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Objective: To compare the safety and efficacy of Varisolve® 1% polidocanol microfoam sclerosant with alternative treatments for patients with varicose veins and trunk vein incompetence. Methods: An open-label, multicentre, prospective trial of 710 patients randomized to receive either Varisolve® or alternative treatment (surgery or sclerotherapy). The endpoint was ultrasound-determined occlusion of trunk vein(s) and elimination of reflux, analysed against a non-inferiority hypothesis. Results: Overall, non-inferiority was demonstrated with 83.4% efficacy for Varisolve® compared with 88.1% for alternative treatment at three months, and the corresponding magnitudes were 78.9 and 80.4% at 12 months. Surgery was superior to Varisolve®, but the success rate of 68.2% for Varisolve® (surgery 87.2%) was poor compared with 93.8% success for Varisolve® achieved in those randomized to Varisolve® or sclerotherapy. Varisolve® was superior to sclerotherapy at 12 months ( P = 0.001). Deep vein thrombosis occurred in 11/437 (2.5%) after Varisolve®, in 1/125 (0.8%) after sclerotherapy and in none after surgery. No pulmonary emboli were detected. Conclusion: Overall, Varisolve® was non-inferior to alternative treatment. Surgery was more efficacious, but Varisolve® caused less pain and patients returned to normal more quickly. The Varisolve® technique is a useful additional treatment for varicose veins and trunk vein incompetence.

For the treatment of superficial basal cell carcinoma, a prospective, noninferiority, randomized controlled multicenter trial with 601 patients showed that 5% imiquimod cream was superior and 5-fluorouracil cream not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) at 1 and 3 years after treatment. No definite conclusion could be drawn regarding the superiority of imiquimod over 5-fluorouracil. We now present the 5-year follow-up results according to the intention-to-treat analysis. Five years after treatment, the probability of tumor-free survival was 62.7% for methyl aminolevulinate photodynamic therapy (95% confidence interval [CI] = 55.3-69.2), 80.5% for imiquimod (95% CI = 74.0-85.6), and 70.0% for 5-fluorouracil (95% CI = 62.9-76.0). The hazard ratio for treatment failure of imiquimod and 5-fluorouracil were 0.48 (95% CI = 0.32-0.71, P < 0.001) and 0.74 (95% CI = 0.53-1.05, P = 0.09), respectively, when compared with methyl aminolevulinate photodynamic therapy. Compared with 5-fluorouracil, imiquimod showed a hazard ratio of 0.65 (95% CI 0.43-0.98, P = 0.04). In conclusion, 5 years after treatment, the results of this trial show that 5% imiquimod cream is superior to both methyl aminolevulinate photodynamic therapy and 5-fluorouracil cream in terms of efficacy for superficial basal cell carcinoma. We therefore consider 5% imiquimod cream as the first choice for noninvasive treatment in most primary superficial basal cell carcinomas.

A randomized controlled trial including 601 patients previously showed that the effectiveness of imiquimod and fluorouracil cream were not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) in patients with superficial basal cell carcinoma after 1 year of follow-up. We now present the 3-year follow-up results. The probability of tumor-free survival at 3 years post-treatment was 58.0% for MAL-PDT (95% confidence interval [CI] = 47.8-66.9), 79.7% for imiquimod (95% CI = 71.6-85.7), and 68.2% for fluorouracil (95% CI = 58.1-76.3). The hazard ratio for treatment failure comparing imiquimod with MAL-PDT was 0.50 (95% CI = 0.33-0.76, P = 0.001). Comparison of fluorouracil with MAL-PDT and fluorouracil with imiquimod showed hazard ratios of 0.73 (95% CI = 0.51-1.05, P = 0.092) and 0.68 (95% CI = 0.44-1.06, P = 0.091), respectively. Subgroup analysis showed a higher probability of treatment success for imiquimod versus MAL-PDT in all subgroups with the exception of elderly patients with superficial basal cell carcinoma on the lower extremities. In this subgroup, the risk difference in tumor-free survival was 57.6% in favor of MAL-PDT. In conclusion, according to results at 3 years post-treatment, imiquimod is superior and fluorouracil not inferior to MAL-PDT in treatment of superficial basal cell carcinoma.

At 2-year follow-up, UGFS was not inferior to surgery when reflux associated with venous symptoms was the clinical outcome of interest. UGFS has the potential to be a cost-effective approach to a common health problem. Registration numbers: NCT01103258 (http://www.clinicaltrials.gov) and NTR654 (http://www.trialregister.nl).

We used foam sclerotherapy in a 51-year-old man and a 33-year-old woman who had symptomatic varicose great saphenous veins and were otherwise healthy. Immediately after the initiation of treatment, transient scotomas developed in the man, and a migraine attack in the woman.On the basis of these observations, we decided to monitor by echocardiography the foam distribution during foam sclerotherapy in 33 consecutive patients with chronic venous insufficiency. The treatment in each patient was carried out according to European consensus guidelines. 2 Briefly, patients received a single injection of 5 ml of 1% polidocanol foam (air-to-liquid ratio, 4:1). The foam was injected with the patient's leg slightly elevated, while the saphenofemoral junction was manually compressed until full vasospasm occurred and blood-flow velocity in the great saphenous vein decreased to zero.In all patients studied, we detected foam microemboli in both the right atrium and ventricle between 45 seconds and 15 minutes after foam injection (Fig. 1A). In five patients, microembolism was also detectable in the left atrium and ventricle (Fig. 1B); however, neurologic signs did not develop in any of them. Careful echocardiographic examination of these five patients showed a right-to-left shunt through a patent foramen ovale. Because the neurologic symptoms observed in the two index patients could have reflected adverse effects of foam sclerotherapy due to a rightto-left shunt, we subsequently examined both patients by echocardiography and detected a patent foramen ovale in each.These findings suggest that foam-induced microembolism is a common phenomenon during foam sclerotherapy. The prevalence of patent foramen ovale, which can be a source of paradoxical embolism, is approximately 26% in the general population. 3 Still, serious neurologic symptoms after foam sclerotherapy, which include scotomas, migraine, and stroke, occur in only 2% or less of patients. 4,5 Thus, the findings in our cohort are in line with previous reports. Although the overall number of neurologic adverse effects during foam sclerotherapy might be underestimated, it appears that neurologic complications develop in relatively few patients with right-to-left shunts and foam microembolism.Nevertheless, we suggest that caution be exercised when foam sclerotherapy is performed in patients with a known patent foramen ovale and that patients with overt neurologic symptoms undergo an additional echocardiographic examination for the presence of a patent foramen ovale. Further prospective studies are needed to evaluate and confirm our observations.

In the treatment of primary incompetent greater saphenous veins, 3% polidocanol foam seems to be more effective than 1% polidocanol foam. The side effects were approximately similar in both groups.

The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.