G. Bartsch

The Relationship between Prostate-Specific Antigen and Prostate Cancer Risk: The Prostate Biopsy Collaborative Group

Purpose: The relationship between prostate-specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesized that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study. Experimental Design: We used data from five European and three U.S. cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally weighted scatterplot smoothing. Results: The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased the risk of cancer (odds ratio for >6- versus 6-core biopsy, 1.35; 95% confidence interval, 1.18-1.54; P < 0.0005); recent screening led to a smaller increase in risk per unit change in PSA (P = 0.001 for interaction term) and U.S. cohorts had higher risk than the European cohorts (2.14; 95% confidence interval, 1.99-2.30; P < 0.0005). Conclusions: Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated. Clin Cancer Res; 16(17); 4374–81. ©2010 AACR.

Factors contributing to the racial differences in prostate cancer mortality.

To analyse, in a retrospective cohort study, differences in rates of surgical treatment for prostate cancer between African‐Americans and White Americans, and to evaluate the extent to which these differences are associated with disparities in survival rates between these groups.

Vascular resistance in the prostate evaluated by colour Doppler ultrasonography: is benign prostatic hyperplasia a vascular disease?

There is a wide variety of topics in this section of the Journal this month. The papers come from Austria, Israel, Scotland, Denmark, England and Australia. I am, as ever, pleased that the Journal continues to receive papers from so many countries, and that the high standard of these papers help us to maintain a quality product of great general interest to the reader.

Pathologic characterization of prostate cancers with a very low serum prostate specific antigen (0–2 ng/mL) incidental to cystoprostatectomy: is PSA a useful indicator of clinical significance?

Cystoprostatectomy specimens removed for bladder malignancy (1988-2000) at two referral centers (Mayo Clinic, Rochester, MN, The University Hospital of Innsbruck, Innsbruck, Austria) were examined for the coincidental finding of prostate cancer (PCA). Centralized examination of the prostate by a single uropathologist was performed if at the time of surgery the patients serum PSA was < or =2.0 ng/mL and there were no suspicious lesions by digital prostate examination. Pathologic grade, stage, morphometric volume, number of tumor foci and association with areas of high grade prostatic intraepithelial neoplasia (HGPIN) were assessed by light microscopy. DNA ploidy and cellular proliferative index were assessed through digital image analysis. Clinically significant cancers were defined as tumors with > or =0.5 cc volume, Gleason 4 or 5 architecture, pT3, positive surgical margin, multifocality >3, nondiploid DNA content or proliferation index >5%. From nearly 1600 cystoprostatectomy specimens, 129 met the enrollment criteria. Thirty-patients (23%) within this group had PCA identified. Sixty percent of these tumors met the criteria for a clinically significant cancer. Nondiploid nuclear content was present in 17%. HGPIN was present in 70% and directly abutting carcinoma in 86% of prostates. The biologic activity of PCA appears to be independent of serum PSA. Any future definition of a clinically significant PCA should not be solely based upon histologic criteria, but needs to encompass clinical parameters (age, co-morbidities) and a noninvasive assessment of tumor volume and biologic doubling time.

Interim Outcome of the Single Stage Dorsal Inlay Skin Graft for Complex Hypospadias Reoperations

PURPOSE Despite high success rates for primary hypospadias repair, some cases require multiple procedures for ultimate reconstruction. We report our experience with single stage dorsal inlay urethroplasty using skin grafts for complex reoperations. MATERIALS AND METHODS A total of 31 patients (mean age 13.8 years) with failed previous hypospadias surgery were included in the study. Indications included fistulas, strictures, diverticula and repair breakdown. The urethral plate had been removed or was severely scarred in all patients. A free penile or groin skin graft was sutured and quilted to the corpora cavernosa, guaranteeing sufficient blood supply. The neourethra was tubularized and covered with a tunica vaginalis or dartos flap, followed by glanuloplasty. Outcome analysis included urethrograms, urethral ultrasound and flow measurements. RESULTS Foreskin was used in 15 cases, penile skin in 12 and inguinal skin in 4. Average graft length was 3.92 cm. A total of 20 patients required glanuloplasty with a skin graft extended to the tip of the glans. After a mean followup of 30.71 months 5 patients underwent redo surgery, for a complication rate of 16.1%. Urethral stricture of the proximal anastomosis was the most frequent finding. CONCLUSIONS This single stage approach using dorsal skin grafts is a reliable method to create a substitute urethral plate for tubularization. Complication rates are equivalent to those of staged procedures. Foreskin should be used as a graft donor site to optimize the outcome if available. This approach represents a safe option for reoperations even if the urethral plate or midline penile skin is grossly scarred.

Evidence for the autoregulation of vesical circulation by intravesical potassium chloride and distension in the normal human bladder

Objectives To determine the influence of distension and intravesical KCl on vesical blood flow in the normal human bladder.

Extracellular Microenvironment and Cytokine Profile of the Ureterovesical Junction in Children With Vesicoureteral Reflux

PURPOSE Vesicoureteral reflux is caused by a defective valve mechanism of the ureterovesical junction. Previous studies have revealed structural and metabolic changes in the intravesical ureter, impairing its contractile properties. Smooth musculature and nerves are replaced by collagen, while matrix degrading enzymes are over expressed. We investigated the presence of regulating cytokines and the extracellular matrix composition to elucidate further the pathophysiology of vesicoureteral reflux. MATERIALS AND METHODS Ureteral endings were obtained from 28 children during antireflux surgery, and 14 age matched autopsy specimens served as controls. Routine histological sections were immunostained for insulin-like growth factor-1, nerve growth factor, transforming growth factor-beta1, tumor necrosis factor-alpha and vascular endothelial growth factor. Smooth muscle staining was supplemented by tenascin C, tetranectin and fibronectin detection. Staining patterns were investigated using computer assisted, high power field magnification analyses. RESULTS Tumor necrosis factor-alpha and transforming growth factor-beta1 were significantly more abundant in vesicoureteral reflux samples, whereas insulin-like growth factor-1, nerve growth factor and vascular endothelial growth factor were more prevalent in healthy controls. Fibronectin was intensely expressed in refluxing ureters, while it was scarce in healthy children. Tenascin C was notable within the urothelium of both groups. Only vesicoureteral reflux samples displayed tenascin C in the musculature and connective tissue. Tetranectin staining was only detected in vesicoureteral reflux. CONCLUSIONS Several cytokines are differentially expressed in primary refluxing ureters, indicating an ongoing tissue remodeling process in the ureterovesical junction region. Additionally, the smooth muscle coat is widely lacking, while extracellular matrix proteins typical for tissue shrinkage and reorganization are over expressed. These alterations are likely to contribute to the malfunctioning active ureteral valve mechanism in primary vesicoureteral reflux.

Influence of blood sampling on protein profiling and pattern analysis using matrix-assisted laser desorption/ionisation mass spectrometry

To describe the influence of blood sampling/sampling tubes on mass spectrometric and clustering results, and on clinical blood variables, in blood samples collected from healthy volunteers and patients with prostate cancer.

Prostate Specific Antigen and Prostate Cancer in Chinese Men Undergoing Initial Prostate Biopsies Compared with Western Cohorts

Purpose: We determined the characteristics of Chinese men undergoing initial prostate biopsy and evaluated the relationship between prostate specific antigen levels and prostate cancer/high grade prostate cancer detection in a large Chinese multicenter cohort. Materials and Methods: This retrospective study included 13,904 urology outpatients who had undergone biopsy for the indications of prostate specific antigen greater than 4.0 ng/ml or prostate specific antigen less than 4.0 ng/ml but with abnormal digital rectal examination results. The prostate specific antigen measurements were performed in accordance with the standard procedures at the respective institutions. The type of assay used was documented and recalibrated to the WHO standard. Results: The incidence of prostate cancer and high grade prostate cancer was lower in the Chinese cohort than the Western cohorts at any given prostate specific antigen level. Around 25% of patients with a prostate specific antigen of 4.0 to 10.0 ng/ml were found to have prostate cancer compared to approximately 40% in U.S. clinical practice. Moreover, the risk curves were generally flatter than those of the Western cohorts, that is risk did not increase as rapidly with higher prostate specific antigen. Conclusions: The relationship between prostate specific antigen and prostate cancer risk differs importantly between Chinese and Western populations, with an overall lower risk in the Chinese cohort. Further research should explore whether environmental or genetic differences explain these findings or whether they result from unmeasured differences in screening or benign prostate disease. Caution is required for the implementation of prostate cancer clinical decision rules or prediction models for men in China or other Asian countries with similar genetic and environmental backgrounds.