Inflammatory Prostatitis Research Articles

Prostatitis/Chronic Pelvic Pain Syndrome

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.

Measurement of nitric oxide may differentiate between inflammatory and non-inflammatory prostatitis

The majority of patients with prostatitis have chronic non-bacterial prostatitis/chronic pelvic pain syndrome of inflammatory type (Category IIIA) or non-inflammatory type (Category IIIB), based on the National Institutes of Health classification. The aim of this study was to investigate whether measurement of nitric oxide (NO) formation in the prostatic urethra can be used as a marker for inflammation in the evaluation of patients with chronic prostatitis/pelvic pain syndrome. A total of 25 men with prostatitis were examined. In 8 patients >10 white blood cells/high-power field (WBC/hpf) were found in expressed prostatic secretion (EPS) (Category IIIA), whereas the other 17 had no signs of inflammation (Category IIIB). NO production was measured using a silicon catheter, with the catheter balloon being placed in the prostatic urethra. Room air (5 ml) was incubated for 5 min and analyzed. NO formation in the urinary bladder was also measured. The NO concentration in the prostatic urethra was significantly higher in the 8 patients with >10 WBC/hpf than in those with <10 WBC/hpf. The NO concentration in the urinary bladder was low in both groups. We found an elevated NO concentration in the prostatic urethra in patients with >10 WBC/hpf in the EPS but not in those with <10 WBC/hpf, which supports the theory of different pathogeneses for Categories IIIA and IIIB. Measurement of NO production in the prostatic urethra can be used to discriminate between the two categories and as the method is easy and fast it may represent an attractive alternative to the four-glass test.

Sperm parameter abnormalities, low seminal fructose and reactive oxygen species overproduction do not discriminate patients with unilateral or bilateral post-infectious inflammatory prostato-vesiculo-epididymitis

We have shown that patients with prostato-vesiculo-epididymitis (PVE) have the worst sperm output compared to patients with prostato-vesiculitis or prostatitis alone. The present study was undertaken to closely examine whether unilateral or bilateral PVE had a different impact on sperm parameters, seminal fructose levels and reactive oxygen species (ROS) overproduction. To accomplish this, 78 patients with persistent post-infectious inflammatory PVE, clearly identified by scrotal and transrectal ultrasonography, and 30 patients with asymptomatic post-infectious inflammatory prostatitis (control group) underwent semen analysis (including seminal leukocyte concentration and number of spermiophagies), seminal fructose measurement and sperm ROS production from 45 and 90% Percoll fractions. Fifty patients turned out to have PVE bilaterally, whereas the remaining 28 had unilateral PVE. Patients with bilateral PVE had sperm concentration and total sperm number significantly lower than those found in patients with unilateral PVE. The other sperm parameters, the physicochemical properties (hyperviscosity, the presence of nonspecific agglutination, delayed liquefaction), seminal fructose levels and ROS production in both 45 and 90% Percoll fractions turned out similar between the two groups. Patients with bilateral or unilateral PVE had sperm parameters, seminal fructose levels and ROS production significantly worst than those found in patients with prostatitis alone. In conclusion, although patients with bilateral PVE had a decreased number of spermatozoa, the other sperm parameters and seminal fructose levels did not reflect the extension of PVE. Therefore, the diagnosis of unilateral or bilateral involvement of this complicated form of male accessory gland infection relies on scrotal and transrectal ultrasonography.

Canadian Laboratory Standards for Sexually Transmitted Infections: Best Practice Guidelines

Sexually transmitted infections (STI) continue to spread, and show no international boundaries. Diseases such as gonorrhea and syphilis, which we thought were under control in Canadian populations, have increased in incidence. Sexually transmitted or associated syndromes such as cervicitis, enteric infections, epididymitis, genital ulcers, sexually related hepatitis, ophthalmia neonatorum, pelvic inflammatory disease, prostatitis and vulvovaginitis present a challenge for the physician to identify the microbial cause, treat the patient and manage contacts. During the past 10 years, new technologies developed for the diagnosis of STIs have provided a clearer understanding of the real accuracy of traditional tests for the diagnosis of infections caused byChlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex viruses, hepatitis B virus, human papillomaviruses, HIV,Haemophilus ducreyi, Trichomonas vaginalisand mycoplasmas. This has presented a major challenge to the diagnostic laboratory, namely, selecting the most sensitive and specific test matched with the most appropriate specimens to provide meaningful and timely results to facilitate optimal patient care.

Prevalence of chronic prostatitis and its effects on male infertility

To investigate the prevalence of chronic prostatitis (CP) in male infertility patients and its effects on male infertility. 534 male patients with complaints of male infertility were interviewed for the history of prostatic disease and underwent digital rectal examination of prostate, analysis of semen and express prostatic secretions (EPS). Bacterial culture of urine was done in 40 randomly selected inflammatory CP patients by pre- and post-message method (pre- and post-massage test, PPMT). 209 out of the 534 patients with male infertility were diagnosed as chronic prostatitis with a prevalence rate of 39.1%, among which 46 with CP type II and IIIA with the prevalence rate of 8.6%, 28 with CP type IIIB (5.2%), and 135 with CP type IV (25.3%) respectively. Positive bacterial culture was found in 10 out of the 40 cases of inflammatory chronic prostatitis (25.0%). The bacterial infection rate was 24.2% (8/33) in the cases of CP type IV. The prevalence rate of liquefaction dysfunction was much higher in the patients of male infertility with CP (22.7%) than in those without CP (14.3%, P < 0.05), however, it had little influence on the quality of semen, pH value, sperm density, and sperm motility. Quite common in patients with male infertility, CP prolongs the time of liquefaction, but has no other reverse influence on semen.

806 Antibiotic treatment of asymptomatic inflammatory prostatitis in patients with elevated PSA: Can biopsies be avoided?

806 Antibiotic treatment of asymptomatic inflammatory prostatitis in patients with elevated PSA: Can biopsies be avoided?

Classification and diagnosis of prostatitis: a gold standard?

The National Institutes of Health Classification System for prostatitis has now been accepted by the North American and International urology community. This categorization system consists of category I (acute bacterial prostatitis), category II (chronic bacterial prostatitis), category III (chronic prostatitis/chronic pelvic pain syndrome - CP/CPPS) and category IV asymptomatic inflammatory prostatitis. The evaluation of a patient with category I and category II bacterial prostatitis consists of history and physical examination and urine culture for lower urinary tract localization cultures, respectively. The clinical tests for the evaluation of CP/CPPS can be classified as mandatory, recommended and optional. Mandatory evaluations include history and physical examination, urinalysis and urine culture. Recommended evaluations include lower urinary tract localization tests, symptom index, flow rate, residual urine determination and urine cytology. Optional evaluations include semen analysis and culture, urethral swab, urodynamics, cystoscopy, imaging, and prostate specific antigen determination. The physician must individualize a rational diagnostic strategy for each patient. There is no 'gold standard' for the diagnosis and evaluation of patients presenting with prostatitis.

Le traitement des prostatites

Purpose. – Prostatitis are frequently recognized in general practice and often are a diagnosis and therapeutic challenge. We review here the updated knowledge on diagnosis and therapy of prostatitis. Current knowledge and key points. – Prostatitis are divided into acute bacterial prostatitis (I), chronic bacterial prostatitis (II), chronic prostatitis/ chronic pelvic pain syndrome (III) and asymptomatic inflammatory prostatitis. Chronic prostatitis/ chronic pelvic pain syndrome are divided into : inflammatory (IIIA) and noninflammatory (IIIB). Treatment of prostatitis should follow evidence based guidelines recently published. Acute prostatitis should be treated by ciprofloxacine 500 mg tid or ofloxacine 200 mg bid or cotrimoxazole 960 mg bid for 4 weeks (CIII). When bacteremia occurs third generation cephalosporin with gentamicin should be used (CIII). In chronic bacterial prostatitis ciprofloxacine 500 mg tid or ofloxacine 200 mg bid or norfloxacine 400 mg bid or cotrimoxazole 960 mg bid for 4 weeks may be used (BIII). Future prospects and projects. – Molecular techniques should improve the etiological diagnosis of prostatitis and their treatment.

The Chronic Pelvic Pain Syndrome After Brachytherapy for Carcinoma of the Prostate

Bacterial inflammatory prostatitis comprises approximately only 5% of cases of “prostatitis-like” pain. Penile, scrotal and perineal pain associated with voiding complaints may represent prostatitis or pudendal neuropathy. Fibrosis of Alcock’s canal may produce compression neuropathy, or pudendal neuralgia.1 CASE REPORT An asymptomatic 67-year-old man with localized carcinoma of the prostate underwent “sandwich” radiation therapy (combined brachytherapy and external beam radiation therapy) elsewhere in 1999. Radiation dosage was unknown. History included transurethral prostatectomy in 1972 and acute prostatitis in 1986. The patient presented with 20-month history of severe burning at the glans and anus associated with constant perineal and rectal pressure. Hourly urinary frequency increased to every 20 minutes after exercising on a treadmill or stair climber machine, or after squatting while gardening. Clothing or diapers touching the glans stimulated dribbling incontinence. Rising from a sitting position caused a voiding reflex. Pain was aggravated by sitting and driving, and intensified following ejaculation. Pain was reduced by standing, was generally relieved when the patient was recumbent and was always relieved by sitting on a toilet. Severe pain while riding a stationery bicycle caused discontinuation of this lifelong activity. On examination the anus and prostate were sensitive. Compression of the sacrospinous ligament bilaterally reproduced the complaints. Pinprick sensation was normal throughout the pudendal distribution. Peau d’orange was noted in a 10 cm. area of gluteal skin. Evaluation showed pyuria with greater numbers of white blood cells in the voiding bottle 3 (post-prostatic massage) urine. Cultures were sterile. Excretory urography was normal. Cystoscopy revealed granulation tissue in a widely patent prostatic urethra. Urodynamic evaluation demonstrated a small capacity bladder with detrusor instability. Colorectal, gastrointestinal and spinal evaluations were normal. National Institutes of Health category IIIA prostatitis and pudendal neuralgia were diagnosed. Treatment included 10 mg. ketorolac every 6 hours for 5 days, 50 mg. amitriptyline at bedtime and 150 mg. clindamycin 3 times daily. Former treatment with 600 mg. gabapentin 3 times daily was continued. After 2 months of therapy symptoms persisted. Therefore, bilateral pudendal nerve perineural corticosteroid injections were begun.2 A “miraculous” relief of pain occurred 10 days after the second injection, and 2 days after starting levofloxacin 500 mg. per day and increasing the dose of gabapentin to 2,700 mg. per day. Symptomatic improvement included relief of pain, absence of urgency and frequency, and cessation of incontinence. Relief continued at 6 months following injections. DISCUSSION Urogenital/rectal pain, irritable bladder and pain following ejaculation are common in pudendal neuralgia. Bacterial prostatitis may induce similar complaints. Radiation therapy may cause neuritis or fibrosis within Alcock’s canal. Sterile aerobic cultures suggest anaerobic prostatitis. Krieger et al identified anaerobic bacteria in 65% of men with chronic

Medical history and etiology of prostate cancer.

The clinical course of prostate cancer is influenced by hormonal therapies; hence it is plausible that clinical syndromes that influence hormonal levels also affect risk of prostate cancer. Hormones may be involved in its etiology as well as various clinical conditions that may be related to hormonal imbalance such as cirrhosis and diabetes mellitus. Cirrhosis induces changes in estrogen metabolism as it is noted in the development of testicular atrophy and gynecomastia due to hyperestrogenism. Autopsy studies are conducted to investigate the relation of cirrhosis with prostate cancer prevalence. Meanwhile the relation between diabetes and prostate cancer is likely to be complex as noted on the discrepancies between study of health professionals and the Cancer Prevention Study. On the other hand several studies have examined vasectomy in relation to risk of prostate cancer. However biologic basis underlying such relation remains to be speculative. In terms of a link between inflammatory states and carcinogenesis prostatitis is considered as having carcinogenic potential. As such study of chronic prostatitis in relation to prostate cancer should be undertaken since the epidemiologic data are insufficient.

Evaluation of the cytokines interleukin 8 and epithelial neutrophil activating peptide 78 as indicators of inflammation in prostatic secretions

Objectives. Chronic prostatitis/chronic pelvic pain syndrome (CPPS) is a disorder characterized by pelvic pain and varying degrees of inflammation exhibited in expressed prostatic secretions (EPS). To provide objective parameters of inflammation, we measured the cytokines interleukin 8 (IL-8) and epithelial neutrophil activating peptide 78 (ENA-78) in EPS of healthy men, men with benign prostatic hyperplasia (BPH), men with bacterial prostatitis (BP), and men with chronic prostatitis/CPPS. Methods. Enzyme-linked immunosorbent assays of the EPS for IL-8 and ENA-78 were done in 63 men: control (n = 9), BPH (n = 6), BP (n = 3), inflammatory CPPS (National Institutes of Health [NIH] category IIIa) (n = 17), noninflammatory CPPS (NIH category IIIb) (n = 17), and asymptomatic inflammatory prostatitis (NIH category IV) (n = 11). Results. IL-8 was detectable in all patients, and ENA-78 was detectable in all except 2 patients (threshold of detection 10 pg/mL for IL-8, 15 pg/mL for ENA-78). Mean levels of IL-8 [ENA-78] were similar in control (3010 pg/mL [423 pg/mL]), BPH (3341 pg/mL [98 pg/mL]), and IIIb (2751 pg/mL [335 pg/mL]) groups. Both cytokine levels were higher in BP (11,175 pg/mL [13,761 pg/mL]), IIIa (10,418 pg/mL [2240 pg/mL]), and IV (8571 pg/mL [1865 pg/mL]) groups. A statistically significant difference between the control group versus BP, IIIa, and IV ( P <0.05) groups was found for IL-8 but not for ENA-78. Conclusions. IL-8 and ENA-78 are frequently elevated in the EPS of men with BP, CPPS IIIa, and asymptomatic inflammatory prostatitis category IV. These cytokines are direct mediators of leukocyte accumulation and activation at inflammatory sites and may be responsible, in part, for the presence of inflammatory reaction in the prostate.

Urinary tissue factor levels in patients with bladder andprostate cancer

Aims Coagulation activation is a recognized complication of cancer in which increased tissue factor (TF) is implicated. TF can be detected in urine (uTF). This study assesses uTF levels in benign and malignant urological disease and correlates the results with conventional markers of tumour progression. Methods Using a simple and reproducible kinetic chromogenic assay, we determined uTF levels in controls (normal volunteers (n=57) and patients with renal stones (n=30)), benign and malignant bladder (n=75) or prostate (n=106) disease and in patients with or without recurrent bladder cancer (n=30). Each benign disease group was stratified as inflammatory (cystitis or prostatitis) or non-inflammatory (negative cystoscopy following haematuria or benign prostatic hypertrophy). Results The controls and the benign non-inflammatory results were indistinguishable. The malignant and inflammatory groups showed raised uTF levels over controls (P<0.001 bladder and P<0.01 prostate). The difference between malignant and benign inflammatory disease was only significant for the bladder group. uTF levels were significantly related to histological tumour grading, prostate serum specific antigen, static bone scan images and recurrence status. Conclusions uTF levels can distinguish, statistically but not without overlap, patients with malignancy from normal controls and benign non-inflammatory conditions. Discrimination between inflammatory and malignant disease has only been demonstrated in the bladder. uTF levels showed a significant association with markers of tumour progression or metastasis and may be useful in predicting bladder tumour recurrence.

EVALUATION OF THE BACTERIAL FLORA OF THE PROSTATE USING A 16S rRNA GENE BASED POLYMERASE CHAIN REACTION

The role of bacteria in the chronic pelvic pain syndrome (nonbacterial prostatitis and prostatodynia) is controversial and difficult to assess because the bacterial flora of the prostate is not well defined. Polymerase chain reaction (PCR) is a highly sensitive molecular method of bacterial detection. It confirms the sterility of tissue with a high level of confidence and detects small numbers of microbial agents that may represent pathogens. We performed PCR to determine bacterial colonization of the prostate in presumably healthy men and in those undergoing simple or radical prostatectomy. We analyzed 28 prostate samples from 18 organ donors from whom prostate tissue was obtained under sterile surgical conditions at organ withdrawal, 14 sterile surgical prostate specimens from 7 patients undergoing radical prostatectomy for prostate cancer who previously underwent transrectal biopsy and 6 sterile surgical specimens from 2 men who underwent simple prostatectomy for benign prostatic hyperplasia (BPH), including 1 with an indwelling catheter for several weeks. For PCR we used 2 sets of primers to detect bacterial 16S rRNA gene sequences. Normal prostate tissue seeded in vitro with known numbers of Escherichia coli was used to assess the sensitivity of PCR. Only 3 of the 28 organ donor samples had histological signs of minimal inflammation and all other samples appeared to be normal without evidence of inflammatory reaction. All of these samples were PCR negative. Of several PCR control reactions the mixture of prostate tissue seeded with known numbers of E. coli demonstrated the high sensitivity of the assay, allowing the detection of as few as 6 bacteria in the presence of 25 mg. of prostate tissue. A focal and heterogeneous distribution of inflammation and infection was noted in the 14 radical prostatectomy specimens. In the prostate cancer and BPH groups there was a strong association of inflammation with positive PCR findings. Of 11 samples 3 without but all 9 with inflammation were PCR positive. PCR is a highly sensitive method for detecting bacteria in the prostate. In our study negative PCR reactions in the prostate tissue of apparently healthy men made the presence of normal bacterial flora in the prostate extremely unlikely. The presence of bacteria and/or inflammation in radical prostatectomy specimens was found to be a localized process. Concordance between inflammation and positive PCR results in simple and radical prostatectomy specimens suggests that bacteria may frequently have a role in histologically inflammatory prostatitis.

Bacteria in the Prostate Tissue of Men With Idiopathic Prostatic Inflammation

Although antibiotics represent the first line of treatment for prostatitis syndromes, physicians can document infection in remarkably few cases. We examined the relationship of genitourinary infection to inflammatory prostatitis in 85 subjects without bacteriuria. Evaluation consisted of cultures of urethra, urine and transperineal prostate biopsies, specifically for commensal and fastidious organisms, and leukocyte counts of expressed prostatic secretions. Men with inflamed expressed prostatic secretions (25) were more likely to have any bacterial isolation (p = 0.01), positive cultures for anaerobic bacteria (p = 0.03), higher total bacterial counts (p = 0.02) and more bacteria, species isolated (p = 0.02) in prostate biopsy cultures than men without expressed prostatic secretion inflammation (60). Bacterial colonization/invasion of the prostate may be associated with inflammatory prostatitis in some cases.

Spondyloarthritis and Enthesopathy

Spondyloarthritis (Sp) is newly defined as arthritis that is clinically, pathologically, and genetically related to and predisposed to ankylosing spondylitis (AS) and Reiter's syndrome (RS) rather than to rheumatoid arthritis (RA). A diagnosis of Sp does not necessarily imply arthritis of the spine and does not depend on the demonstration of roentgenographic sacroiliitis that, in this conceptualization, is recognized not as the essential hallmark, but rather merely as a diagnostic "way station" on a continuum of disease, which may (but need not necessarily) begin with RS or be complicated during its course by AS or RS. Spondyloarthritis is distinctively characterized morphologically and clinically by disproportionate inflammation at the entheses, the sites of attachment of tendons and ligaments to bone. Family history or presence of enthesopathic pain, psoriasis, inflammatory bowel disease, uveitis, recurrent urethritis, prostatitis or cervicitis, keratoderma blennorrhagicum, HLA-B27, and asymmetric pauciarticular lower lower extremity arthritis without rheumatoid factor or rheumatoid nodules suggests a diagnosis of Sp rather than RA.

Early Roentgenologic Changes in Idiopathic Ulcerative Colitis

The early radiologic diagnosis of idiopathic ulcerative colitis is difficult. Although it should be recognized that the roentgen changes are usually not apparent until the clinical findings are well established, it is important that the roentgenologist be aware of the earliest manifestations by which the diagnosis may be made, especially in those cases in which the lesions are not visible by means of sigmoidoscopy, or in which for some reason sigmoidoscopy has been omitted from the examination. The usual roentgenologic description of ulcerative colitis applies to the late stages of the disease, that is, absence of haustration, producing the “lead pipe” effect, shortening of the colon, rapid filling and emptying, shagginess of outline, pseudopolyposis, and fibrosis and rigidity of the wall. A few references to a disordered mucosal pattern, visible on the post-evacuation roentgenogram, are to be found in the literature, but with rare exception only the moderately advanced to advanced stages of the disease are described. Kadrnka and Audeoud (1) are among the few who have observed changes of a somewhat earlier phase. They speak of a marbled pattern and gross dentate appearance of the border of the large bowel, and, by using a colloidal preparation, they found that a finely granular aspect, suggestive of small ulcerations, could be produced on the post-evacuation roentgenogram. Knothe (2) also noted, in addition to the well recognized lack of haustration and rapid filling and narrowing of the colon, a regular fine dentation of the border which he considered a sign of vagal irritation. This appearance could be produced experimentally by the external application of cold or by the administration of pilocarpine; it could be reversed by the use of atropine. It was evident also, Knothe found, in patients with local irritation such as is caused by “mucous colitis” and in others who had peptic ulcer, pelvic inflammatory disease, prostatitis, appendicitis, distant tuberculosis, diverticulitis, and carcinoma of the colon. He concluded that it is an irritative rather than an inflammatory phenomenon. Hodges (3) describes minute serrations on the edge of the filled colon as evidence of diffuse small ulcerations. In a recent review, Ricketts, Kirsner, and Palmer (4) found that in 60, or 39 per cent, of 156 patients with ulcerative colitis the findings on the first roentgenologic examination were normal. In the great majority of cases, ulcerative colitis is of the ascending type, beginning in the rectum and sigmoid and extending proximally toward the cecum; it is in the rectum and sigmoid, therefore, that the earliest roentgen changes may usually be found. On the other hand, de Castro Barbosa, Bargen, and Dixon (5) reported a selected group of 140 patients in whom the rectum and sigmoid were free of disease, the colitis being regional and segmental.