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2020 CUA Abstracts
POD-3.3. Table 1. Efficacy and harms of surgical treatments for post-prostatectomy incontinence
Intervention No of No of Mean followup Proportion 95% confidence I (%) p Quality of
2
studies participants (months) interval evidence
Benefits – Cure rate using the number of pads per day at 12 months
Bulking agents 2 384 20 0.26 0.10 0.51 92.8 <0.001 Very low
Slings 20 1956 16.9 0.58 0.5 1 0.65 89.1 <0.001 Moderate
ProACT 6 406 17.1 0.63 0.58 0.68 22.5 0.264 Low
AUS 9 817 18.6 0.74 0.61 0.83 92.1 <0.001 Moderate
Harms – Reoperation rate at 12 months
Bulking agents –* – – – – – – – –
Slings 16 1865 15.4 0.07 0.04 0.12 91.5 <0.001 Low
ProACT 3 259 11.3 0.23 0.05 0.61 95.5 <0.001 Low
AUS 12 1596 19.2 0.22 0.15 0.31 92.3 <0.001 Low
*No data was available for bulking agents’ reoperation rate.
Introduction: Surgery for post-prostatectomy urinary incontinence (PPI) Methods: pBOO was surgically induced in female Sprague-Dawley rats,
can have a major impact on patients’ lives. Treatment is highly sensitive which were simultaneously treated with a dose of one million or 5 mil-
to patient values and preferences. We provide estimates of effect and lion MSCs. Both two and four weeks after obstruction, mRNA and protein
certainty for efficacy and harms outcomes. markers were visualized in pBOO treated and pBOO-non-treated blad-
Methods: We searched Medline, Embase, and Cochrane central for trials ders via PCR and immunohistochemistry. These results were correlated
and observational studies of bulking agents, male synthetic slings, com- with a urodynamic measure of bladder function.
pressive balloon systems (ProACT), and artificial urinary sphincters (AUS) Results: After pBOO, HIF1α and HIF3α were localized in the lamina pro-
up to September 3, 2018. Efficacy outcome was cure (pads per day) and pria and detrusor layer. After obstruction, transcripts for TGFB1, SMAD2,
harms was reoperation. Secondary outcomes: Clavien 3–5, Incontinence HIF1α, HIF3α, VEGF, mTOR, P70 S6K, COL1, and COL3 increased sig-
Quality of Life (IQOL), and Patient Global Impression of Improvement nificantly above normal levels, while IL-10 levels decreased below nor-
(PGI-I). These were assessed at 12 months and longest followup available. mal levels. MSC treatment was effective at returning the transcripts and
Analyses were performed using random effect models. Risk of bias was proteins to normal levels, especially with 5 million MSCs at four weeks.
assessed with Cochrane and CLARITY tools and quality of evidence using Additionally, high pressure generated by pBOO decreased in treatment
GRADE (PROSPERO 42018073923). groups.
Results: We identified no eligible trials and 85 observational studies: three Conclusions: This data confirms that the IP administration of MSCs is
for bulking agents, 35 for slings, 10 for ProACT, and 37 for AUS, involving effective at mitigating pBOO associated deterioration. Thus, we have
13 100 patients. Data quality was low to very low for most outcomes for provided further insight into the pathophysiology of pBOO, its treatment
each procedure. Data for slings and AUS were moderate quality for effi- with MSCs, and believe this will aid in the progression to clinical trials
cacy outcomes. Cure rates at 12 months were 26.1% for bulking agents, and, ultimately, improve patient care.
58.6% for slings, 63.2% for ProACT, and 74.0% for AUS. Reoperation References
rates at 12 months were 5.0% for slings, 23.8% for ProACT and 22.2% 1. Fusco F, Creta M, De Nunzio C, et al. Progressive bladder remod-
for AUS (Table 1). Clavien 3–5 complications occurred in 2.8% of slings, eling due to bladder outlet obstruction: A systematic review of
2.3% of ProACT, and 9.0% of AUS. IQOL score was reported for slings morphological and molecular evidences in humans. BMC Urol
and ProACT only, with increases of 32 points and 35 points, respectively. 2018;18:15. https://doi.org/10.1186/s12894-018-0329-4
Similarly, PGI-I score was only reported for slings, with an increase of 1.6. 2. Metcalfe PD, Wang J, Jiao H, et al. Bladder outlet obstruction: pro-
Conclusions: Overall, the quality of evidence supporting available inter- gression from inflammation to fibrosis. BJU Int 2010;106:1686-94.
ventions is quite limited for both efficacy and harms. This calls into ques- https://doi.org/10.1111/j.1464-410X.2010.09445.x
tion the rigor with which devices for PPI are evaluated prior to clinical use. 3. Al-Saikan B, Ding J, Tredget E, et al. Benefits of mesenchymal stem
The systematic summary provided can facilitate shared decision-making cells after partial bladder outlet obstruction. Can Urol Assoc J
for men with PPI. 2016;10:1. https://doi.org/10.5489/cuaj.3257
4. Wiafe B, Adesida A, Churchill T, et al. Mesenchymal stem cells
POD-3.4 inhibit hypoxia-induced inflammatory and fibrotic pathways in
bladder smooth muscle cells. World J Urol 2018;36:1157-65.
Intraperitoneal administration of mesenchymal stem cells is https://doi.org/10.1007/s00345-018-2247-1
effective at mitigating detrusor deterioration after partial bladder 5. Wiafe B, Adesida A, Churchill T, et al. Mesenchymal stem cell ther-
outlet obstruction apy inhibited inflammatory and profibrotic pathways induced by
Rutuja Kadam , Bridget Wiafe , Peter D. Metcalfe 1 partial bladder outlet obstruction and prevented high-pressure urine
1
1
1 Department of Surgery, University of Alberta, Edmonton, AB, Canada storage. J Pediatr Urol 2019;15:254.e1-10. https://doi.org/10.1016/j.
Introduction: Partial bladder outlet obstruction (pBOO) results in stress jpurol.2019.03.003
on the bladder and is associated with morbidity. The increased pres- 6. Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mes-
sure generated by the detrusor muscle, required to empty the bladder, enchymal stem cells favors tumor growth in allogenic animals. Blood
results in tissue hypoxia, mechanical stretch, smooth muscle cell hyper- 2003;102:3837-44. https://doi.org/10.1182/blood-2003-04-1193
trophy, and eventually, fibrosis. 1,2 Prior studies show that mesenchymal 7. Spees JL, Olson SD, Ylostalo J, et al. Differentiation, cell fusion,
stem cells (MSCs) can mitigate this progression in vitro and in vivo in a and nuclear fusion during ex vivo repair of epithelium by human
rat model via intravenous (IV) administration. Systemic IV administra- adult stem cells from bone marrow stroma. Proc Natl Acad Sci USA
3-5
tion carries some concerns. Thus, the current investigation focuses on 2003;100:2397-2402. https://doi.org/10.1073/pnas.0437997100
6,7
an indirect intraperitoneal (IP) administration of MSCs. We hypothesize
that IP administration would be useful at mitigating deterioration after
pBOO but require a higher dose.
S34 CUAJ • June 2020 • Volume 14, Issue 6(Suppl2)