Ten Things Pediatricians Need to Know About Urology

Tony Khoury MD FRCSC FAAPWalter R. Schmid Professor of Pediatric Urology

Professor, Department of UrologyUniversity of California, Irvine

Head of Pediatric UrologyChildren's Hospital of Orange County

1. Prenatal Hydronephrosis

Antenatal Hydronephrosis Detected by U/S in 1/400 pregnancies

Represents 30% of prenatal anomalies

Postnatal persistence in 50%

VUR26%

Duplex10%

PUV10%

37%

Bilateral15%

Single kidney2%

Unilateral

Antenatal HydronephrosisUltrasound - Prenatal

AP diameter – SFU grading Empty bladder 20 weeks or more

Grade 1 – slight central split

Grade 2 – central split confined to border, normal parenchyma

Grade 3 – wide split, pelvis outside renal border, caliectasis, normal parenchyma

–Grade 4 – large calyces, thin parenchyma»< half contralateral, or <4mm

SFU Consensus

No Calyx

Normal Calyx

Blunted Calyx

Bulging Calyx

Normal Fetal AP diameter

Week MM

16 4 mm

24 6 mm

28 7 mm

40 10 mm

Antenatal HydronephrosisUltrasound - Postnatal

Careful with the interpretation of the newborn US relative dehydration

Cortical echogenicity

Antenatal HydronephrosisUltrasound - Prenatal

Outcomes Grade 1

97% spontaneous resolution 20-30% incidence of VUR (with any degree of prenatal hydronephrosis)

Grade 2 80% spontaneous resolution 10% OR

Grade 3 30% OR

Grade 4 ≈90% OR

AP Diameter as an Indicator for Pyeloplasty

Key points AHN

Majority resolve, early delivery “never” Infections rare VCUG only indicated if ureter dilated or

bladder abnormal No need for Abx Insist on proper radiology interpretation

2. Incontinence

The Poor Bladder

10

CourageKindness

Generosity

IntelligenceWisdom

Creativity

11

12

Normal Bladder Function

Low pressure filling Low pressure storage Perfect continence Periodic voluntary expulsion

(at low pressure) Resist infection

Detrusor Muscle Properties

Contractile properties well suited for either urine storage or release

Smooth Muscle Connective Tissue

Normal ReflexNormal Reflex

Bladder

Filling

CorticalInhibition

(+)

Stretch Receptors

Low Pressure

Storage

Urethral Control Mechanism

Smooth muscle maintains tone with relatively little expenditure of energyStriated muscle for emergencies

+-

+

Sacralreflex

+

Holding Reflex

Voiding Dysfunction

Wein’s Functional Classification Failure to Store

Because of Bladder Because of Urethra Combined

Failure to Empty Because of Bladder Because of Urethra Combined

+

-

-

+

Diagnostic Studies

Bladder Diary (capacity, urgency, frequency, incontinence)

Uroflow and PVR

Simple Measures to Correct Incontinence

Timed voiding: vibrating alarm Watch Increase water intake Correct constipation

Sensory Urgency

Daytime frequency No Nocturia No incontinence

Self limiting Water Rx Constipation

3. Nocturnal Enuresis

Incidence

80% primary15% resolve / year

5 to 7 million children in the USBoys:Girls 3:1

Hereditary Factors

Norgaard JP, Djurhuus JC, Watanabe H, Stenberg A, Lettgen B. Experience and current status of research into the pathophysiology of nocturnal enuresis. Br J Urol 1997;79:825-35.

Etiology - Dandelions

Anecdotal reports and folk wisdom say children who handle dandelions can end up wetting the bed.

Dandelions are reputed to be a potent diuretic.

English folk names for the plant are "peebeds" and "pissabeds”. In

French dandelions are called pissenlit, which means "urinate

in bed"; likewise "piscialletto", an Italian folkname, and "meacamas" in Spanish.

Pathophysiology

Disturbance atthe

Brainstem Level

Disturbance atthe

Brainstem Level

Nocturnal Polyuria

Nocturnal Polyuria

High Arousal Thresholds

High Arousal Thresholds

Nocturnal DetrusorOveractivity

Nocturnal DetrusorOveractivity

The bedwetting child is regarded as a “deep sleeper”

Supported by Universal parental observation that their enuretic

children are difficult to awaken (Nevéus T, Hetta J, Cnattingius S, Tuvemo T, Läckgren G, Olsson U, Stenberg A (1999) Depth of sleep and sleep habits among enuretic and incontinent children. Acta Paediatr 88:748–752)

Studies on objective arousal thresholds (Wolfish NM, Pivik RT, Busby KA (1997) Elevated sleep arousal thresholds in enuretic boys: clinical implications. Acta Paediatr 86:381–384)

Sleep electroencephalogram (EEG) of enuretic children not different from that of dry children.

NE and Sleep Disturbances

Enuresis may be caused by heavy snoring or sleep apneas due to adenotonsillar hypertrophy.

Possible explanations The constant arousal stimuli from the obstructed

airways causes paradoxically high arousal thresholds The negative intrathoracic pressure causes polyuria

via increased secretion of the atrial natriuretic peptide

Umlauf MG, Chasens ER (2003) Sleep disordered breathing and nocturnal polyuria: nocturia and enuresis. SleepMed Rev 7:403–411

The Marvel of the Hibernating Bear

Urine production Muscle mass Bones Boredom!

Alterations in Vasopressin Secretion and Nocturnal Urine Production

About 50% less urine is normally excreted during the night than during the day.

Due to a circadian rhythm of plasma arginine vasopressin (AVP)

Etiology : ADH

Delay in achieving circadian rise inarginine vasopressin

nocturnal polyuria

overwhelms the bladder

No significant difference in nocturnal urine osmolality

between enuretic and nonenuretic children at any age

Kawauchi and Watanabe (1993)

Nocturnal Polyuria

Weak evidence for presence of true nocturnal polyuria in MSNE

Van Hoeck K, Bael A, Lax H, et al. Urine output rate and maximum volume voided in school-age children with and without nocturnal enuresis. J Pediatr 2007; 151:575–580.

Normal ReflexNormal Reflex

Bladder

Filling

CorticalInhibition

(+)

Stretch Receptors

Low Pressure

Storage

+-

Evaluation

General Child and parent attitude toward NE Confirm that it is PMNE BBD: Bladder Bowel Diary, Uroflow Frequency of NE: number per week and

per night R/O other conditions: DI, CRF, PUV, UTI

Treatment

Remember the Natural History!!

Timing of Treatment

Treatment is rarely successful before Age 7 15% of children are enueretic at age 5

The child needs to be truly motivated for treatment to succeed

Who is more interested in dryness: the parent or the child?

Treatment

Behavioral Interventions Alarms Medications

Important treatment aim is to protect and improve self-esteem.Counsel the parents, warn about psychological damage caused by pressure, shaming, or punishment for a condition the child cannot control

TreatmentBehavioral Interventions

Reducing fluid intake in the evening Reduces incontinence volume Rarely impacts frequency of wetting episodes

Lifting: ineffective Reward System Responsibility to induce motivation

Treatment - Medications

Desmopressin Response

Desmopressin Response

DryDry

Partial ResponsePartial Response

No ResponseNo Response

Desmopressin probably unsuccessful:• If maximum voided volumes <70% of the expected bladder capacity• No nocturnal polyuria (nocturnal urine production less than 130% of the

expected bladder capacity).

Desmopressin + Alarm

Desmopressin + Anticholinergic

Patients with MNE who did not respond to desmopressin alone

Reduction in the number of wet nights compared to desmopressin alone

Austin PF, Ferguson G, Yan Y, et al. Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: randomized, double-blind, placebocontrolled trial. Pediatrics 2008; 122:1027–1032.

Desmopressin Downside

The therapeutic effect of DDAVP is temporary, and once treatment is stopped 50% to 90% of children relapse and resume their original pattern of wetting (Kahan et al, 1998).

DDAVP

Ideal for Overnight Campsand Sleepovers

Behavior Modification

should be considered the first-line approach to the management of

enuresis

Reward System

StickersRewards

Responsibility Reinforcement

Conditioning Therapy

The Wetness Alarm

Alarm Results

Complete resolution 66% 16% relapse after discontinuation Relapses respond well to retreatment Better with overtreatment

Glazener, C. M., J. H. Evans, et al. (2005). "Alarm interventions for nocturnal enuresis in children." The Cochrane database of systematic reviews(2): CD002911.

4. Catheterizable Continent Channels

Clean Intermittent Catheterization

Urethra Manual Dextrerity Balance Issues

Stoma Mitrofanoff

Mitrofanoff

Catheterizable Conduit

The appendix preferred material for a continent cathetrizable conduit.

55

56

10 Years Later

57

58

MACE

MACE Appendiceal Inlay

5. UTI

Pathogenesis of UTI

Access Incubation Adhesion

Time Amount Wet / Dry

Evaluation

Review Urine Culture and Analysis Report Elimination Diary & Drinking Habits US FR & PVR

Investigations for UTI

If no Hx of BBD: US VCUG only if US abnormal

HN HU Bladder

Management

Correction of Predisposing Factors Insufficient water intake Infrequent voiding Incomplete bladder emptying Constipation Poor Hygiene, Fecal soiling Voiding into vagina Chemical urethritis

6. VUR

Indications for Surgical Correction of VUR

1990’s

Breakthrough infections

Non resolution after 4 years of Follow-up

Noncompliance with ABP

New renal scars on therapy

AAP Guidelines 2011

Published literature does not provide evidence supporting the benefit of prophylaxis Rec UTI or renal scarring

Therefore why diagnose VUR when the imaging findings would not affect the nature of treatment?

Swedish Reflux Trial

Antibiotic prophylaxis and endoscopic treatment decreased the infection rate in: Children under 2 y with Grade III-IV VUR

Be Selective

Renal Scarring

Outcome scans (at the 2year visit or 3 to 4 months after the child had met treatment failure criteria) showed no significant differences in the incidence of renal scarring 11.9% in the prophylaxis group and 10.2% in the

placebo group (P = 0.55), Severe renal scars (4.0% and 2.6%, respectively; P =

0.37 New renal scars since baseline (8.2% and 8.4%

P=0.94)

Compliance

Parents of 467 of the children (76.9%) reported having administered the study medication at least 75% of the time,

Parents of 517 children (85.2%) reported having administered it at least 50% of the time.

Parents of 91 children in the prophylaxis group and of 76 children in the placebo group discontinued the study medication.

Antimicrobial Resistance

Stool colonization with resistant E. coli was more common in the prophylaxis group than in the placebo group, but the difference was not significant

Among 87 children with a first febrile or symptomatic recurrence with E. coli, the proportion of isolates that were resistant to TMP-SMX was 63% with prophylaxis and 19% with placebo (P<0.001)

How does this reconcile with the AAP Guidelines?

1. CAP does not reduce renal scarring or CKD2. CAP results in a modest reduction in UTIs3. The likelihood of resistant organisms

causing UTI is higher in the group on CAP4. Do the results with SMX-TMP cross over to

other antibiotics?

Bladder and Bowel Dysfunction

Outcome of Antibiotic Prophylaxis Discontinuation in Patients With Persistent Vesicoureteral Reflux Initially Presenting With Febrile Urinary Tract Infection:

Time to Event Analysis Bruno Leslie, Katherine Moore, Joao L. Pippi Salle, Antoine E. Khoury, Anthony Cook, Luis H.P.

Braga, Darius J. Bägli, Armando J. Lorenzo The Journal of Urology - September 2010 (Vol. 184, Issue 3, Pages 1093-1099

I-II

III-V

Outcome of Antibiotic Prophylaxis Discontinuation in Patients With Persistent Vesicoureteral Reflux Initially Presenting With Febrile Urinary Tract Infection:

Time to Event Analysis Bruno Leslie, Katherine Moore, Joao L. Pippi Salle, Antoine E. Khoury, Anthony Cook, Luis H.P.

Braga, Darius J. Bägli, Armando J. Lorenzo The Journal of Urology - September 2010 (Vol. 184, Issue 3, Pages 1093-1099

BBD

No BBD

The Journal of UrologyVolume 184, Issue 3 , Pages 1134-1144,

September 2010

Summary of the AUA Guideline on Management of Primary

Vesicoureteral Reflux in Children

Craig A. Peters, Steven J. Skoog, Billy S. ArantJr., Hillary L. Copp, Jack S. Elder, R. Guy Hudson, Antoine E. Khoury, Armando J.

Lorenzo, Hans G. Pohl, Ellen Shapiro, Warren T. Snodgrass, Mireya Diaz

BBD is associated with more UTIs on CAP BBD is associated with less reflux resolution

at 24 month BBD is associated with reduced success for

endoscopic therapy but not open surgery BBD is associated with increased incidence

of UTI after surgery

Predicting The Risk For Breakthrough Urinary Tract Infections In Patients With

Primary Vesicoureteral Reflux

Guy Hidas, John Billimek , Alexander Nan, Blake Watts, Maryellen Pribish, Soltani Tandis, Elias Wehbi, Irene

McAleer, Gordon McLorie, Sheldon Greenfield, Sherrie H. Kaplan, Antoine E. Khoury

University of California, Children's Hospital of Orange County, Orange, CA, USA

Prevention of Renal Injury

PrenatalOr

Post UTI

Bladder DysfunctionConstipation

Sex Race

AgeInfant

Vs.>5 y

Grade of VUR

Number of Febrile

UTI

Presence of Parenchymal

changes

VUR is a spectrum

Methods

Retrospective Data Review to Construct Risk

Calculator

Prospective Application of Risk Calculator

To evaluate accuracy

Prospective Validation of Risk Model

We tested the risk model on a prospective cohort of 56 patients with VUR followed for two years

Mean probability prediction of BTUTI using the model was 19.5%

21% (12 patients) actually experienced BTUTI

The model also showed good discrimination between positive versus negative BTUTI cases in this prospective sample (AUROC= 0.80).

VUR BTUTI RiskScore Calculator

http://www.paperact.com/ireflux.html

Categorical risk stratification

• VUR Grade I-III andNo BBD

• Circumcised MaleLow RiskLow Risk

• VUR Grade I-III and BBD• Uncircumcised Male• VUR Grade IV-V, Female,

Presented as PNH

Intermediate Risk

Intermediate Risk

• VUR Grade IV and V• and Female • and Presented as a UTI

High Risk High Risk

% of PopBUTI Risk

67% 8%

27% 27%

6% 62%

VUR Score

Low Risk: Nothing ± Periodic RBUS

Intermediate Risk: CAP + Periodic RBUS

High Risk: early intervention

Females after puberty????

7. Hematuria

Microscopic Hematuria

Microscopic hematuria is a common finding in children.

In two large population-based studies, 3-4% of unselected school-age children between 6 to 15 years of age had a positive dipstick for blood in a single urine sample

Drops to 1% or less for two or more positive samples. Among the 1 percent of children with two or more positive urines for hematuria, only one-third have persistent hematuria (positive repeat test after six months)

Routine office screening with urinalysis for urinary abnormalities is no longer recommended.

The actual time of onset for microscopic hematuria is often unknown

Microscopic Hematuria

Confirmation of microscopic hematuria after a positive dipstick examination requires a microscopic examination of the urine for the presence of red blood cells and casts.

Glomerular VS. NonglomerularBleeding

Extraglomerular Glomerular

Color (if macroscopic) Red or pinkRed, smoky brown, or "Coca‐Cola"

Clots May be present Absent

Proteinuria Usually absent May be present

RBC morphology Normal Dysmorphic

RBC casts Absent May be present

Thin Basement Membrane Disease

Thin basement membrane disease (TBM), also called benign familial hematuria, is an autosomal dominant condition

Hypercalciuria

Defined in children as a urine calcium/creatinineratio >0.2 (mg/mg) in children older than six years of age,

In studies performed in the United States, the prevalence has ranged from as low as 11 percent in the Northeast to as high as 35 percent in the South.

Association between hypercalciuria and hematuria may be more common in areas where there is a higher prevalence of nephrolithiasis.

Transient hematuria

Urinary tract infection (dysuria and pyuria) Trauma Fever Exercise-induced hematuria

Evaluation

Hx: UTI, Stone, Water intake, Trauma, Menstruation

Remember to examine urethral meatus

Recommendation

Observation of children with asymptomatic microscopic hematuria with normal physical examination.

Extensive diagnostic evaluation reserved only in children with: Proteinuria Hypertension Gross hematuria

Gross Hematuria

0

5

10

15

20

25

30

35

40

0

5

10

15

20

25

30

35

40

Nephrology Urology

Gross Hematuria

Terminal Hematuria = Urethral source Exercise induced AVM Ca:Cr ratio >0.2 (mg/mg) Diet: Water + citrate + Less NaCl Consider an US if persistent Cystoscopy rarely indicated

8. Modern Management of the Undescended Testicle

EpidemiologyAt birth:

3-4% of full-term male infants

25-45% of pre-term male infants

At 6 and 12 months:

1% of full-term males

10% of pre-term male infants

10-25% are bilateral

Testicular AscentWell documented in the literatureVarious theories on the etiology:

Patent processus (found in 25-47% at surgery) Spasticity of cremasteric reflex Relative cranial migration due to linear growth

Similar abnormalities of germ cell development have been observed

Barthold and Gonzalez; J Urology 2003

Retractile testicle

Can be manipulated into the scrotum and stays

there for an undefined period of time

Most commonly seen at 5 yrs of age

Hyperactive cremasteric reflex

Should be monitored annually until puberty

7-33% “progress” to cryptorchidism

Physical examination

Warm, relaxed environment

Sweep fingers from internal ring to external ring

Facilitated by use of lubricant

Try supine first, then in a seated, cross-legged position

What is the Role of Imaging?

None

Ultrasound vs. Physical ExamTasian and Copp; Pediatrics 2011 Systematic review and meta-analysis 12 studies (591 testes) US has sensitivity of 45% and specificity of 78%

Conclusion – US does not reliably localize nonpalpable testes and does not rule out an intraabdominal testis.

No change in surgical management based on ultrasound findings!

Bilateral Non-palpable Testes Karyotype and endocrine evaluation

particularly when associated with hypospadias

Surgical exploration still required!

Kollin, Claude, Hesser, Ulf, Ritz, E Martin and Karpe, Bengt(2006) 'Testicular growth from birth to two years of age, and the effect of orchidopexy at age nine months: A randomized, controlled study', Acta Paediatrica, 95:3, 318 - 324

Testicular CancerPettersson et al; NEJM 2007

16,983 men underwent orchiopexy between 1964 and

1999

56 cases of testis cancer (0.3%)

Orchiopexy < 13yrs of age - RR = 2.23

Orchiopexy ≥ 13 yrs of age - RR = 5.40

Testicular Cancer Educate parents

Most common cancer

among men age 15-35yrs

Recommend testicular self-

exams starting in

adolescence

Take home messages Imaging is unnecessary

Normal paternity rates in unilateral cryptorchidism; decreased rates in bilateral

Ideal age for surgery is 6-12 months

Testicular self-exams starting in adolescence

9. DSD

Gender Assignment

4 components of psychosexual development gender identity gender role sexual identity sexual orientation.

Factors Influencing Psychosexual Development

Exposure to androgens Sex chromosomes Compliance Brain structure Social circumstance Family dynamics.

Gender Assignment

3 important factors Expected gender identity Sexual function Fertility potential

Other factors that may be considered include genital appearance gonadal malignant potential need for gonadectomy surgical options prenatal androgen exposure views of the family cultural practices.

The external masculinization score (EMS) has been used to aid this process. (Ahmed SF, Khwaja O and Hughes IA: The role of a clinical score in the assessment of ambiguous genitalia. BJU Int. 85: 120-4,) 2000.

Influence of Sex Hormones on the Developing Brain

Prenatal exposure contributes to gender identity

Current recommendation: genetic males be reared as male micropenis penile agenesis 46,XY males with PAIS 5-alpha reductase deficiency.

The majority of patients with 46,XX CAH and 46,XY CAIS patients identify as female

despite exposure to elevated androgen levels during fetal life.

It is recommended these patients are gender assigned as female

CAH: Prenatal DEX Treatment

Family History Start at 6-7 week of pregnancy Females only (7/8 fetuses treated unnecessarily)

Cell-free Fetal DNA Testing

Cell-free fetal DNA testing, a noninvasive prenatal screening of fetal DNA in maternal circulation, can provide early sex identification and genotyping without amniocentesis or chorionic villus sampling, and thus decreases unnecessary prenatal CAH dexamethasone therapy.

Feminizing Genitoplasty

vaginoplasty clitoroplasty Labioplasty Skin

Buccal mucosa graft

Hypospadias Reconstruction

10. Prepuce

Function of the prepuce

Protection of the glans

Infant “Smegma”

Penile pearls

Penile abscess

Penile cysts

Penile mass

Penile calcifications•Desquamated cells•Helps separation

Infants

XQ-tips

Irrigation

Antiseptics

Phimosis

Physiologic phimosisBy 3 years of age, 90% of foreskins are retractable,

less than 1% of males have phimosis by 17 years of age.

Early forceful retraction is not recommended

"Iatrogenic" Phimosis

Management of Physiologic Phimosis

Steroid + Gentle retraction 95% success Gentle retraction alone 45% success

(p<0.001)

Indications for Circumcision

MedicalSocial

Religious

Hygiene

Cosmetic

• Penile and cervical cancer • Sexually transmitted diseases• Phimosis and lessening of the

risk of balanitis.