Abbreviations & Acronyms 4-HNE = 4-hydroxy-2-nonenal 8-OHdG = 8-hydroxy-2′-deoxyguanosine ART = assisted reproductive technology CCM = cerebral cavernous malformation CREM = cyclic adenosine 3′,5′-monophosphate response element modulator ELV = experimental left varicocele eNOS = endothelial nitric oxide synthase GDNFa1 = glial cell line-derived neurotropic factor receptor a1 GSR = glutathione reductase GPX = glutathione peroxidase GST = glutathione S-transferase HIF1 = hypoxia-inducible factor 1 HO-1 = heme oxygenase 1 ICSI = intracytoplasmic sperm injection IL-1 = interleukin-1 iNOS = inducible nitric oxide synthase IUI = intrauterine insemination IVF = in vitro fertilization MDA = malondialdehyde nNOS = neuronal nitric oxide synthase NO = nitric oxide PDRN = polydeoxyribonucleotide PCNA = proliferating cell nuclear antigen PN = pronuclear O2 -= superoxide anion ROS = reactive oxygen species RNS = reactive nitrogen species SOD = superoxide dismutase TUNEL = terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling VEGF = vascular endothelial growth factor Abstract: Varicocele is the most common and treatable cause of male infertility. Studies of a rat experimental left varicocele model and human testicular biopsy samples have shown the involvement of various factors in its pathophysiology. Among them, oxidative stress plays a major role in impairing spermatogenesis and sperm function. Therefore, in addition to palpation, scrotal ultrasonography and color Doppler ultrasound , evaluation of testicular oxidative stress (e.g. scrotal temperature is a surrogate parameter) is recommended to enable diagnosis and suitable treatment of varicocele. Varicocelectomy increases the fertilization, pregnancy and live birth rates, indicating improved sperm function; it is therefore important even in couples undergoing intracytoplasmic sperm injection. Routine sperm-function tests are warranted to monitor the sperm quality after varicocelectomy and consequent improvement in the outcomes of assisted reproductive technology. Furthermore, the indications of varicocelectomy in assisted reproductive technology should be widened.Key words: assisted reproductive technologies, oxidative stress, varicocele. Role of sperm factors in ICSIVaricocele is the most common cause of male infertility. Its prevalence is notably high (~40%) in couples with male factor infertility compared with the general population (Յ20%).1 While debating the pathophysiology of varicocele, its influence on infertility treatment should be considered. Twenty years ago, we reviewed that varicocele causes spermatogenic disorder, and attempted to detect and treat as many cases as possible. 2 In the 1990s, the widespread application of ICSI lowered the importance of varicocele treatment. Furthermore, the usefulness of varicocele treatment itself was regarded as doubtful. 3,4 In contrast, two recent meta-analyses have shown that varicocelectomy significantly improves sperm concentration and motility in infertile men with palpable varicocel...

Elevation of scrotal temperature is one of the major factors to impair spermatogenesis and steroidogenesis in testis with varicocele. This heat stress is shown to be closely associated with oxidative stress, following the apoptosis of germ cells.

This study indicates that urinary IL-2 at the eighth instillation of BCG may serve as a valuable prognostic factor of treatment efficacy as well as tumor recurrence after treatment.

Objective: To search for a biological marker to distinguish low-risk from high-risk bladder cancer indicating disease progression. Methods: The whole genome-wide copy numbers were screened in 18 patients with bladder cancer using array comparative genomic hybridization (CGH) consisting of 4,030 bacterial artificial chromosome clones. Results: Gain of 5p15.33, including TPPP (tubulin polymerization-promoting protein)and ZDHHC11 (zinc finger DHHC domain-containing protein 11) genes, was detected in 5 of 9 (55.6%) high-grade bladder cancers and no (0%; n = 9) low-grade bladder cancer. To confirm the preliminary data, 5p15.33 gain was studied by fluorescence in situhybridization (FISH) in 100 patients, and the results were compared with biological characteristics. In FISH analysis, gain of 5p15.33 was significantly correlated with higher histological grade (p < 0.0001) and advanced pathological stage (p = 0.0284). Tumors with a gain of 5p15.33 had a significantly higher progression-free survival rate than those without (p = 0.0006, log-rank test). Multivariate analysis revealed that gain of 5p15.33 was a predictor for disease progression in bladder cancer (hazard ratio: 1.887, 95% confidence interval: 1.215–2.968, p = 0.0050). Conclusion: These data suggest that gain of 5p15.33 (TPPP and ZDHHC11) may become a potential biomarker identifying high-risk patients with disease progression in bladder cancer.

This PMS demonstrated that cabazitaxel was generally tolerated and showed promising efficacy in Japanese patients with mCRPC treated in real-world settings. Results are consistent with those of pre-registration clinical trials.