Evaluation of Leukocyte Threshold Values in Semen to Detect Inflammation Involving Seminal Interleukin-6 and Interleukin-8.

OBJECTIVE: To evaluate leukocyte threshold values in semen to detect inflammation involving seminal interleukin (IL)-6 and IL-8. MATERIALS AND METHODS: The levels of leukocytes, IL-6, and IL-8 in semen were determined. The 75th and 90th percentiles of seminal IL-6 and IL-8 were considered as "high" and "very high" concentrations, respectively. Inflammatory semen was defined based on high levels of IL-6 (≥86.75 pg/mL) or IL-8 (≥4460 pg/mL). Very high levels of IL-6 (≥228 pg/mL) or IL-8 (≥12,480 pg/mL) were used to define acute seminal inflammation. On the basis of high and very high levels of IL-6 or IL-8, receiver operating characteristic curves were generated to evaluate leukocyte threshold values. RESULTS: Leukocytes at a cutoff level of 1 × 10(6)/mL had 51% sensitivity and 95% specificity to detect high levels of IL-6, whereas on the basis of very high levels of IL-6, the same cutoff level revealed 82% sensitivity and 90% specificity. Similarly, leukocytospermia demonstrated low sensitivity (56%) to detect high levels of IL-8 but acceptable sensitivity (94%) and specificity (92%) to predict very high levels of IL-8. The cutoff level of 0.315 × 10(6) leukocytes/mL had optimal sensitivity and specificity for predicting high levels of inflammatory cytokines. CONCLUSION: Leukocytospermia demonstrated poor sensitivity to detect seminal inflammation, as defined by high levels of inflammatory cytokines. The optimal threshold value to detect inflammation was found to be 0.315 × 10(6) leukocytes/mL. On the basis of very high levels of IL-6 or IL-8, leukocytospermia is a sensitive and specific marker to predict acute seminal inflammation.

Influence of pathogens and moderate leukocytes on seminal interleukin (IL)-6, IL-8, and sperm parameters.

PURPOSE: To evaluate the role of pathogens and moderate leukocytes on seminal interleukin (IL)-6, IL-8, and sperm parameters in men undergoing infertility investigation. METHODS: Semen samples from men (n = 171) were divided into three groups on the basis of leukocyte count: no leukocytes (L-; ≤ 0.1 × 10(6)/ml Mio/ml), moderate leukocytes (L ±; >0.1 × 10(6)/ml and <1 × 10(6)/ml), and high leukocytes (=leukocytospermia) (L+; ≥ 1 × 10(6)/ml). Each group was further classified into two subgroups, according to the presence (B+) or absence (B-) of pathogens. IL-6, IL-8, and sperm characteristics were analyzed in each subgroup. A correlation test was performed to show the association between inflammatory parameters and sperm characteristics. RESULTS: No significant differences in leukocyte count, cytokine levels, and sperm characteristics were apparent in subgroups with and without pathogens. Grade b motility was significantly lower in subgroup IIa (L ±,B-) than in subgroup Ia (L-,B-)(p < 0.05). More significant limitations in sperm motility (lower rapid progressive motility and increased percentage of immotile sperm) were observed in subgroup IIIa (L+,B-) compared with subgroup Ia (p < 0.05). Moderate and high leukocytes increased significantly cytokine levels (p < 0.001). CONCLUSIONS: Moderate leukocyte counts could be an indicator of male genital tract inflammation. Seminal pathogens have no influence on cytokine levels and sperm parameters.

New method for differentiating chronic prostatitis/chronic pelvic pain syndrome IIIA from IIIB involving seminal macrophages and monocytes.

OBJECTIVES: To evaluate a new method for differentiating inflammatory from noninflammatory prostatitis using the simple and rapid quantification of seminal macrophages and monocytes. METHODS: Patients affected with chronic pelvic pain syndrome (CPPS) were classified as having the IIIA (n = 11) and IIIB (n = 30) subtypes according to the peroxidase positive leukocyte concentration in semen; 18 healthy individuals served as controls. Seminal inflammatory markers, including polymorphonuclear elastase, interleukin (IL)-6 and IL-8, and numbers of macrophages/monocytes (MMs) per 50 fields of 1000 × magnification (high-power field [hpf]), were determined for all patients. RESULTS: The numbers of MMs/50 hpf correlated significantly with the peroxidase positive leukocyte counts and IL-8, IL-6, and polymorphonuclear elastase levels (all P < .001). Data from the analysis of receiver operating characteristic curves (area under the curve 0.912 ± 0.073; P < .001) showed a sensitivity of 90.9% and specificity of 86.7% at a cutoff value of 5 MMs/50 hpf. The positive and negative predictive value was 71.4% and 96.3%, respectively. The median concentrations of IL-6, IL-8, and elastase in the patients with CPPS with ≥ 5 MMs/50 hpf differed significantly (P ≤ .002) from those in the patients with <5 MMs/50 hpf. CONCLUSIONS: The results of our study have shown that the quantification of seminal macrophages and monocytes is a simple, rapid, and reproducible technique by which to differentiate chronic prostatitis/CPPS IIIA from IIIB.

Renal cell carcinoma Fuhrman grade and histological subtype correlate with complete polymorphic deletion of glutathione S-transferase M1 gene.

PURPOSE: We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression. MATERIALS AND METHODS: Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival. RESULTS: Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean +/- SD age 58.5 +/- 14.2 vs 65.4 +/- 12.8 years, p = 0.016). CONCLUSIONS: GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis.

Effect of transdermal electromotive drug therapy on fibrogenic cytokine expression in Peyronie's disease.

OBJECTIVES: To assess the effect of transdermal electromotive drug therapy (EMDT) on transforming growth factor-beta (TGF-beta) and basic fibroblast growth factor (bFGF) expression and their receptors in plaques in patients with Peyronie's disease. METHODS: Tissue was obtained from 13 patients with stable Peyronie's disease who had undergone plaque excision because of penile curvature. Of the 13 patients, 7 underwent EMDT with dexamethasone, verapamil, and lidocaine as first-line therapy before plaque excision and 6 were therapy naive. TGF-beta and bFGF mRNA and protein expression and that of their receptors were measured using real-time polymerase chain reaction and Western blotting. RESULTS: The mean patient age was 52.83 years. The mean interval from the end of EMDT to plaque excision was 7.6 months, with stable disease for >or=5 months. The comparison of TGF-beta mRNA expression in the plaques showed no difference between the EMDT and therapy-naive patients (P = .17). Also, TGF-beta protein expression in the plaques was not significantly different between the EMDT and therapy-naive patients (P = .443). TGF-beta receptor 1 mRNA expression in the plaques was significantly different between the EMDT and therapy-naive patients (P = .023), but no difference was found for TGF-beta receptor 2 mRNA (P = .292). The expression of bFGF mRNA (P = .0005) and bFGF protein expression (P = .034) in the plaques was significantly lower after EMDT. bFGF receptor mRNA expression (P = .619) showed no significant differences. CONCLUSIONS: Patients with Peyronie's had significantly lower bFGF mRNA and bFGF protein expression in the plaques after EMDT. Also, overexpression of TGF-beta protein and the TGF-beta receptor was identified in the EMDT plaques compared with the therapy-naive plaques.

Effect of antibiotic therapy on interleukin-6 in fresh semen and postmasturbation urine samples of patients with chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVES: To investigate the effect of antibiotic therapy on interleukin (IL)-6 in fresh semen and postmasturbation urine samples of patients with chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 128 patients with CP/CPPS prospectively underwent the evaluation of IL-6 in fresh semen and postmasturbation urine samples. At 6 weeks after 4 weeks antibiotic therapy, the IL-6 levels were re-evaluated. RESULTS: Of the 128 patients, 109 (85.2%) were available for our analysis. Of the 109 patients, 72 (66.1%) met the criteria for National Institutes of Health (NIH) classification for inflammatory CP/CPPS (type IIIa) and 37 (33.9%) met the NIH criteria for noninflammatory CP/CPPS (type IIIb). Before antibiotic therapy, 86 patients (78.9%), irrespective of NIH classification, had an increased IL-6 level in fresh semen; 64 (88.9%) patients with CP/CPPS type IIIa and 22 (59.5%) with type IIIb CP/CPPS had increased IL-6 levels. After 4 weeks of therapy, a significant reduction was found in the IL-6 level, with only 44 (40.4%, P = .009) patients showing an increased IL-6 level: 34 patients with type IIIa (47.2%, P = .0000) and 10 with type IIIb (27.0%, P = .0033). An increased IL-6 level was found in the postmasturbation urine sample in 37 patients (33.9%), irrespective of NIH classification: 28 (38.9%) with type IIIa and 9 (24.3%) with type IIIb. At 6 weeks after therapy, only 3 patients (2.8%, P = .000) had an increased IL-6 level: 2 with type IIIa (2.8%, P = .0000) and 1 with type IIIb (2.7%, P = .02). CONCLUSIONS: The IL-6 levels had decreased significantly after antibiotic therapy in patients with CP/CPPS, suggesting a bacterial inflammatory character. The determination of IL-6 in seminal plasma and postmasturbation urine samples is useful as an addition to the diagnostic test for the patient with CP/CPPS and as an efficacy marker for therapy.

Reoperation, myocardial infarction and mortality after transurethral and open prostatectomy: a nation-wide, long-term analysis of 23,123 cases.

OBJECTIVE: To analyse long-term rates of reoperation, myocardial infarction and mortality after transurethral (TURP) and open prostatectomy (open PE) in a nation-wide analysis. MATERIAL AND METHODS: Patients who underwent TURP (n=20,671) or open PE (n=2452) in Austria between 1992 and 1996 entered this study and were followed for up to 8 years. Actuarial cumulative incidences of reoperation (TURP, urethrotomy, bladder neck incision), myocardial infarction and death after 1, 5 and 8 years were calculated. Data were provided by the Austrian Health Institute (OBIG). RESULTS: Actuarial cumulative incidences of a secondary TURP after primary TURP at 1, 5 and 8 years were 2.9%, 5.8% and 7.4%; the respective numbers after open PE 1.0%, 2.7% and 3.4%. The overall incidence of a secondary endourological procedure (TURP, urethrotomy, bladder neck incision) within 8 years was 14.7% after TURP and 9.5% after open PE. The 8 years incidence of myocardial infarction was identical after TURP (4.8%) and open PE (4.9%). In parallel, mortality rates at 90 days (TURP: 0.7%; open PE: 0.9%), one year (2.8% vs. 2.7%), 5 years (12.7% vs. 11.8%) and 8 years (20% vs. 20.9%) was identical after TURP and open PE. CONCLUSIONS: This large-scale, contemporary, nation-wide analysis confirms the higher reoperation rate after TURP compared to open PE. We observed no excess risk of myocardial infarction or death after TURP compared to open PE.

Effect of NIH-IV prostatitis on free and free-to-total PSA.

OBJECTIVE: To examine the effect of asymptomatic prostatic inflammation (NIH category IV prostatitis) on total PSA (tPSA), free serum PSA (fPSA) and the ratio of free-to-total prostate specific antigen (%fPSA). The role of free and %fPSA as a diagnostic tool for distinguishing between cancer and non-malignant diseases of the prostate was also investigated. MATERIAL AND METHODS: In a retrospective study 1090 prostate biopsies performed between January 2000 and September 2003 were evaluated and the levels of serum total and free PSA as well as the f/tPSA ratio were determined in samples obtained immediately before biopsy. 404 patients with full clinical and histological records were included in the study. All patients underwent 6 or 8 core primary prostate needle biopsies. RESULTS: A total of 404 patients were included in the analysis. 100 prostate cancer (PCa) (24.8%), 137 NIH-IV prostatitis (33.9%) and 143 patients with benign prostatic hyperplasias (BPH) (35.4%) were identified. 24 (5.9%) patients presented with both PCa and prostatitis on histology and were excluded from further analysis. The mean (median) levels of tPSA, fPSA and %fPSA were 11.94 ng/ml (8.0), 1.31 ng/ml (1.07) and 0.15 (0.14) for NIH-IV prostatitis; 11.94 ng/ml (8.35), 1.54 ng/ml and 0.13 (0.11) for prostate cancer; and 8.19 ng/ml (7.0), 1.48 ng/ml (1.03) and 0.18 (0.15) for BPH. No significant difference was found in tPSA levels between PCa and prostatitis (p = 0.32), while the difference in tPSA levels between PCa and BPH was significant (p = 0.007). Free PSA alone had no diagnostic power in distinguishing PCa from prostatitis (p = 0. 37) and BPH (p = 0. 61). By contrast, the f/tPSA ratio showed significant between-group differences (PCa versus prostatitis (p = 0. 011), PCa versus BPH (p = 0.0001). CONCLUSIONS: Chronic asymptomatic prostatitis NIH category IV has similar effects on total PSA and free PSA levels in serum as PCa. fPSA alone cannot distinguish prostate cancer from non-malignant inflammatory disease of the prostate. The ratio of free-to-total PSA is significantly different in PCa and NIH category IV prostatitis.

Penile cancer: review of the recent literature.

PURPOSE OF REVIEW: To review recent developments in the diagnosis and treatment of penile cancer, we reviewed the medical literature from 1 May 2002 to 1 June 2003 on the incidence, aetiology, staging, diagnosis and treatment of penile cancer by a Medline search. RECENT FINDINGS: The diagnostic tools and treatment modalities for penile cancer are still controversial. Recently developed diagnostic and therapeutic modalities should help urologists in the management of the disease. SUMMARY: Our review of the recent literature provides an update on diagnostic and therapeutic opinion on penile cancer.