T. Ernesto Figueroa

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.

Pathway analysis supports association of nonsyndromic cryptorchidism with genetic loci linked to cytoskeleton-dependent functions

STUDY QUESTION What are the genetic loci that increase susceptibility to nonsyndromic cryptorchidism, or undescended testis? SUMMARY ANSWER A genome-wide association study (GWAS) suggests that susceptibility to cryptorchidism is heterogeneous, with a subset of suggestive signals linked to cytoskeleton-dependent functions and syndromic forms of the disease. WHAT IS KNOWN ALREADY Population studies suggest moderate genetic risk of cryptorchidism and possible maternal and environmental contributions to risk. Previous candidate gene analyses have failed to identify a major associated locus, although variants in insulin-like 3 (INSL3), relaxin/insulin-like family peptide receptor 2 (RXFP2) and other hormonal pathway genes may increase risk in a small percentage of patients. STUDY DESIGN, SIZE, DURATION This is a case-control GWAS of 844 boys with nonsyndromic cryptorchidism and 2718 control subjects without syndromes or genital anomalies, all of European ancestry. PARTICIPANTS/MATERIALS, SETTING, METHODS All boys with cryptorchidism were diagnosed and treated by a pediatric specialist. In the discovery phase, DNA was extracted from tissue or blood samples and genotyping performed using the Illumina HumanHap550 and Human610-Quad (Group 1) or OmniExpress (Group 2) platform. We imputed genotypes genome-wide, and combined single marker association results in meta-analyses for all cases and for secondary subphenotype analyses based on testis position, laterality and age, and defined genome-wide significance as P = 7 × 10(-9) to correct for multiple testing. Selected markers were genotyped in an independent replication group of European cases (n = 298) and controls (n = 324). We used several bioinformatics tools to analyze top (P < 10(-5)) and suggestive (P < 10(-3)) signals for significant enrichment of signaling pathways, cellular functions and custom gene lists after multiple testing correction. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis, we identified 20 top loci, none reaching genome-wide significance, but one passing this threshold in a subphenotype analysis of proximal testis position (rs55867206, near SH3PXD2B, odds ratio = 2.2 (95% confidence interval 1.7, 2.9), P = 2 × 10(-9)). An additional 127 top loci emerged in at least one secondary analysis, particularly of more severe phenotypes. Cytoskeleton-dependent molecular and cellular functions were prevalent in pathway analysis of suggestive signals, and may implicate loci encoding cytoskeletal proteins that participate in androgen receptor signaling. Genes linked to human syndromic cryptorchidism, including hypogonadotropic hypogonadism, and to hormone-responsive and/or differentially expressed genes in normal and cryptorchid rat gubernaculum, were also significantly overrepresented. No tested marker showed significant replication in an independent population. The results suggest heterogeneous, multilocus and potentially multifactorial susceptibility to nonsyndromic cryptorchidism. LIMITATIONS, REASONS FOR CAUTION The present study failed to identify genome-wide significant markers associated with cryptorchidism that could be replicated in an independent population, so further studies are required to define true positive signals among suggestive loci. WIDER IMPLICATIONS OF THE FINDINGS As the only GWAS to date of nonsyndromic cryptorchidism, these data will provide a basis for future efforts to understand genetic susceptibility to this common reproductive anomaly and the potential for additive risk from environmental exposures. STUDY FUNDING/COMPETING INTERESTS This work was supported by R01HD060769 (the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD)), P20RR20173 (the National Center for Research Resources (NCRR), currently P20GM103464 from the National Institute of General Medical Sciences (NIGMS)), an Institute Development Fund to the Center for Applied Genomics at The Childrens Hospital of Philadelphia, and Nemours Biomedical Research. The authors have no competing interests to declare.

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.

Comparison of bladder rupture pressure after intestinal bladder augmentation (ileocystoplasty) and myomyotomy (autoaugmentation).

OBJECTIVES To compare the risk of bladder rupture of bladder augmentation using ileocystoplasty versus that of autoaugmentation with myomyotomy in a rat model. METHODS Bladder rupture pressure and volume of three groups of female Sprague-Dawley rats were determined by cystometry. The first group of 11 rats had undergone ileocystoplasty using a detubularized 1 -cm segment of ileum. A second group of 9 rats had undergone autoaugmentation with myomyotomy. One month after surgery the animals were studied cystometrically to determine the bladder rupture pressure, then killed. A third group, consisting of 10 nonoperated rats, was studied and served as controls. RESULTS Nonoperated, control rat bladders were able to sustain 154 +/- 43 mm Hg pressure and 2.5 +/- 2.0 mL volume prior to bladder rupture. Conventional ileocystoplasty was noted to increase bladder capacity to 4.0 +/- 1.9 mL, but decrease rupture pressure to 111 +/- 49 mm Hg. Myomyotomy resulted in a mean bladder rupture volume of 1.2 +/- 0.4 mL, with a rupture pressure of 101 +/- 13 mm Hg. The rupture pressure after myomyotomy is significantly lower than that of the native bladder (P < 0.001), whereas the rupture volume after myomyotomy is significantly lower than either after the ileocystoplasty or with the native bladder (P < 0.001). Bladder rupture occurred at the augmented ileal bladder dome in 7 of 11 ileocystoplasty animals and at the anastomotic suture line in 4 animals. Bladder rupture occurred at the area of bladder diverticulum in all 9 myomyotomy animals. Among controls, no specific site pattern of bladder rupture was noted. CONCLUSIONS Bladder augmentation with myomyotomy increases vulnerability to urinary extravasation, evidenced by a significantly reduced rupture pressure and bladder volume at rupture when compared to the native bladder.

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 TGFβ signaling.

Altered infant feeding patterns in boys with acquired nonsyndromic cryptorchidism.

BACKGROUND Genetic and environmental factors likely influence susceptibility to nonsyndromic cryptorchidism, a common disease presenting at birth or in later childhood. We compared cases and controls to define differential risk factors for congenital versus acquired cryptorchidism. METHODS We compared questionnaire and clinical data from cases of congenital cryptorchidism (n = 230), acquired cryptorchidism (n = 182) and hernia/hydrocele (n = 104) with a group of healthy male controls (n = 358). Potential predictor variables (p < 0.2 in univariable analysis) were included in stepwise multivariable logistic regression models. RESULTS Temporary (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4-0.8) or exclusive (OR, 0.6; 95% CI, 0.4-0.9) breastfeeding was reduced and soy formula feeding increased (OR, 1.8; 95% CI, 1.2-2.9) in acquired but not congenital or hernia/hydrocele groups. The highest risk estimates were observed for primary soy formula feeding with limited or no breastfeeding (OR 2.5; 95% CI, 1.4-4.3; adjusted OR, 2.7; 95% CI, 1.4-5.4) in the acquired group. Primary feeding risk estimates were equivalent or strengthened when multivariable models were limited to age greater than 2 years, full-term or not small for gestational age, or Caucasian subjects. Pregnancy complications and increased maternal exposure to cosmetic or household chemicals were not consistently associated with either form of cryptorchidism in these models. CONCLUSIONS Our data support reduced breastfeeding and soy formula feeding as potential risk factors for acquired cryptorchidism. Although additional studies are needed, hormonally active components of breast milk and soy formula could influence the establishment of normal testis position in the first months of life, leading to apparent ascent of testes in childhood. Birth Defects Research (Part A), 2012.

Gross Hematuria in a 3-Year-old Girl Caused by a Large Isolated Bladder Hemangioma

Hemangiomas of the urinary tract can arise anywhere along the system. Although rare, these lesions can result in significant hematuria, with potential for patient morbidity. We report a case of an isolated bladder hemangioma identified in a 3-year-old girl presenting with recurrent high-volume gross hematuria. The lesion was not amenable to endoscopic resection because of its size. We present our operative management strategy as a potential method for other urologists who may be presented with similar scenarios.

Magnetic Resonance Imaging of Renal Abnormalities in Patients with Congenital Osseous Anomalies of the Spine

BACKGROUND Patients with congenital osseous anomalies of the spine are known to have a high prevalence of abnormalities in the renal system and of the spinal cord. Today, the screening tools of choice to detect these abnormalities include ultrasonography of the kidneys and collecting system and magnetic resonance imaging of the spine. A single screening tool that can identify both renal and intraspinal anomalies would be ideal. METHODS Imaging studies of all patients with a congenital osseous anomaly of the spine seen at our institution during a ten-year period were retrospectively reviewed. Only patients who had had both a sonogram of the renal system and a magnetic resonance imaging study of the entire spine were included in the investigation. All studies were reviewed blindly by a pediatric radiologist for this study. RESULTS One hundred and fifty-three patients met the criteria for inclusion in the study. Forty-one patients (27%) had a total of forty-seven renal abnormalities noted on both the sonogram and the magnetic resonance imaging scan. In no instance was a renal anomaly seen on one study and not on the other. CONCLUSIONS When properly performed, screening magnetic resonance imaging scans of the spine can show renal abnormalities, thus obviating the need for a separate screening renal ultrasound study.

Gracilis Muscle Dynamic Urethral Sphincter Myoplasty: Rat Model Experience

PURPOSE Dynamic urethral sphincter myoplasty (skeletal muscle urinary sphincter reconstruction) using a neurovascularly intact gracilis muscle was investigated in a rat model. MATERIALS AND METHODS In female Sprague-Dawley rats, a unilateral gracilis anticus muscle flap was dissected from the medial thigh, preserving the medial muscular insertion, vascular flow, and innervation. This muscle graft was used to completely encircle the urethra and was fixed in position. Urodynamic leak point pressure (LPP) and bladder volume at leakage were measured with cystometry after 1 month, using an 18 gauge catheter placed through the bladder dome with a constant infusion rate of 0.2 ml. per minute. In addition, the effect of electrical stimulation of the gracilis myoplasty (current parameters: 1 to 10 mA, 1 to 60 Hz, 0.05 to 1 msec. duration) on intravesical leak point pressure was noted during cystometry. RESULTS The gracilis muscle measured 3.8 +/- 0.3 cm. in length, 0.5 +/- 0.1 cm. in width and 0.2 +/- 0.1 cm. in thickness. Blood flow rates to the grafted and contralateral gracilis myoplasty were similar at 43 +/- 26 and 51 +/- 30 g.cm.3, respectively (p = 0.46). The leak point pressure (LPP) of control, unstimulated gracilis myoplasty and gracilis myoplasty with electrical stimulation were 28 +/- 8, 32 +/- 12, and 85 +/- 27 mm.Hg (p < 0.01). Bladder volumes at LPP in the 3 respective groups were 0.5 +/- 0.2, 0.6 +/- 0.3 and 1.2 +/- 0.6 ml (p < 0.01). CONCLUSIONS Gracilis myoplasty is not obstructive, as substantiated by unchanged leak point pressure and leak point capacity. Myoplasty with low current stimulation, however, significantly increased LPP and leak point capacity.

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.