Contemporary Urologic Management of Children with Neurogenic Bladder Patricio C. Gargollo, MD Director, Pediatric Urology Minimally Invasive and Robotic Surgery Assistant Professor in Urology, UT Southwestern Medical School Department of Urology, Children's Medical Center, Dallas

Who am I and how did I get here? Baylor University Graduate Harvard Medical School Massachusetts General Hospital and Harvard Medical School 2 years general surgery 4 years urology Children’s Hospital Boston 3 years pediatric urology Advanced fetal care center Advanced Laparoscopic training

Paradigm Shift Medical Therapy and Management Surgical therapy Less Antibiotics Less Radiation Less Screening Less Testing Surgical therapy Laparoscopic Surgery Robotic Assisted Surgery Less Pain Less Scars Less Time in the hospital

Outline Urology Goals Physiology Bladder Function/Malfunction Bowel Function/Malfunction Urology Studies Surgical Treatments

Spina Bifida

Classification Myelomeningocele Meningocele Lipoma of the cord Occulta

Etiology Risk Factors Sex Ethnic Background Diet Medications Diabetes Obesity Socioeconomic status

Prevalence 166,000 affected in the US 1 in 1,000 live births

Texas Scottish Rite 500 active patients with MM 25 newborn patients annually

Spinal Defects Clinic Integrate care among all specialties Provide “one-stop” shopping Patient Population: 500 patients Tuesday s 14-18 patients 12:30-6 pm Patients 1 month-2 years old Seen every 3-6 months Patients 2 years and older Seen every 6 months to 1 year

Spinal Defects Clinic Providers Specialists: Physiatrist Orthopedist Neurosurgeon Urologist Occupational Therapy Physical Therapy Social Work Nursing Project Nicaragua

NGB: Childhood Milestones birth - toilet training (3-4 yrs) continence management (TT- middle school) teenage rebellion transition to adult care

Goals Preserve renal function Achieve social continence No dialysis! Bladder Bowel No diapers! Independence

Neural Pathway

Bladder Function Bladder Sphincter Overactive Underactive Normal

Detrusor Sphincter Dyssynergia Bladder -Overactive Sphincter -Overactive

Neurogenic Detrusor Overactivity Bladder -Overactive Sphincter -Underactive

Areflexic Bladder Bladder Underactive Sphincter -Underactive

Bowel Function

Bowel Function: “Pellets”

Bowel Function:Diarrhea

Urology Studies Renal/Bladder ultrasound VCUG DMSA Urodynamics

Urology Studies Renal/Bladder ultrasound

Urology Studies Renal/Bladder ultrasound

Urology Studies VCUG (Voiding cystourethrogram)

Urology Studies DMSA

Urology Studies UDS (Urodynamics) Bladder Pressure Sphincter Activity Rectal/Abdominal Pressure Sphincter Activity

Pressure Time Activity Time Pressure Time

Management and Outcomes No longitudinal studies of renal function, scarring Few longitudinal studies of bladder compliance

Means to Assess Need for therapy, results, determined by: Imaging Renal US VCUG DMSA Urodynamics

Background Goals for management: Preserve renal function, prevent scarring Preserve bladder compliance No evidence that management impacts outcomes Reported endpoints New HN, VUR Change in UD Augmentation rates

Management Options 3 options for management of children with MM from birth – age 3y: Imaging-based observation Universal therapy (CIC + anticholinergic) UD-based selective therapy

Surrogate Outcomes of Management Incidence of new HN, VUR does HN or VUR predict renal damage? Development of adverse UD parameters does tx prevent changes? does tx restore compliance? Augmentation rates management failure vs management decision?

Newborns: Tx vs Observation No evidence shows universal treatment superiority No study shows impact of tx on care-givers Cost catheters, oxybutynin

Newborn Protocol ≤ 6 wks age High Risk UD filling pressure> 40cm Fluoroscopic UD Renal US, DMSA Renal US q 3mos x1y q 6mos UD, DMSA 1yr, 3yr Tx for: high risk UD + HN, VUR new HN, VUR, ∆ DMSA High Risk UD filling pressure> 40cm Patterns:

Initial Assessment: UD Varying Methods 5-7Fr UD catheters infusion 1.5- 15cc/min monopolar needle vs patch electrodes EMG Varying Terminology upper, lower motor lesions detrusor hypertonicity vs overactivity Varying Diagnoses DSD vs no DSD Inf

Results: Initial UD 71 pts, mean age 3m (2wk – 6m) Category Number of pts “Normal” 16 (23%) No detrusor contraction 22 (31%) <25 cm H2O 9 25-40 cm H2O >40 cm H2O 4 Detrusor overactivity 33 (46%) 12 8 13

Results: Initial UD 71 pts, mean age 3m (2wk – 6m) Category Number of pts “Normal” 16 (23%) No detrusor contraction 22 (31%) <25 cm H2O 9 25-40 cm H2O >40 cm H2O 4 Detrusor overactivity 33 (46%) 12 8 13 “High risk

DLPP or Storage Pressure? Same risk? DLLP 50 cm Pressure during storage is more important than compliance Churchill et al, 1994

Selective Therapy (UD-based) UD identifies high risk before deterioration Therapy prevents renal, bladder damage Preserve renal function, decrease augmentation

Outcomes 71 pts High risk UD 17 (24%) Low risk UD 54 (76%) Treatment Initial UD High risk UD 17 (24%) Low risk UD 54 (76%) F/u UD F/u UD Treatment n=12 Observation n=5 6/54* Δ to  risk UD 1 new HN, 2 new VUR EFP <40 n=12 1 new HN 1 new HN+VUR * UD changes at mean 9mo (4-12) No new HN/VUR

Outcomes Renal damage: no data, f/u DMSA pending 25% f UTI: 9/17 (53%) high risk 9/54 (17%) low risk 10/18 (56%) CIC vs 8/53 (15%) obs , p=.001 18% VUR: 11/71 (15%) initially 3/60 (5%) new

Renal Outcomes: Baseline DMSA 38 patients 35 (92%) normal scan 3 (8%) abnormal scan, congenital nephropathy? Pt DMSA finding Initial UD Pattern EFP Initial u/s Initial VCUG fUTI 1 Unilateral, CRN 20 No hydro No VUR No 2 Unilateral, focal scar 40 3 62 Unilateral SFU Gr 3 Gr 5, 3 Yes

Renal Scar: Risk Factors 95 pts NGB 7±4yrs 32% DMSA renal scar MLR analysis: VUR OR 8.12 (95%CI 2.92 – 23.14) no UD parameter bladder capacity DLPP>40cm H2O DSD detrusor overactivity [40% taking anticholinergics] Leonardo et al, 2007

Renal Scar: Risk Factors DMSA, UD in sequential pts 2005-07 113pts, 64 > 10ys age studied 16 (25%) had abnormal DMSA function < 40%, or focal scar VUR OR 2.06 (1.43 – 2.97) f UTI OR 9.53 (2.64 – 34.34) DLPP 44±20 vs 46±28 ns Compliance 8.8±5.9 vs 12±11 ns Shiroyanagi et al, 2009

Renal Scar (non-NGB) 15% focal DMSA defect 15% VUR I-III 50% VUR IV-V 541 consecutive pts fUTI and/or VUR 15% focal DMSA defect 15% VUR I-III 50% VUR IV-V Recurrent fUTI

Results: Initial U/S, VCUG 14/71 (20%) abnormal HN 3 (4%) VUR 8 (11%) HN+VUR 3 (4%) 8/54 (15%) observation 6/17 (35%) high risk Of 3 HN: 1 obs – started CIC (B to F), HN resolved (u/s at 12mo) 2 tx – both resolved (u/s at 18mo, 11mo) Of 8 VUR: 5 obs: 4 resolved (2.5 mo, 11mo, 10 mo, 11 mo), 1 awaiting f/u imaging 3 tx: 1 resolved 22mo, 1 persisted, 1 awaiting f/u imaging Of 3 HN+VUR: 2 obs (1 resolved hydro, awaiting VUR f/u; 1 resolved VUR, persistent hydro 1 tx: both persisted

Results 18/71 (25%) had treatment by 1 year 14/71 (19%) VUR 12 initial “high risk” 6 initial “low risk” – new loss of compliance 14/71 (19%) VUR 11/71(15%) initially 3/60 (5%) new 18 (25%) with febrile UTI 10/18 (56%) CIC vs 8/53 (15%) obs, p=0.001 Why therapy in the 6 obs pts? Decr fxn on DMSA, increasing EFP New VUR, hydro discovered on w/u for hyperkalemia, hyponatremia Early UD done b/c of baseline hydro (“Mod, mild”) UD sched at age 9mo Febrile UTI New unilateral VUR New HN, VUR: 5 pts fUTIs: 9/17 high risk (8 were on CIC) 9/54 low risk (1 who started getting fUTIs AFTER starting CIC/becoming high-risk)

Conclusions Majority of infants have low risk UD findings 83% of low risk pts have no change in UD or imaging during observation Compliance changes occurred before age 1yr Treated -risk patients lowered bladder pressures No data yet on renal impact Initial management can be tailored by initial UD 83% comes from: 54 obs patients 6 with EFP>40 (incl 1 with imaging changes) 3 with imaging changes =9 with change in UD or imaging So 45/54 (83%) with no change

Conclusions ~25% newborns have potentially adverse imaging and/or UD ~15% VUR ~10% have potentially adverse changes during obs Scar risk of fUTI ± VUR not known with NGB Potentially negative impact of CIC on renal function (fUTI)

Summary of Outcomes Uncertain: Some pts with “normal” or “low risk” UD will convert to “high risk” Some pts with “high risk” UD have no clinical findings Uncertain: Is high bladder pressure alone a risk factor for renal damage? Can therapy (CIC) cause renal damage, ie via febrile UTI?

Management Medical Management Surgical Management Intermittent Catheterization Anticholinergics Surgical Management Bladder Procedures Bladder Outlet Procedures Catheterizable Channels Procedures on the ureters

Neurogenic Voiding Dysfunction Good bladder Bad sphincter Good bladder Good sphincter B. A. Bad bladder Bad sphincter Bad bladder Good sphincter C. D.

Goals Medical Social

Surgical Intervention Last resort when medical therapy fails: Botox, Augmentation +/- BN procedure : injection, suspension, sling, urethral lengthening ((Piipi Salle, Kropp), AUS… last resort is BN closure Mitrofanoff- Monti-Yang +/- Reimplant +/- Malone ACE

Pediatric Reconstruction: Key Points In children- try to preserve bladder, not divert Detubularize & reconfigure bowel: avoid hour glass! Intact bowel P- 60-100 cm H2O Maintain terminal 10-20 cm distal ileum (B12 absorption – megaloblastic anemia, peripheral neuropathy, optic atrophy, dementia) Bladder neck closure as last resort only Consider MACE & Mitrofanoff

Treatment:Bladder CIC: Clean intermittent catheterization

CIC: Clean intermittent catheterization DOES NOT INCREASE INFECTIONS IF DONE CORRECTLY!!!!!!!

Treatment:Bladder CIC: Clean intermittent catheterization

Surgery:Bladder Bladder Botox

Surgery:Bladder Augmentation

Surgery:Bladder Augmentation

Surgery:Bladder Augmentation

Surgery:Bladder Augmentation Increase bladder size Decrease high pressures to kidneys Results: Prevent kidney damage Continence

Intra-op

Intra-op

Intra-op

Intra-op

Catheterizable Stoma Monti-Tube Appendicovesicostomy

Surgery:Mitrofanoff

Surgery:Mitrofanoff

Post-op Care Mitrofanoff or ACE Midline/Umbilicus Suprapubic Tube RLQ or LLQ ACE Midline or RLQ Urethral Foley

Post-op Care Mitrofanoff or ACE Suprapubic Tube ACE Urethral Foley 1. Locations and origins may differ 2. Bag drainage and plugs may differ

Post-op Care POD#1: AMBULATION Flushing “In” VS Irrigation “In and Out” 1) Bladder only 2) Via Mitrofanoff, SPT or urethral foley 3) Additional catheters must be closed 4) Sterile water or saline 60 cc BID 5) This can be tricky but it’s important! 1) ACE Procedure 2) Can be tap water 3) Sit patient on toilet/bedside commode 4) Serial increase in volume POD#1: AMBULATION

Routine Care:FAQs 1. How far does the ACE/Mitrofanoff go in? 2. Can I hurt anything? 3. How long does it take to heal? 4. What are the outcomes? 5. What are the risks?

Key Points Short term and long term issues Behavior and diet changes Many surgeries and treatments Intense post-operative care and teaching Requires both family and nursing support

Surgical Management

Minimally Invasive Pediatric Surgery Shift Extirpative Nephrectomy Reconstructive Ureteral reimplant, augmentation, complex Reconstruction Feasible Nephrectomy, pyeloplasty, ureteral reimplantation Minimally invasive techniques are rapidly being developed and integrated into urologic surgery. Over the last five years, the urologic literature is abound with novel techniques and adaptations to conventional laparoscopy including but not limited to laparoendoscopic single –site surgery (LESS), natural orifice translumental endoscopic surgery (NOTES), and robot-assisted laparoscopic surgery(RALS).[1-3] Robotic surgery in kids has been shown to be feasible, and increasingly complex operations are being undertaken (APV +/- Malone anterograde CE +/-ileocystoplasty)

Robotic Assisted Continent Catheterizable Conduit

Appendicovesicostomy/ ACE 1 2 Robotic System X 3 1 10 cm 1: 8mm working port, mid-clavicular line 2: 12mm camera port, midline 3: 8mm working port, mid-clavicular line X: 5mm port for sutures 2 1750 10 cm 3

Bagrodia, A., Gargollo, P.: Robot-assisted bladder neck reconstruction, bladder neck sling, and appendicovesicostomy in children: description of technique and initial results. J Endourol, 25: 1299, 2011

Complex Reconstruction

Neurogenic Incontinence Various surgical techniques Bladder neck sling for incontinence first described in 1986 Sling without augmentation demonstrated to be safe Continence rates are low (36-57%) Sling with bladder neck reconstruction safe, with 82% continence (Snodgrass J Urol 184, p 1775, 2010) Between 70-95% of patients receiving a bladder outlet procedure also receive enterocystoplasty due to concern for small bladder capacityhigh intravesical pressures from increased outlet resistance, and ensuing upper tract damages; these were from AUS data with near-total occlusion of the outlet; Snodgrass and colleages described stable/improved urodynamic parameters in 26 patients with mean follow up of 39 months

Methods: Technique The patient is placed supine on a surgical bean bag positioner. All potential pressure points are meticulously padded. A 14-French catheter is inserted per urethra once the patient is prepped and draped. Pneumoperitoneum is established using a Veress needle in an infraumbilical location. Given the thin nature of the abdominal wall in most pediatric patients, the working ports are secured to the patient’s skin with TroGARD® (Conmed Corporation 310 Broad St. Utica, NY). Once all ports are secured, the robot (da Vinci Surgical System, Intuitive Surgical, Inc., Sunnyvale, CA) is docked. An inverted V-shaped incision was made at the umbilicus, ultimately serving as the future skin flap to bring to the appendicovesicostomy, and the 12-mm robotic camera was placed after Veress needle insufflation. Under direct visualization, two 8-mm robotic ports were placed: the first in the right midclavicular line slightly superior to the camera port and the second in the left midclavicular line just inferior to the umbilical site. A 12-mm assist port was placed between the left arm and the working camera port (Figure 1). A 12-mm trocar was used in order to accommodate suture needles and Lapra-Ty. 86

Results The patient is placed supine on a surgical bean bag positioner. All potential pressure points are meticulously padded. A 14-French catheter is inserted per urethra once the patient is prepped and draped. Pneumoperitoneum is established using a Veress needle in an infraumbilical location. Given the thin nature of the abdominal wall in most pediatric patients, the working ports are secured to the patient’s skin with TroGARD® (Conmed Corporation 310 Broad St. Utica, NY). Once all ports are secured, the robot (da Vinci Surgical System, Intuitive Surgical, Inc., Sunnyvale, CA) is docked. 88

Results: Patient Characteristics Case Age (years) Sex BMI (kg/m2) Diagnosis Shunt 1 8 F 24.5 MMC N 2 13 27.1 Y 3 M 29 4 5 16.7 LMC 11 31.2 6 7 14.8 Tranverse myelitis 20.2 SCI 17% of patients were normal weight (BMI<25) while 53% were obese or morbidly obese (BMI>30). BMI: Body Mass Index, Shunt: Ventriculoperitoneal shunt

Results: Cumulative outcomes 86% of cases completed robotically One complication (conversion) Two cases of de novo reflux (resolved)

Efficacy, efficiency, safety of robotic APV/BNR/BNS All patients are dry Low profile scars Efficiency: Operative times are longer Hospital durations are shorter Safety: Acceptable complication rate

Complex Reconstruction  Gargollo et. al. Comparison of Open and Robotic Assisted Appendicovesicostomy, Bladder Neck Reconstruction and Bladder Neck Sling IRUS, January 2011 Robotic Cohort Longer operative times Lower Blood loss Lower length of stay Decreased Narcotic Use

Conclusions The present series expands the scope of robotic reconstruction in children Preliminary data demonstrates these procedure are feasible and safe Comparison with open APV with bladder neck reconstruction is required and ongoing

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