Page 2 - CUA 2020_Functional Urology
P. 2

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)
   1   2   3   4   5   6   7