Prostate-specific antigen test in diagnostic evaluation of chronic prostatitis/chronic pelvic pain syndrome.

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 < .0001). A PSA level of 4.0 ng/mL or greater was found in 10% of patients and 7% of controls (P = 0.03). 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.

Impact of the 1998 World Health Organization/International Society of Urological Pathology classification system for urothelial neoplasms of the kidney.

The classification of urothelial neoplasms of the kidney traditionally has been similar to that of urinary bladder tumors. Several years ago, the classification of papillary urothelial neoplasms was revised. The current study focuses on the application of the 1998 World Health Organization (WHO)/International Society of Urological Pathology classification system to 102 renal pelvic urothelial neoplasms and compares it to the 1973 WHO classification scheme. In this study, all tumors were classified as urothelial carcinomas, and the majority (85%) were papillary. Most patients with papillary tumors presented with 'superficial' disease (< or = pT1). With the 1998 system, most papillary carcinomas were high grade, and were more often invasive as compared to low-grade tumors. Only 34% were low-grade papillary tumors and, of these, most (93%) were noninvasive. With the 1973 system, most papillary tumors were grade 2 or 3, with invasion more common in grade 3 tumors. By 1973 criteria, grade 2 tumors were a heterogeneous group; with 1998 criteria, nearly one-half were high grade and the other half low grade. The grade of papillary urothelial carcinomas with both the 1973 and 1998 grading methods was associated with stage (P=0.001). Our study reveals that papillomas and papillary urothelial neoplasms of low malignant potential are uncommon tumors in the kidney. Renal pelvic papillary urothelial neoplasms are most often carcinomas and are more commonly high grade than low grade. Although both the 1973 and 1998 systems showed a significant association with tumor stage, grade 2 papillary carcinomas are a heterogeneous group by 1973 criteria. The 1998 system provides useful information in that it more clearly defines a papillary tumor's grade and selects for a group of tumors, namely low-grade papillary urothelial carcinomas, for which a low likelihood of invasion can be predicted.

Predictors of quality of life and pain in chronic prostatitis/chronic pelvic pain syndrome: findings from the National Institutes of Health Chronic Prostatitis Cohort Study.

OBJECTIVES: To examine the cross-sectional relationship of age, urinary and depressive symptoms and partner status on pain intensity and quality of life (QoL) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS: In all, 463 men enrolled in the National Institutes of Health (NIH) Chronic Prostatitis Cohort Study from seven clinical centres (six in the USA and one in Canada) reported baseline screening symptoms using the NIH Chronic Prostatitis Symptom Index (CPSI). The CPSI provides scores for pain, urinary symptoms and QoL. In addition, a demographic profile, including age and partner (living with another) status, and a depressive symptom score were obtained. Regression modelling of QoL, adjusting for between-centre variability, examined the unique effects of age, partner status, urological symptoms, depressive symptoms and pain. RESULTS: Urinary scores, depressive symptoms and pain intensity scores significantly predicted QoL for patients with CP/CPPS (higher CPSI QoL scores indicated more impairment; median 8.0, range 0-12). On average, for every 1-point increase in urinary scores, there was a corresponding increase in QoL score of 0.118 points (P = 0.001); for every 1-point increase in pain intensity score, there was a corresponding increase in QoL score of 0.722 points (P < 0.001); and for every 1-point decrease in depressive symptoms (lower scores equal poorer mood), the QoL score increased (poorer quality of life) by 0.381 points (P < 0.001). Age and partner status did not significantly contribute to poorer QoL. Urinary scores and depressive symptoms were significant predictors (P < 0.001) of pain in patients with CP/CPPS. CONCLUSIONS: These data show that depressive symptoms and pain intensity significantly predict a poorer QoL in patients with CP/CPPS, and that these effects are independent of partner status, age and urinary status. In particular, pain intensity was the most robust predictor of a poorer QoL. Further data relating pain and psychological factors to CP/CPPS are highly recommended, to aid in determining specific factors for pain and its impact on QoL. These data are essential if empirically guided efforts to manage pain are to progress.

Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is principally defined by pain in the pelvic region lasting more than 3 months. No cause of the disease has been established, and therapies are empirical and mostly untested. Antimicrobial agents and alpha-adrenergic receptor blockers are frequently used. OBJECTIVE: To determine whether 6-week therapy with ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms in men with refractory, long-standing CP/CPPS. DESIGN: Randomized, double-blind trial with a 2 x 2 factorial design comparing 6 weeks of therapy with ciprofloxacin, tamsulosin, both drugs, or placebo. SETTING: Urology outpatient clinics at 10 tertiary care medical centers in North America. PATIENTS: Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment. MEASUREMENTS: The authors evaluated NIH-CPSI total score and subscores, patient-reported global response assessment, a generic measure of quality of life, and adverse events. INTERVENTIONS: Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily; a combination of the 2 drugs; or placebo. RESULTS: The NIH-CPSI total score decreased modestly in all treatment groups. No statistically significant difference in the primary outcome was seen for ciprofloxacin versus no ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments also did not differ significantly for any of the secondary outcomes. LIMITATIONS: Treatment lasting longer than 6 weeks was not tested. Patients who had received less pretreatment may have responded differently. CONCLUSION: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.

Comparative cardiac safety of low-dose thioridazine and low-dose haloperidol.

AIM: To compare the rate of ventricular arrhythmia, sudden death and unexplained or unattended death among users of thioridazine and haloperidol. METHODS: Observational cohort study of thioridazine and haloperidol users in the UK General Practice Research Database (GPRD) using data from 1987 through 29 June 2000. Patients were followed for 30 days following each study prescription. The event of interest was a diagnosis of ventricular arrhythmia, sudden death, or unexplained or unattended death. Cox regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs), to examine potential confounding factors, and to examine dose-response relationships. RESULTS: Use of thioridazine and haloperidol in the GPRD was primarily in older patients, at low dose (median daily dose 31 mg thioridazine, 1.8 mg haloperidol). There was no association between thioridazine use and the rate of ventricular arrhythmia, sudden death, and unexplained or unattended death (adjusted RR 0.9, 95% CI 0.7, 1.1). The rate did not appear to increase with dose for either drug over the range observed. CONCLUSIONS: These results suggest that low-dose thioridazine and haloperidol have similar cardiac safety.

Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls.

PURPOSE: 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). MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data.

OBJECTIVE: To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls. DESIGN: Cohort study of outpatients using administrative data. SETTING: 3 US Medicaid programmes. PARTICIPANTS: Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis. MAIN OUTCOME MEASURE: Diagnosis of cardiac arrest or ventricular arrhythmia. RESULTS: Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses > or =600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038). CONCLUSIONS: The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect.

Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: the National Institutes of Health Chronic Prostatitis Cohort Study.

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 present in expressed prostatic secretion, voided urine 3 or semen at 2 log concentrations higher than at voided urine 1 or 2. Associations between symptoms, and inflammation and infection were investigated using generalized Mantel-Haenszel methods. RESULTS: Of all participants 50% had urethral leukocytes and of 397 with expressed prostatic secretion samples 194 (49%) and 122 (31%) had 5+ or 10+ WBCs in expressed prostatic secretion, respectively. The prevalence of category IIIa ranged from 90% to 54%, depending on the composite set of cut points. None of the index measures were statistically different (p >0.10) for selected leukocytosis subgroups. Based on prostate and semen cultures, 37 of 488 men (8%) had at least 1 localizing uropathogen. None of the index measures were statistically different (p >0.10) for selected bacterial culture subgroups. CONCLUSIONS: Although men with chronic prostatitis routinely receive anti-inflammatory and antimicrobial therapy, we found that leukocytes and bacterial counts as we defined them do not correlate with severity of symptoms. These findings suggest that factors other than leukocytes and bacteria also contribute to symptoms associated with chronic pelvic pain syndrome.

Demographic and clinical characteristics of men with chronic prostatitis: the national institutes of health chronic prostatitis cohort study.

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 perineum and tenderness in the prostate. The highest self-reported diseases were genitourinary (55%), allergies (53%), neurological (40%) and hematopoietic, lymphatic or infectious (40%). This disease has a significant negative impact on mental and physical domains of quality of life. Almost all patients (95%) reported antimicrobial drug use. Of these 488 participants 280 (57%) reported the previous or current use of 5 or more categories of prostatitis related treatments. CONCLUSIONS: Chronic prostatitis/chronic pelvic pain syndrome is a multifactorial problem affecting men of all ages and demographics. Patients with the chronic pelvic pain syndrome have dismal quality of life and many have benefited only minimally from empirical, goal directed therapy. Long-term followup of this cohort may answer important questions on the natural treated history of this syndrome.