Introduction Dapoxetine is a short-acting selective serotonin reuptake inhibitor that was recently approved for the on-demand treatment of premature ejaculation (PE). Aim To evaluate the efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE from the Asia-Pacific region. Methods This randomized, double-blind, parallel-group, placebo-controlled trial enrolled men who were 18 years or older; in a monogamous, heterosexual relationship for at least 6 months; met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, criteria for PE for at least 6 months; and had an intravaginal ejaculatory latency time (IELT) of 2 minutes or less in at least 75% of sexual intercourse episodes. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1–3 hours before intercourse) for 12 weeks. Main Outcome Measures Stopwatch-measured Average IELT, the Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change in PE, treatment-emergent adverse events (TEAEs). Results Of the 1,067 subjects randomized, 858 completed the study. Mean Average IELT increased from approximately 1.1 minutes at baseline (across groups) to 2.4, 3.9, and 4.2 minutes with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively, and geometric mean Average IELT increased from approximately 0.9 minutes at baseline (across groups) to 1.8, 2.7, and 3.1 minutes, respectively (fold-increases of 2.0, 2.8, and 3.3, respectively). All PEP measures and the CGI of change were significantly improved with dapoxetine vs. placebo at study endpoint (P ≤ 0.005 for all). The most common TEAEs with dapoxetine included nausea, dizziness, somnolence, headache, vomiting, diarrhea, and nasopharyngitis; TEAEs led to discontinuation in 0.3%, 1.7%, and 5.1% of subjects with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. Conclusions Dapoxetine treatment significantly prolonged IELT and improved PEP measures and was generally well tolerated in men with PE in the Asia-Pacific region.

BACKGROUNDHeterogeneity of primary tumor volume within tumors of the same classification indicates a need to elucidate the effects of primary tumor volume on treatment outcomes in patients with nasopharyngeal carcinoma (NPC).METHODSFrom 1994 through 1996, 129 patients with newly diagnosed NPC who were treated with high‐dose radiotherapy were enrolled in the study. Computed tomography‐derived primary tumor volume was measured using the summation‐of‐area technique. Correlations between American Joint Committee on Cancer (AJCC) disease stage, primary tumor volume, and disease‐specific survival were assessed using a Cox regression model. Cross‐validation based on receiver operating characteristic (ROC) curve also was examined.RESULTSCompared with the AJCC staging system and the TNM classification system, primary tumor volume was better at determining cumulative survival for patients with NPC. Hazard ratios increased with tumor volume, ranging from 6.68 (95% confidence interval [95% CI], 1.89–23.67) for tumor volumes between 20–40 mL, 18.03 (95% CI, 4.80–67.75) for tumor volumes between 40–60 mL, and 26.06 (95% CI, 7.70–88.20) for tumor volumes > 60 mL. With both tumor volume and T classification in the same Cox regression model, only tumor volume remained statistically significant in the prognosis of NPC. The validation results with ROC curves also revealed that, in predicting patient outcome, primary tumor volume (area under the ROC = 83.33%) was superior to disease stage (area under the ROC = 66.53%) and TNM classification (area under the ROC = 58.61%).CONCLUSIONSThe incorporation of primary tumor volume may lead to a further refinement of the current AJCC staging system, particularly for patients with large primary tumor volumes (> 60 mL), who require more aggressive treatment. Cancer 2004. © 2004 American Cancer Society.

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Our investigation showed the prevalence of enuresis is similar to those reports from the north of Taiwan and most of other western countries, but higher than that of China and Hong-Kong. Difficulty in waking and time of wetting were the only factors significantly associated with the severity of enuresis.

BackgroundHedgehog signalling has been implicated in prostate tumorigenesis in human subjects and mouse models, but its effects on transforming normal basal/stem cells toward malignant cancer stem cells remain poorly understood.MethodsWe produced pCX-shh-IG mice that overexpress Hedgehog protein persistently in adult prostates, allowing for elucidation of the mechanism during prostate cancer initiation and progression. Various markers were used to characterize and confirm the transformation of normal prostate basal/stem cells into malignant cancer stem cells under the influence of Hedgehog overexpression.ResultsThe pCX-shh-IG mice developed prostatic intraepithelial neoplasia (PIN) that led to invasive and metastatic prostate cancers within 90 days. The prostate cancer was initiated through activation of P63+ basal/stem cells along with simultaneous activation of Hedgehog signalling members, suggesting that P63+/Patch1+ and P63+/Smo+ cells may serve as cancer-initiating cells and progress into malignant prostate cancer stem cells (PCSCs). In the hyperplastic lesions and tumors, the progeny of PCSCs differentiated into cells of basal-intermediate and intermediate-luminal characteristics, whereas rare ChgA+ neuroendocrine differentiation was seen. Furthermore, in the metastatic loci within lymph nodes, kidneys, and lungs, the P63+ PCSCs formed prostate-like glandular structures, characteristic of the primitive structures during early prostate development. Besides, androgen receptor (AR) expression was detected heterogeneously during tumor progression. The existence of P63+/AR-, CK14+/AR- and CD44+/AR- progeny indicates direct procurement of AR- malignant cancer trait.ConclusionsThese data support a cancer stem cell scenario in which Hedgehog signalling plays important roles in transforming normal prostate basal/stem cells into PCSCs and in the progression of PCSCs into metastatic tumor cells.