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To report perioperative and postoperative outcomes in men who undergo salvage RASP (sRASP) following some other endoscopic outlet procedure for benign prostate enlargement (BPE) compared to those undergoing RASP for primary treatment (pRASP).A prospectively maintained database consisting of all RASP surgeries (December 2014-October 2019) performed at our institution by 3 different urologists was used. Patients who had received an endoscopic procedure for BPE prior to their RASP (sRASP) were compared to those who had not had a prior outlet procedure (pRASP).In total, 310 men underwent RASP during the study period. Of those, 30 (9.7%) had undergone an endoscopic procedure prior to surgery. There were no significant differences in age, race, ASA, BMI, prostate volume, PSA or rates of preoperative retention (P.05 for all). Men who were treatment-naive had significantly higher preoperative International Prostate Symptom Scores (IPSS) than men who had a prior procedure (18.3 ± 7.7 vs 13.6 ± 6.2, P = .008). However, there were no significant differences in functional or quality of life outcomes between the 2 groups (P.05 for all). There were no significant differences in perioperative or post-operative outcomes between the 2 groups. Furthermore, rates of post-operative complications and incontinence were similar between groups (11% vs 10%, P = .9 and 2% vs 0%, P = 1 respectively).Performing a RASP after prior endoscopic procedure for BPE was found to be safe and effective. Success and complication rates were similar to patients with no prior procedures.

Introduction: Renal colic secondary to kidney stone disease is a common reason for emergency department (ED) visits and often leads to patients receiving narcotic medications. The objective of this study was to describe longitudinal analgesia prescribing patterns for kidney stone patients acutely managed in the ED. Methods: This was a retrospective chart review of patients who presented to the ED between 2013 and 2018 and were subsequently diagnosed with a kidney stone. Encounters during which opioids and nonopioids were administered in the ED and prescribed at discharge were stratified by year, race, ethnicity, insurance status, gender, and location of ED (main academic campus and community-based campus). Patients were excluded if they required hospital admission or a stone-related procedure related to the ED encounter. Results: We reviewed 1620 total encounters for 1376 unique patients. Frequency of patients receiving opioids in the ED decreased from 81% in 2013 to 57% in 2018 (p

Penile fracture is a rare condition that describes the rupture of the corpus cavernosum following direct, high-pressure trauma to the erect penis. There is no standardized management algorithm for these patients. We performed a systematic review of the past 10 years regarding management of penile fractures. A complete PRISMA-P 2015 checklist was performed where we reviewed English articles published over the past 10 years to identify 105 articles, where 63 articles were of relevance and subsequently narrowed to a total of 28 articles into the final review for this study. We determined that immediate penile exploration and tunica repair is considered the most common and current management of penile fractures with experts demonstrating that it leads to the fastest in recovery in erectile function and positive cosmetic outcomes. However, we also determined that the specific algorithm can be variable-down to the suture material, use of catheterization, urethroplasty when involved, and length of recovery/follow-up. In the last several decades, men with penile fracture have been treated, in most cases, with immediate surgical intervention. This review highlights the varying practices regarding surgical exploration, injury repair, and postoperative management in men with a penile fracture. Immediate penile exploration and tunica repair have been the mainstay approach of management.

Objective To report urologic outcomes from a series of IUIs, sustained during nonurologic procedures, with regards to timing of diagnosis and management of the injury. Iatrogenic ureteral injury (IUI) is the most common mechanism of ureteral trauma. Injuries can be intraoperatively diagnosed (IOD) or postoperatively diagnosed (POD). Methods This was a retrospective chart review of adult patients at a single institution who sustained an IUI from a non-urologic procedure between 2008 and 2019. Primary outcome was tube-dependence (ureter stent or nephrostomy tube) and nephrectomy rates at last follow-up. Secondary outcome was the number of additional urologic procedures required to manage subsequent complications of IUI. Results There were 30 patients with IOD and 57 patients with POD. In the IOD group, at mean follow up of 6.3 months, 4 patients (14.3%) were tube dependent. In the POD group, at mean follow up of 13.1 months, 5 patients (10%) were tube dependent (P = .570). Rate of nephrectomy was higher in POD group compared to IOD, but the difference was not statistically significant (12.3% vs 6% respectively, P = .414). Additionally, in the POD group, 56% and 19.3% required a secondary and tertiary procedure to manage IUI complications, respectively. These rates were 16.7% (P Conclusion Delayed diagnosis of IUI was significantly associated with increased number of procedures needed to manage the injury. The rate of nephrectomy and tube dependence in this group was higher but not statistically significant. Delayed diagnosis of IUI is associated with higher treatment burden.

INTRODUCTION AND OBJECTIVE:Renal colic secondary to kidney stone disease is a common reason for emergency department (ED) visits and often leads to patients receiving narcotic medications. With the...

Disorders of pain neural systems are frequently chronic and, when recalcitrant to treatment, can severely degrade the quality of life. The pain pathway begins with sensory neurons in dorsal root or trigeminal ganglia, and the neuronal subpopulations that express the transient receptor potential cation channel, subfamily V, member 1 (TRPV1) ion channel transduce sensations of painful heat and inflammation and play a fundamental role in clinical pain arising from cancer and arthritis. In the present study, we elucidate the complete transcriptomes of neurons from the TRPV1 lineage and a non-TRPV1 neuroglial population in sensory ganglia through the combined application of next-gen deep RNA-Seq, genetic neuronal labeling with fluorescence-activated cell sorting, or neuron-selective chemoablation. RNA-Seq accurately quantitates gene expression, a difficult parameter to determine with most other methods, especially for very low and very high expressed genes. Differentially expressed genes are present at every level of cellular function from the nucleus to the plasma membrane. We identified many ligand receptor pairs in the TRPV1 population, suggesting that autonomous presynaptic regulation may be a major regulatory mechanism in nociceptive neurons. The data define, in a quantitative, cell population–specific fashion, the molecular signature of a distinct and clinically important group of pain-sensing neurons and provide an overall framework for understanding the transcriptome of TRPV1 nociceptive neurons. Perspective Next-gen RNA-Seq, combined with molecular genetics, provides a comprehensive and quantitative measurement of transcripts in TRPV1 lineage neurons and a contrasting transcriptome from non-TRPV1 neurons and cells. The transcriptome highlights previously unrecognized protein families, identifies multiple molecular circuits for excitatory or inhibitory autocrine and paracrine signaling, and suggests new combinatorial approaches to pain control.

To assess life expectancy and biopsy outcomes in men undergoing prostate biopsy at an academic medical center.We analyzed men who underwent prostate biopsy at our medical center between July 2012 and June 2014. Long-term other-cause mortality risk was determined using survival tables. Indications for biopsy and biopsy outcomes were assessed, and compared among men with varying mortality risks.A total of 417 men underwent prostate biopsy, in whom 14-year other-cause mortality risk ranged from 9% to 74%. One hundred ninety-three men (46.3%) were considered low-mortality risk (40% risk of 14-year mortality), 131 (31.4%) intermediate risk (41%-55% 14-year mortality), and 93 (22.3%) high risk (55% 14-year mortality). Of the 417 patients who underwent biopsy, 149 (35.7%) were found to have prostate cancer. There was no significant difference in the rate of positive biopsies (P = .72), distribution of Gleason scores (P = .60), or percentage of positive biopsy cores (P = .74) between mortality risk groups. However, by UCSF Cancer of the Prostate Risk Assessment score, there was significant trend toward higher-risk prostate cancer in men with intermediate and high-mortality risk (P = .04).In this analysis, a large number of men with limited life expectancies underwent prostate biopsy. The majority of these men had negative biopsies or low-risk cancers, suggesting that they were unlikely to benefit from biopsy. To avoid potentially unnecessary prostate biopsies, the practitioner must give serious consideration to a patient's age and medical comorbidities before making a recommendation as to whether biopsy should be performed.

Background: The prevalence of long-term opiate use in treating chronic non-cancer pain is increasing, and prescription opioid abuse and dependence are a major public health concern. To explore alternatives to opioid-based analgesia, the present study investigates a novel allosteric pharmacological approach operating through the cation channel TRPV1. This channel is highly expressed in subpopulations of primary afferent unmyelinated C- and lightly-myelinated Aδ-fibers that detect low and high rates of noxious heating, respectively, and it is also activated by vanilloid agonists and low pH. Sufficient doses of exogenous vanilloid agonists, such as capsaicin or resiniferatoxin, can inactivate/deactivate primary afferent endings due to calcium overload, and we hypothesized that positive allosteric modulation of agonist-activated TRPV1 could produce a selective, temporary inactivation of nociceptive nerve terminals in vivo. We previously identified MRS1477, a 1,4-dihydropyridine that potentiates vanilloid and pH activation of TRPV1 in vitro, but displays no detectable intrinsic agonist activity of its own. To study the in vivo effects of MRS1477, we injected the hind paws of rats with a non-deactivating dose of capsaicin, MRS1477, or the combination. An infrared diode laser was used to stimulate TRPV1-expressing nerve terminals and the latency and intensity of paw withdrawal responses were recorded. qRT-PCR and immunohistochemistry were performed on dorsal root ganglia to examine changes in gene expression and the cellular specificity of such changes following treatment. Results: Withdrawal responses of the capsaicin-only or MRS1477-only treated paws were not significantly different from the untreated, contralateral paws. However, rats treated with the combination of capsaicin and MRS1477 exhibited increased withdrawal latency and decreased response intensity consistent with agonist potentiation and inactivation or lesion of TRPV1-containing nerve terminals. The loss of nerve endings was manifested by an increase in levels of axotomy markers assessed by qRT-PCR and colocalization of ATF3 in TRPV1+ cells visualized via immunohistochemistry. Conclusions: The present observations suggest a novel, non-narcotic, selective, long-lasting TRPV1-based approach for analgesia that may be effective in acute, persistent, or chronic pain disorders.

Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in select prostate tissues and cell lines using MethylPlex–next-generation sequencing (M-NGS). Hidden Markov model–based next-generation sequence analysis identified ∼68,000 methylated regions per sample. While global CpG island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation significantly increased from ∼12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively (P-value < 2 × 10−16). We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer-specific, including numerous novel DMRs. A novel cancer-specific DMR in the WFDC2 promoter showed frequent methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization, and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion-positive and -negative cancers, and we confirmed this observation using pyrosequencing on a tissue panel. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression.

High-throughput sequencing of polyA+ RNA (RNA-Seq) in human cancer shows remarkable potential to identify both novel markers of disease and uncharacterized aspects of tumor biology, particularly non-coding RNA (ncRNA) species. We employed RNA-Seq on a cohort of 102 prostate tissues and cells lines and performed ab initio transcriptome assembly to discover unannotated ncRNAs. We nominated 121 such Prostate Cancer Associated Transcripts (PCATs) with cancer-specific expression patterns. Among these, we characterized PCAT-1 as a novel prostate-specific regulator of cell proliferation and target of the Polycomb Repressive Complex 2 (PRC2). We further found that high PCAT-1 and PRC2 expression stratified patient tissues into molecular subtypes distinguished by expression signatures of PCAT-1-repressed target genes. Taken together, the findings presented herein identify PCAT-1 as a novel transcriptional repressor implicated in subset of prostate cancer patients. These findings establish the utility of RNA-Seq to identify disease-associated ncRNAs that may improve the stratification of cancer subtypes.

Long intervening non-coding RNAs (lincRNAs) have been implicated in diverse biological processes including p53 signaling and chromatin remodeling, but have not been thoroughly profiled in human cancers. Here, we have developed an approach for ab initio reconstruction of poly-A+ transcriptome sequencing (RNA-seq) data for the unbiased discovery of novel transcripts. To accomplish this, we developed AssemblyLine, a method that clusters and filters large collections of transcripts to produce a consensus transcriptome. To demonstrate AssemblyLine, we sequenced a cohort comprised of 81 prostatic tissues (20 benign, 47 localized tumors, and 14 metastases) and 21 prostatic cell lines using the Illumina Genome Analyzer II and generated 1.723 billion sequence fragments. We successfully aligned 1.42 billion reads with Tophat – a program capable of ab initio splice junction discovery – and then used Cufflinks to model sample-specific transcriptomes totaling 8.25 million transcripts. AssemblyLine condensed the 8.25 million original transcripts into 35,415 distinct transcriptional loci, of which 1,859 (5.2%) represented candidate lincRNAs that lacked genomic overlap with known gene annotations. These putative RNAs lacked robust open reading frames suggesting that the vast majority were non-coding. Further, they exhibited evolutionary conservation and were enriched with histone modifications supporting independent transcriptional start sites and active transcription. Together, these results add confidence to AssemblyLine's nomination process and suggest that these novel lincRNAs may be transcriptionally active in prostate cancer. We then selected 106 transcripts that were differentially expressed in localized prostate cancer when compared to benign adjacent tissue (False Discovery Rate < 0.05), and 15 transcripts with profound cancer outlier expression profiles for further study. These 121 Prostate Cancer Associated Transcripts (PCATs) accurately classified benign, localized, and metastatic prostate cancer tissues by unsupervised hierarchical clustering. Consistent with AssemblyLine's nominations, PCR-based experiments on selected transcripts in an independent tissue cohort showed high validation rates for the transcript structure and expression level predictions. Furthermore, in vitro studies of PCAT-1, a novel lincRNA observed in our dataset as highly upregulated in prostate cancer, revealed direct regulation by the histone methyltransferase EZH2. siRNA knockdown of PCAT-1 in LNCaP, a prostate cancer cell line, caused a 25-50% decrease in cell proliferation. Thus, this study establishes a paradigm for ab initio transcriptome annotation and discovery of novel lincRNAs in cancer tissues. Further, these results provide intriguing evidence that lincRNAs are aberrantly expressed and may play a role in prostate cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 929. doi:10.1158/1538-7445.AM2011-929

High-throughput sequencing of polyA+ RNA (RNA-Seq) in human cancer shows remarkable potential to identify both novel disease-specific markers for clinical uses and uncharacterized aspects of tumor biology, particularly non-coding RNA (ncRNA) species. To illustrate this approach, we employed RNA-Seq on a cohort of 102 prostate tissues and cells lines. We found that aberrant expression profiles of novel tissue-specific ncRNAs distinguished benign, cancerous, and metastatic tumors, and we defined a core set of 121 novel ncRNAs whose dysregulation characterizes prostate cancer. Among these, a novel prostate-cancer specific ncRNA (termed PCAT-1) defined a subset of aggressive cancers with low expression of the epigenetic regulator EZH2, a component of the Polycomb Repressive Complex 2 (PRC2) commonly upregulated in metastatic cancers. In vitro chromatin immunoprecipitation, RNA immunoprecipitation, and drug treatment assays for core PRC2 genes indicated that the PRC2 complex directly binds and represses PCAT-1, and that PCAT-1 transcript reciprocally binds PRC2. By contrast, in vitro models with high levels of endogenous PCAT-1 transcript did not recapitulate PRC2-mediated repression, and in these cells siRNA-mediated knockdown of PCAT-1 showed a 25 – 50% decrease in cell proliferation. Using gene expression arrays, we determined that PCAT-1 contributes to the transcriptional regulation of genes in several key biological processes, including cell cycle. These data suggest that PCAT-1 exhibits two biological states: a PRC2-repressed state and an active state that promotes proliferation. Next, we showed that novel ncRNAs may serve a clinical purpose for the non-invasive detection and stratification of prostate cancer patients. We performed qPCR on patient urine samples (n=108) and found that a custom ncRNA expression signature, which includes PCAT-1, both diagnosed prostate cancer effectively and yielded prognostic information. Indeed, a high ncRNA expression signature value correlated with high-grade histology (Gleason score >=7 vs. Gleason score =6; p = 0.01). Taken together, the findings presented herein establish the utility of RNA-Seq to comprehensively identify unannotated ncRNAs, such as PCAT-1, implicated in cancer. Our data suggest that PCAT-1 promotes cell proliferation, that in its inactive state PCAT-1 is mechanistically repressed by PRC2, and that PCAT-1 may serve as a candidate biomarker for non-invasive clinical tests. We further speculate that applying these methodologies to other diseases may reveal key aspects of disease biology and clinically important biomarkers, particularly for diseases that currently lack good non-invasive tests in fluids such as blood serum or urine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4707. doi:10.1158/1538-7445.AM2011-4707