Utility of noninvasive biomarker testing and MRI to predict a prostate cancer diagnosis.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer

Comparison of overall survival and unplanned hospital readmissions between partial and radical nephrectomy for cT1a and cT1b renal masses

Background: The aim of the study was to compare overall survival (OS) and unplanned hospital readmissions (UHRs) within 30 days between partial nephrectomy (PN) and radical nephrectomy (RN) for clinically localized T1 renal tumors. Methods: The National Cancer Database was queried to identify 51,018 patients who had undergone RN ( n = 23,904; 46.9%) or PN ( n = 27,114; 53.1%) for a cT1N0M0 renal mass from 2004 to 2013. OS and UHRs were compared using inverse probability of treatment weighted (IPTW)-adjusted Cox proportional hazards regression models. Results: For patients with a cT1a tumor, IPTW-adjusted analysis showed PN compared with RN was associated with improved OS (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.56, 0.67; p < 0.001) with a 5-year and 10-year IPTW-adjusted OS of 93.0% versus 88.2% and 78.1% versus 71.7%, respectively with no difference in UHR (odds ratio [OR] = 1.02; 95% CI = 0.90, 1.16; p = 0.727). For patients with a cT1b tumor, IPTW-adjusted analysis showed PN compared with RN to be associated with marginally improved OS (HR = 0.89; 95% CI = 0.82, 0.99; p = 0.025) with a 5-year and 10-year IPTW-adjusted OS of 85.3% versus 84.3% and 70.8% versus 63.6%, respectively, with more UHRs for PN (OR = 1.43; 95% CI = 1.19, 1.72; p < 0.001). Conclusions: PN compared with RN was associated with a significant survival benefit for patients with a cT1a renal mass and a modest survival benefit for patients with a cT1b renal mass. PN should be offered over RN when feasible despite a marginal increase in UHRs for PN of cT1b tumors. Randomized controlled trials are necessary to confirm these findings

Kavalactone Kawain Impedes Urothelial Tumorigenesis in UPII-Mutant Ha-Ras Mice via Inhibition of mTOR Signaling and Alteration of Cancer Metabolism

UPII-mutant Ha-ras transgenic mice develop urothelial hyperplasia and low-grade papillary carcinoma, which mimics human non-muscle invasive bladder cancer (NMIBC). We investigated the effects and mechanisms of kawain, a main kavalactone in the kava plant, on oncogenic Ha-ras-driven urothelial carcinoma in these mice. The mice were fed at six weeks of age with vehicle control or kawain (6 g/kg) formulated food for approximately five months. Seventy-eight percent of the mice or more fed with kawain food survived more than six months of age, whereas only 32% control food-fed male mice survived, (p = 0.0082). The mean wet bladder weights (a surrogate for tumor burden) of UPII-mutant Ha-ras transgenic mice with kawain diet was decreased by approximately 56% compared to those fed with the control diet (p = 0.035). The kawain diet also significantly reduced the occurrence of hydronephrosis and hematuria in UPII-mutant Ha-ras transgenic mice. Histological examination and immunohistochemistry analysis revealed that vehicle control-treated mice displayed more urothelial carcinoma and Ki67-positive cells in the bladder compared to kawain treated mice. Global metabolic profiling of bladder tumor samples from mice fed with kawain food showed significantly more enrichment of serotonin and less abundance of xylulose, prostaglandin A2, D2 and E2 compared to those from control diet-fed mice, suggesting decreased shunting of glucose to the pentose phosphate pathway (PPP) and reduced inflammation. In addition, kawain selectively inhibited the growth of human bladder cancer cell lines with a significant suppression of 4E-BP1 expression and rpS6 phosphorylation. These observations indicate a potential impact of kawain consumption on bladder cancer prevention by rewiring the metabolic programs of the tumor cells

Prostate-specific antigen screening and prostate cancer treatment in renal transplantation candidates: A survey of U.S. transplantation centers.

INTRODUCTION: Renal transplantation candidates are a highly screened population. There are currently no guidelines or consensus on prostate cancer (CaP) screening in these patients. In light of the recent United States Preventive Services Task Force recommendations against prostate-specific antigen (PSA) screening, we conducted a survey of transplantation surgeons to gain a better understanding of practice patterns among U.S. centers. MATERIALS AND METHODS: A 14-question multiple-choice online survey was e-mailed to 195 U.S. renal transplantation centers. The questionnaire assessed CaP screening and treatment practices. The survey also evaluated characteristics of the respondent\u27s institution. Descriptive statistics were used for each of the responses, and associations were made with program characterization using logistic or linear regression models. RESULTS: A total of 90 surgeons responded, representing 65 of 195 programs (33% response rate). Overall, 89% of respondents reported routinely screening for CaP in renal transplantation candidates and 71% had set guidelines for PSA screening. The most common age to start PSA screening was 50 years (51%) and 79% of respondents reported no age limit to stop PSA screening. Definitive treatment of CaP was required before proceeding to transplantation in 45% of respondents. Active surveillance was a viable option in 67% of responders. Most respondents (73%) replied that the waiting time for eligibility after treatment depended on the CaP stage and risk. CONCLUSIONS: Although most programs have guidelines on PSA screening in renal transplantation candidates, there is still variation nationwide in screening and treatment practices. AS is a viable treatment option in most of the programs. Our results suggest a benefit of a consensus panel to recommend guidelines in this population

Stimulants for depression: On the up and up?

The use of traditional psychostimulants (methylphenidate and dexamphetamine) and stimulant-like drugs (modafinil and armodafinil) for the treatment of depression is a growing concern given the lack of research evidence supporting their effectiveness. The current article describes the role of stimulants in treating depression - specifically their risks and benefits and their potential use alongside antidepressants. Clinically, the rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived, and this suggests that they likely operate via different mechanisms to conventional antidepressants. More importantly, there is little evidence from randomised controlled trials supporting their efficacy in treating depression, although modafinil has been shown to be effective in reducing prominent depressive symptoms, such as fatigue. Research is urgently required to clarify psychostimulants' mechanisms of action and to evaluate their long-term benefits and risks in the treatment of major and bipolar depression. Ultimately, specificity of action needs to be determined to inform the sophisticated clinical use of psychostimulants in the management of depression. Until then they should only be prescribed if absolutely necessary, and even then their prescription should be facilitatory and time limited unless it is for investigational purposes

Comparison of Perioperative Outcomes for Radical Nephrectomy Based on Surgical Approach for Masses Greater Than 10 cm.

Introduction and Objective: Robot-assisted radical nephrectomy (RRN) is increasingly utilized as an alternative to laparoscopic radical nephrectomy (LRN), but there are concerns over costs and objective benefit. In the setting of very large renal masses (&gt;10 cm), comparison between techniques is limited and it is unclear whether a robotic approach confers any perioperative benefit over LRN or open radical nephrectomy (ORN). In this study, perioperative outcomes of RRN, LRN, and ORN for very large renal masses are compared. Methods: Using the National Cancer Database, patients were identified who underwent radical nephrectomy for kidney tumors &gt;10 cm diagnosed from 2010 to 2015. Patients were analyzed according to surgical approach. Perioperative outcomes, including conversion to open, length of stay, readmission rates, positive surgical margins, and 30- and 90-day mortality were compared among cohorts. Results: A total of 9288 patients met inclusion criteria (RRN = 842, LRN = 2326, ORN = 6120). Compared with ORN, recipients of RRN or LRN had similar rates of 30-day readmission and 30- and 90-day mortality. Length of hospital stay was significantly shorter in RRN (-1.73 days ±0.19; p &lt; 0.0001) and LRN (-1.40 days ±0.12; p &lt; 0.0001) compared with ORN. LRN had a higher rate of conversion to open compared with RRN (odds ratio 1.48; 95% confidence interval 1.10-1.98; p = 0.0087). Conversion to open from RRN or LRN added 1.3 additional days of inpatient stay. Over the study period, RRN use increased from 4.1% to 14.8%, LRN from 20.9% to 25.6%, whereas ORN use decreased from 75% to 59.6%. Conclusions: Minimally invasive approaches are increasingly utilized in very large renal masses. RRN has lower rates of conversion to open but produces comparable perioperative outcomes to LRN. Minimally invasive approaches have a shorter length of inpatient stay but otherwise report similar surgical margin status, readmission rates, and mortality rates compared with ORN

Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation

Epidemiological evidence suggests that kava (Piper methysticum Forst) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers

Ureteroenteric anastomotic revision as initial management of stricture after urinary diversion.

OBJECTIVE: To report our experience with ureteroenteric anastomotic revision as initial treatment of stricture after urinary diversion. METHODS: An institutional review board-approved retrospective study was carried out. A total of 41 patients who underwent primary ureteroenteric anastamotic revision were identified between 2007 and 2015. Data analyzed included patient characteristics, type of diversion, estimated blood loss, operative time, change in renal function, length of stay, postoperative complications and time with nephrostomy/stent. Success of revision was defined as an improvement in hydronephrosis on radiographic imaging and/or reflux during pouchogram. Predictors of length of stay and complications were analyzed using analysis of covariance. RESULTS: A total of 50 renal units were revised with a success rate of 100%. The median length of stay was 6 days (2-16 days). There were a total of 15 complications (one major, 14 minor) in 14 patients (33% 30-day complication rate). The most common were wound infection (n = 4) and arrhythmia (n = 4). Robotic revision (n = 5) had a median length of stay of 3 days (2-4) with no complications. CONCLUSIONS: Primary ureteroenteric anastomotic revisions have an excellent success rate at an experienced center and might obviate the need for multiple interventions. Open revision is associated with mostly minor complications. Robotic revision might reduce the morbidity of open revision in select cases