AUA 2007 Annual Meeting -- abstracts

Latest research and happenings
Post Reply
User avatar
webslave
Maintenance
Maintenance
Posts: 11390
Joined: Wed Oct 30, 2002 3:18 pm
Location: Please give your location so we can help better
Contact:

AUA 2007 Annual Meeting -- abstracts

Post by webslave »

VARIATIONS IN PSYCHOMETRIC PROFILES AND AWAKENING CORTISOL RESPONSES IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME

Rodney U Anderson, MD, Christine A Chan, MD, Elaine K Orenberg, PhD, Veronica Flores. Stanford University, Stanford, CA

Introduction and Objective: Abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis and diurnal cortisol rhythms has been associated with several pain and chronic inflammatory conditions. Chronic stress is a factor in the chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) related to initiation /exacerbation of the syndrome. We tested the hypothesis that men with CPPS have disturbances in psychosocial profiles and HPA axis function.
Methods: 33 men with CP/CPPS (mean age 44 yr., pain duration 54 mo.) and 18 age-matched, asymptomatic controls were given a series of psychometric questionnaires: Type A personality test; Perceived Stress Scale, Beck Anxiety Inventory; and Brief Symptom Inventory (BSI) for distress from physical symptoms. They provided saliva samples on two consecutive days at 9 specific times with strict reference to the time of each subject’s morning awakening for evaluation of free (unbound) cortisol which reliably reflects secretory activity of the HPA axis. Variations in cortisol were represented by 2-day average of slope of the awakening cortisol response (difference between the cortisol levels at wake and wake +30 min.) and the diurnal slope.
Results: CPPS patients had significantly more perceived stress and anxiety than controls (p < 0.001). BSI scores were significantly elevated in all 9 symptom dimensions (somatization, obsessive/compulsive behavior, depression, anxiety, hostility, interpersonal sensitivity, phobic anxiety, paranoid ideation, psychoticism) for CPPS men who ranked in the 94th percentile compared with 46th percentile for controls (p < 0.001); norm is 50th percentile. The NIH-CPSI pain sub score and Global Severity Index of the BSI showed a positive correlation (p <0.05) in CPPS. There was a trend of greater morning responses in cortisol in CPPS (slope 0.92) versus controls (slope 0.61) but not reaching significance (p = 0.06). Free cortisol levels typically increase 50-60% within 30 min after awakening, however, CPPS men showed hyperactive responses and mean increase of 85% versus 57% for controls.

Conclusions: CPPS men scored exceedingly high on all psychosocial variables and showed evidence of dysfunctional HPA axis function reflected in augmented awakening cortisol responses. Whether these observations represent preexisting characteristics of individuals before the onset of CPPS and activated by chronic pain or a consequence of stress associated with this condition remain in question.
Supported by grant from NIDDK, U01 DK065297



BIOPSYCHOSOCIAL FACTORS IN QUALITY OF LIFE IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME

J Curtis Nickel, MD, Dean Tripp, PhD, Shannon Chuai, PhD, Mark S Litwin, MD, Mary McNaughton-Collins, MD. Queen's University, Kingston, ON, Canada; University of Pennsylvania, Philadelphia, PA; UCLA, Los Angeles, CA; Harvard Medical School, Boston, MA

Introduction and Objective: To explore interactions between psychological, environmental, urinary, and demographic predictors of Quality of Life (QOL) in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
Methods: Men (n=253) previously enrolled in the NIH Chronic Prostatitis Cohort study in North American tertiary care clinical centers (6-U.S., 1-Canada) self-reported with validated instruments including the Physical (PCS) and Mental (MCS) Component Summary subscales of the SF-12, demographics, urinary symptoms, depression, current pain, pain coping and catastrophizing, pain control, social support and solicitous responses from a partner. Data were collected through a one-time survey. Covariates determined to be significant (in correlation analysis) were entered into a multivariable regression model prredicting PCS and MCS.
Results: After adjusting for covariates, regression models showed that poorer PCS scores were predicted by worse urinary function (p=0.0002) and increased use of pain-contingent resting as a coping strategy (p=0.026). Further, poorer MCS scores were predicted by greater pain catastrophizing (p=0.002) and lower perceptions of social support (p<0.0001). The helplessness subscale was the primary significant predictor of the catstrophizig scale on follow up regression analyses (p=0.0004) while the family and friends subscales of the social support scale were the primary MCS predictors (p=0.002; p=0.0002).

Conclusions: These data support a biopsychosocial model for QOL in CP/CPPS, suggesting that specific coping and environmental factors (i.e., catastrophizing, pain-contingent resting, social support) are significant in understanding CP/CPPS patient adjustment. These data can be utilized to develop specific cognitive-behavioral programs for men with CP/CPPS that are refractory to standard medical therapy.



ALPHA BLOCKERS VERSUS PHYTOTHERAPY IN THE TREATMENT OF CHRONIC NON-BACTERIAL PROSTATITIS

Mahmoud H Sherief, MD, Ahmed M El-Nashar, MD, Gamal El-Atrash, MD. Suez Canal University, Ismaillia, Egypt

Introduction and Objective: Chronic prostatitis is an important health care problem. Patients suffer lower genitourinary symptoms, especially pain complaints that result in substantially decreased quality of life. The overall prevalence rate of chronic prostatitis was 9%, There is no strong evidence about the etiology of chronic prostatitis.It is likely to be a multifactorial. A spectrum of etiologic mechanisms or more likely a cascade of events after some initiating factors. Several medical treatments have been used for chronic non-bacterial prostatitis as alpha blockers, saw palmetto, non steroidal anti-inflammatory and no consensuses about treatment strategy. Here we evaluated the effect of alpha blockers versus phytotherapy.
Methods: A randomized controlled study of 4 groups of male patients diagnosed to have chronic non-bacterial prostatitis/chronic pelvic pain syndrome (CP-CPPS) according to the NIH classification strategy. Group I of 35 men treated with alpha blockers (Doxazosin)of 2 mg daily. Group II of 35 men treated with phytotherapy (saw palmetto and P. africanum) with the standard dose. Group III of 35men treated with combination of alpha blockers and phytotherapy. Group IV 28 men treated with placebo capsule as a control. NIH-Chronic prostatitis symptom Index (NIH-CPSI) was measured before and 2 month after treatment.
Results: According to the age and the NIH-CPSI ,there was no significant difference between all the studied groups before treatment. Average pain score was 10.6, 11.2, 10.4 and 10.3 for group I ,II ,III ,and IV respectively. Scores for urinary symptoms were 6.1, 5.9, 6.5 and 6.2 respectively. Quality of life scores were 8.2, 8.4, 8.0 and 8.6 respectively. After treatment, there was a statistically significant difference between the placebo group and all the other 3 treatment groups. Pain score was improved by 66.1%, 74.2% and 80.1% for groups I,II and III respectively with only significant difference between the combination group and the alpha blockers one. Urinary symptoms improved by 66.8%,41.3% and 72.2% respectively with significant difference between the combination therapy and the phytotherapy group. Quality of life improved in all 3 groups but better in group III 59.3%,58.4% and 71.4% respectively.

Conclusions: Both alpha blockers and Phytotherapy showed significant effect in the treatment of CP-CPPS. Combination therapy appeared to be more effective. Alpha blockers showed better improvement for urinary symptoms over the phytotherapy.



INITIAL AND LONG TERM RESPONSES TO TERAZOSIN ACCORDING TO TREATMENT PERIODS IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME

In Rae Cho, MD, PhD, JongGu Kim, MD, KeonCheol Lee, MD, PhD, Joon Seong Jeon, MD. Inje University Ilsanpaik Hospital, Koyang/ Kyunggido, Republic of Korea

Introduction and Objective: To evaluate the initial and long-term efficacy of terazosin according to treatment periods compared with standard therapy in patients with CP/CPPS.
Methods: From January 2004 to May 2005, 172 patients, aged 45 or below with small size prostate (=25ml) and , diagnosed as CP/CPPS were enrolled in this study. The patients were randomly placed into two groups; terazosin (T) group - terazosin 3-4mg/day was given for 12 weeks, NT group : anti-inflammatory agents or muscle relaxants for 12 weeks. All patients took levofloxacin 300mg/day for 12weeks. And terazosin group was randomly divided into two groups according to treatment periods: Ta group - administration of terazosin for only 12 weeks, Tb group - administration of terazosin for 24 weeks. The initial effect of terazosin was evaluated at 12week between T group and NT group with the change from baseline in the total and domain scores of NIH-CPSI. We compared the long term effect at 12 month among the three groups with the change from baseline in the total and domain scores of NIH-CPSI. And the number of patients with clinical improvement, defined as at least a 33% decrease in total NIH-CPSI score or 2 or less on NIH-CPSI quality of life item, was also evaluated to compare the long term efficacy of treatment among the three groups after 12months later.
Results: The study comprised of 128 patients who were followed up after 12months later (50 in NT group, 44 in Ta group and 34 in Tb group). At 12week, the change of total NIH-CPSI score and the pain score of T group were more significantly decreased than that of NT group (p=0.015, p=0.002 respectively). At 12 months, the symptom scores in all domains of the NIH-CPSI showed deterioration compared with original baseline score in the NT and Ta groups, but not in the Tb group. At 12 months, of the patients in the Tb group, 61.8% had a great than 33% improvement in the mean NIH-CPSI total score or 2 or less on NIH-CPSI quality of life domain compared with 22.0% and 31.8% of the NT and Ta groups, respectively (p<0.05). No patients dropped out of the study because of adverse event.

Conclusions: Terazosin therapy is safe and results in significant improvement in the total NIH-CPSI score in the initial response compared with standard therapy. And more than 6months of terazosin therapy maintains the beneficial effect for long term periods when treatment is discontinued.



LONG TERM FOLLOW-UP OF CHRONIC PELVIC PAIN SYNDROME TREATED WITH BIOFEEDBACK PHYSICAL THERAPY

Erik B Cornel, MD, PhD, Ernst P van Haarst, MD. Ziekenhuis Groep Twente, Hengelo, The Netherlands; Sint Lucas Andreas Hospital, Amsterdam, The Netherlands

Introduction and Objective: Men with chronic pelvic pain syndrome (CPPS) or chronic prostatitis type III experience chronic pelvic pain of uncertain aetiology with varying degrees of urinary symptoms. We demonstrated earlier a significant decrease in mean total NIH-CPSI and in all specific subdomains after biofeedback physical therapy and pelvic floor re-education for CPPS patients. Our observations and also several other studies appears to emphasize that the pelvic floor plays an important role in the pathophysiology of CPPS. However, the long-term durability of our outcomes has not yet been investigated. The objective of this prospective study was to evaluate the long term effect of biofeedback physical therapy on the symptoms of men with CPPS.
Methods: Between March 2000 to March 2006, 43 consecutive men (mean age 46 years, range from 29 years to 56 years) who were diagnosed with CPPS participated in a pelvic floor biofeedback re-educating program as described previously. The NIH-CPSI total score was used for diagnosis and to monitor the effect of therapy on short and long term follow up.
Results: Of the initial 43 patients at long term follow-up a NIH-CPSI was available of 24 patients (1 patient died, 12 could not be traced, and 6 did not fill in the NIH-CPSI) The follow-up period was 12-60 months (mean 32). The responders did not differ from those lost to follow-up in the initial NIH-CPSI (means 24.3 and 22.6) or in the NIH-CPSI immediately after physical therapy (means 12.0 and 11.8).
Compared to the initial values, at long term follow-up there was still a significant difference of the mean NIH-CPSI and in all subdomains (Wilcoxon signed ranks test, p<0.01). 4 patients had an increase of their NIH-CPSI (by 7, 3, 1 and 1 points). However, none of them felt the need to visit our outpatient clinic again. The other 20 patients improved compared to the initial NIH-CPSI by 1 to 24 points.
Compared to the immediate post-treatment NIH-CPSI values we found at long term follow-up in 11 patients an increase of 4 to 17 points, 3 patients did not change, and 11 patients improved 1 to 15 points.

Conclusions: Our data demonstrate that there is a role for biofeedback physical therapy and pelvic floor re-education in the treatment of CPPS patients. A minority of patients show an increase of NIH-CPSI compared to immediate post treatment scores, but all of them judged their symptoms to be acceptable. Overall, at long term follow-up the results of biofeedback physical therapy for men with Chronic Pelvic Pain Syndrome are still very good.



MINIMAL INVASIVE TREATMENT OF MEN WITH CATHEGORY IIIB (CPPS) PROSTATITIS. A PROSPECTIVE MULTICENTER TRIAL: RESULTS OF THE MICP STUDY

Bob Djavan, MD, Christian Seitz, MD, Martina Nowak, MD, Michael Dobrovits, MD, Mike Harik, MD, Alireza Nouri, Vincent Ravery, MD, Andreas Reisiegl, MD, Piotr Dobronski, MD, Micheal Marberger, MD. Medical University of Vienna, Vienna, Austria; Univ of Paris, Paris, France; Univ of Warsaw, Warsaw, Poland

Introduction and Objective: To prospectively evaluate the efficacy and safety of targeted high-energy transurethral microwave thermo-therapy (TUMT) in patients with chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) in the setting of a multicenter prospective trial.
Methods: In this comparative study 64 patients with Category IIIB CPPS were evaluated and underwent high-energy TUMT without medical pretreatment. Patient evaluation included determination of patients Subjective Global Assessment (SGA), total NIH Chronic Prostatitis Symptom Index (CPSI), pain (VAS score), voiding and quality of life/impact domains of the CPSI, safety data, International Prostate Symptom Score (IPSS), obstructive (OSS) and irritative (ISS) symptom score, peak flow rate (Qmax), and quality of life (QOL) score, total and transition zone (TZ) prostate volume, serum PSA prior to TUMT and at periodic intervals up to 5 years.

Results: 75% and 82% of patients at 1 year, 67% and 77% of patients at 3 years, and 42% and 56% of patients at 5 years reported at least a mild improvement of the SGA and NIH-CPSI, respectively. At 1 year 55% and 60%, at 3 years 48% and 49%, at 5 years 31% and 36% of patients reported a marked improvement of the SGA and NIH-CPSI respectively. Prostate volume did not change significantly whereas total PSA decreased by 20 % from Baseline at 5 years. Adjuvant alpha blocker therapy enhanced the cumulative improvement rates by 16% at 5 years as compared to a matched group of patients treated with HE-TUMT alone. By 36 and 60 months, 71.3% and 84.7% and 65.4% and 62.8% of patients with the combination of HE-TUMT and adjuvant alpha blockade demonstrated a 50% or greater improvement in IPSS and QOL score, respectively, compared with 62.6% , 59.8%, and 57.5% and 54.2% in a matched HE-TUMT group alone.

Conclusions: HE-TUMT provides a significant clinical benefit in patients with Category IIIB CPPS. Adjuvant alpha blockers enhance the efficacy of HE-TUMT and thus, the combination of HE-TUMT and alpha blockers may offer a suitable option for patients having failed medical therapy. Overall, the improvement in patients SGA and NIH-CPSI are durable despite a light decrease over 3-5 years.



IL-8 LEVELS IN EXPRESSED PROSTATIC SECRETION OF BPH WITH CHRONIC PROSTATITIS

Qiang Wei, MD, Qijun Li, MD, Ping Han, MD, Qiang Dong, MD, Yuru Yang, MD. West China Hospital,Sichuan University, Chengdu, China

Introduction and Objective: To investigate the level of the anti-inflammatory cytokine IL-8 in expressed prostatic secretion (EPS) of BPH with chronic prostatitis. To study the sensitivity and specificity of the IL-8 in EPS identifying benign prostate hyperplasia (BPH) with chronic prostatitis from the simple BPH when comparing with the pathologic diagnosis. To analyze the incidence of chronic prostatitis of the patients with BPH, and to make detailed description of these chronic prostatitis. We will also explore the relationship of IL-8 in EPS with WBC/HP, catheter and age.
Methods: The study involved 44 patients with BPH admitted into our department during November 2004 to June 2005 for surgical therapy. Before performing TURP operations, we gained EPS by prostate massage to measure cytokine IL-8 with Enzyme-linked immunosorbent assays, and test WBC count. After the operation, we took pathological section from our department of pathology to study them again by an experienced pathologist.
Results: IL-8 was detectable in all patients(the threshold of detection for IL-8 is 3ng/ml). 21 (47.7%) BPH patients suffered chronic prostatitis. The mean level of IL-8 in EPS was higher in BPH with chronic prostatitis (8175±3789ng/ml vs 2806±1009ng/ml, P=0.000). The catheter and age seemed to have no impact on the level of IL-8 in EPS (P=0.547, P=0.388). In the meantime, WBC/HP in EPS showed a close positive correlation with IL-8. IL-8 of the patients with WBC/HP>10 was much higher than that of those with WBC/HP<10(P=0.000). The sensitivity and specificity of IL-8 in EPS indentifying the BPH with chronic prostatitis from the simple BPH was respectively 85.7% and 91.3% when the cut-point was 3992ng/ml.

Conclusions: IL-8 is usually enhanced in the EPS of BPH patients with chronic prostatitis. This cytokine is the direct mediator of leukocyte accumulation and activation at inflammatory sites and may be responsible, in part, for the presence of inflammatory reaction in the prostate. The result of diagnosis of BPH with chronic prostatitis by the level of IL-8 in EPS is satisfying, with a sensitivity of 85.7% and a specificity of 91.3% when the cut-point is 3992ng/ml. The catheter and age seemed to have no influence on the concentration of IL-8 in EPS. WBC/HP in EPS revealed a close positive correlation with IL-8.



ASSOCIATION BETWEEN PROSTATITIS AND DEVELOPMENT OF BENIGN PROSTATIC HYPERPLASIA

Jennifer L St Sauver, PhD, Debra J Jacobson, MS, Michaela E McGree, MA, Cynthia J Girman, PhD, Michael M Lieber, MD, Steven J Jacobsen, MD, PhD. Mayo Clinic, Rochester, MN; Merck and Company, Inc, North Wales, PA; Southern California Permanente Medical Group, Pasadena, CA

Introduction and Objective: To determine whether physician diagnosed and self-reported prostatitis were associated with development of benign prostatic hyperplasia (BPH) or related urologic outcomes in a population-based sample of 2447 men residing in Olmsted County, Minnesota.
Methods: Medical records were reviewed for physician diagnosis of prostatitis. Additionally, during the twelfth year of the study, participants completed the Chronic Prostatitis Symptom Index (CPSI) to assess presence of prostatitis symptoms. A random subset of 447 men also participated in a clinical evaluation including transrectal ultrasonography and assessment of serum prostate specific antigen (PSA) levels. Examinations and questionnaires were repeated in year 12. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to assess the association between physician diagnosed prostatitis and subsequent physician diagnosis of BPH, prostatism, or enlarged prostate, treatment or surgery for BPH, and acute urinary retention. Odds ratios were also calculated to assess the association between CPSI-based prostatitis and subsequent presence of an enlarged prostate, decreased urinary flow rate, elevated PSA level, increased lower urinary tract symptoms, treatment or surgery for BPH, and acute urinary retention.
Results: Physician diagnosed prostatitis was associated with a 2.4-fold increased odds of receiving a later diagnosis of prostatism, enlarged prostate, or BPH (OR=2.44, 95% CI=1.49, 4.01). CPSI-based prostatitis was associated with an increased odds of developing elevated lower urinary tract symptoms (OR=3.55, 95% CI=1.44, 8.76) and marginally associated with developing a decreased maximum flow rate (OR=5.06, 95% CI=0.97, 26.42). Men with either physician diagnosed or CPSI-based prostatitis were also more likely to receive treatment for BPH compared to men without prostatitis.

Conclusions: In several cases prostatitis was associated with increased odds of later onset of adverse urologic and BPH-related outcomes. Prostatitis may therefore be an early marker or a risk factor for development of later prostatic or urologic problems.



COMPARISON OF THE ECONOMIC IMPACT OF CHRONIC PROSTATITIS/ CHRONIC PELVIC PAIN SYNDROME AND INTERSTITIAL CYSTITIS/ PAINFUL BLADDER SYNDROME

J Quentin Clemens, MD, Sheila O Brown, RN, BSN, Elizabeth A Calhoun, PhD. Northwestern University, Chicago, IL; University of Illinois at Chicago, Chicago, IL

Introduction and Objective: No direct comparisons of the costs of Chronic Prostatitis/ Chronic Pelvic Pain Syndrome (CP/CPPS) and Interstitial Cystitis/ Painful Bladder Syndrome (IC/PBS) have been performed. Such a comparison is relevant because the distinction between the two conditions is not always clear.
Methods: We recruited 62 men with CP/CPPS and 43 women with IC/PBS from the Northwestern University urology clinic. Information about hospitalizations, laboratory tests, physician visits, telephone calls, medication use, and lost productivity was obtained from written questionnaires. Symptom severity was assessed with the NIH Chronic Prostatitis Symptom Index and the Interstitial Cystitis Symptom Index and Problem Index. Costs were estimated using both Medicare rates and non-Medicare rates (ie, private insurance, managed care). Direct medical cost estimates were based on hospital cost-accounting data, the 2005 Physician Fee Schedule Book, and the 2005 Redbook for pharmaceuticals. Indirect costs were based on annual income and hours lost from work.

Results: Mean age was 51 for both cohorts. Yearly income was > $50,000 in 74% of the men and 65% of the women. Direct costs for consumers of resources over the last 3 months are presented in the Table. Sixteen CP/CPPS patients (26%) and eight IC/PBS patients (19%) reported lost wages due to their condition in the last 3 months. In both groups, higher costs were observed in subjects with more severe symptoms. For all patients (those that did and did not incur costs), mean annualized direct medical costs for CP/CPPS were $3017 (Medicare rates) and $6534 (non-Medicare rates), and for IC/PBS were $3632 (Medicare rates) and $7044 (non-Medicare rates). Mean annualized indirect costs for CP/CPPS were $3248 and for IC/PBS were $4216.

Conclusions: Both CP/CPPS and IC/PBS have very similar and substantial direct and indirect costs, with indirect costs accounting for a large proportion of the total. The direct costs of these conditions are significantly higher than the mean yearly costs reported for many other chronic pain conditions (peripheral neuropathy-$917, low back pain-$2144, fibromyalgia-$2274, rheumatoid arthritis-$2533).



PREVALENCE AND RISK FACTORS FOR PROSTATITIS IN A MANAGED CARE POPULATION

J Quentin Clemens, MD, Richard T Meenan, PhD, Maureen C O'Keeffe Rosetti, MS, Teresa M Kimes, MS, Elizabeth A Calhoun, PhD. Northwestern University, Chicago, IL; Center for Health Research, Portland, OR; University of Illinois at Chicago School of Public Health, Chicago, IL

Introduction and Objective: Very few population-based epidemiologic studies of prostatitis have been performed. Previous studies to assess epidemiologic risk factors for prostatitis have utilized patient self-reported data and are therefore subject to recall bias. The aims of this study were: (1) to utilize coded physician diagnoses to calculate the prevalence of prostatitis, and (2) to compare these patients with matched controls in order to determine medical diagnoses that are associated with prostatitis.
Methods: A computer search of the Kaiser Permanente Northwest (Portland, OR) administrative database was performed for the interval 1/98 to 5/04. A medical record diagnosis of ‘acute prostatitis’ (ICD-9 code 601.0), ‘chronic prostatitis’ (ICD-9 code 601.1) or ‘prostatitis not otherwise specified’ (ICD-9 code 601.9) was used to define the presence of prostatitis. Each of these cases was then matched with three controls by age and duration in the health plan. The medical diagnoses (using ICD-9 codes) assigned to each of these individuals were obtained, and the frequency of these diagnoses were compared between cases and controls. To control for the large sample size, only p-values <0.0001 were considered significant.

Results: The database search yielded 171 men with a diagnosis of acute prostatitis, 847 with a diagnosis of chronic prostatitis, and 4781 with a diagnosis of prostatitis NOS. This yielded a combined prevalence rate of 4.5%. The prevalence increased progressively with age, so that approximately 10% of men >70 had been assigned a prostatitis diagnosis at some time. Medical conditions associated with a prostatitis diagnosis are presented in the Table.

Image

Conclusions: Prostatitis is a commonly diagnosed condition in the community setting, affecting approximately 1 in 22 men. Compared with controls, men with prostatitis were more likely to be assigned 35 specific ICD-9 diagnoses, most of which can be categorized as other urologic conditions (10), unexplained somatic symptoms (19), and psychiatric conditions (4). Additional studies to explore possible explanations for these associations are needed.



PRIMARY CARE PHYSICIAN PRACTICE PATTERNS IN THE MANAGEMENT OF CHRONIC PROSTATITIS/ CHRONIC PELVIC PAIN SYNDROME

J Quentin Clemens, MD, Elizabeth A Calhoun, PhD, Mark S Litwin, MD, MPH, Mary McNaughton Collins, MD, MPH. Northwestern University, Chicago, IL; University of Illinois at Chicago, Chicago, IL; David Geffen School of Medicine at UCLA, Los Angeles, CA; Harvard Medical School, Boston, MA

Introduction and Objective: To define primary care physicians’ (PCPs’) practice patterns in managing patients with symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
Methods: We mailed a questionnaire to 556 primary care physicians at Harvard, UCLA, and ACCESS Community Health Network in Chicago, a large federally qualified health center group. It included a vignette which described a man with typical CP/CPPS symptoms, and then asked questions about etiology, management strategies, and familiarity with CP/CPPS.

Results: We received 290 questionnaires (response rate 52%). Respondents were 52.9% male, and had graduated medical school a mean of 19.0 years earlier (range 1-51). Practice type was 38% community-based, 40% hospital-based, and 22% private practice. Respondents reported seeing a mean of 3.2 patients like the one described in the vignette (range 0-50), and reported a mean of 3.4 patients in their practice with a CP/CPPS diagnosis (range 0-30). Approximately half (48%) of respondents were “not at all” familiar with the NIH classification of prostatitis, and 33% reported “never” having seen a patient like the one described in the vignette. Fully 65% of respondents correctly identified the hallmark symptom of CP/CPPS (pelvic pain). Regarding etiology, 71% correctly indicated that CP/CPPS was non-infectious, 37% incorrectly reported that it was caused by a sexually transmitted disease, and 35% incorrectly indicated that it was caused by a psychiatric illness. Male physicians and physicians who see a higher percent of male patients answered more of these questions correctly. Management strategies are presented in the Table.

Image

Conclusions: Although epidemiologic studies suggest that CP/CPPS is common, our data indicate that many PCPs have limited experience in managing men with the condition. They report varying practice patterns regarding diagnosis and treatment and have important knowledge deficits. These findings suggest that educational efforts targeting PCPs may improve the care of patients with CP/CPPS.



SEXUAL DYSFUNCTION IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME: PREVALENCE, CHARACTERISTICS AND IMPACT

Shaun W H Lee, Men Long Liong, Kah Hay Yuen, Wing Seng Leong, Phaik Yeong Cheah, Nurzalina A K Khan, John N Krieger. University of Sciences, Malaysia, Penang, Malaysia; Hospital Lam Wah Ee, Penang, Malaysia; University of Washington, Seattle, WA

Introduction and Objective: Limited information is available on sexual dysfunction in patients with CP/CPPS. We evaluated the prevalence and characteristics of sexual dysfunction in patients from our primary care referral area and determined the impact of sexual dysfunction on patients’ quality of life (QOL).
Methods: Demographic and clinical data were collected from 298 men who met the National Institutes of Health (NIH) criteria for CP/CPPS. Participants completed the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), International Index of Erectile Function-5 (IIEF) and selected questions from the University of Washington Symptom Score. Sexual dysfunction was classified as either erectile dysfunction (ED, IIEF score <21) or ejaculatory difficulty (EJ, one or more of the following: ejaculatory pain, premature ejaculation (intravaginal ejaculation latency time of <2 minutes and occurring in more than half of sexual encounters, or difficulty reaching ejaculation).
Results: : Participants mean age was 42 years old, their mean duration of symptoms was 2.1 + 2.9 years and their mean NIH-CPSI total score was 21.9 + 7.2. Of the 298 men with CP/CPPS, 216 (73%) had self-reported sexual dysfunction. Among the 216 men with sexual dysfunction: 54 (25%) had ED only, 71 (33%) had EJ only, and 91 (42%) had both ED and EJ. Participants with sexual dysfunction had worse CP/CPPS symptoms (mean NIH-CPSI total score 22.4 + 6.9), with worse QOL (NIH-CPSI QOL subscore 8.5 + 2.4) than participants who did not have sexual dysfunction (mean NIH-CPSI total score 20.4 + 7.8, p=0.027 and mean NIH-CPSI QOL subscore 7.7 + 2.7, p=0.01). Men suffering from both ED and EJ reported the worst CP/CPPS symptoms and the worst QOL.

Conclusions: : Three-quarters of CP/CPPS patients from our primary care referral area suffered from sexual dysfunction. Patients with CP/CPPS associated with sexual dysfunction experienced worse symptoms and worse QOL than other patients with CP/CPPS. Sexual dysfunction contributes significantly to the morbidity experienced by patients with CP/CPPS and might represent an important outcome measure in future treatment studies.


NERVE GROWTH FACTOR LEVELS IN PROSTATIC FLUID OF PATIENTS WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME: ASSOCIATION WITH DIAGNOSIS AND TREATMENT RESPONSE

Toyohiko Watanabe, MD, PhD, Shinya Uehara, MD, Daishi Araki, MD, Koichiro Wada, MD, Miyabi Inoue, MD, PhD, Ayano Ishii, MD, PhD, Reiko Kariyama, PhD, Koichi Monden, MD, PhD, Hiromi Kumon, MD, PhD. Okayama University, Okayama, Japan

Introduction and Objective: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder characterized by pelvic pain and varying degrees of inflammation in expressed prostatic secretions (EPS). Nerve growth factor (NGF) has a key role in the peripheral mediator of several types of painful inflammatory conditions. In search of new biomarker to more clearly define CP/CPPS, we investigated whether NGF in EPS correlated with symptom severity in CP/CPPS.
Methods: All CP/CPPS patients underwent a complete history and physical examination, including the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). EPS samples from 16 patients and 3 asymptomatic controls were collected and frozen. The levels of NGF in EPS were measured by enzyme-linked immunosorbent assay. Patients were asked to complete the questionnaires of NIH-CPSI at baseline and 8 weeks after treatment. Responders for treatment were defined as 25% decrease in total NIH-CPSI score from the baseline values. The levels of NGF in EPS were stratified according to prostatitis category based on NIH classification and compared in individuals before and after treatment.
Results: Based on culture results and the white blood counts in EPS, disease was category IIIa in 7 men, and category IIIb in 9. Mean NGF in EPS of CP/CPPS patients and asymptomatic controls were 7555± 3990 pg/ml and 4374± 825 pg/ml, respectively. In CP/CPPS patients NGF were not significantly different in categories IIIa and IIIb EPS but they were higher than in controls. The levels of NGF in CP/CPPS patients correlated directly with pain severity (P=0.042, r=0.521), but not correlated with urinary symptoms and quality of life. There were no significant differences between pre-treatment and post-treatment levels of NGF in EPS. However, in responders NGF levels decreased significantly after successful treatment (P=0.0165).

Conclusions: NGF might contribute to the pathophysiology of CP/CPPS. The NGF level in EPS can change according to pain severity. Therefore, these results may be used as a new biomarker to evaluate the symptoms of CP/CPPS and the effects of treatment.


A PANEL OF POTENTIAL DIAGNOSTIC BIOMARKERS FOR CHRONIC PROSTATITIS/ CHRONIC PELVIC PAIN SYNDROME

Jordan D Dimitrakov, MD, PhD, Jayoung Kim, PhD, Jaeseop Lee, BA, John Quackenbush, PhD, Weidong Zhou, PhD, Lance Liotta, MD, PhD, Emanuel Petricoin, III, PhD, David Zurakowski, PhD, Michael R Freeman, PhD, J Curtis Nickel, MD. Harvard Medical School, BOSTON, MA; Children's Hospital/ Harvard Medical School, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; George Mason University, Manassas, VA; Queen's University, Kingston, ON, Canada

Introduction and Objective: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frustrating clinical syndrome that lacks pathognomonic biomarkers. The objective of the present study was to examine the pre- and post-prostatic massage (pre-M and post-M) urine of CP/CPPS patients and controls in an attempt to discover potential diagnostic biomarkers for CP/CPPS.
Methods: 30 CP/CPPS patients and 30 healthy asymptomatic age-matched controls were enrolled in the study. Inclusion and exclusion criteria were those recommended by the Chronic Prostatitis Collaborative Research Network (CPCRN). Controls were defined as healthy asymptomatic men drawn from the general population with an NIH-CPSI score of zero, a PSA level of less than 2.5 ng/mL and a negative digital rectal exam for prostate cancer. The study included one clinical visit during which pre-M and post-M urine samples and the NIH-CPSI were collected. All subjects provided written informed consent and the study protocol was approved by the IRB at each institution providing samples. Protein identification was conducted at two independent sites, the Center for Applied Proteomics and Molecular Medicine at George Mason University and the Taplin Mass Spectrometry Center at Harvard Medical School. Urine proteins were separated by SDS-PAGE (4-20%) and proteins were visualized by silver or Coomassie Blue (GelCode Blue) staining. Protein spots were excised from the gel and in-gel digested with trypsin (Promega, Madison, WI) according to published protocols. The significance of the difference in upregulation between CP/CPPS cases and controls was evaluated using the Fisher’s exact test.
Results: We identified a total of 177 unique proteins in the post-M of men with CP/CPPS. EASE analysis using GO terms and KEGG pathways revealed several pathways that were upregulated in the post-M CP/CPPS protein set. The most significant GO terms found (P<0.001) and the most significant KEGG pathways (P < 0.1) are shown in Figure 1. The identity of the top six candidates - PSA, ZA2G, NEP, APN, DPP, and THP - was reconfirmed with Western and dot blot analysis.

Conclusions: The post-M of men with CP/CPPS shows a specific proteomic signature that contains several potential diagnostic biomarkers for CP/CPPS.

Image


INTRAPROSTATIC BOTULINUM TOXIN A INJECTION INHIBITS COX-2 EXPRESSION AND SUPPRESSES PROSTATIC PAIN ON CAPSAICIN INDUCED PROSTATITIS MODEL IN RAT

Yao-Chi Chuang, MD, Naoki Yoshimura, Chou-Cheng Huang, Po-Hui Chiang, Michael B Chancellor, MD. Chang Gung Memorial Hospital Kaohsiung, Taiwan, Kaohsiung Hsien, Taiwan; University of Pittsburgh, Pittsburgh, PA

Introduction and Objective: There is increasing evidence that botulinum toxin A (BoNT-A) might have analgesic and antiinflammatory properties. However, the mechanisms by which BoNT-A alters pain and inflammatory process remain largely unexplored. Cyclooxygenase (COX)-2, a key enzyme in the conversion of arachidonic acid to prostaglandins which are important mediators of inflammation and pain. In this study we investigated the effect of intraprostatic BoNT-A administration on pain reaction and COX-2 expression in the prostate and spinal cord in capsaicin -induced prostatitis model in rats.
Methods: Adult male S.D. rats were injected with vehicle or capsaicin (10 mM, 0.1 cc) into the prostate. The nociceptive effects of capsaicin were evaluated for 30 min by using a behavior approach (eyes movement: scoring 1 for normal opening, scoring 5 for complete closing; locomotion: scoring 1 for normal motion, scoring 5 for complete limpness of hindlimbs or motionless ) and then the prostate and L6 spinal cord was removed for histology and COX-2 expression by using western blotting or immunostaining. A second set of animals were injected with BoNT-A (5-20U) (Allergan, Irvine, CA) into the prostates 1 week prior to intraprostatic injection of capsaicin.
Results: Capsaicin induced increase of painful behavior, inflammatory cells accumulation and COX- 2 protein expression in the prostate. Increased COX-2 immunostaining was detected in the ventral horn of L6 spinal cord and prostate glandular cells as well as interstitial inflammatory cells. BoNT-A one week pre-treatment decreased inflammatory cells accumulation, COX-2 expression, and prostatic pain.

Data presented as means ± S. E.
N=6, for each group

Conclusions: Intraprostatic capsaicin injection activates prostatic afferent nerves and spinal motor neurons and induces prostatic pain. BoNT-A pretreatment could inhibit the capsaicin induced COX-2 expression, inflammatory change of prostate and reduce prostate pain. BoNT-A may be the potential drug to treat nonbacterial prostatitis in human.


INCIDENCE AND SIGNIFICANCE OF PROSTATIC STONES IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME

Daniel A Shoskes, MD, Chun-Te Lee, MD, Donel Murphy, RN, John C Kefer, MD, PhD, Hadley M Wood, MD. Cleveland Clinic, Cleveland, OH

Introduction and Objective: Prostatic calcification is common in asymptomatic elderly men however young men with chronic pelvic pain syndrome (CPPS) often have significantly calcified prostates, implicated in symptoms, inflammation and infections. We wished to study the incidence of prostatic calcification in men with CPPS and correlate with other disease features.
Methods: Between July 05 and August 06, 130 new patients at our prostatitis clinic were diagnosed with CPPS. Forty seven had complete evaluations including a transrectal ultrasound (TRUS). Presence of prostatic calcification was correlated with symptoms (NIH chronic prostatitis symptom score (CPSI)), physical exam and cultures. Parametric continuous variables were compared with the student t test, nonparametric variables by the Wilcoxon Mann Whitney test and category variable by the Chi squared test.
Results: Men who underwent TRUS had identical symptoms scores to those who didn't but were older (46.1 to 41.6 years, p=0.02) and had a longer symptom duration (median 60 months vs 12 months, p=0.0001). Twenty two of the 47 men had significant calcification on TRUS (47%). There was no differences in symptoms between men with and without calcification, including total CPSI (23.7 vs 23.9), all subdomains, and incidence of urinary frequency, ejaculatory pain or erectile dysfunction. Men with calcification had significantly longer symptom duration (median 84 vs 27 months, p=0.05) but similar age (49 vs 45 year p=0.21) and prostate size (21.7 cc both groups). Men with calcification were much less likely to have pelvic floor tenderness (50% vs 85%, p=0.03) but were more likely to have positive prostate fluid cultures for Gram positive bacteria or uropathogens (p=0.05) and had a higher median WBC count in the prostatic fluid (3.5 vs 0 WBC per high power field, p=0.058)

Conclusions: Prostatic calcification is common in men with symptomatic CPPS and is associated with greater prostate inflammation, bacterial colonization and symptom duration. Pelvic floor spasm is more commonly seen in CPPS patients without calcification and may point to a separate etiology. This may be an important parameter to stratify within clinical trials, particularly those for antimicrobial or anti-inflammatory therapy.



EVALUATION OF INFLAMMATION IN AUTOPSIED PROSTATES: IS PROSTATITIS MORE ASSOCIATED WITH BPH OR CANCER?

Nicolas B Delongchamps, MD, Vishal Chandan, MD, Richard Jones, PhD, Gregory Threatte, MD, Mary Jumbelic, MD, Gustavo de la Roza, MD, Vincent Ravery, MD, Gabriel P Haas, MD. SUNY Upstate medical University, Syracuse, NY; Bichat-Claude Bernard hospital, Paris, France

Introduction and Objective: Recent studies identified some common molecular pathways in the development of inflammation and prostate cancer (PCa). Moreover, inflammation has been associated with PCa and benign prostatic hyperplasia (BPH) in Radical Prostatectomy specimens. However, the role of inflammation in PCa development remains unclear. We evaluated the association between inflammation, BPH and Pca in autopsied prostates.
Methods: We analysed prospectively 167 autopsied prostates from men deceased with no prior history of PCa. Pathological analysis identified each focus of cancer, BPH nodules and areas of stromal and/or periglandular inflammation. Any tumor focus or BPH nodule involved directly with inflammation was recorded. We distinguished chronic inflammation (CI) versus acute inflammation (AI), based on the predominant presence of lymphocytes versus neutrophils infiltrates. The association between the prevalence of PCa, BPH, and chronic and acute inflammation was statistically assessed.
Results: Pathological evaluation identified inflammatory infiltrates in 113 (68%) glands. Of them, 88 were involved with CI, 6 with AI, and 19 with both. Inflammatory infiltrates were located in the peripheral zone alone in 6 cases (5%), in the transitional zone alone in 37 (33%), and in both in 70 (62%). Ninety-three glands (56%) were involved with BPH and 49 (29%) with PCa. Among them, 27 were involved with both BPH and PCa. 75% (70/93) of the glands harboring BPH were also involved with CI, as compared to only 50% (37/74) of the glands without BPH (p<0.01). Comparatively, the glands with and without any evidence of cancer were similarly involved with CI (55% versus 58%, p>0.1). Among the 27 glands involved with both PCa and BPH, 18 contained areas of CI. Of these cases, CI was directly involving only the BPH nodules in 11, only the cancer foci in 1, both the BPH nodules and the cancer foci in 3, and neither of them in 1, respectively (p=0.006). AI was not associated with either BPH or PCa.

Conclusions: CI is a common finding in autopsied prostates. It does not appear to be associated with PCa prevalence, but with the presence of BPH. In the prostate glands involved with both cancer and BPH, CI was spacially associated with BPH but not with cancer.



THE RELATIONSHIP BETWEEN PROSTATE INFLAMMATION AND LOWER URINARY TRACT SYMPTOMS: EXAMINATION OF BASELINE DATA FROM THE REDUCE TRIAL

J Curtis Nickel, MD, Claus G Roehrborn, MD, Michael P O'Leary, MD, David G Bostwick, MD, MBA, Matthew C Somerville, MS, Roger S Rittmaster, MD. Kingston General Hospital, Kingston, ON, Canada; University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Brigham and Women's Hospital, Boston, MA; Bostwick Laboratories, Glen Allen, VA; GlaxoSmithKline, Research Triangle Park, NC

Introduction and Objective: The ongoing REDUCE trial is a 4-year, phase III, placebo-controlled study to determine if daily dutasteride 0.5 mg reduces the risk of biopsy-detectable prostate cancer. Prior to study entry, all men were biopsied, thus enabling the relationship at baseline between prostate inflammation and lower urinary tract symptoms (LUTS) to be examined.
Methods: Eligible men were 50-75 years old, with serum prostate-specific antigen =2.5 ng/mL and =10 ng/mL (50-60 years) or =3.0 ng/mL and =10 ng/mL (>60 years), and an International Prostate Symptom Score (IPSS) <25 (or <20 if already on alpha-blocker therapy). Acute prostatitis was an exclusion criterion. For a given individual, inflammation was assessed across all cores and the amount of inflammation scored as none (0), mild (1), moderate (2), or marked (3). LUTS was assessed using the IPSS. The relationship between inflammation scores (averaged over all cores) and total IPSS, grouped IPSS (0-3, 4-7, 8-11, 12-15, 16-19, =20), and irritative, obstructive, and nocturia sub-scores was determined using Spearman rank correlations. The contribution of inflammation versus age and body mass index to the overall relationship between inflammation and symptoms was then examined using linear regression analysis.
Results: Statistically significant correlations were found between average chronic inflammation and IPSS variables; however, these were very weak. Both age and average chronic inflammation were significant in the linear regression after adjustment for other covariates; for both variables, higher values were associated with higher IPSS scores.

Conclusions: In the REDUCE population, there is evidence of a relationship between the degree of LUTS and the degree of chronic inflammation. The weakness of this relationship may be due to study entry criteria that selected older men and decreased enrolment of men with a greater degree of inflammation and LUTS. The impact of baseline prostate inflammation on progression of LUTS and/or associated complications will be determined during four-year longitudinal follow-up.



INFLAMMATION DOES NOT INFLUENCE ERECTILE DYSFUNKTION IN PATIENTS WITH CP/CPPS-NIH IIIA AND B

Kersten Wilbrandt, Henning Schneider, MD, Elmar Braehler, Wolfgang Weidner, MD. Justus-Liebig-Universität Giessen, Giessen, Germany; Universitätsklinikum Leipzig, Leipzig, Germany

Introduction and Objective: Erectile dysfunction has a high prevalence in patients with CP/CPPS-NIH III. Beside a number of psychological factors, physical reasons such as diabetes, hyperlipidaemia, hypertension and smoking are causes of erectile dysfunction (ED). The aim of our study was to evaluate questionable differences between men with CP/CPPS-NIH IIIA or IIIB with respect to ED.
Methods: The data of 139 patients, attending to our special prostatitis outpatient department are collected by means of questionnaires, including the NIH-CPSI, the GPSS and the IPSS for symptoms refering to the prostateand the german version of the IIEF for ED. According to our strict criteria (NIH-CPSI, leukocytes in EPS and VB3, four-glass-test, ejaculate analysis including peroxidase positive leucocytes) we classified 35 patients with CP/CPPS-NIH IIIA and 99 with CP/CPPS IIIB. To identify patients with ED we used the erectile function domain of the IIEF. A score of 25 was used to discriminate between patients with or without ED. The t-test for independent samples was used to detect differences between CP/CPPS-NIH IIIA and IIIB in the domain of erectile function (EF).

Results: 134 of 139 men with CP/CPPS completed the IIEF. 35 had CP/CPPS-NIH IIIA, 99 had CP/CPPS NIH IIIB. 63 men (47%) suffered from ED. The t-test for independent samples showed no differences in the IIEF results for both groups (see table) concerning CP/CPPS NIH IIIA and B patients.

Conclusions: The statistical analysis demonstrates the high prevalence of ED in patients with CP/CPPS. Nearly 50% of these patients suffer from ED. The absence of differences in the IIEF between CP/CPPS NIH IIIA and B patients, provides evidence that ED is not depending upon inflammatory reactions of the prostate in these patients.


CHANGES IN SYMPTOMS AND URINARY HB-EGF, EGF, AND ANTIPROLIFERATIVE FACTOR DURING CHRONIC NEUROMODULATION FOR REFRACTORY INTERSTITIAL CYSTITIS

Kenneth M Peters, MD, Richard C Bennett, MD, Ibrahim A Ibrahim, MD, PhD, Kristopher Koch, BS, Chen-Ou Zhang, MD, Susan K Keay, MD, PhD. William Beaumont Hospital, Royal Oak, MI; University of Maryland, Baltimore, MD

Introduction and Objective: Urinary markers (APF activity and HB-EGF levels), voiding frequency, and urgency have been shown to be significantly altered following 5 days of acute percutaneous sacral neuromodulation for refractory interstitial cystitis (IC) (Chai, 2001). The objective of this study was to examine symptom scores and urinary markers during chronic neuromodulation up to 6 months.
Methods: Eleven subjects with refractory IC documented with a cystoscopy and hydrodistension were enrolled in this study. These subjects chose to undergo neuromodulation and agreed to complete voiding diaries, symptom scores, and global response assessment (GRA) along with collection of urine at baseline, 2 weeks post-stim, and 1, 3, and 6 month follow-up. The urine was measured for HB-EGF and EGF by enzyme-linked immunosorbent assay and antiproliferative factor activity by (3)H-thymidine incorporation by primary normal human bladder urothelial cells. Paired t-test was used to analyze results.
Results: 10/11 (91%) subjects had at least a 50% reduction in symptoms during the acute 2-week test and had a permanent implant placed. Three of ten had a pudendal implant placed and 7 of 10 had sacral. 10/11 had APF activity at baseline and in follow-up all 11 demonstrated APF activity. After 2 weeks of stimulation, EGF increased (p<0.007) and no changes were seen in HB-EGF or APF. During the 1, 3, and 6 month follow-up no change was seen in urine markers. Statistical improvements were seen for urinary frequency and voided volume. The majority of subjects reported a moderate or marked improvement on GRA at all time intervals. No differences were seen between those with pudendal vs sacral implants.

Conclusions: Five days of neuromodulation was previously shown to normalize voided volume, frequency, APF and HB-EGF for IC (Chai, 2001). In the current study at 14 days and beyond, there were significant improvements, but not normalization in urinary frequency and voided volume. Only transient changes in APF, EGF and HB-EGF occurred in individual patients. These data suggest that urinary markers for IC do not generally change with chronic neuromodulation.


EVIDENCE FOR CENTRAL HYPEREXITABILITY IN PATIENTS WITH INTERSTITIAL CYSTITIS

Christian O Twiss, MD, Lisa Kilpatrick, PhD, Veronica Triaca, MD, Valerie A Arboleda, BA, Michelle Craske, PhD, Hana Ibrahimovic, BA, Shlomo Raz, MD, Emeran A Mayer, MD, Edward Ornitz, MD, Larissa V Rodriguez, MD, Bruce D Naliboff, PhD. Univeristy of California, Los Angeles, Los Angeles, CA

Introduction and Objective: Pain in interstitial cystitis (IC) appears to have significant central and neuropathic components, as well as involvement of central modulatory pathways including those involving the limbic system. The startle blink reflex (SBR) is a defensive, involuntary eye-blink in response to sudden intense stimuli. This reflex is modulated the amygdala, a component of the limbic system involved in modulation of emotional states and physical sensations. Increases in SBR magnitude represent an objective index of affective response to stimuli, such as threat of pain. To test the hypothesis that IC patients have an upregulation of central pain modulation pathways, we compared the SBRs of healthy controls with that of IC patients.
Methods: SBRs were examined for 6 female IC patients and 19 healthy females under threat and safe periods. During threat periods, subjects would possibly receive aversive electrical stimulation to their bladder region. Each threat period consisted of an early and late phase. If stimulation was to occur, it would occur during the late phase. No stimulation was given during safe periods. SBRs were measured during all phases. Mixed-effects analysis for repeated measures was applied to determine the influence of diagnosis (IC, Control), threat (Danger, Safe) and phase (Early, Late) on the square-root transformed SBRs.

Results: Significant main effects were observed for diagnosis (p=.008), threat (p<.001), and phase, (p<.001) as well as an interaction between all 3 parameters (p=.045). Patients with IC had significantly greater estimated mean SBRs than controls during early and late safe periods (mean+SE SBR 12.4+1.1 vs. 8.5+0.6, p=0.003, and 12.7+1.1 vs. 9.3+0.6, p=0.01, respectively) and during the early danger period (13.9+1.1 vs. 9.7+0.6, p=0.001, respectively). During the late danger period the SBRs of IC patients and controls were similar (15.1+1.1 vs. 14.1+0.6, p=0.46, respectively).

Conclusions: This initial data indicates that IC patients have significantly greater SBRs than controls during baseline and during the non-imminent threat periods of the study. A similar alteration of the startle reflex is observed in humans with anxiety disorders and post-traumatic stress disorder. This is objective evidence IC patients may have upregulation of limbic responses involved in anxiety and stress leading to altered pain perception and abnormal modulation of afferent pain signals. Further investigation is needed to determine if this upregulation is a causative agent or a secondary effect of the IC disease process.


A CASE-CONTROL STUDY OF MEDICAL CO-MORBIDITIES IN WOMEN WITH INTERSTITIAL CYSTITIS

J Quentin Clemens, MD, Richard T Meenan, PhD, Maureen C O'Keeffe Rosetti, MS, Teresa M Kimes, MS, Elizabeth A Calhoun, PhD. Northwestern University, Chicago, IL; Kaiser Permanente Northwest, Portland, OR; University of Illinois at Chicago, Chicago, IL

Introduction and Objective: Previous studies to assess epidemiologic risk factors for interstitial cystitis (IC) have utilized patient self-reported data and historical controls. Such studies are subject to recall bias. The aim of this study was to utilize coded physician diagnoses to compare IC patients with matched controls in order to identify and accurately quantify risk factors that are associated with IC.
Methods: A computer search of the Kaiser Permanente Northwest (Portland, OR) administrative database was performed for the interval 1/98 to 5/03. Women with a medical record diagnosis of ‘interstitial cystitis’ (ICD-9 code 595.1) (n=239) were each matched with three controls by age and duration in the health plan. The medical diagnoses (using three-digit ICD-9 codes) assigned to each of these individuals were obtained, and the frequency of these diagnoses were compared between cases and controls. In order to identify clinical relevant differences, only p-values <0.005 were considered significant.

Results: Medical conditions associated with an IC diagnosis are presented in the Table.

Conclusions: Compared with controls, women with IC were more likely to be assigned 23 specific ICD-9 diagnoses. These diagnoses involve multiple organ systems. The high odds ratios indicate very large, clinically meaningful differences between the groups. Many of these conditions (e.g., fibromyalgia, irritable bowel syndrome, back pain, gastritis) appear to indicate the presence of other unexplained physical symptoms. IC was associated with a history of diagnosed child abuse, although the majority of IC patients (96%) did not have evidence of this diagnosis.

Image



PRULIFLOXACIN VERSUS LEVOFLOXACIN IN THE TREATMENT OF CHRONIC BACTERIAL PROSTATITIS: A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND TRIAL

Gianluca Giannarini, MD, Andrea Mogorovich, MD, Girolamo Morelli, MD, Maurizio De Maria, MD, Francesca Manassero, MD, Cesare Selli, MD. University of Pisa, Pisa, Italy

Introduction and Objective: Oral fluoroquinolones are the first choice of treatment for men with chronic bacterial prostatitis (CBP). Since the various available drugs exhibit different pharmacokinetic and pharmacodynamic properties and different microbial resistance profiles, the aim of our study was to compare the efficacy and safety of Prulifloxacin (PF), a new broad-spectrum fluoroquinolone with long half-life and high urinary concentrations, with those of Levofloxacin (LF) in the treatment of men with CBP
Methods: Ninety-six consecutive men with clinical diagnosis of CBP and evidence of infection were randomized to receive a 4-week oral course of either PF 600 mg or LF 500 mg once daily. All subjects were evaluated with the Meares-Stamey test and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at baseline and 1 week after therapy completion. Patients with microbiological eradication were evaluated for recurrent infection with the Meares-Stamey test 6 months after therapy completion. The primary end point was microbiologic eradication. The secondary end points were clinical efficacy, assessed by reduction in the NIH-CPSI, recurrent infection rate at 6 months, and safety
Results: The microbiologic eradication rate was 72.73% for PF and 71.11% for LF (p=0.86). The clinical success rate was not significantly different, since the reduction in the NIH-CPSI score from study entry to study completion was 10.75 (from 17.22 to 6.47) for PF and 10.73 (from 17.33 to 6.6) for LF (p=0.98). After 2 weeks of treatment there was a trend toward a greater reduction of the symptom score for PF (5.29) than for LF (4.80) (p=0.1005). At 6 months a lower proportion of patients on PF (n=5) had a positive Meares-Stamey test compared to LF (n=11), the difference being only marginally significant (p=0.1008). Safety was comparable in the two groups, with a rate of adverse events of 18.18% for PF and 22.22% for LF (p=0.79)

Conclusions: Our results suggest that oral PF 600 mg once daily is at least as effective and safe as oral LF 500 mg once daily administered for 4 weeks in the treatment of men with CBP. Therapy with both drugs enables the great majority of patients to achieve microbiological eradication of the infecting strain and to significantly improve the symptom complex. Recent studies have shown that the active metabolite of PF has a greater tendency than the other fluoroquinolones to penetrate within bacteria and phagocytes, and this is reflected by a trend to an earlier resolution of subjective symptoms
HAS THIS SITE HELPED YOU?
Say Thanks! by making a small donation
PayPal link at end of page ↓
Please fill out your signature, click here for how to do it
Post Reply