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Prevalence of prostatitis-like symptoms in a population-based study: use of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI).
Joe Downey, J. Curtis Nickel, Duncan Hunter, Janet Clark Kingston, ON, Canada

Introduction and Objectives The NIH-CPSI was employed to determine the prevalence of prostatitis-like symptoms among men at risk (20-74) in a community based study.

Methods: The study was a cross-sectional postal survey of randomly selected men aged 20-74 years in L&A County (a large rural area, one major town and a suburban area with a stable population of men, representative of Canadian demographics) . The questionnaire collected informaton on two domains of chronic prostatitis identified in the NIH-CPSI; pain (location, severity, fequency) and voiding function (irritative, obstructive) as well as demographic, quality of life, general health and health seeking behaviour. The self-reported pain score was used to identify prostatitis-like symptoms (most discriminating domain). Based on analysis of the NIH-CPSI final validation study comparing prostatitis patients to normal controls and BPH patients, the two questions most specific for prostatitis (perineal and/or ejaculatory pain/discomfort)and a total pain score (0-21) of 4 was employed to identify men with significant prostatitis-like symptoms. Demographic questions (age, education) were adapted from the 1996 Census of Canada. Questions on length of symptoms and advice-seeking behaviour were taken from published questions used in BPH population-based studies.

Results 868 men completed the survey. 9.7% (84) of the men were identified as having chronic prostatitis-like symptoms (mean NIH-CPSI pain score; 9.1+/-0.3). Average age (years) of prostatitis population was 50 compared to 52 for men without prostatitis-like symptoms. Prevalence was 11.5% in men <50 years and 8.5% in men 50 years. NIH voiding score (0-10) was 4.1+/-0.5 (compared to 1.5+/-0.1 for normals) in men <50 and 4.7+/-0.4 (compared to 1.9+/-0.1 for normals) in men 50 years. 60% of the prostatitis group sought medical help for their symptoms. Demographics, frequency distributions, sampling and non-response bias will be presented.

ConclusionsThis community based study employing the new prostatitis symptom index confirms that chronic prostatitis-like symptoms in men at risk are very common (10%).
Supported by: Janssen-Ortho, NIH/NIDDK

Akito Terai, Satoshi Ishitoya, Kenji Mitsumori, Osamu Ogawa Kyoto, Japan

Introduction and Objectives Escherichia coli is the predominant pathogen in both acute prostatitis and female acute pyelonephritis. Both strains possess similar virulence characteristics, including a high incidence of P fimbria and a-hemolysin. However, the route of infection in acute prostatitis is generally unknown, except for several case reports showing transmission of urinary tract infection between sex partners. This study was conducted to test our hypothesis of ascending urethral infection in acute prostatitis using molecular epidemiologic methods.

Methods: A total of 900 E. coli isolates from the urine and rectal swab of 9 men with acute prostatitis were examined. The clonality of the urinary and fecal isolates was evaluated by multiplex PCR genotyping of 6 urovirulence determinants and pulsed-field gel electrophoresis. Furthermore, the rectal swab isolates were obtained from a patient and asymptomatic sex partner (wife), both at diagnosis and after 4 weeks of antimicrobial treatment.

Results In 7 of 9 cases, the urinary isolates possessed the P fimbrial gene. The E. coli strains causing acute prostatitis were present in the rectal swab in 6 of 9 patients. In 2 cases, all or most of the rectal swab isolates showed the identical clonality to that of the urinary isolates, while in 4 men, the rectal swab isolates with the same clonality occupied only a minor portion (ranging from 2 to 8 %) of the rectal flora. In a case, all E. coli isolates from the urine of the patient and the rectal swab of both the patient and his sex partner possessed the identical clonality.

ConclusionsThe clonal identity of the urinary and fecal strains in the majority of patients with acute prostatitis, in combination with similar urovirulence traits between prostatitis and pyelonephritis strains, supports our hypothesis that the ascending urethral infection seems to be the most reasonable pathogenetic mechanism in at least some part of acute prostatitis. Furthermore, our observation could also be explained by sexual acquisition or sharing of E. coli strains among the family members.
Supported by: None

Gregory T. MacLennan, R. N. Rao, Allen D. Seftel, Martin I. Resnick Cleveland, OH

Introduction and Objectives The relationship between prostatitis and benign prostatic hyperplasia (BPH) and prostate cancer (PCa) was examined, based on the hypothesis that there may be an association between prostatitis and these other entities, and that this association may involve upregulation of endothelial or inducible nitric oxide synthase (eNOS,iNOS), P53,BCL-2, and nitrotyrosine (NTS).

Methods: Fifty whole mount prostatectomy specimens were examined for the presence and distribution of a chronic inflammatory infiltrate. H & E staining was carried out in all cases. Immunostaining for eNOS,iNOs, p53,BCL-2 and NTS was carried out in 10 cases. The site of inflammation was determined along with any relationship to BPH or PCa.

Results Inflammation was seen in all 50 cases, with peripheral zone inflammation in 95% of specimens (95%), and transition zone inflammation in 88% of cases, without a predilection for either zone. In the cases with transition zone inflammation, the infiltrate was noted within and around BPH. Thus, inflammation involving BPH nodules affected the nodule proper and the adjacent non-adenomatous tissue. Inflammatory infiltrate was associated with PCa in only 57.5% of cases. In these cases, there was no association between the inflammation and the grade of PCa. eNOs, iNOS,p53 and NTS staining of stroma and acini in areas of BPH, prostatitis and PCa was weak, diffuse and indiscriminate. Widespread basal cell staining with BCL-2 was noted, as well as focal staining of luminal secretory cells, in all benign areas, in all 10 cases examined. BCL-2 staining was not seen in luminal cells of prostate cancer acini in these 10 cases. BCL-2 staining was intensified in the basal and luminal cells of benign glands within areas of prostatitis in all 10 cases examined and in benign glands surrounded by malignant acini in 3 of 10 cases.

ConclusionsThese data suggest that while chronic prostatitis is associated with both BPH and prostate cancer, it has a greater tendency to be associated with BPH, without zonal prediliction. When associated with prostate cancer, there was no correlation between the grade of PCa and the inflammation. BCL-2 was prominently expressed in areas of prostatitis. The role of BCL-2 in prostatitis remains to be elucidated.
Supported by: Arthur Sullivan Foundation

Michael R. Ruggieri, Sr., Alan S. Braverman, Sharon Filer-Marten, John P. Gaughan, Michel A. Pontari, & the NIH Chronic prostatitis Clinical Research Network Philadelphia, PA

Introduction and Objectives Semen was analysed for biochemical markers of the various glands that form the semen in nonbacterial prostatitis patients and normal volunteers to provide insight into which glands may be affected in individual patients.

Methods: Semen was obtained from normal volunteers (N=25) and nonbacterial prostatitis patients (N=49) with discomfort or pain in the pelvic region for at least 3 months during the previous 6 months and no history of other causes of pelvic pain. Patients were further separated into type IIIa (N-14) and type IIIb (N=35) based on >10 WBC/HPF in EPS, VB3 or semen. Seminal plasma was stored in aliquots at -80C and assayed for the following: protein, PSA, Zn, Citrate, a-glucosidase, fructose, 6-keto-prostaglandin F1a, prostaglandin E2, prostaglandin F2a, TNFa, IL-1a, IL-1b,IL-6, IL-8 and nitric oxide breakdown products (NO2+NO3).

Results The volume of semen was significantly greater in normal volunteers (2.9 ±0.3 ml) than either group of prostatitis patients (1.7±0.3; 1.9±0.2 ml). There was no statistically significant difference between patients and normal volunteers for the prostate markers (citrate, Zn and PSA), the seminal vesicle markers (fructose, 6-keto-PgF1a, PgF2a and PgE2) or the epididymis marker (a-glucosidase). Both IL-1b and IL-8 were significantly higher in the type IIIa patients with leukocytes (112±62; 5,305±1,092 pg/ml) than type IIIb (29±9; 2,723±363 pg/ml) or normal volunteers (26±11; 2,199±286 pg/ml) but there was no statistically significant difference in the other inflammation markers (TNFa, IL1a, IL-6 and nitric oxide products).

ConclusionsThe lower semen volume in prostatitis patients is consistent with obstruction of one of the glands that forms the semen. The similarity in seminal composition of glandular markers between patients and volunteers suggests compensatory mechanisms in prostatitis patients. The higher cytokines in Type IIIa but not IIIb patients is likely responsible for the increased leukocytes in EPS, VB3 or semen in this subgroup of patients.
Supported by: PHS RO1DK53734

Mary McNaughton-Collins, Michael P. O'Leary, Mark S. Litwin, Elizabeth A. Calhoun, John W. Kusek, Jill Santanna, J. Richard Landis, the Chronic prostatitis Collaborative Research Network Boston, MA; Los Angeles, CA; Chicago, IL; Bethesda, MD; Philadelphia, PA

Introduction and Objectives Health-related quality of life(QOL)was measured in men in the Chronic prostatitis Cohort (CPC) Study, using the Medical Outcomes Short-Form 12 (SF-12) and the NIH Chronic prostatitis Symptom Index (CPSI). Scores for the CPC group were compared with those for the general U.S. male population and patients with other chronic conditions (congestive heart failure (CHF), diabetes (DM).

Methods: Data from the SF-12 and the CPSI were analyzed for the first 218 enrollees in the CPC. The CPSI score was classified as mild (0-9), moderate (10-18) and severe (19-31). Standardized QOL measures for the SF-12 physical component summary (PCS) and mental component summary (MCS) were calculated; means and standard deviations are reported (Table).

Results CPC subjects' MCS scores were worse than those for the most severe subgroups of DM and CHF. Decreasing scores were seen in both domains with increasing chronic prostatitis symptom severity (p<0.01).
Subgroup PCS MCS
General U.S. Male Pop 51.2 50.7
Most severe DM 41.0 51.0
Most severe CHF 36.3 47.6
Overall CPC Study (n=218) 46.3 ± 9.8 43.6 ± 10.0
Mild symptoms (n=36) 49.5 ± 9.1 48.2 ± 9.5
Moderate symptoms (n=133) 47.0 ± 9.5 44.3 ± 9.6
Severe symptoms (n=49) 42.3 ± 9.9 38.5 ± 9.7

ConclusionsWhile the physical domain of QOL is impaired in men with chronic prostatitis, the mental health impact is more profound. Optimal care of these patients requires particular attention to QOL issues.
Supported by: DK53752

Jordan D. Dimitrakov Plovdiv, Bulgaria

Introduction and Objectives Recent evidence suggests that nerve growth factor (NGF) plays a key role in the development of inflammatory pain in animal models of hyperalgesia and in man. NGF may lead to hyperalgesia by directly sensitizing nociceptors, increasing levels of substance P and calcitonin-gene related peptide and the local release of histamine.

Methods: We measured the levels of NGF in post-prostatic massage urine samples of 100 CPPS (Class III-B) patients (mean age 35.4) with negative EPS and post-prostatic massage urine cultures diagnosed using the NIH CHRONIC prostatitis SYMPTOM INDEX (NIH-CPSI) and in the samples of 100 asymptomatic patients (control group). NGF-like immunoreactivity was measured with a fluorometric ELISA using recombinant human NGF (rhNGF, Genentech, Inc) as a standard. The levels of interleukin-1 and tumor necrosis factor-alpha were also measured using ELISA.

Results The levels of NGF were significantly higher in patients with chronic non-bacterial prostatitis (10±3.4 pg/mL) as compared with those of the controls (3.2±1.4 pg/mL). The difference between the two groups was statistically significant (p<0.001). The levels of interleukin-1 and tumor necrosis factor-alpha were also significantly higher in the post-prostatic massage urine of patients with chronic nonbacterial prostatitis with pain as a major symptom as compared with the levels of the controls (p<0.001).

ConclusionsOur findings suggest that interleukin-1 and tumor necrosis factor-alpha can upregulate the expression of NGF in tissue inflammation and nerve injury in chronic prostatitis patients. anti-NGF treatment, using the synthetic human protein trkA-IgG, which sequesters endogenous NGF, may be rational and effective in the management of intractable pain in this group of patients.
Supported by: None

Daniel A. Shoskes, Asha Shahed Torrance, CA

Introduction and Objectives Despite negative cultures for known uropathogens, some men with chronic pelvic pain syndrome respond well to antibiotic therapy. We have shown that a subset of men with NIH category III prostatitis have evidence for bacteria in their prostatic fluid (EPS) by 16S rRNA techniques. In this study we correlate presence of bacterial signal with clinical response to antimicrobial therapy

Methods: EPS and VB1 urine from 47 men with CPPS was analyzed by RT-PCR for bacterial signal using universal primers for 16S rRNA. Signal was positive if found only in the EPS sample or if at least 10x stronger in EPS than VB1. Patients underwent localizing bacterial cultures of VB1, VB2 and EPS. All men were treated with antibiotic therapy +/- prostatic massage for a minimum of 3 weeks.

Results By EPS microscopy, 33 patients were category IIIa (nonbacterial prostatitis) and 14 were category IIIb (prostatodynia). Seventeen of the category IIIa patients had positive localizing cultures for Gram positive bacteria. A total of 23 EPS specimens were positive for bacterial signal: 14/17 of culture positive patients, 7/16 of the remaining IIIa patients and 2/14 of the IIIb patients. Antibiotics were chosen by culture sensitivities (if known) or empirically (if culture negative). No patients with negative bacterial signal improved with antibiotic therapy (negative predictive value 100%). Thirteen patients with positive bacterial signal improved with antibiotic therapy (positive predictive value 57%). Of the 24 patients with negative signal, 15 improved with non-antibiotic therapy, as did 4 patients with positive signal who failed antibiotic therapy (overall improvement in group of 68%)

ConclusionsIn men with category III chronic prostatitis, bacterial signal by 16S rRNA RT-PCR can help predict response to antimicrobial therapy. Men with negative signal can avoid the expense and side effects of unnecessary prolonged courses of antibiotics and be directed to more effective anti-inflammatory or neuromuscular therapies.
Supported by: NIH

In R. Cho, Thomas S. Keener, Hanh V. Nghiem, John N. Krieger Seoul, Korea; Seattle, WA; Ann Arbor, MI

Introduction and Objectives To determine if chronic prostatitis/chronic pelvic pain syndrome (CPPS) is associated with abnormal prostate blood flow.

Methods: We used color Doppler ultrasonography to examine 133 patients (53 with inflammation and 80 without inflammation) and 22 healthy controls. Images were recorded and scored using standardized criteria to characterize the degree and distribution of prostatic vascularity.

Results Flow was observed to the entire prostatic capsule in 77% of patients but only 18% of controls (p < 0.0001). Parenchymal flow was evaluated using several criteria. On a two-point scale, 74% of patients were classified as grade 2 compared to 27% of controls (p < 0.0001). Similar findings were noted on a Doppler spot scale (47% of patients had grade 2 flow compared to 14% of controls, p < 0.004), and patients also had more parenchymal Doppler spots (p < 0.01). Diffuse blood flow throughout the prostatic parenchyma was observed in 63% of patients compared to 36% of controls (p < 0.03). There was no significant difference in the amount or distribution of blood flow in patients with and without inflammation.

ConclusionsChronic prostatitis/CPPS was associated with increased blood flow to the prostatic capsule and diffusely throughout the prostatic parenchyma. Despite technical limitations, color Doppler ultrasonography may provide an objective tool to document prostate blood flow abnormalities in patients with chronic prostatitis/CPPS.
Supported by: NIH grant R01 DK38955

Shingo Yamamoto, Akito Terai, Masayuki Nakano, Kazuyo Yuri, Katsuhisa Nakata, G. Balakrish Nair, Hisao Kurazono, Osamu Ogawa Hamamatsu, Shizuoka; Kyoto; Tsukuba, Ibaraki; Ikeda, Osaka, Japan; Beliaghata, Calcutta, India; Okayama, Okayama, Japan

Introduction and Objectives Recently, a putative virulence island commonly found in uropathogenic E. coli (UPEC) strains has been reported. The island consists of an amino acid protein designated as uropathogenic specific protein (Usp) and small open reading frames (ORFs; orfU1-3). In the present study, we assessed whether the virulence island genes play important roles in pathogenesis of urinary tract infection (UTI).

Methods: A total of 427 E. coli strains consisting of 194, 76 and 107 isolates from the urine of subjects suffering from cystitis, pyelonephritis and prostatitis, respectively and 50 isolates from the feces of healthy individuals were examined for genotypes and serotypes. In addition, several E. coli strains possessing the the usp and/or orfU1-3 genes were constructed for assessment in an experimental pyelonephritis model in mice.

Results The usp gene was found to be significantly more often associated with UPEC strains (79.4 % from cystitis, 93.4 % from pyelonephritis and 88.8 % from prostatitis) than with fecal E. coli strains from healthy individuals (24.0 %). Further, the usp gene was frequently associated with all common serotypes of UPEC (71.7 to 100 %). In the UTI model challenge, the vector possessing the usp gene significantly enhanced infectibity of the E. coli host cell whereas the vector possessing the 3 small proteins at the downstream of the usp gene failed to exhibit the effect.

ConclusionsThe results clearly show that the usp gene contributes to acquisition of UTI and could be a putative major uropathogenic determinant.
Supported by: Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan

Michael E. Franks, Naoki Yoshimura, Teruhiko Yokoyama, William F. Goins, Matthew O. Fraser, William C. de Groat, Joseph C. Glorioso, Michael B. Chancellor Pittsburgh, PA

Introduction and Objectives Chronic urogenital pain syndromes such as interstitial cystitis and chronic prostatitis have been major challenges to all urologists to understand and treat. We propose a revolutionary concept in the treatment of chronic urogenital pain that would be independent of pathophysiology. We hypothesize that the use of gene transfer to produce targeted and localized expression of enkephalin, an endogeneous opioid protein with analgesic properties, can treat urogenital pain.

Methods: Herpes simplex virus (HSV) vectors (1x106-8 pfu) containing LacZ or an opioid precursor protein, human preproenkephalin (PPE) gene were injected into the bladder wall, testis, and prostate of adult Sprague Dawley rats. One to two weeks after HSV-LacZ injection, LacZ staining was performed in bladder tissue and and L6-S1 dorsal root ganglia (DRG). Immunohistochemistry using anti-met-enkephalin polyclonal antibody to determine enkephalin expression was also performed in HSV-PPE injected animals. Cystometric studies using saline and saline containing the C-fiber afferent neurotoxin capsaicin (15-30 mM) were then conducted to compare the bladder intercontraction interval (ICI) of sham (n=9) and HSV-PPE injected animals (n=9) under urethane anesthesia.

Results Following HSV-LacZ vector injection into the bladder wall, positive LacZ staining was observed in the bladder and L6-S1 DRG. Positive staining for enkephalin was also seen in neuronal and nonneuronal tissues at the injection site following HSV-PPE injection into the bladder, testis and prostate. In cystometry, mean ICI was significantly reduced in sham rats by instillation of capsaicin, which stimulates nociceptive afferents, by 45% (3.8 to 2.1 min, p=0.007), while no significant change was noted in ICI of HSV-PPE treated rats after capsaicin (21%, 2.9 to 2.3 min).

ConclusionsNeogenes carried by HSV vectors injected into the urogenital organs can express the genes locally in traget organs and also transfer the genes to afferent nerves. The technique of HSV-PPE gene therapy may be applicable to the treatments of various types of urogenital pain syndromes, including interstitial cystitis, chronic prostatitis, prostadynia, and chronic orchalgia.
Supported by: None

Dan Leibovici, Amnon Zisman, Zehava Chen Levi, Yoram Itshak Siegel, Arie Lindner Zerifin, Israel

Introduction and Objectives Granulomatous prostatitis has been previousley reported following intravesical treatment with Bacillus Clamette-Guerin (BCG). We determined the influence of intravesical BCG on serum Prostate Specific Antigen (PSA).

Methods: 36 consecutive male patients suffering of bladder cancer and candidates for intravesical BCG therapy were included. Patients with an established diagnosis of prostate cancer, or treated with androgen ablation or 5- a reductase inhibitors, were not included. Patients were submitted to a 6 weekly course of intravesical BCG instillations. Prior to any instillation, blood samples were drawn for PSA, and any result above 4 ng/ml was considered clinically significant. The treshold of PSA elevation was defined as a minimal difference of 0.3 ng/ml between the maximal PSA level during treatment and the initial PSA result before treatment. Digital rectal examinations were done prior to instillations 1,3 and 6, and any new firm prostatic nodules were noted. Patients with 2 consecutive PSA results above 4 ng/ml or in whom prostatic nodules were found were offered prostate biopsies.

Results Intravesical BCG was associated with PSA elevations in 30 of 36 patients (80%). Clinically significant PSA elevation (above 4 ng/ml) was observed in 15 patients (41.5%). The average PSA value increased from a baseline of 2.31 ng/ml before treatment to 6.97 ng/ml during treatment with BCG (ranges 5.1 - 21.5 ng/ml, p<0.01). PSA declined to the normal range following termination of the BCG course. Average PSA levels were 4.88 ng/ml and 2.7 ng/ml at 6 weeks and 3 months after treatment, respectively. New firm prostatic nodules were noted in 4 patients during treatment, 3 of them had also significant PSA elevations. Prostate biopsies were performed in 9 patients and revealed caseating granulomatous prostatitis in 4, non-specific inflammation in 2 and benign prostatic hyperplasia in 3. No biopsy demonstrated prostate cancer.

ConclusionsIntravesical BCG is associated with a significant PSA elevation in 40% of patients, and is self limitted. Therefore, mandatory prostate biopsies are not justified in this patient population and follow-up with PSA is recommended.
Supported by: Ezvonot Fund issued by the Ministry of Health and the Ministry of Justice in Israel

Georg Bartsch, Wolfgang Horninger, Hermann Rogatsch, Peter B. Snow, Jeffrey Brandt Innsbruck, Austria; Colorado Springs, CO

Introduction and Objectives The decision whether or not to perform a prostate biopsy is often a difficult one. It is commonly based on absolute cut-off values for DRE, total PSA, and more recently on free PSA. Though single testing is of diagnostic value, accurate determination of the probability of having a positive biopsy by mathematical evaluation of all clinical data (e.g. an artificial neural network) would be desirable.

Methods: Clinical, pathological and serum analysis data were available from 3474 men who participated in prostate cancer screening and underwent prostate biopsy because of abnormal DRE findings and/or elevated PSA levels (>4.0 ng/ml). We have developed and validated an ANN combining age, race, DRE status, PSA, free PSA and TRUS parameters (prostate volume, PSA density, transition zone volume, transition zone density). To investigate the accuracy of the model the study group was divided into a learning set (75%) and a validation set (25%).

Results The neural network was found to be 150% - 200% more specific than the standard variable cutpoints; specificity for the detection of cancer by neural networks or free-PSA cutoff is not affected by the presence or absence of BPH and prostatitis. When the entire population was divided into men with PSA > 4 and PSA 4, ANN analysis yielded a 150% - 300% difference in specificity between the lower and higher PSA groups, which indicates a much lower predictive ability with lower PSA values. At high sensitivity (95%), use of TRUS parameters in the neural network increased the specificity by 25% - 50%.

ConclusionsWhen presetting sensitivity to 95%, neural networks yield a 150% - 200% increase in specificity over standard single variable cutpoints for the diagnosis of prostate cancer. The presence of BPH and prostatitis in a screening population does not appear to affect the accuracy of neural network based prostate cancer diagnosis. With PSA levels below 4 ng/ml, the specificity for predicting the presence of prostate cancer is significantly lower.
Supported by: None

Nirit Rosenblum, Sam Chan, Pablo L. Torre, Herbert Lepor New York, NY

Introduction and Objectives Prostate specific antigen (PSA) level elevations can be caused by prostate cancer, benign prostatic hyperplasia (BPH), inflammatory conditions of the prostate, urinary tract infections and urinary retention. The effect of an antibiotic on PSA levels has not been examined in a randomized study. The present randomized study prospectively evaluates the effect of Ciprofloxacin on serum PSA level in men with elevated PSA (> 4.0 ng/ml) prior to prostate needle biopsy.

Methods: Fifty-three consecutive men with elevated PSA levels (> 4.0 ng/ml) and without a pre-existing diagnosis of prostate cancer were randomized to either a two-day or a two week course of Ciprofloxacin (500 mg BID) immediately prior to prostate needle biopsy. The group receiving two days of Ciprofloxacin, our standard antibiotic prophylaxis regimen prior to prostate needle biopsy, served as the control group. Upon completion of the assigned antibiotic regimen, a serum PSA level was obtained. All men underwent a biopsy independent of the response to Ciprofloxacin.

Results The mean age of men receiving a two-day and a two-week course of Ciprofloxacin was 65.4 and 67.1 years, respectively (p=0.24). The mean baseline PSA level for the two-day and two-week groups was 7.87 and 8.12 ng/ml, respectively (p=0.44). The percentage of men with PSA between 4.0 and 10.0 ng/ml in the two-day and two-week groups was 84% and 82%, respectively. The mean PSA change exhibited following the two-day and two-week Ciprofloxacin course was -0.02 and +0.18, respectively (p=0.42). The percentage of men whose biopsy diagnosis was cancer, prostatic intraepithelial neoplasia (PIN), prostatitis and benign tissue were 48%, 24%, 4% and 24%, respectively in the two-day group compared to 57%, 21%, 4% and 18%, respectively in the two-week group. The mean change in PSA level for those men diagnosed with prostate cancer was +1.19 in the two-day group and +1.17 in the two-week group. For men with PIN, prostatitis and BPH, the decrease in serum PSA levels were comparable following both a courses of Ciprofloxacin.

ConclusionsThis study demonstrates that Ciprofloxacin does not significantly affect serum PSA levels in men presenting with an elevated PSA level. The changes in PSA observed in non-controlled trials following antibiotic administration are due to the variability of PSA measurements rather than a drug effect.
Supported by: None

Jeffrey E. Wong, Willie Underwood, Lauri J. Miller, Sandra Goralnick, Donald L. Kreutzer, Peter C. Albertsen Farmington, CT

Introduction and Objectives Chronic Abacterial prostatitis(CAP) is a chronic inflammatory disease of unknown etiology and pathogenesis. CAP is histologically characterized by the presence of lymphocytes, mast cells, and macophages in prostatic tissue and secretions. We hypothesize that CAP results from an imbalance of cytokines which promotes mast cell mediated tissue injury. Specifically, we hypothesize the T2 cytokine {e.g. interleukin-10(IL-10)} dominate over T1 cytokine {e.g. interleukin-2(IL-2)} in prostatitis. This imbalance results in increased mast cell proliferation, activation, life span and tissue injury mediated via increased expression of Nerve Growth Factor(NGF) and Stem Cell Factor(SCF). Thus, we hypothesize the T2/T1 ratio would directly correlate with NGF and SCF levels in patients with CAP.

Methods: We obtained seminal plasma from 28 men who met the NIH criteria for CAP. Using commercial ELISA assays, IL-10, IL-2, NGF and SCF levels were quantified and expressed in pg/ml. T2/T1(IL-10/IL-2) ratios were calculated and statistical correlations were calculated using linear regression analysis.

Results There were no significant direct correlations when IL-2 or IL-10 were independently compared to NGF or SCF. However, significant direct correlations were obtained when T2/T1(IL-10/IL-2) was compared to NGF(p<0.037) and SCF (p<0.038) in the CAP patients. Additionally, there was a direct correlation between IL-2 and IL-10(p<0.0005).

ConclusionsWe conclude that the dominance of T2(IL-10) to T1(IL-2) cytokines promote mast cell activity which lead to elevated mast cell markers and this is demonstrated by the direct correlation between T2/T1 and NGF as well as SCF in the seminal plasma of CAP patients.
Supported by: National Institutes of Health

J. Curtis Nickel, The Canadian prostatitis Research Group Kingston, ON, Canada

Introduction and Objectives Antibiotics are the most popular choice of therapy for all categories of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This study was designed to determine if culture, leukocyte and/or immune status of prostate specific specimens predict the response to antibiotic therapy.

Methods: Patients with a clinical diagnosis of CP/CPPS (NIH definition) had lower urinary tract evaluation which included standard microscopy and culture of prostate specific specimens and determination of rato of VB3/VB2 antibody levels against panel of identified prostate pathogens (ELISA methodology). Symptom evaluation consisted of NIH-Chronic prostatitis Symptom Index-CPSI (pain scale 0-21), Symptom Severity Index-SSI (scale 0-100), Symptom Frequency Questionnaire-SFQ (scale 0-50) and Quality of Life-QoL (scale 0-6). Patients were stratified according to microscopy, culture and immune status, treated with 12 weeks of ofloxacin, and assessed at 4, 12, 24 and 48 weeks with symptom scores as well as patient and physician global assessments.

Results 102 evaluable patients were stratified (based on leukocyte and culture results) into Cat II CP (14%), Cat IIIA (48%) and Cat IIIB CPPS (38%). 23% were categorized as antibody-positive and 77% as antibody-negative. The average age was 42+/-10 years (92% Caucasian). 57% of patients felt that they had moderate to marked improvement while the physicians felt that 69% showed significant improvement or were cured. All categories of CP/CPPS and both antibody positive and negative patients had significant improvement in NIH-CPSI, SSI, SFQ and QoL scores (p<0.05) compared to baseline. There was no significant difference in response in the stratification based on culture and leukocyte status (i.e Cat II, IIIA and IIIB had same beneficial response). An initial significantly better response for antibody positive group compared to antibody negative group was not durable after antibiotics discontinued.

ConclusionsCulture, leukocyte and immune status of prostate specific specimens do not predict response to antibiotics in CP/CPPS. The perceived beneficial effect of antibiotics in all categories needs to be evaluated in a randomized placebo-controlled trial.
Supported by: Kidney Foundation, Janssen-Ortho, NIH/NIDDK

Theresa M. Koppie, Joseph C. Presti, Katsuto Shinohara, Martha K. Terris, Peter R. Carroll San Francisco; Stanford, CA

Introduction and Objectives Prostate evaluation in men after abdominoperineal resection (APR) poses a challenge for urologists. Diagnosis and staging methods are limited, as access to the rectum for digital rectal exam (DRE), transrectal ultrasound (TRUS) and transrectal biopsy is not possible. Transperineal ultrasound (TPUS) and biopsy have been desribed to evaluate the prostate in this setting. We report our experience with TPUS biopsy for evaluation of the prostate for an elevation in PSA after APR.

Methods: We reviewed the records of 26 patients who underwent TPUS and biopsy for an elevated serum PSA after APR at two institutions. The mean serum PSA in this population was 23.1 ng/dl with median of 9.5 ng/dl (range of 4.1-237 ng/dl). Fifteen patients (58%) underwent APR for colorectal cancer, 10 patients (37%) for ulcerative colitis, and 1 patient (4%) patient for familial polyposis coli. Five patients had previous radiation therapy as part of their treatment for colorectal cancer prior to TPUS biopsy.

Results Of the biopsies performed, 21 biopsies demonstrated prostate cancer, 2 biopsies demonstrated prostatitis, and three were benign. The average Gleason grade was 6.6 with a range from 3-9. Of the 21 patients with prostate cancer, 19 patients were treated. Eight were treated with androgen deprivation therapy, 6 underwent prostatectomy, and 5 were treated with external beam radiation. In patients who underwent prostatectomy, P stage did not correlate with preoperative PSA or Gleason grade. Average time from APR was 13.9 years (range 1-26).

ConclusionsTPUS guided biopsy of the prostate can provide accurate tissue diagnosis in patients with an elevated serum PSA after APR. However, cancer stage is difficult t o predict with the combination of PSA, Gleason grade and TPUS findings. Patients should be screened for prostate cancer prior to APR. Screening for prostate cancer should be performed regularly after APR with PSA.
Supported by: None

Werner W. Hochreiter, Robert B. Nadler, Alisa E. Koch, Phillip L. Campbell, Paul R. Yarnold, Anthony J. Schaeffer Chicago, IL

Introduction and Objectives Cytokines in expressed prostatic secretions (EPS) have been associated with chronic pelvic pain and/or inflammation in EPS. To establish the potential diagnostic value of serial cytokine changes in EPS we evaluated men with benign prostatic hyperplasia (BPH), chronic pelvic pain syndrome (CPPS [NIH category IIIa and IIIb]) and asymptomatic inflammatory prostatitis (NIH category IV).

Methods: Eighteen men underwent periodic cytokine evaluation (mean: 3 measures/patient, range 2-10) at a mean time interval of 3 months (range: 1-6 months). Tumor necrosis factor alpha (TNF-a), interleukin 1 beta (IL-1b), interleukin 8 (IL-8) and epithelial neutrophil activating peptide 78 (ENA-78) were measured by ELISA. Clinical symptoms and inflammatory status (number of white blood cells [WBC] in EPS) were determined.

Results In the absence of antibiotic treatment, 80% of the cases showed an increase of cytokine levels when symptoms developed (mean increase: 1725%) and a decrease of cytokine levels when symptoms disappeared (mean decrease: 49.5%). Similarily, in 73% of the cases an increase of WBC in EPS (<10 WBC/HPF to >10 WBC/HPF) was accompanied by an increase of cytokine levels (mean increase: 1771%) and a decrease of WBC in EPS (>10 WBC/HPF to <10 WBC/HPF) was accompanied by a decrease of cytokine levels (mean decrease: 57%). The degree of cytokine changes was significantly less in cases with stable symptoms (mean increase: 427%; mean decrease: 48%) or stable inflammatory status (mean increase: 440%; mean decrease: 54%). When antibiotic treatment was given, in 93% of the cases cytokine levels decreased (mean decrease: 51%) regardless of changes in symptoms or inflammatory status.

ConclusionsSerial monitoring of TNF-a, IL-1b, IL-8 and ENA-78 in EPS seems to be a reliable diagnostic tool which might be useful in the evaluation of patients with CPPS. Antibiotic treatment has to be taken into consideration as it might decrease cytokine levels.
Supported by: NIH RO1DK53730; Grants from the Department of Clinical Research, University of Berne, Berne, the Cloëtta Foundation, Zürich and the Swiss Society of Urology, Switzerland

J. Quentin Clemens, Robert B. Nadler, Anthony J. Schaeffer, Wade Bushman Ann Arbor, MI; Chicago, IL

Introduction and Objectives Pelvic floor tension myalgia has been identified as a significant component of chronic pelvic pain syndrome (CPPS) in men. Patients with CPPS frequently report subjective improvement with measures that diminish pelvic floor spasm (warm sitz baths, relaxation techniques, etc). Based on these observations, we have enrolled 19 patients with CPPS in a 12-week program of biofeedback-directed pelvic floor re-education and bladder training.

Methods: Instruction in pelvic floor muscle contraction and relaxation was achieved using a non-invasive form of biofeedback (EMPI) at biweekly sessions. Home exercises were combined with a progressive increase in timed-voiding intervals. Pre- and post-treatment assessments included pressure-flow studies (pre-treatment only), daily voiding logs, AUA symptom score and 10-point visual analog pain and urgency scores. Patient compliance with the treatment regimen was also assessed.

Results All patients met the criteria for NIH Type IIIA or IIIB prostatitis. Mean age of the 19 patients was 36 years (range 18-67). Prior treatment included antibiotics (16), alpha-blockers (10) and anticholinergic agents (7). Four patients completed less than 3 treatment sessions. Reasons for withdrawal included sufficient improvement (2), insurance difficulties (1) and unknown (1). Five patients completed 3-5 sessions and 10 attended all 6 sessions. Mean followup was 6 months. Mean AUA symptom scores improved from 14.5 to 7.3 (p<0.01), mean pain scores improved from 4.7 to 1.0 (p<0.01), mean urgency scores improved from 4.8 to 2.5 (p<0.01), and mean daytime voiding frequency decreased from q1 to q3 hours (p<0.01). Neither urodynamic evidence of obstruction nor the presence of inflammatory cells in the prostatic fluid altered treatment results.

ConclusionsThis preliminary study suggests that a formalized program of neuromuscular re-education of the pelvic floor muscles together with interval bladder training can provide significant and durable improvement in pain, urgency and frequency in patients with CPPS.
Supported by: None

Rosebud O. Roberts, Erik J. Bergstralh, Jennifer A. Besse, Noel R. Peterson, Michael M. Lieber, Steven J. Jacobsen Rochester, MN

Introduction and Objectives Although prostate biopsy is a relatively safe procedure, post-biopsy infection can have serious consequences. Few studies, however, have assessed risk factors for biopsy-related complications. This study assesses the prevalence of biopsy-related complications and the risk factors for these complications in a community-based cohort.

Methods: All 1,729 Olmsted County, MN men with a first prostate biopsy performed between 1980 and 1997 were identified. Community medical records for study subjects were reviewed to identify urologic conditions 6 to 8 weeks prior to the biopsy and complications following the prostate biopsy.

Results Of the 2,199 prostate biopsies performed for study subjects, 370 (17%) were associated with at least one complication. The most common compliations were gross hematuria (n=272, 12%), pain (n=43, 2%), acute urinary retention (n=40, 1.8%) and urogenital infections (n=30, 1.4%). Men with a history of urogenital infections (urinary tract infection, prostatitis, orchitis, epididymitis) were 1.7 times more likely to develop at least one biopsy-related complication (95% Confidence Interval (CI)=1.0, 2.7), and were also 8.3 times more likely to develop a post-biopsy infection (95% CI=2.1, 33.1) after simultaneous adjustment for pre-biopsy antibiotic therapy, age, prostate specific antigen level, digital rectal examination findings, and number of biopsy cores.

ConclusionsThese findings suggest that prostate biopsy-related complications are common in community-dwelling men. Furthermore, these findings suggest it may be possible to identify men in whom measures may be undertaken prior to a prostate biopsy that may reduce the occurrence of complications.
Supported by: AR30582 and Fraternal Order of Eagles

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