Urinary Analysis of FGFR3 and TERT Gene Mutations Enhances Performance of Cxbladder Tests and Improves Patient Risk Stratification.

PURPOSE: Cxbladder tests are urinary biomarker tests for detection of urothelial carcinoma. We developed enhanced Cxbladder tests that incorporate DNA analysis of 6 single nucleotide polymorphisms for the FGFR3 and TERT genes, in addition to the current 5 mRNA biomarkers and clinical risk factors. MATERIALS AND METHODS: Two multicenter, prospective studies were undertaken in: (1) U.S. patients with gross hematuria aged ≥18 years and (2) Singaporean patients with gross hematuria or microhematuria aged >21 years. All patients provided a midstream urine sample and underwent cystoscopy. Samples were retrospectively analyzed using enhanced Cxbladder-Triage (risk stratifies patients), enhanced Cxbladder-Detect (risk stratifies patients and detects positive patients), and the combination enhanced Cxbladder-Triage × Cxbladder-Detect. RESULTS: In the pooled cohort (N=804; gross hematuria: n=484, microhematuria: n=320), enhanced Cxbladder-Detect had a sensitivity of 97% (95% CI 89%-100%), specificity of 90% (95% CI 88%-92%), and negative predictive value of 99.7% (95% CI 99%-100%) for detection of urothelial carcinoma. Overall, 83% of patients were enhanced Cxbladder-Detect-negative (ie, needed no further work-up). Of 133 enhanced Cxbladder-Detect-positive patients, 59 had a confirmed tumor, of which 19 were low-grade noninvasive papillary carcinoma or papillary urothelial neoplasm of low malignant potential. In total, 40 tumors were high-grade Ta, T1-T4, Tis, including concomitant carcinoma in situ. Of the 74 patients with normal cystoscopy, 41 were positive by single nucleotide polymorphism analysis. Enhanced Cxbladder-Triage and enhanced Cxbladder-Detect had significantly better specificity than the first-generation Cxbladder tests (P < .001). CONCLUSIONS: This study in ethnically diverse patients with hematuria showed the analytical validity of the enhanced Cxbladder tests.

MODY5 Hepatocyte Nuclear Factor 1ß (HNF1ß)-Associated Nephropathy: experience from a regional monogenic diabetes referral centre in Singapore.

From our monogenic diabetes registry set-up at a secondary-care diabetes center, we identified a nontrivial subpopulation (~15%) of maturity-onset diabetes of the young (MODY) among people with young-onset diabetes. In this report, we describe the diagnostic caveats, clinical features and long-term renal-trajectory of people with HNF1B mutations (HNF1B-MODY). Between 2013 and 2020, we received 267 referrals to evaluate MODY from endocrinologists in both public and private practice. Every participant was subjected to a previously reported structured evaluation process, high-throughput nucleotide sequencing and gene-dosage analysis. Out of 40 individuals with confirmed MODY, 4 (10%) had HNF1B-MODY (harboring either a HNF1B whole-gene deletion or duplication). Postsequencing follow-up biochemical and radiological evaluations revealed the known HNF1B-MODY associated systemic-features, such as transaminitis and structural renal-lesions. These anomalies could have been missed without prior knowledge of the nucleotide-sequencing results. Interestingly, preliminary longitudinal observation (up to 15 years) suggested possibly 2 distinct patterns of renal-deterioration (albuminuric vs. nonalbuminuric chronic kidney disease). Monogenic diabetes like HNF1B-MODY may be missed among young-onset diabetes in a resource-limited routine-care clinic. Collaboration with a MODY-evaluation center may fill the care-gap. The long-term renal-trajectories of HNF1B-MODY will require further studies by dedicated registries and international consortium.

Polypoid Cystitis and Bilateral Hydronephrosis Mimicking Urothelial Carcinoma.

Background: Polypoid cystitis is infrequently seen in noncatheterized patients, occasionally posing challenging treatment options. We present a rare case of polypoid cystitis with bilateral upper tract obstruction mimicking a bladder tumor, needing staged endoscopic management. Case Presentation: A 45-year-old Asian man with a bladder tumor presented with lower urinary tract symptoms. Subsequent transurethral resection of bladder tumor histology revealed polypoid cystitis. This had caused intramural edema and obstruction of the distal ureters that were managed with initial local resection, ureteral dilatation with a period of ureteral stenting, and oral steroids. Subsequent intravenous urogram and diuretic renogram showed resolution of obstruction and resolution of hydronephrosis. He also had mixed lower urinary tract symptoms and hematuria managed with combination of solifenacin, finasteride, and tamsulosin. Conclusion: Polypoid cystitis with ureteral obstruction needs to be considered in differentials of a bladder tumor, and management may include a combination of endoscopic resection, ureteral stenting, and in resistant cases oral steroids can be considered to aid resolution of inflammation in the absence of infection.

Symptom prevalence, bother, and treatment satisfaction in men with lower urinary tract symptoms in Southeast Asia: a multinational, cross-sectional survey.

PURPOSE: The overall objective of the survey was to systematically examine patients' perspectives on lower urinary tract symptoms (LUTS) and their treatment in Southeast Asia. METHODS: A multinational cross-sectional survey involving adult men seeking consultation at urology outpatient clinics because of LUTS in Southeast Asia was conducted using convenience sampling. Self-reported prevalence, bother, treatment and treatment satisfaction of selected LUTS including urgency, nocturia, slow stream, and post-micturition dribble were evaluated. RESULTS: In total, 1535 eligible patients were enrolled in the survey. A majority of respondents were aged 56-75 years, not employed, and had not undergone prostate operation before. Overall, the self-reported prevalence of nocturia was 88% (95% CI 86-90%), slow stream 61% (95% CI 59-63%), post micturition dribble 55% (95% CI 52-58%), and urgency 52% (95% CI 49-55%). There were marked differences in the country specific prevalence of LUTS complaints. Frequently, symptoms coexisted and were combined with nocturia. More than half of patients felt at least some degree of bother from their symptoms: 61% for urgency, 57% for nocturia, 58% for slow stream, and 60% for post-micturition dribble. Before seeing the present urologists, nearly half of patients have received some form of prescribed treatment and more than 80% of patients indicated they would like to receive treatment. CONCLUSION: Men who sought urologist care for LUTS often presented with multiple symptoms. Nocturia emerged as the most common symptom amongst the four core symptoms studied.

Colonisation with methicillin-resistant Staphylococcus aureus prior to renal transplantation is associated with long-term renal allograft failure.

Renal transplant recipients are at an increased risk of developing Methicillin-resistant Staphylococcus aureus due to their immunosuppressed status. Herein, we investigate the incidence of MRSA infection in patients undergoing renal transplantation and determine the effect of MRSA colonisation on renal allograft function and overall mortality. Between January 1st 2007 and December 31st 2012, 1499 consecutive kidney transplants performed in our transplant unit and a retrospective 1:2 matched case-control study was performed on this patient cohort. The 1-, 3- and 5-year overall graft survival rates were 100%, 86% and 78%, respectively, in MRSA positive recipients compared with 100%, 100% and 93%, respectively, in the control group (P < 0.05). The 1-, 3- and 5-year overall patient survival rates were 100%, 97% and 79%, respectively, in MRSA positive recipients compared with 100%, 100% and 95%, respectively, in the control group (P = 0.1). In a multiple logistic regression analysis, colonisation with MRSA pre-operatively was an independent predictor for renal allograft failure at 5 years (hazard ratio: 4.6, 95% confidence interval: 1-30.7, P = 0.048). These findings demonstrate that the incidence of long-term renal allograft failure is significantly greater in this patient cohort compared with a matched control population.

Ex vivo reconstruction of the donor renal artery in renal transplantation: a case-control study.

Transplantation of renal allografts with anatomic variability or injured vasculature poses a challenge to the transplanting surgeon but can be salvaged for transplantation with ex vivo bench reconstruction of the vasculature. We investigated whether renal allograft function is impaired in these reconstructed allografts; compared to the donor-matched, un-reconstructed allograft. Reconstructed allografts were transplanted into 60 patients at our institution between 1986 and 2012. A control group was selected from the matched pair of the recipient in deceased donor transplantation. We found no significant difference in the overall graft and patient survival rates (P = 1.0, P = 0.178). Serum creatinine levels were not significantly higher in the study group at 1, 3 and 12 months postoperatively. There were two cases of vascular thrombosis in the study group that were not related to the ex vivo reconstruction. A significantly greater proportion of reconstructed patients were investigated with a colour duplex ultrasound postoperatively (0.007). Although we have demonstrated a higher index of suspicion of transplant failure in patients with a reconstructed allograft, this practice has proven to be a safe and useful technique with equivocal outcome when compared to normal grafts; increasing the organ pool available for transplantation.

Outcome of deceased donor renal transplantation in patients with an ileal conduit.

Renal transplantation in recipients with an ileal conduit is uncommon and occasionally controversial as it has been associated with high morbidity and mortality rates. We report on 17 patients with an ileal conduit who received a deceased donor renal transplant at our institution between January 1986 and December 2012. We retrospectively reviewed their allograft and surgical outcome. There were four mortalities at five, five, 39, and 66 months post-transplant. Sixteen of 17 grafts functioned immediately; one patient had primary non-function secondary to vascular thrombosis. Thirteen of 17 (76.5%) grafts were functioning at a mean follow-up period of 105 months. The mean serum creatinine at follow-up was 111 µM (±38.62). Five patients had seven episodes of urosepsis requiring hospital admission, and five patients received treatment for renal stone disease. We conclude that given improvements in immunosuppression, surgical technique, infection treatment, and selection criteria, we believe that renal transplantation in the patient with an ileal conduit yields excellent graft survival, although there is a high morbidity rate in this cohort of patients in the long term.

Ureteral diverticulum: a review of the current literature.

INTRODUCTION: Ureteral diverticulum is a rare urological condition with only 45 cases described in the literature. These previously reported cases vary in their presentation, diagnosis and management and there is no consensus in the literature on the best diagnostic tool available. We describe our experience on diagnosing and managing this condition in two patients and provide a descriptive review of the current literature on ureteral diverticulum. MATERIALS AND METHODS: A Medline search was performed to identify all reported cases of ureteral diverticulum. Key words used were: ureteral diverticulum; abortive bifid ureter; congenital diverticulum; acquired diverticulum. We also reviewed the records of two patients who presented consecutively to our institution with a ureteral diverticulum. The clinical and radiological characteristics of this entity were then evaluated. RESULTS: Forty-one manuscripts were identified, encompassing single case reports and case series, the largest of which contained seven patients. Two additional cases were diagnosed in our institution; a true congenital diverticulum and an abortive bifid ureter which is synonymous with a true ureteral diverticulum. Both were uncomplicated cases and were managed conservatively. Retrograde pyelography was used for definitive diagnosis of this lesion. CONCLUSION: Ureteral diverticulum may present as an incidental finding or with a secondary complication. Conservative management is advocated in the literature for non-complicated cases. Retrograde pyelography is our diagnostic tool of choice.

Dual kidney transplantation with organs from extended criteria cadaveric donors.

PURPOSE: The critical shortage of kidneys available for transplantation has led to alternate strategies to expand the pool. Transplantation of the 2 kidneys into a single recipient using organs suboptimal for single kidney transplantation was suggested. We assessed results in 24 grafts allocated for dual kidney transplantation vs those in a control group of 44 designated for single kidney transplantation. Each group underwent pretransplant biopsy and recipients were age matched. MATERIALS AND METHODS: Dual kidney transplantation was done in 24 of 1,091 transplants (2.1%) from 2001 to 2008. In patients with dual kidney transplant vs single kidney transplant mean recipient age was 60.6 vs 60.8 years, mean HLA-A, B and DR mismatches were 3.3 vs 2.9, and average patient waiting time was 15.6 vs 13.9 months. All grafts were perfused with University of Wisconsin solution with a mean cold ischemia time of 17.9 hours. On donor dual kidney biopsy in the dual kidney transplant vs single kidney transplant group the average fibrosis rate was 30% (range 25% to 45%) vs 25% (range 3% to 40%) and the glomerulosclerosis rate was 17.9% (range 3.2% to 40.7%) vs 7.1% (range 0% to 50%). RESULTS: Good postoperative renal function was noted in 14 dual kidney transplantation cases. Acute tubular necrosis requiring dialysis developed in 5 patients as well as acute rejection in 1. Two dual kidney recipients (8%) died in the postoperative period with no single kidney deaths. One patient underwent bilateral transplantectomy. Mean anesthesia time was longer in the dual group (371 vs 212 minutes). Patient and graft survival was equivalent to that in the control group at 36 months. CONCLUSIONS: Careful selection of marginal kidneys based on clinical and histological criteria allows the use of organs that would not ordinarily be sufficient for transplantation with acceptable outcomes. This is a valid strategy to address the organ shortage.

The effects of low-frequency endo-anal electrical stimulation on faecal incontinence: a prospective study.

BACKGROUND AND AIMS: Faecal incontinence is a distressing problem that is often not amenable to surgical correction. Chronic low-frequency electrical stimulation of damaged axons is thought to reduce synaptic resistance, increase the size of motor units by axonal sprouting and increase the rate of conduction of the pudendal nerve. The aim of this study was to prospectively evaluate the effect of chronic low-frequency endo-anal electrical stimulation on faecal incontinence using a home-based unit and hospital-supervised therapy. MATERIALS AND METHODS: Forty-eight patients with faecal incontinence completed a prospective randomised trial. Patients were allocated randomly to one of two groups; group 1 was exposed to endo-anal pudendal nerve stimulation daily at home with a portable home unit, group 2 attended the physiotherapy department for endo-anal electrical stimulation under supervision. RESULTS: Continence scores improved significantly after treatment in both groups (p<0.001). Both groups showed improved manometric scores, although only group 1 showed significant improvement in both resting and squeeze pressures (mean total resting pressure 184-224 mmHg, p<0.001; mean total squeeze pressure 253-337 mmHg, p<0.001). This was also reflected by an improvement in quality of life in both groups. CONCLUSIONS: Low-frequency endo-anal electrical stimulation significantly improves continence scores and quality of life in patients with faecal incontinence not amenable to surgical correction. It leads to improved manometric values when carried out on a daily basis with a portable home unit.