Determining age-specific prostate-specific antigen for healthy Indian men: A retrospective study.

Introduction: Prostate cancer usually affects older men and accounts for considerable cancer-associated mortality in men globally. In India, there is a rise in prostate cancer, and the published literature to determine age-specific prostate-specific antigen (PSA) is limited by a small sample size. The objective of our study was to determine age-specific PSA for Indian men based on a very large cohort of apparently healthy men undergoing health screening. Methods: This was a retrospective study using the hospital-based database of men who had undergone PSA blood tests as a part of health screening at two tertiary referral centers in South India between January 1, 2011, and August 31, 2018. Anonymous data were extracted, and statistical analysis was performed. Results: During this period, 99,386 men underwent PSA blood tests. Non-Indian patients and patients with PSA levels either <0.2 or >20 were excluded from the study, leaving 86,728 patients who were further analyzed. Seventy percent of patients were below 60 years of age, and the mean PSA for the study cohort was 1.2 ng/mL (standard deviation 1.74), with a median PSA of 0.7 ng/mL (interquartile range 0.4-1.1). The 95th percentile serum PSA level was 1.40, 1.70, 3.10, 5.80, 8.82, and 11.31 ng/mL for age groups of ≤40, 41-50, 51-60, 61-70, 71-80, and >80 years, respectively. The mean, median, and 95th percentile PSA reportedly increased for each decade of life (P = 0.0005). Conclusions: Results of this study indicated a positive correlation between serum PSA level and age in Indian men. These values are lower than the age-specific PSA defined for Caucasian men. These findings provide a basis for establishing new age-specific reference ranges of PSA for Indian men which will help in clinical decision-making.

Assessment of Age and Duration of Symptoms on Outcomes of Emergency Scrotal Exploration for Acute Scrotal Pain.

OBJECTIVE: To study the effects of age and duration of symptoms on the outcomes of scrotal explorations for acute scrotal pain at our institution. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Bradford Teaching Hospital NHS Trust, from January 2006 to December 2017. METHODOLOGY: Retrospective data was collected from electronic case records of the patients who required scrotal exploration for suspected torsion of the testis. Group difference between continuous variables (age and duration of symptoms) were assessed by Kruskal Wallis and independent samples Mann-Whitney U-tests. The Fisher Exact and Chisquare tests were used to analyse relationships between categorical data. RESULTS: In total, 502 patients required scrotal exploration. The median age (years) and duration of symptoms (hours) were 16.4 years (1.3 - 77) and 4 hours (1 - 336), respectively. Torsion of the testis was found in 231 (46%), torsion of the testicular appendix in 126 (25%), epididymal inflammation in 46 (9.2%), and no cause identified in 99 (19.7%). Immediate orchidectomy for non-viable testis performed in 34 (14.7% of TT group and 6.8% of the overall cohort). Duration of symptoms was significantly associated with risk of orchidectomy in torsion patients 4 vs. 27 hours (p <0.0001). Overall 47 (9.3%) patients presented after 12 hours, 22 (46.8%) had TT. There were 13 (2.6%) patients older than 40 years and 8 (61.5%) of these had torsion. CONCLUSION: The most commonest diagnosis for patients presenting with acute scrotal pain was torsion of the testis followed by torsion of appendix testis. Testicular salvage was inversely related to the duration of symptoms. Patient's age did not predict the need for orchidectomy. This data supports the practice of urgent scrotal exploration for acute scrotal pain with a clinical suspicion of torsion regardless of age and duration of symptoms.

Early surgical outcomes and oncological results of robot-assisted partial nephrectomy: a multicentre study.

OBJECTIVE: To describe a multicentre experience of robot-assisted partial nephrectomy (RAPN) in northern England, with focus on early surgical outcomes and oncological results. PATIENTS AND METHODS: All consecutive patients undergoing RAPN at four tertiary referral centres in northern England in the period 2012-2015 were included for analysis. RAPN was performed via a transperitoneal approach using a standardized technique. Prospective data collection was performed to capture preoperative characteristics (including R.E.N.A.L. nephrometry score), and peri-operative and postoperative data, including renal function. Correlations between warm ischaemia time (WIT), positive surgical margin (PSM) rate, complication rates, R.E.N.A.L. nephrometry scores and learning curve were assessed using univariate and multivariate analyses. RESULTS: A total of 250 patients (mean age 58.1 ± 13 years, mean ± sd body mass index 27.3 ± 7 kg/m2 ) were included, with a median (range) follow-up of 12 (3-36) months. The mean ± sd tumour size was 30.6 ± 10 mm, mean R.E.N.A.L. nephrometry score was 6.1 ± 2 and 55% of tumours were left-sided. Mean ± sd operating console time was 141 ± 38 min, WIT 16.7 ± 8 min and estimated blood loss 205 ± 145 mL. There were five conversions (2%) to open/radical nephrectomy. The overall complication rate was 16.4% (Clavien I, 1.6%; Clavien II, 8.8%; Clavien III, 6%; Clavien IV/V; 0%). Pathologically, 82.4% of tumours were malignant and the overall PSM rate was 7.3%. The mean ± sd preoperative and immediate postoperative estimated glomerular filtration rates were 92.8 ± 27 and 80.8 ± 27 mL/min/1.73 m2 , respectively (P = 0.001). In all, 66% of patients remained in the same chronic kidney disease category postoperatively, and none of the patients required dialysis during the study period. 'Trifecta' (defined as WIT < 25 min, negative surgical margin status and no peri-operative complications) was achieved in 68.4% of patients overall, but improved with surgeon experience. PSM status and long WIT were significantly associated with early learning curve. CONCLUSION: This is the largest multicentre RAPN study in the UK. Initial results show that RAPN is safe and can be performed with minimal morbidity. Early oncological outcomes and renal function preservation data are encouraging.

Localising prostate cancer: comparison of endorectal magnetic resonance (MR) imaging and 3D-MR spectroscopic imaging with transrectal ultrasound-guided biopsy.

BACKGROUND: Magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) have been gaining acceptance as tools in the evaluation of prostate cancer. We compared the accuracy of transrectal ultrasound (TRUS)-guided biopsy and dynamic contrast-enhanced MRI combined with three-dimensional (3D) MRSI in locating prostate tumours and determined the influence of prostate weight on MRI accuracy. PATIENTS AND METHODS: Between March 1999 and October 2006, 507 patients with localised prostate cancer underwent radical prostatectomy (RP) at the Jules Bordet Institute. Of these, 220 had undergone endorectal MRI (1.5 T Siemens Quantum Symphony) and 3D-MRSI prior to RP. We retrospectively reviewed data on tumour location and compared the results obtained by MRI and by TRUS-guided biopsy with those obtained on histopathology of the RP specimen. RESULTS: Patient data were as follows: median age 62.4 years (45-74); median PSA 6.36 ng/ml (0.5-22.6); 73.6% of patients had non-palpable disease (T1c); median biopsy Gleason score 6 (3-9); median RP specimen weight 50 g (12-172); median pathological Gleason score 7 (4-10); 68.64% of patients had organ-confined (pT2) disease. Tumour localisation was correlated with RP data in a significantly higher percentage of patients when using MRI rather than TRUS-guided biopsy (47.4 vs. 36.6%, p < 0.0001). MRI was marginally superior to TRUS-guided biopsy in detecting malignancy at the prostate apex (48.3 vs. 41.9%, p = 0.0687) and somewhat better at the prostate base (46 vs. 39.1%, p = 0.0413). It was highly significantly better at mid-gland (52 vs. 41.1%, p = 0.0015) and in the transition zone (40.1 vs. 24.3%, p < 0.0001). MRI had higher sensitivity in larger (≥50 g) than smaller (<50 g) prostates (50.3 vs. 42.2%, p = 0.0017). CONCLUSIONS: MRI was superior to TRUS-guided biopsy in locating prostate tumours except at the gland apex. MRI was more accurate in larger (≥50 g) than smaller prostates.

Hoechst 33342 side population identification is a conserved and unified mechanism in urological cancers.

Mutation within the adult human stem cell (SC) compartment has been proposed as a factor in the initiation and promotion of carcinogenesis. Isolation of these cancer stem cells (CSCs) has proven difficult, limiting their subsequent phenotypic, functional, and genetic characterization. We have used the Hoechst 33342 dye efflux technique to isolate an epithelial side population (SP) from genitourinary (GU) cancers, which is enriched for cells with SC traits. With informed consent, samples were taken from patients with primary tumors and undergoing surgery for prostatic (CaP), invasive bladder transitional cell (TCC), and renal cell carcinomas (RCC). Single cell epithelial suspensions were extracted from these and incubated with Hoechst 33342. Hoechst SP/non-SP profiles were then generated by flow cytometry using standardized protocols. SP/non-SP cell cycle status was established by Hoechst 33342 and Pyronin Y staining. Immunocytochemistry staining was performed for markers suggested as stem markers as well as lineage-specific markers. Functionality was determined using colony-forming assays and long-term monolayer culture. A characteristic verapamil-sensitive SP was isolated from all 3 urological malignancies and represented 0.57% +/- 0.11% (CaP), 0.52% +/- 0.49% (TCC), and 5.9% +/- 0.9% (RCC) of the total epithelial population. Cell cycle analysis showed that the SP had enhanced numbers of cells in G(0) as compared to the total cell population (CaP 12.4% +/- 3.2 vs. 3.8% +/- 1.0, RCC 23.2% +/- 3.4 vs. 1.8% +/- 0.9, and TCC 28.5% +/- 4.9 vs. 4% +/- 1.3). Immunocytochemistry demonstrated an increased expression of proliferative and putative stem markers within the SP fraction. Cultures confirmed significant enhancement of colony-forming ability and proliferative capacity of the SP fraction. A characteristic SP enriched for stem-like cells has been isolated from the 3 most common urological malignancies. This provides strong evidence that Hoechst 33342 efflux is a conserved and unified mechanism in GU cancer.

Characterization of the Hoechst 33342 side population from normal and malignant human renal epithelial cells.

The fundamental changes which predispose for renal cell carcinoma (RCC) are poorly characterized. It is hypothesized that "cancer stem cells" may be influential in carcinogenesis, and the epithelial side population (SP) is enriched for stemlike cells in other epithelial cancers. In this study, we have isolated and characterized the SP and non-SP (NSP) populations from normal (NK) and malignant (RCC) human kidney tissue. NK specimens were taken from patients undergoing non-renal cancer surgery and paired malignant and macroscopically normal tissue samples were taken from patients undergoing surgery for RCC. The Hoechst 33342 dye efflux technique was used to isolate epithelial SP and NSP from normal and malignant human renal tissue. Cellular subpopulations were phenotyped for lineage, cell cycle, and putative stem cell markers, and functionally characterized using in vitro colony-forming and proliferation assays. The SP constituted 3.8 +/- 0.4 and 5.9 +/- 0.9% of epithelial cells in NK and RCC, respectively, of which 14.1 +/- 3.5 and 13.2 +/- 3.6% were shown to be in G(0). SP cells demonstrated greater proliferative potential in colony-forming efficiency, long-term culture, and spheroids assays and were shown to be maintained upon tissue culture passage. We have shown that the renal SP is enriched for quiescent cells, with a high proliferative capacity and stemlike properties. The population is, however, heterogeneous, confirming that the terms "SP cell" and "stem cell" cannot be used interchangeably.

Diclofenac for treatment of nocturia caused by nocturnal polyuria: a prospective, randomised, double-blind, placebo-controlled crossover study.

OBJECTIVES: To investigate the efficacy of diclofenac 50 mg enteric-coated tablet (Non-Steroidal Anti-Inflammatory Drug) in the treatment of nocturnal polyuria. MATERIALS AND METHODS: 26 patients (20 male and 6 female) with a mean age of 72 years (range 52-90) diagnosed with nocturnal polyuria were recruited. The study period comprised 2 weeks of either placebo or active medication taken at 2100 h. Following one-week rest period, patients were crossed over to the other medication for a further 2 weeks. Frequency volume charts were completed during the second week of each of the two study periods along with feedback forms to assess any subjective improvement in symptoms during each of the study periods. RESULTS: A significant improvement in the symptoms was noted for diclofenac when compared with the placebo. The mean nocturnal frequency decreased from 2.7 to 2.3 (p<0.004) and the mean ratio of night-time to 24 h urine volume decreased from 44% to 39% (p<0.001). No significant side effects were reported. CONCLUSIONS: NSAIDs are effective in the treatment of nocturnal polyuria causing a decrease in nocturnal frequency with subjective symptom improvement. Our study suggests a novel treatment option for this common condition.