A Review of Sclerosing Foam Stability in the Treatment of Varicose Veins.

BACKGROUND: Varicose veins are common clinical entities. Foam sclerotherapy is a minimally invasive and simple procedure; however, the side effects, efficacy, and stability of sclerosing foam are not ideal. OBJECTIVE: To summarize the current studies on sclerosing foam stability and promote foam sclerotherapy development. MATERIALS AND METHODS: We reviewed the literature before June 2018 and included only representatives studies on sclerosing foam stability. We summarized the foam half-life time (FHT) of polidocanol (POL) under 17 preparation conditions and the FHT of sodium tetradecyl sulfate under 21 preparation conditions. The preparation conditions included various combinations of temperature, liquid-gas ratio, preparation method, etc. RESULTS: The FHT of POL varied between 40 and 4,000 seconds under different conditions. The FHT of sodium tetradecyl sulfate varied from 25.7 to 390 seconds. The higher the drug concentration, the lower the temperature required to increase foam stability. The addition of surfactant greatly increased foam stability. For different gas compositions, the FHT sequence was as follows: CO2 < CO2 + O2 < O2 < air. CONCLUSION: Foam stability can be improved by changing the preparation conditions; therefore, the role of surfactants and predictive methods for FHT are worth investigating further.

Mechanochemical ablation causes endothelial and medial damage to the vein wall resulting in deeper penetration of sclerosant compared with sclerotherapy alone in extrafascial great saphenous vein using an ex vivo model.

BACKGROUND: Nonthermal, tumescentless devices are the next generation of minimally invasive devices to treat varicose veins. We aimed to investigate the effects of mechanochemical ablation (MOCA) using ClariVein (Vascular Insights, Quincy, Mass) on ex vivo great saphenous vein with histology and immunofluorescent staining. METHODS: Extrafascial great saphenous veins were harvested during surgery for varicose veins and were treated ex vivo for 10 to 11 minutes with either liquid sclerotherapy or the use of ClariVein, with and without 3% sodium tetradecyl sulfate. Veins were sectioned and subjected to hematoxylin and eosin staining and immunofluorescent staining for endothelial and smooth muscle cell markers (CD31 and α-actin) to assess overall damage and cell death in the vein wall compared with control sections. RESULTS: Histologic observations confirmed intimal damage from ClariVein, as has been previously shown; however, medial damage was also evident, which was not observed in control or liquid sclerotherapy sections. Immunofluorescent staining in the three sections studied showed a 42% decrease in CD31 staining and 27% mean reduction in α-actin staining up to a depth of 300 µm with liquid sclerotherapy. This cytotoxic effect was significantly enhanced by MOCA with a reduction in CD31 staining just above 60% and a 46% mean decrease in α-actin staining noted up to a depth of 300 µm. Far greater reductions in staining compared with sclerotherapy were observed up to a depth of 600 µm. CONCLUSIONS: MOCA using 3% sodium tetradecyl sulfate increases the penetration of the sclerosant and its effect into the vein wall and shows superior rates of tissue destruction compared with liquid sclerotherapy alone. In this model, it appears not solely to damage the endothelium but also to shear the medial layer, creating small lesions into which sclerosant can flow and exert its cytotoxic effect.

Interaction of detergent sclerosants with cell membranes.

Commonly used detergent sclerosants including sodium tetradecyl sulphate (STS) and polidocanol (POL) are clinically used to induce endovascular fibrosis and vessel occlusion. They achieve this by lysing the endothelial lining of target vessels. These agents are surface active (surfactant) molecules that interfere with cell membranes. Surfactants have a striking similarity to the phospholipid molecules of the membrane lipid bilayer. By adsorbing at the cell membrane, surfactants disrupt the normal architecture of the lipid bilayer and reduce the surface tension. The outcome of this interaction is concentration dependent. At high enough concentrations, surfactants solubilise cell membranes resulting in cell lysis. At lower concentrations, these agents can induce a procoagulant negatively charged surface on the external aspect of the cell membrane. The interaction is also influenced by the ionic charge, molecular structure, pH and the chemical nature of the diluent (e.g. saline vs. water). The ionic charge of the surfactant molecule can influence the effect on plasma proteins and the protein contents of cell membranes. STS, an anionic detergent, denatures the tertiary complex of most proteins and in particular the clinically relevant clotting factors. By contrast, POL has no effect on proteins due to its non-ionic structure. These agents therefore exhibit remarkable differences in their interaction with lipid membranes, target cells and circulating proteins with potential implications in a range of clinical applications.

Visualized sclerotherapy of varicose veins.

BACKGROUND: The spread and movement of sclerosant after injection during sclerotherapy is difficult to monitor. OBJECTIVE: To develop a new visualization method that allows monitoring of sclerosant dosage and flow during sclerotherapy. METHODS: We used a photodynamic eye (PDE) to perform indocyanine green (ICG) imaging. ICG produces strong fluorescence detectable using PDE and allows monitoring of sclerosant spread through blood vessels in real time. We performed visualized sclerotherapy on 50 limbs, comprising high ligation and sclerotherapy (35 limbs), stripping and sclerotherapy (10 limbs), and sclerotherapy alone (5 limbs). RESULTS: In all cases, fluorescence imaging of the injected sclerosant was possible. No complications resulted from combining ICG and polidocanol in any of the patients, all of whom received follow-up evaluations at 1 week, 1 month, and 3 months after treatment. CONCLUSIONS: Our new method not only avoids the risk of radiation exposure, but also allows for simple observation of sclerosant range of access, determination of the dosage for each lesion, and accurate administration of therapy to target lesions. This method will contribute to further advances in sclerotherapy, given that it allows administration of sclerosant and visual confirmation of optimal injection dosage, speed, and movement of sclerosant after injection. The authors have indicated no significant interest with commercial supporters.

Development and in-vitro evaluation of modified release tablets including ethylcellulose microspheres loaded with diltiazem hydrochloride.

In this study, development of modified release tablet formulations containing diltiazem hydrochloride-loaded microspheres to be taken once rather than two or three times a day was attempted. For this purpose, ethylcellulose microspheres were prepared by emulsion-solvent evaporation technique. The influence of emulsifier type and drug/polymer ratio on production yield, encapsulation efficiency, particle size, surface morphology and in-vitro release characteristics of the microspheres was evaluated. Suitable microspheres were selected and tabletted using different tabletting agents, Ludipress, Cellactose80, Flow-Lac100 and excipients Compritol888 ATO, KollidonSR. Tablets were evaluated from the perspective of physical and in-vitro drug release characteristics. It was seen that type and ratio of the excipients played an important role in the tabletting of the microspheres. As a result, two tablet formulations containing 180 mg diltiazem hydrochloride and using either Compritol888 ATO or KollidonSR were designed successfully and maintained drug release for 24 h with zero order and Higuchi kinetics, respectively.

Single-session alcohol-retention sclerotherapy for simple renal cysts: comparison of 2- and 4-hr retention techniques.

OBJECTIVE: The objectives of our study were to evaluate the feasibility of ethanol sclerotherapy in treating simple renal cysts with prolonged ethanol retention and to compare the therapeutic results of 2- and 4-hr retention techniques. MATERIALS AND METHODS: We retrospectively reviewed 36 renal cysts in 33 patients treated by ethanol sclerotherapy with a single-session single-injection technique during the past 6 years. After complete aspiration of the cystic fluid, 95% ethanol was injected into the cyst and was retained for 4 hr in 14 cysts (group 1) and for 2 hr in 22 cysts (group 2). The average maximal diameter and aspirated volume of the cysts were 8.3 cm and 223 mL in group 1 patients and 7.9 cm and 167 mL in group 2, respectively. The ablated cysts were followed up regularly by sonography, CT, or both at 3- to 6-month intervals for at least 1 year. The nonparametric Mann-Whitney U test was used to compare differences in characteristics, treatment results, and laboratory data of the subjects in the two groups. The level of statistical significance was set at a p value of less than 0.05. RESULTS: Technically, all the patients tolerated the procedures. One patient had gross hematuria 10 days after the procedure. She underwent surgical deroofing treatment and was excluded in the later statistical analysis. After sclerotherapy, 14 cysts disappeared completely and 16 cysts showed marked regression with residual maximal diameter of less than 3 cm. The overall volume reduction rate was 97.6% in all 35 cysts. The mean residual longest diameters and average volume reduction rates of the treated cysts were 1.9 cm and 97.9% in group 1 patients and 1.1 cm and 97.3% in group 2 patients, respectively, which showed no statistical significance of volume reduction rate with a p value 0.149. CONCLUSION: The single-session prolonged ethanol-retention technique is safe and efficacious for the treatment of renal cysts. There is no statistical difference in therapeutic efficacy between 2- and 4-hr ethanol-retention techniques.

Renal chemoembolization with mitomycin c/Ethibloc: pharmacokinetics and efficacy in an animal model.

BACKGROUND AND PURPOSE: Arterial embolization can be an alternative treatment for kidney malignancy. We investigated the efficacy of renal embolization with a combination of an occlusive agent (Ethibloc) and the cytotoxic substance mitomycin C (MMC) in an animal model. MATERIALS AND METHODS: In 32 rats with implanted Yoshida sarcoma, nephrectomy was carried out 15, 30, 60, or 90 minutes after chemoembolization (1 mg v 2 mg of MMC/mL of Ethibloc) or chemoperfusion (1 mg of MMC/mL of NaCl) of the tumor-bearing kidney. The MMC tissue concentration was measured in the kidney specimens. Six dogs also underwent chemoembolization or chemoperfusion with monitoring of MMC serum concentration at the same intervals. We compared the survival time of rats with Yoshida sarcoma after chemoembolization (N = 15), chemoperfusion (N = 18), embolization (N = 18), nephrectomy (N = 21), and no treatment (N = 25). RESULTS: The MMC tissue concentration in the rat model was much higher after chemoembolization than after chemoperfusion for at least 1.5 hours. The MMC serum concentration in the dogs showed a high initial peak (0.6 mg/L) after chemoperfusion, then dropped quickly to the same level seen 30 minutes after chemoembolization with 1 mg of MMC/mL of Ethibloc (0.15 mg/L). The MMC serum concentration following chemoembolization with 2 mg of MMC/mL of Ethibloc stayed higher (0.3-0.25 mg/L) for 60 minutes. The survival rates after nephrectomy were equal to those after chemoembolization (80% survival after 30 days), with poorer survival being seen after embolization (75%) and chemoperfusion (70%). In the control group, all rats were dead at the 27th day. CONCLUSION: Chemoembolization produces persistently high tissue concentrations of MMC and avoids toxic peak serum levels. It improves the efficacy of organ ablative vasoocclusion in renal malignancies.

Efficacy of topical phenol decontamination strategies on severity of acute phenol chemical burns and dermal absorption: in vitro and in vivo studies in pig skin.

Pure phenol is colorless and used in the manufacture of phenolic resins, plastics, explosives, fertilizers, paints, rubber, textiles, adhesives, pharmaceuticals, paper, soap, and wood preservatives. The purpose of this study was to compare the efficacy of several phenol decontamination strategies following dermal exposure using the pig as a model for human exposure, and then assess the effect of the two best treatments on phenol absorption in the isolated perfused porcine skin flap (IPPSF). Six anesthetized Yorkshire pigs were exposed to 89% aqueous phenol for 1 min using Hilltop chambers (10 skin sites/pig; 400 microl/site). Exposure to phenol was followed by one of 10 different decontamination procedures: 1-, 5-, 15-, and 30-min water wash; Ivory soap solution; polyethylene glycol (PEG 400); PEG 400/industrial methylated spirits (IMS); PEG 400/ethanol (EtOH); polyvinyl pyrrolidone (PVP)/70% isopropanol (IPA); and 70% IPA. For each of the last five strategies, 1-min treatment washes were repeatedly alternated with 1-min water washes for a total of 15 min. Evaluation was based on scoring of erythema, edema, and histological parameters such as intracellular and intercellular epidermal edema, papillary dermal edema, perivascular infiltrates, pyknotic stratum basale cells, and epidermal-dermal separation. It was concluded that PEG 400 and 70% IPA were superior to the other treatments investigated and equally efficacious in the reduction of phenol-induced skin damage. In addition, phenol absorption was assessed utilizing the two most effective in vivo treatments in the IPPSF. The assessment of percutaneous absorption of phenol found the PEG 400, 70% IPA, and 15-min water treatments significantly (P < 0.05) reduced phenol absorption relative to no treatment.