A retrospective study assessing the accuracy of [18F]-fluorocholine PET/CT for primary staging of lymph node metastases in intermediate and high-risk prostate cancer patients undergoing robotic-assisted laparoscopic prostatectomy with extended lymph node dissection.

BACKGROUND: Previous studies have investigated [18F]-fluorocholine (FCH) positron emission tomography with computed tomography (PET/CT) in primary staging of men with intermediate or high-risk prostate cancer and have generally shown high specificity and poor sensitivity. FCH PET/CT is not recommended for the primary staging of metastases in the European guidelines for prostate cancer. However, it has been an option in the Swedish recommendations. Our aim was to assess PET/CT for primary staging of lymph node metastases before robotic-assisted laparoscopic prostatectomy (RALP) with extended pelvic lymph node dissection (ePLND) in patients with intermediate or high-risk prostate cancer. METHOD: We identified all men with prostate cancer undergoing FCH PET/CT for initial staging followed by RALP and ePLND at Skåne University Hospital between 2015 and 2018. The result from PET/CT scan was compared with pathology report as the reference method for calculation of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: In total, 252 patients were included in the final analysis. Among 85 patients with a suspicion of regional lymph node metastases on FCH PET/CT only 31 had pathology-proven metastases. The sensitivity was 43% (95% CI 0.32-0.55) and the specificity 70% (95% CI 0.63-0.76) for PET/CT to predict lymph node metastases. PPV was 36% and NPV was 75%. Risk group analyses showed similar results. CONCLUSION: Our study emphasizes the poor performance of FCH PET/CT to predict lymph node metastasis in intermediate and high-risk prostate cancer. The method should be replaced with newer radiopharmaceuticals, such as prostate-specific membrane antigen ligands.

Exogenously administered opioids contract the female rat intrinsic urethral sphincter in vivo.

BACKGROUND AND OBJECTIVE: Previous studies have reported immunoreactive opioid nerve fibers in the detrusor and lower urinary tract sphincters. However, there is a paucity of in vivo studies demonstrating the direct effect of endogenous opioids in these structures. In the present study, we investigated the contractile actions of intra-arterially administered exogenous Dynorphin-A, Met-enkephalin, Leu-enkephalin, morphine, and the opioid antagonist naltrexone on the female rat intrinsic urethral sphincter in vivo. METHODS: Intraurethral pressure was recorded by a catheter placed at the maximum pressure zone of the intrinsic urethral sphincter in anesthetized female Sprague-Dawley rats. The effects of different opioids were studied and expressed as means and as percentages of pressure change (cmH(2)O) of the baseline intraurethral pressure. RESULTS: Dynorphin-A, Met-enkephalin, and Leu-enkephalin evoked rapid, long-lasting contractile effects on the female rat urethra. The greatest intraurethral pressure increase was evoked by Dynorphin-A (89.2 +/- 15.3%). For Met-enkephalin, intraurethral pressure increased by 70.2 +/- 21.8% and for Leu-enkephalin, the pressure increase was 60.6 +/- 20%. Morphine, however, evoked inconsistent intraurethral pressure changes, increasing the urethral pressure in three subjects and lowering the pressure in the remaining six subjects. The opioid antagonist naltrexone reduced the intraurethral pressure by a mean of -19.0 +/- 5.8%. CONCLUSION: Results of the present study suggest that endogenous opioids by their contractile action on the intrinsic urethral sphincter may play a role in the control of continence in rats, additional to cholinergic and noradrenergic pathways.

The value of the UroVysion assay for surveillance of non-muscle-invasive bladder cancer.

OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally followed by repeat cystoscopy and urine cytology. A fluorescence in situ hybridisation technique called UroVysion (UV) is now available for clinical diagnosis of urothelial cancer cells. The aim of the present study was to compare UV analysis with routine follow-up methods. METHODS: We studied an unselected cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in 2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay. The UV assay was evaluated with regards to sensitivity, specificity, and positive predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed. UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70% sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The specificity of UV was 95%. UV detected all six CIS cases in the study and was predictive in two additional patients who developed CIS within 1 yr of inclusion. Cytology was positive in four of those eight CIS cases and atypical in the other four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of patients with non-muscle-invasive bladder cancer, but it may be valuable as a supplement to traditional measures for detecting CIS. Before any conclusions can be drawn regarding the efficacy of novel markers of bladder cancer, they must be studied in bladder cancer patients undergoing endoscopic surveillance.

Calcitonin gene-related peptide and substance P induce pronounced motor effects in the female rat urethra in vivo.

OBJECTIVE: This study was performed to investigate the influence of calcitonin gene-related peptide (CGRP) and substance P (SP) on the intra-urethral pressure in female rats, as both these neuropeptides have been demonstrated to occur in nerve fibres throughout all layers of the intrinsic external urethral sphincter of the rat. MATERIAL AND METHODS: Both CGRP and SP were administered intra-arterially relatively close to the bladder in ketamine-anaesthetized female rats. The maximum urethral pressure (MUP) was recorded continuously using a 4 F microtip single-transducer catheter. RESULTS: Pronounced effects on the intra-urethral pressure were found with both CGRP and SP. CGRP at the maximum dose given (10 micrograms) induced an immediate, pronounced, long-lasting decrease in pressure from 28 +/- 4 to 10 +/- 2 cmH(2)O, amounting to 65% of the MUP. SP (10 micrograms) instead induced a forceful, phasic, peak-like contractile response with a 170% increase in urethral pressure from 33 +/- 6 to 87 +/- 6 cmH(2)O of the initial control level of MUP. Antagonists to CGRP and SP did not induce any pressure changes per se. CONCLUSION: These results indicate that both CGRP and SP are of importance for the peripheral motor regulation of the external urethral sphincter, and hence possibly also of physiological importance for lower urinary tract function during essential parts of the micturition cycle.