Urinary tract infection due to anaerobic bacteria in a two-month-old infant.

The significance of anaerobic bacteria as a pathogen in urinary tract infection (UTI) in children is unclear. A two-month-old infant presenting with poor feeding received a diagnosis of polymicrobial anaerobic UTI by next-generation sequencing and was found to have obstructive uropathy. Anaerobic bacteria may be a cause of UTI in children with urinary tract obstruction.

Necessity of performing voiding cystourethrography for children with unilateral multicystic dysplastic kidney.

BACKGROUND: The purpose of this study was to resolve the clinical question as to whether all patients with unilateral multicystic dysplastic kidney (MCDK) should receive voiding cystourethrography (VCUG). METHODS: This is a retrospective study using cross-sectional analysis. Seventy-five children with unilateral MCDK were enrolled, excluding patients with other genetic or chromosome abnormalities, spinal cord diseases, or anal atresia. We reviewed their records from medical charts and calculated risk factors for abnormal VCUG using multivariate logistic regression analysis. RESULTS: Abnormal VCUG findings were present in 24 of 75 patients (32.0%), specifically, vesicoureteral reflux (VUR) in 8 (10.6%), including high-grade VUR in 2 (2.7%), and only lower urinary tract or bladder disease in 16 (21.3%). In multivariate analysis, only abnormal findings by ultrasonography was an independent risk factor for abnormal VCUG findings with statistical significance in multivariate analysis (OR 6.57; 95% CI 1.99-26.26; P = 0.002). When we excluded five patients who showed similar findings by ultrasonography and VCUG, abnormal findings by ultrasonography were again calculated as an independent risk factor (OR 4.44; 95% CI 1.26-28.42; P = 0.02). Sensitivity, specificity, positive predictive value, and negative predictive value of abnormal findings by ultrasonography to predict urologic anomalies by VCUG in these children were 83%, 59%, 49%, and 88%, respectively. Two children required a third ultrasonography to detect abnormal findings. CONCLUSIONS: We can select, using only abnormal findings by ultrasonography, children with unilateral MCDK who should undergo VCUG. We would also like to emphasize that ultrasonography should be performed repeatedly to detect congenital anomalies of the urinary tract.

Gradual bone transfer for the correction of the pubic diastasis using the Ilizarov technique in closure of bladder and cloacal exstrophy.

BACKGROUND: In the patient of the cloacal exstrophy, cloaca with local abdominal wall is disrupted and exposed inner surface of the bladder needs early closure. Pelvic osteotomies are required for severe cases whose bladder cannot be closed by the suture of soft tissue only. We developed a technique involving the gradual positioning of bone fragments using a light, Ilizarov external fixator. The usefulness of the technique was assessed. METHODS: We enrolled 3 patients with cloacal exstrophy and 1 with bladder exstrophy as a gradual transfer group and 6 patients who were treated by other osteotomies as a control group. The patients aged 6.7-8.4 months at the time of surgery were followed up for 4.0-8.6 years. An external fixator with carbon fiber half-rings was placed to internally rotate and anteriorly move the distal bone fragment over 2 weeks. Then, the bladder was closed. Computed tomography (CT) images were used to assess the pelvis form. Wound dehiscence and number of the surgeries after the osteotomies are also compared between the two groups. RESULTS: CT analysis of correction of the pelvic deformity achieved more and less decreasing its volumetric capacity in the gradual transfer group. No patients had wound dehiscence after the primary closure with pelvic osteotomy in the gradual transfer group but all had them in the control group. The mean number of the surgeries after the osteotomies were 2.25 in the gradual transfer group whereas 5.5 in the control group. CONCLUSIONS: Sufficient closure of the abdominal wall and bladder was achieved in all cases in the gradual transfer group. The correction of pelvic bones were more with less decreasing of their pelvic capacities, no patients had wound dehiscence after the closure and there was an effect to decrease the number of the surgeries after the treatment by this method.

Association of variants in genes involved in environmental chemical metabolism and risk of cryptorchidism and hypospadias.

We hypothesized that single-nucleotide polymorphisms (SNPs) of genes involved in environmental endocrine disruptors (EEDs) metabolism might influence the risk of male genital malformations. In this study, we explored for association between 384 SNPs in 15 genes (AHR, AHRR, ARNT, ARNT2, NR1I2, RXRA, RXRB, RXRG, CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP3A4, CYP17A1 and CYP19A1) and risk of cryptorchidism (CO) and hypospadias (HS) in 334 Japanese (JPN) males (141 controls, 95 CO and 98 HS) and 187 Italian (ITA) males (129 controls and 58 CO). In the JPN study group, five SNPs from ARNT2 (rs2278705 and rs5000770), CYP1A2 (rs2069521), CYP17A1 (rs4919686) and NR1I2 (rs2472680) were significantly associated at both allelic and genotypic levels with risk of at least one genital malformation phenotype. In the ITA study group, two SNPs in AHR (rs3757824) and ARNT2 (rs1020397) were significantly associated with risk of CO. Interaction analysis of the positive SNPs using multifactor dimensionality reduction demonstrated that synergistic interaction between rs2472680, rs4919686 and rs5000770 had 62.81% prediction accuracy for CO (P=0.011) and that between rs2069521 and rs2278705 had 69.98% prediction accuracy for HS (P=0.001) in JPN population. In a combined analysis of JPN and ITA population, the most significant multi-locus association was observed between rs5000770 and rs3757824, which had 65.70% prediction accuracy for CO (P=0.055). Our findings indicate that genetic polymorphisms in genes involved in EED metabolism are associated with risk of CO and HS.

Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients.

BACKGROUND/PURPOSE: The effect of low-dose bisphenol A (BPA) exposure on human reproductive health is still controversial. To better understand the molecular basis of the effect of BPA on human reproductive health, a genome-wide screen was performed using human foreskin fibroblast cells (hFFCs) derived from child hypospadias (HS) patients to identify novel targets of low-dose BPA exposure. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles of hFFCs were measured after exposure to 10 nM BPA, 0.01 nM 17ß-estradiol (E2) or 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 24 h. Differentially expressed genes were identified using an unpaired Student's t test with P value cut off at 0.05 and fold change of more than 1.2. These genes were selected for network generation and pathway analysis using Ingenuity Pathways Analysis, Pathway Express and KegArray. Seventy-one genes (42 downregulated and 29 upregulated) were identified as significantly differentially expressed in response to BPA, among which 43 genes were found to be affected exclusively by BPA compared with E2 and TCDD. Of particular interest, real-time PCR analysis revealed that the expression of matrix metallopeptidase 11 (MMP11), a well-known effector of development and normal physiology, was found to be inhibited by BPA (0.47-fold and 0.37-fold at 10 nM and 100 nM, respectively). Furthermore, study of hFFCs derived from HS and cryptorchidism (CO) patients (n = 23 and 11, respectively) indicated that MMP11 expression was significantly lower in the HS group than in the CO group (0.25-fold, P = 0.0027). CONCLUSIONS/SIGNIFICANCE: This present study suggests that an involvement of BPA in the etiology of HS might be associated with the downregulation of MMP11. Further study to elucidate the function of the novel target genes identified in this study during genital tubercle development might increase our knowledge of the effects of low-dose BPA exposure on human reproductive health.

Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients.

BACKGROUND/PURPOSE: We hypothesized that polymorphic differences among individuals might cause variations in the effect that environmental endocrine disruptors (EEDs) have on male genital malformations (MGMs). In this study, individual variation in the genetic response to low-dose bisphenol A (BPA) was investigated in human foreskin fibroblast cells (hFFCs) derived from child cryptorchidism (CO) and hypospadias (HS) patients. METHODOLOGY/PRINCIPAL FINDINGS: hFFCs were collected from control children without MGMs (n=5) and child CO and HS patients (n=8 and 21, respectively). BPA exposure (10 nM) was found to inhibit matrix metalloproteinase-11 (MMP11) expression in the HS group (0.74-fold, P=0.0034) but not in the control group (0.93-fold, P=0.84) and CO group (0.94-fold, P=0.70). Significantly lower levels of MMP11 expression were observed in the HS group compared with the control group (0.80-fold, P=0.0088) and CO group (0.79-fold, P=0.039) in response to 10 nM BPA. The effect of single-nucleotide polymorphism rs5000770 (G>A), located within the aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) locus, on individual sensitivity to low-dose BPA was investigated in the HS group. A significant difference in neurotensin receptor 1 (NTSR1) expression in response to 10 nM BPA was observed between AA and AG/GG groups (n=6 and 15, respectively. P=0.031). However, no significant difference in ARNT2 expression was observed (P=0.18). CONCLUSIONS/SIGNIFICANCE: This study advances our understanding of the specificity of low-dose BPA effects on human reproductive health. Our results suggest that genetic variability among individuals affects susceptibility to the effects of EEDs exposure as a potential cause of HS.

Transverse testicular ectopia with splenogonadal fusion: a case report.

Both transverse testicular ectopia (TTE) and splenogonadal fusion (SGF) are rare congenital abnormalities. We report a case with both TTE and SGF, simultaneously. As far as we know, this is the first reported case. In order to identify a case of TTE or SGF, it is necessary to consider that the testes and ectopic spleens have similar patterns on ultrasonograph and magnetic resonance imaging.

Prepubertal testicular tumors: a 20-year experience with 40 cases.

Testicular tumors are rare in children. In addition, prepubertal testicular tumors (PTT) are fundamentally different from their postpubertal counterparts.We reviewed our 20-year experience with 40 cases to suggest an algorithm for the appropriate surgical approach for patients with PTT. All tumors ultrasonographically suspected of being benign were confirmed to be benign postoperatively. There was a significant difference between median preoperative a-fetoprotein (AFP) levels of infants with yolk sac tumor and teratoma. The majority of our cases were benign, with the most common histopathological subtype being teratoma, as recently reported. Testis-sparing surgery was carried out in five patients with teratoma and three patients with epidermoid cyst. Other than one patient with teratoma, none of the patients developed recurrence or testicular atrophy after testis-sparing surgery. When testis-sparing surgery is considered, our algorithm based on ultrasonographic findings and preoperative AFP levels might be helpful.

A new technique of concealed penis repair.

PURPOSE: Phimosis associated with concealed penis is not amenable to ordinary circumcision. To our knowledge we describe a new technique to repair concealed penis. MATERIALS AND METHODS: From September 2003 to January 2008, 57 consecutive patients with concealed penis were treated using our technique. Median age at surgery was 33 months (range 7 months to 34 years). The technique consists of 3 steps. Step 1 is a ventral incision to slit the narrow ring of the prepuce and expose the glans. Step 2 is a circumferential skin incision made between 2 edges of the ventral diamond-shaped skin defect, followed by midline incision of the dorsal inner prepuce to make 2 skin flaps connected to the glans. Step 3 is skin coverage. Two skin flaps are brought down and sutured together on the ventral side of the penis. The suture line between the penile shaft skin and the flap eventually becomes elliptical. Medical records were reviewed for voiding function, scar formation, and replies from older patients and the parents of younger children about impressions of the surgical results. RESULTS: Median followup was 26 months. No patient had voiding problems. Lymphedema persisted due to suture line constriction in 2 patients who underwent incision of the constriction. All older patients and the parents of younger children were satisfied with the surgical results. CONCLUSIONS: Our new method is easy to design and perform to correct concealed penis. It provides a good cosmetic appearance and seems to be applicable in all cases with deficient penile shaft skin.

Utility of spinal MRI in children with anorectal malformation.

BACKGROUND: The association between spinal cord anomalies and imperforate anus is well recognized. Until now, the incidence of tethered cord has been assumed to be higher in patients with high-type imperforate anus. However, recent reports suggest that tethered cord is as common in patients with a low lesion as in those with a high lesion. OBJECTIVE: To review the incidence of spinal cord anomalies in those with a low lesion and those with a high (including intermediate) anorectal malformation (ARM), and to determine the best diagnostic imaging strategy. MATERIALS AND METHODS: A group of 50 consecutive patients with postoperative ARM and in whom spinal MRI had been performed were identified retrospectively. We reviewed and compared the following factors between those with a high lesion and those with a low lesion: (1) clinical symptoms, (2) spinal cord anomalies, and (3) vertebral anomalies. RESULTS: The incidence of spinal cord anomalies was no different between those with a high lesion and those with a low lesion, and spinal cord anomalies were present regardless of the presence of vertebral anomalies or symptoms. CONCLUSION: Owing to the high incidence of spinal cord anomalies in patients with imperforate anus, MRI is the best imaging tool for detecting such anomalies regardless of the level of the lesion.

One-stage repair of severe hypospadias using modified tubularized transverse preputial island flap with V-incision suture.

PURPOSE: Although hypospadias repair for preserving the urethral plate is popular among pediatric urologists, applying this procedure to severe hypospadias is controversial. We report the outcome of applying additional modifications to the modified tubularized transverse preputial island flap (TPIF) procedure reported previously [Patel RP, Shukla AR, Austin JC and Canning DA. Modified tubularized transverse preputial island flap repair for severe proximal hypospadias. BJU Int 2005;95:901-4] for repairing severe hypospadias. MATERIALS AND METHODS: We retrospectively evaluated our series of 22 patients (mean age 17.5 months) who underwent the modified TPIF with an additional simple modification of meatoplasty with V-incision suture. Patients were followed for a mean period of 18 months. RESULTS: After releasing the chordee, the hypospadiac orifice was retracted to become penile in five patients (22.7%), penoscrotal in six (27.3%), scrotal in nine (40.9%), and perineal in two (9.1%). The median length of the neourethra was 46 mm. One-stage repair was successful in 19 patients (86.4%) without any complications. CONCLUSION: Our modified TPIF procedure yielded favorable outcomes functionally and cosmetically with a low postoperative morbidity rate. Such a procedure can be considered useful for repairing severe hypospadias when the urethral plate cannot be preserved.

Endoscopic fetal urethrotomy for anterior urethral valves: a preliminary report.

Anterior urethral valves are a rare congenital anomaly associated with distal urethral obstruction, which can result in a poor prognosis. We report on the endoscopic creation of a fetal urethrotomy for obstructive uropathy resulting from anterior urethral valves. A 33-year-old woman was evaluated at 17 weeks gestation due to fetal megacystis. The diagnosis of anterior urethral valves was confirmed by the characteristic sonographic feature of a dilated membranous penile urethra. Oligohydramnios with normal-appearing kidneys and favorable urinary electrolytes led to fetal intervention. Ablation on the ventral site of the fetal penis for a cutaneous urethrotomy was performed using a YAG laser under a 1-mm fetoscope at 19 weeks gestation. Urine was drained from the incision and the dilated penis and the distended bladder shrunk with an increase in amniotic fluid. However, the fetus died unexpectedly on postoperative day 3, and chorioamnionitis was suspected as the etiology. While the outcome was unfavorable, our preliminary experience shows that fetal urethrotomy for obstructive uropathy can be achieved in utero using an endoscopic laser approach. Further experience will be required to evaluate the therapeutic value of this new procedure in the management of fetal anterior urethral valves.

Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities.

BACKGROUND: We have recently suggested that homozygosity for a specific 'AGATA' haplotype within a approximately 50 kb linkage disequilibrium (LD) block of the gene for estrogen receptor alpha (ESR1) may raise the susceptibility to cryptorchidism by enhancing estrogenic effects of environmental endocrine disruptors (EEDs). METHODS: Haplotype analysis of ESR1 was performed in 328 Japanese subjects, i.e. 70 patients with micropenis (MP), 43 patients with hypospadias (HS), 80 patients with spermatogenic failure (SF) and 135 control males. Genotyping was performed by the 5' nuclease assay. RESULTS: The LD block was identified in each of the patient groups and in the control males. The frequency of homozygotes for the specific 'AGATA' haplotype was markedly higher in the HS patients [P = 0.0000033, odds ratio [OR] = 11.26] and slightly higher in the MP patients (P = 0.034, OR = 3.64) than in the control males, and the 'AGATA' haplotype was strongly associated with HS (P = 0.0000022, OR = 11.26) and weakly associated with MP (P = 0.040, OR = 3.64) in a recessive mode. There was no significant difference between the SF patients and the control males. CONCLUSIONS: Our results support the hypothesis that homozygosity for the specific ESR1 'AGATA' haplotype may increase the susceptibility to the development of male genital abnormalities in response to estrogenic EEDs.

Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese patients with cryptorchidism.

BACKGROUND/AIMS: Although insulin-like factor 3 (INSL3) and its receptor leucine-rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor affecting testis descent (LGR8/GREAT) are essential for the gubernacular development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with cryptorchidism (CO), and there is no report documenting a positive association of CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development of CO. METHODS: Sixty-two Japanese CO patients and 60 fertile males were studied. INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and LGR8/GREAT was examined by denaturing high-performance liquid chromatography followed by direct sequencing for exons with abnormal chromatogram patterns. RESULTS: No definitive mutation was identified in both genes. Six polymorphisms were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr polymorphism in INSL3 was strongly associated with CO (p=0.0024, odds ratio=5.3, 95% confidence interval=1.7-17). CONCLUSION: The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of CO.