Increased pediatric sub-specialization is associated with decreased surgical complication rates for inpatient pediatric urology procedures.

INTRODUCTION: Increased case volumes and training are associated with better surgical outcomes. However, the impact of pediatric urology sub-specialization on perioperative complication rates is unknown. OBJECTIVES: To determine the presence and magnitude of difference in rates of common postoperative complications for elective pediatric urology procedures between specialization levels of urologic surgeons. The Nationwide Inpatient Sample (NIS), a nationally representative administrative database, was used. STUDY DESIGN: The NIS (1998-2009) was retrospectively reviewed for pediatric (≤18 years) admissions, using ICD-9-CM codes to identify urologic surgeries and National Surgical Quality Improvement Program (NSQIP) inpatient postoperative complications. Degree of pediatric sub-specialization was calculated using a Pediatric Proportion Index (PPI), defined as the ratio of children to total patients operated on by each provider. The providers were grouped into PPI quartiles: Q1, 0-25% specialization; Q2, 25-50%; Q3, 50-75%; Q4, 75-100%. Weighted multivariate analysis was performed to test for associations between PPI and surgical complications. RESULTS: A total of 71,479 weighted inpatient admissions were identified. Patient age decreased with increasing specialization: Q1, 7.9 vs Q2, 4.8 vs Q3, 4.8 vs Q4, 4.6 years, P < 0.01). Specialization was not associated with race (P > 0.20), gender (P > 0.50), or comorbidity scores (P = 0.10). Mortality (1.5% vs 0.2% vs 0.3% vs 0.4%, P < 0.01) and complication rates (15.5% vs 11.7% vs 9.6% vs 10.9%, P < 0.0001) both decreased with increasing specialization. Patients treated by more highly specialized surgeons incurred slightly higher costs (Q2, +4%; Q3, +1%; Q4 + 2%) but experienced shorter length of hospital stay (Q2, -5%; Q3, -10%; Q4, -3%) compared with the least specialized providers. A greater proportion of patients treated by Q1 and Q3 specialized urologists had CCS ≥2 than those seen by Q2 or Q4 urologists (12.5% and 12.2%, respectively vs 8.4% and 10.9%, respectively, P = 0.04). Adjusting for confounding effects, increased pediatric specialization was associated with decreased postoperative complications: Q2 OR 0.78, CI 0.58-1.05; Q3 OR 0.60, CI 0.44-0.84; Q4 OR 0.70, CI 0.58-0.84; P < 0.01. DISCUSSION: Providers with proportionally higher volumes of pediatric patients achieved better postoperative outcomes than their less sub-specialized counterparts. This may have arisen from increased exposure to pediatric anatomy and physiology, and greater familiarity with pediatric techniques. LIMITATION: The NIS admission-based retrospective design did not enable assessment of long-term outcomes, repeated admissions, or to track a particular patient across time. The study was similarly limited in evaluating the effect of pre-surgical referral patterns on patient distributions. CONCLUSIONS: Increased pediatric sub-specialization among urologists was associated with a decreased risk of mortality and surgical complications in children undergoing inpatient urologic procedures.

Prevalence of renal anomalies after urinary tract infections in hospitalized infants less than 2 months of age.

OBJECTIVE: Our aim was to determine the incidence of anatomical abnormalities after a urinary tract infection (UTI) in infants <2 months of age hospitalized in the neonatal intensive care unit (NICU). STUDY DESIGN: This was a retrospective, single-center cohort study of infants <2 months of age in the NICU with a UTI and documented renal imaging. RESULT: We identified 141 infants with UTIs. The mean gestational age and birth weight were 28 weeks and 1254 g, respectively. The most commonly identified pathogen was coagulase-negative Staphylococcus (28%, 44 of 156). A major abnormality was found on at least one imaging study for 4% (5 of 118) of infants. Major abnormalities were noted on 4% (5 of 114) of renal ultrasounds and 2% (2 of 82) of voiding cystourethrography examinations. CONCLUSION: Among infants in the NICU <2 months of age at the time of a UTI, the prevalence of major anatomical abnormalities is <5%.

Acute abdominal symptoms and signs in children and young adults with spina bifida: ten years' experience.

BACKGROUND/PURPOSE: Diagnosis and management of the acute abdomen in patients with spina bifida (SB) can be problematic. There are at least 4 clinical factors that can predispose to the development of acute abdominal symptoms and signs, and patients with a thoracic level lesion can have a partially insensate abdomen. The authors analyzed their accumulated experience to determine the annual incidence of acute abdominal signs and symptoms in children and young adults with spina bifida, the differential diagnosis, the operative management, and the outcome. The pertinent literature was reviewed. METHODS: Cases were ascertained during a 10-year period at 1 institution and reviewed retrospectively. RESULTS: Twenty-two episodes of acute abdominal symptoms and signs in 19 children and young adults with SB were ascertained over 10 years at 1 institution, for an annual incidence of 0.74%. More patients had a thoracic level lesion (n = 12; 60%) than in the clinic population as a whole (27%; P =.04), but the gender distribution was similar (58% girls), as was the prevalence of ventriculoperitoneal shunts (VPS; 95%). The median age was 13 years (range, 1 year to 26 years). Hospitalization was necessary for 19 (86%) of the 22 episodes. The duration of symptoms before diagnosis was a median of 3 days (range, 1 to 14 days). Most patients (82%) presented with abdominal pain. Fever was present in 27%, shock in 23%, and peritoneal signs in 23%. There were 14 different final diagnoses, 10 (71%) of which were associated with a predisposing factor. Of the 22 episodes, 18 (82%) could be attributed to an underlying factor: (1) neurogenic bladder (9; 41%); (2) neurogenic bowel (3; 14%); (3) VPS (4; 18%); (4) complications from previous surgery (2; 9%). Thirteen patients (59%) underwent a total of 20 surgical procedures of 12 different kinds. Despite awareness of the complexities involved, 3 patients (14%) died: 1 from complications resulting from bladder perforation; 1 from urosepsis and shock; and 1 from peritonitis caused by VPS infection. CONCLUSION: The differential diagnosis of the acute abdomen in patients with SB is broad, conditions requiring surgery are frequently diagnosed, and the mortality rate is substantial, despite aggressive management.

Genitourinary complications of sickle cell disease.

PURPOSE: In the last half century the molecular biology, pathophysiology and natural history of sickle cell disease have been well defined. Sickle cell disease causes microvascular occlusion, which is manifested in most organ systems. The genitourinary tract is most commonly affected by hematuria, urinary tract infection and priapism but other more serious sequelae have been identified. MATERIALS AND METHODS: We performed a computerized MEDLINE search from 1965 to the present and a bibliographic review of cross references. These references were analyzed for meaningful findings and case reports. RESULTS: The diagnosis and management of sickle cell disease have advanced rapidly with a significant increase in the life expectancy of affected patients and recognition of a greater number of genitourinary complications. Renal function may be mildly altered or lost completely. Patients with sickle cell disease are at increased risk for urinary tract infection. Priapism is a painful complication of sickle cell disease that is poorly understood and challenging to treat and prevent. Testicular infarction has also been noted. Furthermore, renal medullary carcinoma, a highly lethal tumor, develops almost exclusively in young patients with sickle cell trait. CONCLUSIONS: Heightened awareness of the genitourinary complications of sickle cell disease may prevent end stage disease, including renal failure and impotence. New forms of therapy for sickle cell disease, such as hydroxyurea, may prevent these complications in the future.

Long-term efficacy of simple behavioral therapy for daytime wetting in children.

PURPOSE: Behavioral therapy has proved benefit for children with daytime wetting but most studies have used biofeedback techniques and provide no long-term assessment of results. We previously reported similar results using simple behavioral therapy without biofeedback. We report the long-term efficacy of behavioral therapy for daytime wetting. MATERIALS AND METHODS: Our program of behavioral therapy included timed voiding, modification of fluid intake, positive reinforcement techniques and pelvic floor (Kegel) exercises to promote pelvic floor strengthening and relaxation. Questionnaires to assess therapeutic efficacy were mailed to patients who had completed therapy more than 1 year previously. RESULTS: A total of 48 patients responded. Mean ages at the time of the initial clinic visit and questionnaire were 8.2 and 12.9 years, respectively. Improvement in symptoms was noted in approximately 74% of the cases during the first year following therapy. At a mean of 4. 7 years after treatment 59.4% of the patients had improved daytime urinary control, 51.1% improved daytime urinary frequency and 45.6% improved daytime urinary urgency. The frequency of urinary tract infections decreased in 56.4% of the cases. Measures of psychological well-being were also noted to be improved in a majority of patients. A total of 77.3% of the patients stated that they would recommend the program to others. CONCLUSIONS: Simple behavioral therapy without biofeedback techniques is an effective and durable first line therapy for children with daytime wetting.

The incidence of nephrolithiasis in patients with spinal neural tube defects.

PURPOSE: Bladder stones are common in patients with spinal neural tube defects but there are little data on the incidence of renal calculi in this population. We examined the incidence, nature and risk factors of nephrolithiasis in our clinic population of patients with neural tube defects. MATERIALS AND METHODS: We retrospectively reviewed the charts and radiological studies of 327 patients followed at our neural tube defects clinic with routine radiological imaging of the urinary tract. Additional confirmatory studies were performed when stones were noted. RESULTS: Renal calculi were identified in 20 patients with neural tube defects (6.1%). The incidence of nephrolithiasis increased with age. Renal stones were noted in 19 patients (10.7%) 12 years old or older. Management of the stones in these patients resulted in overall 53% stone-free and 87% recurrence rates after intervention. Major risk factors for new and/or recurrent renal stone formation were bacteriuria in 95% of the cases, lower urinary tract reconstruction in 80%, pelvicalicectasis in 70%, vesicoureteral reflux in 65%, a thoracic level spinal defect in 60% and renal scarring in 55%. CONCLUSIONS: These data suggest that there is a higher incidence of nephrolithiasis in patients with neural tube defects than in the general population and the risk of stone recurrence is also elevated. Most patients with stones had undergone lower urinary tract reconstruction. Other risk factors were bacteriuria, pelvicalicectasis, vesicoureteral reflux and a thoracic level neural tube defect.

Analysis of homeobox gene HOXA10 mutations in cryptorchidism.

PURPOSE: Cryptorchidism is the most common congenital abnormality of the genitalia. However, its exact etiology remains to be defined. Homeobox (HOX) containing genes have a key role in the morphogenesis of segmental structures along the primary body axis, including the urogenital mesenchyma. In male mice with a targeted deletion of the HOXA10 gene cryptorchidism manifests in the absence of other major defects. Because to our knowledge this gene has never been examined for alterations in humans, we evaluated whether mutations of HOXA10 are associated with cryptorchidism in humans. MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted from human blood or tissue samples from 16 noncryptorchid control subjects and 45 cryptorchid boys. To screen for mutations exons 1 and 2 of the HOXA10 gene were amplified individually by polymerase chain reaction using 6 overlapping oligonucleotide primer pairs. Single strand conformational polymorphism (SSCP) analysis of the amplified radiolabeled DNA fragments was performed. Variant band shifts were detected due to abnormal migration of the denatured DNA fragment compared to controls, suggesting an alteration in the DNA sequence. Sequence analysis of these variant bands was then done to define any mutations. RESULTS: SSCP analysis revealed variants in 2 controls. Of the 45 samples from cryptorchid patients 30 had SSCP variants in exon 1. No variants were found in other regions of the gene. Sequence analysis revealed several DNA polymorphisms in exon 1 in controls and boys with cryptorchidism. Other nucleotide changes (point mutations) were noted only in exon 1 in the DNA of 5 cryptorchid patients, of whom 1 had a 24 nucleotide deletion. CONCLUSIONS: Our initial analysis of the HOXA10 gene in humans demonstrates that genetic alterations of this gene may be present in some boys with cryptorchidism. HOXA10 polymorphisms exist in normal control subjects as well as in cryptorchid patients. Further analysis of the function of the mutated protein will elucidate the role of this gene as a potential causative factor of testicular descent.

Insights into causes of sexual ambiguity.

Our understanding of the causes of sexual ambiguity has progressed from the determination of the hormonal etiologies to defining the genetic basis of intersex disorders. The localization of specific genes involved in the process of sexual differentiation has made it possible to determine the mutations and other molecular events that result in sexual ambiguity. With this information, some disorders can now be diagnosed before birth and possibly even treated in utero.

Androgen receptor gene alterations are not associated with isolated cryptorchidism.

PURPOSE: Multiple theories of testicular descent exist but there is no consensus. Cryptorchidism is a component of the androgen insensitivity syndrome, suggesting that testicular descent may be at least partially under the control of androgenic stimulation. To determine whether isolated cryptorchidism may be caused by androgen insensitivity, we screened a population of boys with isolated cryptorchidism for the presence of androgen receptor gene alterations. MATERIALS AND METHODS: Deoxyribonucleic acid (DNA) was isolated from tissue collected from 21 patients with isolated cryptorchidism during orchiopexy. Patient selection was biased to maximize the likelihood of detection of a genetic etiology of cryptorchidism. The DNA was screened for androgen receptor gene alterations in exons 2 to 8 using single strand conformational polymorphism analysis. RESULTS: No abnormalities in the androgen receptor gene were detected by single strand conformational polymorphism analysis in any patient. CONCLUSIONS: Mutations of the androgen receptor gene in the hormone and DNA binding domains of the protein appear to be an unlikely cause of isolated cryptorchidism.

Outcome based comparison of surgical approaches for pediatric pyeloplasty: dorsal lumbar versus flank incision.

PURPOSE: Dismembered pyeloplasty for the correction of ureteropelvic junction obstruction can be performed through a flank or dorsal lumbar incision. We compared the records of children who had undergone pyeloplasty by each approach to determine if 1 technique was more advantageous. MATERIALS AND METHODS: We retrospectively reviewed the records of 33 consecutive children undergoing simple dismembered pyeloplasty by a single pediatric urologist from 1992 to 1996. The flank approach was used exclusively in the first group of patients who underwent repair in 1992 to 1993 and the dorsal lumbar incision was used exclusively in the second group after 1993. Data were obtained from hospital and clinic records, and both groups were compared with the 2-tailed t test. RESULTS: Pyeloplasty was done by dorsal lumbar incision in 16 cases and via the flank approach in 17. One patient in each group had undergone simultaneous bilateral pyeloplasties. Although overall comparison of both groups revealed no differences in operative time, in children older than 1 year pyeloplasty through a dorsal lumbar incision (108.5 minutes) was statistically significantly faster than the flank approach (144.4 minutes). Hospital stay was approximately 2 days shorter in infants who had a dorsal lumbar (25.7 hours) versus a flank incision (73 hours), and this difference did reach statistical significance if the bilateral pyeloplasty patients were excluded. Hospital costs were less for the dorsal lumbar group but the difference was not statistically significant. Success and complication rates were similar between groups with 2 patients in each group requiring additional procedures. Review of other series of repair of ureteropelvic junction obstruction demonstrated that the dorsal lumbar repair had equivalent or shorter operative times and lengths of hospitalization compared to newer endoscopic methods, and the outcomes were superior. CONCLUSIONS: The dorsal lumbar incision is a safe and efficacious approach to pyeloplasty and may be more cost-effective. In our series it was significantly faster in patients older than 1 year and resulted in shorter hospital stays in those younger than 1 year old.

Current concepts in the biology and management of Wilms tumor.

PURPOSE: There have been a number of advances that have increased our understanding of the biology of Wilms tumor during the last decade. This information is now being incorporated into current pediatric oncology protocols. We present a summary of these advances and outline the current treatment of Wilms tumor. MATERIALS AND METHODS: The medical literature was reviewed with an emphasis on the molecular biology of Wilms tumor. RESULTS: The development of Wilms tumor involves several genes, including WT1, the Wilms tumor suppressor gene at 11p13. In addition, certain chromosomal regions (16q and 1p) might be used as prognostic factors for determining the intensity of therapy. CONCLUSIONS: Future protocols conducted by pediatric oncology groups will incorporate biological studies. The goal is to identify patients at low risk for relapse which will allow a reduction in treatment intensity and subsequent toxicity. Children at an increased risk for relapse can be selected for more intensive treatment.

Laparoscopic management of persistent Müllerian duct remnants associated with an abdominal testis.

In recent years, laparoscopy has evolved from a purely diagnostic procedure in the management of nonpalpable testis to a definitive therapeutic intervention. Additional genital malformations occur in association with cryptorchidism, but reports of laparoscopic management of such entities do not exist. Herein, we describe the laparoscopic removal of persistent Müllerian duct remnants (uterus and round ligament) in combination with an orchiectomy of an abnormally small abdominal testis. This technique expands the versatility of laparoscopic management of cryptorchidism to include the resection of associated congenital anomalies.

Comparison of onlay and tubularized island flaps of inner preputial skin for the repair of proximal hypospadias.

PURPOSE: Transverse island flaps of inner preputial skin have provided a reliable technique for the repair of proximal hypospadias. The flap may be used to create a neourethra by tubularizing the flap after urethral transection or applying the flap as an onlay patch onto an intact urethral plate. We retrospectively analyzed our experience with these 2 techniques to compare outcomes. MATERIALS AND METHODS: During 11 years 132 patients underwent hypospadias repair by a single surgeon using an onlay (58) or tubularized (74) island flap technique. Surgical results were reviewed retrospectively. RESULTS: At a mean followup of 20.3 months the overall complication rate was 36% for tubularized and 31% for onlay repair, and fistula rates were 14 and 17%, respectively. Despite similar fistula rates tubularized repairs tended to have larger fistulas that required more complex repair (p = 0.0147). In 9 patients who underwent tubularize repair diverticula developed, whereas no diverticula developed after onlay repair (p = 0.0162). The rates of urethral stricture, wound infection, residual chordee and cosmetic complications were not statistically significantly different between repairs. The use of double faced repair in 30 patients provided no difference in outcome in comparison to the overall study cohort. CONCLUSIONS: Hypospadias repair using transverse island flaps offers reliable and durable outcomes. While overall complication rates were not greatly different between tubularized and onlay flap repairs, onlay repair tended to result in fistulas of smaller size and diverticula did not develop.

A renal size nomogram for the patient with myelomeningocele.

PURPOSE: Renal anatomy and function are usually monitored in the myelomeningocele population using routine ultrasound as the child grows. Clinical questions arise when a renal unit is of marginal size when evaluated with nomograms derived from normal patient populations. Our goal was to construct a renal size nomogram using ultrasound for the myelomeningocele population to help the clinician identify abnormal growth. MATERIALS AND METHODS: We reviewed the charts and radiological files of 96 patients with myelomeningocele followed at our institution. Images of 930 renal units were included to construct the nomogram. Patients were excluded from study due to hydronephrosis or hydroureter, solitary kidney, recurrent symptomatic urinary tract infection, vesicoureteral reflux, reconstructive surgery or known high bladder storage pressure. RESULTS: A renal size nomogram was constructed by plotting patient age against maximal renal length on real-time ultrasound. Expected mean and standard deviations were calculated for each age group. CONCLUSIONS: Previous studies using excretory urography have shown that kidneys in the myelomeningocele population are smaller than in a healthy control population. Ultrasound is now the modality most commonly used to monitor renal anatomy. The creation of a renal nomogram based on ultrasound should help the clinician identify abnormal renal growth more accurately.

Molecular biology and function of the androgen receptor in genital development.

PURPOSE: The rapidly growing field of molecular biology has caused exponential growth in our knowledge of the processes of embryogenesis. Since the cloning of the androgen receptor gene in 1988, investigators have been able to clarify many of the molecular events of male sexual differentiation that are mediated through the androgen receptor. We reviewed the current state of knowledge of the androgen receptor and its role in male genital development. MATERIALS AND METHODS: An intensive literature search was conducted to review reports on the androgen receptor and sexual differentiation since 1988. This review also includes ongoing research from our laboratory on the role of the androgen receptor in human genital development, as well as collaboration with other investigators. RESULTS: We reviewed the basic molecular biology of androgenic action mediated through the androgen receptor. This information has been integrated into the current understanding of human male sexual differentiation to clarify how androgens virilize the undifferentiated embryo. Defects in function of the androgen receptor may be manifested as a spectrum of phenotypes of the androgen insensitivity syndrome, and these phenotypes of male pseudohermaphroditism have been reviewed on a clinical and molecular basis. New molecular techniques have augmented the evaluation and diagnosis of the androgen insensitivity syndrome, and some groups have successfully diagnosed the condition prenatally. CONCLUSIONS: Basic scientific research of androgen receptor function and its role in male sexual development has provided a clearer understanding of the mechanisms responsible for the spectrum of defects secondary to the androgen insensitivity syndrome. This knowledge will enable clinicians to offer more accurate diagnosis and insightful counseling to affected patients and their families.

Renal ultrasound changes after pyeloplasty in children with ureteropelvic junction obstruction: long-term outcome in 47 renal units.

PURPOSE: We evaluated the use of renal ultrasound for monitoring pyelocaliectasis after pyeloplasty in children. MATERIALS AND METHODS: Changes in pyelocaliceal dilatation following pyeloplasty were assessed by serial ultrasound. Of 104 children 0 to 12 years old who underwent pyeloplasty between 1982 and 1992, 44 (47 renal units) were monitored with serial ultrasound for at least 2 years (range 2 to 9, mean 3.8). Patient ages at pyeloplasty were 0 to 3 months (17), 4 to 12 months (8), 1 to 6 years (13) and 7 to 12 years (6). Preoperative and postoperative ultrasound was reviewed by a single pediatric radiologist blinded to the date of surgery. The degree of pyelocaliectasis was graded as 0 to 4 according to the classification of the Society for Fetal Urology. RESULTS: Preoperative ultrasound revealed grade 4 pyelocaliectasis in 26 kidneys (55%) and grade 3 disease in 21 (45%). Grade was the same or worse 1 month after pyeloplasty in the majority of kidneys (92%) studied at this interval. Of the 47 renal units assessed 43 (91%) showed improvement in pyelocaliectasis during postoperative followup. Only 38% of the kidneys improved during the first 6 months of followup, while 81% were improved 2 years postoperatively. Improvement to grade 0 or 1 dilatation occurred in only 9 kidneys (19%). The rate of resolution of pyelocaliectasis was not related to preoperative grade or patient age at pyeloplasty. CONCLUSIONS: Improvement on renal ultrasound after pyeloplasty appears to be gradual. Less than half of the patients had improvement in the initial 6 months after pyeloplasty and pyelocaliectasis rarely resolved completely. While renal ultrasound can provide an accurate and cost-effective means of monitoring children on a long-term basis after pyeloplasty, sonographic evaluation in the early postoperative period commonly shows increased or unchanged pyelocaliectasis.

Androgen receptor gene mutations are rarely associated with isolated penile hypospadias.

PURPOSE: Hypospadias has no known single etiology but it has been linked to androgen insensitivity caused by mutations of the androgen receptor gene. The purpose of this study was to search for such mutations in cases of various degrees of isolated hypospadias to determine whether such an association exists and, if so, with any particular anatomical subgroup. MATERIALS AND METHODS: Isolated deoxyribonucleic acid from the penile tissue of 40 patients undergoing reconstructive surgery was screened for mutations of the coding regions of the androgen receptor gene using single strand conformational polymorphism analysis. In cases with abnormal single strand conformational polymorphism findings sequence analysis of the deoxyribonucleic acid was performed to define the mutation. RESULTS: A missense mutation of exon 2 of the androgen receptor gene was noted in 1 patient with isolated distal penile shaft hypospadias. Sequence analysis revealed that the mutation changed amino acid residue 546 from proline to serine. No abnormalities were detected in the other 39 patients. CONCLUSIONS: Isolated distal shaft hypospadias is associated with mutations of the androgen receptor gene but these mutations appear to be a rare cause of hypospadias.