A Scaled Proteomic Discovery Study for Prostate Cancer Diagnostic Markers Using ProteographTM and Trapped Ion Mobility Mass Spectrometry.

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate cancer progression. Additionally, optimized machine learning classifier analysis reveals proteomic signatures capable of detecting the disease prior to biopsy, performing on par with an accepted clinical risk calculator benchmark.

Metabolic activity diffusion imaging (MADI): II. Noninvasive, high-resolution human brain mapping of sodium pump flux and cell metrics.

We introduce a new 1 H2 O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion-weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio ), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady-state trans-membrane water cycling (AWC), kio reflects the cytolemmal Na+ , K+ ATPase (NKA) homeostatic cellular metabolic rate (c MRNKA ). A digital 3D "library" contains thousands of simulated single diffusion-encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel-by-pixel experimental SDE decay library matchings that can be used to advantage. They yield proof-of-concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s-1 ; likely reflecting mostly exchange within myelin. The kio •V product map displays brain tissue c MRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting-state brain 18 FDG-PET tissue glucose consumption rate (t MRglucose ) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented.

Optimizing the Sequence of Chemotherapy for Upper Tract Urothelial Carcinoma with Clinically Positive Regional Lymph Nodes.

PURPOSE: Upper tract urothelial carcinoma with clinically positive regional lymph nodes is an aggressive disease state with a high propensity for metastasis and death. The current literature is limited regarding national practice patterns and outcomes in this patient population. MATERIALS AND METHODS: We identified 1,658 patients in the NCDB (National Cancer Database) who had cN+M0 upper tract urothelial carcinoma. Patients were stratified into treatment groups. We compared baseline patient and tumor characteristics between the groups, and completed survival analysis using a multivariate Cox regression model. RESULTS: There were 1,658 patients in the final study population. Preoperative chemotherapy was the least performed treatment. That group comprised 6.8% of the overall population and was associated with the highest median overall survival of 36 months compared to 21 months for adjuvant chemotherapy, 14 for chemotherapy only, 10 for surgery without perioperative chemotherapy and 5 for no treatment. On multivariate analysis preoperative chemotherapy was associated with improved median overall survival compared to that in the adjuvant chemotherapy group (HR 0.58, 95% CI 0.38-0.87). There was no statistically significant difference in survival between the chemotherapy only and the surgery only groups. Of patients in the preoperative chemotherapy group 34.6% achieved pN0 status compared to 10.3% of those who underwent surgery as initial therapy. CONCLUSIONS: Preoperative chemotherapy was the least performed treatment strategy in the management of cN+M0 upper tract urothelial carcinoma but it was associated with the highest median overall survival. There was no difference in survival between the chemotherapy only and the surgery only groups. Overall these results suggest that initial chemotherapy is appropriate in this population when feasible.

Unconventional Bladder Preservation: Factors Predicting Failure to Receive Definitive Surgery following Chemotherapy for Nonmetastatic Muscle Invasive Bladder Cancer in the National Cancer Database.

PURPOSE: Neoadjuvant chemotherapy is an important adjunct to cystectomy for managing muscle invasive bladder cancer. Using the National Cancer Database we investigated factors that predict failure to undergo surgery following multi-agent chemotherapy for nonmetastatic muscle invasive bladder cancer. MATERIALS AND METHODS: We performed a cohort study in patients diagnosed with cT2-4aN0M0 urothelial cell carcinoma of the bladder between 2004 and 2013 who underwent multi-agent chemotherapy. We excluded those with surgery prior to chemotherapy, clinical T4b disease and those who received radiotherapy. Socioeconomic and clinical predictors, including time from diagnosis to treatment, were analyzed using logistic regression for the receipt of surgery after chemotherapy. Cox proportional hazards modeling was applied to perform time dependent analysis. RESULTS: Of the 4,640 patients who met our study inclusion and exclusion criteria 4,244 (91%) proceeded to surgery. Negative predictors of surgery included African American or Hispanic race (OR 0.58, p = 0.007 and 0.48, p = 0.002, respectively), increasing age (OR 0.44, p <0.001) and greater time between diagnosis and chemotherapy initiation (fourth quartile greater than 59 days, OR 0.51, p <0.001). African American race (HR 0.79, p <0.001), Medicare (HR 0.86, p <0.001) and other government insurance (HR 0.73, p <0.001) were associated with delayed chemotherapy. CONCLUSIONS: Increasing age, African American or Hispanic race and longer time to chemotherapy predicted failure to undergo surgery. Furthermore, African American race was associated with delayed chemotherapy. Chemotherapy was also delayed in patients on Medicare or other government insurance. Longer time to neoadjuvant chemotherapy is a modifiable risk factor that should be closely observed in multimodal cancer treatment.

Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma.

BACKGROUND: Patients with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) resulting from fumarate hydratase (FH) mutations may present with skin, uterine, and renal tumors, with each having unique pathologic features. This study investigated the association between prospectively identified suspicious pathology (SP) and FH mutations when patients were referred for genetic testing. METHODS: This was an institutional review board-approved cohort study of patients receiving FH testing from 2008 to 2013. SP was defined as a report of HLRCC histologic features identified during a prospective pathologic assessment. The association between SP and FH mutations was analyzed. RESULTS: FH testing was performed in 29 patients with a median age of 37 years; 15 (52%) were female, and 18 (62%) were white. Pathologists reported SP from kidney tumors (11 of 18), leiomyomas (9 of 15: uterus [n = 8] and bladder [n = 1]), and metastatic tumors (3 of 6) in 23 of 39 associated specimens (59%) from 21 of the 29 patients (72%). Patients with SP were younger (35 vs 51 years; P = .010), and those with kidney tumors more often had stage pT3 or higher renal cell carcinoma than those without SP (100% vs 33%; P = .006). FH mutations were present in 8 patients with SP (38%) and in 1 patient without SP (13%; P = .37); 7 of these patients had kidney cancer (n for SP = 7), all with N1 disease. Analyzing SP by tissue type identified only SP from renal tumors as being significantly associated with positive testing for an FH mutation (P = .013). CONCLUSIONS: SP from kidney tumors was statistically associated with FH mutations. An expert pathologic assessment of renal tumors will facilitate the clinical identification of HLRCC cases, and this will result in genetic testing and targeted cancer screening for patients and at-risk family members. Cancer 2017;123:2452-58. © 2017 American Cancer Society.

Association of rise in C-reactive protein with decline in renal function following partial nephrectomy.

INTRODUCTION: To investigate association of C-reactive protein (CRP), a marker of systemic inflammation, with renal functional decline patients undergoing partial nephrectomy (PN) for renal mass. MATERIALS AND METHODS: Retrospective study of patients who underwent PN between February 2006-March 2011, with ≥ 6 months follow up. Data was analyzed between two groups: CRP increase ≥ 0.5 mg/L from 6 months postoperative ('CRP rise,' CRPR), versus no CRP increase = 0.5 ('CRP stable,' CRPS). Primary outcome was change in estimated glomerular filtration rate (ΔeGFR, mL/min/1.73 m²), with de novo postoperative stage III chronic kidney disease (stage III-CKD, eGFR < 60 mL/min/1.73 m²) being secondary. Multivariable analysis (MVA) was conducted to identify risk factors for development of de novo stage III-CKD. RESULTS: A total of 243 patients (206 CRPS/37 CRPR) were analyzed. Demographics and R.E.N.A.L. nephrometry scores were similar. CRPR had significantly higher median ΔeGFR (-13.7 versus -32.0 mL/min/1.73 m², p < 0.001) and de novo stage III-CKD at last follow up (43.2% vs. 3.7%, p < 0.001). Median time to CRP rise was 10 (IQR 6.5-12) months. Median time from CRP rise to de novo stage III-CKD was 9 (IQR 7.5-11) months. MVA found RENAL score (OR 1.89, p = 0.001), hypertension (OR 4.75, p = 0.016), and CRP rise (OR 55.76, p < 0.001) were associated with de novo stage III-CKD. Sensitivity of CRP increase ≥ 0.5 for predicting CKD was 69.6%, specificity 93.3%, positive predictive value 55.2%, and negative predictive value 96.3%. CONCLUSION: Rise in CRP postoperatively is independently associated with renal functional decline after PN and may be useful in identifying patients to evaluate for renoprotective strategies. Further studies are requisite to clarify etiology of this association.

Survival outcomes after radical and partial nephrectomy for clinical T2 renal tumours categorised by R.E.N.A.L. nephrometry score.

OBJECTIVE: We evaluated survival outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) for clinical T2 renal masses (cT2RM) controlling for R.E.N.A.L. nephrometry score. PATIENTS AND METHODS: A two-centre study comprised of 202 patients with cT2RM who underwent RN (122) or PN (80) between July 2002 and June 2012 (median follow-up 41.5 months). Kaplan-Meier analysis compared overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) among the entire cohort and within categories of R.E.N.A.L. nephrometry score of ≥10 and <10. Association between procedure and PFS and OS was analysed using Cox-proportional hazard. RESULTS: There were no significant differences between PN and RN in clinical T stage and R.E.N.A.L. nephrometry scores. For RN and PN, the 5-year PFS was 69.8% and 79.9% (P = 0.115), CSS was 82.5% and 86.7% (P = 0.407), and OS was 80% and 83.3% (P = 0.291). Cox regression showed no association between RN vs PN and PFS; a R.E.N.A.L. nephrometry score of ≥10 was associated with a shorter PFS (hazard ratio 6.69, P = 0.002). Kaplan-Meier analysis for RN vs PN showed no difference in PFS for entire cohort or within the R.E.N.A.L. nephrometry score categories of ≥10 and <10. The PFS was better for those with R.E.N.A.L nephrometry scores of <10 vs ≥10 (P < 0.001) and for cT2a vs cT2b tumours (P = 0.012). OS was no different between cT2a and cT2b tumours; patients with R.E.N.A.L. nephrometry scores of ≥10 were more likely to die from disease (P < 0.001) or any cause (P < 0.001) vs those with R.E.N.A.L. nephrometry scores of <10. CONCLUSIONS: PN may be oncologically effective for cT2RM. A R.E.N.A.L nephrometry score of ≥10 is negatively associated with OS among cT2RM compared with a score of <10 and provides additional risk assessment beyond clinical T stage. Further follow-up and prospective randomised investigation is requisite to confirm efficacy of PN for cT2RM.

Impact of renal surgery for cortical neoplasms on lipid metabolism.

OBJECTIVE: To examine the incidence of and risk factors for development of hyperlipidaemia in patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) for renal cortical neoplasms, as hyperlipidaemia is a major source of morbidity in chronic kidney disease (CKD). PATIENTS AND METHODS: We conducted a two-centre retrospective analysis of 905 patients (mean age 57.5 years, mean follow-up 78 months), who underwent RN (n = 610) or PN (n = 295) between July 1987 and June 2007. Demographics, preoperative and postoperative hyperlipidaemia were recorded. De novo hyperlipidaemia was defined as that ocurring ≥6 months after surgery in cases where laboratory values met National Cholesterol Education Program Adult Treatment Panel III definitions. The Kaplan-Meier method was used to assess freedom from de novo hyperlipidaemia. Multivariable analysis was conducted to determine the risk factors for de novo hyperlipidaemia. RESULTS: There were no significant differences with respect to demographics, preoperative glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (P = 0.123) and hyperlipidaemia (P = 0.144). Tumour size (cm) was significantly larger in the RN group vs the PN group (7.0 vs 3.7; P < 0.001). Significantly greater postoperative GFR <60 mL/min/1.73 m(2) was noted in the RN group (45.7 vs 18%, P < 0.001). Significantly, more de novo hyperlipidaemia developed in the RN group than in the PN group (23 vs 6.4%; P < 0.001). The mean time to development of hyperlipidaemia was longer for PN than for RN (54 vs 44 months; P = 0.03). Five-year freedom from de novo hyperlipidaemia probability was 76% for RN vs 96% for PN (P < 0.001). Multivariable analysis showed that RN (odds ratio [OR] 2.93; P = 0.0107), preoperative GFR <60 mL/min/1.73 m(2) (OR 1.98; P = 0.037) and postoperative GFR <60 mL/min/1.73 m(2) (OR 7.89; P < 0.001) were factors associated with hyperlipidaemia development. CONCLUSION: Patients who underwent RN had a significantly higher incidence of and shorter time to development of de novo hyperlipidaemia. RN and pre- and postoperative eGFR <60 mL/min/1.73 m(2) were associated with development of hyperlipidaemia. Further follow-up and prospective investigation are necessary to confirm these findings.

Determinants of renal functional decline after open partial nephrectomy: a comparison of warm, cold, and non-ischemic modalities.

INTRODUCTION: Renal functional decline after partial nephrectomy (PN) may be related to a variety of nonmodifiable and modifiable factors, including ischemia time (IT) and modality. We sought to determine the impact of these factors on renal functional degeneration after PN. MATERIALS AND METHODS: Multicenter retrospective analysis (n = 347) was performed, identifying patients who underwent open PN using warm, cold, and non-ischemic techniques. Primary outcome was development of de novo chronic kidney disease (CKD), (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2), at 1 year follow up. Univariate and multivariable analysis (MVA) were performed examining factors associated with ischemia technique and the development of de novo CKD. RESULTS: Median follow up 34.7 months. Two hundred and forty-one patients underwent warm ischemic, 31 cold ischemic, and 75 clampless PN. Patient characteristics were similar between groups. Clampless group had lower mean RENAL scores (6.4) than cold (7.9, p = 0.005) and warm (7, p = 0.037) ischemia groups. Cold ischemia cohort had longer median IT than the warm cohort (50min versus 25 min, p = 0.001). There were no significant differences in proportion of patients developing de novo CKD (warm 14.9%, cold 15%, clampless 8.7%, p = 0.422). MVA demonstrated that neither ischemic modality nor IT ≥ 30 minutes was associated with development of de novo CKD, while RENAL scores of increasing complexity (RENAL score 7-9 OR 4.32, p = 0.003; RENAL score ≥ 10 OR 15.42, p < 0.001) were independently associated with de novo CKD. CONCLUSIONS: Increasing tumor complexity, as indicated by the RENAL score, was an overriding determinant of post PN renal functional outcome. Prospective investigation is requisite to elucidate risk and protective factors for renal functional degeneration after PN.

Multiplex imaging of localized prostate tumors reveals altered spatial organization of AR-positive cells in the microenvironment.

Mapping the spatial interactions of cancer, immune, and stromal cell states presents novel opportunities for patient stratification and for advancing immunotherapy. While single-cell studies revealed significant molecular heterogeneity in prostate cancer cells, the impact of spatial stromal cell heterogeneity remains poorly understood. Here, we used cyclic immunofluorescent imaging on whole-tissue sections to uncover novel spatial associations between cancer and stromal cells in low- and high-grade prostate tumors and tumor-adjacent normal tissues. Our results provide a spatial map of single cells and recurrent cellular neighborhoods in the prostate tumor microenvironment of treatment-naive patients. We report unique populations of mast cells that show distinct spatial associations with M2 macrophages and regulatory T cells. Our results show disease-specific neighborhoods that are primarily driven by androgen receptor-positive (AR+) stromal cells and identify inflammatory gene networks active in AR+ prostate stroma.

Impact of tumour morphology on renal function decline after partial nephrectomy.

OBJECTIVE: To examine the association of renal morphology with renal function after partial nephrectomy (PN). PATIENTS AND METHODS: We conducted a multi-institutional retrospective analysis of 322 PNs performed between 2003 and 2011. The RENAL nephrometry score for each lesion was determined and the estimated glomerular filtration rate (eGFR) was calculated preoperatively and at last follow-up. We divided patients into two RENAL nephrometry score groups, low (<8) and high (≥8), and analysed and compared the outcomes of each group. The primary outcome was median change in eGFR between preoperative and last follow-up (ΔeGFR). The secondary outcome was eGFR <60 mL/min/1.73 m(2) at last follow-up. Multivariable analysis was conducted to evaluate the risk factors for eGFR <60 mL/min/1.73 m(2) at last follow-up. RESULTS: The median (interquartile range) follow-up was 25.2 (13.5-39.3) months. Low (n = 165) and high (n = 157) RENAL score groups were well-matched for baseline eGFR. The median tumour size (4.2 vs 2.4 cm, P < 0.001) was greater for the high group. In all, 64% of the low and 88.2% of the high RENAL score group (P < 0.001) had decreased eGFR at last follow-up. Median eGFR was -7 for the low vs -13.8 mL/min/1.73 m(2) for the high group (P = 0.001); eGFR <60 mL/min/1.73 m(2) at last follow-up was 27.3% for the low vs 37.6% for the high group (P = 0.057). Linear regression analysis showed that for each 1-point increase in RENAL score, there was 2.5% decrease in eGFR (P = 0.002); for each 1-cm increase in tumour size, there was 1.8% decrease in eGFR (P = 0.013). Area under curve analyses showed no significant difference between RENAL score and tumour size for prediction of de novo eGFR <60 mL/min/1.73 m(2) (P = 0.920) and ΔeGFR ≥50% (P = 0.85). Multivariable analysis showed that increasing RENAL score (odds ratio [OR] 1.24, P = 0.046) and decreasing preoperative eGFR (OR 1.10, P < 0.001) were risk factors for eGFR <60 mL/min/1.73 m(2) at last follow-up. CONCLUSIONS: Increasing RENAL nephrometry score is an independent risk factor for eGFR <60 mL/min/1.73 m(2) after PN. RENAL nephrometry score may serve as an additional measure for risk stratification before PN, but further investigation is required.

Does radical nephrectomy increase the risk of erectile dysfunction compared with partial nephrectomy? A cohort analysis.

UNLABELLED: Study Type - Therapy (prospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction (ED) is a form of endothelial dysfunction that is prevalent in patients with chronic kidney disease (CKD). We hypothesized that partial nephrectomy (PN) would limit development of ED compared with radical nephrectomy (RN), primarily due to renal function preservation, and found that patients undergoing RN had significantly higher de novo ED compared with a contemporary, well-matched cohort undergoing PN; in addition to RN, hypertension, CKD and diabetes mellitus were associated with developing ED. To our knowledge, this is the first study demonstrating an increased risk of ED after RN compared with PN. OBJECTIVES: • To evaluate prevalence and risk factors for development of erectile dysfunction (ED) in patients who underwent radical nephrectomy (RN) and partial nephrectomy (PN). • ED is a form of endothelial dysfunction that is prevalent in patients with chronic kidney disease (CKD). PN confers superior renal functional preservation compared with RN; however, the impact on ED is unclear. METHODS: • This was a retrospective study of 432 patients (264 RN/168 PN, mean age 58 years, mean follow-up 5.8 years) who underwent surgery for renal tumours between January 1998 and December 2007. • The primary outcome was rate of de novo ED postoperatively. Secondary outcomes included development of CKD (estimated GFR < 60 mL/min/1.73 m(2) ) and response to phosphodiesterase-5 inhibitors. • Multivariate analysis was performed to determine risk factors for de novo ED postoperatively. RESULTS: • RN and PN groups had similar demographics and comorbidities. • Tumour size (cm) was larger for RN (RN 7.0 vs PN 3.7, P < 0.001) and more preoperative ED existed in PN vs RN (P= 0.042). No differences were observed for preoperative CKD, hyperlipidaemia and diabetes mellitus. • Postoperatively, higher rates of de novo ED (29.5% vs 9.5%, P < 0.001) and CKD (33.0% vs 9.8%, P < 0.001) developed in RN vs PN cohorts, respectively. • Of men with ED, 63% responded to phosphodiesterase inhibitors, without significant difference between the two groups (P= 0.896). • Multivariate analysis demonstrated de novo ED to be associated with RN (odds ratio [OR] 3.56, P < 0.001), hypertension (OR 2.32, P= 0.014), preoperative (OR 8.77, P < 0.001) and postoperative (OR 2.64, P= 0.001) CKD, and postoperative diabetes mellitus (OR 2.93, P < 0.001). CONCLUSIONS: • Patients undergoing RN had significantly higher de novo ED compared with a contemporary, well-matched cohort undergoing PN. In addition to RN, hypertension, CKD and diabetes mellitus were associated with developing ED. • Further investigation on effects of surgically induced nephron loss on ED is requisite.

Differentiation of clear from non-clear cell renal cell carcinoma using CT washout formula.

INTRODUCTION: To further elucidate potential patterns of contrast enhancement for renal neoplasm subtypes, we investigated utility of contrast washout formula to differentiate renal tumor histology after multiphase computerized tomography (CT). MATERIALS AND METHODS: Single center retrospective cohort study of 163 patients with multiphase CT for renal masses obtained October 2007 to July 2012. Pathology confirmed clear cell (CC-RCC; n = 92), papillary (Pa-RCC; n = 43), chromophobe (Ch-RCC; n = 6), oncocytoma (OC; n = 11), or angiomyolipoma (AML; n = 11) histology. Two radiologists in consensus and blinded to histology recorded tumor size, morphology, and attenuation measurements in Hounsfield Units (HU). Data were analyzed between subgroups based on histology. Enhancement washout of the tumor was calculated by the formula (Mass nephrographic HU-Mass delayed HU)/(Mass nephrographic HU-Mass non-contrast HU) and used to calculate sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Tumor size was largest among CC-RCC (p < 0.001). Homogeneous composition was more common among Pa-RCC and Ch-RCC (p < 0.001). Median washout for Ch-RCC (0.27) was significantly different from that of OC (0.54, p = 0.05). Overall 25 (15.3%) of tumors had washout < 0. Tumors with washout value < 0 were Pa-RCC 24/43 (56%), and Ch-RCC 1/6 (14%). Washout value < 0 had a specificity of 99.2% for Pa-RCC and 100% for non-CC-RCC. Washout value ≥ 0 had a sensitivity and NPV of 100% for CC-RCC, OC, and AML. Washout value ≥ 0 had a specificity of 35.2% and a PPV of 66.7% for CC-RCC. CONCLUSIONS: Enhancement washout value < 0 is highly specific for Pa-RCC and non-CC-RCC. Washout value ≥ 0 is highly sensitive for CC-RCC, OC, and AML while there was a significant difference in median washout between OC and Ch-RCC. Further prospective investigation is requisite to confirm these findings.

Are repeat prostate biopsies safe? A cohort analysis from the SEARCH database.

PURPOSE: Patients question whether multiple biopsy sessions cause worse prostate cancer outcomes. Therefore, we investigated whether there is an association between the number of prior biopsy sessions and biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: Men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who underwent radical prostatectomy between 1988 and 2010 after a known number of prior biopsies were included in the analysis. Number of biopsy sessions (range 1 to 8) was examined as a continuous and categorical (1, 2 and 3 to 8) variable. Biochemical recurrence was defined as a prostate specific antigen greater than 0.2 ng/ml, 2 values at 0.2 ng/ml or secondary treatment for an increased prostate specific antigen. The association between number of prior biopsy sessions and biochemical recurrence was analyzed using the Cox proportional hazards model. Kaplan-Meier estimates of freedom from biochemical recurrence were compared among the groups. RESULTS: Of the 2,739 men in the SEARCH database who met the inclusion criteria 2,251 (82%) had only 1 biopsy, 365(13%) had 2 biopsies and 123 (5%) had 3 or more biopsies. More biopsy sessions were associated with higher prostate specific antigen (p<0.001), greater prostate weight (p<0.001), lower biopsy Gleason sum (p=0.01) and more organ confined (pT2) disease (p=0.017). The Cox proportional hazards model demonstrated no association between number of biopsy sessions as a continuous or categorical variable and biochemical recurrence. Kaplan-Meier estimates of freedom from biochemical recurrence were similar across biopsy groups (log rank p=0.211). CONCLUSIONS: Multiple biopsy sessions are not associated with an increased risk of biochemical recurrence in men undergoing radical prostatectomy. Multiple biopsy sessions appear to select for a low risk cohort.

Trends in adverse events of benign prostatic hyperplasia (BPH) in the USA, 1998 to 2008.

OBJECTIVE: To determine if the adverse events (AEs) of benign prostatic hyperplasia (BPH) have declined in tandem with increased use of oral therapy. MATERIALS AND METHODS: We used the Nationwide Inpatient Sample, a 20% sample of USA community hospitals, weighted to estimate national numbers to characterize the prevalence of AEs of BPH from 1998 to 2008. We calculated the age-adjusted prevalence of BPH and associated conditions and analyzed prevalence trends with regression modelling. RESULTS: Of 134 million estimated eligible discharges during the study period, 7,464,730 (5.6%) had either a primary or secondary diagnosis of BPH. The age-adjusted prevalence of BPH among all hospitalizations, irrespective of primary diagnosis, increased from 4.3% to 8% (P < 0.001) during the study period. The age-adjusted prevalence of BPH as a primary diagnosis decreased from 0.88% to 0.48% (P < 0.001). Discharges for BPH surgery decreased 51% (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.45-0.54, P-trend <0.001) over time. Discharges for primary BPH with acute renal failure increased >400% (OR 4.28, 95% CI 3.22-5.71, P-trend <0.001). There were no significant changes in discharges for primary BPH with urinary retention (P-trend = 0.636), bladder stones (P-trend = 0.117), or urinary infection (P-trend = 0.101) over time. CONCLUSIONS: Increased hospitalizations for BPH with acute renal failure and stable hospitalizations for other AEs of BPH indicate that severe AEs of BPH persist despite widespread use of oral therapies in the USA. Further studies are needed to explain these trends.

Comparison of rates and risk factors for development of anaemia and erythropoiesis-stimulating agent utilization after radical or partial nephrectomy.

OBJECTIVE: To examine the incidence of and risk factors for the development of anaemia and erythropoiesis-stimulation agent (ESA) treatment in patients undergoing radical nephrectomy (RN) and partial nephrectomy (PN) because anaemia is a significant cause of morbidity in chronic kidney disease. PATIENTS AND METHODS: The study comprised a retrospective review of 905 patients (610 RN/295 PN; mean age, 57.5 years; mean follow-up, 6.4 years) who underwent surgery for renal tumours at two institutions from July 1987 to June 2007. Demographics, disease characteristics and pre- and postoperative (i.e. renal function, metabolic parameters, anaemia and ESA treatment) were recorded. Data were analyzed within subgroups based on treatment (RN vs PN). Multivariate analysis was conducted to determine the risk factors for developing anaemia after surgery. RESULTS: Tumour size (cm) was significantly larger for RN (RN 7.0 vs PN 3.7; P < 0.001). No significant differences were noted with respect to demographics and preoperative anaemia (RN 16.4% vs PN 18.6%; P = 0.454) and ESA-treatment (RN 0.7% vs PN 1.4%; P = 0.499). After surgery, significantly less de novo anaemia (PN 4.1% vs RN 17.5%; P < 0.001) and ESA utilization (PN 2.7% vs RN 13.4%; P < 0.001) occurred in the PN cohort. Multivariate analysis showed that age ≥60 years (odds ratio, OR, 1.62; P = 0.008), African American ethnicity (OR, 2.30; P < 0.001), smoking (OR, 1.60; P = 0.013), glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (OR, 4.09; P < 0.001), ≥1+ proteinuria (OR, 2.19; P < 0.03), metabolic acidosis (OR, 4.08; P = 0.007) and RN (OR, 2.58; P < 0.001) were significantly associated with de novo anaemia. CONCLUSIONS: Patients who underwent RN had a significantly higher prevalence of anaemia and ESA-treatment compared to a well-matched cohort that underwent PN. In addition to RN, age ≥60 years, African American ethnicity, history of smoking, GFR < 60 mL/min/1.73 m(2), proteinuria and metabolic acidosis were associated with developing anaemia.

SNPs at SMG7 Associated with Time from Biochemical Recurrence to Prostate Cancer Death.

BACKGROUND: A previous genome-wide association study identified several loci with genetic variants associated with prostate cancer survival time in two cohorts from Sweden. Whether these variants have an effect in other populations or if their effect is homogenous across the course of disease is unknown. METHODS: These variants were genotyped in a cohort of 1,298 patients. Samples were linked with age, PSA level, Gleason score, cancer stage at surgery, and times from surgery to biochemical recurrence to death from prostate cancer. SNPs rs2702185 and rs73055188 were tested for association with prostate cancer-specific survival time using a multivariate Cox proportional hazard model. SNP rs2702185 was further tested for association with time to biochemical recurrence and time from biochemical recurrence to death with a multi-state model. RESULTS: SNP rs2702185 at SMG7 was associated with prostate cancer-specific survival time, specifically the time from biochemical recurrence to prostate cancer death (HR, 2.5; 95% confidence interval, 1.4-4.5; P = 0.0014). Nine variants were in linkage disequilibrium (LD) with rs2702185; one, rs10737246, was found to be most likely to be functional based on LD patterns and overlap with open chromatin. Patterns of open chromatin and correlation with gene expression suggest that this SNP may affect expression of SMG7 in T cells. CONCLUSIONS: The SNP rs2702185 at the SMG7 locus is associated with time from biochemical recurrence to prostate cancer death, and its LD partner rs10737246 is predicted to be functional. IMPACT: These results suggest that future association studies of prostate cancer survival should consider various intervals over the course of disease.

Obesity and prostate enlargement in men with localized prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? Obesity is associated with prostate enlargement in men without prostate cancer. This study demonstrates an association between obesity and prostate enlargement in men with prostate cancer, and leads to possible implications for prostate cancer screening and diagnosis. OBJECTIVE: • To determine if obesity is associated with prostate size in men with prostate cancer. PATIENTS AND METHODS: • We examined preoperative body mass index (BMI) and whole prostate weight in a cohort of 16,325 patients undergoing radical prostatectomy for localized prostate cancer from 1975 to 2008 at a single institution. • We used multivariable regression modelling adjusting for age, year of surgery, preoperative serum prostate-specific antigen (PSA), pathological stage and Gleason grade. RESULTS: • Of the entire cohort, 13,343 (82%) patients had a prostate weight of at least 40 g. These men were older (P < 0.001), had a higher preoperative BMI (P < 0.002), higher preoperative PSA (P < 0.001), and were more likely to have pT2 disease (P < 0.001). • In multivariable regression, preoperative BMI was associated with increased prostate weight: for each 1 kg/m(2) increase in BMI, prostate weight increased by 0.45 g (95% CI 0.35-0.55, P-trend < 0.001). • Compared with men with BMI < 25 kg/m(2) , men with a BMI ≥35 kg/m(2) had a 40% (odds ratio 1.40, 95% CI 1.01-1.95) increased risk of prostate weight of at least 40 g and a 70% (odds ratio 1.70, 95% CI 1.32-2.20) increased risk of prostate weight of at least 50 g. CONCLUSIONS: • In men with localized prostate cancer, obesity is associated with an increased risk of prostate enlargement. • These data validate other observations linking obesity with prostate enlargement and may have important ramifications for prostate cancer diagnosis in obese men.

Bladder perforation associated with hot tub.

INTRODUCTION: Bladder perforation is a rare and life-threatening event. Timely diagnosis may prevent further injury-related morbidity and mortality. Aim. To present a case of bladder injury associated with masturbation in a hot tub. METHODS: This report describes a case of bladder perforation in a 54-year-old female who presented to the emergency department 2 days after masturbation with a water jet. RESULTS: Following percutaneous drainage and intraoperative closure of the bladder, the patient was discharged on postoperative day four and has had no sequelae. CONCLUSION: Cross-sectional imaging and cystography can facilitate immediate diagnosis and expeditious treatment of bladder injury associated with masturbation in a hot tub.