of the 41 demographic and disease-specific variables collected.

Subjects in the anterior accessory saphenous vein group and those in the great saphenous vein group demonstrate statistically significant differences as compared to the control group with respect to the following disease-specific features: mean VCSS, presence of C2 and C3 disease. The anterior accessory saphenous vein group also showed statistically significant differences in gender compared to both great saphenous vein and control, as well as mean body mass index compared to the control. Log-linear modeling revealed equivalent disease severity when comparing patients with saphenofemoral junction reflux to the great saphenous vein or anterior accessory saphenous vein.

Patterns of reflux from the saphenofemoral junction to either the anterior accessory saphenous vein or great saphenous vein possess similar disease severity and commonly suffer complications of venous stasis.

[Please check the following sentence for clarity: “Point-of-care devices measuring international normalized ratio have clinical appeal, reports of ‘off-label’ in-hospital/primary care use report improved time to intervention/dose adjustment.”]Point-of-care devices measuring international normalized ratio have clinical appeal, reports of ‘off-label’ in-hospital/primary care use report improved time to intervention/dose adjustment. We evaluated the accuracy and precision of a device for such multiple patient use compared to a reference laboratory.

The point-of-care international normalized ratio result of patients on oral anticoagulation at the Vascular Surgery clinic was compared to the reference to check for statistical and clinical correlation. This was a prospective case–control study design with sample size calculated for sensitivity of 87.5%, precision 5% and desired confidence level 95%.

There were 168 patients tested; 55% were male, the mean age was 45.4. Sixty per cent were in the target international normalized ratio range. Tests were done for statistical and clinical correlation. The international normalized ratio range using the point-of-care device was 0.8–7.5 (reference lab 0.8–10), mean international normalized ratio was 2.22 ± 1.6 (point-of-care device) compared to 2.46 ± 1.3 (reference lab). The mean absolute difference was 0.79 ± 0.92 and the mean relative difference was 8.1% ± 1.03. Data was analysed using a Bland–Altman plot yielding a mean of 0.738 (standard deviation 0.92). Concordance between the tests was 75% with r2 = 0.52 on linear regression. Using an error grid plot, excellent clinical correlation was seen in 63.8%. In 5.4% major corrective action was needed but potentially missed if relying on the point-of-care device.

The accuracy and precision of this point-of-care device is moderate. It may have potential utility only where access to a reference lab is difficult.