Medical therapy versus transurethral resection of the prostate (TURP) for the treatment of symptomatic benign prostatic enlargement (BPE): a cost minimisation analysis.

PURPOSE: A cost minimisation analysis compares the costs of different interventions' to ascertain the least expensive over time. We compared different prostate targeted drug treatments with TURP to identify the optimal cost saving duration of a medical therapy for symptomatic benign prostatic enlargement (BPE). METHODS: The Evolution registry is a prospective, multicentre registry, conducted by the European Association of Urology Research Foundation (EAUrf) for 24 months in 5 European countries. Evolution was designed to register the management of symptomatic BPE in clinical practice settings in 5 European countries. Direct cost evaluation associated with prostate targeted medical therapies and TURP was also recorded and analysed. RESULTS: In total, 1838 men were enrolled with 1246 evaluable at 24 months. Medical therapies were more cost saving than TURP for treatment durations ranging from 2.9 to 70.4 years. Cost saving depended on both medication class and individual country assessed. Daily tamsulosin monotherapy was more cost saving than TURP for ≤ 13.9 years in Germany compared to ≤ 32.7 years in Italy. Daily finasteride monotherapy was more cost saving for ≤ 5.9 years in France compared to ≤ 36.9 years in Spain. Combination therapy was more cost saving for ≤ 5.9 years for Italian patients versus ≤ 13.8 years in Germany. CONCLUSIONS: BPE medical management was more cost saving than TURP for different specific treatment durations. Information from this study will allow clinicians to convey medical and surgical costs over time, to both patients and payors alike, when considering BPE treatment.

Miniaturised percutaneous nephrolithotomy versus flexible ureteropyeloscopy: a systematic review and meta-analysis comparing clinical efficacy and safety profile.

PURPOSE: This study aims to comparatively evaluate clinical outcomes of mini-PCNL and FURS for treating urinary tract calculi in a single session. METHODS: A systematic search using electronic databases was performed for studies comparing mini-PCNL and FURS for the treatment of urinary tract calculi. The primary outcome measurements were stone-free rates (SFRs) and complication rates for both techniques. Secondary outcome measurements were to compare patient demographics, operative duration, and inpatient stay. Meta-analysis was performed with Review Manager version 5.3 software. RESULTS: Sixteen studies on 1598 patients (n = 877 for mini-PCNL and n = 721 for FURS) met inclusion criteria. Demographics including age (p = 0.26), body mass index (BMI) (p = 0.51), and gender ratio (p = 0.6), were similar in both groups. Overall, SFR was significantly greater in the mini-PCNL group compared to the FURS group (n = 763/877, 89.3 ± 8.4% versus n = 559/721, 80.1 ± 13.3% [OR 2.01; 95% CI 1.53-2.64; p < 0.01]). Duration of inpatient stay was significantly greater in the mini-PCNL group compared to the FURS group (n = 877, 4 ± 1.6 days versus n = 721, 2.5 ± 2.2 days, respectively [WMD: 1.77; 95% CI 1.16-2.38, p < 0.01]. Overall complication rates were not significantly different between mini-PCNL and FURS (n = 171/877, 19.5 ± 19.1% versus n = 112/721, 15.5 ± 18.9%, respectively [OR 1.43; 95% CI 0.85-2.4, p = 0.18]). CONCLUSIONS: Mini-PCNL is associated with greater SFRs and longer inpatient stay compared to FURS. Complication rates were similar for both techniques. The advantages and disadvantages of both technologies should be familiar to urologists and conveyed to patients prior to urological intervention for nephrolithiasis.

15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells.

15-Lipoxygenase (15-LOX)-2 is expressed in benign prostate secretory cells and benign prostate produces 15S-hydroxyeicosatetraenoic acid (15S-HETE) from exogenous arachidonic acid (AA). In contrast, 15S-LOX-2 and 15S-HETE formation are reduced in prostate carcinoma (Pca). The mechanisms whereby reduced 15-LOX-2 may contribute to Pca development or progression are not known. We investigated the expression of peroxisome proliferator-activated receptor (PPAR) gamma in benign and malignant prostate tissues and the ability of 15S-HETE to activate PPARgamma-dependent transcription and modulate proliferation of the Pca cell line PC3. In contrast to benign prostate and similar to most Pca tissues, 15-LOX-2 mRNA was not detected in PC3 cells, and they did not produce detectable 15-HETE from [14C]AA. By reverse transcription-PCR, PPARgamma mRNA was present in 18 of 18 benign and 9 of 9 tumor specimens. The PPARgamma ligand BRL 49653 and 15S-HETE caused a dose-dependent inhibition of PC3 proliferation in a 14-day soft agar colony-forming assay (IC50 of 3 and 30 microM, respectively). 15S-HETE (10 microM) caused greater inhibition than 10 microM 15R-HETE. At 3 days, BRL 49653 and 15S-HETE caused a slight increase in cells in G0-G1 and a corresponding decrease in cells in S phase. In PC3 cells transiently transfected with a luciferase reporter linked to a PPAR response element, 1 microM BRL 49653 and 10 microM 15S-HETE caused approximately threefold and greater than twofold induction of PPAR-dependent transcription, respectively. By quantitative real-time reverse transcription-PCR and Northern analysis, 3-day treatment with BRL 49653 and 15S-HETE caused a reduction of PPARgamma expression but a marked up-regulation of the PPAR response element containing adipocyte type fatty acid binding protein. These results support the hypothesis that 15-LOX-2-derived 15S-HETE may constitute an endogenous ligand for PPARgamma in the prostate and that loss of this pathway by reduced expression of 15-LOX-2 may contribute to increased proliferation and reduced differentiation in prostate carcinoma.

Alterations in lipoxygenase and cyclooxygenase-2 catalytic activity and mRNA expression in prostate carcinoma.

Recent studies in prostate tissues and especially cell lines have suggested roles for arachidonic acid (AA) metabolizing enzymes in prostate adenocarcinoma (Pca) development or progression. The goal of this study was to more fully characterize lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) gene expression and AA metabolism in benign and malignant prostate using snap-frozen tissues obtained intraoperatively and mRNA analyses and enzyme assays. Formation of 15-hydroxyeicosatetraenoic acid (15-HETE) was detected in 23/29 benign samples and 15-LOX-2 mRNA was detected in 21/25 benign samples. In pairs of pure benign and Pca from the same patients, 15-HETE production and 15-LOX-2 mRNA were reduced in Pca versus benign in 9/14 (P=.04) and 14/17 (P=.002), respectively. Under the same conditions, neither 5-HETE nor 12-HETE formation was detectable in 29 benign and 24 tumor samples; with a more sensitive assay, traces were detected in some samples, but there was no clear association with tumor tissue. COX-2 mRNA was detected by nuclease protection assay in 7/16 benign samples and 5/16 tumors. In benign and tumor pairs from 10 patients, COX-2 was higher in tumor versus benign in only 2, with similar results by in situ hybridization. Paraffin immunoperoxidase for COX-2 was performed in whole mount sections from 87 additional radical prostatectomy specimens, with strong expression in ejaculatory duct as a positive control and corroboration with in situ hybridization. No immunostaining was detected in benign prostate or tumor in 45% of cases. Greater immunostaining in tumor versus benign was present in only 17% of cases, and correlated with high tumor grade (Gleason score 8 and 9 vs. 5 to 7). In conclusion, reduced 15-LOX-2 expression and 15-HETE formation is the most characteristic alteration of AA metabolism in Pca. Increased 12-HETE and 5-HETE formation in Pca were not discernible. Increased COX-2 expression is not a typical abnormality in Pca in general, but occurs in high-grade tumors.

Reduced 15-lipoxygenase-2 immunostaining in prostate adenocarcinoma: correlation with grade and expression in high-grade prostatic intraepithelial neoplasia.

Arachidonic acid (AA) metabolites are implicated in the oncogenesis of several tumors, including prostate cancer. 15-Lipoxygenase-2 (15-LOX-2) is a novel AA-metabolizing enzyme with a limited tissue distribution, which includes prostate, lung, skin, and cornea. Previous studies have shown that 15-LOX-2 is present in benign prostate secretory cells and reduced in prostate adenocarcinoma and that production of the 15-LOX-2 metabolite 15S-hydroxyeicosatetraenoic acid is reduced in malignant compared with benign prostate. The objective of this study was to determine the frequency with which 15-LOX-2 immunostaining is reduced in prostate carcinoma and to correlate reduced expression with tumor differentiation (grade) and other pathologic parameters in radical prostatectomy specimens. Paraffin immunoperoxidase with a polyclonal antibody specific for 15-LOX-2 was performed on tumors and benign portions from 70 cases, and the percentage of tumor immunostaining for 15-LOX-2 was assessed. Whereas uniform 15-LOX-2 immunostaining was observed in secretory cells of benign glands, it was markedly reduced or absent in most adenocarcinomas: 23 of 70 tumors showed completely absent 15-LOX-2 immunostaining, and 45 of 70 cases showed negative immunostaining in more than 50% of the tumor. The extent of reduced 15-LOX-2 immunostaining correlated with tumor differentiation, with retained expression particularly in Gleason score 5 tumors versus a significant reduction of 15-LOX-2 in higher-grade tumors (mean +/- SD tumor 15-LOX-2 positive: Gleason score 5 = 67%+/-30%, Gleason score 6 = 16%+/-30%, Gleason score 7 = 23%+/-28%, Gleason score > or =8 = 41%+/-46%). In 16 cases with multifocal tumors or different foci of the same tumor with different grades, the higher-grade foci had significantly reduced 15-LOX-2 expression compared with the lower-grade foci. In peripheral zone tumors without complete loss of 15-LOX-2 expression, there was a significant inverse relationship between 15-LOX-2 immunostaining and tumor volume. There was not a significant correlation between 15-LOX-2 immunostaining and serum PSA or pathologic stage. In a subset of 27 cases, 15-LOX-2 expression in high-grade prostatic intraepithelial neoplasia (HGPIN) glands was significantly reduced compared with benign glands. These data show that in contrast to the uniform expression of 15-LOX-2 in differentiated secretory cells of benign prostate, reduced 15-LOX-2 is a common alteration in prostate carcinoma, and this correlates with tumor cell differentiation. That reduced expression is seen in HGPIN suggests that this may be an early alteration in carcinoma development.

Prediction of tumour volume and pathological stage in radical prostatectomy specimens is not improved by taking more prostate needle-biopsy cores.

OBJECTIVE: To determine what, if any, additional prognostic information is available from the prostate needle biopsy by comparing the number of biopsy cores obtained with the pathology assessed from the radical retropubic prostatectomy (RRP) specimen. PATIENTS AND METHODS: The results from 135 consecutive patients who underwent RRP at a single institution were reviewed. Needle biopsy information (number of cores, percentage of positive cores, laterality of the positive cores, and Gleason sum) were compared with the pathological data of the RRP specimen, including stage, Gleason sum and tumour volume. Patients were further stratified into those with six or fewer cores (96 men) or more than six cores (39 men). Clinical data, including biopsy information and pathological findings, were compared using univariate and multivariate models. RESULTS: Overall, univariate analysis showed that the total prostate-specific antigen (PSA) level, number of positive cores, bilateral positive cores and percentage of positive cores were directly correlated with tumour volume (P=0.01). Also, PSA and percentage of positive cores were directly correlated with extracapsular extension (P=0.008 and P=0.01, respectively). In the multivariate model, the most important independent predictors of RRP tumour volume and pathological stage were the preoperative PSA level and percentage of cancer in the biopsy (P<0.01). There was no significant relationship between the number of cores obtained and the predicted pathology of the RRP specimen. There were no differences in the number of positive cores, bilateral positive cores or percentage tumour in the cores between men with more or less than six biopsies. In men with more than six core biopsies, there was no significant increase in prognostic information for tumour volume and extracapsular extension, or a correlation between the Gleason sum on biopsy and the RRP specimen. Taking more than six biopsies did not result in a significantly greater detection of potentially indolent tumours (defined as a tumour volume of <0.5 mL). CONCLUSIONS: While taking more prostate needle biopsy cores seems to improve the detection of prostate cancer, there appears to be no major improvement in prognostic information over that gained from traditional sextant biopsies. Furthermore, the results suggest that the percentage of positive cores is the best predictor of both pathological stage and tumour volume, from among the information readily available from prostate needle biopsy. Given the variability in the number of cores obtained for diagnosis in clinical practice, these results add credence to the use of the percentage of positive cores in the biopsy set, with known predictors such as PSA and Gleason score, into future models that attempt to predict tumour biology.