Pediatric Renal Angiomyolipomas in Tuberous Sclerosis Complex.

PURPOSE: Tuberous sclerosis complex is a genetic disorder characterized by the growth of hamartomas in multiple organs. Up to 80% of patients with tuberous sclerosis complex will have at least 1 angiomyolipoma in their lifetime. We describe the incidence and natural history of angiomyolipoma in a pediatric tuberous sclerosis complex population and analyze tumor growth to determine optimal renal imaging intervals in an effort to improve counseling, treatment and followup. MATERIALS AND METHODS: We performed a retrospective chart review of all patients with tuberous sclerosis complex from 2004 to 2014. Patients were included if they had a clinical or genetic diagnosis of tuberous sclerosis complex and had undergone at least 1 renal imaging study. RESULTS: A total of 145 patients were analyzed. Median age was 14 years (range 0 to 28). Overall incidence of angiomyolipoma was 50.3%. Median age at first angiomyolipoma detection was 11 years (range 2 to 26). Median yearly angiomyolipoma growth rate stratified by age at first detection was 0.0 mm for patients 0 to 6 years old, 0.9 mm for those 7 to 11 years old, 2.5 mm for those 12 to 16 years old and 1.8 mm for those 17 years old or older. Median yearly angiomyolipoma growth rate stratified by tumor size at first detection was 0.1 mm for tumors 0.6 to 0.9 cm, 1.8 mm for those 1.0 to 1.9 cm and 4.3 mm for those 2.0 to 2.9 cm. A total of 35 patients (24.1%) received mTOR (mammalian target of rapamycin) inhibitors. Eight patients underwent a total of 13 surgical interventions, of whom 2 had previously been treated with mTOR inhibitors. Median patient age at surgical intervention was 18.0 years and median angiomyolipoma size was 5.0 cm. CONCLUSIONS: Angiomyolipoma growth in children with tuberous sclerosis complex can be rapid and unpredictable. We recommend yearly renal ultrasound in all patients with tuberous sclerosis complex, with consideration of magnetic resonance imaging in those at risk for rapid growth and future intervention (ie those older than 11 years and/or those with renal angiomyolipomas larger than 2 cm).

Can a simple question predict prolonged uroflow lag times in children?

OBJECTIVE: It is our experience that some children with bowel and bladder dysfunction (BBD) who have bladder neck dysfunction had a tendency to complain of dizziness when we subjected the patients with dizziness to tilt-table testing to confirm the diagnosis of autonomic dysfunction. From these findings we postulated that patients who complain of dizziness are likely to have prolonged lag times that are a proxy for bladder neck dysfunction (BND). STUDY DESIGN: This was an Institute Review Board-approved study in which we enrolled new patients in a sequential fashion who were referred to our outpatient urology offices for evaluation of BBD over a 3-month period. All patients were asked if they frequently experienced dizziness when they rapidly stood from a sitting or lying down position or when they raised their head rapidly. An analysis of the following parameters was undertaken: prevalence of dizziness, bladder neck dysfunction, and comorbid psychiatric problems. Uroflowmetry findings were analyzed as well. RESULTS: Tilt-table group: In the tilt-table group the median age of the patients was 14.5 (4.5-18) years for the five males and five females who were tested. All males and four out of five females experienced a blood pressure drops of 20 mmHg or more on table tilting and three experienced syncope. All patients had prolonged lag times, with an average lag time of 16.5 s. All these patients were able to tolerate alpha-blockers once they were adequately hydrated and salt loaded. Alpha-blocker dosing was increased gradually. In the questionnaire group, 212 patients were initially enrolled: 125 girls and 87 boys. Eleven of 12 males and eleven of 16 females had prolonged lag times when dizziness was present. Sensitivity was 92% and 69%, specificity was 80% and 91% respectively for male and females. Analysis of the psychiatric history revealed a statistically significant association with dizziness and neuropsychiatric problems in the patients and family members. CONCLUSION: We have been able to show a high degree of sensitivity in male patients and a high degree of specificity in female patients that a simple question, "Do you get dizzy on rising in the morning or with rapid standing?", is a reliable marker for BND in children. We have also seen that there is an association between dizziness and psychiatric problems in patients and in family members. It appears from our results and the available literature that autonomic dysfunction is commonly associated with BND and dizziness can be a simple proxy question to identify this problem.

Current urologic care for testicular germ cell tumors in pediatric and adolescent patients.

Testicular germ cell tumors make up 0.5% of pediatric malignancies, and 14% of adolescent malignancies. Young boys have primarily pure teratoma and pure yolk sac histologies; however, adolescent histology is mostly mixed nonseminomatous germ cell tumor. Surgical excision of the primary tumor is the crux of treatment. Chemotherapy, retroperitoneal lymph node dissection, and targeted treatment of distant metastases make even widely disseminated disease treatable. Since the discovery of platinum-based chemotherapy, testicular germ cell tumors are a highly curable disease. However, adolescents remain the group with the highest mortality. Focus has expanded beyond survival to emphasize quality of life issues when optimizing treatment algorithms.

In utero exposure to benzophenone-2 causes hypospadias through an estrogen receptor dependent mechanism.

PURPOSE: Additives such as benzophenone-2 are commonly used in cosmetic products and food container plastics to filter out ultraviolet light. In pregnant women exposure may result in transplacental transfer of benzophenone-2 to fetuses. Benzophenone-2 is estrogenic in vitro and in the rat uterotropic assay. Estradiol causes hypospadias in mice and estrogen-like compounds are also postulated to cause hypospadias. We determined whether hypospadias would develop in male mice exposed to benzophenone-2 in utero and whether this outcome depended on estrogen receptor pathways. MATERIALS AND METHODS: Timed pregnant C57BL/6 mice were administered benzophenone-2 (6.25 mg) or control vehicle by oral gavage from gestational days 12 through 17 and they were sacrificed on day 18. Fetuses were weighed and sexed, anogenital distance was measured and genital tubercles were harvested for paraffin sections or quantitative reverse transcriptase-polymerase chain reaction analysis of genes purportedly involved in genital tubercle development. RESULTS: Eight of 57 benzophenone-2 treated male fetuses (14%) whose genital tubercles were examined histologically had hypospadias (p = 0.0064). Co-administration of benzophenone-2 with the estrogen receptor antagonist EM-800 resulted in normal genital tubercles, ie no hypospadias, in 26 of 26 mice. Likewise no EM-800 or control treated male genital tubercles showed hypospadias. Benzophenone-2 treated male mice had no changes in body mass adjusted anogenital distance relative to controls. Reverse transcriptase-polymerase chain reaction revealed that genital tubercles of benzophenone-2 treated male mice expressed higher levels of estrogen receptor-beta relative to male controls (p = 0.04). CONCLUSIONS: These findings suggest that benzophenone-2 may cause hypospadias via signaling through the estrogen receptor. Further study of human benzophenone-2 exposure and its effects is needed to support this hypothesis.