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In the past numerous chemokines have been noted in the expressed prostatic secretions of patients with chronic prostatitis/chronic pelvic pain syndrome. We examined the functional effects of chemokines in expressed prostatic secretions of patients with chronic pelvic pain syndrome.We studied the functional effects of expressed prostatic secretions on human monocytes by examining monocyte chemotaxis in response to monocyte chemoattractant protein-1, a major chemoattractant previously identified in chronic prostatitis/chronic pelvic pain syndrome cases. We determined effects on cellular signaling by quantifying intracellular calcium increase in monocytes and nuclear factor-κB activation in normal prostate epithelial cells.Results show that the monocyte chemoattractant protein-1 in expressed prostatic secretions is nonfunctional with an inability to mediate human monocyte chemotaxis, or mediate signaling in monocytes or prostate epithelial cells. This lack of functionality could be extended to other proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, when incubated with expressed prostatic secretions from patients with chronic pelvic pain syndrome. The mechanism underlying this apparent ability to modulate proinflammatory cytokines involves heat labile extracellular proteases that mediate the inhibition of immune and prostate epithelial cell function.These results may have implications for the design of specific diagnostic and therapeutic methods targeted toward the complete resolution of prostate inflammatory insults.

Background Pelvic pain is a major component of the morbidity associated with urinary tract infection (UTI), yet the molecular mechanisms underlying UTI-induced pain remain unknown. UTI pain mechanisms likely contrast with the clinical condition of asymptomatic bacteriuria (ASB), where individuals have significant bacterial loads yet lack symptoms.

The overlap of pain and urinary voiding symptoms is common for urologic patients. The etiology of these syndromes is frequently multifactorial and due to disorders of the bladder and/or prostate. The evaluation and treatment of these syndromes continues to evolve. Here we summarize the general approach to evaluation and treatment of these pain syndromes.

Uropathogenic Escherichia coli (UPEC) causes most community-acquired and nosocomial urinary tract infections (UTI). In a mouse model of UTI, UPEC invades superficial bladder cells and proliferates rapidly, forming biofilm-like structures called intracellular bacterial communities (IBCs). Using a gentamicin protection assay and fluorescence microscopy, we developed an in vitro model for studying UPEC proliferation within immortalized human urothelial cells. By pharmacologic manipulation of urothelial cells with the cholesterol-sequestering drug filipin, numbers of intracellular UPEC CFU increased 8 h and 24 h postinfection relative to untreated cultures. Enhanced UPEC intracellular proliferation required that the urothelial cells, but not the bacteria, be filipin treated prior to infection. However, neither UPEC frequency of invasion nor early intracellular trafficking events to a Lamp1-positive compartment were modulated by filipin. Upon inspection by fluorescence microscopy, cultures with enhanced UPEC intracellular proliferation exhibited large, dense bacterial aggregates within cells that resembled IBCs but were contained with Lamp1-positive vacuoles. While an isogenic fimH mutant was capable of forming these IBC-like structures, the mutant formed significantly fewer than wild-type UPEC. Similar to IBCs, expression of E. coli iron acquisition systems was upregulated by intracellular UPEC. Expression of other putative virulence factors, including hlyA , cnf1 , fliC , kpsD , and the biofilm adhesin yfaL also increased, while expression of fimA decreased and that of flu did not change. These results indicate that UPEC differentially regulates virulence factors in the intracellular environment. Thus, immortalized urothelial cultures that recapitulate IBC formation in vitro represent a novel system for the molecular and biochemical characterization of the UPEC intracellular life cycle.

Recurrent urinary tract infections (UTIs) are very common, particularly among women in their reproductive years. Alternatives to antibacterial prophylaxis are needed, particularly measures to increase host defences. Various bacterial lysates have been proposed with this indication. The objective of this review and meta-analysis was to assess the efficacy and safety of bacterial lysates in the management of recurrent UTIs. Electronic databases identified 11 studies with the descriptors 'urinary tract infection', 'immunotherapy' or 'vaccines' and 'double blind'. Seven of the studies dealt with an oral immunostimulant (OM-89), of which about five (1000 adult patients) were retained for analysis with an observation period of 6-12 months. The mean number of UTIs was significantly lower in OM-89-treated patients in all the trials analysed (mean 39%), as was the use of antibacterials. Four of the studies dealt with a vaginal vaccine, of which three small studies were retained for analysis (220 adult patients). The results suggest that this vaginal vaccine is effective when administered with a booster cycle (no recurrent UTI in 50% vs. 14% with placebo). No blind controlled studies could be identified with other bacterial lysates claiming the same indication. In conclusion, among the various immunotherapeutic products, studies were published only for one product (OM-89) that are in accordance with current standards. This product was shown to be effective under conditions of daily practice. The second product (vaginal vaccine) also appears to be effective but adequate phase III studies are necessary.

Uropathogenic E. coli (UPEC) expressing type 1 pili underlie most urinary tract infections (UTIs). UPEC adherence to the bladder urothelium induces a rapid apoptosis and exfoliation of terminally-differentiated urothelial cells, a critical event in pathogenesis. Of the four major uroplakin proteins that are densely expressed on superficial urothelial cells, UPIa serves as the receptor for type 1-piliated UPEC, but the contributions of uroplakins to cell death are not known. We examined the role of differentiation and uroplakin expression on UPEC-induced cell death. Utilizing in vitro models of urothelial differentiation, we demonstrated induction of tissue-specific differentiation markers including uroplakins. UPEC-induced urothelial cell death was shown to increase with enhanced differentiation but required expression of uroplakin III: infection with an adenovirus encoding uroplakin III significantly increased cell death, while siRNA directed against uroplakin III abolished UPEC-induced cell death. In a murine model of UTI where superficial urothelial cells were selectively eroded to expose less differentiated cells, urothelial apoptosis was reduced, indicating a requirement for differentiation in UPEC-induced apoptosis in vivo. These data suggest that induction of uroplakin III during urothelial differentiation sensitizes cells to UPEC-induced death. Thus, uroplakin III plays a pivotal role in UTI pathogenesis.

In the urinary tract, the innate immune system detects conserved bacterial components and responds to infection by activating the proinflammatory transcription factor NF-κB, resulting in cytokine secretion and neutrophil recruitment. UropathogenicEscherichia coli(UPEC), however, has been shown to evade the host innate immune response by suppressing NF-κB activation in urothelial cells, which results in decreased cytokine secretion and increased urothelial apoptosis. To understand the molecular basis of UPEC modulation of inflammation, we performed a genetic screen with UPEC strain NU14 to identify genes which are required for modulation of urothelial cytokine secretion. Disruption ofampG(peptidoglycan permease),waaL(lipopolysaccharide O antigen ligase), oralr(alanine racemase) resulted in increased urothelial interleukin-8 (IL-8) and IL-6 release from urothelial cell cultures. Targeted deletion of these genes also resulted in elevated urothelial cytokine production during UPEC infection. Conditioned media from bacterial cultures of NU14 ΔampGand NU14 ΔwaaLcontained a heat-stable factor(s) which stimulated greater urothelial IL-8 secretion than that in NU14-conditioned medium. In a mouse model of urinary tract infection, NU14 ΔampG, NU14 ΔwaaL, and NU14 Δalrwere attenuated compared to wild-type NU14 and showed reduced fitness in competition experiments. Instillation of NU14 ΔampGor NU14 ΔwaaLincreased bladder neutrophil recruitment, indicating that enhanced urothelial cytokine secretion during urinary tract infection results in an altered host response. Thus, UPEC evasion of innate immune detection of bacterial components, such as lipopolysaccharide and peptidoglycan fragments, is likely an important factor in the ability of UPEC to colonize the urinary tract.

Chronic prostatitis/chronic pelvic pain syndrome remains an enigmatic medical condition. Creation of the National Institutes of Health-funded Chronic Prostatitis Collaborative Research Network (CPCRN) has stimulated a renewed interest in research on and clinical aspects of chronic prostatitis/chronic pelvic pain syndrome. Landmark publications of the CPCRN document a decade of progress. Insights from these CPCRN studies have improved our management of chronic prostatitis/chronic pelvic pain syndrome and offer hope for continued progress.

OBJECTIVES To evaluate the current and future states of resident research experience in urology residencies in the United States. METHODS Round table discussion with leading educators and Urology faculty from a university urology residency. RESULTS Research exposure has rapidly diminished in urology residencies for a variety of reasons. There are multiple barriers to resident research and only a small number of residencies will be able to provide protected time. Nevertheless, an understanding of research methodology and biostatistics is required to be a successful clinician. CONCLUSIONS Some barriers to resident research can be addressed by better integration of residency and fellowships. Flexibility in the format of resident education may allow introduction of new methods to encourage resident research scholarship. An education program with a research curriculum is needed for all residencies.

Chronic pelvic pain syndrome (CPPS), formerly known as chronic abacterial prostatitis, is characterised by pelvic or perineal pain without evidence of urinary tract infection. It manifests as pain in a variety of areas including the perineum, rectum, prostate, penis, testicles and abdomen [Litwin MS, McNaughton-Collins M, Fowler Jr FJ, Nickel JC, Calhoun EA, Pontari MA, et al. The National Institutes of Health chronic prostatitis symptom index: development and validation of a new outcome measure. Chronic Prostatitis Collaborative Research Network. J Urol 1999;2:369–75]. It is also frequently associated with symptoms including urinary urgency, frequency, hesitancy and poor or interrupted flow. CPPS may be associated with white cells in the prostatic secretions (inflammatory) (NIH-3A), or white cell absence in the prostatic secretions (non-inflammatory) (NIH-3B) [Krieger JN, Nyberg Jr L, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;3:236–7].

UropathogenicEscherichia coli(UPEC), the most frequent cause of urinary tract infection (UTI), is associated with an inflammatory response which includes the induction of cytokine/chemokine secretion by urothelial cells and neutrophil recruitment to the bladder. Recent studies indicate, however, that UPEC can evade the early activation of urothelial innate immune response in vitro. In this study, we report that infection with the prototypic UPEC strain NU14 suppresses tumor necrosis factor alpha (TNF-α)-mediated interleukin-8 (CXCL-8) and interleukin-6 (CXCL-6) secretion from urothelial cell cultures compared to infection with a type 1 piliatedE. coliK-12 strain. Furthermore, examination of a panel of clinicalE. coliisolates revealed that 15 of 17 strains also possessed the ability to suppress cytokine secretion. In a murine model of UTI, NU14 infection resulted in diminished levels of mRNAs encoding keratinocyte-derived chemokine, macrophage inflammatory peptide 2, and CXCL-6 in the bladder relative to infection with anE. coliK-12 strain. Furthermore, reduced stimulation of inflammatory chemokine production during NU14 infection correlated with decreased levels of bladder and urine myeloperoxidase and increased bacterial colonization. These data indicate that a broad phylogenetic range of clinicalE. coliisolates, including UPEC, may evade the activation of innate immune response in the urinary tract, thereby providing a pathogenic advantage.

Urinary tract infections are common complications of pregnancy; upper tract infections in particular may lead to significant morbidity for both the mother and fetus. Bacteriuria is a significant risk factor for developing pyelonephritis in pregnant women. Therefore, proper screening and treatment of bacteriuria during pregnancy is necessary to prevent complications. All women should be screened for bacteriuria in the first trimester, and women with a history of recurrent urinary tract infections or anomalies should have repeat bacteriuria screening throughout pregnancy. Treatment of bacteriuria should include 3-day therapy with appropriate antimicrobials, and women should be followed closely after treatment because recurrence may occur in up to one third of patients.

Chronic prostatitis can cause pain and urinary symptoms, and can occur either with an active infection (chronic bacterial prostatitis [CBP]) or with only pain and no evidence of bacterial causation (chronic pelvic pain syndrome [CPPS]). Bacterial prostatitis is characterised by recurrent urinary tract infections or infection in the prostate with the same bacterial strain, which often results from urinary tract instrumentation. However, the cause and natural history of CPPS are unknown and not associated with active infection.We conducted a systematic overview and aimed to answer the following clinical questions: What are the effects of treatments for chronic bacterial prostatitis? What are the effects of treatments for chronic pelvic pain syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).At this update, searching of electronic databases retrieved 131 studies. After deduplication and removal of conference abstracts, 67 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 51 studies and the further review of 16 full publications. Of the 16 full articles evaluated, three systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for 14 PICO combinations.In this systematic overview, we categorised the efficacy for 12 interventions based on information relating to the effectiveness and safety of 5 alpha-reductase inhibitors, allopurinol, alpha-blockers, local injections of antimicrobial drugs, mepartricin, non-steroidal anti-inflammatory drugs (NSAIDs), oral antimicrobial drugs, pentosan polysulfate, quercetin, sitz baths, transurethral microwave thermotherapy (TUMT), and transurethral resection of the prostate (TURP).

Summary Introduction Augmentation enterocystoplasty and appendicovesicostomy are complex pediatric urologic procedures. Although there is literature identifying long-term outcomes in these patients, the reporting of short-term postoperative outcomes has been limited by small numbers of cases and lack of prospective data collection. Here we report 30-day outcomes from the first nationally based, prospectively assembled cohort of pediatric patients undergoing these procedures. Objective To determine 30-day complication, readmission and reoperation after augmentation enterocystoplasty and appendicovesicostomy in a large national sample of pediatric patients, and to explore the association between preoperative and intraoperative characteristics and occurrence of any 30-day event. Study design We queried the 2012 and 2013 American College of Surgeons National Surgical Quality Improvement Program Pediatric database (ACS-NSQIPP) for all patients undergoing augmentation enterocystoplasty and/or appendicovesicostomy. Surgical risk score was classified on a linear scale using a validated pediatric-specific comorbidity score. Intraoperative characteristics and postoperative 30-day events were reported from prospectively collected data. A composite measure of complication, readmission and/or reoperation was used as primary outcome for the multivariate logistic regression. Results There were 461 patients included in the analysis: 245 had appendicovesicostomy, 97 had augmentation enterocystoplasty and 119 had both procedures. There were a total of 110 NSQIP complications seen in 87 patients. The most common complication was urinary tract infection (see Table for 30-day outcomes by patient). The composite measure of any 30-day event was seen in 27.8% of the cohort and this was associated with longer operative time, increased number of procedures done at time of primary surgical procedure and higher surgical risk score. Discussion The ACS-NSQIPP provides a tool to examine short-term outcomes for these complex urologic procedures that has not been possible before. Although ACS-NSQIP has been used extensively in the adult surgical literature to identify rates of complications, and to determine predictors of readmission and adverse events, its use in pediatric surgery is new. As in the adult literature, the goal is for standardization of practice and transparency in reporting outcomes that may lead to reduction in morbidity and mortality. Conclusion In this cohort, any 30-day event is seen in almost 30% of the patients undergoing these urologic procedures. Operative time, number of concurrent procedures and higher surgical risk score all are associated with higher odds of the composite 30-day event of complication, readmission and/or reoperation. These data can be useful in counseling patients and families about expectations around surgery and in improving outcomes. Table . 30-day events by patient. Patients, n = 461 Any NSQIP complications 87 (18.9) UTI 43 (9.3) Wound complications Superficial SSI 19 (4.1) Deep SSI 4 (0.9) Organ SSI 5 (1.1) Dehiscence 8 (1.7) Pneumonia 1 (0.2) Reintubation 1 (0.2) Bleeding/transfusion 19 (4.1) Sepsis 8 (1.7) Central line infection 1 (0.2) Renal failure 1 (0.2) Other 30-day outcomes Readmission 62 (13.5) Reoperation 32 (6.9) Composite 30-day event 128 (27.8) Data given as n (%).

We describe our experience with 2-stage proximal hypospadias repair. We report outcomes, and patient and procedure characteristics associated with surgical complications.We retrospectively studied patients with proximal hypospadias who underwent staged repair between January 1993 and December 2012. Demographics, preoperative management and operative technique were reviewed. Complications included glans dehiscence, fistula, meatal stenosis, nonmeatal stricture, urethrocele/diverticula and residual chordee. Cox proportional hazards model was used to evaluate the associations between time to surgery for complications and patient and procedure level factors.A total of 134 patients were included. Median patient age was 8.8 months at first stage surgery and 17.1 months at second stage surgery, and median time between surgeries was 8 months. Median followup was 3.8 years. Complications were seen in 71 patients (53%), with the most common being fistula (39 patients, 29.1%). Reoperation was performed in 66 patients (49%). Median time from urethroplasty to surgery for complication was 14.9 months. Use of preoperative testosterone decreased risk of undergoing surgery for complication by 27% (HR 0.73, 95% CI 0.55-0.98, p = 0.04). In addition, patients identified as Hispanic were at increased risk for undergoing surgery for complications (HR 2.40, 95% CI 1.28-4.53, p = 0.01).We review the largest cohort of patients undergoing 2-stage hypospadias repair at a single institution. Complications and reoperation rates were approximately 50% in the setting of complex genital reconstruction.

Dietary carcinogens, such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and chronic inflammation have each been implicated as etiologic agents in prostate cancer. We hypothesized that bacterial prostatitis would accelerate PhIP-induced preinvasive lesions in the rat prostate. Male Fischer 344 rats were assigned into 4 groups: Control (untreated), PhIP (200 ppm in the diet for 20 weeks), Escherichia coli (E. coli, prostatic inoculation in week 10), or PhIP + E. coli. Study animals were monitored for a total of 52 weeks and were euthanized as necessary based on strict criteria for health status and tumor burden. Animals treated with E. coli initially developed acute and chronic inflammation in all lobes of the prostate, whereas inflammation was observed predominantly in the ventral lobe at time of death. PhIP + E. coli–treated animals exhibited a marked decrease in survival compared with PhIP-alone–treated animals as a result of an increase in the number of invasive cancers that developed at multiple sites, including the skin, small intestine, and Zymbal's gland. Despite their earlier mortality, PhIP + E. coli–treated animals developed an increased average number of precancerous lesions within the prostate compared with PhIP-treated animals, with a significantly increased Ki-67 index. Multiplexed serum cytokine analysis indicated an increase in the level of circulating IL6 and IL12 in PhIP + E. coli–treated animals. Elevated serum IL6 levels correlated with the development of precancerous lesions within the prostate. These results suggest that bacterial infections and dietary carcinogens, two conceivably preventable cancer risk factors, may synergistically promote tumorigenesis. Cancer Prev Res; 8(8); 683–92. ©2015 AACR.

A 38-year-old man reports pelvic pain, dysuria, and urinary urgency for the past 4 weeks. He has had several similar episodes over the past 2 years; urine cultures were not performed. He is sexually active and reports frequent discomfort after ejaculation. He is otherwise healthy and takes no medication. He has no fever, chills, or flank pain. How should he be evaluated and treated?

Cognitive/behavioral and environmental variables are significant predictors of patient adjustment in chronic pain. Using a biopsychosocial template and selecting several pain-relevant constructs from physical, cognitive/behavioral, and environmental predictors, outcomes of pain and disability in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were explored. Men (n = 253) from a North American multi-institutional NIH-funded Chronic Prostatitis Cohort Study in 6 US and 1 Canadian centers participated in a survey examining pain and disability. Measures included demographics, urinary symptoms, depression, pain, disability, catastrophizing, control over pain, pain-contingent rest, social support, and solicitous responses from a significant other. Regressions showed that urinary symptoms (beta = .20), depression (beta = .24), and helplessness catastrophizing (beta = .29) predicted overall pain. Further, affective pain was predicted by depression (beta = .39) and helplessness catastrophizing (beta = .44), whereas sensory pain was predicted by urinary symptoms (beta = .25) and helplessness catastrophizing (beta = .37). With regard to disability, urinary symptoms (beta = .17), pain (beta = .21), and pain-contingent rest (beta = .33) were the predictors. These results suggest cognitive/behavioral variables (ie, catastrophizing, pain-contingent rest) may have significant impact on patient adjustment in CP/CPPS. Findings support the need for greater research of such pain-related variables in CP/CPPS.This article explores predictors of patient adjustment in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Cognitive/behavioral variables of catastrophizing and pain-contingent rest respectively predicted greater pain and disability. Catastrophic helplessness was a prominent pain predictor. These findings inform clinicians and researchers on several new variables in CP/CPPS outcomes and suggest future research.

Urinary tract infections (UTIs) cause patient morbidity and have a substantial economic impact. Half of all women will suffer a UTI at least once, and 25% of these women will have recurrent infections. That 75% of previously infected women do not become reinfected strongly suggests a role for an adaptive immune response. The goal of this study was to characterize the adaptive immune responses to uropathogenic Escherichia coli (UPEC), the predominant uropathogen. A novel murine model of UTI reinfection was developed using the prototypic cystitis UPEC isolate NU14 harboring a plasmid encoding OVA as a unique antigenic marker. Bacterial colonization of the bladder was quantified following one or more infections with NU14-OVA. Animals developed anti-OVA serum IgG and IgM titers after the initial infection and marked up-regulation of activation markers on splenic T cells. We observed a 95% reduction in bacterial colonization upon reinfection, and splenic leukocytes showed Ag-specific proliferation in vitro. Adoptive transfer of splenic T cells or passive transfer of serum from previously infected mice protected naive syngeneic mice from UPEC colonization. These findings support our hypothesis that adaptive immune responses to UPEC protect the bladder from reinfection and form the basis of understanding susceptibility to recurrent UTI in women.

Objectives To determine whether prostate-specific antigen (PSA), the percent free PSA, or free PSA isoforms may be used as diagnostic markers for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; National Institutes of Health category IIIa and IIIb). Methods We evaluated 421 patients enrolled in the Chronic Prostatitis Cohort Study and 112 age-matched controls. Subjects were stratified by the number of white blood cells (WBCs) in their expressed prostatic secretions and pain as determined by the National Institutes of Health Chronic Prostatitis Symptom Index. Results Total PSA, free PSA, and [−2]proPSA ([−2]pPSA) were significantly elevated in those with CP/CPPS compared with controls (mean PSA 1.97 ng/mL versus 1.72 ng/mL, P = 0.03; mean free PSA 0.76 ng/mL versus 0.70 ng/mL, P = 0.01; and [−2]pPSA 2.38 ng/mL versus 1.80 ng/mL, P = 0.04). The percent free PSA was not significantly different between the patients and controls. For those with CP/CPPS, the percent free PSA was significantly lower as the WBC count rose in the expressed prostatic secretions (0 WBCs = 43.29 versus more than 25 WBCs = 26.52; P Conclusions Men with elevated PSA values and CP/CPPS should be treated as one would any other patient screened for prostate cancer with an elevated PSA level. Although PSA, free PSA, and [−2]pPSA were slightly elevated in men with CP/CPPS, the low sensitivity and specificity do not warrant using them as biomarkers for CP/CPPS.

We review the diagnosis, categorization, and treatment of prostatitis/chronic pelvic pain syndrome based on the National Institutes of Health (NIH) classification. Prostatitis is an extremely common syndrome that afflicts 2%–10% of men. Formerly a purely clinical diagnosis, prostatitis is now classified within a complex series of syndromes (NIH category I–IV prostatitis) that vary widely in clinical presentation and response to treatment. Acute bacterial prostatitis (category I) and chronic bacterial prostatitis (category II) are characterized by uropathogenic infections of the prostate gland that respond well to antimicrobial treatment. In contrast, chronic prostatitis/chronic pelvic pain syndrome (category III), which accounts for 90%–95% of prostatitis cases, is of unknown etiology and is marked by a mixture of pain, urinary, and ejaculatory symptoms with no uniformly effective therapy. Asymptomatic inflammatory prostatitis (category IV) is an incidental finding of unknown clinical significance. This review describes the current status of prostatitis syndromes and explores the future prospects of new diagnostic tools and therapies.

Purpose: We evaluated the efficacy and tolerability of pentosan polysulfate sodium (PPS) for the treatment of men with chronic pelvic pain syndrome (CPPS), National Institutes of Health (NIH) category III. Materials and Methods: In a 16-week double-blind study 100 men with a clinical diagnosis of CPPS were randomized to receive 300 mg PPS or placebo 3 times daily. Clinical Global Improvement (CGI) was the primary outcome measure. Additional outcome measures were the NIH-Chronic Prostatitis Symptom Index (CPSI), Subjective Global Assessment and Symptom Severity Index assessment tools. Results: Significantly more patients receiving PPS experienced moderate to marked improvement based on CGI assessment (18 or 37% vs 8 or 18%, p = 0.04). However, mean CGI scores were not significantly different between the PPS group (1.0) and placebo groups (1.0 vs 0.6, p = 0.107). All NIH-CPSI domains suggested a positive effect for PPS and for total NIH-CPSI the difference approached statistical significance (−5.9 or 22% vs −3.2 or 12%, p = 0.068). The PPS group showed significantly greater improvement in NIH-CPSI quality of life domain scores than the placebo group (−2.0 or 22% vs −1.0 or 12%, p = 0.031). Of patients receiving PPS 67% and 80% of those receiving placebo completed the 16-week study. Diarrhea, nausea and headache were the most common adverse events. Conclusions: Pentosan polysulfate (900 mg daily) was more likely than placebo to provide relief for CPPS symptoms.

1. The diagnosis of asymptomatic bacteriuria should be based on results of culture of a urine specimen collected in a manner that minimizes contamination (A-II) (table 1). • For asymptomatic women, bacteriuria is defined as 2 consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts 10 cfu/mL (B-II). • A single, clean-catch voided urine specimen with 1 bacterial species isolated in a quantitative count 10 cfu/mL identifies bacteriuria in men (BIII). • A single catheterized urine specimen with 1 bacterial species isolated in a quantitative count 10 cfu/mL identifies bacteriuria in women or men (A-II). 2. Pyuria accompanying asymptomatic bacteriuria is not an indication for antimicrobial treatment (A-II). 3. Pregnant women should be screened for bacteriuria by urine culture at least once in early pregnancy, and they should be treated if the results are positive (A-I). • The duration of antimicrobial therapy should be

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disabling condition that is poorly understood. The National Institutes of Diabetes and Digestive and Kidney Diseases-sponsored Collaborative Research Network has developed a symptom index, formed a cohort study, a case control study, a full-scale randomised clinical trial, a resource utilisation study and clinical trials, as well as basic research studies, in an effort to better understand and manage patients with this condition. Cohort, case control and resource utilisation studies have confirmed the substantial impact of CP/CPPS. Clinical trials in basic research suggest that anti-inflammatory therapy and alpha-blocker therapy may be effective. The minority of patients with acute or chronic bacterial prostatitis continues to respond favourably to oral fluoroquinolone therapy.

In summary, prostatitis is a complex syndrome that spans a spectrum from acute prostatitis with a straightforward presentation to CP-CPPS with a complex array of symptoms. The identification of prostatic or pelvic pain becomes a requirement for the diagnosis of CP-CPPS. The NIH system of prostatitis categorization is a refinement of the traditional classification of prostatitis by Drach et al, which was based on the localization test of Meares and Stamey. The NIH categorization system allows for a framework to define the disease process, and the NIH-CPSI was created to quantify the symptoms of chronic prostatitis. Integral to the classification of prostatitis is the presence or absence of inflammation, determined by looking for leukocytes in the EPS, seminal fluid, and VB3 specimens. In addition, the role of bacteria as a cause in category III prostatitis continues to be debated. Future research into using inflammatory markers (eg, tumor necrosis factor-alpha, interleukin-2) and using PCR to identify the presence of bacteria may further refine the pathophysiology of prostatitis. The mainstream treatment of chronic prostatitis involves antimicrobials, non-steroidal anti-inflammatory medications, and alpha-blockers. The potential role of asymptomatic category IV chronic prostatitis in the etiology of prostate cancer may be delineated further with future research.

Urinary tract infection (UTI) is an exceedingly common problem prompting seven million office visits and one million hospitalizations in the United States each year (1). Advances in the understanding of both host and bacterial factors involved in UTI have led to many improvements in therapy. While there have also been advances in the realm of antimicrobials, there have been numerous problems with multiple drug resistant organisms. Providing economical care while minimizing drug resistance requires appropriate diagnosis, evaluation, and treatment of urinary tract infections.

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a multifactorial problem affecting men of all ages and demographics. Currently, there is a relative dearth of epidemiological information on CPPS. It is clear that patients with CPPS have a dismal quality of life and many have benefited only minimally from empiric, goal-directed therapy. Long-term follow-up of the CPPS cohort will answer important questions about the natural and treated history of this syndrome. Similarly, ongoing and future studies will provide community-based and prevalence estimates for CPPS, morbidity rates for men with CPPS, and the rates of symptom improvement and symptom deterioration for these men, as well as the probability of benefits and harm from different treatments. Although men with CP routinely receive anti-inflammatory and antimicrobial therapy, recent studies suggest that leucocyte and bacterial counts do not correlate with severity of symptoms. These findings suggest that factors other than leucocytes and bacteria contribute to the symptoms associated with CPPS. The probability of benefits and harm from different treatments for CPPS, and reliable and valid measures to define these outcomes are eagerly awaited.

Chronic prostatitis has been traditionally characterized by inflammation and/or infection of the prostate gland, objectively categorized by white blood cells and cultured bacteria in prostate specific specimens. We compared leukocyte counts and localization rates for bacterial cultures of segmented urine samples (VB1, VB2, VB3), expressed prostatic secretion (EPS) and semen in men diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to men without pelvic pain (controls).A total of 463 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study and 121 age matched men without urinary symptoms had leukocyte counts performed and 5-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, EPS, VB3) and semen. All risk factor comparisons between case and control analyses were tested using generalized Mantel-Haenszel methods, and multivariable models were developed using logistic regression methods, adjusting for clustering by clinical center within both methods.Men with CP/CPPS had statistically higher leukocyte counts in all segmented urine samples and EPS, but not in semen compared to asymptomatic control men. However, the control population also had a high prevalence of leukocytes. Of the men with CP/CPPS 50% and 32% had 5 or more, or 10 or more white blood cells (WBCs) per high power field, respectively, in EPS compared to 40% and 20% of the control population. Similarly, 32% and 14% of the patients with CP/CPPS had 5 or more, or 10 or more WBCs per high power field in VB3 compared to 19% and 11% in the control population. Localization of uropathogenic bacteria in EPS, VB3 and/or semen was similar in men with CP/CPPS (8.0%) and asymptomatic men (8.3%).Men with CP/CPPS have significantly higher leukocyte counts in all segmented urine samples and EPS but not in semen as compared to controls. There is no difference in rates of localization of bacterial cultures for men with CP/CPPS compared to control men. The high prevalence of WBCs and positive bacterial cultures in the asymptomatic control population raises questions about the clinical usefulness of the standard 4-glass test as a diagnostic tool in men with CP/CPPS.

Patients with complicated UTIs are a diverse group. These patients have upper UTIs and structural or functional abnormalities that reduce the efficacy of antimicrobial therapy. They are at increased risk for morbidity such as bacteremia and sepsis, perinephric abscess, renal deterioration, and emphysematous pyelonephritis. Appropriate urinary tract imaging, antimicrobials, medical and surgical therapies, and follow-up are required to avoid potentially devastating outcomes.

There is substantiating evidence to support the role of the immune system in the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inflammation of the prostate is mediated through the cytokine-induced expression of several factors such as chemokines, inducible nitric oxide synthase, and cyclooxygenase-2. The balance between the effects of proinflammatory and anti-inflammatory cytokines determines the outcome of the inflammatory process. Several proinflammatory and anti-inflammatory cytokines have been identified in CPPS patients, their roles characterized, and their inter-relationships defined. Study of this system will provide further insights into the etiology of CP/CPPS, and lead the way for the development of novel therapeutic approaches for this morbid condition.

Members of the Chronic Prostatitis Collaborative Research Network (CPCRN) met in a 1-day symposium to review recent findings and to debate unanswered issues in the diagnosis and management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The meeting was focused on producing an overview summary statement that would, as nearly as possible, represent the consensus views of the attendees. As discussed below, the participants agreed that a history, physical examination, and urinalysis/urine culture are mandatory for the evaluation of all patients presenting with CP/CPPS, with other assessments categorized as recommended or optional, depending on the history and physical findings. Observations and suggestions regarding first- and second-line therapies are also offered, with the recognition that randomized, placebo-controlled trials to guide selection of therapies for chronic nonbacterial prostatitis are currently lacking.

Purpose: We examine whether leukocytes and bacteria correlate with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome.Materials and Methods: All 488 men screened into the National Institutes of Health Chronic Prostatitis Cohort Study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, were used to measure symptoms. Urethral inflammation was defined as white blood cell (WBC) counts of 1 or more (1+) in the first voided urine. Participants were classified as category IIIa based on WBC counts of 5 or more, or 10 or more (5+, 10+) in the expressed prostatic secretion, or 1+ or 5+ either in the post-expressed prostatic secretion urine (voided urine 3) or semen. Uropathogens were classified as localizing if the designated bacterial species were absent in voided urine 1 and voided urine 2 but present in expressed prostatic secretion, voided urine 3 or semen, or prese...

Purpose: We describe the study design of the National Institutes of Health Chronic Prostatitis Cohort (CPC) study characterizing men with chronic prostatitis/the chronic pelvic pain syndrome.Materials and Methods: All 488 men screened into the CPC study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, was used to measure symptoms. A comprehensive history, physical examination and demographic profile were obtained from each participant. Generalized Mantel-Haenszel procedures were used to investigate baseline associations between selected factors and symptoms.Results: Chronic prostatitis/chronic pelvic pain syndrome is a chronic syndrome affecting men over a wide age range. The majority of CPC study participants are white, well educated and affluent. However, lower education, lower income and unemployment were associated with more severe symptoms. Patients most frequently reported pain in the ...

Random amplified polymorphic DNA fingerprinting was used to distinguish among Escherichia coli bacterial strains creating urinary tract infections (UTIs) in women. Bacteria bound more avidly to cells from postmenopausal donors with history of UTIs (PK) compared with cells from women without history of UTIs (AO). Nonpiliated bacterial strains did not adhere to the cell lines. Increasing S-IgA concentrations has no effect on AO cell bacterial binding, whereas bacterial adhesion to PK cell epithelium increased with increasing S-IgA concentration.

e538 Background: Despite the potential side effects associated with treating prostate cancer, many men choose treatment over observation. The relative treatment benefits and harms to heath related quality of life outcomes (HRQOL) remain poorly understood. In particular, there is a paucity of data detailing the differences in perceived treatment outcomes in African American (AA) and Hispanic men. We prospectively evaluated the functional and psychosocial effects of prostate cancer treatment in men and hypothesize that there may be differences in outcomes in Caucasian men vs. AA/Hispanic men. Methods: We enrolled 105 men with recently diagnosed prostate cancer at our institution in an internet-based study which used validated questionnaires to longitudinally assess HRQOL domains such as sexual and urinary function, bowel function, anxiety, and depression, at 1, 3, 6, and 12 months following treatment. Linear mixed models were used to examine changes in self-reported measures at enrollment (pre-treatment) and at each post-treatment follow-up assessment. We focused our analysis on the 62 patients who chose radical prostatectomy as treatment: 49 of these men were non-Hispanic white; 13 were AA or Hispanic. Results: Despite significant declines in functional outcomes such as erectile function (P < .001 for both groups), anxiety was significantly lowered post-treatment in both groups as well. Significant reductions in anxiety were noted for Caucasian men (4.6 points , P < 0.001) and were even greater for AA/Hispanic men (7.9 points, P < .001). When controlling for differences in income, marital status, education, and improvements in urinary score, the impact on anxiety remained significant (P < 0.05) at 3, 6, and 12 months . Based on previous analysis, these improvements are both statistically and clinically significant improvements. Conclusions: We found significant reductions in anxiety after prostate cancer surgery. While these reductions were found in all men, AA and Hispanic men reported a greater reduction in anxiety compared to the Caucasian cohort. This suggests that AA/Hispanic men may have a different perspective regarding prostate cancer and treatment outcomes. Further work is necessary to elucidate this difference in perspective.

Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI.Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection.The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine EAP. Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia led to extracellular signal-regulated kinase (ERK)1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS.

The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain.Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14-S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain.Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF.Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain.