David Ewan Connor

Background: The recent global shortage of sterile saline highlighted a lack of published information and guidance regarding the components used in tumescent anaesthesia (TA) for endovenous interventions of venous disease. The aim of this study was to identify current practices in the usage of TA. Methods: An online survey was sent to members of the Australasian College of Phlebology and the mailing list of the International Union of Phlebology. Results: 87 medical practitioners either partially or fully completed the survey, with the majority of respondents being Phlebologists (54%). The vast majority of survey participants use lignocaine (92.5%), adrenaline (55%), sodium bicarbonate (67.1%) in a base fluid of sterile normal saline (90.8%) in the preparation of TA. The majority of administration was through mechanical pumps (68.1%), with 27.8% using syringes. 21.7% reported reusing the same tumescent bag for more than one patient. Only 36.2% obtained consent specifically for TA. Two thirds recorded the anaesthetic dose, as mg/kg (23.5%), or total dose (45.6%) Only 40.6% of participants reported storing intralipid. 7.9% of respondents in this survey had experienced Local Anaesthetic Systemic Toxicity, with one death reported. Conclusions: The survey identified some variability in the volume of components used, and considerable variability in consenting practices, documentation, patient observations, the storage of Intralipid and the re-use of single use intravenous fluid bags between patients.

The aims of this study were to investigate the binding of platelets to colorectal cancer (CRC) cells, platelet activation by CRC cells, and determine the effect of platelets and platelet releasate containing extracellular vesicles on CRC cell proliferation, migration and invasion following aspirin pretreatment. Platelets from healthy individuals were pretreated with aspirin before co-incubation with CRC cells. Platelet activation by CRC cells was analysed by flow cytometry and the binding of platelets to CRC cells investigated using immunofluorescence microscopy. Platelet releasate containing extracellular vesicles was generated by centrifugation. The effect of platelets and platelet releasate on CRC cell proliferation was investigated using carboxyfluorescein succinimidyl esterand dimethylthiazol-carboxymethoxyphenyl-sulfophenyl-tetrazolium assays. Migration and invasion were examined using Transwell assays. HCT15 and HCT116 CRC cells activated platelets, with higher numbers of CRC cells activating more platelets, however aspirin was unable to inhibit platelet activation. Platelets are also able to bind to HCT15 and HCT116 cells. Platelets and platelet releasate did not affect HCT15 and HCT116 proliferation, however, aspirin directly inhibited the proliferation of both cell lines. Platelets and platelet releasate significantly increased the migration and invasion of HCT116, but not HCT15 cell lines. Platelets adhere to and are activated by CRC cells lines, with aspirin unable to inhibit this activation. CRC proliferation was not affected by platelets, however the effect on cancer cell migration and invasion was dependent upon the cell line, suggesting the effects of platelets and platelet releasate containing extracellular vesicles may be patient specific. The inhibitory effect of aspirin on colorectal cancer proliferation is a direct effect on the cancer cell and independent of platelets and extracellular vesicles.

Objectives: Commercially available cyanoacrylates are known to release formaldehyde during degradation. However, it is unknown whether venous adhesive cyanoacrylates used in the treatment of saphenous veins release formaldehyde. Formaldehyde is a known contact allergen, carcinogen and sensitiser. Methods: VenaSeal ^® , VenaBlock ^® , Glubran ^® Tiss 2, Histoacryl ^® , and Supaglue ^® were investigated in vitro. All adhesive agents were polymerised in phosphate-buffered saline, sealed in glass bottles and incubated at 37°C for up to 12 weeks. Headspace-gas chromatography mass spectrometry was used to measure formaldehyde release at set time intervals. Results: Peak levels of formaldehyde were detected in all cyanoacrylate samples within 2 weeks of incubation, with peak levels ranging from 0.05% to 0.17% w/w. These peak concentrations emerged as early as 2 weeks post-polymerisation and remained consistently elevated throughout the 12-week observation period. Glubran Tiss 2 demonstrated the lowest formaldehyde release at 0.05% w/w, while VenaSeal exhibited the highest, reaching a peak of 0.17% w/w at 2 weeks, similar to commercial SupaGlue. Notably, VenaSeal maintained formaldehyde levels above 0.1% w/w for the duration of the 12-week testing period. Conclusion: Formaldehyde is released during the post-polymerisation degradation of medical cyanoacrylates. Despite all products containing n-butyl cyanoacrylate (n-BCA), formaldehyde release varied—likely due to undisclosed formulation differences. VenaSeal released the highest level (0.17% w/w) compared to other products tested, suggesting that formulation influences degradation behaviour.

Objective: To characterise the microscopic structure of thrombus induced by direct effect of sclerosants (sclerothrombus) compared with that of post-sclerotherapy retained coagulum (trapped blood; sclerocoagulum) and thrombus in acute superficial venous thrombosis (SVT). Methods: Scanning electron microscopy (SEM) and fluorescence microscopy were used to assess the structural architecture of thrombus samples. Sclerothrombus samples were generated in vitro following incubation of whole blood or platelet-rich plasma with detergent sclerosants sodium tetradecyl sulphate (STS) or polidocanol (POL). Sclerocoagulum samples were collected from patients treated for varicose veins with STS 1.5% foam. Samples of naturally occurring thrombus were collected from patients with SVT. Results: Acute sclerothrombus contained a mesh-like distribution of branched fibrin fibers dispersed with red cells and microparticles. STS-induced sclerothrombus showed thicker fibrin strands with less branching and contained more microparticles when compared to POL-induced clots. Sclerothrombus at 1 week exhibited a fibrin sponge structure. Sclerocoagulum showed a disorganised distribution of thin, tortuous and branching fibers containing large gaps dispersed with haemolysed red cells and cell debris. SVT contained a smooth fibrin mesh of relatively thick fibrin strands with scarce branching and fewer microparticles. Conclusion: The three entities of sclerothrombus, sclerocoagulum and SVT are distinct and distinguishable entities. Whilst sclerothrombus and SVT demonstrate features of a fibrin clot, sclerocoagulum is haemolysed blood containing disorganised fibrin strands.

Background: Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. Objectives: To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. Methods: An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. Results: Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. Conclusion: Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy.