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Objective: To determine the rate of stone formation amongst patients of the exstrophy-epispadias complex with augmentation cystoplasty. We hypothesize that bowel segment choice influences the rate of stone formation after bladder augmentation and the rate of complications from bladder stone surgery., Methods: An IRB-approved institutional database of 1512 exstrophy-epispadias patients was reviewed retrospectively. Patients that had a history of bladder augmentation and were seen at our institution between 2003 and 2023 were included., Results: Out of 259 patients, bladder stones developed in 21.6% (56), of which the bowel segment used was colon in 147 patients and ileum in 100. Stones formed in 19% of colon augments compared to 29% ileal augments, however, this was not statistically significant (P = .07). The most common primary stone component was dahllite, followed by struvite for all augments (Table 1). The median time to stone treatment after augmentation was 4.14 years (0.75-31). Seventy-four percentage of patients had a recurrence that required a second surgery. The median time from first to second surgery and second to third surgery was 1.4 years and 2.22 years, respectively. Bladder stone surgery complications occurred in 14% of patients, vesicocutaneous fistula being the most common, and complications did not differ by augment type. Median follow-up after first stone intervention was 6.07 years (0-19.5)., Conclusion: The treatment of bladder stones in the exstrophy-epispadias complex remains challenging. Interventions to prevent recurrence are crucial as the majority of patients will require 2 or more stone surgeries in their lifetime., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Despite the availability of Bacille Calmette Guérin (BCG) vaccines, Mycobacterium tuberculosis currently infects billions of people and millions die annually from tuberculosis (TB) disease. New TB vaccines are urgently needed., Methods: We studied the ability of AERAS-402, a recombinant, replication-deficient adenovirus type 35 expressing the protective M. tuberculosis antigens Ag85A, Ag85B, and TB10.4, to boost BCG immunity in an area of low TB endemicity., Results: In volunteers primed with BCG 3 or 6 months prior to AERAS-402 boosting, significant CD4(+) and CD8(+) T cell responses were induced. Ag85-specific responses were more strongly boosted than TB10.4-specific responses. Frequencies of TB-specific CD8(+) T cells reached>50 fold higher than pre-AERAS boosting levels, remarkably higher than reported in any previous human TB vaccine trial. Multiparameter flow cytometric assays demonstrated that AERAS-402-boosted CD4(+) and CD8(+) T cells were multifunctional, producing multiple cytokines and other immune effector molecules. Furthermore, boosted T cells displayed lymphoproliferative capacity, and tetramer analyses confirmed that antigen-specific CD8(+) T cells were induced. BCG and AERAS-402 vaccinations given 3 and 6 months apart appeared equivalent., Conclusions: Our results indicate that AERAS-402 is a promising TB vaccine candidate that can significantly enhance both CD4(+) and CD8(+) TB-specific T cell responses after BCG priming. ClinicalTrials.gov Identifier: NCT01378312., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: To outline the management strategies applied to the adolescent patient population with exstrophy/epispadias and incontinence at our institution. These patients present a difficult management problem. At the same time they are dealing with difficult issues, including body image and sexual awareness, the added burden of ongoing incontinence causes major anxieties and lifestyle restrictions. In many, incontinence has persisted despite numerous operations., Methods: A total of 25 (19 male and 6 female) patients who remained incontinent into adolescence or early adulthood were reviewed. Of the 25 patients, 19 had exstrophy, 4 had cloacal exstrophy, and 1 male and 1 female had epispadias. Six patients had undergone eight prior attempts at continent reconstruction, one had undergone cutaneous diversion, and one had problems after ureterosigmoidostomy., Results: The mean age at continence surgery was 12.9 years. Of the 25 patients, 18 underwent bladder augmentation, with a continent stoma in 17 and an artificial sphincter in 1. An additional 5 patients underwent bladder neck transection, with a new continent stoma in 3. The ureterosigmoidostomy was converted to a Mainz II pouch. One patient underwent continent neobladder formation. Nine patients (36%) developed complications during follow-up. Three required stoma revision for stenosis and one for prolapse. Pouch stones occurred in 4 patients, and vesicocutaneous fistula developed in 1. All achieved full urinary continence. The mean follow-up was 72.4 months., Conclusions: Some children with exstrophy/epispadias reach adolescence and remain incontinent. For these patients, modern reconstructive techniques provide hope of continence. With careful preoperative assessment, exact surgical precision, and regular follow-up, a successful outcome can be expected in virtually all cases without the need for external urine collection devices.

Objectives: To provide a complete look at the bony pelvis in children with classic bladder exstrophy: dimensions, orientation, and relationships., Methods: Three-dimensional computed tomography was used in 6 boys and 1 girl, 5 of whom underwent primary closure and 2 who underwent reclosure at 4 and 8 months. These exstrophy pelves (intrapelvic angles and osseous dimensions) were compared with 26 age and sex-matched controls., Results: The iliac wing angle was 11.4 degrees larger in the classic bladder exstrophy cases. The sacroiliac joint angle was 9.9 degrees more externally rotated in the exstrophy cases. The pelvis was rotated 14.7 degrees in the superoinferior plane in the exstrophy cases. The mean pubic diastasis was 4.2 cm (0.6 cm in controls). The inter-triradiate distance in the patients with classic bladder exstrophy averaged 6.0 cm (4.2 cm in controls)., Conclusions: These new findings provide a better understanding of the bony pelvis, especially its posterior portion, in patients with classic bladder exstrophy. The results of this study revealed the orientation of the sacroiliac joints to be more externally oriented than previously thought and the pelvis to be rotated inferiorly, a previously unknown observation. Both of these factors will be important in the planning of newer osteotomies and pelvic reconstruction.

Introduction: The modern Young-Dees-Leadbetter bladder neck reconstruction is a procedure that has evolved during the past 82 years. During this time, the modifications and contributions of several urologic surgeons have improved the procedure and ultimate patient outcomes. We review the evolution and describe in detail our version of the Young-Dees-Leadbetter bladder neck reconstruction procedure., Technical Considerations: Optimally, patients should have a minimal bladder capacity of 85 mL and be mature enough to participate in a postoperative voiding program. Adequate radical exposure of the lateral aspects of the bladder and bladder neck are important. Cephalotrigonal or cross-trigonal ureteral reimplantation is typically performed to mobilize the ureters in relation to the proposed bladder neck and correct reflux. A mucosal template 15 mm wide by 30 mm long is created that will serve as the reconstituted posterior urethra and bladder neck. Triangular lateral bladder mucosal wedges are marked and demucosalized. The neourethra is closed over an 8F Firlit tube. The demucosalized flaps are brought over the urethra sequentially in a "vest-over-pants" fashion with the final layer consisting of suspension sutures. Finally, ureteral stents and a suprapubic tube are used, but no urethral catheter is left in place., Conclusions: The modern Young-Dees-Leadbetter bladder neck reconstruction is the result of the contributions of various urologic surgeons during 82 years. When patients are appropriately selected, it is an effective method of lower urinary tract reconstruction in cases of congenital urinary incontinence.

We report a rare case and description of a benign pediatric renal mass. To our knowledge, this tumor has never been described in urologic published reports. It is possible that the identification of this renal tumor could spare a child the toxic adjuvant chemotherapy that would be administered if confused with histologically similar tumors such as clear cell sarcoma of the kidney.

Objectives: To delineate factors that may predict eventual urinary continence after bladder neck reconstruction (BNR) in the bladder exstrophy population., Methods: The records of 65 patients who underwent all phases of bladder exstrophy reconstruction at our institution between 1975 and 1997 with greater than 1-year follow-up were reviewed and data analyzed., Results: Fifty patients (77%) are continent day and night and voiding per urethra without need for augmentation or intermittent catheterization. Nine (14%) patients have social continence, dry for more than 3 hours during the day. Two patients required continent diversion for continence after failed BNR. Four patients are completely incontinent. The mean age of BNR was 4 years with a mean and median capacity of 93 and 85 cc (range 45 to 175). Analysis of bladder capacity measurements prior to BNR revealed that patients with a bladder capacity greater than 85 cc median capacity at the time of BNR had better outcomes. No correlation was found between the age of BNR and obtaining eventual continence. The mean time to daytime continence was 14 months (range 4 to 21) and the mean time to nighttime continence was 22 months (range 11 to 33)., Conclusions: Determinants of continence in the bladder exstrophy population are multifactorial. In our experience, 77% of patients are completely dry, day and night, and 91% can achieve social continence, being dry for at least 3 hours. However, with careful evaluation of bladder capacity and bladder growth, urinary continence may be improved in this population with better patient selection.

Objectives: Interest has increased in combining procedures during reconstruction of bladder exstrophy in an effort to reduce the number of procedures required for reconstruction and to improve results. This study illustrates our technique of reconstruction and summarizes our current experience with the combination of epispadias repair and bladder closure during initial reconstruction or following prior failed bladder closure., Methods: Twenty-four boys with classic bladder exstrophy underwent combined bladder closure and epispadias repair. The mean patient age was 20 months, and 18 boys had a prior failed closure. Osteotomies were performed in all patients., Results: No instances of bladder prolapse or dehiscence were noted on follow-up. Urethrocutaneous fistula developed in 7 patients. Eventual bladder neck reconstruction has been performed in 11 boys (6 boys are dry day and night, 3 are dry during the day with occasional wet episodes at night, 2 have required follow-up bladder augmentation and continent diversion for persistent incontinence), and 1 boy had augmentation at the same time as bladder neck reconstruction. Twelve boys are awaiting adequate capacity for bladder neck reconstruction, and 1 is awaiting bladder augmentation and continent stoma construction., Conclusions: Epispadias closure can be safely combined with bladder closure in select patients with classic bladder exstrophy. Complication rates and cosmesis approximate that achieved with staging the two procedures. This achievement represents strict patient selection and attentive follow-up.

Manganese (Mn)-deficiency or Mn-excess can lead to adverse biological consequences. Central nervous system tissues, rich in dopaminergic neurons, are the targets whether the Mn gains entrance by inhalation, oral ingestion, or intravenous administration. Risk assessments with Mn need to ensure that brain concentrations in the globus pallidus and striatum stay within the range of normal. This paper first provides a critical review of the biological factors that determine the disposition of Mn in tissues within the body. Secondly, it outlines specific data needs for developing a physiologically based pharmacokinetic (PBPK) model for Mn to assist in conducting risk assessments for inhaled and ingested Mn. Uptake of dietary Mn appears to be controlled by several dose-dependent processes: biliary excretion, intestinal absorption, and intestinal elimination. Mn absorbed in the divalent form from the gut via the portal blood is complexed with plasma proteins that are efficiently removed by the liver. Absorption of Mn via inhalation, intratracheal instillation or intravenous infusions bypasses the control processes in the gastrointestinal tract. After absorption into the blood system by these alternate routes, Mn is apparently oxidized by ceruloplasmin and the trivalent Mn binds to the iron carrying protein, transferrin. Brain uptake of Mn occurs via transferrin receptors located in various brain regions. Transferrin-bound trivalent Mn is not as readily removed by the liver, as are protein complexes with divalent Mn. Thus, Mn delivered by these other dose routes would be available for uptake into tissues for a longer period of time than the orally administered Mn, leading to quantitative differences in tissue uptake for different dose routes. Several important data gaps impede organizing these various physiological factors into a multi-dose route PK model for Mn. They include knowledge of (1) oxidation rates of Mn in blood, (2) uptake rates of protein-bound forms of Mn by the liver, (3) neuronal transfer rates within the CNS, and (4) quantitative analyses of the control processes that regulate uptake of ingested Mn by the intestines and liver. These data gaps are the main obstacles to developing a risk assessment strategy for Mn that considers contributions of both inhalation and ingestion of this essential nutrient in determining brain Mn concentrations.

Objectives: To describe a unique approach to the management of duplicate bladder exstrophy combining initial bladder closure and epispadias repair. Bladder exstrophy has been successfully managed by staged surgical repair with early bladder closure, subsequent epispadias repair, and, finally, bladder neck reconstruction. Duplicate bladder exstrophy is a rare variant of the exstrophy complex with fewer than 20 cases reported., Methods: A male newborn presented with the appearance of both bladder exstrophy and a ruptured omphalocele. Repair of the omphalocele and bilateral orchiopexy was performed shortly after birth, but bladder closure was delayed until there was complete healing of the omphalocele defect, and the investigators believed the infant was ready for abdominal wall and bladder exstrophy closure. At age 8 months, bladder closure was performed with the intraoperative finding of a duplicate bladder lying posterior to the exstrophied bladder. The left ureter drained on the exstrophic bladder plate, and the right ureter drained into the posterior (internalized) duplicate bladder. After anterior innominate and vertical iliac osteotomies, the left ureter was reimplanted into the posterior bladder. A portion of the exstrophied bladder was then tubularized to construct a neourethra of the epispadic penis., Results: The child has done well with an excellent cosmetic appearance of the abdominal wall and a straight phallus. The bladder subsequently required a Mitrofanoff-type continent stoma along with bladder augmentation, which was performed at the time of his Young-Dees-Leadbetter bladder neck reconstruction (age 3.5). The child is currently continent but requires intermittent clean catheterization through his appendicovesicostomy., Conclusions: The investigators report a unique and unexpected variant of bladder exstrophy and its successful management.

Objectives: To analyze and identify collagen subtypes in the primary obstructed and refluxing megaureter of childhood., Methods: Anticollagen monoclonal antibodies to collagen types I, III, and IV were used in control ureters (n = 4), obstructed (n = 7), and refluxing (n = 13) megaureters. Additionally, all were stained with Masson's trichrome to further define the extracellular matrix. After staining and serial sectioning, representative ureteral sections, focusing on the muscularis and lamina propria regions, were digitized and analyzed with a color image analysis system., Results: Immunohistochemical studies demonstrated increases in collagen types I and III for both obstructed and refluxing megaureters compared with controls (P <0.05). Collagen type IV was not detected in statistically significant amounts in any ureter. In control ureters most was type I (83% +/- 9%) collagen. Obstructed megaureters produced similar results with virtually all collagen being type I (84% +/- 26%) with very little type III collagen present, 5.3% +/- 3%. Refluxing megaureters contained only 55% +/- 15% type I collagen. However, there was an increase in type III collagen (16% +/- 4%) versus (4.5% +/- 2%) in controls (P <0.05)., Conclusions: These data suggest that the greater contribution of type III collagen may play a role in the pathophysiology of refluxing megaureters. Because type III collagen is a less distensible fiber, it may cause an intrinsically stiffer ureter and play a role in the lower surgical success in the reimplantation of refluxing megaureters.

Purpose: The aim of this study was to report complications involving paraexstrophy skin flaps in the female bladder exstrophy closure., Materials and Methods: Bladder exstrophies in three female patients were initially closed using paraexstrophy skin flaps, with an osteotomy being performed in only 1 patient. A dehiscence occurred in all, and a reclosure was performed at a mean of 10 (range: 7-18) months after the initial closure., Results: Two patients underwent successful reclosure and are awaiting bladder neck reconstruction. The third patient, who had complete procidentia, had a bladder which failed to grow after successful reclosure and underwent augmentation cystoplasty., Conclusions: Closure of bladder exstrophy in female patients using paraexstrophy skin flaps can be associated with an increased complication rate and should be used judiciously in the exstrophy patient.

Objectives: To identify whether nutritional abnormalities, specifically vitamin B12 deficiency, folate deficiency, and low carotene levels, are long-term sequelae of the use of ileum and/or colon for lower urinary tract reconstruction in pediatric patients., Methods: Serum levels of vitamin B12, methyl malonic acid (MMA), carotene, and folate were measured 3 to 13 years (mean 6) after surgery in patients less than 18 years old at the time of operation., Results: Thirteen (44.8%) of 29 patients had abnormal nutritional serum levels, with 5 (38.5%) of 13 having more than one abnormal value. Vitamin B12 was low in 4 (14%) of 29 patients; MMA was abnormally high in 7 (26%) of 27; and both folate and carotene levels were low in 4 (14.8%) of 27. No patient with reconstruction with colon alone (n = 3) had abnormal values, and no patient had any clinical signs or symptoms of vitamin B12 deficiency or fat malabsorption., Conclusions: Nutritional abnormalities can occur in patients after lower urinary tract reconstruction with ileum. No patient in this study had symptomatic abnormalities; however, long-term clinical effects may be significant. The implications of low folate levels in women of childbearing age must also be taken into consideration because of the potential association with congenital anomalies.

We present a case of inflammatory (pseudosarcomatous) myofibroblastic tumor of the bladder in a child, along with a review of the literature. The benign nature of this rare disorder needs to be recognized so that superfluous radical therapy can be avoided. The clinical features and microscopic, ultrastructural, and immunohistochemical characteristics that help to identify this entity are described. To date, 72 such cases involving the bladder have been reported in the literature including the present one.

Objectives: The sigmoid colon lends itself well to bladder augmentation particularly in patients requiring reimplantation of ureters or Mitrofanoff valves for continence. We have modified the sigmoid augment to improve ease of catheterization and ureteral reimplantation., Methods: Seven children underwent sigmoid "tail" bladder augmentation for various indications. Appendix or tapered ileum was used to create the catheterizable stoma. This technique uses a 3 to 5-cm segment of nondetubularized colon, fixed to the abdominal wall to ease catheterization. Durability of the modification and ease of catheterization were assessed., Results: All patients are dry day and night with intermittent catheterization. One patient with mild leakage has been managed with pseudoefedrine. Postoperative bowel obstruction and abscess developed in 1 patient., Conclusions: The sigmoid "tail" modification does not appear to confer increased morbidity and the short nondetubularized segment fixed to the posterior aspect of the anterior abdominal wall stabilizes the catheterizable stoma improving ease of catheterization.

Objectives: To determine serum levels of prostate-specific antigen (PSA) in men born with bladder exstrophy and to investigate the clinical utility of this test in the bladder exstrophy population., Methods: Ten men aged 19 to 45 years with a history of bladder exstrophy underwent digital rectal examination and free and total serum PSA determinations. Immunohistochemistry for PSA and prostate-specific acid phosphatase (PSAP) was performed on archival prostate tissue from 1 man with bladder exstrophy., Results: Free and total serum PSA levels for all patients were measurable and below the upper limit for established age-specific reference ranges for normal men. Both PSA and PSAP were detectable by immunohistochemistry in prostate epithelial cells of a man with bladder exstrophy., Conclusions: Men born with bladder exstrophy have detectable serum PSA levels. However, because prostate cancer in men with bladder exstrophy has not been reported, whether PSA will have a clinical role as a serum tumor marker for prostate cancer in this population remains to be determined. If so, the PSA reference range for men with the exstrophy condition will need to be defined. Because prostate histology in men with exstrophy resembles that of normal men, careful clinical monitoring for benign and malignant tumors should not be overlooked in this particular population.

A 66-year-old woman presented with clitoromegaly since childhood, primary amenorrhea, no breast development, and a large right inguinal hernia. A mosaic karyotype was identified containing a predominant 45,X cell line and a cell line with 46 chromosomes, one X chromosome, and a small dicentric Y chromosome with a breakpoint in band qII.2. The patient underwent hysterectomy, bilateral gonadectomy, inguinal hernia repair, clitoral recession, and formation of a neointroitus. A dysgerminoma was identified in the right dysgenetic gonad. This report demonstrates the natural history of untreated mixed gonadal dysgenesis and the importance of early evaluation and treatment, as well as the molecular characterization of a dicentric Y chromosome.

Objectives: To define the possible cause of failure and the eventual potential of the bladder in 23 exstrophy patients, who underwent more than two failed prior attempts at closure., Methods: Twenty-three patients were selected from the exstrophy data base who had two or more prior closures. Eighteen patients had undergone 2 previous closures and 5 patients 3 previous closures for either complete dehiscence or significant prolapse. At the time of initial closure, 19 patients did not have an osteotomy. At secondary closure, 10 underwent osteotomy while at third closure 5 had an osteotomy. At the time of reclosure at our institution all underwent an osteotomy., Results: Reoperative repair at our institution was successful in all patients. Six patients achieved a bladder size suitable for bladder neck reconstruction and of them 3 are dry. The bladder size was inadequate in 9 patients and 8 are being monitored for possible bladder growth., Conclusions: Tension-free closure with osteotomy and immobilization are important factors both in an initial or any subsequent closure. The chance of obtaining an adequate bladder capacity for bladder neck plasty and eventual continence, following multiple reclosures, is markedly diminished.

Objectives: We evaluated our experience with the Cantwell-Ransley epispadias repair to determine the lessons that have been learned with the increased experience and follow-up., Methods: A total of 75 boys (60 with bladder exstrophy and 15 with complete epispadias) underwent a Cantwell-Ransley epispadias repair at our institute in the last 6 years. Primary repair was performed in 58 boys (45 with exstrophy and 13 with epispadias), and secondary repair was performed after prior failed closure in 17 boys (12 at the secondary exstrophy closure, 3 with exstrophy, and 2 with complete epispadias)., Results: At a mean follow-up of 28 months, all patients had a horizontal or downward angled penis while standing. The incidence of urethrocutaneous fistulas in the immediate postoperative state was 21% and at 3 months was 15%. The incidence of urethrocutaneous fistulas was no more in those patients in whom paraexstrophy skin flaps were used at anterior closure than in those in whom the urethral plate was left intact. Two patients developed a urethral stricture at the proximal anastomotic area, and 4 patients had minor skin separation of the dorsal penile skin closure. Catheterization or cystoscopy, or both, has been performed in 60 patients and revealed an easily negotiable urethral channel in all., Conclusions: The Cantwell-Ransley epispadias repair offers a straighter urethra, better correction of chordee and cosmesis, and a lower fistula rate in the exstrophy or epispadias patient.

Objectives: The outlook for children with Wilms' tumor has improved with the use of multimodal therapy, and survival rates now exceed 85%. Yet, 15% of children with tumors with favorable histologic findings continue to recur unpredictably. We previously reported that nuclear morphometry (the distribution of nuclear roundness factor [NRF], lowest values for ellipticity, and age) when combined in a multivariate analysis accurately predicted response to therapy for patients with histologically favorable Wilms' tumors., Methods: To investigate further the nuclear shape changes associated with disease recurrence, we analyzed histologic sections taken from primary tumors and postmultimodal therapy metastatic lesions for 7 children who had a recurrence with initially histologically favorable primary tumors., Results: Mean NRF was significantly lower (P = 0.0001) in the metastatic lesion (35 +/- 5) group when compared with the primary tumor group (50 +/- 5). The percent coefficient of variation for NRF was also significantly lower (P = 0.006) in the metastatic lesion when compared with the primary tumor. Nuclear area was increased (P = 0.02), although the nuclear perimeter was unchanged (P = 0.1)., Conclusions: (1) Nuclei in metastatic lesions from Wilms' tumors with favorable histologic findings after multimodal therapy are more round and exhibit less variable distribution, suggesting clonal homogeneity within the metastatic lesion. (2) Nuclei in the metastatic lesions have greater area than in the primary tumors yet have an unchanged perimeter, which may be due to internal nuclear expansion secondary to increased cellular deoxyribonucleic acid (DNA) ploidy. Although the results of this study are promising, we are currently extending this hypothesis to a larger group of patients.

The transfer of toxic chemicals to breast milk represents an important, although not widely recognized, chemical exposure route for the infant. For an increasing number of nursing mothers who resume their professional activities after giving birth, the obvious benefits of breast-feeding must be evaluated versus the risk of the lactational transfer of occupational chemicals to the infant. In this article, we review qualitative and quantitative data on occupational chemicals that may contaminate the breast milk of lactating women in the work force, and we discuss the possible use of physiologically based pharmacokinetic models to aid in the assessment of risk for infants whose mothers are occupationally exposed to chemicals.

Two unusual presentations of childhood renal cell epithelial tumors including one whose unique clinical manifestation was polycythemia are described. One was a renal cell carcinoma which was so poorly differentiated that ancillary histopathologic techniques were necessary to arrive at the correct diagnosis. The other case represented the opposite extreme being so well-differentiated as to raise the differential diagnosis of renal cell carcinoma versus renal cell adenoma with blastemal areas. These case studies exemplify the practical role for specialized histopathologic techniques in diagnosing pediatric renal tumors, which may not be feasibly or even accurately categorized into known renal tumor types using routine diagnostic methods.

A family is presented in which 4 of 4 (100%) siblings demonstrate vesicoureteral reflux on voiding cystogram. Mechanisms of inheritance are reviewed.

Testicular neoplasms constitute 1 percent of all childhood malignancies and rank eighth in childhood cancer mortality. From 1970 to 1988, 25 testicular tumors in children eighteen years and under were seen. The majority of the patients were white (88%). Pathologic analysis of the tumors revealed that 68 percent were germinal and 32 percent were nongerminal. Staging was undertaken in all patients with serum markers, chest x-ray film, and computerized tomography scans or lymphangiography. All patients underwent radical orchiectomy, and further therapy was given dependent on tumor type and stage. The survival among this cohort was excellent, with only 3 patients succumbing to their disease. Detailed results of treatment, and approaches to avoid excess treatment morbidity are reviewed.

Two patients with ileal conduits underwent planned urinary undiversion; in both patients, the previously constructed ileal conduit was utilized to augment the continent urinary reservoir. Both patients are totally continent with stable upper urinary tracts; neither individual suffers from diarrhea or intestinal absorption abnormalities. This variation in the construction of the continent urinary reservoir allows for the usage of less terminal ileum, and as a result, the risk of intractable diarrhea as well as folate and vitamin B12 malabsorption should be diminished. The criteria that must be met to utilize the ileal conduit in the construction of the continent urinary reservoir include: (1) adequate remaining conduit length after mobilization, and (2) a normal-appearing conduit with sufficient mesenteric length after mobilization.

The Trisomy 16 (Ts16) mouse has been proposed as a model for Down Syndrome (DS) in humans, based on genetic homology between mouse chromosome 16 (MMU 16) and human chromosome 21 (HSA 21). Translocations of HSA 21 resulting in trisomy for only a portion of the genetic information contained on this chromosome can result in a DS phenotype. Thus, these translocations help to define a "DS region" of the chromosome. A number of genes from this DS region of HSA 21 have been mapped to MMU 16. Techniques for localizing genes on chromosomes have been used to identify the portion of MMU 16 which corresponds to the DS region of HSA 21. This region appears to be highly conserved between mouse and human, providing further support for a mouse model of DS.

To determine which form of urinary diversion is most effective for each type of hypospadias, we polled all full-time practicing pediatric urologists in the United States and Canada. Each was asked to complete a questionnaire, specifying the method of urinary diversion used, based on the severity of the hypospadias. Ninety-eight per cent (84 of 86) of the urologists contacted replied to the survey. Our findings suggest that: Urinary diversion is usually not necessary for very mild types of hypospadias. Intraurethral drainage is the preferred form of diversion for moderate types of hypospadias. Suprapubic drainage with an intraurethral stent is the favored means of diversion for severe types of hypospadias. Perineal urethrostomy is rarely used today in hypospadias surgery.

Thirty patients with previously untreated Stage C and D carcinoma of the prostate were treated with subcutaneously implanted estradiol pellets in an effort to determine the efficacy of this mode of therapy in the control of advanced prostatic carcinoma. Serum levels of gonadotropins, testosterone, and estradiol were obtained prior to institution of therapy and at monthly intervals thereafter. Twenty-eight patients were followed for at least one year. Sixteen patients were hormonally castrate at six months following 1-pellet implantation. In these 16 patients the means serum testosterone level was 43.6 ng./dl. with a serum luteinizing hormone (LH) of 13.3 mlU/ml. and a serum estradiol of 19.2 ng./dl. Twenty-two patients were hormonally castrate at twelve months following 1 or more pellet implantations. In this group the mean serum testosterone level was 51.5 ng./dl. with a serum LH of 16.2 mlU/ml. and a serum estradiol of 22 ng./dl. Fifteen patients who were taking narcotics for pain relief either became pain free or had a marked decrease in need for analgesics. Increased weight improvement in over-all well-being was noted in 86 per cent of patients. pellet implantation intervals ranged from four to ten months, with a mean interval of 5.85 months between implantations. Complications attributable to this mode of therapy were no more apparent than with oral estrogens. In addition to better compliance, subcutaneously implanted estrogen pellets appear to provide a safe, reliable, and effective method of tumor control and palliation in advanced carcinoma of the prostate.

Trisomy of the whole or distal part of human chromosome 21 (HSA 21) (Ts21) results in Down Syndrome (DS), which is characterized in part by mental retardation and associated neurological abnormalities. Structural abnormalities observed frequently include reduced brain weight, decreased number and depth of sulci in the cerebral cortices, neuronal heterotopias, and reduced numbers of specific populations of neurons, such as granule cells, in the cerebral cortices. Abnormalities in the structure of cells, primarily of the dendrites, are observed in portions of the neuraxis, such as the hippocampus, cerebellum, and cerebral cortices. Functional abnormalities in membrane properties in peripheral structures and in neurotransmitter enzyme systems in both peripheral and central structures are observed also. Brains of DS individuals over the age of 40 exhibit the characteristic neuropathologic and neurochemical stigmata of Alzheimer's disease (AD). The cholinergic and noradrenergic systems appear to be particularly vulnerable. To elucidate the mechanisms responsible for these abnormalities, identification of the genes located in the distal part of HSA 21 and the systematic study of animal model systems with close genetic homology are essential.

Spontaneous aneuploidy in the mouse is uncommon, but specific mating schemes have been developed that produce aneuploid conceptuses at high frequencies. The most commonly reported aneuploid condition in the mouse is autosomal trisomy, in which there is an extra copy (in whole or in part) of a chromosome. In this review, we present several of the schemes used in producing trisomic, partially (tertiary) trisomic, and monosomic conceptuses and summarize the developmental consequences that are associated with each of the autosomal trisomies of the mouse.

Many humans with trisomy 21 (Down Syndrome (DS)) have psychomotor and cognitive retardation, congenital heart disease, and hematologic abnormalities. Partial genetic homology exists between mouse chromosome 16 and human chromosome 21; thus, studies of the development of mice with trisomy 16 (Ts16) may provide important insights into the pathogenesis of these defects and into the mechanisms by which they arise in humans. Since Ts16 mice do not survive the late fetal period, chimeras have been formed between Ts16 and normal (2N) mouse embryos to rescue the Ts16 cells for postnatal studies. In this preliminary study of the postnatal development of such chimeras, we examined the proportion of Ts16 cells in a variety of tissues, including the coat, blood, placenta, heart, and brain. The Ts16 cells made significant contributions to almost all tissues examined. Aspects of the behavior and the neurochemistry of adult Ts16 less than-greater than 2N chimeras were found to differ significantly from control (2N less than-greater than 2N) chimeras and from animals of the two donor embryo strains. Ts16 cells comprised a substantial, but not predominant, proportion of cells in each brain region examined. Suggestions for definitive analyses are reviewed.