Validation of the modified Bosniak classification system to risk stratify pediatric cystic renal masses: An international, multi-site study from the pediatric urologic oncology working group of the societies for pediatric urology.

BACKGROUND: Pediatric cystic renal lesions are challenging to manage as little is known about their natural course. A modified Bosniak (mBosniak) classification system has been proposed for risk stratification in pediatric patients that takes ultrasound (US) and/or computed tomogram (CT) characteristics into account. However, literature validating this system remains limited. OBJECTIVE: To determine if the mBosniak classification system correlates with pathologic diagnoses. The hypothesis is that mBosniak classification can stratify the risk of malignancy in children with renal cysts. STUDY DESIGN: Patients treated for cystic renal masses with available imaging and pathology between 2000 and 2019 from five institutions were identified. Clinical characteristics and pathology were obtained retrospectively. Characteristics from the most recent US, CT, and/or magnetic resonance imaging (MRI) were recorded. Reviewers assigned a mBosniak classification to each scan. mBosniak scores 1/2 were considered low-risk and 3/4 high-risk. These groups were compared with pathology (classified as benign, intermediate, malignant). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated to assess this categorization as a screening tool to guide surgical intervention. Agreement between imaging modalities was also explored. RESULTS: 99 patients were identified. High-risk imaging findings were correlated with malignant or intermediate pathology with a sensitivity of 88.3%, specificity of 84.6%, PPV of 89.8%, NPV of 82.5%, +LR of 5.7, and -LR of 0.14. The sensitivity for detecting malignant lesions only was 100%. There was substantial agreement between US/CT (n = 55; κ = 0.66) and moderate agreement between US/MRI (n = 20; κ = 0.52) and CT/MRI (n = 13; κ = 0.47). DISCUSSION: The mBos classification system is a useful tool in predicting the likelihood of benign vs. intermediate or malignant pathology. The relatively high sensitivity and specificity of the system for prediction of high-risk lesions makes this classification applicable to clinical decision making. In addition, all malignant lesions were accurately identified as mBosniak 4 on imaging. This study adds substantial data to the relatively small body of literature validating the mBosniak system for risk stratifying pediatric cystic renal lesions. CONCLUSIONS: Pediatric cystic renal lesions assigned mBosniak class 1/2 are mostly benign, whereas class 3/4 lesions are likely intermediate or malignant pathology. We observed that the mBosniak system correctly identified pathology appropriate for surgical management in 88% of cases and did not miss malignant pathologies. There is substantial agreement between CT and US scans concerning mBos classification.

Robotic upper tract surgery in infants 6 months or less: is there enough space?

Robot-assisted laparoscopic surgery (RALS) has recently been described in children < 1 year old. However, little data exist on robotic utilization in infants ≤ 6 months old, likely due to concerns for limited intraabdominal space and decreased distance between ports in this cohort. We hypothesized that the robotic approach can be successfully used for infants ≤ 6 months old. A prospectively collected database of patients undergoing urologic robotic surgery at our institution was reviewed. Patients ≤ 6 months and ≥ 4 kg were included. Patient demographics, intraoperative details, hospital length of stay, and complications were reviewed. Descriptive statistics were performed. Twelve patients ≤ 6 months old underwent urologic robotic surgery by three surgeons at our institution (2013-2019): pyeloplasty (6), ureteroureterostomy (4), heminephrectomy (1), and nephrectomy (1). Median age at surgery was 4.75 months (IQR 4, 6). Median weight was 7.09 kg (IQR 6.33, 7.78). Median console time was 105 min (IQR 86, 123). For all procedures, 8-mm robotic arm ports were used. No procedures were converted to open. Median post-operative hospital stay was 24 h (IQR). Febrile UTI was the only complication occurring within 30 days of surgery (n = 4, 33%; 7-20 days, Clavien grade 2). For those undergoing pyeloplasty or ureteroureterostomy (n = 10), postoperative ultrasound showed improved (n = 9) or stable hydronephrosis (n = 1). At a median follow-up of 19.73 months (IQR 4.27, 38.32), no patient required an unplanned secondary intervention. Robotic upper urinary tract surgery is feasible and safe in patients ≤ 6 months of age and can be performed successfully with the same technique as for older children.

Significant rate of lower urinary tract dysfunction in patients with sacrococcygeal teratomas.

BACKGROUND: Sacrococcygeal teratoma (SCT) is the most commonly occurring presacral tumor and can affect the lower urinary tract by direct mass effect, or as a sequela from surgical resection. Despite the potential impact on urologic function, there is no current standard for urological involvement or follow-up for these patients. The purpose of this study was to evaluate the need for urologic involvement for lower urinary tract dysfunction (LUTD) in patients with SCTs at our institution. METHODS: We performed a retrospective chart review of patients diagnosed with SCT and managed at our institution between 1990 and 2019. Data collected included: patient demographics, surgical and pathology reports, presence of tethered cord or anorectal malformation, and need for urologic involvement for LUTD. LUTD included acute urinary retention, need for chronic intermittent catheterization, and/or urinary incontinence. Acute urinary retention was defined as requiring catheterization to empty the bladder for a limited time (outside the standard post-operative indwelling catheter time period) and the eventual return to spontaneous voiding. Chronic intermittent catheterization was defined as those with urinary retention that has persisted and required continued catheterization at the time of chart review. Urinary incontinence was defined as urine leakage in children older than 3 years of age. Patients with unavailable records were excluded. Comparison between groups was performed with Mann Whitney and chi-squared tests. RESULTS: Forty-five patients with SCTs were identified. LUTD was identified in 23 patients (51%). The most common reason for LUTD was urinary retention (n = 16, 70%): 9 patients had acute retention and 7 had chronic retention (Fig. 1). Nine patients (39%) had urinary incontinence: 2 of these patients (4% of all SCT patients) had urinary fistulas (vesicovaginal (n = 1) and urethrovaginal (n = 1)). Only 5 patients (22%) had LUTD recognized preoperatively. Nine patients had concomitant tethered cord, and 7 of these (78%) had LUTD. Of patients with LUTD, Altman type IV was the most common location (n = 10, 43%). There was no significant difference in tumor type between those with and without LUTD. Patients without LUTD had significantly shorter follow-up. CONCLUSIONS: Greater than 50% of patients with SCTs have known LUTD. Two of these patients were found to have urinary fistulas requiring urinary diversion. A multidisciplinary team including urology should be involved upfront in the management of patients with SCTs, and LUTD should be routinely assessed at follow-up visits. Evaluation for a urinary fistula should occur in the presence of urinary incontinence.

Utilization of Augmentation Cystoplasty for Myelomeningocele Patients Remained Stable Over the Past Decade.

OBJECTIVE: To understand the utilization of augmentation cystoplasty (AC) for the management of neurogenic bladder in children with myelomeningocele (MMC). AC carries considerable risk. To mitigate this, recent studies have emphasized alternatives to AC, but it is unknown if these interventions have resulted in fewer ACs being performed. Our goal was to evaluate the use of AC in MMC patients over the past decade. We hypothesized that the use of AC had decreased and that the age at AC increased. METHODS: Using the Pediatric Health Information System, we studied patients with MMC who had an AC between January 2009 and December 2018. International Classification of Disease procedure codes were used to identify AC procedures. We quantified trends in AC utilization by estimating the annual proportion of MMC admissions with an AC. We also assessed trends in patient age at the time of AC. RESULTS: Proportion of AC per MMC admissions across the study period was 4.8%. There was no significant annual trend in the overall number of ACs performed each quarter over the past decade nor was there any change in the estimated annual incidence rate ratio of AC (1.01, 95% confidence interval 0.96, 1.05; P =.75). The estimated annual change in patient age at procedure remained relatively constant over the study period (-0.03 years, 95% confidence interval -0.13, 0.07; P = .51). CONCLUSION: Practice patterns for the utilization of AC in MMC did not change significantly over the past decade despite prominent voices in the literature emphasizing alternative interventions in this patient population.

Phenazopyridine: A Preoperative Way to Identify Ureteral Orifices.

OBJECTIVE: To identify difficult to see ureteral orifices (UOs), urologists need a method to stain the urine. Phenazopyridine, a urinary analgesic which discolors the urine orange, can be administered orally preoperatively. We evaluated the usefulness of phenazopyridine in identifying the UOs and optimal timing of administration. METHODS: Adult patients undergoing endoscopic procedures at the Stratton VA were prospectively enrolled. Preoperative metabolic panels were reviewed. Exclusion criteria were renal insufficiency (creatinine clearance <50 mL/min), severe hepatitis or severe liver disease, glucose-6-phosphate dehydrogenase deficiency, previous hypersensitivity to phenazopyridine, or pregnancy. In phase 1, patients undergoing office flexible cystoscopy were administered 200 mg phenazopyridine the morning of the procedure. Because of the robust orange color of the urine, phase 2 was implemented. In phase 2, patients undergoing rigid cystoscopy in the operating room took 200 mg phenazopyridine at 7 PM the night before surgery. Upon entry into the bladder, UOs were identified and urine color was graded (0 = no dye, 1 = weak, 2 = moderate, and 3 = strong). Patients were assessed postoperatively for side effects. RESULTS: Five patients were included in phase 1. The mean time from medication to cystoscopy was 153 minutes (range 17-304 minutes). One-third of patients had excretion of grade 3 orange urine that obscured inspection of the bladder mucosa. The study design was adjusted and we transitioned to phase 2. Twenty-three patients were enrolled in phase 2. The mean time from phenazopyridine dose to cystoscopy was 14 hours (range 13-17 hours). Seventy-three percent of patients had grade 2 efflux from the UOs. CONCLUSION: Phenazopyridine can successfully identify UOs and can be administered as early as the evening before the procedure.

Use of Nonprostate Ultrasound in Urology Practice.

INTRODUCTION: Ultrasound imaging is necessary for the care of urology patients, and urology residents are encouraged to learn ultrasound technique and interpretation. However, there is limited mandated education in this field. Currently the only ultrasound procedure considered an index case is transrectal ultrasound for prostate biopsy. We investigated the current use of nonprostate ultrasound in urological practice. METHODS: We reviewed ABU (American Board of Urology) certification and recertification logs of practicing urologists from 2012 to 2014. We obtained data for the codes 76700-76776 (kidney), 76870 (scrotal), 76999 (unlisted) and 93975-93981 (Doppler including penile). Codes 51798 (post-void residual) and 76950 (ultrasound for interstitial radiotherapy) were excluded from the study. We analyzed the results based on self-identified demographic information provided by the urologists. RESULTS: The practices of 2,427 urologists were reviewed and of these, 43% billed for at least 1 renal, scrotal or penile ultrasound. General and subspecialist urologists perform similar percentages of ultrasound studies, except for pediatrics (0% penile) and andrology (40% penile). Of those who reported on practice type (2,067) 82% self-identify as in private practice and performed more ultrasound studies than academic urologists, including renal 42% vs 23%, scrotal 33% vs 15% and penile 8% vs 6%, respectively. Men performed more nonprostate ultrasounds than women (44% vs 36%, p <0.001). CONCLUSIONS: In addition to prostate ultrasound, renal and scrotal ultrasound is relevant to all urologists regardless of practice model or subspecialty. Graduating residents can expect to perform ultrasound examinations in their practices and, therefore, in addition to prostate ultrasound we should train residents in renal and scrotal ultrasound.

Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair.

Protein phosphatase magnesium-dependent-1A (PPM1A) dephosphorylates SMAD2/3, which suppresses TGF-ß signaling in keratinocytes and during Xenopus development; however, potential involvement of PPM1A in chronic kidney disease is unknown. PPM1A expression was dramatically decreased in the tubulointerstitium in obstructive and aristolochic acid nephropathy, which correlates with progression of fibrotic disease. Stable silencing of PPM1A in human kidney-2 human renal epithelial cells increased SMAD3 phosphorylation, stimulated expression of fibrotic genes, induced dedifferentiation, and orchestrated epithelial cell-cycle arrest via SMAD3-mediated connective tissue growth factor and plasminogen activator inhibitor-1 up-regulation. PPM1A stable suppression in normal rat kidney-49 renal fibroblasts, in contrast, promoted a SMAD3-dependent connective tissue growth factor and plasminogen activator inhibitor-1-induced proliferative response. Paracrine factors secreted by PPM1A-depleted epithelial cells augmented fibroblast proliferation (>50%) compared with controls. PPM1A suppression in renal cells further enhanced TGF-ß1-induced SMAD3 phosphorylation and fibrotic gene expression, whereas PPM1A overexpression inhibited both responses. Moreover, phosphate tensin homolog on chromosome 10 depletion in human kidney-2 cells resulted in loss of expression and decreased nuclear levels of PPM1A, which enhanced SMAD3-mediated fibrotic gene induction and growth arrest that were reversed by ectopic PPM1A expression. Thus, phosphate tensin homolog on chromosome 10 is an upstream regulator of renal PPM1A deregulation. These findings establish PPM1A as a novel repressor of the SMAD3 pathway in renal fibrosis and as a new therapeutic target in patients with chronic kidney disease.-Samarakoon, R., Rehfuss, A., Khakoo, N. S., Falke, L. L., Dobberfuhl, A. D., Helo, S., Overstreet, J. M., Goldschmeding, R., Higgins, P. J. Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair.

Stone volume is best predictor of operative time required in retrograde intrarenal surgery for renal calculi: implications for surgical planning and quality improvement.

Retrograde intrarenal surgery (RIRS) is highly successful at eliminating renal stones of various sizes and compositions. As urologists are taking on more complex procedures using RIRS, this has led to an increase in operative (OR) times. Our objective was to determine the best predictor of OR time in patients undergoing RIRS. We retrospectively reviewed the records of patients undergoing unilateral RIRS for solitary stones over a 10 year time span. Stones were fragmented and actively extracted using a basket. Variables potentially affecting OR time such as patient age, sex, BMI, lower pole stone location, volume, Hounsfield units (HU), composition, ureteral access sheath (UAS) use, and pre-operative stenting were collected. Multivariable linear and stepwise regression was used to evaluate the predictors of OR time. There were 118 patients that met inclusion criteria. The median stone volume was 282.6 mm3 (IQR 150.7-644.7) and the mean OR time was 50 min (±25.9 SD). On univariate linear regression, stone volume had a moderate correlation with OR time (y = 0.022x + 38.2, r 2 = 0.363, p < 0.01). On multivariable stepwise regression, stone volume had the strongest impact on OR time, increasing time by 2.0 min for each 100 mm3 increase in stone volume (p < 0.001). UAS added 13.5 (SE 3.9, p = 0.001) minutes and renal lower pole location added 9 min (SE 4.3, p = 0.03) in each case they were used. Pre-operative stenting, HU, calcium oxalate stone composition, sex, and age had no significant effect on OR time. Amongst the main stone factors in RIRS, stone volume has the strongest impact on operative time. This can be used to predict the length of the procedure by roughly adding 2 min per 100 mm3 increase in stone volume.

Cyclical estrogen and free radical damage to the rabbit urinary bladder.

INTRODUCTION AND HYPOTHESIS: There are a number of lower urinary tract dysfunctions (LUTD) that occur primarily in women. Our hypothesis is that cyclical estrogen will produce LUTD in part by the generation of free radicals and oxidative damage to cellular and subcellular membranes. METHODS: Twenty female rabbits were divided into five groups: control, ovariectomized (Ovx), Ovx receiving continuous estrogen, Ovx receiving cyclical estrogen ending off estrogen, and Ovx receiving cyclical estrogen ending on estrogen. Statistical analyses used ANOVA followed by the Tukey analysis for individual differences. RESULTS: High estrogen increased bladder mass, contraction, compliance, and blood flow and decreased oxidative damage. Low estrogen decreased bladder mass, contraction, compliance, and blood flow and increased oxidative damage. CONCLUSIONS: The decreased blood flow associated with increased oxidative damage demonstrates that cyclical damage to cellular membranes occurs. This supports the hypothesis that cycling estrogen may play a role in the etiology of LUTD of women.

Effect of letrozole on urinary bladder function in the female rabbit.

OBJECTIVE: To investigate the effect of letrozole (a potent aromatase inhibitor that effectively inhibit the synthesis of oestrogen) on bladder contraction with changes in morphology and biochemistry. MATERIALS AND METHODS: Sixteen female New Zealand white rabbits were separated into four equal groups; groups 1-3 were given oral letrozole for 1, 2 and 3 weeks, and group 4 was given saline and served as the control group. At the end of the medication period each rabbit was anaesthetized and the bladder muscle strips were used for contractile, histological and biochemical studies. RESULTS: The concentration of serum oestrogen was significantly lower and testosterone was significantly higher in letrozole-treated rabbits than in the control group. The rabbits treated for 1 week with letrozole showed significant decreases in the contractile responses to electrical field stimulation, ATP and carbachol, but not to KCl. Contractility returned to normal in the rabbits treated for 2 and 3 weeks. Letrozole resulted in an increased volume percentage of collagens and decreased bladder compliance. The volume percentage of the smooth muscle component also changed, with a significant decrease at 1 week and then a gradual increase at 2 and 3 weeks. Contractile dysfunction was absent at 2 and 3 weeks, which was consistent with no change in sarcoplasmic reticulum Ca(2+)-ATPase content or mitochondrial function. CONCLUSIONS: The bladder contractility decline in the first week and was restored at 2 and 3 weeks. The present study unexpectedly showed the possibility that testosterone might be as important as oestrogen in the contractile function of the female bladder.