Development and internal validation of a screening tool for chronic prostatitis (S-CP).

PURPOSE: We developed a simple self-checkable screening tool for chronic prostatitis (S-CP) and internally validated it to encourage men (in the general population) with possible chronic prostatitis to consult urologists. METHODS: The expert panel proposed the S-CP, which comprises three domains: Area of pain or discomfort (6 components), accompanying Symptom (6 components), and Trigger for symptom flares (4 components). We employed logistic regression to predict chronic prostatitis prevalence with the S-CP. We evaluated the predictive performance using data from a representative national survey of Japanese men aged 20 to 84. We calculated the optimism-adjusted area under the curve using bootstrapping. We assessed sensitivity/specificity, likelihood ratio, and predictive value for each cutoff of the S-CP. RESULTS: Data were collected for 5,010 men-71 (1.4%) had a chronic prostatitis diagnosis. The apparent and adjusted area under the curve for the S-CP was 0.765 [95% confidence interval (CI) 0.702, 0.829] and 0.761 (0.696, 0.819), respectively. When the cutoff was two of the three domains being positive, sensitivity and specificity were 62.0% (95% CI 49.7, 73.2) and 85.4% (95% CI 84.4, 86.4), respectively. The positive/negative likelihood ratios were 4.2 (95% CI 3.5, 5.2) and 0.45 (95% CI 0.33, 0.60), respectively. The positive/negative predictive values were 5.7 (95% CI 4.2, 7.6) and 99.4 (95% CI 99.1, 99.6), respectively. CONCLUSION: The reasonable predictive performance of the S-CP indicated that patients (in the general population) with chronic prostatitis were screened as a first step. Further research would develop another tool for diagnostic support in actual clinical settings.

Low quality of life in men with chronic prostatitis-like symptoms.

BACKGROUND: Chronic prostatitis (CP) can impair health-related quality of life (QOL), but the full impact of CP, including the impact of CP-like symptoms in men who have no CP diagnosis (CPS), is unknown. We estimated the impact of diagnosed CP (DCP) and CPS on Health-related QOL. METHODS: From a representative nationwide survey of men aged 20-84 in Japan, we determined the prevalence of DCP and also of CPS. For CPS, we used Nickel's criteria, which were used previously to estimate the prevalence of CP and are based on the NIH Chronic Prostatitis Symptom Index. To test the robustness of Nickel's criteria, we used two other definitions of CPS (two sensitivity analyses). We measured QOL with the Short-Form 12-Item Health Survey. We compared the participants' QOL scores with the national-norm scores, and with the scores of men who had benign prostatic hyperplasia (BPH). RESULTS: Among the 5 010 participants, 1.4% had DCP and 3.7% had CPS. The sensitivity analyses resulted in CPS prevalence estimates of 3.1% and 4.5%. CPS was particularly common in younger participants (5.7% of those in their 30 s had CPS). QOL was very low among men with CP: In most areas (domains) of QOL, their scores were more than 0.5 standard deviation below the national-norm mean. Their mental-health scores were lower than those of men with BPH. The lowest scores among all 8 QOL domains were in role-functioning. CONCLUSIONS: CP is common, but it is underdiagnosed, particularly in younger men. Whether diagnosed or only suspected, CP's impact on QOL is large. Because CP is common, and because it substantially impairs individuals' QOL and can also reduce societal productivity, it requires more attention. Specifically, needed now is a simple tool for urologists and for primary care providers, to identify men, particularly young men, whose QOL is impaired by CP.

Early efficacy of silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVES: To evaluate the early efficacy of the alpha(1A)-adrenoceptor selective drug, silodosin, for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia. METHODS: A total of 68 patients with an International Prostate Symptom Score (IPSS) of >==8 and a Quality of Life (QOL) index of >==2 were included. Changes in the IPSS and QOL index were evaluated before and after 1, 2, 3, 4, 5, 6, 7, 14, and 28 days of twice daily oral administration of 4 mg silodosin. Next, changes in IPSS subscores as well as voiding, storage, and post micturition symptoms were assessed. Changes in total IPSS based on symptom severity were also determined. RESULTS: Total IPSS and QOL index improved significantly from 19.38 +/- 7.46, 4.68 +/- 1.07 at baseline to 15.81 +/- 7.40, 4.22 +/- 1.30 at day 1. The subscores of voiding, storage, and post micturition symptoms were significantly decreased from 8.93 +/- 3.95, 7.97 +/- 3.88, and 2.49 +/- 1.70 at baseline to 7.28 +/- 4.09, 6.52 +/- 3.47, and 2.02 +/- 1.56 at day 1, respectively. This trend continued throughout the study. Regardless of severity, total IPSS were significantly decreased at day 1 and maintained throughout the study. CONCLUSIONS: Silodosin may be considered a promising treatment for benign prostatic hyperplasia/lower urinary tract symptom patients.

The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer.

BACKGROUND: Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value. METHODS: TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence. RESULTS: Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer. CONCLUSION: The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt).

Noninvasive detection of alterations in chromosome numbers in urinary bladder cancer cells, using fluorescence in situ hybridization.

BACKGROUND: Bladder cancers have a high potential for recurrence and sometimes become invasive even in superficial cases. In this process, gene mutations in tumor suppressor genes such as p53, on chromosome 17, or p16, on chromosome 9, are thought to be important. In order to investigate whether the detection of alterations in chromosome number might be used as an alternative to invasive techniques for the assessment of clinical bladder cancer, fluorescence in situ hybridization (FISH) was employed to analyze chromosome numbers in a series of patients. METHODS: A total of 40 patients with transitional cell carcinomas (stages Ta to T4, including carcinoma in situ [CIS]) were examined for abnormal numbers of chromosomes 9 and 17, by FISH, using 41 and 42 samples of voided urine, respectively. Tumor grades were as follows: G1:G2:G3 = 4:21:17. Urinary cytology and presence of bladder tumor antigen (BTA) were also checked in the same samples. One hundred cells were examined in each sample, and abnormality was concluded to be present when more than 20% of cells demonstrated polysomy (defined as three or more chromosomes). RESULTS: Seventeen of 41 samples (41.5%) were abnormal with regard to chromosome 9, and 17 of 42 (40.5%) were abnormal for chromosome 17. Both chromosomes were affected in 13 cases, of which 8 were positive for urinary cytology and BTA. Univariate analysis, performed with urinary cytology, BTA, tumor grade, tumor stage, involvement of vessels, pattern of invasion, number of tumors, and prognosis as parameters, demonstrated a significant influence of urinary cytology (P = 0.0368 and P = 0.0278 for chromosomes 9 and 17, respectively), BTA (P = 0.0094 for chromosome 17), involvement of vessels (P = 0.0262 for chromosome 17), pattern of invasion (P = 0.0028 and P = 0.0327 for chromosomes 9 and 17), grade (P = 0.0213 and P = 0.0174 for chromosomes 9 and 17), and stage (P = 0.0457 for chromosome 17). All the other parameters also tended to be linked with the changes in chromosomes, except for tumor number. Multivariate analysis demonstrated significant differences for tumor grade (P = 0.0166) and pattern of invasion (P = 0.0006) for chromosome 9. CONCLUSION: Voided-urine FISH is an effective noninvasive method for the detection of altered chromosome numbers in bladder cancer cells, and may provide an indication of tumor progression when combined with urinary cytology and BTA.

Growth Competition between W Mutant and Wild-type Cells in Mouse Aggregation Chimeras: (aggregation chimera/W mutation/c-kit oncogene/celluler competition/mouse).

The dominant spotting (W) locus of the mouse has been demonstrated to be identical with the c-kit proto-oncogene. The c-kit is strongly expressed in hematopoietic organs and the brain of mice. In homozygotes and double heterozygotes of the W mutant alleles (hereafter W mutant), development of erythrocytes, mast cells, melanocytes and germ cells is deficient. The deficiency of erythrocytes, mast cells and melanocytes is attributed to a defect of precursor cells, but the cause of the germ cell deficiency is not clear. We investigated the effect of the W mutation on proliferative potential of cells composing various organs by examining aggregation chimeras between W mutant and wild-type (+/+) embryos. Proportions of +/+ components were significantly greater in the male germ cells and hematopoietic cells. In contrast, the average proportions of +/+ components were comparable to those of W mutant components in other organs including the brain. The present result suggests that the W (c-kit) gene plays an important role in development of the male germ cells and hematopoietic cells and that it does not promote the proliferation of major cell population in the brain, in spite of the strong expression of the W (c-kit) gene in the brain.

Kidney Proximal Tubule Cells Originate from Approximately Four Progenitor Cells and Make Distinct Patches in Mouse Aggregation Chimeras: (aggregation chimera/kidney proximal tubule/beige mouse/pool size/patch size).

Giant lysosomal granules of bgJ /bgJ mutant mice were used as a marker to investigate the histological composition of kidney proximal tubule cells. Embryos of the bgJ /bgJ genotype and those of the +/+ genotype were aggregated, and lysosomes of their proximal tubule cells were histochemically stained with the ß-glucuronidase activity. Tubules composed of bgJ /bgJ -type epithelial cells alone, tubules composed of +/+-type epithelial cells alone and tubules containing both types of epithelial cells were observed in cross sections. When the long straight portion of proximal tubules was reconstructed from serial sections, most of the tubules were of the mixed type, and distinct patches of bgJ /bgJ -type or +/+-type epithelial cells were detectable. These patches appeared to extend to the longitudinal rather than the circumferential direction. This suggests the clonal proliferation followed the mixing of embryonic progenitor cells for proximal tubule cells. Estimation from proportions of bgJ /bgJ -type proximal tubules in total examined proximal tubules gave a pool size of approximately four primordial precursor cells for proximal tubules in both right and left kindeys. The fact that the proportion of bgJ /bgJ -type components was comparable between the right and left kidneys of each chimera suggests that all proximal tubule cells in both right and left kidneys may originate from common primordial precursor cells.