An evaluation of the real world use and clinical utility of the Cxbladder Monitor assay in the follow-up of patients previously treated for bladder cancer.

BACKGROUND: Surveilling recurrent urothelial carcinoma (UC) requires frequent cystoscopy, which is invasive, expensive and time-consuming. An accurate urinary biomarker has the potential to reduce the number of cystoscopies required during post-treatment surveillance. OBJECTIVE: To audit the clinical utility of a new surveillance protocol incorporating the Cxbladder Monitor (CxbM) test in real-world practice. METHODS: Three hospitals implemented a new surveillance protocol. Patients were risk stratified, and then provided urine samples for CxbM testing. Low-risk CxbM-positive patients and all high-risk patients had cystoscopy at 2-3 months. Low-risk CxbM-negative patients had cystoscopy at ~ 12 months. RESULTS: 443 CxbM tests were conducted on samples from 309 patients: 257 (83.2%) low-risk and 52 (16.8%) high-risk. No pathology-confirmed recurrences were seen in low-risk CxbM-negative patients (n = 108) during the first post-CxbM cystoscopy undertaken a mean ± SD 10.3 ± 3.9 months after testing. Three recurrences were detected during cystoscopy at 2.7 ± 3.4 months in 53 low-risk CxbM-positive patients. In 49 high-risk patients, 39 (79.6%) were CxbM-negative with no pathology-confirmed recurrences. Ten high-risk patients (20.4%) were CxbM-positive with four confirmed recurrences; 2 high-grade and 2 low-grade. The median time to first cystoscopy was 12.13 (95% CI: 11.97-12.4) months in patients with a CxbM-negative result versus 1.63 (95% CI: 1.13-2.3) months in patients with a CxbM-positive result (p < 0.00001). No positive cases were missed, no patients progressed to invasive or metastatic disease, and no patient died of cancer over 35 months of follow-up. CONCLUSIONS: CxbM accurately identified a high proportion of patients (77.8%) who were safely managed with only one cystoscopy per year. Including CxbM in the protocol for patient surveillance provided clinical utility by reducing the average number of annual cystoscopies by approximately 39%, thereby sparing patients the potential discomfort and anxiety, without compromising detection rates. No advantage was observed for risk stratification prior to CxbM.

Effects of bariatric surgery on untreated lower urinary tract symptoms: a prospective multicentre cohort study.

OBJECTIVE: To evaluate the effects of bariatric surgery on lower urinary tract symptoms (LUTS) in a prospective cohort study. PATIENTS AND METHODS: Patients undergoing bariatric surgery were recruited into the study. LUTS were assessed using the International Prostate Symptoms Score (IPSS) in men and Bristol Female Lower Urinary Tract Symptoms Score Questionnaire (BFLUTS) in women. Serum glucose, insulin and prostate-specific antigen (PSA) levels were recorded; insulin resistance was quantified using the Homeostasis Model Assessment (HOMA-IR) method. Patients were assessed before surgery, and at 6-8 weeks and 1 year after surgery. Weight loss, change in body mass index (BMI), total symptoms score as well as individual symptoms were tested for statistical significance with correction for multiple testing using Bonferroni method. Linear regression analysis was performed with total symptoms score change at 1 year as the outcome variable and BMI, age, total symptoms score before surgery, HOMA-IR, glucose level before surgery, insulin level before surgery, change in insulin level after surgery, weight loss and BMI loss as predictor variables. RESULTS: In all, 86 patients were recruited and 82% completed at least one follow-up after surgery. There was significant weight loss and reduction of BMI after surgery (P < 0.001). At 6 weeks, there was a significant reduction in overall symptom score (P < 0.001) and this improvement was sustained at 1 year. Linear regression analysis showed that total symptoms score at baseline, HOMA-IR, preoperative insulin level and change in insulin level postoperatively were predictive of the change in total symptoms score while the amount of weight loss was not. CONCLUSIONS: The study confirms the improvement in LUTS after weight loss but there is no correlation between the improvement and the time course or degree of weight loss. Rather there is a suggestion that the improvement in symptoms is linked to improvement in insulin resistance seen as a result of both bariatric surgery and weight loss.

A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria.

PURPOSE: We investigated whether the RNA assay uRNA® and its derivative Cxbladder® have greater sensitivity for the detection of bladder cancer than cytology, NMP22™ BladderChek™ and NMP22™ ELISA, and whether they are useful in risk stratification. MATERIALS AND METHODS: A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospectively from 11 urology clinics in Australasia. Voided urine samples were obtained before cystoscopy. The sensitivity and specificity of the RNA tests were compared to cytology and the NMP22 assays using cystoscopy as the reference. The ability of Cxbladder to distinguish between low grade, stage Ta urothelial carcinoma and more advanced urothelial carcinoma was also determined. RESULTS: uRNA detected 41 of 66 urothelial carcinoma cases (62.1% sensitivity, 95% CI 49.3-73.8) compared with NMP22 ELISA (50.0%, 95% CI 37.4-62.6), BladderChek (37.9%, 95% CI 26.2-50.7) and cytology (56.1%, 95% CI 43.8-68.3). Cxbladder, which was developed on the study data, detected 82%, including 97% of the high grade tumors and 100% of tumors stage 1 or greater. The cutoffs for uRNA and Cxbladder were prespecified to give a specificity of 85%. The specificity of cytology was 94.5% (95% CI 91.9-96.5), NMP22 ELISA 88.0%, (95% CI 84.6-91.0) and BladderChek 96.4% (95% CI 94.2-98.0). Cxbladder distinguished between low grade Ta tumors and other detected urothelial carcinoma with a sensitivity of 91% and a specificity of 90%. CONCLUSIONS: uRNA and Cxbladder showed improved sensitivity for the detection of urothelial carcinoma compared to the NMP22 assays. Stratification with Cxbladder provides a potential method to prioritize patients for the management of waiting lists.

COVID-19 and the impact on urology service provision at Capital & Coast District Health Board.

AIM: To determine the impact on the Capital & Coast District Health Board (CCDHB) urology service of the implementation of nationwide healthcare restrictions in response to the COVID-19 pandemic. METHODS: This is an observational retrospective study over a 21 working day period during the implementation of National Hospital Response Framework Alert (NHRFA) level 2. We obtained patient data during this period and a corresponding control period prior to the pandemic. The data was focussed on the volume of operating theatre cases, outpatient consultations, procedural clinic appointments and the estimated avoided outpatient travel. RESULTS: Total urology admissions decreased by 27% during the 21-day NHRFA level 2 period. However, acute surgical procedures increased by 30% whereas elective surgical procedures decreased by 32%. Outpatient consultations overall decreased by 32% during NHRFA level 2 despite virtual phone consultations increasing by 274%. Procedural clinic appointments decreased by 85%. The virtual platform also saved each patient an estimated 22.7km of average travel. CONCLUSION: The data demonstrate the effects of restrictions in response to a crisis and set a precedent for future management in such scenarios. The data also show how service efficiency can be optimised while providing an environmentally friendly alternative for routine clinical practice.

Expression of Components of the Renin-Angiotensin System by Cancer Stem Cells in Renal Clear Cell Carcinoma.

This study investigated the expression of components of the renin-angiotensin system (RAS) by cancer stem cells (CSCs) we have recently demonstrated in renal clear cell carcinoma (RCCC). Fifteen RCCC tissue samples underwent immunohistochemical staining for components of the RAS: renin, pro-renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), and angiotensin II receptor 2 (AT2R). Immunofluorescence co-staining or double immunohistochemical staining of these components of the RAS with stemness-associated markers OCT4 or KLF4 was performed on two of the samples. Protein and transcript expression of these components of the RAS in six RCCC tissue samples was investigated using western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, angiotensin II receptor 1 (AT1R) was investigated using RT-qPCR only. Immunohistochemical staining demonstrated expression of renin, PRR, and ACE2 in 11, 13, and 13 out of 15 RCCC samples, respectively, while AT2R was expressed in all 15 samples. ACE was detected in the endothelium of normal vasculature only. Double immunohistochemical staining demonstrated localization of ACE2, but not renin, to the KLF4+ CSCs. Immunofluorescence staining showed localization of PRR and AT2R to the OCT4+ CSCs. Western blotting confirmed protein expression of all components of the RAS except renin. RT-qPCR demonstrated transcript expression of all components of the RAS including AT1R, but not AT2R, in all six RCCC tissue samples. This study demonstrated expression of PRR, ACE2, and AT2R by the CSCs within RCCC. Further studies may lead to novel therapeutic targeting of CSCs by manipulation of the RAS in the treatment of this aggressive cancer.

Obstructive uropathy as the etiology of renal failure in ovarian hyperstimulation syndrome.

OBJECTIVE: To make people aware that there is potential for obstructive uropathy to complicate ovarian hyperstimulation syndrome (OHSS) and cause renal impairment. DESIGN: Case report. SETTING: Hospital. PATIENT(S): A 28-year-old Caucasian female presenting with acute severe OHSS. INTERVENTION(S): Bilateral JJ stenting. MAIN OUTCOME MEASURE(S): Resolution of renal impairment. RESULT(S): Successful treatment of renal failure. CONCLUSION(S): Patients with severe OHSS and renal impairment should be evaluated with renal ultrasound to rule out hydronephrosis and therefore an obstructive uropathy. Patients potentially at risk for such a complication from OHSS may include those with prior abdominal or pelvic surgery.