Emergence of the natural history of Myhre syndrome: 47 patients evaluated in the Massachusetts General Hospital Myhre Syndrome Clinic (2016-2023).

Myhre syndrome is an increasingly diagnosed ultrarare condition caused by recurrent germline autosomal dominant de novo variants in SMAD4. Detailed multispecialty evaluations performed at the Massachusetts General Hospital (MGH) Myhre Syndrome Clinic (2016-2023) and by collaborating specialists have facilitated deep phenotyping, genotyping and natural history analysis. Of 47 patients (four previously reported), most (81%) patients returned to MGH at least once. For patients followed for at least 5 years, symptom progression was observed in all. 55% were female and 9% were older than 18 years at diagnosis. Pathogenic variants in SMAD4 involved protein residues p.Ile500Val (49%), p.Ile500Thr (11%), p.Ile500Leu (2%), and p.Arg496Cys (38%). Individuals with the SMAD4 variant p.Arg496Cys were less likely to have hearing loss, growth restriction, and aortic hypoplasia than the other variant groups. Those with the p.Ile500Thr variant had moderate/severe aortic hypoplasia in three patients (60%), however, the small number (n = 5) prevented statistical comparison with the other variants. Two deaths reported in this cohort involved complex cardiovascular disease and airway stenosis, respectively. We provide a foundation for ongoing natural history studies and emphasize the need for evidence-based guidelines in anticipation of disease-specific therapies.

Prolonged urinary retention can and does occur after any type of ureteral reimplantantion.

OBJECTIVE: Transient urinary retention has been recognized as a complication of bilateral ureteroneocystostomy (UNC), when performed extravesically. The objective of this study was to review a collective surgeons' experiences of unilateral extra- and unilateral and/or bilateral intra-vesical ureteral reimplanation, where urinary retention greater than 6 weeks, or what we have termed, "prolonged urinary retention" (PUR), occurred. MATERIALS AND METHODS: We retrospectively reviewed charts to identify PUR after any open or robotic reimplant, other than bilateral extravesical, between 1998 and 2015 as reported by five surgeons. RESULTS: During the review period, ten cases were documented where PUR was encountered. Bilateral Cohen reimplants (5), unilateral extravesical open reimplant with ureteral tapering (3), unilateral Cohen reimplant (1) and unilateral extravesical robotic reimplant with tapering (1) were associated with PUR. Younger males predominated (70%). The mean age at operation of the patients was 3.1 years. Eventually 7/10 patients were able to void normally, with periods ranging from 6 weeks to 8 years. The remaining three patients are still unable to void more than 5 years after UNC. A majority of the samples (6/10) were suspected to have bowel and bladder dysfunction (BBD), but neurologically all were normal. CONCLUSION: PUR can occur as a potential complication following any type of UNC and is associated with the risk of significant morbidity, including permanent urinary retention. Patients and caregivers should be counseled accordingly.

Treatment patterns, testicular loss and disparities in inpatient surgical management of testicular torsion in boys: a population-based study 1998-2010.

OBJECTIVES: To examine temporal trends in inpatient testicular torsion (TT) treatment and testicular loss (TL), and to identify risk factors for TL using a large nationally representative paediatric cohort, stratified to established high prevalence TT cohorts (neonatal TT [NTT]; age <1 years) and adolescent TT (ATT; age 12-17 years). METHODS: Boys (age ≤17 years, n = 17 478) undergoing surgical exploration for TT were identified within the Nationwide Inpatient Sample (1998-2010). Temporal trends in inpatient TT management (salvage surgery vs orchiectomy) and TL were examined using estimated annual percent change methodology. Multivariable logistic regression models were used to identify risk factors for TL. RESULTS: Teaching hospitals treated 90% of boys with NTT, compared with 55% with ATT (P < 0.001). Of boys with NTT, 85% lost their testis, compared with 35% with ATT (P < 0.001). Inpatient management of NTT declined during the study period, from 7.5/100 000 children in 1998 to 3/100 000 in 2010 (estimated annual percent change -4.95%; P < 0.001). The decrease was similar but less dramatic in ATT. TL patterns did not improve. In adjusted analyses, for NTT, orchiectomy was more likely at teaching hospitals. For ATT, orchiectomy was more likely in children with comorbidities (odds ratio 5.42; P = 0.045), Medicaid coverage or self-pay (P < 0.05) and weekday presentation (P = 0.001). Regional or racial disposition was not associated with TL. CONCLUSIONS: There has been a gradual decrease in inpatient surgical treatment for both NTT and ATT, presumably as a result of increased outpatient and/or non-operative management of these children. Concerningly, TL patterns have not improved; targeted interventions such as parental and adolescent male health education may lead to timely recognition/intervention in children at-risk for ATT. We noted no regional/racial disparities in contrast to earlier studies.

National practice patterns and outcomes of pediatric nephrectomy: comparison between urology and general surgery.

PURPOSE: In adults nephrectomy is under the purview of urologists, but pediatric urologists and pediatric general surgeons perform extirpative renal surgery in children. We compared the contemporary performance and outcome of all-cause nephrectomy at pediatric hospitals as performed by pediatric urologists and pediatric general surgeons. MATERIALS AND METHODS: We queried the Pediatric Health Information System to identify patients 0 to 18 years old who were treated with nephrectomy between 2004 and 2013 by pediatric urologists and pediatric general surgeons. Data points included age, gender, severity level, mortality risk, complications and length of stay. Patients were compared by APR DRG codes 442 (kidney and urinary tract procedures for malignancy) and 443 (kidney and urinary tract procedures for nonmalignancy). RESULTS: Pediatric urologists performed more all-cause nephrectomies. While pediatric urologists were more likely to operate on patients with benign renal disease, pediatric general surgeons were more likely to operate on children with malignancy. Patients on whom pediatric general surgeons operated had a higher average severity level and were at greater risk for mortality. After controlling for differences patients without malignancy operated on by pediatric urologists had a shorter length of stay, and fewer medical and surgical complications. There was no difference in length of stay, or medical or surgical complications in patients with malignancy. CONCLUSIONS: Overall compared to pediatric general surgeons more nephrectomies are performed by pediatric urologists. Short-term outcomes, including length of stay and complication rates, appear better in this data set in patients without malignancy who undergo nephrectomy by pediatric urologists but there is no difference in outcomes when nephrectomy is performed for malignancy.

Pediatric nephrectomy: incidence, indications and use of minimally invasive techniques.

PURPOSE: There is a paucity of knowledge regarding nephrectomy in contemporary United States pediatric populations. Usage patterns, indications and demographics of children undergoing nephrectomy are unknown. Given the significant increases in the use of minimally invasive nephrectomy in adults, we hypothesized similar trends may be seen in the pediatric population. MATERIALS AND METHODS: An estimated total of 27,615 children undergoing nephrectomy between 1998 and 2010 was extracted from the Nationwide Inpatient Sample. Trends in use were analyzed with the estimated annual percent change methodology using linear regression and proportions by chi-square. Determinants of minimally invasive nephrectomy were evaluated using generalized linear models adjusted for clustering with generalized estimating equations. RESULTS: The annual incidence of pediatric nephrectomy was 2.90 per 100,000 patient-years and remained stable. Nephrectomy was most common in children 0 to 1 year old (36%) and least common in children 6 to 9 years old (14%). However, nephrectomy for malignancy was most common in children 3 to 4 years old. Minimally invasive nephrectomy usage increased from 1.1% to 11.6% during the study period (estimated annual percent change 72.82%, p = 0.007). On multivariable analysis patients with malignancy (OR 0.07, p <0.001) had a lower rate of minimally invasive nephrectomy. Increased use was associated with increasing age (OR 1.07, p <0.001), treatment at a teaching institution (OR 1.95, p = 0.008) and increasing hospital volume (OR 1.01, p = 0.001). CONCLUSIONS: While the annual incidence of nephrectomy is stable, the use of minimally invasive nephrectomy is expanding in the pediatric population. Benign pathology and increasing age as well as nephrectomy at high volume teaching institutions are independently associated with minimally invasive nephrectomy use.

Predictors of admission in patients presenting to the emergency department with urinary tract infection.

PURPOSE: Previous studies examining the management of urinary tract infections (UTI) showed marked variability in the economical burden of care, with a tenfold increase in costs when patients require admission to the hospital. We sought to examine the patient and emergency department (ED) characteristics associated with hospitalization in patients presenting to the ED with UTI. METHODS: An estimate of 10,798,343 patients with a primary diagnosis of UTI was presented to the ED from 2006 to 2009 and was abstracted from the Nationwide Emergency Department Sample. Univariable and multivariable analyses examined patient and hospital characteristics of those admitted with UTI. RESULTS: Between 2006 and 2009, 10.8 million patients presented to the ED in the United States for the treatment of UTI and 1.8 million patients (16.7 %) were admitted to the hospital for further management. Admitted patients were older, and a higher proportion had pyelonephritis, was male, and had Medicare. Admitted patients were also more likely to be seen at urban teaching hospitals, and/or treated at zip codes with higher median incomes. Following multivariable analysis, the independent predictors of admission included pyelonephritis (OR 5.29, 95 % CI 5.23-5.35), male gender (OR 1.58, 95 % CI 1.56-1.59), and advancing age (OR 1.037, 95 % CI 1.037-1.037). CONCLUSIONS: Expansion in ED utilization for the management of UTI has exceeded previous estimates. While the preponderance of patients presenting to the ED for UTI is discharged home, 16.7 % are admitted for further management. Predictors of inpatient admission on multivariable analyses included pyelonephritis, advancing age, and male gender.

Robotic nephrolithotomy and pyelolithotomy with utilization of the robotic ultrasound probe.

INTRODUCTION: The treatment of large renal stones in children can be challenging often requiring combination therapy and multiple procedures. The purpose of this video is to describe our technique of robotic nephrolithotomy and pyelolithotomy for complex renal stone disease in children, and to demonstrate the utility of the robotic ultrasound probe to aid with stone localization. MATERIALS AND METHODS: Robotic nephrolithotomy/pyelolithotomy was carried out in four consecutive patients. A robotic ultrasound probe (Hitachi-Aloka, Tokyo, Japan) under console surgeon control was used in all cases. RESULTS: Two patients underwent robotic pyelolithotomy, one patient underwent robotic nephrolithotomy, whilst the fourth patient underwent robotic pyelolithotomy and nephrolithotomy along with Y-V pyeloplasty for concurrent ureteropelvic junction obstruction. Mean operative time, blood loss and hospital stay was 216 minutes, 37.5 mL and 2 days, respectively. The robotic ultrasound probe aided identification of calculi within the kidney in all cases. For nephroli¬thotomy it was helpful in planning the incision for nephrotomy. After nephrotomy or pyelotomy, stones were removed using a combination of robotic Maryland forceps, fenestrated grasper or Prograsp. Antegrade nephroscopy introduced through a laparoscopic port was used in all patients for confirmation of residual stone status. Two patients did not require a ureteral stent in the post-operative period. One patient had a minor complication (Clavien Grade 2 - dislodged malecot catheter). All patients were stone free at last follow-up. CONCLUSIONS: Robotic nephrolithotomy and pyelolithotomy with utilization of the robotic ultrasound probe offers a one-stop solution for complex renal stones with excellent stone-free rates.

Factor analysis of the pediatric symptom checklist in a population of children with voiding dysfunction and/or nocturnal enuresis.

The research objective was to identify the factor structure of the pediatric symptom checklist (PSC) in children with voiding dysfunction and/or nocturnal enuresis who were seen in a pediatric urology clinic. Retrospective chart reviews were conducted for 498 consecutive patients, ages 6-16, who were seen over a 13-month period. The PSC, a 35-item measure used to screen for psychosocial difficulties, was completed by the patient's caregiver. Confirmatory factor analyses using three previous models were conducted. A four factor model comprised of internalizing, externalizing, attention problems, and chronic illness factors represented the best fit to the data. Within this population, the PSC appears to capture internalizing and externalizing problems, difficulties with attention, and possible side effects of a medical condition. This information could aid clinicians in assessing adjustment difficulties within this population and concurrently allow researchers to examine whether these specific factors are related to other relevant outcomes.

Awake Combined Spinal Caudal Anesthesia for Longer-Duration Urologic Surgery in Infants: A Case Series.

Awake combined spinal caudal anesthesia has been used as an anesthetic technique for longer-duration infraumbilical surgeries in infants. Literature on the safety and feasibility of this technique is limited. We share our experience with 27 infants undergoing longer-duration urologic surgery using awake combined spinal and caudal anesthesia without the use of systemic sedatives or inhalational agents. We describe our technique, safety considerations, and details surrounding the optimal timing of caudal catheter activation for prolongation of surgical anesthesia.

Effect of metastatic site on emergency department disposition in men with metastatic prostate cancer.

INTRODUCTION: Though the prevalence of metastatic prostate cancer is decreasing, the rate of admission from the emergency department (ED) is increasing. Little is known about the implications of metastatic site on a patient's ED course and admission. MATERIALS AND METHODS: A weighted estimate of 15,367 patients with metastatic prostate cancer who presented to the ED between January 1, 2006 and December 31, 2009 was abstracted from the Nationwide Emergency Department Sample (NEDS). Descriptive statistics were used to elaborate patient and hospital characteristics of the metastatic prostate cancer population and logistic regression models were fitted to identify predictors of admission. RESULTS: The most common site of metastasis in patients with metastatic prostate cancer presenting to the ED was bone (80.6%), followed by liver (13.2%), lung (9.3) and other genitourinary sites (8.1%). Over the study period, there was an increase in prevalence of the four commonest metastatic sites, and admission rates varied between metastatic sites (83.2% for bone to 95.2% for nodal metastasis). Substantial variability in the rate of inpatient mortality was noted. Increasing age, Northeast region, increased comorbidity burden, and the presence of nodal metastases and other urinary metastases were shown to be independent predictors of hospital admission. CONCLUSIONS: The commonest metastatic site in patients presenting to United States EDs with metastatic prostate cancer between 2006 and 2009 was bone. Patients presenting with nodal metastases were most likely to be admitted. Independent predictors of hospitalization included age, Northeast region, increased comorbidities, nodal metastases and other urinary metastases.

History of recurrent urinary tract infection is not predictive of abnormality on voiding cystourethrogram.

PURPOSE: The American Academy of Pediatrics recently recommended against routine voiding cystourethrograms (VCUGs) in children 2 to 24 months with initial febrile UTI, raising concern for delayed diagnosis and increased risk of UTI-related renal damage from vesicoureteral reflux (VUR). We assessed factors potentially associated with higher likelihood of abnormal VCUG, including UTI recurrence, which could allow for more judicious test utilization. METHODS: We retrospectively reviewed all initial VCUGs performed at Children's Hospital of Michigan between January and June, 2010. History of recurrent UTI was ascertained by evidence of two or more prior positive cultures or history of "recurrent UTI" on VCUG requisition. Outcomes assessed included rates of VUR or any urologic abnormality on VCUG. RESULTS: Two hundred and sixty-two patients met inclusion criteria. VUR was detected in 21.3 %, urologic abnormality including VUR in 27.4 %. Degree of bladder distension, department of referring physician, study indication, positive documented urine culture, and history of recurrent UTI or UTI and other abnormality were all not associated with increased likelihood of VUR or any urologic abnormality on VCUG. CONCLUSION: VUR and VCUG abnormality are no more likely when performed after recurrent UTI or for UTI plus other abnormality. This reasons against postponing VCUG until after UTI recurrence, as positive findings are no more likely in this setting.

National trends and disparities in the use of minimally invasive adult pyeloplasty.

PURPOSE: Minimally invasive pyeloplasty might have several advantages compared to open pyeloplasty in the management of ureteropelvic junction obstruction. Nonetheless, minimally invasive pyeloplasty appears to be underused in North America. We examined specific patient and hospital characteristics that may be associated with these disparities. MATERIALS AND METHODS: The Nationwide Inpatient Sample was used to identify a national estimate of 29,456 patients with ureteropelvic junction obstruction treated with minimally invasive pyeloplasty (laparoscopic or robotic) and open pyeloplasty between 1998 and 2009. The rates of use of minimally invasive and open pyeloplasty were assessed according to year of surgery, and patient and hospital characteristics. The determinants of minimally invasive pyeloplasty were evaluated using logistic regression models adjusted for clustering. RESULTS: Overall 15.3% of patients underwent minimally invasive pyeloplasty between 1998 and 2009. The use of minimally invasive pyeloplasty increased remarkably during the study period from 2.4% to 55.3%, a 23-fold increase. On multivariable logistic regression analysis African-American race (OR 0.584, p = 0.015) and other insurance status (including uninsured patients, OR 0.613, p = 0.013) were associated with a lower rate of minimally invasive pyeloplasty. Patients treated at teaching (OR 1.788, p = 0.003) and/or urban (OR 4.819, p <0.001) institutions were significantly more likely to undergo minimally invasive pyeloplasty. CONCLUSIONS: In the last decade there has been a dramatic increase in the use of minimally invasive pyeloplasty in the United States and in 2009 a slight majority underwent minimally invasive pyeloplasty. Nonetheless, treatment disparities exist. African-American patients with other insurance status (including those uninsured) treated at nonteaching, rural hospitals were less likely to undergo minimally invasive pyeloplasty. Efforts should be made to understand these treatment disparities and broaden the availability of minimally invasive pyeloplasty.

Febrile urinary tract infection, vesicoureteral reflux, and renal scarring: current controversies in approach to evaluation.

The ideal approach to the radiological evaluation of children with urinary tract infection (UTI) is in a state of confusion. The conventional bottom-up approach, with its focus on the detection of upper and lower urinary tract abnormalities, including vesicoureteral reflux, has been challenged by the top-down approach, which focuses on confirming the diagnosis of acute pyelonephritis before more invasive imaging is considered. Controversies abound regarding which approach may best assess the ultimate risk for reflux-related renal scarring. Evolving practices motivated by the emerging evidence, the desire to minimize unnecessary interventions, as well as improve compliance with recommended testing, have added to the current controversies. Recent guideline updates and ongoing clinical trials hopefully will help in addressing some of these concerns.

Dietl crisis: Presentation and imaging findings in a 7-year-old boy.

Intermittent ureteropelvic junction obstruction, or Dietl crisis, is a rare entity with sparse reports in published literature. Establishing the diagnosis is challenging given its intermittent nature. We report a case of Dietl crisis, focusing on ultrasound (US) and magnetic resonance urography (MRU) findings in a 7-year-old boy with recurrent episodes of colicky abdominal pain prompting multiple visits to the emergency department. Severe left hydronephrosis was visualized on US during one episode with complete resolution on follow-up US. MRU demonstrated severe left hydronephrosis with delayed calyceal transit time, time-to-peak enhancement, and excretion. There was no aberrant blood vessel. Surgical pyeloplasty provided complete symptomatic resolution. MRU can be a valuable tool in eliciting and dynamically confirming the diagnosis of Dietl crisis.

Trimethoprim in vitro antibacterial activity is not increased by adding sulfamethoxazole for pediatric Escherichia coli urinary tract infection.

PURPOSE: The combination of trimethoprim/sulfamethoxazole is often used to treat uncomplicated urinary tract infections in children. The rationale for combining trimethoprim and sulfamethoxazole is that they may act synergistically to increase antibacterial activity. However, approximately 3% of patients show allergic reactions to sulfamethoxazole, of which some are serious (liver failure and Stevens-Johnson syndrome). We determined whether adding sulfamethoxazole is necessary to increase in vitro antibacterial activity for pediatric urinary tract infection compared to that of trimethoprim alone. MATERIALS AND METHODS: We prospectively identified 1,298 children with urinary tract infection (greater than 100,000 cfu/ml Escherichia coli) from a total of 4 American regions. In vitro susceptibility of bacterial isolates to sulfamethoxazole, trimethoprim and trimethoprim/sulfamethoxazole was determined using disk diffusion. Ampicillin susceptibility was tested at 2 sites. At 1 site all uropathogens from consecutive urinary isolates were evaluated. RESULTS: E. coli susceptibility to trimethoprim was 70%, comparable to the 70% of trimethoprim/sulfamethoxazole (p = 0.9) and higher than the 56.9% of sulfamethoxazole (p <0.05). This susceptibility pattern was without regional differences. At 2 sites susceptibility to trimethoprim was significantly higher than to ampicillin. At 1 site the susceptibility of other uropathogens to trimethoprim and trimethoprim/sulfamethoxazole was similar to that of E. coli. CONCLUSIONS: In children with urinary tract infection in vitro susceptibility to trimethoprim was comparable to that to trimethoprim/sulfamethoxazole and significantly higher than to sulfamethoxazole. This finding was similar at all sites. Adding sulfamethoxazole appears unnecessary and may represent a risk to patients. Trimethoprim can be used as an alternative to trimethoprim/sulfamethoxazole based on in vitro antibacterial susceptibility. Routine trimethoprim/sulfamethoxazole use for urinary tract infection should be carefully reevaluated.

Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis.

PURPOSE: The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to screening of siblings and offspring of index patients with vesicoureteral reflux and infants with prenatal hydronephrosis. From this evidence clinical practice guidelines are developed to manage the clinical scenarios insofar as the data permit. MATERIALS AND METHODS: The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children, clearly stating the number of children undergoing screening for vesicoureteral reflux. Vesicoureteral reflux should have been diagnosed with a cystogram and renal outcomes assessed by nuclear scintigraphy. The screening articles were extracted into data tables developed to evaluate epidemiological factors, patient and renal outcomes, and results of treatment. The reporting of meta-analysis of observational studies elaborated by the MOOSE group was followed. The extracted data were analyzed and formulated into evidence-based recommendations regarding the screening of siblings and offspring in index cases with vesicoureteral reflux and infants with prenatal hydronephrosis. RESULTS: In screened populations the prevalence of vesicoureteral reflux is 27.4% in siblings and 35.7% in offspring. Prevalence decreases at a rate of 1 screened person every 3 months of age. The prevalence is the same in males and females. Bilateral reflux prevalence is similar to unilateral reflux. Grade I-II reflux is estimated to be present in 16.7% and grade III-V reflux in 9.8% of screened patients. The estimate for renal cortical abnormalities overall is 19.3%, with 27.8% having renal damage in cohorts of symptomatic and asymptomatic children combined. In asymptomatic siblings only the rate of renal damage is 14.4%. There are presently no randomized, controlled trials of treated vs untreated screened siblings with vesicoureteral reflux to evaluate health outcomes as spontaneous resolution, decreased rates of urinary infection, pyelonephritis or renal scarring. In screened populations with prenatal hydronephrosis the prevalence of vesicoureteral reflux is 16.2%. Reflux in the contralateral nondilated kidney accounted for a mean of 25.2% of detected cases for a mean prevalence of 4.1%. In patients with a normal postnatal renal ultrasound the prevalence of reflux is 17%. The prenatal anteroposterior renal pelvic diameter was not predictive of reflux prevalence. A diameter of 4 mm is associated with a 10% to 20% prevalence of vesicoureteral reflux. The prevalence of reflux is statistically significantly greater in females (23%) than males (16%) (p=0.022). Reflux grade distribution is approximately a third each for grades I-II, III and IV-V. The estimate of renal damage in screened infants without infection is 21.8%. When stratified by reflux grade renal damage was estimated to be present in 6.2% grade I-III and 47.9% grade IV-V (p <0.0001). The risk of urinary tract infection in patients with and without prenatal hydronephrosis and vesicoureteral reflux could not be determined. The incidence of reported urinary tract infection in patients with reflux was 4.2%. CONCLUSIONS: The meta-analysis provided meaningful information regarding screening for vesicoureteral reflux. However, the lack of randomized clinical trials for screened patients to assess clinical health outcomes has made evidence-based guideline recommendations difficult. Consequently, screening guidelines are based on present practice, risk assessment, meta-analysis results and Panel consensus.

Summary of the AUA Guideline on Management of Primary Vesicoureteral Reflux in Children.

PURPOSE: The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to children with diagnosed reflux including those young or older than 1 year without evidence of bladder and bowel dysfunction and those older than 1 year with evidence of bladder and bowel dysfunction. From this evidence clinical practice guidelines were developed to manage the clinical scenarios insofar as the data permit. MATERIALS AND METHODS: The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children with vesicoureteral reflux and a defined care program that permitted identification of cohort specific clinical outcomes. The reporting of meta-analysis of observational studies elaborated by the MOOSE (Meta-analysis Of Observational Studies in Epidemiology) group was followed. The extracted data were analyzed and formulated into evidence-based recommendations. RESULTS: A total of 2,028 articles were reviewed and data were extracted from 131 articles. Data from 17,972 patients were included in this analysis. This systematic meta-analysis identified increasing frequency of urinary tract infection, increasing grade of vesicoureteral reflux and presence of bladder and bowel dysfunction as unique risk factors for renal cortical scarring. The efficacy of continuous antibiotic prophylaxis could not be established with current data. However, its purported lack of efficacy, as reported in selected prospective clinical trials, also is unproven owing to significant limitations in these studies. Reflux resolution and endoscopic surgical success rates are dependent upon bladder and bowel dysfunction. The Panel then structured guidelines for clinical vesicoureteral reflux management based on the goals of minimizing the risk of acute infection and renal injury, while minimizing the morbidity of testing and management. These guidelines are specific to children based on age as well as the presence of bladder and bowel dysfunction. Recommendations for long-term followup based on risk level are also included. CONCLUSIONS: Using a structured, formal meta-analytic technique with rigorous data selection, conditioning and quality assessment, we attempted to structure clinically relevant guidelines for managing vesicoureteral reflux in children. The lack of robust prospective randomized controlled trials limits the strength of these guidelines but they can serve to provide a framework for practice and set boundaries for safe and effective practice. As new data emerge, these guidelines will necessarily evolve.

Cryptorchidism and testicular cancer: separating fact from fiction.

PURPOSE: We dissected prevailing assumptions about cryptorchidism and reviewed data that support and reject these assumptions. MATERIALS AND METHODS: Five questions about cryptorchidism and the risk of testicular cancer were identified because of their implications in parent counseling and clinical management. Standard search techniques through MEDLINE were used to identify all relevant English language studies of the questions being examined. Each of the 5 questions was then examined in light of the existing data. RESULTS: The RR of testicular cancer in a cryptorchidism case is 2.75 to 8. A RR of between 2 and 3 has been noted in patients who undergo orchiopexy by ages 10 to 12 years. Patients who undergo orchiopexy after age 12 years or no orchiopexy are 2 to 6 times as likely to have testicular cancer as those who undergo prepubertal orchiopexy. A contralateral, normally descended testis in a patient with cryptorchidism carries no increased risk of testis cancer. Persistently cryptorchid (inguinal and abdominal) testes are at higher risk for seminoma (74%), while corrected cryptorchid or scrotal testicles that undergo malignant transformation are most likely to become nonseminomatous (63%, p <0.0001), presumably because of a decreased risk of seminoma. CONCLUSIONS: Orchiectomy may be considered in healthy patients with cryptorchidism who are between ages 12 and 50 years. Observation should be recommended in postpubertal males at significant anesthetic risk and all males older than 50 years. While 5% to 15% of scrotal testicular remnants contain germinal tissue, only 1 case of carcinoma in situ has been reported, suggesting that the risk of malignancy in these remnants is extremely low.