ObjectivesTo study the relationship between sperm DNA fragmentation (SDF) and reactive oxygen species (ROS) levels in infertile patients with varicocele, and to examine the beneficial effect of varicocelectomy and elucidate predictors of improvement after repair.Patients, subjects and methodsWe prospectively studied 60 patients with varicocele and abnormal semen variables who attended the outpatient clinic complaining of infertility for ≥12 months. In all, 25 patients (41.7%) had bilateral varicoceles and 35 (58.3%) had left varicoceles. The DNA fragmentation index (DFI%, percentage of sperm with denatured nuclei), ROS and total non-enzymatic antioxidant capacity (TAC) were measured. Inguinal varicocelectomy was performed in all patients. At 3–6 months postoperatively, all measurements were repeated. A control group, comprised of 20 normozoospermic fertile men, was included. Regression analysis was used to examine predictors of improvement.ResultsThe mean (SD) DFI% in the 60 infertile patients with varicocele was 29.9 (8.3) and 7.56 (2.84)% in the controls; ROS levels were 4.49 (0.9) in patients and 2.62 (0.8) photons/min in controls; and the TAC was 0.97 (0.4) in patients and 1.5 (0.5) mM in controls; with highly significant differences between the patients and controls. The DFI% showed a positive correlation with ROS levels, whilst the total motile sperm count (TMSC) had a significant negative correlation with DFI%, ROS levels and grade of varicocele, whilst there was significant positive correlation with TAC. The grade of varicocele and duration of infertility were related to the presence of higher levels of ROS and increased of DFI%. Postoperatively, improvement (measured as a >50% increase in TMSC) occurred in 40 of 55 (73%) patients available at follow-up, with a significant reduction in the mean (SD) DFI% from 29.49 (8.58) to 18.78 (7.23)%, ROS levels from 4.49 (0.88) to 3.27 (1.3) photons/min (both P < 0.001), and a significant increase in the mean (SD) TAC from 1.01 (0.44) to 2.05 (0.51) mM (P < 0.001). Responders had a shorter infertility duration and lower preoperative DFI% and ROS levels. Regression analysis showed that DFI% is a predictor of improvement after varicocelectomy.ConclusionSDF was shown to have a negative impact on improvement after varicocelectomy. Hence, DFI% could be recommended as a prognostic test in infertile patients with varicocele to help decision-making as regards the necessity and the anticipated outcome of varicocelectomy in patients with infertility.

BACKGROUND Ablative fractional laser-assisted therapy is increasingly used to facilitate drug delivery and intensify clinical efficacy of topically applied drugs. OBJECTIVE To evaluate the effectiveness of combined ablative fractional CO2 laser and topically applied 5-fluorouracil (5-FU) or verapamil hydrochloride in the treatment of hypertrophic scars (HTSs) and keloids and to examine their possible effects on TGF-β1 expression. PATIENTS AND METHODS Thirty patients with HTSs and keloids were randomly treated with combined CO2 laser followed by topical verapamil or 5-FU application or CO2 laser monotherapy. All patients received 4 treatments at 1-month intervals. Subjective and objective assessment was obtained using the Vancouver Scar Scale (VSS). Histological changes and immunohistochemical staining for TGF-β1 were performed. RESULTS Compared with baseline, there was a significant reduction in the VSS 1 month after the last treatment session in all groups (p < .05). Laser-assisted 5-FU delivery tended to show a higher extent of improvement in scar characteristics than laser-assisted verapamil hydrochloride delivery, without significance. No significant side effects were reported in all patient groups. TGF-β1 expression was significantly decreased after laser sessions. CONCLUSION Combined fractional CO2 laser and topical 5-FU or verapamil hydrochloride offer a safe therapy for HTSs and keloids.

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Actinic keratoses (AKs) and squamous cell carcinoma in situ (SCCIS) are precursor lesions for cutaneous squamous cell carcinoma (cSCC), the second most common form of cancer. Current topical therapies for AKs and SCCIS promote skin inflammation to eradicate lesions and do not directly target the biological mechanisms driving growth. We hypothesized that topical small molecule inhibitors targeting kinases promoting keratinocyte growth in AKs and SCCIS could induce regression of these lesions with less inflammation. To test this hypothesis, we determined the efficacy of topical dasatinib, 5‐fluorouracil and BEZ‐235 in inducing regression of cSCCs in the K14‐Fyn Y528 transgenic mouse model. Topical dasatinib induced regression of cSCC with less inflammation, no ulceration and no mortality compared to 5‐fluorouracil. Topical BEZ‐235 induced cSCC regression similar to dasatinib without erythema or ulceration. These data indicate that topical small molecule kinase inhibitors targeting drivers of AK/SCCIS/cSCC growth represent a promising therapeutic approach to treat these common skin lesions.

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