Jason P. Van Batavia

Retinoid Signaling in Progenitors Controls Specification and Regeneration of the Urothelium

The urothelium is a multilayered epithelium that serves as a barrier between the urinary tract and blood, preventing the exchange of water and toxic substances. It consists of superficial cells specialized for synthesis and transport of uroplakins that assemble into a tough apical plaque, one or more layers of intermediate cells, and keratin 5-expressing basal cells (K5-BCs), which are considered to be progenitors in the urothelium and other specialized epithelia. Fate mapping, however, reveals that intermediate cells rather than K5-BCs are progenitors in the adult regenerating urothelium, that P cells, a transient population, are progenitors in the embryo, and that retinoids are critical in P cells and intermediate cells, respectively, for their specification during development and regeneration. These observations have important implications for tissue engineering and repair and, ultimately, may lead to treatments that prevent loss of the urothelial barrier, a major cause of voiding dysfunction and bladder pain syndrome.

Dysfunctional Elimination Syndromes—How Closely Linked are Constipation and Encopresis with Specific Lower Urinary Tract Conditions?

PURPOSE It is recognized that there is a strong association between bladder and bowel dysfunction. We determined the association of constipation and/or encopresis with specific lower urinary tract conditions. MATERIALS AND METHODS We reviewed our database of children with lower urinary tract dysfunction and divided cases into 3 categories of bowel dysfunction (constipation, encopresis and constipation plus encopresis) and 4 lower urinary tract conditions (dysfunctional voiding, idiopathic detrusor overactivity disorder, detrusor underutilization disorder and primary bladder neck dysfunction). Associations between bowel dysfunction types and each lower urinary tract condition were determined. RESULTS Of 163 males and 205 females with a mean age of 8.5 years constipation was the most common bowel dysfunction (27%). Although encopresis is generally thought to reflect underlying constipation, only half of children with encopresis in this series had constipation. Dysfunctional voiding was associated with the highest incidence of bowel dysfunction. All but 1 patient with encopresis had associated urgency and detrusor overactivity, and the encopresis resolved in 75% of patients after initiation of anticholinergic therapy. Constipation was significantly more common in girls (27%) than in boys (11%, p <0.01), while encopresis was more common in boys (9%) than in girls (3%, p = 0.02), likely reflecting the higher incidence of dysfunctional voiding in girls and idiopathic detrusor overactivity disorder in boys. CONCLUSIONS Active bowel dysfunction was seen in half of the children with a lower urinary tract condition. Constipation was more common in patients with dysfunctional voiding, while encopresis was significantly increased in those with idiopathic detrusor overactivity disorder and in those with dysfunctional voiding, severe urgency and detrusor overactivity. Anticholinergics, despite their constipating effect, given for treatment of detrusor overactivity resolved encopresis in most children with this bowel dysfunction.

Simplifying the diagnosis of 4 common voiding conditions using uroflow/electromyography, electromyography lag time and voiding history.

PURPOSE Noninvasive uroflowmetry with simultaneous electromyography is useful to triage cases of lower urinary tract symptoms into 4 urodynamically defined conditions, especially when incorporating short and long electromyography lag times in the analysis. We determined the prevalence of these 4 conditions at a single referral institution and the usefulness of uroflowmetry with simultaneous electromyography and electromyography lag time to confirm the diagnosis, guide treatment and monitor response. MATERIALS AND METHODS We retrospectively reviewed the records of 100 consecutive normal children who presented with persistent lower urinary tract symptoms, underwent uroflowmetry with electromyography as part of the initial evaluation and were diagnosed with 1 of 4 conditions based on certain uroflowmetry/electromyography features. The conditions included 1) dysfunctional voiding--active pelvic floor electromyography during voiding with or without staccato flow, 2a) idiopathic detrusor overactivity disorder-A--a quiet pelvic floor during voiding and shortened lag time (less than 2 seconds), 2b) idiopathic detrusor overactivity disorder-B--a quiet pelvic floor with a normal lag time, 3) detrusor underutilization disorder--volitionally deferred voiding with expanded bladder capacity but a quiet pelvic floor, and 4) primary bladder neck dysfunction--prolonged lag time (greater than 6 seconds) and a depressed, right shifted uroflowmetry curve with a quiet pelvic floor during voiding. Treatment was tailored to the underlying condition in each patient. RESULTS The group consisted of 50 males and 50 females with a mean age of 8 years (range 3 to 18). Dysfunctional voiding was more common in females (p <0.05) while idiopathic detrusor overactivity disorder-B and primary bladder neck dysfunction were more common in males (p <0.01). With treatment uroflowmetry parameters normalized for all types. Electromyography lag time increased in idiopathic detrusor overactivity disorder-A cases and decreased in primary bladder neck dysfunction cases. CONCLUSIONS Noninvasive uroflowmetry with simultaneous electromyography offers an excellent alternative to invasive urodynamics to diagnose 4 urodynamically defined conditions. It identifies the most appropriate therapy for the specific condition and objectively monitors the treatment response.

Adolescent Varicocele: Influence of Tanner Stage at Presentation on the Presence, Development, Worsening and/or Improvement of Testicular Hypotrophy Without Surgical Intervention

PURPOSE Testicular asymmetry in adolescents with varicocele can worsen, remain unchanged or decrease on followup. We determined the incidence of testicular asymmetry at presentation by Tanner stage and the correlation between Tanner stage at presentation and subsequent changes in percent asymmetry (ability for catch-up growth or progressive asymmetry) without surgical intervention. MATERIALS AND METHODS We retrospectively studied the records of 115 boys with a mean age of 14.1 years (range 9.2 to 20.0) with grade 2 or 3 left varicocele who underwent testicular volume measurement at 2 visits at least that were a minimum of 6 months apart. Of the patients 92% and 8% underwent Doppler duplex ultrasound and orchidometry, respectively. Patients were divided into 2 groups, including those with less than 15% and those with 15% or greater asymmetry. Catch-up growth was defined as less than 15% asymmetry at any subsequent visit. RESULTS At presentation 58%, 64%, 67%, 35% and 39% of Tanner 1 to 5 cases showed 15% or greater testicular asymmetry, respectively. When Tanner 1 to 3 cases were combined and compared with Tanner 4 and 5 cases, the difference in initial asymmetry was significant (64% vs 38%, p = 0.007). Although it was not statistically significant, there was a trend toward more catch-up growth for the later Tanner stages, including 27% for Tanner 1 to 3 vs 53% for Tanner 4 and 5 (p = 0.06). CONCLUSIONS Slightly more than 50% of children and adolescents referred with varicocele have 15% or greater testicular asymmetry at presentation. Initial asymmetry is statistically more common in cases of earlier Tanner stages (1 to 3). Adolescents with 15% or greater testicular asymmetry who present at higher Tanner stages (4 and 5) show a trend toward a higher incidence of catch-up growth, although it is not significant.

Primary Bladder Neck Dysfunction in Children and Adolescents III: Results of Long-Term α-Blocker Therapy

PURPOSE Primary bladder neck dysfunction is a nonneurogenic voiding disorder frequently overlooked in pediatrics. The diagnosis classically is made by videourodynamics but can also be made with noninvasive uroflow studies with pelvic floor electromyography. We report our long-term results using alpha-blocker therapy in patients with primary bladder neck dysfunction. MATERIALS AND METHODS We reviewed 51 neurologically normal children (mean age 11.6 years, range 3.5 to 17.8) meeting criteria for primary bladder neck dysfunction who underwent alpha-blocker therapy for at least 1 year. All patients were symptomatic with abnormal flow parameters and an electromyogram lag time of 6 seconds or more on initial uroflow/electromyography. Pretreatment and on-treatment uroflow/electromyogram studies were performed in all patients. Average and maximum uroflow rates, electromyogram lag times and post-void residual volumes were compared. RESULTS After a mean followup of 46.2 months (range 12 to 124) mean average and maximum uroflow rates improved from 7.0 to 12.4 cc per second and from 12.4 to 20.3 cc per second, respectively, while mean electromyogram lag time decreased from 30.8 to 5.8 seconds (all p <0.01). Of the patients 85% reported subjective symptomatic relief. A total of 15 patients (29%) stopped alpha-blocker therapy for various reasons, none related to side effects. Repeat off-treatment uroflow/electromyogram studies showed that measured parameters reverted to pretreatment values (all p <0.05). Eight of these 15 patients eventually resumed alpha-blocker therapy, while only 3 remained asymptomatic off of the alpha-blocker. CONCLUSIONS alpha-Blocker therapy continues to benefit children with primary bladder neck dysfunction even after 3 years of treatment. Few patients can come off of alpha-blocker therapy without returning to their pretreatment state, suggesting the condition is likely chronic in most patients.

Ureterorenoscopy for Upper Tract Urothelial Carcinoma: How Often Are We Missing Lesions?

OBJECTIVE To determine the ability of ureterorenoscopy (URS) to identify the precise number and location of all lesions as compared with pathologic review of nephroureterectomy specimens, which have not been previously determined. Upper tract urothelial carcinoma (UTUC) comprises 5% of all urothelial malignancies in the United States. With advances in endoscopic equipment, there has been a move toward using flexible ureteroscopes to perform URS as part of the diagnostic evaluation and management. METHODS We identified patients who had undergone URS with biopsy before radical nephroureterectomy for UTUC. Operative reports for each procedure were reviewed and compared with the surgical pathology reports. RESULTS URS correctly identified the number and location of lesions in 57 of 76 patients (75%). The most common locations for missed lesions were in the ureter (9 patients) and renal pelvis (8 patients). Carcinoma in situ was missed on the initial biopsy for 9 patients. Three of 11 patients (27%) with a solitary lesion in the distal ureter visualized by URS had a missed lesion in the renal pelvis. URS with biopsy accurately predicted the grade of UTUC lesions in 79% of cases, whereas 65% of patients were upstaged on final pathology. CONCLUSION URS with biopsy can accurately map UTUC in the majority of patients. However, up to 25% of patients will have missed lesions, and nearly 50% of these patients will have a missed carcinoma in situ lesion. Undergrading and understaging of UTUC lesions remain shortcomings with potentially severe consequences.

Prevalence of Urinary Tract Infection and Vesicoureteral Reflux in Children with Lower Urinary Tract Dysfunction

PURPOSE Lower urinary tract dysfunction is a common pediatric urological problem that is often associated with urinary tract infection. We determined the prevalence of a urinary tract infection history in children with lower urinary tract dysfunction and its association, if any, with gender, bowel dysfunction, vesicoureteral reflux and specific lower urinary tract conditions. MATERIALS AND METHODS We retrospectively reviewed the charts of children diagnosed with and treated for lower urinary tract dysfunction, noting a history of urinary tract infection with or without fever, gender, bowel dysfunction and vesicoureteral reflux in association with specific lower urinary tract conditions. RESULTS Of the 257 boys and 366 girls with a mean age of 9.1 years 207 (33%) had a urinary tract infection history, including 88 with at least 1 febrile infection. A total of 64 patients underwent voiding cystourethrogram/videourodynamics, which revealed reflux in 44 (69%). In 119 of the 207 patients all infections were afebrile and 18 underwent voiding cystourethrogram/videourodynamics, which revealed reflux in 5 (28%). A urinary tract infection history was noted in 53% of girls but only 5% of boys (p <0.001). Patients with detrusor underutilization disorder were statistically more likely to present with an infection history than patients with idiopathic detrusor overactivity disorder or primary bladder neck dysfunction (each p <0.01). CONCLUSIONS Females with lower urinary tract dysfunction have a much higher urinary tract infection incidence than males. This association was most often noted for lower urinary tract conditions in which urinary stasis occurs, including detrusor underutilization disorder and dysfunctional voiding. Reflux was found in most girls with a history of febrile infections. Since reflux was identified in more than a quarter of girls with only afebrile infections who were evaluated for reflux, it may be reasonable to perform voiding cystourethrogram or videourodynamics in some of them to identify reflux.

Can Staccato and Interrupted/Fractionated Uroflow Patterns Alone Correctly Identify the Underlying Lower Urinary Tract Condition?

PURPOSE Worldwide, uroflowmetry without simultaneous electromyography is often the only testing performed during the initial assessment of children with lower urinary tract symptoms. Various alterations in uroflow pattern are thought to indicate particular types of lower urinary tract conditions, specifically staccato uroflow indicating dysfunctional voiding and intermittent/fractionated uroflow indicating detrusor underactivity. We determined how reliable uroflow pattern alone is as a surrogate for simultaneously measured pelvic floor electromyography activity during voiding, and how well staccato and interrupted uroflow actually correlate with the diagnoses they are presumed to represent. MATERIALS AND METHODS We reviewed uroflow/electromyography studies performed during the initial evaluation of 388 consecutive neurologically and anatomically normal patients with persistent lower urinary tract symptoms. We identified those with staccato, interrupted/fractionated and mixed uroflow based on current International Childrens Continence Society guidelines. RESULTS A total of 69 girls (58.5%) and 49 boys (41.5%) met inclusion criteria. Staccato uroflow was noted in 60 patients, interrupted/fractionated uroflow in 28 and a combination in 30. An active electromyography during voiding confirmed the diagnosis of dysfunctional voiding in 33.3% of patients with staccato, 46.4% with interrupted/fractionated and 50% with mixed uroflow patterns. CONCLUSIONS Diagnoses based on uroflow pattern appearance without simultaneous electromyography to support them can be misleading, and reliance on uroflow pattern alone can lead to overdiagnoses of dysfunctional voiding and detrusor underactivity. When assessing patients with uroflow, an accompanying simultaneous pelvic floor electromyography is of utmost importance for improving diagnostic accuracy and thereby allowing for the most appropriate therapy.

Robotic Surgery in Pediatric Urology

Minimally invasive laparoscopic procedures for urological diseases in children have proven to be safe and effective, with outcomes comparable to open procedures. Technical advances, including improved instruments and high-definition cameras, have contributed to the expanded role of minimal invasive surgery (MIS) in children. The major drawback to laparoscopy has been the relatively steep learning curve due to the technical difficulties of suturing and the limitations of instrument dexterity and range of motion. Recently, robotic-assisted laparoscopic surgery (RAS) has gained popularity in both adult and pediatric urology. RAS has several advantages over conventional laparoscopic surgery, particularly in the improved exposure via magnified 3-dimensional view and simplification of suturing with the increased degree of freedom and movement of the robotic arm. This review discusses the role of RAS in pediatric urology and provides technical aspects of RAS in specific urologic procedures as well.

Short Pelvic Floor Electromyographic Lag Time: A Novel Noninvasive Approach to Document Detrusor Overactivity in Children with Lower Urinary Tract Symptoms

PURPOSE Noninvasive uroflow with simultaneous electromyography can measure electromyographic lag time, ie the interval between the start of pelvic floor relaxation and the start of urine flow (normally 2 to 6 seconds). Intuitively one would expect that in patients experiencing urgency secondary to detrusor overactivity the lag time would be short or even a negative value. We studied whether short electromyographic lag time on uroflow with electromyography actually correlates with documented detrusor overactivity on urodynamics. MATERIALS AND METHODS We reviewed 2 separate and distinct cohorts of 50 neurologically and anatomically normal children with persistent lower urinary tract symptoms who were evaluated by uroflow with simultaneous electromyography and videourodynamics. Group 1 consisted of 30 boys and 20 girls (mean age 7.8 years, range 4 to 19) selected based on electromyographic lag time of 0 seconds or less on screening uroflow with electromyography who subsequently underwent videourodynamics. Group 2 consisted of 14 boys and 36 girls (median age 8.4 years, range 5 to 18) selected based on the presence of detrusor overactivity on videourodynamics whose screening uroflow with electromyography was then reviewed. Correlations between short electromyographic lag time and videourodynamically proved detrusor overactivity were analyzed. RESULTS For group 1 urodynamics confirmed the presence of detrusor overactivity in all patients with an electromyographic lag time of 0 seconds or less. For group 2 mean ± SD electromyographic lag time was 0.1 ± 1.7 seconds, and 35 patients (70%) with urodynamically proved detrusor overactivity had a lag time of 0 seconds or less. CONCLUSIONS In patients with lower urinary tract symptoms an electromyographic lag time of 0 seconds or less is 100% predictive of detrusor overactivity. This short electromyographic lag time has 100% specificity and 70% sensitivity for diagnosing detrusor overactivity (88% if less than 2 seconds). Thus, diagnosing the presence or absence of detrusor overactivity in most children with lower urinary tract symptoms and a quiet pelvic floor during voiding can be done reliably via uroflow with simultaneous electromyography.