The Effect of chemo- and radiotherapy on tumor necrosis in soft tissue sarcoma- does it influence prognosis?

BACKGROUND: Soft tissue sarcomas (STSs) are a heterogeneous group of tumors. Wide surgical resection is standard, often combined with neoadjuvant chemotherapy, radiotherapy, or both. Studies have shown the predictive value of tumor necrosis in bone sarcoma (BS); however, the role of necrosis in STS after neoadjuvant therapies is still unclear. This study aimed to investigate the role of chemo- and radiotherapy in the formation of tumor necrosis and to evaluate the influence of tumor necrosis on overall survival and local recurrence-free survival. Data from BS patients and patients who did not receive neoadjuvant therapy were compared. METHODS: A total of 779 patients with STS or BS were treated surgically. In all patients, tumor-specific factors such as type, size, or grading and the type of adjuvant therapy were documented. Local recurrence (LR), the diagnosis of metastatic disease, and survival during follow-up were evaluated. RESULTS: A total of 565 patients with STS and 214 with BS were investigated. In STS, 24.1% G1 lesions, 34.1% G2 lesions, and 41.8% G3 lesions were observed. Two hundred twenty-four of the patients with STS and neoadjuvant therapy had either radiotherapy (RTx) (n = 80), chemotherapy (CTx) (n = 93), or both (n = 51). Three hundred forty-one had no neoadjuvant therapy at all. In STS, tumor necrosis after neoadjuvant treatment was significantly higher (53.5%) than in patients without neoadjuvant therapy (15.7%) (p < 0.001). Patients with combined neoadjuvant chemo-/radiotherapy had substantially higher tumor necrosis than those with radiotherapy alone (p = 0.032). There was no difference in tumor necrosis in patients with combined chemo-/radiotherapy and chemotherapy alone (p = 0.4). The mean overall survival for patients with STS was 34.7 months. Tumor necrosis did not influence survival in a subgroup of G2/3 patients. In STS with no neoadjuvant therapy and grading of G2/3, the correlation between necrosis and overall survival was significant (p = 0.0248). There was no significant correlation between local recurrence (LR) and necrosis. CONCLUSION: STS shows a broad spectrum of necrosis even without neoadjuvant chemo- or radiotherapy. After CTx or/and RTx necrosis is enhanced and is significantly pronounced with a combination of both. There is a trend toward higher necrosis with CTx than with RTx. Grading substantially influences the necrosis rate, but necrosis in soft-tissue sarcoma following neoadjuvant therapy does not correlate with better survival or a lower local recurrence rate, as in bone sarcomas.

Precision Oncology in Soft Tissue Sarcomas and Gastrointestinal Stromal Tumors.

Soft tissue sarcomas (STSs), including gastrointestinal stromal tumors (GISTs), are mesenchymal neoplasms with heterogeneous clinical behavior and represent broad categories comprising multiple distinct biologic entities. Multidisciplinary management of these rare tumors is critical. To date, multiple studies have outlined the importance of biological characterization of mesenchymal tumors and have identified key molecular alterations which drive tumor biology. GIST has represented a flagship for targeted therapy in solid tumors with the advent of imatinib which has revolutionized the way we treat this malignancy. Herein, the authors discuss the importance of biological and molecular diagnostics in managing STS and GIST patients.

Patterns of Local Recurrence and Risk of Skin Recurrence in Soft Tissue Sarcomas After Surgical Resection.

PURPOSE: Although there is a theoretical risk of skin seeding during surgical resection of soft tissue sarcomas (STSs), current consensus guidelines recommend against routine use of bolus during radiation therapy (RT). However, the risk of skin recurrence has not been systematically assessed. We aimed to assess the patterns of local recurrence (LR) in patients with STS treated with surgery with or without RT. METHODS AND MATERIALS: We performed a retrospective analysis of adults with STSs evaluated at our institution between 2007 and 2021. For patients who developed LR, the depth was evaluated. Progression-free survival and overall survival were analyzed from time of first LR using the Kaplan-Meier method. Cumulative incidence of distant metastasis was calculated with competing risk analysis from date of LR. RESULTS: Of the 206 patients evaluated, 20 had LR (9.7%). Among patients with LR, 5 patients (25.0%) were treated with surgery alone and 15 patients (75.0%) with surgery and RT. In patients treated with RT, 46.7% had preoperative RT, 53.3% had postoperative RT, and bolus was used in 46.7%. Surgical margins were close (<1 mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). LR occurred in the deep subfascial tissue in 9 patients (45%), subcutaneous tissue in 10 patients (50.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone, and the tumor involved the skin at presentation. In patients treated with RT, LR occurred within the RT field in 13 patients (86.7%). At 1 year after LR, progression-free survival was 70.3%, overall survival was 81.7%, and cumulative incidence of distant metastasis was 5.9%. CONCLUSIONS: Skin recurrences were rare after surgical resection of STSs and only occurred in a tumor that involved the skin at initial presentation. These findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

Usefulness of antegrade foam sclerotherapy for portal hypertensive variceal bleeding.

PURPOSE: This study investigates the usefulness of antegrade variceal embolization using sclerosant foam to evaluate technical success and clinical outcomes in cases of hypertensive variceal bleeding. METHODS: A total of 16 patients underwent percutaneous antegrade variceal embolization using foam sclerotherapy from August 2019 to January 2022. Among the patients, 12 cases were of gastroesophageal varices, two were rectal varices, and one case each was duodenal and jejunal varices, respectively. Sodium tetradecyl sulfate (STS) foam was used as a detergent for variceal bleeding sclerotherapy at various anatomical locations. The detergent was used in a foam form to promote clinical outcomes and enable the effective embolization of the entire blood vessel wall, including the ventral side, against gravity. Furthermore, STS foam could be used to help sufficiently deliver the drug to distal segments. A balloon catheter was also used to block the antegrade flow and prevent the dilution of the sclerosant. Technical success was defined as the completion of sclerotherapy for variceal bleeding as planned before the procedure to achieve the disappearance of variceal bleeding. Clinical success was defined as the complete obliteration of varices without recurrent bleeding during the follow-up period after the procedure. RESULTS: Technical success was 81.3%, and clinical success was 84.6%. Additionally, 15/16 of the procedures were emergencies, and there were no complications related to the procedure. CONCLUSION: Antegrade foam sclerotherapy using 3% STS for variceal bleeding is clinically safe and effective. Moreover, antegrade foam sclerotherapy can be a useful treatment option for patients with active variceal bleeding in emergency cases.

Efficacy and safety of embolo-sclerotherapy of arteriovenous malformations with foam sodium tetradecyl sulphate.

BACKGROUND: To evaluate the efficacy and safety of embolo-sclerotherapy (EST) particularly with foamed sclerotherapy in the treatment of arteriovenous malformations (AVMs). METHODS: All patients with AVM who underwent interventional therapy i.e. EST from January 1st, 2015 - December 31st, 2019 were identified through a prospective database. Types of AVM were classified according to Schobinger's classification. The outcome measures assessed efficacy and complications. The former was divided into four groups: no response, mild response, moderate response, and complete response. Complications were defined as any tissue or functional damage, distal embolization or tissue reaction. Continuous variables were compared using analysis of variance (ANOVA) F test and discrete variables were analysed using χ2 tests. P<0.05 was considered significant. RESULTS: A total of 65 patients were included. There was no statistical difference amongst the volume of foam STS 3% or alcohol used across all types of AVM. Overall, majority of patients (86.2%) reported some degree of improvement following interventional therapy. Six (9.2%) patients experienced complications including necrosis and amputation. The proportions of complication were significantly different across the categories (P=0.009). Patients with type III AVM seemed to report more complications than others. CONCLUSIONS: Foam sclerotherapy was clinically effective and safe for patients with AVM. This study showed that foam sclerotherapy with STS 3% provided a safe and efficacious alternative sclerosant to ethanol despite it was not often reported to be used to treat AVM. However, a combination of embolic agents is likely required to treat type IV AVMs.

Resensitization in suspected penicillin allergy.

BACKGROUND: The diagnosis of allergic reactions to penicillins (AR-PEN) is very complex as there is a loss of sensitization over time, which leads to negative skin tests (STs) and specific IgE in serum, and even to tolerance to the drug involved. However, STs may become positive after subsequent exposure to the culprit drug (resensitization), with the risk of inducing potentially severe reactions. The exact rate of resensitization to penicillins is unknown, ranging from 0% to 27.9% in published studies. OBJECTIVES: To analyze the rate of resensitization in patients with suggestive AR-PEN by repeating STs (retest) after an initial evaluation (IE). MATERIAL AND METHODS: Patients with suspected AR-PEN were prospectively evaluated between 2017 and 2020. They underwent STs, and a randomized group also underwent a drug provocation test (DPT) with the culprit. Only patients with negative STs and/or DPT were included. All included cases were retested by STs at 2-8 weeks. RESULTS: A total of 545 patients were included: 296 reporting immediate reactions (IRs) and 249 non-immediate reactions (NIRs). Eighty (14.7%) cases had positive results in retest (RT+): 63 (21.3%) IRs and 17 (6.8%) NIRs (p < 0.0001). The rate of RT+ was higher in anaphylaxis compared with all other reactions (45.8% vs 9.1%, p < 0.0001). The risk of RT+ was higher from the fifth week after IE (OR: 4.64, CI: 2.1-11.6; p < 0.001) and increased with the patient's age (OR: 1.02; CI: 1.01-1.04; p = 0.009). CONCLUSIONS: Due to the high rate of resensitization, retest should be included in the diagnostic algorithm of IRs to penicillins after an initial negative study, especially in anaphylaxis, to avoid potentially severe reactions after subsequent prescriptions of these drugs.

Combined sclerotherapy followed by surgical resection of a large extracranial venous malformation in a 14-month-old child: preoperative workup and technical note.

INTRODUCTION: Venous malformations affect around 2 per 10,000 newborn and are the most common type of congenital vascular malformation. They are always present at birth and are often misdiagnosed with hemangiomas. Accurate diagnosis and adequate targeted therapy through a multidisciplinary approach is advocated for a successful treatment, considering a combination of modalities in complex cases. We present here the workup and treatment of a venous malformation in a 14 month old child by combining a preoperative sclerotherapy with sodium tetradecyl sulfate (STS) followed by complete surgical excision respecting the calvarium. CASE PRESENTATION: A large right extracranial fronto-parietal venous malformation and scalloping of the underlying calvarium, attached to the pericranium, surgically excised after preoperative sclerotherapy with STS in a 14-month-old child. RESULTS: The patient had an uneventful postoperative course with complete resection of the lesion, satisfying cosmetic appearance and no complications. Histopathological examination confirmed a venous malformation. CONCLUSION: We demonstrated the workup and the rationale of the combined sclerotherapy followed by surgical resection of a large growing extracranial venous malformation. Preoperative direct contrast injection and sclerotherapy allowed to rule out significative extracranial to intracranial venous inflow and reduce blood loss for the surgical procedure, respectively. Complete removal of the malformation minimized the impact on future growth of the calvarium.

A systematic review and network meta-analysis of the effectiveness of sclerotherapy for venous malformation.

OBJECTIVE: Sclerotherapy for venous malformation has been widely used; however, no guidelines are available to assess the effectiveness of different sclerotherapy agents. We conducted a systematic review and network meta-analysis to investigate the effectiveness of sclerotherapy agents for venous malformations. METHODS: Three electronic databases were searched from their inception (1950) to April 29, 2021. Studies comparing the effectiveness of different sclerotherapy agents were included. The risk of bias within and across studies was assessed. Pairwise meta-analyses were conducted, followed by a network meta-analysis. We also assessed inconsistency and publishing bias using various approaches. RESULTS: Seven studies with 547 patients in six arms were included in the present study. We defined the response and complete response as two separate outcomes. Significant differences were observed in four comparisons with respect to the response (ethanol vs bleomycin, ethanol vs polidocanol, ethanol vs sodium tetradecyl sulfate, polidocanol vs sodium tetradecyl sulfate). No statistically significant differences were found in the other comparisons. The evidence network revealed that for the response outcome, ethanol ranked first, followed by pingyangmycin, polidocanol, sodium morrhuate, bleomycin, and, finally, sodium tetradecyl sulfate. For the complete response outcome, pingyangmycin had the best results, followed by sodium morrhuate, polidocanol, ethanol, bleomycin, and, finally, sodium tetradecyl sulfate. Major complications, such as facial nerve palsy, serious local swelling, and necrosis, had occurred mostly in the ethanol group and rarely in the other groups. Because of the limited data, no further analysis of major complications was conducted. Our confidence in the comparisons and rankings was low. We found no verified inconsistency or publishing bias in the present study using the existing approaches. CONCLUSIONS: Ethanol showed a significantly better response statistically compared with the other agents. However, ethanol had also resulted in the highest incidence of complications. Pingyangmycin showed the second-best response, best complete response, and a low rate of complications, respectively. Overall, pingyangmycin achieved excellent performance and balance in terms of the different outcomes. However, they could not be adequately recommended from the available data. More superior trials, especially randomized controlled trials, are needed in the future.

Efficacy and safety of foam sclerotherapy with sodium tetradecyl sulfate as preferred sclerosant of venous malformations based on experience from a single specialist center.

OBJECTIVE: We have assessed the efficacy and safety of interventional therapy for venous malformations (VMs), with foam sclerotherapy as the treatment of choice according to our experience at a single specialist center. METHODS: All the patients with VMs who had undergone interventional therapy (ie, embolo-sclerotherapy and/or open surgery) from January 1, 2015 to December 31, 2019 were identified through a prospective database. The VM types were classified according to the Puig classification. The outcome measures assessed included the efficacy and complications. The former was divided into four groups: no response, mild response, moderate response, and complete response. The complications were defined as any tissue or functional damage, distal embolization, or tissue reaction. The continuous variables were compared using the analysis of variance F test, and discrete variables were analyzed using the χ2 tests. P values < .05 were considered statistically significant. RESULTS: A total of 207 patients were included. Puig type I lesions were significantly less likely to have received foam sclerotherapy using sodium tetradecyl sulfate (STS) 3% (P ≤ .001) and more likely to have been surgically excised (P ≤ .001). At the patient's first procedure during the study period, the volumes of foam STS 3% were significantly different across all types of VM (P ≤ .001). The patients with type I VMs had received a lower volume of STS 3% compared with those with type II and III VMs. The efficacy outcome categories were significantly different across all types of VMs (P ≤ .001). Overall, only 14 patients (6.8%) had reported no improvement in efficacy, and 38 patients (18%) had not attended follow-up. Therefore, 154 patients (74.8%) had experienced some form of efficacious outcome. Ten patients (4.8%) had developed complications such as hematoma, thrombophlebitis, and ulceration. The incidence of complications differed significantly across the categories (P = .030), with more complications reported for those with type I VMs. CONCLUSIONS: We found that intervention with foam sclerotherapy using STS 3% is clinically effective and safe for patients with VMs and was most successful for those with Puig type I and II VMs.

Factors Affecting Adverse Events after Venous Malformation Sclerotherapy.

PURPOSE: To evaluate factors that contribute to adverse events (AEs) after embolization of venous malformations (VMs) using sclerosing agents. MATERIALS AND METHODS: A retrospective review of patients who underwent direct puncture embolization of VMs with a sclerosing agent and adjunctive techniques, also termed as sclerotherapy, from 2016 to 2021 was performed. Three-hundred one embolizations in 137 patients (median age, 19.0 years; interquartile range, 12.8-31.5 years) were evaluated. The VM characteristics and embolization details were analyzed. Anticoagulation was also evaluated based on D-dimer levels. Cutaneous and noncutaneous AEs were analyzed. The AEs were categorized using Society of Interventional Radiology guidelines. RESULTS: VMs involving tissue planes were subcutaneous (n = 104), intramuscular (n = 84), and combined (n = 113). Overlying skin involvement was observed in 56% of the patients. Sodium tetradecyl sulfate was mainly used (83%). Periprocedural anticoagulation was used in 9% of the patients. Most AEs were minor (30/301, 9.7%), and only 1.7% (5/301) were major (21 cutaneous and 14 noncutaneous AEs). Age below 18 years (odds ratio, 4.4502; 95% confidence interval, 1.5607-12.6890; P = .0052) and overlying skin involvement (odds ratio, 7.1794; 95% confidence interval, 1.6226-31.7656; P = .0094) were factors associated with cutaneous AEs. All noncutaneous AEs developed in patients with intramuscular VMs; however, this association was not statistically significant. There was no severe hematologic AE or permanent consequence. CONCLUSIONS: The overall AE rate after VM embolization was 11.6%; however, major AEs were rare (1.7%). Cutaneous AEs were associated with young age and overlying skin involvement. All noncutaneous AEs developed in patients with intramuscular VMs.

Elimination of light chain tailing in reducing capillary electrophoresis with sodium dodecyl sulfate analysis of a monoclonal antibody.

Capillary electrophoresis with sodium dodecyl sulfate (CE-SDS) is a common analytical technique for investigating the purity and molecular size heterogeneity of monoclonal antibody (mAb) drugs. In reducing CE-SDS analysis of mAb-A, the light chain (LC) peak exhibited severe tailing, seriously affecting the purity analysis. The purposes of this investigation are to clarify the source of tailing and develop a more appropriate CE-SDS method to eliminate LC tailing. The degree of LC tailing was closely related to the mAb concentration, SDS concentration, and injection amount, and more hydrophobic detergents, such as sodium hexadecyl sulfate (SHS) and sodium tetradecyl sulfate (STS), could be used instead of SDS to obtain better peak shapes. The results also indicated that the tailing was caused by the binding problem associated with SDS, and SHS/STS could provide a more stable and uniform complexation for the LC. In summary, the method we developed successfully eliminated the LC tailing and provided a robust characterization of mAb-A in reducing CE-SDS analysis.

Sodium Tetradecyl Sulphate Sclerotherapy for Lateral Malleolar Bursitis of the Ankle.

Background: The aim of this study was to evaluate clinical outcomes of sodium tetradecyl sulphate (STS) sclerotherapy for conservative treatment of lateral malleolar bursitis of the ankle. Methods: We reviewed data from 20 consecutive patients (20 ankles) who underwent STS sclerotherapy between August 2018 and June 2019. After aspiration of fluid from the lateral malleolar bursal sac, 2 mL (20 mg) STS was injected into the sac. Clinical outcomes and side effects and complications were evaluated at 2 weeks, 3 months, 1 year, and 2 years after sclerotherapy. Responses to treatment were assessed according to degree of fluctuation, shrinkage of the bursal sac, and soft-tissue swelling. The 36-item short form survey (SF-36) was completed for each patient before and after therapy. Results: Complete response was observed in 17 patients (85%), and partial response was observed in 3 patients (15%) after STS sclerotherapy. SF-36 physical component scores improved from 62.2 (interquartile range, 5.2) before therapy to 70.0 (interquartile range, 7.9) at last follow-up (p < 0.05). One patient (5%) experienced transient hyperpigmentation at the injection site. No major complications occurred. Conclusions: STS sclerotherapy was an effective and safe treatment for patients with lateral malleolar bursitis of the ankle.

Safety of High-Dose 3% Sodium Tetradecyl Sulfate for Sclerotherapy of Renal Cysts in Patients with Autosomal Dominant Polycystic Kidney Disease.

This study assessed the safety profile of high-volume (>10 mL) 3% sodium tetradecyl sulfate (STS) sclerotherapy for the treatment of renal cysts in patients with autosomal dominant polycystic kidney disease. A total of 211 sclerotherapy treatments were performed in 169 patients over a 5-year period, with a comparison of 2 patient cohorts based on the STS volumes used. The first cohort (n = 112) received a high volume (greater than 10 mL) of STS, and the second cohort (n = 57) received a low volume (less than 10 mL). The minor adverse event rate for the cohorts was 14.5% and 9.6%, respectively (P = .310), with postprocedure pain being the most common event. One major adverse event occurred, for which the patient required hospitalization for infection after low-volume STS treatment. Doses of STS higher than those currently recommended by the Food and Drug Administration for intravascular use allow large renal cysts to be treated safely in the setting of autosomal dominant polycystic kidney disease.

Analysis of adverse events with sclerosants reported to the United States Food and Drug Administration.

OBJECTIVES: To analyze adverse events (AEs) related to sclerosants reported through the Federal Adverse Event Reporting System (FAERS). METHODS: We queried the FAERS database for all cases associated with sclerosants. Reports were analyzed and stratified based on severity of cases and patient death. RESULTS: A total of 1215 cases with 3124 reactions were identified among 4 sclerosants. "General disorder and administration site conditions" reaction group was prevalent in all sclerosants. For polidocanol, deep vein thrombosis and pulmonary embolism were the most common severe reactions while cardiac arrest was frequent in death cases. Anaphylaxis was common in fatalities of sodium tetradecyl sulfate. Ethanolamine oleate was associated with procedural errors, while morrhuate sodium resulted in few cases. CONCLUSION: Our analysis supports previous studies concerning common local symptoms, but also reveals serious and death associated reaction profiles specific to individual sclerosants. Practitioners should be knowledgeable on both non-lethal and fatal AEs for each sclerosant. The multitude of reports concerning serious reactions and deaths we report herein provide a cautionary reminder to venous practitioners and patients that sclerotherapy is not a trivial procedure.

Strain Ultrasound Elastography of Aneurysm Sac Content after Randomized Endoleak Embolization with Sclerosing vs. Non-sclerosing Chitosan-based Hydrogels in a Canine Model.

PURPOSE: To compare the mechanical properties of aneurysm content after endoleak embolization with a chitosan hydrogel (CH) with that with a chitosan hydrogel with sodium tetradecyl sulfate (CH-STS) using strain ultrasound elastography (SUE). MATERIALS AND METHODS: Bilateral common iliac artery type Ia endoleaks were created in 9 dogs. Per animal, 1 endoleak was randomized to blinded embolization with CH, and the other, with CH-STS. Brightness-mode ultrasound, Doppler ultrasound, SUE radiofrequency ultrasound, and computed tomography were performed for up to 6 months until sacrifice. Radiologic and histopathologic studies were coregistered to identify 3 regions of interest: the embolic agent, intraluminal thrombus (ILT), and aneurysm sac. SUE segmentations were performed by 2 blinded independent observers. The maximum axial strain (MAS) was the primary outcome. Statistical analysis was performed using the Fisher exact test, multivariable linear mixed-effects models, and intraclass correlation coefficients (ICCs). RESULTS: Residual endoleaks were identified in 7 of 9 (78%) and 4 of 9 (44%) aneurysms embolized with CH and CH-STS, respectively (P = .3348). CH-STS had a 66% lower MAS (P < .001) than CH. The ILT had a 37% lower MAS (P = .01) than CH and a 77% greater MAS (P = .079) than CH-STS. There was no significant difference in ILT between treatments. The aneurysm sacs embolized with CH-STS had a 29% lower MAS (P < .001) than those embolized with CH. Residual endoleak was associated with a 53% greater MAS (P < .001). The ICC for MAS was 0.807 (95% confidence interval: 0.754-0.849) between segmentations. CONCLUSIONS: CH-STS confers stiffer intraluminal properties to embolized aneurysms. Persistent endoleaks are associated with increased sac strain, an observation that may help guide management.

Inframalleolar access in endovenous treatment of venous ulcers and C5 disease with nonthermal nontumescent techniques.

PURPOSE: To evaluate the use of inframalleolar access for endovenous ablation when treating advanced venous disease with nonthermal nontumescent (NTNT) techniques. METHODS: This single-center retrospective study included 109 patients with advanced venous disease, treated using inframalleolar access between May 2018 and March 2020. NTNT techniques included ClariVein (Merit Medical Systems, South Jordan, Utah) and ScleroSafe (VVT Medical, Kefar Sava, Israel). Outcomes measured were postprocedure pain, leg edema, ulcer healing and recurrence rates, and venous insufficiency recurrence. RESULTS: Seventy-seven patients (70%) were treated with ClariVein and 32 (30%) with ScleroSafe. Postprocedure pain score (range, 0-10) after 1 week decreased from a preprocedure median of 5 (interquartile range, 3-6) to 1 ((interqartiel range, 0-2) (P = .0001). Complete wound healing was achieved in 38 patients (43.7%) after 30 days and in 71 patients (81.6%) after 90 days. One patient developed an ulcer recurrence and six developed venous insufficiency recurrence. There was no reported nerve or skin injuries. CONCLUSIONS: NTNT ablation techniques using inframalleolar access are effective and safe without risk of nerve damage. Their use facilitates ulcer healing and limits pain in patients with advanced disease.

Adverse neurological events after sodium tetradecyl sulfate foam sclerotherapy - A prospective, observational study of 8056 treatments.

BACKGROUND: Ultrasound guided foam sclerotherapy (UGFS) is a flexible and highly utilised tool in the treatment of varicose veins (VVs), both as a primary treatment and as an adjunct to other treatments. Concern remains regarding the risk of neurological adverse events (AEs) such as migraine, visual disturbance and serious adverse events (SAEs) such as cerebrovascular accident that have been reported after UGFS treatments. AIM: To determine the incidence of neurological AEs and SAEs after UGFS. METHODS: A prospective, multicentre, post-authorisation safety study across Europe (both private and government) was performed between January 2015-2020. Neurological adverse events after UGFS with Fibrovein® (Sodium Tetradecyl Sulfate) 1 and 3% physician generated foam. RESULTS: 8056 patients underwent treatment. There were 46 AE (including 5 SAEs), 30 (65%) SAEs were in female patients. Mean age was 55 years with mean body mass index (BMI) of 27. Univariable logistic regression demonstrate that UGFS only treatment (i.e. no adjunctive treatment), liquid-to-gas ratio, gas type and total foam volume (1% sodium tetradecyl sulfate, STS) were significantly associated with the odds of experiencing the outcome. Multivariable logistic regression model exhibits that migraine and total foam volume (1% STS) maintained statistical significance thus associated with the odds of adverse events. CONCLUSIONS: This study demonstrates that UGFS with Fibrovein is safe with a very low incidence of neurological AEs and SAEs. Past history of migraine, use of physiological gas (O2/CO2) and increasing volumes of 1% foam increase the risk of AEs.