A new method for stranded whole transcriptome RNA-seq.

This report describes an improved protocol to generate stranded, barcoded RNA-seq libraries to capture the whole transcriptome. By optimizing the use of duplex specific nuclease (DSN) to remove ribosomal RNA reads from stranded barcoded libraries, we demonstrate improved efficiency of multiplexed next generation sequencing (NGS). This approach detects expression profiles of all RNA types, including miRNA (microRNA), piRNA (Piwi-interacting RNA), snoRNA (small nucleolar RNA), lincRNA (long non-coding RNA), mtRNA (mitochondrial RNA) and mRNA (messenger RNA) without the use of gel electrophoresis. The improved protocol generates high quality data that can be used to identify differential expression in known and novel coding and non-coding transcripts, splice variants, mitochondrial genes and SNPs (single nucleotide polymorphisms).

Systematic review of prospective studies focused on regionalization of care in surgical oncology.

To perform a systematic review of studies prospectively analyzing the impact of regionalization of complex surgical oncology care on patient outcomes. High volume care of complex surgical oncology patients has been repeatedly associated with improved outcomes. Most studies, however, are retrospective and have not prospectively accounted for confounders such as financial ability and social support. Four electronic databases (Ovid MEDLINE®, Ovid EMBASE, Cochrane Library (Wiley), and EBSCHOHost) were searched from inception until August 25, 2018. Two authors independently reviewed 5887 references, with a third independent reviewer acting as arbitrator when needed. Data extracted from 11 articles that met inclusion criteria. Risk of bias assessments conducted using MINORS criteria for the non-randomized, observational studies, and the Cochrane tool for the randomized-controlled trial. Of the 11 studies selected, we found 7 historically-controlled trials, two retrospective cohort studies with prospective data collection, one prospective study, and one randomized-controlled trial. 73% of studies were from Northern Europe, 18% from Ontario, Canada, and 9% from England. Pancreatic surgery accounted for 36% of studies, followed by gynecologic oncology (27%), thoracic surgery (18%), and dermatologic surgery (9%). The studies reported varying outcome parameters, but all showed improvement post-regionalization. Included studies featured poor-to-fair risk of bias. 11 studies indicated improved outcomes following regionalization of surgical oncology, but most exhibit poor methodological rigor. Prospective evidence for the regionalization of surgical oncology is lacking. More research addressing patient access to care and specialist availability is needed to understand the shortcomings of centralization.

Impact of Body Mass Index on Outcomes Following Anatomic GreenLight Laser Photoselective Vaporization of the Prostate.

Introduction: Obesity can lead to increased risk of perioperative complications in surgical patients, but evidence is lacking regarding the impact of obesity on bladder outlet surgery outcomes. We sought to assess the safety and efficacy of GreenLight photoselective vaporization of the prostate (PVP) in obese patients by comparing functional outcomes and complications in men, stratified according to the body mass index (BMI). Materials and Methods: A retrospective analysis was undertaken of 424 men who underwent 180W GreenLight PVP between 2012 and 2016 at two tertiary medical centers. Patients were stratified based on the World Health Organization (WHO) classification of obesity as determined by BMI. Normal weight men had BMI <25 kg/m2, overweight men had BMI between 25 and 30 kg/m2, and obese men had BMI greater than 30 kg/m2. Primary endpoints examined were differences in intraoperative outcomes and incidence of intraoperative and postoperative complications between BMI groups. Secondary endpoints were improvements in the International Prostate Symptom Score, quality of life score, and the uroflowmetry variables, maximum urinary flow rate and postvoid residual. Results: The BMI groups did not differ regarding operative time or lasing time after matching for prostate volume, but overweight patients in the matched cohort still required higher mean energy use than normal weight men (258.6 kJ vs 233.9 kJ; p = 0.017). No significant differences between BMI groups were observed for intraoperative complications, postoperative complications, or readmission rates. All functional parameters were significantly improved at 24 months for each group, with no differences in improvement between groups. On multivariable analysis, BMI was not a significant predictor for outcomes following PVP. Conclusions: Increased BMI has a negligible effect on intraoperative parameters and does not affect postoperative complication rates or functional outcomes. GreenLight XPS 180W PVP is a safe and effective procedure in overweight and obese men.

Immunotherapy in prostate cancer: current state and future perspectives.

Metastatic castrate resistant prostate cancer (PCa) remains an incurable entity. In the era of immunotherapy, the complex PCa microenvironment poses a unique challenge to the successful application of this class of agents. However, in the last decade, a tremendous effort has been made to explore this field of therapeutics. In this review, the physiology of the cancer immunity cycle is highlighted in the context of the prostate tumor microenvironment, and the current evidence for use of various classes of immunotherapy agents including vaccines (dendritic cell based, viral vector based and DNA/mRNA based), immune checkpoint inhibitors, Chimeric antigen receptor T cell therapy, antibody-mediated radioimmunotherapy, antibody drug conjugates, and bispecific antibodies, is consolidated. Finally, the future directions for combinatorial approaches to combat PCa are discussed.

Use of Botulinum Toxin A (BoNT-A) in Detrusor External Sphincter Dyssynergia (DESD): A Systematic Review and Meta-analysis.

We performed a systematic review to examine the efficacy and outcomes of Botulinum Toxin A (BoNT-A) as the primary intervention strategy for patients with detrusor external sphincter dyssynergia. Eleven studies were included in the analysis (n = 353; 16% female, 84% male). BoNT-A was effective in 60%-78% of patients for reducing postvoid residual, mean detrusor pressure, detrusor leak point pressure, and mean urethral pressure 1 month after injection. Most patients required reinjection after an average of 4-9 months. BoNT-A was not associated with any significant adverse events, and may improve quality of life, as well as urodynamic parameters for detrusor external sphincter dyssynergia.

Concordance Between Biopsy and Radical Prostatectomy Pathology in the Era of Targeted Biopsy: A Systematic Review and Meta-analysis.

CONTEXT: Multiparametric magnetic resonance imaging (mpMRI)-targeted transrectal prostate biopsy (TBx) may better predict pathology at radical prostatectomy than systematic transrectal prostate biopsy (SBx). OBJECTIVE: To assess concordance between biopsy and radical prostatectomy pathology in men undergoing a TBx as compared with those undergoing an SBx. EVIDENCE ACQUISITION: Four electronic databases (Ovid MEDLINE, Ovid EMBASE, the Cochrane Library [Wiley], and EBSCHOHost) were searched from inception until July 2018. Studies were included if they were published after 2012, conducted both SBx and TBx, and compared the biopsy results with final pathology after radical prostatectomy for ≥50 patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. Bias was appraised using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. EVIDENCE SYNTHESIS: Our search yielded 10 studies including 1215 men. However, our inclusion criteria applied only to a proportion of men included in these studies. The median age was 65 yr and the median prostate-specific antigen level was 7.2 ng/ml. In the eight studies examining upgrading at prostatectomy, pathology from SBx was significantly more likely to be upgraded relative to TBx (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.48-4.14, p = 0.001). We found no significant difference in downgrading (OR 1.13, 95% CI 0.48-2.67, p = 0.783) between TBx and SBx. For both biopsy-naïve men and men with a prior negative biopsy, results from SBx were more likely to be upgraded than TBx at prostatectomy (OR 1.6 [95% CI 1.02-2.27, p < 0.001] and OR 4.23 [95% CI 1.68-8.48, p = 0.003], respectively). CONCLUSIONS: Pathologic upgrading at prostatectomy was less likely with mpMRI-targeted biopsy versus systematic biopsy alone, without concurrent increase in downgrading. This increased accuracy should improve confidence in management decisions based on MRI-targeted biopsy pathology. PATIENT SUMMARY: We reviewed the ability of multiparametric magnetic resonance imaging -targeted biopsy to predict cancer grade at radical prostatectomy. We found that targeted biopsy provides more accurate assessment of Gleason score at prostatectomy than systematic biopsy.

Meta-analysis and systematic review of interventional therapy versus anticoagulation for isolated femoropopliteal deep venous thrombosis.

OBJECTIVE: Percutaneous endovenous intervention (PEVI) is gaining acceptance for select patients with symptomatic proximal lower extremity deep venous thrombosis (DVT), but the benefits are uncertain in patients with isolated femoropopliteal DVTs. We performed a systematic review and meta-analysis of the literature to assess the safety and effectiveness of PEVI vs systemic anticoagulation for patients with isolated femoropopliteal DVT. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library from inception to March 2018. All studies comparing clinical outcomes between PEVI and systemic anticoagulation were included. The main end points were post-thrombotic syndrome and bleeding complications. Secondary outcomes included femoropopliteal patency rate, venous obstruction, and recurrent DVT. RESULTS: No studies directly comparing PEVI with systemic anticoagulation in isolated femoropopliteal DVTs were identified by the systematic review. A traditional literature review identified one randomized controlled trial comparing the two, which found no difference in rates of post-thrombotic syndrome in PEVI vs systemic anticoagulation (risk ratio, 0.96; 95% confidence interval, 0.82-1.11; P = .56). We additionally identified five retrospective case series containing patients with isolated femoropopliteal DVTs, of which two reported on patency rates (46%-100% at 2 years). CONCLUSIONS: More data are required to definitively state that PEVI should be the preferred intervention for patients with isolated femoropopliteal DVTs, although the initial evidence is promising.