Robotic excision and ureteroureterostomy of blind-ending ureteral 'Duplication'.

INTRODUCTION: Duplicated ureteral anatomy can be a reconstructive challenge. Blind-ending ureteral duplication has been reported with recommendations for surgical excision. OBJECTIVE: This video reviews the importance of exposure of anatomic landmarks in surgical excision of a blind-ending ureteral duplication. MATERIALS AND METHODS: This is a retrospective case report of a patient who presented with a blind-ending ureteral duplication. DISCUSSION: A 13-year-old female presented with a right-sided abdominal mass. Abdominal and pelvic imaging revealed a tubular structure adjacent to and below the right kidney, possibly connecting to the right lower pole. While initially observed, the patient re-presented with urosepsis. A retrograde pyelogram showed no connection between the right ureter and this structure. The patient underwent robotic-assisted excision of this structure. Intra-operatively, it was connected to the right lower pole calyces. A ureteroureterostomy to the orthotopic ureter was performed. Although the structure was adjacent to the bladder dome, there was no communication distally. Postoperatively, the patient did well; follow-up imaging showed a non-dilated lower pole. The pathology of this structure was benign urothelium. CONCLUSIONS: Surgical management of aberrant ureteral duplications should focus on identifying known landmarks and should be considered to prevent symptomatic infections and renal scarring.

Report on The Society for Fetal Urology panel discussion on the selection criteria and intervention for fetal bladder outlet obstruction.

INTRODUCTION: The Society for Fetal Urology panel section at the 2016 Fall Congress featured a multidisciplinary discussion on appropriate patient selection, the conservative versus surgical management, and postnatal renal outcome of fetuses with lower urinary tract obstruction (LUTO). SELECTION CRITERIA FOR INTERVENTION: Rodrigo Ruano shared his experience of prenatal intervention, presenting the outcome of 111 fetuses with severe LUTO treated with vesicoamniotic shunting (VAS) (n = 16), cystoscopy (n = 34) or no intervention (n = 61) in a non-randomized series. Multivariate analysis at the 6-month follow-up suggested a significantly higher probability of survival with fetal intervention versus no intervention. A clear trend for normal renal function was present in the fetal cystoscopy group, but not in the VAS group. In cases in which there was a postnatal diagnosis of posterior urethral valves (n = 57), fetal cystoscopy was effective in improving both the 6-month survival rate and renal function, while VAS was associated with an improvement in the 6-month survival rate. In an attempt to better define which fetuses would benefit from intervention, Michael Braun explained the proposed LUTO classification system that incorporates: (1) fetal urinary biomarkers of renal injury; (2) amniotic fluid levels as a surrogate for the severity of obstruction; and (3) imaging studies to identify signs of renal dysplastic or cystic changes. Intervention was not recommended in patients at low risk of either renal disease or pulmonary hypoplasia (Stage 1). Vesicoamniotic shunting was performed in patients at high risk of either progressive renal injury or pulmonary hypoplasia without evidence of severe pre-existing renal damage (Stage 2). For those patients, who at the time of evaluation had evidence of severe renal disease (Stage 3), fetal intervention was individualized and often based on bladder capacity and bladder refilling after vesicocentesis. He went on to present the nephrologic outcome of fetuses managed over the last 3 years utilizing the selection criteria. Craig Peters supported the concept of selective criteria and discussed the cautious viewpoint, namely: (1) the procedure may be unnecessary, as it is possible for patients to do well, in spite of severe prenatal obstruction; and (2) the risk of giving partial treatment by allowing the baby to survive to delivery with the daunting postnatal journey of renal and pulmonary insufficiency. CONCLUSION: Standardized patient selection utilizing a staging system is undoubtedly the way forward and will enable comparable long-term renal and bladder functional outcome studies.

Reoperative robotic pyeloplasty in children.

INTRODUCTION: Reoperative pyeloplasty for recurrent ureteropelvic junction obstruction (UPJO) can be technically challenging and is associated with greater morbidity and lower success rates than an initial repair. Robotic-assisted laparoscopic pyeloplasty (RALP) previously has been demonstrated to be a safe and effective approach for management of recurrent UPJO; however, the length of follow-up has been limited. The objective of this study was to confirm the safety and efficacy of RALP for UPJO in children following failed previous pyeloplasty and provide clinical benchmarks for intermediate length follow-up in this patient population. METHODS: An IRB approved retrospective chart review was performed for all patients undergoing reoperative RALP from June 2006 to December 2014. All cases were performed by surgeons from two institutions for persistent UPJO following failed initial pyeloplasty. Information including demographic information, radiographic studies, and operative interventions performed between the initial repair and reoperative surgery, reoperative RALP intraoperative data, postoperative clinical course and imaging studies, and subsequent interventions following reoperative RALP were extracted. RESULTS: Twenty-three children underwent reoperative RALP. Eleven patients had right- and 12 left-sided repairs. Median age at reoperative RALP was 4.0 years and median interval between surgeries was 1.3 years. Indications for repeat repair included pain, infection, and/or radiographic evidence of worsening obstruction and/or deteriorating renal function. Mean operative time was 198 min from incision to port closure. Mean length of stay was 2.3 days. Six complications occurred in five patients within 30 days postoperatively, including ileus, pneumonia, and urinary tract infection. Median length of follow-up was 26 months (range 4-45 months) for all patients and 31 months (range 16-45 months) in 18 patients with >12 months of follow-up. More than 80% of patients presenting with flank pain prior to reoperative RALP had resolution of this symptom. To date, 78% of patients with >12 months of follow-up have not required further operative intervention. Excellent results have been achieved in 14 of 18 patients (78%) with sufficient postoperative follow-up in terms of length of follow-up (>12 months), symptom resolution, and/or improved imaging results. CONCLUSIONS: RALP following previous pyeloplasty is technically feasible with acceptable operative times, lengths of stay, and complication rates. Reoperative RALP is our preferred modality for repair of recurrent UPJO with the vast majority of patients having successful outcomes based on imaging, resolution of symptoms, and the rare need for further intervention across an intermediate length follow-up period.

Changes in the pore network structure of Hanford sediment after reaction with caustic tank wastes.

At the former nuclear weapon production site in Hanford, WA, caustic radioactive tank waste leaks into subsurface sediments and causes dissolution of quartz and aluminosilicate minerals, and precipitation of sodalite and cancrinite. This work examines changes in pore structure due to these reactions in a previously-conducted column experiment. The column was sectioned and 2D images of the pore space were generated using backscattered electron microscopy and energy dispersive X-ray spectroscopy. A pre-precipitation scenario was created by digitally removing mineral matter identified as secondary precipitates. Porosity, determined by segmenting the images to distinguish pore space from mineral matter, was up to 0.11 less after reaction. Erosion-dilation analysis was used to compute pore and throat size distributions. Images with precipitation had more small and fewer large pores. Precipitation decreased throat sizes and the abundance of large throats. These findings agree with previous findings based on 3D X-ray CMT imaging, observing decreased porosity, clogging of small throats, and little change in large throats. However, 2D imaging found an increase in small pores, mainly in intragranular regions or below the resolution of the 3D images. Also, an increase in large pores observed via 3D imaging was not observed in the 2D analysis. Changes in flow conducting throats that are the key permeability-controlling features were observed in both methods.

B cell infiltration and lymphonodular hyperplasia in bladder submucosa of patients with persistent bacteriuria and recurrent urinary tract infections.

PURPOSE: We defined chronic inflammatory cell types in bladder submucosa and the presence of umbrella cells on the surface of bladder epithelium in patients 5 to 21 years old with persistent bacteriuria due to neurogenic bladder and recurrent urinary tract infections associated with vesicoureteral reflux. MATERIALS AND METHODS: Bladder mucosa biopsies from 12 patients and 6 controls were fixed in Carnoy's solution and examined for T cells (CD3, CD4, CD8), B cells (CD79) and plasma cells (CD138). The number of cells in a defined area of submucosa was determined by counting all nuclei in the area. A contiguous section was also stained for uroplakin expression with a monoclonal antibody against uroplakin III to ascertain the integrity of bladder umbrella cells. RESULTS: B cells, plasma cells and lymphoid nodules were found only in patient biopsies. T cell expression was evident in patient and control biopsies. Uroplakin staining of surface epithelium was uniform from control biopsies but spotty or entirely absent from patient biopsies. CONCLUSIONS: Patients with persistent bacteriuria or recurrent urinary tract infections had significant B cell infiltration in the submucosa, including lymphoid nodules. These inflammatory changes are likely due to antigenic stimulation from repeated exposure to bacteria. These changes are associated with frequent absence of uroplakin on surface epithelium.

Absence of bacterial reservoirs in the bladder epithelium of patients with chronic bacteriuria due to neurogenic bladder.

PURPOSE: Bacteriuria is common in patients with neurogenic bladder who are on clean intermittent catheterization for bladder emptying. In a longitudinal study patients carried 1 or 2 clones of Escherichia coli in the urine during months of surveillance. An explanation for persistent bacteriuria in this population could be that periurethral E. coli inoculated during clean intermittent catheterization would attach via type I adhesin, invade superficial bladder epithelial cells and establish reservoirs. Resurgence of bacteria from these reservoirs in bladder epithelium could later reenter the urine and establish a recurrent episode of bacteriuria. We investigated whether bacterial reservoirs were present in the superficial epithelium of patients with neurogenic bladder and chronic bacteriuria. MATERIALS AND METHODS: Bladder biopsies were obtained from patients with neurogenic bladder and a history of chronic recurrent bacteriuria. Biopsies were fixed in Carnoy's solution to preserve the material overlying the luminal surface of the superficial bladder epithelium. Following fixation biopsies were stained with hematoxylin and eosin to detect intracellular bacterial reservoirs and with periodic acid-Schiff for exopolysaccharide of biofilm. Fluorescence in situ hybridization was done to visualize individual bacteria. RESULTS: No evidence of bacterial reservoirs was found in the superficial bladder epithelium of 9 patients with neurogenic bladder. On hematoxylin and eosin staining epithelium with an intact luminal surface had no intracellular bacterial pods. On periodic acid-Schiff staining no biofilm or collection of exopolysaccharide surrounding bacterial communities was found. No collections or individual bacteria were seen on fluorescence in situ hybridization stained sections examined at 1,000x magnification with oil immersion. CONCLUSIONS: Bacterial reservoirs do not appear to be an important source of bacteriuria in patients with chronic recurrent bacteriuria due to neurogenic bladder.

Fracture-associated and idiopathic subchondral vertebral lesions: a magnetic resonance study in autopsy specimens with histologic correlation.

OBJECTIVE: The aim of this study was to describe and compare the magnetic resonance (MR) and histological appearance of subchondral vertebral lesions that are idiopathic or that develop with vertebral fractures. MATERIALS AND METHODS: T1- and T2-weighted spin-echo images and radiographs were obtained in 81 cadaveric spine specimens. All subchondral vertebral lesions that were considered to be idiopathic or associated with vertebral end plate fractures were selected. Lesions due to growth disturbance were excluded. Radiographs and MR images were analyzed in consensus by two radiologists, and sampled specimens were analyzed by a pathologist. RESULTS: Eleven idiopathic and ten fracture-associated vertebral lesions were available. On T1-weighted images, all lesion signal intensity was low and homogeneous. On T2-weighted images, all idiopathic lesions showed a heterogeneous signal with a central low or intermediate signal component and a peripheral high or intermediate component. All but one fracture-related lesions showed a homogeneous intermediate to high signal intensity. Histological analysis of idiopathic lesions showed a central acellular fibrous connective tissue in all cases surrounded by loose connective tissue in nine cases. Herniated disk material and cartilage metaplasia were found in one lesion only. Fracture-associated lesions contained herniated disk material, necrotic tissue, and loose connective tissue with a peripheral component of loose fibrovascular connective tissue in four cases only. CONCLUSION: MR and histological appearance of idiopathic and fracture-associated subchondral vertebral lesions differ, suggesting that they might have a different origin.

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions.

AIMS: Caveolae are cholesterol-rich plasmalemmal microdomains that serve as sites for sequestration of signaling proteins and thus may facilitate, organize, and integrate responses to extracellular stimuli. While previous studies in the bladder have demonstrated alterations in caveolae with particular physiologic or pathologic conditions, little attention has been focused on the functional significance of these organelles. Therefore, the purpose of this study was to investigate the role of caveolae in the modulation of receptor-mediated signal transduction and determine the presence and localization of caveolin proteins in bladder tissue. METHODS: Contractile responses to physiologic agonists were measured in rat bladder tissue before and after disruption of caveolae achieved by depleting membrane cholesterol with methyl-beta-cyclodextrin. Stimulation with agonists was repeated after caveolae were restored as a result of cholesterol replenishment. RT-PCR, immmunohistochemistry, and Western blotting were used to determine the expression and localization of caveolin mRNA and proteins. RESULTS: Following caveolae disruption, contractile responses to angiotensin II and serotonin were attenuated, whereas responses to bradykinin and phenylephrine were augmented. Cholesterol replenishment restored responses towards baseline. Carbachol and KCl induced contractions were not affected by caveolae disruption. Ultrastructure analysis confirmed loss of caveolae following cholesterol depletion with cyclodextrin and caveolae restoration following cholesterol replacement. Gene and protein expression of caveolin-1, -2, and -3 was detected in bladder tissue. Immunoreactivity for all three caveolins was observed in smooth muscle cells throughout the bladder. CONCLUSIONS: The functional effects of cholesterol depletion on specific agonist-induced contractile events and the expression of all three caveolins in bladder smooth muscle support a central role for caveolae in regulation of selective G-protein-coupled receptor signaling pathways in bladder smooth muscle. Thus, caveolae serve to differentially regulate bladder smooth muscle by a stimulus-dependent potentiation or inhibition of bladder contraction.

Renal biopsy in congenital ureteropelvic junction obstruction: evidence for parenchymal maldevelopment.

The renal histologic changes associated with congenital ureteropelvic junction obstruction (UPJO) and the relationship to clinical imaging have not been well studied. In order to better understand the histologic alterations of congenital UPJO and their relationship with clinical imaging and outcomes, we examined renal biopsies from 61 patients undergoing pyeloplasty for congenital UPJO. Glomeruli were analyzed for various injury patterns and the tubulointerstitium was examined for tubular atrophy/simplification and fibrosis. Two methods were used to evaluate tubular mass: glomerular density and morphometric measurement of tubular size and density. Control specimens were obtained from age-matched autopsy specimens without renal pathology. Glomerular changes were identified in 73% of all biopsies and were present in a range from 1.7 to 91% of glomeruli in each patient. Overt tubulointerstitial changes were present in 26% of all biopsies. Fibrosis was noted to occur with tubulointerstitial changes in a significantly greater fraction of children over the age of 1 year (P=0.026). Increased glomerular density was associated with severe hydronephrosis (P<0.02). Normal glomerular density was inversely correlated with age (P<0.001), but this relationship was more variable in UPJO (P<0.01). Among patients with intact differential function preoperatively (>45%), postoperative functional decline was predicted only by increased glomerular density. 20 biopsies without overt tubulointerstitial changes were analyzed morphometrically and showed a significant reduction in proximal tubular (PT) size, but unchanged density. Distal tubular (DT) size was unchanged in UPJO, but density was increased. The PT/DT ratio was therefore markedly decreased in UPJO (P<0.0001). Both PT and DT sizes were significantly larger in children with a diuretic renogram washout time less than 20 min than those with greater than 20 min, a common threshold for functionally significant obstruction (P<0.05). Capsular thickness was significantly increased in UPJO. In all, 36% of biopsies had a thickness >0.5 mm and this was associated with greater degrees of tubulointerstitial changes and glomerular alterations. Congenital UPJO produces a variety of renal parenchymal changes, which may in part reflect abnormal development. Some of these alternations are seen in clinical imaging and may help predict outcomes, but there is significant discordance between conventional imaging and histological findings.

Neonatal scrotal haematoma: mimicker of neonatal testicular torsion.

OBJECTIVE: To describe the clinical features of neonatal scrotal haematoma and distinguish them from those of neonatal testicular torsion. PATIENTS AND METHODS: Five neonates presenting with an acute scrotum and initial diagnosis of neonatal testicular torsion were found to have neonatal scrotal haematoma. In one case the diagnosis was surgical and in four subsequent cases the diagnosis was by colour Doppler ultrasonography, and surgery was avoided. Four of the five children had risk factors associated with neonatal scrotal haematoma, including bleeding diathesis, birth trauma and high birth weight. CONCLUSIONS: The importance of including haematoma in the differential diagnosis of the acute neonatal scrotum is emphasized, as is the value of contemporary Doppler ultrasonography in making this diagnosis.

Animal models of fetal renal disease.

Fetal models of urinary tract disease have been used for many years and have provided unique and important insights into the pathophysiology of these conditions. This review will summarize the principal model systems used and the current directions of investigation. These models (including rabbit, opossum, sheep and recently swine) have demonstrated that in utero obstruction of the urinary tract alters renal growth, differentiation and produces stereotypical patterns of tissue response, particularly fibrosis. New molecular understanding of these processes has identified specific mechanisms that may be key elements in the development of renal dysfunction due to obstruction. These factors include the renin-angiotensin system (RAS) and its interaction with TGF-beta in altering growth regulation and tissue fibrosis. These factors offer the prospect of clinical utility as markers of disease progression as well as pharmacologic therapy. Gene knockout systems have opened a new horizon of molecular models of congenital obstructive uropathy with insights into the role of the RAS in particular. It remains to be defined how closely these knockouts represent the human conditions they resemble. Continued application of fetal models of urinary obstruction, integrating large animal and knockout systems offers promise for improved diagnosis and treatment in these challenging conditions.

Natural history of vesicoureteral reflux in girls after age 5 years.

PURPOSE: Expectations concerning the likelihood that vesicoureteral reflux will resolve during a given interval are predominantly based on experience with children younger than 5 years. We assess the natural course of vesicoureteral reflux in girls older than 5 years. MATERIALS AND METHODS: We reviewed the diagnostic and followup cystograms, medical records and renal imaging studies of 200 girls with vesicoureteral reflux, of whom 97 were diagnosed before age 60 months and 103 were diagnosed at or after age 60 months. Vesicoureteral reflux was considered to have resolved when a followup radionuclide cystogram demonstrated no reflux. RESULTS: Vesicoureteral reflux demonstrated at or after age 60 months by a radionuclide or radiographic examination (index study) resolved in 43% of cases during a mean followup interval of 41 months. The yearly percent chance of resolution approached or exceeded 20% through age 11 years. For girls with moderate vesicoureteral reflux on the index study unilateral moderate vesicoureteral reflux was associated with a higher overall percent chance of resolution and a shorter time from index study to resolution. Evidence of new or progressive parenchymal injury was not indicated in any of 92 girls who underwent serial renal ultrasonograms. CONCLUSIONS: Vesicoureteral reflux resolution continues after age 5 years at a rate similar to that in younger children. Continued medical management in the anticipation of spontaneous resolution is safe and appropriate for most patients.

Partial ureteral obstruction dysregulates the renal renin-angiotensin system in the fetal sheep kidney.

OBJECTIVES: To investigate whether partial ureteral obstruction (PUO) in the fetus induces dysregulation of the renin-angiotensin system (RAS) and of transforming growth factor-beta 1 (TGF-beta1) and tissue inhibitors of metalloproteinase (TIMP1) expression. Previous studies have indicated that renal and urinary tract development depend on an intact renal RAS. Fetal urinary obstruction is distinct from postnatal obstruction. It has been suggested in postnatal animal studies that dysregulation of the RAS, and subsequent increased expression of TGF-beta1 and TIMP1, leads to changes in extracellular matrix composition. METHODS: Bilateral PUO was created in 4 fetal sheep. Seven animals (four obstructed and three controls) were killed at birth and their kidneys removed. Semiquantitative reverse transcriptase-polymerase chain reaction was used to quantify the levels of renin, angiotensinogen, angiotensin receptor type 1 (AT1 receptor), angiotensin receptor type 2 (AT2 receptor), TGF-beta1, and TIMP1. These messages were normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA. RESULTS: All obstructed animals had moderate to severe hydronephrosis with enlarged kidneys (mean weight 22.0 g versus 9.4 g for the control animals; P <0.05). The increase in the levels of renin, angiotensinogen, AT1 receptor, TGF-beta1, and TIMP1 mRNA was significant in the PUO group compared with the control group (P <0.05). AT2 receptor levels did not increase, but the AT1/AT2 mRNA ratio was significantly increased over normal (P <0.005). Also, a significant linear correlation was found between the increased renal weight and increased TGF-beta1 mRNA levels (P <0.005). CONCLUSIONS: Our findings suggest that fetal PUO can cause upregulation of the renal RAS and increased expression of TGF-beta1 and TIMP1, which may alter the balance between the generation and degradation of the extracellular matrix. The coordinate increases in renin, angiotensinogen, and AT1 receptor mRNA levels in chronic fetal PUO may represent a maladaptive response that contributes to interstitial fibrosis and prolonged vasoconstriction. RAS components and growth factors, particularly TGF-beta1, may be considered relevant targets in the prevention and treatment of congenital obstructive nephropathy.

Developmental regulation of mitogen-activated protein kinase-activated kinases-2 and -3 (MAPKAPK-2/-3) in vivo during corpus luteum formation in the rat.

The current study investigates the activation in vivo and regulation of the expression of components of the p38 mitogen-activated protein kinase (MAPK) pathway during gonadotropin-induced formation and development of the rat corpus luteum, employing a sequential PMSG/human CG (hCG) treatment paradigm. We postulated that the p38 MAPK pathway could serve to promote phosphorylation of key substrates during luteal maturation, since maturing luteal cells, thought to be cAMP-nonresponsive, nevertheless maintain critical phosphoproteins. Both p38 MAPK and its upstream activator MAPK kinase-6 (MKK6) were found to be chronically activated during the luteal maturation phase, with activation detected by 24 h post hCG and maintained through 4 days post hCG. The p38 MAPK downstream protein kinase target termed MAPK-activated protein kinase-3 (MAPKAPK-3) was newly induced at both mRNA and protein levels during luteal formation and maturation, while mRNA and protein expression of the closely related MAPKAPK-2 diminished. Two potential substrates for MAPKAPKs, the small heat shock protein HSP-27 and the cAMP regulatory element binding protein CREB, were monitored in vivo for phosphorylation. HSP-27 phosphorylation was not modulated during luteal maturation. In contrast, we observed sustained luteal-phase CREB phosphorylation in vivo, consistent with upstream MKK6/p38 MAPK activation and MAPKAPK-3 induction. MAPKAPK-3-specific immune complex kinase assays provided direct evidence that MAPKAPK-3 was in an activated state during luteal maturation in vivo. Cellular inhibitor studies indicated that an intact p38 MAPK path was required for CREB phosphorylation in a cellular model of luteinization, as treatment of luteinized granulosa cells with the p38 MAPK inhibitor SB 203580 strongly inhibited CREB phosphorylation. Transient transfection studies provided direct evidence that MAPKAPK-3 was capable of signaling to activate CREB transcriptional activity, as assessed by means of GAL4-CREB fusion protein construct coexpressed with GAL4-luciferase reporter construct. Introduction of wild-type, but not kinase-dead mutant, MAPKAPK-3 cDNA, into a mouse ovarian cell line stimulated GAL4-CREB- dependent transcriptional activity approximately 3-fold. Thus MAPKAPK-3 is indeed uniquely poised to support luteal maturation through the phosphorylation and activation of the nuclear transcription factor CREB.

Tubularized incised plate urethroplasty: expanded use in primary and repeat surgery for hypospadias.

PURPOSE: We evaluated the impact of tubularized incised plate urethroplasty on primary and repeat hypospadias repair. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all boys who underwent hypospadias repair at our institution during a recent 3-year period. The level of the hypospadias defect, technique of repair, primary repair versus reoperation, age at surgery and complications were recorded. RESULTS: A total of 520 hypospadias repairs were done from May 1996 through June 1999. We began to perform tubularized incised plate urethroplasty in November 1996. During the ensuing consecutive 32 months 181 primary and 25 repeat hypospadias repairs were done using this technique. Mean patient age at surgery was 22 months (range 3 months to 30 years). During the 6 months immediately before we began to use this method the Mathieu flip-flap procedure was the most commonly performed technique, accounting for 38% of all hypospadias repairs. In contrast, during the last 6 months reviewed tubularized incised plate urethroplasty accounted for 63% of all repairs, including 41 of 65 primary operations (63%) and 4 of 6 reoperations (67%), while no Mathieu procedures were performed. Postoperative followup was 6 to 38 months for tubularized incised plate repair. Overall meatal stenosis and a urethrocutaneous fistula developed in 1 and 14 boys, respectively (7% complication rate). CONCLUSIONS: Tubularized incised plate urethroplasty has become the preferred technique of primary and repeat hypospadias repair at our institution. The technique has few complications as well as proved success and versatility that continues to expand its applicability and popularity.

Relationship of family history and outcome after breast conservation therapy in women with ductal carcinoma in situ of the breast.

PURPOSE: The purpose of this study was to evaluate the relationship between a family history of breast or ovarian cancer and outcome after breast-conserving surgery and radiation in women presenting with an initial diagnosis of ductal carcinoma in situ (DCIS) of the breast. METHODS AND MATERIALS: A total of 146 consecutive women with a pathologic diagnosis of ductal carcinoma in situ as their first diagnosis of any breast cancer were identified; 28 (19%) had a positive family history of breast or ovarian cancer in a first-degree relative, 27 (19%) had a positive family history in a second-degree relative, and 91 (62%) had no family history. Pathologic, clinical, and treatment factors, and clinical outcomes for each family history group were compared. Cosmesis and complications were recorded at each follow-up. Patients were treated between 1978 and 1995, and the median follow-up was 7.1 years. RESULTS: Patients with a positive family history in a first- or second-degree relative each had an 8% incidence of local failure at 10 years, while the negative family history group demonstrated a 16% local failure rate (p = 0.33). Overall survival at 10 years for patients with a positive family history in a first- or second-degree relative was 100% and for those with a negative family history was 91% (p = 0.08). The negative family history group had a higher median age that may account for the difference in overall survival. Cause-specific survival (CSS) was 97%, 100%, and 99%, respectively, at 10 years (p = 0.25). There were no differences in the cosmetic results or complication rates between women with a positive or negative family history. CONCLUSION: We have shown that a family history of breast and/or ovarian cancer is not associated with an adverse outcome for women treated with breast conservation therapy for DCIS. Local recurrence, cause-specific survival, overall survival, cosmesis, and complication rates were comparable to that of similarly treated women with negative family histories. Therefore, a positive family history is not a contraindication for breast conservation therapy in women with DCIS.

99m Technetium dimercapto-succinic acid renal scintigraphy abnormalities in infants with sterile high grade vesicoureteral reflux.

PURPOSE: Although vesicoureteral reflux associated with bacteriuria may cause renal scarring, sterile reflux is thought not to cause renal injury. We determined the incidence and associated characteristics of renal abnormalities using 99mtechnetium(Tc) dimercapto-succinic acid (DMSA) renal scintigraphy in infants with high grade vesicoureteral reflux but no history of urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed the results of 99mTc-DMSA renal scintigraphy and renal ultrasonography performed during the first 6 months of life in infants with vesicoureteral reflux detected during the postnatal evaluation of prenatal hydronephrosis or sibling reflux screening. Those with a history of urinary tract infection, or evidence of ureteropelvic junction or bladder outlet obstruction were excluded from study. RESULTS: Of the 28 male and 6 female infants who met study criteria vesicoureteral reflux was bilateral in 25 and unilateral in 9. Reflux grade was IV or V, II or III and I in 38, 18 and 3 of the 59 refluxing renal units, respectively. 99mTc-DMSA renal scintigraphy revealed parenchymal abnormalities in 24 refluxing renal units (41%) in 22 patients (65%), of whom 19 (86%) were male and 15 (68%) had bilateral reflux. We noted differential uptake less than 40% with and without cortical defects in 10 and 7 refluxing units, respectively, and cortical defects only in 7. Of the 24 refluxing units with abnormalities 21 were associated with grade IV or V and 3 with grade II or III reflux. Ultrasound showed evidence of renal injury in only 7 of the 17 patients (41%) in whom 99mTc-DMSA scintigraphy was abnormal. CONCLUSIONS: In our study the majority of infants with high grade reflux had decreased differential function and/or cortical defects. Parenchymal defects detected by 99mTc-DMSA renal scintigraphy were often not identified by renal ultrasound. Therefore, 99mTc-DMSA renal scintigraphy is especially useful for initially evaluating infants with high grade, sterile vesicoureteral reflux.

Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells.

Cyclic mechanical stretch of bladder smooth muscle cells (SMC) increases rates of DNA synthesis and stimulates transcription of the gene for heparin-binding epidermal growth factor-like growth factor (HB-EGF), an ErbB1/EGF receptor ligand that has been linked to hypertrophic bladder growth. In this study we sought to clarify the signaling pathways responsible for mechanotransduction of the stretch stimulus. HB-EGF mRNA levels, DNA synthesis, and AP-1/Ets DNA binding activities were induced by repetitive stretch of primary culture rat bladder SMC. Inhibitors of the p38 SAPK2 pathway, the angiotensin receptor type 1 (AT1), and the ErbB2 tyrosine kinase reduced each of these activities, while an inhibitor of the extracellular signal-regulated kinase mitogen-activated protein kinase (Erk-MAPK) pathway had no effect. Stretch rapidly activated stress-activated protein kinase 2 (p38 SAPK2) and Jun NH(2)-terminal kinase (JNK)/SAPK pathways but not the Erk-MAPK pathway and induced ErbB2 but not ErbB1 phosphorylation. Angiotensin II (ANG II) a bladder SMC mitogen previously linked to the stretch response, did not activate ErbB2, and ErbB2 activation occurred in response to stretch in the presence of an ANG receptor inhibitor, indicating that activation of the AT1-mediated pathway and the ErbB2-dependent pathway occurs by independent mechanisms. p38 SAPK2 and JNK/SAPK signaling also appeared to be independent of the ErbB2 and AT1 pathways. These findings indicate that stretch-stimulated DNA synthesis and gene expression in normal bladder SMC occur via multiple independent receptor systems (e.g., AT1 and ErbB2) and at least one MAPK pathway (p38 SAPK2). Further, we show that the Erk-MAPK pathway, which in most systems is linked to receptor-dependent cell growth responses, is not involved in progression to DNA synthesis or in the response of the HB-EGF gene to mechanical forces.

Ureteropelvic junction obstruction: morphological and clinical studies.

This study included 27 patients with ureteropelvic (UPJ) obstruction. Both renal parenchyma and the junctional abnormality were examined and correlated with clinical findings. Renal biopsies were categorized into grades 1-4. Those with normal or minimal findings (grade 1 and 2, respectively) had excellent renal function as assessed by radionuclide studies. Those with grade 4 had severe histological abnormalities associated with poor renal function. Grade 3 renal changes were seen in patients whose renal function varied greatly and did not correlate with the extent of the limited histological abnormalities. Although there was great variation in the renal biopsies, glomerulosclerosis was a consistent finding, associated with extracapillary proliferation and periodic acid-Schiff-positive material (? Tamm-Horsfall protein) in the urinary space of glomeruli in 91% (10/11) of grade 3 or 4 renal biopsies. No extracapillary proliferation was seen in grade 1 renal biopsies. The UPJ obstruction area was consistently inflamed and markedly thickened due to varying degrees of perifascicular fibrosis and muscular hypertrophy. Extensive fibrosis with associated muscular atrophy was the most-severe change in this spectrum.