Search

We introduce a new

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.

493 Background: Standard treatment (tx) for high-risk NMIBC is transurethral resection of bladder tumor (TURBT) followed by BCG induction and maintenance. However, ≈50% of pts experience recurrence and/or progression after tx and may be ineligible for or refuse cystectomy. The PD-L1/PD-1 pathway may be involved with immune escape in NMIBC following BCG exposure. Here, we report results of atezo (anti–PD-L1) ± BCG in BCG-unresponsive, high-risk NMIBC. Methods: This multicenter study (NCT02792192) enrolled pts with BCG-unresponsive NMIBC with carcinoma in situ who had repeat TURBT. Cohort 1A and 1B pts received atezo 1200 mg IV q3w for ≤96 wk. Cohort 1B pts also received standard BCG induction (qw × 6 doses) and maintenance (qw × 3 doses at 3 mo), with optional maintenance courses at 6, 12, 18, 24, and 30 mo. For cohort 1B only, de-escalation was allowed for ≤3 BCG dose levels (full dose 50 mg, 66% and 33% of full dose). Co-primary outcomes were safety and complete response (CR) rate at 6 mo (6-mo bladder biopsy required). Duration of CR and 3-mo CR rate (key secondary outcomes) and 12-mo CR rate (exploratory) were also shown. Results: Cohorts 1A and 1B enrolled 12 pts each. Median age was 74 y; most pts had ECOG PS 0 (n = 7 [58%] in each cohort). At data cutoff (Sep 29, 2020), median atezo tx duration was 22.7 wk in cohort 1A and 31.6 wk in 1B. Following dose de-escalation in cohort 1B, the recommended BCG dose was 50 mg. BCG dose modification/interruption occurred in 4 pts (33%) due to an AE. The most common reason for tx discontinuation was disease recurrence or progression in both cohorts. Three pts (25%) in cohort 1A had atezo-related Gr 3 AEs (most common: maculopapular rash, n = 2); no atezo- or BCG-related Gr ≥3 AEs were seen in cohort 1B. Three dose-limiting toxicities occurred (1 [8%] in cohort 1A and 2 [17%] in cohort 1B), all reported as AEs of special interest. No Gr 4/5 AEs were reported. CRs, which appeared durable, were seen in both cohorts (Table). Conclusions: In this first report of atezo + BCG in NMIBC, atezo as mono- and combination therapy was well tolerated, with no new safety signals or tx-related deaths. Preliminary data suggested clinically meaningful activity, especially with atezo + BCG, requiring confirmation in a larger setting. Clinical trial information: NCT02792192. [Table: see text]

Objective To characterize the incidence, presentation, management, and relapse of a large population of bilateral testicular germ cell tumors (TGCT) from a single institution. Patients and Methods We identified bilateral TGCT diagnosed between January 1989 and February 2014. We categorized synchronous and metachronous TGCT, noting time between first and second TGCT, histology (seminoma vs nonseminoma [NSGCT]), stage, and treatments. Kaplan-Meier survival estimates characterized relapse. Results Of 5132 patients with TGCT, 128 (2.5%) had bilateral TGCT. Bilateral TGCT increased over time—1.7% in 1989-1994 up to 3.8% in 2010 to February 2014. The 35 (27%) synchronous cases of TGCT had 20 (57%) concordant seminoma, 5 (14%) concordant NSGCT, and 10 (29%) discordant NSGCT. The 93 (73%) metachronous cases had median time interval to second TGCT of 73 months (range: 5 months-28.6 years). Compared with first TGCT, 39 (42%) had discordant histology, 29 (31%) had concordant seminoma, and 25 (27%) had concordant NSGCT. Stage at first tumor was statistically similar to second TGCT (second stage I, II, II in 69%, 22%, 10%). Increasing duration between first and second TGCT was not associated with higher stage (II or III) at second TGCT (P = .09). Treatment at first tumor was not associated with stage at second tumor. Relapse following bilateral diagnosis was 16.8% (95% confidence interval 10.5%-26.2%) at 5 years. Conclusion Incidence of bilateral TGCT increased with >25% of metachronous TGCT presenting ≥10 years after first TGCT; possible causes include increased survivorship and referral bias. Stage was statistically similar at first and second tumor; stage at second tumor was not associated with time interval between tumors or prior treatment modality at first tumor.

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.

Genome-wide association studies have identified multiple single-nucleotide polymorphsims (SNPs) associated with prostate cancer (PCa). Although these SNPs have been clearly associated with disease risk, their relationship with clinical outcomes is less clear. Our aim was to assess the frequency of known PCa susceptibility alleles within a single institution ascertainment and to correlate risk alleles with disease-specific outcomes.We genotyped 1354 individuals treated for localised PCa between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to phenotypic data. We investigated associations between 61 SNPs and disease-specific end points using multivariable analysis and also determined if SNPs were associated with PSA at diagnosis.Seven SNPs showed associations on multivariable analysis (P0.05), rs13385191 with both biochemical recurrence (BR) and castrate metastasis (CM), rs339331 (BR), rs1894292, rs17178655 and rs11067228 (CM), and rs11902236 and rs4857841 PCa-specific mortality. After applying a Bonferroni correction for number of SNPs (P0.0008), the only persistent significant association was between rs17632542 (KLK3) and PSA levels at diagnosis (P=1.4 × 10(-5)).We confirmed that rs17632542 in KLK3 is associated with PSA at diagnosis. No significant association was seen between loci and disease-specific end points when accounting for multiple testing. This provides further evidence that known PCa risk SNPs do not predict likelihood of disease progression.

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.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.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).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.

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.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, eGFR60 mL/min/1.73 m²) being secondary. Multivariable analysis (MVA) was conducted to identify risk factors for development of de novo stage III-CKD.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, p0.001) and de novo stage III-CKD at last follow up (43.2% vs. 3.7%, p0.001). 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, p0.001) 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%.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.

Contains fulltext : 167299.pdf (Publisher’s version ) (Closed access) Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 x 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 x 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 x 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P

The transcriptional coactivator PPARγ coactivator-1α (PGC-1α) has been characterized as a broad regulator of cellular energy metabolism. Although PGC-1α functions through many transcription factors, the PGC-1α partners identified to date are unlikely to account for all of its biologic actions. The orphan nuclear receptor estrogen-related receptor α (ERRα) was identified in a yeast two-hybrid screen of a cardiac cDNA library as a novel PGC-1α-binding protein. ERRα was implicated previously in regulating the gene encoding medium-chain acyl-CoA dehydrogenase (MCAD), which catalyzes the initial step in mitochondrial fatty acid oxidation. The cardiac perinatal expression pattern of ERRα paralleled that of PGC-1α and MCAD. Adenoviral-mediated ERRα overexpression in primary neonatal cardiac mycoytes induced endogenous MCAD expression. Furthermore, PGC-1α enhanced the transactivation of reporter plasmids containing an estrogen response element or the MCAD gene promoter by ERRα and the related isoform ERRγ. In vitro binding experiments demonstrated that ERRα interacts with PGC-1α via its activation function-2 homology region. Mutagenesis studies revealed that the LXXLL motif at amino acid position 142–146 of PGC-1α (L2), necessary for PGC-1α interactions with other nuclear receptors, is not required for the PGC-1α·ERRα interaction. Rather, ERRα binds PGC-1α primarily through a Leu-rich motif at amino acids 209–213 (Leu-3) and utilizes additional LXXLL-containing domains as accessory binding sites. Thus, the PGC-1α·ERRα interaction is distinct from that of other nuclear receptor PGC-1α partners, including PPARα, hepatocyte nuclear factor-4α, and estrogen receptor α. These results identify ERRα and ERRγ as novel PGC-1α interacting proteins, implicate ERR isoforms in the regulation of mitochondrial energy metabolism, and suggest a potential mechanism whereby PGC-1α selectively binds transcription factor partners.

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.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.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, p0.001) were independently associated with de novo CKD.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.

Objective. To report our contemporary experience with partial cystectomy after neoadjuvant chemotherapy. Patients and Methods. Retrospective review of patients who underwent neoadjuvant chemotherapy and partial cystectomy for urothelial cell carcinoma of the bladder at Memorial Sloan Kettering Cancer Center from 1995 to 2013. Log-rank test and Cox regression models were used to analyze variables possibly associated with recurrence-free, advanced recurrence-free (free from recurrence beyond salvage with intravesical therapy or radical cystectomy), and overall survival. Results. All 36 patients had a solitary tumor Conclusion. Partial cystectomy following neoadjuvant chemotherapy provides acceptable oncologic outcomes in highly selected patients with muscle-invasive bladder cancer.

Nephrogenic adenoma is a rare benign lesion of the urinary tract that is associated with a history of irritation or injury of the urothelium. Predisposing factors include infection, calculi, surgery, trauma, and renal transplantation. Nephrogenic adenoma commonly presents with lower urinary tract symptoms or hematuria. We present the case of recurrent nephrogenic adenoma in a 10-year-old boy with a history of prune belly syndrome and discuss management of this disease in the pediatric population. To our knowledge this represents the first reported case of recurrent nephrogenic adenoma associated with prune belly syndrome.

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.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 and10. Association between procedure and PFS and OS was analysed using Cox-proportional hazard.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 and10. The PFS was better for those with R.E.N.A.L nephrometry scores of10 vs ≥10 (P0.001) 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 (P0.001) or any cause (P0.001) vs those with R.E.N.A.L. nephrometry scores of10.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 of10 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.

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).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).Tumor size was largest among CC-RCC (p0.001). Homogeneous composition was more common among Pa-RCC and Ch-RCC (p0.001). 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 washout0. Tumors with washout value0 were Pa-RCC 24/43 (56%), and Ch-RCC 1/6 (14%). Washout value0 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.Enhancement washout value0 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.

To examine the association of renal morphology with renal function after partial nephrectomy (PN).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 eGFR60 mL/min/1.73 m(2) at last follow-up. Multivariable analysis was conducted to evaluate the risk factors for eGFR60 mL/min/1.73 m(2) at last follow-up.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, P0.001) was greater for the high group. In all, 64% of the low and 88.2% of the high RENAL score group (P0.001) 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); eGFR60 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 eGFR60 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, P0.001) were risk factors for eGFR60 mL/min/1.73 m(2) at last follow-up.Increasing RENAL nephrometry score is an independent risk factor for eGFR60 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.

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.• 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.• 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 GFR60 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.• RN and PN groups had similar demographics and comorbidities. • Tumour size (cm) was larger for RN (RN 7.0 vs PN 3.7, P0.001) 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%, P0.001) and CKD (33.0% vs 9.8%, P0.001) 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, P0.001), hypertension (OR 2.32, P= 0.014), preoperative (OR 8.77, P0.001) and postoperative (OR 2.64, P= 0.001) CKD, and postoperative diabetes mellitus (OR 2.93, P0.001).• 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.

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.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.Tumour size (cm) was significantly larger for RN (RN 7.0 vs PN 3.7; P0.001). 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%; P0.001) and ESA utilization (PN 2.7% vs RN 13.4%; P0.001) 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; P0.001), smoking (OR, 1.60; P = 0.013), glomerular filtration rate (GFR)60 mL/min/1.73 m(2) (OR, 4.09; P0.001), ≥1+ proteinuria (OR, 2.19; P0.03), metabolic acidosis (OR, 4.08; P = 0.007) and RN (OR, 2.58; P0.001) were significantly associated with de novo anaemia.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, GFR60 mL/min/1.73 m(2), proteinuria and metabolic acidosis were associated with developing anaemia.

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.• To determine if obesity is associated with prostate size in men with prostate cancer.• 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.• Of the entire cohort, 13,343 (82%) patients had a prostate weight of at least 40 g. These men were older (P0.001), had a higher preoperative BMI (P0.002), higher preoperative PSA (P0.001), and were more likely to have pT2 disease (P0.001). • 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-trend0.001). • Compared with men with BMI25 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.• 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.

To determine if the adverse events (AEs) of benign prostatic hyperplasia (BPH) have declined in tandem with increased use of oral therapy.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.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% (P0.001) during the study period. The age-adjusted prevalence of BPH as a primary diagnosis decreased from 0.88% to 0.48% (P0.001). Discharges for BPH surgery decreased 51% (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.45-0.54, P-trend0.001) over time. Discharges for primary BPH with acute renal failure increased400% (OR 4.28, 95% CI 3.22-5.71, P-trend0.001). 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.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.

The transcriptional coactivator PPARgamma coactivator-1alpha (PGC-1alpha) has been characterized as a broad regulator of cellular energy metabolism. Although PGC-1alpha functions through many transcription factors, the PGC-1alpha partners identified to date are unlikely to account for all of its biologic actions. The orphan nuclear receptor estrogen-related receptor alpha (ERRalpha) was identified in a yeast two-hybrid screen of a cardiac cDNA library as a novel PGC-1alpha-binding protein. ERRalpha was implicated previously in regulating the gene encoding medium-chain acyl-CoA dehydrogenase (MCAD), which catalyzes the initial step in mitochondrial fatty acid oxidation. The cardiac perinatal expression pattern of ERRalpha paralleled that of PGC-1alpha and MCAD. Adenoviral-mediated ERRalpha overexpression in primary neonatal cardiac mycoytes induced endogenous MCAD expression. Furthermore, PGC-1alpha enhanced the transactivation of reporter plasmids containing an estrogen response element or the MCAD gene promoter by ERRalpha and the related isoform ERRgamma. In vitro binding experiments demonstrated that ERRalpha interacts with PGC-1alpha via its activation function-2 homology region. Mutagenesis studies revealed that the LXXLL motif at amino acid position 142-146 of PGC-1alpha (L2), necessary for PGC-1alpha interactions with other nuclear receptors, is not required for the PGC-1alpha.ERRalpha interaction. Rather, ERRalpha binds PGC-1alpha primarily through a Leu-rich motif at amino acids 209-213 (Leu-3) and utilizes additional LXXLL-containing domains as accessory binding sites. Thus, the PGC-1alpha.ERRalpha interaction is distinct from that of other nuclear receptor PGC-1alpha partners, including PPARalpha, hepatocyte nuclear factor-4alpha, and estrogen receptor alpha. These results identify ERRalpha and ERRgamma as novel PGC-1alpha interacting proteins, implicate ERR isoforms in the regulation of mitochondrial energy metabolism, and suggest a potential mechanism whereby PGC-1alpha selectively binds transcription factor partners.