Androgen therapy may precipitate obstructive sleep apnea in men. Despite increasing androgen use in older men, few studies have examined sleep and breathing. Randomized, double-blind, placebo-controlled studies examining effects of testosterone simultaneously on sleep, breathing, and function in older men are not available. Seventeen community-dwelling healthy men over the age of 60 yr were randomized to receive three injections of im testosterone esters at weekly intervals (500 mg, 250 mg, and 250 mg) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout. Polysomnography, anthropometry, and physical, mental, and metabolic function were assessed at baseline and after each treatment period. Testosterone treatment reduced total time slept ( approximately 1 h), increased the duration of hypoxemia ( approximately 5 min/night), and disrupted breathing during sleep (total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour) (all P < 0.05). Despite expected effects on body composition (increase in total and lean mass, reduction in fat mass, P < 0.05, bioimpedance method), upper airway dimensions did not change (acoustic reflectometry). Driving ability (computer simulation), physical activity (accelerometry, Physical Activity Scale in the Elderly), quality of life (SF36, Functional Outcomes of Sleep Questionnaire), mood (Profile of Mood States Questionnaire), sleepiness (Epworth, Stanford scales), and insulin resistance (homeostasis model) also were not changed by treatment. Short-term administration of high-dose testosterone shortens sleep and worsens sleep apnea in older men but did not alter physical, mental, or metabolic function. These changes did not appear to be due to upper airway narrowing. Further study of longer-term lower-dose androgen therapy on sleep and breathing is needed to evaluate its safety in older men.

IMPORTANCE Ovarian cancer has the highest mortality rate among gynecologic malignant tumors. Data are lacking on the survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with ovarian cancer who underwent primary or interval cytoreductive surgery.OBJECTIVE To assess the clinical benefit of HIPEC after primary or interval maximal cytoreductive surgery in women with stage III or IV primary advanced ovarian cancer. DESIGN, SETTING, AND PARTICIPANTSIn this single-blind randomized clinical trial performed at 2 institutions in South Korea from March 2, 2010, to January 22, 2016, a total of 184 patients with stage III or IV ovarian cancer with residual tumor size less than 1 cm were randomized (1:1) to a HIPEC (41.5 °C, 75 mg/m 2 of cisplatin, 90 minutes) or control group. The primary end point was progression-free survival. Overall survival and adverse events were key secondary end points. The date of the last follow-up was January 10, 2020, and the data were locked on February 17, 2020. EXPOSURES Hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.MAIN OUTCOMES AND MEASURES Progression-free and overall survival. RESULTSOf the 184 Korean women who underwent randomization, 92 were randomized to the HIPEC group (median age, 52.0 years; IQR, 46.0-59.5 years) and 92 to the control group (median age, 53.5 years; IQR, 47.5-61.0 years). After a median follow-up of 69.4 months (IQR, 54.4-86.3 months), median progression-free survival was 18.8 months (IQR, 13.0-43.2 months) in the control group and 19.8 months (IQR, 13.7-55.4 months) in the HIPEC group (P = .43), and median overall survival was 61.3 months (IQR, 34.3 months to not reported) in the control group and 69.5 months (IQR, 45.6 months to not reported) in the HIPEC group (P = .52). In the subgroup of interval cytoreductive surgery after neoadjuvant chemotherapy, the median progression-free survival was 15.4 months (IQR, 10.6-21.1 months) in the control group and 17.4 months (IQR, in the HIPEC group (hazard ratio for disease progression or death, 0.60; 95% CI, 0.37-0.99; P = .04), and the median overall survival was 48.2 months (IQR, 33.8-61.3 months) in the control group and 61.8 months (IQR, 46.7 months to not reported) in the HIPEC group (hazard ratio, 0.53; 95% CI, 0.29-0.96; P = .04). In the subgroup of primary cytoreductive surgery, median progression-free survival was 29.7 (IQR, 17.2-90.1 months) in the control group and 23.9 months (IQR, 12.3-71.5 months) in the HIPEC group, and the median overall survival was not reached in the control group and 71.3 months (IQR, 45.6 months to not reported) in the HIPEC group. CONCLUSIONS AND RELEVANCEThe addition of HIPEC to cytoreductive surgery did not improve progression-free and overall survival in patients with advanced epithelial ovarian cancer. Although the results are from a subgroup analysis, the addition of HIPEC to interval cytoreductive surgery provided an improvement of progression-free and overall survival.

Purpose To retrospectively analyze whether Prostate Imaging Reporting and Data System (PI-RADS) version 2 is helpful for the detection of clinically significant prostate cancer. Materials and Methods Institutional review board approved this retrospective study. A total of 425 patients with prostate cancer who had undergone magnetic resonance (MR) imaging and radical prostatectomy were included. Preoperative parameters such as prostate-specific antigen, biopsy Gleason score, greatest percentage of the core, percentage of the positive core number, and score at PI-RADS version 2 with MR imaging were investigated. Two independent readers performed PI-RADS scoring. Clinically significant prostate cancer was defined as follows: (a) Gleason score of 7 or greater, (b) tumor volume of 0.5 cm(3) or greater, or a (c) positive extracapsular extension or seminal vesicle invasion. The reference standard was based on review of surgical specimen. Logistic regression was conducted to determine which parameters are associated with the presence of clinically significant cancer. Interreader agreement (ie, score ≥4 or not) was investigated by using κ statistics. Results At univariate analysis, all of the preoperative parameters were significant for clinically significant prostate cancer (P < .05). However, multivariate analysis revealed that PI-RADS score was the only significant parameter for both readers (reader 1: odds ratio = 28.170, P = .002; reader 2: odds ratio = 5.474, P = .007). The interreader agreement was excellent for PI-RADS score of 4 or greater (weighted κ = 0.801; 95% confidence interval: 0.737, 0.865). Conclusion The use of PI-RADS version 2 may help preoperatively diagnose clinically significant prostate cancer. (©) RSNA, 2016.

SummaryExpression of carbonic anhydrase IX (CA9) was shown to be strongly involved in high incidences of metastasis and poor prognosis in various human tumors. In this study, we investigated the possible role for CA9 in tumor metastases in vitro, using a gene transfection tool in the human cervical carcinoma cell line C33A. Gene expression profiling of CA9-transfected cells (C33A/CA9) and vectortransfected cells (C33A/Mock) was investigated by DNA microarray. The biological functions of differentially expressed genes between the C33A/CA9 and C33A/Mock cells included cell growth, regulation of cell-cell and cell-extracellular matrix adhesion and cytoskeletal organization. Immunofluorescent stain and Matrigel culture showed cytoskeletal remodeling, disassembled focal adhesion, weakened cell-cell adhesion and increased motility in C33A/CA9 cells. These invasive and metastatic phenotypes were associated with Rho-GTPase-related epithelial-mesenchymal transition. Inhibition of the Rho/Rho kinase pathway by a ROCK inhibitor (Y27632) and si-Rho (short interference RNA against RhoA) showed that Rho-GTPase signaling was involved in cellular morphologic and migratory changes. The effect of CA9 on Rho-GTPase signaling was also confirmed by silencing CA9 expression. Our results suggest that CA9 overexpression induces weakening of cell adhesions and augmented cell motility by aberrant Rho-GTPase signal transduction. Our study shows an underlying mechanism of CA9-related enhanced metastatic potential of tumor cells.

The proposed shape features and TIPs improved the HCFs and DFs, respectively, and the feature concatenation further enhanced the quality of features for differentiating AMLwvf from ccRCC in abdominal CE CT images.

Renal papillary necrosis is not a pathologic entity but rather a descriptive term for a condition--necrosis of the renal papillae--that has various possible causes. The renal medulla and papillae are vulnerable to ischemic necrosis because of the peculiar arrangement of their blood supply and the hypertonic environment. The etiology of renal papillary necrosis includes diabetes, analgesic abuse or overuse, sickle cell disease, pyelonephritis, renal vein thrombosis, tuberculosis, and obstructive uropathy. Renal papillary necrosis has been diagnosed with the use of intravenous urography and ultrasonography, but contrast material-enhanced computed tomography (CT) may better depict a full range of typical features, including contrast material-filled clefts in the renal medulla, nonenhanced lesions surrounded by rings of excreted contrast material, and hyperattenuated medullary calcifications. In the presence of papillary sloughing, CT may depict hydronephrosis and filling defects in the renal pelvis or ureter, which also may contain calcifications. During healing, the epithelialized papillary tip appears blunted. Shrinkage of the kidney, a common sequela, also may be detected at CT. Multi-detector row CT depicts these and other features more clearly and directly than single-detector row CT, given the advantages of thinner sections and multiplanar reformation, and it may help identify the condition at an earlier stage, when effective treatment can reverse the ischemic process. Familiarity with the CT features of the condition therefore is useful for its successful diagnosis and management.

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• No subject with PI-RADS <4 had BCR after RP • PI-RADSv2 was the only predictor of BCR in multivariate analysis • Two-year, BCR-free survival following RP was lower for PI-RADS≥4 than for PI-RADS<4 • Inter-rater agreement was good for PI-RADS ≥4 or not.