Inappropriate imaging for management of cryptorchidism: Has the choosing Wisely® recommendation reduced occurrence?

INTRODUCTION: Cryptorchidism is one of the most common referral diagnoses to pediatric urologists. It is well recognized in the urologic community that diagnostic imaging is unnecessary in the work-up of these patients, and the Choosing Wisely® recommendation (CWR) on this subject re-emphasized this in 2013. Many boys, however, still are sent for testing prior to referral. OBJECTIVE: The purpose of our study was dual in nature. We pursued, first, to identify any factors that make patients more likely to be sent for imaging prior to referral, and second, to determine if rates of diagnostic imaging for cryptorchidism decreased after the release of the CWR. STUDY DESIGN: We included all boys who had surgery for cryptorchidism by Urology at our institution between January 2007 and August 2018. Demographics and clinical data were collected including height, weight, race, insurance type, pre-referral imaging status, testis location at time of surgery, and distance from our medical center. Chi-squared analysis was utilized to compare imaging use before and after CWR. Influence of other clinical and socioeconomic factors on imaging utilization was also evaluated using chi-squared and two-sample t tests. Those found to be significant at the 0.2 level were analyzed in multivariate logistic regression. Significance was set at 0.05. RESULTS: 1010 boys were available for analysis. Of the 256 patients (25.3%) with pre-referral studies, 7 had axial exams (CT or MRI), and the remainder underwent ultrasounds. Children living closer to the medical center were more likely to undergo imaging (p < 0.01) as were boys with testes not found in the inguinal canal at the time of surgery (p = 0.007). Race, insurance status, age at first visit, and increased body mass index were not found to be influential. Similarly, the release of CWR had no impact on the imaging usage (p = 0.61). CONCLUSION: Utilization of pre-referral diagnostic imaging remains inappropriately high despite evidence demonstrating the ineffectiveness of the studies. Boys living closer to the medical center and those with non-inguinal testes are more likely to undergo these studies, but no other factors were found to have an effect. Further, the Choosing Wisely® recommendation has not improved rates of inappropriate imaging use in boys with cryptorchidism in our referral area. Our findings indicate the need for increased efforts to disseminate this evidence-based guideline more widely to primary care providers in order to promote more cost-effective and timely care of boys with undescended testes.

Contemporary Management of Vesicoureteral Reflux.

The past 30 years have seen broad changes in the diagnosis and management of vesicoureteral reflux (VUR). Recently, a clinical debate has generated an open discussion in academic circles. New evidence has shifted treatment patterns away from widespread surgical management and recently brought into question some pharmacologic treatments. VUR is usually not hazardous by itself but is a significant risk factor for urinary tract infection (UTI) and less commonly, renal scarring and insufficiency. Given the costs and morbidity of UTI as well as the potential for significant renal injury, our approach remains conservative. Careful follow-up, parental education about pathophysiology and management of VUR and UTI, and management of bowel and bladder dysfunction (BBD) when present, are the foundation of treatment. Additionally, though we recognize the limitation of continuous antibiotic prophylaxis (CAP), we believe the benefits outweigh the risks and costs for many patients. Careful observation can be considered in patients with a single medical home, parental understanding of what UTI signs and symptoms are, low grade VUR, no history of complicated UTIs and close follow-up. Surgical management remains a relevant option for select patients who fail conservative measures with breakthrough UTIs or failure to resolve. Minimally invasive surgical options are available with acceptable outcomes though open ureteroneocystostomy still carries the highest success rate.

Risk Factors Associated with Severity and Outcomes in Pediatric Patients with Hemorrhagic Cystitis.

PURPOSE: Hemorrhagic cystitis is a complication of treatment of pediatric cancer with considerable variation in severity and morbidity. This study presents an analysis of hemorrhagic cystitis severity and treatment outcomes in a large pediatric population. MATERIALS AND METHODS: Patients with hemorrhagic cystitis treated at St. Jude Children's Research Hospital® were identified from 1990 to 2010. Demographic data were gathered along with information pertaining to initial primary diagnosis, hemorrhagic cystitis diagnosis and treatment, and mortality. Statistical analyses were performed to evaluate associations between risk factors and severity of hemorrhagic cystitis as well as treatment outcomes. RESULTS: Of the 285 patients who met inclusion criteria 54% were male. Mean age was 11.41 years. Mean time from initial primary diagnosis to hemorrhagic cystitis onset was 29 months. Noninvasive treatment was performed in 246 patients (86%) and operative intervention was required in 14 (4.9%). Bivariate analysis demonstrated that pelvic radiation therapy (p = 0.0002), any radiation therapy (p = 0.005), acute lymphocytic leukemia (p = 0.01), bone marrow transplantation (p = 0.0225), cyclophosphamide exposure (p = 0.0419) and BK virus positivity (p = 0.0472) were predictors of higher grade hemorrhagic cystitis. Factors correlating with the need for invasive management on bivariate analysis included pelvic radiation therapy (p = 0.0266), bone marrow transplantation (p = 0.0007), hematological malignancy (p = 0.0066), ifosfamide exposure (p = 0.0441) and male gender (p = 0.0383). Multivariate analysis showed independent effects of pelvic radiation therapy (p = 0.001) and delayed onset of hemorrhagic cystitis (p = 0.0444). CONCLUSIONS: Severity of hemorrhagic cystitis and failure of noninvasive management correlate with several identifiable risk factors. Prospective identification of patients with these risk factors may allow for targeted early intervention in those at highest risk.

Subsequent Neoplasms in Adult Survivors of Childhood Genitourinary Tumors.

Treatment for childhood genitourinary tumors such as Wilms tumor, rhabdomyosarcoma, and germ cell tumors has progressed to the point that cure can be expected in many cases. However, survivorship is often coupled with a variety of late effects, of which subsequent neoplasms may be the most concerning if not the most life threatening. Here, we review current literature to assess and report issues relating to subsequent neoplasms in patients with a history of childhood genitourinary tumors, including causative factors, overall risks, the most prevalent subsequent neoplasms, and current recommendations for surveillance and screening.

Cellular calcium mobilization in response to phosphoinositide delivery.

Intracellular calcium [Ca(2+)](i) is mobilized in many cell types in response to activation of phosphoinositide (PIP(n)) signaling pathways involving PtdIns(4,5)P(2) or PtdIns(3,4,5)P(3). To further explore the relationship between increases in intracellular PIP(n) concentrations and mobilization of [Ca(2+)](i), each of the seven phosphorylated phosphoinositides (PIP(n)s) were delivered into cells and the metabolism and physiological effects of the exogenously administered PIP(n)s were determined. The efficient cellular delivery of fluorophore-tagged and native PIP(n)s was accomplished using histone protein, neomycin, and dendrimeric polyamines. PtdIns(4,5)P(2) fluorophore-tagged analogs with short- and long-acyl chains were substrates for cellular enzymes in vitro and for phospholipases in stimulated fibroblasts. PtdIns(4)P, PtdIns(3,4)P(2) and PtdIns(4,5)P(2), each induced calcium mobilization rapidly after exogenous addition to fibroblasts. PtdIns(3,4,5)P(3) induced a significant, but smaller increase in intracellular calcium. These observations suggest that PIP(n)s other than PtdIns(4,5)P(2) or PtdIns(3,4,5)P(3) may have direct roles in signaling involving [Ca(2+)](i).

Metastasis suppression by breast cancer metastasis suppressor 1 involves reduction of phosphoinositide signaling in MDA-MB-435 breast carcinoma cells.

Several molecules that suppress metastasis without suppressing tumorigenicity have been identified, but their mechanisms of action have not yet been determined. Many block growth at the secondary site, suggesting involvement in how cells respond to signals from the extracellular milieu. Breast cancer metastasis suppressor 1 (BRMS1)-transfected MDA-MB-435 cells were examined for modifications of phosphoinositide signaling as a potential mechanism for metastasis suppression. 435/BRMS1 cells expressed <10% of phosphatidylinositol-4, 5-bisphosphate compared with parental cells, whereas levels of the PtdIns(4)P and phosphatidylinositol-3-phosphate were unchanged. Inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] were decreased in 435/BRMS1 cells by approximately 50%. Phosphatidylinositol-3,4,5-trisphosphate levels were undetectable in 435/BRMS1 cells, even when stimulated by exogenous insulin or platelet-derived growth factor. Immunofluorescence microscopy to examine cellular distribution confirmed that phosphatidylinositol-4,5-bisphosphate distribution with cells was unchanged but was uniformly decreased throughout the cell. Although the gross morphology of 435/BRMS1 cells is similar to the parent, filamentous actin was more readily apparent in 435/BRMS1. Intracellular calcium, measured using Fluo-3 and Fura-2 fluorescent calcium indicator dyes, was somewhat lower, but not statistically different in 435/BRMS1 compared with parental cell. However, when stimulated with platelet-derived growth factor, MDA-MB-435 cells, but not 435/BRMS1 cells mobilized intracellular calcium. Taken together, these results implicate signaling through phosphoinositides in the regulation of breast cancer metastasis, specifically metastasis that can be suppressed by BRMS1.