Faculty Bibliography

Background and Objective/UNASSIGNED:Glucocorticoids, secreted from the adrenal gland, are commonly used in the treatment of castration-resistant prostate cancer (CRPC) because of their anti-inflammatory and anti-toxic effects. However, glucocorticoids have been reported to have the opposite effects within the course of treatment. Many studies have shown that glucocorticoid receptors (GRs) are involved in the establishment of a dominant population of androgen-independent malignant cells, which may result in CRPC. In this review, we summarized the mechanisms of GRs in CRPC and the clinical application of glucocorticoids based on the present evidence. Methods/UNASSIGNED:We summarized the isoforms of GRs and the mechanisms involved in CRPC. An updated literature search was performed from the ClinicalTrials database, the National Center for Biotechnology Information database and European Union Drug Regulating Authorities Clinical Trials database. The focus was on the timeframe from 2017 to 2022. At least one primary or secondary outcome [prostate-specific antigen (PSA) response rate, progression-free survival (PFS) or overall survival (OS) and median time to PSA progression] according to studies should be included. Key Content and Findings/UNASSIGNED:, guidelines of CSCO, etc.). Based on the collected data, prednisone appears to be the most widely used steroid hormone, followed by dexamethasone. Comparisons of the PSA response rate and the median time to PSA progression revealed that the efficacy of the 2 hormones is similar; however, further research on the effect of steroid hormone in CRPC is still required. Conclusions/UNASSIGNED:Various GR isoforms may play an important part in the development of CRPC, whose mechanism remains unclear. Most clinical trials have focused on the use of prednisone in the last 5 years. The efficacy of prednisone and dexamethasone is similar.

PURPOSE:UGN-101 (mitomycin for pyelocalyceal solution) is a recently approved chemoablative treatment for low-grade (LG) upper tract urothelial carcinoma (UTUC). While approved for retrograde or antegrade administration, previous reports discuss only patients treated by retrograde approach. We report our techniques for antegrade administration along with early outcomes from our cohort of patients who have undergone UGN-101 administration via nephrostomy. MATERIALS AND METHODS:UGN-101 is administered as 6 weekly instillations in patients who have undergone endoscopic ablation of LG UTUC. We outline our approach in patients thought to have LG UTUC from initial ureteroscopy to nephrostomy placement, UGN-101 administration and eventual nephrostomy removal. We discuss early durability of response along with adverse events with special attention to ureteral strictures. RESULTS:Eight patients underwent antegrade UGN-101 administration during the study period, all of whom underwent followup ureteroscopy with complete response in 4 patients. Three patients reported 5 adverse events-3 grade 1, 1 grade 2 requiring 1 week delay of treatment and 1 asymptomatic ureteral stricture. Median followup was 7 months. CONCLUSIONS:We outline our approach for antegrade administration of UGN-101 and discuss early results along with adverse events. Future studies should evaluate our method's potential to increase patient comfort, improve logistics and decrease risk of adverse events.

Patients who undergo radical cystectomy (RC) are at elevated risk of venous thromboembolism and associated morbidity and mortality. Guidelines recommend extended thromboprophylaxis (ETP), typically with heparins, but adherence is low. Outside urology, low-dose apixaban has been used for postoperative ETP with success. We describe our first experiences with low-dose apixaban for ETP after RC for bladder cancer. In our sample of 72 patients who underwent RC for cancer and subsequently received apixaban 2.5 mg twice daily for ETP, there were no symptomatic thromboembolic events and no major bleeding events. Other complication rates were in line with historical reports. Our experience with apixaban 2.5 mg twice daily for ETP after RC demonstrates safety and potential efficacy. A transition from injectable to oral thromboprophylaxis has the potential to improve adherence and patient satisfaction, while allowing the possibility of further extending prophylaxis beyond 28 d, which may be beneficial in selected patients. Further evaluation of apixaban for thromboprophylaxis in urologic cancer surgery is warranted. PATIENT SUMMARY: Home injectable heparin is used for 4 weeks after bladder removal surgery to prevent blood clots. We evaluated our use of the oral medication apixaban for prevention of blood clots after bladder removal surgery and found that none of our patients had major bleeding events or symptomatic blood clots. We conclude that there should be further evaluation of the use of oral instead of injectable medication to prevent blood clots after urology surgery.

OBJECTIVE:To evaluate optimal regimens for perioperative antimicrobial prophylaxis in transurethral procedures by examining antimicrobial susceptibility patterns in the United States. MATERIALS AND METHODS:Through several methods, we attempted to attain an antibiogram for each state. We focused on microbes known to cause infections after transurethral surgeries and antibiotics referred to in current or prior recommendations and compared susceptibility rates across states using Kruskal Walis tests and the Dwass, Steel, Critchlow-Fligner tests. We also examined susceptibility to (non-ceftazidime) third generation cephalosporins. RESULTS:Data is included from 40 states. For each microbe studied, there was significant variability in sensitivity to antibiotics studied. Current first line recommendations for antimicrobial prophylaxis include first generation cephalosporins with 82%, 80%, and 87% mean coverage for E coli, Proteus, and Klebsiella respectively and trimethoprim-sulfamethoxazole with 74%, 80%, and 93% coverage, respectively. Susceptibility to aminoglycosides is 91%, 92%, and 96%, respectively and to third generation cephalosporin, it is 92%, 99%, and 94%. CONCLUSION:Current first line recommended antimicrobials for prophylaxis in transurethral procedures provide overall poor predicted coverage based on our database of antibiograms. Alternatives exist that have higher predicted susceptibility, though clinical significance of this and risk of resultant antimicrobial resistance is unknown. Urologists should consider local patterns when selecting antimicrobial prophylaxis for their patients.