Page 3 - CUA2019 Abstracts - BPH

2019 CUA Abstracts

a prostate between 30 cc and 80 cc. WATER II is a prospective, multi- MP-7.9
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centre, single-arm international clinical trial of Aquablation in men with The role of p75NTR receptor in the urothelial and smooth muscle
a prostate between 80 cc and 150 cc. We compare baseline parameters cell response to lipopolysaccharide
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and six-month outcomes in 116 WATER (W-I) and 101 WATER II (W-II) Laura Ran Yan , Abubakr Mossa , Philippe Cammisotto , Lysanne
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study subjects undergoing Aquablation. Students’ t-test or Wilcoxon tests Campeau 1,2
were used for continuous variables and Fisher’s test for binary variables. 1 Department of Surgery, Lady Davis Institute, Montréal, QC, Canada;
Results: Mean operative time was 33±17 minutes in W-I and 37±13 2 Faculty of Medicine, McGill University, Montréal, QC, Canada
minutes in W-II. The average length of stay post-procedure was 1.4±0.7 Introduction: In cystitis, bacterial lipopolysaccharide (LPS) binds to toll-
days (W-I) vs. 1.6±1.1 days (W-II). Mean changes in International Prostate like receptors (TLRs) on urothelial cells, producing inflammatory mediators
Symptom Score (IPSS) and IPSS quality of life were substantial and aver- such as tumour necrosis factor alpha (TNF-α) and nuclear factor kappa B
aged (at six months) 16.9 and 3.5 points, respectively, in W-I and 17.4 (NFkB). Inflammation is also accompanied by an increased activation
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and 3.2 points in W-II (p=0.6046 and 0.2607, respectively). By three of p75NTR, an intrinsic receptor present in bladder tissue. Intriguingly,
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months, Clavien-Dindo grade 2 or higher events occurred in 19.8% of p75NTR activation produces similar inflammatory mediators as TLRs
W-I subjects and 34.7% of W-II subjects (p=0.4680). One W-I subject and both receptors share common pathways that lead to caspase activa-
(0.9%) and six W-II subjects (5.9%) required postoperative blood trans- tion. Nonetheless, communication between the two receptors has not
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fusion (p=0.0517). Both cohorts preserved erectile function. Additional been shown to augment the latter outcomes. The objective of this research
outcomes are listed in Table 1. was to determine if p75NTR can enhance the inflammatory response of
Conclusions: Aquablation clinically normalizes outcomes between urothelial and bladder smooth muscle cells in response to LPS.
patients with a 30–80 cc prostate and patients with an 80–150 cc prostate Methods: Urothelial and smooth muscle cells cultured from Sprague
treated for LUTS/BPH with an expected increase in the risk of complica- Dawley rat bladders were subjected to one of the four treatments: con-
tion. It is an effective and potentially volume-independent treatment of trol, 4 mg/mL THX-B (p75NTR antagonist), 1 mg/mL LPS, or LPS+THX-B.
BPH with acceptable complications. Their expression of TNF-α and NFkB was measured by immunoblot-
This paper has a figure, which may be viewed online at: ting and immunocytochemistry. Urothelial tight junctions’ integrity was
https://2019.cua.events/webapp/lecture/180 measured by immunoblotting of occludin expression and confirmed by
References immunocytochemistry.
1. Gilling PJ, Barber NJ, Bidair M, et al. WATER: A double-blind, ran- Results: We found that LPS induced an increase in TNF-α in urothelial cells,
domized, controlled trial of Aquablation vs. transurethral resection of an effect that was significantly weakened by the p75NTR antagonist (Fig.
the prostate in benign prostatic hyperplasia. J Urol 2018;5:1252-61. 1). Furthermore, p75NTR inhibition in urothelial cells prevented occludin
https://doi.org/10.1016/j.juro.2017.12.065 reduction by LPS as seen in the protein level and immunocytochemistry
2. Desai M, Bidair M, Bhojani N, et al. WATER II (80–150 mL) proce- (Fig. 2). We demonstrated that in smooth muscle cells, LPS activated NFkB
dural outcomes. BJU Int 2019;123:106-12. https://doi.org/10.1111/ instead of TNF-α, an effect attenuated by p75NTR antagonism (Fig. 3).
bju.14360 Conclusions: Together, our findings suggest that the p75NTR intracellu-
lar pathway enhances the LPS-induced inflammation in urothelial cells
MP-7.7 through TNF-α by promoting desquamation and in smooth muscle cells
Robotic competency and perception among Canadian chief via NFκB. This research strongly suggests that blocking p75NTR could be
urology residents an effective drug target in different inflammatory conditions of the bladder
Michael A. Di Lena , Gregory Hosier , Richard D. Di Lena , Naji J. Touma , in order to decrease the activation of TLRs by LPS.
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Michael J. Leveridge 1 This paper has figures, which may be viewed online at:
1 Urology, Queen’s University, Kingston, ON, Canada https://2019.cua.events/webapp/lecture/184
Introduction: Robotic-assisted surgery is continuing to expand in popu- We acknowledge Dr. Uri Saragovi for providing the p75NTR blocker
larity, with its use becoming more ubiquitous in Canada in both the (THX-B).
academic and community settings. As was seen previously with laparo- References
scopic surgery, its implementation does have significant implications on 1. Pålsson-McDermott E, O’Neill L. Signal transduction by the lipopoly-
residency training. There is now a need for graduating residents to have saccharide receptor, toll-like receptor-4. Immunology 2004;113:153-
competencies in robotics while maintaining competencies in more tra- 62. https://doi.org/10.1111/j.1365-2567.2004.01976.x
ditional surgical modalities. With robotic integration well underway, we 2. Ryu J, Tooke K, Malley S, et al. Role of proNGF/p75 signaling in blad-
aim to report on current trainee exposure, competencies, and attitudes der dysfunction after spinal cord injury. J Clin Invest 2018;128:1772-
to robotic surgery in graduating Canadian residents. 86. https://doi.org/10.1172/JCI97837
Methods: All 2019 graduating Canadian urology residents were asked to 3. Bhakar A, Howell J, Paul C, et al. Apoptosis induced by p75NTR
participate in a survey designed to assess current resident exposure, surgi- overexpression requires Jun kinase-dependent phosphorylation
cal competency, and perception of robotic-assisted surgery. Descriptive of BAD. J Neurosci 2003;23:11373-81. https://doi.org/10.1523/
statistics and non-parametric testing were used to summarize the findings. JNEUROSCI.23-36-11373.2003
Results: A total of 33 graduating chief urology residents completed the sur- 4. Barcelona PF, Sitaras N, Galan A, et al. p75NTR and its ligand
vey; 84.8% of residents reported having a robot at their training centre. For proNGF activate paracrine mechanisms etiological to the vascu-
those in hospitals with access to robotics, 60.7% of residents participated lar, inflammatory, and neurodegenerative pathologies of diabetic
in more than 10 cases as a console operator, however, 39.3% of residents retinopathy. J Neurosci 2016;36:8826-41. https://doi.org/10.1523/
spent, on average, less than 10 minutes as the primary operator. Of all JNEUROSCI.4278-15.2016
residents, 69.7% felt that robotics will become the gold standard in certain
urological surgeries but only 39.4% anticipate using robotic surgery in MP-7.10
their future practice. When assessing future training of residents, 57.6% Environmental contaminants impair male fertility over four
believe that all residents should receive training on robotic surgery during generations: Partial rescue by folic acid supplementation
their residency, with 36.3% believing that trainees should leave residency Maryse Lessard , Pauline M. Herst , Phanie L. Charest , Pauline Navaro ,
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competent to perform robotic procedures. Sarah Kimmins , Jacquetta Trasler , Amanda J. MacFarlane , Mathieu
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Conclusions: This national survey shows that overall there is an increase Dalvai , Janice L. Bailey 1
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in robotic exposure to Canadian urology residents, however, it may not 1 Centre for Research on Reproduction, Development and Intergenerational
translate to console operative experience. Going forward, residency cur- Health, Université Laval, Québec City, QC, Canada; School of Nutrition,
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ricula will need to be adapted to formalize robotic surgical experience Faculty of Agricultural and Food Sciences, Université Laval, Québec City,
for Canadian surgical residents. QC, Canada; Department of Pharmacology and Therapeutics, McGill
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S132 CUAJ • June 2019 • Volume 13, Issue 6(Suppl5)