Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer: A Systematic Review and Meta-Analysis.

Importance: Cardiovascular (CV) events remain a substantial cause of mortality among men with advanced and metastatic prostate cancer (PCa). The introduction of novel androgen receptor signaling inhibitors (ARSI) has transformed the treatment landscape of PCa in recent years; however, their associated CV toxic effects remains unclear. Objective: To assess the incidence of CV events with addition of ARSI to standard of care (SOC) in locally advanced (M0) and metastatic (M1) PCa. Data Sources: Systematic searches of PubMed, Scopus, Web of Science, EMBASE, and ClinicalTrials.gov were performed from inception up to May 2023. Study Selection: Randomized clinical trials of ARSI agents (abiraterone, apalutamide, darolutamide, enzalutamide) that reported CV events among individuals with M0 and M1, hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). Data Extraction and Synthesis: A systematic review was performed in accordance with PRISMA guidance. Two authors screened and independently evaluated studies eligible for inclusion. Data extraction and bias assessment was subsequently performed. Main Outcomes and Measures: A random-effects meta-analysis was performed to estimate risk ratios for the incidence of all grade and grade 3 or higher CV events (primary outcomes), in addition to hypertension, acute coronary syndrome (ACS), cardiac dysrhythmia, CV death, cerebrovascular event, and venous thromboembolism (secondary outcomes). Sources of heterogeneity were explored using meta-regression. Results: There were 24 studies (n = 22 166 patients; median age range, 63-77 years; median follow-up time range, 3.9-96 months) eligible for inclusion. ARSI therapy was associated with increased risk of all grade CV event (risk ratio [RR], 1.75; 95% CI, 1.50-2.04; P < .001) and grade 3 or higher CV events (RR, 2.10; 95%, 1.72-2.55; P < .001). ARSI therapy also was associated with increased risk for grade 3 or higher events for hypertension (RR, 2.25; 95% CI, 1.74-2.90; P < .001), ACS (RR, 1.93; 95% CI, 1.43-1.60; P < .01), cardiac dysrhythmia (RR, 1.64; 95% CI, 1.23-2.17; P < .001), cerebrovascular events (RR, 1.86; 95% CI, 1.34-2.59; P < .001) and for CV-related death (RR, 2.02; 95% CI, 1.32-3.10; P = .001). Subgroup analysis demonstrated increased risk of all CV events across the disease spectrum (M0 HSPC: RR, 2.26; 95% CI, 1.36-3.75; P = .002; M1 HSPC: RR, 1.85; 95% CI, 1.47-2.31; P < .001; M0 CRPC: RR, 1.79; 95% CI, 1.13-2.81; P = .01; M1 CRPC: RR, 1.46; 95% CI, 1.16-1.83; P = .001). Conclusions and Relevance: This systematic review and meta-analysis found that the addition of ARSIs to traditional ADT was associated with increased risk of CV events across the prostate cancer disease spectrum. These results suggest that patients with prostate cancer should be advised about and monitored for the potential of increased risk of CV events with initiation of ARSI therapy alongside conventional hormonal therapy.

Modern methods in managing urachal adenocarcinoma.

Objectives: We sought to evaluate modern diagnostic and treatment options for urachal adenocarcinoma (UAC) and to provide clarity regarding the available options and their outcomes for this poorly understood yet damaging disease. Material and methods: We conducted a systematic literature search in PubMed and Medline focusing on updated management of UAC. Results: Surgical intervention continues to be the mainstay of treatment for localized UAC. However, with the increased availability of molecular and genetic profiling, chemotherapy has consistently demonstrated promising response rates and survival outcomes, especially for a disease that commonly presents in a metastatic stage. The role of checkpoint inhibitors remains under investigation. Cross-sectional imaging is vital during postoperative surveillance. However, there may also be a role for the adoption of cystoscopy to detect bladder recurrence. Conclusions: Although the importance of surgical resection remains unchanged, improved survival outcomes with chemotherapy have been found in small retrospective studies. Randomized trial data are required to further assess the influence of systemic treatment as a primary or adjuvant therapy. Moreover, a stringent follow-up regimen incorporating evaluation for distant and local recurrence of UAC must be evaluated and adopted.

Lower vs standard pressure pneumoperitoneum in robotic-assisted radical prostatectomy: a systematic review and meta-analysis.

Robotic-assisted laparoscopic radical prostatectomy (RARP) has been traditionally performed at a pneumoperitoneum insufflation pressure of 12-15 mmHg. This meta-analysis and systematic review aims to assess the current evidence comparing lower to standard pressure pneumoperitoneum in RARP. Systematic searches of MEDLINE, COCHRANE, SCOPUS and EMBASE were performed to identify articles published up until November 2021 comparing lower pressure with standard pressure pneumoperitoneum in RARP. Standard pressure was defined as > 12 mmHg and lower pressure ≤ 12 mmHg. Estimated blood loss, length of operation, length of hospital stay, post-operative ileus, 30-day readmissions, Clavien-Dindo complications and rate of positive surgical margins were extracted as endpoints of interest. Our searches identified 165 abstracts of which 4 articles with 1319 patients were eligible. Cumulative analysis demonstrated reduced length of stay when a lower pressure was used: WMD - 0.23 (- 0.45 to - 0.02) days (p = 0.03) as well as a reduced rate of post-operative ileus: OR 0.41 (0.22 to 0.77) (p = 0.006). There was no significant increase in length of operation WMD - 1.79 (- 15.96 to 12.38) (p = 0.8), estimated blood loss WMD - 2.89 (- 29.41 to 23.62) (p = 0.83), 30-day readmissions or positive surgical margins OR 1.04 (0.78 to 1.38) (p = 0.81) and RD - 0.01 (- 0.04 to 0.01) (p = 0.3) when using a lower pressure. We have demonstrated reduced length of stay and rates of post-operative ileus, when performing RARP at a lower pressure without a significant increase in length of operation, estimated blood loss, positive surgical margins or complications. The recommendation to use lower pressure pneumoperitoneum is moderate to weak and more randomised control trials are required to validate these results.

The role of imaging in immunoglobulin G4-related disease of the upper urinary tract.

Background: Immunoglobulin G4-related disease remains a modern, relatively unknown field in the urological world. An increasing number of cases require urological input, often with invasive diagnostics and aggressive medical treatment first-line. Given this, we sought to evaluate modern radiological options of disease affecting the upper urinary tract, to provide clarity and reduce diagnostic burden and delay in this poorly understood yet potentially debilitating disease process. Summary: We conducted a systematic literature search including PubMed and Medline, focusing on immunoglobulin G4-related disease affecting the upper urinary tract, before reviewing articles assessing different radiological modalities in diagnosis. Consistent computed tomography findings have been demonstrated in the literature and contributed to recent breakthroughs in classification criteria, however invasive biopsy remains a mainstay in work-up, given the difficulties in comparing against malignancy. Early work in positron-emission tomography and magnetic resonance imaging has shown promise in radiologically distinguishing from other differentials, especially diffusion-weighted imaging showing high sensitivity levels, but not yet enough to formulate protocols and cause histological investigation to be redundant. Key messages: Our article has highlighted repeated findings in the literature of computed tomography appearances of IgG4-RD in the upper urinary tract, however invasive work-up remains a mainstay given the overlap with malignancy. Prospective, comparative studies into magnetic resonance imaging and positron-emission tomography are now required, given their early results, to improve consistency in reporting and reduce patient burden when investigating this benign, yet debilitating disease process.

Bacteriuria resistance patterns and the suitability of urinalysis as an initial diagnostic tool in a post-antibiotic era.

AIMS: Urinalysis is used as a first-line investigation throughout healthcare to indicate bacteriuria and guide treatment of potential urinary tract infections. In light of rising bacterial multi-resistance, we aim to analyse its diagnostic accuracy, determine its usefulness in a present-day setting and evaluate current antibiotic resistance patterns across a Trust population. METHODS: A retrospective case series of 712 paired urinalysis and urine culture results was obtained over a 1-month period. Sensitivity, specificity and diagnostic accuracy were calculated, and resistance profiles of commonly used Trust antibiotics assessed using statistical analysis. RESULTS: A high false negative rate of nitrites on urinalysis, with sensitivity of 38.4%, was found. Leucocyte sensitivity was 87.6% and specificity 39.7%, with no improvement in diagnostic accuracy seen when combining both. Positive urine culture growth demonstrated a substantial resistance pattern to trimethoprim of 48%, compounded by a statistically significant correlation with gentamicin resistance (p < 0.0001). CONCLUSION: Our study has highlighted a reduced accuracy of urinalysis compared with previous literature, questioning its usefulness in the real world. We have consolidated growing published trends doubting the efficacy of trimethoprim, revealing co-existing resistance patterns between commonly used antibiotics. This will have implications for future antibiotic-prescribing protocols and requires further research to ensure guidelines are progressive in consciously managing this growing concern in modern-day healthcare.

Robot-assisted laparoscopic pyeloplasty versus laparoscopic pyeloplasty for pelvi-ureteric junction obstruction in the paediatric population: a systematic review and meta-analysis.

BACKGROUND: Owing to the improved vision and instrument manipulation in robot-assisted procedures, we sought to evaluate the comparative outcomes of robot-assisted laparoscopic pyeloplasty (RALP) and laparoscopic pyeloplasty (LP) in a paediatric patients with pelvi-ureteric junction obstruction (PUJO). METHODS: We conducted a systemic literature search of online sources, including PubMed, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, and respective bibliographic reference lists. Success rate, operative time, hospital length of stay, postoperative complication rate and re-intervention rate were our primary outcomes. Combined overall effect sizes were calculated using fixed-effect or random-effects models. RESULTS: We identified 14 observational studies reporting a total of 2254 paediatric patients with PUJO, who underwent LP (n = 1021) or RALP (n = 1233). Our analysis demonstrated that RALP was associated with a significantly higher success rate [odds ratio (OR) 2.51; 95% confidence interval (CI) 1.08-5.83, p = 0.03] and shorter length of hospital stay [mean difference (MD) -1.49; 95% CI -2.22 to -077; p < 0.0001] compared with LP. Moreover, nonsignificant reductions in postoperative complications (OR 0.61; 95% CI 0.36-1.02; p = 0.06) and re-intervention (OR 0.43; 95% CI 0.15-1.21; p = 0.11) were found in favour of RALP. There was no difference in procedure time between the two approaches (MD -0.15; 95% CI -30.22 to 29.93, p = 0.99). CONCLUSIONS: Our meta-analysis of observational studies demonstrated that RALP is safe and may have higher success rate compared with the more traditional laparoscopic approach in a paediatric population. Moreover, it may be associated with lower postoperative complications and re-intervention rates. Evidence from randomized trials is required.

Retrieval of Gallbladder Via Umbilical Versus Epigastric Port Site During Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this study was to evaluate the comparative efficacy of gallbladder retrieval via the epigastric and umbilical port during laparoscopic cholecystectomy. METHODS: We systematically searched MEDLINE, EMBASE, CINAHL, CENTRAL, the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, ISRCTN Register, and bibliographic reference lists. Postoperative pain intensity, port-site infection, hernia, bleeding, and retrieval time were outcome parameters. Combined overall effect sizes were calculated using fixed-effect or random-effects models. RESULTS: We identified 5 randomized controlled trials and 1 prospective cohort study reporting a total of 2394 patients who underwent laparoscopic cholecystectomy with retrieval of the gallbladder via the umbilical port (n=1194) or epigastric port (n=1200). Our initial analysis demonstrated that gallbladder retrieval via the umbilical port was associated with a nonsignificant reduction in pain assessed by visual analogue scale at 24 hours [mean difference (MD): -0.49, 95% confidence interval (CI): -1.06 to 0.08, P=0.09] compared with the epigastric port. However, after sensitivity analysis and eliminating the source of heterogeneity, it reached statistical significance (MD: -0.66, 95% CI: -0.85 to -0.48, P<0.00001). Moreover, gallbladder retrieval via the umbilical port was associated with significantly shorter retrieval time (MD: -1.83, 95% CI: -3.18 to -0.49, P=0.008) but similar risk of port-site infection (odds ratio: 1.99, 95% CI: 0.53-7.44, P=0.31) and hernia (odds ratio: 0.33, 95% CI: 0.03-3.20, P=0.34). CONCLUSIONS: Our analysis demonstrated that retrieval of the gallbladder via the umbilical port may be associated with less postoperative pain in patients undergoing laparoscopic cholecystectomy compared with epigastric port retrieval. It may also be associated with shorter gallbladder retrieval time. However, the available evidence is limited.

Aquablation: a novel and minimally invasive surgery for benign prostate enlargement.

Aquablation is a minimally invasive surgical technology for benign prostate enlargement, which uses high-pressure saline to remove parenchymal tissue through a heat-free mechanism of hydrodissection. Early results show this to be a promising surgical strategy with a strong morbidity profile and reduced resection time. This review serves to provide an overview of the technique and evaluate its safety and efficacy.