Anatomic findings associated with epispadias in boys: Implications for surgical management and urinary continence.

INTRODUCTION: Pre-operative physical examination of male epispadias allows for classification of epispadias level as glanular (GE), penile (PE) or penopubic (PPE), and for delineation of anatomic anomalies. The incidence of associated extragenital abnormalities, such as vesicoureteral reflux (VUR), bladder neck (BN) abnormality and abnormal pubic diastasis (PD), and their impact on urinary continence has not yet been systematically studied. OBJECTIVE: The goal of this study was to evaluate whether the more proximal level of epispadias correlated with associated extragenital anatomic anomalies seen on initial imaging or endoscopic evaluation, and whether these pre-operative findings contributed to subsequent surgical management and impacted on achieving urinary continence. It was hypothesized that the more severe forms of epispadias may be associated with a higher frequency of associated anomalies. STUDY DESIGN: The study was an IRB-approved, retrospective case study of all male patients treated initially for isolated epispadias at the current institution between 1994 and 2011. Data collection was achieved by chart and radiology review evaluating PD, BN appearance, presence of VUR, surgical treatment, and urinary continence. RESULTS: A total of 26 patients were identified and divided into three groups based on appearance at physical examination: four glanular (GE), eight penile (PE), and 14 penopubic (PPE); 17 patients had an abnormal BN. Reflux was noted in nine of 20 patients who had a voiding cystourethrogram (VCUG), two of which had an episode of pyelonephritis. Of the 22 patients past the age of toilet training, 17 were continent (64% (9/14) penopubic, 63% (5/8) penile, and 75% (3/4) glanular). DISCUSSION: Anatomic classification for male epispadias did not provide sufficient information regarding extragenital findings. This study provided new information regarding PD, BN appearance, presence of reflux, and ultimate urinary continence. Pubic diastasis and BN abnormalities were more frequently seen in more severe forms of epispadias, whereas VUR seemed more prevalent in less severe forms. A template for pre-operative evaluation was outlined. Limitations of the study were its retrospective design and relatively small cohort of patients, which reflected the rarity of the condition. CONCLUSION: Based on the information generated, additional anatomic information was generated regarding boys with epispadias. This information will help guide the evaluation and the management of these patients in the future.

Preliminary report: Surgical outcomes following genitoplasty in children with moderate to severe genital atypia.

INTRODUCTION: Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches. OBJECTIVE: The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia. STUDY DESIGN: This 11-site, prospective study included children aged ≤2 years, with Prader 3-5 or Quigley 3-6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings. RESULTS: Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) (Summary Figure). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied. DISCUSSION: In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population. CONCLUSION: In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management.

Variation in the clinical and genetic evaluation of undervirilized boys with bifid scrotum and hypospadias.

BACKGROUND: Bifid scrotum and hypospadias can be signs of undervirilization, yet boys presenting with these findings often do not undergo genetic evaluation. In some cases, identifying an underlying genetic diagnosis can help to optimize clinical care and improve guidance given to patients and families. OBJECTIVES: The aim of this study was to characterize current practice for genetic evaluation of patients with bifid scrotum, and to identify approaches with a good diagnostic yield. METHODS: A retrospective study of the Boston Children's Hospital electronic medical records (1993-2015) was conducted using the search term "bifid scrotum" and clinical data were extracted. Data were abstracted into a REDCap database for analysis. Statistical analysis was performed using SPSS, SAS, and Excel software. RESULTS: The search identified 110 subjects evaluated in the Urology and/or Endocrinology clinics for bifid scrotum. Genetic testing (including karyotype, microarray, or targeted testing) was performed on 64% of the subjects with bifid scrotum; of those tested, 23% (15% of the total cohort of 110 subjects) received a confirmed genetic diagnosis. Karyotype analysis, when performed, led to a diagnosis in 17% of patients. Of the ten instances when androgen receptor gene sequencing was performed, a pathogenic mutation was identified 20% of the time. CONCLUSION: This study demonstrated that the majority of individuals with moderate undervirilization resulting in bifid scrotum do not receive a genetic diagnosis. Over a third of the analyzed subjects did not have any genetic testing, even though karyotype analysis and androgen receptor (AR) sequencing were both relatively high yield for identifying a genetic etiology. Increased utilization of traditional genetic approaches could significantly improve the ability to find a genetic diagnosis.

Prospective assessment of cosmesis before and after genital surgery.

INTRODUCTION: Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center. OBJECTIVE: The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery. STUDY DESIGN: This prospective, observational study included children aged <2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty. RESULTS: Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P < 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P < 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings. DISCUSSION: This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life. CONCLUSION: In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences.

Prepubertal presentation of varicocele does not affect outcomes.

INTRODUCTION: Varicoceles in prepubertal boys are uncommon and little is known of the natural history. Historically, a large percentage of these boys have undergone surgical repair with the belief that such early presentation carried a worse prognosis, making assessment of longitudinal outcomes difficult. OBJECTIVE: While there may be concern that varicocele could represent a progressive disease and therefore prepubertal presentation would portend a worse prognosis, we hypothesized that there would be no difference between the prepubertal boys and other adolescents with varicocele. STUDY DESIGN: We retrospectively reviewed a database of boys at a single institution with a documented left-sided varicocele between 1995 and 2011. Inclusion criteria were one or more of the following: 1. Clinician-documented Tanner 1 status, 2. Right testis orchidometric or ultrasound calculated volume of ≤3 cc's. Patients were drawn from a prospectively maintained database of all boys presenting to the outpatient urology clinic receiving a diagnosis of varicocele. A cohort of adolescent boys was assembled by matching as closely as possible with respect to testis volume disparity and grade of varicocele. All matches were within 2% of volume difference. Volume was calculated using the length*width*height*0.71 formula. Testis size disparity was set to a threshold of ≥20% using the Lambert formula: (VolumeRight - VolumeLeft)/VolumeRight*100%. Our primary outcome was defined as hypotrophy or the need for surgery for hypotrophy at the termination of the study. We planned a single subgroup analysis of boys based on presentation with or without hypotrophy. The decision for surgery or observation was made by the individual clinician at the time of patient assessment. RESULTS: On presentation, the prepubertal cohort was younger (10.8 vs 14.1 years), and with smaller left (2.4 vs 11.6 cc) and right (2.4 vs 11.6 cc) testis volume. There were no significant differences with respect to varicocele grade and volume differentials at presentation. At the end of the study, 76% of the prepubertal cohort had neither hypotrophy nor the requirement for operation, compared with 83% of the matched cohort (P = 0.71, Fisher's exact test). Similarly, there were no significant differences in outcome when comparing prepubertal boys with initial symmetry or hypotrophy to their matched cohort of older adolescents. DISCUSSION: The prepubertal varicocele is a rare clinical problem for which little data exists to guide the clinician. In a review of Pubmed indexed English language manuscripts, we were only able to find five papers with information on Tanner stage; only 31 prepubertal boys have longitudinal data reported. This study approximately doubles the number of boys for whom such data is available in the literature. Our chief limitation was sample size. A power analysis indicated that a final-analysis cohort of 90 prepubertal boys would be required to detect a 20% difference in outcome between that group and a matched cohort of pubertal or post-pubertal boys. We propose that given the lack of evidence for worse outcomes in prepubertal boys with varicocele that prepubertal status, in and of itself, not be considered an additional indication for correction of varicocele. CONCLUSION: In our retrospective cohort of prepubertal boys with left testis varicocele and their matched cohort, we did not detect a difference in the rate of good outcomes, defined as the absence of hypotrophy and lack of need for surgical intervention. While we may have suspected, as have others, that prepubertal presentation would have conveyed a more pressing need to intervene, it is likely that these boys represent the very same patients that we see more commonly later in their adolescence, and should thus be managed in a similarly conservative fashion.

Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation.

PURPOSE: To assess the safety and efficacy of total lymphoid irradiation (TLI) in patients experiencing chronic rejection following bilateral lung transplantation (BLT). PATIENTS AND MATERIALS: Eleven patients received TLI for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Radiation therapy (RT) was prescribed as 8 Gy delivered in 10 0.8-Gy fractions, 2 fractions/week, via mantle, paraaortic, and inverted-Y fields. Serial pre- and post-RT pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements [use of methylprednisolone, murine anti-human mature T-cell monoclonal antibody (OKT3), polyclonal antithymocyte globulin (ATG), and tacrolimus] were monitored. RESULTS: In the 3 months preceding TLI, the average decrease in forced expiratory volume in 1 s (FEV1) was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). Only 4 of 11 patients completed all 10 TLI treatment fractions. Reasons for discontinuation included progressive pulmonary decline (four patients), worsening pulmonary infection (two patients), and persistent thrombocytopenia (one patient). Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related-donor transplants; he is alive and well. Six patients died. Two of these deaths were due to pulmonary infection from organisms isolated prior to the start of RT; the other four deaths were from progressive pulmonary decline. The four remaining patients had durable positive responses to TLI (mean follow-up of 47 weeks; range 24-72). Comparing the 3 months preceding RT to the 3 months following treatment, these four patients had improvements in average FEV1 (40% decline vs. 1% improvement) and fewer median number of immunosuppressive augmentations (3.5 vs. 0). None of these patients has developed lymphoproliferative disease or has died. Features suggestive of a positive response to TLI included longer interval from transplant to RT, higher FEV1 at initiation of RT, and absence of preexisting pulmonary infection. CONCLUSION: Total lymphoid irradiation for chronic allograft rejection refractory to conventional medical management following BLT was tolerable. A subset of patients experienced durable preservation of pulmonary function and decreased immunosuppressive requirements. Patients with rapidly progressive allograft rejection, low FEV1, or preexisting infection were least likely to benefit from irradiation. Early initiation of TLI for patients experiencing chronic allograft rejection following BLT may be warranted.

Evaluation of the effect of experimental cyclosporine toxicity on male reproduction and renal function. Reversal by concomitant human chorionic gonadotropin administration.

Administration of cyclosporine to rats has been shown to impair testicular function, resulting in a decrease in sperm counts and fertility. In order to determine whether or not the deleterious effects of CsA could be reversed by hormonal therapy, mature male Sprague Dawley rats were treated with CsA (40 mg/kg/day, s.c.) alone or in combination with human chorionic gonadotropin (hCG) (5 micrograms/day/r; s.c.) for 14 days. Cyclosporine administration decreased the body weight (290 +/- 5.30 vs. 339 +/- 8.7 g; P less than 0.05) and reproductive organ weights (testis 1.49 +/- 0.42 vs. 1.60 +/- 0.03 g; epididymis 0.41 +/- 0.02 vs. 0.49 +/- 0.002 g; seminal vesicle 0.61 +/- 0.09 vs. 1.60 +/- 0.05 g; prostate 0.28 +/- 0.04 vs. 0.60 +/- 0.06 g; P less than 0.05) testicular sperm counts (5.80 +/- 0.42 vs. 8.49 +/- 0.48 x 10(7)/100 mg tissue; P less than 0.05) and epididymal sperm counts, (28.2 +/- 0.95 vs. 51 51.62 +/- 2.17 x 10(7)/100 mg tissue; P less than 0.05) and fertility (25% vs. 100%). Serum levels of LH were elevated (101.98 +/- 21.48 vs. 25.6 +/- 5.18 ng/ml; P less than 0.05) and testosterone was decreased (0.48 +/- 0.07 vs. 2.06 +/- 0.56 ng/ml; P less than 0.05). The administration of hCG to the CsA-treated rats restored the reproductive organ weights (testis 1.56 +/- 0.043 g; seminal vesicle 1.04 +/- 0.05 g; prostate 0.70 +/- 0.06 g) and sperm counts (testicular 7.88 +/- 1.0 x 10(7)/100 mg tissue; epididymal 59.86 +/- 4.16 x 10(7)/100 mg tissue; P less than 0.05) Serum levels of testosterone (18.63 +/- 4.45 ng/ml) and LH (431.65 +/- 31.41 ng/ml) were significantly elevated, as compared with control and CsA-treated groups (P less than 0.05). All the rats in the gonadotropin-treated group were fertile, as compared with 25% in the CsA-treated group. CsA reduced the kidney weight (1.17 +/- 0.02 vs. 1.27 +/- 0.03 g; P less than 0.05) and increased the levels of serum creatinine (0.97 +/- 0.07 vs. 0.59 +/- 0.03 mg/dl; P less than 0.05): these changes were ameliorated by the administration of hCG (kidney weight 1.35 +/- 0.03 g; creatinine 0.76 +/- 0.09 mg/dl).

Rare variant of isolated lower pole hydronephrosis: primary obstructive megaureter.

Hydronephrosis in the lower pole moiety of a duplex system is relatively uncommon, usually associated with vesicoureteric reflux. We report on a patient with primary obstructive megaureter of a lower pole moiety that we believe is the first case report in the literature.

Incidental ganglioneuroblastoma.

A case is described in which an incidental ganglioneuroblastoma was discovered at the time of surgical correction of upper pole hydronephrosis secondary to an obstructing ectopic ureterocele in a duplicated system. We believe this is the first case of incidental ganglioneuroblastoma reported in the urologic literature. The management of this patient's disease is discussed as is the entity of incidental neuroblastoma.

Laparoscopic diagnosis and management of transverse testicular ectopia.

Transverse testicular ectopia (TTE) is a rare genitourinary anomaly. We report a case of TTE in a 14-year-old boy diagnosed and managed laparoscopically. The clinical features and etiology of this rare testicular anomaly are reviewed.

Neonatal gross hematuria as a presenting sign of posterior urethral valves.

Neonatal gross hematuria is a rare clinical entity. Only occasionally is it associated with obstructive uropathy in the neonate. We report a case in which gross hematuria was the presenting sign in a patient with posterior urethral valves. The differential diagnosis of neonatal gross hematuria with particular attention to obstructive uropathy is reviewed.

Control of prolonged, benign, renal hematuria by silver nitrate instillation.

Four patients with protracted benign hematuria underwent silver nitrate instillation of the upper collecting system. The doses varied from 10 ml. of 0.25 per cent silver nitrate to 14 ml. of 1 per cent silver nitrate. In all 4 cases the hematuria resolved within four days without significant complications. At follow-up extending from three to twenty-four months there have been no recurrences of gross hematuria. Silver nitrate instillation appears to be a safe and effective method of treating benign renal hematuria, thus obviating the need for extirpative surgery.

Large-cell calcifying Sertoli cell tumor of the testis: case report and review of the literature.

Large-cell calcifying Sertoli cell tumor (LCCSCT) is a rare sex cord-stromal tumor found predominantly in the pediatric population. This tumor has distinctive histopathologic features and clinical associations. LCCSCT has also been noted in association with the Carney complex, and in patients with Peutz-Jeghers syndrome. The propensity to metastasize is low, and radical orchiectomy has traditionally been the treatment of choice.

Infection stones in children: a twenty-seven-year review.

OBJECTIVE: The objective of this study was to determine the relationship between urinary tract infection and pediatric urolithiasis and to characterize the pediatric infection stone former. METHODS: Two hundred seventy consecutive pediatric stone formers presenting over a twenty-seven-year period were studied. Of these, 161 children (60%) had infection-related stones. Account was taken of stone composition, anatomic location, associated anatomic lesions, and the rate of stone recurrence over a median follow-up of three years. RESULTS: The mean age of children with infection stones was 4.9 years, with two-thirds being under six years of age. Proteus mirabilis accounted for 82 percent of pure urine cultures. Seventy percent of stones were renal and 30 percent were ureteral or intravesical. One-third of patients had anatomic lesions (pelviureteric obstruction, primary obstructed megaureter, and others) contributing to stone formation. Recurrent stones occurred in 14 percent of cases. CONCLUSIONS: This study reaffirms the predominance of urinary tract infection secondary to P. mirabilis as the leading cause of pediatric urolithiasis in the United Kingdom. The significant recurrence rate suggests the importance of prophylactic antibiotics, surgical correction of congenital anomalies, and long-term follow-up of this patient population.

The spectrum of Sertoli cell tumors in children.

The spectrum of Sertoli cell tumors in children covers a wide range of testis and ovarian tumors classified as sex cord-stromal tumors. Sertoli cell tumor of the testis is extremely rare in the pediatric population. The American Academy of Pediatrics Section on Urology Prepubertal Testicular Tumor Registry has reported a total of six cases of Sertoli cell tumor of the testis, accounting for 1.3% of the 430 cases reported to the registry as of October 1996. Despite their rarity, Sertoli cell variants of sex cord-stromal tumors have generated keen interest because of their variable histologic appearance and biologic behavior, including endocrine activity. Because sex cord-stromal tumors occur in the ovary and testis, a primitive cellular origin to these tumors is likely in males and females.

Cyclosporine: its effects on testicular function and fertility in the prepubertal rat.

The authors examined the effects of the immunosuppressive drug cyclosporine (CsA) on the male reproductive system in prepubertal rats. Twenty-one-day-old rats were subcutaneously injected with either cremaphorsaline vehicle or CsA (1 and 2 mg/kg/d). The animals were treated until they were 66 days old. Cyclosporine did not affect the weights of the body or testis but decreased the weights of all sex accessory organs. Quantitative analysis of the tubules in stage VII of spermatogenesis revealed a decline in the cell counts of pachytene spermatocytes and step VII spermatids. Testicular and epididymal sperm counts and motility were decreased by 50% and fertility by 60%. Cyclosporine lowered serum testosterone despite an elevation of LH, indicating that the drug directly inhibited testosterone synthesis. Serum creatinine levels were normal in the treated animals, precluding renal failure as the cause for this impairment. Intratesticular concentrations of pregnenolone and 17-hydroxy progesterone were significantly elevated, while those of progesterone, androstenedione, and testosterone were markedly reduced. Determination of steroidogenic enzyme activities indicated that the administration of CsA inhibited the activity of delta 5-3B-hydroxy steroid dehydrogenase-delta 5-4 isomerase (3 beta-HSD). These results clearly indicate that CsA in the doses used is harmful to the male reproductive function in prepubertal rats.

Use of the silastic sheath in bladder neck reconstruction.

OBJECTIVE: The study compared two populations of patients undergoing bladder neck reconstruction using the silastic sheath in two major pediatric centers. The success with this technique was markedly different in the two centers. The purpose of the study was to determine factors that might explain the divergent results. PATIENTS AND METHODS: Fifteen patients treated in Indianapolis were compared with 94 patients treated in London with the silastic sheath technique of bladder neck reconstruction. Eighty-seven percent of the Indianapolis patients had myelomeningocele whereas 86% of the London group had exstrophy/epispadias. Median age of the Indianapolis patients was 11 years whereas it was 8.4 years in London. Seventy-three percent of patients in Indianapolis were female and 79% in London were male. Patients were followed for a minimum of eight years in Indianapolis and a mean of seven years in London. Similar surgical technique was employed in the two centers but, over time, the London approach included use of a non-reinforced silastic wrapped loosely around the bladder neck with the interposition of omentum. RESULTS: Both groups achieved continence rates exceeding 90%. Of the Indianapolis patients, two-thirds experienced erosion of the silastic at a mean of 48 months. With modifications in the London technique, the erosion rate of silastic was lowered from 100% to 7%. CONCLUSION: Direct, snug wrap of silastic without omentum around the Young-Dees tube as well as simultaneous bladder augmentation placed patients at increased risk for erosion. The silastic sheath technique may be less applicable to myelomeningocele patients. It seems most applicable to older male patients with exstrophy or epispadias undergoing Young-Dees bladder neck reconstruction who have the ability to void.