Summary There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, FLI1) or mutations (SPOP, FOXA1, IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1-mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

What ' s known on the subject? and What does the study add? During radical prostatectomy, urological surgeons have tried to identify the " cord-like NVB " at the lateral aspect of the prostate. However, little histological or physiological investigation was conducted to verify that the NVB identifi ed at surgery really included the cavernous nerve. Recently, there have been observations that refute the dogma that the cavernous nerve is always within the NVB.In this study, we have described a hammock-like distribution of the nerves on which the prostate rests, demonstrating that the NVB is more a network of multiple fi ne dispersed nerves than a distinct structure. We presented a novel nerve-sparing approach to complete hammock preservation. This risk-stratifi ed approach for determining the degree of nerve sparing based on the patient ' s likelihood of ipsilateral EPE seeks to categorize patients for optimal balance between oncological outcomes and functional outcomes. OBJECTIVES• To report the potency and oncological outcomes of patients undergoing robotassisted radical prostatectomy (RARP) using a risk-stratifi ed approach based on layers of periprostatic fascial dissection.• We also describe the surgical technique of complete hammock preservation or nerve sparing grade 1. PATIENTS AND METHODS• This is a retrospective study of 2317 patients who had robotic prostatectomy by a single surgeon at a single institution between January 2005 and June 2010.• Included patients were those with ≥ 1 year of follow-up and who were potent preoperatively, defi ned as having a sexual health inventory for men (SHIM) questionnaire score of > 21; thus, the fi nal number of patients in the study cohort was 1263.• Patients were categorized pre-operatively by a risk-stratifi ed approach into risk grades 1 -4, where risk grade 1 patients received nerve-sparing grade 1 or complete hammock preservation and so on for risk grades 2 -4, as long as intraoperative fi ndings permitted the planned nerve sparing.• We considered return to sexual function post-operatively by two criteria: i) ability to have successful intercourse (score of ≥ 4 on question 2 of the SHIM) and ii) SHIM > 21 or return to baseline sexual function. RESULTS• There was a signifi cant difference across different NS grades in terms of the percentages of patients who had intercourse and returned to baseline sexual function ( P < 0.001), with those that underwent NS grade 1 having the highest rates (90.9% and 81.7%) as compared to NS grades 2 (81.4% and74.3%), 3 (73.5% and 66.1%), and 4 (62% and 54.5%).• The overall positive surgical margin (PSM) rates for patients with NS grades 1, 2, 3, and 4 were 9.9%, 8.1%, 7.2%, and 8.7%, respectively ( P = 0.636).• The extraprostatic extension rates were 11.6%, 14.3%, 29.3%, and 36.2%, respectively ( P < 0.001).• Similarly, in patients younger than 60, intercourse and return to baseline sexual function rates were 94.9% and 84.3% for NS grade 1 as compared to 85.5% and 77.2% for NS grades 2, 76.9% and 69% for NS grades 3, and 64.8% and...

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One of the central goals of human genetics is to discover the genes and pathways driving human traits. To date, most of the common risk alleles discovered through genome-wide association studies (GWAS) map to nonprotein-coding regions. Because of our relatively poorer understanding of this part of the genome, the functional consequences of trait-associated variants pose a considerable challenge. To identify the genes through which risk loci act, we hypothesized that the risk variants are regulatory elements. For each of 12 known risk polymorphisms, we evaluated the correlation between risk allele status and transcript abundance for all annotated protein-coding transcripts within a 1-Mb interval. A total of 103 transcripts were evaluated in 662 prostate tissue samples [normal (n = 407) and tumor (n = 255)] from 483 individuals [European Americans (n = 233), Japanese (n = 127), and African Americans (n = 123)]. In a pooled analysis, 4 of the 12 risk variants were strongly associated with five transcripts (NUDT11, MSMB, NCOA4, SLC22A3, and HNF1B) in histologically normal tissue (P ≤ 0.001). Although associations were also observed in tumor tissue, they tended to be more attenuated. Previously, we showed that MSMB and NCOA4 participate in prostate cancer pathogenesis. Suppressing the expression of NUDT11, SLC22A3, and HNF1B influences cellular phenotypes associated with tumor-related properties in prostate cancer cells. Taken together, the data suggest that these transcripts contribute to prostate cancer pathogenesis.expression quantitative trait loci | prostate cancer risk SNPs | multi-ethnic

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Palmar plate fixation of distal radial fractures is becoming a standard treatment for this common injury. Ruptures of the extensor pollicis longus tendon have been reported in 8.6% of cases after this procedure. Although palmar plate fixation has also been associated with flexor pollicis longus (FPL) tendon problems, the majority of reported cases pre-date the use of newer anatomically precontoured locking plates. In this paper seven cases of FPL rupture are presented. This complication does not appear to be unique to one type of implant. The possible aetiologies for FPL ruptures are discussed and ways to reduce the incidence of this complication are suggested.

•  Age and nerve sparing influence recovery of orgasm and erectile function after RALP. •  Men ≤60 years old and those who undergo BNS are most likely to maintain normal sexual function.