Mario De Gennaro

Evaluation and treatment of nonmonosymptomatic nocturnal enuresis: A standardization document from the International Children's Continence Society

PURPOSE This document represents the consensus guidelines recommended by the ICCS on how to evaluate and treat children with nonmonosymptomatic nocturnal enuresis (NMNE). The document is intended to be clinically useful in primary, secondary and tertiary care. MATERIALS AND METHODS Discussions were held by the board of the ICCS and a committee was appointed to draft this document. The document was then made available to the members of the society on the web site. The comments were vetted and amendments were made as necessary to the document. RESULTS The main scope of the document is the treatment of NMNE with drugs other than desmopressin-based therapy. Guidelines on the assessment, and nonpharmacologic and pharmacologic management of children with NMNE are presented. CONCLUSIONS The text should be regarded as an expert statement, not a formal systematic review of evidence-based medicine. It so happens that the evidence behind much of what we do in the care of enuretic children is quite weak. We do, however, intend to present what evidence there is, and to give preference to this rather than to experience-based medicine, whenever possible.

Long-Term Efficacy of Percutaneous Tibial Nerve Stimulation for Different Types of Lower Urinary Tract Dysfunction in Children

PURPOSE We evaluated the efficacy of percutaneous tibial nerve stimulation for different types of pediatric lower urinary tract dysfunction. MATERIALS AND METHODS A total of 14 children with idiopathic overactive bladder, 14 with dysfunctional voiding, 5 with underactive bladder, 4 with underactive valve bladder and 7 with neurogenic bladder resistant to conventional therapy underwent percutaneous tibial nerve stimulation weekly for 12 weeks. The stimulation effect was evaluated by comparing bladder diary, flowmetry and urinalysis before and after treatment. Improved patients were followed by bladder diary and urinalysis. Followup data at 1 and 2 years were compared with those obtained after stimulation. Data were analyzed using Fishers exact test. RESULTS Symptom improvement was significantly greater in nonneurogenic than in neurogenic cases (78% vs 14%, p <0.002). Of patients 18% with underactive bladder and 50% with underactive valve bladder were unresponsive. Of 14 overactive bladder cases 12 and all 14 of dysfunctional voiding were improved (p not significant). Of improved patients 5 of 12 with overactive bladder and 12 of 14 with dysfunctional voiding were cured (p <0.01). On uroflowmetry voided volume and post-void residual urine became normal in a greater number of dysfunctional voiding than overactive bladder cases (57% vs 20% and 57% vs 25%, each p not significant). At 1 year of followup the cure rate was greater in dysfunctional voiding than in overactive bladder cases (71% vs 41%) and it remained the same at the 2-year evaluation. Chronic stimulation was necessary to maintain results in 29% of dysfunctional voiding and 50% of overactive bladder cases. CONCLUSIONS Percutaneous tibial nerve stimulation is reliable and effective for nonneurogenic, refractory lower urinary tract dysfunction in children. Efficacy seems better in dysfunctional voiding than in overactive bladder cases. There is evidence that percutaneous tibial nerve stimulation should be part of the pediatric urology armamentarium when treating functional incontinence.

Current State of Nerve Stimulation Technique for Lower Urinary Tract Dysfunction in Children

PURPOSE A variety of electrical nerve stimulation methods has been used through the years to treat lower urinary tract dysfunction. Relevant literature was reviewed to analyze techniques and available biomedical devices, technique applicability, indications and usefulness in pediatrics. MATERIALS AND METHODS An extensive search was performed on PubMed® and MEDLINE® for scientific publications on intravesical, transcutaneous, sacral spine and root, and tibial nerve stimulation in children with lower urinary tract dysfunction of nonneurogenic and neurogenic origin. Relevant articles and controlled studies in adult patients were also considered. The search covered the period 1990 to 2009 and we found approximately 400 articles, of which 29 related to pediatrics. RESULTS Due to feasibility problems with placebo studies the majority of the studies were noncontrolled, some of them clinical trials on acute urodynamic changes during electrical stimulation or experimental research in animals. Overall only a few randomized trials were found. Regarding types of electrostimulation and indications in children the recent literature emphasizes stimulation far from the anal-genital region, such as sacral transcutaneous electrical nerve stimulation, mainly for refractory overactive bladder. Intravesical stimulation is the procedure of choice to enhance sensation in patients with incomplete neurogenic lesions. Percutaneous tibial nerve stimulation is tolerated by children but has been poorly studied. Sacral neuromodulation using implanted devices remains questionable and needs further clarification of its indications. Magnetic stimulation has rarely been used in children to date. More experimental studies are needed to assess the method of action and refine the parameters of stimulation. CONCLUSIONS Clinical controlled trials vs sham devices and predictable variables for successful response are urgently needed to address an apparently renewed focus on the use of nerve stimulation in the treatment of pediatric lower urinary tract symptoms.

Validity of the International Consultation on Incontinence Questionnaire-Pediatric Lower Urinary Tract Symptoms: A Screening Questionnaire for Children

PURPOSE Lower urinary tract symptoms are common in pediatric patients. To our knowledge no validated instruments properly designed to screen lower urinary tract symptoms in the pediatric population have been published to date. In the International Consultation on Incontinence Questionnaire Committee the psychometric properties of a screening questionnaire for pediatric lower urinary tract symptoms were assessed. MATERIALS AND METHODS The 12-item International Consultation on Incontinence Questionnaire-Pediatric Lower Urinary Tract Symptoms was developed in child and parent self-administered versions, and produced in English, Italian and German using a standard cross-cultural adaptation process. The questionnaire was self-administered to children 5 to 18 years old and their parents presenting for lower urinary tract symptoms (cases) or to pediatric/urological clinics for other reasons (controls). A case report form included history, urinalysis, bladder diary, flowmetry/post-void residual urine volume and clinician judgment on whether each child did or did not have lower urinary tract symptoms. Questionnaire psychometric properties were evaluated and data were stratified into 3 age groups, including 5 to 9, 10 to 13 and 14 to 18 years. RESULTS A total of 345 questionnaires were completed, of which 147 were negative and 198 were positive for lower urinary tract symptoms. A mean of 1.67% and 2.10% of items were missing in the child and parent versions, respectively. Reliability (Cronbachs α) was unacceptable in only the 5 to 9-year-old group. The high ICC of 0.847 suggested fair child/parent equivalence. Sensitivity and specificity were 89% and 76% in the child version, and 91% and 73.5% in the parent version, respectively. CONCLUSIONS The questionnaire is an acceptable, reliable tool with high sensitivity and specificity to screen for lower urinary tract symptoms in pediatric practice. Problems related to literacy suggest use of the child versions for patients older than 9 years. In research this questionnaire could be used to recalibrate the prevalence of lower urinary tract symptoms in children.

Effects of botulinum toxin type a in the bladder wall of children with neurogenic bladder dysfunction: a comparison of histological features before and after injections.

PURPOSE Botulinum toxin type A has gained popularity in urology. Most reported studies have been in adults at urology centers and most have addressed long-term safety. Since botulinum toxin type A treatment for neurogenic bladder dysfunction requires repeat injections, verifying that such treatment does not induce fibrosis in children seems essential. MATERIALS AND METHODS The study was approved by the institutional review board and patients were enrolled after we obtained written consent. Patients with neurogenic bladder dysfunction not responding to conventional treatment (anticholinergics and clean intermittent catheterization) were treated with 10 IU/kg botulinum toxin type A up to a maximum of 300 IU. Endoscopic cold cup biopsies were obtained from the posterolateral bladder wall 1.5 to 2 cm above the ureteral orifice. Bladder wall findings were categorized into 3 groups, including inflammatory infiltration, edema and fibrosis. Each criterion was then graded as mild or severe and analyzed by Fishers exact test (p <0.05). RESULTS A total of 46 bladder wall biopsies were obtained from 40 patients 2 to 18 years old. Biopsies were evaluated in groups 1 and 2, including group 1-20 from patients with no botulinum toxin type A injection and group 2-20 after botulinum toxin type A injection. Group 2 was subdivided into group 3-10 biopsies after 1 injection and group 4-10 after multiple injections. Six patients underwent biopsy twice, that is before the first and second treatments. Histological changes were present in all biopsies. When comparing groups 1 and 2, there was no statistically significant difference in inflammation and edema. However, there was a significant difference in fibrosis between groups 1 and 4 (p <0.05) with apparently decreased fibrosis after multiple injections. CONCLUSIONS In our experience repeat botulinum toxin type A injections into the detrusor in children do not lead to increased fibrosis in the bladder wall. This study confirms the long-term safety of botulinum toxin type A in the pediatric population.

DETRUSOR HYPOCONTRACTILITY EVOLUTION IN BOYS WITH POSTERIOR URETHRAL VALVES DETECTED BY PRESSURE FLOW ANALYSIS

PURPOSE We evaluated the natural evolution of detrusor voiding contractility in boys who underwent posterior urethral valve ablation using pressure flow analysis, which is a mathematical computerized analysis of pressure flow studies. MATERIALS AND METHODS Among 30 boys with posterior urethral valves who were being prospectively followed, even if asymptomatic on serial pressure flow studies, 11 were included in our study. These 11 patients had had at least 2 evaluations performed between ages 5 and 15 years, a minimum interval of 4 years between the first and last examination, and all pressure flow studies records available for mathematical analysis of voiding contractility. The first examination had been done at ages 5 to 10 years (average 7 +/- 2.04) and the last one at ages 9 to 15 (12.5 +/- 2.5), including 6 evaluated after puberty. All but 1 patient underwent valve endoscopic resection as a newborn and none received urinary diversion. Voiding symptoms, post-void residual, cystometric bladder capacity and bladder instability were considered. Voiding phase maximal detrusor pressure and flow rate were evaluated and detrusor contractility was calculated by the pressure flow analysis parameters of contraction velocity, detrusor contractile power expressed as watt factor and Schafers nomogram. Contraction velocity and contractile power factor were considered low if below 2 standard deviations of previously determined normal values. True hypocontractility was diagnosed when at least 2 pressure flow analysis parameters were low. RESULTS True hypocontractility was detected in 3 of the 11 boys at the first examination and in 8 at the last pressure flow analysis. The remaining 8 and 3 cases of first and last examinations, respectively, were considered to have normal contractility even if 4 of the 8 and 1 of the 3 had 1 low pressure flow analysis parameter (covert hypocontractility). Detrusor contractility worsened in 6 patients, hypocontractility was detected at the first pressure flow analysis in 2, hypocontractility changed to normal in 1 and pressure flow analysis remained normal in 2. Of the 6 boys followed through puberty 5 had hypocontractility, including 3 with cystometric bladder capacity greater than 700 ml., high post-void residual and strained voiding. Of the 11 patients 8 had detrusor instability, including 7 with urge symptoms, at first evaluation which was not found at last examination. CONCLUSIONS Pressure flow analysis extensively used in men has been confirmed as a useful tool to assess voiding contractility in children. The majority of boys with posterior urethral valves have progressive impairment of detrusor contractility at voiding many years after relief of obstruction. The pattern of hypocontractility, which is detected early on pressure flow analysis, follows a prolonged phase of instability in many cases and leads to an over distended bladder in most patients followed after puberty. Questions arise if this evolution may be prevented by early (pharmacological or rehabilitative) treatment and if it is partially determined by extensive use of drugs acting against unstable detrusor contractions.

Effectiveness of Trigonoplasty to Treat Primary Vesicoureteral Reflux

Among the surgical procedures to treat vesicoureteral reflux trigonoplasty is a conservative technique that preserves the integrity of the vesicoureteral junction. Since its introduction in 1984 by Gil Vernet it gained only little attention in small series. Between 1986 and 1989 we performed trigonoplasty in 51 children 4 months to 13 years old, of whom 47 had primary vesicoureteral reflux. Our study includes 44 patients who have sufficient followup and 69 refluxing units. Reflux was grade II in 25 units, grade III in 39 and grade IV in 5. Patients were arbitrarily divided into 2 age groups: less than (13) and greater than (31) 3 years old. All children underwent standard preoperative assessment. The operation, with technical modifications (absorbable sutures in all cases and muscular incision added in 12), was performed after failed conservative treatment in all patients except 5 who were operated on at diagnosis. Surgery was successful in 97.7% of the patients and in 92.3% of the children less than 3 years old. The only recurrence was noted on 1 side of a 2-year-old child who had had grade IV bilateral reflux. Considering that reimplantation threatens the integrity of the vesicoureteral junction and endoscopic injections still have unclear side effects, indications for trigonoplasty can be extended to higher grades of reflux if ureteral tapering is not required and a sufficient intramural length of ureter can be obtained.

Bladder After Total Urogenital Mobilization for Congenital Adrenal Hyperplasia and Cloaca—Does it Behave the Same?

PURPOSE Followup of total urogenital mobilization for persistent urogenital sinus is well established anatomically and functionally. Nevertheless, studies comparing bladder function in different subsets of patients with urogenital sinus, such as congenital adrenal hyperplasia and cloaca, are scant. MATERIALS AND METHODS We reviewed the records of patients with congenital adrenal hyperplasia and cloaca who underwent total urogenital mobilization and urodynamics in the last 10 years. Those with a short urogenital sinus (less than 2.5 cm) not requiring an abdominal approach and without spinal dysraphism were selected for study. Urodynamics were performed postoperatively before and after toilet training, and compared between patients with congenital adrenal hyperplasia and cloaca. Methods, definitions and units conformed to International Continence Society/International Childrens Continence Society standards. For the emptying phase we defined bladder outlet obstruction as maximum detrusor pressure greater than 70 cm H(2)O and underactive detrusor as maximum detrusor pressure less than 20 cm H(2)O plus post-void residual urine greater than 25 ml. RESULTS Six patients with congenital adrenal hyperplasia and 6 with cloaca met study criteria. Three patients with congenital adrenal hyperplasia and 4 with cloaca underwent urodynamics before and after toilet training at a median age of 2 (range 2 to 4) and 5 years (range 3 to 8), respectively. Urodynamics were done in 1 patient with congenital adrenal hyperplasia before toilet training, and in 2 with congenital adrenal hyperplasia and 2 with cloaca after toilet training. All patients had normal urodynamics except 1 with congenital adrenal hyperplasia and detrusor overactivity, which normalized after toilet training. In all cloaca cases urodynamics were abnormal. Before toilet training bladder outlet obstruction was found in 2 patients, detrusor underactivity was found in 1 and detrusor overactivity was found in the remaining 1. After toilet training a detrusor underactivity pattern was found in 4 patients and bladder outlet obstruction was found in 2. All patients except 1 with cloaca had post-void residual urine before and after toilet training (median 100 ml, range 25 to 200). After toilet training all patients with congenital adrenal hyperplasia became spontaneously dry and all with cloaca were placed on clean intermittent catheterization. CONCLUSIONS In the long term patients with cloaca show bladder outlet obstruction or underactive/acontractile detrusor patterns, which are not noted in patients with congenital adrenal hyperplasia. Therefore, in patients with cloaca urogenital sinus length may not be as good an indicator of functional results as it is in patients with congenital adrenal hyperplasia. Whether additional rectal dissection and repositioning surgical procedures in cloaca cases may have a role in explaining such a difference remains to be clarified.

Female pelvic congenital malformations. Part I: embryology, anatomy and surgical treatment

This review covers the most important female congenital pelvic malformations. The first part focuses on the embryological development of the urogenital and anorectal apparatus, morphological features, and the diagnostic and surgical approach to abnormalities. Comprehension of the embryological development of the urogenital and anorectal apparatus is essential to understand the morphology of congenital pelvic abnormalities and their surgical treatment. Congenital pelvic malformations are characterized by specific common features; the severity of which often subverts the pelvic morphology completely and makes it difficult to comprehend before surgery. The development of imaging, mainly magnetic resonance imaging and ultrasound, in the investigation of pelvic floor disorders has recently become a fundamental tool for surgeons to achieve better understanding of the anatomy. Forty years ago, the primary aim of clinicians was to save the lives of such patients and to achieve anatomical normality. However, nowadays, functional reconstruction and recovery are essential parts of surgical management. Introduction of minimally invasive surgery has allowed the improvement of cosmetic results that is so important in paediatric or adolescent patients after reconstructive surgery. The option of sharing the complexity of pelvic congenital diseases by entrusting specific competencies to subspecialists (paediatric urologists, urogynaecologists, neurourologists, paediatric endocrinologists and neonatologists) has improved the quality of care for patients. However, at the same time, active interaction between various specialists remains fundamental. The exchange of knowledge and expertise, not only during the diagnostic-therapeutic process but also during follow-up, is crucial to obtain the best anatomical and functional results throughout the life of the patient.

Distal hypospadias repair by urethral sliding advancement and Y-V glanuloplasty.

Different techniques are available today for repairing distal (coronal and subcoronal) hypospadias but none is universally recommended. We developed the technique of a distal urethral advancement glanuloplasty operation that is specifically intended for distal hypospadias repair even with mild chordee. Mobilization of the distal urethra is performed for 1.0 to 1.5 cm. after subcoronal circumcision and a deep Y-shaped incision of the glans. The mobilized urethra is dorsally split and slid forward to the tip of the dart of the glans previously prepared. Glanuloplasty is performed using the 2 lateral flaps of glans tissue. From January 1987 to December 1989 we used this technique in 74 cases of distal hypospadias with mild or no chordee (patient age 18 months to 9 years, mean 3.5 years). A transurethral catheter was left indwelling for 3 to 4 days. Hospitalization time was 5 (plus or minus 1.5) days. Results after 4 to 40 months of followup are encouraging cosmetically and functionally. All patients were cured. In 3 cases (4%) meatal stenoses occurred requiring meatotomy and in 8 boys meatal dilations were performed on an outpatient basis. In 1 case (1.3%) a fistula developed, which was subsequently repaired without further complications. This operation may be successfully used in most cases of distal hypospadias, with a low complication rate and excellent cosmetic results. It also may be used if mild chordee is present, thus reducing the indications for flip-flap urethroplasty in those cases when meatal advancement procedures may not be effective.