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ObjectiveThis evaluated the long-term outcome after endoscopic thoracic sympathectomy (ETS) from below Dl to D4, using a single-site access technique for primary hyperhidrosis of the upper limbs. Summary Background DataPrimary hyperhidrosis of the upper limbs is a distressing and often socially disabling condition. Endoscopic thoracic sympathectomy is considered the treatment of choice, causing minimal morbidity and high initial success rates. However, data regarding long-term results are scarce. MethodsTwo hundred seventy of 323 patients (83.7%), in whom 480 sympathectomies were performed, answered a questionnaire after a mean of 14.6 years postoperatively regarding the early postoperative result, side effects, and complications caused by the operation and long-term results with particular emphasis on patient satisfaction. ResultsThere was no postoperative mortality and no major complications requiring surgical reintervention. A majority of the patients (98.1 %) were relieved, and 95.5% were satisfied initially. Permanent side effects included compensatory sweating in 67.4%, gustatory sweating in 50.7% and Horner's trias in 2.5%. However, patient satisfaction declined over time, although only 1.5% recurred. This left only 66.7% satisfied, and a 26.7% partially satisfied. Compensatory and gustatory sweating were the most frequently stated reasons for dissatisfaction. Individuals operated for axillary hyperhidrosis without palmar involvement were significantly less satisfied (33.3% and 46.2%, respectively).

Stromal remodeling, in particular fibroblast-to-myofibroblast differentiation, is a hallmark of benign prostatic hyperplasia (BPH) and solid tumors, including prostate cancer (PCa). Increased local production of TGFβ1 is considered the inducing stimulus. Given that stromal remodeling actively promotes BPH/PCa development, there is considerable interest in developing stromal-targeted therapies. Microarray and quantitative PCR analysis of primary human prostatic stromal cells induced to undergo fibroblast-to-myofibroblast differentiation with TGFβ1 revealed up-regulation of the reactive oxygen species (ROS) producer reduced nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and down-regulation of the selenium-containing ROS-scavenging enzymes glutathione peroxidase 3, thioredoxin reductase 1 (TXNRD1), and the selenium transporter selenoprotein P plasma 1. Consistently, NOX4 expression correlated specifically with the myofibroblast phenotype in vivo, and loss of selenoprotein P plasma 1 was observed in tumor-associated stroma of human PCa biopsies. Using lentiviral NOX4 short hairpin RNA-mediated knockdown, pharmacological inhibitors, antioxidants, and selenium, we demonstrate that TGFβ1 induction of NOX4-derived ROS is required for TGFβ1-mediated phosphorylation of c-jun N-terminal kinase, which in turn is essential for subsequent downstream cytoskeletal remodeling. Significantly, selenium supplementation inhibited differentiation by increasing ROS-scavenging selenoenzyme biosynthesis because glutathione peroxidase 3 and TXNRD1 expression and TXNRD1 enzyme activity were restored. Consistently, selenium depleted ROS levels downstream of NOX4 induction. Collectively, this work demonstrates that dysregulated redox homeostasis driven by elevated NOX4-derived ROS signaling underlies fibroblast-to-myofibroblast differentiation in the diseased prostatic stroma. Further, these data indicate the potential clinical value of selenium and/or NOX4 inhibitors in preventing the functional pathogenic changes of stromal cells in BPH and PCa.

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