Classification, epidemiology and implications of chronic prostatitis in North America, Europe and Asia.

The last decade has seen a resurgence of interest and exciting new research on chronic prostatitis and related syndromes. One important reason for this enthusiasm is the recognition that chronic prostatitis syndromes represent an important worldwide health care problem. New data suggesting that chronic prostatitis syndromes may have important long-term consequences are a second reason for the resurgence of research interest. This article reviews the new classification of chronic prostatitis syndromes. Emphasis is then given to summarizing new data on the epidemiology of chronic prostatitis. We concentrated on population-based studies employing reasonable case-definitions to survey various populations from North America, Europe and Asia. These studies suggest that prostatitis syndromes are common, with 2-10% of adult men suffering from symptoms compatible with chronic prostatitis at any time. Approximately 15% of men suffer from symptoms of prostatitis at some point in their lives. Preliminary epidemiological and biological studies also suggest that chronic prostatitis may be associated with an increased risk for development of benign prostatic hyperplasia and prostate cancer. These findings support the conclusions that chronic prostatitis is an important international health care problem that merits increased priority from clinicians as well as increased clinical and basic science research.

Short tandem repeat polymorphism linkage to the androgen receptor gene in prostate carcinoma.

BACKGROUND: Due to high polymorphism, common sequences, and ubiquitous presence, short tandem repeats (STRs) may enhance genomic typing to determine prostate carcinoma (CaP) predisposition. The human phosphoglycerate kinase (PGK1) gene is located within Xq11-Xq13, a region implicated in familial prostate carcinoma, androgen insensitivity, perineal hypospadias, and other genitourinary abnormalities. The PGK1 STR is the most polymorphic site described in the Xq11-Xq13 interval and was investigated for its ability to detect differences comparing a heterogeneous CaP population versus controls. METHODS: We compared PGK1 STR allele sizes in 103 localized CaP patients with 299 control subjects to evaluate the STR's ability to detect potential CaP predisposing genetic factors. Allele sizes were measured with an automated DNA sequencer after polymerase chain reaction (PCR) based copying of the PGK1 STR region. Allele sizes were compared using chi square and Mann-Whitney U tests. RESULTS: Among 402 subjects, there were 10 distinct allele sizes consisting of five common and five relatively rare alleles. The PGK1 STR, 12 allele (12 tetrameric repeats) was more common among patients with CaP (p=0.03). Allele 13 was more common in CaP patients > 60 years old than among younger patients (p< 0.005). CONCLUSIONS: Our findings suggest that STRs in the Xq11-Xq13 region and other regions may provide a means to rapidly scan genetic loci in large populations of CaP patients and controls. Within limitations, STRs offer the advantage of relatively uniform protocols that could potentially provide a means to comprehensively scan genomes at known predisposing loci.

Consensus development of a histopathological classification system for chronic prostatic inflammation.

OBJECTIVE: To develop a standardized histopathological classification system for chronic prostatitis (standardized description of prostatic inflammatory infiltrates) based on a literature review, extensive prospective evaluations in two recognized prostatitis research centres and widespread consensus of international urological centres identified as having major expertise or interest in chronic prostatitis. METHODS: Relevant articles for review were identified by a Medline search undertaken by the Cochrane Review Group in Prostate Diseases and Urologic Malignancies, and cross-checking bibliographies of retrieved studies, reviews, book chapters and abstracts of the American Urological Association and International Prostatitis Collaborative Network Annual Meetings. Initial drafts were based on classification systems independently developed by the Prostatitis Research Centers at Queen's University in Canada and University of Washington in the USA. A collaborative draft was distributed to 20 urological/pathological clinical centres who participated in the North American Chronic Prostatitis Collaborative Research Network and First International Prostatitis Collaborative Network. A consensus classification system was then distributed to the participating panel for acceptance. RESULTS: The literature review identified a reasonably consistent description of inflammatory infiltrate locations and patterns that were further incorporated into the draft based on the Queen's University and University of Washington proposals. Eighteen (90%) of the identified Prostatitis Centers participated in the revision of the draft and the final consensus process. The final consensus document classifies prostatic inflammation according to its extent and grade/severity in each tissue compartment (location). Conclusion The consensus of the expert panel was that this classification system can be used in the evaluation of prostatic inflammation in prostate biopsies, transurethral resected prostate chips or prostatectomy specimens. A standardized accepted framework to describe histopathological prostate inflammation will prove useful in evaluating prostate disease.

Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model.

OBJECTIVE: To develop a model to predict transmission of HIV-1 from men to women. DESIGN: HIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated with epidemiological studies of HIV-1 transmission to develop a probabilistic model. SETTINGS: Semen samples were collected from patient subjects in Seattle Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocervical biopsy specimens were obtained from women in Chicago, Illinois. PARTICIPANTS: Eighty-six men (not receiving antiretroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the number of endocervical CCR5 receptors were determined. MAIN OUTCOME MEASURES: Prediction of transmission of HIV-1 from men to women per episode of vaginal intercourse based on the absolute burden of HIV (volume x HIV RNA copies/ml seminal plasma). RESULTS: The model suggests efficient heterosexual transmission of HIV-1 when semen viral burden is high. When semen contains 100 000 copies of non-syncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen, transmission probability is 3 per 10 000 episodes of intercourse. CONCLUSIONS: This model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.

Comparison of complications after radical and partial nephrectomy: results from the National Veterans Administration Surgical Quality Improvement Program.

OBJECTIVE: To determine whether radical nephrectomy causes less morbidity, less mortality and is associated with a shorter hospital stay than is partial nephrectomy. PATIENTS AND METHODS: A total of 1885 nephrectomies (1373 radical and 512 partial) conducted between 1991 and 1998 in the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program were evaluated. Using multivariate analyses, outcomes were risk-adjusted based on 45 preoperative variables to compare mortality and morbidity rates. RESULTS: The unadjusted 30-day mortality was 2.0% for radical and 1.6% for partial nephrectomy (P = 0.58). Risk-adjusting the two groups did not result in a statistically significant difference in mortality. The 30-day overall morbidity rate was 15% for radical and 16.2% for partial nephrectomy (P = 0.52); risk-adjusted morbidity rates were not statistically different. There were no statistically significant differences in the rates of postoperative progressive renal failure, acute renal failure, urinary tract infection, prolonged ileus, transfusion requirement, deep wound infection, or extended length of stay. CONCLUSIONS: Partial nephrectomy carried out in the VA program has low morbidity and mortality rates, comparable with the complication rates after radical nephrectomy.

Bacterial dna sequences in prostate tissue from patients with prostate cancer and chronic prostatitis.

PURPOSE: Although bacterial genetic material has been detected in prostate tissue from patients with various disorders, the prevalence of these organisms is unknown. We tested the hypothesis that bacterial detection rates differ between patients with prostate cancer and those with the chronic prostatitis/pelvic pain syndrome. MATERIALS AND METHODS: Sterile prostate biopsies were obtained during radical retropubic prostatectomy from 107 patients with prostate cancer and using a perineal approach from 170 with the chronic prostatitis/pelvic pain syndrome. Numerous controls were also evaluated. Bacterial ribosomal encoding DNA (165 rDNA) sequences were detected using a polymerase chain reaction assay. Selected positives were cloned, sequenced and compared with DNA databases. RESULTS: Bacterial DNA sequences were detected in 21 (19. 6%) of 107 patients with prostate cancer compared to 79 (46.4%) of 170 with chronic prostatitis (p <0.0001). These bacteria included urogenital pathogens, other described microorganisms and bacteria not reported previously. CONCLUSIONS: Bacterial DNA sequences may be identified in prostate tissue from many patients. Bacterial detection rates in prostate tissue appear to differ among populations, with higher rates among patients with the chronic prostatitis/pelvic pain syndrome than among those with prostate cancer. Future studies of the role of various bacteria in the prostate may provide insight into the pathophysiology of prostate disease.

Amniotic fluid interleukin-6 and preterm delivery: a review.

OBJECTIVE: To evaluate the potential role of amniotic fluid (AF) interleukin (IL)-6 as a predictor of preterm delivery and to consider possible explanations for the proportion of women with elevated AF IL-6 who deliver preterm yet lack microbiologically detectable intra-amniotic infection. DATA SOURCES: We searched the English language human literature in MEDLINE, 1966 through September 1999, using the keywords "labor/infant," "premature," "cytokines/interleukin-6," and "AF." We also examined abstracts from the 1999 meetings of the Society for Maternal-Fetal Medicine and the Society for Epidemiologic Research. We identified other studies by reviewing the reference lists of published articles. METHODS OF STUDY SELECTION: The MEDLINE search yielded 55 citations. We focused on studies that reported on the association between AF IL-6 and preterm delivery. TABULATION, INTEGRATION, AND RESULTS: There is consensus in the literature that elevated AF IL-6 is a stronger predictor of preterm delivery than intra-amniotic infection detected by either microbiologic culture or polymerase chain reaction (PCR). Among women with elevated AF IL-6, PCR could detect a higher proportion of intra-amniotic infection than culture. A number of women with elevated AF IL-6 (33-70%) deliver preterm and do not have evidence of intra-amniotic infection by either culture or PCR. Possible explanations for this observation are considered. CONCLUSION: Elevated AF IL-6 is strongly associated with preterm delivery and merits future consideration in clinical settings to predict preterm delivery and guide patient care. Development of improved polymerase chain reaction-based clinical methods to detect intra-amniotic infection is necessary to better understand the relationship between elevated AF IL-6, intra-amniotic infection, and preterm delivery.

Prostate histopathology and the chronic prostatitis/chronic pelvic pain syndrome: a prospective biopsy study.

PURPOSE: The chronic prostatitis/chronic pelvic pain syndrome is a common clinical syndrome characterized by lower genitourinary tract symptoms, particularly pain in the perineum or genitalia, voiding symptoms, such as dysuria or frequency, and sexual dysfunction in the absence of uropathogens in the urine or prostatic secretions. The term prostatitis is based on the presumption that prostatic inflammation is important in the pathophysiology of this syndrome. To our knowledge there has been no systematic characterization of the degree and nature of inflammation in the prostate in symptomatic cases. MATERIALS AND METHODS: Prostate histopathology in 368 biopsies from 97 patients with the chronic prostatitis/chronic pelvic pain syndrome was characterized.. RESULTS: Prostatic inflammation was detected in only 33% of patients, including 29% with mild (less than 10 leukocytes per 1 mm. field) and 4% with moderate (between 10 and 200) or severe (more than 200) infiltrate. Of the 3 patients with moderate inflammation 1 had glandular, 1 periglandular and 3 multifocal or diffuse distribution of leukocytes in the interstitium. Some patients had more than 1 pattern of inflammation. CONCLUSIONS: The finding of moderate or severe inflammation in only 5% of 97 patients argues for the need to reevaluate current concepts of the pathophysiology of the chronic prostatitis/chronic pelvic pain syndrome.

A hemizygous short tandem repeat polymorphism 3' to the human phosphoglycerate kinase gene.

The human phosphoglycerate kinase (PGK) gene is located within Xq11-Xq13, a region implicated in genitourinary diseases including: prostate cancer, androgen insensitivity, perineal hypospadias, and other genetic abnormalities. The PGK gene and the androgen receptor gene are in linkage disequilibrium. PGK has been mapped extensively for nuclease-sensitive sites, methylation sites, and flanking DNA sequences. A PGK-associated BstXI polymorphism has been used to determine clonality of neoplastic tissues. Using fluorescent PCR product analysis and DNA sequencing, we discovered that a short tandem repeat (STR) in the 3' flanking region of the PGK gene is polymorphic. Among 231 individuals, there were nine distinct alleles, including eight based on variations in the number of TATC repeats. The PGK STR demonstrated hemizygosity, consistent with its X-chromosomal location and with an absence of cross-hybridizing autosomal homologs. The polymorphic PGK STR shows promise for rapid investigation of neoplastic clonality, for personal identification, and for studies of inherited predisposition to urologic disorders.

Early and persistent human immunodeficiency virus type 1 (HIV-1)-specific T helper dysfunction in blood and lymph nodes following acute HIV-1 infection.

Without potent antiretroviral therapy, most human immunodeficiency virus type 1 (HIV-1)-infected persons experience a progressive decline in CD4+ T cells and impairment in T helper function. It is unclear how soon after infection T cell dysfunction occurs. T helper responses were examined in blood and lymphoid tissue of 39 untreated patients with acute HIV-1 infection. Within the first 3 months, lymphoproliferative responses to mitogen, recall antigens, and HIV-1 antigens were impaired. After 6-9 months, responses to phytohemagglutinin and recall antigens improved. However, HIV-1-specific lymphoproliferation remained largely undetectable throughout 2 years of infection, and results were similar upon evaluation of lymphoid cells. Rare patients with HIV-1-specific responses had significantly lower plasma HIV-1 RNA levels than did nonresponders. These results indicate that T helper dysfunction occurs early after HIV-1 acquisition and that untreated individuals rarely recover HIV-specific helper responses; these findings lend support for early therapeutic intervention to prevent the destruction and further impairment of the T helper cells.

Role of human papillomavirus typing in diagnosis and clinical decision making for a giant verrucous genital lesion.

A 60-year-old man presented with a 12.0 x 10.0-cm exophytic, verrucous genital plaque. Multiple biopsy specimens were evaluated by standard histologic analysis and polymerase chain reaction assays for human papillomavirus (HPV) deoxyribonucleic acid. All biopsy specimens showed histopathologic changes consistent with giant condyloma of Buschke-Lowenstein (GCBL), were uniformly positive for HPV 6/11, and showed a weaker signal for HPV 16. Published reports suggest that the presence of HPV may be useful in differentiating GCBL from verrucous carcinoma (VC), but absence of "high-risk" HPV types in GCBL cannot exclude focally invasive squamous cell carcinoma. Screening for HPV may be a helpful adjunct in differentiating GCBL from VC, but histopathologic criteria for malignancy should take precedence over HPV typing when determining management.

Primary penile lymphoma: diagnostic difficulties and management options.

A 76-year-old man presented with a painless penile ulcer. After an extensive negative workup, CO(2) laser excision was performed with penile reconstruction. Histologic examination revealed an anaplastic, large cell lymphoma with CD30(+) cells. Computed tomography scans of the thorax, abdomen, and pelvis were negative. He received no adjuvant therapy and was without evidence of recurrence after 18 months. We review published reports and discuss the management options for this rare lesion.

Diverse and related 16S rRNA-encoding DNA sequences in prostate tissues of men with chronic prostatitis.

Treatment of chronic prostatitis/chronic pelvic pain syndrome is often empirical because clinical culture methods fail to detect prostate-associated pathogens in >90% of patients. Previously, we tested a variety of specific-microorganism PCRs and began a DNA sequence study after we found that 77% of prostatitis patients were PCR positive for prokaryotic rRNA-encoding DNA sequences (rDNAs) despite negative cultures using optimal techniques. In the present study, 36 rDNA clones from 23 rDNA-positive patients were sequenced. This study represents more than twice the total rDNA sequence and more than twice the number of patients in the previous study. The increased number of patients and clones sequenced allowed enhanced phylogenetic analyses and refinements in our view of rDNA species inhabiting the prostate. A continuum of related rDNAs that might be arbitrarily described as two major groups of rDNAs and several minor groups was found. Sequences termed Pros A, identified in 8 (35%) of 23 rDNA-positive patients, grouped with Aeromonas spp. in phylogenetic studies. Sequences termed Pros B, identified in 17 (74%) of 23 rDNA-positive patients, were distinct from previously reported sequences, although all were >90% similar to known gram-negative bacteria. Of the nine patients for whom multiple rDNAs were sequenced, six had biopsy specimens containing rDNAs from more than one species. Four (17%) patients had rDNAs different from those of the Pros A and Pros B groups. Of these four, one patient had rDNA similar to that of Flavobacterium spp., another had rDNA similar to that of Pseudomonas testosteroni, and two patients had rDNAs <70% similar to known rDNAs. These findings suggest that the prostate can harbor bacteria undetectable by traditional approaches. Most of these diverse sequences are not reported in environments outside the prostate. The sequence similarities suggest adaptation of limited groups of bacteria to the microenvironment of the prostate. Further studies may elucidate the relationship of prostate-associated bacteria to chronic prostatitis/chronic pelvic pain syndrome.

Human herpesvirus 8 in the prostate glands of men with Kaposi's sarcoma.

The epidemiology of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) resembles that of a sexually transmitted pathogen. However, human herpesvirus 8 (HHV-8), the proposed cause of KS, is found in semen only infrequently and at low titers. To determine whether HHV-8 was present in the urogenital tract, transrectal ultrasound-guided prostate biopsies were obtained from six men with KS (five with concurrent HIV infection) and four without KS (three with concurrent HIV) and assayed for HHV-8 by PCR. Nine of the 10 men were seropositive for HHV-8. Five of nine HHV-8-seropositive men had HHV-8 DNA detected in prostate tissue by solution-based PCR. All five currently had KS or had it previously. In two subjects, prostate tissue was the only identified source of HHV-8. In situ PCR on serial sections of prostate indicated that HHV-8 infection was localized to discrete areas of the prostate. When detected, HHV-8 DNA was present in the nuclei of >90% of the glandular epithelial cells. In situ hybridization for HHV-8 mRNA revealed that between 1 and 5% of cells harboring HHV-8 DNA expressed viral transcripts associated with HHV-8 replication (T1.1 transcript), while >90% expressed gene products associated with viral latency (T0.7 transcript). Intermittent replication of HHV-8 in the prostate and subsequent shedding of virus in semen may be crucial factors for determining whether HHV-8 can be transmitted through sexual activity.

Bladder petechiae after cystoscopy and hydrodistension in men diagnosed with prostate pain.

PURPOSE: We determined if men with prostate pain syndromes have petechiae in the bladder after hydrodistension. MATERIALS AND METHODS: A total of 60 men with the diagnosis of prostate pain and without bacteriuria underwent cystoscopy and hydrodistension under a general or regional anesthetic. RESULTS: Of the 60 men 35 (58%) had moderate to severe petechiae similar in appearance to women with interstitial cystitis after hydrodistension. Men with moderate to severe bladder petechiae had fewer leukocytes in expressed prostatic secretions, smaller bladder capacities and less often testicular pain than men with more normal appearing bladders after hydrodistension. Symptomatic improvement 2 to 6 weeks after hydrodistension was more common in men with moderate to severe petechiae than in those with fewer petechiae. Absence of rectal pain predicted symptomatic improvement after hydrodistension. CONCLUSIONS: We suggest that bladder petechiae, and possibly interstitial cystitis or a related condition, may be more frequently associated with prostate pain syndromes in men than previously appreciated.

Absence of detectable human herpesvirus 8 in the semen of human immunodeficiency virus-infected men without Kaposi's sarcoma.

The prevalence of human herpesvirus 8 (HHV-8)/Kaposi's sarcoma (KS)-associated herpesvirus was investigated in the semen of 99 human immunodeficiency virus (HIV)-infected men (median CD4 cell count, 357/mm3) by use of a polymerase chain reaction (PCR) assay capable of detecting <10 copies of HHV-8 DNA. Of the subjects, 95 (96%) self-identified as men who have sex with men (MSM), and 3 had a history of clinical KS. Seminal cell specimens were negative for HHV-8 in 98 subjects. None of the 26 without KS (27.1% of 96 tested) who were seropositive for HHV-8 by IFA for latency-associated nuclear antigens had HHV-8 detected in their semen. The only subject with any evidence for seminal HHV-8 DNA was seropositive for HHV-8 and had active KS. HHV-8 was detected in 10 (10.4%) of 96 peripheral blood mononuclear cell specimens. The prevalence of HHV-8 DNA by PCR in semen of HIV-infected MSM without KS is low.

Broad-spectrum bacterial rDNA polymerase chain reaction assay for detecting amniotic fluid infection among women in premature labor.

We amplified bacterial 16S rRNA encoding DNA (rDNA) with the polymerase chain reaction (PCR) to detect amniotic fluid infection in 69 women in premature labor whose membranes were intact. Bacterial rDNA was detected by PCR in samples from 15 (94%) of 16 patients with positive amniotic fluid cultures. Bacteria were detected by PCR in samples from 5 (36%) of 14 patients with negative cultures and elevated interleukin (IL)-6 levels vs. 1 (3%) of 39 patients with negative cultures and IL-6 levels of < or = 2,000 pg/mL (P < .01). The median amniotic fluid cytokine levels and the pregnancy outcomes were similar for patients with positive amniotic fluid cultures and those with negative cultures and positive rDNA PCR assays. The association between amniotic fluid infection and premature labor may be underestimated on the basis of amniotic fluid culture results. The broad-spectrum bacterial 16S rDNA PCR assay may prove useful for diagnosing amniotic fluid infection.

Bacteria in the prostate tissue of men with idiopathic prostatic inflammation.

PURPOSE: 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. MATERIALS AND METHODS: Evaluation consisted of cultures of urethra, urine and transperineal prostate biopsies, specifically for commensal and fastidious organisms, and leukocyte counts of expressed prostatic secretions. RESULTS: 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). CONCLUSIONS: Bacterial colonization/invasion of the prostate may be associated with inflammatory prostatitis in some cases.

Prokaryotic DNA sequences in patients with chronic idiopathic prostatitis.

Half of all men experience symptoms of prostatitis at some time in their lives, but the etiology is unknown for more than 90% of patients. Optimal clinical and culture methods were used to select 135 men with chronic prostatitis refractory to multiple previous courses of antimicrobial therapy. The subjects had no evidence of structural or functional lower genitourinary tract abnormalities of bacteriuria or bacterial prostatitis by traditional clinical tests, or of urethritis or urethral pathogens by culture. Specific PCR assays detected Mycoplasma genitalium, Chlamydia trachomatis, or Trichomonas vaginalis in 10 patients (8%). Broad-spectrum PCR tests detected tetracycline resistance-encoding genes, tetM-tetO-tetS, in 25% of patients and 16S rRNA in 77% of subjects. The tetM-tetO-tetS-positive cases constituted a subset of the 16S rRNA-positive cases. Patients with 16S rRNA were more likely to have > or = 1,000 leukocytes per mm3 in their expressed prostatic secretion than men whose prostate biopsy specimens were negative for 16S rRNA (P < 0.001). Based on direct sequencing and repetitive cloning, multiple sources of 16S rRNA were observed in individual patients. Sequences of 29 cloned PCR products revealed 16S rRNAs distinct from those of common skin and gut flora. These findings suggest that the prostate can harbor microorganisms that are not detectable by traditional approaches. These organisms may be associated with inflammation in the expressed prostatic secretions. Molecular methods hold great promise for identifying culture-resistant microorganisms in patients with chronic prostatitis.