Association of Obesity, Metabolic Syndrome, and Diabetes With Urinary Incontinence and Chronic Kidney Disease: Analysis of the National Health and Nutrition Examination Survey, 2003-2020.

PURPOSE: Diabetes and obesity, components of the metabolic syndrome (MetS), are risk factors for urinary incontinence (UI) and chronic kidney disease (CKD). We interrogated US population-based data to explore independent, sex-specific associations between nondiabetic MetS, with and without obesity, and UI and/or CKD. MATERIALS AND METHODS: We analyzed data from 8586 males and 8420 females ≥20 years from the National Health and Nutrition Examination Survey. Multivariable logistic regression models were used to examine associations of UI or CKD with diabetes and 4 nondiabetic obesity/metabolic phenotypes: non-MetS/nonobese, MetS/nonobese, non-MetS/obese, and MetS/obese. Multinominal logistic regression models were used to assess associations of co-occurring UI/CKD with obesity/metabolic phenotypes. RESULTS: Male MetS/obese participants had increased odds of any UI (1.25; 95% CI 1.00-1.57) and urgency UI (1.36; 1.03-1.80), compared with non-MetS/nonobese participants. Female MetS/obese participants had increased odds of any UI (2.16; 95% CI 1.76-2.66), stress UI (1.51; 1.21-1.87), and mixed UI (1.66; 1.31-2.11) compared with non-MetS/nonobese participants. The odds of co-occurring UI/CKD were increased relative to either condition alone in persons with diabetes, and in males with MetS/obese phenotypes and females with MetS phenotypes as compared to same sex participants with neither obesity nor MetS. CONCLUSIONS: We found novel associations between MetS/obese and urgency UI in males without diabetes, and between SUI and both MetS and obesity in females without diabetes. Odds estimates for UI/CKD were increased by existing obesity or MetS as compared to those for UI or CKD alone. Improved understanding of modifiable factors associated with UI will inform prevention and treatment opportunities.

First trimester phthalate exposure and male newborn genital anomalies.

BACKGROUND: Anti-androgenic phthalates are environmental chemicals that affect male genital development in rodents leading to genitourinary birth defects. We examined whether first trimester phthalate exposure may exert similar effects in humans leading to an increased incidence of newborn male genital anomalies in a multi-center cohort study. METHODS: We recruited first trimester pregnant women within The Infant Development and the Environment Study (TIDES) from 2010 to 2012 from four study centers and limited analyses to all mother/male infant dyads who had complete urinary phthalate and birth exam data (N=371). We used multivariate logistic regression to determine the odds of having a genital anomaly in relation to phthalate exposure. RESULTS: Hydrocele was the primary abnormality observed in the cohort (N=30) followed by undescended testes (N=5) and hypospadias (N=3). We observed a statistically significant 2.5 fold increased risk (95% CI 1.1, 5.9) of having any anomaly and 3.0 fold increased risk (95% CI 1.2, 7.6) of isolated hydrocele in relation to a one log unit increase in the sum of di-ethylhexyl phthalate (DEHP) metabolites. CONCLUSIONS: First trimester urinary DEHP metabolite concentrations were associated with increased odds of any newborn genital anomaly, and this association was primarily driven by isolated hydrocele which made up the majority of anomalies in newborn males. The association with hydrocele has not been previously reported and suggests that it may be an endpoint affected by prenatal phthalate exposures in the first trimester of development. Future human studies should include hydrocele assessment in order to confirm findings.

Phenotype specific association of the TGFBR3 locus with nonsyndromic cryptorchidism.

PURPOSE: Based on a genome-wide association study of testicular dysgenesis syndrome showing a possible association with TGFBR3, we analyzed data from a larger, phenotypically restricted cryptorchidism population for potential replication of this signal. MATERIALS AND METHODS: We excluded samples based on strict quality control criteria, leaving 844 cases and 2,718 controls of European ancestry that were analyzed in 2 separate groups based on genotyping platform (ie Illumina® HumanHap550, version 1 or 3, or Human610-Quad, version 1 BeadChip in group 1 and Human OmniExpress 12, version 1 BeadChip platform in group 2). Analyses included genotype imputation at the TGFBR3 locus, association analysis of imputed data with correction for population substructure, subsequent meta-analysis of data for groups 1 and 2, and selective genotyping of independent cases (330) and controls (324) for replication. We also measured Tgfbr3 mRNA levels and performed TGFBR3/betaglycan immunostaining in rat fetal gubernaculum. RESULTS: We identified suggestive (p ≤ 1× 10(-4)) association of markers in/near TGFBR3, including rs9661103 (OR 1.40; 95% CI 1.20, 1.64; p = 2.71 × 10(-5)) and rs10782968 (OR 1.58; 95% CI 1.26, 1.98; p = 9.36 × 10(-5)) in groups 1 and 2, respectively. In subgroup analyses we observed strongest association of rs17576372 (OR 1.42; 95% CI 1.24, 1.60; p = 1.67 × 10(-4)) with proximal and rs11165059 (OR 1.32; 95% CI 1.15, 1.38; p = 9.42 × 10(-4)) with distal testis position, signals in strong linkage disequilibrium with rs9661103 and rs10782968, respectively. Association of the prior genome-wide association study signal (rs12082710) was marginal (OR 1.13; 95% CI 0.99, 1.28; p = 0.09 for group 1), and we were unable to replicate signals in our independent cohort. Tgfbr3/betaglycan was differentially expressed in wild-type and cryptorchid rat fetal gubernaculum. CONCLUSIONS: These data suggest complex or phenotype specific association of cryptorchidism with TGFBR3 and the gubernaculum as a potential target of TGFß signaling.

Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling.

Cryptorchidism, or undescended testis, is a common male genital anomaly of unclear etiology. Hormonal stimulation of the developing fetal gubernaculum by testicular androgens and insulin-like 3 (INSL3) is required for testicular descent. In studies of the orl fetal rat, one of several reported strains with inherited cryptorchidism, we studied hormone levels, gene expression in intact and hormone-stimulated gubernaculum, and imaging of the developing cremaster muscle facilitated by a tissue clearing protocol to further characterize development of the orl gubernaculum. Abnormal localization of the inverted gubernaculum was visible soon after birth. In the orl fetus, testicular testosterone, gubernacular androgen-responsive transcript levels, and muscle-specific gene expression were reduced. However, the in vitro transcriptional response of the orl gubernaculum to androgen was largely comparable to wild type (wt). In contrast, increases in serum INSL3, gubernacular INSL3-responsive transcript levels, expression of the INSL3 receptor, Rxfp2, and the response of the orl gubernaculum to INSL3 in vitro all suggest enhanced activation of INSL3/RXFP2 signaling in the orl rat. However, DNA sequence analysis did not identify functional variants in orl Insl3. Finally, combined analysis of the present and previous studies of the orl transcriptome confirmed altered expression of muscle and cellular motility genes, and whole mount imaging revealed aberrant muscle pattern formation in the orl fetal gubernaculum. The nature and prevalence of developmental muscle defects in the orl gubernaculum are consistent with the cryptorchid phenotype in this strain. These data suggest impaired androgen and enhanced INSL3 signaling in the orl fetus accompanied by defective cremaster muscle development.

Evaluation and treatment of cryptorchidism: AUA guideline.

PURPOSE: Cryptorchidism is one of the most common pediatric disorders of the male endocrine glands and the most common genital disorder identified at birth. This guideline is intended to provide physicians and non-physician providers (primary care and specialists) with a consensus of principles and treatment plans for the management of cryptorchidism (typically isolated non-syndromic). MATERIALS AND METHODS: A systematic review and meta-analysis of the published literature was conducted using controlled vocabulary supplemented with key words relating to the relevant concepts of cryptorchidism. The search strategy was developed and executed by reference librarians and methodologists to create an evidence report limited to English-language, published peer-reviewed literature. This review yielded 704 articles published from 1980 through 2013 that were used to form a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data. RESULTS: Guideline statements were created to inform clinicians on the proper methods of history-taking, physical exam, and evaluation of the boy with cryptorchidism, as well as the various hormonal and surgical treatment options. CONCLUSIONS: Imaging for cryptorchidism is not recommended prior to referral, which should occur by 6 months of age. Orchidopexy (orchiopexy is the preferred term) is the most successful therapy to relocate the testis into the scrotum, while hormonal therapy is not recommended. Successful scrotal repositioning of the testis may reduce but does not prevent the potential long-term issues of infertility and testis cancer. Appropriate counseling and follow-up of the patient is essential.

The orl rat is more responsive to methacholine challenge than wild type.

BACKGROUND: This study presents an animal model of native airway hyperresponsiveness (AHR). AHR is a fundamental aspect of asthma and reflects an abnormal response characterized by airway narrowing following exposure to a wide variety of non-immunological stimuli. Undescended testis (UDT) is one of the most common male congenital anomalies. The orl rat is a Long Evans substrain with inherited UDT. Since boys born with congenital UDT are more likely to manifest asthma symptoms, the main aim of this study was to investigate the alternative hypothesis that orl rats have greater AHR to a methacholine aerosol challenge than wild type rats. METHODS: Long Evans wild type (n = 9) and orl (n = 13) rats were anesthetized, tracheostomized, and mechanically ventilated at 4 weeks of age. Escalating concentrations of inhaled methacholine were delivered. The methacholine potency and efficacy in the strains were measured. Respiratory resistance was the primary endpoint. After the final methacholine aerosol challenge, the short-acting ß2-adrenoceptor agonist albuterol was administered as an aerosol and lung/diaphragm tissues were assayed for interleukin (IL)-4, IL-6, and tumor necrosis factor (TNF)-α. Histological and histomorphometrical analyses were performed. RESULTS: The methacholine concentration-response curve in the orl group indicated increased sensitivity, hyperreactivity, and exaggerated maximal response in comparison with the wild type group, indicating that orl rats had abnormally greater AHR responses to methacholine. Histological findings in orl rats showed the presence of eosinophils, unlike wild type rats. ß2-Adrenoceptor agonist intervention resulted in up-regulation of IL-4 diaphragmatic levels and down-regulation of IL-4 and IL-6 in the lungs of orl rats. CONCLUSION: orl rats had greater AHR than wild type rats during methacholine challenge, with higher IL-4 levels in diaphragmatic tissue homogenates. Positive immunostaining for IL-4 was detected in lung and diaphragmatic tissue in both strains. This model offers advantages over other pre-clinical murine models for studying potential mechanistic links between cryptorchidism and asthma. This animal model may be useful for further testing of compounds/therapeutics options for treating AHR.

Epidemiology of Infantile Ureteropelvic Junction Obstruction in the US.

OBJECTIVE: To describe sex- and diagnosis-specific comorbidities, outcomes, and secular trends associated with ureteropelvic junction obstruction (UPJO) in a large, real-world population diagnosed with hydronephrosis in infancy. MATERIALS AND METHODS: We identified all infants ≤1 year old with ≥1 claim in the Optum Clinformatics 2007-2020 nationwide population database and used univariable and multivariable Cox regression analyses to estimate associations of demographic and clinical characteristics of infants with a UPJO diagnosis with surgical status. RESULTS: Of 22,349 infants with hydronephrosis (1.1% of infants; males-1.4%, females-0.7%), 1722 (7.7%; 7.9%-males, 7.2%-females) had UPJO. Follow-up was ≥1 year in 1198 (70%) and ≥3 years in 555 (32%) cases, and UPJO repair was performed in 542 children (31.5%; 32.3%-males, 29.5%-females); 77.7% within 1 year and 97.3% within 3 years. UPJO repair was associated with prior urinary tract infection (UTI) (hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.12-1.76) and South (HR 1.42, 95% CI 1.14-1.78) or Midwest (HR 1.60, 95% CI 1.26-2.04) geographic region but did not change over time. CONCLUSION: This population-based study provides a real-world view of postnatally diagnosed hydronephrosis, focusing on UPJO, for which 522 cases (∼1/3) had ≥3 years continuous coverage. UPJO-associated comorbidities were more common in females, and the frequencies of UPJO-associated surgery and comorbidities were higher than in other studies. Other than UTI, no other associated kidney or urinary tract diagnoses were associated with UPJO repair. We identified unique sex- and diagnosis-specific differences in associated comorbidities and interventions in children diagnosed with UPJO in the first year of life.

Transcriptome analysis of the dihydrotestosterone-exposed fetal rat gubernaculum identifies common androgen and insulin-like 3 targets.

Androgens and insulin-like 3 (INSL3) are required for development of the fetal gubernaculum and testicular descent. Previous studies suggested that the INSL3-exposed fetal gubernacular transcriptome is enriched for genes involved in neural pathways. In the present study, we profiled the transcriptome of fetal gubernaculum explants exposed to dihydrotestosterone (DHT) and compared this response to that with INSL3. We exposed fetal (Embryonic Day 17) rat gubernacula to DHT for 24 h (10 and 30 nM) or 6 h (1 and 10 nM) in organ culture and analyzed gene expression relative to that of vehicle-treated controls using Affymetrix arrays. Results were annotated using functional, pathway, and promoter analyses and independently validated for selected transcripts using quantitative RT-PCR (qRT-PCR). Transcripts were differentially expressed after 24 h but not 6 h. Most highly overrepresented functional categories included those related to gene expression, skeletal and muscular development and function, and Wnt signaling. Promoter response elements enriched in the DHT-specific transcriptome included consensus sequences for c-ETS1, ELK1, CREB, CRE-BP1/c-June, NRF2, and USF. We observed that 55% of DHT probe sets were also differentially expressed after INSL3 exposure and that the direction of change was the same in 96%. The qRT-PCR results confirmed that DHT increased expression of the INSL3-responsive genes Crlf1 and Chrdl2 but reduced expression of Wnt4. We also validated reduced Tgfb2 and Cxcl12 and increased Slit3 expression following DHT exposure. These data suggest a robust overlap in the DHT- and INSL3-regulated transcriptome that may be mediated in part by CREB signaling and a common Wnt pathway response for both hormones in the fetal gubernaculum.

Insulin-like 3 exposure of the fetal rat gubernaculum modulates expression of genes involved in neural pathways.

Insulin-like 3 (INSL3) signaling directs fetal gubernacular development and testis descent, but the actions of INSL3 in the gubernaculum are poorly understood. Using microarray gene expression profiling of fetal male rat gubernaculum explants exposed to 10 or 100 nM INSL3, significant changes in expression were identified for approximately 900 genes. Several of the genes showing the largest inductions regulate neuronal development or activity, including Pnoc (34-fold), Nptx2 (9-fold), Nfasc (4-fold), Gfra3 (3-fold), Unc5d (3-fold), and Crlf1 (3-fold). Bioinformatics analysis revealed BMP and WNT signaling pathways and several gene ontologies related to neurogenesis were altered by INSL3. Promoter response elements significantly enriched in the INSL3-regulated gene list included consensus sequences for MYB, REL, ATF2, and TEF transcription factors. Comparing in vivo gene expression profiles of male and female rat fetal gubernaculum showed expression of the Bmp, Wnt, and neurodevelopmental genes induced by INSL3 was higher in males. Using quantitative RT-PCR, the microarray data were confirmed, and the induction of Bmp3, Chrdl2, Crlf1, Nptx2, Pnoc, Wnt4, and Wnt5a mRNA levels were examined over a range of INSL3 concentrations (0.1-100 nM) in male and female gubernaculum. In both sexes, an increasing gene expression response was observed between 0.1 and 10 nM INSL3. These data suggest that INSL3 signaling in the fetal gubernaculum induces morphogenetic programs, including BMP and WNT signaling, and support other rodent data suggesting a role for these pathways in development of the gubernaculum.

Genetic and environmental contributors to cryptorchidism.

Cryptorchidism is a common congenital anomaly that shows familial clustering and increased prevalence in first-degree relatives, suggesting that genetic factors contribute to the etiology. Animal models and some human data suggest that environmental exposures may also contribute to risk. Potential variables during development that may contribute to the occurrence of cryptorchidism in the genetically susceptible individual include maternal hormonal influences as well as other environmental factors that affect hormonal signaling. In a subset of affected males, genetic and/or environmental factors may also contribute to associated infertility and malignancy. This review will discuss the limited state of knowledge regarding the etiology of non-syndromic cryptorchidism. Non-syndromic cryptorchidism is a common and complex disorder of un known etiology with geographic and perhaps temporal variability (1,2). Although presumed to be multifactorial in etiology, few specific genetic or environmental factors have been clearly linked to the disease in man. Hormonal pathways that participate in testicular descent and the effects of chemical exposures on this process have been studied in animal models. In man (3-5) and animal strains with cryptorchidism (6,7), there is evidence for multilocus genetic susceptibility. However, despite promising gene candidates, few genomic variants have been linked to non-syndromic cryptorchidism. Humans are exposed to a wide variety of potentially anti-androgenic and/or estrogenic environmental chemicals, but the degree to which these may contribute to the pathogenesis of cryptorchidism is not clearly known. Potential factors that may contribute to the etiology of cryptorchidism are discussed.

Undescended testis: current theories of etiology.

PURPOSE OF REVIEW: Nonsyndromic cryptorchidism or undescended testis is a structural defect of infants and children whose etiology is unknown but likely related to a combination of genetic susceptibility and environmental factors. This review will focus on factors that may contribute to the etiology of this common and complex disease. RECENT FINDINGS: The incidence of cryptorchidism is estimated to be 2-4% or higher in some populations. Data suggesting increasing prevalence are conflicting, possibly related to problems with diagnostic accuracy. Increased risk of cryptorchidism in first-degree relatives suggests a significant genetic contribution to susceptibility. Sequence variants within key candidate genes, such as insulin-like 3 and relaxin/insulin-like family peptide receptor 2, in cases of nonsyndromic cryptorchidism are infrequent and of unclear significance. Epidemiological data suggest that fetal growth restriction, maternal factors such as smoking, alcohol use and gestational diabetes, and exposure to environmental chemicals may contribute to risk, although data are inconsistent. SUMMARY: The available evidence suggests a significant genetic contribution to cryptorchidism susceptibility that may be modulated by environmental risk factors. Additional studies are needed to define these factors, their complex interaction and their effects on testicular development and descent.

Perspective: A Neuro-Hormonal Systems Approach to Understanding the Complexity of Cryptorchidism Susceptibility.

Nonsyndromic cryptorchidism is a common multifactorial, condition with long-term risks of subfertility and testicular cancer. Revealing the causes of cryptorchidism will likely improve prediction and prevention of adverse outcomes. Herein we provide our current perspective of cryptorchidism complexity in a synthesis of cumulative clinical and translational data generated by ourselves and others. From our recent comparison of genome-wide association study (GWAS) data of cryptorchidism with or without testicular germ cell tumor, we identified RBFOX family genes as candidate susceptibility loci. Notably, RBFOX proteins regulate production of calcitonin gene-related peptide (CGRP), a sensory neuropeptide linked to testicular descent in animal models. We also re-analyzed existing fetal testis transcriptome data from a rat model of inherited cryptorchidism (the LE/orl strain) for enrichment of Leydig cell progenitor genes. The majority are coordinately downregulated, consistent with known reduced testicular testosterone levels in the LE/orl fetus, and similarly suppressed in the gubernaculum. Using qRT-PCR, we found dysregulation of dorsal root ganglia (DRG) sensory transcripts ipsilateral to undescended testes. These data suggest that LE/orl cryptorchidism is associated with altered signaling in possibly related cell types in the testis and gubernaculum as well as DRG. Complementary rat and human studies thus lead us to propose a multi-level, integrated neuro-hormonal model of testicular descent. Variants in genes encoding RBFOX family proteins and/or their transcriptional targets combined with environmental exposures may disrupt this complex pathway to enhance cryptorchidism susceptibility. We believe that a systems approach is necessary to provide further insight into the causes and consequences of cryptorchidism.

Cryptorchidism: pathogenesis, diagnosis, treatment and prognosis.

Cryptorchidism is a common genital anomaly diagnosed at birth or during childhood. Genetic and/or environmental factors that alter expression or function of hormones crucial for testicular descent, insulin-like 3, and testosterone, may contribute to cryptorchidism. When identified at birth, surgical treatment is indicated by 6 months of age if testes fail to descend, or at the time of diagnosis in older children. A laparoscopic approach is preferred for abdominal testes. Early surgical therapy may reduce the risk of subfertility and/or malignancy.

Iatrogenic ureteral injury after laparoscopic cholecystectomy in a 13-year-old boy.

We present a report of a delayed ureteral injury after a laparoscopic cholecystectomy. The patient presented with one episode of gross hematuria after surgery. He was treated with ureteral stent drainage and did well with no long-term sequelae.

The orl rat with inherited cryptorchidism has increased susceptibility to the testicular effects of in utero dibutyl phthalate exposure.

Phenotype results from interactions between genetics and environment, but for most environmental chemical exposures, such interactions are theoretical. The phenotypic response of the testis to in utero dibutyl phthalate (DBP) exposure was compared between two strains of Long-Evans (LE) rats, the orl substrain with inherited cryptorchidism and an outbred (wt) strain. orl and wt LE rats were exposed daily between gestational day (GD) 12 and GD21 to DBP dose levels ranging from 50 to 200 mg/kg by oral gavage and sensitive phthalate testicular end points examined at either GD19, GD21, or postnatal day (PND) 21. At 50 mg/kg DBP, GD19 expression of Cyp17a1, Insl3, and Scarb1 was significantly reduced in orl but not wt testis. At GD21, statistically significant differential strain effects (orl more sensitive than wt) were observed for testicular expression of Scarb1 at 50 and 200 mg/kg DBP and Star at 200 mg/kg DBP. Similarly, DBP exposure disproportionately increased GD21 seminiferous cord diameters and numbers of multinucleated germ cells in the orl strain. At PND21, body weight-corrected testis weights were lowered significantly by DBP exposure at all dose levels in the orl strain but not in wt rats. While the frequency of undescended testes after 200 mg/kg DBP exposure in the orl strain appeared increased, these data were not statistically significant. These results demonstrated enhanced sensitivity of the orl rat to phthalate exposure as compared to its parent strain, a potentially important model of the effects of gene-environment interaction on development of male reproductive malformations.

Altered expression of muscle- and cytoskeleton-related genes in a rat strain with inherited cryptorchidism.

Development of the fetal gubernaculum is a prerequisite for testicular descent and dependent on insulin-like 3 and androgen, but knowledge of downstream effectors is limited. We analyzed transcript profiles in gubernaculum and testis to address changes occurring during normal and abnormal testicular descent in Long Evans wild-type (wt) and cryptorchid (orl) fetuses. Total RNA from male wt and orl gubernacula (gestational days [GD]18-20), wt female gubernacula (GD18), and testis (GD17 and 19) was hybridized to Affymetrix GeneChips. Statistical analysis of temporal, gender, and strain-specific differences in gene expression was performed with the use of linear models analysis with empirical Bayes statistics and analysis of variance (gubernaculum) and linear analysis (testis). Overrepresented common gene ontology functional categories and pathways were identified in groups of differentially expressed genes with the Database for Annotation, Visualization, and Integrated Discovery. Transcript profiles were dynamic in wt males between GD18-19 and GD20, comparatively static in orl GD18-20 gubernaculum, and similar in wt and orl testis. Functional analysis of differentially expressed genes in wt and orl gubernaculum identified categories related to metabolism, cellular biogenesis, small GTPase-mediated signal transduction, cytoskeleton, muscle development, and insulin signaling. Genes involved in androgen receptor signaling, regulated by androgens, or both were overrepresented in differentially expressed gubernaculum and testis gene groups. Quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed differential expression of genes related to muscle development, including Myog, Tnnt2, Fst, Igf1, Igfbp5, Id2, and Msx1. These data suggest that the orl mutation results in a primary gubernacular defect that affects muscle development and cytoskeletal function and might alter androgen-regulated pathways.

Influence of type of conduit and site of implantation on the outcome of continent catheterizable channels.

OBJECTIVE: Continent catheterizable channels (CCC) using the Mitrofanoff principle are essential for pediatric urinary tract reconstruction. There is controversy over the influence of type of CCC (appendix vs. Yang-Monti) and site of implantation (augmentation vs. native bladder) on outcome. PATIENTS AND METHODS: A retrospective record review was conducted of all patients undergoing CCC since 1999, excluding patients who underwent seromuscular colocystoplasty. We analyzed the type of channel, site of implantation, complications requiring re-operation, and the revision rate according to type of CCC, type of stoma, site of implantation (bladder vs. augmentation) and segment used for augmentation (ileum vs. sigmoid colon). RESULTS: There were 41 patients with a mean age of 11.2 years and a mean follow-up of 33.3 months. Of these, 33 CCC were constructed with appendix and eight with a Yang-Monti technique (4 ileal, 4 sigmoid); 31 patients also had an enterocystoplasty (19 sigmoid, 9 ileal and 3 others). Overall revision rate was 27%; revision was required in 8/33 (24%) appendiceal and 3/8 (38%) Yang-Monti CCC (P=0.7). Revisions were required in 4/21 CCC implanted in the native bladder and 7/20 implanted in augmented bladder (P=0.3). The majority of revisions were at skin level. CONCLUSIONS: Although there was no statistical difference in revision rate according to type of CCC, type of stoma or site of implantation, complications appeared to be more common in patients requiring a more complex reconstruction.

Failure of shortening and inversion of the perinatal gubernaculum in the cryptorchid long-evans orl rat.

PURPOSE: Failure of testicular descent occurs in about 65% of spontaneously cryptorchid Long-Evans orl rats. Development of the fetal gubernaculum is dependent on expression of leucine rich G protein coupled receptor (also known as G protein coupled receptor affecting testicular descent) and its ligand, insulin-like 3. We studied testicular descent and mRNA expression of insulin-like 3 and leucine rich G protein coupled receptor in Long-Evans orl and Long-Evans wild-type rats during perinatal development. MATERIALS AND METHODS: Long-Evans orl and Long-Evans wild-type males obtained at gestational days 18 to 21 and day of birth were preserved in RNAlater for at least 24 hours. The size and position of the testes, kidneys and gubernacula were determined by microdissection and image analysis. Leucine rich G protein coupled receptor mRNA expression was analyzed in fetal gubernacula (gestational days 18 to 21) using real-time reverse transcriptase polymerase chain reaction with SYBR Green detection. Insulin-like 3 mRNA expression in fetal testis (gestational days 18 and 20) was determined by semiquantitative reverse transcriptase polymerase chain reaction. RESULTS: Testicular position was similar in Long-Evans orl and Long-Evans wild-type fetal rats. However, gubernacula were narrow (p < 0.001) and elongated (p < or = 0.01) in Long-Evans orl compared to Long-Evans wild-type fetuses at all time points. Inversion of both gubernacula occurred by the day of birth in 45% of Long-Evans orl and 100% of Long-Evans wild-type males (p < 0.001). Leucine rich G protein coupled receptor mRNA expression decreased with age and, similar to insulin-like 3 mRNA, was not consistently different between strains. CONCLUSIONS: These data suggest that the impaired shortening of the Long-Evans orl gubernaculum may interfere with the timing and quality of its inversion at birth, leading to failure of testicular descent in some newborn males. However, fetal testicular descent and the expression of leucine rich G protein coupled receptor and insulin-like 3 mRNA appear to be normal in this strain.

Comparison of laparoscopic and open partial nephrectomy for duplication anomalies in children.

PURPOSE: We compared the outcome of laparoscopic vs open PN for duplication anomalies at our institution. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients undergoing PN within the last 4 years. RESULTS: A total of 34 patients (16 females) were divided into 2 groups. Group 1 consisted of 20 patients undergoing open PN between 2000 and 2003, and group 2 consisted of 14 patients undergoing laparoscopic PN between 2003 and 2004. Mean patient age was 21 months in group 1 and 18 months in group 2. Diagnosis was ectopic ureter in 18 patients, ureterocele in 11, VUR in 4 and ureteropelvic junction obstruction in 1. Cystoscopy was performed as part of the procedure in 30% of the patients in group 1 and 100% of those in group 2. Simultaneous lower tract procedures were performed in 3 patients in group 1 and 2 patients in group 2. Mean duration of PN was 115 minutes for group 1 and 180 minutes for group 2. There was no significant bleeding or need for transfusion except in 1 patient in the open group. Median hospitalization was 3 days for group 1 and 2 days for group 2. Mean analgesic requirement was 2.3 doses of opioids and 2 doses of ketorolac for group 1, and 3.2 doses of opioids for group 2. Acetaminophen only was used in 3 of 20 patients in group 1 and 5 of 14 in group 2. There were 2 complications in each group, namely 1 case of ureteral bleeding and 1 lower pole ureteral injury in group 1, and 1 omental hernia and 1 urinoma in group 2. CONCLUSIONS: Laparoscopic PN is feasible even in small infants, and the results are comparable to the open procedure. Length of hospitalization was shorter in the laparoscopic group. In our series the learning curve for this technique was rapid, and after a few cases the procedure could be done in the same time as open surgery, with the advantages offered by laparoscopy.