AUA 2012 Meeting: Selected Abstracts

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AUA 2012 Meeting: Selected Abstracts

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Note that these are not published studies. Some may go on to become published studies, but many will not, so treat accordingly.
ALTERATIONS IN THE PELVIC FLOOR MUSCULATURE ON PELVIC MRI IN PATIENTS WITH INTERSTITIAL CYSTITIS
A. Lenore Ackerman
Una J. Lee
Nelly Tan
Shlomo Raz
Steven S. Raman
Larissa V. Rodriguez
Los Angeles, CA


Introduction and Objectives
In women with Interstitial Cystitis (IC), the pelvic musculature is hypothesized to undergo tonic contraction, which can be a source of pelvic pain. While pelvic muscle hypertonicity produces minimal changes on physical or pathological examination, we speculated it would manifest as differences in pelvic floor appearance on MRI. We retrospectively compared Magnetic Resonance Imaging (MRI) findings, specifically levator measurements, in women with IC to control women without pain to test this hypothesis.

Methods
Fifteen women with IC and 15 age-matched controls without pain, all aged 20 to 67 years, received pelvic MRI, which were reviewed in blinded fashion by two radiologists. We took quantitative measurements of the pelvic musculature, including the puborectal line (H-line), distance of the posterior puborectalis to the pubococcygeus (M-line), vaginal length, urethral length and cross-sectional area, levator width and length, and levator angle formed by the posterior margins of the levators. A paired, two-tailed T test was used to compare MRI measurements and clinical factors, such as age, parity, age at menarche, and duration of symptoms, between IC and control patients.

Results
There were no significant differences in age, parity, symptom duration, or age at menarche between IC patients and controls. Patients with IC exhibited significantly shorter bilateral levator muscles compared with controls (right: 5.3±0.2 vs. 5.7±0.3, left: 5.3±0.2 vs. 5.8±0.3 cm, P<0.02), resulting in widening of levator angle (30.5±3.5 vs. 21.2±3.2°, P<0.03). The H-line was significantly smaller in IC patients (4.8±0.6 vs. 6.2±0.7 cm, P<0.05), while the M-line did not differ between groups. While total urethral length did not differ, the distance from the vaginal cuff (2.2±0.3 vs. 1.7±0.5 cm, P<0.05) and bladder neck (1.6±0.3 vs. 1.3±0.2 cm, P<0.03) to the puborectal line was significantly longer in IC patients than in controls.

Conclusions

Patients with IC appear to have pelvic floor hypertonicity on MRI, manifest as shortened levator length, increased levator angle, and decreased puborectal distance. Levator tightening may lift the pelvic floor, resulting in elevation of the bladder neck and vaginal cuff seen in IC patients in comparison to controls. These observations support the theory that some patients with IC experience pelvic floor muscle overtensioning, which may contribute to or amplify patient pain. Future prospective studies will be necessary to determine MRI utility in helping further our understanding of IC phenotype and pathophysiology.

NIDDK U01 DK070234
The prevalence of interstitial cystitis/ bladder pain syndrome (IC/BPS) and chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) in men; results of the RAND Interstitial Cystitis Epidemiology (RICE) male study
Anne M. Suskind
Sandra H. Berry
Brett A. Ewing
Marc N. Elliott
Marika J. Suttorp
J. Quentin Clemens
Ann Arbor, MI


Introduction and Objectives
As part of the RICE study, we previously developed validated case definitions to identify IC/BPS and CP/CPPS. Using population-based screening methods, we applied these case definitions to determine the prevalence of these conditions in men.

Methods
A total of 6,072 households were contacted by phone to screen for men who had symptoms of IC/BPS or CP/CPPS. An initial 296 men screened positive, of which 149 met the inclusionary criteria and completed the telephone interview. Fifty-two of them met exclusion criteria and were later excluded from analysis. For IC/BPS, two case definitions were applied (high sensitivity and high specificity definitions), while for CP/CPPS, a single case definition (with both high sensitivity and specificity) was used. These case definitions were used to classify subjects into groups based on diagnosis. Weighted prevalence estimates, with 95% confidence intervals, were calculated.

Results
Based on our sample of 97 subjects, 23% met the high specificity definition of IC/BPS, 16% met the case definition of CP/CPPS, and 8% met both definitions (see figure). The IC/BPS weighted prevalence estimate for the high sensitivity definition was 4.2% (3.1-5.3%), and for the high specificity definition was 1.9% (1.1-2.7%). The CP/CPPS weighted prevalence estimate was 1.8% (0.9-2.7%). Based on 2006 U.S. census data, these values equate to 2 million men in the U.S. with each IC/BPS and CP/CPPS.
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Conclusions

Symptoms of IC/BPS and CP/CPPS are widespread among men in the United States. The prevalence of IC/BPS symptoms in men approaches that in women, suggesting that this condition may be underdiagnosed and undertreated in the male population.

Relative Contribution of UPOINT Domains to Symptom Severity and Phenotype Clustering in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome
Daniel Shoskes
Mary Samplaski
Jianbo Li
Cleveland, OH


Introduction and Objectives
The UPOINT system characterizes men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) according to 6 domains (Urinary, Psychosocial, Organ Specific, Infection, Neurologic/Systemic and Tenderness of Skeletal Muscles) which can guide multimodal therapy. Some domains have multiple possible criteria and the lumping of these criteria has never been validated. Furthermore, patterns of domain and subdomain clustering may give clues as to etiology or temporal staging of the syndrome. We examined the contribution and clustering patterns of UPOINT domains and subdomains to symptom severity

Methods
Records were reviewed from CP/CPPS patients including 120 men characterized by UPOINT alone and 100 characterized by subdomains: U.V (voiding), U.V (storage), P.C (catastrophizing), P.D (depression), O.B (bladder), O.P. (prostate), I.E (prostatic fluid bacteria), I.U (urethritis), N.N (neurologic), N.S (systemic). The Chronic Prostatitis Symptom Index (CPSI) measured symptom severity

Results
For U, P and I, subdomains had similar incidences but for N, N.Neurologic > N.Systemic (77% vs 11%) and O.Prostate>O.Bladder (51% vs 33%). By cluster analysis with multidimensional scaling, the U, O.Prostate and T, domains clustered together and P, I, N, and O.Bladder clustered together. In the larger group without subdomains, the groupings were O/U/T and P/I/N. Domains whose contribution to total CPSI was significant by multivariable analysis were U, P and T and to the pain subscore of CPSI were P and T only. Only P independently contributed to the QOL subscore.

Conclusions

UPOINT domain criteria capture a homogeneous group for each domain except for divergence between Organ Specific Bladder vs Prostate. The clustering of domains specific to the pelvis (O/U/T) vs those that are systemic (P/N) suggests 2 patient populations who may differ in pathophysiology and treatment response. The primary drivers of pain in CPPS are pelvic floor tenderness and psychologic depression and catastrophizing.
NIH DK57267, DK68557 and P01 DK44935
Colon-to-bladder afferent cross-sensitization to enhance bladder and urethral pain behaviors in rats with TNBS-induced colitis
Satoru Yoshikawa
Naoki Yoshimura
Pittsburgh, PA


Introduction and Objectives
There is a significant overlap in chronic pelvic pain syndrome in women, which includes interstitial cystitis/bladder pain syndrome (IC/BPS), irritable bowel syndrome (IBS) and endometriosis. Previous animal studies also demonstrated that experimental colitis leads to the electrophysiological hyperexcitability of afferent neurons innervating the bladder, resulting in frequent voiding in rats. However, it is not directly examined whether colon irritation increases pain sensation in the lower urinary tract. This study therefore investigated whether pain behavior in response to bladder and urethral irritation is enhanced in rats with experimental colitis.

Methods
In female SD rats, experimental colitis was induced by trinitrobenzene sulfonic acid (TNBS, 50mg/mL in 50% ethanol, 0.4mL) through a transanally placed catheter. In some rats, capsaicin was administered subcutaneously for 2 consecutive days (total: 125 mg/kg) starting 6 days before behavioral studies to desensitize capsaicin-sensitive C-fiber afferent pathways. At 10 days after TNBS application, resiniferatoxin (RTx, 0.3µM) was instilled into the bladder for 1 min via a urethral catheter, and then two types of nociceptive behaviors such as licking (lower abdominal licking; pudendal nerve-dependent urethral pain behavior) and freezing (motionless head turning; pelvic nerve-dependent bladder pain behavior) were scored every 5sec for 15min.

Results
In TNBS-treated rats, intravesical application of RTx showed significantly increased licking behavior with a peak in the early phase (0-5 min) (p<0.001) and freezing behavior with a peak in the late phase (10-15min) (p<0.001) compared to vehicle-treated rats, in which RTX application induced minimal changes in pain behavior (Fig). C-fiber desensitization by capsaicin pretreatment dramatically and significantly suppressed these enhanced pain behaviors (p<0.001 and p<0.001, respectively).

Conclusions

These results indicate that colitis (10 days) enhances pain sensation (i.e., hyperalgesia) derived from the bladder and urethra due to colon-to-bladder afferent cross-sensitization via activation of C-fiber afferent pathways. These mechanisms might contribute to overlapped pain symptoms in IC/BPS and IBS.
Chronic pelvic pain syndrome: Back to the brain
Livio Mordasini
Christian Weisstanner
George N. Thalmann
Roland Wiest
Thomas M. Kessler
Bern, Switzerland


Introduction and Objectives
Chronic pelvic pain syndrome (CPPS) impairs the life of millions of men worldwide and represents a serious economic problem for every health care system. There is a large number of purported therapeutic approaches but the effectiveness is very limited. Treatment of CPPS is a challenge and the ideal therapy remains to be elucidated. Growing evidence supports the presence of central pathomechanisms involved in CPPS maintaining pain perception in spite of excessive anti-microbial and anti-inflammatory therapies. We therefore assessed brain morphology in men with CPPS and compared it to a cohort of age-matched healthy volunteers.

Methods
We investigated a consecutive series of 20 men with treatment refractory CPPS. Inclusion criteria were National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score ≥ 15 and failed pharmacological therapy with alpha-blockers, tetracyclines, and nonsteroidal anti-inflammatory drugs.
We employed neuroimaging using voxel-based morphometry (VBM), investigated and compared regional brain volume and density of men with CPPS and of a cohort of age-matched healthy volunteers.

Results
Mean age of the 20 patients was 42 years (standard deviation (SD) ± 14.34) with a mean NIH-CPSI total score of 28 (SD ± 6.36) and pain index of 6 (SD ± 1.93) on a visual analogue scale, respectively. Highly significant differences (p < 0.0001 for gray matter (GM), T = 3.1 for white matter (WM)) were found between patients with CPPS and healthy controls with a substantial reduction regarding regional GM and WM volume in right anterior cingulate cortex in patients with CPPS.

Conclusions

Substantial volume reduction in the anterior cingulate cortex in patients with CPPS suggests an essential role of this brain region involved in emotional pain processing. Central pathomechanisms of CPPS may be responsible for the often unsatisfactory results of conventional treatments focused on peripheral dysfunction. Thus, the anterior cingulated cortex may be a promising target for the development of new therapies for CPPS.
NIH DK082315
FREQUENCY AND DURATION SPECTRUM OF UROLOGIC CHRONIC PELVIC PAIN SYMPTOM FLARES
Siobhan Sutcliffe
Graham Colditz
Ratna Pakpahan
David Song
Rebecca Bristol
Vivien Gardner
Gerald Andriole
H. Henry Lai
St. Louis, MO


Introduction and Objectives
Based on anecdotal clinical evidence, urologic chronic pelvic pain symptom exacerbations, commonly referred to as flares, are believed to occur approximately once a year and last approximately one week. However, no studies, to our knowledge, have investigated the frequency and duration of flares in interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients. Therefore, we conducted a study to describe the spectrum of frequency and duration of flares among IC/BPS and CP/CPPS participants at the Washington University site of the ongoing Multidisciplinary Approaches to the study of chronic Pelvic Pain (MAPP) study.

Methods
At their six month study visit, participants were asked to complete an additional form on their frequency and duration of flares, defined as “symptoms that are much worse than usual”. Specifically, they were asked whether they had ever had flares that lasted: 1) less than one hour; 2) more than an hour but less than one day; and 3) more than one day. For each question to which they responded affirmatively, they were also asked to report the average frequency and duration of each type of flare.

Results
24 female and 16 male participants have provided information on frequency and duration of flares. The distribution of flares by sex is provided in the table.

The distribution of flares appeared to differ by sex (p=0.07), with female participants being considerably more likely to have days-long flares than male participants (91.7 vs 50.0%, p=0.0068). For either sex, minutes-long flares lasted <1-60 minutes and occurred 6 times/day to once every 2 months; hours-long flares lasted 1-23 hours and occurred 3 times/week to 1-2 times/year; and days-long flares lasted 2 days to several months and occurred twice per week to less than once per year.

Conclusions

Our findings suggest that there may be a previously unappreciated wide spectrum of frequency and duration of urologic chronic pelvic pain flares that may vary by sex. Future research should investigate the spectrum of symptoms and bother associated with these flares.
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TARIS Biomedical, Inc.
Ascending dose cohort study of LiRIS® (lidocaine-releasing intravesical system) in women with moderate to severe interstitial cystitis
J. Curtis Nickel
Stephen S. Steele
Julie Lekstrom-Himes
Neal Shore
Robert M. Moldwin
Kenneth M. Peters
Robert D. Mayer
Philip M. Hanno
Kingston, Canada


Introduction and Objectives
LiRIS is a novel intravesical drug-delivery system, deployed and retrieved using standard urological procedures, which releases lidocaine into the bladder lumen over two weeks. This phase 1b open-label, ascending dose cohort study studied the tolerability, safety, efficacy and limited pharmacokinetics of LiRIS in women with moderate to severe IC.

Methods
Eighteen women with IC meeting the NIDDK criteria for glomerulations and/or Hunner’s lesions having baseline bladder pain of 4 or greater on a 10 cm visual analogue scale were enrolled. Patients received either the LiRIS 200 mg (cohort 1) or LiRIS 650 mg (cohort 2) for two weeks. LiRIS safety, efficacy, cystoscopic appearance of the bladder pre-and post- LiRIS, and limited PK were collected.

Results
Both LiRIS 200 mg and LiRIS 650 mg were well tolerated. Efficacy endpoints are summarized in the Table. Clinically meaningful reductions were seen in pain, urgency, voiding frequency and disease questionnaires. Cystoscopic exam showed improvement on Day 14 (day of LiRIS removal) compared with Day 1 (day of LiRIS insertion) including resolution of Hunner’s lesions in 6 of 7 patients with baseline lesions. Global Response Assessment (7-item Likert scale) showed an overall responder rate of 69% at Day 14 (day of LiRIS removal) which was maintained with an overall responder rate of 69% two weeks later (Day 28). Extended follow-up suggests the pain response was maintained to Day 60. The adverse events were typical of those seen in patients with IC and consistent with a cystoscopic procedure. The majority of adverse events reported were mild to moderate in intensity with no LiRIS related serious adverse events. The systemic levels of lidocaine were very low; no adverse events were attributable to lidocaine exposure.

Conclusions

LiRIS 200 mg and LiRIS 650 mg were safe and well tolerated and showed preliminary efficacy including mucosal healing and extended duration of effect in patients with moderate to severe IC.
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