Current Practices in Genetic Testing for Prostate Cancer: The Indian Scenario.

BACKGROUND: Despite genetic testing being recommended by international guidelines for the selection of targeted therapy for prostate cancer (PCa), limited data are available on genetic testing for PCa in India. OBJECTIVES: The objective is to understand the current genetic testing practice pattern for PCa in India. MATERIALS AND METHODS: A panel of 9 experts developed and validated a premeeting online questionnaire comprising 12 objective questions. The questionnaire was circulated from February 2022 to May 2022 among medical oncologists and uro-oncologists across pan-India, followed by response collection over 3 months. Descriptive statistics were used to summarize results and concluding statements were formulated on current genetic testing practice patterns for PCa. RESULTS: A total of 103 responses were received. Genetic testing was advised by 35.9% of the participants in <5% of patients with PCa. Patients with a family history of PCa (88.3%) were most commonly referred for genetic testing. Nearly half (50.2%) of the participants routinely tested for homologous recombination repair (HRR) genes; 52% used blood and tissue as the most preferred specimen for performing genetic testing and 44.7% followed the testing sequence of tumor tissue followed by blood. Major barriers to genetic testing were affordability and scarcity of genetic counselors, while a major change could be brought by making it cost-effective and improving access to medication. CONCLUSIONS: We observed a lower prescription frequency of genetic testing for the HRR gene across pan-India. Improving the quality and access to genetic testing and the availability of cost-effective-targeted therapies will aid in delivering personalized care to patients with metastatic PCa.

Perioperative and functional outcomes following robot-assisted partial nephrectomy: Descriptive analysis of Indian study group on partial nephrectomy database.

Introduction: There is an unmet need for high-quality data for Robot-assisted partial nephrectomy (RAPN) in the Indian population. Indian study group on partial nephrectomy (ISGPN) is a consortium of Indian centers contributing to the partial nephrectomy (PN) database. The current study is a descriptive analysis of perioperative and functional outcomes following RAPN. Methods: For this study, the retrospective ISGPN database was reviewed, which included patients who underwent RAPN for renal masses at 14 centers across India from September 2010 to September 2022. Demographic, clinical, radiological, perioperative, and functional data were collected and analyzed. Ethics approval was obtained from each of the participating centers. Results: In this study, 782 patients were included, and 69.7% were male. The median age was 53 years (interquartile range [IQR 44-62]), median operative time was 180 min (IQR 133-240), median estimated blood loss was 100 mL (IQR 50-200), mean warm ischemia time was 22.7 min and positive surgical margin rates were 2.5%. The complication rate was 16.2%, and most of them were of minor grade. Trifecta and pentafecta outcomes were attained in 61.4% and 60% of patients, respectively. Conclusions: This is the largest Indian multi-centric study using the Indian Robotic PN Collaborative database to evaluate the outcomes of robot-assisted PN, and has proven its safety and efficacy in the management of renal masses.

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.

Catheter squeeze technique to solve urinary catheter drainage problem.

Background: Urinary catheter insertion is one of the basic techniques used in patient care to drain the bladder. Around 30 million urinary catheters are inserted annually in the USA alone.2 Often, when inserting a urinary catheter, it is noticed that urine does not drain right away. Method: This article will discuss the 'urinary catheter squeeze' technique that can help healthcare providers resolve this problem. Results: We have a simple solution called the 'catheter squeeze technique' to address the problem of urine not draining. The clinician who inserts the catheter can assess the outcome of this technique immediately, as it provides immediate results. Conclusion: There are several theories regarding why urine may not properly drain into a catheter after it is inserted, and various methods are employed to address this issue. Our "catheter squeeze technique" is a simple approach that requires no tools or assistance, and its effectiveness can be observed immediately after insertion.

Robot assisted laparoscopic adrenalectomy: Should this be the new standard?

INTRODUCTION: Minimal invasive surgeries (MIS) for large size adrenal tumors are still debatable. The objective is to evaluate the contemporary peri- and post-operative outcomes of patients undergoing (open = OA, laparoscopic = LA, and robotic = RA) adrenalectomies in three institutions. MATERIALS AND METHODS: Retrospectively gathered peri- and post-operative data of 235 patients, underwent adrenalectomy at three Institutions over a 7-year period (2013-2020) were analyzed. All patients underwent thorough radiological and endocrine workup. RESULTS: Two hundred and thirty five patients who underwent adrenalectomy (OA (n = 29), LA (n = 146), and RA (n = 60)) were assessed. OA (n = 29) versus Minimally invasive surgery (n = 206) showed significant differences (median, p value) in larger tumour size, cm (9.4 vs 5, (p = 0.0001)), longer operative time, mins (240 vs 100, (p = 0.0001)), longer hospital stay, days (8 vs 3,(p = .0001)), Higher readmission rates (14% vs 1.9%), higher blood loss, ml (400 vs 100, (p = 0.0001)) requiring blood transfusion (14% vs 4.3%) (p = 0.03), higher intraoperative complication (21% vs 6%) (p = 0.0004), and post op complications (17% vs 5.3%) (p = 0.01). Amongst the MIS (RA vs LA), RA appeared be have better outcomes in terms of shorter operative time, less blood loss and less intra operative complications with a p value <0.05. These results were consistent for the assessment of patients who had ⩾6 cm tumor size. The postoperative complication rates were lowest with RA (3.3%) compared to OA (17%) and LA (6.1%). CONCLUSIONS: Contemporary practice of adrenalectomy shows that robotic adrenalectomy is safe and effective irrespective of the tumor size.

Expert survey on management of prostate cancer in India: Real-world insights into practice patterns.

To gain insights on the diverse practice patterns and treatment pathways for prostate cancer (PC) in India, the Urological Cancer Foundation convened the first Indian survey to discuss all aspects of PC, with the objective of guiding clinicians on optimizing management in PC. A modified Delphi method was used, wherein a multidisciplinary panel of oncologists treating PC across India developed a questionnaire related to screening, diagnosis and management of early, locally advanced and metastatic PC and participated in a web-based survey (WBS) (n = 62). An expert committee meeting (CM) (n = 48, subset from WBS) reviewed the ambiguous questions for better comprehension and reanalyzed the evidence to establish a revote for specific questions. The threshold for strong agreement and agreement was ≥90% and ≥75% agreement, respectively. Sixty-two questions were answered in the WBS; in the CM 31 questions were revoted and 4 questions were added. The panelists selected answers based on their best opinion and closest to their practice strategy, not considering financial constraints and access challenges. Of the 66 questions, strong agreement was reached for 17 questions and agreement was achieved for 22 questions. There were heterogeneous responses for 27 questions indicative of variegated management approaches. This is one of the first Indian survey, documenting the diverse clinical practice patterns in the management of PC in India. It aims to provide guidance in the face of technological advances, resource constraints and sparse high-level evidence.

Gonadotropin-releasing hormone agonists in prostate cancer: A comparative review of efficacy and safety.

Androgen deprivation therapy (ADT) using gonadotropin-releasing hormone agonist (s) (GnRH-A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH-A. All GnRH-A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (≤50 ng/dL in a month and ≤20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ≤50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate-specific antigen suppression. In neoadjuvant setting, when only goserelin was used, the 10-year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10-year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10-year survival rate of 87%, and triptorelin had an 8-year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH-A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH-A. Goserelin appears to be the most convenient of all the GnRH-A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH-A for ADT in prostate cancer.

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.

Avoid cruising on the uroflowmeter: evaluation of cruising artifact on spinning disc flowmeters in an experimental setup.

AIMS: The aim of our study was to access the variability of maximum flow rate (Q(max)), average flow rate (Q(av)) and flow pattern while varying the point of impact of flow on the flowmeter. METHODS: Water was delivered through a motorised tube holder in a standardised experimental set up. Flow was directed in 4 different directions on the funnel; 1) Periphery, 2) Base, 3) Centre and, 4) in a cruising motion from the periphery of the funnel to the centre and back again. The variation in the Q(max), Q(av) and the flow pattern were studied at 4 different flow rates. The variables recorded when the flow was directed at the centre of the funnel was taken as baseline. RESULTS: There was a significant difference in the Q(max) and Q(av)when the point of impact was at the periphery or in a cruising motion compared to the centre. The difference was more marked with cruising motion with a characteristic flow pattern. The maximum percentage difference in Q(av) was 4.1%, whereas the difference in Q(max) was higher at 16.6% on comparing crusing motion with the values from the centre. CONCLUSION: We have demonstrated a significant variation in Q(max), Q(av) and flow pattern with change in the point of impact on the flowmeter. Though the changes in Q(av) were statistically significant, the alteration in the recorded Q(max) values was more striking. Our study emphasizes the importance of combining Q(av) and flow pattern along with Q(max) in interpretation of results of uroflowmetry.

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.