Latest Publications - Division of Urology, University of Toronto

Our faculty’s research is frequently accepted for inclusion in the most prestigious peer-reviewed scientific journals, with over 330 articles published in 2015 alone. Below you will find the most recent publications.

The abstracts below are updated daily. For a more complete list, please visit this PubMed link.

A Simple Guide for Simple Orchiectomy in Transition-Related Surgeries.

A Simple Guide for Simple Orchiectomy in Transition-Related Surgeries.

Sex Med Rev. 2020 Jan 17;:

Authors: Francis C, Grober E, Potter E, Blodgett N, Krakowsky Y

Abstract
BACKGROUND: To date, there is no literature on orchiectomy as a stand-alone procedure in the transgender surgical context.
AIM: To propose a simple guide to aid health-care professionals caring for transgender and gender nonconforming individuals seeking bilateral simple orchiectomy.
METHODS: We use expert opinion to provide a novel guide for simple orchiectomy in the transition-related context for health-care professionals caring for transgender and gender nonconforming individuals. A review of relevant literature was also performed focusing on simple orchiectomy and vaginoplasty surgeries for transgender and gender nonconforming individuals.
MAIN OUTCOME MEASURE: We describe the indications, surgical approach, preoperative and postoperative assessment, and the risks and benefits of bilateral simple orchiectomy in the context of gender surgery.
RESULTS: This article is the first, to our knowledge, to describe a structured guide to bilateral simple orchiectomy in the context of gender surgery for health-care professionals caring for transgender and gender nonconforming individuals.
CLINICAL IMPLICATIONS: Bilateral scrotal orchiectomy is a simple surgical procedure that has a defined role in the surgical management of many transgender individuals.
STRENGTHS AND LIMITATIONS: This article provides an approach to simple orchiectomy in the context of gender surgery for health-care professionals. Only guidelines written in English were included. The quality of the included guidelines was not evaluated, but this was beyond the scope of this review.
CONCLUSION: We present a novel guide for health-care professionals caring for transgender and gender nonconforming individuals seeking bilateral simple orchiectomy in the context of gender surgery. Francis C, Grober E, Potter E, et al. A Simple Guide for Simple Orchiectomy in Transition-Related Surgeries. Sex Med Rev 2020;XX:XXX-XXX.

PMID: 31959532 [PubMed - as supplied by publisher]

Aquablation for Benign Prostatic Hyperplasia in Large Prostates (80-150 cc): 1-Year Results.

Aquablation for Benign Prostatic Hyperplasia in Large Prostates (80-150 cc): 1-Year Results.

Urology. 2019 Jul;129:1-7

Authors: Bhojani N, Bidair M, Zorn KC, Trainer A, Arther A, Kramolowsky E, Doumanian L, Elterman D, Kaufman RP, Lingeman J, Krambeck A, Eure G, Badlani G, Plante M, Uchio E, Gin G, Goldenberg L, Paterson R, So A, Humphreys M, Kaplan S, Motola J, Desai M, Roehrborn C

Abstract
OBJECTIVE: To report 12-month safety and effectiveness outcomes of the Aquablation procedure for the treatment of men with symptomatic benign prostatic hyperplasia (BPH) and large-volume prostates.
METHODS: One hundred and one men with moderate-to-severe BPH symptoms and prostate volumes of 80-150 cc underwent a robotic-assisted Aquablation procedure in a prospective multicenter international clinical trial. Functional and safety outcomes were assessed at 12 months postoperatively.
RESULTS: Mean prostate volume was 107 cc (range 80-150). Mean operative time was 37 minutes and mean Aquablation resection time was 8 minutes. The average length of hospital stay following the procedure was 1.6 days. Mean International Prostate Symptom Score improved from 23.2 at baseline to 6.2 at 12 months (P <.0001). Mean International Prostate Symptom Score quality of life improved from 4.6 at baseline to 1.3 at 12-month follow-up (P <.0001). Significant improvements were seen in Qmax (12-month improvement of 12.5 cc/sec) and postvoid residual (drop of 171 cc in those with postvoid residual >100 at baseline). Antegrade ejaculation was maintained in 81% of sexually active men. No patient underwent a repeat procedure for BPH symptoms. There was a 2% de novo incontinence rate at 12 months, and 10 patients did require a transfusion postoperatively while 5 required take back fulgurations. At 12 months, prostate-specific antigen reduced from 7.1 ± 5.9 ng/mL at baseline to 4.4 ± 4.3 ng/mL.
CONCLUSION: The Aquablation procedure is demonstrated to be safe and effective in treating men with large prostates (80-150 cc) after 1 year of follow-up, with an acceptable complication rate and without a significant increase in procedure or resection time compared to smaller sized glands. ClinicalTrials.gov number, NCT03123250.

PMID: 31059728 [PubMed - indexed for MEDLINE]

Exploring targets of TET2-mediated methylation reprogramming as potential discriminators of prostate cancer progression.

Exploring targets of TET2-mediated methylation reprogramming as potential discriminators of prostate cancer progression.

Clin Epigenetics. 2019 03 27;11(1):54

Authors: Kamdar S, Isserlin R, Van der Kwast T, Zlotta AR, Bader GD, Fleshner NE, Bapat B

Abstract
BACKGROUND: Global DNA methylation alterations are hallmarks of cancer. The tumor-suppressive TET enzymes, which are involved in DNA demethylation, are decreased in prostate cancer (PCa); in particular, TET2 is specifically targeted by androgen-dependent mechanisms of repression in PCa and may play a central role in carcinogenesis. Thus, the identification of key genes targeted by TET2 dysregulation may provide further insight into cancer biology.
RESULTS: Using a CRISPR/Cas9-derived TET2-knockout prostate cell line, and through whole-transcriptome and whole-methylome sequencing, we identified seven candidate genes-ASB2, ETNK2, MEIS2, NRG1, NTN1, NUDT10, and SRPX-exhibiting reduced expression and increased promoter methylation, a pattern characteristic of tumor suppressors. Decreased expression of these genes significantly discriminates between recurrent and non-recurrent prostate tumors from the Cancer Genome Atlas (TCGA) cohort (n = 423), and ASB2, NUDT10, and SRPX were significantly correlated with lower recurrence-free survival in patients by Kaplan-Meier analysis. ASB2, MEIS2, and SRPX also showed significantly lower expression in high-risk Gleason score 8 tumors as compared to low or intermediate risk tumors, suggesting that these genes may be particularly useful as indicators of PCa progression. Furthermore, methylation array probes in the TCGA dataset, which were proximal to the highly conserved, differentially methylated sites identified in our TET2-knockout cells, were able to significantly distinguish between matched prostate tumor and normal prostate tissues (n = 50 pairs). Except ASB2, all genes exhibited significantly increased methylation at these probes, and methylation status of at least one probe for each of these genes showed association with measures of PCa progression such as recurrence, stage, or Gleason score. Since ASB2 did not have any probes within the TET2-knockout differentially methylated region, we validated ASB2 methylation in an independent series of matched tumor-normal samples (n = 19) by methylation-specific qPCR, which revealed concordant and significant increases in promoter methylation within the TET2-knockout site.
CONCLUSIONS: Our study identifies seven genes governed by TET2 loss in PCa which exhibit an association between their methylation and expression status and measures of PCa progression. As differential methylation profiles and TET2 expression are associated with advanced PCa, further investigation of these specialized TET2 targets may provide important insights into patterns of carcinogenic gene dysregulation.

PMID: 30917865 [PubMed - indexed for MEDLINE]

Deconstructing Cell-Free Extract Preparation for in Vitro Activation of Transcriptional Genetic Circuitry.

Deconstructing Cell-Free Extract Preparation for in Vitro Activation of Transcriptional Genetic Circuitry.

ACS Synth Biol. 2019 02 15;8(2):403-414

Authors: Silverman AD, Kelley-Loughnane N, Lucks JB, Jewett MC

Abstract
Recent advances in cell-free gene expression (CFE) systems have enabled their use for a host of synthetic biology applications, particularly for rapid prototyping of genetic circuits and biosensors. Despite the proliferation of cell-free protein synthesis platforms, the large number of currently existing protocols for making CFE extracts muddles the collective understanding of how the extract preparation method affects its functionality. A key aspect of extract performance relevant to many applications is the activity of the native host transcriptional machinery that can mediate protein synthesis. However, protein yields from genes transcribed in vitro by the native Escherichia coli RNA polymerase are variable for different extract preparation techniques, and specifically low in some conventional crude extracts originally optimized for expression by the bacteriophage transcriptional machinery. Here, we show that cell-free expression of genes under bacterial σ70 promoters is constrained by the rate of transcription in crude extracts, and that processing the extract with a ribosomal runoff reaction and subsequent dialysis alleviates this constraint. Surprisingly, these processing steps only enhance protein synthesis in genes under native regulation, indicating that the translation rate is unaffected. We further investigate the role of other common extract preparation process variants on extract performance and demonstrate that bacterial transcription is inhibited by including glucose in the growth culture but is unaffected by flash-freezing the cell pellet prior to lysis. Our final streamlined and detailed protocol for preparing extract by sonication generates extract that facilitates expression from a diverse set of sensing modalities including protein and RNA regulators. We anticipate that this work will clarify the methodology for generating CFE extracts that are active for biosensing using native transcriptional machinery and will encourage the further proliferation of cell-free gene expression technology for new applications.

PMID: 30596483 [PubMed - indexed for MEDLINE]