Abstract Aims To determine the role of opioid and β‐adrenergic receptors in bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). Methods In α‐chloralose anesthetized cats, 30‐min PNS was applied repeatedly for 3–9 times to induce poststimulation or persistent bladder underactivity. Then, naloxone (opioid receptor antagonist, 1 mg/kg, IV) or propranolol (β‐adrenergic receptor antagonist, 3 mg/kg, IV) was given to reverse the bladder underactivity. After the drug treatment, an additional 30‐min PNS was applied to counteract the drug effect. Repeated cystometrograms were performed by slowly (1–2 mL/min) infusing the bladder with saline via a urethral catheter to determine the bladder underactivity and the treatment effects. Results Prolonged (2–4.5 h) PNS induced bladder underactivity evident as a large bladder capacity (169 ± 49% of control) and a reduced amplitude of bladder contraction (59 ± 17% of control). Naloxone fully reversed the bladder underactivity by reducing bladder capacity to 113 ± 58% and increasing the amplitude of bladder contraction to 104 ± 34%. After administration of naloxone an additional 30‐min PNS temporarily increased the bladder capacity to the underactive bladder level (193 ± 74%) without changing the amplitude of the bladder contraction. Propranolol had no effect on bladder underactivity. Conclusions A tonic enkephalinergic inhibitory mechanism in the CNS plays a critical role in the bladder underactivity induced by prolonged PNS, while the peripheral β‐adrenergic receptor mechanism in the detrusor is not involved. This study provides basic science evidence consistent with the clinical observation that comorbid opioid usage may contribute to voiding dysfunction in patients with Fowler's syndrome.
285 Background: Widespread availability of NGS and an expanding repertoire of targeted therapies has garnered significant enthusiasm for the concept of NGS directed therapy. FoundationOne (Foundation Medicine, Cambridge, MA) is a validated comprehensive genomic profiling (CGP) assay intended to guide therapy decisions based upon tumor specific genetic variations. We reviewed our experience with FoundationOne testing in advanced genitourinary (GU) cancer and examined whether NGS effected therapy in a meaningful way. Methods: Retrospective review of patients with advanced GU cancer seen between 2/1/2013–8/13/2018 who had FoundationOne CGP testing. We then compared the duration patients were maintained on NGS directed therapy to the duration of each non-NGS therapy. Results: A total of 73 patients were identified with NGS testing for prostate (25, 34%), urothelial (30, 41%), and kidney (18, 25%) cancer. 11 (15%) of these patients had therapy directed against a genetic alteration indicated by NGS. Of the treated patients, 46% (5) had urothelial, 36% (4) had kidney, and 18% (2) had prostate cancer. The average duration that each non-NGS therapy was effective in patients with urothelial, kidney, and prostate cancer was 165, 417, and 382 days respectively. Duration of NGS directed therapy averaged 226, 367, and 278 days for urothelial, kidney, and prostate cancer. The range of the duration of response to NGS directed therapy for urothelial, kidney, and prostate cancer was 66-616 days, 106-467 days, and 28-528 days. Four (36%) patients treated with NGS directed therapy achieved a duration of response greater than the average duration of all other non-NGS directed therapy they had received (Table). Conclusions: A minority of patients received NGS directed therapy following NGS testing. Treated patients demonstrated varying responses with 4 patients experiencing a longer duration of response compared to non-NGS directed therapy. Our experience illustrates that NGS has a limited but evolving role in the management of advanced GU malignancies at this time while also demonstrating a benefit to a subset of patients. Future studies should focus on identifying which patients are most likely to benefit from this technology.
