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The treatment landscape of renal cell carcinoma has changed with the introduction of targeted therapies. While the clinical benefit of cabozantinib is well-established for Japanese patients who have received prior treatment, the economic benefit remains unclear. The objective of this study was to assess the cost-effectiveness of cabozantinib compared with everolimus, axitinib, and nivolumab in patients with advanced renal cell carcinoma who have failed at least one prior therapy in Japan. A cost-effectiveness model was developed using a partitioned survival approach and a public healthcare payer's perspective. Over a lifetime horizon, clinical and economic implications were estimated according to a three-health–state structure: progression-free, post-progression, and death. Key clinical inputs and utilities were derived from the METEOR trial, and a de novo network meta-analysis and cost data were obtained from publicly available Japanese data sources. Costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were estimated. Costs and health benefits were discounted annually at 2%. Cabozantinib was more costly and effective compared with everolimus and axitinib, with deterministic incremental cost-effectiveness ratios of ¥5,375,559 and ¥2,223,138, respectively. Compared to nivolumab, cabozantinib was predicted to be less costly and more effective. Sensitivity and scenario analyses demonstrated that the key drivers of cost-effectiveness results were the estimation of overall survival and treatment duration, relative efficacy, drug costs, and subsequent treatment costs. METEOR was an international trial but did not enroll any patients from Japan. Efficacy and safety data from METEOR were used as a proxy for the Japanese population following validation by clinical experts, and alternative assumptions specific to clinical practice in Japan were evaluated in scenario analyses. In Japan, cabozantinib is a cost-effective alternative to everolimus, axitinib, and nivolumab for the treatment of patients with advanced renal cell carcinoma who have received at least one prior line of therapy. [ABSTRACT FROM AUTHOR]

Although reactive oxygen species in semen are associated with unfavorable results with respect to assisted reproductive technology, their effects based on the detailed stages of embryo development are unclear. We investigated the relationship between reactive oxygen species in semen and the oocyte fertilization rate, cleavage rate, and blastulation rate of intracytoplasmic sperm injections. This retrospective study enrolled 77 couples who underwent intracytoplasmic sperm injection and analyzed 887 eggs from 141 cycles of intracytoplasmic sperm injection. The reactive oxygen species level in semen was compared between the fertilized and nonfertilized groups, between the good-cleavage-embryo and non-developed-embryo groups, and between the good-quality-blastocyst and poor-quality-blastocyst groups. The cut-off level of reactive oxygen species was calculated to predict good-cleavage-embryo and good-quality-blastocyst development. The fertilization rate was 65.4%, and the mean reactive oxygen species levels were not significantly different between the fertilized and nonfertilized groups. The reactive oxygen species level was significantly higher in the non-developed-embryo group than in the good-cleavage-embryo group (P = 0.0026) and was significantly lower in the good-quality-blastocyst group than in the poor-quality-embryo group (P = 0.015). Cleavage embryos and blastocysts were divided into high- and low-reactive-oxygen-species groups using a cut-off value of 6601 and 4926 relative light units, as calculated from the receiver operating characteristic curve. The rates of good-cleavage embryos and good-quality blastocysts were lower in the high-reactive-oxygen-species group than in the low-reactive-oxygen-species group, which were both statistically significant. To conclude, reactive oxygen species in semen is considered to have an adverse effect on both the early and late stages of embryo development in intracytoplasmic sperm injection. Abbreviations: GnRH, gonadotropin-releasing hormone; ICSI, intracytoplasmic sperm injection; IVF, invitro fertilization; LPO, lipid peroxidation; NADPH, nicotinamide adenine dinucleotide phosphate; RLU, relative light units; ROC, receiver operating characteristic; ROS, reactive oxygen species [ABSTRACT FROM AUTHOR]

Background: Real-world treatment patterns of bone metastatic castration-resistant prostate cancer (mCRPC) in Japan were examined, focusing on treatment patterns and resource use differences attributed to symptomatic skeletal events (SSEs).Methods: Urologists (N = 176) provided retrospective chart data for patients with mCRPC (N = 445) via online surveys. Descriptive analyses and chi-square tests evaluated treatment patterns and their differences by SSE presence; generalized linear mixed models examined healthcare resource utilization differences as a function of SSEs.Results: Patients were on average 73.6 years old (SD = 8.3), diagnosed with prostate cancer 5.1 years (SD = 6.2), castration-resistant 2.3 years (SD=2.0), and had 7.9 bone metastases sites (SD=12.4). Novel anti-hormones showed increased adoption as mCRPC treatment. Simultaneously, luteinizing hormone-releasing hormone (LHRH) agonist/antagonist use was common (43.6% of patients in 1st line), even as CRPC treatment had started. SSEs were uncommon (2-3% per treatment line; 5% at any time), but were associated with increased opioids, strontium-89, bisphosphonates, and NSAIDs use, plus increased healthcare visits (all p < .05).Conclusions: LHRH agonist/antagonist treatment combinations remain the mCRPC treatment mainstay in Japan. However, novel anti-hormone therapies are becoming well-accepted in practice. SSEs were associated with increased healthcare resource and analgesic use, highlighting the need for efficient symptom management. [ABSTRACT FROM AUTHOR]

Objective:More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [–2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. Materials and methods:The subjects were 50 consecutive men with a PSA level of 2.0–10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. Results:In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). Conclusion:PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer. [ABSTRACT FROM AUTHOR]

Density gradient centrifugation can separate motile sperm from immotile sperm and other cells for assisted reproduction, but may also remove antioxidants from seminal plasma, resulting in oxidative stress. Therefore, we investigated reactive oxygen species (ROS) concentrations and distribution in semen before and after density gradient centrifugation. We assessed semen volume, sperm concentration, sperm motility, and ROS levels before and after density gradient centrifugation (300 x g for 20 minutes) in 143 semen samples from 118 patients. The ROS removal rate was evaluated in ROS-positive samples and ROS formation rate in ROS-negative samples. Thirty-eight of 143 untreated samples (26.6%) were ROS-positive; sperm motility was significantly lower in these samples than in ROS-negative samples (p< 0.05). After density gradient centrifugation, only seven of the 38 ROS-positive samples (18.42%) exhibited a ROS-positive lower layer (containing motile sperm) with a ROS removal rate of 81.58%, whereas the upper layer was ROS-positive in 24 samples (63.16%). In the ROS-negative group (n= 105), ROS was detected in 19 samples after centrifugation (18.10%, ROS generation rate), of which 18 were ROS-positive only in the upper layer or interface and the other was ROS-positive in both layers. Density gradient centrifugation can separate motile sperm from immotile sperm as well as remove ROS (including newly generated ROS). This data supports the view that density gradient centrifugation can select motile spermatozoa without enhancing oxidative stress. Abbreviations: ROS: reactive oxygen species; SOD: superoxide dismutase; GPx: glutathione peroxidase; DNA: deoxyribonucleic acid; DGC: density gradient centrifugation; IUI: intrauterine insemination; IVF:in vitrofertilization; HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; EDTA: ethylenediaminetetraacetic acid; HTF: HEPES-buffered human tubal fluid; IMSI: intracytoplasmic morphologically selected sperm injection; SMAS: sperm motility analyzing system; CASA: computer-assisted semen analyzer; WHO: World Health Organization [ABSTRACT FROM PUBLISHER]

Objective. This study investigated the correlation between the operation time and the stone size as determined by multiple modalities and the computed tomography (CT) densities of bladder calculi using holmium: yttrium garnet (Ho:YAG) laser lithotripsy. Material and methods. A total of 68 patients underwent cystolithotripsy from March 2010 to October 2011. Thirty-six of these patients underwent cystolithotripsy using a Ho:YAG laser for bladder calculi by a single surgeon. The stone size was assessed by six modalities: sum of the stones' diameters: stone burden; maximum stone's diameter; number of stones; sum of the area using axial CT; sum of area using kidney-ureter-bladder (KUB) films; and volume using CT. In addition, the stone's CT density was measured by: the mean CT density of the maximum stone's whole area; maximum CT density of the maximum stone's whole area; and mean CT density of the maximum stone's center area. Correlations between the operation time and the stone size and the stone CT density were assessed. Results. A total of 36 patients (30 male and six female) who underwent cystolithotripsy using a Ho:YAG laser for bladder calculi were enrolled in this study. Spearman correlation showed that the area and volume were strongly correlated with the operative time. The multipliers between the stone size and stone CT density showed no advantages based on the stone area or volume alone. Conclusion. The area and volume of the stones correlated more closely with the operation time than the stone burden for bladder calculi lithotripsy using a Ho:YAG laser. [ABSTRACT FROM AUTHOR]