AUA 2011 - Highlights

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AUA 2011 - Highlights

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Here are the relevant abstracts presented 14-19 May 2011 in Washington at the AUA 2011. Please note that these are NOT peer-reviewed, published studies, and many will not be published, so always read them cum grano salis. Also note that I have omitted abstracts from obscure centers in developing countries. My comments are interspersed in red.
My comment: Hopefully this will soon lead to the commercial availability of these well-desgned wands
Source of Funding: The clinical trial was supported by the National Center for Pelvic Pain Research, Sebastopol, CA
SAFETY AND EFFECTIVENESS OF AN INTERNAL PELVIC MYOFASCIAL TRIGGER POINT WAND FOR UROLOGICAL CHRONIC PELVIC PAIN SYNDROMES
Rodney Anderson
David Wise
Timothy Sawyer
Brian Nathanson
Stanford, CA


INTRODUCTION AND OBJECTIVES: Urologic chronic pelvic pain syndromes challenge physicians seeking adequate treatment alternatives. Pelvic muscle tenderness phenotypes occur often in these patients and pelvic myofascial physical therapy is helpful. We evaluated safety and tolerability of an internal therapeutic trigger point wand to enable patient self-treatment and determined effectiveness in decreasing pelvic muscle tenderness.

METHODS: A curved wand served as an extended finger to locate and release painful myofascial trigger points; an integrated algometer sensor monitors point pressure to prevent excessive or dangerous force. Patients used the wand weekly after education and careful supervision by a physical therapist. Assessments of pain sensitivity were conducted at pretreatment, 1 and 6 months; adverse events were documented. There were 169 patients enrolled in the study from October 2008 through mid-December 2009 with intent to obtain a 6-month follow-up. 92% of patients were men and 8% women with a median age of 41 years (25th percentile, 75% percentile; 32.5, 52.5).

RESULTS: 113 of the enrolled 169 patients completed 6 months of wand use; 56 patients withdrew but none for adverse events. Pelvic muscle sensitivity scores relative to pretreatment were available for 109 patients at 6 months. The median (25thpercentile, 75th percentile) sensitivity before wand use was 7.5 (6, 8.5); it decreased significantly after one month of wand use to a median of 5 (4, 6.5), p<0.001 (paired Wilcoxon matched-pairs signed-ranks test). At 6 months the median sensitivity decreased further to 4 (2.5, 5.5); the median difference in sensitivity was 2.5 (1.5, 4) compared with pretreatment values (p< 0.001). Eighty-seven percent (95/109) of patients reported some (>0) reduction in muscle sensitivity and 93% indicated they were very satisfied or moderately satisfied with use of the wand. There were no serious side effects and rare transient episodes of mucosal bleeding.

CONCLUSIONS: This pilot trial represents an attempt to relieve the painful symptoms of UCPPS in a select population who were seeking treatment beyond the unsuccessful traditional multi-modal therapies they had previously received. Patient self-treatment utilizing a therapeutic wand for myofascial TrP release appears to be a safe, viable and economical chronic pelvic pain management option.
My comment: This is a worrying finding that deserves further study.
Source of Funding: Cleveland Clinic
GREATER ENDOTHELIAL DYSFUNCTION AND ARTERIAL STIFFNESS IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME-A POSSIBLE LINK TO CARDIOVASCULAR DISEASE
Daniel Shoskes
Dona Prots
Jeffrey Karns
Aaron Shoskes
Joi Horhn
Cleveland, OH


INTRODUCTION AND OBJECTIVES: Men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have a significantly higher rate of self reported cardiac disease than controls but no mechanism for an association is known. Endothelial dysfunction and peripheral arterial stiffness correlate with cardiac disease and mortality. We wished to study these markers of vascular dysfunction in men with CP/CPPS compared to asymptomatic controls.

METHODS: Twenty one men with symptomatic, untreated CP/CPPS and 14 asymptomatic controls were tested with an Endo-PAT machine (Itamar Medical, Israel) that assessed the Augmentation Index(AI), a measure of arterial stiffness and Reactive Hyperemia Index (RHI), a measure of nitric oxide mediated endothelial vasodilation. Both elevated AI and diminished RHI suggest vascular and endothelial disease. Symptom severity in patients was measured by the NIH Chronic Prostatitis Symptom Index (CPSI) and patient phenotype characterized by the UPOINT system. All values except symptom duration met the D'Agostino test for normality and therefore parametric statistics were used with significance set at p<0.05

RESULTS: Ages were similar in the CP/CPPS group (22-63 years, median 40) and controls (19-57, median 40). Patients had median symptom duration of 24 months (range 3-440), mean CPSI scores of 24.7+/-5.1 (range 18-37) and mean UPOINT domains of 2.9+/-1.1 (range 1-5). AI was significantly higher (greater arterial stiffness) in CPPS patients vs controls (5.0% +/-2.3 vs. -6.0%+/-3.0, p=0.006). RHI was significantly lower (more endothelial dysfunction) in CPPS patients (1.76+/-1.2 vs 2.21+/-1.7, p=0.03). Age had a negative correlation to RHI (Spearman R -0.48, p=0.03) but not AI. There was no correlation between symptom duration, severity or phenotype (number or type of UPOINT domains) and RHI or AI

CONCLUSIONS: Men with CP/CPPS have evidence for increased arterial stiffness and vascular endothelial dysfunction. This is the first mechanistic correlation found to explain the higher incidence of self reported cardiac disease in these patients. Plausible mechanisms include chronic pain affecting vascular function and chronic stress and catecholamine release predisposing both to vascular changes and CP/CPPS. Noninvasive Endo-PAT testing may allow stratification of CP/CPPS patients by vascular dysfunction, which may require specific treatment, or at least further assessment of cardiac risk
My comment: ESWT can also affect muscular spasm, because we know it reduces hypertonia of the wrist and finger muscles in patients affected with spasticity (cerebral palsy).
Source of Funding: None
IS THERE EVIDENCE FOR ESWT THERAPY IN MEN WITH CHRONIC NONBACTERIAL PROSTATITIS/CHRONIC PELVIC SYNDROME?: PRELIMINARY RESULTS OF A CONTROLLED STUDY
Michael Mathers
Stephan Degener
Stephan Roth
Theodor Klotz
Remscheid, Germany


INTRODUCTION AND OBJECTIVES: Chronic prostatitis/pelvic pain syndrome (CPPS) is a common condition of unclear aetiology. Treatment modalities are often empirical with an uncertain outcome. Prostatic calcifications are often found, but a link to symptoms is controversial. There is a need for new treatment alternatives. Extra corporal shock wave lithotripsy (ESWT) might be a possible treatment option.

METHODS: : A total of 24 men with CPPS refractory to multiple prior therapies were treated by extra corporal shock wave lithotripsy (ESWT). 14 men (verum group) were treated with ultrasound controlled ESWT of the prostate, 10 patients (sham group) with the ESWT focused to the filled bladder. The treatments were performed once weekly for at least three times in a prone position with a filled bladder on an classical shock wave lithotriptor (Modulith Storz CPX). 4 patients of the sham group changed to the verum group after three ESWT treatments. The first 5 patients were treated with an antibiotic for 5 days. The national Institute of health chronic prostatitis symptom index (NIH-CPSI), the International prostatic symptoms Score (IPSS), transrectal ultrasound and blood tests were performed at the beginning, after 4 weeks and after 3 months of therapy. Urine tests were performed before and after each ESWT treatment. Two patients (one patient in the verum, and one patient of the sham group) were lost to follow up.

RESULTS: Mean NiH-CPSI total score +/- SD decreased from 26.1 +/- 1,8 to 12.0 +/- 1.5 (p< 0,0001) in the verum group after 3 months. Significant improvement was seen in each sub score domain. The sham group showed a lesser decrease of NIH-CPSI score: 26.4 +/- 1.7 to 18.3 +/- 1.7 (p< 0,01). The IPSS score showed a similar improvement. 9 patients of the verum group however only 1 patient of the sham group reported on an immediate improvement of symptoms within 24 hours after the first ESWT. In three patients of the verum group and two patients of the sham group bacterial growth was found after ESWT. 2 patients of the verum group reported on a slight gross hematuria for several hours. After three to six months 7 patients of the verum group received a new series of ESWT treatment because of the reoccurrence of symptoms.

CONCLUSIONS: ESWT of the prostate in patients with CPPS seems to be a promising effective treatment. More prospective placebo controlled trials are required.
My comment: Dr Shoskes addresses the critics of UPOINT
Source of Funding: None
INCLUSION OF AN ERECTILE DYSFUNCTION DOMAIN TO THE UPOINT PHENOTYPE DOES NOT IMPROVE CORRELATION WITH SYMPTOM SEVERITY IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME
Mary Samplaski
Jianbo Li
Daniel Shoskes
Cleveland, OH


INTRODUCTION AND OBJECTIVES: The UPOINT phenotyping system classifies men with category III prostatitis (chronic pelvic pain syndrome (CPPS)) into 6 domains which can then guide uni- or multi-modal therapy. We have shown correlation between number of positive domains and symptom severity as well as an 84% success rate with UPOINT guided therapy. This was confirmed in a large Italian cohort but a German cohort only correlated domain number with symptom severity if a 7th erectile dysfunction (ED) domain was added ("S" giving "UPOINTS"). We wished to evaluate the addition of an ED domain to UPOINT in our patients

METHODS: 100 recent CPPS patients were classified with the UPOINT system. An additional "S" domain was positive for men with self reported ED. Subdomains were created based on the diagnostic criteria used (eg. Psychosocial divided into Depression and Catastrophizing subgroups, Urinary into Voiding and Storage, Organ Specific into Bladder and Prostate, Infection into bacterial and atypical, N into Neurologic and Systemic). Symptom severity was assessed with the NIH Chronic Prostatitis Symptom Index (CPSI).

RESULTS: The 100 men had a median age of 42 (range 18-79) and median symptom duration of 15 months (range 3-360). The mean total CPSI score was 24.8+/-7.1. The "S" domain was positive in 28%. There again was a stepwise positive correlation between number of positive UPOINT domains and symptom severity (Pearson r=0.27, p=0.006). Addition of the "S" domain slightly reduced this correlation (Pearson r=0.25, p=0.01) primarily due to higher symptom severity with 2 domains than with 3. Absence or presence of ED had no impact on total CPSI (24.8 vs 24.7) or the subscores for pain (11.5 vs 11.6) or quality of life (8.8 vs 8.9). By univariate linear regression, the domains and subdomains significantly impacting total CPSI were P-catastrophizing, P-depression and Tenderness; again the "S" domain had no impact. By multivariable analysis, number of UPOINT domains was the strongest predictor of total CPSI (OR 4.1, CI 1.5-6.7, p=0.002), a relationship lost with UPOINTS (OR 1.0, CI -2.1-4.2, p=0.53)

CONCLUSIONS: While ED is common in men with CPPS, in our patients it did not impact symptom severity or quality of life independently. The addition of a 7th ED domain ("UPOINTS") did not improve the correlation between phenotype and symptom severity. While symptoms of ED should be sought and appropriately treated in men with CPPS, data in our patients does not support the utility of using ED as an independent UPOINT domain
My comment: Another installment in the TENS aka EMS saga.
Source of Funding: None
THE EFFICACY OF ELECTROMAGNETIC STIMULATION FOR TREATMENT OF CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME PATIENTS WHO DO NOT RESPOND TO PHARMACOTHERAPY.
Woojoong Kim
Jae Seung Lee
Geonseok Lee
Wonjin cho
Ha na Lee
YOUNG SUK Lee
DeokHyun Han
Kyu-Sung Lee
Seoul, Korea, Republic of


INTRODUCTION AND OBJECTIVES: We investigated the effect of electromagnetic stimulation (EMS) as primary treatment for men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) who did not respond to pharmacotherapy, evaluating the changes in their pain and lower urinary tract symptoms.

METHODS: The patients with CP/CPPS symptoms for at least 3 months in spite of medication were included. Inclusion criteria were > 18 years, total score of NIH-CPSI > 15, score of item 1 and item 2 in NIH-CPSI > 1. All patients underwent EMS for 6 weeks (total 12 sessions). The primary end-point was the change of total and pain scores of NIH-CPSI 24 weeks after treatment. Patients were evaluated by NIH-CPSI, International Prostate Symptom Score(IPSS), Benefit Satisfaction and Willingness (BSW) questionnaire, patient perception of symptom improvement (PPSI), voiding diary and complications.

RESULTS: A total of 46 men were included. 37 patients who completed this study were analyzed. Nine of 46 patients dropped out - 7 in withdrawal of consent, 1 in unsatisfactory therapeutic effect, 1 in adverse effect of EMS. Figure 1 shows the changes of total and pain scores of NIH-CPSI. Total and pain scores of NIH-CPSI were significantly decreased immediately after treatment and maintained till 24 weeks after treatment. At 24 weeks, 22 patients (59.5%) shows 6 or greater improve of total NIH-CPSI score. Total and and sub-domain sum of IPSS, 24-hr micturition number were improved significantly after treatments. In BSW, 75.7%, 70.3% and 78.4% patients reported positive answer to the benefit, satisfaction and willingness domain respectively 24 weeks after treatment. PPSI measured by visual analog scale was maintained from immediately after treatment (45.0) till 24 wks (45.9). There were 4 adverse events, including 1 increased postvoid residual, 1 hip joint pain, 1 urethral discharge, and 1 reflux esophagitis.

CONCLUSIONS: In this study, EMS significantly improved pain and lower urinary tract symptoms in CP/CPPS patients who did not respond medical treatments and more than 70 % patients were satisfied with EMS. These data suggest that EMS could be considered as a safe and effective treatment option for CP/CPPS patients who do not respond to pharmacotherapy.
My comment: A weak thumbs up?
Source of Funding: This study was sponsored by Pfizer Inc. Editorial Support was provided by Michelle Jenvey of UBC Scientific Solutions and was funded by Pfizer Inc.
TANEZUMAB THERAPY FOR CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS): PRELIMINARY ASSESSMENT OF EFFICACY AND SAFETY IN A RANDOMIZED CONTROLLED TRIAL
J. Curtis Nickel
Gary Atkinson
John Krieger
Ian W Mills
Michael Pontari
Daniel A Shoskes
Tim Crook
Kingston, Canada


INTRODUCTION AND OBJECTIVES: Nerve growth factor (NGF) levels correlate with pain severity in CP/CPPS. Because tanezumab, a humanized monoclonal antibody, selectively inhibits NGF, we evaluated the safety and efficacy of tanezumab for pain associated with CP/CPPS.

METHODS: This double-blind, randomized, placebo-controlled, proof-of-concept study enrolled patients with moderate to severe CP/CPPS (NIH Chronic Prostatitis Symptom Index (NIH CPSI) ?15). Patients who completed ?4 diary entries and had a diary-derived mean average pain score ?4 on the Numeric Rating Scale (NRS, range 0?10), were randomized to receive a single IV dose of tanezumab 20 mg or placebo, then followed for 16 weeks. Statistical analysis was an exploratory, estimation approach using ANCOVA and 90% confidence intervals; there was no hypothesis testing. The primary efficacy endpoint was the change from baseline to week 6 in average daily NRS pain score. Secondary endpoints included the change from baseline to week 6 in NIH CPSI total score, and micturition and urgency episode frequency per 24 hours. Adverse events (AEs) were also reported.

RESULTS: Overall, 62 patients (age 21?72 years, 72.6% category IIIb) were randomized and received treatment. At week 6, tanezumab marginally improved average daily NRS pain and urgency episode frequency versus placebo, but this was not statistically proven (Table). There was no notable improvement in NIH CPSI total score or micturition frequency for tanezumab versus placebo at week 6 (Table). Overall, 80.0% of tanezumab and 65.6% of placebo patients experienced an AE. Paresthesia was the most common AE in the tanezumab group (26.7%; placebo: 6.3%).

CONCLUSIONS: This exploratory study suggests that tanezumab might provide some symptom improvement compared with placebo, for patients with CP/CPPS, although it is also possible there was no treatment effect. The decrease in NIH CPSI total score was less than the accepted minimally clinically important change of 4 points while the definition of a clinically significant change in NRS-measured pain for CP/CPPS is unknown, and requires further investigation. These findings support additional efforts to define which patient phenotypes may prove amenable to NGF-directed therapy.
My comment: Silodosin is a drug used to treat BPH, and looks like it warrants further study in CPPS
Source of Funding: Supported by Watson Laboratories, Inc.
EFFECTS OF SILODOSIN IN MEN WITH MODERATE OR SEVERE CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME: A DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY
J. Curtis Nickel
Michael O'Leary
Herbert Lepor
Kim Caramelli
Heather Thomas
Lawrence A. Hill
Gary Hoel
Kingston, Canada


INTRODUCTION AND OBJECTIVES: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by debilitating lower urinary tract symptoms (LUTS) and urogenital pain in the absence of urinary tract infection. Silodosin, a uroselective alpha-blocker, is effective in the treatment of LUTS associated with benign prostatic hyperplasia. This double-blind, placebo-controlled phase 2 study evaluated the safety and efficacy of two different doses of silodosin in patients with moderate to severe CP/CPPS.

METHODS: Patients aged ?18 years, with National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score ?15, NIH-CPSI pain score ?8, and pelvic pain for ?3 months before screening were randomized to silodosin 4 mg or 8 mg per day, or placebo. The primary efficacy endpoint was change from baseline to week 12 in NIH-CPSI total score. A significance level of 2.5% was applied to all comparative analyses.

RESULTS: Of 151 participants, 76.2% completed the study. Median age was 48.2 years; 80.1% of patients had experienced pain for at least 1 year. NIH-CPSI total score decreased significantly with silodosin 4 mg compared with placebo (Table). Silodosin 4 mg vs placebo also provided significant improvement (mean ± standard deviation) in NIH-CPSI urinary symptom score (-2.2 ± 2.7 vs -1.3 ± 3.0; P=.010), NIH-CPSI quality of life impact score (-4.1 ± 3.1 vs -2.7 ± 2.5; P=.010), and Medical Outcomes Study Short Form 12 physical component score (4.2 ± 8.1 vs 1.7 ± 9.0; P=.049). In addition, 56% of patients receiving silodosin 4 mg versus 29% receiving placebo reported marked or moderate improvement during global response assessment. Silodosin 4 mg was well tolerated, with treatment-related incidences of dizziness and headache lower than those for placebo; 26.9% of patients receiving silodosin 4 mg experienced retrograde ejaculation (placebo, 1.9%). Treatment with silodosin 8 mg instead of 4 mg provided no additional clinical benefit.

CONCLUSIONS: The results suggest that silodosin 4 mg may provide an effective treatment option for patients with CP/CPPS.
My comment: The most well known SNS device is the Medtronic InterStim. This is a surgical intervention that could be tried in the most refractory patients, perhaps.
Source of Funding: None
OUTCOMES OF SACRAL NERVE STIMULATION IN PATIENTS WITH OR WITHOUT INTERSTITIAL CYSTITIS/CHRONIC PELVIC PAIN SYNDROME
Daniel Woodruff
Charlie Bengtson
Bradley Wilson
Tomas Griebling
Kansas City, KS


INTRODUCTION AND OBJECTIVES: Sacral nerve stimulation (SNS) is approved for urinary urgency/frequency, urge urinary incontinence and non-obstructive idiopathic urinary retention. Many of these patients also have conditions such as interstitial cystitis (IC) or chronic pelvic pain syndrome (CPPS). Although IC/CPPS is not a primary indication for SNS, anecdotal reports suggest some patients have symptomatic improvements. This study examined clinical outcomes of SNS using a validated instrument, and compared results in those with and without IC/CPPS.

METHODS: Prospective data were collected in patients undergoing SNS by a single surgeon. Subjects completed the American Urological Association (AUA) Symptom Index at each pre- and post-operative visit. Patients were divided into two groups based on whether or not they also had an established diagnosis of IC/CPPS. Total AUA Symptom Score (AUA-SS), quality of life (AUA-QoL) and filling and voiding subscores (AUA-F; AUA-V) were analyzed. Within group analyses were performed using paired t-tests and repeated measures ANOVA. Between group analyses used two-sample t-tests for means, and one-way and factorial ANOVA. Results were considered significant at p < 0.05.

RESULTS: Sixty-eight subjects (19 men, 49 women), median age 58 (range 21-86), underwent SNS for clinically indicated symptoms and met inclusion criteria. Group 1 (n = 26) also had IC/CPPS, and Group 2 (n = 42) did not. Median followup was 4.4 years. Mean AUA-SS improved from 27.3 to 14.9 in Group 1 and 21.7 to 12.1 in Group 2 (both, p < 0.0001). Overall, 20 (29%) patients experienced ?15 points improvement in total AUA-SS. Mean preoperative AUA-F subscores were worse in Group 1 (13.6) versus Group 2 (10.7) (p < 0.0001). Other preoperative parameters were equivalent between groups. Within-group analyses showed improvements in all postoperative variables (AUA-SS, AUA-QoL, AUA-F, AUA-V) for both groups (p < 0.0001). Despite statistically significant improvement within groups, mean postoperative AUA-F subscores remained higher in Group 1 versus Group 2 (p = 0.038).

CONCLUSIONS: To our knowledge, this is the largest study to prospectively compare voiding outcomes after SNS in patients with or without IC/CPPS with a validated instrument. These data demonstrated both groups experienced significant improvement in almost all voiding parameters measured by AUA-SS and its component subscores. Patients should be counseled regarding realistic goals that can be potentially achieved using SNS for voiding symptoms based on presence or absence of IC/CPPS.
My comment: More evidence of crosstalk and how bowel problems can cause inflammation in the bladder
Source of Funding: NIH R01 DK066658 and DK49430
RELEASE OF MAST CELL INFLAMMATORY MEDIATORS CONTRIBUTES TO ENHANCED SENSORY MECHANISMS IN THE URINARY BLADDER AFTER COLON IRRITATION.
Jocelyn J Fitzgerald
William C de Groat
Elena Ustinova
Michael A Pezzone
Pittsburgh, PA


INTRODUCTION AND OBJECTIVES: There is considerable clinical overlap between Irritable Bowel Syndrome (IBS) and other Chronic Pelvic Pain disorders, e.g. cystitis. Colitis induced in rats by trinitrobenzenesulfonic acid (TNBS) causes cross-sensitization (C-S) of the urinary bladder (UB) as evidenced by pathologic functional changes. This study examined the role of mast cell (MC) recruitment and/or activation and MC secretory products acting on the PAR-2 receptor (PAR-2R) in this type of C-S.

METHODS: 7-12 days after intracolonic application of TNBS in female rats, voiding interval (VI) in metabolic cages, urothelial permeability (UTP), and afferent nerve firing (ANF) were measured. VI and UTP after TNBS were also measured in a MC deficient mouse model and in rats that were fed a MC stabilizing agent (ketotifen 10 mg/kg/day for 5 days in the drinking water). PAR-2R expression, whole bladder PAR-2R mRNA levels, and bladder strip contractility (BSC) in response to the PAR-2 agonist, SLIGRL (100?M) or compound 48/80 (50?g/ml), a MC degranulating agent, were measured. VI was also examined in a separate group of TNBS mice that were injected intraperitoneally with either control liposomes or liposomes containing PAR-2R siRNA.

RESULTS: In TNBS treated rats, VIs decreased from 287 ± 41 sec in controls to 181 ± 8 sec in TNBS (p=0.015), and ANF induced by capsaicin or UB distension was enhanced 2-3 fold (p<0.05). VI normalized in both the mast cell deficient mouse and in rats pre-treated with Ketotifen. Ketotifen did not reverse UB mastocytosis but normalized UTP measured by fluorescein uptake which increased from 0.99 ± 0.22 ug/ml of plasma in controls to 3.01 ± 0.64 ug/ml in TNBS (p=0.012). In TNBS, PAR-2R immunoreactivity increased in the urothelium, whole bladder mRNA increased by 60 percent, and the facilitatory effect of a PAR-2R agonist (SLIGRL) on UB capsaicin-sensitive afferents significantly increased two fold. BSCs induced by 48/80 (50µg/ml), a MC stimulating agent or by a SLIGRL (100 ?M) were enhanced in TNBS. The enhanced BSC in response to SLIGRL in TNBS rats was attenuated by a cocktail of neurokinin 1, 2, and 3 receptor antagonists (2?M). Mice treated with TNBS and control liposome had a >40% decrease in bladder VI, while mice treated with liposome-containing PAR-2 siRNA had normal VI.

CONCLUSIONS: These data indicate that UB dysfunction in the TNBS-induced, C-S model is mediated by increased release of inflammatory mediators from MCs that enhance sensory mechanisms in the UB.
My comment: Interesting study on pain correlations
Source of Funding: None
PREDICTIVE FACTORS OF PAIN SEVERITY IN PATIENTS WITH INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME
Jennifer Rothschild
Marguerite Thomer
Susan Messing
Robert Mayer
Rochester, NY


INTRODUCTION AND OBJECTIVES: Patients with the visceral hypersensitivity syndrome Bladder Pain Syndrome/Interstitial Cystitis (IC) present with a wide spectrum of severity of pain as well as urinary frequency. The causes of such diversity is complex but the severity of pain does impact the distress experienced as well as the modalities of therapy needed to control suffering. Finding correlates of pain severity may allow better insight into etiology and therapy.

METHODS: Institutional approval was obtained for data review of 186 patients with a clinical diagnosis of BPS/IC who completed an intake form including characteristics of their IC/BPS as well as comorbid illnesses and report of current pain on a 0-to-10 scale. Statistics were performed using SAS Statistical software with P<0.05 as possibly clinically significant.

RESULTS: Pain severity did not appear to correlate by age or gender, duration of symptoms, rapidity of onset, report of dietary food sensitivities or exacerbation of symptoms during menstrual cycle. Increased pain scores were associated with reported dysmenorrhea, IC onset with a precipitating event of pelvic surgery, any history of pelvic surgery, more than 5 vaginal infections a year, abuse, asthma, and migraine. A logistic regression model looked at the association of severe (7-10) vs mild (0-3) pain with history of abuse, dysmenorrhea and history of onset of IC symptoms following pelvic surgery. The patients with history of abuse, dysmenorrhea, and pelvic surgery have an 82% (95%CI, 49-96%) predicted probability of a severe pain score (> 7) while those having none of these factors have a predicted probability of 5% (95%CI, 1-20%)

CONCLUSIONS: Although the causes of BPS/IC are unknown and likely multifactorial, the findings suggest that once the bladder does develop a hypersensitive state, those with a history of prior pelvic noxious stimuli will be at risk for experiencing substantial pain possibly related to sacral sensitization and in contrast, actual duration of IC itself does not appear to be significant. Risk factors for dysfunctional coping (social stress and history of abuse) also predict more severe pain though likely by different mechanisms. Finally, those patients with migraines and/or asthma also have increased pain profiles and possible mechanisms for this are worthy of additional investigation although these do not appear to be strong independent indicators of severe pain.
My comment: Perhaps caffeine is not the bogeyman everyone suspects it is?
Source of Funding: The Fishbein Family IC Research Foundation Grant
THE EFFECTS OF CAFFEINE ON THE SYMPTOMS OF INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME: A RANDOMIZED, PLACEBO-CONTROLLED DOUBLE BLIND STUDY
Amin Herati
Barbara Shorter
Mostafa Sadek
Helen Levey
Zhamshid Okhunov
Robert Moldwin
Lake Success, NY


INTRODUCTION AND OBJECTIVES: Caffeine is a widely consumed stimulant among the adult US population and well known to exacerbate symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS). The purpose of this study is to define the relationship between caffeine and IC symptoms by assessing changes in irritative voiding symptoms and pelvic pain.

METHODS: Consecutive IC/PBS patients were randomized to receive either a pill containing 100mg of caffeine or placebo using a four block randomization scheme. All subjects were asked to abstain from caffeine for one to two days prior to the start of the study and to complete a questionnaire consisting of a modified O?Leary Sant symptoms and problem index (0SSPI), global response assessment (GRA), and a visual analog pain score (VAS). Patients were also instructed to maintain a voiding diary starting two days prior to commencing the study and continuing until two days after taking his or her assigned pill. Symptoms were followed by asking the patients to record their pain levels using the GRA and VAS pain scores every 4 hours for the first 16 hours and then once every eight hours for the next 32 hours, for a total of 48 hours. Continuous variables were compared using a two sample t-test, and Pearson?s correlation was used to determine if an association was present between the OSSPI scores and the observed pain response and voided volumes.

RESULTS: Thirty patients with IC/PBS were enrolled in this study, fourteen of which were randomized to the caffeine arm and sixteen were randomized to the placebo arm. Four patients (28.6%) in the caffeine arm and one patient (6.2%) in the placebo arm dropped out before completing the study. Reasons cited for withdrawal included fear of the discomfort associated with the caffeine pill and caffeine withdrawal headaches. Both arms were comparable in baseline VAS scores, IC Symptom and Problem index scores (p = 0.73, p=0.08, and p= 0.1, respectively). No significant differences were found in the VAS and GRA at each of the time intervals assessed between the two groups after administration of caffeine or placebo pill. No correlation was also identified between the baseline symptom scores, GRA and VAS pain scores, and the volume voided after administration of the assigned pill.

CONCLUSIONS: Although caffeine has been anecdotally associated with symptom exacerbation in IC/PBS, our randomized, placebo-controlled, double-blind study did not demonstrate a difference in irritative voiding symptoms or a difference in voiding volume.
My comment: More confirmation on the comorbid conditions named in other studies
Source of Funding: None
PHENOTYPING MEN WITH INTERSTITIAL CYSTITIS/PAINFUL BLADDER
Adam Stewart
Edward Kim
Ragi Doggweiler
Frederick Klein
Knoxville, TN


INTRODUCTION AND OBJECTIVES: Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) is most commonly characterized by urgency and frequency of urination, painful urination, and chronic pelvic pain. IC/PBS is less commonly diagnosed in men. Men with refractory pelvic pain and lower urinary tract symptoms who are ultimately found to have IC/PBS frequently demonstrate a common constellation of non-genitourinary symptoms. The purpose of this study was to review the signs, symptoms, and co-morbidities of men with pelvic pain and voiding dysfunction in order to make an earlier diagnosis and institute treatment in men with IC/PBS.

METHODS: A retrospective analysis of male patients who underwent cystoscopy and hydrodistension for pelvic pain and lower urinary tract symptoms in the last 6 years was performed. Most patients? workup included a detailed history and physical, urine and semen cultures, and multiple courses of antibiotics. The diagnosis of IC/PBS was based on glomerulations found in the bladder mucosa after cystoscopic hydrodistension under general anesthesia. Demographic and treatment related outcomes were reviewed.

RESULTS: From January 2005 to July 2010, 166 men underwent cystoscopy with hydrodistension under general anesthesia for clinical symptoms of IC/PBS. A total of 96 men demonstrated National Institute of Diabetes and Digestive and Kidney Diseases objective criteria for IC/PBS. In addition to their chronic pelvic pain, 84% of these men had common associated co-morbidities including chronic gastrointestinal complaints (45%), anxiety/depression (41%), chronic back pain (38%), chronic joint pain/neuropathy (26%), and/or migraines (11%). Also, 35% of patients have a history of narcotic and/or benzodiazepine dependence.

CONCLUSIONS: Based on our experience, men with IC/PBS demonstrate characteristic psycho-social, chronic pain, and gastrointestinal problems that concomitantly and adversely affect quality of life which are similar to those found in women. These clinical findings support the role of a multi-disciplinary approach for males with IC/PBS and should alert the urologist to have a low threshold for cystoscopy with hydrodistension.
Source of Funding: DK083538
MEDICAL FACTORS ARE POOR PREDICTORS OF PERCEPTION OF PAIN AND URGENCY IN INTERSTITIAL CYSTITIS (IC)
Jeffrey Janata
Lu Zhang
Robert Elston
Chelimsky Thomas
Gisela Chelimsky
Tony Buffington
Cleveland, OH


INTRODUCTION AND OBJECTIVES: From 1993 to 1997, 581 women were enrolled and followed in the NIDDK?s Interstitial Cystitis Data Base (ICDB). The availability of new statistical methods has improved our ability to extract important observations from datasets since the ICDB was last examined. Associations between IC and disorders with increased pain sensitivity such as fibromyalgia (FM), migraine headache, and irritable bowel syndrome (IBS) led us to hypothesize that patients with IC who also reported having these disorders would report higher levels of pain or urgency than those who did not.

METHODS: Lasso regression analysis was employed using only individual ICDB subjects (n=236) for whom records were available at both baseline and at two years. On the basis of Akaike's AIC (A information criterion) we chose the tuning parameter to include ~200 non-zero coefficients. We examined data at baseline, 2-years and their difference to indicate change, using the original scale and a log conversion, choosing the one with the lower AIC.

RESULTS: No association was found between personal or family medical history of migraine, IBS or FM and pain or urgency. A positive association was found between pain severity and having a college education plus having a history of abdominal or pelvic surgery. Exacerbation of pain between baseline and 2 years was associated with history of gastric or intestinal ulcer plus having had a laparoscopy. No association was found between urgency and any of the hypothesized comorbidities.

CONCLUSIONS: Presence of co-morbidities was not associated with higher levels of pain or urgency. Based on preliminary evaluation, the positive associations identified may represent consequences or contributors to IC pain. Patients with higher pain levels may be more likely to have had a procedure, particularly if their level of education allowed a cogent history. Alternatively, invasive procedures in the presence of biopsychosocial risk factors may have increased the risk of a painful outcome. (Bruns) Candidate risk factors might include anxiety, catastrophization, early adverse experience, and others. Additional investigations are needed to determine the relative importance of these possibilities. Reference Bruns and Disorbio J Clin Psychol Med Settings 2009;16:127
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carld
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Re: AUA 2011 - Highlights

Post by carld »

My guess on the cardiovascular issues associated with UCPPS is simply the stress men feel from this disorder can contribute to the hardening of the arteries via the (HPA) axis??? I think if the medical researchers followed other chronic debilitating conditions...you would also find an increase in cardiovascular diseases...

Also should mention the often sedentary lifestyle many men go through as a result of our sub group that can last for years while in their 40's or perhaps earlier in their 30's...

Just my opinion... :-D


http://pubmed.ncbi.nlm.nih.gov/9401628
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I encourage anxiety prone UCPPS people to consider L-Theanine
Age, 44 onset age 37 Feb 2006 Freq. need to urinate. Sensation of having to urinate soon after going. Perineum discomfort/burning/tightness, pubic area discomfort @ times,poor urine stream, post urine dripping/spray. All symptoms have improved with my protocol. At the worst I give it a 1 to 2 on irritation and discomfort and frequency. Helps: Elavil 5mg for anxiety and mast cell protection, (will only take it as needed) self internal PT as needed, stretching, walking, stairmaster cardio workout and light weights, reducing stress, moment to moment relaxation, deep breathing relaxation and using a Theracane. Makes worse: sitting for long periods, stress, over focusing on it. Currently 95%-98% recovered. Stay positive, relaxed and control your anxiety.
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webslave
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Re: AUA 2011 - Highlights

Post by webslave »

I agree, Carl. The link between CP/CPPS and heart disease is most likely due to the common factor: stress.
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gmccormack
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Re: AUA 2011 - Highlights

Post by gmccormack »

Thanks for posting this.

This AUA is somewhat disappointing and boring, there is nothing that sticks out as a ground breaking medication or more data on etiology of what exactly is going on in most patients diagnosed with CPPS.

I researched ESWT awhile back, called several hospitals, and its only really done heavily in European countries mainly Austria, Germany, and Switzerland. I think this has some potential but no one in the US using ESWT has a clue about CPPS.
Age: | Onset Age: | Symptoms: | Helped By: | Worsened By: | Other comments:
critthinker
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Re: AUA 2011 - Highlights

Post by critthinker »

gmccormack, check out my post on ESWT experience in Austria if you're interested in learning more about it.
Age: 27 | Onset Age: 26 | Symptoms: Pelvic pain (began w/ introduction into bladder/prostate of highly resistant strain of bacteria that was acquired via a Botox injection intended to treat levator ani syndrome) | Helped By: Paxil for anxiety, Trigger point release and trigger point injections, stretches, hot baths, Prosta-Q | Worsened By: Stress/anxiety, Sitting down for long periods,
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