The prognostic value of testicular microlithiasis as an incidental finding for the risk of testicular malignancy in children and the adult population: A systematic review. On behalf of the EAU pediatric urology guidelines panel.

INTRODUCTION: The exact correlation of testicular microlithiasis (TM) with benign and malignant conditions remains unknown, especially in the paediatric population. The potential association of TM with testicular malignancy in adulthood has led to controversy regarding management and follow-up. OBJECTIVE: To determine the prognostic importance of TM in children in correlation to the risk of testicular malignancy or infertility and compare the differences between the paediatric and adult population. STUDY DESIGN: We performed a literature review of the Medline, Embase and Cochrane controlled trials databases until November 2020 according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) Statement. Twenty-six publications were included in the analysis. RESULTS: During the follow-up of 595 children with TM only one patient with TM developed a testicular malignancy during puberty. In the other 594 no testicular malignancy was found, even in the presence of risk factors. In the adult population, an increased risk for testicular malignancy in the presence of TM was found in patients with history of cryptorchidism (6% vs 0%), testicular malignancy (22% vs 2%) or sub/infertility (11-23% vs 1.7%) compared to TM-free. The difference between paediatric and adult population might be explained by the short duration of follow-up, varying between six months and three years. With an average age at inclusion of 10 years and testicular malignancies are expected to develop from puberty on, testicular malignancies might not yet have developed. CONCLUSION: TM is a common incidental finding that does not seem to be associated with testicular malignancy during childhood, but in the presence of risk factors is associated with testicular malignancy in the adult population. Routine monthly self-examination of the testes is recommended in children with contributing risk factors from puberty onwards. When TM is still present during transition to adulthood a more intensive follow-up could be considered.

EAU-ESPU pediatric urology guidelines on testicular tumors in prepubertal boys.

BACKGROUND: Testicular tumors in prepubertal boys account for 1-2% of all solid pediatric tumors. They have a lower incidence, a different histologic distribution and are more often benign compared to testicular tumors in the adolescent and adult group. This fundamental difference should also lead to a different approach and treatment. OBJECTIVE: To provide a guideline for diagnosis and treatment options in prepubertal boys with a testicular mass. METHOD: A structured literature search and review for testicular tumors in prepubertal boys was performed. All English abstracts up to the end of 2019 were screened, and relevant papers were obtained to create the guideline. RESULTS: A painless scrotal mass is the most common clinical presentation. For evaluation, high resolution ultrasound has a detection rate of almost 100%, alpha-fetoprotein is a tumor marker, however, is age dependent. Human chorionic gonadotropin (HCG) was not a tumor marker for testis tumors in prepubertal boys. CONCLUSION: Based on a summary of the literature on prepubertal testis tumors, the 2021 EAU guidelines on Pediatric Urology recommend a partial orchiectomy as the primary approach in tumors with a favorable preoperative ultrasound diagnosis.

Update of the EAU/ESPU guidelines on urinary tract infections in children.

INTRODUCTION/BACKGROUND: Urinary tract infections (UTIs) are common in children and require appropriate diagnostic evaluation, management and follow-up. OBJECTIVE: To provide a summary of the updated European Association of Urology (EAU) guidelines on Pediatric Urology, which were first published in 2015 in European Urology. STUDY DESIGN: A structured literature review was performed of new publications between 2015 and 2020 for UTIs in children. The guideline was updated accordingly with relevant new literature. RESULTS: The occurrence of a UTI can be the first indication of anatomical abnormalities in the urinary tract, especially in patients with a febrile UTI. The basic diagnostic evaluation should include sufficient investigations to exclude urinary tract abnormalities, but should also be as minimally invasive as possible. In recent years, more risk factors have been identified to predict the presence of these anatomical anomalies, such as a non-E. Coli infection, high grade fever and ultrasound abnormalities. When these risk factors are factored into the diagnostic work-up, some invasive investigations can be omitted in a larger group of children. In addition to the treatment of active UTIs, it is also essential to prevent recurrent UTIs and consequent renal scarring. With the increase of antimicrobial resistance good antibiotic stewardship is needed. In addition, alternative preventative measures such as dietary supplements, bladder and bowel management and antibiotic prophylaxis could decrease the incidence of recurrent UTI. CONCLUSION: This paper is a summary of the updated 2021 EAU guidelines on Pediatric Urology. It provides practical considerations and flowcharts for the management and diagnostic evaluation of UTIs in children.

Efficacy of transcutaneous posterior tibial nerve stimulation in children with functional voiding disorders.

AIMS: To assess the efficacy of transcutaneous posterior tibial nerve stimulation (TPTNS) on functional voiding disorder (FVD) and investigate the utility of urine biomarkers (UBs: nerve growth factor, transforming growth factor-beta 1, and tissue inhibitor of metalloproteinases 2) in diagnosis and follow-up. METHODS: A total of 44 children were included to this randomized controlled trial prospectively. After randomization, 20 of 30 children with storage phase dysfunction those were unresponsive or noncompliant to medical treatment received TPTNS treatment (test group) and 10 children underwent TPTNS with no current (sham group) for 12 weeks. Fourteen healthy children constituted the nonsymptomatic group. UB levels, dysfunctional voiding and incontinence scoring system (DVISS), voiding diary, and quality of life (QoL) scores were assessed before and after treatment in the treatment groups. RESULTS: QoL scores, overall and day-time DVISS scores were significantly decreased in both sham and test groups (p < 0.05). In addition to these findings, the frequency of incontinence and urgency episodes were also significantly reduced (p < 0.05) in the TPTNS treatment group. This effect in the test group was still valid 2 years after intervention. There was no significant difference in UBs measurements between treatment and nonsymptomatic groups and between pretreatment and posttreatment measurements of test and sham groups. CONCLUSIONS: TPTNS is an efficient minimally invasive treatment in children with FVD who do not respond to medical treatment. TPTNS provides a significant improvement on episodes of frequency, episodes of incontinence, overall and day-time DVISS scores, and QoL scores. The effectiveness of treatment continues even at the end of the second year of intervention. UBs were not found to be predictive in terms of diagnosis and evaluating the treatment response.

Determinants of outcomes in chronic pediatric peritoneal dialysis: a single center experience.

BACKGROUND: In situations where it may take a long time to perform renal transplantation peritoneal dialysis may become a long-term maintenance treatment, especially in countries with low donor rates. Therefore, we aimed to evaluate peritonitis, catheter revision and survival rates in children on chronic peritoneal dialysis (CPD); and to define related factors in a single tertiary center from a WHO upper middle income country. METHODS: Between January 1998 and September 2018, data of pediatric patients receiving CPD with a followup longer than 3 months were retrospectively analyzed. Demographic, clinical and catheter-related data were collected. Patients were grouped as being operated before/after 2009 in order to evaluate the effects of 2 different periods on outcomes. RESULTS: A total of 229 catheters in 132 patients were included in the study. The female to male ratio was 60/72. The mean age at the time of dialysis was 8.9 ± 5.5 years. The median follow-up period was 22.5 months (IQR 8.25-50; range 3-139). Peritonitis incidence in 1998-2008 and 2009-2018 periods was 0.13 episodes/patient-year and 0.09 episodes/ patient-year, respectively. The overall revision rate was 1 per 46.7 patient-months. Peritonitis history was the only independent risk factor for access revision (p=0.003). Peritoneal dialysis failure was observed in 25% (33/132) of patients. The need for catheter revision due to any cause, the presence of peritonitis, history of HD and infancy were independent risk factors for PD failure. The overall mortality rate was 15.2%(20/132). Having a history of temporary PD catheter placement and being infant were independent risk factors for mortality. CONCLUSIONS: Access revision is still an important complication leading to PD failure despite the development of surgical techniques. Peritonitis is the most important cause of access revision and PD failure.

EAU/ESPU guidelines on the management of neurogenic bladder in children and adolescent part II operative management.

BACKGROUND: Treatment in children and adolescents with a neurogenic bladder is primarily conservative with the goal of preserving the upper urinary tract combined with a good reservoir function of the bladder. However, sometimes-even in childhood-conservative management does not prevent the development of a low-compliant bladder or overactive detrusor. MATERIAL & METHODS: After a systematic literature review covering the period 2000-2017, the ESPU/EUAU guideline for neurogenic bladder underwent an update. RESULTS: In these patients, surgical interventions such as botulinum toxin A injections into the detrusor muscle, bladder augmentation, and even urinary diversion may become necessary to preserve the function of the upper (and lower) urinary tracts. The creation of a continent catheterizable channel should be offered to patients with difficulties performing transurethral clean intermittent catheterization. However, a revision rate of up to 50% needs to be considered. With increasing age continence of urine and stool becomes progressively more important. In patients with persistent weak bladder outlets, complete continence can be achieved only by surgical interventions creating a higher resistance/obstruction at the level of the bladder outlet with a success rate of up to 80%. In some patients, bladder neck closure and the creation of a continent catheterizable stoma is an option. CONCLUSION: In all these patients close follow-up is mandatory to detect surgical complications and metabolic consequences early.

EAU/ESPU guidelines on the management of neurogenic bladder in children and adolescent part I diagnostics and conservative treatment.

BACKGROUND: In childhood, the most common reason for a neurogenic bladder is related to spinal dysraphism, mostly myelodysplasia. AIMS: Herein, we present the EAU/ESPU guidelines in respect to the diagnostics, timetable for investigations and conservative management including clean intermittent catheterization (CIC). MATERIAL AND METHODS: After a systematic literature review covering the period 2000 to 2017, the ESPU/EUAU guideline for neurogenic bladder underwent an update. RESULTS: The EAU/ESPU guideline panel advocates a proactive approach. In newborns with spina bifida, CIC should be started as soon as possible after birth. In those with intrauterine closure of the defect, urodynamic studies are recommended be performed before the patient leaves the hospital. In those with closure after birth urodynamics should be done within the next 3 months. Anticholinergic medication (oxybutynin is the only well-investigated drug in this age group-dosage 0.2-0.4 mg/kg weight per day) should be applied, if the urodynamic study confirmed detrusor overactivity. Close follow-up including ultrasound, bladder diary, urinalysis, and urodynamics are necessary within the first 6 years and after that the time intervals can be prolonged, depending on the individual risk and clinical course. In all other children with the suspicion of a neurogenic bladder due to various reasons as tethered cord, inflammation, tumors, trauma, or other reasons as well as those with anorectal malformations, urodynamics-preferable video-urodynamics, should be carried out as soon as there is a suspicion of a neurogenic bladder and conservative treatment should be started soon after confirmation of the diagnosis of neurogenic bladder. With conservative treatment the upper urinary tract is preserved in up to 90%, urinary tract infections are common, but not severe, complications of CIC are quite rare and continence can be achieved at adolescence in up to 80% without further treatment. DISCUSSION AND CONCLUSIONS: The transition into adulthood is a complicated time for both patients, their caregivers and doctors, as the patient wants to become independent from caregivers and treatment compliance is reduced. Also, transition to adult clinics for patients with neurogenic bladders is often not well-established.

Are EAU/ESPU pediatric urology guideline recommendations on neurogenic bladder well received by the patients? Results of a survey on awareness in spina bifida patients and caregivers.

AIMS: The Paediatric Urology Guidelines Panel reports initial experience with patient involvement in spina bifida patient groups to gather information on their awareness of the guidelines and reflection of guideline recommendations. METHODS: The survey was delivered to spina bifida patients/parents via the national society groups in Turkey, Germany, and The Netherlands. Questions included demographic features, medical status, awareness, and agreement on the recommendations given in the guidelines and future expectations. RESULTS: A total of 291 patients from 3 countries responded to the survey. Mean age was 13.9 ± 12.2 years, male/female ratio 138/151, 75% of all surveys were completed by the caregivers. The medication was taken by 78% of patients (64% anticholinergics). Complete dryness rates for urine and stool were 24% and 47%, respectively. The agreement rates on the recommendations regarding urodynamics, intermittent catheterization, anticholinergics drug use, bowel management, and life-long follow-up were 97%, 82%, 91%, 77%, and 98%, respectively. Only 8% of responders were aware of the European Association of Urology/European Society for Pediatric Urology guidelines. The priorities of patients for future expectations were as the following: quality of life (QoL), surgical techniques, development of new medications and sexuality/fertility issues. Male spina bifida patients preferred new medications and sex/fertility issues more, whereas females favored QoL issues improvement more. CONCLUSIONS: Although the native language of the involved patients was different from English, awareness of guidelines was 8%. The general approval of the recommendations given in the guidelines is quite high. The national society groups showed a great interest to get involved in the creation of the guidelines to improve health care for spina bifida patients.

Management of undescended testes: European Association of Urology/European Society for Paediatric Urology Guidelines.

CONTEXT: Undescended testis is the most common endocrinological disease in the male newborn period. Incidence varies between 1.0% and 4.6% in full-term neonates, with rates as high as 45% in preterm neonates. Failure or delay of treatment can result in reduced fertility and/or increased testicular cancer risk in adulthood. OBJECTIVE: To provide recommendations for the diagnosis and treatment of boys with undescended testes which reduce the risk of impaired fertility and testicular cancer in adulthood. EVIDENCE ACQUISITION: Embase and Pubmed were searched for all relevant publications, from 1990 to 2015 limited to English language. Data were narratively synthesized in light of methodological and clinical heterogeneity. The risk of bias of each included study was assessed. EVIDENCE SYNTHESIS: There is consensus that early treatment, by 18 months at the latest, for undescended testes is mandatory to avoid possible sequelae regarding fertility potential and cancer risk. The current standard therapy is orchidopexy, while hormonal therapy is still under debate. However, in some individuals the successful scrotal placement of previously undescended testes may not prevent potential negative long-term outcomes regarding fertility and testicular malignancy. CONCLUSIONS: There is good evidence for early placement of undescended testes in the scrotal position to prevent potential impairment of fertility and reduce the risk of testicular malignancy. No consensus exists on the various forms of hormonal treatment, which are assessed on an individual basis.

Urinary tract infections in children: EAU/ESPU guidelines.

CONTEXT: In 30% of children with urinary tract anomalies, urinary tract infection (UTI) can be the first sign. Failure to identify patients at risk can result in damage to the upper urinary tract. OBJECTIVE: To provide recommendations for the diagnosis, treatment, and imaging of children presenting with UTI. EVIDENCE ACQUISITION: The recommendations were developed after a review of the literature and a search of PubMed and Embase. A consensus decision was adopted when evidence was low. EVIDENCE SYNTHESIS: UTIs are classified according to site, episode, symptoms, and complicating factors. For acute treatment, site and severity are the most important. Urine sampling by suprapubic aspiration or catheterisation has a low contamination rate and confirms UTI. Using a plastic bag to collect urine, a UTI can only be excluded if the dipstick is negative for both leukocyte esterase and nitrite or microscopic analysis is negative for both pyuria and bacteriuria. A clean voided midstream urine sample after cleaning the external genitalia has good diagnostic accuracy in toilet-trained children. In children with febrile UTI, antibiotic treatment should be initiated as soon as possible to eradicate infection, prevent bacteraemia, improve outcome, and reduce the likelihood of renal involvement. Ultrasound of the urinary tract is advised to exclude obstructive uropathy. Depending on sex, age, and clinical presentation, vesicoureteral reflux should be excluded. Antibacterial prophylaxis is beneficial. In toilet-trained children, bladder and bowel dysfunction needs to be excluded. CONCLUSIONS: The level of evidence is high for the diagnosis of UTI and treatment in children but not for imaging to identify patients at risk for upper urinary tract damage. PATIENT SUMMARY: In these guidelines, we looked at the diagnosis, treatment, and imaging of children with urinary tract infection. There are strong recommendations on diagnosis and treatment; we also advise exclusion of obstructive uropathy within 24h and later vesicoureteral reflux, if indicated.

Treatment of retrocaval ureter by pure laparoscopic pyelopyelostomy: experience on 4 patients.

OBJECTIVES: To present our experience and the feasibility of pure laparoscopic pyelopyelostomy for treatment of retrocaval ureter (RCU). METHODS: RCU was detected in 4 male (ages: 4, 16, 36, 48) patients, with complaints of flank pain. In all the patients, Type 1 RCU was present and the right ureter was involved. All patients underwent intraoperative retrograde pyelography before laparoscopy. The patients were operated upon using the transperitoneal approach in the lateral decubitis position, with two 10 mm and two 5 mm ports. After the ureter was released from the superior and inferior parts of the inferior vena cava, the dilated renal pelvis was transected and the ureter was brought in an anterolateral position to the vena cava. After the completion of the posterior wall anastomosis of pyelopyelostomy with 4-0 polyglactin sutures in a continuous manner, a double-J-stent was placed and the anterior wall was anastomosed in a watertight manner. A drain was placed in the operative area and the operation was completed. RESULTS: Mean operation time was 210 minutes. No intraoperative complications occurred. In one patient, antegrade double-J-stent placement failed, and the stent was therefore placed in the retrograde way without any complications. Postsurgery, the urethral catheter was removed on the first day, and the drain on the second. All patients were discharged 48 hours after surgery. The third month postoperative follow-up confirmed that the anastomoses were patent and patients were symptom-free. CONCLUSIONS: Pure laparoscopic pyelopyelostomy seems technically feasible and reliable for RCU treatment. Our experience showed that laparoscopy should be the standard treatment option for such patients.

Association of vitamin D receptor gene Taq I polymorphism with recurrent urolithiasis in children.

OBJECTIVE: Urolithiasis has a strong familial component. However, to date, no specific genetic abnormality has been identified. It has been reported that allelic variation in the vitamin D receptor (VDR) gene may affect calcium absorption and excretion. Urolithiasis is a multifactorial disease in which both genetic and environmental factors have an effect on onset and severity of disease. In the present study, the role of Taq I polymorphism of vitamin D receptor gene in urolithiasis was studied. METHODS: Eighty children with calcium stone disease (40 with single episode of stone disease and 40 with recurrence) and 40 controls were enrolled. Polymorphic sites were amplified by polymerase chain reaction, digested with Taq I restriction enzymes and analyzed by gel electrophoresis. Allelic or genotypic frequencies were calculated and associations between them and the presence of hypercalciuria, family history and stone recurrence were evaluated. RESULTS: Incidence of Taq I tt genotypes was significantly higher in patients with recurrent calcium-stone disease compared to the controls. In addition, the frequency of the 't' allele was higher in recurrent calcium-stone formers. Taq I t allele was found to be associated with increased risk of recurrence. No association between Taq I polymorphism and a positive family history was found in the present study. The frequency of hypercalciuria was higher in patients with the 'tt' genotype. CONCLUSION: Taq I t allele of the VDR gene may be a risk factor for severe urolithiasis and recurrent stone disease.

An electron microscopic examination of the intravesical ureter in children with primary vesico-ureteric reflux.

OBJECTIVE: To determine the structure of the intravesical distal ureteric wall of patients with primary vesico-ureteric reflux (VUR), and to compare the findings with previous reports. MATERIALS AND METHODS: Specimens of the distal intravesical ureteric segments were taken surgically from children undergoing ureteric reimplantation surgery for primary VUR. There were 24 distal intravesical ureteric specimens from 15 children (nine female and six male). Ultra-thin sections were cut from the specimens and examined with a transmission electron microscope. RESULTS: The appearance of the muscular layers of the specimens of different grades differed markedly. There were intercellular oedematous areas in the muscular layer in specimens from patients with grade 2 and 3 VUR. In specimens from grade 4 VUR there were also intracytoplasmic vacuoles in the smooth muscle cells. The most marked and striking changes were in the specimens from children with grade 5 VUR, in which there were large intercellular oedematous areas and prominent large intracytoplasmic vacuoles. CONCLUSION: Refluxing ureters differ from normal ureters in having disorganized smooth muscle fibres and altered smooth muscle cell structure, leading to incompetence of the valve mechanism. Although we cannot confirm that these pathological changes in the smooth muscle layer of the intravesical ureteric wall are caused by VUR we conclude that, with increasing degrees of reflux, the degree of smooth muscle damage increases, and that the rate of spontaneous resolution decreases.

Use of the holmium:YAG laser for ureterolithotripsy in children.

OBJECTIVE: To review our experience with rigid ureteroscopy and holmium:YAG laser for treating ureteric calculi in children. PATIENTS AND METHODS: The study included 35 children who were treated with rigid ureteroscopy for ureteric calculi between November 1997 and June 2003 (15 boys and 20 girls; mean age 6.2 years, range 1-14). The mean (range) stone size was 8 (4-15) mm and the duration of anaesthesia 46.6 (15-90) min. The stone was in the distal third of the ureter in 33 children and in the proximal third in two. We used a 7.5/8/10 F rigid ureteroscopes with routine dilatation of the ureteric orifice. For lower ureteric stones, lithotripsy was carried out with holmium:YAG laser in 29 cases, a pneumatic impactor in two and forceps extraction in two. Both stones in the proximal ureter were pushed back into the collecting system. All the ureters were stented using JJ stents in 31 and ureteric catheters in four cases. The mean postoperative follow-up was 12 (2-30) months. RESULTS: Excluding the two stones pushed back, the stone-free rate after a one-stage procedure was 82% (27/33). With repeated procedures in the six (ESWL in two) remaining cases the success rate was 97% (32/33). The ureter was perforated in two patients within the first five in the series. There was no pyelonephritis or gross haematuria after surgery. CONCLUSION: Ureteroscopy and lithotripsy using the holmium:YAG laser is effective and safe for treating ureteric stones in children, in experienced hands. The results would be even better using smaller and flexible ureteroscopes.