Effects of metformin and silodosin as supplementary treatments to abiraterone on human telomerase reverse transcriptase (hTERT) level in metastatic castration-resistant prostate cancer (mCRPC) cells: An in vitro study.

The antiproliferative properties of metformin and silodosin have been observed in prostate cancer. Furthermore, it is hypothesized that the molecular pathways related to these drugs may impact the levels of human telomerase reverse transcriptase (hTERT) in prostate cancer cells. The aim of this study was to assess the effect of metformin and silodosin on the levels of hTERT in metastatic castration-resistant prostate cancer (mCRPC) cells. The present study employed an experimental design with a post-test-only control group. This study utilized the PC3 cell line as a model for mCRPC. A viability experiment was conducted using the CCK-8 method to determine the inhibitory concentration (IC50) values of metformin, silodosin, and abiraterone acetate (AA) after a 72-hour incubation period of PC3 cells. In order to investigate the levels of hTERT, PC3 cells were divided into two control groups: a negative control and a standard therapy with AA. Additionally, three experimental combination groups were added: metformin with AA; silodosin with AA; and metformin, silodosin and AA. The level of hTERT was measured using sandwich ELISA technique. The difference in hTERT levels was assessed using ANOVA followed by a post hoc test. The IC50 values for metformin, silodosin, and AA were 17.7 mM, 44.162 mM, and 66.9 µM, respectively. Our data indicated that the combination of metformin with AA and the combination of metformin, silodosin and AA decreased the hTERT levels when compared to control, AA, and silodosin with AA. The administration of metformin resulted in a reduction of hTERT levels in the PC3 cell line, but the impact of silodosin on hTERT levels was not statistically significant compared to AA group.

A systematic review and meta-analysis of intraarterial chemotherapy for non muscle invasive bladder cancer: Promising alternative therapy in high tuberculosis burden countries.

INTRODUCTION: Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence. Intravesical Bacillus Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC. Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results. We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC. METHODS: We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study. RESULTS: Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p<0.001). Some RCT's had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades. CONCLUSIONS: The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results.

Giant bladder calculi due to four years neglected cystostomy.

Giant bladder calculi are rare and long-term usage of cystostomy could cause stone formation. Due to the lack of evidence on giant bladder calculi and the long-term usage of cystostomy can cause bladder calculi formation, we provide a case study of a man with a neglected cystostomy with giant bladder calculi for 4 years. A fixed mass was discovered in the suprapubic region. Ultrasound examination revealed 4.1 × 5.5 cm bladder calculi and contracted left kidney. Bipolar voiding cystourethrography portrayed stricture in pars pendular and membranacea, uneven bladder wall, and 4.5 × 4.5 cm bladder calculi. The stone was extracted, and the bladder filling test revealed a small bladder capacity. Since the patient refused urethral reconstruction and bladder augmentation, he was discharged with another cystostomy catheter. Six-month follow-up revealed no forming stones. Neglected cystostomy catheter can cause giant bladder calculi. Prompt diagnosis and treatment should be made to manage this condition to reduce the likelihood of bladder cancer.

Male Reproductive Tract Involvement and Sperm Parameters in SARS-CoV-2 Patients: A Systematic Review and Meta-Analysis.

PURPOSE: There is a growing concern regarding the impact of SARS-CoV-2 infection on the male reproductive tract due to ACE2 receptor expression, however, its impact remains unclear. We performed this review to evaluate whether SARS-CoV-2 infection affects the male reproductive system. MATERIALS AND METHODS: We conducted a search in the Embase, Scopus, and MEDLINE databases, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Eligible studies comprised articles reporting viral RNA presence in semen, sperm parameters, and orchitis or orchiepididymitis occurrence in SARS-CoV-2 patients. Observational studies' quality was determined using the Newcastle-Ottawa Scale (NOS). Case reports were assessed using the Joanna Briggs Institute (JBI)'s checklist. RESULTS: A total of 32 relevant articles were included. Viral RNA was found in 7% of infected patients' semen (95% CI, -0.01 to 0.15) from 3 studies. There were also only 7% of patients with orchitis or orchiepididymitis clinical manifestations (95% CI, 0.05-0.10). The semen volume and concentration were 2.34 mL (95% CI, 1.87-2.81) and 51.73 million/mL (95% CI, 31.60-71.85). The progressive and total motility percentages were 36.11% (95% CI, 28.87-43.35) and 43.07% (95% CI, 28.57-57.57), respectively. The morphology was 6.03% (95% CI, -1.05 to 13.10). There is a difference in semen volume between moderate and severe infections (MD, 0.52; 95% CI, 0.27-0.76; p<0.0001) and concentration between mild and moderate (MD, 18.74; 95% CI, 1.02-36.46; p=0.04), mild and severe (MD, 43.50; 95% CI, 13.86-73.14; p=0.004), as well as moderate and severe (MD, 22.25; 95% CI, 9.33-35.17; p=0.0007). CONCLUSIONS: SARS-CoV-2 infection may result in decreased sperm concentration in severe cases and the mechanism relates to potential reproductive tract inflammation. The absence of large viral RNA detection in the semen indicates a systemic effect, although this is largely unproven.

The role of tranexamic acid in reducing bleeding during transurethral resection of the prostate: An updated systematic review and meta-analysis of randomized controlled trials.

Introduction: Transurethral resection of the prostate (TURP) is regarded as the current gold standard surgical intervention for benign prostatic hyperplasia (BPH). However, this procedure is associated with significant chances of intraoperative and postoperative bleeding. Several studies have reported the role of tranexamic acid in prostatic surgeries, but, its role in TURP is still unclear. This review aims to evaluate the role of tranexamic acid in reducing the blood loss during TURP. Materials and Methods: A systematic search was performed on Medline, Scopus, Embase, and Cochrane, up to December 2021. Relevant randomized controlled trials (RCTs) evaluating the role of tranexamic acid in TURP were screened using our predefined eligibility criteria. Data were expressed as odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CIs). All analyses were performed using RevMan 5.4 (Cochrane Collaboration, UK). Results: Six trials were included in this meta-analysis, comprising of 582 patients with BPH who underwent TURP. The meta-analysis revealed an insignificant difference in the rate of blood transfusion (OR 0.68, 95% CI 0.34, 1.34, P = 0.27) but, a significantly lower amount of blood loss and a lower reduction in the hemoglobin (Hb) levels in the patients receiving tranexamic acid as compared to the control group (MD - 127.03, 95% CI - 233.11, -20.95, P = 0.02; MD - 0.53, 95% CI - 0.84, -0.22, P < 0.01; respectively). Also, the operative time (P = 0.12) and the length of hospitalization (P = 0.59) were similar between the two groups. Conclusion: The administration of tranexamic acid was not found to be effective in reducing the need for blood transfusion, the operative time, and the length of hospitalization during the TURP. However, it could reduce the amount of blood loss and the fall in the Hb levels.

The role of hyperbaric oxygen therapy in Fournier's Gangrene: A systematic review and meta-analysis of observational studies

ABSTRACT Purpose: Management of Fournier's Gangrene (FG) includes broad-spectrum antibiotics with adequate surgical debridement, which should be performed within the first 24 hours of onset. However, this treatment may cause significant loss of tissue and may delay healing with the presence of ischemia. Hyperbaric oxygen therapy (HBOT) has been proposed as adjunctive therapy to assist the healing process. However, its benefit is still debatable. Therefore, this systematic review and meta-analysis aimed to evaluate the effect of HBOT as an adjunct therapy for FG. Materials and Methods: This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol to obtain studies investigating the effect of HBOT on patients with FG. The search is systematically carried out on different databases such as MEDLINE, Embase, and Scopus based on population, intervention, control, and outcomes criteria. A total of 10 articles were retrieved for qualitative and quantitative analysis. Results: There was a significant difference in mortality as patients with FG who received HBOT had a lower number of deaths compared to patients who received conventional therapy (Odds Ratio 0.29; 95% CI 0.12 - 0.69; p = 0.005). However, the mean length of stay with Mean Difference (MD) of -0.18 (95% CI: -7.68 - 7.33; p=0.96) and the number of debridement procedures (MD 1.33; 95% CI: -0.58 - 3.23; p=0.17) were not significantly different. Conclusion: HBOT can be used as an adjunct therapy to prevent an increased risk of mortality in patients with FG.

Prognostic value of neutrophil-to-lymphocyte ratio (NLR) in penile cancer: A systematic review and meta-analysis.

Background: Penile cancer is rare among male malignancies. Various biomarkers have been used to predict the prognosis of cancer, one of which is the neutrophil to lymphocyte ratio (NLR). Therefore, we conducted this systematic review and meta-analysis to evaluate the prognostic value of NLR in penile cancer. Methods: This review was conducted following the PRISMA guideline. Several databases, including Scopus, Science-direct, and PubMed, were systematically searched. The primary outcomes were lymph node metastasis (LNM), cancer-specific survival (CSS), and overall survival (OS). All statistical analyses were processed using Review Manager (RevMan) version 5.4. Results: A total of six retrospective studies were included in the analysis. The cut-off values of NLR in the included studies ranged from 2.6 to 3.59. Meta-analysis showed that penile cancer patients with high NLR had worse LNM and CSS based on the univariate analysis (OR 3.56, 95% CI 2.38, 5.32, p < 0.01; HR 4.19, 95% CI 2.19, 8.01, p = 0.0; respectively). Furthermore, the meta-analysis revealed that NLR is an independent predictor of LNM and CSS (OR 6.67, 95% CI 2.44, 18.22, p < 0.01; HR 2.15, 95% CI 1.23, 3.73, p < 0.01; respectively). However, NLR failed to show as independent predictor for OS (HR 1.69,95% CI 0.95,3.00, p = 0.07). Conclusion: NLR is an independent predictor of LNM and CSS. However, NLR is not proven to be an independent predictor of OS in this study.

The efficacy and safety of mitomycin C intra urethral injection to prevent recurrent urethral stricture: A systematic review and meta-analysis.

Objectives: Direct Vision Internal Urethrotomy (DVIU) is regarded as the most popular and frequently used minimal invasive approach for treating urethral stricture. However, the application of this procedure is limited due to the high recurrence rate. Recent trials have the benefit of mitomycin C as adjuvant therapy to reduce the stricture recurrence in DVIU procedures. In this meta-analysis, we aim to determine the efficacy of mitomycin C as adjuvant therapy for DVIU. Methods: A systematic literature search was carried out from Embase, ScienceDirect, and PubMed published up to September 2021. Relevant Randomized Controlled Trials (RCTs) were screened using our eligibility criteria. The quality assessment of the RCT was assessed using Cochrane RoB 2. The outcome was measured as an Odds Ratio (OR) with 95% Confidence Intervals (CIs). Statistical analyses were performed using RevMan 5.4. Results: We included four RCTs in the meta-analysis, with a total of 392 patients with urethral strictures undergoing DVIU. The pooled analysis showed a significantly lower recurrence rate in patients undergoing DVIU with additional treatment of mitomycin C compared to the control group (OR 0.27, 95% CI 0.16-0.45, p < 0.0001). Conclusion: Our findings highlight the benefit of adjuvant treatment with mitomycin C to reduce the incidence of urethral stricture recurrence after DVIU procedures.

The role of hyperbaric oxygen therapy in Fournier's Gangrene: A systematic review and meta-analysis of observational studies.

PURPOSE: Management of Fournier's Gangrene (FG) includes broad-spectrum antibiotics with adequate surgical debridement, which should be performed within the first 24 hours of onset. However, this treatment may cause significant loss of tissue and may delay healing with the presence of ischemia. Hyperbaric oxygen therapy (HBOT) has been proposed as adjunctive therapy to assist the healing process. However, its benefit is still debatable. Therefore, this systematic review and meta-analysis aimed to evaluate the effect of HBOT as an adjunct therapy for FG. MATERIALS AND METHODS: This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol to obtain studies investigating the effect of HBOT on patients with FG. The search is systematically carried out on different databases such as MEDLINE, Embase, and Scopus based on population, intervention, control, and outcomes criteria. A total of 10 articles were retrieved for qualitative and quantitative analysis. RESULTS: There was a significant difference in mortality as patients with FG who received HBOT had a lower number of deaths compared to patients who received conventional therapy (Odds Ratio 0.29; 95% CI 0.12 - 0.69; p = 0.005). However, the mean length of stay with Mean Difference (MD) of -0.18 (95% CI: -7.68 - 7.33; p=0.96) and the number of debridement procedures (MD 1.33; 95% CI: -0.58 - 3.23; p=0.17) were not significantly different. CONCLUSION: HBOT can be used as an adjunct therapy to prevent an increased risk of mortality in patients with FG.

Comparison of ureteral stent diameters on ureteral stent-related symptoms: A systematic review and meta-analysis.

Ureteral stents may induce complications that may disrupt the quality of life of patients. Several factors that may cause these symptoms are the design, material, diameter, length, and position of the stent. The impact of its diameter varies among current reports, thus we aimed to compare the symptoms between 6 Fr and 5 Fr or less ureteral stents. A systematic search and screening were performed in the Embase, Medline, and Scopus databases. Eligible studies included randomized controlled trials (RCTs). Cochrane risk of bias tool 2 was used to evaluate the studies. Seven RCTs were included in this review. Urinary symptoms were discussed qualitatively. From the included studies, the use of a relatively smaller stent diameter yielded an overall lower rate of Ureteral Stent Symptom Questionnaire score and urinary symptoms compared to a stent with a larger diameter. There was no significant difference in migration rate (OR: 1.55, 95% CI: 0.67-3.57, P » .31), visual analogue scale (MD: 0.42, 95% CI: 2.04 to 1.20, P » .61), analgesic use duration (MD: 0.06, 95% CI: 1.02 to 0.91, P » .91), and stone-free rate probability (OR: 1.29, 95% CI: 0.48-3.45, P » .62) between patients with 5 Fr or less and 6 Fr ureteral stents. Smaller ureteral stent size is suggested for reducing ureteral stent-related symptoms, without significant differences in the incidence of stent migration, pain, analgesic use, and stone-free rate.

Endoscopic Combined Intrarenal Surgery vs Percutaneous Nephrolithotomy for Large and Complex Renal Stone: A Systematic Review and Meta-Analysis.

Background: Managing complex and large renal stones with percutaneous nephrolithotomy (PCNL) is difficult because of the likelihood of residual stones and multiple access. Endoscopic combined intrarenal surgery (ECIRS) is introduced as an improvement to the procedure to manage stones in one session. The objective of this systematic review and meta-analysis is to compare the efficacy and safety between ECIRS and PCNL for treating large and complex renal stones. Materials and Methods: We conducted a systematic review in the Embase, Scopus, and MEDLINE databases based on the 2020 Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Eligible studies comprised both randomized and nonrandomized studies comparing ECIRS and PCNL. Results: A total of five nonrandomized studies and one randomized controlled trial were included. The analysis was divided into two subgroups based on the PCNL type, a conventional PCNL (cPCNL) and a mini-PCNL (mPCNL). The one-step stone-free rate (SFR) of ECIRS were significantly higher compared with both the cPCNL (odds ratio [OR] 5.14, 95% confidence interval [CI] 2.54 to 10.4, p < 0.001) and mPCNL (OR 4.27, 95% CI 2.57-7.1, p < 0.001). There were no significant differences in mean operative time and hemoglobin drop between both groups (p > 0.05). The use of auxiliary procedures was significantly higher in both PCNL groups compared with the ECIRS group (OR 0.19, 95% CI 0.13-0.30, p < 0.001). The overall complication rate of ECIRS was lower compared with PCNL (OR 0.43, 95% CI 0.21-0.85, p = 0.02), especially urosepsis, in which the incidence was lower compared with cPCNL (OR 0.14, 95% CI 0.02-0.78, p = 0.02), but not mPCNL (p > 0.05). Conclusion: ECIRS is an effective and safe treatment particularly for large and complex nephrolithiasis, with significantly higher one-step SFR, a lower necessity for auxiliary procedures, and a lower complication rate compared with PCNL.

Local anesthetics versus systemic analgesics for reducing pain during Extracorporeal Shock Wave Lithotripsy (ESWL): A systematic review and meta-analysis.

Extracorporeal Shock Wave Lithotripsy (ESWL) is one of the treatment options for patients with renal and ureteral calculi. Even though the procedure is less invasive compared to others, pain caused by the procedure is a major concern. Several studies recommended the use of either local or systemic analgesia with varying results. We aimed to compare the use of local anesthetics and systemic analgesics from randomized controlled trials evaluating pain management during ESWL. A systematic search adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis protocol was performed in theMedline, ScienceDirect, and Cochrane library databases. The bias was evaluated using the Cochrane risk of bias tool. Mean difference (MD) was used to analyze continuous outcomes. A total of seven studies were obtained. The topical anesthesia used was eutectic mixture of local anesthetic cream and xylocaine gel. In contrast, the local injection anesthesia used was subcutaneous prilocaine and intracutaneous sterile water injection. The systemic analgesics used were intramuscular and oral forms of sodium diclofenac. There is no significant difference between the visual analogue scale results between the local and systemic groups (P> .05). The differences in ESWL frequency were also insignificant (P > .05). Additional analgesics supplementation (MD 8.44, 95% CI 2.28-14.61, P» .007) and the duration of the procedure (MD 1.39, 95% CI 0.21-2.56, P» .02) were significantly lower in the local group. Local anesthesia in ESWL shows a similar degree of pain and frequency but has a shorter duration and fewer analgesics supplementation than systemic analgesics.

Intraurethral lidocaine use during urodynamics in female patients: A systematic review and meta-analysis.

Pain and discomfort may occur in catheterization during a urodynamic examination. A lidocaine gel combined with a water-based lubricant is sometimes used to reduce pain during catheterization. Several studies claimed that intraurethral lidocaine administration could cause inaccurate urodynamic parameters results. However, its definite effects in urodynamics testing on humans are still not clear. We aimed to evaluate the effects of intraurethral lidocaine on pain and urodynamic study parameters in patients undergoing an invasive urodynamic examination. A systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was performed in the MEDLINE, PubMed, and ScienceDirect databases for randomized controlled trials (RCTs). The bias of the studies is evaluated using the Cochrane risk of bias tool by two independent reviewers. The analyses of continuous outcomes were displayed as mean difference (MD), whereas odds ratio is used to analyze dichotomous data. Heterogeneity between studies is determined using the I2 value. A total of three RCTs out of 622 discovered that articles were eligible for analysis. Forest plot analysis of the mean visual analogue scale difference of the studies indicated an insignificant difference between the lidocaine and placebo group (MD -7.68; 95% CI -34.04 to -18.68, P » .57). All urodynamic parameter results were also similar between the two groups (P > .05). Routine intraurethral lidocaine injection prior to a urodynamic study does not affect pain intensity and urodynamic parameters.

Profile of POT1 as telomerase shelterin component discriminatesbetween cervical cancer and normal cervical cells.

BACKGROUND/AIM: Telomerase activity is influenced by hTERT transcriptional regulation, shelterin, and posttranscriptional alternative splicing. Telomerase shelterin such as POT1 is highly correlated with various cancers. However, the profile of POT1 in cervical cancer has not been clearly identified. Therefore, it is important to identify its profile in cervical cancer biopsy tissue and normal cervical smears. MATERIALS AND METHODS: Biopsy tissue of cervical cancer patients and normal cervical smears were characterized using SDS-PAGE and western blot. Sixteen biopsy tissues of cervical cancer patients and 15 normal cervical smears were measured for POT1 level using ELISA. RESULTS: The inline band at 70 kDa indicated that all samples had protein that was identified as POT1. Western blot showed that telomerase antibody only recognized POT1 in biopsy tissue of cervical cancer patients. There was a significant difference (P = 0.01) in POT1 level between biopsy tissue of cervical cancer patients and normal cervical smears. CONCLUSION: POT1 was identified at 70 kDa in biopsy tissue of cervical cancer patients and its level was higher than that in normal cervical smears. The high level of POT1 in the biopsy tissue of cervical cancer patients showed the influence of this shelterin component in cervical carcinogenesis and also cell immortalization.