mp76-02 the development and validation a new nomogram for diagnosing bladder outlet obstruction in...

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Urodynamics/Incontinence/Female Urology: Non-neurogenic Voiding Dysfunction Moderated Poster Tuesday, May 20, 2014 1:00 PM-3:00 PM MP76-01 INVESTIGATION INTO CONSTITUTIVE EXPRESSION OF NERVE GROWTH FACTOR IN BLADDER BY BLADDER WALL INJECTION OF NGF ANTISENSE Pradeep Tyagi*, Mahendra Kashyap, Pittsburgh, PA; Michael Chancellor, Royal oak, MI; Naoki Yoshimura, Pittsburgh, PA INTRODUCTION AND OBJECTIVES: Overexpression of nerve growth factor NGF in bladder has been established as a key molecular mediator in the lower urinary tract symptoms. Overactive bladder pa- tients responding to intradetrusor injection of botulinum toxin showed a reduced NGF expression in histological specimens. In our previous study, bladder instillation of NGF antisense was able to directly sup- press the inducible NGF expression in urothelium following acetic acid insult, but the effect of intravesical treatment on the detrusor expression of NGF was inconclusive. Therefore in the present study, we explored the direct effect of bladder wall injection of NGF antisense on the NGF expression in different regions of the bladder. METHODS: Adult female Sprague-Dawley rats were given bladder wall injection (10-20mL) of either saline (sham) (n¼3) or NGF antisense (0.1-10mM) complexed with liposomes under isourane anesthesia(n¼6). Total volume of injection was split into four sites around the bladder. Abdomen was sutured back after surgery and an- imal returned to cages. 48h after injection, open transurethral cystom- etry under urethane anaesthesia (dose 1g/kg, subcutaneously) was performed with saline infused at 0.04ml/min. Bladder was harvested following sacrice for measuring NGF protein levels by ELISA. RESULTS: Cystometric parameters were indistinct between sham and the treated groups. The measured tissue specic NGF levels were normalized to the respective protein concentration and expressed as pg/mg of protein. There was insignicant difference in the NGF levels of two tissue regions from sham group with 295.8 10.26pg/mg in urothe- lium and 273.9 46.28pg/mg in detrusor(n¼3). In contrast, bladder wall injection of NGF antisense reduced the constitutive production of NGF in both urothelium and detrusor regions. Paired analysis of NGF levels in urothelium and detrusor for the antisense treated group found signi- cant reduction in detrusor relative to the higher levels in urothelium 262.0 15.76pg/mg vs 286.8 23.28pg/mg, respectively (p<0.05). CONCLUSIONS: Gene silencing of NGF gene in detrusor following bladder wall injection supports the intradetrusor injection of NGF antisense complexed with liposome as a potential treatment for refractory overactive bladder associated with NGF overexpression in bladder smooth muscle. NGF antisense is able to suppress both constitutive and inducible expression of NGF in bladder, and inducible NGF expression has implications in the OAB pathophysiology. Source of Funding: NIH DK057267,DK088836 and DOD SC100134,PR110326 MP76-02 THE DEVELOPMENT AND VALIDATION A NEW NOMOGRAM FOR DIAGNOSING BLADDER OUTLET OBSTRUCTION IN WOMEN Eskinder Solomon*, Habiba Yasmin, Julie Jenks, Mahreen Pakzad, Rizwan Hamid, Jeremy Ockrim, Julian Shah, Tamsin Greenwell, London, United Kingdom INTRODUCTION AND OBJECTIVES: Bladder outlet obstruc- tion (BOO) in men has been extensively researched and the ICS BOO nomogram is widely used. In women however, the criteria for obstruction is less dened and there are two main reasons why a well-accepted nomogram remains elusive. Blaivis and Groutz (Neuro&Urodyn 2000;19:553e64) have previously proposed a female BOO nomogram that plots maximum detrusor pressure (not necessarily at Qmax) against freeow Qmax. The validity of using non-concurrent pressure-ow values to dene resistance is debatable and a subsequent publication has reported an unlikely high prevalence of BOO when using the Blaivis-Groutz nomogram (Massolt et al, Neuro&Urody 24(3) 237-242). The aim of this study is to develop and validate a criteria for classifying BOO in women derived from concurrent Pdet.Qmax and Qmax based on radiographic evidence of increased urethral resistance. METHODS: Retrospective video-urodynamics and clinical data of 186 women were analysed. The women were divided into six groups. The rst four groups are categorised according to the primary cause of BOO; functional obstruction; anatomical obstruction; anti-incontinence surgery obstruction and cystocele. The fth group consists of patients without voiding symptoms or stress urinary incontinence (SUI) and the sixth where SUI is demonstrated. The detrusor pressure at peak ow (Pdet.Qmax) were plotted against peak ow (Qmax) for voids with a volume > 100 ml. Cluster analysis was performed to derive an axis (BOO criterion) that best divides the denitively obstructed and unob- structed. The sensitivity and specicity of the BOO criterion was then validated by applying it to a further 350 women who have undergone video-urodynamics in our unit. RESULTS: The axis of Pdet.Qmax ¼ 2Qmax best divides the women with and without evidence of radiographic BOO in the original cohort. In the validation cohort, the criterion Pdet.Qmax > 2Qmax identies BOO in women with sensitivity of 0.94, specicity of 0.93 and accuracy of 0.94. The gure below shows: Pdet.Qmax and Qmax for the valida- tion cohort CONCLUSIONS: The criterion Pdet.Qmax > 2Qmax denes BOO in women with excellent accuracy and should be utilised for uro- dynamic diagnosis of BOO in women. Source of Funding: None MP76-03 REGRESSION TO THE MEAN IN A PROSPECTIVE STUDY OF UROLOGICAL CHRONIC PELVIC PAIN SYNDROME (UCPPS) Alisa Stephens*, Philadelphia, PA; J. Quentin Clemens, Ann Arbor, MI; J. Richard Landis, Philadelphia, PA INTRODUCTION AND OBJECTIVES: Regression to the Mean (RTM) is the tendency for the rst measurement to be more extreme relative to the mean value than later measurements. We describe the occurrence of RTM in the measurement of symptoms and its inuence on one year change among men and women with UCPPS in the Multidisciplinary Approach to Pelvic Pain (MAPP) Network Epidemi- ology and Phenotyping Study. METHODS: Symptoms were assessed in 424 participants with UCPPS over one year. Participants who had completed at least 6 e882 THE JOURNAL OF UROLOGY â Vol. 191, No. 4S, Supplement, Tuesday, May 20, 2014

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e882 THE JOURNAL OF UROLOGY� Vol. 191, No. 4S, Supplement, Tuesday, May 20, 2014

Urodynamics/Incontinence/Female Urology:Non-neurogenic Voiding Dysfunction

Moderated Poster

Tuesday, May 20, 2014 1:00 PM-3:00 PM

MP76-01INVESTIGATION INTO CONSTITUTIVE EXPRESSION OF NERVEGROWTH FACTOR IN BLADDER BY BLADDER WALL INJECTIONOF NGF ANTISENSE

Pradeep Tyagi*, Mahendra Kashyap, Pittsburgh, PA;Michael Chancellor, Royal oak, MI; Naoki Yoshimura, Pittsburgh, PA

INTRODUCTION AND OBJECTIVES: Overexpression of nervegrowth factor NGF in bladder has been established as a key molecularmediator in the lower urinary tract symptoms. Overactive bladder pa-tients responding to intradetrusor injection of botulinum toxin showed areduced NGF expression in histological specimens. In our previousstudy, bladder instillation of NGF antisense was able to directly sup-press the inducible NGF expression in urothelium following acetic acidinsult, but the effect of intravesical treatment on the detrusor expressionof NGF was inconclusive. Therefore in the present study, we exploredthe direct effect of bladder wall injection of NGF antisense on the NGFexpression in different regions of the bladder.

METHODS: Adult female Sprague-Dawley rats were givenbladder wall injection (10-20mL) of either saline (sham) (n¼3) or NGFantisense (0.1-10mM) complexed with liposomes under isofluraneanesthesia(n¼6). Total volume of injection was split into four sitesaround the bladder. Abdomen was sutured back after surgery and an-imal returned to cages. 48h after injection, open transurethral cystom-etry under urethane anaesthesia (dose 1g/kg, subcutaneously) wasperformed with saline infused at 0.04ml/min. Bladder was harvestedfollowing sacrifice for measuring NGF protein levels by ELISA.

RESULTS: Cystometric parameters were indistinct betweensham and the treated groups. The measured tissue specific NGF levelswere normalized to the respective protein concentration and expressedaspg/mgofprotein. Therewas insignificant difference in theNGF levelsoftwo tissue regions from sham group with 295.8� 10.26pg/mg in urothe-lium and 273.9� 46.28pg/mg in detrusor(n¼3). In contrast, bladder wallinjection of NGF antisense reduced the constitutive production of NGF inboth urothelium and detrusor regions. Paired analysis of NGF levelsin urothelium and detrusor for the antisense treated group found signifi-cant reduction in detrusor relative to the higher levels in urothelium262.0� 15.76pg/mg vs 286.8� 23.28pg/mg, respectively (p<0.05).

CONCLUSIONS: Gene silencing of NGF gene in detrusorfollowing bladder wall injection supports the intradetrusor injection ofNGF antisense complexed with liposome as a potential treatment forrefractory overactive bladder associated with NGF overexpression inbladder smooth muscle. NGF antisense is able to suppress bothconstitutive and inducible expression of NGF in bladder, and inducibleNGF expression has implications in the OAB pathophysiology.

Source of Funding: NIH DK057267,DK088836 and DODSC100134,PR110326

MP76-02THE DEVELOPMENT AND VALIDATION A NEW NOMOGRAM FORDIAGNOSING BLADDER OUTLET OBSTRUCTION IN WOMEN

Eskinder Solomon*, Habiba Yasmin, Julie Jenks, Mahreen Pakzad,Rizwan Hamid, Jeremy Ockrim, Julian Shah, Tamsin Greenwell,London, United Kingdom

INTRODUCTION AND OBJECTIVES: Bladder outlet obstruc-tion (BOO) in men has been extensively researched and the ICS BOOnomogram is widely used. In women however, the criteria for obstruction

is less defined and there are two main reasons why a well-acceptednomogram remains elusive. Blaivis and Groutz (Neuro&Urodyn2000;19:553e64) have previously proposed a female BOO nomogramthat plots maximum detrusor pressure (not necessarily at Qmax) againstfreeflow Qmax. The validity of using non-concurrent pressure-flowvalues to define resistance is debatable and a subsequent publicationhas reported an unlikely high prevalence of BOO when using theBlaivis-Groutz nomogram (Massolt et al, Neuro&Urody 24(3) 237-242).The aim of this study is to develop and validate a criteria for classifyingBOO in women derived from concurrent Pdet.Qmax and Qmax based onradiographic evidence of increased urethral resistance.

METHODS: Retrospective video-urodynamics and clinical dataof 186 women were analysed. The women were divided into six groups.The first four groups are categorised according to the primary cause ofBOO; functional obstruction; anatomical obstruction; anti-incontinencesurgery obstruction and cystocele. The fifth group consists of patientswithout voiding symptoms or stress urinary incontinence (SUI) and thesixth where SUI is demonstrated. The detrusor pressure at peak flow(Pdet.Qmax) were plotted against peak flow (Qmax) for voids with avolume > 100 ml. Cluster analysis was performed to derive an axis(BOO criterion) that best divides the definitively obstructed and unob-structed. The sensitivity and specificity of the BOO criterion was thenvalidated by applying it to a further 350 women who have undergonevideo-urodynamics in our unit.

RESULTS: The axis of Pdet.Qmax ¼ 2Qmax best divides thewomen with and without evidence of radiographic BOO in the originalcohort. In the validation cohort, the criterion Pdet.Qmax > 2Qmaxidentifies BOO in women with sensitivity of 0.94, specificity of 0.93 andaccuracy of 0.94.

The figure below shows: Pdet.Qmax and Qmax for the valida-tion cohort

CONCLUSIONS: The criterion Pdet.Qmax > 2Qmax definesBOO in women with excellent accuracy and should be utilised for uro-dynamic diagnosis of BOO in women.

Source of Funding: None

MP76-03REGRESSION TO THE MEAN IN A PROSPECTIVE STUDY OFUROLOGICAL CHRONIC PELVIC PAIN SYNDROME (UCPPS)

Alisa Stephens*, Philadelphia, PA; J. Quentin Clemens, Ann Arbor, MI;J. Richard Landis, Philadelphia, PA

INTRODUCTION AND OBJECTIVES: Regression to the Mean(RTM) is the tendency for the first measurement to be more extremerelative to the mean value than later measurements. We describe theoccurrence of RTM in the measurement of symptoms and its influenceon one year change among men and women with UCPPS in theMultidisciplinary Approach to Pelvic Pain (MAPP) Network Epidemi-ology and Phenotyping Study.

METHODS: Symptoms were assessed in 424 participants withUCPPS over one year. Participants who had completed at least 6