Month: July 2023

Background: Primary avalvular varicose anomalies (PAVA) are found in 4.6% patients with primary varicose veins and can be confused with neovascular tissue. These veins can be found in all compartments of the leg and are found more commonly in patients with pelvic venous reflux. Little is known about these atypical vessels and so we are reporting the histopathologic features of PAVA compared to a typical varicosity.

Methods: A section of PAVA was removed under ultrasound guidance from a patient undergoing routine endovenous thermoablation for varicose veins, along with several varicosities extracted by phlebectomy. Venous tissue was fixed in buffered formalin and underwent routine histological processing into paraffin wax. Sections were cut 4 microns thick and were stained with haematoxylin and eosin (H&E), Martius Scarlett Blue (MSB) and immunohistochemical staining for smooth muscle actin (SMA). Stained sections were examined by a board-certified pathologist.

Results: PAVA showed distinct differences from “normal” varicose veins. There were multiple protrusions into the lumen of the abnormal vessel, due to an irregularly enlarged media. The media was rich in collagen and there was a reduction in the smooth muscle cells found circumferentially throughout the media and adventitia. Varicosities removed by phlebectomy appeared normal, with all three tunicae clearly visible.

Conclusions: Although the samples only came from one patient, they showed clear differences histologically PAVA and “normal” varicose venous tissue. This early report needs to be confirmed in a larger sample of patients and more work is needed to understand the exact derivation of PAVA.

Whiteley, M. S., Bankowska, A., Santos, S. J. D., Ashpitel, H. F., & Salguero-Bodes, F. J. (2023, April 10). Histopathological and immunohistochemical investigation of primary avalvular varicose anomalies (PAVA) in a patient with primary varicose veins and PAVA. https://doi.org/10.31219/osf.io/ej8ha

Introduction: Endovenous thermal ablation (EVTA) is the first line treatment of symptomatic truncal venous reflux. Linear Endovenous Energy Density (LEED) is the measure of energy used per cm of treated vein. The rate of application of energy influences thermal spread and tissue damage. However, time is absent from LEED. The aim of this study was to test the effect of time during EVTA in a validated in-vitro model.

Methods: We used a bipolar radofrequency catheter and the previously validated porcine liver model to assess any thermal effects. We used combinations of power and pullback speeds giving LEEDs of 40, 60, 80 and 100 J/cm. High-resolution digital images of the ablation tracts were taken. Each setting was repeated 5 times. Thermal spread was measured using digital measuring software, tissue carbonisation assessed by a defined scale and any device-tissue sticking during treatment was recorded.

Results: LEED was significantly positively correlated to thermal spread (r(20) = .86, P < .00001) and carbonisation of the tissue (r(24) = .82, p < .00001). Power was significantly correlated with carbonisation (r(24) = .50, p = .009) but not with thermal spread (r(20) = .34, p = .121). Pullback had no significant correlations with thermal spread or carbonisation. Catheter sticking was only found when the power was >= 15 W or the LEED was >= 80 J/cm.

Conclusion: LEED is a good measure of EVTA but does not take into account the time of energy application to tissue. Power, which does include time, has a significant correlation with tissue carbonisation, and is also important in device-tissue sticking. Pullback has no significant correlation to any tissue effects. Quoting the LEED alone in reporting EVTA is inadequate. It is essential to include the power used when LEED is quoted.

Nielsen, A. G., Croucher, A. A., Muschamp, S. D., Losty, E., Worthington, T., Kiely, M. J., & Whiteley, M. S. (2022, November 24). Linear Endovenous Energy Density (LEED) Should Always be Quoted with the Power Used, in Endovenous Thermal Ablation – Results from an In-Vitro Porcine Liver Model Study. https://doi.org/10.31219/osf.io/v8znr

A description of the changes in the management of superficial venous disease that have occurred in the first two decades of the 21st century are explored. A brief overview of traditional techniques prior to this evolution is also described. Special focus is placed upon the treatment of difficult recurrent venous disease. Newer innovations at the time of writing are mentioned and their possible applications for future development suggested.

Price, B. A. (2023, February 20). The Evolution of the Treatment of Varicose Veins in the 21st Century. https://doi.org/10.31219/osf.io/5ph7g

Aims: Pelvic vein embolisation is the recognised treatment for symptomatic pelvic vein reflux. There is a requirement to ablate incompetent pelvic veins without using an implantable device. The aim of this study was to assess the use of the Clarivein® device as a potential method of ablating incompetent pelvic veins.

Methods: An ovine model was employed that utilised a freshly euthanased female adult sheep (ewe). At post-mortem examination, the ovarian veins were identified on each side. A Clarivein® catheter was then introduced directly into both right and left ovarian veins proximally and passed caudally. The device was activated and withdrawn at 7sec/cm. The same methodology was used in a nearby retro-peritoneal mesenteric vein for comparison.

Results: In the ewe, the distal ovarian veins lie in a peritoneal fold similar to the broad ligament in the human. In this area, the vein is relatively unsupported compared to the ovarian vein trunk which is retroperitoneal, but lying on the posterior abdominal wall. In the unsupported section, the vein rotated instantly with the wire, entangling itself and ensnaring the device. However, the mesenteric vein that lay directly on the posterior abdominal wall allowed passage and treatment by the rotating wire, without any ensnaring of the device.

Conclusion: The rotation of the Clarivein® wire tip requires the vein to have sufficient supporting tissue to resist being rotated with the wire, becoming entangled with the device. This was not found in the pelvic veins lying within the peritoneal folds around the ovaries, but was found in retroperitoneal veins lying on the posterior abdominal wall. This suggests that the Clarivein® catheter should not be used in pelvic varicosities, but there might be a place for this or similar devices to treat retroperitoneal veins that are held against the abdominal or pelvic wall by the parietal peritoneum.

Whiteley, M. S., Nemchand, J. L., La Ragione, R. M., & Beckett, D. (2023, June 21). Clarivein® might have a role in the treatment of truncal pelvic vein reflux, but not in the treatment of pelvic varicosities – results from an ovine model. https://doi.org/10.31219/osf.io/byfvg

Introduction: High Intensity Focused Ultrasound (HIFU) is a new extra-corporeal, non-invasive thermoablative technique to treat superficial venous incompetence in leg veins, which left untreated can cause symptomatic varicose veins and venous leg ulcers. To date, there is limited data surrounding the treatment outcomes of HIFU. This study aims to show the 1-year results of using HIFU, using the first CE marked HIFU machine for the treatment of varicose veins (Theraclion, Paris, France).

Method: Patients were treated with the HIFU machine with pulses of either 4 or 8 seconds. This study includes 51 patients, and 79 legs, with 43 truncal veins and 146 incompetent perforator veins. Patients were invited back for scans 1-2 weeks, 6-8 weeks, 6 months and 1 year after their treatment to identify the technical success rate of the HIFU treatment. No patients underwent phlebectomy, either at the time of HIFU treatment nor subsequently. Those patients with residual varicosities were treated with foam sclerotherapy as an adjunctive treatment.

Results: Twenty-four patients who had truncal veins treated with HIFU returned at 1 year. Successful ablation of the target vein was found in 79.1%. The 1-year results for the treatment of incompetent perforator veins with HIFU was 84.5%, out of 71 scanned 1 year after treatment. The overall percentage success decreased slightly between 1-2 weeks post-treatment and 1-year post-treatment.

Conclusion: The results produced by HIFU are similar to those of early EVTA. Some patients had adjunct ultrasound guided foam sclerotherapy to residual varicosities. The percentage success is expected to increase with experience and improved technology provided by the later generation machines.

Whiteley, M. S., Kiely, M. J., Croucher, A. A., Taylor, L., Hughes, B. E., Josserand, E., & Abu-Bakr, O. (2022, October 24). One-year results of treatment of incompetent truncal veins and incompetent perforators using 8 and 4 second pulses of High Intensity Focused Ultrasound (HIFU). https://doi.org/10.31219/osf.io/fzc5k

Objective To identify the effects of patient risk factors and pelvic venous reflux (PVR) patterns on treatment outcomes of Pelvic Vein Embolisation (PVE) for Pelvic Congestion Syndrome (PCS).

Methods We performed a retrospective cohort review assessing population, intervention, comparison and outcomes (PICO) for women undergoing PVE for PCS January 2017–January 2021. We identified 190 patients who had completed both questionnaires and who had given consent for their information to be used for research (Median age 46, IQR 40-52) – 110.The distribution of pathological pelvic venous reflux found on transvaginal duplex ultrasound (TVDUS) was analysed for all patients. Pre- and post-procedure symptom burden scores were studied using a standardised questionnaire protocol. We used inferential univariate non-parametric statistics to describe our data.

Results 190 cases were reviewed; 62.6% (119/190) premenopausal, 11.1% (21/190) perimenopausal and 25.3% (48/190) postmenopausal; 10.1% (19/188) nulliparous. There was a statistically significant improvement in all symptoms and the appearance of varicosities on TVDUS post-PVE (p<0.05). The locations of veins requiring embolisation were analysed; 82.8% (154/186) required embolisation of at least one internal iliac vein tributary and ovarian vein embolisation. Age, parity, menopausal status and previous laparoscopy did not affect symptom improvement (p>0.05). No significant complications were identified.

Conclusions PVE is an effective treatment for pelvic pain due to PCS. Our results highlight the importance of internal iliac vein reflux as an important predictor in diagnosis and management. PCS should not be limited as a diagnosis for multiparous women of childbearing age as a significant proportion of patients who benefited from PVE were either nulliparous and/or postmenopausal.

Strong, S. M., Cross, A. C., Sideris, M., & Whiteley, M. S. (2022, November 14). Pelvic Congestion Syndrome affects nulliparous and post-menopausal women, and the treatment of internal iliac vein reflux is critical: A retrospective cohort study looking at treatment outcomes following Pelvic Vein Embolisation. https://doi.org/10.31219/osf.io/9g3yb

Objectives: Endovenous thermal ablation (EVTA) is the first-line treatment for varicose veins. Many in-vitro models have been made to study the effects of EVTA on the vein wall. Models using explanted human great saphenous vein (GSV) use anticoagulated blood passed into the vein during treatment, either static or being pumped to simulate “physiological flow”. The objective of this study was to investigate whether there is any evidence that there is actually any blood in GSVs being treated by EVTA.

Methods: 9 consecutive patients (11 GSV’s) had their intraluminal GSV diameters measured with ultrasound on standing, lying, 10° head down (Trendelenburg position) and 10° head down with tumescence and an endovenous laser device within the vein. The size of the vein lumen was noted and the vein interrogated longitudinally with colour duplex ultrasound to look for any venous flow.

Results: There was a progressive reduction of luminal diameter from standing to lying 10° head down. When 10° head down with a 4FG endovenous laser device in position and tumescence around the vein, 10 of the 11 GSVs showed no lumen at all and 1 showed a very minor “out-pouching” on one side of the device at one level, which did not communicate with any lumen above or below, and showed no flow.

Results: There was a progressive reduction of luminal diameter from standing to lying 10° head down. When 10° head down with a 4FG endovenous laser device in position and tumescence around the vein, 10 of the 11 GSVs showed no lumen at all and 1 showed a very minor “out-pouching” on one side of the device at one level, which did not communicate with any lumen above or below, and showed no flow.

Whiteley, M. S., & Fernandez-Hart, T. J. (2023, April 4). Veins undergoing endovenous thermal ablation have little or no blood intra-luminally casting doubt on the results of many ex-vivo vein ablation studies. https://doi.org/10.31219/osf.io/vef4m

Background: Sclerotherapy is used widely for the treatment of varicose veins. Little has been written on the mechanism of action of detergent sclerosants on the vein wall, and very little on osmotic sclerosants. We compared the damage profile inflicted by a detergent sclerosant (3% Sodium Tetradecyl Sulphate (3% STS)) to that of an osmotic sclerosant (70% dextrose) using explanted human veins.

Methods: Ten varicose vein samples were harvested during routine phlebectomy surgery. Each sample was divided into three segments that were treated for two minutes with (1) normal saline (control), 3% STS, or 70% dextrose. Treated samples were incubated for 24 hours (37℃, 5% CO2), fixed in buffered formalin, paraffin embedded, and sectioned for staining with haematoxylin and eosin (H&E) and immunohistochemical (IHC) markers (caspase-3 (C3), smooth muscle actin (SMA), and CD31).

Results: Both sclerosants produced cell death deep to the endothelium and into the tunica media of the vein. However, 3% STS exerted a significantly greater damage profile than 70% dextrose across all layers, destroying 75% more endothelial cells (P<0.0001) and 30-33% more smooth muscle cells across the tunica media (P<0.01). Efficacy of 70% dextrose in damaging peripheral cells of the tunica media was poor. Patterns of IHC reactivity were consistent with damage observed in H&E-stained sections. Minimal C3 reactivity was detected, and necrosis was the observed cell-death rather than apoptosis in all treated samples.

Conclusion: Despite 3% STS showing more efficacy than 70% dextrose in extent and penetration of damage inflicted, both treatments were efficacious in inducing transmural cell death in this ex-vivo study. Therefore, 70% dextrose may be more appropriate for the ablation of thinner-walled veins, and 3% STS for thicker walled veins. In addition, the observation of necrotic cell death challenges the previously reported mechanism of apoptosis after sclerotherapy.

Cross, A. C., Walker, K., Setyo, L., Borkowski, E. A., La Ragione, R. M., & Whiteley, M. S. (2022, November 11). Comparison of detergent and osmotic sclerotherapy agent action on ex-vivo human vein – a histological and immunocytochemical analysis. https://doi.org/10.31219/osf.io/kgd27

Background: Catheter-based endovenous thermal ablation (EVTA) under tumescent anaesthesia is the standard treatment for truncal venous reflux. Doctors often use vein diameter alone to select treatment settings and protocols. Adequate venous ablation requires thermal energy to penetrate the vein wall deeply and probably transmurally. Hence the thicker the vein wall when constricted during treatment, the deeper the required thermal penetration. We constructed a mathematical model to predict vein wall thickness (VWT) during EVTA of veins of different diameters, initial wall thicknesses and device diameters.

Methods: A mathematical model was constructed under the simplifying assumptions that the vein is a perfect circle, that the wall has a constant volume and that it constricts uniformly without folding. A set of representative vein diameters and thicknesses, and common device diameters were applied to the model to study the variables.

Results: Numerical analysis predicted that vein walls would thicken when constricted compared to their initial state. Veins that initially had thicker walls and larger diameters, had thicker walls when constricted than thin walled or small diameter veins, using the same size EVTA devices. For each vein, as the diameter of the device decreased, the constricted VWT increased. Sensitivity analysis of the variables affecting the constricted VWT revealed that the initial VWT was most important, followed by device diameter and finally initial diameter of the vein.

Conclusion: Our model shows that for a range of vein sizes and wall thicknesses, the constricted VWT increases markedly with decreasing device size. Although doctors often use vein diameter to select treatment parameters, this model suggests that initial VWT followed by the size of EVTA device are more important variables. Furthermore, the current trend to make EVTA devices thinner may be disadvantageous, as this increases the constricted VWT at treatment, making adequate thermal penetration harder to achieve.

Fernandez-Hart, T. J., Santos, S. J. D., & Whiteley, M. S. (2023, April 10). Vein wall thickness (VWT) and catheter size are more important than vein diameter in optimising endovenous thermal ablation (EVTA) – results of a mathematical model of how VWT changes when veins constrict under tumescence. https://doi.org/10.31219/osf.io/ptfka