Faculty Bibliography

PURPOSE: To our knowledge the pathogenesis of malignancy associated with ileal cystoplasty, ureterosigmoidostomy and ileal conduits is currently unknown. To gain further insights into the mechanism of neoplastic transformation we studied histological changes in a canine augmentation cystoplasty model. MATERIALS AND METHODS: Enterocystoplasty and gastrocystoplasty were performed using a 5 to 7 cm. patch of ileum in 8 dogs and gastric antrum in 6. Specimens were harvested 4 months postoperatively. Representative 3 microm sections of the enterovesical and gastrovesical junctions were stained with hematoxylin and eosin. Uroplakin expression was assessed using an indirect peroxidase method subjected to double staining with alcian blue and periodic acid-Schiffreagent. RESULTS: The bladder portion of the augmentation cystoplasty had 3 to 4 stratified cell layers covered with a distinctive umbrella cell layer. Strong uroplakin staining was visible in all cell layers except the basal layer. At the enterovesical and gastrovesical junctions 6 to 10 layers of hyperplastic, urothelial appearing cells covered the glandular epithelium of the ileal and gastric segments. These cells expressed uroplakins. At this junction zone there was a marked decrease of underlying enteric glands, which had atrophied in proportion to the degree of urothelial hyperplasia. Double staining of uroplakin stained sections with alcian blue and periodic acid-Schiff reagent revealed mucosubstances in hyperplastic urothelial cells covering the enteral segments, indicating that the cells co-expressed uroplakins and mucins. CONCLUSIONS: Histological changes in this experimental canine model of augmentation cystoplasty indicated that the overgrowth of hyperplastic transitional epithelium develops at the enterovesical and gastrovesical junctions. These cells express not only uroplakins, but also mucosubstances. Our results suggest that the migrated hyperplastic urothelial cells have undergone changes characteristic of the enteric and gastric epithelium, which may have important implications in the pathogenesis of malignancy in bladder augmentations

PURPOSE: Prenatal sonography has evolved through advancements in imaging technology and observer experience. This review focuses on our current knowledge of the sonographic appearance of normal and abnormal fetal genitalia. MATERIALS AND METHODS: A MEDLINE computerized reference and manual bibliography reviews were performed to find pertinent peer-reviewed articles on the sonographic appearance of normal and abnormal fetal genitalia. RESULTS: The sonographic appearance of the normal fetal genitalia has been defined. The male phallus can be visualized as early as 10 to 11 weeks of gestation, while testicular descent is not seen before 26 weeks. Hydroceles are commonly detected. In the female subject the labia majora and labia minora are visible by 15 weeks. Hydrometrocolpos due to uterovaginal anomalies can be seen as early as 26 weeks. CONCLUSIONS: Advances in prenatal sonography enable one to diagnose late first trimester gender. Sonography of the fetal genitalia complements fetal sex determination in cases of intersex, X-linked disorders or gender specific fetal anomalies, and is an important tool with increasing indications in prenatal medicine

PURPOSE/OBJECTIVE:We investigated the role of peptide growth factors and androgens in the developing human prostate. MATERIALS AND METHODS/METHODS:We performed immunohistochemical staining of prostate tissue sections from human fetuses 9.5, 11.5, 13, 16.5, 18 and 20 weeks in gestation. RESULTS:The temporal and spatial expression of these growth factors was related to the gestational androgen surge. Before the androgen surge (9.5 to 11.5 weeks) transforming growth factor (TGF)-alpha, TGF-beta1 and TGF-beta3 but not TGF-beta2 were present in the mesenchyme. The epithelium exhibited no detectable staining for any of the growth factors. During the androgen peak (13 to 16.5 weeks) TGF-beta1 decreased and TGF-beta2 increased in the mesenchyme, and TGF-alpha, TGF-beta1 and TGF-beta3 increased in the epithelium. With declining androgen levels TGF-alpha, TGF-beta2 and TGF-beta3 remained unchanged but TGF-beta1 increased in the mesenchyme with no change in the tested peptide growth factor levels in the epithelium. CONCLUSIONS:These data suggest that androgens regulate the differential expression of TGF-alpha and TGF-beta, and support a role for peptide growth factors as the direct mediators of androgen action on the mesenchymal and epithelial interactions responsible for prostate development.

Although many genetic alterations are known to be associated with human transitional cell carcinoma (TCC) of the urinary bladder, relatively little is known about the roles of these molecular defects, singular or in combination, in bladder tumorigenesis. We have developed a transgenic mouse model of bladder tumorigenesis using a 3.6-kb promoter of uroplakin II gene to drive the urotheliums-specific expression of oncogenes. In this study, we demonstrate that transgenic mice bearing a low copy number of SV40T transgene developed bladder carcinoma in situ (CIS), whereas those bearing high copies developed CIS as well as invasive and metastatic TCCs. These results indicate that the SV40T inactivation of p53 and retinoblastoma gene products, defects frequently found in human bladder CIS and invasive TCCs, can cause the aggressive form of TCC. Our results also provide experimental proof that CIS is a precursor of invasive TCCs, thus supporting the concept of two distinct pathways of bladder tumorigenesis (papillary versus CIS/invasive TCC). This transgenic system can be used for the systematic dissection of the roles of individual or combinations of specific molecular events in bladder tumorigenesis

Recurrent urinary tract infections (UTIs) and vesicoureteral reflux are common diagnosis' in infants and children who are referred to a urologist. Recurrent UTIs in these patients can be challenging, especially when radiographic evaluation reveals no structural abnormality. Prophylaxis and correction of voiding and bowel dysfunction are important treatment strategies. Febrile UTIs are commonly associated with reflux and should be treated aggressively to avoid renal scarring and its sequelae. Based on a comprehensive survey of the literature, long-term treatment strategies for children with reflux are now available

PURPOSE: We determine whether smooth and skeletal muscle or nerve density is altered in the lower genitourinary or gastrointestinal tract of male human fetuses with myelomeningocele at 20 weeks of gestation. MATERIALS AND METHODS: We serially cross sectioned the lower genitourinary and gastrointestinal tracts in 7 male fetuses (mean age 20 weeks of gestation) with myelomeningocele and 4 age matched controls. Immunohistochemical staining was performed using Masson's trichrome stain and antibodies to smooth and skeletal muscle actin. S-100 protein staining for Schwann cell localization and neurofilament protein was also done. Fluorescein and rhodamine double immunolabeling was used to demonstrate the co-expression of smooth and skeletal muscle. RESULTS: Peripheral neural innervation of the bladder, prostate and rectum was markedly decreased in myelomeningocele. Masson's trichrome and smooth muscle actin staining also demonstrated that smooth muscle was less well differentiated in myelomeningocele specimens. Scant smooth muscle was present in the myelomeningocele bladder and bladder neck with an excess of collagen in an interfascicular and intrafascicular distribution. Double immunofluorescence staining revealed persistent co-expression of smooth and skeletal muscle actin by myocytes in the myelomeningocele detrusor, while in the control bladder there was only smooth muscle expression. The skeletal muscle component of structures in fetuses with myelomeningocele, including the external sphincter, was similar to that in controls. Prostatic size, ductal morphogenesis and smooth muscle were decreased compared to those in controls. CONCLUSIONS: A global defect exists in the development of smooth muscle in myelomeningocele in the lower genitourinary and gastrointestinal tracts by 20 weeks of gestation. Peripheral nerve density is decreased in smooth muscle in myelomeningocele, suggesting that an intact nervous system is important for the development of normal smooth muscle. Fetal surgery with coverage of the spinal cord in select cases may prevent progressive environmental injury to the somatic nervous system during the second half of gestation. However, achieving normal autonomic function is unlikely due to the extent of early global organ maldevelopment