The Incidence and Characteristics of Pelvic-Origin Varicosities in Patients with Complex Varices Evaluated by Ultrasonography.

OBJECTIVE: The purpose of this study was to evaluate the incidence of gonadal vein refluxes associated with lower-extremity varicose veins with Doppler ultrasonography (DUS). METHOD: A total of 6279 patients with venous disease-related symptoms of the lower extremity were evaluated with DUS in the vascular lab. Gonadal vein reflux using abdominal ultrasound was further evaluated in patients with unusual varices, defined as varices in the inguinal, inner or upper thigh and the vulvar area without refluxes in the saphenofemoral junction (SPJ). Those patients who showed gonadal vein reflux were diagnosed as having pelvic-origin varicosity. RESULTS: Unusual varices were found in a total of 237 patients (3.8%), and of these patients, pelvic-origin varicosity was discovered with transabdominal ultrasound in 156 (65.8%). A total of 66.7% (n = 38/57) of unusual varix patients with pelvic pain had gonadal vein reflux. The measurement of gonadal vein diameter was larger in ultrasonography than CT scans (8.835 vs. 8.81, p < 0.001). Two patients with severe symptoms but no obstructive venous diseases were treated with gonadal vein embolization. CONCLUSION: The incidence of pelvic-origin varicosities was 2.5% (n = 156/6279). However, more than half of the patients with unusual varices had gonadal vein reflux and 24.4% of these patients also presented with pelvic pain. The evaluation of pelvic-origin varicosities should be performed in patients who present with unusual forms of varices of the lower extremity.

The particularities of connective fibers from the wall of varicose veins extirpated by cryostripping.

INTRODUCTION: The varicose vein affects more than 30% of the general population. Significantly increased rates were noticed in women and older population. From the histopathological point of view, venous arterialization, smooth muscle cell hypertrophy, and hyperplasia are the main changes noticed in varicose vein disease. Some of the main therapeutic methods used in the management of varicose disease are injection sclerotherapy, conservative, surgical, saphenous vein inversion and removal, high saphenous ligation, ambulatory phlebectomy, transilluminated powered phlebectomy, endovascular management, cryostripping. AIM: The aim of this study was to evaluate the morphology of connective fibers from the wall of the varicose veins extirpated by cryostripping. PATIENTS, MATERIALS AND METHODS: The study included 109 samples taken by cryostripping method. Hematoxylin-Eosin, Masson's trichrome, Silver and Orcein staining were applied. The assessment of fibers was made according to score values between 0 and 3. RESULTS: It was found no major structural differences in terms of alterations of collagen fibers induced by the applied surgical procedure. It was noticed duplications and multiplications of the internal elastic lamina, as diffuse and nodular forms. Depletion of elastic fibers at the media was a lesion identified in most of the specimens. The depletion of reticulin fibers correlates with the accumulation of collagen fibers, which partially or completely replace the network in the media and intima. No correlation was found between changes in the reticulin network and the time between prelevation and buffered formalin fixation, the maximum time investigated being five days. CONCLUSIONS: The Orcein staining in the venous vessel evaluation panel may be a useful investigation.

A comparative analysis of deep learning and hybrid iterative reconstruction algorithms with contrast-enhancement-boost post-processing on the image quality of indirect computed tomography venography of the lower extremities.

PURPOSE: To examine whether there is a significant difference in image quality between the deep learning reconstruction (DLR [AiCE, Advanced Intelligent Clear-IQ Engine]) and hybrid iterative reconstruction (HIR [AIDR 3D, adaptive iterative dose reduction three dimensional]) algorithms on the conventional enhanced and CE-boost (contrast-enhancement-boost) images of indirect computed tomography venography (CTV) of lower extremities. MATERIALS AND METHODS: In this retrospective study, seventy patients who underwent CTV from June 2021 to October 2022 to assess deep vein thrombosis and varicose veins were included. Unenhanced and enhanced images were reconstructed for AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images were obtained using subtraction software. Objective and subjective image qualities were assessed, and radiation doses were recorded. RESULTS: The CT values of the inferior vena cava (IVC), femoral vein ( FV), and popliteal vein (PV) in the CE-boost images were approximately 1.3 (1.31-1.36) times higher than in those of the enhanced images. There were no significant differences in mean CT values of IVC, FV, and PV between AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images. Noise in AiCE, AiCE-boost images was significantly lower than in AIDR 3D and AIDR 3D-boost images ( P < 0.05). The SNR (signal-to-noise ratio), CNR (contrast-to-noise ratio), and subjective scores of AiCE-boost images were the highest among 4 groups, surpassing AiCE, AIDR 3D, and AIDR 3D-boost images (all P < 0.05). CONCLUSION: In indirect CTV of the lower extremities images, DLR with the CE-boost technique could decrease the image noise and improve the CT values, SNR, CNR, and subjective image scores. AiCE-boost images received the highest subjective image quality score and were more readily accepted by radiologists.

[Two Cases of Bleeding from the Ileal Conduit Due to Ectopic Varices].

Case 1 : A 75-year-old man was emergently admitted to our hospital with a complaint of continuous bleeding from the ileal conduit. The conduit was constructed by a total pelvic resection for sigmoid colon cancer that invaded the urinary bladder 24 years ago. Swollen cutaneous mucosa was seen around the ileal conduit, but no obvious bleeding spot was observed. The contrast-enhanced computed tomographic (CT) scan and 3D visualization revealed varices extending to the abdominal wall. Percutaneous transhepatic embolization successfully stopped the bleeding, but it was needed again after two years. Case 2 : A 72-yearold man with a history of open cystectomy and ileal conduit for bladder cancer came to our hospital two years after the surgery, complaining of continuous bleeding from the conduit. The skin around the stoma site was discolored purple, but no obvious bleeding site or bloody urine was observed. The CT scan similar to Case 1 revealed varices in the ileal conduit, and percutaneous transhepatic embolization successfully stopped the bleeding, but it was needed again after five months. After that, three months passed without recurrence.

Interventional Radiology for Bleeding Ectopic Varices: Individualized Approach Based on Vascular Anatomy.

Ectopic varices are rare but potentially life-threatening conditions usually resulting from a combination of global portal hypertension and local occlusive components. As imaging, innovative devices, and interventional radiologic techniques evolve and are more widely adopted, interventional radiology is becoming essential in the management of ectopic varices. The interventional radiologist starts by diagnosing the underlying causes of portal hypertension and evaluating the afferent and efferent veins of ectopic varices with CT. If decompensated portal hypertension is causing ectopic varices, placement of a transjugular intrahepatic portosystemic shunt is considered the first-line treatment, although this treatment alone may not be effective in managing ectopic variceal bleeding because it may not sufficiently resolve focal mesenteric venous obstruction causing ectopic varices. Therefore, additional variceal embolization should be considered after placement of a transjugular intrahepatic portosystemic shunt. Retrograde transvenous obliteration can serve as a definitive treatment when the efferent vein connected to the systemic vein is accessible. Antegrade transvenous obliteration is a vital component of interventional radiologic management of ectopic varices because ectopic varices often exhibit complex anatomy and commonly lack catheterizable portosystemic shunts. Superficial veins of the portal venous system such as recanalized umbilical veins may provide safe access for antegrade transvenous obliteration. Given the absence of consensus and guidelines, a multidisciplinary team approach is essential for the individualized management of ectopic varices. Interventional radiologists must be knowledgeable about the anatomy and hemodynamic characteristics of ectopic varices based on CT images and be prepared to consider appropriate options for each specific situation. ©RSNA, 2024 Supplemental material is available for this article.

Ultrasound assessment of the risk of venous thromboembolic complications in thrombosis of varicose transformed tributaries of the great saphenous vein.

OBJECTIVE: Aim: To evaluate the ultrasound criteria for venous thromboembolic complications in patients with thrombosis of varicose veins of the tributaries of the great saphenous vein (GSV). PATIENTS AND METHODS: Materials and Methods: The results of ultrasound examination of 52 patients with thrombosis of varicose veins of the tributaries of GSV were analyzed. The indicators of venous hemodynamics were compared with the control group (CG) (n=32). RESULTS: Results: Varicose transformation of GSV and failure of its valvular apparatus were detected in 44 (84.6%) patients, in 8 (15.4%) patients the superficial venous highway was intact. Vertical reflux was diagnosed in varicose ectasia of GSV: local reflux in 14 (31.8%), widespread reflux in 14 (31.8%), and total reflux in 16 (36.4%) patients. The diameter of GSV in tributary varicothrombophlebitis was 8.9±0.27 mm (p<0.05 vs. CG) and 11.2±0.25 mm (p<0.05 vs. CG) in the horizontal and vertical positions, respectively. The proximal and distal borders of thrombosis exceeded the clinical ones by 15.26±1.21 cm (p<0.05) and 7.94±1.32 cm (p<0.05), respectively. The spread of tributary thrombophlebitis to the superficial venous highway was detected in 14 (26.9%) patients, among whom 12 (85.7%) patients had unfixed apices of thrombotic masses. CONCLUSION: Conclusions: The results obtained convincingly demonstrate the need for early ultrasound examination of patients with tributary thrombophlebitis, which allows to identify the real limits of the thrombotic process, timely diagnose the transition of the thrombotic process to superficial and deep venous lines, effectively predict the risk of venous thromboembolic complications and choose the optimal surgical tactics.

Exome sequencing identifies novel genetic variants associated with varicose veins.

BACKGROUND: Varicose veins (VV) are one of the common human diseases, but the role of genetics in its development is not fully understood. METHODS: We conducted an exome-wide association study of VV using whole-exome sequencing data from the UK Biobank, and focused on common and rare variants using single-variant association analysis and gene-level collapsing analysis. FINDINGS: A total of 13,823,269 autosomal genetic variants were obtained after quality control. We identified 36 VV-related independent common variants mapping to 34 genes by single-variant analysis and three rare variant genes (PIEZO1, ECE1, FBLN7) by collapsing analysis, and most associations between genes and VV were replicated in FinnGen. PIEZO1 was the closest gene associated with VV (P = 5.05 × 10-31), and it was found to reach exome-wide significance in both single-variant and collapsing analyses. Two novel rare variant genes (ECE1 and METTL21A) associated with VV were identified, of which METTL21A was associated only with females. The pleiotropic effects of VV-related genes suggested that body size, inflammation, and pulmonary function are strongly associated with the development of VV. CONCLUSIONS: Our findings highlight the importance of causal genes for VV and provide new directions for treatment.

Deep vein thrombosis after sclerotherapy and endovenous laser ablation of varicose veins - an observational study.

Background: The risk of developing deep vein thrombosis (DVT) after endovenous ablation of varicose veins varies in the literature. Little is known about the characteristics of this complication and associated factors. This study aimed: 1) to study the occurrence of DVT after ultrasound-guided foam sclerotherapy (UGFS) alone or combined with endovenous laser ablation (EVLA) for lower-limb varicose veins; 2) to identify factors associated with DVT. Patients and methods: The study included all outpatients aged 18 years or older who underwent UGFS and EVLA or UGFS alone at the University Hospital of Zurich between 2011 and 2015. Data were extracted from the hospital electronic medical record. Patients were surveyed about their level of pain after the procedure and their level of satisfaction with the procedure. Duplex ultrasound was used to assess the deep venous system 7-10 days and 6-8 months after the procedure. Regression analysis was used to examine the association of patient and procedure characteristics with the development of DVT. Results: A total of 334 patients (561 procedures performed in 393 different sessions) were included: 73% of the patients underwent combined UGFS and EVLA and 27% underwent UGFS alone. DVT occurred in 24 (7.2%) patients, of whom 88% underwent combined procedures and 17% underwent interventions involving both the great and small saphenous veins on the same session. DVT occurred in 8.2% of patients receiving thromboprophylaxis and in 9.5% of patients not receiving thromboprophylaxis. DVT occurred in 5.2% of women and 11.9% of men. No factors associated with a diagnosis of DVT after intervention were identified. Pain and satisfaction levels did not differ between patients with and without DVT. Conclusions: This study adds to the knowledge of the risk of DVT following UGFS alone or combined with EVLA. Further studies are needed to revise thromboprophylaxis.

Quantitative evaluation of lower limb varicose veins using photoacoustic imaging.

PURPOSE: Varicose veins in the lower extremities are dilated subcutaneous varicose veins with a diameter of ≥ 3 mm, caused by increased venous pressure resulting from backflow of blood due to venous valve insufficiency (Gloviczki in Handbook of venous disorders: guidelines of the American venous forum, Hodder Arnold, London, 2009). When diagnosing varicose veins, the shape and thickness of the blood vessels should be accurately visualized in three dimensions. In this study, we investigated a new method for numerical evaluation of vascular morphology related to varicose veins in the lower extremities, using a photoacoustic imaging (PAI) system, which can acquire high-resolution and three-dimensional images noninvasively. METHODS: Nine patients with varicose veins participated in the study, and their images were captured using an optical camera and PAI system. We visualized the vascular structure, created a blood presence density (BPD) heat map, and examined the correlation between BPD and location of varicose veins. RESULTS: The obtained photoacoustic (PA) images demonstrated the ability of this method to visualize vessels ranging from as small as 0.2 mm in diameter to large, dilated vessels in three dimensions. Furthermore, the study revealed a correlation between the high-density part of the BPD heat map generated from the PAI images and the presence of varicose veins. CONCLUSION: PAI is a promising technique for noninvasive and accurate diagnosis of varicose veins in the lower extremities. By providing valuable information on the morphology and hemodynamics of the varicose veins, PAI may facilitate their early detection and treatment.

Radio-pathologic correlation: no pial angioma-subarachnoid varicose network drainage pathway in Sturge-Weber syndrome.

PURPOSE: The traditional imaging findings reported in Sturge-Weber syndrome (SWS) include endpoints of cortical injury-cortical atrophy and cortical calcifications-but also what has been termed a "leptomeningeal angiomatosis," the latter recognized and reported as a leptomeningeal enhancement on magnetic resonance imaging (MRI). The objective of this study is to demonstrate through neuropathological correlation that the "leptomeningeal angiomatosis" in patients with Sturge-Weber syndrome (SWS), represents a re-opened primitive venous network in the subarachnoid space that likely acts as an alternative venous drainage pathway, seen separately to abnormal pial enhancement. MATERIALS AND METHODS: Retrospective review of MR imaging and surgical pathology of patients that underwent surgery for epilepsy at a tertiary, children's hospital. A pediatric radiologist with more than 20 years of experience reviewed the MR imaging. Surgically resected brain specimens that had been sectioned and fixed in 10% paraformaldehyde for histologic processing, following processing and paraffin embedding, were cut into 5-µm unstained slides which were subsequently stained with hematoxylin and eosin (H&E). Slides were re-examined by a board-certified pediatric neuropathologist, and histologic features specifically relating to cerebral surface and vascularity were documented for correlation with MR imaging of the resected region performed prior to resection. RESULTS: Five patients were reviewed (3 boys and 2 girls; the median age at the onset of seizures was 12 months (IQR, 7 to 45 months); the median age at surgery was 33 months (IQR, 23.5 to 56.5 months)). Surgical procedures included the following: 4, hemispherotomy (right: 2, left: 2) and 1, hemispherectomy (right). A subarachnoid space varicose network was present on both MRI and histology in 4 patients. Calcifications were seen on both MRI and histology in 3 patients. Abnormal leptomeningeal enhancement was present in 5 patients and seen separately from the subarachnoid vascular network in 4 patients. CONCLUSION: Histopathology confirmed the MRI findings of a subarachnoid space varicose network seen separately from leptomeningeal enhancement and presumed to represent an alternative venous drainage pathway to compensate for maldevelopment of cortical veins, the primary abnormality in SWS. No pial-based angioma was identified.

Factors associated with clinical severity in chronic venous disease: The role of functional parameters.

INTRODUCTION: Chronic venous disease (CVD) is a highly prevalent disease that presents a wide spectrum of clinical expressions due to abnormalities in the venous system. Patients often have major functional changes that can limit daily activities. However, the functional factors associated with the severity of the disease remain poorly understood. OBJECTIVE: To identify the functional factors associated with CVD severity. METHODS: Seventy-five patients with CVD (92.0% females, 49.6 ± 13.3 years) were evaluated through clinical examination, lower limb perimetry, ankle range of motion (AROM), and lower limb muscle strength by the Heel Rise test, and Sit-to-stand test. Patients were stratified according to the disease severity as mild (telangiectasia, varicose veins, or edema in the lower limbs) or severe CVD (trophic changes or venous ulcer). RESULTS: Patients with severe CVD (n = 13) were older (p = 0.002), predominantly male (p = 0.007), with reduced AROM in dorsiflexion (p = 0.028) and inversion (p = 0.009), reduced lower limb strength by the Heel Rise test (p = 0.040), and greater circumference of the calf (p = 0.020), ankle (p = 0.003), and plantar arch (p = 0.041) when compared to mild CVD (n = 62). Advanced age, male sex, lower ankle range of motion in dorsiflexion, and greater ankle and plantar arch circumferences were associated with CVD severity. However, the ankle circumference (OR 1.258, 95% CI: 1.008-1.570; p = 0.042), together with advanced age and male sex, was the only functional variable that remained independently associated with CVD severity. CONCLUSION: The increased ankle circumference was a determinant of the CVD severity and may assist in risk stratification and guide treatment goals in this population.

Key Regulators of Angiogenesis and Inflammation Are Dysregulated in Patients with Varicose Veins.

Varicose veins (VVs) are the most common manifestation of chronic venous disease (CVD) and appear as abnormally enlarged and tortuous superficial veins. VVs result from functional abnormalities in the venous circulation of the lower extremities, such as venous hypertension, venous valve incompetence, and venous reflux. Previous studies indicate that enhanced angiogenesis and inflammation contribute to the progression and onset of VVs; however, dysregulations in signaling pathways associated with these processes in VVs patients are poorly understood. Therefore, in our study, we aimed to identify key regulators of angiogenesis and inflammation that are dysregulated in patients with VVs. Expression levels of 18 genes were analyzed in peripheral blood mononuclear cells (PBMC) using real-time PCR, as well as plasma levels of 6 proteins were investigated using ELISA. Higher levels of CCL5, PDGFA, VEGFC, TGF-alpha, TGF-beta 1, and VEGF-A, as well as lower levels of VEGFB and VEGF-C, were found to be statistically significant in the VV group compared to the control subjects without VVs. None of the analyzed factors was associated with the venous localization of the varicosities. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors in PBMC and plasma from VVs patients, providing new insight into molecular mechanisms that could contribute to the development of VVs and point out promising candidates for circulatory biomarkers of this disease.

Varicose Vein Education and Informed coNsent (VVEIN) Study: A Randomized Controlled Pilot Feasibility Study.

BACKGROUND: The primary aim of this study was to assess the feasibility of introducing a digital health education tool (dHET) for varicose vein surgery. METHODS: This randomized, feasibility study allocated 40 patients, into dHET (n = 20) or standard consent (SC) (n = 20) groups. Primary outcomes were related to feasibility. Secondary outcomes were knowledge recall, anxiety, and satisfaction. RESULTS: Recruitment and retention rates were 100% and 97.5%, respectively. Acceptability was also rated high, confirming feasibility. There was also no evidence of a difference between groups for early knowledge recall (14 [12-17] vs. 14 [11-16]; P = 0.72) or delayed (at 2 weeks) knowledge recall (15 [13-16] vs. 15 [13-16]; P = 0.89). The dHET module took significantly longer to complete compared to SC (13 min [12-18] vs. 9 min [8-12]; P < 0.01). However, the control group asked significantly more questions about the intended procedure (P = 0.03). There was no evidence of a difference between groups for patient anxiety or satisfaction. CONCLUSIONS: This trial shows that the addition of a dHET is feasible and noninferior to SC. Digital consent provides a unique opportunity to promote patient education and autonomy for better shared decision making. It also offers better documentation of the consent process.

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.