Essential of paediatric urology

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PAEDIATRICUROLOGYESSENTIALSOF

This excellent and superbly illustrated text provides surgical trainees and non-specialists with an updated andextensively revised account of the urological disorders of childhood. The second edition reflects the manyadvances and innovations in paediatric urology since the first edition was published in 2002 and incorporatessuggestions and feedback from readers and reviewers of the first edition of Essentials of Paediatric Urology.There are new chapters such as “Minimally invasive paediatric urology”, which covers the innovative andrapidly advancing contribution made by laparoscopic surgery to effective patient care and "The Child as aPatient", which highlights the important differences of approach to caring for children and adults and providesclarification of the legal and ethical issues surrounding consent. There is also a new multiple choice questionchapter with cross-references to the text, as requested by many readers of the first edition, thus providing anaide-memoire for those undergoing speciality examinations.

This popular text was never intended to duplicate the large reference books written primarily for specialists.Instead it fulfils a unique role as the only textbook of paediatric urology written primarily for trainees andthose practising adult urology, paediatric surgery and paediatric urology. The second edition continues tomeet this need as well as providing a ready source of reference for non-specialists including paediatriciansand nurses. Like the first edition, the second is accessible and concise with a visual format characterised byextensive use of colour illustrations, flow charts and diagrams.

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SECONDEDITION

ESSENTIALS OF

PAEDIATRICUROLOGYSECOND ED IT IONEDITED BY

DAVID FM THOMASPATRICK G DUFFYANTHONY MK RICKWOOD

PAEDIATRICUROLOGY

ESSENTIALS OFTHOMAS • DUFFY • RICKW

OODSECONDEDITION

Essentials ofPaediatric Urology

Second Edition

Edited by

David FM Thomas FRCP FRCPCH FRCSSt James’s University Hospital

Leeds, UK

Patrick G Duffy MB BCH BAO FRCS(I) FEBUGreat Ormond Street

Hospital for Sick ChildrenLondon, UK

Anthony MK Rickwood MA FRCSFormerly of Royal LiverpoolHospital for Sick Children

Liverpool, UK

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© 2008 Informa UK Ltd

First published in the United Kingdom in 2002

Second edition published in the United Kingdom in 2008 by Informa Healthcare, Telephone House, 69-77 Paul Street,London EC2A 4LQ. Informa Healthcare is a trading division of Informa UK Ltd. Registered Office: 37/41 Mortimer Street,London W1T 3JH. Registered in England and Wales number 1072954.

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Although every effort has been made to ensure that drug doses and other information are presented accurately in this publication,the ultimate responsibility rests with the prescribing physician. Neither the publishers nor the authors can be held responsible forerrors or for any consequences arising from the use of information contained herein. For detailed prescribing information or instruc-tions on the use of any product or procedure discussed herein, please consult the prescribing information or instructional materialissued by the manufacturer.

A CIP record for this book is available from the British Library.

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To our wives: Marilyn, Zara and Valerie.

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Contents

List of Contributors ix

Preface xi

Acknowledgements xiii

1 Embryology 1David FM Thomas

2 Renal physiology and renal failure 15Richard Trompetor

3 Diagnostic imaging 25Melanie P Hiorns

4 Urinary tract infection 43Stuart J O’Toole

5 Vesicoureteric reflux 57David FM Thomas and Ram Subramaniam

6 Upper tract obstruction 73David FM Thomas

7 Duplication anomalies, ureterocoeles and ectopic ureters 93Anthony MK Rickwood, Nicholas P Madden and Su-Anna M Boddy

8 Posterior urethral valves and other urethral abnormalities 109Divyesh Desai and Patrick G Duffy

9 Cystic renal disease 121David FM Thomas

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10 Prenatal diagnosis 133HK Dhillon

11 Stone disease in children 143Patrick G Duffy, David FM Thomas and Martyn E Flett

12 Urinary incontinence 157Henrik A Steinbrecher, Padraig S Malone and Anthony MK Rickwood

13 Neuropathic bladder 171Henrik A Steinbrecher, Padraig S Malone and Anthony MK Rickwood

14 The urinary tract in anorectal malformations,multisystem disorders and syndromes 189Duncan T Wilcox

15 Bladder exstrophy and epispadias 199Peter Cuckow

16 Hypospadias 213Duncan T Wilcox and Pierre DE Mouriquand

17 The prepuce 233Kim AR Hutton

18 Testis, hydrocoele and varicocoele 247Nicholas P Madden

19 The acute scrotum 265David FM Thomas

20 Disorders of sex development 275Henri Lottman and David FM Thomas

21 Genitourinary malignancies 295Patrick G Duffy and Neil J Sebire

22 Urogenital trauma 307David FM Thomas

23 Laparoscopic paediatric urology 317Imran Mushtaq

Contentsvi

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Contents vii

24 Adolescent urology 331Christopher RJ Woodhouse

25 Children and young people as urological patients 341David FM Thomas

Appendix I Self-assessment section: Questions 349

Appendix II Self-assessment section: Answers 371

Index 375

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Contributors

Su-Anna M Boddy MS FRCS

Department of Paediatric UrologySt George’s HospitalLondonUK

Peter Cuckow MB BS FRCS (Paed)

Department of Paediatric UrologyGreat Ormond Street Hospital for Sick ChildrenLondonUK

Divyesh Y Desai MBBS MS MCHIR (UROL) FEAPU


HK Dhillon FRCS (ED)


Patrick G Duffy MB BCH BAO FRCS (I) FEBU


Martyn E Flett MB MCH BSC FRCS (PAED)


Melanie P Hiorns MRCP FRCR

Department of RadiologyGreat Ormond Street Hospital for Sick ChildrenLondonUK

Kim AR Hutton MBCHB CHM FRCS (PAED)

Department of Paediatric SurgeryUniversity Hospital of WalesCardiffWalesUK

Henri Lottman MD FEBU

Hôspital Necker-Enfants MaladesService de Chirurgie Viscérale Pédiatrique ParisFrance

Nicholas P Madden MA FRCS

Department of Paediatric Surgery and UrologyChelsea and Westminster HospitalLondonUK

Padraig S Malone MB MCH FRCSI FRCS

Department of Paediatric UrologySouthampton General Hospital SouthamptonUK

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Contributorsx

Pierre DE Mouriquand MD FRCS (ENG) EFAPU

Department of Paediatric UrologyClaude-Bernard University Debrousse HospitalLyonFrance

Imran Mushtaq MD FRCS (PAEDS)


Stuart J O’Toole MD FRCS (PAEDS)

Department of Surgical PaediatricsRoyal Hospital for Sick Children GlasgowScotlandUK

Anthony MK Rickwood MA FRCS

(Formerly)Department of Paediatric UrologyRoyal Liverpool Hospital for Sick Children LiverpoolUK

Neil J Sebire MB BS BCLINSCI DRCOG MD MRCPATH

Institute of Child Health andDepartment of Paediatric UrologyGreat Ormond Street Hospital for Sick ChildrenLondonUK

Henrik A Steinbrecher BSC MS FRCS (PAEDS)

Department of Paediatric UrologySouthampton University HospitalSouthamptonUK

Ram Subramaniam MD

Department of Paediatric SurgerySt James’s University Hospital LeedsUK

David FM Thomas FRCP FRCPCH FRCS

Department of Paediatric SurgerySt James’s University Hospital LeedsUK

Richard Trompetor MB FRCP FRCPCH

Department of NephrologyGreat Ormond Street Hospital for Sick ChildrenLondonUK

Duncan T Wilcox MD FRCS

Department of Paediatric UrologyUniversity of TexasSouthwestern Medical CenterDallas, TXUSA

Christopher RJ Woodhouse MB BS FRCS FEBU

Department of Paediatric UrologyThe Institute of UrologyLondonUK

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Preface

The specialty of paediatric urology has seen manyadvances and innovations since the publication ofthe first edition of Essentials of Paediatric Urology.This new edition has been extensively updated,revised and rewritten to reflect exciting develop-ments in areas such as laparoscopic paediatricurology, endoscopic correction of reflux, theincreasing use of MRI and the introduction of newsurgical procedures for hypospadias and bladderexstrophy. The scope of this new edition rangesfrom complex anomalies managed by specialistpaediatric urologists to common conditions suchas testicular maldescent, urinary infection andincontinence, which constitute a substantial part ofeveryday practice for urologists, general paediatricsurgeons and paediatricians.

We have sought to retain the accessible, didacticformat that proved a popular feature of the firstedition and wherever possible have also endeav-oured to include suggestions and helpful feedbackfrom trainees and other readers of the first edition.Throughout the book our over-riding aim hasbeen to provide a concise and up-to-date accountof the diagnosis and management of the urologi-cal conditions of childhood which is factual andevidence-based.

The contributors include internationally recog-nised authorities in their field – many of whom areregular contributors to the British Association ofPaediatric Urologists postgraduate training courseheld annually in Cambridge.

The content of the new edition has beendesigned to encompass the syllabus tested by theintercollegiate examinations in Urology and Paedi-atric Surgery, the Fellowship of the EuropeanBoard of Urology and the in-service examination ofthe European Society of Paediatric Urology. A newfeature of the second edition is a self-assessmentsection of multiple choice questions which isintended to provide a valuable learning and revisionaid for surgeons preparing for British, Europeanand North American Board Examinations.

It has also been our intention that the secondedition of Essentials of Paediatric Urology shouldretain the book’s role as a source of easy referencefor paediatricians, paediatric nephrologists, radiol-ogists and nurse specialists.

David FM ThomasPatrick G Duffy

Anthony MK Rickwood

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Acknowledgements

Our sincere thanks to Sue Gamble for her invalu-able help in the preparation and editing of thismanuscript. We are also indebted to Paul Brown,Medical Artist, and his colleagues in the Depart-ment of Medical Illustration at St James’s Univer-sity Hospital for their unrivalled professionalismand unfailing ability to meet the most unrealisticof deadlines. We should also like to acknowledgethe many helpful and constructive suggestions we

received from Richard England, Alex Lee,Jonathan Sutcliffe and Arash Taghizadeh, whokindly proofread the manuscript from a trainee’sperspective.

Finally, we owe a debt of gratitude to ourpublishing team at Informa Healthcare, especiallyAlan Burgess and his colleagues, Jonathan Mazliahand Oliver Walter; they ensured that the secondedition of ‘Essentials’ made crucial deadlines.

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Embryology

David FM Thomas

Introduction

A working knowledge of the embryology of thegenitourinary tract provides the basis for under-standing the structural anomalies encountered inpaediatric urological practice. Although this chapterwill concentrate predominantly on the clinicalaspects of embryology of the genitourinary tractit will also touch on some of the relevant basicscience and summarise developments in therapidly advancing field of developmental biology.

Genetic basis of genitourinarytract malformations

Chromosomal abnormalitiesThe nuclear DNA present in the normal humansomatic cell is represented by 23 pairs of chromo-somes: 22 pairs of autosomes and one pair of sexchromosomes, a karyotype expressed as 46XY(male) or 46XX (female).

Following the sequence of two meiotic divisionsduring gametogenesis each spermatazoon or oocytecarries only one unpaired copy of each autosomeand one sex chromosome – either X or Y. Fusionof the nuclear DNA of the gametes at the time offertilisation imparts the normal diploid status tothe fertilised zygote.

Structural chromosomal abnormalities occureither during the formation of the gametes

(gametogenesis) or during the first few cell divisionsof the fertilised zygote. Examination of sponta-neously aborted embryos reveals a high percentageof profound chromosomal abnormalities inconsis-tent with survival of the embryo. The most seriouschromosomal abnormalities compatible with survivalto term are trisomy 21 – Down’s syndrome (47XXor 47XY) – and trisomies 13 and 18.

Trisomies result from the failure of a pair ofchromosomes to separate fully during gameto-genesis, with the result that an additional copyof a chromosome or fragment of chromosomebecomes incorporated into the nucleus of a gamete(usually by a process termed translocation ornon-disjunction). The converse of the process,which gives rise to trisomic states, also results inthe formation of a gamete that is lacking a copy ofa particular chromosome. The zygote formed byfertilisation will therefore have only one copy ofthis chromosome – termed monosomy. Completeautosomal monosomic states are uniformly lethalbut some partial monosomies created by deletionof part of a chromosome are compatible withsurvival and are associated with specific syndromes.Deletion of a particular portion of chromosome 11 has been implicated in the aetiology of someWilms’ tumours.

A similar process of faulty separation affectingthe sex chromosomes is encountered in, forexample, Klinefelter’s syndrome (47XXY) or Turnersyndrome (45X). Monosomic forms (45X)account for approximately 50% of cases of Turner

1

Topics coveredGenetic basis of genitourinary malformationsEmbryogenesis

Upper urinary tractLower urinary tractGenital tracts

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syndrome, mosaicism (45X/46XX ) is present inapproximately 30% of cases while a structuraldeletion on one of the X chromosomes accountsfor approximately 20%. Abnormalities of thesex chromosomes often occur in mosaic form,mosaicism being defined as the presence of twochromosomally distinct cell lines derived from thesame zygote. In addition to translocation and non-disjunction, structural defects involving identifi-able segments of chromosomes include deletion,inversion, duplication and substitution.

The genetic imbalance arising from structuralchromosomal abnormalities is expressed as profounddisturbances of embryological development acrossa number of systems, including the genitourinarytract (Table 1.1).

Gene mutations occur in structurally intactchromosomes at the level of the nucleotidescomprising the individual genes. Such mutationsare not visible on microscopy but are amenable tostudy by techniques such as PCR (polymerasechain reaction) and FISH (fluorescent in situhybridisation). The role of individual genes canbe elucidated by studying the effects of so-called‘knock out’ deletion in transgenic mice.

Specific gene mutations have been identified in a number of inherited conditions affecting thegenitourinary tract, e.g. autosomal dominant poly-cystic kidney disease, X-linked Kallmann’s syndromeand renal coloboma syndrome (mutation of thePAX2 gene encoding for a transcription factorexpressed during development of the eye and urinarytract).

However, the majority of the congenitalanomalies encountered in paediatric urology do nothave such a clearly defined genetic basis. They eitherarise sporadically or are inherited as autosomaldominant traits with variable expression andpenetrance. Conditions such as vesicoureteric reflux,upper tract duplication, hypospadias, etc., whichexhibit a familial tendency are generally believed torepresent the interaction of multiple genes, ratherthan a single gene mutation. The extent to whichexternal factors in the fetal or the wider environmentinfluence the expression of genes involved inregulating the development of the genitourinarytract is poorly understood. However, it is known,for example, that gene expression and regulationwithin the differentiating fetal kidney is markedlyaffected by early urinary tract obstruction.

Essentials of paediatric urology2

Chromosome defect or syndrome Frequency (%) Genitourinary anomalies

Turner syndrome 45X0 60–80 Horseshoe kidneyDuplication

Trisomy 18 (Edwards’ syndrome) 70 Horseshoe kidneyRenal ectopiaDuplicationHydronephrosis

Trisomy 13 (Patau syndrome) 60–80 Cystic kidneyHydronephrosisHorseshoe kidneyUreteric duplication

4p (Wolf–Hirschorn syndrome) 33 HypospadiasCystic kidneyHydronephrosis

Trisomy 21 (Down’s syndrome) 3–7 Renal agenesisHorseshoe kidney

Table 1.1 Chromosome defects associated with urinary tract anomalies


Embryogenesis

Human gestation spans a period of 38 weeks, fromfertilisation to birth. Conventionally, pregnancy isdivided into three trimesters, each of 3 months’duration. The formation of organs and systems(embryogenesis) takes place principally betweenthe third and 10th weeks of gestation. Throughoutthe remainder, the fetal organs undergo differenti-ation, branching, maturation and growth. In eachovulatory cycle a small number of germ cells(primary oocytes) within the ovary are stimulated toresume the long-arrested meiotic division. Of these,usually only one progresses to be extruded from theovary into the fallopian tube at the midpoint ofthe menstrual cycle. At the time of fertilisation theprotective zona pellucida of the oocyte is penetratedby the fertilising spermatazoon, thereby triggeringthe final meiotic division to create the definitiveoocyte and second polar body (consisting of non-functional DNA). Fertilisation is defined as thefusion of the nuclear DNA of the male and femalegametes (spermatazoon and definitive oocyte). Inthe ensuing 5 days, the fertilised zygote undergoesa series of mitotic doubling cell divisions termedcleavage (Figure 1.1).

Implantation of the spherical mass of cells(blastocyst) into the primed uterine endometriumoccurs approximately 6 days after fertilisation.Proliferation of the embryonic cell mass over theensuing 10 days is accompanied by the appearanceof two cavities – the amniotic cavity and the yolksac. The embryo is destined to develop from thecells interposed between these two cavities. Theectodermal tissues of the embryo derives fromthe layer of cells on the amniotic surface of theembryonic disc, whereas the endodermal deriva-tives have their origins in the layer of cells adjacentto the yolk sac (Figure 1.2). Inpouring of cellsfrom the amniotic surface via the primitive streakcreates a third layer of embryonic tissue, theintraembryonic mesoderm, which subdivides intoparaxial, intermediate and lateral plate mesoderm.It is from the intermediate block of intraembryonicmesoderm that much of the genitourinary tract is

derived. Segmentation and folding of the embryobegins during the third and fourth weeks of gesta-tion, and towards the end of this period the precur-sor of the embryonic kidney begins to take shape.

Embryology 3

4-Cell embryo(Day 2)

Morula(Day 4)

Blastocystimplants intoendometriumat 5 days

2-Cell embryo(Day 1)

Penetration ofoocyte triggersmeiosis. Fusionof nuclei createsfertilised zygote

Ovulation

Figure 1.1 Key stages in the 5–6 days from fertilisa-tion to implantation.

Embryonicdisc

Primitive streak

Cloacal membrane

Ectoderm

Intraembryonicmesoderm

Endoderm

Amnioticcavity

Yolk sac

Cross-section

Figure 1.2 Embryonic disc at 16 days. Formation ofintraembryonic mesoderm by inpouring of cells at theprimitive streak.


In vitro fertilisation (IVF)Many of the more severe congenital abnormalitiesof the genitourinary tract frequently carry a signif-icant risk of infertility or subfertility. Examples inmales include oligospermia or azoospermia due tocryptorchidism, impaired ejaculation in men witha history of posterior urethral valves or bladderexstrophy and erectile dysfunction in men withneurological impairment associated with spinabifida. Causes of infertility or reduced fertility infemales include Turner syndrome, spina bifida andcloacal anomalies. With the development of in vitrotechniques, the outlook for fertility is not always asbleak as was once the case. In the technique ofintracytoplasmic sperm injection (ICSI), spermato-zoa are harvested directly from the testis orepididymis and a single spermatozoon is selectedand injected into an oocyte. The fertilised zygoteis then inserted into the uterus. This techniqueis particularly applicable to men with obstructiveazoospermia or oligospermia. Other techniquessuch as gamete intrafallopian transfer (GIFT) orzygote intrafallopian transfer (ZIFT) may also beapplicable, depending upon the cause of infertility.

Upper urinary tract (Figure 1.3)

In the cervical portions of the paired blocks ofintermediate mesoderm the primitive precursor ofthe kidney, the pronephros, first appears in thefourth week of gestation. This structure rapidlyregresses in the human embryo. The midzonemesonephros, however, continues to differentiate,giving rise to tubular structures which, althoughultimately destined to contribute to the definitivegonad, function briefly in an excretory role. In the mesenchyme lying lateral to the developingmesonephros, the mesonephric ducts appear, advanc-ing caudally to fuse with the terminal portion ofthe hindgut (the primitive cloaca). Canalisation ofthe mesonephric ducts creates a patent excretoryunit which is believed to function transiently.

At the beginning of the fifth week, the uretericbuds arise from the distal portion of the paired

mesonephric ducts and advance towards the mostcaudal portion of the blocks of intraembryonicmesoderm – the metanephros. Fusion of theureteric bud and metanephric blastema at around32 days initiates the process of nephrogenesis.Between the sixth and 10th weeks the lobulatedembryonic kidneys ascend up the posteriorabdominal wall, deriving their blood supplysequentially at different levels until the definitivelumbar position is achieved (Figure 1.4).

NephrogenesisThe formation of nephrons within the developingkidney is an example of ‘reciprocal induction’. The


Pronephros

Mesonephros

Metanephros

Cloaca

Mesonephricduct

Ureteric bud Metanephricblastema

Intermediatemesoderm

Figure 1.3 Embryonic precursors of the upperurinary tract, metanephros (kidney), ureteric bud.

Mesonephros

Gonad

Paramesonephricduct

Metanephricblastema/kidney

Mesonephric duct Ureter

Figure 1.4 Embryonic genitourinary tract at 6–8weeks.


ureteric bud derivatives give rise to the renal pelvis,major calyces, minor calyces and collecting ducts,whereas the glomeruli, convoluted tubules andloop of Henle are derived from metanephricmesenchyme. Urine production commences ataround the 10th week, when continuity is estab-lished between the distal convoluted tubules andcollecting ducts. Proliferation of the ureteric budderivatives ceases at around 15 weeks, but newgenerations of nephrons continue to appear sequen-tially within the renal cortex until 36 weeks. At thattime the process of nephrogenesis ceases and thenumber of nephrons within each kidney remainsfixed for life. There is considerable variation in thenumber of nephrons within a normal kidney, with amedian value of approximately 700 000.

Nephrogenesis is the subject of extensiveresearch to identify the molecules responsiblefor cell-to-cell signalling. A large number havealready been identified, including growth factors,transcription factors (DNA-binding proteins thatregulate gene expression) and adhesion molecules.The rennin–angiotensin system has recently beenfound to play an important role in regulating earlydifferentiation and development of the urinarytract. Two different tissue receptors are responsiblefor mediating the actions of angiotensin 2. Whereasstimulation of the angiotensin type 1 receptorpromotes cellular proliferation and the releaseof growth factors, stimulation of the angiotensintype 2 receptor, which is expressed mainly in theembryo and fetus, mediates apoptosis (programmedcell death) and diminished cell growth. Differingpatterns of renal malformation are observedin transgenic ‘knock out’ mice, depending onwhether the gene encoding for the type 1 or thetype 2 receptor is deleted. Targeted ablation ofthe uroplakin 3 gene results in a convincingexperimental model of primary vesicouretericreflux. But, whereas the wealth of informationbeing revealed by molecular biology is advancingour understanding of inherited renal disease,experimental findings do not always translatereadily into the clinical setting. For example,screening of patients with vesicoureteric refluxfor mutations of the angiotensin receptor 2 gene

and uroplakin 3 gene have yielded uniformlynegative results.

Clinical considerationsThe normal embryological development of theupper tract is heavily dependent on the role of theureteric bud. Faulty or failed interaction betweenthe ureteric bud and metanephric mesenchymeresults in renal agenesis or differing patterns ofrenal dysplasia.

Renal agenesis

One or both kidneys may be congenitally absent,either as part of a syndrome or as an isolatedanomaly. The origins of renal agenesis include:

• Intrinsic defect of embryonic mesenchyme. Theassociation between unilateral renal agenesisand ipsilateral agenesis of the paramesonephricduct derivatives in girls provides evidence of afundamental defect of mesenchymal tissue (seebelow).

• Failed induction of nephrogenesis.• Involution of a multicystic dysplastic kidney.

This common renal anomaly has been shown toinvolute both in utero and in postnatal life tomimic the findings of renal agenesis.

The empirical recurrence risk of bilateral renalagenesis is 3.5%. In contrast, unilateral renal agene-sis is often a ‘silent’ condition and its inheritance ispoorly documented.

Renal dysplasia

‘Dysplasia’ is a histological diagnosis in whichthe internal architecture is disordered and charac-terised by the presence of immature ‘primitive’undifferentiated tubules and the inappropriate(metaplastic) presence of cartilage and fibromuscu-lar tissue. The kidney is usually smaller thannormal. Renal dysplasia results from faulty interac-tion between the ureteric bud and metanephrictissue, or from a major insult to the embryonic andfetal kidney, e.g. severe obstructive uropathy.

Embryology 5


Cystic anomalies

The patterns of cystic renal disease and their aetiol-ogy are considered in Chapter 9. There is someevidence to suggest that defective development ofthe ureteric bud is implicated in the causation ofmulticystic dysplastic kidney.

Abnormalities of renal ascent and fusion

This spectrum of renal anomalies including pelvickidney, horseshoe kidney and crossed renal ectopiadates from the sixth to the ninth weeks of gestation,when the embryonic kidney is ascending to itsdefinitive lumbar position. Horseshoe kidney has areported autopsy incidence of 1:400 (Figure 1.5).Fusion of the lower poles of metanephric tissue inter-feres with the normal process of renal ascent, vascu-larisation and rotation. Pelvic kidney (Figure 1.6)and crossed fused renal ectopia (Figure 1.7) provide

further examples of anomalies resulting from defectsof ascent and fusion of the embryonic kidney.

Fetal renal functionThe fetus is in effect, dialysed by the placenta,which fulfils the homeostatic excretory role of thekidney until the time of delivery. For this reason,anephric fetuses may survive until term. The fetalkidneys, however, do serve the important role ofproducing increasing volumes of urine, the mostimportant constituent of amniotic fluid. By the36th week of gestation it is estimated that fetalurine accounts for approximately 90% of theamniotic liquor. A reduction in the production offetal urine as a result of renal damage (agenesis ordysplasia) or obstructive uropathy causes oligohy-dramnios and consequent moulding deformitiesof the fetus and pulmonary hypoplasia. Amnioticfluid in sufficient volume is an essential factorcontributing to normal fetal lung development.


Figure 1.5 Abnormality of renal ascent and fusion –horseshoe kidney.

Figure 1.6 Abnormality of ascent – pelvic kidney.


Lower urinary tract (Figure 1.8)

The lower urinary tract originates from the cloaca,the section of primitive hindgut into which themesonephric ducts and embryonic ureters drain.Between the fourth and sixth weeks of gestation,the cloaca is subdivided by the descent of theurorectal septum towards the perineum and bylateral ingrowth of the folds of Rathke. The effectis to compartmentalise the cloaca into the urogeni-tal canal anteriorly and the anorectal canal posteri-orly. While the bladder is taking shape in the upperportion of the urogenital canal, the distal ureter and mesonephric duct begin to separate. Themesonephric ducts migrate caudally to join into thedeveloping posterior urethra, whereas the uretersremain relatively fixed at their point of entry in thedeveloping bladder (Figure 1.9). The adjacentmesenchyme of the pelvis undergoes differentiationinto the detrusor, a smooth muscle component of

the bladder wall, in response to induction bycontact with the embryonic urothelium. In thefemale the urethra is derived entirely from thedistal portion of the urogenital canal, whereas inthe male the urogenital canal gives rise to theposterior urethra and the anterior urethra iscreated by the closure of the urogenital groove.The allantois protrudes from the dome of the fetalbladder like an elongated diverticulum, extendinginto the umbilical cord. Subsequently, the obliter-ated allantois persists as the median umbilicalligament. Rarely, the allantois remains patent,giving rise to a congenital umblical urinary fistula(patent urachus) or an encysted remnant.

Clinical considerationsThe spectrum of cloacal anomalies encounteredin clinical practice correlates closely with varyingdegrees of failed or incomplete descent of theurorectal septum. The embryological origins of

Embryology 7

Figure 1.7 Abnormality of ascent and fusion –crossed fused renal ectopia.

Cloaca

Cloacalmembrane

Rathkefolds

Bladder

Urogenitalsinus

Anorectalcanal

GenitaltubercleUrogenitalmembraneAnalmembrane

Urorectalseptum

AllantoisPrimitive hindgut

Figure 1.8 Compartmentalisation of cloaca intothe urogenital compartment and anorectum by thedescent of the urorectal septum – 4–6 weeks.


bladder exstrophy and epispadias are less readilyapparent, but probably result from early defects ofthe cloacal membrane. Incomplete ureteric dupli-cation results from bifurcation of the ureteric bud.Complete ureteric duplication is characterised by apattern of ureteric anatomy in which the ureterdraining the upper pole paradoxically enters theurinary tract more distally than the lower poleureter (in some cases draining ectopically into thevagina). This anatomical configuration (described

by the Meyer–Weigert law) occurs when themesonephric duct separates from the embryoniclower pole ureter and descends towards the devel-oping posterior urethra (with a tendency to takethe upper pole ureter with it).

Genital tracts

The internal and external genitalia of both sexes aregenetically ‘programmed’ to differentiate passivelydown a ‘default’ female pathway unless activelyswitched down a male pathway by the geneticinformation carried by the testis-determining gene(SRY). Until the sixth week of gestation, thegenitalia of both sexes share identical embryonicprecursors. Differentiation of the gonads andgenital tracts is initiated by the migration ofprimordial germ cells from the yolk sac, acrossthe coelomic cavity to condensations of primitivemesenchyme in the lumbar region of the embryo.By a process of reciprocal interaction, the germ cellsand surrounding mesenchyme form the primitivesex cords within the embryonic gonad. At aroundthis time (6 weeks), the paired paramesonephricducts appear as cords of coelomic epithelium lyinglateral to the mesonephric ducts. From this stageonwards, the pathways of male and female differen-tiation diverge.

FemaleInternal genitalia (Figure 1.10)

Although the primitive sex cords degenerate, second-ary sex cords derived from genital ridge mesodermenfold the primordial germ cells to form primitivefollicles. Differentiation of the genitalia down afemale pathway cannot be entirely explained by theabsence of the SRY gene. Normal development of theovary does appear to at least be partly dependent onthe presence of the two normal X chromosomes,since patients with Turner syndrome who have asingle X chromosome (X karyotype) typically havepoorly formed, dysgenetic ovaries.

In the female, the initial phase of gametogenesis(transition from primordial germ cell to primary


Kidney

Mesonephricduct (vas deferens)

Ureter

Ureter

Ureter

Vas deferens

Vas deferens

Trigone

Figure 1.9 Changing anatomical relationships ofureters and mesonephric duct derivatives.


oocyte) occurs within the fetal ovaries. During fetal life these primary oocytes embark on the firstphase of meiotic division before entering a longphase of arrested division, which resumes againonly at puberty. In the absence of testosterone, themesonephric ducts regress (leaving only vestigialremnants – the epoöphoron, paroöphoron andGartner’s cysts). The paramesonephric ducts persistin the form of the fallopian tubes. Distally, the fusedportions of the paramesonephric ducts give rise tothe uterus and upper two-thirds of the vagina.

At the junction of the paired paramesonephricducts with the urogenital sinus a condensation oftissue, the sinuvaginal bulb, develops. Between the10th and 20th weeks of gestation displacement ofthe sinuvaginal bulb in the direction of the fetalperineum separates the developing vagina from theurethra. During this process, canalisation of thevagina occurs. The upper two-thirds of the vagina isderived from the paramesonephric ducts, whereasthe distal third has its origins in the urogenital sinusand the introitus and external genitalia are derivedfrom ectoderm (Figure 1.11).

External genitalia

In the absence of androgenic stimulation, theexternal genitalia of the embryo and fetus differen-tiate passively down a female pathway. The genitaltubercle gives rise to the clitoris, the urogenitalsinus contributes the vestibule of the vagina, whilethe urogenital folds persist as the labia minora, andthe labioscrotal folds persist as the labia majora.

MaleInternal genitalia (Figure 1.12)

Current evidence indicates that differentiation ofthe male genitalia is initiated by a single testis-determining gene (SRY) located on the Y chromo-some and then mediated through other Ychromosomal and autosomal ‘downstream’ genes.The gene product expressed by the SRY gene isresponsible for stimulating the medullary sex cordsto differentiate into secretory pre-Sertoli cells.From the seventh week onwards these pre-Sertolicells secrete anti-müllerian hormone (AMH) –otherwise termed müllerian inhibiting substance(MIS), a glycoprotein that plays a central role insubsequent differentiation of the male genital tract.

In the male the paramesonephric ducts disappearcompletely, with the exception of vestigial remnants(the appendix testis and utriculus). At least threeimportant properties are ascribed to MIS:

1. MIS stimulates regression of the paramesonephricducts.

2. Production of testosterone by the Leydig cellsof the embryonic testis is initiated by MIS fromthe ninth week of gestation. During the 12thto 14th weeks of gestation the fetus is exposedto very high levels of androgenic stimulation.

3. The first stage of testicular descent is mediatedby the action of MIS on the gubernaculum,which anchors the embryonic testis in thevicinity of the developing inguinal canal.

Embryology 9

Gartner’s cyst

Fusedparamesonephricducts (ureterovaginalcanal)

Fallopiantube

OvaryEpoöphoronParoöphoron

GonadMesonephros

Paramesonephricduct

Mesonephricduct

Ureter

Figure 1.10 The undifferentiatedgenital tract is genetically pro-grammed to proceed down thepathway of female differentiationunless switched down the malepathway by the SRY gene.


In contrast to the germ cell differentiation initiatedin the female embryo, male primordial germ cellsare inhibited from further division within theembryonic gonad. Although gametogenesis doesnot commence until after puberty the testis is not

entirely quiescent in childhood since there isevidence that the fetal gonocyte germ cell pooltransforms into adult type gonocytes in early child-hood. The mesonephric duct derivatives differenti-ate between the eighth and 12th weeks of gestationto give rise to the epididymis, rete testis, vas defer-ens, ejaculatory ducts and seminal vesicles. Thisoccurs in response to exposure to testosterone(probably by diffusion) from the developing testis.

The development of the prostate gland isdependent upon circulating testosterone andprovides a further example of reciprocal induction.Proliferation and branching of the endodermallining of the urethra (which gives rise to the ductsand glanular acini of the prostate gland) inducesdifferentiation of surrounding mesenchyme toform the capsule and smooth muscle, a processthat ceases after the 15th week of gestation.

External genitalia (Figure 1.13)

A number of factors are responsible for the differ-entiation of the male external genitalia, includingthe synthesis of testosterone by the fetal testis, theconversion of testosterone into dihydrotestos-terone by the enzyme 5α-reductase and thepresence of androgen receptors within the targetcells. Androgenic stimulation of the genital tuber-cle results in the development of the male phallus.From the seventh week of gestation the maleurogenital sinus advances on to the phallus as theurethral groove. Ingrowth of this urethral grooveis associated with the appearance of urethral platetissue destined to canalise and form the definitivemale anterior urethra. Closure of the urethra iscomplete by around 15 weeks, with ingrowth ofectoderm from the tip of the glans forming theterminal portion of the urethra.

The testis

Tesicular descent is believed to occur in twodistinct phases, the first initiated by MIS, thesecond being dependent upon exposure to testos-terone. Experimental studies in rats have indicatedthat the gubernaculum plays a key role in testicu-lar descent (although the precise mechanism may


Fusedparamesonephricducts

Sinuvaginal bulb(urogenital sinus)

Genital canal

Vaginal plate

Uterus

Vagina(paramesonephric origin)

Vagina (urogenital sinus)

Figure 1.11 Development of the lower femalegenital tract between 10 and 20 weeks.


be subject to some species variation). Extendingfrom the testis down to the region of the labioscro-tal swellings, the gubernaculum has the effect ofanchoring the fetal testis in the proximity of the future inguinal canal. Under the influence oftestosterone, a second more active phase of testic-ular descent occurs between 25 and 30 weeks,when the gubernaculum contracts in length,dragging the testis down the inguinal canal intothe scrotal position it occupies at birth. During the

course of its descent the testis is accompanied by asac-like protrusion of peritoneum, the processusvaginalis.

Clinical considerationsAbnormalities of female internalgenitaliaPatterns of faulty development of the paramesonephricduct derivatives include agenesis, hypoplasia, defective

Embryology 11

Epididymis

Vasdeferens

Seminalvesicle

ProstaticutricleProstate

TestisMIS MIS

Testis TestisTestosterone

Figure 1.12 Differentiation of themale genital tract in response tomüllerian inhibitory substance andtestosterone.

Genital tubercle

Urogenital fold

Labioscrotal fold

Ectodermal ingrowth

(genital tubercle)ShaftLabiumminorum(urogenitalfold)

Urogenital groove(urogenital sinus)

Labiummajorum

(labioscrotal fold)

UrogenitalmembraneCloacal

membraneAnalmembrane

Male Female

{

Urethra (urogenital sinus) Vestibule

Glans (genital tubercle) Clitoris

Scrotum

Figure 1.13 Differentiation of the external genitalia determined by androgenic stimulation.


canalisation and duplication. Unilateral agenesis ofparamesonephric duct derivatives (absent fallopiantube, hemiuterus, etc.) may be accompanied byunilateral renal agenesis, suggesting a fundamentalunderlying defect of the original ipsilateral interme-diate mesoderm. Agenesis of the upper two-thirds ofthe vagina (Rokitansky syndrome) reflects a failure ofthe paramesonephric ducts to fuse distally and mergewith the urogenital sinus. Transverse vaginal septaand short atretic segments can be attributed todefective canalisation (Figure 1.14), whereas dupli-cation anomalies such as bicornuate uterus representincomplete fusion of the distal paramesonephricducts (Figure 1.15).

Female external genitalia

The aetiology and classification of disorders ofsexual development (DSD) are considered in moredetail in Chapter 20. The most commonly encoun-tered example in Western Europe is virilisation ofthe external genitalia in a female with a 46XXgenotype resulting from congenital adrenal hyper-plasia. In affected individuals, the internal repro-ductive tract differentiates normally but theexternal genitalia virilise in response to high levelsof circulating androgens of adrenal origin.

Male internal genitalia

The rare genetically determined syndrome of MIS deficiency is characterised by bilateralundescended testes accompanied by the presenceof persistent paramesonephric duct structures,including fallopian tubes and uterus. A receptordefect is responsible for approximately 50% ofcases, whereas the remaining cases are genuinelyattributable to a deficiency of this hormone. Withthe exception of the undescended testes, the exter-nal genitalia virilise normally as this is not depend-ent on MIS.

The persistence of a müllerian sac-like prostaticutricle is predominantly a feature of impaired viril-isation and patients with proximal hypospadias orDSD account for more than 90% of cases.

In the syndrome of androgen insensitivity, theexternal genitalia exhibit a receptor defect todihydrotestosterone (the derivative of testosteroneactive in the peripheral tissues). As a result, theexternal genitalia differentiate passively down thefemale pathway despite a male phenotype andnormal male internal genitalia.

Male external genitalia

Hypospadias results from varying degrees ofincomplete closure of the urethral groove (althoughdistal glanular hypospadias may simply representfailure of ectodermal ingrowth). Severe hypospadias,particularly when accompanied by cryptorchidismand a persistent müllerian utriculus, is evidentlythe outcome of a generalised virilisation defect.However, although isolated endocrinopathies have


Figure 1.14 Canalisation defect – transverse vaginalseptum.

Figure 1.15 Fusion defect – bicornuate uterus.


occasionally been identified in such cases, as yet nosingle endocrine defect has been implicated in theaetiology of hypospadias.

Similarly, there is no single unifying aetiologyfor cryptorchidism. Bilateral cryptorchidism ismore likely to represent the influence of anendocrinopathy or imbalance of the pituitary–gonadal axis, whereas local mechanical factors(possibly related to the gubernaculum or theprocessus vaginalis) are likely to play a moreimportant role in the unilateral cryptorchidism.The combination of a blind-ending vas and histo-logical findings of calcification and haemosiderinin ‘nubbins’ of residual testicular tissue suggeststhat most cases of so-called testicular ‘agenesis’result from testicular torsion in utero.

Key points

• The genitourinary tract is commonlyaffected in children with chromosomalabnormalities.

• The ureteric bud plays a pivotal role innephrogenesis and the embryologicaldevelopment of the upper tract.

• A number of important congenitalanomalies can be ascribed to defects of the ureteric bud.

• The undifferentiated genital tract ofboth sexes is ‘programmed’ todifferentiate passively down a femalepathway unless positively directeddown a male pathway by the presence of the SRY gene and associated

downstream genes andtheir products.

• Although single gene mutations havebeen implicated in the aetiology ofsome inherited genitourinaryabnormalities, most of the conditionsencountered in paediatric urologyoccur on a sporadic basis or resultfrom the interaction of multiple genes.

• In vitro fertilisation techniques (IVF) offer the prospect of fertility to somepatients whose genitourinarymalformations would previously havebeen a bar to parenthood.

Further reading

Hutson JM, Terada M, Baiyun Z, Williams MPL. Normaltesticular descent and aetiology of cryptorchidism.Advances in Anatomy, Embryology and Cell Biology.Berlin: Springer Verlag, 1996: 132

Larsen WJ (ed). Human Embryology. Edinburgh: ChurchillLivingstone, 2002

McNeal JE. Anatomy and embryology. In: Fitzpatrtick JM,Kane RJ (eds). The Prostate. Edinburgh: ChurchillLivingstone, 1989: 3–9

Stahl DA, Koul HK, Chacko JK, Mingin GC. Congenitalanomalies of the kidney and urinary tract (CAKUT): acurrent review of cell signalling processes in ureteraldevelopment. J Pediatr Urol 2006; 2: 2–9

Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonicstem cell lines derived from human blastocysts. Science1998; 282: 1145–1147

Woolf AS, Price KL, Scambler PJ, Winyard PJ. Evolvingconcepts in human renal dysplasia. J Am Soc Nephrol2004; 15(4): 998–1007

Embryology 13



Renal physiology andrenal failure

Richard Trompetor

Renal physiology in the fetusand newborn

IntroductionAlthough the kidney plays a key role in enablingthe newborn infant to adapt to the postnatal physi-ological environment, it is immature and its abilityto regulate and maintain normal homeostasis isreduced, particularly in premature neonates. Avariety of different pathological insults andmetabolic demands can further impair the physio-logical function of the kidney in this age group. Asa consequence, the nephrological management ofneonates differs in several important respects fromthe management of older children.

In the later stages of pregnancy the fetus is in a stateof physiological volume expansion. Amniotic fluid isswallowed, absorbed in the gastrointestinal tract and‘recycled’ into the amniotic cavity via the kidneys.Fetal urine is the major constituent of amniotic fluidand production increases with gestational age fromapproximately 10 ml/h at 23 weeks’ gestation toapproximately 30 ml/h at 32 weeks’ gestation andcontinuing at that rate until the end of pregnancy.Oligohydramnios is usually a consequence of renaldysfunction or urinary tract obstruction.

The formation of new nephrons (nephrogenesis) inhumans is confined to intrauterine life and is completeby 36 weeks’ gestation – although in prematureinfants born before 36 weeks the normal pattern of

nephrogenesis continues after birth. Nephrogenesismay be affected by a number of prenatal factors,notably early urinary tract obstruction.

In the fetus, glomerular filtration rate (GFR) isproportional to body weight, but even when thefetal GFR has been corrected for body weight itremains considerably reduced, corresponding to30–50% of the weight-corrected adult value.Creatinine is not a useful indicator of fetal renalfunction as it freely crosses the placental barrier –with the result that fetal plasma creatinine valuesmirror those in the maternal circulation. Amnioticfluid volume is a crude index of urine productionand thus of fetal renal function, and measurementof electrolytes and osmolality in amniotic fluid andfetal urine can also provide a guide to fetal renalfunction. Normal fetal urine is characterised by ahigh flow rate (>5 ml/kg/h), a low osmolality andrelatively low sodium concentration.

The GFR at birth correlates closely with gesta-tional age, being approximately 5 ml/min/m2 inpremature infants born at 28 weeks’ gestation and12 ml/min/m2 in infants born at term (40 weeks).Postnatally there is a sharp increase in GFR, whichdoubles by 2 weeks of age; however, it is not until2 years of age that the corrected GFR reaches thecorresponding adult-corrected value.

The low GFR in newborn infants is of consid-erable relevance to clinical management: e.g.in the interpretation of laboratory results andthe calculation of fluid requirements and drug

2

Topics coveredFetal and neonatal renal functionRenal impairment in infancy and childhood

Medical management Renal replacement therapy

02-Thomas-8043.qxd 2/29/2008 7:01 PM Page 15

dosages. This is particularly important in sickpremature babies. Although the neonatal kidneycan cope with most normal demands its functionalreserve is limited and may be overwhelmed bysome of the stresses commonly encountered inthe neonatal period. Several vasoactive systems,such as the renin–angiotensin system, intrarenaladenosine, the prostaglandins and atrial natriureticpeptide, are up-regulated in the neonatal periodand are important for the maintenance of GFR.Overstimulation of the renin–angiotensin system(for example by hypoxia) or inhibition of therenin–angiotensin system (by angiotensin-convertingenzyme inhibitors) can both predispose to renalfailure.

Water metabolismNewborn infants are born in a state of overexpan-sion of extracellular water, which is inverselyproportional to maturity. Following delivery, anacute isotonic volume contraction occurs withcorresponding weight loss. This phenomenon,which is part of the normal physiological adapta-tion to extrauterine life, is most pronounced andprolonged in premature infants.

The ability of the kidney to regulate waterbalance is not fully developed at birth. In responseto a hypotonic fluid challenge, term and pretermneonates produce urine with an osmolality of 50and 70 mosm/kg H2O, respectively. At this age thekidney has the capacity to increase urine flow andwater clearance in response to a waterload, but thisresponse is impaired and water excretion isprolonged. As a consequence, newborn infants arepoorly equipped to cope with fluid overload andare at greater risk of dilutional hyponatraemia.

The capacity of the neonatal kidney to produceconcentrated urine is also limited and, in the firstweek of life, the maximum urine concentrationsachieved by preterm and term neonates followingfluid restriction are 600 and 800 mosm/kg H2O,respectively. This limited concentrating capacityreflects a reduced responsiveness of the immaturekidney to vasopressin and an inability to maintaina corticomedullary osmotic gradient.

Sodium balanceNewborn infants have a limited capacity toconserve sodium when challenged by sodiumrestriction and a limited ability to excrete sodiumin response to a sodium load. In the first week oflife, urinary sodium excretion is high and inverselyproportional to the maturity of the neonate.Premature infants have an obligatory urinarysodium loss with consequent negative sodiumbalance. Plasma sodium and chloride concentra-tions often fall to low levels and urinary sodiumexcretion remains high relative to plasma sodium.This imbalance is thought to be a consequence ofrenal immaturity rather than redistribution ofsodium within body fluid compartments.

Disturbances in plasma sodium include:

1. Early-onset hyponatraemia (plasma sodium<130 mmol/l) occurring in the first week oflife. This is due to water retention and sodiumdepletion.

2. Late-onset hyponatraemia. This is usually theresult of inadequate sodium intake, renal sodiumwasting and free water retention.

3. Early-onset hypernatraemia (plasma sodium>150 mmol/l). This is usually iatrogenic inaetiology, resulting from repeated administra-tion of hypertonic sodium bicarbonate solutionto correct acidosis in severely ill neonates.

4. Late-onset hypernatraemia is due to theadministration of sodium supplements andinadequate free water.

The clinical consequences of excessive or inade-quate sodium intake are potentially serious, andcareful monitoring of sodium and water balance isessential in at-risk infants.

Potassium balancePostnatal plasma potassium levels differ in term andpreterm infants. In the term infant potassium levelsfall rapidly in the first week of life (although thereis considerable individual variation). In contrast, agradual rise in the plasma level of potassium is seen



Renal physiology and renal failure 17

in preterm infants, reaching a maximum at aboutthe third to fourth week of life. Elevated plasmapotassium levels may be a consequence of hypoxia,metabolic acidosis, catabolic stress, oliguric renalfailure and inadequate excretion by the immaturedistal nephron. The impaired ability of renaltubules to respond to aldosterone coupled withlow ATPase activity in the potassium-secretingepithelial cells of the distal nephron contribute toimpaired potassium excretion.

Acid–base balanceBy comparison with adults, neonates are acidotic:this is both respiratory and metabolic in aetiologyand is usually accompanied by cardiopulmonarycompensation. The capacity of the newborn infantto excrete an acid load is limited but the renalthreshold for bicarbonate resorption increases withadvancing maturation as the renal acidificationmechanisms develop. Although late-onset metabolicacidosis in premature infants is usually mild andrarely associated with clinical symptoms, moresevere acidosis gives rise to poor feeding andgrowth impairment. Supplements may be neededto ensure that plasma bicarbonate concentration ismaintained above 17 mmol/l.

Renal impairment in infancyand childhood

IntroductionA major reduction in the number of functioningnephrons as a result of congenital or acquireddamage gives rise to two distinct but related patho-logical states: first, since damaged nephrons areincapable of repair or regeneration, renal dysfunc-tion occurs; second, a series of secondary physiolog-ical, metabolic and hormonal changes then ensue asrenal function progressively declines. Treatment isdirected at decreasing the rate of progression ofchronic renal failure (CRF) and addressing thesequelae of renal dysfunction. The principal conse-quences of untreated CRF in children are:

• growth retardation• sexual immaturity• psychomotor or intellectual retardation.

Treatment must be initiated early in the course ofrenal dysfunction and should generally increase inintensity in parallel with progression of the disease.Chronic renal failure supervenes when the GFRdecreases to less than 25–30% of normal (correspon-ding to a plasma creatinine concentration of approx-imately 150–200 μmol/l) and clinical manifestationsusually become apparent at this stage.

IncidenceData from the United States and European registriesindicate that the incidence of chronic renal failure isapproximately 10–12 per million children in the agegroup 0–19 years. Since the number of childrenwith CRF is small compared with the adult popula-tion, there are fewer centres specialising in the treat-ment of renal failure in this age group.

The term end-stage renal disease (ESRD) is usedto describe the phase when renal dysfunction hasprogressed to the point where native renal functionhas failed and the individual becomes dependent oneither dialysis or renal transplantation for survival.According to data from the North AmericanPediatric Renal Transplant Cooperative Study, themost common renal disease diagnoses in childrenaged 0–17 years undergoing transplantation werehypoplastic–dysplastic kidneys, obstructive uro-pathy, focal segmental glomerulosclerosis, refluxnephropathy and systemic immunological disease.Congenital renal disorders accounted for 50% ofrenal failure in children under the age of 5 years.

Chronic renal failure

MeasurementIn adults, the progression of renal disease can bedemonstrated by a significant decline from apredictable normal adult value for GFR. Inchildren, this calculation is inherently more diffi-cult since both absolute GFR and actual GFR


must be adjusted for surface area during earlychildhood. In addition, corrected values for GFRnormally increase in the first year of life. Againstthe background of evolving function it is moredifficult to define the progression of renal impair-ment. Formulae based on the logarithmic value forserum creatinine concentration or reciprocal serumcreatinine concentration versus time have beenderived to predict the interval before dialysis ortransplantation is required. However, the predic-tive value of these formulae is subject to the limitedreliability of creatinine clearance as a measure ofGFR in the later stages of deteriorating function.As a broad guide, the serum creatinine concentra-tion at 6 months of age can be used to predict thetiming of renal replacement therapy (Table 2.1).

The point at which dialysis treatment becomesnecessary varies between individual children butonce the serum creatinine exceeds 500 μmol/l itbecomes unlikely that even the optimal medicalmanagement can avert the need for renal replace-ment therapy.

Growth and developmentThe causes of growth failure and poor intellectualdevelopment in children with CRF are multifactorialbut the principal factors involved are poor nutrition,

renal osteodystrophy, salt wasting, metabolic acidosis,anaemia and hormonal changes.

Malnutrition

Malnutrition in children with CRF is characterisedby food refusal, anorexia, nausea and vomiting.Anorexia is common in children with CRF andmay be secondary to increased levels of gastricpolypeptide; in addition, an increased incidence offoregut motility disorders predispose to gastroin-testinal reflux and vomiting. Growth velocity inchildhood is greatest in the first year of life andthus the impact of chronic disease and malnutri-tion is correspondingly more severe in this agegroup. Early therapeutic intervention is vital inorder to prevent growth failure and indicationsfor intervention include:

• failure to maintain expected weight gain despitethe addition of calorie supplements to the diet

• recurrent vomiting, despite the use of prokineticmedications

• parental stress.

In a significant percentage of infants, voluntaryoral intake is inadequate to meet energy or volumerequirements and feeding by nasogastric, nasojeju-nal or gastrostomy tube is necessary to ensureadequate water and dietary intake. Supplementalfeeding is given either by bolus or as a continuousovernight infusion. Infants who are tube fed atnight can be fed orally during the day. In thosechildren in whom it is necessary to administer theentire diet via tube feeding it is nevertheless impor-tant to maintain oral stimulation to help them toeat normally following renal transplantation.

In infancy, the dietary protein intake can becontrolled and the most appropriate food is eitherhuman milk or a humanised milk formula witha low phosphate content. At any given level ofprotein intake, increasing the overall energy intakewill enhance the efficient utilisation of protein.Most humanised milks have a protein-to-calorie


Table 2.1 Relationship between renal function at6 months and onset of end-stage renal disease(ESRD)

Prognosis (predictedSerum creatinine age of onset of(μmol/l) at end-stage renal6 months of age disease)

<150 Good prognosis150–300 ESRD 10+ years200–350 ESRD 5–10 years350–600 ESRD <5 years>600 Uncertain outcome



ratio of 2–3 g of protein per 100 kcal (8–12%calories as protein). Human milk has a protein-to-calorie ratio of 1.6 kcal per 100 kcal (approxi-mately 6% calories as protein). Infant formulascontaining 1.6–2 g of protein per 100 kcal are safeand meet the recommended dietary allowance(RDA) for protein intake in infancy.

Whenever possible, the serum urea level shouldbe kept <20 mmol/l by maintaining adequatecalorie intake and ensuring sufficient water is avail-able to avoid extracellular fluid volume depletion.There is a consensus that dietary intake of carbo-hydrate should approximate to 100% of the RDAfor the appropriate height and age. Calculatedenergy intake may need to be increased in children

with a low weight to height ratio. Energy supple-ments such as polyunsaturated corn oil, complexcarbohydrates or medium-chain triglycerides arewidely favoured because of their high caloriedensity and low cost.

A typical growth pattern in infancy and child-hood is illustrated in Figure 2.1. In this casegrowth (weight) remains below the third percentileand deviates from this percentile with the onset ofpuberty.

Figure 2.2 illustrates the growth pattern forboth height and weight in an infant in whomnasogastric tube feeding was instituted at the ageof 2 years, with resulting improvement in bothweight and height. At approximately 3 years ofage, overnight feeding was commenced, withfurther improvement in both weight and heightreflected in growth lines crossing the percentiles.

Renal osteodystrophy (Figure 2.3)

Disorders of mineral metabolism in children withCRF invariably affect skeletal growth and develop-ment, with resultant bone deformities and, in mostcases, deceleration of linear growth.

The crucial roles played by the kidney inbone and mineral homeostasis include:

• regulating calcium, phosphorus and magnesiummetabolism

• participating in the catabolism of parathyroidhormone (PTH)

• excreting aluminium and β2-microglobulin • synthesizing calcitriol or 1,25-hydroxyvitamin D3.

The primary site of vitamin D synthesis is locatedin the proximal nephron, where 25-hydroxyvitaminD is converted by the action of the 1α-hydroxylaseenzyme to 1,25-dihydroxyvitamin D3 (calcitriol) –its most potent and active metabolite (Figure 2.3).In renal failure, enzymatic activity decreases,leading to reduced production of calcitriol and thedevelopment of secondary hyperparathyroidism.In addition, urinary excretion of aluminium and

Hei

ght

Age (years)

A

B

C

3

50

97

Centiles

Figure 2.1 Growth pattern (height) in a child withuntreated chronic renal failure. Growth maintainedbelow the third percentile with downward deviationfrom the centile at puberty.


β2-microglobulin is impaired and may contribute tocertain forms of renal osteodystrophy.

Secondary hyperparathyroidism

This common feature of ESRD has a number ofcontributory factors:

• phosphate retention• hypocalcaemia• impaired calcitriol synthesis • alterations in secretion of PTH and reduced

sensitivity of the skeleton to the calcaemicactions of PTH.

Clinical manifestations

Osteodystrophy can present with non-specific signsand symptoms or may go unnoticed. A reductionin physical activity can be a subtle early symptomand it is important to be aware that radiographic

changes are not always a reliable guide to the sever-ity of the underlying bone disease.

Approximately 30–50% of children with CRFexhibit short stature and in 60% of children receiv-ing regular dialysis treatment growth velocity isbelow the normal range. In early renal osteodys-trophy bone pain is non-specific, but as the diseaseprogresses pain may be localised to the lower backand weight-bearing joints in ambulatory patients.The onset of a limp should be thoroughly evalu-ated because of the prevalence of slipped femoralepiphysis; indeed, all epiphyses can be affected andfractures can occur.

Skeletal deformity is a significant feature of long-standing untreated CRF in children, with thepatterns of deformity being age-related. In youngerchildren skeletal abnormalities are similar to thosedue to vitamin D-deficient rickets, i.e. rachiticrosary, metaphyseal widening at the wrist andankle, craniotabes and frontal bossing. In older


0.5

60

70

80

90

100

110

Hei

ght (

cm)

1

2 3 4 5

Age (years)

1.5 2

5

Wei

ght (

kg)

10

15

20

0.5 1

Age (years)

1.5 2

(a)(b)

Figure 2.2 (a) Impact on growth (height) with the introduction of nasogastric enteral feeding in a 2-year-oldchild with CRF. (b) Improved weight gain following introduction of nasogastric feeding in the same child.


children deformities of the long bones are moreevident, particularly affecting the lower extremities,i.e. valgus and varus deformity of the knee.

Muscle weakness and a waddling gait are charac-teristic of the myopathy associated with CRF andresemble the proximal muscle weakness seen inpatients with vitamin D deficiency. Although softtissue calcification is seen more frequently inadults, it can also occur in children with ESRD: themost commonly affected sites are blood vessels,lung, kidney, myocardium, central nervous systemand gastric mucosa. The aetiology of soft tissuecalcification is usually a high serum calcium–phosphate product resulting from poor control ofsecondary hyperparathyroidism.

The principal radiographic features of renalosteodystrophy relate to increased bone resorption,typically at the subperiosteal or endosteal surfaces ofcortical bones. The extent of bone resorption corre-lates with parathyroid hormone levels and the sitesinvolved characteristically include the distal ends ofthe clavicles, ischial and pubic surfaces, sacroiliac

joints, junction of the metaphysis and diaphysis oflong bones, and the phalanges. The radiologicalappearances are characterised by a diffuse ‘ground-glass’ appearance, generalised mottling and focallucent or sclerotic areas.

Treatment of osteodystrophy

Even in the earliest phase of chronic renal insuffi-ciency, i.e. a GFR of 50–80 ml/min/1.73 m2,some patients have a raised level of parathyroidhormone, and if untreated the severity of second-ary hyperparathyroidism worsens as renal functionfurther declines.

Dietary manipulation

When the GFR falls to less than 30 ml/min/1.73 m2

phosphate excretion decreases and it is necessary torestrict dietary phosphate intake. Phosphorus ispresent in nearly all foods and its highest concen-tration is in meat and dairy products. The averagedietary phosphate intake is between 900 and 1500mg per 24 hours, of which approximately 50% isabsorbed. Restriction to below 800 mg in 24hours is desirable, but such a diet may becomeunpalatable, with implications for long-termcompliance; the use of phosphate-binding agentsthen plays an integral role in management.

Phosphate-binding agents

Calcium-containing salts such as calcium carbonateand calcium acetate are currently the majorphosphate-binding agents used for limiting intestinalphosphate absorption. Calcium carbonate is themost widely used calcium salt as it is inexpensive,well tolerated and contains 40% elemental calcium.The dosage of calcium carbonate is matched todietary intake and should be taken with or immedi-ately after food. Hypercalcaemia is the most impor-tant complication associated with long-term use.

Vitamin D therapy

Vitamin D replacement is indicated in patientswith chronic renal failure. A number of vitamin D


Phosphate

GFR

1α-Hydroxylase

1,25(OH)2 D3

Ca2+

H+

PTH

Osteoclastic bone resorption – (secondaryhyperparathyroidism)

Rickets

Figure 2.3 Pathogenesis of renal osteodystrophy.


sterols have been used to control secondaryhyperparathyroidism, including dihydrotachy-sterol, 25-hydroxyvitamin D3, 1α-hydroxyvitaminD3 and 1,25-dihydroxyvitamin D3. Of these, 1α-hydroxyvitamin D3 is the most widely used vitamin Danalogue and, at a daily dosage of 0.02–0.1 μg/kg/day, it is both safe and effective. Hypercal-caemia is the main side effect, but calcium levelswill fall in response to a temporary reduction orcessation of therapy.

Assessment of therapy

Serial measurements of total serum calcium,ionised calcium, phosphate and intact PTH levelsare important in assessing the efficacy of dietaryand therapeutic intervention. Calcium and phosphatelevels should be maintained within normal ranges forage (total calcium 2.41–2.77 mmol/l; ionised calcium1.16–1.45 mmol/l; phosphate 1.2–2.1 mmol/l),whereas intact PTH levels should be below6.0 pmol/l.

Sodium chloride and bicarbonateObligatory urinary salt loss is a common featureof chronic renal failure in infants with structuralabnormalities of the urinary tract – notably renaldysplasia (with or without posterior urethralvalves). Since the sodium concentration of mostinfant formula feeds is low, affected infants arefrequently in negative sodium balance and salt andsodium bicarbonate supplementation is thereforerequired to maintain adequate extracellular fluidvolume and prevent metabolic acidosis. Sodiumchloride is added to the feed or diet until the serumsodium concentration rises to 135–140 mmol/l.Up to 5 mmol/kg body weight per day may berequired and the level of supplementation isdecreased if oedema or hypertension supervenes.

Treatment of anaemia

The availability of recombinant human erythropoi-etin (r-Hu EPO) has proved a major advance in

the treatment of anaemia associated with CRF orESRD in children. The benefits include:

• correction of the anaemia of renal failure,improvement in tissue oxygenation, exercisetolerance and haemostatic activity

• improved myocardial function resulting fromreduction in the ventricular hypertrophy associ-ated with anaemia

• reduced risk of developing HLA antibodies byobviating the need for blood transfusion.

Subcutaneous administration is practical for predial-ysis patients and for those on peritoneal dialysis,whereas the intravenous route is used to administererythropoietin to patients on haemodialysis. Mostchildren require between 100 and 200 internationalunits per kg body weight per week and it is oftennecessary to prescribe iron in conjunction with r-HuEPO to treat the functional iron deficiency. Thetarget haemoglobin concentration should be 10.5–12.5 g/dl (9.5–11.5 g/dl for children <6 months).

Treatment of growth failure

Even with assiduous control of nutrition, bonedisease, anaemia, salt wasting and acidosis, themajority of children probably do not achieve theirgenetic growth potential. Recombinant humangrowth hormone is effective in improving growthvelocity both before and after renal transplantation.

Renal replacement therapy

A detailed review of chronic dialysis and renaltransplantation in children is beyond the scope ofthis chapter. As a modality of long-term treatment,peritoneal dialysis (PD) is extremely successful inchildren of all ages, including very small infants.Continuous cycling peritoneal dialysis (CCPD)utilising an automated cycler overnight hasbecome the system of choice, allowing relativefreedom from therapy during the day (Figure 2.4).




Continuous ambulatory peritoneal dialysis (CAPD)using a portable or wearable system is also widelyused and is not dependent on access to machines.

A reliable peritoneal catheter is the cornerstoneof successful PD and this should be inserted by asurgeon who has expertise in this area of work.Evidence is emerging to indicate that the complica-tion rate is lower when a laparoscopic technique isused for dialysis catheter insertion. Exemplary PDtechnique and attention to detail are necessary ifcomplications such as peritonitis are to be avoided.

Chronic haemodialysis may be required whilea patient is being assessed for peritoneal dialysis, or

when it has been necessary to abandon PD follow-ing repeated infections or a loss of ultrafiltrationcapacity. Chronic haemodialysis is not the long-term management of choice since it invariablyrelies on access to a dialysis centre and the servicesof highly skilled nursing and support staff. Thisform of dialysis is dependent on adequate vascularaccess such as internal jugular catheters or anarteriovenous fistula (Figure 2.5). Haemodialysistreatment is performed intermittently and its effec-tiveness is therefore transient.

Renal transplantation is the treatment ofchoice for any child with ESRD. Successful trans-plantation overcomes the problems of providingadequate nutrition, corrects renal osteodystrophy,improves growth and avoids the frequently disfig-uring operations associated with dialysis access.

Outcome data from both single-centre studiesand large registries demonstrate that the outlookfor successful transplantation is continuing toimprove and recipient age at the time of transplan-tation no longer has a negative effect on outcome.The overall relative risk of death, however, isapproximately 13 times higher than that of theage-related population of children in the UK.Over the past three decades, there has been asteady increase in living donor recipients, whichcan account for up to 60% of transplants in somepaediatric centres, with parents representing over

Figure 2.5 Haemodialysis via a subclavian vascularaccess catheter.

Figure 2.4 Compact peritoneal dialysis machine for automated overnight home dialysis.


80% of living donors. In order to obviate the needfor dialysis, pre-emptive renal transplantation isrecommended whenever possible, thus optimisingthe potential for growth and neurodevelopment.Increasingly, laparoscopic living related organdonation is practised and data from single-centrestudies would indicate that this method ofharvesting does not have a negative effect onoutcome.

Patient survival exceeds 95% at 5 years andbeyond. The most common cause of graft loss ischronic rejection (40%), with other causes, includ-ing acute rejection, renal vascular thrombosis,recurrence of primary disease and poor compliancewith medication, each accounting for less than10%. Figures for graft survival indicate that graftretention has improved over the last decade. Forliving related recipients the current figure is 85%graft survival at 5 years, and 75% graft survival at5 years for kidneys derived from deceased donors.Causes of death following transplantation inchildren are infection (25%), cardiovascular events,haemorrhage (25%) and malignancy (8%). Therehas been a changing trend in immunosuppressivetreatment in childhood renal transplantation overthe past two decades, with the use of less cortico-steroid therapy, a switch from ciclosporin A totacrolimus as the calcineurin inhibitor of choiceand an increasing use of monoclonal antibodiesthat prevent T-cell proliferation.

The care of infants and children with CRF/ESRD and their families is complex and depend-ent upon a multidisciplinary approach utilising theskills of doctors, nursing staff, dieticians, teachers,psychologists and social workers. Although it isnow technically possible to treat CRF/ESRD in aninfant or child of virtually any age or size, theparental expectation of such treatment must be

explored before embarking upon a course of life-long therapy. After careful consideration, someparents of small infants with very severe renalpathology may opt for non-treatment in view ofthe profound impact of CRF/ESRD and its treat-ment on the quality of life of affected children.

Key points

• The immature kidney has limitedcapacity to respond to physiologicalstress. Careful management of fluidand electrolyte balance is importantin sick or compromised infants.

• Chronic renal failure in children israre. Its management is complexand demands the expertise andresources of a skilledmultiprofessional team.

• Renal transplantation is thetreatment of choice for end-stagerenal disease in children.

• Chronic renal failure and its treatmentcarries major implications for qualityof life and in some situations parentsmay take the ethically justifiabledecision not to initiate treatment.

Further reading

Barratt TM, Avnel ED, Harmon WE (eds). PaediatricNephrology, 4th edn. Baltimore: Lippincott Williamsand Wilkins, 1999

Kher KK, Makker SP, Schnaper HW (eds). Clinical PediatricNephrology, 2nd edn. London: Martin Dunitz, 2006



Diagnostic imaging

Melanie P Hiorns

Introduction

Imaging departments make a crucial contributionboth to the diagnosis of urological conditions andto their treatment – in the form of interventionalradiology. The child’s age and ability to cooperateare important considerations when determining the choice of investigations. These factors alsodictate the possible need for sedation or generalanaesthesia. Many departments now offer dedicatedchild-friendly facilities and play therapists whoseinvolvement can be invaluable in alleviating thedistress of children undergoing the more invasiveinvestigations. Imaging of the urinary tract providesinformation on anatomy, function, or frequently,both. In most instances a combination of imagingmodalities will be required to provide the informa-tion needed to plan the most appropriate form of management. The most commonly used imagingtests are ultrasound (US), dimercaptosuccinic acid(DMSA) scintigraphy, mercaptoacetyltriglycine(MAG3) dynamic diuresis renography with orwithout cystography and micturating cystourethrog-raphy (MCUG).

Magnetic resonance imaging (MRI) is alsobeing used increasingly to provide both morpho-logical and functional information. Computedtomography (CT) may occasionally be used inchildren, but in the majority of cases the clinical

question can be answered by the modalities listedabove without the need for ionising radiation. Forthis reason, CT should never be employed as thefirst-line investigation.

Although the plain abdominal X-ray (AXR) stillhas role to play when looking for calcification andfor underlying skeletal abnormalities, it is now usedon a very selective basis. Similarly, the intravenousurogram (IVU) is now performed only infrequently.

Interventional radiological techniques are beingincreasingly used as an alternative to open surgeryfor procedures such as drainage and stenting, removalof calculi and percutaneous guided tumour biopsy.

Ultrasound and Doppler

Ultrasound is almost invariably the investigationof first choice for suspected urinary tract pathol-ogy in children. The advantages include:

• no exposure to ionising radiation• low cost• non-invasive and painless• excellent anatomical resolution, due to the

lower amount of fat present in children, andtheir small body habitus

• high sensitivity for the detection of renal stones,cysts and for conditions causing dilatation.

3

Topics coveredDiagnostic imaging

Ultrasound or ultrasonography (US)Micturating cystourethrography (MCUG)Alternative methods of cystography (DIC and IRC) DMSA scintigraphy

Dynamic diuresis renography (MAG3 and DTPA)Cross-sectional imaging: magnetic resonance imaging

(MRI) and computed tomography (CT) Intravenous urography or urogram (IVU)Abdominal X-ray (AXR)

Interventional techniques


The limitations of ultrasound include:

• observer dependence• poor sensitivity in the detection of renal scarring• limited anatomical delineation of complex

malformations• lack of functional information• poor visualisation of pathology in non-dilated

ureters.

Scanning techniqueScanning should be performed with a full bladderto facilitate visualisation of any dilatation of thedistal ureter and to identify intravesical lesionssuch as ureteroceles.

Since a degree of upper tract dilatation mayresult solely from an overfull bladder, the kidneysshould be rescanned following voiding.

Doppler ultrasound to assess perfusion is alsoperformed if there are concerns regarding renalblood flow: for example, in renal artery stenosis,arteriovenous malformations, hypertension andtransplant kidneys.

Measurements in the lower urinary tractA bladder wall thickness of up to 3 mm is consid-ered normal. Thickening of the bladder wall, ifassociated with significant residual volume, issuggestive of bladder outflow obstruction. Othercauses of bladder wall thickening include inflam-mation and infiltration.

A significant residual volume of urine is defined asone exceeding 10% of age-adjusted expected capacity.

The bladder volume is either calculated automat-ically using the software provided, or as follows:

• In children under 2 years of age, bladder volume(ml) = 0.49 × depth × height × width (cm) + 3.

• In older children, bladder volume (ml) = depth× height × width (cm) × 0.9.

These formulae cannot be applied to patients withan irregular bladder or those who have undergonebladder augmentation.

Assessment of the upper urinary tractMeasurements of renal length are obtained with thechild supine and values compared with publishedage-adjusted data. Renal echogenicity is assessed bycomparison with an adjacent organ, typically thespleen or liver. The kidneys are often hyperechoiccompared to the liver in the first few months of lifeor in premature infants, but then revert to beinghypoechoic. End-stage kidneys are also echo-brightand lose their normal internal architecture.

It is very important to note that reflux cannot bereliably detected or assessed by conventional ultra-sound and that additional investigations will berequired if reflux is suspected.

IndicationsThe most common indications for renal ultrasoundinclude the investigation of congenital abnormali-ties (including antenatally diagnosed hydronephro-sis), urinary tract infection, stone disease (Figure3.1) or nephrocalcinosis (Figure 3.2).

An anterior–posterior (AP) renal pelvismeasurement of up to 7 mm is considered normal,whereas 7–10 mm is equivocal and over 10 mmabnormal (although not necessarily indicative ofpathology).

Urinary tract infection (UTI) is a commonreason for referral for US and in the acute phasemay confirm the presence of an obstructed ordilated system and/or the presence of calculi ordebris within it. Ultrasound may also demonstrateevidence of focal pyelonephritis within the renalparenchyma. Although US is capable of detectingrenal scars, it is considerably less sensitive thanDMSA for this purpose.

Calculi as small as 1–2 mm can be visualised inthe renal pelvis or upper ureter but the mid-ureteris difficult to examine by US due to overlyingbowel gas and bowel contents. A stone at thevesicoureteric junction may also be demonstrated ifthe patient has a full bladder, allowing visualisationof this area. US is more sensitive than plain radiog-raphy in the assessment of calculi in the kidney. It isthe first examination in the suspected diagnosis of



Diagnostic imaging 27

Figure 3.1 Urinary calculi. (a) Abdominal X-rayshows stones in the right ureter. (b) Ultrasound (US)demonstrating the same stones in the lower ureterby US. (c) Further calculi are shown in the kidneywith characteristic acoustic shadowing. (d) US ina different patient showing a staghorn calculus and(e) DMSA demonstrating complete loss of functionin the affected kidney.

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Figure 3.2 Other examples of calcification in theurinary tract. (a) Ultrasound (US) showing nephro-calcinosis and calculi occurring together in thesame kidney. The nephrocalcinosis shows the typicalarching calcification around the renal pyramids andthe stone casts an acoustic shadow. (b) Calculus inthe urethra demonstrated on plain X-ray. (c) Bladderstone on abdominal X-ray. (d) US appearances of thesame stone. (e) US in a different patient showing thespecks of echogenicity in medullary calcinosis.

(a) (b)

(c)(d)

(e)


renal calculi in children; however, if the findings areinconclusive, it may still be appropriate to progressto other forms of imaging such as CT.

US provides valuable anatomical informationon a range of anatomical abnormalities such asupper tract duplication (Figure 3.3) but additionalimaging (e.g. DMSA, MRI) is generally requiredif surgical intervention is envisaged.

Renal cystic disease is optimally imaged by USbut it is important for the operator to accuratelydistinguish true cystic disease from hydronephro-sis (Figures 3.4 and 3.5).

US plays a role in the investigation of someurethral abnormalities, including syringocele,posterior urethral valves or stone disease, butfull assessment invariably requires a micturatingcystogram.

US is generally the initial modality used toassess an abdominal or pelvic mass, or a massarising within the kidney, yielding informationwhich typically includes the organ of origin, thepresence of solid or cystic components and thepresence of calcification. Ultrasound may alsodetect metastases in other solid abdominal organssuch as the liver. In the case of suspected renaltumours it also permits evaluation of thecontralateral kidney, the integrity of the capsule ofthe affected kidney and the presence or absenceof tumour extension within the renal vein or theinferior vena cava (IVC).

Finally, US plays an important role in the initialimaging of renal trauma, yielding information onthe integrity of the kidney and the renal capsule andthe presence of haematoma. It can also provide someinformation on renal blood flow and perfusion(Figure 3.6).

Doppler ultrasonographyIn addition to their use in renal trauma, Dopplerstudies of the renal artery or vein are used for theassessment of tumour extension within the renalvein or IVC, in suspected renal vein thrombosisand in the investigation of hypertension.

Micturating cystourethrography (voiding cystourethrography)

The MCUG, also known as a voiding cystourethro-gram (VCUG), remains a key investigation in theexamination of the bladder and the urethra foranatomical abnormalities (Figure 3.7). MCUG isindicated in male infants with bilateral hydronephro-sis to look for urethral obstruction. It should also beperformed in any child with a thickened bladderwall, poor stream and incomplete emptying inwhom there is a need to exclude a urethral abnor-mality or other cause of outflow obstruction.

Urethral trauma is still most commonlyexamined by MCUG, although this may be supple-mented by a retrograde urethrogram in malepatients. The MCUG also retains a central role inthe diagnosis and assessment of vesicoureteric reflux,albeit on a more selective basis than in the past (seeChapter 5).

TechniqueThe procedure should be covered by the adminis-tration of a prophylactic antibiotic and shouldideally be delayed for 4–6 weeks after any acuteinfective episode has been treated. The child ispositioned on the fluoroscopy table and, using asterile technique, a small-calibre (6F) catheter ispassed per urethra and water-soluble contrast mediais introduced. Steep oblique or true lateral views areneeded to demonstrate posterior urethral valves andectopically inserted ureters while early filling viewsare best for visualising ureteroceles (Figure 3.8).One of the principal drawbacks of MCUG is theburden of ionising radiation, although this can besubstantially reduced by using ‘grabbed’ digitalimages and by removing the grid on the imagingintensifier. Although MCUG is still considered thegold standard technique for demonstrating reflux itis important to note that reflux may occur intermit-tently throughout the course of an examination ormay be seen on one occasion but not on another. It




Figure 3.3 (Continued)

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Figure 3.3 Imaging of duplex kidneys in differentpatients. (a) Ultrasound (US) showing a scarred upperpole in the right upper moiety. (b) US in another patientdemonstrating marked dilatation of the upper pole due todistal ureteric obstruction by a ureterocele and moderatelower pole dilatation associated with lower pole reflux.(c) MCUG in a different patient showing reflux into boththe upper and lower moiety on the right. (d) Refluxdemonstrated in the same patient by indirect MAG3cystogram showing an increase over the right kidneyduring voiding. (e) DMSA scan in another patient demon-strating near total loss of function in the lower pole ofduplex kidney due to scarring/dysplasia. (f) Dilated distalureter and associated ureterocele visualised on US.

(e)

(f)

is important to recognise that the possibility ofreflux cannot be entirely discounted by a singlenegative MCUG.

Isotope cystographyDirect radionuclide cystography

Direct radionuclide cystography (DIC) is a sensi-tive test for reflux and carries a lower radiationdose than MCUG. However, it still entails arequirement for urethral catheterisation to permitinstillation of the radionuclide, technetium-99m(99mTc) (20 MBq). Unlike the contrast MCUG, itprovides no anatomical information and does notpermit grading of severity. For these reasons its useis limited and largely confined to follow-up.

Indirect MAG3 renocystography

Indirect MAG3 renocystography (IRC) avoids the need for urethral catheterisation since the MAG3radionuclide is injected intravenously. In essence, itfollows the same pattern as a conventional dynamicrenogram, with extended imaging in an area of inter-est over the ureter and bladder. The principal limita-tion is the low sensitivity for the detection of lowergrades of vesicoureteric reflux. The examination isalso unreliable in the presence of dilated upperurinary tracts since in this situation it becomesimpossible to determine how much isotope has beenretained in the collecting system as a consequence ofstasis/hydronephrosis and how much has returned tothe kidney because of reflux from the bladder.Adequate hydration is crucial for a good-qualityexamination and visualisation of reflux is generallylimited to the resting and voiding phases of bladderfunction. Since this technique is limited to coopera-tive potty-trained children, its use lies mainly inexcluding clinically significant reflux in older girlswith UTIs, and for the follow-up of known reflux.

DMSA scintigraphy (static renography)

Technetium-99m DMSA binds to the proximalconvoluted tubules, with only 10% of the injected


dose being excreted in the urine. It provides staticimages of functioning renal tissue and generates ameasure of relative rather than absolute renalfunction. DMSA plays a valuable role indocumenting the presence and progression ofrenal scarring and is also the modality of choicefor identifying small, poorly functioning kidneys,ectopic renal tissue and cryptic or occult duplica-tion anomalies (Figures 3.9 and 3.10). DMSA isalso a valuable modality for demonstrating fusionanomalies such as horseshoe kidney (Figure 3.11).It may be used in the acute phase of a UTI toshow areas of the renal parenchyma that may be

involved in pyelonephritis and can also be used inthe assessment of renal trauma to delineate whichareas of renal tissue are still functioning (seeFigure 3.6).

TechniqueThe dose of injected 99mTc DMSA is dependent onbody surface area, which is calculated from thepatient’s age and weight. Typically, between 15MBq and a maximum of 100 MBq are given.Images are then acquired approximately 2–3 hoursafter the tracer has been injected.


(a) (b)

(c)

(d)

Figure 3.4 Cystic disease. Ultrasound appearances of (a) autosomal recessive polycystic kidney disease withbright parenchyma and multiple tiny cysts compared with (b) autosomal dominant polycystic kidney disease withmultiple large hypoechoic cysts, (c) cystic dysplasia with scattered cysts and (d) multicystic dysplastic kidneywith multiple cysts and septa containing no intervening renal parenchyma.



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(b)

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Figure 3.5 Ultrasound in a patient with (a) autosomal dominant polycystic kidney disease compared with adifferent patient with (b) marked hydronephrosis. Initial appearances are very similar but a skilled sonographerwill be able to demonstrate that in the case of the hydronephrosis (b) the ‘cysts’ all interconnect since they are,in fact, calyces in a dilated collecting system.

Figure 3.6 Renal trauma. (a) Ultrasound (US) shows alaceration in the mid part of the right kidney. (b) RepeatUS 3 months later showing shrinkage of the lower poleand reduction in blood flow on Doppler. (c) DMSAappearances at 3 months in this patient.



(b)

(c) (d)

Figure 3.7 Examples of urethral abnormalities demonstrated by MCUG. (a) Typical appearance of a posteriorurethral valve with an abrupt change in calibre of the urethra at the level of the valve leaflet with (b) a heavilytrabeculated bladder indicating long-standing outflow obstruction. (c) Urethral stricture best demonstrated with asimultaneous retrograde urethrogram. MCUG alone (d) does not delineate the distal extent of the stricture.

The advantages of 99mTc DMSA include thehigh sensitivity in the detection of parenchymalpathology, measurement of differential renalfunction and the visualisation of ectopic kidneys.Disadvantages include the need for intravenous

cannulation and the delay between injection and theacquisition of images. The radiation burden is higherthan in dynamic renography (such as MAG 3), asthe isotope is largely ‘trapped’ in the kidney untilit decays.

(a)



(a) (b)

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Figure 3.8 Ureterocele. (a) MCUG shows a large ureterocele as a filling defect at the bladder base with (b) associ-ated reflux into the dilated lower moiety of a duplex kidney. (c) Ultrasound showing the ureterocele at the bladderbase and (d) MAG3 renogram shows reflux on the left and the photopenic area of the ureterocele in the bladder.

Dynamic renography (MAG3 and DTPA)

It seems increasingly likely that dynamic renogra-phy will ultimately be replaced by functionalMRI but, for the time being, it remains thestandard diagnostic investigation for obstructionin most units. The dynamic renogram permits

simultaneous assessment of renal function anddrainage and is therefore used in the assessmentof upper tract dilatation and for certain forms ofduplex system (see Figure 3.3).

Differential renal function data are usuallyacquired at about 1–2 minutes after the injection ofthe isotope, whereas drainage is estimated by assess-ing the renogram curve (the normal pattern being



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Figure 3.9 DMSA images of ectopically located renal tissue: (a) ectopic left pelvic kidney; (b) horseshoe kidneywith functioning tissue crossing the midline; and (c) crossed fused ectopic kidney with (d) ultrasound demonstratingthe two fused moieties in this patient.

an early peak followed by a rapidly descendingphase) – see also Chapter 6.

The most commonly used isotope is now 99mTcMAG3, which relies on tubular extraction (Figure3.12). This has the advantage of lower backgroundactivity and a higher kidney to background ratiothan diethylenetriamine pentaacetic acid (DTPA),which is excreted by filtration. However, DTPAdoes have the advantage that it offers the possibilityof simultaneous imaging and formal measurementof glomerular filtration rate (GFR), by taking timedblood samples to measure clearance of DTPA.

Cross-sectional imaging

Whereas US is a form of ‘cross-sectional’technique, the term is more commonly appliedto CT and MRI. The role of CT in paediatricimaging is limited by the high ionising radiationdose. MRI does not involve exposure to radia-tion but does require patients to remain still(or to be sedated or anaesthetised). It is contraindi-cated in patients with most types of metallicimplants, although this is not a common consid-eration in children.



MRI

Apart from the lack of ionising radiation, the advan-tages of MRI over CT are the multiplanar imagesand the superior delineation of different tissue types.In this context MRI is particularly suited to urolog-ical imaging because of its excellent delineation ofwater/urine-containing structures.

T1-weighted images provide anatomical detail,whereas T2 images are a better guide to pathology.Fat suppression techniques can also be added toenhance pathological diagnosis as they allow differ-entiation between fat and pathological tissue, bothof which may be bright (high signal) on non-fatsuppressed T2 sequences. Gadolinium enhancement(an intravenous MRI contrast medium) is extremely

(a)

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Figure 3.10 Pelvic kidney. (a) MCU shows reflux into an abnormally sited kidney. (b) MAG3 demonstratesfunctioning parenchyma in an abnormal pelvic position with rising renogram curve.

POST ANT

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Figure 3.11 Horseshoe kidney. (a) DMSA demonstrates the presence of functioning renal tissue across themidline in this patient. (b) Coronal reconstruction from a CT angiogram for vascular anatomy presurgery alsodemonstrates the configuration of the kidney (a nephrostomy tube is in place in the right moiety).



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Figure 3.12 Pelviureteric junction obstruction. (a)Ultrasound shows hydronephrosis of the right kidneyand the associated (b) MAG3 demonstrating delayedtransit of isotope with poor drainage after micturitionin the kidney and (c) rising excretion curve in the rightkidney indicating accumulating isotope and poordrainage.

helpful in assessing tumour vascularity and indemonstrating kidney function and excretion.

MRI in children

This technique remains challenging, as scan timescan be up to 30 minutes or even longer, and thepatient must remain absolutely still for theduration of the scan. Infants under 6 months canbe immobilised using a ‘feed and wrap’ technique,in which they sleep through the study. Beyond thisage, general anaesthesia is usually required topermit a satisfactory MRI scan in patients up toabout the age of 7 or 8, after which they can lie stillon their own.

As a result of recent technical developments,sequences are getting faster and, for the main part,images in children are now extremely good.

Techniques and indications

MRI is now the examination of choice for the assess-ment of renal tumours (Figures 3.13 and 3.14). MRangiography (MRA) also makes an informativecontribution. For example, it is possible to confirmthe presence of aberrant ‘crossing vessels’ giving riseto pelviureteric obstruction (Figure 3.15). MRangiography is also used in the preoperative evalua-tion of abdominal vasculature in children prior torenal transplantation (Figure 3.16).


In specialist centres, MR urography (MRU) isnow being increasingly applied to the evaluationof both upper and lower tract abnormalities. Itprovides high resolution images of the parenchymaand collecting system at all phases of kidneyfunction (vascular, filtration, excretion) and alsoprovides high-quality images of the ureters. Itis likely that this technique will become increas-ingly widespread in children who are old enough

to cooperate. Heavily T2-weighted sequences aregenerally used for MRU, as these highlightwater/urine-containing structures, which is anextremely useful property in the morphologicalassessment of the urinary tract.

MRI has the potential to combine anatomicaldetail with the functional information convention-ally obtained from MAG3 or DMSA scans. Studiesare being undertaken to validate the quality andreliability of the functional information yielded byMRI against DMSA. If it emerges that MRU iscapable of yielding functional information of


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Figure 3.13 Wilms’ tumour. (a) MRI with intravenouscontrast in the transverse plane shows bilateral Wilms’tumour in a horseshoe kidney. (b) DMSA in the samepatient showing the bilateral tumours as photopenicareas since they do not contain normally functioningrenal tissue.

Figure 3.14 Nephroblastomatosis. (a) CT with intra-venous contrast reconstructed in the coronal planeshowing extensive nephroblastomatosis in bothkidneys (the misregistration at the level of the dia-phragm is due to the patient taking a breath during thescan). (b) MRI in the same patient demonstratesthe same finding (in the transverse plane) but withoutthe need for ionising radiation.

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(b)



(a) (b)

Figure 3.15 MRI in a patient with a ‘crossing vessel’ causing pelviureteric obstruction. (a) The heavilyT2-weighted sequence shows the marked hydronephrosis of the right kidney. (b) A T1-weighted sequence aftergadolinium shows the main right renal artery but also an accessory right renal artery ‘crossing’ the distendedrenal pelvis to cause the right pelviureteric junction obstruction. MRI has shown both the renal pelvic anatomyand the dynamic vascular anatomy in the same examination.

comparable quality, it will be increasingly adoptedin the routine investigation of upper tract pathology.

Computed tomographyUS can answer many of the questions in childrenthat are more commonly addressed by CT inadults, and for this reason CT should not beconsidered as a first-line investigation in children.The principal exception is in children who havesuffered multiple injuries and in whom additionalinformation is simultaneously required on severalorgan systems. CT is highly sensitive for detectingcontusions, lacerations, perinephric fluid collec-tions and areas of avascularity. Pelvic CT shouldalso be included in the study to look for evidenceof bladder rupture and extra- or intraperitonealleakage of urine

Although CT has previously been used as themain modality for the assessment of tumours,MRI is fast becoming the preferred technique. CTalso has a role in the investigation of stone disease

Figure 3.16 MR angiography: coronal images follow-ing intravenous gadolinium performed in the work-upfor renal transplant showing a normal aorta, iliac andfemoral arteries.


in patients in whom US has been unsuccessful.This consideration may apply to patients with avery marked scoliosis or those who are obese.

Technique

Intravenous access is usually required for theadministration of contrast material, although thescan can be performed without the need forcontrast if it is being performed solely to look for calcification. Very young children may beable to sleep through the scan if they are feddirectly prior to the study but toddlers may needsedation or a general anaesthetic. By 4 or 5 years of age, however, most children will toleratea CT scan without the need for sedation oranaesthetic.

Modern multi-detector CT scanners acquire theimages very rapidly, typically in 10–15 secondsfollowing the start of the scan. A vascular lesionwould typically be imaged at approximately 15seconds after the start of injection and, for tumoursor trauma, imaging is performed 25–30 secondsafter injection (therefore in the late arterial/earlyvenous phase). Every effort should be made to keepthe radiation dose to a minimum. In this context,the clinician should be aware that even withmodern CT scanners the dose from a combinedabdominal and pelvic CT examination is in theregion of 200–300 times greater than the dose of achest X-ray.

Intravenous urogram

Although the IVU has largely been replaced by thecombination of US, DMSA and MRI, it retains alimited role in providing information in certainspecific areas such as:

• delineating the level of an acute obstruction,e.g. due to calculi

• correlating the position of calculi demonstratedon US with the exact anatomy of the collectingsystem to allow planning for percutaneousnephrolithotomy or for lithotripsy.

Abdominal X-ray

Historically, the plain abdominal X-ray was oftena starting point in the investigation of abdominalor loin pain. However, the diagnostic yield is lowand abnormal findings of urological relevance aregenerally restricted to the detection of urinary tractcalculi, spinal anomalies (although MRI is prefer-able), abdominal or pelvic mass lesions and consti-pation. US can provide most of the informationpreviously sought by abdominal X-ray and hasrendered this investigation largely redundant.

Interventional techniques

Before any interventional technique is undertaken,it is important to ensure that all the relevant preop-erative investigations (notably clotting studies)have been undertaken and full informed consenthas been obtained.

ArteriographyArteriography may be indicated when renal arterystenosis is suspected. However, this diagnosis isusually pursued firstly by US, and then by MRI.Conventional arteriography for suspected renalartery stenosis does, however, have the advantagethat it can be combined with angioplasty under thesame anaesthetic. Arteriography is also useful inmiddle aortic syndrome, and again angioplastymay be used. Some renal and bladder arteriove-nous malformations are treatable by embolisation.

VenographySelective sampling of renal veins (for renin) and theinferior vena cava may be indicated in childrenwhose hypertension is thought to arise from exces-sive renin production by a scarred or dysplastickidney. Venography and embolisation is a widelyaccepted technique for the treatment of varicoceles.

Antegrade pyelographyNowadays, the principal indication lies in theinvestigation of distal obstruction in the upper



urinary tract. Antegrade pyelography via percuta-neous renal puncture can be performed by aninterventional radiologist or by a urologist.

Percutaneous nephrostomyPercutaneous nephrostomy is often performedunder US control but may be combined withfluoroscopy. The procedure is usually performedunder general anaesthesia in children. Percutaneousnephrostomy is generally preferred to open surgicalnephrostomy and drainage, the main indicationbeing decompression and drainage of acutelyobstructed or infected hydronephrosis usually dueto pelviureteric junction (PUJ) obstruction.

Renal and tumour biopsyAlthough ultrasound-guided procedures can gener-ally be performed using sedation and local anaesthe-sia in compliant older children, general anaesthesia isrequired for the younger age group. Multiple coresshould be acquired, and these should preferablyundergo immediate microscopic examination toconfirm that adequate tissue has been obtained. Thisis important to minimise the possible need for arepeat procedure and further anaesthetic.

Key points

• Many of the conditions encountered inpaediatric urological practice arerelated to underlying congenitalabnormalities of the urinary tract. Acombination of imaging techniques isusually required to provide thedegree of anatomical and functionalinformation needed to plan surgicalmanagement.

• Ultrasound is invariably the initialinvestigation of choice in children.Intravenous urography is no longeremployed routinely and its use in thisage group is now limited to a fewselective indications.

• Dynamic and/or static renography isroutinely used to assess functionalparameters across a broad range ofpaediatric urological conditions. Withfurther development, however, it ispossible that MR urography will takeover this role for the investigation ofupper tract obstruction.

• MRI is being increasingly adopted inpaediatric practice because of itsability to combine excellent anatomicaldetail with functional information,without exposure to radiation. Theprincipal limitation is the need forsedation or general anaesthesia inyounger children.

• The role of CT in children is limitedby the high radiation dosage. Theonly indication for CT as a first-lineinvestigation is in the evaluation ofmajor abdominal trauma.

• Interventional techniques such aspercutaneous nephrostomy and guidedtumour biopsy have largely replacedopen surgery for these indications.

Further reading

Fotter R (ed). Paediatric Uroradiology. Berlin: Springer-Verlag, 2001: 434

Gordon I, Riccabona M. Investigating the newborn kidney:update on imaging techniques. Semin Neonatol 2003;8(4): 269–278

Moorthy I, Wheat D, Gordon I. Ultrasonography in the evaluation of renal scarring using DMSA scan as thegold standard. Pediatr Nephrol 2004; 19(2): 153–156

Riccabona M. (Paediatric) magnetic resonance urography:just fancy images or a new important diagnostic tool?Curr Opin Urol 2007; 17(1): 48–55

Riccabona M, Fotter R. Urinary tract infection in infants andchildren: an update with special regard to the changingrole of reflux. Eur Radiol 2004; 14 (Suppl 4): L78–88

Sury MR, Harker H, Begent J, Chong WK. The manage-ment of infants and children for painless imaging. ClinRadiol 2005; 60(7): 731–741



Urinary tract infection

Stuart J O’Toole

Introduction

Urinary tract infection (UTI) is one of thecommonest disorders of childhood, affecting anestimated 82 000 children a year in the UK. Theinvestigation and management of children withUTI generates a substantial workload for paedi-atric urologists and paediatric nephrologists as wellas for general paediatricians. The presentation ofUTI in this age group is varied and the diagnosiscan sometimes be problematic, particularly inyoung infants in whom the clinical picture is oftennon-specific and reliable urine samples are difficultto obtain. Despite these diagnostic difficulties, thegreater awareness of the importance and preva-lence of UTI in children coupled with the avail-ability of sensitive dipstick reagent strips hasresulted in the detection of UTI on a far greaterscale than in the past. As a consequence of betterdiagnosis of UTI by general practitioners, manymore children with mild or asymptomatic lowertract urinary infections are now being referred for investigation. To a large extent, however,recent protocols for the investigation and manage-ment of childhood UTI date from a time whenchildren referred for investigation tended to bethose with more severe infection. The use ofoutdated protocols has had the result that manychildren with lower tract UTIs have been

subjected to unnecessary (and often needlesslyinvasive) investigations. Moreover, the burden ofunnecessary investigations has significant financialimplications for the National Health Service. Toaddress these concerns the UK’s National Institutefor Health and Clinical Excellence (NICE) hasrecently produced new guidelines based on anextensive analysis of the published evidence. Theseguidelines are intended to encompass referralpractice, a more selective approach to diagno-stic imaging and evidence-based recommendations on management. The NICE guidelines have been criticised by some clinicians on the groundsthat they might lead to under investigation ofsome children with clinically significant UTIs,scarring and reflux. Where appropriate, referencewill be made to the 2007 NICE guidelines in this chapter.

Epidemiology

Urinary infection is one of the commonest bacter-ial infections occurring in children and, withimproved diagnostic sensitivity, it is apparent thatthe true incidence is far higher than was previ-ously thought: in the 1960s this was put at 0.02%for boys and 0.04% for girls, whereas currentestimates have increased 20-fold (Table 4.1). In

4

Topics coveredEpidemiology of childhood urinary infection Pathogenesis

Infecting organisms Host factors

Diagnosis Specimen collection, urine analysis

Clinical features Age differences Upper and lower tract infection

Investigation NICE guidelines

Management


the first 12 months of life urinary infections are more common in boys but thereafter (andparticularly above 3 years of age) UTIs occurpredominantly in girls.

Pathogenesis of urinary tract infection

Although urinary tract infection can arise throughhaematogenous spread (or direct transmission of

bacteria from other organs in the case of vesicoin-testinal and genitourinary fistulae), most UTIs arecaused by urethral ascent of organisms whichcolonise the perineum or preputial sac. Onceorganisms have gained access to the lower urinarytract, whether they go on to produce an estab-lished infection is determined by the interplay ofa number of factors set out in Figure 4.1. Recentresearch in experimental animals indicates that theconcept of organisms multiplying within bladderurine is misconceived and that bacterial replicationoccurs predominantly at an intracellular level, withorganisms being shed into the urine from infectedurothelial cells.

OrganismsIn the urinary tract, as in other systems, the occur-rence of infection depends upon the balancebetween host resistance and the virulence of theinfecting organism. Escherichia coli is the causativeorganism in some 85% of cases of UTI. Thefimbriated forms of E. coli have the ability toadhere to receptors on the urothelial surface and

Table 4.1 The age-related incidence of urinarytract infection in boys and girls

Age (years) Boys (%) Girls (%)

<1 1.0 0.8<3 2.2 2.1<7 2.8 8.2<16 3.6 11.3Lifetime 13.7 53.1


UTIstasis

Host susceptibility

Organism

Anatomical Obstruction

Vasicoureteric reflux

Functional Neuropathic bladder Voiding dysfunction

Constipation

Virulence factorse.g. pili or fimbrae

ForeskinAge

Breast-feeding

NativeImmunity

Figure 4.1 Host and pathogen factors involved in the pathogenesis of UTI in children.


are thus particularly effective at colonising theurinary tract. These are classified on the basis ofhaemagglutination of red blood cells and expres-sion of the P blood group antigen. P-fimbriatedE. coli are particularly potent pathogens by virtueof their adherence properties. Other commoninfecting organisms, in approximately descendingorder of frequency, are Proteus vulgaris, Klebsiella,Enterobacter and Pseudomonas.

Urinary stasisScientifically robust evidence linking urinary stasisto urinary infection is sparse, especially with regardto vesicoureteric reflux (VUR). Nonetheless, thereis a large accumulated body of clinical experienceto indicate that factors which impair the effective-ness with which organisms are cleared from theurinary tract do indeed predispose to urinary infection. Stasis may result from anatomical abnormalities producing obstruction or reflux, orfrom functional disorders interfering with bladderemptying.

Anatomical abnormalities Increased awareness of urinary infection inchildren coupled with better diagnosis has hadthe result that many more children with mild,lower tract infections are now being referred forinvestigation than in the past. Consequently, therelative proportion of children with significantunderlying urological abnormalities has decreasedand whereas previous studies reported an incidenceof underlying abnormalities of up to 30% inchildren with UTI more recent estimates have putthe figure closer to 10%. Even when anomaliesare identified on investigation many, such asminor grades of VUR, incomplete duplicationanomalies, anomalies of position or fusion, etc.,are of little clinical significance. In practice,dysfunctional voiding characterized by infrequenttoileting and impaired bladder emptying is nowa much more common predisposing cause ofurinary infection, particularly in girls.

Host susceptibilityMany host factors can increase a child’s susceptibil-ity to urine infection. Premature infants are atincreased risk (although breast-feeding appearsto confer some protection). Other host factorsincluding immunoglobulin A (IgA) secretion andblood group secretor status have also been linked tosusceptibility to UTI. The presence of a foreskin isan undoubted risk factor, the reported incidence ofurinary infection being 10–20 times higher in uncir-cumcised boys compared with their circumcisedpeers. However, this increased susceptibility occurspredominantly in the first year of life. Although theincreased risk of urinary infection in uncircumcisedboys has been cited as one of the justifications forroutine neonatal circumcision, calculations based ona recent meta-analysis of 400 000 boys suggest thatover 100 boys would have to be circumcised inorder to prevent one boy with a normal urinary tractdeveloping urinary infection.

Although routine neonatal circumcision cannotbe regarded as a cost-effective public health measurefor preventing UTIs, the benefit of circumcision is more apparent in boys with recurrent UTIs and those with urinary tract abnormalities. Forexample, there is some persuasive anecdotalevidence (backed by limited evidence from a smallnumber of observational studies) that circumcisionreduces the risk of UTI in boys with posteriorurethral valves. However, this has never beensubjected to a prospective controlled study.

Laboratory diagnosis ofurinary tract infection

Urine collection‘Clean catch’ midstream urine sample

A midstream urine (MSU) sample yields the mostreliable results and children who are toilet-trainedcan nearly always cooperate with this method ofcollection.

Urinary tract infection 45


For infants and children unable to provide a midstream specimen, there are non-invasivealternatives.

Non-invasive alternatives

• Adhesive collection bags attached around thegenitalia represent the easiest and mostcommonly employed means of collecting urinespecimens in the very young, However, theresults are only reliable if the appropriate precau-tions have been taken and the voided specimenis sent promptly for culture. When these criteriaare not met, contamination is common.

• Absorbent urine collection pads placed insidethe nappy are being used increasingly as analternative to collection bags. Cotton wool ballsmay also be used but are less reliable. Urinewhich has soaked into the pad is aspirated witha syringe and sent for microscopy and culture.Contamination is common.

Invasive techniques

• Suprapubic needle aspiration is the ideal methodof collection in sick infants in whom an urgentdiagnosis is required. The procedure should beperformed under ultrasound guidance, with priorconfirmation that there is urine in the bladder.

• Urethral catheterisation is invasive andunpleasant, and is rarely used for these reasons.

Although it is always preferable to obtain a urinesample before commencing treatment, there maybe situations (e.g. a severely ill infant) when antibi-otic treatment is justified even if a urine samplecannot be obtained.

Urine storage and transport Once collected, the specimen should ideally becultured within 4 hours to minimise the risk ofcontaminating organisms multiplying and yieldinga false-positive result. Where this is not possible(for example in children presenting outside workinghours), the sample can be refrigerated for up to24 hours at +4.0ºC or transferred to a vesselcontaining boric acid preservative.

Urine dipsticksThe introduction of urine dipsticks with leucocyteesterase and nitrite reagents has made an importantcontribution to the earlier diagnosis of UTI.

NICE makes the following recommendations:

• Leucocyte esterase and nitrite both positive –definite evidence of UTI. Antibiotic treatmentshould be commenced.

• Leucocyte esterase negative, nitrite positive –presumptive evidence of UTI. Antibiotic treat-ment should be commenced and a urine samplesent for culture.

• Leucocyte esterase positive, nitrite negative –a urine sample should be sent for microscopy and culture but antibiotic treatment should notbe commenced unless there is good clinicalevidence of UTI.

• Leucocyte esterase negative, nitrite negative –negative result. Antibiotic treatment should notbe started. Nor is it necessary to send urine formicroscopy and culture.

A positive result for protein does not denote infec-tion. A trace of proteinuria is a common findingand is not a cause for concern. Heavier proteinuriamay, however, signify renal disease and referral toa paediatric nephrologist should be considered ifthe finding is confirmed on a further test.

Urine microscopyWhen performed on a fresh uncentrifuged sampleof urine, microscopy can be very useful in facilitatinga prompt diagnosis. This is of particular impor-tance in the acute situation when there is a need tocommence treatment without awaiting the resultsof culture. Different techniques are available, butresults are generally expressed as absolute values orcounts per high-powered field. Significant pyuriais defined as >10 WBC/mm3. The concentrationof motile bacteria can also be quantified, with107 bacteria per ml being deemed significant.This figure corresponds to 8 organisms per high-powered field. The interpretation of microscopyfindings is summarised in Table 4.2.



Urine culture Provided the urine sample has been collectedwithout contamination, the criterion for the bacte-riological diagnosis of urinary infection is a puregrowth of >105 bacterial colony-forming units(CFUs) per ml. On the other hand, in specimensobtained by suprapubic aspiration, any growth ofa Gram-negative organism is significant, as is agrowth of greater than >500–1000 Gram-positiveorganisms. With the availability of sensitivecombination dipsticks, it has been questionedwhether urine culture is routinely necessary in allcases. According to NICE guidelines, it is notnecessary when both leucocyte esterase and nitritedipstick results are positive. Although urine culturemay not be strictly necessary to confirm thediagnosis of UTI, there is, nevertheless, a strongargument for sending a urine specimen for cultureto identify the causative organism and establish itsantibiotic sensitivities. This procedure may be animportant consideration at a time when multipleantibiotic resistance is becoming more prevalent.

Clinical presentation anddiagnosis

History and examination It is important, to establish whether there is anyfamily history of urological abnormalities, particu-larly VUR. The antenatal history is also impor-tant, specifically whether any abnormality wasdetected on antenatal ultrasound. In older, toilet-trained children it should also be routine toenquire about:

• voiding history (volume, frequency, stream,urgency)

• fluid intake (volume, type)• bowel habit.

Although physical examination is usually unreward-ing, it should be routinely performed and includethe abdomen, genitalia, spine and lower limbs,plus, in all cases, measurement of blood pressure.This can be difficult in small children but all paedi-atric outpatient departments should have theappropriate equipment and paediatric bloodpressure cuffs.

Clinical features Early diagnosis and prompt treatment of UTIis important, but the presentation can be non-specific and dependent on the nature of the infec-tion and the age of the patient. Table 4.3summarises the clinical features of UTI in childrenat different ages. It is important to maintain a highdegree of suspicion and ensure that a urine sampleis collected and tested for infection in any childwith an unexplained fever exceeding 38.0°C.

In addition to age-related differences, the otherprincipal determinant of clinical presentation iswhether the child is suffering from lower or upperurinary tract infection (Table 4.4).

Lower tract infection

The symptoms are typically those of cystitis,with dysuria being almost universal. In addition,urinary frequency is common and often associatedwith secondary enuresis. By contrast, suprapubicpain occurs comparatively rarely. There is no fever


Table 4.2 NICE guidelines on the interpretation of urine microscopy

Microscopy results Pyuria positive Pyuria negative

Bacteriuria positive The infant or child should be The infant or child should beregarded as having UTI regarded as having UTI

Bacteriuria negative Antibiotic treatment should The infant or child should bebe started if clinically UTI regarded as not having UTI


or any general malaise; indeed, many olderchildren are able to continue attending schoolduring the course of their illness.

Upper tract infection (pyelonephritis)

Fever is the most reliable clinical feature of upperurinary tract infection and, indeed, it is doubtfulwhether pyelonephritis ever occurs in its absence.Although the fever associated with pyelonephritisis usually high, any temperature exceeding 38ºCshould be regarded as suspicious. In children whohave been admitted as emergencies or seen inAccident and Emergency Departments, fever, or itsabsence, is nearly always recorded but this is lesswell documented in referrals from general practice.

In this context, the 2007 NICE guidelines state:

Infants and children who have bacteriuria andfever of 38°C or higher should be consideredto have acute pyelonephritis/upper urinarytract infection. Infants and children presentingwith fever lower than 38°C with loinpain/tenderness and bacteriuria should also beconsidered to have acute pyelonephritis/upperurinary tract infection. All other infants andchildren who have bacteriuria but no systemicsymptoms or signs should be considered tohave cystitis/lower urinary tract infection.

Other presenting features of UTI

The occurrence of haematuria is not in itselfindicative of the severity of the infection or of its site. Haemorrhagic cystitis is the commonestcause, although urinary tract calculi should besuspected whenever the infecting agent is Proteus.Stones may be present in the upper urinary tracteven in the absence of any constitutional symptoms.In some boys referred with haematuria (with orwithout documented infection), the history maybe one of postmicturition bleeding rather thanhaematuria proper. This is usually due to urethritis.

Epididymo-orchitis is an occasional presenta-tion of urinary infection in boys of all ages and

Table 4.4 Symptoms of urinary tract infections

Lower urinary tract Upper urinary tract

Frequency/nocturia FeverDysuria VomitingSecondary enuresis General malaiseSuprapubic pain Loin painHesitancy Upper/central

abdominal pain


Table 4.3 Presenting features of UTI in children at different ages

Frequency Infant and toddler Older child

Common Fever FrequencyIrritability DysuriaVomitingLethargy

Less common Offensive urine Offensive urinePoor feeding IncontinenceFailure to thrive Abdominal pain

Uncommon Jaundice FeverFailure to thrive VomitingHaematuria Haematuria

Loin tenderness


should arouse suspicion of some predisposingabnormality, such as urethral obstruction distal tothe ejaculatory ducts or a duplication anomalywith the upper pole ureter draining ectopically intoan ejaculatory duct (see Chapter 7).

Neonates and infants

With few exceptions, the clinical presentation iswith a non-specific febrile illness, usually accompa-nied by vomiting and quite often by diarrhoea.Because there are many possible explanations forthis clinical picture, it is advisable to performappropriate dipstick analysis – or ideally send urinefor microscopy and culture in any infant with anotherwise unexplained febrile illness. In practice,however, obtaining a reliable sample for microscopyand culture may be difficult. Other, rarer, non-specific features of urinary infection in this age groupinclude failure to thrive (or frank weight loss) andprolonged jaundice in neonates. The occurrence ofhaematuria can occasionally serve as a sign of urinarytract infection, which usually manifest as a blood-stained nappy. In male infants, UTI occasionallypresents with epididymo-orchitis.

Children aged 2 years and older

Even as early as 2 years of age most children cangive some account of their symptoms and by 4years, if not earlier, an accurate history can nearlyalways be obtained. Furthermore, except when thesymptoms relate entirely to the upper renal tracts,it usually becomes apparent from the history thaturinary infection is the likeliest diagnosis. Equally,in the majority of cases it is possible to determine,on clinical grounds, whether the infection involvedthe upper urinary or the lower urinary tract.

Upper abdominal pain is an occasionalsymptom of renal infection but it may be difficultto distinguish this from the non-specific patternof central abdominal pain, which is a commonsymptom in children. True loin pain is rare and, ifprolonged, with or without associated vomiting, ismore likely to signify urinary obstruction thaninfection.

Potential pitfalls and sources ofdiagnostic confusion include:• Fever, loin pain and dysuria in an older

child. This triad of urinary tract symptomsassociated with pyelonephritis can also bemimicked by acute inflammation of a retrocea-cal or pelvic appendix. In acute appendicitis, acarefully taken history should reveal that anypain on voiding is localized to the abdomenrather than the urinary tract. Moreover, thefever is usually lower in appendicitis thanpyelonephritis and the pain associated withappendicitis is more likely to be provoked orexacerbated by extension of the hip.

• Dysuria in the absence of other features ofUTI. Symptoms associated with vulvovaginitisin young girls are not uncommonly ascribed toUTI. Moreover, pyuria may be evident on urinemicroscopy. Whereas urine culture is generallynegative, it may reveal a mixed growth of organ-isms. From the history it should be possibleto distinguish between localized symptoms ofdysuria due to vulvovaginitis and dysuria, whichis included as part of a broader clinical picture ofgenuine lower urinary tract infection.

• Likewise, dysuria associated with balanitis maybe confused with UTI in boys.

Investigation:diagnostic imaging

Established protocols and previous guidelines have been increasingly questioned on the groundsthat they have resulted in overinvestigation ofchildren with lower tract infections and are notcost-effective.

Whereas the rationale for new guidelines iswidely accepted, it nevertheless remains likely thatthe majority of paediatric clinicians (includingpaediatric urologists) will continue to advise thatall children presenting with proven urinary infec-tion should undergo some form of investigation.However, it is important to adopt a selective



Table 4.5 Strengths and weaknesses (‘pros and cons’) of the different imaging modalities availablefor the investigation of UTI in children

Investigation Pros Cons

Renal ultrasound with Detects dilatation and Poor at detecting scarring orpostvoid bladder views allows measurement of reflux

renal size Operator dependentDetects major scarringProvides information onbladder dysfunctionVisualises calculiCheap and well tolerated

DMSA Most sensitive test for renal Relatively expensive andscarring and differential time consumingfunction Requires IV cannulation

Indirect cystogram Detects reflux during Child must be cooperative(MAG3) normal voiding and potty trained

Provides differential renal Misses low-grade refluxfunction Requires IV cannulationAvoids the need forurethral catheterisation

Contrast micturating Most reliable test for Requires urethralcystourethrogram (MCUG) detection of reflux catheterisation and incurs

Excludes urethral and other exposure to radiationbladder pathology

approach which avoids submitting normal childrento unnecessarily invasive and costly investigationswhile at the same time identifying those childrenwho have significant abnormalities such as refluxand renal scarring.

The technical aspects of the most widelyused investigations – ultrasonography, dimercap-toruccinic acid (DMSA) scintigraphy, micturatingcystourethrography (MCUG), indirect isotopecystography – are considered in Chapter 3.

The strengths and weaknesses of the differentimaging modalities are summarised in Table 4.5.

UltrasonographyUltrasonography is non-invasive and entails noexposure to radiation. Consequently, it representsthe ideal initial screening procedure and should beundertaken in all cases. Ultrasonography reliably

detects obstructive and non-obstructive urinarytract dilatation, major degrees of renal scarring ordysplasia, most urinary calculi and almost all clini-cally significant duplication anomalies. Other,more subtle, indicators of pathology detected byultrasonography include disparity in renal size(> 1 cm difference in length measurement), abnor-malities of renal echo-texture and distal uretericdilatation suggestive of VUR.

Because false-positive results are rare, all childrenfound to have any of these abnormalities should be investigated further. Ultrasonography is alsoof value in detecting evidence of voiding dysfunc-tion (bladder wall thickening, significant residualurine).

When an abnormality has been revealed byultrasonography, the choice of further imaging isguided by a combination of factors, including thenature of the abnormality detected on ultrasound,the severity of infection (upper or lower tract) and



the age of the child. The most widely used investi-gations are DMSA (and MCUG if VUR issuspected) or mercaptoacetyltriglycine (MAG3) inthe case of suspected upper tract obstruction.

In the majority of cases, however, ultrasonogra-phy is normal, in part because of the high false-negative rates in the detection of renal scarring andmild to moderate reflux. For example, grade IIIVUR is associated with a false-negative rate of25–50%, whereas renal scarring is missed on ultra-sound in 15–45% of cases.

The most controversial aspects of diagnosticimaging therefore relate to children with urinaryinfection whose ultrasound findings are normal.

Indications for further imagingThe 2007 NICE guidelines advocate a far morelimited use of DMSA and MCUG than waspractised previously. For example, according tothe NICE guidelines, DMSA and MCUG are nolonger routinely indicated for infants under 6months of age whose urinary infection ‘respondswell to treatment within 48 hours’.

Likewise, for children in the age range 6 monthsto 3 years with normal ultrasound findings theNICE guidelines recommend that DMSA shouldbe reserved for those with recurrent or ‘atypical’UTIs, as defined by the criteria listed in Table 4.6.

However, many children are treated initiallywith antibiotics in a community setting and it maybe difficult to establish in retrospect whether theirUTI was accompanied by fever or not. Similarly,when children are seen for the first time as out-patients it may not be apparent from the informa-tion accompanying the referral whether their UTI‘responded well to treatment within 48 hours’.Ultrasound is not a sensitive test for renal scarringin young children and it has been argued by thecritics of the guidelines that without a DMSA scanmany children with scarring and underlying VURwill be missed. However, the guidelines do envis-age an MCUG for younger children in whom thereis evidence of dilatation on ultrasound, a familyhistory of VUR or a non-E. coli infection.

For urologists, perhaps the most contentiousaspect of the NICE guidelines relates to theimaging schedule for children aged 3 years and


Table 4.6 Clinical features which merit further investigation (including those identified by NICE asdenoting ‘atypical’ infection)

• Severe infection with systemic symptoms indicating upper tract infection (pyelonephritis)• Family history of VUR and/or renal scarring • Poor urinary stream • Palpable bladder or other abdominal mass (although these will generally be evident as abnormalities

on ultrasound) • Raised creatinine • Failure to respond to treatment with suitable antibiotics within 48 hours • Infection with organisms other than E. coli• Age – although this is a weak discriminator, it is a factor when considering further investigation in

view of the greater susceptibility of infants and young children to renal scarring. Most paediatricurologists would continue to advise further investigation in boys presenting with UTI in the first 6months of life, more with a view to the detection of reflux than urethral obstruction (which usuallygives rise to detectable abnormalities on ultrasound)

• Recurrent infection, defined by the NICE guidelines as:– two or more episodes of UTI with acute pyelonephritis/upper urinary tract infection, or – one episode of UTI with acute pyelonephritis/upper urinary tract infection plus one or more episodes

of UTI with cystitis/lower urinary tract infection, or – three or more episodes of UTI with cystitis/lower urinary tract infection


upwards which makes no provision for an MCUG,even for children with recurrent or ‘atypical’ UTIs.In view of the well-documented failings of ultra-sound as a means of detecting low-to-moderategrade VUR, it is evident that many children with these grades of VUR will be missed on theimaging protocol recommended by NICE. Doesthis matter? Although the risk of new scarring is admittedly low in children aged 3 years, itundoubtedly occurs. Moreover, scarring is not the only factor of importance when consideringpossible investigation for VUR. Children whoseVUR is associated with urinary infection mayexperience recurrent episodes of symptoms and illhealth which interferes with schooling and gener-ates considerable anxiety within the family. Forthese reasons, it seems likely that the majority of paediatric urologists will continue to consideran MCUG for older children experiencing recur-rent symptomatic UTIs since the information on whether or not they have reflux is clinicallyrelevant to the management options, particularlyendoscopic correction.

Some suggested imaging protocols incorporat-ing modified NICE guidelines are illustrated inFigures 4.2a, 4.2b and 4.2c.

Management

Initial management

Older children and those with mild to moderateUTI are mostly treated by their general practi-tioner in the first instance and then referred subse-quently for investigation on an outpatient basis.However, the NICE guidelines recommend thatinfants under 3 months of age and older childrenwith a clinical picture of pyelonephritis should bereferred promptly to a paediatric specialist.

For infants under 3 months of age and for olderchildren with presumed pyelonephritis (the groupsat particular risk of renal scarring) treatmentusually comprises an intravenously administeredantibiotic such as cefotaxime or ceftriaxone. TheNICE guidelines recommend intravenous (IV)antibiotics for 2–4 days followed by an oral anti-biotic for a total duration of 10 days. If anaminoglycoside such as gentamicin is used, it isimportant to monitor blood levels.

Alternatively, oral antibiotics may be considered(e.g. a 7–10-day course of cephalosporin or co-amoxiclav) depending upon the severity of theclinical picture.


Ultrasound

Abnormal

Appearances of PUJobstruction/duplex kidney, etc.

Pelvicaliceal dilatationand/or ureteric dilatation

and/or bladder abnormality

MCUGDMSA

Normal

Afebrile/lowertract UTI

No additionalimaging butMCUG andDMSA iffurther UTI

Febrile or‘atypical’ UTI

MCUGDMSA

MAG3DMSA,MCUG, as appropriate

Figure 4.2a Imaging protocol incorporating modified NICE guidelines for infants aged 0–6 months.



Ultrasound

Abnormal




MCUGDMSA

Normal

Afebrile/lower tract UTI

No additionalimaging but

DMSA if furtherUTIs. MCUG

depending uponresult of DMSA

Febrile or‘atypical’ UTI orrecurrent UTIs

DMSA

MAG3DMSA,

MCUG, as appropriate

Normal

No additional imaging but

consider MCUG if

further UTIs

Abnormal

MCUG

Figure 4.2b Imaging protocol incorporating modified NICE guidelines for young children aged 6 months to3 years.

Ultrasound

Abnormal




MCUGDMSA

Normal

Afebrile/lowertract UTI

No additional imaging but

consider DMSA and/or MCUG if

further UTIs

Febrile or atypical UTI or recurrent UTIs. Consider DMSA, depending on age

and clinical features

DMSA

MAG3DMSA,

MCUG, as appropriate

Normal

No additional imaging. Consider MCUG if

further UTIs

Abnormal

MCUG

Figure 4.2c Imaging protocol incorporating modified NICE guidelines for children aged 3 years and upwards.



An early ultrasound scan is advisable in allchildren admitted to hospital since they may havean abnormality needing urgent drainage before theinfection can be brought under control. Examplesinclude upper tract obstruction complicated bypyonephrosis for which percutaneous nephros-tomy is required or, rarely, infravesical obstructionrequiring percutaneous suprapubic catheterisation.

Oral antibiotics are the first-line treatmentfor afebrile, lower urinary tract infection afterthe age of 3 months. Although the NICE guide-lines advocate a course of an agent such astrimethoprim, cephalosporin, nitrofurantoin oramoxicillin limited to 3 days, many clinicians stillfavour a longer course. The antibiotic should beswitched to a more appropriate alternative if this isindicated by the results of sensitivities obtainedfrom the MSU.

Longer-term managementIn a small number of children investigations willidentify a significant urinary tract abnormalityrequiring surgical intervention or other ongoingmanagement. However, the majority of childrendo not fall into this category and most do notrequire routine urological follow-up. Nevertheless,some children, predominantly girls, are troubledby recurrent UTIs despite the absence of anyunderlying urological abnormality. For these childrenit is essential to identify and treat any predisposingfactors, of which dysfunctional voiding is by farthe most important (see Chapter 12). The role ofconstipation is more difficult to define, but there isundoubtedly an association between these two‘elimination disorders’.

Treatment is aimed at establishing a routineof regular and complete voiding coupled withmeasures designed to break the cycle of ‘holdingback’ in children who also have habitual constipa-tion. Even in the absence of VUR, a period ofantibiotic prophylaxis may be helpful in breakingthe cycle of infection and allowing the bladder tosettle down.

Other conservative measuresThe parents of children with recurrent UTI arevery keen to do whatever they can to preventfurther infections. In recent years cranberry juicehas become increasingly popular as prophylaxisagainst infection and although robust evidencedemonstrating its effectiveness in children islacking, some benefit has been shown in adultwomen. Probiotic yoghurts have also increased in popularity and, while there is little in the way of scientific evidence supporting their use,anecdotally they do seem to be effective in somechildren. If parents do opt for these alternativetherapies, this should not be at the expense of thethree most important measures – increased fluidintake, treatment of constipation and, mostimportantly, treatment of voiding dysfunction toimprove the frequency and effectiveness ofbladder emptying.

Key points

• Urinary tract infection is one of thecommonest disorders of childhood and many more children withrelatively asymptomatic lower tracturinary infections are now beingreferred for investigation thanin the past.

• Care is needed to obtain anuncontaminated urine sample for reagentdipstick testing and microscopyand culture whenever possible.

• It is important to confirm thediagnosis of urinary infection beforesubmitting a child to any investigationmore invasive than ultrasonography.

• Ultrasonography is the investigationof first choice, but it is not a sensitivetest for detecting vesicoureteric refluxand scarring.



• Further investigation is indicated ifthe initial ultrasound scan reveals anabnormality of the urinary tract. Thechoice of further imaging tests isguided largely by the ultrasoundappearances.

• Further investigation (to lookprimarily for vesicoureteric refluxand/or renal scarring) may also bejustified despite normal ultrasoundfindings. The indications for furtherinvestigation and the choice ofimaging are determined by theage of the child, severity ofinfection and factors such asfamily history.

• Dysfunctional voiding is an importantfactor predisposing to lower tracturinary infection in girls with normalurinary tracts. Management should bedirected towards improving voidingfunction and treating constipationwhen present.

Further reading

Christian MT, McColl JH, MacKenzie JR, Beattie TJ. Riskassessment of renal cortical scarring with urinary tractinfection by clinical features and ultrasonography. ArchDis Child 2000; 82(5): 376–380

Michael M, Hodson EM, Craig JC, Martin S, Moyer VA.Short compared with standard duration of antibiotictreatment for urinary tract infection: a systematicreview of randomised controlled trials. Arch Dis Child2002; 87(2): 118–123

National Institute for Health and Clinical Excellence.Guidelines on urinary tract infection in children, 2007.www.nice.org.uk/CG054

Reid G. The potential role of probiotics in pediatricurology. J Urol 2002; 168(4 Pt 1): 1512–1517

Singh-Grewal D, Macdessi J, Craig J. Circumcision for theprevention of urinary tract infection in boys: a system-atic review of clinical trials and observation studies.Arch Dis Child 2005; 90(8): 853–858

Verrier Jones K. Time to review the value of imaging afterurinary tract infection in infants. Arch Dis Child 2005;90(7): 663–664



Vesicoureteric reflux

David FM Thomas and Ram Subramaniam

Introduction

Reflux can be defined as the retrograde flow of urine within the upper urinary tract. Whereas theterm is often used synonymously with vesicouretericreflux (VUR), it can also occur at the level of therenal papilla – intrarenal reflux (IRR).

VUR is not a single pathological entity; rather,it represents a pattern of disordered function whichhas different causes, exhibits varying patterns ofnatural history and has a broad spectrum of clini-cal significance.

When complicated by urinary tract infection in childhood, VUR is an important cause ofsymptomatic ill health, which, if undiagnosed anduntreated can result in failure to thrive. In thelonger term, renal scarring (reflux nephropathy)poses threats of late morbidity which includehypertension, complications of pregnancy, renalimpairment and end-stage renal failure.

During the last two decades the conventionalmanagement of VUR has been based upon exper-imental and clinical studies undertaken in the1970s and early 1980s. More recently, some of theaccepted principles of management have beenchallenged by the findings of newer studies and theintroduction of new treatment modalities. After aperiod of two or three decades which saw a broadconsensus on the investigation and management ofVUR, this common urological condition of child-hood is once again generating controversy.

The aim of this chapter is to summarise what isknown of the aetiology, pathophysiology and naturalhistory of VUR and to provide an overview ofcurrent thinking on the clinical management. Inaddition, it will highlight some of the currentcontroversies and areas of research.

Aetiology of vesicoureteric reflux

The anatomy of a normal vesicoureteric junctionprovides a valvular mechanism which prevents the retrograde flow of urine into the upper tract,even at increased pressure during voiding. Theterminal ureter transverses the bladder wall andruns in a submucosal tunnel to open on the trigone.This anatomical arrangement imparts a flap-valvemechanism in which the intramural and submu-cosal portions of the distal ureter are compressedagainst the backing of the detrusor muscle by thepressure of urine within the bladder. The compe-tence of this passive flap-valve mechanism may bereinforced at the time of voiding by active elonga-tion of the intravesical ureter within a Waldeyer’ssheath. In addition, there is experimental evidenceto suggest that concentric contraction of smoothmuscle within the distal ureteric wall may confer afurther active protection against reflux.

In children with significant primary VUR, theureteric orifice is characteristically located laterally

5

Topics coveredAetiology and genetic basis of refluxReflux nephropathyClinical features

Investigation; diagnostic imagingConservative managementEndoscopic correction and other surgical optionsCurrent controversies


on the base of the bladder rather than in thenormal anatomical position on the trigone. Theresulting length of intramural and submucosalureter is shorter, creating a deficiency of the flat-valve mechanism. Both the absolute and relativelengths of the submucosal tunnel tend to increasewith age, thus accounting for the spontaneousresolution of VUR.

Ureteric duplication provides a clear example ofthe role of the ureteric bud as a crucial determinantof the position of the ureteric orifice and thepotential for reflux.

Classification of vesicoureteric reflux

Reflux has been traditionally classified into primaryand secondary VUR.

Primary VUR This form of VUR is due to an anatomical abnor-mality of the vesicoureteric junction, which resultsin weakness of the normal flap-valve antirefluxmechanism described above.

Secondary VURThe term secondary VUR describes VUR associ-ated with abnormal bladder function and elevatedintravesical pressure due to conditions such asneuropathic bladder (Figure 5.1) and posteriorurethral valves. Secondary VUR has a tendency toresolve when bladder pressures are restored tomore physiological levels: for example, after bladderaugmentation for neuropathic bladder or follow-ing resection of posterior urethral valves.

VUR and voiding dysfunction It is now apparent that the traditional distinctionbetween primary and secondary VUR was oversim-plistic. Non-neuropathic bladder dysfunction isnow thought to play a significant role in theaetiology of many instances of so-called ‘primaryVUR’ (Figure 5.2). This is particularly true of girls

with low-grade VUR in whom voiding dysfunction(characterised by detrusor instability or detrusor–sphincter dyssynergia) is coupled with ‘borderline’competence of the ureterovesical junction. Typically,these girls present with daytime wetting andurinary infection (Figure 5.3).

The aetiology of high-grade primary VUR ininfant boys, which had previously been regarded asa purely anatomical abnormality, has been calledinto question by the findings of urodynamicstudies revealing markedly elevated intravesicalpressures. Moreover, appearances of increasedbladder wall thickness on ultrasound and subtleradiological abnormalities in the urethra have alsobeen invoked as possible evidence of transientintravesical obstruction in utero.

There is growing evidence of a two-way interac-tion between VUR and bladder function in somepatients with high-grade reflux. At the time ofvoiding, large volumes of urine reflux into thecapacious dilated upper tracts, thus impairing theefficiency of bladder emptying. Urine which hasrefluxed into the upper tracts then returns to thebladder to refill it almost immediately aftervoiding. In these circumstances, it is very difficult


Figure 5.1 Secondary reflux. Characteristic appear-ances of reflux associated with trabeculated neuro-pathic bladder in a child with spina bifida.


for the bladder to function effectively as a storageorgan. Evidence is emerging to indicate thatsuccessful correction of the reflux can result inmarked improvement in voiding function in someof these patients.

Incidence and genetic factors

Our knowledge of the incidence of VUR dateslargely from studies undertaken in healthy children inthe 1950s and 1960s which identified an incidence of1–2% in the general paediatric population.

The familial component of VUR is well recog-nised. VUR can be demonstrated in more than30% of the infant siblings of children withknown VUR, and in up to 50% of the offspringof affected parents.

The mode of inheritance remains unclear but thehigh incidence of VUR in siblings and patterns ofvertical transmission have previously been inter-preted as evidence of autosomal dominant inheri-tance with variable penetrance.

Despite the widely accepted genetic basis of VUR,disappointing progress has been made in identifyingthe causative gene(s). Although mutation of the PAX2gene has been identified in some familial cases ofVUR linked to a syndrome characterised by opticnerve defects, screening studies for PAX2 mutations inchildren with non-syndromic VUR have yieldeduniformly negative results. Likewise, screening studiesin patients with primary VUR have failed to identifyany evidence of mutations of other putative genessuch as AGTR2 or UP3.

Vesicoureteric reflux 59

Laterally sitedureteric orifice

Short submucosal tunnel Raised intravesical pressure

Detrusor/sphincterdyssynergia

Detrusorinstability

Anatomy Bladder function

Figure 5.2 The balance between functional and anatomical factors in the aetiology of VUR.

Figure 5.3 Micturating cystourethrogram illustratingthe importance of bladder dysfunction in the aetiologyof ‘primary’ VUR. Five-year-old girl presenting withwetting and recurrent UTIs. No neurological abnor-mality. MCU demonstrates low-grade right VUR, finetrabeculation and probable sphincter–detrusor dyssyn-ergia. Good response to antibiotic prophylaxis, anti-cholinergic and voiding regimen.


Nevertheless, some valuable insights are emerg-ing from genetic research. For example, a majorresearch programme in Dublin has identifiedevidence of an X-linked form of familial VUR.Moreover, familial VUR in boys appears to carry ahigher risk of congenital renal damage than girls,regardless of grade of reflux.

This is a rapidly changing area of research butcurrent knowledge suggests that most instances offamilial VUR result from the interaction of multiplegenes rather than an isolated single gene mutation.

Gender differences Important differences in the aetiology, naturalhistory and presentation of VUR between boysand girls are summarised in Table 5.1.

Reflux nephropathy

Aetiology of reflux nephropathyInfective

The experimental work published by Hodson andby Ransley and Risden in the 1970s identified

the role of IRR in the aetiology of infective scarring.Whereas the conical outline of the normal renalpapilla prevents the reflux of urine into theparenchyma from the collecting system, morpho-logically abnormal ‘compound’ papillae permitIRR. In the presence of VUR and lower tract infec-tion, organisms are transported to the renal collect-ing system and parenchyma, where pyelonephritisand scarring ensue if the infection remainsuntreated. Fimbriated strains of Echerichia coli areparticularly virulent because of their ability toadhere to urothelial surface receptors.

It is important to recognise, however, that whilemost renal scarring is associated with VUR, theappearances of postinfective scarring can occasion-ally be seen in children with no evidence of VUR.In such cases, it is assumed that either VUR waspresent previously but subsequently resolved or,alternatively, that scarring resulted from the occur-rence of pyelonephritis (possibly by blood-borneinfection) in a non-refluxing system.

Acquired renal scarring may coexist with pre-existing congenital renal damage. But once infec-tion has supervened, it becomes virtuallyimpossible to determine the relative contributionsof congenital and acquired renal components,except in those cases which come to nephrectomy.

Congenital

The prenatal detection of VUR provides an oppor-tunity to study patterns of renal damage in infantsand children (predominantly males with high-grade VUR) whose kidneys have never beenexposed to infection. Sibling screening provides afurther valuable means of investigating congenitalreflux nephropathy.

The findings of these studies, coupled withother recent evidence, can be summarised asfollows:

• Severe renal damage (renal dysplasia) ispredominantly a feature of grade V reflux and isprobably a consequence of faulty interactionbetween the ureteric bud and the metanephricblasphema (Figure 5.4).


FemalePresents clinically – usually with urinary infectionPeak incidence in early to mid-childhood – age2–7 yearsVUR generally low grade, i.e. grades I–IIIFunctional factors important in aetiology:dysfunctional voiding, detrusor instability,constipation

MalePresents clinically or detected prenatallyClinical presentation usually in infancy or earlychildhood – 0–2 yearsOften moderate to high-grade VUR, i.e. gradesIII–VAnatomical factors important in aetiology (+intrauterine bladder dysfunction???)

Table 5.1 Summary of gender-related differencesin vesicoureteric reflux between males and females


• Lesser degrees of congenital renal damage tendto take the form of global reduction in function-ing renal tissue (renal hypoplasia) rather thanfocal scarring.

• The development of mild to moderate renalscarring appears to be mainly dependent onurinary tract infection.

• By contrast, congenital factors play a greaterrole in severe scarring, which is seen predomi-nantly in conjunction with high-grade reflux,particularly in males.

Aetiology of Reflux Nephropathy:implications for management

Although a detailed review of the evidence isbeyond the scope of this chapter, the key pointscan be summarised as follows:

• Reflux of sterile urine at physiological voidingpressures does not result in renal scarring anddoes not impede renal growth.

• The occurrence of pyelonephritis and develop-ment of renal scarring are not always related to VUR. In most instances, however, acquiredrenal scarring is the consequence of sympto-matic upper tract infection associated withVUR and IRR.

• Renal scarring occurs maximally after the firstepisode of pyelonephritis (Ransley’s ‘big bang’hypothesis).

• The risk of renal scarring is greatest in infancyand early childhood.

• Conversely, the risk of infective scarringdecreases significantly beyond the age of 4 years,although a small risk persists throughout child-hood.

• Pyelonephritis is more likely to give rise to focalscarring of mild to moderate severity, whereasgross functional impairment is more commonlycongenital in origin.

• To pose a risk of renal scarring, urinary infectionmust be sufficiently severe to give rise tosymptomatic pyelonephritis. Asymptomaticbacteriuria, a relatively common finding in oldergirls, does not give rise to renal scarring.

• The bulk of infective scarring has alreadyoccurred when children are first diagnosed and are referred for investigation. Althoughfresh scars can develop thereafter, the risk is low providing surveillance is maintained andfurther infections do not go unrecognised oruntreated.

Clinical significance of reflux nephropathy Renal tissue which is congenitally dysplastic or hasbeen scarred by pyelonephritis becomes non-functioning and, when extensive, results in signifi-cantly reduced overall renal functional reserve.Reflux nephropathy accounts for 22% of cases ofend-stage renal failure in children and young peoplein the UK.

Even when renal damage is not sufficient toresult in end-stage renal failure, long-term studieshave demonstrated significant reduction in glomeru-lar filtration rate (GFR) in individuals with bilat-eral scarring dating from childhood. Hyperperfusionand hyperfiltration damage in the remaining non-scarred tissue are believed to be the mechanismslargely responsible for progressive deterioration,leading to chronic renal failure.

The reported incidence of hypertension attribut-able to reflux nephropathy varies from less than


Figure 5.4 DMSA scan at around 1 month of age in an infant with unilateral grade V reflux detectedprenatally; 9% differential function in the affectedkidney. No urinary infection prior to DMSA imaging.


5% in paediatric studies to 25–40% in some late-outcome studies. However, it should be notedthat the long-term studies have mostly looked atthe outcome of patients who experienced severeurinary infections in childhood at a time whenscarring was assessed by intravenous urography(IVU). It seems unlikely that the more subtle scarswhich can now be identified by the more sensitivemodality of dimercaptosuccinic acid (DMSA)imaging will carry a comparable long-term risk ofhypertension.

In one large UK study of children with hyper-tension, reflux nephropathy was the most commonsingle cause, accounting for 14% of cases. For anindividual child with evidence of renal scarring, therisk of progressing to renal failure is difficult toquantify, but is currently likely to be substantiallyless than the figure of 0.1% historically quoted inthe literature.

Presentation of vesicoureteric reflux

Symptomatic Symptomatic urinary tract infection (UTI)remains by far the commonest form of clinicalpresentation. The incidence of VUR in childrenundergoing investigation for UTIs is traditionallyquoted as around 30%. However, this figure datesfrom a time when children being referred for inves-tigation tended to have infections at the moresevere end of the spectrum. Nowadays, the increasedawareness of UTI amongst general practitioners,coupled with the availability of simple sensitivediagnostic reagent stick tests, has resulted in farlarger numbers of children being diagnosed withmild, predominantly lower tract infections.

It would be difficult to document the incidenceof VUR in children currently being diagnosedwith UTI because the indications for micturatingcystourethrography (MCU) are far more selective.

Pain is not generally regarded as a symptomof primary VUR. However, loin pain is a well-recognised feature of pyelonephritis and the

occurrence of pain may also signal the presence ofsecondary pelviureteric junction obstruction orsome other complicating factor.

VUR occasionally comes to light for the firsttime in individuals presenting with renal insuffi-ciency and/or hypertension who have little, ifany, history of urinary infection. Congenitalnephropathy and renal dysplasia are the most likelyexplanations in this situation.

Asymptomatic The term ‘prenatally diagnosed VUR’ describes adiagnostic sequence in which prenatally detecteddilatation of the fetal urinary tract leads to postna-tal investigations which may include MCU.

Primary VUR (usually of moderate to highgrade) accounts for 15–20% of clinically signifi-cant prenatally detected uropathies. Publishedreports of prenatally detected VUR have consis-tently identified a predominance of males, with amale to female ratio of around 5 to 1.

Asymptomatic VUR also comes to light duringthe course of sibling screening. Data derived from159 families with known familial reflux demon-strated that sisters of index female patients had asignificantly higher incidence of reflux than broth-ers of female patients. The Dublin group also foundthat when reflux occurred in brothers, it tended tobe high grade and carried a greater risk of congen-ital renal damage.

Investigations

The investigations of urinary tract infection aredescribed in more detail in Chapters 3 and 4. Thefollowing diagnostic considerations apply specifi-cally to VUR.

Ultrasound Although non-invasive, ultrasound has a highfalse-negative rate when used as the first-line testfor the investigation of urinary infections inchildren. Comparing ultrasound and MCU in 272



refluxing units, one large American study foundnormal ultrasound appearances in 201 (74%). Ofthe refluxing units missed on ultrasound, 28%were grade III VUR or higher.

DMSADMSA is the most sensitive modality for visual-ising scarring and quantifying differential renalfunction (Figure 5.5a and b). It is not, however, atest for VUR per se. Indeed, as a means ofindirectly identifying children with VUR, thesensitivity of DMSA is less than 50%. In practicethis high false-negative rate may not be too impor-tant since there is growing evidence that VURassociated with normal DMSA findings is gener-ally low-grade reflux with a high spontaneousresolution rate. Moreover, there is also someevidence to suggest that kidneys exposed to VURwhich nevertheless appear normal on the initialDMSA scan are less susceptible to scarring.

Micturating cystourethrography Although invasive, the conventional radiologi-cal contrast study remains the gold standard investigation for the diagnosis and evaluation ofVUR. It permits accurate grading of the severityof VUR, which is important when assessingprognosis and planning treatment. The mostwidely used grading system is the one devised by the International Reflux Study Committee(Figure 5.6).

Unlike indirect isotope cystography, MCUpermits anatomical visualisation: for example, ofthe male urethra, bladder trabeculation, para-ureteric diverticula, etc.

The role of the MCU in follow-up is controver-sial, but as a rule this invasive investigation shouldonly be performed if the findings are likely to influ-ence management. An MCU need not beperformed routinely after ureteric reimplantation,since this is an operation with a uniformly high


L R

POST

Figure 5.5 (a) DMSA scan demonstrating renal scarring with patchy cortical damage to the left kidney on initialinvestigation of a child presenting with urinary infection. (b) DMSA demonstrating bilateral focal scarring in a boywith bilateral VUR and a history of recurrent pyelonephritis. Differential function: 51% left; 49% right. Differentialfunction is an unreliable guide to individual kidney function in the presence of symmetrical renal damage.

(a) (b)


success rate. Likewise, an MCU is not requiredbefore discontinuing prophylaxis in children whohave been well and infection free.

Indirect micturatingcystourethrographyThis investigation, which utilises intravenouslyinjected mercaptoactyletriglycine (MAG3), is lessinvasive than a contrast study since it does notrequire urethral catheterisation. However, it doesentail the need for intravenous injection andexposure to radiation, albeit of a lower dosage thanan MCU. The technique is best suited to childrenwho have acquired bladder control and, conversely,is of much more limited value in infants and youngchildren – the age group at the greatest risk ofinfective renal scarring. A further drawback is thatindirect cystography is considerably less sensitivethan a contrast MCU for the detection of low-grade VUR.

The main role of indirect cystography istherefore as a follow-up investigation, particu-larly in older children.

Intravenous urographyIntravenous urography (IVU) is rarely performed,having been superseded by DMSA for the visuali-sation of renal scarring.

VideourodynamicsVideourodynamic investigations have been usedfor research studies and have demonstrated urody-namic evidence of voiding dysfunction in up to50% of girls with low to moderate grade VUR. Inroutine clinical practice, however, there is littleplace for urodynamics except, perhaps, in casesassociated with neuropathic bladder dysfunction.

Sibling screening It would clearly be desirable to look for VUR inthe siblings of children with known VUR and theoffspring of affected parents. In practice, however,routine screening is limited by the lack of a reliablenon-invasive screening test. Ultrasound has a highfalse-negative rate; indirect nuclear cystography isunsuited to use in young infants; and contrastmicturating cystography is an invasive investiga-tion which carries a risk of morbidity in this agegroup. Ideally, the options, benefits and potentialdrawbacks should be discussed with parents ofsiblings of children with known VUR.

Despite limited sensitivity for the detection oflow or moderate grades of VUR, ultrasound is areasonable first-line screening test. If this is negativeor if parents opt to forego screening, it is impor-tant that they and the general practitioner areaware of the importance of checking an MSUpromptly if there is any suspicion of UTI orunexplained febrile illness. Screening is mostworthwhile in the first year of life but, conversely,serves little useful purpose in siblings who arealready beyond the age of 5 years.

Management of VUR

The rationale for medical or ‘conservative’management is based on the evidence that sterile


I II III IV V

Figure 5.6 Grades of reflux (International RefluxStudy Committee classification). Grade I: into ureter only; grade II: to upper tract (pelvic calyces),no dilatation; grade III: mild to moderate dilatation but minimal blunting of calyces; grade IV: moderatedilatation, loss of angles of fornices, papillaryimpressions in calyces still present; grade V: grossdilatation and tortuosity, and the impressions ofpapillae no longer visible.


VUR does not give rise to renal scarring, coupledwith the well-documented tendency for mild or moderate VUR to resolve spontaneously (Table 5.2).

Conservative or ‘medical’management The conventional approach to medical manage-ment comprises:

• Continuous antibiotic prophylaxis: typically,trimethoprim 1–2 mg/kg/day, usually as a singlenight-time dose.

• Urine surveillance: the availability of reagentstrips which test for nitrites and leucocytesmake it much easier for parents or generalpractitioners to make a provisional diagnosis.Nevertheless, wherever possible, a freshlycollected midstream urine (MSU) specimenshould be examined by microscopy andculture.

• Treatment of any underlying bladderdysfunction: a regular voiding regimen,including double voiding where there isevidence of significant postvoid residualon bladder ultrasound. Anticholinergics,

e.g. oxybutynin, should be considered ifthere are symptoms suggesting detrusorinstability.

• Treatment of constipation: similar to otherforms of habitual constipation; i.e. a regimencomprising a faecal softener and a laxative,with the dosage titrated against the child’sresponse.

• Commitment: medical management should notbe confused with benign neglect. Parentalcommitment is vital to ensure compliance withthe medical regimen. Older children must bemotivated to modify their voiding habits tocorrect voiding dysfunction. Effective arrange-ments are needed to ensure that urine samplesare collected and examined promptly to facili-tate diagnosis and treatment of breakthroughinfections. If this commitment is lacking or thenecessary level of primary healthcare support isnot available, surgical intervention may bepreferable.

Controversies surrounding medical management

Although the pattern of medical managementdescribed above has been the mainstay of treat-ment since the 1970s, it is being increasinglychallenged. A number of well-designed studies areunderway or are planned to address a number ofimportant questions. For example:

• What is the most effective regimen foradministering antibiotic prophylaxis –continuous treatment with a single agent or alternating courses of two antibiotic agents?

• Does continuous prophylaxis have anyadvantage over treatment of individual infec-tions as and when they occur?? At least onerandomised prospective controlled study failedto demonstrate a difference in the number ofUTIs experienced by girls on prophylaxiscompared with those who were not.

• What is the optimum duration of prophy-laxis?? (There is already a trend to earlier cessation


Distribution of Spontaneous Grade of different grades resolution rate reflux of reflux (%) for each grade (%)

I 7 83II 53 60III 32 46IV 6 9V 2 0

Table 5.2 Distribution of grades of reflux andspontaneous resolution for each grade in 844refluxing ureters. Data from the Children’s Hospital National Medical Centre, Washington.Skoog SJ, Bellman AB, Majd M, 1987


of prophylaxis – particularly in boys once they areout of nappies and have achieved bladdercontrol.)

• Can endoscopic treatment now be regarded asa reasonable first-line alternative to medicalmanagement in children with low to moder-ate grades of VUR?? Although low to moderategrade VUR has a high tendency to resolvespontaneously, it is also the case that these gradesof VUR can usually be corrected with a singleendoscopic injection. Opinion remains divided.

• Finally comes the contentious question – isthere any benefit in treating VUR at all??This viewpoint cites evidence that severereflux-related renal damage is largely congen-ital, and thus not amenable to treatment.Moreover, the low rate of new scars inchildren on follow-up can be advanced asevidence that most infective scarring hasalready occurred and that any further inter-vention is a waste of time.

These arguments can be countered by thelarge body of clinical and experimental evidenceindicating that pyelonephritis does indeed causerenal scarring. Moreover, sibling studies havefound a significantly higher incidence of renaldamage in index patients (those whose VUR cameto light following infection) compared with theirinfant siblings whose VUR has been detected byscreening (i.e. before the occurrence of infection).

This finding can be interpreted as evidence thatacquired infective damage is not uncommon.

Finally, the theoretical arguments for ignoringVUR tend to focus on renal scarring and renalfailure, while ignoring the impact of recurrentinfection and ill health on schooling and well-being of affected individuals in childhood.

Indications forsurgical intervention Indications for surgery are relative rather thanabsolute and fall into three broad categories:

Functional

The occurrence of symptomatic breakthroughinfection despite medical management representsthe most common indication to proceed to surgi-cal intervention. The options are endoscopic treat-ment or ureteric reimplantation.

Anatomical

VUR that occurs in conjunction with abnormali-ties such as paraureteric diverticulum or uretericduplication has a lower tendency to resolve thanuncomplicated primary reflux. Nevertheless, thepresence of VUR into the lower pole of a duplexsystem is not an automatic indication for surgicalintervention. High-grade reflux (grade IV or V),which is associated with significant functionalimpairment in the ipsilateral kidney, is very unlikelyto resolve spontaneously. Surgery (usually uretericreimplantation) is a reasonable first-line option insuch cases after the age of 12 months.

Parental preference

In the internet age, parents are increasingly awareof the arguments supporting early endoscopictreatment for low to moderate grade VUR as analternative to long-term continuous antibioticprophylaxis.

Endoscopic correction Since the first experimental description in 1984,endoscopic correction of VUR has become anestablished and widely used form of management.Several implant materials have been used forsubureteric injections, including polytetrafluoroeth-ylene (PTFE, Teflon), collagen, polydimethyl-siloxane (PDMS, Macroplastique), autologouschondrocytes and Deflux (dextranomer–hyaluronicacid copolymer).

The technique of subureteric injections was firstpopularised by O’Donnell and Puri who publishedhigh success rates for the correction of VUR usingTeflon as the injectable implant material. The



suburetic injection of Teflon acquired the acronymof the STING procedure.

Implant material

Tef lon paste is a suspension of PTFE particles inglycerin. It is inert, highly crystalline and has a lowcoefficient of friction. After injection, the glycerinis absorbed into the tissues, the implant achieves afirm consistency and is subsequently encapsulatedby thin fibrous tissue. Following the introductionof the STING procedure, concerns were expressedregarding the potential for distant migration ofPTFE particles. These concerns centred on thenon-biodegradable nature of PTFE and the findingsof animal studies. (Although these have beenchallenged by other authors.)

Dextranomer–hyaluronic acid copolymer(Deflux) consists of dextranomer microspheres ofan average size of 80–250 µm in sodium hyaluronate:1 ml of the mixture consists of 0.5 ml microspheresand 0.5 ml sodium hyaluronate. Experimentalwork has shown that by 1 year the microspheresare surrounded by fibroblasts and collagen. Thisbiodegradable substance has been extensivelytested and, so far, there has been no evidence ofimmunogenic properties or potential for malig-nant transformation.

Macroplastique (PDMS) consists of a paste ofsilicone particles whose size is designed to preventmigration.

Because of its availability, ease of injection andthe low theoretical risks of particle migration,Deflux is currently the most widely used injectablematerial.

Technique of injection

Under general anaesthesia, a cystoscope with aworking channel (9–14 Fr) is introduced into thebladder. Under direct vision, a rigid or flexibleneedle is introduced through the working channeland advanced under the mucosa at a 6 o’clockposition at the ureteric orifice (Figure 5.7a). If therefluxing ureteric orifice is wide enough to admit

the tip of the scope, then an intraureteric injectionis preferred. The implant is injected until a moundor ‘volcanic’ bulge is visualised (Figure 5.7b). Theendpoint is reached when the ureteric orifice iselevated sufficiently as to create a crescent-shapedor slit-like orifice at the top of the mound, whichgives the appearance of a nipple (Figure 5.7c).

Once the injection is completed satisfactorily,the needle is left in place for a further 10–15seconds to allow the gel to set. This is particularlyimportant if Deflux is used. Multiple punctures inthe mucosa are undesirable because they permitleakage of the implant and it becomes difficult toachieve the ‘mound’ configuration needed toachieve satisfactory correction of VUR.

Results

Some authors have reported success rates in excessof over 93% with endoscopic correction for reflux.However, a high percentage of patients in thesereported series had low-grade reflux, which has ahigh potential for spontaneous resolution (and forwhich antibiotic prophylaxis may not always bewarranted).

The use of endoscopic treatment for low-gradeVUR has been heavily criticised by some paedi-atric urologists as unnecessary intervention.These criticisms have, however, been counteredby the arguments that the need for prolongedadministration of prophylactic antibiotics can beaverted by a single day-case procedure. Betweenthese points of view there is general acceptancethat endoscopic correction has a distinct role in the algorithm of management of VUR, alongwith conservative management and surgicalreimplantation.

Endoscopic correction is probably most benefi-cial in grade III–IV VUR associated with break-through UTIs. The indications for treatingasymptomatic low or moderate grades VUR aremore controversial. Endoscopic treatment ismuch less successful in correcting severe VUR(grade V) and reflux may persist despite repeatedinjections.



A study undertaken using data recorded on thePediatric Health Information System in the UnitedStates reviewed over 4500 recorded antirefluxprocedures (open reimplantation and endoscopiccorrection) performed in children in 2002–2004.It was found that since the introduction ofminimally invasive procedures the overall numberof interventions for reflux had increased – althoughopen surgery rates remained unchanged. Fromthese findings, it is apparent that in the UnitedStates, at least, endoscopic correction is beingincreasingly favoured as an alternative to conserva-tive management.

Ureteric reimplantation

The cross-trigonal advancement procedure devisedby Cohen remains the open operation of choice forthe majority of paediatric urologists (Figure 5.8).The appeal of this procedure lies in its relativesimplicity, its high success rate in correcting VUR(97% or thereabouts) and the low incidence ofpostoperative obstruction.

Postoperative stenting of the reimplanted ureteris not routinely necessary, but the bladder isdrained for a short period postoperatively witheither a suprapubic or urethral catheter. Creating


Figure 5.7 (a–c) Technique of endoscopic injectionfor correction of VUR – see text for details.

(a) (b)

(c)


an effective antireflux flap valve requires a submu-cosal tunnel with a length approximately three orfour times greater than the diameter of thereimplanted ureter. Achieving this ratio whenreimplanting a dilated ureter into a small bladderis not always technically feasible. In this situation,the diameter of the distal ureter can be reduced byplication, e.g. the Starr technique.

The Politano–Leadbetter type of reimplanta-tion, coupled with a psoas hitch, is often preferableto the Cohen technique when reimplanting agrossly dilated megaureter.

Extravesical antireflux operations of the typeoriginally described by Lich and Gregoir (Figure 5.9)are favoured by some paediatric urologists. Thebenefits centre on the reduced incidence of post-operative haematuria and discomfort. However,extravesical techniques are less suited to dilatedureters. There is also evidence of postoperativevoiding dysfunction, which may amount tourinary retention in rare cases.

Endoscopic reimplantation This technique is being developed in some special-ist centres as a minimally invasive alternative toconventional open reimplantation. The bladder isfilled with carbon dioxide and a Cohen reimplanta-tion performed using endoscopes introduced percu-taneously into the bladder. There is a considerabletechnical ‘learning curve’, but in skilled andexperienced hands the results are comparable tothose obtained by open surgery.

Alternatives toureteric reimplantation Circumcision

There is some anecdotal evidence that circumcisionmay be beneficial in reducing the incidence ofurinary infection in boys with high-grade VUR.But in the absence of any formal prospective trial,there is insufficient evidence to justify routinely


Figure 5.8 Ureteric reimplantation: Cohen technique.(a) Intravesical mobilisation of ureter. (b) Creation ofsubmucosal tunnel. (c) Ureter reimplanted across thewidth of the trigone. The Cohen cross-trigonal reimplan-tation can be performed bilaterally and, if necessary,combined with ureteric plication of a mild to moderatelydilated ureter.

(a) (b)

(c)


performing ‘prophylactic’ circumcision on all boyswith prenatally detected VUR or sibling VUR.Nevertheless, it is a reasonable option to consider ona selected basis.

Vesicostomy The creation of a temporary bladder stoma is aneffective way of decompressing the refluxing upper

tracts and facilitating drainage. The procedure iswell tolerated and the incidence of complications islow. Cutaneous vesicostomy has largely replacedureterostomy in young infants whose VUR iscomplicated by sepsis or impaired renal function.Closure of the vesicostomy can be undertaken asan isolated procedure or in combination withdefinitive correction of VUR during the second orthird year of life (Figure 5.10).


Figure 5.9 Ureteric reimplantation: Lich–Gregoirtechnique. Extravesical mobilisation and reimplantationin detrusor tunnel. Unsuitable for dilated ureters.(a) Refluxing ureter exposed and mobilised extravesi-cally. (b) Detrusor muscle incised in the line of thewater. Bladder mucosa exposed but not opened.(c) Detrusor closed around distal ureter to enclose itwithin detrusor tunnel.

(a) (b)

(c)


Nephroureterectomy

The role of nephrectomy is being reappraisedin the light of concerns regarding the potentiallong-term risk of hyperfiltration damage to theremaining solitary kidney. However, this risk maybe more than offset by the risk of hypertensivedamage generated by a grossly scarred kidneywhich is left in situ.

The occurrence of infection strengthens thearguments for nephrectomy, particularly whendifferential function in the affected kidney is lessthan 10% and the contralateral kidney is normal.

When removing the kidney, it is also importantto ensure that the ureter is also removed in itsentirety to avert the risk of infection associatedwith a residual ‘refluxing stump’. Removing the entire length of the ureter by open surgeryusually requires two incisions, and for this reason

laparoscopic nephroureterectomy is becoming anincreasingly attractive alternative.

Transureteroureterostomy (TUU)

This is a useful procedure to manage recurrentVUR or ureteric obstruction following failed uretericreimplantation. One ureter is reimplanted usingthe Politano–Leadbetter technique; the contralat-eral ureter is disconnected from the bladder, swungacross the midline retroperitoneally and anasto-mosed to the reimplanted ureter.

Management of secondary VUR Secondary VUR has a tendency to improve orresolve completely when more physiological bladderpressures have been restored by the treatment ofoutflow obstruction or bladder augmentation.Although it may occasionally prove necessary toresort to open antireflux surgery for secondary VUR,reimplanting dilating ureters into thick-walledneuropathic or ‘valve’ bladders can be technicallydifficult and is best avoided unless there arecompelling indications. The failure rate (persistingreflux) and incidence of complications are bothhigher than for primary VUR.

As for primary VUR, however, the treatmentalgorithm has been changed by the introduction ofan endoscopic treatment. Favourable results havebeen reported for endoscopic treatment and thisapproach is certainly a simpler alternative to opensurgery in the thick-walled bladder.

Which is more effective: medicalor surgical management? Although a number of prospective controlled trialshave been undertaken to answer this question,none have demonstrated a clear advantage of onetreatment modality over the other.

An analysis of eight trials found no difference in theoverall frequency of UTIs after 1–2 years and 5 years,although the incidence of febrile UTIs was lowerfollowing reimplantation. Controlled trials have notdemonstrated any difference in the incidence of freshrenal scars, which in any event are relatively rare inboth surgically and medically treated groups.


Figure 5.10 Immediate postoperative appearancesof cutaneous vesicostomy performed in a male infantwith high-grade primary VUR-breakthrough infectionsand failure of conservative management.


In everyday clinical practice, however, medicaland surgical treatments do not prove equally effec-tive. Whereas some children thrive and remaininfection-free on antibiotic prophylaxis, othersexperience symptomatic breakthrough infectionswhich are only controlled by endoscopic correctionor ureteric reimplantation.

This paradox probably reflects the difficulty ofdesigning trial methodologies to encompass themany different variables, which include age,gender, grade of reflux, patterns of bladderdysfunction, constipation, patient and parentalcompliance with voiding regimens and antibioticprophylaxis, etc.

The principal conclusion that can be drawn fromthe trial data is that medical management can besafely adopted as the first-line treatment for themajority of children with VUR.

Surgical treatment is undertaken for specificindications. Nowadays, if there is an informedparental preference, endoscopic treatment may beconsidered as an alternative to long-term antibioticprophylaxis.

Key points

• Voiding dysfunction plays an importantrole in the aetiology of ‘primary’VUR, particularly in girls. Activetreatment of voiding dysfunction is an important aspect of medicalmanagement.

• Reflux nephropathy may result fromcongenital damage (dysplasia), infectivescarring or a combination of both.

• VUR is not a single entity.Management should beindividualised to encompassindividual contributory factors.

• Endoscopic correction is particularlyindicated for moderate-gradereflux associated with breakthroughinfection. The role of endoscopiccorrection as an alternative tolong-term antibiotic prophylaxisfor asymptomatic low-gradereflux is controversial.

Further reading

Guidelines on the management of primary vesicoureteralreflux in children. American Urological Assocation.www.auanet.org/guidelines/main_reports/vesi_reflux.pdf

Pirker ME, Colhoun E, Puri P. Renal scarring in familialvesicoureteral reflux: is prevention possible? J Urol2006; 176(4 part2): 1842–1846

Ransley PG, Risdon RA, Goldy ML. High pressure sterilevesicoureteral reflux and renal scarring: an experimentalstudy in the pig and minipig. Contrib Nephrol 1984;39: 320–343

Stenberg A, Hensle T, Lackgren G. Vesicoureteral reflux: anew treatment algorithm. Curr Urol Rep 2002; 3(2):107–114

Van der Voort JH, Verrier-Jones K. Vesico ureteric reflux:definition and conservative management. In: Stringer MD,Oldham KT, Mouriquand PDE (eds). Paediatric Surgeryand Urology: Long Term Outcomes. Cambridge:Cambridge University Press 2006: 555–570

Verrier Jones K. Prognosis for vesico ureteric reflux. ArchDis Child 1999; 81: 287–289

Yeung CK, Godley ML, Dhillon HK et al. The characteris-tics of primary VUR in male and female infants withprenatal hydronephrosis. Br J Urol 1997; 80: 319–327



Upper tract obstruction

David FM Thomas

Introduction

Despite the important role of upper tract obstruc-tion within paediatric and adult urology, there isno satisfactory scientific definition of what consti-tutes obstruction. One useful working definition,however, characterises obstruction as ‘someimpedence to the flow of urine, which causesgradual and progressive damage to the kidney’.

The terminology used by urologists and radiol-ogists has not been helpful in advancing ourunderstanding of obstruction, particularly whenpathological and descriptive terms such as ‘pelvi-ureteric junction (PUJ) obstruction’, ‘idiopathichydronephrosis’ or ‘vesicoureteric junction obstruc-tion’ and ‘primary megaureter’ have often beenused interchangeably.

This confusion is exemplified by the use of theterm ‘hydronephrosis’. Although this is often used todenote pelviureteric junction obstruction, it isimportant to note that hydronephrosis is not adiagnosis in itself but a descriptive term denotingpathological dilatation of the renal pelvis and calyces.When this is accompanied by dilatation of the ureter,the corresponding term ‘hydroureteronephrosis’ isused. Hydronephrosis (upper tract dilatation), maybe a feature of a number of acquired or developmen-tal urological disorders, including:

• obstruction to urinary drainage• vesicoureteric reflux

• dysplasia and developmental abnormalities ofthe upper urinary tract

• pathologically high urinary output (flowuropathy).

The introduction of isotope renography was a majoradvance in the diagnosis of obstruction, but even thiscan be unreliable or potentially misleading in certainclinical situations. In the absence of a precise scien-tific definition of obstruction or a universallyreliable test, clinical decision-making will continue todepend upon information from a number of differ-ent investigations, each with its own limitations.

Pathophysiology of obstruction

Acute obstruction can be reproduced experimen-tally, thus allowing the sequence of physiologicalevents within the obstructed kidney to be studiedin some detail. However, acute obstruction isrelatively uncommon in children and is generallythe result of acute pelviureteric junction obstruc-tion or impaction of a urinary calculus at the pelvi-ureteric or vesicoureteric junction. Within theacutely obstructed kidney, urine is reabsorbedfrom the collecting system into the interstitium,intrarenal pressure rises and renal blood flow falls.Unless there is prompt relief of obstruction,progressive nephron damage supervenes, leading

6

Topics coveredPathophysiology of acute and chronic upper tractobstructionDiagnosisUltrasound

Isotope renography Other modalitiesPelviureteric junction obstruction Vesicoureteric junction obstruction


to the loss of approximately 50% of functioningnephrons after 6 days and the irreversible loss of allrenal function within 6 weeks. The timescale ofrenal damage is rapidly accelerated by the presenceof urinary infection (pyonephrosis).

In clinical paediatric practice, chronic or inter-mittent obstruction is far more common thanacute upper tract obstruction, but because of thedifficulty in creating reliable experimental modelswe have far less understanding of the relevantpathophysiology. Investigating chronic or inter-mittent obstruction in a clinical setting is also moreproblematic and the risk of functional deteriora-tion is more difficult to predict.

In the past, the majority of children with uppertract obstruction presented clinically with symptomssuch as pain or urinary infection and the decision toadvise surgical intervention was easier to justify.

However, with the advent of prenatal detectionof upper tract dilatation, it has become apparentthat mild to moderate upper tract dilatation ismore prevalent in healthy, asymptomatic infantsthan was previously recognised. In many cases thepresence of dilatation is not associated with activeobstruction or renal impairment. In such cases, thenatural history is often one of progressive improve-ment. Even when the presence of obstruction isestablished by appropriate investigation, thepotential still exists for spontaneous resolution.

The natural history of asymptomatic upper tractobstruction is not always benign, and someobstructed kidneys are at undoubted risk of progres-sive functional deterioration which may proveirreversible. The paediatric urologist is thereforefaced with the practical dilemma of distinguishingthose infants whose dilatation/obstruction isdestined to follow a benign course from those whoare destined to suffer functional deterioration in theaffected kidney unless the obstruction is relieved.

Investigation of upper tract obstruction

Although the presence of dilatation does notnecessarily signify active obstruction, it is generally

true that obstruction does not occur withoutevidence of dilatation. The early stage of acuteobstruction, for example by an impacted calculus,is a rare exception to this rule.

UltrasoundNowadays, the diagnostic pathway almost invari-ably starts with the ultrasound finding of dilatation(Figure 6.1). It should be emphasised, however,that it is not possible to distinguish reliablybetween different causes of dilatation nor to estab-lish the diagnosis of obstruction purely on thebasis of ultrasound findings.

The measurement that has proved to be of mostvalue is the anteroposterior (AP) diameter of therenal pelvis measured at the renal hilum. In theneonate, this figure should not normally exceed6 mm. Significant obstruction that represents athreat to renal function is most unlikely to bepresent when the AP diameter is less than 15 mm.Conversely, an AP diameter exceeding 50 mm isalmost invariably associated with diminishedfunction, either at the time of initial assessment orduring the course of follow-up.

The sensitivity of ultrasound in the diagnosis ofobstruction can be enhanced by including anassessment of the renal cortex and the degree ofcalyceal dilatation.

Ureteric dilatation must always be regarded asan abnormal finding, as the normal-calibre uretercannot be visualised on ultrasound.

Resistive index

Resistive index is measured by the use of a Dopplerultrasound probe directed at a branch of the renalartery. Studies aimed at identifying the correlationbetween resistive index and various parameters ofobstruction have generally been unrewarding.Measurement of resistive index is not a sufficientlysensitive measure of obstruction to serve any usefulrole in clinical practice. In a different context,colour Doppler has also been used to visualise jetsof urine emerging from the ureteric orifice.Whereas a correlation has been described betweenreduced frequency of ureteric jets and upper tract



obstruction, it is unlikely that the technique willprove sufficiently sensitive to replace standarddiagnostic modalities.

Isotope renographyIsotope renography is the principal investigationused to diagnose upper tract obstruction. Technetium-99m (99mTc) MAG3 (mercaptoacetyltriglycine) is theradiopharmaceutical agent of choice for this purposeand has largely replaced 99mTc DTPA (diethylenetri-amine pentaacetic acid). 99mTc MAG3 has the advan-tage of superior gamma camera images to DTPA,coupled with faster clearance rate and lowerbackground activity. Studies can be performed morerapidly and background subtraction calculations areeasier. However, DTPA renography has the advan-tage that diagnostic imaging can be combined witha clearance study for the purpose of calculatingglomerular filtration rate (GFR).

The following phases of the dynamic renogramare routinely analysed in the investigation ofobstruction.

Differential renal function

Differential renal function is derived by comparingisotope uptake in the two kidneys, which in turn is areflection of renal blood flow. Although 99mTc MAG3

is superior to DTPA for the calculation of differentialfunction, static scintigraphy with DMSA (dimercap-tosuccinic acid) remains the gold standard since itprovides a more reproducible value for differentialfunction, particularly when function is severelyimpaired. Regardless of whether differential functionis assessed by 99mTc MAG3 or 99mTc DMSA, thevalues provide a comparative (i.e. differential) ratherthan absolute measure of renal function.

Renogram curves

Diuresis renography provides a means of distin-guishing between obstructed and non-obstructeddilatation.

The characteristics of the uptake and drainagecurves, as defined by O’Reilly and associates, fallinto four patterns (Figure 6.2):

• Type 1. Normal uptake with prompt washout.• Type 2. Rising uptake curve; no response to

diuretic (obstruction).• Type 3a. Initially rising curve, that falls rapidly in

response to diuretic (non-obstructive dilatation).• Type 3b. Initially rising curve which neither falls

promptly nor continues to rise.

Whereas type 1 and type 3a curves are normal andnon-obstructed, the clinical significance of type 2and type 3b curves remains problematic. Drainagecurves can be particularly difficult to interpret inthe first few months of life (the period of so-called‘transitional nephrology’) when immaturity of therenal tubules may impair the response of thekidney to diuretic stimulation. Many paediatricurologists have sought to overcome this difficultyby basing their decision on whether or not toproceed to pyeloplasty in infants with an asympto-matic, prenatally detected PUJ obstruction not ondrainage curve data, but on differential function inthe affected kidney.

Pressure/flow studiesDeveloped and popularised by Whitaker in the1970s, this investigation was designed to quantifyobstruction by measuring the hydrostatic pressure

Upper tract obstruction 75

Calyces

Renalpelvis

Figure 6.1 Postnatal ultrasound confirming antena-tal ultrasound appearances of grossly hydronephrotic(dilated) right kidney with marked dilatation of renalpelvis and calyces with thinned cortex (renal pelvic APdiameter = 32 mm).


within the kidney when the collecting system isdirectly filled with fluid at different flow rates. It isan invasive investigation, requiring percutaneousrenal puncture under general anaesthesia. Pressure/flow studies are now rarely performed, havingbeen largely superseded by dynamic renography.

Intravenous urographyAlthough the intravenous urogram (IVU) has beensuperseded by dynamic renography, there are raresituations when it can provide valuable anatomicalinformation which is not forthcoming from otherimaging modalities. Examples include, PUJ obstruc-tion in a duplex kidney (Figure 6.3), mid uretericobstruction and retrocaval ureter, although this isalso well demonstrated on computed tomography(CT) and magnetic resonance imaging (MRI).

Magnetic resonance imaging (Figure 6.4)Dynamic contrast-enhanced MR imaging has thepotential to combine the anatomical informationyielded by ultrasound with the functional informa-tion provided by renal scintigraphy. The informationis provided by a single study that does not entailexposure of the child to ionising radiation. Practicaldrawbacks include the significantly higher cost andthe requirement for general anaesthesia or sedationto facilitate MR imaging in infants and youngerchildren. Furthermore, in its current stage of devel-opment, the information provided by the functional


Figure 6.2 Patterns of uptake and drainage curveson isotope renography, as classified by O’Reilly andassociates.

Type 2

Type 1

3b

3a

Time

Lasix IV

Act

ivity

Act

ivity

Renogram curves

Time

Figure 6.3 Intravenous urogram demonstratingdilatation confined to the lower pole of a duplex kidney(PUJ obstruction in an incomplete duplication – ‘bifidsystem’). The IVU retains a useful role in delineatingureteric or caliceal anatomy in unusual variants ofupper tract obstruction.


component of dynamic contrast-enhanced MR isless reliable than the information on differentialfunction and drainage provided by 99mTc MAG3.

Nevertheless, anyone who has seen the imagesproduced by this new imaging modality cannot failto be impressed by the quality of the anatomicaldetail. The technique is currently under evaluationin a number of specialist centres and it is too earlyto say whether the overall value of the additionalinformation provided by dynamic contrast-enhanced MR will be sufficient to justify itswidespread introduction as the gold standardinvestigation for obstruction.

It is quite possible that the informationobtained at less cost from ultrasound and dynamicrenography will be judged to be sufficient for thepurposes of routine investigation.

Even if this proves to be the verdict on the use ofMR in uncomplicated upper tract obstruction, thisimaging modality will undoubtedly play a valuablerole in helping to delineate the anatomy of unusualforms of obstruction such as retrocaval ureter.

Retrograde pyelographyAlthough this was once performed routinely toconfirm the anatomical level of obstruction priorto surgery, it has been largely rendered redundantby the introduction of other imaging modalities,notably ultrasound. However, there are stilloccasional situations where a retrograde pyelo-gram may be very helpful in establishing the levelof obstruction where this is in doubt.

Antegrade pyelographyRenal puncture under ultrasound guidance and theinjection of contrast into the collecting system canbe particularly helpful in visualising obstructiondistal to the pelviureteric junction and also in theinvestigation of suspected recurrent PUJ obstruc-tion following previous pyeloplasty.

Diagnostic pathway

In summary, the clinical investigation of the dilatedupper tract is designed to answer the followingquestions:

• Is the dilatation due to active obstruction?Isotope renography is the first-line investiga-tion, but other modalities may be needed toexclude reflux and non-obstructive dilatation.

• At what anatomical level is the obstruction(and what is the most likely pathology)?Ultrasound generally provides this informationbut contrast-enhanced MR urography shouldnow be considered the next investigation ofchoice. Antegrade or retrograde pyelographymay occasionally be required.

• Is the function in the obstructed kidneysufficient to justify a conservative procedure


Figure 6.4 Magnetic resonance scan with contrastdemonstrating bilateral PUJ obstruction.


or would nephrectomy be more appropri-ate? Isotope renography with 99mTc MAG3will generally suffice but where renal function isgrossly impaired 99mTc DMSA is a more accuratemeasure of function and a more reliable predic-tor of potential functional recovery.

Summary• There is no scientifically rigorous definition of

obstruction and, at present, no gold standarddiagnostic test.

• Dynamic contrast-enhanced MR imaging is a promising new diagnostic modality since it provides both anatomical and functionalinformation. But further evaluation is requiredbefore it can be considered as a viable alterna-tive to ultrasound and dynamic renography forthe routine investigation of upper tractobstruction. Cost and the need for generalanaesthesia or sedation in younger children aresignificant drawbacks.

• Although 99mTc MAG3 is the isotope of choicefor most aspects of investigation of obstruction,99mTc DMSA provides more reliable informa-tion on differential function in poorly function-ing kidneys and is a more reliable predictor of

the functional outcome to be anticipatedfollowing pyeloplasty.

Pelviureteric junction obstruction

PUJ obstruction is a heterogeneous disorder with anumber of different anatomical causes. Moreover,there is considerable variation both in the severity ofobstruction and in the natural history of the condi-tion. Estimates derived from antenatal screeningplace the incidence of PUJ obstruction in the range1:750–1:1000. Analysis of data held on the USPediatric Health Information System databaseshowed that the pyeloplasty rate had doubled from74 per 100 000 in 1992 to 140 per 100 000 in 2004.

The male to female ratio is approximately equaland the left kidney is more commonly affectedthan the right, by a ratio of approximately 2:1.

The condition usually occurs on a sporadic basis,but familial inheritance has been reported. PUJobstruction is more common in children withother urinary tract anomalies such as multicysticdysplastic kidneys and the VACTERL spectrum ofanorectal and vertebral anomalies.


Figure 6.5 Aetiology of pelviureteric junction obstruction. (a) Intrinsic stenosis. Obstruction due to narrowingof a segment of ureter which is usually localised to the region of the pelviureteric junction but may extend overa length of several centimetres. (b) Ureteric folds. Tortuous segment of proximal ureter giving rise to varyingdegrees of obstruction. Straightening of this segment with growth may explain the spontaneous resolution ofobstruction observed in a proportion of prenatally detected cases. (c) Extrinsic obstruction by crossing lower polevessels.

(a) (b) (c)


Pathology and aetiology of PUJ obstructionAlthough the findings on diagnostic imaging,notably MR urography, can be helpful in pointingto the likely anatomical cause of the obstruction, itis not usually until the time of operation that thiscan be established with certainty.

Intrinsic obstruction (Figure 6.5a)

Typically, the obstruction is caused by a shortstenotic segment at the pelviureteric junction.However, in some cases, the stenosis may extenddistally from the PUJ to involve a more extensivesegment of the proximal ureter.

Ureteric folds (Figure 6.5b)

In these cases, the PUJ is of normal calibre but theproximal ureter is tortuous and kinked. Thisanatomical variant may be associated with self-limiting obstruction, which resolves as the proxi-mal ureter straightens with growth.

High insertion of the pelviureteric junction

The PUJ is sited high on the dilated renal pelvis ratherthan at its most dependent part. Although this maybe a primary abnormality, it is generally thought to bea secondary phenomenon resulting from upwardsdisplacement of the PUJ by the dilating pelvis; i.e. aneffect rather than a cause of the obstruction.

Extrinsic obstruction: lower pole or‘crossing vessels’ (Figure 6.5c)

Aberrant or crossing lower pole vessels are foundin more than 30% of older children and adultsundergoing pyeloplasty.

In some cases, the lower pole vessels appear tobe incidental to an intrinsic PUJ obstruction but inother cases, particularly older children presentingwith intermittent loin pain, the operative findingsstrongly suggest that the crossing vessels areindeed responsible for the obstruction.

This impression is reinforced by the observationthat symptoms are invariably relieved followingpyeloplasty, in which the reconstructed pelvi-ureteric junction is relocated anterior to the vessels.

Further evidence of the causative role of lowerpole vessels can be deduced from reports thatsymptoms can be relieved by laparoscopic mobili-sation and repositioning of the PUJ in relation tothe vessels, without the need for dismemberedpyeloplasty (see Chapter 23).

In contrast to older children, lower pole vesselsaccount for less than 5% of infants with prenatallydetected PUJ obstruction requiring pyeloplasty.

Variants of PUJ obstructionHorseshoe kidney

The majority of horseshoe kidneys are asympto-matic and of no urological concern. Of the compli-cations that can occur, obstructed drainage is themost common. This may be due to distortion ofthe proximal ureter as it loops over the renalisthmus or compression from the aberrant vascula-ture found at the renal hilum of horseshoe kidneys(Figures 6.6 and 6.7).


Figure 6.6 PUJ obstruction in a horseshoe kidneycaused by distortion of the proximal ureter loopingover the renal isthmus (or compression by aberrantvasculature).


Retrocaval ureter

This rare anomaly, which more commonly affectsthe right ureter, is a consequence of the abnormaldevelopment of the posterior cardinal veins, theprecursors of the inferior vena cava. A number ofanatomical patterns have been described. If thisdiagnosis is raised by the ultrasound findings, MRurography should then be performed as the investi-gation of choice. Laparoscopic correction is prefer-able to open surgery, provided this is undertaken byan experienced minimally invasive surgeon.

Intraluminal obstruction

Rare cases of ureteric obstruction caused by intra-luminal fibroepithelial polyps have been described;they occur more frequently in the midureter thanthe pelviureteric junction.

Idiopathic ‘functional’ obstruction

The renal pelvis normally expels urine byperistaltic contraction initiated from pacemakersites located in the minor calyces. Failure ofperistaltic activity or discoordination of thepacemaker activity is believed to account for casesof ‘obstruction’ in which the pelviureteric junctionis patent and no extrinsic compression can beidentified. Although such cases are encountered inadult practice, they are rare in children, in whomone of the anatomical factors listed above isalmost invariably present.

Secondary PUJ obstruction

Gross vesicoureteric reflux (e.g. grades IV and V)can result in tortuosity and kinking of the proximalureter, which can occasionally cause obstructeddrainage from the kidneys. This phenomenon isbest seen on MCUG films taken after voiding


Figure 6.7 Intravenous urogram demonstrating dilata-tion associated with obstruction in the left limb of ahorseshoe kidney.

Figure 6.8 ‘Secondary’ PUJ obstruction associated with vesicoureteric reflux. (a) Dilatation of the right renalcollecting system seen on the early phase of a micturating cystogram. (b) Progressive dilatation throughout thecourse of the MCU study. The degree of dilatation is grossly disproportionate to the severity of the reflux. PUJobstruction subsequently confirmed by isotope renography (performed with a bladder catheter in situ to elimi-nate confusion due to reflux of isotope).

(a) (b)



(Figure 6.8). A dynamic renogram performedwith a bladder catheter in situ can also be veryhelpful in establishing the diagnosis of secondaryPUJ obstruction in the presence of reflux.

Natural history of PUJ obstructionThe natural history of PUJ obstruction is variable.Whereas the obstruction resolves spontaneouslyin some cases, in others it increases in severity,giving rise to progressive functional deterioration.In a substantial proportion of cases, the obstruc-tion remains stable for many years, with little orno impact on renal function. In a study of theconservative management of prenatally detectedPUJ obstruction, undertaken at Great OrmondStreet Hospital, 17% of obstructed kidneys requiredpyeloplasty because of deteriorating function,27% showed evidence of resolving obstructionand 56% remained stable, with persisting obstruc-tion but no functional deterioration over thecourse of the study. To confuse the picturefurther, it is well documented that progressiveobstruction and dilatation can arise de novo in apreviously normal or mildly dilated kidney.Likewise, antenatally detected dilatation canresolve completely in infancy, only to recur assymptomatic, ‘full blown’ obstruction in laterchildhood (Figure 6.9).

PresentationPUJ obstruction is the most common clinicallysignificant uropathy detected on prenatal ultra-sound (Figure 6.10). It should be noted, however,that mild to moderate degrees of obstruction maynot be present or may not have given rise todetectable dilatation at the time when routine fetalanomaly scans are performed in the secondtrimester. Mild to moderate PUJ obstruction morecommonly comes to light on scans performed inlater pregnancy, or may remain undetected if nofurther scans are performed after the secondtrimester. The severity of the dilatation (AP diame-ter of the renal pelvis) is a more accurate predictorof functional impairment than the gestational age

at which dilatation was first detected. Where theAP diameter exceeds 50 mm, differential functionis almost invariably impaired.

Urinary tract infection used to be the common-est mode of presentation in infants and youngchildren before the advent of prenatal ultrasound.Infection within the obstructed system mayprogress to pyonephrosis, characterised by highfever, systemic ill health and ultrasound findings ofdebris within the dilated collecting system.

It is not uncommon for PUJ obstruction topresent with pain, typically in children aged 4years and upwards. Unlike non-specific abdominalpain, the symptoms arising from an obstructedkidney usually last for several hours or several days.Although the pain is typically sited in the region ofthe loin, it may be experienced predominantly inthe epigastrium and central abdomen, giving riseto possible diagnostic difficulties. In older childrenwhose PUJ obstruction presents with intermittentpain, the underlying cause of obstruction is oftenrelated to aberrant crossing vessels.

Haematuria may occur spontaneously, but ismore commonly the consequence of minor trauma –to which obstructed kidneys are more susceptible(Figure 6.11). A grossly dilated kidney cansometimes present as an abdominal mass mimick-ing a Wilms’ tumour. However, the distinction canbe readily made with ultrasound and CT or MRIif necessary.

Occasionally, a dilated kidney comes to light asan incidental finding on an ultrasound scanperformed for unrelated symptoms such as abdom-inal pain. In these circumstances, it is important totake a careful history to establish whether the painis genuinely related to PUJ obstruction or whetherthe dilatation is an incidental finding in a child withnon-specific abdominal pain or abdominal pain ofsome unrelated aetiology.

InvestigationThe diagnostic pathway has already been consid-ered above. Typically, the sequence comprisesultrasound followed by 99mTc MAG3 dynamicrenography. The use of DMSA scintigraphy or99mTc DMSA scintigraphy is reserved for poorly


functioning obstructed kidneys where the choiceof procedure lies between pyeloplasty or nephrec-tomy. Other imaging modalities are only requiredin complicated cases: for example, to investigatesecondary PUJ obstruction in the presence of grossvesicoureteric reflux.

Management

In the past, children with PUJ obstruction almostinvariably presented with symptoms and in thissituation it was not difficult to justify the decisionto proceed to surgery.


(a)

(c)

(d)

0.00.0

0.4

0.8

1.2

kcts/secFurosemide

Furosemide

ksec1.0 2.0

(b)

Figure 6.9 Unpredictable natural history of PUJ obstruction. (a) An ultrasound at 1 month of age. Appearancessuggestive of PUJ obstruction – with good thickness renal cortex, AP diameter of renal pelvis (not shown) 18mm. Conservative management was adopted. (b) Follow-up MAG3 study at 36 months showing type 3a O’Reillycurve (non-obstructed). Conservative management was maintained. (c) Ultrasound at 4 years of age. Completeresolution of dilatation, normal appearances of kidney. The child was discharged from further follow-up. (d) At 9years of age he represented acutely with pain and infection. This ultrasound scan demonstrates severe dilata-tion due to recurrent PUJ obstruction. Pyeloplasty was curative.


By contrast, the majority of infants with prenatallydetected PUJ obstruction are asymptomatic andtheir pathology would have remained undiagnosed(at least in infancy) if it had not been for the infor-mation yielded by the antenatal ultrasound scan.

The indications for pyeloplasty in children withprenatally detected PUJ obstruction remaincontroversial, although there is a broad consensusin favour of conservative management in thepresence of normal differential function (defined asgreater than 40% in the affected kidney).

Conservative management is therefore initi-ated when differential function in the obstructedkidney exceeds 40%. In practice, kidneys with

well-preserved differential function usually have arenal pelvic AP diameter of less than 30 mm. In15–20% of infants with prenatally detected PUJobstruction, the dilatation is present bilaterally. Inthis situation, less reliance can be placed on therenographic assessment of differential function andgreater weight must be attached to the severity ofdilatation. Bilateral pyeloplasty may occasionallybe indicated when the dilatation is of equal sever-ity and both drainage curves have a symetricallyobstructed pattern. In practice, however, it is rareto encounter bilateral obstruction of equal severity,and in this situation it may be appropriate tooperate on a more severely dilated kidney andmonitor the contralateral kidney.

The indications for pyeloplasty can be brieflysummarised as:

• Symptomatic PUJ obstruction, e.g. pain,infection, palpable renal mass.

• Asymptomatic obstruction with reducedfunction (less than 35–40%) at the time ofinitial evaluation, particularly if the AP diame-ter of the renal pelvis exceeds 30 mm.

• Failure of conservative management, i.e.deteriorating function or increasing dilatation(which often precedes functional deterioration).

• Persisting asymptomatic obstruction whichshows no evidence of resolution (on ultra-sound and 99mTc MAG3), despite stabledifferential function.

The point at which conservative managementshould be abandoned in an asymptomatic child withstable obstruction is determined by clinical judge-ment and by the outcome of informed discussionwith the parents. Rather than persist for an unspec-ified period with repeated ultrasound and isotopeimaging, it may be thought preferable to proceed topyeloplasty or, in some circumstances, to dischargethe child from further formal follow-up.

Surgical options

Whether performed by an open approach or laparo-scopically, the Anderson–Hynes dismembered


Figure 6.10 Prenatal ultrasound. Marked dilatationof a fetal kidney – PUJ obstruction confirmed bypostnatal investigations.

Figure 6.11 CT scan demonstrating a grosslydilated right kidney with a thin rim of renal cortex. Thiskidney has ruptured after trauma, leading to exten-sive extravasation.


pyeloplasty is universally regarded as theoperation of choice.

Operative technique (Figure 6.12)

Once the anatomy of the pelviureteric junction hasbeen displayed, the ureter is divided and incised fora short length (‘spatulated’) just distal to thepelviureteric junction. A portion of the redundantdilated renal pelvis is then excised. For theinitial stages of the anastomosis, most paediatricurologists favour interrupted sutures and, even inunstented pyeloplasty, it is advisable to minimisethe risk of stenosis by performing the anastomosisover a tube, which is then withdrawn prior toclosure of the renal pelvis. If a transanastomoticstent is positioned to facilitate postoperativedrainage, this can be introduced before, during orafter the construction of the anastomosis.

Much has been written about the differentmethods of postoperative drainage, but publishedstudies have mostly failed to demonstrate anystatistically significant advantage of one methodover another.

Currently, the most widely used techniquesinclude the use of an in-dwelling JJ stent (whichis removed cystoscopically some weeks after thepyeloplasty) or a nephro stent – in effect a JJ stentwith an extension which traverses the renal pelvis,exits through the parenchyma and emerges fromthe skin. This is left on free drainage for the firstday or two then clamped prior to discharge fromhospital.

The soft, deformable characteristics of thenephro stent are such that it can subsequently beremoved without difficulty by simple traction onthe length of tube emerging from the skin (usuallyaround the 10th to 14th postoperative day). Manysurgeons prefer to avoid any form of transanasto-motic stent, relying instead on simple extrarenaldrainage. Nephrostomy drainage alone is thoughtto be inadvisable since diversion of urine above anunstented anastomosis may encourage adherenceof the edges of anastomosis, leading to a greaterrisk of recurrent obstruction.

Open pyeloplasty

For open pyeloplasty the anterior extraperitonealapproach is ideally suited to infants and youngchildren (Figure 6.13a) but access is more limitedin older children with a narrower subcostal angle.The posterior lumbotomy approach (Figure6.13b) is favoured by some surgeons but offersless flexibility to deal with unexpected operativefindings. The supra-12 loin approach (Figure 6.13c),conserving the 12th rib, can be employed for allages and can be readily extended to afford greateraccess if unexpected problems are encountered.However, it is associated with greater postopera-tive discomfort and carries a risk of subcostal nerveneuropraxia in infants.


Figure 6.12 Anderson–Hynes dismembered pyelo-plasty. The procedure of choice in children.


Laparoscopic pyeloplasty

Laparoscopic pyeloplasty was introduced intoadult urological practice in the mid 1990s andthereafter gained acceptance to the point that it isnow increasingly regarded as the gold standardfor adult pyeloplasty. The first series of laparo-scopic pyeloplasties in children appeared in theliterature toward the end of the 1990s and, withthe introduction of better instrumentation forchildren, paediatric laparoscopic pyeloplasty hassubsequently gained growing acceptance. Theoperative details are considered at greater lengthin Chapter 23.

Laparoscopic vs open pyeloplasty?

The experience of laparoscopic pyeloplasty to dateand the relative merits and drawbacks can bebriefly summarised as follows:

• The cosmetic outcome of laparoscopic pyelo-plasty is superior to a conventional surgicalincision. This advantage is particularly relevantto older children in whom a supra-12 loinincision can leave a relatively conspicuous scar.The cosmetic benefit is more arguable ininfants, since pyeloplasty can be accomplishedthrough a small anterolateral abdominal incisionin this age group.

• Laparoscopic pyeloplasty is associated with ashorter hospital stay and reduced postoperativeanalgesic requirement. However, the operativetime can be significantly longer than for openpyeloplasty.

• The retroperitoneal laparoscopic approach ispreferable to the transperitoneal approach inview of the risk of intraperitoneal urinaryleakage and the potential for adhesion forma-tion. However, the retroperitoneal approach is


Muscle cut/split

Extraperitonealexposure

Sandbagunder loin

Figure 6.13 Surgical approach to the kidney. (a)Anterior subcostal incision, extraperitoneal exposure ofthe kidney. (b) Posterior lumbotomy. (c) ‘Supra-12’ loinincision.

(a)

(c)

(b)


more technically challenging, particularly ininfants and young children.

• Robotic pyeloplasty is limited to a smallnumber of centres and is currently under evalu-ation. The operative time is longer than forconventional laparoscopic pyeloplasty andsubstantially longer than the operative time foropen pyeloplasty.

• Laparoscopic pyeloplasty has a significant‘learning curve’, during which time the earlycomplication rate is higher than that for openpyeloplasty. In the hands of an experiencedlaparoscopic surgeon, however, the complica-tion rates and overall success rates are likely tobe comparable to those obtained by open pyelo-plasty, i.e. overall long-term success rate ofgreater than 95%.

• The laparoscopic approach offers considerableergonomic advantages over open surgery forthe correction of certain variants of PUJobstruction: for example, PUJ obstructionoccurring in a horseshoe or pelvic kidney andretrocaval ureter.

• Although laparoscopic surgery is best suited toolder children, its use has been safely extendedto pyeloplasty in infants under 1 year of age.However, the benefits, in terms of reducedhospital stay and analgesic requirement are verymarginal in view of the ease of approach offeredby an anterolateral muscle-splitting subcostalincision in this age group.

Postoperative follow-up

Postoperative follow-up typically comprises ultra-sound and isotope renography. Some paediatricurologists do not feel it is necessary to submit thechild to a MAG3 study if ultrasonography at 6–12months clearly demonstrates resolution of thedilatation, indicating that obstruction has beensuccessfully relieved. Assessing the postoperativeultrasound findings in a grossly dilated system canprove problematic, as considerable dilatation oftenpersists for a long time, despite a technicallysuccessful pyeloplasty. Similarly, it may be a matterof years rather than months before the isotope

renogram drainage curve reverts to normal in thesecases. In the longer term, pyeloplasty has beenshown to be a highly effective operation with avery low incidence of recurrent obstruction.

Other surgical optionsPercutaneous nephrostomy

The insertion of a pigtail nephrostomy catheterinto the collecting system to provide temporarydrainage is a particularly valuable manoeuvre inchildren presenting with pyonephrosis. Temporarypercutaneous drainage usually permits rapidcontrol of infection and enables potential recoveryof function to be assessed with a DMSA scan priorto definitive surgery.

Ureterocalicostomy (Figure 6.14)

In this procedure, the ureter is detached from therenal pelvis and anastomosed directly to the mostdependent lower pole calyx. Although it is rarelyappropriate in the primary management of PUJobstruction, ureterocalicostomy may ensure moreeffective drainage than pyeloplasty in, for example,recurrent PUJ obstruction or PUJ obstructioncomplicating a horseshoe kidney.

Endopyelotomy and balloon dilatation

Although these techniques have been described asalternatives to open pyeloplasty in children, theresults are markedly inferior to those obtained byopen pyeloplasty. There is little evidence to justifythis form of intervention as a primary treatment.Balloon dilatation may, however, have a verylimited role in the treatment of mild to moderaterecurrent PUJ obstruction in older children.

Nephrectomy

When deciding whether to advise pyeloplasty ornephrectomy, most paediatric urologists supply anarbitrary ‘cut off ’ for differential function in therange of 10–15%. Functional imaging withDMSA provides more reliable information onwhich to base a decision whether to proceed to



nephrectomy or pyeloplasty. As already indicated,a period of temporary percutaneous nephrostomydrainage may be helpful in borderline case.

Vesicoureteric junction obstruction

The classification of ureteric dilatation (mega-ureter) and its causes can be simplified into threebroad categories:

• Obstructed megaureter: the obstruction isusually intrinsic, i.e. primary stenosis of thedistal ureter or vesicoureteric junction, butoccasionally, the obstruction may be extrinsicand secondary to, for example, a tumour orscarring/fibrosis. Most cases are due to primaryobstruction at the vesicoureteric junction, andhence the synonym ‘VUJ obstruction’.

• Non-refluxing, non-obstructed megaureter:the ureter is dilated but is not actively

obstructed. The aetiology of such cases is oftenunclear but it is believed that many representthe legacy of ‘burnt-out’ VUJ obstruction, inwhich the original obstruction has resolved,leaving residual dilatation of a ‘flabby’ ureter.

• Refluxing megaureter.

Obstructed megaureterThis condition is usually characterised by a markeddiscrepancy between the calibre of the distal uretericsegment and the dilated, tortuous ureter proximal toit. In cases coming to surgery, the obstruction isusually found to be associated with the presence ofa stenotic ureteric segment of varying length abovethe vesicoureteric junction (Figure 6.15). Inoccasional cases, however, the calibre of the distalureter is normal and is only narrow in relation to thedilated ureter above it. In the absence of demonstra-ble stenosis, this form of megaureter is presumed toresult from an adynamic, aperistaltic distal segmentof ureter, which fails to propagate bolus transmis-sion of urine into the bladder.

The true prevalence of megaureter is difficult toquantify since, in the days before prenatal diagno-sis, many cases almost certainly did not come tolight. Figures derived from routine prenatal ultra-sound screening suggest an overall incidence in therange of 1:1500–1:2000. Megaureter occurs morefrequently in males and the left side is more


Figure 6.14 Ureterocalicostomy. The ureter is discon-nected from the renal pelvis and the pelviureteric junctionclosed. The ureter is then anastomosed directly to thelower pole calyx. A useful procedure to facilitate depend-ent drainage in a grossly dilated system or horseshoekidney and in cases of recurrent PUJ obstruction.

Figure 6.15 Obstructed megaureter. The ureter hasbeen mobilised and divided at the level of the bladder.Dilatation of the ureter proximal to a short stenoticsegment at the vesicoureteric junction.


commonly affected than the right. It generallyoccurs on a sporadic basis.

Presentation Prenatal detection

Obstructed megaureter constitutes approximately10% of prenatally detected uropathies of clinicalsignificance. Although the dilated ureter maybe visualised on prenatal ultrasonography, it isoften the dilatation of the renal collecting systemthat is detected initially. The distinction betweenobstructed and refluxing megaureters can never bemade by ultrasound alone and a postnatal MCUGshould be undertaken routinely to exclude VURor, in boys, outflow obstruction due to posteriorurethral valves.

Symptomatic presentation

Urinary infection used to be the most commonform of presentation and, despite the advent ofprenatal diagnosis, unsuspected cases can stilloccasionally present in this fashion.

The spectrum of severity may vary from mild,predominantly lower tract symptoms to a severesystemic febrile illness caused by the presence ofpus and infected debris within the obstructedcollecting system (pyoureteronephrosis).

Vesicoureteric junction obstruction can alsopresent occasionally with intermittent loin andabdominal pain, in a manner similar to intermit-tent PUJ obstruction (Figure 6.16). Other modesof presentation include abdominal swelling (rare)or complications secondary to the presence ofcalculi within the obstructed system.

InvestigationsUltrasound

Ultrasound is a valuable investigation for demon-strating ureteric dilatation, particularly when renalfunction is poor and the excretion of isotope traceror radiological contrast is impaired. The ultra-sound scan should visualise the dilated ureterthroughout its course and should also assess the

severity of pelvicalyceal dilatation. Where theureteric diameter is less than 1 cm, significantobstruction is unlikely to be present and differen-tial function in the affected kidney is usually wellpreserved. Even when the ureteric diameter exceeds1 cm, differential renal function may still benormal and the degree of caliceal dilatation may bemild in relation to the extent of the ureteric dilata-tion. Such findings usually denote low-gradeobstruction, with little threat to renal function.

Micturating cystourethrogram

As already stated, an MCUG should always beundertaken to distinguish between obstructionand vesicoureteric reflux as the possible cause ofureteric dilatation.

Isotope renography

Drainage curve data can be very difficult to assessin grossly dilated ureters. In particular, clearance ofisotope from the kidney may be interpreted asevidence of a non-obstructed system, whereascloser scrutiny of the ‘hard copy’ gamma cameraimages reveals that the tracer has simply emptiedfrom the kidney into a capacious dilated ureter.

The sensitivity of isotope renography can beimproved by drawing regions of interest overdifferent portions of the ureter to estimate uretericemptying, but, even with this modification, it maystill prove very difficult to distinguish betweenobstructed and non-obstructed dilatation from thedrainage curve. Differential function may prove tobe the most helpful piece of information whenplanning management.

ManagementPrenatally detected obstructedmegaureter

The majority of infected infants are healthy andasymptomatic at birth. Conservative management isinitiated where differential renal function is greaterthan 35–40%, with surgery being undertaken on aselective basis for the indications set out below. In



one series of 40 patients with 57 megaureters, only10% required surgery because of impaired renalfunction on initial assessment. Of those managedconservatively, 53% showed complete resolution onultrasonography, while 43% remained stable orimproved on follow-up. However, another group ofauthors who analysed the longer-term outcome in

79 children reported an operation rate of 30%,citing indications which included differentialfunction < 40%, ureteric diameter >1.3 cm andsevere pelvicaliceal dilatation. The mean age atoperation in this series was 14.3 months.

A high incidence of resolution or improvementin infants with prenatally detected primary


(a)

(c)

(b)

Figure 6.16 (a) Intravenous urogram in a 12-year-oldgirl with a long history of intermittent abdominal paindiagnosed as ‘abdominal migraine’. Ultrasound (notshown) and IVU performed between episodes of painwere consistent with non-obstructive dilatation. (b) MAG3renogram shows good preservation of function and awashout response to diuretic. The findings were inter-preted as non-obstructive dilatation consistent with ‘burntout’ obstructed megaureter. (c) However, an ultrasoundscan performed acutely during an episode of paindemonstrated a dramatic increase in the severity ofcaliceal dilatation. Diagnosis: intermittent vesicouretericjunction obstruction. Her symptoms resolved completelyfollowing surgery.


megaureter has now been reported by a number ofstudies. The optimum duration of follow-up is notknown, but, in practice, if the dilatation resolves orshows progressive improvement on ultrasoundand if differential function was normal on initialassessment, children can probably be safely dis-charged after 4–5 years. Where there is evidence ofpersisting dilatation, it is probably prudent tomaintain ultrasound follow-up on an infrequentbasis until the teens in view of the low risk ofdeterioration.

Indications for surgeryPrenatally detected obstructed megaureter

Surgical intervention should be considered ifdifferential function is impaired on initial assess-ment (differential function less than 35%). Ideally,however, the study should be repeated at 3–6months of age before proceeding to intervention.

Deteriorating renal functional follow-up is afurther indication for surgery, although this is arare occurrence.

Symptomatic complications

Mild to moderate urinary infection is not anautomatic indication to proceed to surgery if theother parameters (differential function, uretericdiameter 1 cm or less) are favourable. A period ofantibiotic prophylaxis and a trial of conservativemanagement is appropriate in such cases, butwhen obstructed megaureter is complicated byrecurrent or severe infections, it should bemanaged surgically. Other indications include painor, rarely, abdominal mass.

Surgical treatmentDefinitive treatment consists of excising theobstructing distal segment and reimplanting theureter into the bladder by a technique which facil-itates good upper tract drainage without permit-ting vesicoureteric reflux. However, these twingoals may be difficult to achieve, particularly in

infants with grossly dilated ureters and relativelysmall bladders.

Wherever possible, reimplantation of a mega-ureter should be avoided in the first year of life,because of these technical difficulties and growinganecdotal evidence that dissection in the region ofthe distal ureter and bladder neck can result in adegree of neurological impairment, with a possibleimpact on continence in later childhood.

Alternatives to open surgery in the first year of lifeSuccessful medium-term drainage with a paedi-atric in-dwelling ureteric JJ stent has been reportedfrom a number of centres. If endoscopic insertionis not feasible, open cystostomy, dilatation of theureteric orifice and insertion of a JJ stent is welltolerated. The stent can usually be safely left in situfor up to 6 months, after which time it may befeasible to proceed to definitive surgery. However,it is apparent that, in some infants, the combina-tion of dilatation and prolonged in-dwelling stentdrainage is sufficient to correct the obstructionwithout the need for further surgery.

Although upper tract diversion by terminal orring ureterostomy was once widely practised ininfants with obstructed megaureter, there are nowvery few indications for this approach. Uretericreimplantation is best deferred until 12 months ofage upwards, but, depending on the circumstances,may be considered from 6 months upwards,according to the anatomical features and the experi-ence of the surgeon.

Surgical treatment from 1 year of age upwardsMild ureteric dilatation (ureteric diameter approximately 1 cm or less)

In these cases the ureter can be mobilised intraves-ically, as for a conventional ureteric reimplantation,and the ureter reimplanted in a conventionalCohen cross-trigonal tunnel after excision of thestenotic distal segment.



Moderate to severe dilatation

The dilated ureter is identified extravesically andmobilised down to the bladder, where the stenoticsegment is identified and excised. In olderchildren, it may be feasible to reimplant the uretervia the original hiatus, but because of the difficultyin creating the optimum ratio of ureteric width tolength of submucosal tunnel required to preventreflux, plication or tapering of the distal ureter isusually advisable. Where the ureter is grosslydilated, plication or tapering of the distal ureter iscombined with a Politano–Leadbetter reimplanta-tion, which creates a longer antireflux submucosaltunnel (Figure 6.17).

A psoas hitch procedure is also performed toanchor the bladder to the psoas muscle in theregion of the entry point of the ureter into the

bladder. This manoeuvre minimises the risk ofkinking and obstruction during bladder filling.Although tapering (‘remodelling’) of the distalureter has been claimed to restore ureteric peristal-sis, this is very doubtful. Plication by the Starr orKalicinski technique is more straightforward butcreates a bulkier ureter and, theoretically, a greaterrisk of postoperative reflux (Figure 6.18).

The presence of bilateral obstructed mega-ureters represents an indication for transureter-oureterostomy, in which one ureter is reimplantedusing the Leadbetter–Politano procedure andpsoas hitch while the contralateral ureter isdisconnected from the bladder, rerouted acrossthe midline and anastomosed to the reimplantedureter.

Follow-up

Postoperative imaging with ultrasound andisotope renography is undertaken after 6–12months. However, a longer period of follow-upmay be required before there are demonstrableimprovements in the drainage curve component ofan MAG3 study. Likewise, where the ureter hasbeen grossly dilated for a prolonged period beforesurgery, considerable patience may be neededbefore significant improvement is seen on ultra-sound. Any postoperative vesicoureteric reflux isusually mild and self-limiting but, when it occurs,a more prolonged period of postoperative antibi-otic prophylaxis may be indicated.


Figure 6.17 The Politano–Leadbetter reimplanta-tion procedure combined with psoas hitch, which isoften better suited to megaureters than the Cohencross-trigonal reimplantation technique.

Figure 6.18 Method of ureteric plication using theStarr technique.

(a) (b) (c)


Key points

• PUJ obstruction is a heterogeneouscondition with a number of differentcauses and a variable natural history.

• Hydronephrosis due to PUJ obstructionaccounts for 30–50% of clinicallysignificant prenatally detecteduropathies. A renal pelvic AP diameterexceeding 30 mm is associated with asignificant likelihood of functionalimpairment. Conversely, an AP diameterof less than 15 mm is most unlikely todenote significant obstruction.

• Conservative management of prenatallydetected PUJ obstruction is appropriatewhen differential function is wellpreserved and dilatation is mild tomoderate in severity.

• Magnetic resonance imaging cancombine anatomical and functionalinformation in a single investigation.Further evaluation is required todetermine whether the benefits justifythe additional cost and the requirementfor anaesthesia in younger children.

• The advantages of laparoscopicpyeloplasty (ideally via a retroperitonealapproach) include better cosmesis,

reduced postoperative pain and shorterhospital stay. Current evidence suggeststhe technique is better suited to olderchildren and has few advantages overopen pyeloplasty in infants.

• Reimplantation of an obstructedmegaureter should be avoided in the first year of life, when it has a higherfailure rate and carries a greater risk ofmorbidity.

Further reading

Bonnard A, Fouquet V, Carricaburu E, Aigrain Y,El-Ghoneimi A. Retroperitoneal laparoscopic vs openpyeloplasty in children. J Urol 2005; 173(5):1710–1713

Boubaker A, Prior JO, Meyrat B et al. Unilateral uretero-pelvic junction obstruction in children: long termfollow up after unilateral pyeloplasty. J Urol 2003;170(2 Part 1): 575–579

Dhillon HK. Prenatally diagnosed hydronephrosis: theGreat Ormond Street experience. Br J Urol 1998;81(Suppl 2): 39–44

Jayanthi VR, Koff SA. Upper tract dilatation. In: StringerMD, Oldham KT, Mouriquand PDE (eds). PaediatricSurgery and Urology: Long Term Outcomes. Cambridge:Cambridge University Press, 2006: 533–539

Shukla AR, Cooper J, Patel RP et al. Prenatally detectedprimary megaureter: a role for extended follow-up.J Urol 2005; 178: 1353–1356



Duplication anomalies,ureterocoeles and ectopicureters

Anthony MK Rickwood, Nicholas P Madden and

Su-Anna M Boddy

Introduction

Some degree of upper urinary tract duplication isfound in 0.8% of postmortem examinations and ina rather higher proportion (2–3%) of patients under-going intravenous urography (IVU) for variousindications. In approximately 40% of cases thecondition is bilateral. The anomaly is transmitted asan autosomal dominant trait with incompletepenetrance, so that among members of affectedfamilies the incidence is of the order of 8%.

The great majority of duplications are of theincomplete variety, with confluence of the ureters

occurring at some point above the ureteric orifice.These forms of duplication rarely give rise toclinical problems. In contrast, complete duplicationanomalies are often of clinical significance in termsof symptoms, renal function or both. However,complete duplication anomalies are far rarer, affectingappreciably less than 0.1% of individuals, the major-ity being females. Clinical presentation is nearlyalways during childhood, and nowadays around 50%of patients are detected by prenatal ultrasonography.Complete duplication occurs bilaterally in approxi-mately 25% of cases but in cases of bilateral duplica-tion the pattern of abnormal anatomy is notsymmetrical. So, for example, it is possible for thechild to have a ureterocoele on one side and anectopic ureter in the contralateral upper tract.

Duplication anomalies(Table 7.1)

EmbryologyNormal ureteric and renal embryogenesis aredescribed in Chapter 1. A single ureteric bud whicharises normally from the mesonephric duct but whichthen undergoes bifurcation leads to a variable degree

7

Topics coveredEmbryology and classificationPathologyClinical presentation Investigations

Management Duplex-system ureterocoeleSuprasphincteric ectopic ureterInfrasphincteric ectopic ureterDuplex-system vesicoureteric refluxSingle-system ureterocoele and ectopic ureter

Table 7.1 Classification of complete duplicationanomalies

Lower polarVesicoureteric reflux

Upper polarDuplex-system ureterocoeleSuprasphincteric ureteric ectopia

Boys – vas, seminal vesicle, ejaculatory ductGirls – bladder neck, proximal urethra

Infrasphincteric ureteric ectopiaGirls only – introitus, distal vagina


of incomplete duplication of the upper renal tract.Complete duplication occurs when two ureteric budsarise separately from the mesonephric duct.

As a rule, the more extreme the degree ofectopia of the ureteric bud the greater the likelihoodthat it will come to penetrate an abnormal zoneof metanephric tissue with resultant dysplasia(Figure 7.1). An accessory ureteric bud which arisesin a caudal position on the mesonephric duct andconnects with the lower renal pole is absorbed intothe urogenital sinus, so that the ureteric orificeopens in a superior and lateral position in relation tothe trigone, an anatomical configuration commonlypredisposing to vesicoureteric reflux to the lowerpole of the kidney (Figure 7.2).

An accessory bud that arises from the meso-nephric duct in a more cephalad position than the

normal site and which drains the upper renal polewill come to enter the urinary tract in a distallyectopic location (Meyer–Weigart law). It maydrain into either the bladder, the urethra or theurogenital sinus (Figure 7.3). In females, suchectopic ureters may be sited above the sphinctermechanism (suprasphincteric), close to or at thelevel of the striated sphincter (although usuallybelow the bladder neck), or distal to the sphincter(infrasphincteric), either at the introitus or in thedistal vagina. In males, the termination is alwayssuprasphincteric, connecting with the vas, theseminal vesicle or, most often, the ejaculatory duct.


AB C

D

E

F

G

D C B AE F

GH

Figure 7.1 Stephen’s hypothesis (see ‘Furtherreading’). A ureteric bud arising from the normal regionof origin on the mesonephric duct (AEF) makescontact with the central zone of metanephric blastema,initiating normal nephrogenesis, the formation of ahealthy kidney and a ureteric orifice located on thetrigone. By contrast, a ureteric bud arising from anabnormal site on the ureteric bud is more likely tomake contact with a peripheral zone of metanephricblastema, with consequent renal dysplasia and anectopic ureteric orifice.

Figure 7.2 Embryological basis of complete duplica-tion with lower pole reflux. (a) Accessory ureteric bud(red) arising caudally on the mesonephric duct(green) at around 6 weeks subsequently becomesincorporated into the superolateral portion of thetrigone (b), with a short submucosal tunnel predispos-ing to reflux. Relative positions of ureteric orifices ontrigone also illustrated.

(a)

(b)


PathologyUreteric ectopia is usually associated with adysplastic renal pole, while the ureter itself isfrequently dilated, either as a consequence ofreflux, obstruction or dysmorphism. Even in theabsence of dysplasia, the affected pole typicallyexhibits some degree of dilatation, the onlycommon exception being in some girls with infra-sphincteric ectopia.

Duplex-system ureterocoeles (defined ascystic dilatation of the terminal portion of theureter draining the upper pole) may lie entirelywithin the bladder (Figure 7.4a,b) or mayencroach beyond the bladder neck (ectopic urete-rocoele) (Figure 7.4c,d). In the rare and mostextreme form, caecoureterocoele, which isconfined to girls, the ureterocoele prolapsesdeeply posterior to the urethra (Figure 7.4e). Aswould be expected, dysplasia of the upper poleparenchyma is the rule with duplex-system urete-rocoeles, usually to the extent that the upper polehas little if any useful function.

In addition to the primary anomaly, duplex-system ureterocoeles may be associated with oneor more of the following:

•• Coexisting vesicoureteric reflux to theipsilateral lower pole is present in 50% ofcases and is usually of moderate severity (e.g.grade I–III reflux). More severe lower polereflux is generally associated with significantlyimpaired function of that pole.

•• Obstruction of the ipsilateral lower poleureter is rare but when it occurs is due toextrinsic compression by a tense ureterocoeleor dilated upper pole ureter. In this situationlower pole function is usually well preserved asthe obstruction is a secondary phenomenonand hence is not associated with dysplasia.

•• Dilatation of the ipsilateral upper pole ureteris usually, although not always, associated withcorresponding dysplasia of the upper pole.Although conventionally ascribed to obstruc-tion by a stenotic ureteric orifice, this dilatation(which may be massive) in reality representsprimary dysmorphism of the ureteric wall.

•• Bladder outflow obstruction is usuallycaused by an ectopic ureterocoele. This cancompromise upper tract renal function on thecontralateral side.

•• Contralateral vesicoureteric reflux is often anincidental finding and is present in 25% of casesbut seldom exceeds grade III in severity.

•• Prolapse of the ureterocoele into the urethrais a rare complication confined to girls.

Duplication anomalies, ureterocoeles and ectopic ureters 95

Figure 7.3 Embryological basis of complete duplica-tion with upper pole ureteric ectopia. (a) Accessoryureteric bud (blue) with an abnormally cephalad site oforigin on the mesonephric duct (green). (b) By 12weeks the upper pole ureter has been carried with themesonephric duct to an abnormally distal ectopiclocation (Meyer–Weigart law). Relative positions ofureteric orifices on trigone/bladder neck also illustrated.

(a)

(b)


Incidence

Duplex-system ureterocoeles occur in approxi-mately 0.02% of individuals, of whom 80% arefemale. A slight majority of ureterocoeles are left-sided and in 10% of cases the lesion is bilateral.

Ectopic ureter is still rarer, affecting some 0.01%of individuals, mostly females.

Some degree of contralateral duplication,usually incomplete, is found in 80% of cases, andin 10% of cases of infrasphincteric ectopia theanomaly exists bilaterally. The incidence ofcomplete duplication with lower pole reflux isdifficult to determine as not all cases can bedetected by prenatal ultrasonography, nor do allaffected individuals present clinically. At a best


Figure 7.4 Ureterocoeles: embryology and classification. (a) Delay in canalisation of the upper ureteric bud ataround the time it makes contact with the upper pole metanephric blastema results in cystic dilatation subse-quently resulting (b) in the formation of a duplex ureterocoele. (c) Single-system orthotopic ureterocoele.(d) Duplex ectopic ureterocoele. (e) Caecoureterocoele. Large ureterocoele extending distally downward fromthe deficient trigone towards the perineum in a plane between the urethra anteriorly and the vagina posteriorly.

(a) (b)

(e)

(d)(c)


estimate, no more than 0.04% of the populationare affected.

Clinical presentationDuplex-system ureterocoele

Approximately 60% of children with theseanomalies are currently identified by prenatal ultra-sonography. Clinical presentation, usually duringinfancy, is most commonly with urinary infection,typically with marked constitutional upset andoccasionally with Gram-negative septicaemia. Other,rarer, modes of presentation include acute orchronic urinary retention and, in females, urethralprolapse of the ureterocoele (Figure 7.5).

Suprasphincteric ectopic ureter

These anomalies are frequently detected prenatallyby virtue of dilatation of the upper pole ureter orcollecting system. Clinical presentation is almostinvariably with urinary infection, which, in males,may be manifest as epididymo-orchitis (Figure 7.6).

Infrasphincteric ectopicureter (Figure 7.7)

If not picked up prenatally, the clinical presentationis classically characterised by constant dribbling ofurine superimposed upon an otherwise normalpattern of micturition, a clinical picture that distin-guishes it from all other causes of incontinence.

However, the history is not always so straight-forward. Some girls remain dry overnight, whereasothers with a vaginal ectopic ureter are neverthelessable to remain dry for brief periods during the day.Occasionally the clinical picture is further confusedby secondary changes in the pattern of normal


Figure 7.5 Prolapsed ureterocoele emerging at theintroitus of a newborn infant.

Figure 7.6 Micturating cystogram showing refluxinto distal portion of an ectopic upper pole ureter in amale.

Figure 7.7 Diagrammatic representation of duplex-system infrasphincteric ureter.


micturition: for example, marked urinary frequencyprompted by the parents’ increasingly desperateefforts get their daughter dry. Lastly, where theaffected upper renal pole is severely dysplastic, thequantity of urine produced by it may be so reducedthat it pools within the vagina, becomes infectedand presents as vaginal discharge. Vaginal dischargeis a relatively common complaint and this rarepresentation of ureteric ectopia represents one ofthe few significant underlying causes.

Physical examination is usually unrewarding,although occasionally the presence of constant, slight,urinary leakage may be observed at the introitus.

InvestigationsUltrasound

Ultrasound is the investigation of first choice byvirtue of its ability to pick up dilatation of theupper or lower pole of the duplex kidney. Dilata-tion confined to the lower pole may be due to:

• Vesicoureteric reflux. In this situation it isusually also possible to visualise a dilated ureterbehind the bladder.

• Pelviureteric junction obstruction. When PUJobstruction affects a duplex kidney, it almostalways involves the lower pole (see Chapter 6).

Dilatation affecting only the upper renal pole maybe due to:

• Duplex-system ureterocoele. In such cases theassociated ureterocoele is always readily imagedwithin the bladder (Figure 7.8), provided it is full.

• Ureteric ectopia. As a rule, the dilated distalureter can be visualised behind the bladder. Insome girls with infrasphincteric ectopia the upperrenal pole is not hydronephrotic but is small anddysplastic and consequently difficult or impos-sible to detect by ultrasonography (‘crypticduplication’).

Dilatation affecting both renal poles is almostalways due to duplex-system ureterocoele.

DMSA scintigraphy

Dimercaptosuccinic acid (DMSA) scintigraphyshould be undertaken routinely to assess the distribu-tion of function in the duplex kidney (Figure 7.9).Areas of interest drawn around the upper and lower


Figure 7.8 Bladder ultrasonography demonstratinga large ureterocoele within the bladder and the dilatedupper pole ureter behind the bladder.

Figure 7.9 DMSA scintigrapy in a child with bilateralduplex-system ureterocoeles. Left upper renal pole isnon-functioning and there is only minimal function inthe thin rim of renal parenchyma overlying the grosslydilated right upper pole. Both lower poles exhibitnormal function.


poles enable the differential function of each moietyto be calculated. DMSA is also of occasional use indetecting ‘cryptic duplication’ (Figure 7.10) (seeChapter 3).

Micturating cystourethrography(MCU)

An MCU is an essential investigation for patientssuspected of having lower pole vesicouretericreflux. In the presence of a complete duplicationanomaly, reflux is almost always restricted to thelower renal pole (Figure 7.11). Reflux into bothpoles is usually indicative of incomplete duplica-tion. Where the reflux differs in severity betweenthe two moieties and is more marked in the lowerpole (Figure 7.12), the ureteric confluence is likelyto be very low, and immediately proximal to theureteric orifice. Cystography is also routinelyadvisable in patients with duplex-system uretero-coele in view of the high incidence of reflux, bothipsilateral and contralateral. Similarly, in supra-sphincteric ectopia, the cystogram may demon-strate reflux to the upper pole during voiding.

Intravenous urography

The IVU retains an occasional role in the evalua-tion of duplex systems, particularly in the detectionof ‘cryptic duplication’, the radiological signs ofwhich may include an ‘absent’ upper calyx andlateral and downward displacement of the lowermoiety, an appearance on IVU which has beenlikened to a ‘drooping flower’ (Figure 7.13).A further radiological sign is the ‘scalloped’appearance of the lower polar ureter. With theexception of the ‘absent’ upper pole calyx, theseradiological signs are caused by the presence of adilated, non-visualised, drainage system arisingfrom the upper renal pole. In addition, the discov-ery of an incomplete duplication anomaly on oneside may raise the possibility of ‘cryptic duplication’in the contralateral upper tract.


Figure 7.10 DMSA scintigraphy in a case of ‘cryptic’duplication. The subtle defect at the left upper polerepresents a non-functioning, non-dilated moiety.

Figure 7.11 Micturating cystogram demonstratingbilateral lower pole vesicoureteric reflux. Note theabsence of upper pole calyces and ‘drooping flower’appearance of the lower pole pelvicaliceal systems. Onthe left there is lateral displacement of the kidney and‘scalloping’ of the ureter, owing to the presence of agrossly dilated upper pole ureter terminating ectopically.


Cystoscopy and examination underanaesthetic

Cystoscopy is routinely advisable for the assess-ment of duplex-system ureterocoeles, principally inorder to determine whether or not the lesion isectopic (Figure 7.14). In girls with a suprasphinc-teric ectopic ureter, the ectopic ureteric orifice isvisualised on cystoscopy immediately below thebladder neck. Examination under anaesthetic mayalso reveal an ectopic orifice in girls with infra-sphincteric ectopia, although failure to identify anectopic orifice is not unusual and by no meansexcludes this diagnosis.

Methylene blue test

With the introduction of magnetic resonanceimaging (MRI), the methylene blue test for an

ectopic ureter associated with a ‘cryptic duplica-tion’ is now of largely historic interest. Methyleneblue is instilled into the bladder via a catheter,which is then removed, and a pad is placed uponthe vulva. If subsequent wetting of the pad is ‘blue’the incontinence is due to a bladder problem, butif the fluid on the pad is ‘clear’ the diagnosis ofinfrasphincteric ectopia is confirmed.

Magnetic resonance imaging(Figure 7.15 )

MRI is an attractive form of investigation, since ithas the potential to clarify anatomy and provide


Figure 7.12 Micturating cystography demonstratingbilateral vesicoureteric reflux. Incomplete duplicationon the right. (The disparity between the upper andlower pole reflux on the right is indicative of uretericconfluence just proximal to the ureteric orifice.)

Figure 7.13 Intravenous urogram demonstrating leftduplication with non-functioning upper pole. A leftupper calyx is not visualised, the lower pole isdisplaced laterally and downwards (‘drooping flower’)and the lower pole ureter is deviated (‘scalloped’) bythe presence of the grossly dilated upper pole ureter.


functional information without exposure to radia-tion. The major disadvantage is the requirement forgeneral anaesthesia or sedation in children to ensurethey remain still while the scan is being performed(see also Chapter 3). Nevertheless, this investiga-tion is undoubtedly justified in children withcomplex or elusive forms of duplication in view ofthe superior quality of the images and anatomicalinformation yielded by MRI. Indeed, the recentdevelopment of fast three-dimensional scanners,combined with MR urography, represents a majoradvance in the investigation of duplex systems.

Management Duplex-system ureterocoele

Management of this anomaly is influenced by anumber of factors, including the mode of presenta-tion and the presence of any associated or second-ary effects of the ureterocoele on the upper renalpole, the ipsilateral lower renal pole, the bladderand the contralateral upper renal tract.

In an appreciable proportion of cases detectedby prenatal ultrasonography, none of these

considerations apply as the affected infants areasymptomatic and the urinary tract is normal,apart from the ureterocoele itself and the small andseverely dysplastic upper renal pole. Whether anysurgical intervention is indicated in such cases,especially for those with small ureterocoeles,remains debatable.

There are several options for surgicalintervention.

Endoscopic ureterocoele incision(Figure 7.16)

The indications for this technique of decompress-ing a ureterocoele are:


Figure 7.14 Endoscopic appearances of a duplexureterocoele at the level of the bladder neck.

Poorly functioningupper pole

Ectopic ureterposterior to thebladder anddraining distallyinto the vagina

Figure 7.15 MR urogram demonstrating an ‘occult’duplex ectopic ureter which had been suspected fromthe history but could not be confirmed by conventionalimaging techniques: (a) upper pole moiety and associ-ated ectopic ureter clearly visualised; (b) transverseimage demonstrating the ectopic ureter lying posteriorto the bladder base.

Bladder

Ectopic ureter

(a)

(b)



•• in antenatally detected cases where the uretero-coele is prolapsing, or risks obstructing thebladder outlet

•• as a temporising measure in patients presentingacutely with gross upper polar sepsis.

Although endoscopic incision is the least-invasiveform of intervention, it does carry the risk of induc-ing upper pole reflux. To minimise this risk, it isimportant to make the incision in the ureterocoeleas close to the bladder wall as possible. Favourablemedium-term results published from some centresindicate that endoscopic incision alone may repre-sent adequate treatment in selected cases, principallythose detected antenatally. However, in other cases,and probably a majority, some more definitive formof surgery is eventually required. Further long-term

outcome studies are required to fully evaluate theindications and effectiveness of endoscopic incision.

Upper pole heminephrectomy

This procedure is usually the first choice in caseswhere upper polar function is severely compro-mised. When performed via an open surgicalapproach, the upper moiety is excised, togetherwith as much of the ureter as can be safelymobilised and excised through the same incision.The ureterocoele is aspirated and drained via theureteric stump, which is left in situ (Figure 7.17a).The laparoscopic approach is being used increas-ingly and has the advantage that the ureter can beremoved almost in its entirety (see Chapter 23).Surgery confined to removal of the upper poleand a varying length of ureter (the ‘simplifiedapproach’) represents definitive treatment in themajority of patients, with subsequent excision ofthe ureteric stump and ureterocoele and reimplan-tation of the lower polar ureter being required inonly 10–20% of cases.

Pyelopyelostomy (Figure 7.17b)

This procedure is only appropriate for the smallpercentage of cases in which there is a usefuldegree of function in the upper pole which isaccompanied by a degree of dilatation of the lowerrenal pole pelvis/proximal ureter. The upper polepelvis is divided, separated from the ureter andanastomosed to the pelvis of the lower pole. Thedefunctioned upper pole ureter and ureterocoeleare then aspirated to ensure they are emptied andfully decompressed.

Ureterocoele excision andreimplantation (Figure 7.17c)

This procedure is employed when there is usefulupper pole function and no dilatation of the lowerpole. In these circumstances the ureterocoele isusually intravesical and the upper pole ureter onlymoderately dilated, thereby enabling straightfor-ward reimplantation of the conjoined ureters(Figure 7.18), once the ureterocoele has been

Figure 7.16 Diagrammatic illustration of the simplestform of intervention – endoscopic puncture.



excised. As a rule it is preferable to delay thisoperation until after 1 year of age, because of therisk of interfering with bladder function.

Nephrectomy

Nephrectomy is appropriate when the function ofboth renal poles is severely compromised. Reflux-ing ureters should be excised, but a non-refluxingureteric stump may be left in situ provided theureterocoele is aspirated.

Upper pole heminephrectomy,ureterectomy and ureterocoeleexcision (Figure 7.17d)

This is the most extensive operation for a duplex-system ureterocoele. It requires the use of twoincisions and is a potentially lengthy and technicallychallenging surgical undertaking (Figure 7.19).Particular care is required when excising a caecourete-rocoele in view of the risk of damage to the bladderneck and striated sphincter mechanism. Other

Figure 7.17 Open surgical options. (a) Normal lower pole, non-functioning upper pole – managed by upperpole heminephrectomy, excision of the proximal ureter via the same incision, and aspiration of the residual upperpole ureteric stump (‘simplified approach’). (b) Functioning upper pole, dilated lower pole – management bypyelopyelostomy. Excision of proximal upper pole ureter and aspiration of ureteric stump. (c) Functioning upperpole, non-dilated lower pole – management by excision of ureterocoele and reimplantation of conjoined duplexureters. (d) Heminephroureterectomy with excision of ureterocoele (often necessitating lower pole uretericreimplantation). Definitive surgical treatment, but a major procedure requiring two separate incisions.

(a) (b)

(d)(c)



possible iatrogenic complications include vesicovagi-nal fistula. To minimise the risk of complications thebulk of the ureterocoele should be excised fromabove, the detrusor and mucosal defect closed, andany remaining distal lip resected endoscopically frombelow. Reimplantation of the ipsilateral lower poleureter is often required, and care is needed whenmobilising the dilated upper pole ureter to avoiddamaging or devascularising the healthy lower poleureter. An alternative approach consists of laparo-scopic upper tract surgery (heminephroureterec-tomy) coupled with an open bladder procedure toaccomplish excision of the ureterocoele and anyassociated intravesical procedures.

Suprasphincteric ectopic ureter

Indications for surgical intervention are relative,not absolute, and centre on recurrent urinary infec-tion resulting from the presence of the ectopicureter. In the great majority of cases, with negligi-ble upper polar function, heminephrectomy issufficient. However, when this form of ectopicureter is also associated with upper pole reflux itis necessary to remove the ureter. This can beachieved by an open approach, using a separateabdominal incision to take the dissection and excisionof the ureter down as close to the urethra as ispracticable. Alternatively, this procedure can beperformed laparoscopically. In the rare case with auseful degree of function in the upper pole, theectopic ureter may be reimplanted into the bladder.If, as is usual, the distal ureters are conjoined, it isnecessary to reimplant them both together en bloc.

Infrasphincteric ectopic ureter

As previously indicated, the main problem with thisanomaly lies in its diagnosis rather than treatment. Itis always worth bearing in mind that in some 10%of cases the lesion is bilateral and that the finding ofa duplex system on one side should always promptconsideration of the possible presence of a crypticcontralateral upper pole associated with an ectopicureter. Excision of the affected upper renal pole(s)invariably cures the presenting complaint. Uretericreimplantation (or pyelopyelostomy) may be consid-ered for the very occasional case having usefulfunction in the upper pole.


As a rule, management of vesicoureteric refluxin the presence of a duplication anomaly runsalong the same lines described for reflux generally(Chapter 5). There are, however, two particularfeatures relating to complete duplication anomalieswhich may influence management.

Persistent reflux, lower pole reflux

This condition, especially if severe, is less likelyto resolve spontaneously than is the case with

Figure 7.18 Duplex ureters in common sheath aftertransvesical mobilisation.

Figure 7.19 Intraoperative appearance of largeureterocoele exposed transvesically.



single-system reflux. For this reason antirefluxsurgery is more commonly required (although onlywhere there are positive indications, such as break-through infections while on antibiotic prophylaxis,or infections following discontinuation of prophy-laxis). Because endoscopic correction (STINGprocedure) tends to be less effective in the presenceof complete duplication, open surgical reimplanta-tion is more often required than with reflux intosingle ureters. The adjacent ureteric orifices arecircumcised together and the underlying uretersthen mobilised en bloc in their common sheath.

Lower pole dysplasia

In a proportion of cases DMSA scintigraphy demon-strates grossly impaired function in the affectedlower pole that almost invariably representscongenital dysplasia rather than acquired infectivescarring. When surgical intervention is indicated,this should take the form of lower pole nephrec-tomy, along with excision of the ureter down to thepoint where it enters a common sheath with theupper polar ureter.

Pelviureteric junction obstruction

This condition almost invariably affects the lowerpole and is managed as other PUJ obstructions(see Chapter 6).

Single-system ureterocoeleand ectopic ureter

Single-system ureterocoelesClinical features

These lesions, which occur more commonly in boysthan girls, almost always lie entirely within the bladder(orthotopic ureterocoeles). Whereas the anomaly canbe detected prenatally, it also comes to light in laterchildhood as a largely incidental finding on ultra-sonography or intravenous urography.

Single-system ureteroceles which present clini-cally usually do so with urinary infection but, very

occasionally, they may also present with bladderoutflow obstruction causing intermittent retention,or symptoms related to calculi. Upper tract dilata-tion is absent or of mild to moderate severity and,in most cases, renal function is normally preserved(Figure 7.20).

Management

Indications for surgical intervention comprise:

•• symptoms• upper renal tract obstruction.

Endoscopic incision is the simplest and least-invasive form of treatment but, because of the risk

Figure 7.20 Intravenous urogram demonstrating aright-sided orthotopic (single-system) ureterocoelewith brisk uptake of contrast, indicating good preser-vation of renal function.



of inducing reflux, some paediatric urologistsbelieve it is preferable to excise the ureterocoeleand to reimplant the underlying ureter.

Opinion is divided on the management of smallorthotopic ureterocoeles, with some advocating‘prophylactic’ endoscopic incision and others favour-ing simple observation.

Single-system ectopic ureterSingle vaginal ectopic ureter(Figure 7.21)

This anomaly is less common than duplex-systemectopia as a cause of urinary incontinence in girls.

The ureter terminates ectopically in the vagina,usually around the junction of the middle anddistal thirds, and the clinical presentation is thesame as for infrasphincteric duplex-systemectopia, namely continuous dribbling of urinesuperimposed upon otherwise normal micturi-tion. Similarly, this condition presents diagnosticrather than therapeutic difficulties, partly becausethe affected kidney, being small and dysplastic, isdifficult to image, and partly because it may lieectopically anywhere from the lumbar region tothe pelvis.

An initial ultrasound examination often reports‘unilateral renal agenesis’, but a more purposefulsearch may locate the kidney. DMSA scintigraphyand MRI may be helpful in locating a small kidneywhich cannot be visualised by ultrasound. Thediagnosis may also be confirmed by identificationof the ectopic orifice and retrograde contraststudies or, as a last resort, by laparoscopy. Nephrec-tomy is curative.

Unilateral urethral ectopic ureterIn this rare anomaly, virtually confined to girls,the single ureter terminates ectopically in theproximal urethra. The function of the overlyingkidney is usually impaired – sometimes severelyso – presumably as a result of congenital dysplasia.The ureter is usually sufficiently dilated to bedetectable by ultrasonography.

When not picked up by prenatal ultrasonogra-phy, the anomaly generally presents with urinaryinfection. In symptomatic cases with useful renalfunction, the ureter can be reimplanted into thebladder, if necessary with trimming if the ureter ismarkedly dilated. Otherwise, nephrectomy isindicated.

Bilateral single ectopic uretersThis exceptionally rare anomaly affects girlsmore often than boys. Both single ureters termi-nate ectopically in the proximal urethra. Thebladder neck and external urethral sphincter are

Figure 7.21 The anatomy of a single-system infra-sphincteric ectopic ureter. The arrow indicates that theaffected kidney may be sited ectopically.



incompetent, and the bladder itself is usually small(Figure 7.22). As a rule both kidneys are affectedby a degree of dysplasia (sometimes severely so),while the ureters tend to be dilated and are thusdetectable by ultrasonography. Presentation maybe either with continuous dribbling incontinencein childhood or with symptoms of renal insuffi-ciency in infancy.

Treatment requires reimplantation of the ectopicureters into the bladder, plus augmentation cysto-plasty when the bladder is small. Finally, it is neces-sary to deal with the sphincteric incompetence,either by bladder neck repair or by bladder neckclosure along with a Mitrofanoff procedure.

Key points

• Incomplete duplication is relativelycommon and is often of little or noclinical significance. By contrast,complete duplication is rarer and ismore frequently associated withsymptoms, impaired function or both.

• Complete duplication anomaliescan be divided, on the basisof their embryology, into thoseaffecting principally the upperrenal pole (ureterocoele,suprasphincteric or infrasphinctericectopic ureter) or those affecting thelower renal pole (vesicoureteric reflux,pelviureteric junction obstruction).

• Renal dysplasia of the upper orlower pole is common in all formsof complete duplication.

• Infrasphincteric ectopic ureter in girls,leading to urinary incontinence,often presents problems with diagnosticimaging because the affectedupper renal pole tends to beseverely dysplastic. However, MRI isbecoming a valuable imagingtechnique for investigating cryptic orcomplex duplex systems.

• Experience with laparoscopicheminephrectomy is limited atpresent but this approach has theadvantage of permitting access tomost or all of the upper pole ureter,thus avoiding the need for asuprapubic incision.

• Open bladder surgery maystill be required for large ureterocoeles.Although the endoscopic punctureof ureterocoeles is simple andrelatively non-invasive, the long-termresults have yet to be fully evaluated.

Figure 7.22 Intravenous urogram in a child withbilateral single ectopic ureters. Both ureters draininfravesically and the bladder is of small capacity.



Further reading

Denes FT, Danilovic A, Srougi M. Outcome of laparoscopicupper pole nephrectomy in children with duplexsystems. J Endourol 2007; 21(2): 162–168

Mackie GG, Stephens FD. Duplex kidneys: a correlation ofrenal dysplasia with position of the ureteral orifice.J Urol 1975; 114: 274–280

Rickwood AMK, Reiner I, Jones M, Pournaras C.Current management of duplex-system ureterocoeles;

experience with 41 patients. Br J Urol 1992; 70:196–200

Shankar KR, Vishwanath N, Rickwood AMK. Outcome ofpatients with prenatally detected duplex system uretero-cele: natural history of those managed expectantly.J Urol 2001; 165: 1226–1228

Siomou E, Papadopoulou F, Kollios K et al. Duplex collect-ing system diagnosed during the first 6 years of life afterfirst urinary infection: a study of 63 children. J Urol2006; 175(2): 678–681


Posterior urethral valves andother urethral abnormalities

Divyesh Y Desai and Patrick G Duffy

Introduction

With the exception of strictures, urethral obstruc-tion in childhood is congenital in origin and of the various causes of urethral obstruction onlyposterior urethral valves commonly give rise tosecondary changes in the upper renal tracts –sometimes with devastating consequences. Thereis increasing evidence to indicate that the conse-quences of outflow obstruction are due as much tosecondary effects upon bladder function as to theunderlying obstruction itself. Moreover, the earlierthe obstruction develops the worse the impact onthe upper tracts, to the extent that obstructiondating from early fetal life is commonly compli-cated by renal dysplasia.

Posterior urethral valves

Hugh Hampton Young in 1919 described the first classification of this condition based onpostmortem dissection studies. Posterior urethralvalves carried a mortality rate of almost 100%during the early years of the 20th century andremained as high as 50% until the 1950s.

By contrast, the mortality reported in one recentseries was only 0.3%, but this improvement has

come at the expense of a greater proportion ofyoung patients in chronic renal failure.

Posterior urethral valves occur only in males, inwhom the incidence is of the order of 1 in4000–6000. Although a few familial cases havebeen recorded, including in siblings, there is noestablished genetic predisposition.

AnatomyRecent studies have challenged Young’s classifi-cation, based on postmortem studies, whichidentified three types of valvular obstruction.Dewan and Ransley’s anatomical and endoscopicstudies point to a single configuration comprisingan obliquely orientated congenital obstructiveposterior urethral membrane (COPUM) with avariably sized eccentric aperture located within it(Figure 8.1), arising from the verumontanum,extending through the region of the externalurethral sphincter to attach to the anterior urethralwall. Following urethral instrumentation, includ-ing catheterisation, the membrane is disrupted inthe midline to result in the appearance of twoseparate, side-by-side valve leaflets described as theclassical type I valves by Young. Type III valves areuncommon (5%) and are best described as a trans-verse perforated membrane in the bulbar urethra

8

Topics coveredPosterior urethral valves

Anatomy/pathophysiologyPresentation/investigationTreatment

PrognosisLong-term management

Anterior urethral diverticulumUrethral duplication Other urethral pathology


with no attachment to the verumontanum. More-over, type II valves, which are described as leafletsthat extend upwards from the verumontanum, arenon-obstructive folds of mucosa of no clinicalsignificance.

PathophysiologyThe valvular obstruction develops at approxi-mately 7 weeks’ gestation as a result of abnormalembryogenesis at the confluence of mesonephricducts and the urogenital sinus membrane. Theconsequent dilatation of the fetal urinary tract maybe detectable by ultrasonography as early as the14th week of gestation.

Studies of experimentally induced fetal bladderoutflow obstruction in animals have establishedthe following:

• Early outflow obstruction leads to abnormali-ties in bladder wall components with anincrease in the collagen element, aberrations inthe nerve supply and renal dysplasia (which ischaracterised on histology by the presence ofprimitive tubules and the persistence of abnor-mal mesenchymal derivatives such as cartilageinterspersed between normal renal tissue).

• Obstruction in later gestation results in thetypical sequelae of chronic bladder outflowobstruction and raised intravesical pressure,without the occurrence of renal dysplasia.

Clinical experience indicates that the consequencesof obstruction by posterior urethral valves in manmay exist at these extremes or at any point betweenthem. Thus, the long-term prognosis in an individ-ual with this disorder is determined by a combina-tion of the degree of early abnormal development,involving the urethra, bladder, kidneys and theureters, and the severity of late secondary effects ofoutflow obstruction on the bladder and the upperurinary tract.

The relative contributions made by these differ-ent factors to the functional outcome of bladder aswell as renal function is often difficult to deter-mine, and therefore predicting long-term outcomesis usually difficult. The urinary tracts of boys with posterior urethral valves must therefore bemonitored through childhood, particularly duringteenage and adolescent years.

PresentationThe fetus

Currently more than 80% of cases are detected onprenatal ultrasound. Although the underlyingurethral anomaly dates from the seventh to theninth week of gestation, dilatation of the urinarytract may not develop until much later inpregnancy. Fifty five per cent of cases of prenatallydetected posterior urethral valves are picked up onroutine maternal ultrasound performed between16 and 20 weeks. In the remaining cases, theappearances of the fetal urinary tract are normal inthe second trimester, and the condition is detectedin later pregnancy as a result of scans performedfor obstetric indications.

Functional outcome is closely linked to thegestational age at which dilatation becomes appar-ent, and studies have shown that when the condi-tion is detected at 16–20 weeks the prognosis islikely to be poor, especially if oligohydramnios is


Figure 8.1 Endoscopic appearance of intact valvemembrane prior to endoscopic ablation.


also present. In pregnancies which proceed toterm, a severely affected infant often demonstratesfeatures of Potter’s syndrome at birth (characteris-tic facies – Potter’s, skeletal ‘moulding’ deformi-ties), and death supervenes in the early newbornperiod as a result of pulmonary hypoplasia.

In the absence of second-trimester oligohydram-nios the functional prognosis is linked to the sever-ity of dilatation and other prognostic features onsecond-trimester ultrasound (Table 8.1).

Various biochemical constituents of fetal urine(sodium, calcium, B2-microglobulin, osmolality)have been studied as possible prognostic markers,but there is considerable overlap with normalvalues and predictive sensitivity is poor (seeChapter 10).

In cases where dilatation develops later in gesta-tion, the prognosis is generally good. In additionto dilatation and renal dysplasia (bright kidneys),other findings detected by fetal ultrasound includelung hypoplasia, urinary ascites and perinephricurinomas.

The neonate

Symptoms usually relate to bladder outflowobstruction or, less often, to the effects of impairedrenal function. Listlessness, poor feeding, irritabil-ity and failure to thrive are common. The urinarystream, if witnessed, is usually poor. The bladder ispalpable in most instances; the kidneys may also bepalpated. Urinary ascites occurs as an occasionalcomplication.

The infant

Presentation in infancy is generally with a urinaryinfection (Chapter 4) and in the majority of casesphysical signs are absent.

Gram-negative sepsis and renal failure withgross electrolyte disturbance were common formsof presentation but with increasing detection byprenatal ultrasound and heightened awareness ofurinary infection among infants they have becomeunusual. Chronically impaired renal function isusually manifest as poor growth.

The older child

Presenting features may include manifestations of renal failure such as growth retardation,urinary infections or voiding symptoms (typicallyprolonged voiding, rather than a poor urinarystream as such). In addition, the diagnosis ofposterior urethral valves is occasionally madeduring the investigation of diurnal or nocturnalenuresis.

InvestigationsPrenatal

The presence of posterior urethral valves can onlybe inferred from the ultrasound appearances of adistended fetal bladder and dilated upper tracts(Figure 8.2), as the alternative diagnoses includeurethral atresia (always lethal), prune-belly syndrome,megacystis–microcolon intestinal hypoperistalsissyndrome, and marked primary vesicouretericreflux. However, the diagnosis can be made withmore certainty if there is dilatation of the posteriorurethra – the so-called ‘keyhole sign’ (Figure 8.3).

Postnatal

Ultrasonography is the initial investigation, therelevant findings comprising upper tract dilatation(which is sometimes only unilateral), perinephricurinoma (occasionally), thickening of the bladderwall, with or without residual urine, and, if

Posterior urethral valves and other urethral abnormalities 111

Table 8.1 Ultrasound features of posteriorurethral valves in the fetus

Male fetusBilateral upper tract dilatationPersistently distended full bladder

Predictors of poor functional outcome andearly-onset renal failureDetection before 24 weeks’ gestationBladder wall thickening Echo-bright kidneys (renal dysplasia)Oligohydramnios


voiding views can be obtained, dilatation of theposterior urethra.

Micturating cystourethrography (MCU) providesthe definitive diagnosis, with a range of findings,as illustrated in Figures 8.4–8.6. Vesicouretericreflux is present in 40–60% of cases at the time ofinitial evaluation and is unilateral in approximatelytwo-thirds of cases.

Initial assessment also includes measurement ofelectrolyte balance and renal function (it should be noted that in the first 48 hours of life serum creati-nine levels are a reflection of maternal renal function).


Figure 8.2 Prenatal ultrasound demonstrating markeddilatation of both fetal kidneys and the fetal bladder. Thefetal spine and thorax are clearly visible in both theselongitudinal images.

Figure 8.3 Ultrasound appearances illustrating thediagnostic ‘keyhole sign’. Dilated (thick-walled) bladderand dilated posterior urethra.

Figure 8.4 Newborn infant: micturating cystourethro-gram (MCU) findings. Grossly dilated posterior urethra,indentation by prominent bladder neck, small trabecu-lated bladder.

Figure 8.5 Newborn preterm infant, prenatal diagno-sis. Heavily trabeculated bladder with diverticulum,prominent bladder neck, and demarcation betweendilated posterior urethra and non-dilated distal urethraat the site of the valve membrane.


TreatmentThe fetus

The rationale for fetal intervention derives fromexperimental studies, which demonstrated thatexperimentally induced obstructive renal damagecould be ameliorated by intrauterine decompres-sion of the obstructed fetal bladder. However, theextent to which these experimental findings can betranslated to humans remains unclear. In clinicalpractice, prenatal intervention, in the form ofvesicoamniotic shunting, has a chequered historyand the weight of published experience indicatesthat it may have a limited role. Evaluating thepossible benefits of vesicoamniotic shunting duringpregnancy in the management of posterior urethralvalves is subject to the following limitations:

• Posterior urethral valves can be difficult todiagnose with certainty.

• Renal failure may not supervene until late child-hood or adolescence; thus it is difficult to assessthe true impact of intervention.

• There are no controlled trials to compare theoutcome in boys who were treated in uteroagainst those who were not.

In order to address this very important issue, aUK-wide trial is currently underway (PLUTO).This is a multicentre trial, which will assess theeffects of prenatal vesicoamniotic shunting onknown outcomes of bladder and renal functionin boys with posterior urethral valves. Theresults may enable us to address more clearlythe role of intervention in bladder outflowobstruction.

Experience with intrauterine valve ablation wasreported with enthusiasm and optimism, but nolong-term outcomes are available.

Termination of pregnancy is the most commonform of prenatal intervention, particularlywhen severe dilatation and associated oligohy-dramnios are detected in early pregnancy. In thesecircumstances decompression of the obstructedurinary tract is of little if any benefit for renalfunction, since irreversible renal dysplasia isalmost invariably present. However, there isreasonable evidence of some beneficial effect onpulmonary hypoplasia.

Elective preterm delivery represents anotherform of intervention, and it may be beneficial incases of rapidly progressing late-onset dilatation. Itis important to balance lung maturity with the riskof progressive renal damage in deciding theoptimum timing for preterm delivery.

Between these extremes, vesicoamniotic shunt-ing may have a role in the presence of early obstruc-tion and preserved renal function. However, theprocedure carries an appreciable risk of fetalmorbidity, which although only 5% in skilled handsis higher in some published series.

Two previous studies of the long-term outcomeof shunting reported high intrauterine and neonatalmortality rates and an incidence of renal failure ofmore than 50% amongst survivors. A more recentstudy, however, reported that survivors experiencednormal neurodevelopment, acceptable renal andbladder function and a satisfactory quality of life.

Although the role of fetal intervention remainscontroversial, there is universal agreement thatprenatal diagnosis has been beneficial by ensuringthat the treatment of posterior urethral valves canbe undertaken promptly and the risk of serioussepsis minimised.


Figure 8.6 MCU in a boy presenting in the first yearof life with urinary infection. Smooth-walled non-trabeculated bladder, unilateral grade IV reflux.


The neonate

To minimise risk of electrolyte disturbances or ofurinary infection the obstruction should berelieved promptly.

Urethral or suprapubic bladderdrainage

The usual primary treatment, this will remain for7–10 days to obtain baseline renal function.

Endoscopic valve ablation

Modern miniaturised endoscopes (Figure 8.7) areused even in small premature neonates. The valveleaflets are incised from margin to base (ratherthan fully resected), conventionally at the 4 and 8o’clock positions (Figure 8.8). Unless significantintraoperative bleeding is encountered, postopera-tive catheterisation is unnecessary.

Vesicostomy

Vesicostomy drainage may be preferred in thosewith markedly impaired renal function, especiallyif deteriorating despite catheterisation, and/or inthose with gross bilateral vesicoureteric reflux.

The stoma is created at the apex of the bladderto minimise the risk of prolapse. Closure is under-taken after subsequent valve ablation, within 6–18months, depending on the initial indication forselecting vesicostomy and the child’s level of renalfunction (Figure 8.9).

Supravesical diversion

Bilateral end ureterostomies or pyelostomies arenow rarely performed because:

• defunctioning the bladder may adversely affectits later performance

• a vesicostomy usually provides equally effectivedrainage and is more easily managed by parents.

Refluxing ureterostomy

Refluxing ureterostomy is an innovative method ofovercoming the high bladder pressures during


Figure 8.7 Cold knife and cutting resectoscope loopfor use with neonatal resectoscope. The availability ofinstruments designed for neonatal use has simplifiedmanagement and greatly reduced the incidence ofinstrumentation-induced urethral trauma.

Valve leaflets

Resectoscopeloop

Verumontanum

Figure 8.8 Position of the cutting loop prior toablation of the valve membrane.


storage and voiding which persist in infancy despiterelief of obstruction. In addition, the procedurealso maximises drainage from the ipsilateral kidneyand at the same time maintains bladder cycling.The urinary tract is usually reconstituted between2 and 3 years of age in preparation for potty training.

Urinary leaks

Urinary ascites and perinephric collections or‘urinomas’ usually respond to a short period ofbladder drainage. Large or persistent perirenalcollections may require ultrasound-guided percu-taneous aspiration or open drainage (in combina-tion with open nephrostomy).

The infant

Urinary infection in infants with previouslyundiagnosed posterior urethral valves is oftencomplicated by septicaemia and gross disturbances

of electrolyte and acid–base balance, of whichhyperkalaemic acidosis is the most serious form.The metabolic disturbances and underlying sepsisdemand vigorous treatment, which should be under-taken in cooperation with a paediatric nephrolo-gist. Surgical treatment of the bladder outflowobstruction is best deferred until the general condi-tion has been stabilised, usually after 2–7 days.Vesicostomy may occasionally be required as theprimary intervention.

The older child

With few exceptions, endoscopic ablation of thevalves is the initial treatment.

PrognosisApproximately one-third of individuals haveimpaired renal function in the long term, althoughthis may not become manifest until adolescence.Factors implicated in the aetiology of chronic renalfailure include:

• Primary renal dysplasia.• Secondary damage resulting from bladder

outflow obstruction; this occurs principally inutero, but may also occur postnatally if undiag-nosed obstruction persists after birth.

• Urinary infection, often in association withvesicoureteric reflux.

• Secondary damage resulting from bladderdysfunction, which persists after relief of outflowobstruction.

The importance of this last component, which ismanifest clinically as impaired continence, has onlybeen fully recognised in recent years with thepublication of studies demonstrating that patternsof bladder dysfunction change over time. Typicallythere is a tendency for detrusor overactivity to bereplaced by detrusor failure, along with progressiveenlargement of bladder capacity and increasingresidual volumes of poorly concentrated urine.

Urodynamic studies undertaken in the authors’unit have shown a uniform pattern of bladder


Figure 8.9 Cutaneous vesicostomy is the mostcommonly used form of temporary diversion.


function 1 year after satisfactory valve ablation.During the filling phase, the functional capacity ofthe bladder is reduced, there is evidence of detru-sor overactivity but compliance is unimpaired. Thevoiding phase is characterised by a distinctivebiphasic or polyphasic detrusor pressure profile,high voiding detrusor pressures and incompletebladder emptying.

By the age of 5 years, bladder function hasevolved and falls into three distinct patterns basedon voiding bladder dynamics. There is a tendencyfor detrusor overactivity to diminish and forbladder capacity to increase over the course oftime but a small proportion of cases showevidence of bladder decompensation as early as5 years of age.

Predictors of a poor renal function

Prenatal

• Maternal oligohydramnios, regardless of thegestational age.

• Early detection on prenatal ultrasound of‘bright’ kidneys and pelvicaliceal dilatation.

Postnatal

• Presentation in the first 12 months of life (ifundetected prenatally).

• Proteinuria.• Bilateral vesicoureteric reflux.• Impaired continence at 5 years of age upwards.

Indicators of good renal function

• Presentation in later childhood.• Protection of the upper tracts by a ‘pop-off ’

phenomenon.

Of these, the most common is unilateral high-gradevesicoureteric reflux in which the affected ipsilateralkidney has negligible or zero function where thecontralateral kidney is normal (VURD syndrome).

The protective value of the ‘pop-off ’ phenome-non has probably been overstated, and recent

evidence suggests that although this may impartsome medium-term benefit, a proportion of boysnevertheless progress to renal failure. Other lesscommon forms of ‘pop-off ’ mechanism includeurinary ascites, perinephric urinoma and a largebladder diverticulum.

Follow-up andlong-term managementAll boys with posterior urethral valves requirelong-term follow-up. A suggested protocol isgiven in Table 8.2. Differential renal function ismonitored, by MAG3 (mercaptoacetyltriglycine)renography or by DMSA (dimercaptosuccinicacid) scintigraphy, once overall function hasstabilised. Upper tract dilatation often improvesfollowing valve ablation, but usually persists eitherunilaterally or, more commonly, bilaterally. Possi-ble explanations include:

• incomplete relief of bladder outflow obstruction• persistent vesicoureteric reflux• ureterovesical obstruction secondary to occlu-

sion of the ureterovesical junction by a thick-walled bladder (rare)

• upper tract obstruction due to high-pressurebladder dysfunction (non-compliance, instability)

• ureteric decompensation, particularly in conjunc-tion with polyuria.


Table 8.2 Follow-up protocol for patients withposterior urethral valves

Routine at every visitHeight and weightBlood pressureUrinary tract ultrasonographyUrine dipstickSerum creatinine and electrolytes

As indicatedIsotope renography (MAG3 or DMSA)Flow rateUrodynamicsFormal estimation of GFR


A high obligatory output of dilute urine occurswhen the concentrating ability of the kidneysdeclines with the onset of early chronic renal failure(tubular defect). The urinary tract may demon-strate increasing dilatation in response to this largeurine output. Investigation should therefore beaimed at reassessing glomerular and tubular renalfunction.

Vesicoureteric reflux resolves in 30–60% of casesfollowing valve ablation. However, resolution isless likely in the presence of bladder dysfunction orwhen function in the affected renal unit is poor.

Neonatal circumcision is performed routinelyby some surgeons to minimise the risk of infection,although the benefits are largely anecdotal.Breakthrough urinary infections despite antibioticprophylaxis may improve following circumcisionand the need for antireflux surgery or nephroureterec-tomy is rare.

Bladder dysfunction

Diurnal enuresis secondary to bladder dysfunctionoften responds to detrusor antispasmodics such asoxybutynin or alternative anticholinergics. Inter-mittent catheterisation should be considered whereincontinence is associated with an impairedvoiding and a large volume of residual urine. Inpractice, urethral self-catheterisation rarely provesacceptable to boys with posterior urethral valves,because, in contrast to patients with neuropathicbladder, their urethral sensation is normal. For thisreason, effective long-term intermittent catheteri-sation is usually dependent on the creation of acontinent catheterisable (Mitrofanoff) channel.

Augmentation cystoplasty

The role of augmentation cystoplasty in boys withposterior urethral valves is controversial. Althoughcontinence is usually improved, this is at theexpense of impaired voiding in at least 40% ofindividuals, which in turn calls for intermittentcatheterisation. Whether the procedure also securesits more important objective of long-term preser-vation of renal function remains to be definitively

established. Bladder function continues to evolveduring childhood, with a tendency towards improve-ment as far as its storage dynamics are concerned.At the present time bladder augmentation wouldbe considered for boys less than 3–4 years of agewith severe renal dysfunction, for whom renaltransplantation is on the horizon. In this situationone does not have the luxury of awaiting sponta-neous improvements in bladder function and it isessential to ensure a safe lower urinary tract priorto renal transplantation. The long-term complica-tions of enterocystoplasty (mucus stone formation,metabolic disturbance, etc.) can be avoided byaugmenting the bladder with dilated ureter (urete-rocystoplasty). This technique is often more appli-cable to boys with posterior urethral valves thanchildren undergoing augmentation for neuro-pathic bladder since they are more likely to have adilated ureter associated with a non-functioningipsilateral kidney.

Other urethral abnormalities

Anterior urethral valves,diverticula and megalourethraThese anomalies, which are confined to males, areeight times less prevalent than posterior urethralvalves. In many respects they constitute a contin-uum of urethral pathology while also beingdistinct entities in their own right. For example, itis difficult to define the point at which the urethraldilatation proximal to anterior urethral valvesconstitutes a diverticulum, and similarly the pointat which an extensive diverticulum becomes amegalourethra.

Anterior urethral valves

As classically described, these take the form ofeither a fenestrated diaphragmatic membrane or amucosal cusp arising from the ventral wall of theurethra. In 40% of cases the valve is sited at the bulbar urethra, whereas in 30% it is at thepenoscrotal junction and in 30% in the penile



urethra. The presentation is with obstructivesymptoms, such as a poor urinary stream,hesitancy or urinary retention. Secondary changesin the upper urinary tracts are rare. Micturatingcystourethrography demonstrates the obstruction,and treatment is by endoscopic incision.

Urethral diverticulum

In the more common wide-mouthed form, usuallylocated in the region of the penoscrotal junction,the distal lip may give rise to a form of valvularobstruction as the diverticulum undergoes progres-sive distension. Presentation is either with obstruc-tive symptoms or with postmicturition dribbling.The rarer saccular lesions have a narrow neck andmay occur anywhere along the length of the penileurethra, including in the fossa navicularis. Presen-tation is with urinary infection – rarely associatedwith stone formation within the diverticulum.Treatment is by endoscopic incision or resection ofthe obstructing lip or, rarely, by a perineal approachfor the excision of a large diverticulum.

Megalourethra

This rare condition is characterised by markeddilatation of the penile urethra in the absence ofany evident obstruction. Megalourethra may beassociated with lack of corpus spongiosum or, inthe extreme form, with complete absence of thecorpora cavernosa. In such cases the penis amountsto little more than a floppy sac comprised of skinexternally and urethral mucosa internally. Anassociation exists between megalourethra andother congenital abnormalities, particularly prune-belly syndrome.

Cowper’s glandcysts (syringocoele)These paired structures, located on either side ofthe urethra at the level of the urogenital diaphragm,are each drained by a duct that courses distallythrough the corpus spongiosum to enter the bulbarurethra. Distension of the ducts, or of the glandsthemselves, may cause urethral compression or, ifthe anterior wall of the cyst ruptures into the

urethra, may result in an obstructive membrane.Treatment is as for anterior diverticulum.

Urethral duplicationsThese rare anomalies may be sagittal or collateral.Of these, the sagittal pattern is more common andtakes the form of two channels running one abovethe other in the sagittal plane, whereas in the collat-eral form the duplicate urethras run side by side.The most common sagittal configuration comprisesan orthotopic principal urethral channel and anepispadiac accessory urethra lying dorsal to it.

In some cases both urethras leave the bladderseparately and remain separate throughout theirlength, whereas in other cases the duplicateurethras unite distally to form a single channel. Inthe so-called ‘spindle’ variety the urethra separatesinto two components before reuniting again moredistally, whereas in ‘Y’ duplications, an accessoryurethra diverges from the main channel to emergein the perianal region or the perineum. Recon-struction is dependent upon individual anatomybut nearly always entails excision of the narroweraccessory urethra.

Posterior urethral polypsThese fibroendothelial lesions arise from theverumontanum. Small polyps are usually discov-ered incidentally during the course of endoscopyfor some unrelated purpose, whereas the largerlesions, with a polypoid head floating freely on anextended stalk, tend to obtrude through the bladderneck to give rise to acute, transient episodesof urinary retention. Haematuria or frank urethralbleeding may also occur. Diagnosis is bycystourethroscopy or MCU (Figure 8.10). Mostpolyps can be excised endoscopically, although forlarge polyps an open transvesical approach may berequired.

Urethral stricturesThe aetiology, investigation and management ofpost-traumatic strictures is considered in Chapter22. Occasionally, however, a urethral stricture isdiscovered in a boy with no antecedent history of



external injury, urethral instrumentation orcatheterisation. In very young boys the aetiologycan be assumed to be congenital, but in the olderage group the possibility of previously unrecog-nised trauma must be entertained. Whethercongenital or acquired, such strictures are generallymild and respond well to endoscopic urethrotomy.Formal urethroplasty is rarely required.

Cobb’s collarThe clinical status of this anomaly is arguable andits principal significance is as an occasional radio-logical finding on MCU comprising a short,narrowed segment of urethra immediately distal tothe urogenital membrane. On endoscopy, thefindings consist of little more than a soft, non-obstructing concentric ring. Although Cobb’scollar has sometimes been implicated as a possiblecause of voiding disorders, notably enuresis, theconsensus is that in children it is essentially a radio-logical or endoscopic finding without clinicalsignificance.

UrethritisAlthough the existence of this condition in boys isrecognised by paediatric urologists, it has received

little attention in the literature: the clinical featuresare non-specific and the aetiology is poorly under-stood. The condition is uncommon but occurs inboys aged 6 years and upward, with presentingfeatures that include dysuria, penile discomfort andurethral discharge or urethral bleeding – usuallyconsisting of no more than spotting on the under-clothes. Attempts to culture a specific organism areunrewarding. In the absence of other features,cystourethroscopy is not indicated, as it rarelymakes a practical contribution to clinical manage-ment. However, when urethroscopy is performed,the findings are characterised by erythema of theanterior and bulbar urethra, with a granularappearance and strands of fibrinous exudate. Thereis no specific treatment and the condition is self-limiting, although it sometimes runs a protractedcourse.

Key points

• The original classification devised byYoung is outdated. Congenital urethralobstruction generally conforms to auniform anatomical pattern, althoughthere is considerable variability in theseverity of obstruction and the degree of congenital damage to the uppertracts.

• The majority of cases are detectedprenatally. The gestational age atdiagnosis and the characteristics of the prenatal ultrasound findings provide a guide to prognosis. Prenatalintervention improves the outcome oflung function in the presence of severe oligohydramnios but there is little if any evidence that prenatalintervention benefits renal function.

• Despite relief of the urethral obstructionin early postnatal life, bladder function is abnormal in up to 70% of boys. Thepattern evolves during childhood and if unaddressed may contribute to


Figure 8.10 MCU outlining a posterior urethralpolyp prolapsing from its point of origin into themembranous and bulbar urethra.


deteriorating upper tract function and the onset of renal failure in latechildhood or early adult life.

• Approximately one-third of individualswith posterior urethral valves aredestined to develop chronic renal failure (as a consequence of dysplasia,obstruction, infection and bladderdysfunction). Careful follow-up should be maintained into adulthood.

Further reading

Clark TJ, Martin WL, Divakaran TG et al. Prenatal bladderdrainage in the management of fetal lower urinary tract

obstruction: a systematic review and meta-analysis.Obstet Gynaecol 2003; 102: 367–382

Cuckow P. Posterior urethral valves. In: Stringer MD, OldhamKT, Mouriquand PDE (eds). Paediatric Surgery andUrology: Long-Term Outcomes. Cambridge: CambridgeUniversity Press, 2006: 540–554

Holmdahl G, Sillen U. Boys with posterior urethral valves:outcome concerning renal function, bladder functionand paternity at ages 31 to 44. J Urol 2005; 174:1031–1034

Holmes N, Harrison MR, Baskin LS. Fetal surgery forposterior urethral valves: long-term postnataloutcomes. Paediatrics 2001; 108: 36–42

Ylinen E, Ala-Houhala M, Wikström S. Prognostic factorsof posterior urethral valves and the role of antenataldetection. Pediatr Nephrol 2004; 19: 874–879



Cystic renal disease

David FM Thomas

Introduction

Cystic pathology of the kidney is relativelycommon across the age range from childhood into late adulthood. The pattern of renal cysticdisease in infancy and childhood differs from thatencountered in adults, with multicystic dysplastickidney (MCDK) and the autosomal recessive formof polycystic kidney disease (ARPKD) assuminggreater importance than autosomal dominantpolycystic kidney disease (ADPKD).

The introduction of routine ultrasound imaginginto obstetric practice has revealed that the trueprevalence of asymptomatic unilateral multicysticdysplastic kidney is considerably higher than waspreviously suspected, but only a small percentageare clinically evident at birth and the majority ofunilateral MCDKs clearly remained undetected inthe past.

The terminology previously used to describe thedifferent clinical and pathological forms of cysticrenal disease has given rise to understandable confu-sion. In particular, terms such as ‘dysplastic’,‘hypoplastic’, ‘shrunken’, ‘polycystic’ and ‘multicys-tic’ have often been used loosely or interchangeablyin the literature with little regard to differencesin histology and developmental biology. In clinicalpractice, confusion most commonly arises from thefailure to distinguish between multicystic dysplastickidney, a sporadic structural abnormality which,when unilateral, carries a good prognosis, and

polycystic kidney disease, an inherited disordercharacterised by diffuse pathology of the parenchymaof both kidneys.

Embryology and pathology

The different types of cystic renal disease encounteredin childhood are so diverse that their embryology,inheritance and pathology are more convenientlysummarised under the relevant headings. The Potterclassification represented the first systematic attemptto categorise the differing forms of cystic renalpathology, but has been rendered obsolete byadvances in molecular biology and genetics whichhave found little scientific justification for the group-ings devised by Potter.

Polycystic renal diseaseThis important group of disorders is characterisedby the presence of microscopic or macroscopiccystic tissue distributed diffusely throughout theparenchyma of both kidneys. There are no histo-logical features of dysplasia.

Two major forms of polycystic renal disease are encountered: i.e. autosomal recessive (the typemost commonly encountered in children) andautosomal dominant, which, although sometimesevident on renal ultrasound in childhood, is oflittle clinical impact until adult life.

9

Topics coveredPrevalence of different forms of cystic renaldiseases in childhoodAutosomal recessive polycystic kidney disease(ARPKD)

Autosomal dominant polycystic kidney disease(ADPKD)Multicystic dysplastic kidney (MCDK)Multilocular renal cystSimple renal cyst


Autosomal recessive polycystickidney disease (ARPKD) (Figure 9.1)

Incidence

1:10 000–1:40 000.

Pathology

Typically the kidneys retain their normal outlinebut are considerably enlarged. The pelves, calycesand ureter are normal in morphology. The renalparenchyma is extensively replaced by cylindrical,radially orientated cysts which are usually less than2 mm in diameter. Liver involvement is almostinvariable, with a pattern of bile duct abnormali-ties termed ‘biliary dysgenesis’.

Genetics

ARPKD arises as a result of mutations of thepolycystic kidney and hepatic disease 1 gene(PKHD1). The less severe mutations are compati-ble with survival and are thought to permit someexpression of the gene product – a protein fibro-cystin. Major mutations, however, are associatedwith lethal forms of the disorder.

Presentation

ARPKD is associated with characteristic ultra-sound appearances of diffuse bilateral renalenlargement (Figure 9.2). Ultrasound findings ofoligohydramnios or reduced bladder volume arepredictors of severe functional impairment. Termi-nation of pregnancy is an option when the condi-tion is detected in the second trimester, butultrasound evidence of the disorder is not alwaysapparent at this stage in gestation, or may not besufficiently diagnostic until later in pregnancy.

Clinical features

In the neonatal period clinical features includereadily palpable abdominal masses and, in moresevere cases, pulmonary hypoplasia and ‘mould-ing’ deformities, e.g. Potter’s facies, talipes, etc.Occasionally ARPKD does not come to light untillater childhood, when it presents with hypertensionor manifestations of hepatic fibrosis, such as portalhypertension or bleeding oesophageal varices.


Figure 9.1 Autosomal recessive polycystic renaldisease. Diffuse bilateral renal enlargement.

Figure 9.2 Prenatal ultrasound appearances ofautosomal recessive polycystic kidney disease.


Diagnosis is with ultrasound and, in somecases, computed tomography (CT). Renal biopsymay also be indicated.

Treatment

Initial ventilatory support may be required for themanagement of respiratory distress and pulmonaryhypoplasia in severely affected infants. The require-ment for ventilation does not carry the universallypoor prognosis that was once the case. Medicalmanagement is directed at the treatment of hyper-tension, prevention of malnutrition and measuresdesigned to minimise anaemia and renal bonedisease. Children progressing to end-stage renalfailure are managed by dialysis and transplantation,with native nephrectomy being indicated to controlhypertension or create space for the transplantedkidney. Specific treatment may be required for thecomplications of hepatic disease.

Prognosis

Infants who do not have pulmonary hypoplasiahave a high expectation of surviving beyond theneonatal period and, in those who do, the 5-yearsurvival rate is 87%, with a 67% survival rate at15 years.

Autosomal dominant polycystickidney disease (ADPKD) (Figure 9.3)Incidence

The most commonly inherited form of renaldisease, ADPKD has a reported prevalence rangingfrom 1:200 to 1:1000. It is essentially a disorderof adult life, accounting for approximately5–10% of adults on end-stage renal replacementprogrammes.

Pathology

Histologically, the cysts are lined by tubular epithe-lium and the intervening renal parenchyma may

be normal or show evidence of glomerulosclerosis.Extrarenal manifestations include hepatic cysts andcerebral aneurysms.

Genetics

Mutations of the PKD1 gene, which is located onchromsome 16, account for 85% of cases. Thisgene encodes for a glycoprotein which is believedto play an important role in cell matrix interaction.A second gene defect caused by mutations of thePKD2 gene on chromosome 4 accounts for themajority of the remaining cases. One study foundthat the mean age of death or onset of end-stagerenal failure was 53 years in patients with thePKD1 mutation, as opposed to 69 years in thosewith the PKD2 mutation. The variability ofthe phenotype, sometimes in members of a singlefamily, suggests that genetic factors are subject toconsiderable heterogeneity.

Presentation

ADPKD is occasionally identified during routineprenatal ultrasound examination. In addition, asymp-tomatic individuals can sometimes be diagnosedon ultrasound screening of the offspring or otheryoung family members of patients known to havethe disorder.

Cystic renal disease 123

Figure 9.3 Autosomal dominant polycystic kidneydisease. Discrete cysts of varying size interspersedbetween areas of normal renal parenchyma.


In the majority of cases, however, clinicalpresentation is in adult life with hypertension,abdominal pain, palpable abdominal masses, haema-turia or other urinary symptoms.

Management

The condition is managed expectantly, withfollow-up aimed at the detection and early treat-ment of complications, notably hypertension. Cystdrainage or nephrectomy are occasionally indicatedin the management of severe hypertension, or tocontrol pain or urinary infection.

Prognosis

When the autosomal dominant form of polycystickidney disease is diagnosed on ultrasound in child-hood, either incidentally or during family screen-ing, the prognosis for renal function is generallygood, with 80% of children maintaining normallevels of renal function into adult life. In contrast,when detected prenatally or in the neonatal period,ADPKD disease carries a poor prognosis.

Multicystic dysplastic kidney(MCDK) (Figure 9.4)Prior to the introduction of routine antenatal ultra-sound, MCDK was regarded as a relatively rare

anomaly which generally presented as an abdomi-nal mass in the neonatal period. Nephrectomy was routinely undertaken in such cases. It is now evident, however, that the true prevalence of MCDK is far higher than was previouslysuspected, but in the majority of cases the lesion isclinically undetectable and the affected infant isentirely asymptomatic and outwardly normal. Themanagement of prenatally detected MCDK andthe arguments surrounding ‘prophylactic’ removalof asymptomatic kidneys remain a source ofcontroversy.

Incidence

Current evidence from a number of sourcesindicates a prevalence for unilateral MCDK in therange 1:2500–1:4000 live births. Bilateral MCDK,a lethal anomaly, has an estimated incidence of1:20 000 pregnancies.

Aetiology/embryology

Proximal ureteric atresia (or, more rarely, distalureteric obstruction) is almost invariably found inassociation with MCDK (Figure 9.5). Completeureteric obstruction at an early stage in embryonicdevelopment has therefore been invoked as thecause of the MCDK malformation.

Faulty development of the ureteric bud andmetanephric mesenchyme may also be implicated(see Chapter 1). Familial occurrence of MCDK hasbeen reported, and although MCDK generallyappears to behave as a sporadic anomaly, in some families it may rarely be inherited as anautosomal dominant trait with variable penetrance(Figure 9.6). Nevertheless, the overall risk offamilial occurrence is extremely low and routinescreening of siblings and other first-degreerelatives for MCDK is not justified.

Pathology

MCDK comprises an irregular collection of tensenon-communicating cysts of varying size lined by cuboidal or flattened tubular epithelium. Renalparenchyma, where present, is dysplastic and


Figure 9.4 Multicystic dysplastic kidney. Kidneyreplaced by collection of cysts of varying size. Uretericatresia.


consists of small islands or flattened plates ofabnormal tissue interposed between cysts.

Although the entire kidney is usually affected,there have been case reports of segmental MCDKin which the cystic changes and characteristic histol-ogy are confined to a segment of an otherwise,relatively normal kidney.

Presentation

MCDKs present in one of three ways:

• Clinically – usually as an abdominal mass in theneonatal period. Only a small proportion of allMCDKs now present in this fashion. Typicallythe surface of a palpable MCDK is ‘knobbly’and irregular in contour, contrasting with otherneonatal renal masses, e.g. hydronephrosis orpolycystic kidney, which have a smoothersurface on palpation.

• Incidental postnatal ultrasound finding in aninfant with coexisting congenital anomalies, e.g.oesophageal atresia.

• Prenatal ultrasound. The majority of prena-tally diagnosed MCDKs (> 80%) are small andclinically undetectable at birth.


Figure 9.5 Nephrectomy specimen. Multicysticdysplastic kidney. (Courtesy of Mr PG Ransley.)

Not scanned

Normal renal ultrasound

Unilateral multicysticdysplastic kidney

N

NNN

N N

N

N

NNP

Figure 9.6 Familial occurrence of MCDK. Pedigree of affected family. Probable autosomal dominant pattern ofinheritance. Most MCDKs occur as a sporadic anomaly.


Diagnosis

Although the prenatal ultrasound appearances ofMCDK can occasionally be difficult to distinguishfrom those of marked hydronephrosis, most experi-enced radiologists can make the diagnosis with ahigh degree of accuracy. Postnatally the diagnosisis confirmed by a combination of ultrasound andisotope imaging. MCDKs are characterised by atotal absence of isotope uptake (0% differentialfunction) on DMSA (dimethylsuccinic acid). Insome centres MAG3 (mercaptoacetyltriglycine) isfavoured, as this yields additional information ondrainage in the contralateral kidney.

The role of the micturating cystourethrogram(MCU) in the evaluation of infants with prenatallydetected MCDK is controversial. When performedroutinely, it reveals a 20–30% incidence of low-grade contralateral or ipsilateral vesicouretericreflux (VUR). However, the clinical significance ofthis finding is arguably often low, since this low-grade VUR usually resolves in early life and rarelygives rise to infection. In the author’s experienceless than 3% of children with MCDK requiredsurgical correction of reflux, and it is thereforethe author’s preference to reserve MCU for thoseinfants in whom there is ultrasound evidence ofureteric or contralateral renal dilatation. This selective approach to the use of micturatingcystourethrography is endorsed by recently reportedstudies. However, it is important that parents andgeneral practitioners are aware that otherwisenormal ultrasound appearances do not exclude thepossibility of low-grade VUR, and the occurrenceof a documented urinary tract infection (UTI) oran unexplained febrile illness is an indication toproceed to MCU.

Natural history

A number of studies have documented the poten-tial for prenatally detected MCDKs to involute –i.e. to disappear on ultrasound – both prenatallyand postnatally. In the cases recorded on the USNational Multicystic Kidney registry, only 14%disappeared completely on ultrasound, whereas

45% demonstrated reduction in size, 35%remained unchanged in size and 5% demonstratedenlargement. However, the duration of follow-upwas not specified. In a study in the author’s unit,involution was observed in 52% of prenatallydetected MCDKs at median follow-up of 66months (range 24–144 months), with approxi-mately 30% of MCDKs having involuted (disap-peared) in the first 12 months of life. Thisexperience is endorsed by the findings of anotherUK study which reported complete involution of33% of MCDKs by 2 years of age, increasing to47% at 5 years and 59% at 10 years.

The documented tendency for MCDKs toinvolute spontaneously, coupled with the relativerarity with which unilateral renal agenesis is dia-gnosed in utero, has been interpreted as evidencethat a proportion of cases of apparent renal agene-sis diagnosed in adult life or at postmortem may infact represent involuted MCDKs.

Complications

Hypertension is a rare but well-documented compli-cation of MCDK and nephrectomy is undoubtedlywarranted when it occurs. But how common isthis complication?

In 1988, the authors of an early study of prena-tally detected MCDK reported the findings of aliterature search which had identified only ninecases of hypertension responding to nephrectomyin the preceding 20-year period. A recent (2006)review of reported cases over the previous decadeidentified a total of 31 cases of hypertension, ofwhich at least six definitely responded to nephrec-tomy. Nevertheless, when viewed in the context ofthe prevalence of MCDK (1:2500–1:4000), thenumber of published case reports represents a loworder of risk for developing hypertension.

In the US registry, 426 children were managedconservatively, of whom five (1%) developed hyper-tension. In a UK prospective study of 165 patients(of whom 43 were followed for 10 years), nonedeveloped hypertension.

The possible link between MCDK and hyper-tension can be studied from a different angle. If



hypertension occurs on an appreciable scale thisshould be reflected in the published literature onrenal hypertension in childhood, but this is not thecase. No cases of MCDK were encountered in454 children with hypertension presenting to thepaediatric nephrology unit at the Hospital for Sick Children, Great Ormond Street, London.Similarly, two published series of children in othercentres with ‘surgical’ causes of renal hypertensionundergoing nephrectomy did not include a singleMCDK.

In summary, from the evidence currentlyavailable, it appears that the risk of hyperten-sion associated with MCDK is very low (of theorder of 1% or less) and is not sufficient tojustify ‘prophylactic’ nephrectomy in asympto-matic infants and children.

It is also important to note that removal of thekidney does not necessarily obviate the risk ofhypertension and the need for blood pressuremonitoring, since there have been reports of hyper-tension associated with pathology in the remainingcontralateral kidney.

Malignant potential

In a review of 26 published series totalling 1041children with MCDKs no cases of malignancywere reported over periods of follow-up extendingup to 23 years. Moreover, no instances of malig-nancy were encountered amongst the childrenrecorded on the US MCDK registry. As withhypertension it is also possible to view thequestion from a different angle by asking, ‘Howcommonly does MCDK figure in published seriesof Wilms’ tumours?’ In the United States, detaileddata on 7500 Wilms’ tumours were collected overan 18-year period as part of the National Wilms’Tumor Study. Out of these 7500 tumours, onlyfive arose in MCDKs.

On current estimates of the true prevalence ofMCDK this represents an individual lifetime riskof the order 1:2500. Given that Wilms’ tumour isnow largely curable, the lifetime risk of dying froma Wilms’ tumour arising in an MCDK has been

calculated to be comparable to the risk of mortal-ity associated with general anaesthesia. Althoughopinion remains divided, the available evidencedoes not justify submitting asymptomatic infantsor children to nephrectomy as a prophylacticmeasure.

Other complications

Symptoms such as pain or haematuria have beenascribed to MCDKs in rare cases reported in theadult literature. These symptoms are seldom, ifever, seen in association with MCDK in the paedi-atric age group. When urinary infection occurs inchildren with MCDK it is more likely to be due tounderlying VUR or some coexistent anomalyrather than the MCDK itself (which does notcommunicate with the rest of the urinary tractbecause of the presence of ureteric atresia).

Management

Coexisting anomalies

Contralateral pelviureteric junction (PUJ) obstruc-tion is present in 5–10% of cases and is managedconservatively or surgically according to its sever-ity. Vesicoureteric reflux is generally low grade andis usually managed conservatively by antibioticprophylaxis and urine surveillance or by endoscopiccorrection if appropriate.

Multicystic dysplastic kidney

Nephrectomy is undoubtedly justified for thoserare instances when MCDK presents in the neona-tal period as a large, clinically evident abdominalmass. Depending on factors such as the size ofthe mass and the presence or absence of otheranomalies, surgery can usually be deferred until4–6 weeks of age or later.

The arguments for the ‘prophylactic’ removal ofasymptomatic MCDKs centre principally on theperceived risks of malignancy and hypertension,and have already been considered above. Specialistopinion in the UK generally favours conservativemanagement. Nevertheless it is widely accepted



that hypertension, increasing size or the appearanceof unusual or worrying features on ultrasoundfollow-up are indications to proceed to nephrectomy.

Ultrasound follow-up is maintained on anannual basis until 5 or 6 years of age. Althoughsome paediatric urologists insist on the disappear-ance of the MCDK before discharging the child,this has not been the author’s practice. Measure-ment of blood pressure in infants or fractiousyoung children can be difficult but becomes easieras the child gets older. At the time of dischargefrom surgical follow-up, it is prudent to arrangefor blood pressure to be checked by a paediatricianor GP on an annual basis thereafter, continuinginto adult life.

Nephrectomy

The traditional approach to removal of an MCDKentails the use of a small incision anterior to the tipof the 12th rib or a posterior lumbotomy incision.Aspiration of cyst fluid facilitates removal througha limited incision. More recently, laparoscopicnephrectomy has gained popularity as the proce-dure of choice. Ideally, this should be performedretroperitoneally rather than via a transperitonealapproach because of the potential risk of intraperi-toneal complications (see Chapter 23). Thebenefits of laparoscopic nephrectomy may be fairlymarginal in view of the simplicity and low morbid-ity with which MCDKs can be removed via a smallincision.

Multilocular renal cyst(Figure 9.7)This rare renal lesion, also described as cysticnephroma, benign multilocular cystic nephroma,etc., may give rise to diagnostic difficulty, typicallybeing misdiagnosed as a cystic Wilms’ tumour.

Aetiology

It remains unclear whether multilocular renal cystshould be regarded as a neoplasm or a develop-mental anomaly. Although malignancy ascribed tothis lesion has been reported in adult life, multilocularrenal cyst is not generally considered a premalignant

lesion. It occurs sporadically with no evidence ofan inherited basis.

Incidence

Experience in the Yorkshire region of the UKsuggests that the incidence is approximately1:200 000–1:250 000. The condition demon-strates a bimodal age distribution, with one peakin infancy and a second peak in early adult life,separated by an unexplained hiatus in distribution.Children account for 30–50% of cases.

Presentation

Most cases present with haematuria, loin pain oran abdominal mass, although multilocular cyst canoccasionally come to light as an incidental findingon ultrasound during the investigation of unrelatedsymptoms.

Diagnosis is by ultrasound complemented byCT and possibly magnetic resonance imaging (MRI).DMSA is also helpful to delineate functional tissueif nephron-sparing surgery is under consideration(Figure 9.8). Typically the multilocular cysticlesion is localised within the renal parenchyma, but may extend into the collecting system ordistort the renal capsules. An experienced paedi-atric radiologist should be able to distinguishmultilocular renal cyst from other forms of renalpathology, but even with sophisticated imaging itmay be difficult to distinguish from a cystic variantof Wilms’ tumour.


Figure 9.7 Multilocular renal cyst.


Management

Nephrectomy is the accepted form of treatment. In view of the benign nature of the lesion nephron-sparing surgery, i.e. partial nephrectomy,might be considered in certain circumstances, suchas a multilocular renal cyst in a solitary kidney.

Simple renal cyst (Figure 9.9)Although a common finding in adults, simple or‘solitary’ renal cysts are only occasionally encoun-tered in childhood and are thus likely to be acquiredrather than congenital in aetiology. Although it hasbeen stated that simple cysts do not give rise toproblems, this is not invariably the case and the

author has treated a number of children with painarising in simple renal cysts which has responded to


Figure 9.8 (a) Ultrasound scan. Multilocular cysticlesion in the right kidney of a 2-year-old girl present-ing with haematuria. (b) Non-functioning lesion in themidzone of the right kidney demonstrated on DMSA,not amenable to nephron-sparing surgery. (c)Nephrectomy specimen. Distortion of the renal outlineby the tense intrarenal lesion. Histology confirmedbenign multilocular cyst.

Rt

Figure 9.9 Simple renal cyst – rare in childhood.

(a) (c)

(b)


surgical removal or deroofing of the cyst. Never-theless, it is also important to note that a simplecyst may be an incidental unrelated finding in achild with non-specific abdominal pain. Dilatationof the upper pole of a duplex kidney is sometimesmistaken on ultrasound for a simple cyst by radiol-ogists unfamiliar with paediatric urology. Rarelya child may present with abdominal pain or othersymptoms which are genuinely attributable tothe presence of a large, tense simple renal cyst(Figure 9.10). Management is the same as forsymptomatic renal cysts in adults, and comprisespercutaneous cyst aspiration and injection ofalcohol, or laparoscopic or open deroofing andsubtotal excision of the cyst wall. Recurrence isuncommon.

Key points

• Despite the potentially confusingterminology it is important tohave a clear understanding ofthe various patterns of cysticrenal disease in view of theimportant differences inclinical significance and prognosis.

• Autosomal recessive polycystic kidneydisease is detected prenatally orpresents in the newborn period.

• Autosomal dominant polycystic kidneydisease does not generally come tolight with symptoms until adulthood andis generally asymptomatic in thosechildren in whom the condition has been identified by ultrasound screening.

• Multicystic dysplastic kidney (MCDK) is adevelopmental abnormality of the kidneywhich is more prevalent in the generalpopulation than was previously recognised.

• Current evidence suggests that the riskof malignancy associated with MCDK is not significantly increased over thenormal paediatric population. The risk of hypertension appears to be of theorder of 1% in childhood. This low order of risk does not justify routine‘prophylactic’ nephrectomy.

• A lifelong annual blood pressure checkis advisable. Removal of the MCDKdoes not obviate the need for thisprecaution in view of reported cases ofhypertension arising from the remainingcontralateral kidney.


Figure 9.10 Ultrasound appearances of large simple cyst in the lower pole of the left kidney of a 7-year-oldboy presenting with abdominal pain and a palpable mass. The condition was successfully managed by laparo-scopic partial excision/deroofing.


Further reading

Aslam M, Watson AR. Unilateral multicystic dysplastickidney: long term outcomes. Arch Dis Child 2006;91(10): 820–823

Belk RA, Thomas DFM, Mueller RF et al. A family studyand the natural history of prenatally detected unilateralmulticystic dysplastic kidney. J Urol 2002; 167: 666–669

Greenbaum LA, Avner ED. Cystic kidney diseases. In:Kher KK, Schnaper HW, Makker SP (eds). Clinical

Pediatric Nephrology, 2nd edn. London: InformaHealthcare, 2007: 261–273

Manzoni GM, Caldamone AA. Multicystic kidney. In:Stringer MD, Oldham KT, Mouriquand PDE (eds).Paediatric Surgery and Urology: Long-term Outcomes.Cambridge: Cambridge University Press, 2006: 683–694

Narchi H. Risk of Wilms’ tumour with multicystic kidney:a systematic review. Arch Dis Child 2005; 90(2):147–149




Prenatal diagnosis

HK Dhillon

Introduction

The first case reports of the detection of urinarytract malformations by prenatal (antenatal) ultra-sound first appeared in the literature in the mid1970s, but it was not until the early to mid 1980sthat maternal ultrasound was routinely incorpo-rated into obstetric practice in the UK. Since then,a substantial body of experience has accumulatedand the management of infants with prenatallydetected uropathies constitutes a major componentof paediatric urological practice. Abnormalities ofthe genitourinary tract are amongst the common-est anomalies detected in utero. This partly reflectsthe relatively high incidence of congenital anomalieswithin the genitourinary system, but is also becausethe common anomalies are usually associated withdilatation or cystic pathology which is relativelyeasy to visualize on ultrasound. Unfortunately,relatively few long-term studies have been under-taken to document the late outcome of prenatallydetected uropathies. As a consequence, there arestill some unresolved controversies surroundingearly surgical intervention or conservative manage-ment of conditions such as prenatally detectedpelviureteric junction (PUJ) obstruction, multi-cystic dysplastic kidney, and vesicoureteric reflux(VUR). Whereas progress has been made in identi-fying criteria to identify subpopulations at greatestrisk of later functional deterioration or clinicalcomplications, research has tended to focus on

short- to medium-term outcomes. Further evidenceof long-term follow-up studies would be particu-larly valuable in helping to establish which prena-tally detected uropathies are not destined to poseany threat of morbidity and which, indeed, may notwarrant any investigation.

The investigation and management of infantswith prenatally detected urinary tract abnormali-ties is guided by three important considerations:

• The majority of infants with prenatally detectedurinary tract abnormalities are outwardlynormal and healthy at birth. As such, theycannot be considered as patients in the conven-tional sense. This is particularly true of infantswith isolated unilateral anomalies in whomrelevant clinical findings are present in fewerthan 5% of cases. Bilateral renal pathology ismore likely to be associated with relevant physi-cal signs or coexisting syndromes, but, never-theless, the majority of infants with prenatallydetected bilateral uropathy are asymptomaticand outwardly normal at birth.

• Only a very small proportion of infants withprenatally detected uropathies (< 5%) haverenal insufficiency of sufficient severity torequire nephrological support and, overall, themajority of affected infants do not require anyform of early surgical intervention.

• The prenatal detection of a fetal urinary tractabnormality often generates disproportionate

10

Topics covered Obstetric ultrasound: current practice Prenatal management

CounsellingFetal intervention

Postnatal management Diagnostic imagingProtocols and guidelines


parental anxiety during the pregnancy. Parentswho have been told that their unborn childhas a kidney abnormality tend to assume theworst, including a scenario involving dialysis andrenal transplantation. In our experience, only aminority of parents receive accurate counsellingon the prognosis of the urological abnormalitydiagnosed in utero. Paediatric urologists should,ideally, play a far greater role in prenatalcounselling but the pressure of heavy clinicalworkloads can make this difficult to achieve.

Obstetric ultrasound – current practice

Nuchal pad translucency was developed as anultrasound screening test at 10–12 weeks’ gesta-tion in high-risk pregnancies, particularly forDown’s syndrome. Although this early scan isbeing extended into the lower-risk obstetricpopulation, its sensitivity for the detection ofurinary tract abnormalities is poor.

Routine fetal anomaly scanning is undertakenbetween 15 and 20 weeks, at a time when thediagnostic sensitivity of ultrasound has greatlyincreased. This timing enables severe congenitalmalformations to be diagnosed with sufficientaccuracy to permit an informed decision on termi-nation of pregnancy. In one study of 560 termi-nated pregnancies, neonatal and infant deaths,abnormalities of the urinary tract were incrimi-nated as the sole or contributory cause of death in323 instances, of which 221 occurred in utero as aresult of termination of pregnancy, intrauterinedeath or stillbirth, while 102 occurred postnatally,usually from pulmonary hypoplasia.

The sensitivity and specificity of ultrasono-graphy for the detection of urinary tract abnor-malities is influenced by the quality of theequipment used, the experience of the ultrasonog-rapher or radiologist performing and interpretingthe scan and by maternal size and obesity.

Anomalies such as renal ectopia or renal agene-sis which are not accompanied by dilatation areconsiderably more difficult to detect than those

characterised by dilatation or cystic disease.Although virtually every major, potentially lethalurinary tract abnormality is detectable in thesecond trimester, non-lethal abnormalities, includ-ing most cases of PUJ obstruction, VUR andduplication, are not necessarily associated withdetectable dilatation at this stage in gestation. Theprenatal detection of anomalies at the milder endof the pathological spectrum is therefore depend-ent upon scans being performed later in pregnancy.If prenatal scanning is limited to a single fetalanomaly scan in the second trimester, manyanomalies are destined to remain undetected inpregnancy. Gestational age at the time of scanningis, therefore, the most important factor determin-ing the sensitivity of prenatal urological diagnosis.Figures 10.1–10.3 illustrate the appearances ofsome common upper tract abnormalities on prena-tal ultrasound scans at 22 weeks’ gestation.

Incidence

The incidence of prenatally detected urinary tractanomalies reported from different centres variesconsiderably, depending on the gestational age atwhich ultrasound screening is routinely performed.However, the incidence of significant prenatallydetected uropathies averages around 1:500 to1:600 pregnancies. By contrast, mild dilatation isa common prenatal finding, being identified at


Figure 10.1 Unilateral severe hydronephrosis withclubbed calyces and echogenic cortex at 22/40weeks.


some stage in approximately 1:100 pregnancies.However, it is often a transient finding with atendency to resolve spontaneously during thecourse of pregnancy.

Management

Prenatal managementThe potential to influence the clinical outcome of aprenatally detected uropathy by active interventionduring pregnancy is limited to the severe end of thespectrum of obstructive pathology and comprises

fetal surgery (generally vesicoamniotic shunting) ortermination. Although there has been a suggestionthat preterm delivery and early postnatal treatmentmay improve the outcome for some boys withposterior urethral valves, there is insufficientevidence to justify elective preterm delivery.

When the urinary tract anomaly has beendetected prenatally, there are several options.

Counselling

Counselling should ideally encompass:

• the differential diagnosis, insofar as this can beestablished with the ultrasound informationavailable

• an explanation of the investigations that arelikely to be advised following delivery

• a broad outline of prognosis.

If the need for postnatal surgery is envisaged, parentsshould be reassured that this is rarely of a serious orlife-threatening nature. Unfortunately, it is oftenimpossible to provide a detailed prediction of whatthe future holds since the prenatal ultrasoundfindings are non-specific in approximately 70% ofcases. For example, the discovery of unilateralureteric and renal dilatation at 34 weeks’ gestationwould involve a discussion covering megaureters,VUR and duplex kidneys.

For logistical reasons, counselling for prenatallydetected uropathies of mild or moderate severity,particularly those detected in later pregnancy, ismostly undertaken in the hospital where themother is receiving her routine obstetric care.When the anomaly is at the more severe end of thespectrum, particularly when detected on second-trimester fetal anomaly scanning, the options mayinclude termination of pregnancy and, possibly,fetal intervention. In this situation, prompt refer-ral to a fetal medicine centre is indicated for moredetailed investigation and counselling.

Fetal intervention

The indications for possible intervention duringpregnancy are limited to the severe end of the patho-logical spectrum where the ultrasound findings and

Prenatal diagnosis 135

Figure 10.2 Bilateral severe hydronephrosis at22/40 weeks.

Figure 10.3 Multicystic dysplastic kidney at 22/40weeks.


the results of additional investigations point to astrong probability of intrauterine death or earlypostnatal demise. Termination of pregnancy mayalso be included in the options following thediscovery of a major, non-lethal malformation,which, nevertheless, carries grave implications forquality of life.

Bilateral renal agenesis or bilateral multicysticdysplastic kidneys are examples of anomalies whichare clearly incompatible with survival. In one studyrenal agenesis and multicystic dysplasia (or acombination of pathologies) accounted for morethan 60% of terminations of pregnancy for urolog-ical anomalies. By contrast, the prognosis ofurethral obstruction (typically posterior urethralvalves), is more difficult to predict, since there is abroad spectrum of severity ranging from urethralatresia with oligohydramnios and pulmonaryhypoplasia to mild degrees of urethral valveobstruction in which renal function is largelyunimpaired. Nevertheless, the high overall level ofmorbidity due to congenital urethral obstruction isreflected in the statistic that males constitute 90%of children undergoing treatment for renal failurein the first 4 years of life.

Fetal intervention is subdivided into:

• diagnostic procedures intended to assessfunctional prognosis and detect chromosomalabnormalities

• termination of pregnancy• therapeutic intervention, usually in the form of

vesicoamniotic shunting.

Karyotype

Chromosomal analysis can be performed byexamining exfoliated cells in amniotic fluid, bysampling blood from the umbilical cord (cordo-centesis) or by chorionic villus sampling.

Fetal urine sampling

Conventional tests of renal function such as creati-nine clearance or measurement of plasma creatinineand urea have no validity in intrauterine life since

the fetus is effectively ‘dialysed’ by the placenta,with the result that levels of creatinine, urea, etc., infetal plasma mirror those in the maternal circula-tion. However, the composition of fetal urine hasbeen studied with the aim of developing a moreselective approach to fetal intervention. Ideally, themeasurement of urinary constituents as indicatorsof renal function would be used to select fetuseswith potentially recoverable function for treatment,as opposed to those with irreversible renal dyspla-sia. Since urine sampling is an invasive procedure,data derived from normal fetuses without urinarytract anomalies are relatively scanty.

Biochemical parameters which have been identi-fied as predictors of poor functional outcomeinclude:

• fetal urinary sodium of >100 mEq/l after 20weeks’ gestation

• elevated urinary calcium (>1.2 mmol/l)• increased levels of urinary and serum β2-

microglobulin.

Unfortunately, there is a considerable overlapbetween pathological and normal values. The diffi-culty is compounded by the limited data derivedfor normal fetuses at different gestational ages. Inthe hope of developing more sensitive prognostictests, attention has recently switched from markersof excretory renal function to molecules which areexpressed during renal differentiation and whichmay be implicated in renal dysplasia, e.g. TGF-β1

(transforming growth factor beta-1).

Vesicoamniotic shunting

The rationale for this therapeutic intervention isderived from the premise that decompression ofthe obstructed urinary tract in utero will avertprogressive renal damage and functional deteriora-tion. Although open fetal surgery via hysterotomyand fetoscopy and valve ablation have beenreported, the method which has been most widelypractised comprises ultrasound-guided percuta-neous insertion of a pigtail shunt catheter into the



fetal bladder to drain urine into the amniotic fluid(Figure 10.4). With few exceptions, the publishedresults of fetal intervention (either open fetal surgeryor vesicoamniotic shunting) have been disappoint-ing. Results reported by the Fetal Surgery Registerin the mid 1980s documented an overall mortalityrate of 59% in a series of 73 fetuses. A subsequentreview of the literature noted a 45% incidence ofprocedure-related morbidity, including prematurelabour. Two long-term outcome studies have beenpublished – from Detroit and San Francisco. In theDetroit series, 34 fetuses underwent intrauterinedecompression – of whom 13 (38%) neverthelessdied in utero or postnatally. Fifty-seven per cent ofthose children who survived more than 2 yearsdeveloped renal insufficiency – of whom themajority required early renal transplantation. TheSan Francisco group analysed the late outcomedate for 36 fetuses treated between 1981 and1999 – all of whom had been selected for treat-ment on the basis of favourable urinary biochem-istry. In 14 fetuses the diagnosis was posteriorurethral valves: of these, six did not survive toterm, but eight survivors were assessed at the meanage of 11.6 years. By this stage, five were in renalfailure and only three (21% of the total number offetuses with posterior urethral valves) were alivewith normal renal function.

Whereas the published results of vesicoamni-otic shunting do not lend support to its use inroutine clinical practice, it is important to notethat shunting has generally been confined to fetusesat the severe end of the obstructed spectrum,typically with oligohydramnios. In these fetuses,renal dysplasia and damage is already well estab-lished by the time treatment is undertaken andthe potential to improve the prognosis by thisstage is very limited. One cannot, therefore,dismiss the possibility that shunting might bebeneficial in less severely affected fetuses wherebladder distension and bilateral upper tract dilata-tion is not accompanied by oligohydramnios orseverely deranged urine biochemistry. Ideally, acontrolled trial could have resolved this question,but, for a number of practical and ethical reasons,

a statistically meaningful controlled trial is nowno longer possible.

Termination of pregnancy

With the increasing prevalence and accuracy ofprenatal diagnosis, there is a growing tendency forparents in the UK to opt for termination ofpregnancy following the discovery of a urologicalabnormality which is inconsistent with survival –or which carries a poor prognosis for quality oflife. Sympathetic and informed counselling isessential to ensure that parents have access to theinformation they need to reach an informed (andoften very difficult) decision about their unbornchild. It is important, for example, that they havea realistic picture of what is entailed in the manage-ment of renal failure in childhood, in terms ofhospitalisation, medication, surgery and the diffi-culties inherent in dialysis and transplantation.


Figure 10.4 Vesicoamniotic shunt. A double pigtailcatheter is inserted percutaneously via trochar andpositioned to drain urine from the obstructed fetalbladder into the amniotic fluid.


Termination of pregnancy is being increasinglyrequested following the prenatal diagnosis ofmajor anomalies such as cloacal and ‘classic’bladder exstrophy. As a consequence, the numberof infants being born with these anomalies isdeclining and only two referral centres in Englandand Wales are recognised by the government forthe management of new cases of the exstrophyepispadias complex.

There are considerable variations in the attitudesto termination of pregnancy in different countries.Nevertheless, even in the United States, a studyin Boston found that elective termination ofpregnancy had been performed in 65% of pregnan-cies following the detection of spina bifida, 46% ofpregnancies following the prenatal diagnosis ofposterior urethral valves, 31% for prune-bellysyndrome and 25% for bladder exstrophy.

Postnatal management

Antibiotic prophylaxis

This should generally be commenced for allnewborn infants with prenatally detected uropathiespending the outcome of postnatal investigation,notably a micturating cystogram. Exceptionsinclude:

• infants with mild isolated renal dilatation withan anteroposterier (AP) diameter of ≤10 mmand normal calyces

• multicystic dysplastic kidney with an entirelynormal contralateral kidney

• ectopic kidney without evidence of dilatation.

The antibiotic most widely used is trimethoprim ina single daily dose of 2 mg/kg, usually adminis-tered at night.

Postnatal ultrasound

Urinary output is often reduced in the first day oflife, with the result that an abnormal urinary tractmay appear less dilated when not subjected to arepresentative diuretic load. For this reason, the

initial postnatal scan should ideally be deferreduntil after 48 hours of age, i.e. when normalurinary output has been established. However, thisoptimal timing may be difficult to achieve, sincemany mothers now opt for early discharge fromhospital. The timing of the initial ultrasoundscan is, therefore, best guided by the prenatalfindings.

Prompt postnatal ultrasound and referral toa specialist unit are essential for fetuses withsuspected lower urinary tract obstruction, assignified by bilateral upper tract dilatation,thick-walled bladder, ureteric dilatation, etc.

Bilateral dilatation without bladder or uretericinvolvement also merits early ultrasound – ideallybetween 3 and 7 days of age. In contrast, unilateraldilatation with a normal contralateral kidneycarries a low risk of early morbidity and the initialpostnatal scan can reasonably be deferred andperformed on an outpatient basis at some point inthe first 10–14 days of life.

In most specialist centres, the AP diameter ofthe renal pelvis in the transverse plane is nowroutinely measured. Although this measurement issubject to factors such as operator variability andthe degree of hydration, the measurement of renalpelvic diameter is nevertheless preferable to subjec-tive descriptions such as ‘mild’, ‘moderate’, ‘gross’hydronephrosis, ‘full’, or ‘baggy’ renal pelvis. Inaddition to documenting the AP diameter of therenal pelvis, it is important to record the appear-ances of the calyces and renal parenchyma.

Micturating cystourethrogram (MCU)

The role of the MCU in the routine postnatalevaluation of infants with prenatally detecteddilatation remains controversial, with practicevarying considerably between different centres.

However, the following conditions are gener-ally regarded as being definite indications for apostnatal MCU:

• abnormal bladder (particularly a thick-walledbladder or other evidence of outflow obstruction)



• bilateral upper tract dilatation• dilatation of one or both ureters seen on either

on pre- or postnatal ultrasound• duplex kidneys (in view of the high incidence of

lower pole reflux).

The question of whether infants with mild dilata-tion (<15 mm AP diameter) should routinely beinvestigated by MCU remains controversial.

The available evidence suggests that theincidence of underlying reflux associated with mildrenal pelvic dilatation is of the order of 10–15%.In most instances, however, it is low-grade VURwhich occurs more commonly in males and carriesa high probability of spontaneous resolution in thepresence of two normal kidneys on a DMSA(dimercaptosuccinic acid) scan. In practical terms,the information provided by an MCU is only likelyto influence the clinical outcome in a very smallpercentage of infants with prenatally detected milddilatation. Moreover, the MCU is an invasive andpotentially distressing procedure which carriessome risk of morbidity in its own right (predomi-nantly infection). For these reasons, many paedi-atric urologists no longer advocate routine MCU ifdilatation is confined to the renal pelvis (i.e. noevidence of ureteric and/or calyceal dilatation), andthe AP diameter of the pelvis is <15 mm. Somecases of low-grade VUR will be missed by thisapproach, but this is outweighed by the benefit ofa greatly reduced burden of unnecessary investiga-tion into healthy infants.

If an MCU is not undertaken, the child’s parentsand general practitioner should, nevertheless, bealerted to the importance of having the urinechecked for possible infection in the event of anunexplained febrile illness or more specific featuresof urinary infection.

Isotope imaging

The choice of imaging modality is determinedlargely by the findings on postnatal ultrasonogra-phy and MCU (when this has been performed).The principal role of 99mTc DMSA lies in confirm-ing total absence of function in a multicystic

kidney and for studying differential function andrenal damage associated with congenital VUR.

99mTc MAG3 (mercaptoacetyltriglycine) is theisotope most widely used for the diagnosis ofobstruction. It is important to note, however, thatdrainage curve data cannot be relied upon inyoung infants, even following the administrationof diuretic. Since the information derived fromDMSA scintigraphy or diuretic renography rarelyinfluences practical management in the first fewweeks or months of life, isotope imaging is bestdeferred until 1–3 months of age.

A rational approach todiagnosis and management

Diagnostic pathwaysSuggested diagnostic pathways for the postnatalinvestigation of different prenatally detected urinarytract abnormalities are illustrated in Figures 10.5–10.8. These are suggested as broad guidelines, butit may be necessary to take additional factors intoaccount when planning the timing and nature ofpostnatal investigation in individual cases.

Mild dilatation (pyelectasis)

Dilatation of the renal pelvis in the range AP diame-ter 5–10 mm is a common finding, being present atsome stage in approximately 1 in 100 pregnancies.As already stated, however, this is often a transientfinding which has resolved or improved in morethan 50% of cases by the third trimester. Mild dilata-tion has been studied as a possible marker ofchromosome abnormalities. When this is an isolatedfinding, the risk of chromosomal abnormalities is nohigher than for the general fetal population. Milddilatation does, however, carry a higher associationwith chromosomal abnormalities if it occurs inconjunction with other congenital abnormalities.The significance of mild dilatation as a possiblemarker of underlying VUR has already been consid-ered above. Regardless of its cause, the morbidity




Prenatal ultrasound

Renal dilation [no ureteric dilatation or bladder abnormality]

Bilateral

No reflux or urethral obstruction(presumed PUJ or VUJ obstruction)

MCU

Posteriorurethral valves Primary vesicoureteric reflux MAG3

Unilateral AP renalpelvic diameter >15 mm

Figure 10.5 Diagnostic pathway for postnatal investigation of prenatally detected dilatation confined to therenal collecting system(s).

MCU

DMSA

Surgical treatment

Prenatal ultrasound

Bilateral or unilateral renal dilatation± Ureteric dilatation (with or without renal dilatation)± Bladder abnormality (dilated or thick-walled bladder – with or without renal or ureteric dilatation)

Postnatal ultrasound of 24−72 hours

Posteriorurethral valves Primary vesicoureteric reflux

MAG3

No reflux or urethral obstruction(presumed PUJ or VUJ obstruction)

Figure 10.6 Diagnostic pathway for postnatal investigation of renal dilatation which is accompanied by uretericdilatation and/or a bladder abnormality.



generated by mild dilatation appears to be minimal.In a follow-up study, totalling 122 child-years offollow-up, there were only two episodes of morbid-ity related to the urinary tract, neither of which were

due to reflux. In a questionnaire case–control studyreported from the Netherlands, the incidence ofurinary tract symptoms in children with a history ofprenatally detected mild dilatation was comparedwith normal controls in the age range 4–9 years. Nodifference was found in the incidence of eitherurinary tract infection or incontinence between thetwo groups.

It is important to alleviate the anxiety whichmay inevitably be created in the minds of parentsfollowing the discovery of mild dilatation and toensure that infants are not overinvestigated.

Key points

• The sensitivity of ultrasound for theprenatal detection of urinary anomaliesis dependent upon a number of factors,most importantly gestational age atscanning.

Prenatal ultrasound

Postnatal ultrasound of 1–14 days

Renal dilatation unilateral <15 mm No ureteric dilatation or bladder abnormality

Repeat ultrasound3 months

MCU if urinarytract infection

Figure 10.7 Diagnostic pathway for postnatal inves-tigation of mild unilateral dilatation (renal pelvicanteroposterior diameter <15 mm), without coexistingureteric dilatation or bladder abnormality.

Prenatal ultrasound

Unilateral multicystic dysplastic kidney

Contralateral kidney normal Contralateral kidney abnormalUreteric dilatation [with or without renal dilatation]

MCU

No refluxContralateral [or bilateral] reflux

MAG3DMSA

Figure 10.8 Diagnostic pathway for the investigation of prenatal ultrasound appearances suggesting multicys-tic dysplastic kidney (see also Chapter 9).


• The majority of infants with prenatallydetected uropathies are entirelyasymptomatic and outwardly normalat birth.

• Although information on the long-termoutcome and natural history ofasymptomatic prenatally detecteduropathies is being acquired, muchis still unknown. Surgical interventionis generally unwarranted unless thereare clear-cut indications.

• The published results of vesicoam-niotic shunting relate largely tofetuses with severe degrees of renalimpairment. A possible benefit fromfetal intervention in less severelyaffected cases (where there is a betterprospect of improving the functionaloutcome) cannot be discounted.

• The combination of prenatal diagnosisand termination of pregnancy isresulting in declining numbers ofreferrals of severe but non-lethalurological malformations such asprune-belly syndrome and cloacaland classic bladder exstrophy.

• Mild dilatation (pyelectosis) is acommon finding of minimal clinicalsignificance. The role of micturatingcystography is controversial, but theavailable evidence suggests that thisis no longer justified on a routinebasis.

Further reading

Dhillon HK. Antenatal diagnosis of urinary tractanomalies. In: Burge DM, Griffiths DM, SteinbrecherHA, Wheeler RA (eds). Paediatric Surgery. London:Hodder Arnold, 2005: 435–439

Dhillon HK. Perinatal urology. In: Godbole P, Gearhart JP,Wilcox DT (eds). Clinical Problems in PediatricUrology. Oxford: Blackwell Publishing, 2006: 9–19

Godley ML, Desai D, Yeung CK et al. The relationshipbetween early renal status, and the resolution of vesico-ureteric reflux and bladder function at 16 months. BJUInt 2001; 87: 475–462

Holmes N, Harrison MR, Baskin LS. Fetal surgery for poste-rior urethral valves: long-term postnatal outcomes. Paedi-atrics 2001; 108: 36–42

Thomas DFM. Fetal urology and prenatal diagnosis:current themes. Fetal and Maternal Medicine Review2004; 15: 343–364



Stone disease in children

Patrick G Duffy, David FM Thomas and Martyn E Flett

Introduction

Urinary calculi (stones) are rare in children, whoare estimated to account for only 2–3% of allpatients with stone disease. Infection remains amajor aetiological factor, particularly in boys, butthe proportion of affected children with an under-lying biochemical predisposition appears to beincreasing. For this reason, metabolic evaluation isessential for every child. The rate of stone recur-rence is lower in children compared with adults.The majority of stone disease is now managed, asin adults, by lithotripsy or endourologicaltechniques and, as a consequence, the incidence ofopen surgery has decreased dramatically.

Incidence and epidemiology

Geographical variations in the incidence of stonedisease in children reflect differences in the preva-lence of environmental, dietary and geneticfactors. In the UK the estimated incidence ofurinary calculi in children is approximately 3 newcases per million of the population per year. Arecent review suggests that although infectivecalculi are more common in boys under 5 yearsof age there is also an increased incidence ofmetabolic abnormalities. The greater frequency ofinfection in uncircumcised infants and differingcultural attitudes to neonatal circumcision mayhelp to explain the higher incidence of stone

disease in certain European countries comparedwith the United States where neonatal circumci-sion remains commonplace.

The incidence of stones is twice as high in boysas it is in girls. Moreover, the peak age of presen-tation is younger in boys, being 3 years vs 4 yearsin girls. This gender difference reflects in part therole of bacterial colonisation and subsequenturinary infection in uncircumcised boys.

A geographical ‘stone belt’ extending from theBalkans across Turkey, Pakistan and northern Indiais characterised by a high incidence of endemicbladder stones in children. Chronically inadequatedietary intake of protein has been implicated, butrelative dehydration associated with the climate anddiarrhoeal illness may also be a contributory factor.

A study reported from London found that theproportion of paediatric stones secondary to infec-tion has fallen from 60% to 30% over a 30-yearperiod. This decrease parallels other series fromaround the world, with an increased relativeproportion of metabolic abnormalities in richerdeveloped countries and a corresponding decreasein infective and endemic stones.

Pathology/aetiology

Urinary calculi are composed of crystalline andmatrix components in varying proportions. Matrix,a gelatinous glycoprotein, is a particular feature ofinfective stones, which are typically soft and crumbly

11

Topics coveredIncidence and epidemiologyPathology/aetiologyClinical presentation

Diagnostic imaging, metabolic screeningOpen stone surgeryMinimally invasive modalitiesStone recurrence


in composition. Metabolic stones, e.g. cystine andxanthine, are predominantly crystalline and corre-spondingly harder. The terminology historically usedto describe the crystalline structure of urinary calculi(‘struvite’, ‘brushite’, ‘weddellite’, etc.) is uninforma-tive, and in this chapter stones are categorised byreference to their chemical composition.

Factors involved in stone formation•• Urinary concentration, ionic activity and

solubility of stone-forming constituents.Stone formation is initiated by the precipitationof urinary constituents from solution, followedby crystal formation. In turn, this process isinfluenced by the urinary excretion rate of thestone-forming substance, the level of hydrationand the urinary pH.

•• Presence of abnormal urinary metabolitesor pathologically elevated concentration ofnormal urinary constituents. When a metabo-lite is excreted in high concentrations its satura-tion point in the urine is exceeded and crystaldeposition occurs, progressing to stone forma-tion. Reduced urinary output, leading to ahigher urinary concentration of the metaboliteand unfavourable urinary pH, will acceleratethis process.

•• Urinary infection. Certain bacterial species,notably Proteus, Klebsiella and Pseudomonas, arecapable of the enzymatic splitting of urea toproduce NH3, with consequent elevation of theurinary pH and precipitation of ammoniumsalts. Infection is also a key factor in the produc-tion of the proteinaceous matrix component ofcalculi.

•• Anatomical abnormalities of the urinarytract. Urinary infection associated with under-lying urological abnormalities predisposes tostone formation by the mechanisms outlinedabove. Stasis of urine within an obstructed ordilated urinary tract creates an environment inwhich stone-forming substances are more likelyto precipitate out of solution and thus initiate

stone formation. This process can occur insterile urine, but not uncommonly infection andstasis coexist.

•• Foreign materials. Non-absorbable foreignbodies, usually surgical in origin (stents,fragments of catheters, non-absorbable suturesor staples) act as a nidus of encrustation andstone formation.

•• Prematurity. Ex-premature children (born atless than 37 completed weeks’ gestation) are atmuch greater risk of nephrocalcinosis andnephrolithiasis. Approximately 20% of babiesborn under 32 weeks’ gestation developnephrocalcinosis and 5–9% have calculi. Therisks are increased with increasing prematurityof birth, decreasing birth weight, co-morbidityand the use of furosemide, thiazides and otherdrugs. Premature and formula-fed babies haveincreased solute excretion (e.g. oxalate).Babies receiving parenteral nutrition have ahigher oxalate and calcium but lower citrateexcretion, contributing to higher calciumoxalate saturation.

Aetiology: clinical aspectsInfective calculi

Infective stones initially comprise a combination ofmagnesium, ammonium phosphate and glycopro-tein matrix in varying proportions. Calciumphosphate and other inorganic constituents thenbecome incorporated into the expanding stonemass. Their consistency is variable, with areas ofhard calcified material embedded within softer, lessdensely calcified matrix. Calcified areas are radio-opaque but the softer matrix component, whichmay extend throughout much of the collectingsystem, is radiolucent or only faintly apparent onplain X-ray. The descriptive term ‘staghorn’ refersto an infective calculus that has adopted the config-uration of the renal pelvis and calyces (fancifullylikened to the antlers of a stag). Rarely, the infec-tive process progresses to involve the entire renalparenchyma in a chronic inflammatory mass –xanthogranulomatous pyelonephritis (see below).



Metabolic calculi

Calcium

Hypercalciuria is the commonest metabolic abnor-mality found in children with calculi, occurring in upto 25% of patient in some series. Urinary calciumexcretion is much higher in infants than in olderchildren. In children, hypercalciuria is very rarelyassociated with hypercalcaemia. The majority ofchildren have no identifiable underlying tubulopathyor other disorder. Elevated urinary calcium levels are,however, more frequent in certain groups: ex-prema-ture infants, children with significant neurologicaldefects impairing mobility and as a side effect ofdrugs (furosemide). In newborn infants, the combi-nation of hypercalciuria and nephrocalcinosis pointsto the presence of a renal tubular defect – a majordisorder of calcium metabolism.

Oxalate

Hyperoxaluria is found in 10–20% of children withstones and half of these have primary hyperoxaluria.Secondary hyperoxaluria can occur as a result ofcongenital enteropathies and after surgical smallbowel resection. Children with cystic fibrosis havea higher incidence of renal stones and commonlyhave hyperoxaluria. Two rare genetically determinedmetabolic disorders are expressed as excessiveproduction of oxalic acid: urolithiasis and nephrocal-cinosis. The infantile form of primary hyperoxaluriais rapidly progressive and is characterised by thedeposition of oxalate throughout the tissues. Asecond form presents with calculi in adult life. Acombination of renal and orthotopic liver transplan-tation has been advocated for severe forms, with theaim of treating not simply the renal complicationsbut also the underlying hepatic enzyme deficiency.

Cystine

Cystine is one of four amino acids affected by arecessive inherited disorder of renal tubularreabsorption (the others being lysine, arginine andornithine). The solubility of cystine is relatively poorand its elevated concentration within the collecting

system results in crystal deposition and stone forma-tion. Although cystine itself is only weakly radio-opaque, the incorporation of calcium within theaggregation of amino acid crystals forms hardstones, which are clearly visualised on plain X-ray.

Uric acid

Metabolic disorders of uric acid metabolism arerare in children, but acute deposition of uric acidcrystals within the urinary tract can occur as a resultof massive cell breakdown, e.g. following the intro-duction of cytotoxic treatment for leukaemia orlymphoma. In these conditions uric acid crystallinedebris ‘silts up’ the collecting systems, leading toanuric renal failure. Uric acid is radiolucent andthus cannot be directly visualised on plain X-ray.

Xanthine

Xanthine oxidase deficiency, a rare autosomalrecessive disorder, results in the deposition ofinsoluble non-opaque xanthine stones within theurinary tract.

Underlying urological conditions Predisposing urological abnormalities can be identi-fied in approximately 20–30% of children withurinary calculi, a far higher figure than in adults.Although vesicoureteric reflux (VUR) may play anaetiological role by promoting urinary infection, itmay represent a secondary phenomenon, particu-larly following the passage of ureteric calculi. Refluxshould therefore be reassessed some months afterstone clearance if antireflux surgery is envisaged.

The role of obstruction and stasis is generallyeasier to establish. Although uncommon, stonesassociated with primary pelviureteric junction(PUJ) obstruction are characteristically small andmultiple (fancifully likened to melon seeds). Stonesforming within megaureters can occasionallypresent acutely with complete upper tract obstruc-tion following impaction at the vesical junction.

The use of intestinal segments for bladder recon-struction (enterocystoplasty) is accompanied by a

Stone disease in children 145


significant risk of stones, amounting to 30–40% insome series. A combination of factors includesstasis, the presence of intestinal mucus within theurine acting as a nidus for crystalline deposition,and chronic low-grade bacteriuria. Regular bladderwashouts reduce the risk, principally by ensuringmore effective clearance of urinary mucus thanintermittent catheterisation alone.

Clinical presentation

AgeStones may develop from as early as 2–3 monthsof life. In children there is a higher prevalence inearly childhood (less than 5 years), predominantlydue to an excess of infective stones secondary tourinary tract infection.

Urinary infectionAlthough older children may present with recog-nisable symptoms of urinary infection, the clinicalpicture in infants may be deceptively non-specific,consisting of vague ill health, low-grade fever andfailure to thrive. The isolation of Proteus from achild’s urine should always prompt investigationfor possible underlying stone disease.

HaematuriaMacroscopic or microscopic haematuria is acommon feature of calculi, but there is only a poorcorrelation between the severity of haematuria andthe extent and distribution of stones within theurinary tract. Absence of blood on microscopy orreagent strip testing does not exclude the possibil-ity of stones.

Passage of stone material per urethramOccasionally stones come to light when a fragmentor some softer matrix material is passed perurethram. In infants the presence of unusualmaterial and streaks of blood in the nappy may beincorrectly ascribed to balanitis.

PainAcute renal colic of the pattern and severityencountered in adults is not a prominent feature ofthe symptomology in children. When pain doesoccur it is often a poorly localised symptom in afractious, unwell child.

Abdominal massXanthogranulomatous pyelonephritis (see below)presents with general ill health which may beaccompanied by a palpable abdominal mass – aclinical picture resembling Wilms’ tumour.

Diagnosis

The role of diagnostic imaging can be consideredat two levels.

Initial screening for possible calculiUltrasound

In experienced hands ultrasound is a sensitivemodality for the detection of renal calculi. Dependingon their physical characteristics (chemical compo-sition, hardness, etc.), calculi can be directlyvisualised on ultrasound. In addition, solid stonescast an ‘acoustic shadow’, which serves to distin-guish calculi from other echogenic lesions withinthe renal collecting system (Figure 11.1). Uretericcalculi and small bladder calculi may sometimes bedifficult to detect on ultrasound.

Abdominal X-ray

Until recently a plain abdominal radiograph hasbeen considered mandatory to look for possiblecalculi in any child undergoing investigation forhaematuria. Similarly, the investigation of urinaryinfection in boys less than 5 years of age has previ-ously included a routine plain abdominal X-ray(Figure 11.2). Likewise, a documented Proteusurinary infection at any age was thought to merita plain abdominal X-ray, except in older girls with



uncomplicated urinary infection of mild ormoderate severity. However, the sensitivity ofultrasound for the detection of calculi is now suchthat this can be employed as the first-line investi-gation in the majority of instances, with abdomi-nal X-ray being undertaken on a selected basis (seeChapter 3).

Unenhanced spiral computed tomography

This procedure is rapidly being adopted as theinitial investigation of choice for adults withsuspected stone disease. Spiral computed tomog-raphy (CT) provides an accurate diagnosis withinminutes, avoids the potential risk of adversereaction to contrast media and will positivelydemonstrate the presence of radiolucent calculithat cannot be directly visualised by conventionalradiology. However, the radiation dosage isestimated to be three to five times greater than thatof an intravenous urography (IVU), although thisnevertheless amounts to only a quarter of therecommended limit of medical radiation exposurefor a child in a year. Other drawbacks include therequirement for more complex equipment thanIVU and greater difficulty in interpreting theimages of the collecting system. The role of spiralCT as front-line diagnostic modality in childrenrequires further evaluation.

Evaluation prior to treatment of proven stone diseaseDMSA

Regardless of whether open surgery or minimallyinvasive treatment is planned, differential functionin the affected kidney(s) should be documented onDMSA (dimercaptosuccinic acid), and re-evalu-ated after treatment.

Intravenous urography

For a number of reasons the IVU retains a valuable, iflimited, role in the diagnostic evaluation of stones –for example, by permitting visualisation of non-opaque stones and the matrix component of infectivestaghorn calculi. Information on calyceal anatomy isimportant in planning percutaneous nephrolitho-tomy (PCNL) and external shockwave lithotripsy


Figure 11.1 Ultrasound appearances of renal calculi,illustrating ‘acoustic shadow’.

Figure 11.2 Plain X-ray revealing multiple infectivecalculi in the left kidney.


(ESWL). Ureteric calculi are best localised by intra-venous urography (Figure 11.3). Finally, the IVUmay be helpful in identifying any underlyinganatomical abnormality predisposing to urolithiasis.

Additional investigations

Micturating cystography

Micturating cystography (MCU) is not routinelyrequired. Infection and the passage of stonematerial to the bladder may result in transientVUR, which resolves once the infection has beentreated and stone clearance achieved. However,when ureteric dilatation persists postoperatively, orin the event of further infection, an MCU shouldbe performed.

Dynamic renography

Dynamic renography, e.g. MAG3 (mercaptoacetyl-triglycine), DTPA (diethylenetriamine pentaaceticacid), is undertaken if obstruction is suspected.However, the diagnosis of obstruction should notbe made in the presence of a large calculus withinthe renal pelvis. Assessment of a possible pelvi-ureteric junction (PUJ) obstruction can only bemade after a period of time following the completeremoval of the stone.

Computed tomography

As already indicated, the potential role ofunenhanced spiral CT in the initial diagnosis ofstone disease is still undergoing evaluation inchildren. However, CT has a well-establishedrole in the diagnosis of xanthogranulomatouspyelonephritis and for visualising non-opaquecalculi.

Metabolic investigations

Underlying metabolic disorders are not alwaysreliably reflected in the chemical composition ofthe stones they give rise to. For this reason urinarybiochemistry is more useful than the time-honoured practice of sending stones for labora-tory investigation. The presence of urinaryinfection does not exclude the possibility ofmetabolic stones, as the two aetiologies maycoexist. Every child with stone disease, regardlessof the perceived aetiology, should thereforeundergo metabolic screening after the eradicationof infection (Table 11.1).

Stone screening

Stone screening can be reliably undertaken on arandom ‘spot’ sample of 2–5 ml of urine, althoughan early morning specimen may be preferable forsome studies. Twenty-four hour urine collectionsare impracticable in children and are only requiredfor the specific investigation of rare metabolicdisorders.


Figure 11.3 Intravenous urogram demonstrating acalculus in a single (orthotopic) ureterocoele. The IVUis also useful in helping to establish the nature of thepredisposing anatomical abnormality.


Management

Some form of intervention is almost invariablyrequired to physically remove the stone(s) or reducethem to fragments, which can then be passedspontaneously. In adult practice minimally invasivemodalities have become the mainstay of treatment.With improvements in the technology and increas-ing experience these techniques are now effectivelyused in paediatric practice, making the need foropen surgery significantly less common. However,there are aspects of treatment unique to paediatricstone disease that need specific consideration:

• Sixty per cent of stones in children are infectivein origin and often bulky; as such, they may notbe amenable to ESWL. However, some authorshave published evidence to support thecontention that even large calculi in infantsunder 1 year of age respond well to ESWL.

• General anaesthesia is necessary for youngerchildren in view of the discomfort and to ensurethey remain still. The majority of ESWL proce-dures in adults are performed without generalanaesthesia.

• PCNL and ureteroscopy can now be performedwith suitable instruments in children; however,the instruments used in children are, nevertheless,

relatively large in relation to body size because ofthe need to insert probes for stone disintegrationof large calculi.

Open stone surgery

Kidney Following exposure and mobilisation of thekidney, isolated stones within the collectingsystem can usually be removed with stone forcepsvia an incision in the renal pelvis without unduedifficulty (Figure 11.4). The bulk of a staghorncalculus can also be removed by this approach, butthe subsequent removal of fragments impacted inthe calyces, necessary to achieve total stone clear-ance, often proves time-consuming and frustrat-ing. Some of the manoeuvres that can facilitatethis task are illustrated in (Figure 11.5). With theadvent of ESWL it is often preferable to treat anysmall residual fragments by ESWL at a later date,rather than incur the haemorrhage and parenchy-mal damage associated with multiple incisions inthe renal cortex.

Techniques dating from the days of extensiveopen stone surgery in adults (anatrophic nephrolitho-tomy, renal cooling, etc.) have only a very limitedapplication in paediatric practice. To minimise therisk of unsuspected retained fragments, intraoper-ative ‘on-table’ X-rays of the kidney are mandatoryto confirm that stone clearance has been achieved(Figure 11.6). Intraoperative X-rays may also helpthe surgeon decide when to abandon nephrolitho-tomy in favour of postoperative ESWL.

Extrarenal drainage is essential in view of theconsiderable leakage of urine that may occur fromthe incision sites in the kidney postoperatively.Following extensive renal surgery a short period ofnephrostomy or indwelling JJ stent drainage mayalso be indicated (Figures 11.7 and 11.8).

UreterIn the absence of obstruction, severe pain or infec-tion, a small stone (e.g. <5 mm) can be managed

Table 11.1 Metabolic screening protocol

Fasting blood sample for plasma levels of urea,electrolytes, creatinine, calcium, phosphate, uricacid

Early morning urine sample (pH to exclude renaltubular acidosis)

‘Spot’, i.e. untimed, urine sample 2–5 ml (dividedin the laboratory into two aliquots)

First aliquot acidified and analysed forcreatinine, calcium, magnesium, cystine, oxalate

Second aliquot alkalinised and analysed forcreatinine and uric acid



expectantly in the hope that it will pass sponta-neously into the bladder, from where it will bepassed by voiding or will be accessible to

endoscopic removal. If the stone fails to pass or isaccompanied by symptoms or obstruction, thefollowing options are considered.

Ureteroscopy

This procedure can be performed in any age group.The stone is disintegrated with a laser probe – seebelow.

Stone basket

Stone extraction using a basket is not of practicaluse in paediatric practice. After disintegration,most fragments pass spontaneously.

Ureterolithotomy

Stones in the distal ureter can be removed via aPfannenstiel incision. Midureteric stones are bestapproached transperitoneally via an obliquemuscle-cutting incision. The ureter is closedloosely with a few interrupted absorbable suturesto minimise the risk of stricture formation.


Figure 11.4 Pyelolithotomy. Open removal of acalculus from the renal pelvis.

Figure 11.5 Additional intraoperative manoeuvres for the clearance of calyceal calculi or fragments. (a) Surgi-cal exposure of calyceal neck by dissection at the renal hilum. (b) Nephrolithotomy. (c) High-pressure salineirrigation.

(a) (b) (c)


BladderStones which have recently passed into the bladderfrom the upper tracts can be managed conserva-tively in the expectation that they will be passedfrom the bladder by voiding, but stones arising denovo within the bladder, or bladder stones formingaround the nidus of an upper tract fragment, areoften too large to pass spontaneously by the timethey are diagnosed.

Open surgery (cystolithotomy) remains thepreferred option for very large stones, particularlythose forming within augmented bladders. Wherethe bladder neck has been formally closed inconjunction with augmentation and the creation ofa Mitrofanoff stoma, open cystolithotomy is thesimplest and most effective surgical option.

UrethraUrethral calculi are rare in children and result fromimpaction of a calculus (or post-ESWL fragments)during its passage through the urethra, or in situstone formation within an anatomical abnormality,such as a müllerian remnant or the urethral stumpof a rectourethral fistula following surgery for ananorectal anomaly.

Urethral calculi can be removed or crushedusing rigid endoscopic biopsy forceps. Meatotomy


Figure 11.6 Intraoperative ‘on-table’ X-ray to confirmstone clearance.

Figure 11.7 Multiple infective calculi, removed bypyelonephrolithotomy from the patient illustrated inFigure 11.2.

Figure 11.8 Plain abdominal X-ray of the patientillustrated in Figures 11.2 and 11.7. Total stone clear-ance achieved, indwelling JJ stent in situ.


may be required to release a stone impacted withinthe fossa navicularis.

Minimally invasive treatment

KidneyExternal shockwave lithotripsy (Figure 11.9)

Shockwaves generated either by high-tension sparkor by piezoelectric energy are transmitted througha fluid to the patient. Using ultrasound or X-raylinked to the shockwave generator, this energy isfocused on the renal stone(s). Unlike adults, in thepaediatric age group general anaesthesia is frequentlyrequired to ensure that a suitable position ismaintained throughout the duration of treatment,to provide analgesia and ensure cooperation withthe procedure. Repeated general anaesthetics maybe required to achieve stone clearance.

ESWL has been demonstrated to be valuable forthe treatment of small or non-infective stones inolder children, and also for ‘mopping up’ residualfragments following PCNL or open stone surgery.

Percutaneous nephrolithotomy

A percutaneous track is established to permit the introduction of an endoscope into the renalcollecting system. Under direct vision the stone isremoved or disintegrated most commonly with an

ultrasonic probe (Figure 11.10). Although PCNLhas so far been largely limited to older children andadolescents, the availability of instrumentsdesigned specifically for paediatric use will extendthe role of this modality.

UreterUreteric stones, once visualised by semirigid orflexible ureteroscopy (Figure 11.11a and b), arefragmented by laser (pulse dye laser or holmium).Infrequently, where large fragments remain, a JJstent may be required.


Figure 11.9 Child beingtreated under general anaes-thesia by a current generationStorz lithotripter. Stone locali-sation and imaging during thetreatment is achieved by acombination of X-Ray C armand ultrasound.

Figure 11.10 Percutaneous nephrolithotomy (PCNL).


BladderEndoscopic treatment is now feasible for the major-ity of bladder stones. The stone is shattered using alithoclast (employing the principle of a pneumatic

drill) passed down the channel of a paediatric cysto-scope (Figure 11.12). Larger fragments are removedby vigorous irrigation and suction, whereas smallfragments can be left to pass spontaneously.

Complications

Open stone surgeryComplications include haemorrhage, particularly aftermultiple nephrotomies, retained or displaced stonefragments, prolonged urinary leakage and parenchy-mal damage resulting in loss of renal function.

Open ureterolithotomy carries a risk of uretericstricture. Ureteric damage (perforation, avulsion)may also result from injudicious attempts atureteric basket extraction.

Minimally invasive modalitiesInitial concerns regarding the safety of thesetechniques in children, particularly the risk ofparenchymal damage and subsequent hyperten-sion, have not been borne out in practice, althoughthe long-term outcomes have yet to be fullydocumented.


Figure 11.11 (a) Ureteroscopy and laser lithotripsy.(b) Ureteroscopic view demonstrating two individual5 mm calculi prior to laser fragmentation. Note guidewire running in 11 o’clock position.

Figure 11.12 Endoscopic fragmentation of bladdercalculus by lithoclast.

(a)

(b)


Parenchymal damage is an anticipated riskassociated with PCNL, but, as with ESWL in thisage group, the findings of postoperative DMSAscans have generally shown very little evidence ofsignificant scarring. Ureteroscopy may result intransient reflux and carries a possible risk of fibro-sis and vesicoureteric junction obstruction, but inthe hands of an experienced endourologist the riskof complications appears to be low.

Results

A recent review of 15 years of paediatric experienceconfirmed that the minimally invasive managementof calculi is both safe and effective. In this series 218renal units were managed by ESWL (140 renalunits), PCNL (43 renal units) or ureteroscopy (35renal units). The incidence of underlying urologicalabnormalities was around 20%. The overall successrate in clearing stones <20 mm by ESWL was 85%(comparable with other recent published studies).However, in cases of larger or staghorn calculi, theresults were significantly worse. For these and certainother stones there has therefore been a gradual shiftto the use of PCNL – for which a clearance rate of79% was achieved in this series. PCNL had a7% retreatment rate (although 37% of childrenrequired some additional procedures), albeit with acomplication rate of only 6%. For ureteric stones,ureteroscopy and laser lithotripsy with the holmiumlaser was highly effective, achieving 100% clearance.

Conclusions based on the published literature canbe briefly summarised as follows: renal calculi whichare <20 mm are most effectively treated by ESWL,whereas larger stones and especially staghorn calculiare better treated by PCNL. For ureteric stones,ureteroscopy and lithotripsy with the holmium laseris now the modality of choice. In addition, there isstill an occasional place for open surgery.

RecurrenceInfective calculi

The recurrence risk can be minimised by correct-ing any underlying predisposing anatomical

abnormality and by maintaining infection-freeurine with antibiotic prophylaxis for 12 monthsfollowing surgery.

Metabolic calculi

A high fluid intake is essential. In addition, anumber of specific measures can be employed, e.g.pyridoxine in primary hyperoxaluria, D-penicil-lamine in cystinuria, and allopurinol in conjunc-tion with a low-purine diet for xanthinuria.

Xanthogranulomatouspyelonephritis

This rare manifestation of stone disease is charac-terised by features of chronic sepsis – weight loss,anaemia, elevated erythrocyte sedimentation rate(ESR) – and the presence of an inflammatory masswhich may extend to involve adjacent viscera. Thediagnosis is confirmed by a combination of ultra-sound, CT (Figure 11.13) and DMSA, whichreveals absent or minimal function in the affectedkidney. Treatment consists of nephrectomy.Although open nephrectomy is generally prefer-able in view of the dense inflammatory adhesionsand risk of damage to adjacent organs, the use oflaparoscopic nephrectomy for this condition hasalso been reported.


Figure 11.13 CT scan. Xanthogranulomatouspyelonephritis of the right kidney, illustrating calculiembedded within a non-functioning inflammatoryrenal mass. Normal left kidney.


Key points

• Urinary calculi are rare in childhood.Urinary infection is an importantaetiological factor, but underlyingmetabolic predisposition is beingincreasingly recognised as a majorcause.

• Every child presenting with calculishould be thoroughly evaluated toidentify any underlying metabolicdisorder or urological malformation.

• Urine biochemistry should becombined with stone analysis todiagnose metabolic disorders.

• Minimally invasive modalities such asESWL, PCNL and endoscopiclithotripsy have now largelysuperseded open techniques in thetreatment of children’s stones.

• Careful follow-up, with maintenance ofsterile urine and appropriate treatmentof any metabolic disorder, is essentialto minimise the risk of stonerecurrence.

Further reading

Argyropoulos AN, Tolley DA. Optimizing shock wavelithotripsy in the 21st century. Eur Urol 2007; 52:344–354

Choong S, Whitfield H, Duffy P et al. The management ofpaediatric urolithiasis. BJU Int 2000; 86(7): 857–860

Fraser M, Joyce AD, Thomas DFM, Eardley I, Clark PB.Minimally invasive treatment of urinary tract calculi inchildren. Br J Urol 1999; 84: 339–342

Raza A, Turna B, Smith G, Moussa S, Tolley DA. Paediatricurolithiasis: 15 years of local experience with minimallyinvasive endourological management of paediatriccalculi. J Urol 2005; 174(2): 682–685

van’t Hoff WG. Aetiological factors in paediatric urolithia-sis. Nephron Clin Pract 2004; 98: c45–48




Urinary incontinence

Henrik A Steinbrecher, Padraig S Malone

and Anthony MK Rickwood

Introduction

Urinary incontinence by day (diurnal), night(nocturnal) or both day and night is commonduring childhood. It can be defined as the ‘invol-untary loss of urine from the urinary tract’. It isoften a cause of major social morbidity in affectedindividuals: it causes children to be stigmatised bytheir peers and has a disruptive impact within theirfamilies. Children who wet, therefore, deserve asmuch attention as children with other urologicaldisorders.

The terminology currently recommended by theInternational Children’s Continence Society willbe employed throughout this chapter. A simpleclassification used in this chapter is shown inFigure 12.1. Although organic (anatomical) causesof incontinence are rare (accounting for well under1% of referrals from general practice), it is essen-tial that they are excluded in the first instance sincethey almost always require active treatment (oftensurgical) and, in some instances, pose a threat torenal function. Only when an organic cause hasbeen excluded can the complaint be assumed to befunctional in aetiology. The problem then essen-tially becomes social rather than medical, andbecause the natural history of almost all thesedisorders is benign, any decision regarding activemanagement should rest principally with parentsand the young patient.

Developmentof bladder control

During infancy, voiding is a reflex act which ismediated and coordinated at brainstem level.Nevertheless, the arousal characteristically occurringpremicturition indicates the existence of sensoryinput to higher centres. As a result, for example,voiding rarely, if ever, occurs during sleep. Althoughreflex voiding contractions are not under any volun-tary control, they are nonetheless accompanied byrelaxation of the sphincter complex (detrusor–sphincter synergia) and detrusor contractions are

12

Topics coveredDevelopment of bladder controlPatient assessment

Organic urinary incontinenceFunctional diurnal incontinenceNocturnal enuresis

Childhood urinaryincontinence

Nocturnal Diurnal

FunctionalFunctional Neuropathic

Obstructive Structural

Figure 12.1 Simple classification of childhood urinaryincontinence.


sustained until the bladder is empty. This pattern ofnormal reflex voiding is sometimes disturbed ininfants with organic bladder outflow obstruction(e.g. posterior urethral valves), while studies of boyswith gross vesicoureteric reflux have shown high-pressure dysfunctional voiding even in the absenceof demonstrable urethral obstruction.

During the first year of life the frequency ofvoiding remains fairly constant, at approximately 20times per day, declining over the next 2 years toaround 11 times per day, and by the age of 7 yearssettling to an average of five times per day. Thisdecreased frequency is associated with a growth-related increase in bladder capacity that is dispropor-tionately greater than the volume of urine produced.

Successful toilet training is dependent uponseveral factors, the most important being thedevelopment of voluntary inhibition of the voidingreflex. Following successful toilet training, thenormal bladder cycle consists of the followingstages, each under neurological modulation:

1. As the bladder fills, the urethral sphinctercontracts via modulation from T10–12 lumbarsympathetic pathways and S2–4 voluntarysomatic control.

2. The urethral sphincter relaxes via S2–4 volun-tary somatic control.

3. The pelvic floor relaxes via S2–4 voluntarysomatic control.

4. The detrusor contracts in response to stimula-tion via parasympathetic S2–4 pathways.

5. Urinary flow occurs to completion.6. The urethral sphincter contracts via S2–4

voluntary somatic control.

In some young children – perhaps even the major-ity – there is a transitional phase where this abilityto inhibit the voiding reflex is related to fillingvolume, so that once this is reached there is only ashort interval between the first perception of adesire to void and the necessity to do so. Usuallyby 5 years of age, a mature filling/voiding cycleexists, with maintenance of detrusor stabilitydespite a strong desire to void. At the appropriatetime, voiding to completion occurs by sustained

detrusor contractions accompanied by synergisticsphincter relaxation.

Patient assessment

ClinicalExclusion of organic disease (Table 12.1) alwaysrepresents the first priority and is usually possibleon the basis of history, physical examination and,when appropriate, ultrasonography of the urinarytracts. More invasive investigations, includingurodynamics, are only required occasionally.

History

Whenever dealing with a child with urinary incon-tinence, the three fundamental questions to beaddressed are:

• Does the wetting occur principally orentirely by night, principally or entirely byday, or both by day and night?

• Is the problem primary (i.e. lifelong) orsecondary (i.e. of onset following toilet trainingand after a period when the child was dry)?

• In the case of daytime wetting, does thisoccur continuously or only intermittently?

For practical purposes, purely night-time wettingthat is primary and unaccompanied by any daytimesymptoms (primary monosymptomatic nocturnalenuresis) never has an underlying organic basis.Bedwetting that is of secondary onset or is associ-ated with daytime symptoms, by contrast, can very


Table 12.1 Organic causes of childhood urinaryincontinence

Urinary infection (Intermittent leakage)Neuropathic (Continuous/intermittent leakage)Bladder outflow obstruction (Intermittent leakage)Structural (Continuous leakage)

Exstrophy/epispadiasUreteric ectopia (girls)Congenital short urethra (girls)Urovaginal confluence (girls)


occasionally result from bladder outflow obstruc-tion or neurological disease. It should be noted thatpolyuric states (e.g. diabetes mellitus or insipidus)typically cause nocturia, not bedwetting.

Although wetting confined solely to the daytimeis usually functional, in girls there are two otheranatomical possibilities deserving consideration,one being retrograde filling of the vagina duringvoiding that leads to slight urinary leakage for thefirst half hour or so thereafter. Typically this occursin girls with partial occlusion of the introitus dueto extensive labial adhesions (Figure 12.2). Theother possibility is that of an ectopic ureter. Urine

may pool within the dilated ureter or vagina,leaking out only when the child is active andupright but not while the child is asleep and lyingflat. A number of key considerations are helpfulwhen evaluating the history:

• Both primary and secondary wetting arecompatible with either a functional disorderor organic disease.

• Although secondary wetting is usuallyfunctional in aetiology, it can also occur as aresult of bladder outflow obstruction orneurological disease.

• A congenital structural anomaly can bevirtually discounted as a cause of wetting ina child who was previously dry.

• Daytime wetting that is truly continuousalways has an underlying organic cause,either structural or neurological.

• Although intermittent daytime wetting is veryoccasionally indicative of bladder outflowobstruction or neurological disease, it is offunctional origin in the great majority ofcases, particularly when the wetting occursinfrequently.

Typical information to be obtained in a history ofa child with wetting is listed in Table 12.2.

Physical examination

The examination of a child with incontinenceshould include the abdomen, spine and genitalia,along with assessment of the lower limbs and gaitand a simple lower limb neurological examination.Salient features on examination include:

• A palpably enlarged bladder, with or withoutpalpable kidneys, is indicative of outflow obstruc-tion, whether organic or neurological. A palpablebladder that is also expressible is virtually pathog-nomonic of neurological disease: this is all themore likely in the presence of gross constipation.

• Examination of the male genitalia will identifyprimary epispadias, pathological phimosis(balanitis xerotica obliterans) and meatal stenosis

Urinary incontinence 159

Figure 12.2 Six-year-old girl presenting withdribbling upon standing up after voiding. Examinationrevealed extensive occlusion of the introitus by labialadhesions, resulting in retrograde filling of the vaginaduring voiding. Symptoms were cured by separation ofthe labial adhesions.


(including, occasionally, stenosis of a hypospadiacorifice). Examination of the female genitaliawill identify primary epispadias (Figure 12.3) aurogenital sinus anomaly (Figure 12.4), fusedlabia minora and imperforate hymen. Anectopic ureteric orifice is only very rarelyevident on gross inspection, although in someaffected individuals urine may be seen leakingfrom the introitus. To avoid distress in older girlsand adolescents, it is generally more appropriateto undertake the examination under sedation oranaesthesia. Regardless of the setting, examina-tion of the genitalia should always be carried outin the presence of a chaperon.

• Hairy patches, swellings, cutaneous haeman-giomata and sinuses of the spine are stronglyindicative of underlying spinal dysraphism(although blind-ending pits overlying the tipof the coccyx are of no neurological signifi-cance). Sacral agenesis is detectable clinicallyby palpable absence of the lowermost sacralsegments and, in most cases, by the appear-ance of flattening of the upper buttocks.

• Neurological disease is suggested by exagger-ated lower limb reflexes (or frank clonus) orby wasting of the calves or deformities of thefeet, especially if asymmetrical. The lower-most sacral segments should be examined for


Table 12.2 History of a child with wetting

Example Comment

Number of episodes of Day = 5/7, 3×/day Accurate data should be obtained for wetting/day and or Night = 7/7, 1×/night ease of follow-up assessment. Terms nights/week (early morning) such as ‘occasional’ and ‘sometimes’

are unhelpfulFrequency of voiding/day Day/night = 7/1and voiding/nightPresence of urgency/ Child crouches down on heel, pushing Vincent’s curtsey sign on perineum to prevent leakageUrge incontinenceStress incontinence Laugh, exercise, coughStream – onset, presence Hesitancy may be caused by obstruction. of hesitancy A normal stream does not exclude

obstructionStream characteristic Stop/start, continuous Sign of obstruction or detrusor instabilityFluid intake, last drink ml/day of cola, blackcurrant, Cola drinks and blackcurrant juice have taken, type of drink taken water been incriminated as possible causes of

bladder instabilityBowel habit Bowels open 1–2×/day, It is vital to get a bowel history in

no pain, no blood, children with incontinencenormal motions

Use of shampoos, soaps, etc. Hair wash in bath, child It has been speculated that changes in sits in soapy water, etc. perineal bacterial flora can predispose

to urinary infections and secondary bladder instability

Family history of wetting Parents wet until This aspect of the history is only relevantteens, siblings wet to night-time wetting

Drug history, other health Asthma, cystic Some medical illnesses and their history fibrosis, ADHD treatment affect bladder function

ADHD, attention-deficit hyperactivity disorder.


motor and sensory integrity. An abnormalgait should also arouse suspicion of neuro-logical disease.

InvestigationsAn ultrasound scan of the abdomen and urinarytract is advisable for all children referred withdaytime wetting and should, whenever practicable,include estimation of postvoid residual urine inaddition to measurement of bladder wall thicknessand visualisation of the upper tracts. Findings ofpossible significance include:

• Duplication anomalies are of relevance towetting only in girls. Uncomplicated duplica-tion is unlikely to be significant, whereas theidentification of hydronephrosis or dysplasia inthe upper pole of a duplex kidney is strongly

suggestive of an ectopic ureter. It should benoted, however, that the ultrasound appear-ances of the kidney may be normal, in whichevent the demonstration of a dilated ureterbehind the bladder may provide the clue to thepresence of an ectopic ureter.

• Upper tract dilatation may be indicative oforganic bladder outflow obstruction or neuro-pathic bladder and while these conditions usuallygive rise to bilateral dilatation, they are notexcluded by the finding of unilateral dilatation.

• Bladder wall thickening, although suggestiveof bladder outflow obstruction or neuropathy, isalso commonly found, albeit to a minor extent,in children with functional detrusor overactivityand/or detrusor–sphincter dyssynergia.

• The presence of residual urine within thebladder after voiding is suggestive of bladderoutflow obstruction or neuropathy. However,this finding should be interpreted with caution,especially in younger children who commonlyhave a significant residual urine (exceeding 10%of expected bladder capacity) on some occasionsbut not others. Hence, whenever there is doubt,the examination should be repeated.


Figure 12.3 Female epispadias. Bifid clitoris withwide urethral meatus. This anomaly in females isinvariably associated with sphincter weaknessincontinence.

Figure 12.4 Anatomy of common urogenital sinuswith urovaginal confluence. (See also Chapter 14,Cloacal anomalies.)


A urinary flowmeter is often helpful in providingadditional information, albeit with the provisothat flow rate needs to be carefully interpreteddepending on the volume of urine voided.However, a flow rate of less than 15 ml/s or aurinary flow with a stop/start ‘staccato’ pattern issuggestive of anatomical or functional bladderoutflow obstruction.

Although urine culture is usually negative, girlswith asymptomatic bacteriuria represent a notableexception. In these patients the bacteriuria andthe wetting may be separate manifestations of acommon, single underlying pathology, typicallycharacterised by incomplete bladder emptyingfrom whatever cause.

Urodynamic examinations should be employedsparingly and selectively in children because theyare invasive and potentially distressing. The indica-tions include:

• suspicion of neuropathic bladder• suspicion of genuine stress incontinence• severe wetting that fails to respond to empirical

treatment based upon a clinical diagnosis.

Magnetic resonance imaging (MRI) of the spinalcord, cauda equina and sacrum is indicated shouldthere be suspicion of neurological disease.

Cystourethroscopy may be indicated, particu-larly for boys, when some form of anatomicalbladder outflow obstruction is suspected. This exami-nation may also be of occasional therapeuticbenefit, e.g. endoscopic resection of late presentingurethral valves.

Additional investigations are occasionallynecessary to confirm or exclude the presence of anectopic ureter and these usually take the form ofMRI (ideally MR urography) or laparoscopy. Inthe methylene blue test, the dye is instilled intothe bladder via a catheter, which is then removedand a pad placed over the vulva. Subsequentleakage of clear urine onto the pad confirms thepresence of an ectopic ureter: ‘blue’ leakage, bycontrast, indicates that the wetting problem is ofbladder origin.

Organic urinary incontinencein children (see Table 12.1)

Urinary infectionAcute lower urinary tract infection commonlycauses wetting in children (usually girls) whosebladder control is quite normal at other times.Once the infection is treated, the wetting usuallyrapidly resolves, although in a few cases, it persistsfor some time afterwards. The indications for inves-tigation are essentially the same as for the investi-gation of any child of comparable age presentingwith urinary infection of similar severity.

Spinal neurological diseaseClinical features suggestive of underlying neuro-logical disease comprise:

• urinary incontinence of unusual severity,especially if accompanied by constant dribblingof urine

• marked disturbance of bowel habit, particularlyif associated with faecal soiling

• an expressible bladder • any suggestion of lower limb locomotor

problems, clumsy gait, etc.

A spinal X-ray, traditionally undertaken as thefirst-line investigation in the presence of one ormore of the features listed above, is of limited valueas a normal examination does not exclude thepresence of neurological pathology, while theisolated laminal defects at L5 or S1 that arecommonly found are only very rarely of any signif-icance (unlike the occasional discovery of laminal orvertebral defects at two or more levels). For theseand other reasons, MRI of the spine has becomethe investigation of first choice in such cases and, inthe event of a positive finding or continuing suspi-cion of neurological disease, the opinion of a paedi-atric neurologist should be sought at an early stage.

Ultrasound may disclose upper tract dilatation(bilateral or unilateral), marked thickening of thebladder wall or a large residual urine volume.



Exstrophy/epispadiasSee Chapter 15.

Congenital short urethraAs with epispadias, the history is one of continuousurinary leakage and the urethral meatus is typicallyboth wide and patulous. The diagnosis isconfirmed by endoscopy. It has been suggested thatthis anomaly is a variant of primary epispadias.

Urogenital sinus anomaliesIsolated lesions that are not associated withanorectal or cloacal anomalies sometimes presentwith urinary incontinence, due either to neuro-pathic bladder resulting from an associated spinalanomaly, or to a form of urogenital sinus anomaly(urovaginal confluence) associated with an incom-petent sphincteric mechanism (see Figure 12.4). Inthe latter case there is always continuous daytimeurinary leakage. All urogenital sinus anomalies arecharacterised by a single vulval orifice that resem-bles neither vagina nor urethra.

Labial adhesionsLabial adhesions may contribute to retrogradefilling of the vagina on voiding and subsequentdribbling when the girl stands up from the toilet.While it is important to consider the diagnosis oflabial adhesions in girls with postvoid dribbling,this phenomenon can also occur in the absence oflabial adhesions.

Bladder outflow obstructionThis condition occurs far more commonly in boysthan in girls. Causes in boys include posteriorurethral valves, urethral stricture (including posthypospadias repair), syringocele, meatal stenosis(e.g. following circumcision) and pathologicalphimosis due to balanitis xerotica obliterans. Ingirls, haematocolpos or hydrocolpos due toimperforate hymen or vaginal atresia may presentwith bladder outflow obstruction, generally at or

after puberty and with an accompanying history ofprimary amenorrhoea. Causes affecting both sexesare pelvic tumours and severe constipation,although these conditions more often present withurinary retention than incontinence.

The urinary stream is usually impaired but manyboys are unaware of this (as are their parents). If thereis suspicion of bladder outflow obstruction, it is oftenhelpful to observe the child voiding, where this ispossible, or alternatively obtain a measurement offlow rate. With few exceptions, incontinent episodesare associated with urgent micturition, which in turnis the consequence of obstructive detrusor overactiv-ity. Residual urine, if not detectable clinically, is nearlyalways found on ultrasonography, often in conjunc-tion with thickening of the bladder wall. The upperrenal tracts, however, usually remain undilated, evenin some cases of posterior urethral valves. In girls,hydrocolpos or haematocolpos is always demonstra-ble by ultrasonography.

All patients suspected of having bladder outflowobstruction deserve examination under anaesthetic,cystoscopy, or both. It is important to be aware thatthe clinical picture may resemble primary detrusoroveractivity and, for a while at least, there may bea symptomatic response to detrusor antispasmod-ics. The speed at which wetting symptoms resolvefollowing relief of obstruction is very variable and,while some children become dry within a matter ofweeks or months, it is not uncommon for theincontinence to persist for longer, occasionally evenfor years. In that event, the use of antispasmodics isentirely appropriate.

Genuine stress incontinence andthe wide bladder neck anomalyAmong girls presenting with urinary incontinence,only a very small proportion are found to havegenuine stress incontinence, typically with a charac-teristic clinical history and appropriate urodynamicfindings. The ‘wide bladder neck anomaly’ isperiodically described in the literature, althoughwhether this is a genuine entity remains open todoubt. It has recently been shown that girls



involved in strenuous sporting activity such asgymnastics can demonstrate stress incontinenceand that patients with cystic fibrosis have up to a30% incidence of this complaint. During videouro-dynamic examination of girls, it is not uncommonto find the bladder neck slightly open, but rarely, ifever, is it possible to demonstrate stress urinaryleakage. In doubtful cases, an empirical trial ofan α-adrenergic agonist (e.g. ephedrine) may beemployed, and in the event of a clear-cut clinicalresponse, genuine stress incontinence may beassumed even if this has not been confirmedurodynamically. In exceptional cases, it may benecessary to consider a bladder neck sling proce-dure for patients who have reached adolescence.

Ureteric ectopiaSee Chapter 7.

Non-neuropathic neuropathicbladderSee below under ‘Functional diurnal urinaryincontinence’.

Functional diurnalurinary incontinence

Among 7 year olds, some 3% of girls and 2% ofboys experience functional daytime wetting at leastonce a week. Some 30% of the former and 50% ofthe latter also have nocturnal incontinence.Functional diurnal enuresis in children is distin-guishable in several forms (Table 12.3), almost all ofthem with a benign natural history and with detru-sor overactivity as the underlying common cause.

The overactive bladderAetiology

More than of 80% of children with daytimewetting have urgency and in the great majority thisis due to an overactive bladder, typically at theendstage of filling. The cause is unknown and may

be multifactorial. It is, however, likely that in manyinstances the phenomenon represents no morethan delayed maturity of bladder control and thataffected children remain at that transition phasewherein detrusor inhibition is still volume related.Why this should occur is seldom obvious, as withfew exceptions they are otherwise well-adjustedindividuals who have experienced nothing outof the ordinary by way of toilet training. There isno familial predisposition to this complaint.Urgency may also feature prominently among thesymptoms of children whose detrusor overactivityis a secondary response to functional outflowobstruction associated with dyssynergia.

Clinical features

The majority of affected children experience incon-tinence associated with urgency of micturition,and experience only a transient interval betweenthe first desire to void and the necessity of doingso. Indeed some children claim that they do notrealise they are voiding at all. Children attempt tocounter urgent urinary leakage by contraction ofthe striated urethral sphincter and pelvic floormuscles and may reinforce this process by variousmanoeuvres, characteristically by crouching withthe heel pressed into the perineum (Vincent’scurtsey sign). Sometimes urinary leakage is consid-erable (flooding), but is mostly relatively slight,


Table 12.3 Functional diurnal enuresis

Detrusor instabilityUrge syndrome

uncomplicateddysfunctional voiding

Deferred voidingLazy bladderOccult neuropathic bladder

?Detrusor instability or central (CNS)Giggle incontinence

Non-detrusor instabilityDiurnal frequency syndromeSensory urgency


consisting of damp patches only. However, leakageof as little as 2 ml is sufficient to stain boys’trousers and a similar volume may embarrass girlsby the resulting urinary malodour. Some childrenfind their problem worse in cold weather, while inothers overactivity may be precipitated by certaindrinks, particularly fizzy drinks. An element ofdaytime frequency exists in a majority of cases anda proportion – more boys than girls – are alsotroubled by nocturnal enuresis.

The urge syndrome has two subcategories:

• Uncomplicated urgency is clinically distin-guishable by a normal, smooth, uninterruptedurinary stream, and is urodynamically charac-terised by detrusor–sphincter synergia and,usually, by voiding to completion. Girls andboys are almost equally affected. Only seldomis there a history of urinary infection. Minordegrees of constipation are common. It hasbeen suggested that an appreciable proportionof these children exhibit features of the atten-tion-deficit hyperactivity disorder (ADHD).

• Dysfunctional voiding is clinically recognisableby a urinary stream that is fluctuant or inter-rupted (‘staccato’ voiding), and the urodynamicpicture during intentional micturition is one ofdetrusor–sphincter dyssynergia, either withincomplete relaxation of the sphincter or withalternating phases of contraction and relaxation.Incomplete voiding is common. It is thoughtthat these children, having learned to amelioratethe consequences of detrusor instability byvoluntary contraction of the urethral sphincter,subsequently and behaviourally come to lacksphincter inhibition during deliberate voiding.Girls are affected almost exclusively andupwards of 90% experience recurrent urinaryinfections. Some 30% have vesicouretericreflux, with or without associated renal scarring,and there is evidence that such reflux developssecondarily as a result of repetitive episodesof abnormally high intravesical pressure conse-quent upon a combination of detrusor over-activity and detrusor–sphincter dyssynergia.Although degrees of constipation are sometimes

found, these children only rarely exhibit featuresof any psychological disorder (see Hinman’ssyndrome below).

Prognosis

Spontaneous resolution is the rule, with only 2–3%of patients troubled into adult life. Among thosemore intractably affected, moving to live independ-ently away from home often tends to effect the finalcure. The chance of spontaneous resolution duringany 1 year is of the order of 1 in 6.

Investigation

A positive urine culture merits other appropriateinvestigations (Chapters 3 and 4).

Ultrasonography commonly demonstratesminor thickening of the bladder wall, while signif-icant residual urine (>10% of expected bladdercapacity) is suggestive of dysfunctional voiding. Ifnecessary, uncomplicated urgency can be distin-guished from dysfunctional voiding by flowmetry.

Urodynamic examination is seldom needed fordiagnostic purposes: unlike in adult men, bladderoutflow obstruction is only a very rare cause ofurgency in boys, while in girls, unlike in adultwomen, it is only very rarely necessary to distin-guish detrusor overactivity from genuine stressincontinence.

Management

Active measures are seldom effective before 5 yearsof age. Thereafter, there are several options.

Ameliorative measures

School authorities should be made aware of theproblem so that the child is allowed to go to thetoilet as necessary. Inconspicuous incontinencepads are available in children’s sizes.

Simple bladder retraining

Strategies include a fluid intake evenly distributedthroughout the day, the avoidance of drinks known toprecipitate bladder overactivity, and a regimen of



timed voiding, beginning at hourly intervals and, ifsuccessful, slowly extending these by degrees. Duringthe course of history taking, it will often emerge thatthe affected child voids rarely, if at all, during thecourse of a normal school day, an admission that maycome as a surprise to the parents. It is important,therefore, for the child to try and establish a regularvoiding routine based around breaks and lunchtime.Significant constipation should be treated.

Detrusor antispasmodics

Oxybutynin is immediately and unequivocallyeffective in 60–70% of cases and troublesome sideeffects are less common than in adults. As a rule,treatment must be continued for at least 3 months,although in a few instances for rather longer thanthat and occasionally for more than a year. Manypatients find slow-release oxybutynin more effec-tive than the conventional preparation, whiletolterodine represents an alternative agent forthose unable to tolerate oxybutynin in any form.

Cognitive bladder retraining

Although effective in as many as 80% of cases,including those unresponsive to detrusor antispas-modics, this technique, because it is more demand-ing than simple retraining, is unsuitable for childrenunder 8 years of age. As it is also both time-consum-ing and expensive, it is best employed on a selectivebasis, being most useful in well-motivated girlstroubled by dysfunctional voiding. Conducted by atrained urotherapist, children in age- and sex-matched pairs undergo a structured programme thatfirst introduces them to the elements of bladderanatomy and physiology and thereafter, using non-invasive biofeedback techniques, teaches them torecognise and then control their bladder signals.

Botulinum toxin A

There is increasing evidence from adult practicethat the injection of up to 400 units of botulinumtoxin A into the bladder produces a dramaticimprovement in symptoms and objective urody-namic parameters, a therapeutic effect that canlast for up to 7 months, including in patients

unresponsive to first-line treatments. Similar resultshave lately been reported from a small number ofpaediatric trials. The toxin is injected at about 30sites using a rigid cystoscope under general anaes-thesia and, although injection into the trigonal areais usually avoided, it has recently been suggestedthat this trigonal sparing is unnecessary. Accordingto some authorities, this form of treatment shouldnowadays be employed as the next step, shouldanticholinergic medication fail.

Neuromodulation

This is a well-established technique in adults, butbecause it is invasive and involves the implantationof sacral nerve electrodes, it is rarely used inchildren. However, the use of transcutaneous electri-cal nerve stimulation (TENS) is worth considering.Two electrodes are placed over S4 dermatomes onthe buttocks and lower limbs and used for anumber of hours. Some patients respond very wellto this and the improvement may be incrementalwith successive cycles of treatment.

Sensory urgencyA few children, mostly girls, who exhibitsymptoms typical of the urge syndrome yet arewholly unresponsive to treatment, are found onurodynamic examination to have sensory ratherthan motor urgency. Apart from a very smallnumber of cases with chronic or interstitial cysti-tis, the aetiology of this complaint is no lessobscure than that of its adult counterpart. Bladderoverdistension under general anaesthesia producessymptomatic relief in some individuals and the useof intravesical oxybutynin has also been described.

Diurnal urinary frequencyof childhoodMore commonly affecting boys than girls, andprincipally those aged 4–7 years old, this complaintis characterised by the sudden onset of gross daytimeurinary frequency, as often as every 10–15 minutes.It is pathognomonic of this disorder that the daytimefrequency is not accompanied by any correspondingdegree of nocturia: night-time voiding seldom



occurs more than twice and typically not at all.Bedwetting may happen during the first few days,and occasionally diurnal enuresis also, but otherwiseincontinence is not a feature of the condition andother urinary symptoms are conspicuously absent.Urine culture and ultrasonography are normal andthe frequency is wholly unresponsive to detrusorantispasmodics. The aetiology is unknown, althoughthe discrepancy between bladder behaviour awakeand asleep is compatible with a behavioural origin.The complaint is always self-limiting, usually over3–12 weeks. A handful of children experience recur-rent cycles over a period of 1–2 years.

Deferred voidingThis problem is common in 4–6 year olds of bothsexes, but only occasionally in older individuals,many of whom have a behavioural disorder. Urgentmicturition, owing to presumed detrusor instability,is a consistent feature, but the wetting arises princi-pally because the child defers micturition until it istoo late. In most cases, it is apparent that otheractivities, e.g. playing outdoors, take precedenceover the social desirability of continence. Treatmentis unnecessary for youngsters as the condition is self-limiting. Older children with behavioural disordersdeserve the attentions of a clinical psychologist.

Lazy bladderThis condition, virtually confined to girls, typicallycomes to light at 8–10 years of age and may presentwith daytime incontinence, urinary infection orincidental detection of a palpable and usually visiblydistended bladder postmicturition. The upper renaltracts are always undilated and the urodynamic pictureis one of low-pressure retention with detrusor–sphincter dyssynergia and non-sustained detrusorcontractions. Detrusor overactivity is a furtherfeature in most cases. Lazy bladders are almostcertainly behavioural in origin, resulting from exces-sive reliance on hold manoeuvres over a prolongedperiod of time. It is usually self-limiting, character-istically resolving quite suddenly during the courseof puberty. Only symptomatic children need treat-ment, supplemented by antibiotic prophylaxis in the

event of urinary infection. Daytime incontinencerepresents a difficult problem in these cases as detru-sor antispasmodics must obviously be used withcaution. Intermittent catheterisation works well iftolerated. Cognitive bladder retraining representsthe most effective remedy.

Giggle incontinenceLargely confined to girls, this complaint typicallypresents around 9–12 years of age. The history isunmistakably one of urinary leakage occurring withgiggling or laughing but at no other time. In mostinstances there is an otherwise entirely normalpattern of micturition. Urodynamic examinationmay disclose detrusor instability, either sponta-neous or provoked, but is more often whollyunremarkable, even during giggling. The aetiologyis unknown, although there is often a familyhistory. Whether the complaint is truly self-limitingis open to doubt and the apparent improvementthat usually occurs through puberty and into adultlife may, in reality, represent no more than adapta-tion to avoid the precipitating circumstances.

Frequent episodes call for treatment. Oxybu-tynin is helpful in some cases and imipramine inothers. Ritalin (methylphedinate) is the mostconsistently effective agent. Because it is mostlyused in the treatment of ADHD, the parents ofchildren with giggle incontinence may reject its useon account of the perceived stigma attached toADHD and unfavourable media coverage. Never-theless, it can prove dramatically effective in girlsfor whom severe giggle incontinence has a majorimpact on their school and social life.

Non-neuropathic neuropathicbladderIn children with this rare disorder the bladderbehaves as though ‘neuropathic’ yet there is noidentifiable neurological disease. The condition isdistinguishable from severe dysfunctional voidingor lazy bladder by the radiological features of saccu-lation and elongation of the bladder (‘fir-tree’bladder), which, in most instances, are accompa-nied by secondary changes in the upper renal tracts.



In the classic form, Hinman’s syndrome, thereis almost always a background of domestic turmoilor a history of severe physical or psychologicalupset occurring at, or shortly after, the time oftoilet training. It is likely that affected children,because they are profoundly fearful of wettingthemselves, grossly overuse their external urethralsphincter to counteract unstable detrusor contrac-tions in a desperate attempt to stay dry. This leadsto excessive intravesical pressures, to detrusorhypertrophy and, ultimately, to detrusor non-compliance, with consequent secondary upper renaltract complications. Presentation, typically at5–8 years of age, is with unusually severe urinaryincontinence, compounded in most cases byurinary infections and marked disturbance ofbowel habit. A few children have evidence of renalinsufficiency. The natural history is variable, with atendency towards spontaneous resolution postpu-bertally. However, because of the risk to the upperrenal tracts in the absence of treatment, an expec-tant approach is not a safe option and managementshould be instituted along the lines described forthe true neuropathic bladder (Chapter 13).

In the other form of this complaint it wouldappear that there is some genuine but unidentifiableneurological lesion. There is never any backgroundof psychological disturbance and presentation isoften with episodic urinary retention, sometimesdating back to early infancy. Somewhat curiously,bowel habit is usually normal. So far as treatment isconcerned, any distinction between these twocategories of non-neuropathic bladder is academic.

Primary monosymptomaticnocturnal enuresis

Some 5–10% of 7 year olds wet the bed three ormore times a week, a figure that does include a fewchildren with secondary nocturnal enuresis and aslightly higher proportion who also have daytimesymptoms, with or without actual wetting.However, the substantial majority who wet thebed have primary monosymptomatic nocturnalenuresis and, of these, two-thirds are boys.

The aetiology of this complaint is multifactorialand in any individual one or more factors mayapply. Established aetiological factors comprise:

• A positive family history (upwards of 75% ofcases).

• Impaired functional bladder capacity, clinicallymanifest by a degree of daytime frequency.

• Uninhibited nocturnal detrusor contractions.Although demonstrable in approximately athird of patients, these also occur in asympto-matic children. Diurnal urgency of micturitionis a clinical indicator of such detrusor activity.

• Sleep arousal difficulty. Nocturnal enuresis doesnot, as is commonly supposed, result from deepsleep, as bedwetting occurs at all stages of thesleep cycle, but many affected children lack thenormal arousal from sleep that should occur asfunctional bladder capacity is approached.

• Absence of a circadian rhythm of vasopressinrelease. Levels of vasopressin normally increaseat night, but in as many as 75% of bedwetters(and a still higher proportion of those with apositive family history) such an increase is absentor diminished and leads to a nocturnal urinaryoutput exceeding the functional bladder capacity.

Although nocturnal enuresis is sometimes a manifes-tation of psychosocial problems or of behaviouraldisorders, the great majority of bedwetters arenormally adjusted children. The clinical features varyfrom one patient to another. Some children wetevery night or almost so, whereas others are troubledless often and tend to experience alternating spells ofwet and dry nights. Some children wet more thanonce a night, and the time of wetting varies betweenindividuals. With only occasional exceptions, thewetting does not wake the child. As indicated previ-ously in this chapter, secondary enuresis shouldprompt suspicion of organic disease. However, thisis an unlikely explanation if, as is often the case, theonset has coincided with some physical or emotionalupset. Except for those children with coexistingdaytime symptoms and those with ‘suspicious’secondary enuresis, investigation is unnecessary, withthe exception of excluding infection. The prognosis




is excellent, with spontaneous resolution by the timeof physical maturity occurring in 97–99% of affectedindividuals. The probability of cessation in any 1 yearis approximately 1 in 6.

Treatment, if sought, should not commencebefore 5 years of age. The type of treatmentdepends in some measure on the clinical features,while its likelihood of success is heavily dependenton the motivation of the child and the family. Itshould be emphasised that all medications representtreatment rather than cure, although symptomatictreatment may help to expedite cessation of theunderlying problem earlier than would otherwisehave been the case. The parents should be encour-aged to take a positive attitude towards the problemand scolding and punishment are to be condemned.Possible active measures are as follows:

• Star charts, combined with rewards, are partic-ularly suited to the younger patient.

• Enuretic alarms, which alert and sensitise the childto respond appropriately to a full bladder duringsleep, serve to convert this signal from one ofmicturition to one of inhibition of micturition andwaking (Figure 12.5a and b). This measure, bestdeferred until at least 7 years of age, achieves asuccessful outcome in 60–75% of cases and, unliketreatment with medication, such success is onlyseldom followed by relapse. Failures tend to occurin least-motivated children and in those with abackground of domestic disharmony or a historyof daytime symptoms.

• Desmopressin has a vasopressin-like action and,whether administered intranasally (Desmospray)or orally (Desmotabs, Desmomelt), is effective inupwards of 70% of patients. The relapse rateafter cessation of treatment is high (30–50%)and is to some extent dependent on the durationof treatment. Desmopressin may be used forshort periods, to cover special occasions, or for amore extended duration, up to 12 months.Whenever used over a prolonged period, thedosage should be periodically reduced or stoppedin order to determine whether the treatmentneeds be continued. Predictors of success includea positive family history or wetting soon after

going to sleep, whereas predictors of failure areconcurrent daytime symptoms.

• Detrusor antispasmodics, such as oxybutynin,are principally of value in children who are alsotroubled by daytime urgency and frequency.When given on this selective basis, these drugsare effective in up to two-thirds of cases.

• Imipramine is nowadays considered an unfash-ionable treatment of last resort. Nevertheless, itsefficacy has been confirmed in several well-conducted trials. Its mode of action is unknown.

• Combination of treatments. In some patients,treatments that are unsuccessful individually mayprove to be effective when used in combination.Examples are desmopressin with oxybutynin anddesmopressin with an enuretic alarm. However,imipramine should never be prescribed inconjunction with desmopressin.

Figure 12.5 (a) Enuresis alarm. The pad is placedunder the bed sheet, with bedside battery-poweredbuzzer. (b) Compact enuresis alarm suitable for thetreatment of nocturnal enuresis or ambulatory treatmentof diurnal enuresis. The buzzer device is pinned to thepyjamas (or clothes when used in the daytime) and thesensor worn between two pairs of underclothes.

(a)

(b)



Key points

• The initial priority is to excludeorganic causes of urinaryincontinence, although theseare rare.

• Primary monosymptomatic nocturnalenuresis seldom, if ever, has anunderlying organic basis.

• Most organic (anatomical orneurological) causes of daytimewetting can be excluded on the basisof history, examination andultrasonography.

• Organic causes of daytime wettingare classifiable as neurological,obstructive and structural, the lastcategory being confined almostexclusively to girls.

• Functional diurnal enuresis is dueto detrusor instability in thegreat majority of cases, andthe natural history of this

complaint in children is one ofspontaneous resolution.

Further reading

Chandra M. Nocturnal enuresis in children. Curr OpinPediatr 1998; 10: 167–173

Chung K, Yeung CK, Sreedhar B et al. Differences in charac-teristics of nocturnal enuresis between children andadolescents: a critical appraisal from a large epidemio-logical study. BJU Int 2006; 97(5): 1069–1073

Koff SA. Relationship between dysfunctional voiding andreflux. J Urol 1992; 148: 1703–1705

Lackgren G, Nevéus T. Non-neuropathic bladder-sphincterdysfunction. In: Stringer MD, Oldham KT, Mouri-quand PDE (eds). Pediatric Surgery and Urology:Long-Term Outcomes. Cambridge: Cambridge Univer-sity Press, 2006: 643–651

Neveus T, von Gontard A, Hoebeke P et al. The standardi-zation of terminology of lower urinary tract function inchildren and adolescents: report from the Standardisa-tion Committee of the International Children’s Conti-nence Society. J Urol 2006; 176(1): 314–324

van Gool JD, Vijversberg MA. Functional daytime inconti-nence: clinical and urodynamic assessment. Scand JUrol Nephrol 1992; 141: 58–69


Neuropathic bladder

Henrik A Steinbrecher, Padraig S Malone

and Anthony MK Rickwood

Introduction

Until the late 1950s, when the development ofshunting devices to treat hydrocephalus led to thesurvival of large numbers of patients born withmyelomeningocoele, neuropathic bladder was a raredisorder in children and received correspondinglylittle attention. Thereafter, unfortunately, it soonbecame apparent that children with myelomeningo-coele presented with urological problems, as wellas others, over and above those experienced byadults with spinal cord injury. The particular diffi-culties were:

• a preponderance of female patients, with evidentimplications for the management of incontinence

• a high incidence of secondary upper renal tractcomplications in patients of both sexes,although in boys more commonly.

Conduit urinary diversion quickly became estab-lished as the means of overcoming both problemsin children with spina bifida and remained invogue until the mid-1970s, by which time itslimitations were apparent and alternative strategieshad become available. The first of these, cleanintermittent self-catheterisation (CISC), remainsthe mainstay of treatment today. Employed as thesole means of treatment, however, CISC, even

when practicable, achieves continence in only aminority of patients (10–20%) and does notalways protect the upper renal tracts. Subsequentdevelopments, addressing these drawbacks, havecomprised more effective medication, augmenta-tion cystoplasty, sphincter-enhancing proceduresand the Mitrofanoff principle.

Aetiology (Table 13.1)

MyelomeningocoeleDespite a markedly declining incidence duringrecent years, myelomeningocoele remains themost common cause of congenital neuropathicbladder. The condition results from partial failureof tubularisation of the neural crest and, becausethe normal process proceeds caudally, the conusmedullaris is almost always involved, with onlysome 6% of patients escaping neuropathic bladderand bowel. The untubularised neural crest (neuralplaque) contains grossly disorganised tissue and,consequently, the extent of the plaque determinesthe degree of paralysis. Regardless of the neurolog-ical deficit, 25–30% of patients retain positiveconus reflexes (anocutaneous, glans-bulbar), andamong these a minority with low-level sacral orlumbosacral myelomeningocoele have incompletecord lesions with sensory sparing and, occasionally,

13

Topics coveredAetiologyPathophysiologyPatient assessment

InvestigationManagementBowel management


motor sparing also. Other features of relevance tourological management include:

• Hydrocephalus – although almost invariablypresent, this does not always require shunting. Theseverity of hydrocephalus broadly matches theextent of the neural plaque and because, with someexceptions, the severity of hydrocephalus alsoreflects the level of intelligence, myelomeningo-coele patients are unique in that increasing physicaland intellectual disabilities tend to go hand-in-hand. In some patients CISC, or the manipulationrequired to handle an artificial urinary sphincter,may be precluded by the impaired manual dexter-ity often associated with hydrocephalus.

• Mobility – almost all patients with a neurologi-cal level above L3 (i.e. lacking normal quadri-ceps function) ultimately come to lead awheelchair existence, no matter what degree ofmobility they may have achieved during child-hood. For someone with reasonably goodmobility a bladder capacity sufficient for 2-hourly intervals between voiding is (just about)adequate, whereas for a wheelchair-boundpatient at least twice that capacity is desirable.

• Spinal deformity – the incidence and severity ofthese deformities relates to the extent of theneural plaque. Kyphoscoliosis, the most severe

deformity, is largely limited to thoracolumbarlesions and in some instances may make it physi-cally impossible for patients of either sex toperform urethral self-catheterisation.

• Congenital upper urinary tract anomalies –although more prevalent than among the popula-tion at large, the nature of these anomalies(typically unilateral renal agenesis, or anomalies ofposition or fusion) is such that only rarely do theyaffect practical management.

Other congenital cord lesionsBecause these lesions are not associated with hydro-cephalus nor, as a rule, with major neurologicaldeficits or spinal deformities, urological manage-ment is seldom influenced by factors other than thebladder dysfunction itself. Most affected patients,including those with incomplete cord lesions, havenegative conus reflexes. The commonest of theselesions is lumbosacral lipoma.

Sacral agenesis (Figure 13.1)

Sacral agenesis may occur as a feature of anorectalanomalies or as an isolated lesion: in the latterinstance, the mother is often an insulin-dependentdiabetic. The implications of sacral agenesis inchildren with anorectal malformations are consid-ered in Chapter 14. Regardless of whether it is anisolated or a coexisting anomaly, the cord lesionassociated with sacral agenesis is invariably incom-


Table 13.1 Aetiology of childhood neuropathicbladder

Congenital Acquired

Myelomeningocoele Cord trauma

Spina bifida occulta Cord infarctionDiastematomyelia PrematurityLumbosacral lipoma Cardiac and aortic Intraspinal cysts surgeryTethered cord

Sacral agenesis TumoursSacrococcygeal teratomaNeuroblastoma

Transverse myelitis

Figure 13.1 Sacral agenesis – characteristicwasting of the buttocks.


plete and, uniquely, any peripheral neurologicaldeficit bears no predictable relation to bladder orsphincter dysfunction.

Acquired cord lesions

These are rare. Cord trauma may occur at any levelbut is most common in the mid-dorsal region.Patients affected by transverse myelitis usually makean excellent recovery except for the bladder, whichremains affected in upwards of 50% of cases. Othercauses include spinal artery thrombosis (occurring insick or premature infants) and spinal tumours.

Because of the small numbers, the risk of second-ary upper renal tract complications is unquantifi-able, although they undoubtedly occur morecommonly than in adults with spinal cord injury.Girls and boys appear to be at roughly equal risk.

Pathophysiology

Basic considerationsIn essence, clinical management aims to replicate,so far as possible, normal bladder function, namely:

• filling and storage, i.e. by ensuring adequatelow-pressure functional capacity

• emptying, i.e. to maximise effective bladdercapacity and minimise the risk of stasis-relatedinfection

• voiding at will – in patients with neuropathicbladder, normal voluntary control of voiding isabsent and some unphysiological or artificialmeans must be employed, either by abdominalcompression or straining (possible only whenthere is some element of sphincteric incompe-tence) or by CISC, whether per-urethrally or viaa Mitrofanoff channel.

ClassificationAs with acquired forms, congenital neuropathicbladder dysfunction is largely determined by the siteof the cord lesion, albeit with the difference that anintermediate pattern of dysfunction is commonlyseen. Urodynamic investigation, essential for eluci-dating the several patterns of bladder dysfunctionassociated with neuropathic bladder, should alwaysconsider the bladder–sphincter complex togetherrather than as separate entities. Basic features of theequipment used for videourodynamic investigation(also termed videocystometry) are illustrated inFigure 13.2. In some instances, electromyography(EMG) recordings of pelvic floor musculature arealso measured using surface or needle electrodes.

Neuropathic bladder 173

Figure 13.2 Videourodynamic equipment(videocystometry). Two catheters (or a singledouble-lumen catheter) are inserted into thebladder urethrally or suprapubically to permitfilling and simultaneous intravesical pressurerecording (TBP = total bladder pressure on thetraces illustrated below). Electronic subtraction ofintra-abdominal pressure, measured by a rectalballoon catheter (RP = rectal pressure), providesa measurement of true detrusor pressure (IDP =intrinsic detrusor pressure). Anatomical informa-tion is obtained by using radiographic contrast forthe study, although X-ray screening time shouldbe kept to a minimum.


Important practical considerations when conduct-ing a urodynamic examination are that:

• It is best performed by the clinician also respon-sible for the patient’s management.

• It should, if at all possible, be combined withsimultaneous cystography.

• Slow filling is employed, at no more than 10%of expected bladder capacity per minute(expected functional capacity in ml is calculatedas follows: 0–2 years, capacity = weight (kg) ×7; 2–12 years, capacity = (age + 2) × 30).

• The presence or absence of sphincteric incom-petence should be assessed periodically duringfilling by manoeuvres that raise intra-abdominalpressure (standing, coughing, application ofsuprapubic pressure).

• In the presence of gross sphincteric incompe-tence it may be necessary to occlude the bladderneck by a Foley balloon catheter in order to fillthe bladder to expected capacity.

A number of different classifications of thepathophysiology of neuropathic bladder havebeen described. The one adopted here is foundedupon the three basic patterns revealed by urody-namic examinations, along with the ways in whichthese influence both bladder filling and emptying.

In suprasacral cord lesions (contractilebladder) the conus medullaris is intact (Figure13.3) and so too, although isolated from highercentres, is the innervation of both detrusor andexternal urethral sphincter. Conus reflexes arepositive. Detrusor contractility is enhanced. Thesphincteric mechanism, usually including thebladder neck (Figure 13.4), is intact and voidingoccurs solely by detrusor contractions, almostalways accompanied by detrusor–sphincter dyssyn-ergia (i.e. loss of the usual coordination betweendetrusor contraction and sphincter relaxation). Thismay be termed dynamic sphincteric obstruction.Repetitive high-pressure detrusor overactivity mayultimately lead to secondary changes in the detru-sor itself and, in turn, to detrusor non-complianceand/or upper renal tract complications.

In sacral cord lesions (acontractile bladder) theconus medullaris is destroyed (see Figure 13.3), asis the innervation of both detrusor and externalurethral sphincter. Conus reflexes are negative anddetrusor contractility is absent. Some degree ofsphincteric incompetence is always present so thatvoiding occurs either by overflow or by raisingintra-abdominal pressure. During such voiding,any obstruction is located at the level of the exter-nal urethral sphincter (Figure 13.5), and is termedstatic sphincteric obstruction. Unlike detrusor–sphincter dyssynergia, static sphincteric obstruc-tion represents a fixed urethral resistance, constantin any individual patient but varying unpredictablyfrom one patient to another.

More severe degrees of obstruction result in goodfunctional capacity at the expense of large volumes ofresidual urine (see Figure 13.5), whereas minimalobstruction, equating to gross sphincteric incompe-tence, is associated with greatly reduced functionalcapacity and negligible residual urine (Figure 13.6).An inevitable consequence of voiding by abdominalstraining against a fixed urethral resistance is thatfunctional


T 9

a b

101112L 1

23456

L 1234

D +ACR +

D −ACR −

Figure 13.3 Suprasacral (a) and sacral (b) cordlesions: note that bladder innervation is determined bythe distal, not the proximal, extent of the lesion (D =reflex detrusor activity, ACR = anocutaneous reflex).


capacity scarcely exceeds residual urine, and hencethat effective capacity is virtually zero. Acontractilebladders may be smooth or sacculated. A degree ofdetrusor non-compliance is common and, whenpresent, serves to further limit functional capacitywhere urethral resistance is low, or results in excessivelyraised intravesical pressure where the resistance is high.

Intermediate bladder dysfunction is charac-terised by a combination of detrusor hyperreflexia,typically generating low pressures, and some degreeof sphincteric incompetence (Figure 13.7). Conusreflexes are negative. Sacculation (Figure 13.8) iscommon, as is detrusor non-compliance. Duringvoiding the appearance of any urethral obstructionmore closely resembles that of static sphinctericobstruction than detrusor–sphincter dyssynergia.

The factors responsible for impaired bladdercapacity are summarised in Table 13.2. In patientswith myelomeningocoele the patterns of dysfunctionare: contractile 25%, acontractile 15% and interme-diate 60%. Contractile dysfunction is appreciablyrarer with all other forms of congenital cord lesion.

Incomplete cord lesionsIncomplete cord lesions, with sacral sensory sparing(and sometimes motor sparing also), are of clinicalsignificance principally when associated with contrac-tile bladder dysfunction (conus reflexes positive).Such patients retain some sensation of bladderfullness and typically experience gross urgency ofmicturition. A proportion achieve spontaneous, ifprecarious, urinary continence. It is, however, impor-tant to note that despite acquiring continence thesepatients may nevertheless have urodynamic abnor-malities predisposing to upper tract complications.Urethral sensation is usually largely intact withincomplete cord lesions and in some instances to theextent that the discomfort experienced during CISCprecludes per-urethral self-catheterisation.

Secondary upper renal tract complicationsSuch complications, typically as obstruction orreflux, are prevalent in all children with neuropathic


A

A

B

C

TBP20

(cm H2O)

RP20

(cm H2O)

IDP20

(cm H2O)

VR (ml/sec)

100

1 2 3Minutes

4 5

A.G.

B C

Figure 13.4 Contractile bladder.The bladder neck is closed at rest(A) and remains so despite a risein intra-abdominal pressure (B). Areflex detrusor voiding contractionis accompanied by detrusor–sphincter dyssynergia and which isinitially complete (C) (TBP = totalbladder pressure, RP = rectalpressure, IDP = intrinsic detrusorpressure).


bladder, whatever the cause. Twenty per cent ofchildren with myelomeningocoele are affected bythe age of 2 years. The incidence thereafter is diffi-cult to determine and may be influenced (for betteror for worse) by the effects of treatment. At anestimate, however, 50% of boys are at risk of uppertract complications by the time they completepuberty; the percentage in girls is somewhat smaller.

Factors responsible for secondary complicationsare summarised in Table 13.3.

• Urinary infection is extremely common and, inthe very young, may lead to renal scarring evenin the absence of vesicoureteric reflux. Mostinfections result from bladder dysfunction, andtheir treatment consequently hinges more uponimproving bladder function rather than repeti-tive courses of antibiotics.

• Vesicoureteric reflux may be primary or, moreoften, secondary. In the case of secondary reflux,treatment is aimed principally at correcting theunderlying abnormality of bladder function.

• Bladder outflow obstruction, whether in theform of detrusor–sphincter dyssynergia or staticsphincteric obstruction, is an invariable precur-sor to secondary upper urinary tract obstructionor reflux. However, it leads to these complica-tions only when associated with raised intraves-ical pressure due to detrusor overactivity, detrusornon-compliance, or a combination of both.The relative importance of these two factorsis debatable, with conventional urodynamicspointing to detrusor non-compliance as themore important factor whereas ambulatory studieshave tended to implicate detrusor overactivity.When considering detrusor non-compliance,


A

0

TBPcm H2O

RPcm H2O

20406080

A

B

B

0204060

IDPcm H2O

0204060

VoidRateml/sec 5

1 2Minutes

15

Figure 13.5 Acontractile bladder. During abdominalstraining there is persistent narrowing at the level ofthe external urethral sphincter (A), which ultimatelybecomes complete (static sphincteric obstruction)despite continued straining (B): baseline intravesicalpressure falls following this partial voiding.

A

A

H.W

B

B

80

TBP

RP (cm H2O)

IDP (cm H2O)

MVR (ml/sec)

20

10

I.F100 ml

Figure 13.6 Acontractile bladder. The bladder neckis closed at rest (A) but the sphincteric mechanismbecomes totally incompetent with a rise in intra-abdominal pressure (B).


baseline pressures exceeding 20 cmH2O withinthe physiological range of capacity on conven-tional slow-fill urodynamics should be regardedas being ‘unsafe’. Whatever the detrusor behav-iour, secondary upper renal tract complicationsnever occur in the presence of gross sphinctericincompetence and a permanently empty bladder.This happy state may, of course, be reversed ifsphincteric incompetence is treated withoutconsidering the possible subsequent effects ofdetrusor malfunction.

Natural history of neuropathicbladder malfunctionNeuropathic bladder dysfunction can change overthe course of time, in terms of both severity or, less

often, the particular pattern of dysfunction.Whatever change occurs, however, is almost invari-ably for the worse. Although no time of life is free ofthis problem, the periods of greatest risk are duringthe first 2 years, when some 30% of neonatally ‘safe’bladders become ‘unsafe’, and subsequently duringthe course of puberty. In this latter age group, boysare at greater risk than girls, possibly because prostaticgrowth increases urethral resistance.

Patient assessment

HistoryGeneral features to be ascertained from the history comprise mobility, intelligence and social


S.S.

80

TBPcm H2O

6040200

80

RPcm H2O

6040200

80

IDPcm H2O

6040200

VoidRateml/sec

2010

1 2 3 4Minutes

5 6 7

A

A

B

C

B C

Figure 13.7 Intermediate bladder. Voiding occurs both by detrusor hyperreflexia (A) and by raising extra-abdominal pressure (B).


background, plus the nature and effectiveness ofany bowel management. With regard to the urinarytract:

• Continuous dribbling, particularly if exacer-bated by coughing, crying or standing, is almost

pathognomonic of some degree of sphinctericincompetence.

• A discrete, spontaneous urinary stream istypical of a contractile bladder, whereas a streamthat is also interrupted is typical of detrusor–sphincter dyssynergia.

• Urinary infections, especially if febrile, arestrongly suggestive of upper renal tract compli-cations, actual or impending.

ExaminationThe relevant features are that:

• Bladder distension is indicative of outflowobstruction.

• An expressible bladder is pathognomonic ofbladder neuropathy with some measure ofsphincteric incompetence.

• A bladder that cannot be expressed, bycontrast, implies either sphincteric competenceor a bladder that is virtually empty by reason ofgross sphincteric incompetence.

• Neurological examination, which can belimited to the lowermost sacral segments, isaimed at demonstrating the presence or absenceof conus reflexes and the existence of any sacralsensory or motor sparing. It should be borne inmind that because they are associated withsphincteric competence, positive conus reflexescarry an excellent prognosis for continence.Most patients with positive reflexes become dryon CISC alone or in combination with ananticholinergic drug; few patients come toaugmentation cystoplasty and none to sphincterenhancement procedures.


Figure 13.8 Cystographic appearances of neuro-pathic bladder (intermediate type) showing bothsacculation and static sphincteric obstruction.

Table 13.2 Causes of impaired bladder capacity

Contractile bladder Acontractile bladder Intermediate bladder

Detrusor overactivity Sphincteric incompetence Sphincteric incompetenceDetrusor non-compliance Detrusor overactivity Combinations Detrusor non-compliance

Combinations


Neonatal assessmentThe expressibility (or otherwise) of the bladder isreadily determinable neonatally, similarly thepresence or absence of conus reflexes and, asjudged by general arousal to perianal pinprick, theexistence of sacral sensory sparing. No matter howslight the neurological deficit, a neuropathicbladder is certain if the bladder can be readilyexpressed, if the conus reflexes are negative, or ifthere is no sensory sparing. By contrast, bladderfunction may prove to be normal if the bladdercannot be expressed and conus reflexes are positiveand there is sacral sensory sparing, a combinationof findings that is sadly rare.

Investigations

Imaging studiesUltrasonography of the urinary tracts, with estimation of the volume of residual urine wherepracticable and relevant, represents the bestmeans of both initial assessment and follow-up.The frequency of ultrasound examinations for the latter purpose is determined by what isknown of bladder dysfunction and hence theperceived risk of upper tract complications.Among other imaging studies, DMSA scintigra-phy is of value in patients with vesicouretericreflux or those experiencing febrile urinary infec-tion. Micturating cystography, to confirm orexclude vesicoureteric reflux or bladder outflowobstruction, is best combined with simultaneousurodynamic examination.

UrodynamicsSome of the technical aspects of urodynamics havebeen considered above and are illustrated in Figure13.2. The principal indications for this examina-tion are to:

• identify the ‘unsafe’ bladder in neonates andplan for its immediate treatment

• determine the cause(s) of secondary upperurinary tract complications

• plan the treatment of incontinence.

Management

Basic considerationsIn order of priority, the aims of management are:

• to preserve renal function• to prevent progressive bladder damage (fibrosis as

a result of high-pressure storage and emptying)• to achieve social continence (ideally without

dependence on appliances and in a manner thepatient may practise independently).

Consequently, all schemes of management incor-porate the following basic principles:

• Renal function always takes precedence overcontinence.

• Treatment must relate realistically to the patient’sother characteristics and abilities as a whole (i.e.age, sex, mobility, intelligence, dexterity, defor-mity, social circumstances).

• Treatment must also relate to the nature of thebladder dysfunction.

• When bladder dysfunction is complex its treat-ment may also need to be more complex (e.g.CISC combined with a measure to improvebladder capacity, or with more than one measurewhen the reduced capacity is the outcome oftwo or more factors).

• Measures that are non-invasive and/or reversibletake priority over those that are neither (i.e.medical management should always be triedbefore surgery is considered).


Table 13.3 Causes of secondary upper renaltract complications

Urinary infectionVesicoureteric refluxBladder outflow obstruction plus detrusoroveractivity and/or non-compliance


In practice, when CISC proves to be ineffective onits own, any additional measures are invariablydirected at securing adequate low-pressurefunctional bladder capacity.

General management ofimpaired/high-pressure bladder capacityDetrusor overactivity

• Medication (anticholinergics).• Botulinum toxin A injection (repetitive).• Augmentation cystoplasty.

Medical management of detrusor overactivityusually comprises treatment with oxybutynin and,because this agent is effective in most cases,augmentation cystoplasty is rarely required for thisindication alone. For patients in whom side effectsare not tolerated, oxybutynin may be adminis-tered, in the same dosage, by the intravesical route.

Tolterodine, an alternative anticholinergic agent,is probably equally efficacious and is claimed tohave a lower incidence of side effects. There arenow a number of extended-release preparationsavailable and these appear to be more effective withfewer side effects: extended-release oxybutynin isprobably the best. Oxybutynin is also nowproduced in dermal patch form. Newer, more selec-tive, anticholinergic agents are being developed andare currently undergoing clinical trials.

Botulinum toxin A injection is usually employedas a temporising measure until young patientsacquire the maturity and compliance with man-agement that is needed before proceeding toaugmentation cystoplasty. The duration of actionof botulinum toxin injection is approximately7 months.

Detrusor non-compliance

• Augmentation cystoplasty.

Although the cause of detrusor non-complianceremains disputed, there is general agreement thatthe phenomenon is unresponsive to any currentlyavailable medication.

Sphincteric incompetence

• Medication (α-adrenergic agonists).• Periurethral/bladder neck injections with a

bulking agent.• Bladder neck suspension.• Bladder neck sling.• Urethral lengthening procedures (Kropp or

Pippi Salle procedures).• Artificial urinary sphincter.• Periurethral inflatable constrictor (Lima).• Bladder neck closure.

The treatment of sphincteric incompetenceremains less than satisfactory. Marginal degreesof incompetence may respond to α-adrenergicagonists (e.g. ephedrine), but anything moremajor calls for surgery. As is evident from thelength of the list above, there is as yet no singleprocedure that guarantees success. It must also bere-emphasised that a safe and successful outcomefrom treating sphincteric incompetence is depend-ent on measures to ensure adequate managementof any coexisting detrusor overactivity and/ordetrusor non-compliance.

Surgery for impaired/high-pressure bladder capacityAugmentation cystoplasty

Enterocystoplasty

Despite the morbidity inherent in prolongedexposure of intestinal epithelium to urine (Table 13.4),enterocystoplasty remains the principal means ofbladder augmentation as it employs a material thatis universally available and, with a few exceptions,secures consistent and satisfactory urodynamicoutcomes. Intestinal segments in common usage areileum, ileocaecum, sigmoid colon and stomach.With the exception of stomach, all require detubu-larisation to obviate high-pressure peristaltic activity.As a rule, a clam-patch cystoplasty (Figures 13.9 and13.10) is used when the urodynamic problem isprincipally detrusor overactivity, and a pouchedaugmentation (Figure 13.11) when the bladder issmall and non-compliant. Despite detubularisation,



troublesome peristaltic activity may still occur, evento the extent of necessitating further augmentation.As this occurs most commonly following sigmoidcystoplasty, the use of this bowel segment is bestavoided where possible.

Autoaugmentation

Excision or incision of the detrusor muscle overthe bladder dome creates, in effect, a large, broad-mouthed diverticulum. Although avoiding thepotential complications of enterocystoplasty, theurodynamic outcome in terms of increased capac-ity and reduction of overactivity is rather lessimpressive or predictable. Moreover, the long-termresults are not encouraging as fibrosis and contrac-tion of the diverticulum occurs. However, forisolated overactivity, satisfactory outcomes arereported from some units.

Ureterocystoplasty (Figure 13.12)

The dilated ureter, once opened along its fulllength, is usually anastomosed to the bladder as aclam patch; the overlying kidney is removed ifhaving no useful function or, if otherwise, isdrained by transureteroureterostomy. Because itfurnishes a urodynamic outcome the equal ofenterocystoplasty, ureterocystoplasy is the proce-dure of choice whenever a suitably dilated ureter isavailable. Unfortunately, this is rarely the case.


Posterior Anterior

Figure 13.9 Clam ileocystoplasty viewed laterally.(a) Bladder opened and incised down to the trigone tocreate a ‘clam’ configuration. (b) Segment of ileumisolated on its mesentery, opened (detubularised) andsutured on to the bladder.

Posterior Anterior

(a)

(b)

Figure 13.10 Operative photograph showingcompleted clam ileocystoplasty.


Autoaugmentation plus demucosalised enterocystoplasty

The epithelial diverticulum created by a standardautoaugmentation is covered by a demucosalisedenteric patch, usually of stomach or colon.Although this technique enjoys the theoreticaladvantage of creating an augmentation lined byurothelium rather than intestinal epithelium, thelong-term outcome has yet to be assessed. Fibrosisand contraction of the patch is still a problem.

Augmentation with tissue-engineered neobladder

Only very recently developed for human use, thistechnique entails replacing much of the neuro-pathic bladder with a cup-like Vicryl ‘construct’into which the patient’s own urothelial and detru-sor cells have been seeded and grown in vitro priorto reconstructive surgery. Although the resultsobtained in the first seven patients treated by thismeans confirmed its feasibility, the functional


Table 13.4 Complications of enterocystoplasty

Mucus productionCatheter blockageInfectionBladder stone

Metabolic changesHyperchloraemic alkalosisElectrolyte disturbanceSystemic alkalosis (gastrocystoplasty)

Spontaneous perforation

Metaplasia/malignancy

Bowel problemsDiarrhoeaVitamin B12 deficiency

Dysuria/haematuria (gastrocystoplasty only)

Figure 13.11 Sigmoid pouch cystoplasty. (a) Segmentof sigmoid colon isolated on its mesentery. (b) Colonicsegment detubularised, then reconfigured as a pouch.The use of this form of enterocystoplasty is generallylimited to small, non-compliant bladders.

Figure 13.12 Ureterocystoplasty.

(a)

(b)


outcomes were disappointing, with little, if any,increase in bladder capacity. Presently, then, thisapproach must be regarded as being in the experi-mental phase.

Sphincter-enhancement procedures

These are two general categories of sphincter-enhancement procedure:

• The artificial sphincter, which, because it can beturned ‘on’ and ‘off ’ at will, theoretically enablesvoiding by abdominal straining alone.

• Other procedures, which, in creating or enhanc-ing a fixed urethral resistance, necessitatevoiding by CISC.

Artificial urinary sphincter (Figure 13.13)

This device has several drawbacks:

• Cost.• Infection and/or urethral erosion, necessitating

device removal.• Need for revisionary procedures. When the

entire device has been inserted, revision isalmost always required within 12 years ofimplantation.

Although voiding is ideally achieved by abdominalstraining alone, in practice some 80% of patientsuse CISC as the sole or a supplementary means ofvoiding. This proportion is less if preliminarytransurethral sphincterotomy is undertaken, butthe effect of this procedure is not always perma-nent. Additionally, very few patients who have alsoundergone augmentation can achieve adequateemptying without CISC.

Despite these disadvantages, the artificialurinary sphincter remains the best option forboys and renders upwards of 80% reliably dry.Because the device is designed for adults, it is notsuitable for children under 8 years of age. Thesphincter cuff is usually implanted at the bladder

neck, although the bulbar urethra is an alternativesite after puberty. When augmentation cysto-plasty is undertaken simultaneously, it is prefer-able to implant the sphincter cuff alone, as thiscombination will be sufficient in itself to securecontinence in some patients, thereby obviatingany need to implant the other components of thesystem.

Inflatable periurethral constrictor(Figure 13.14)

This new device is cheaper and has fewer compo-nents than the artificial sphincter. Three cuff sizesare available and these can also be adjusted at thetime of surgery. As with the artificial sphincter, thecuff is implanted around the bladder neck orbulbar urethra, while the reservoir is positionedsubcutaneously in the iliac fossa, the inguinal


Control pump

Pressure-regulatingreservoir

Cuff

Figure 13.13 American Medical Systems AMS 800artificial urinary sphincter. Components comprise thecuff, which is implanted around the urethra; the pump,which is implanted in the scrotum; and the pressure-regulating balloon, which is sited in a plane betweenthe peritoneum and the abdominal wall musculature.(Reproduced with permission from American MedicalSystems UK Ltd, Hanwell, Middlesex, UK.)



Figure 13.14 (a) Lima cuff urethral constrictor with itstwo constituent parts; the periurethral cuff and theimplantable inflation reservoir. (b) Lima constrictor withcuff around bladder neck. (c) Lima constrictor withreservoir inserted in subcutaneous area of right iliacfossa.

region or the scrotum. Accessible by means ofpercutaneous puncture, the reservoir is subse-quently filled under manometric control to thepressure required to achieve continence in anupright position. Voiding or CISC can be achievedwithout need to empty the cuff, although it can bedeactivated or reactivated at any time by emptyingor refilling the reservoir.

Injection of periurethral bulking agents (collagen, silicone, Deflux)

Such agents are of limited value, and securecomplete continence only in those patients withinherently marginal sphincteric incompetenceor those who are virtually dry as a result ofprevious surgery but require a minor degree ofadditional outflow resistance to achieve an idealresult.

Bladder neck suspension and slings

If combined with simultaneous augmentationcystoplasty, a Marshall–Marchetti bladder necksuspension achieves success in upwards of 80% ofgirls. The results of bladder neck slings may proveto be marginally superior.

Pippi Salle procedure (Figure 13.15)

This urethral lengthening procedure is suitable forgirls but not for boys.

Bladder neck closure

Bladder neck closure necessitates a simultaneousMitrofanoff procedure and, in many cases, anaugmentation cystoplasty. Although successfulin more than 90% of cases, both boys andgirls, bladder neck closure should be considered a

(a)

(c)

(b)



procedure of last resort, to be employed only whenalternatives have failed or are impracticable. Oncethe bladder neck has been closed there remainsonly one, limited, means of endoscopic access tothe bladder, an important consideration in view ofthe incidence of bladder stones following Mitro-fanoff procedures and enterocystoplasties.

Other surgical proceduresemployed with neuropathicbladderMitrofanoff procedure

The principal indications are:

• patients undergoing bladder neck closure• patients in whom urethral CISC is impractica-

ble by reason of deformity, or is unacceptablebecause of urethral sensation.

The appendix, if available and of sufficient length,is the conduit of first choice. The best alternativeis a Monti tube (Figure 13.16), which, ifconstructed of ileum, provides an easily catheteris-able conduit some 7 cm long. When necessary, agreater length can be obtained by end-to-endanastomosis of two or more such tubes or bythe so-called spiral Monti. Stomal stenosis at thejunction between the conduit and skin of theabdominal wall is the most common complication

and the risk can be minimised by the use of multi-ple skin flaps or by siting the stoma in the umbilicus.In obese patients or those with spinal deformities,it is important that the stoma be visible and readilyaccessible in the sitting position.

Cutaneous vesicostomy

This simple and effective temporising means ofreversing established upper renal tract complica-tions is mainly employed in infants. To reduce therisk of prolapse the stoma should be sited as nearthe apex of the bladder as possible.

Endoscopic urethral sphincterotomy

For boys, sphincterotomy is equally effective intreating detrusor–sphincter dyssynergia and staticsphincteric obstruction but inevitably leads toincontinence if the bladder neck is incompetent.Hence this procedure is of only limited use, eitheras a preliminary manoeuvre prior to the insertionof an artificial urinary sphincter or, occasionally,for infants and severely disabled patients.

Conduit urinary diversion

Once the mainstay of treatment, this procedure isnowadays almost exclusively reserved for severelydisabled patients. Careful siting of the stoma iscritical in patients with spinal deformities. When

Figure 13.15 The Pippi Salle procedure.

Figure 13.16 Monti tube fashioned from ileum. Thisis the most satisfactory alternative to the appendix forthe creation of a continent catheterisable conduit(Mitrofanoff procedure).


the ureters are undilated, the upper renal tracts arebest preserved by constructing a sigmoid conduitwith antirefluxing ureterocolic anastomoses.

Management in neonates and infantsAlthough the upper renal tracts represent theimmediate concern, any active treatment shouldavoid compromising later continence. Neonatesidentified as having an ‘unsafe’ bladder are bestcommenced on intermittent catheterisation at thisstage, and oxybutynin (or botulinum toxin A) mayalso be considered if there is marked detrusoroveractivity. In other circumstances, regular(4-monthly) ultrasound surveillance during thefirst 2 years of life is usually sufficient.

Despite every effort, major upper renal tractcomplications may still occur and are usually bestmanaged by a temporising cutaneous vesicostomy.Endoscopic sphincterotomy represents an alterna-tive for male infants with a contractile bladder anda competent bladder neck.

Management of the severely disabledLess ambitious management, limited to protectingthe upper renal tracts and securing dryness with aminimum dependence on others, is advisable forpatients with impaired intellect, poor dexterity or,most commonly, an inability to balance withoutsupport when sitting. A penile appliance is appro-priate for boys and endoscopic sphincterotomyshould be undertaken if there is any element ofbladder outflow obstruction. An indwellingurethral catheter, if properly handled, is suitable forlong-term management of girls. Where thesemeasures fail or are considered socially unaccept-able, a conduit urinary diversion may be offered topatients of either sex.

Bowel managementIt is self-evidently highly desirable that faecal incon-tinence is not neglected at the expense of dealing

with its urinary equivalent: all children deserveto be clean as well as dry. Assessment and treat-ment should begin at the same time as urologicalmanagement.

The effects of spinal cord lesions on the rectum andanal sphincter are similar to those on the bladder/sphincter mechanism and faecal incontinence mayresult from constipation, overflow incontinence,sphincteric incompetence or any combination ofthese mechanisms. As a rule, initial treatment involvesavoiding gross constipation by means of an appropri-ate diet or laxative medication, and ensuring regularcolonic emptying by a variety of methods that includeabdominal straining, manual evacuation, purgatives,suppositories or retrograde enemas.

If these measures fail, or if an older child becomesunwilling to continue treatment with enemas orsuppositories, an antegrade continence enema(ACE) procedure should be considered. Utilising theMitrofanoff principle to provide continent catheteraccess to the proximal or distal colon, the ACEprocedure enables the colon to be regularly and fullyevacuated by means of a variety of solutions rangingfrom tap water to phosphate. If, as is often the case,the appendix is not available for this purpose, aMonti ileal tube may be used instead, or, alternatively(and especially if no major urological surgery is to beundertaken at the same time) a percutaneousendoscopically guided tube postitioned in thecaecum under colonoscopic vision. Measurement ofthe colonic transit time is often helpful in determin-ing where an ACE procedure should be positioned.If the transit time is prolonged, a left-sided ACE isthe preferred site as it is associated with fewerproblems (e.g. pain and colonic distension) follow-ing introduction of antegrade enema fluid. Wherepracticable and if wished, an ACE procedure can beperformed at the same time as bladder reconstruc-tion, thereby achieving faecal and urinary continenceat the one operation.

Since its introduction in 1989, over 1000 ACEprocedures have been performed, and for patientswith a neuropathy a high success rate (exceeding80%) is coupled with a significant increase in the‘quality of life’ score. The commonest long-term



complication is stomal stenosis. If the ACE fails oris deemed not suitable, a permanent colostomyremains an acceptable option.

Key points

• Secondary upper renal tractcomplications are far moreprevalent among children withcongenital neuropathic bladder thanamong adults with acquired lesions,and occur in both boys and girls.

• Bladder function is determined bywhether the conus medullaris isintact or destroyed: in the formerinstance, conus reflexes are positiveand the sphincteric mechanism isalmost always competent. Positiveconus reflexes carry a goodprognosis for continence.

• Especially among myelomeningo-coele patients, management maybe influenced by non-urologicalconsiderations (intelligence,mobility, spinal deformity).

• Intermittent catheterisationrepresents effective managementonly when there is adequatelow-pressure functional bladdercapacity. In 80–90% of patientsthis is lacking.

• Impaired bladder capacity maybe the result of detrusor

overactivity, detrusor non-complianceor sphincteric incompetence, eithersingly or in some combination.Of these, sphincteric incompetenceis the most difficult to treat.

• Secondary upper renal tractcomplications occur only whenintravesical pressure becomesraised as a result of detrusorhyperreflexia and/or detrusornon-compliance and never occurwhen gross sphinctericincompetence leads to apermanently empty bladder.

Further reading

Godbole P, Wilcox DT. Surgery for neuropathic bladder andincontinence. In: Stringer MD, Oldham KT, Mouri-quand PDE (eds). Paediatric Surgery and Urology:Long-Term Outcomes. Cambridge: Cambridge Univer-sity Press, 2006: 631–642

McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognos-tic value of urodynamic testing in myelomeningocoele.J Urol 1981; 126: 205–209

Mundy AR. Urodynamic and Reconstructive Surgery of theLower Urinary Tract. Edinburgh: Churchill Living-stone, 1993

Mundy AR, Stephenson TD, Wein AJ (eds). Urodynamics:Principles, Practice and Application, 2nd edn.Edinburgh: Churchill Livingstone, 1994

Williams MPL, Katz Z, Escala J, Rickwood AMK. Peripheralneurology as a predictor of bladder dysfunction in congen-ital neuropathic bladder. Br J Urol 1988; 62: 51–53




Anorectal anomalies

Anorectal anomalies comprise a spectrum of congen-ital malformations in which the anus fails to opennormally on to the perineum. At one end of thisspectrum are the minor anomalies in which the analcanal is present but the anus is covered by perinealskin (Figure 14.1). The severe forms of anomaly arecharacterised by a high termination of the rectumand the presence of a congenital fistula connectingthe rectum to the lower urinary tract (Figure 14.2aand b). In females the most severe expression of theanomaly is the cloacal malformation, in which therectum, urethra and vagina join to form a singleconfluent channel draining by a common openingon the perineum (Figure 14.3).

Incidence and aetiologyThe incidence of anorectal malformations isapproximately 1 in 5000 live births, with a slight male to female preponderance of 3 to 2. The embryological defect resulting in congenitalcloacal anomalies can be ascribed to a failure of thenormal ‘compartmentalisation’ of the primitivecloaca by the urorectal septum and Rathke’s folds.At a more fundamental level, the aetiology ofanorectal anomalies, including persistent cloaca,

remains poorly understood. Although the observedassociation with genetically determined conditionssuch as Down’s syndrome points to a geneticcomponent in some cases, it is most unlikely thatthe complex spectrum of anorectal malformationswill prove to be the outcome of a simple genemutation, although knockouts of certain genesincluding ephrin B and Sonic Hedgehog do lead toanorectal anomalies in mice.

ClassificationA simple classification system is given in Table 14.1.Approximately two-thirds of girls have the ‘low’

14

Topics coveredAnorectal anomalies

Associated anomalies – urogenital/spinalLower urinary tract dysfunctionSurgical management

VACTERL and CHARGE associationsEctopic/horseshoe kidney

The urinary tract in anorectalmalformations, multisystemdisorders and syndromes

Duncan T Wilcox

Figure 14.1 Characteristic appearances of theperineum in an infant with low anorectal anomaly.


form of the anomaly, in which the anorectal canaldescends through the pelvic floor to terminate atthe level of the perineum. Although the anus mayend blindly, there is frequently a perineal fistulabetween it and the vaginal vestibule. By contrast,two-thirds of boys have a ‘high’ anomaly, with therectum ending above the levator musculature andterminating via a rectourinary fistula. Conse-quently, the functional outlook for boys is worse.However, cloacal anomalies in girls represent anexception to this general rule and for this reasonmust be considered separately.


Figure 14.2b (a) Perineum of male infant withbuttocks parted. High anorectal malformation withabsent anus. Note area of decreased pigmentation atthe site of where the anus should be. (b) Meconiumdischarging from the urethral meatus of a male infantwith rectourethral fistula associated with high anorec-tal anomaly. Note also the presence of hypospadias.

Male Female

Anorectal anomaly Anorectal anomaly without fistula without fistula

Perineal fistula Perineal fistulaRectourethral fistula Vestibular fistulaRectovesical fistula Cloaca

Table 14.1 Simple classification of anorectalmalformations

Figure 14.3 Cloacal anomaly. Single perineal orificedraining the urinary, genital and lower gastrointestinaltracts in a female infant.

(a)

(b)


Associated anomalies (Table 14.2)

Anorectal malformations are frequently associ-ated with abnormalities in other systems, withmost published series reporting a 50–60% rate ofcoexisting anomalies. Of these, the most commonis the VACTERL association (previously termedthe VATER syndrome), which comprises verte-bral, anorectal, cardiac, tracheo-oesophageal, renaland limb (typically radial) anomalies. Not allcomponents of the VACTERL association areexpressed in every patient, the most commonbeing vertebral, anorectal and renal abnormalities.The anomalies of most relevance to urologists arethose affecting the genitourinary tract and spine.

Urinary tract anomalies

Coexisting anatomical anomalies of the upper andlower urinary tract occur in approximately 60% of patients with anorectal malformations. Of these, the most common is vesicoureteric reflux(Figure 14.4), which in some series has beenreported to be present in more than half thepatients studied. The pattern of urinary anomaliesidentified is illustrated in Table 14.3. In addition tostructural anomalies, up to 6% of children developrenal impairment, an incidence which increases tonearly 50% of girls with cloacal anomalies. Conse-quently, early detection of renal impairment is animportant aspect of management.

Genital anomalies

Abnormalities of the male external genitalia arecommonly present, including undescended testes(20%), bifid scrotum (15%), hypospadias (18%)

Urinary tract in anorectal malformations, multisystem disorders and syndromes 191

Anomaly Incidence (%)

Vertebral 25–40Cardiac 20

Tetralogy of FallotASD/VSD

Gastrointestinal 15Tracheo-oesophageal fistulaDuodenal atresiaHirschsprung’s disease

Genitourinary 60

Table 14.2 Other anomalies associated withanorectal malformations

Figure 14.4 Coronal view of a distal loopagram.Contrast shows bilateral vesicoureteric reflux (gradeIV on right).

Urinary anomaly Patients (n = 45)

Vesicoureteric reflux 16Hydronephrosis 6Crossed fused ectopia 3Dysplastic kidney 3Bladder diverticulum 2Renal agenesis 1Horseshoe kidney 1Megaureter 1Prune-belly syndrome 1

Table 14.3 Pattern of structural anomalies of theurinary tract in 45 children with anorectalmalformations treated at the Hospital for SickChildren, Great Ormond Street


and (rarely) absence of the vas deferens. Anomaliesof the female genital tract are less readily apparent,but vaginal and uterine duplications, as well asvaginal septae, are well documented and may bepresent in up to 30% of girls with anorectalanomalies. Cloacal malformations are associatedwith an even higher incidence of anomalies of theinternal genitalia. In addition, clitoral hypertrophyhas been reported.

Spinal anomalies

The incidence of vertebral anomalies in childrenwith anorectal malformations has been reported to be as high as 40%. Many of these children have associated intraspinal pathology, carrying arisk of tethered cord syndrome and, in turn, urolog-ical, neurological and orthopaedic complications.Because early neurosurgical intervention may beeffective in averting progressive neurological deteri-oration in some patients, it is important to identifypossible cord tethering at an early stage. Investiga-tion of the spine should therefore be undertakenroutinely in all children with anorectal anomalies,with more detailed investigation of the spinal cordin those in whom a problem is identified.

Initial imaging should include both anteroposte-rior and lateral radiological views of the sacrum toidentify sacral anomalies. The most commonlyidentified lesions are partial and complete sacralagenesis (Figure 14.5). If the sacrum is radiologi-cally normal, intraspinal pathology is unlikely to bepresent although it has been reported. Consequently,most centres usually undertake further investiga-tions. In infants under 4 months of age spinalultrasound has proved to be very sensitive inidentifying intraspinal anomalies, although it is lessaccurate than magnetic resonance imaging (MRI)for visualising the specific intraspinal pathology. Inone recently published series no spinal anomalieswere missed on ultrasound. It is therefore currentlyrecommended that neonates with anorectalmalformations should be investigated initially withsacral radiographs and spinal ultrasound, withMRI being reserved for those in whom neuro-surgery is being considered.

Lower urinary tract dysfunctionBladder dysfunction may be the result of a congen-ital neuropathy associated with a coexisting spinalanomaly, or it may represent neurological damageacquired during surgical repair of the anorectalmalformation. In one series, 25% of children withanorectal anomalies were found to have severelower urinary tract dysfunction, which in everyinstance was associated with a demonstrable sacralabnormality. The majority of children with severebladder dysfunction were incontinent, and a thirdhad reflux nephropathy, highlighting the impor-tance of investigating the lower urinary tract inchildren whose anorectal anomaly is accompaniedby a sacral abnormality. In addition to those childrenwith bladder neuropathy associated with a congen-ital spinal anomaly, a further 20% of children


Figure 14.5 Plain radiograph demonstrating sacralagenesis.


experienced deterioration of bladder functionfollowing surgical repair of their anorectal malfor-mation; in half of them this proved to be perma-nent. In summary, up to 20% of patients withanorectal malformations suffer from urinary incon-tinence. Moreover, bladder dysfunction, whenpresent, can lead to renal damage in a third ofpatients. Consequently, awareness and appropriateinvestigation of these children is necessary tominimise the risk of ongoing renal damage.

Urological investigation ofchildren with anorectalanomaliesThe radiological investigations of the spine andurinary tract in children with anorectal malforma-tions are summarised in (Figures 14.6 and 14.7).Whether all children should also be routinely inves-tigated by urodynamics is debatable, although, asmight be expected, there is a high incidence ofabnormal urodynamic findings in those with sacralabnormalities. In addition, despite the use of amidline posterior approach for surgical correctionof the anorectal anomaly, up to 10% of childrendevelop demonstrable and permanent bladderdysfunction following surgery. Initial urodynamicassessment and urodynamic follow-up are advis-able for all children with sacral anomalies, and/orsigns of bladder dysfunction. Routine clinicalfollow-up should be continued (including renaland bladder ultrasound) until urinary continencehas become established. The onset of newsymptoms or a change in the pattern of existingsymptoms, both of which might indicate theonset of neurological deterioration, merits formalurodynamic assessment.

Surgical management ofanorectal anomaliesA detailed account of the surgical management ofanorectal anomalies is beyond the scope of thischapter. In general, these children undergocolostomy shortly after birth, followed by formalrepair at approximately 3 months of age. The

technique most widely employed is the posteriorsagittal anorectoplasty originally described andpopularised by Peña (Figure 14.8).

Urological complications of surgeryAlthough the introduction of the midline poste-rior sagittal approach has reduced the incidence of neuropathic bladder, approximately 10% ofchildren develop new or increased bladder dysfunc-tion following this procedure. Mobilisation and


UltrasoundMCUG

No reflux

No abnormalitiesAbnormalityReflux

DMSA scan MAG3 scan

Figure 14.7 Diagnostic algorithm for the investiga-tion of the urinary tract in an infant with an anorectalanomaly.

Sacral radiographsSpinal ultrasound

If consideringneurosurgery

MRI

Abnormality No abnormalities

Figure 14.6 Diagnostic algorithm for the investiga-tion of the spine in an infant with an anorectalanomaly.


division of the rectourethral fistula is an integralstep in the operation and, as such, may inevitablycause some damage to the immediately adjacentautonomic pelvic nerves. The urethra itself is alsoat risk during this dissection. Urethral damageoccurred in 12% of patients during the olderabdominoperineal operations for anorectalanomalies, but this complication is much rarerwith posterior sagittal anorectoplasty. Injuries tothe vas deferens have also been reported. Thecomplexity of the surgery, and hence the risk ofcomplications, is greatest in children with severeanorectal anomalies associated with the presence ofa fistula between the rectum and the urinary tract.

Cloacal anomaliesCloacal anomalies account for approximately 10%of anorectal malformations in girls. The cloacalmalformation is characterised by confluence of theurethra, rectum and vagina to form a commonchannel draining by a single opening on theperineum (see Figure 14.3). Cloacal anomalies arecurrently classified according to whether thecommon channel is less or greater than 3 cm inlength, as measured on cystoscopy. In addition tothe renal anomalies seen with anorectal anomalies,cloacal malformations are accompanied by a highincidence of vaginal abnormalities. Septate vaginaand/or bicornuate uterus have been reported in45% of cases, and up to 5% have an absent vagina.

The initial management of a child with a cloacalanomaly requires not only diversion of the faecalstream, usually by a colostomy, but also drainage ofthe urinary tract and, where necessary, decompres-sion of hydrocolpos. In some patients satisfactorybladder drainage can be achieved by intermittentcatheterisation of the common channel, but it maybe necessary to place a suprapubic catheter. Rarely,both vesicostomy and vaginostomy are required tosecure adequate infection-free drainage. However,this approach is best avoided as it can complicate thedefinitive repair. Cloacal malformations are nowmostly corrected using the posterior sagittalapproach, particularly in cases where the commonchannel exceeds 3 cm in length. Where the commonchannel is short (<3 cm) it may be feasible to use aperineal approach to relocate all three orifices on tothe perineum by mobilisation of the urogenital sinus.

The functional results of surgery for thesechildren reflect the length of the common channel.In the ‘low’ confluence anomalies, where thecommon channel is less than 3 cm, 70% of childrenwill be continent of urine and 50% continent offaeces. In contrast, only 30% of children with achannel length greater than 3 cm will be continentof urine and faeces. The sexual outcome is not welldocumented, although some women are known tobe sexually active and there are reports of success-ful pregnancy following cloacal repair.

Syndromes and associationsinvolving the urinary tract

Abnormalities of the genitourinary tract are oftenseen in association with or as part of a clinicalsyndrome. Two of the most important associa-tions are:

• VACTERL association, which comprises verte-bral, anorectal, cardiac, tracheal, oesophageal(esophageal), renal and limb anomalies. Thoseaspects of greatest relevance to the urologisthave already been considered above.

• CHARGE association, which consists ofcoloboma of the eye, heart anomalies, choanal


Levator musclecomplex

Rectum prior totailoring

Site ofanoplasty

Closure ofrectourethralfistula

Figure 14.8 Posterior sagittal anorectoplasty. Withthe patient prone, the rectum is approached via asagittal incision. The rectourethral fistula is dividedand the rectum tailored before being positionedthrough the levator complex and external sphincterand brought down onto the perineum.


atresia, mental retardation, genital and earanomalies. In one series of 32 children withCHARGE, the overall incidence of genitouri-nary tract abnormalities was 69% (Table 14.4).

Abnormal migration and fusion of the kidney

Ectopic kidneyEctopic kidneys can be divided into simple, horse-shoe and crossed renal ectopia.

Simple ectopic kidney

The ectopically sited kidney may be locatedanywhere along the embryological path of ascentfrom the pelvis to the renal fossa. Pelvic kidneys arethe most common of renal ectopias, accounting for60% of all cases. In 90% the anomaly is unilateraland with a slight left-sided preponderance. Inaddition to its abnormal location, a pelvic kidneyis frequently hypoplastic and irregular in shape(Figure 14.9). Other ectopic kidneys lie at somepoint between the pelvis and the normal positionor, very rarely, within the thorax.

Genital and contralateral urinary abnormalitiesare often associated with ectopic kidneys and

include absence of the vagina, retrocaval ureter,bicornuate uterus, supernumerary kidney and ipsilat-eral ectopic ureter. The ectopic kidney can be acomponent of more complex syndromes, such asthe Mayer–Rokitansky–Küster–Hauser syndrome,Fanconi’s anaemia or conjoined twins.

Horseshoe kidney

Horseshoe kidneys are encountered in 1:400 and1:1800 autopsies and the anomaly is morecommon in males. In 95% of cases the lower poles of the two kidneys are joined by an isthmusof renal tissue which may consist of normal


Figure 14.9 Intravenous urogram demonstratingectopic kidney – pelvic right kidney.

Incidence (%)

Genital anomalies 56HypospadiasMicropenisUndescended testicleVaginal and uterine atresia

Urinary tract anomalies 42Duplex kidneyVesicoureteric refluxRenal agenesisHydronephrosis

Table 14.4 Genitourinary malformations in theCHARGE association


parenchyma or dysplastic or fibrous tissue. In about40% of cases the isthmus lies at the level of L4, justbeneath the origin of the inferior mesenteric artery,in 20% in the pelvis (Figure 14.10) and in theremaining 40% at the level of the lower poles ofnormally placed kidneys. A small proportion ofhorseshoe kidneys are fused at their upper poles.The ureters arch anteriorly to pass over the isthmus,thus explaining the relatively high incidence ofpyeloureteric anomalies (20%) associated withhorseshoe kidney (Figure 14.11a and b). Horse-shoe kidney is commonly found in association withother abnormalities or syndromes, notably Turner’ssyndrome and abnormalities of the central nervoussystem, the gastrointestinal tract and the skeletaland cardiovascular systems.

Crossed renal ectopia

There are four varieties of crossed renal ectopia:

• with renal fusion (85% of cases) • without fusion (<10%)• solitary• bilateral.


Figure 14.10 Intravenous urogram – horseshoekidney.

Figure 14.11 (a) Intravenous urogram demonstrat-ing dilatation due to obstruction in the left side of ahorseshoe kidney. (b) DMSA scan in the same patientdemonstrating reduced isotope uptake in the centralpart of the left kidney (dilated collecting system) andfunctioning tissue outlining the isthmus connecting theright and left kidneys.

(a)

(b)



There is a slight male predominance, and crossingfrom left to right occurs more frequently than fromright to left. The point of fusion is usually betweenthe upper pole of the crossed kidney and the lowerpole of the normally positioned kidney (unilateralfused type) (Figure 14.12). Associated anomaliesare commonly found with renal ectopia. Inaddition, renal ectopia may also be a component ofmore complex syndromes, such as VACTERL andagenesis of the corpus callosum.

Presentation and investigation of abnormalities of ascent and fusionAbnormalities of ascent and fusion are mostcommonly incidental findings, typically on prenatalor postnatal ultrasound examinations. Conversely,

non-dilated pelvic ectopic kidneys may be difficultto visualise on ultrasound, and absence of thekidney in the renal fossa may be misinterpreted asrenal agenesis. In such cases the presence of ectopicfunctioning renal tissue is best demonstrated byDMSA (dimercaptosuccinic acid) renography.Crossed fused renal ectopia may sometimes presentclinically as an incidentally discovered mass duringthe course of abdominal examination. The occur-rence of pain or symptoms associated with urinaryinfection generally denotes additional pathology,such as vesicoureteric reflux or pelviureteric junctionobstruction. Investigation of an uncomplicatedectopic or horseshoe kidney can reasonably belimited to ultrasound and a DMSA scintigram.Additional investigations are indicated if there ishydronephrosis or a history of documented infectionraising the possibility of reflux. However, it isimportant to stress that the majority of patients areuntroubled by their abnormally placed kidney, andsurgical intervention should be confined to correct-ing coexisting pathology, obstruction or reflux.When surgery is warranted it should be borne inmind that the anatomy may be abnormal and thatthe blood supply can have an aberrant course.

Key points

• Children with anorectal anomalieshave a high incidence of urinary tractabnormalities and functional urinaryproblems. In addition to urinaryincontinence, the bladder dysfunctionin children with anorectalmalformations poses a potentialthreat of urinary tract infection,renal damage and chronicrenal failure.

• Early recognition and effectivemanagement of urologicalproblems in children with anorectalmalformations is essential tominimise these risks.

Figure 14.12 Intravenous urogram – crossed fusedrenal ectopia.


• In view of the high incidence ofgenitourinary tract anomalies in theCHARGE association all affectedinfants should be screenedappropriately, initially by urinarytract ultrasound, and then withadditional modalities such asrenography where indicated.

• Anomalies of ascent and fusion,including pelvic kidney, horseshoekidney and crossed ectopia, aremainly asymptomatic incidentalfindings. Surgical intervention isonly required when there iscomplicating pathology such anobstruction or reflux.

Further reading

Bauer S. Anomalies of the kidney and ureteropelvic junction.In: Walsh PC, Retik AB, Vaughan ED, Wein AJ (eds).Campbell’s Textbook of Urology, 7th edn, Vol 2.Philadelphia: WB Saunders, 1998: 1708–1730

Boemers TM, Beek FJ, Bax NM. Guidelines for the urolog-ical screening and initial management of lower urinarytract dysfunction in children with anorectal malformations– the ARGUS protocol. BJU Int 1999; 83: 662–671

Peña A, Levitt MA. Anorectal malformations: experience withthe posterior sagittal approach. In: Stringer MD, OldhamKT, Mouriquand PDE (eds). Pediatric Surgery andUrology: Long-Term Outcomes, 2nd edn. Cambridge:Cambridge University Press, 2006: 401–415

Peña A. Anorectal malformations. Semin Pediatr Surg1995; 4: 35–47

Ragan DC, Casale AJ, Rink RC, Cain MP, Weaver DD.Genitourinary anomalies in the CHARGE association.J Urol 1999; 161: 622–625



Bladder exstrophy andepispadias

Peter Cuckow

Introduction

This chapter covers one of the most challengingconditions in paediatric urology. In addition to thecomplex surgery needed to correct the severe bladderabnormalities and genital deformities, there may besecondary problems relating to renal function andfertility. Because of the low incidence of bladderexstrophy and related conditions (Table 15.1), veryfew individual surgeons have had the opportunity toacquire sizeable series of patients. Even thoseworking in major centres serving large populationsmay see only one or two new patients each year.In the UK it was therefore decided to concentratebladder exstrophy surgery in two supraregionalcentres, thus enabling a smaller number of paediatricurologists to develop and maintain higher levels ofexpertise than was possible when cases were distrib-uted between more centres. Concentrating exstro-phy management in two supraregional centres hashad the added benefit of facilitating the developmentof new treatment strategies and new clinical and

laboratory research initiatives which will hopefullycontribute to improved outcomes for children bornwith this complex of severe anomalies.

Embryology and anatomy

The three distinct anomalies which constitute theexstrophy–epispadias complex are believed torepresent a spectrum of abnormalities arising fromfailure of development of the lower abdominalwall during the early weeks of gestation.

Bladder exstrophyFailure of migration of mesoderm to the area ofthe cloacal membrane, and subsequent lack of devel-opment of an intermediate layer between its inner(endodermal) and outer (ectodermal) layers, leads torupture and exposure of an open bladder plate andurethra. These structures occupy a triangular spacebetween a low-set umbilicus superiorly, split rectusabdominis muscles on each side and an open pelvic

15

Topics covered Embryology and anatomyBladder exstrophy: management and outcomes

Cloacal exstrophy: management and outcomes Primary epispadias: management and outcomes

Table 15.1 Incidence and sex distribution of the exstrophy–epispadias complex

Incidence per live births Male to female ratio

Bladder exstrophy 1:50 000 3:1Primary epispadias 1:120 000 5:1Cloacal exstrophy 1:300 000 6:1


ring inferiorly. The penile root remains attachedto the inferior border of the inferior pubic rami oneither side so that each hemicorpus has to traversethe intervening gap (known as the pubic diastasis) tounite with the contralateral corporeal body in themidline. The result is a foreshortened penis in males.The bladder plate is continuous with the urethralplate, on which are sited the openings of the ejacula-tory ducts at the level of the prostate (the verumon-tanum). The exposed urethral plate covers thedorsal surface of the corporeal bodies and glans(Figure 15.1). The testes are usually descended.Failure of development of the lower anterior abdom-inal wall and pelvic ring also imparts a relativelyanterior position to the anus. In females the bladdercomponent is identical, the clitoral corpora areseparated and a short urethral plate runs between theopen bladder and the vagina (Figure 15.2).

Cloacal exstrophyCloacal exstrophy is a more severe variant in whichthere is probably an additional failure of septation ofthe cloaca, so that the bladder anteriorly is notseparated from the hindgut posteriorly. This has theeffect of bringing both bladder and bowel compo-nents to the surface, with a central bowel field that liesin the midline between two separated halves of thebladder. There can be extensive prolapse of the proxi-mal colon and ileum and one or two appendices maybe seen on the bowel field. A second opening inferi-orly indicates a rudimentary loop of distal hindgut.The anus is imperforate and the sacrum is shortenedwith a high incidence of myelomeningocoele andspinal dysraphism. The pubic diastasis in these patientsmay be so great that the penile corpora fail to meet inthe midline and are completely separated. In addition,the testes are often undescended and absent from thescrotum or hemiscrotum. Superiorly there is usuallyan associated exomphalos (Figure 15.3).

Primary epispadiasThe embryological origins of epispadias are poorlyunderstood. In primary penile epispadias there isvariable diastasis that tends to be less severe than inbladder exstrophy. The pelvic ring is often complete,

with an apparently normal abdominal wall. As aresult the anus is appropriately sited and the scrotumalso appears normal. The urethra opens on thedorsal aspect of the penis. Depending on the sever-ity of the epispadias, the urethra may open distallyon the glans (glanular epispadias), on the shaft


Abdominal wall muscle

Umbilical cord

Open bladder

Pubic bones

Open penis

Anus

Figure 15.1 Newborn male infant with bladderexstrophy.

Abdominal wall muscle

Umbilical cord

Open bladder

Pubic bones

Open urethra

Labia minora anddivided clitoris

Vagina

Figure 15.2 Newborn female infant with bladderexstrophy.

Exomphalos

Two hemibladders

Midline bowel field

Separated corpora

Figure 15.3 Newborn male infant with cloacalexstrophy.


(penile epispadias) or proximally at the junctionwith the anterior abdominal wall (pubic or peno-pubic epispadias) (Figure 15.4). Underlying deficien-cies of the bladder neck and proximal urethra andstriated sphincter complex determine the degree ofassociated incontinence. As a general rule, however,the severity of incontinence correlates with theposition of the urethral opening, being most severein proximal epispadias. In these cases the posteriorurethra merges with the bladder neck and theverumontanum may lie at the level of the bladderneck or even within the bladder itself. The uretericorifices often lie close together and are normal ornarrowed in calibre, contrasting with the widerefluxing orifices seen in exstrophy.

In female primary epispadias the urethra is wideopen on its dorsal surface and the clitoris is separ-ated on either side with its attached labiumminorum. The urethra is short and wide and thebladder neck is deficient, leading to severe stress-type incontinence in all patients (Figure 15.5).

Antenatal diagnosis

The detection rate of cases of bladder exstrophy byantenatal ultrasound is currently around 40% at 18

weeks’ gestation. Diagnostic features includeinability to visualise urine in the fetal bladder; low-set umbilical cord; a short, wide penis; and abulging bladder plate. Cloacal exstrophy may beconfused with other abdominal wall defects suchas gastroschisis, but is more likely to be detectedbecause of the presence of other abnormalitiessuch as myelomeningocoele and renal and cardiacanomalies. Antenatal diagnosis provides an oppor-tunity for parents to consider termination ofpregnancy, but counselling should take into accountthe improving outcomes of intervention, particu-larly in classic bladder exstrophy.

Classic bladder exstrophy

Presentation and clinical featuresIf not detected antenatally, classic bladder exstro-phy presents at birth with a visible bladder platebelow a low-set umbilical cord. The mucosa maybecome quite inflamed and polypoid, especiallyafter a few hours’ exposure following delivery. Theshaft of the penis is usually short and thick with agood-sized glans. Although the genitalia are usuallyrecognisably male or female, there may be some

Bladder exstrophy and epispadias 201

Figure 15.4 Male primary epispadias: (a) glanular; (b) penile; and (c) penopubic.

(a) (b) (c)


confusion over gender in the referring hospital.The scrotum is present in boys with the distinctiveupwards direction of the rugae and the testes areusually palpable within it.

Classic bladder exstrophy has few associatedanomalies and babies are usually born at or closeto term and are otherwise well. Inguinal herniasare present in up to 80% of boys and 15% of girlsbut may not become apparent until after primaryclosure.

Initial neonatal management andprimary closureBecause affected newborns are born at term andrarely have other medical problems, they can beput to the breast and require no medical interven-tion in the delivery suite. Vitamin K should beadministered, particularly if surgery is anticipatedin the next few hours. While transfer to an appro-priate specialist centre is arranged, the exposedbladder plate is protected with a cling-film wrapinside the nappy. Antibiotics or intravenous accessare not required at this stage unless indicatedby the presence of other complications such asprematurity. If necessary, transfer can be delayedfor a few hours to enable both parents to accom-pany the baby.

Following transfer, the child is assessed at thespecialist centre, a baseline renal ultrasound isperformed and oral antifungal prophylaxis iscommenced as a prelude to surgery in the first 48hours of life

Surgical technique (Figure 15.6)

An epidural catheter provides optimal postopera-tive analgesia, broad-spectrum antibiotics areadministered and the abdomen and lower limbs areprepared and draped within the operative field.Ureteric catheters (usually 6 Fr feeding tubes) areinserted and the bladder plate is dissected free ofthe skin and rectus muscles on either side. Anylarge polyps are usually excised at this time and themucosal defects repaired. In boys, exposure of theexternal inguinal ring enables the hernial sacs to beidentified and ligated. The umbilical root is usuallyexcised after dividing its vessels, as this is a sourceof infection postoperatively. It is usually possible toperform this dissection extraperitoneally and it isthen continued inferiorly to the level of theverumontanum on either side of the proximalurethral plate. In girls, the dissection is continuedto just above the vaginal opening. Deep dissectionon either side of the bladder neck enables thebladder and proximal urethra to be closed in the


Figure 15.5 Female primary epispadias.


midline with interrupted 4/0 absorbable sutures.The ureteric catheters are brought out throughthe bladder closure and then through separatepunctures lateral to the rectus muscles and awayfrom the midline muscle and skin closure. Afine silicone stent is used across the urethralopening and secured to the bladder plate with afine absorbable suture. Unless the diastasis is wide,pressure on the iliac crests will bring the pubicrami together in front of the bladder neck, whichdrops back into the pelvis. Interrupted horizontalmattress sutures of heavy-gauge PDS (polydiox-anone) are used to approximate the pubic rami andfurther interrupted sutures used to join the rectusmuscles above it. The subcutaneous layers and skinare closed with interrupted absorbable sutures.

Finally, a frog-leg plaster is applied to the lowerlimbs to immobilise them in the first few days.

Postoperatively, all tubes are left on free drainageand adequate analgesia maintained with theepidural catheter. Feeding is recommenced early,with expressed breast milk if necessary, andprophylactic antifungal agents are continued. Theureteric catheters are removed after 10 days andthe urethral stent after 2–3 weeks, at which timethe plaster cast is also removed. Ultrasound evalu-ation of the upper urinary tract is performed afterall catheters have been removed to assess bladderemptying and the upper tracts before discharge.Regular follow-up with ultrasound is scheduled toevaluate progress and to help plan later interven-tions for continence and genital reconstruction.


Figure 15.6 (a) Primary closure of a newborn male exstrophy. (b) Separation of the bladder plate. (c) Closureof bladder with ureteric catheters. (d) Appearance after abdominal wall closure with plaster cast.

(a) (b)

(c) (d)


Complications are relatively common aftermajor reconstructive surgery of this nature, andmay include wound breakdown and partial orcomplete dehiscence, which occurs in up to 10%of patients. Factors contributing to this dehis-cence include pooling of urine at the new urinarymeatus, the use of stents emerging through themidline closure and retention of the umbilicalstump. All of these factors predispose to woundinfection, which, in combination with tension(and ischaemia), leads to dehiscence. Partialdehiscence which does not expose the bladdermay be left to heal by secondary intention. Amore serious dehiscence comprising either exposureof the bladder plate or prolapse of the bladder willrequire reclosure, for which pelvic osteotomiesmay be indicated.

The ureters in classic bladder exstrophy dipinto the pelvis and enter the bladder throughwide orifices without the normal antirefluxoblique tunnel. It is not surprising, therefore thatvesicoureteric reflux is almost invariably presentafter primary bladder closure. Moreover, a tighturethral closure causing outflow obstruction canlead to upper tract dilatation and renal damage ifinfection supervenes. Close surveillance is requiredto identify upper tract dilatation and a period ofintermittent catheterisation of the tight bladderoutlet is sometimes required.

The role of pelvic osteotomy

The pelvis in newborn exstrophy patients is suffi-ciently flexible to allow closure of the bladderwithout osteotomy in the majority of cases. Butwhere the pubic diastasis is wide or when closureis delayed, division of the bony pelvis between theanterior superior iliac spine and the greater sciaticnotch creates great pelvic mobility and allows atension-free closure of the pubis. When usedroutinely, osteotomy extends the operating time byup to 2 hours, increases blood loss and prolongspostoperative immobility. Nowadays it is thereforereserved for revision cases and cloacal exstrophy.Postoperative fixation of the bony pelvis is achievedwith frog-leg plasters in babies and externalfixators in older children.

Secondary procedures forcontinence and genitalreconstructionIn girls, primary closure can occasionally be suffi-cient to impart continence and create a satisfactorycosmetic appearance. In the overwhelming major-ity of exstrophy patients, however, further proce-dures will be required to achieve continence andfor the reconstruction of functionally and cosmet-ically acceptable genitalia. Until further conti-nence procedures are performed, the inadequateoutlet resistance results in dribbling incontinence.Although urinary tract infections are uncommon,some surgeons place patients on prophylacticantibiotics.

Continence surgery There are currently three accepted strategies inbladder exstrophy management. The firstapproach, popularised by Mitchell, aims to createcontinence by complete anatomical reconstructioncarried out at the time of initial bladder closure.The bladder plate is fully mobilised and the penilecorpora and urethral plate completely separatedbefore closure of the bladder and reconstructionof the urethra and penis. Although good resultshave been reported by the proponents of thiscomplex single-stage reconstruction, it neverthe-less represents a daunting surgical challenge in anewborn infant and major complications havebeen reported.

The more traditional staged reconstruction,popularised by Jeffs and Gearhart, has been thestandard approach for many years. Following con-ventional bladder closure at birth, epispadias repairis subsequently performed in the first 2 years oflife. This is then followed by a bladder neck recon-struction when the required bladder capacity hasbeen attained, usually by 5 years of age. If inconti-nence persists because bladder capacity fails toincrease sufficiently after the bladder neck repair, afurther bladder neck reconstruction may be under-taken in conjunction with augmentation entero-cystoplasty and the formation of a Mitrofanoffcatheterisable conduit.



The third option is the Kelly operation, which isnow the procedure of choice at Great OrmondStreet Children’s Hospital. After successful neona-tal closure of the bladder, an examination underanaesthetic is performed at 3 months to check thebladder and its outlet. Irrespective of bladder size,the operation is performed from 6 months of age.Initially, the bladder is reopened in the midlineand both ureters reimplanted using the Cohentechnique. The soft tissues, including the urethra,penile corpora and pelvic floor, are then fullymobilised before reconstructing the bladder outlet,urethra, sphincter and penis.

Detachment of the penile corpora from thelower border of the inferior pubic rami must becombined with release of the pudendal pediclewhich runs from the greater sciatic notch to thebase of the penis in Alcock’s canal and lies on theinternal obturator fascia, beneath the pelvic floormuscles. Following this manoeuvre, the base of thepenis can move freely towards the midline and lienext to the contralateral corpus. This eliminatesthe effect of the pubic diastasis and increases penileprotrusion and apparent length (Figure 15.7a).

Dissection of the urethral plate from the corporaand the glans enables it to be tubularised around


I II

Figure 15.7 (a) The Kellyoperation. (I) From the right of thepatient, the penile corpora andurethral plate are dissected andthe bladder is held to the left, thebase of the corpus is separatedfrom the pubis and movesmedially, the pelvic floor hasbeen released and the pudendalpedicle is seen (arrowed).(II) From below the penis, theurethra has now been detached,tubularised and brought betweenthe mobile corpora; muscle isbeing wrapped around it. (b)Kelly operation: postoperativeappearances.

(a)

(b)


an 8 Fr stent. The level of the bladder neck isdefined between the verumontanum and theureteric orifices and mucosal triangles removed oneither side, before closing it and then the bladderabove. In the majority of boys the length of theurethral plate is inadequate and would limit thefinal penile length. For this reason the urethralplate is separated form the corpora, allowing it tobe brought down between the penile corpora to ahypospadiac position. At this point, it lies anteriorto the muscles running between the bases of thecorpora, which are loosened by the corporalmobility. These can then be wrapped around theurethra with loose sutures, in a position that willbe just below the verumontanum and where thephysiological sphincter is sited in normal males.

The corporeal bodies are joined in the midlinewith external rotation to eliminate the dorsalchordee and to secure the position of the urethrabelow them. The new urinary meatus is secured onthe ventral surface and the dorsal glans is recon-structed before replacing the shaft skin. Theabdominal wall is reclosed with strong absorbablesutures and at this stage an umbilicoplasty isusually performed. A two-stage distal urethralreconstruction (analogous to hypospadias repair),using posterior auricular skin grafts, is completedduring the next year. In the author’s practice theKelly operation undoubtedly offers a superiorcosmetic result to the conventional staged repair(Figure 15.7b).

The Kelly procedure can also be performed ingirls. The two components of the bifid clitoris aremobilised, with the labia minora left attached andtheir pudendal pedicles are also identified andpreserved. Reconstruction of the bladder neckand urethra is undertaken in a similar fashion tomales. The mobility of the hemiclitori enables themto be brought together in the midline. No furtherprocedures will be needed in girls, as genital recon-struction is completed in a single stage.

Continence outcomesThe published continence rates following surgicalreconstruction of bladder exstrophy have generated

considerable confusion, and some controversy.Although continence rates as high as 70% havebeen reported by some centres, very few surgeonshave been able to match them and there is a percep-tion that selection according to bladder capacityand other factors may have played a role in somereported results. In practice, fewer than 25% ofboys are likely to achieve both continence andvoiding without the need of catheterisation follow-ing a traditional staged reconstruction.

In the assessment and reporting of functionaloutcomes it would be helpful if a standardiseddefinition of what constitutes ‘continence’ could beagreed and applied equally to all patients and treat-ment modalities. Only in this way can meaningfulcomparisons be made. The author has proposedthe simple grading system shown in Table 15.2 forcontinence.

Using this schema, the author has assessed theoutcome of 50 patients who have undergone theKelly procedure. Of those patients followed forover 2 years, the majority (92%) have a significantdry interval during the daytime. However, some ofthese patients still need to wear pads because ofincontinence related to reduced bladder capacity.Nevertheless, 71% of children are in normal under-wear and are dry by day. Night-time continencerequires a larger bladder capacity and, for this


Table 15.2 Grading system for continence

Grade Description

0 Dribbles urine all the timewith no control

I Able to retain urine witha ‘dry interval’; some controlbut still wearing protection

II Sufficient dry intervals byday; in underwear and notneeding protection; wet atnight

III Dry by day and night;no protection or accidents;‘normal child’


reason, only 25% of children are currently dry atnight. Experience has shown that the Kelly proce-dure provides a relatively predictable degree ofoutflow resistance and that the subsequent degreeof continence depends upon the potential of thebladder to enlarge in response to the increasedoutflow resistance.

Persisting incontinence is due either to inade-quate outflow resistance and/or inadequate bladdercapacity. Further surgery is usually required,although if residual incontinence is mild somedegree of further improvement can be expectedwith increasing age, particularly around puberty.For more severe persisting incontinence a repeatbladder neck reconstruction is performed incombination with ileocystoplasty and the forma-tion of a Mitrofanoff catheterisable conduit.Ideally this should be timed to provide continenceby the age of 6 years. If wetting persists despitethis form of reconstruction, urodynamics areindicated and, depending on the findings, cysto-scopic injection of a bulking agent such as Deflux(dextranomer/hyaluronic acid copolymer) into theregion of the bladder outlet may sometimesimprove continence. When incontinence persistsdespite all these measures, there may be no optionother than to proceed to surgical closure of thebladder neck.

Late outcomesWoodhouse has documented the late outcomes ofsizeable numbers of patients born with bladderexstrophy. Although these results may reflect theresults of outdated surgical approaches, such asureterosigmoidostomy, the findings highlight theimportance of careful long-term follow-up for allpatients. Renal damage can be demonstrated in25% of patients, due to a combination of lower tractobstruction, vesicoureteric reflux and urinary infec-tion. Evidence of renal insufficiency is present in upto 10% of patients. For those patients who haveachieved continence following a tight bladder neckprocedure in childhood, there is a risk of decompen-sation and detrusor failure in the late teens. Whenthis occurs, intermittent catheterisation via urethra

or a cystoplasty with a Mitrofanoff conduit is neces-sary. Stone formation is relatively common andoccurs in up to 25% of patients. The risk of malig-nancy in the reconstructed exstrophy bladder hasbeen estimated to be in the region of 4% at30 years follow-up.

Males experience normal libido and 90% ofpatients can achieve erections, although somerequire corrective surgery for severe persistentchordee to allow penetration. The majority canexperience orgasm but have slow or retrogradeejaculation, reflecting the abnormalities of proxi-mal urethral anatomy. Fertility is significantlyreduced, probably as a result of disruption of theejaculatory ducts during bladder neck surgery.Fertility may also be affected by episodes ofepididymo-orchitis which occur in up to one-thirdof men. The potential to achieve paternity bynormal means is as low as 5%.

For females the prospects for fertility are normalbut surgery to the introitus may be required tofacilitate intercourse. Pregnancy is often compli-cated by vaginal prolapse although, in future, thismay prove to be less problematic after modernsurgical procedures. Delivery by Caesarean sectionis recommended and it is prudent to have a urolo-gist in attendance for patients who have previouslyundergone bladder augmentation.

Unfortunately some patients are still encoun-tered who have experienced multiple failed opera-tions for bladder exstrophy, perhaps with loss ofpenile corpora and compromise of their renalfunction. In these situations major and complexrevisional surgery is required.

Cloacal exstrophy

Initial presentation andmanagementCloacal exstrophy is more often diagnosed prena-tally than bladder exstrophy because of the associ-ated anomalies, which are listed in Table 15.3.Affected babies are frequently born prematurelyand initially the cloacal exstrophy may be only one



of many problems. It is usual to delay primaryclosure while other medical problems affecting thegastrointestinal tract and cardiorespiratory systemsare evaluated and treated if necessary. Occasionally,surgical reconstruction may have to be delayed forseveral months. During this time the exstrophiedbladder/bowel plate is protected with cling filmand barrier creams applied to the surroundingskin. In the case of very low birth weight babies,enteral feeding is established, a target weight of2.5–3 kg is set and closure deferred until this hasbeen attained. When an exomphalos is present, thisusually contracts spontaneously without the needfor surgical intervention.

Routine preoperative evaluation includesurinary tract and spinal cord ultrasound examina-tions. Iliac osteotomies are routinely performed atthe time of closure because of the surgical delayand because of the wider diastasis invariably presentin these patients. The use of osteotomies usuallypermits a tension-free abdominal wall closure butwhen it is not possible to reduce the abdominalcontents and close the abdominal wall, a silo isattached over the upper abdomen to reducetension. This is then reduced and removed over the

ensuing days. The bladder/bowel plate is dissectedfree from the skin and rectus muscles superolater-ally and the abdominal cavity is entered. The proxi-mal and distal bowel loops of bowel joiningthe midline bowel plate are identified andseparated from the two hemibladders. A tubulariseddistal hindgut tube is created which is usuallybrought out in the left iliac fossa as an endcolostomy (in preference to an incontinent analcanal). The hemibladders are joined and closed,reconstructing a bladder outlet and proximalurethra (Figure 15.8).

Gender of rearingIn the past, males with cloacal exstrophy wereoften assigned to female gender because of theseverity of their genital anomaly and difficulty inreconstructing male genitalia in the presence ofwide diastasis and short, widely separated corpora.Gender reassignment also necessitated early bilat-eral orchidectomy and a later ileovaginoplasty,usually at the time of definitive continent recon-struction. With the introduction of the Kellyoperation, however, it is now possible to performfull corporeal mobilisation and achieve a moresatisfactory penile reconstruction. It is hoped thatthis will avoid the need for gender reassignment inthe majority of cases.

Initial outcomesPrematurity and severe cardiac anomalies are asignificant threat to early survival, together withcomplications of a short bowel and parenteralnutrition. Nonetheless, the majority of affectednewborns now survive to childhood. Careful surveil-lance of the upper urinary tracts helps to optimiserenal function and prevent progression to renalfailure. Magnetic resonance imaging (MRI) isused by neurosurgeons to assess the need for cordsurgery and orthopaedic surgeons are involvedto correct any limb problems. Colostomy compli-cations occur in around 50% of patients andit is occasionally necessary to remove thereconstructed hindgut and create an ileostomy inits place.


Table 15.3 Associated anomalies in cloacalexstrophy

Anomaly Cases affected (%)

Renal anomaliesEctopic kidney, 7agenesis, hydronephrosis

Sacral agenesis 60

Spinal dysraphismMyelomeningocoele, 50lipoma, tethered cord

Orthopaedic deformityClub foot, hip and 40pelvic deformity

Small bowel defectsMalrotation, duodenal 65atresia, short gut

Cyanotic heart disease <10



Continence and long-termoutcomesThe dual insult of exstrophy and neuropathymeans all of these patients will need an entero-cystoplasty to achieve continence and to ensurestorage of urine at safe pressures. Augmentation ofthe bladder may be a challenge when there is onlya short length of small bowel. In addition, theabsence of a usable appendix requires the use ofsome alternative to create a catheterisable conduit.However, most patients can be successfullymanaged by a combination of ileocystoplasty andthe formation of a Monti or small bowel catheter-isable conduit. If there is insufficient small intes-tine, the alternatives for augmentation includea patch of stomach or a hindgut segment. Themore complicated forms of reconstruction carry agreater risk of failure and any coexisting renalinsufficiency will increase it further and add tooverall morbidity.

Despite advances in reconstructive surgery somepatients with severe forms of this anomaly may beleft with lifelong urinary incontinence.

Patients who have been reared as males andwho survive to adulthood are then confrontedwith serious issues regarding their sexual function.Moreover, the combination of small penilesize and surgical damage to vasa deferentia and

ejaculatory mechanisms result in very high ratesof infertility.

Males who have undergone gender reassignmentdo not appear to experience gender dysphoria,providing their testes have been removed in earlychildhood. For these patients the surgical consider-ations relate mainly to vaginal reconstruction.

Primary epispadias

PresentationBoys with primary epispadias are rarely identifiedprenatally but the anomaly is almost invariablydetected at birth. In less severe (glanular) forms ofthe anomaly the prepuce is intact and the conditionmay not become apparent until the prepucebecomes retractile.

In girls, by contrast, the diagnosis may be consid-erably delayed, particularly as most paediatricianshave not seen this rare anomaly and miss it at thepostnatal check. The anomaly classically presents inchildhood with a failure of potty training or ahistory of dribbling or stress incontinence. In somecases there is a long history of attendance at wettingclinics. To an experienced examiner or someonewho has knowledge of this rare anomaly the appear-ances of the genitalia are diagnostic see Figure 15.5.

Figure 15.8 Male cloacalexstrophy, closed at 3 months.Osteotomies enable thebladder plates and hemiphallito be brought together in themidline. In addition, there hasbeen an end colostomy andumbilicoplasty.



ManagementMales

The Cantwell–Ransley epispadias repair is favouredby many surgeons and can be performed in the firstyear of life. In this procedure the urethral plate isfully mobilised off the penile corpora from theproximal urinary outlet and corporeal bodies but isleft attached to the glans. The urethral plate is thentubularised and brought to a ventral position,below the corpora cavernosa, which are thenapproximated dorsal to the urethra. Rotation of thecorpora eliminates the dorsal curvature of the penisand a distal Heineke–Mikulicz procedure in theglans with dorsal glans reconstruction brings themeatus into a more ventral position.

This operation is best suited to patients withgood penile length in whom it is usually successfulin creating a terminal urethral orifice and goodcosmesis of the glans. Where the penis is smaller,however, the outcome may be a short phallus witha rather buried appearance. In these patients a moreradical penile mobilisation such as that provided bythe Kelly operation enables length to be enhanced,particularly if there is a pubic diastasis.

Epispadias is commonly associated with incon-tinence and on cystoscopy there is demonstrableweakness of the bladder outlet with the verumon-tanum lying close to the bladder neck or evenwithin the bladder.

Although it is not possible to reliably assess conti-nence in infants who are still in nappies, someindication is provided by the penile anatomy (sever-ity of epispadias) and the cystoscopic findings.Patients with distal anomalies and good penile size,whose verumontanum is below the bladder neckand who appear to void without dribbling, are bestmanaged by the Cantwell–Ransley repair. For thosewith a more severe form of the anomaly, the Kellyprocedure is more appropriate and is analogous totechnique employed in bladder exstrophy.

Outcome

The long-term outcome for sexual function isusually good, and normal fertility is retained unless

there have been urethral complications orepididymo-orchitis. However, ejaculation may beslow or even retrograde. Patients who have onlyundergone penile reconstruction (the majority) willrequire additional bladder neck/sphincter surgery iftheir continence is impaired. Injection of a bulkingagent into the bladder neck may improve short-term continence but its effect is not long-lived. Thesurgical options include a bladder neck repair orartificial urinary sphincter. In practice, it is difficultto reproduce a physiological bladder neck andsphincter mechanism and for some patients it maybe necessary to progress to bladder augmentationand a Mitrofanoff conduit. Although the Kellyoperation offers enhanced penile length, it remainsto be seen whether the more aggressive approach tosphincteric reconstruction will translate intoimproved continence in due course.

Girls

Since the majority of girls with epispadias are incon-tinent, reconstructive surgery must be directed tocorrection of the incontinence as well as the genitalabnormality. Good results have been reported fordistal urethral reconstruction, but more proximalbladder neck surgery may also be required. TheKelly procedure offers good prospects of continencecoupled with an improved external cosmetic appear-ance. There should be few implications for sexualfunction or fertility, although delivery should be byelective Caesarean section.

Key points

• The exstrophy–epispadias complexencompasses a group of rareanomalies which occur morecommonly in males.

• Cloacal exstrophy is now usuallydetected antenatally, as areapproximately 40% of cases of bladderexstrophy. Epispadias, however, isalmost invariably diagnosed at birth.



• Most infants with uncomplicated orclassic bladder exstrophy areotherwise healthy, and surgicalcorrection can be undertaken safelywithin the first few days of life. Thecosmetic and functional resultsobtained with the one-stage Kellyoperation may prove to be superiorto those achieved with conventionalstaged repair.

• Late morbidity is common in exstrophypatients and may include incontinence,sexual dysfunction and renalimpairment. It is hoped that newertechniques will offer better long-termresults.

• Cloacal exstrophy is often associatedwith prematurity or other medicalproblems which take priority overearly surgical correction.Reconstruction presents aformidable challenge. Although it isusually possible to create a urinaryreservoir, most patients are left

with a permanent colostomy. Itmay be necessary to considergender reassignment in severelyaffected males.

• Primary epispadias is commonlyassociated with incontinence due todeficiency of the bladder neck andsphincter complex.

Further reading

Gearhart JP, Jeffs RD. Exstrophy–epispadias complex andbladder anomalies. In: Walsh PC, Retik AB, VaughanED, Wein AJ (eds). Campbell’s Textbook of Urology,7th edn. Philadelphia: WB Saunders, 1998: 1939–1990

Kelly JH, Eraklis AJ. A procedure for lengthening thephallus in boys with exstrophy of the bladder. J PediatrSurg 1971; 6: 645–649

Woodhouse CRJ. Exstrophy and epispadias. In: Long-TermPaediatric Urology. London: Blackwell, 1991: 127–150

Woodhouse CRJ. Genitoplasty in exstrophy and epispa-dias. In: Stringer MD, Oldham KT, Mouriquand PDE(eds). Paediatric Surgery and Urology: Long-TermOutcomes. Cambridge: Cambridge University Press,2006: 583–594



Hypospadias

Duncan T Wilcox and Pierre DE Mouriquand

Introduction

Hypospadias is an association of three anatomicalanomalies:

• an abnormal ventral opening of the urethralmeatus

• ventral curvature (chordee) of the penis• a hooded foreskin, which is deficient ventrally.

However, not all three of these features are presentin every case.

Hypospadias is better defined as a hypoplasia ofthe tissues forming the ventral aspect of the penisbeyond the division of the corpus spongiosum.It is characterised by a ventral triangular defectwhose apex is the division of the corpus spongio-sum; the sides are represented by the two pillars ofatretic spongiosum and the base is the glans.

HistoryIn the second century Galen described the problemof infertility associated with a proximal meatusand penile chordee, and was the first to usethe term hypospadias. The modern treatment ofhypospadias dates from the second half of the 19thcentury, when the techniques in current use were

first described. For example, Thiersch and Duplaydescribed tubularisation of the urethral plate,whereas Duplay also described a technique verysimilar to the meatal advancement and glanulo-plasty later popularised by Duckett in the 1970s.In 1860, Poisson reported a meatal-based flip-flaprepair which was later popularised with greatsuccess by Mathieu. Although techniques for thecorrection of hypospadias have continued toevolve, these advances have been largely built onthe foundations laid by the pioneers of hypospa-dias surgery in the late 19th century.

Aetiology and incidence

The incidence of hypospadias is generally quotedat 1 in 300 live male births (0.33%). However,data from different countries show considerablevariation, with reported incidences ranging from0.2% in Sweden to 0.7% in the Netherlands.There has been a growing perception that hypospa-dias is becoming more common and, while thismay be explained in part by better reporting ofminor forms, evidence is mounting to a genuineincrease in the underlying incidence. The apparentincrease in the incidence of hypospadias, coupledwith the increasing incidence of testicular cancer

16

Topics covered Aetiology and incidenceDisorders of sex development and associatedanomaliesSurgical principlesOverview of surgical techniques

Chordee correction Tubularisation

Two-staged repair Urethral repositioning Pedicle- and meatal-based flaps

Outcome and complications


and declining semen quality, have been cited asexamples of the possible impact of oestrogenicenvironmental pollutants (‘endocrine disruptors’)on normal virilisation of the male fetus. In addition,endocrinopathy, low birth weight and highermaternal age (possibly mediated by placentalinsufficiency) have been identified by some studiesas possible aetiological factors. Hypospadias ismore common in monozygotic twins and in theoffspring of fathers who have hypospadias, indicat-ing that there may be a polygenic inheritance. Theconcept of a genetic component has been strength-ened by the finding of hypospadias associated withspecific gene (Ins l3) knockout mice. The overallincidence of hypospadias in first-degree malerelatives of affected boys is 7–10%, rising to10–20% in brothers of boys with severe forms ofthe condition.

Intersex and associatedanomalies

Severe forms of hypospadias can present withsimilar appearances to disorders of sex develop-ment (DSD), especially when severe hypospadiasis associated with undescended testicles and aprostatic utricle. In some series up to 50% ofpatients with both hypospadias and cryptorchidismhave been found to have an underlying genetic,gonadal or phenotypic sexual abnormality. It isessential that patients with hypospadias andundescended testicles are fully investigated so thatDSD can be excluded. With the exception of anincreased overall incidence of undescended testis,other anomalies in patients with isolated hypospa-dias are rare. Abnormalities of the urinary tractare unusual, occurring in approximately 2% ofpatients; consequently, routine ultrasound of thesechildren is unnecessary. The overall incidence ofundescended testis is in the range 5–10%, rising to50% in those with the severe perineal or penoscro-tal forms. These severe forms are also associatedwith a persistent prostatic utricle in 20% of cases,

which on occasions can make urethral catheterisa-tion of the bladder difficult. But since it is rarelynecessary to remove the utricle, routine cystogra-phy or cystoscopy to identify a utricle is notrequired unless the child is symptomatic.

Classification

Although many classifications have been describedbased on the position of the ectopic urethralmeatus (Figure 16.1), the level of division of thecorpus spongiosum may provide a more accuratemeans of distinguishing anterior hypospadiaswith little or no chordee from posteriorhypospadias with chordee and hypoplasia of thetissues forming the ventral aspect of the penis(Figure 16.2).


Glanular

Coronal

Distal

Mid shaft

Proximal

Perineal

Figure 16.1 Standard classification of hypospadias.


The authors’ classification therefore recognisesthree main types of hypospadias:

1. Hypospadias with a distal division of thecorpus spongiosum with little or no chordee.

2. Hypospadias with a proximal division of thecorpus spongiosum with a marked degree ofhypoplasia of the ventral tissue and a signifi-cant degree of chordee.

3. Patients with hypospadias despite multiple previ-ous operations (previously termed ‘hypospadiascripples’).

Specific surgical principles

Although more than 300 different techniques havebeen described for the repair of hypospadias, the lastdecade has seen the emergence of a growing consen-sus amongst specialist hypospadias surgeons. For themajority of patients this comprises either tubularisa-tion of the urethral plate or a two-stage repair usuallyinvolving a free flap. This chapter will concentrate onthese two techniques, but other methods which arestill in current use will also be described.

Regardless of the particular type of repair, thereare three specific components to the surgicalcorrection of hypospadias:

• correction of the penile chordee• reconstruction of the urethra (urethroplasty) • skin coverage of the penis aimed at achieving

a normal cosmetic appearance.

Correction of penile chordeePenile chordee can result from a number of factors,including abnormal tethering of the penile shaftskin on to the underlying structures, tethering ofthe urethral plate to the corpora cavernosa, oratretic corpora spongiosum tissue extending fromthe abnormal meatus to the glans. Finally, chordeemay be due to an intrinsic flexion deformity of thecorpora cavernosa (Figure 16.3). Correction ofpenile chordee can involve a number of steps,which should be addressed in the following order:

1. Degloving the penis by fully mobilizing theoverlying skin. In the majority of patients(80%), this is all that is required to correct thechordee.

2. Excision of the atretic and fibrous corporaspongiosum proximally and distally to theabnormal meatus.

3. Dissection of the urethral plate, which iscarefully elevated off the corpora cavernosa.(Not all surgeons perform this step, optinginstead to go straight to a dorsal plication.)

Hypospadias 215

Figure 16.2 Deceptively severe case illustrating thepotential pitfalls of classification based on the positionof the urethral meatus. The urethra terminates with anopening on the glans but the entire urethra is ‘paperthin’, and this case is, in effect, a proximal form ofhypospadias with chordee.


In some patients ventral curvature of the penispersists despite these steps, in which case it isnecessary to plicate the dorsal aspect of the tunica albuginea (Nesbit procedure; Figure 16.4). Thecorrection of penile chordee is controversial, withsome surgeons preferring to plicate the tunicaalbuginea if chordee persists once the penis hasbeen degloved. We prefer to avoid plication, as thelong-term results are unknown and the manoeuvremay affect penile growth, leading to secondarydeformities. When correction of the penile chordeeis completed and confirmed with an artificial salineerection test, it is necessary to reconstruct theurethra.

UrethroplastyReconstruction of the urethra can be performed ina single stage or in a two-stage procedure. Mostsurgeons now opt for a single-stage repair wheneverthis is possible. As a general rule, a single-stagerepair is appropriate for distal, mid shaft and proxi-mal hypospadias without significant chordee.A two-stage repair is generally reserved for perinealhypospadias with chordee and for ‘hypospadiascripples’. The majority of surgeons now perform

tubularisation of the urethral plate as their preferredone-stage method.

Tubularising the urethral plate (Figure 16.5)

Currently the most widely used single-stage repairis a Duplay-type tubularisation incorporating avertical incision in the urethral plate, as describedby Snodgrass. This modification allows the urethralplate to be tubularised without tension. Inaddition, it is has been asserted that epithelialisa-tion of the urethral plate incision may contributeto the circumference of the neourethra.

In this procedure the urethral plate is markedand then incised (Figure 16.5a); its width is thenassessed. The urethral plate is incised and thenrolled into a tube once any chordee has beencorrected (Figures 16.5b). Some surgeons alsofavour a modification in which a free graft ofpreputial skin is inlaid into an incision in theurethral plate to reduce the risk of contraction andstenosis of the neourethra (Figures 16.5b,c). If the


Fibrouschordee

Urethralplate

Intrinsiceabnormalitycorbora

Ventral skin

Figure 16.3 Causes of penile curvature associatedwith hypospadias.

Figure 16.4 Correction of intrinsic chordee by plica-tion on the dorsal aspect of the corpora, followingmobilisation of the overlying neurovascular bundles(as described by Baskin).


urethral plate is wide and sufficiently supple to betubularised over an 8 Fr catheter, it can be rolledinto a tube without the need for a urethral plateincision (Duplay procedure) (Figure 16.5d).Once the neourethra is formed, a vascularised

de-epithelialised pedicle of tissue is placed overthe anastomosis to reduce fistula formation(Figure 16.5e). The glanuloplasty is performed byreapproximating the glans wings in two layers. Theskin is then reconfigured, ensuring that there is

Hypospadias 217

Figure 16.5 Key steps in the tubularised incised plate (Snodgrass) repair (see text for explanation).

(a) (b) (c)

(d) (e) (f)


adequate coverage on the ventral surface so thatpenile chordee does not recur (Figure 16.5f). Adripping stent or urethral catheter is usually leftdraining for 7 days.

Two-stage repair (Figures 16.6 and 16.7)

The first stage of the operation involves correctingthe chordee as described above (Figure 16.7a,b),preparing the glans and harvesting the free flap(Figure 16.7c). Once the chordee has beencorrected a midline ventral incision is made fromthe most dorsal part of the new meatus on theglans to the current meatus. Glans wings arecreated so that the glans opens widely (‘like abook’). The ideal material for the flap should beeasy to harvest, without leaving a long-standingcosmetic defect. It should be supple and non-hairbearing. The most commonly used graft material

is inner preputial skin. However, postauricularWolfe skin grafts can also be used for primaryrepair. Buccal skin and bladder mucosa are lessfrequently used for standard two-stage repairs, butdo have a role in ‘salvage’ hypospadias.

When the donor graft has been taken, the fatand subepithelial tissue are removed to enhancegraft revascularisation (Figure 16.7c). The graftis then placed into the glans and tacked withabsorbable sutures; ‘windows’ are made in thegraft to allow haematomas to escape, and a fewmidline quilting sutures are placed to anchor thegraft to on its base (Figure 16.7d,e). A firm dress-ing is applied, with a catheter, which holds thegraft in place and minimises haematoma forma-tion. After 1 week the dressing and catheter areremoved. The second stage of the repair is usuallyperformed after 6 months. This step involvestubularisation of the graft into the neourethra(Figure 16.7f,g) and then placing a second vascu-larised layer over the anastomosis (Figure 16.7h).Once this is completed the glans is recreated andthe penile skin closed (Figure 16.7i). This secondstage is very similar to one-stage tubularisation ofthe urethral plate already described.

Other techniques which are still in current usageare described below.

Urethral repositioning

The MAGPI procedure (Figure 16.8), an acronymof ‘meatal advancement and glanuloplasty incor-porated’ was originally described by Duckett. It ismore accurately described as a refashioning of theglans penis, with only minor meatal advancement.It is only suitable for cases in which the urethra ismobile – which can be confirmed if simpletraction can move the meatus to the tip of theglans. A vertical incision between the tip of theglans and the meatus is created (Figure 16.8a,b)and then closed transversely, thereby advancingthe meatus. A circumferential incision is made inthe skin below the corona and the meatus. The glanu-loplasty is then performed in two layers (Figure16.8c,d), and finally the penis is circumcised andthe skin closed. It is not normally necessary to


Figure 16.6 Severe proximal hypospadias, unsuitedto a single-stage repair.


Hypospadias 219

(a)

(c)

(d)

(b)






(e) (f)

(g) (h)


leave a urinary catheter in for this procedure.Many authors have described alternativetechniques in which the urethra is mobilised andrepositioned at the tip of the glans. Urethralmobilisation was reported over 100 years ago, buthas recently been repopularised by Koff andcolleagues. The technique requires mobilisation ofthe urethra to the scrotum and has not gainedwidespread acceptance.

Pedicle flaps

Two types of pedicle flap are commonly used, themeatal-based flap and the preputial flap. Both ofthese procedures utilise skin flaps which remainattached at some point to the urethral plate.

Meatal-based flap(Mathieu procedure) (Figure 16.9)

The urethral plate is incised (Figure 16.9a) andthe glans flaps developed. A flap of proximalpenile skin is created using the meatus as the base(Figure 16.9b). The flap is then placed on to theurethral plate and both lateral edges are sutured toit. Adjacent subcutaneous tissue is used to cover(‘waterproof ’) the suture line (Figure 16.9c).Once the neourethra is created, the glanuloplasty isperformed (Figure 16.9d). A urinary catheter isleft in for 4–7 days, although some authors havereported that no drainage is necessary. As a rule themaximum length of this flap should be no morethan three times the width of the base and inpractice this technique is unsuited for a urethro-plasty exceeding 1.5 cm.

Preputial flap (onlay island flapprocedure) (Figure 16.10)

The urethral plate is incised vertically using twoparallel incisions. The penis is then degloved backto its base using a circumferential subcoronalincision. Once this is complete, the penile chordee,if present, is corrected. The glans flaps are thencreated and the proximal thin urethra is cut backuntil normal urethral tissue is found. A pedicle flapis then created out of the inner prepuce, as shownin Figure 16.10a. The preputial flap is broughtaround the side of the penis to its ventral surfaceand sutured to the urethral plate (Figure 16.10b,c).Once the neourethra has been created in thisfashion, the subcutaneous pedicle is anchored tothe tunica albuginea lateral to the urethral anasto-mosis (Figure 16.10d). This ‘waterproofing’ subcu-taneous flap covers the anastomosis and providessupport for the neourethra. Occasionally it is neces-sary to divide the urethral plate in order to correctthe chordee. In these rare cases the preputial flapcan be tubularised, thereby creating the neourethraalone. The lateral glans wings are then approxi-mated in two layers to recreate the glans, and theskin is closed (Figure 16.10e).

Hypospadias 221


(i)

Figure 16.7 Key steps in the two-stage repair (seetext for explanation).



Figure 16.8 Urethral repositioning, key steps in the MAGPI repair (see text for explanation).

(a) (b)

(c) (d)


Hypospadias 223

Figure 16.9 Key steps in a perimeatal-based flap (Mathieu) repair (see text for explanation).

(a)

(c) (d)

(b)



Figure 16.10 Key steps in pedicle flap repair (see text for explanation).

(a) (b)

(c) (d) (e)


The Koyanagi procedure and its variants arealternative procedures for severe proximal hypospa-dias. It aims at using the urethral plate and theneighbouring strip of ventral tissues along with theinner aspect of the preputial hood, which is trans-ferred ventrally with its pedicle. This large andwell-vascularised material is freed from the ventralaspect of the corpus spongiosum down to the baseof the penis. This allows the penis to straightenand to build an extended plate which is subse-quently tubularised.

Covering the penisWhen the urethra has been reconstructed, it isnecessary to recreate the meatus and glans. Glanu-loplasty is performed by bringing the two wings ofthe glans around to cover the urethra; the glans isthen closed in two layers. The distal end of theneourethra is sutured to the new meatus, therebycreating a slit-like meatus. Once this is complete, theresidual inner preputial skin adjacent to the coronalsulcus is brought around the ventral side of the penisto create a circumferential mucosal ‘cuff ’ or ‘collar’surrounding the glans. Skin cover is provided bymoving the excess skin from the dorsal side to theventral side: this gives a good cosmetic result that issuperior to the Byars flaps previously used. Thefollowing techniques are common variants.

Chordee without hypospadias(Figure 16.11)

In most cases this is a misnomer since they do infact represent a form of hypospadias in which thedistal penile urethra is flimsy, despite the presenceof a glanular meatus and circumferential prepuce.It may be possible to achieve good correction bydegloving the shaft and excising chordee tissuewhile preserving an intact urethra. At the time ofoperation, however, it may prove necessary toexcise the abnormal urethra back to healthyspongiosum-supported urethra and proceed tourethroplasty as if it were the correspondingdegree of true hypospadias.

Megameatus intact prepuce (Figure 16.12)

Because there is no external clue to the presence ofthis variant, it sometimes comes to light for the firsttime in a boy who is about to undergo circumcision.In this situation the planned circumcision should beabandoned, the child returned to the ward and thefindings discussed with the parents. If the parentsopt for surgical correction of the glanular defect,referral to a specialist is advisable. A suitabletechnique has been described by Duckett, who alsospecifically cautioned against the use of the MAGPIrepair in view of its high failure rate when used forthe attempted repair of this variant.

‘Salvage’ or ‘redo’ surgery often calls foringenuity and familiarity with a number of differ-ent techniques. Where the neourethra is largelyintact and the surrounding skin is healthy, a proce-dure using locally available skin may suffice, butwhere there is extensive scarring and, particularlyin the presence of residual chordee, it is usuallypreferable to abandon the unhealthy existingneourethra and perform a substitution procedurewith an onlay or tubularised free graft. Postauricu-lar skin is suitable, but buccal skin, harvested fromthe lower lip (Figure 16.13) or cheek, is morewidely used for this purpose.

Hypospadias 225

Figure 16.11 Chordee without hypospadias.


General surgical principles

MagnificationThe precision needed to perform this delicatesurgery means that most surgeons use some formof optical magnification. Operating microscopes

have almost unlimited magnification power, butthey are cumbersome and often too powerful formost cases of hypospadias. Most surgeons thereforeuse standard operating loupes which are easy to useand provide magnification in the range 2.5–4.3×.The most important consideration, however, is thatthe surgeon should feel comfortable using theoptical magnification.

SuturesThe suture material used needs to be fine gauge,absorbable and easy to use. Historically chromiccatgut was the most commonly used suture, butwith developments in suture technology others arenow available. We prefer 7-0 or 6-0 polydioxanone(PDS): these fine absorbable monofilament suturesprovide excellent strength and disappear beforesuture tracts are formed.

HaemostasisA bloodless operating field is essential for thissurgery. It can be obtained by using one of thethree following techniques:


Figure 16.12 Megameatus intact prepuce variant. (a) Normal external appearances before the prepuce isretracted. (b) Glanular anomaly revealed by retraction of the prepuce; deep glans groove with ‘fish mouth’megameatus.

(a)

Figure 16.13 Buccal mucosa graft – site on buccalaspect of the lower lip marked out prior to harvestingof the buccal skin graft for salvage repair.

(b)


• A tourniquet at the base of the penis providesan excellent bloodless operating field. Care mustbe taken not to leave the tourniquet for longbecause of the theoretical risk of reperfusioninjury.

• Adrenaline 1:100 000 can also be used, up to amaximum dose of 10 mg/kg. Although there isa theoretical risk that excessive vasoconstrictionmight compromise the vascularity of skin flaps,there is no evidence that this occurs in practice.

• Bipolar diathermy is generally preferred, but thesafe use of monopolar diathermy has beendescribed. Diathermy may be inadequate tocontrol bleeding from the glans. It is currentlyour policy to use a tourniquet followed by acompressive dressing at the end of the operation.

AntibioticsPractice varies with respect to the use of prophy-lactic antibiotics, ranging from none to a course ofantibiotics while the catheter is in situ. A recenttrial suggests that antibiotic coverage of the opera-tion is beneficial.

Urinary drainageThe indications for postoperative urinary diversiondepend upon the type of reconstruction. Someforms of distal hypospadias repair may not requireany form of urethral catheter drainage. We usetransurethral catheter drainage for all but the mostminor repairs. In general this takes the form of a6–8 Fr dripping stent. Use of a standard Foleyindwelling urinary catheter carries the concern thatthe deflated balloon might distend or disrupt thedelicate suture lines of the anastomosis whenthe catheter is withdrawn. Some surgeons favourthe use of a suprapubic catheter, but we do not feelthis is necessary, except perhaps after complex or‘salvage’ redo surgery.

DressingThe dressing serves many purposes, which ideallyinclude gentle compression of the penis to reducehaemorrhage and oedema, immobilisation andprotection from contact to reduce postoperative

pain. Many dressings are available and are subjectto preference of the surgeon. These include silasticfoam, a clean bandage and bio-occlusive dressings(Tegaderm). The dressings stay in place forbetween 2 and 7 days, depending on the complex-ity of the repair.

Outcome

The results of hypospadias repair reflect the sever-ity of the original defect and the type of operationperformed.

Tubularisation of the urethral plateThe technique of tubularisation, as originallydescribed by Duplay, has a secondary operation rate of around 10%, principally for urethral fistulae. This technique does have the advantage of creating a slit-like meatus, which is morecosmetically appealing. The outcome following theSnodgrass repair (tubularised incised plate) appearsto be at least as good. In an early multicentre experi-ence with the tubularised incised plate hypospadiasrepair, the results in 148 boys were reported from6 paediatric urology centres. Complications includedfistulae in 5%, meatal stenosis in 2% and partialglans dehiscence in 5%. Comparable results havebeen confirmed in later studies for the use of thetubularised incised plate (Snodgrass) repair for bothproximal and distal hypospadias, with approxi-mately 10% of patients requiring reoperation.Concerns have been expressed about the potentiallong-term risk of stenosis as a consequence ofscarring in the incised portion of the urethral plate.However, in a long-term follow-up study only asmall percentage required dilatation. Moreover,measurement of voiding flow rates showed that33/48 patients had normal peak flow rates whencorrected for age and 46/48 patients had a postvoidresidual of less than 10%.

Two-stage repairBracka has reviewed his personal series of 600 patientsmanaged by two-stage repair. In the majority of cases

Hypospadias 227


the neourethra had been fashioned from a freegraft derived from inner preputial skin. The first-stage operation required revision in 4% of patientsfor persistent chordee or to increase the area ofmeatal skin, whereas the complications of thesecond stage were fistulae in 6% of patients, with‘redo’ or ‘salvage’ repairs having a higher fistularate of 10% (compared with 3% for primaryprocedures). A higher fistula rate was encounteredin patients operated on in the earlier part of theseries before the introduction of a vasculariseddartos flap between neourethra and the skin.Urethral stenoses occurred in 7% of patients. Thisfigure was attributable, in part, to balanitis xerot-ica obliterans. Long-term functional outcomes inpatients following a two-stage repair have recentlybeen reported by a number of centres. Up to 40%of patients report spraying of the urinary streamand some described having to ‘milk’ the penisfollowing voiding to empty the neourethra toavoid postvoid dribbling. In one study of thefunctional outcome in 43 adults following recon-struction with buccal mucosal grafts, sevenpatients (16%) had urinary symptoms, of whomtwo had experienced severe urinary symptoms. Inall, 26% of patients described problems withurinary spraying. This technique does, however,give an excellent cosmetic result.

Urethral advancementDuckett reported his experience with the MAGPIprocedure for the correction of glanular hypospa-dias in his series of over 1000 patients. Of these,only 1.2% required a secondary procedure. Partialmeatal regression is, however, a relatively commonproblem with this procedure and leads to aninferior cosmetic result.

Pedicle flapsIn the Mathieu repair distal strictures are rare (1%)and fistulae occur in approximately 4% of cases.However, the meatus is often crescentic in appear-ance, giving a poor cosmetic result. Wide glansmobilisation and a midline dorsal incision of theurethral plate may reduce this problem.

Preputial flapsThis method of repair is often reserved for themore complex cases of hypospadias: consequently,the rate of complications is higher. There is widevariability in the published fistula rate, from4% to 69%.

Psychosexual outcomeSexual function following successful hypospadiascorrection should be unaffected, with normalerectile function and normal prospects of fertility,providing the patient does not have coexistingundescended testicles. The long-term psychosocialand psychosexual outcome of men who haveundergone hypospadias surgery is not welldocumented and those studies that have beenundertaken have arrived at differing conclusions.Moreover, because these are long-term retrospec-tive studies, their findings reflect the outcome oftechniques which have been superseded by neweroperations in the intervening decades. One recentstudy found that men who had been operated onfor hypospadias had similar psychosocial outcomesto age-matched controls who had undergoneinguinal herniotomy.

Complications

EarlyOperations to correct hypospadias carry the risk ofcomplications that are common to all surgicalinterventions, but which can severely affect theoutcome of the procedure. Because of the vascu-larity of the penis, haemorrhage can often be aconcern. Intraoperatively, bleeding can usually becontrolled by one of the methods previouslydiscussed. Postoperatively, most surgeons preventdelayed haemorrhage with a compressive bandage;this also acts to reduce the postoperative oedemathat occurs following most hypospadias repairs. Itis essential to minimise haematoma formation, asthis can act as a focus for infection and subsequentfistula formation. Care needs to be taken to avoid



wound infections and the need for meticuloushaemostasis and tissue handling is paramount.Infection, haematoma formation and ischaemictissue flaps can all lead to poor wound healing,resulting in fistulae and/or complete breakdown of the repair. Complete dehiscence of the repair is fortunately rare, but when it does occur thesubsequent secondary or ‘salvage’ repair is adaunting task.

LateThe long-term complications of hypospadiassurgery are well known and, sadly, all too common.Their incidence rate depends on the initial severityof the hypospadias, the choice of procedure andthe skill and experience of the surgeon.

FistulaeFistulae are the most common complicationsfollowing hypospadias surgery, and can occur inup to 30% of patients. A fistula can presentacutely immediately after the catheter is removed,or many years after the repair. If the fistulaappears acutely many surgeons would replacethe catheter for 14 further days with the aimof allowing it to close spontaneously. Althoughthis approach may be effective, many early fistu-lae persist and require further treatment. Thelocation of a hypospadias fistula varies, but it isoften just proximal to the junction of the glansand penile shaft. Occasionally large or multiplefistulae occur, usually indicating that the originalurethroplasty was unsatisfactory and needs to berepeated.

Before attempting to repair a fistula it is imper-ative to exclude meatal and/or distal urethral stric-tures, as this will predispose to recurrence of thefistula. Fistulae are sometimes associated withurethral diverticula, which need to be excised at thetime of the fistula repair.

Repair of hypospadias fistulae should not bedismissed lightly and in some series there has beena 50% recurrence rate. The timing of the closureis important. Although early closure was favouredin the past, it is now recommended that an

interval of at least 6 months should elapse after theoriginal repair before fistula closure is attempted.Many techniques have been described. Simpleclosure, consisting of freshening and then closingthe fistula edges and the overlying skin, is associ-ated with a high recurrence rate and is not recom-mended by the authors. A flap-based repair hasalso been described, in which the fistula isdissected down to the urethra and the urethraldefect closed by inserting absorbable sutures.A flap of skin is then formed from which a vascu-larised subcutaneous layer is created and placedover the urethral repair. Once the urethra iscovered, the skin flap is advanced to close the skindefect. Although more complex, this technique ismore effective, with Duckett reporting a 90%success rate.

In some cases the fistula is very large and repre-sents a failure of the original urethroplasty. Surgerythat is limited to fistula closure in these cases isgenerally doomed to failure, and in these circum-stances a repeat urethroplasty is invariablyrequired. The use of a urinary catheter followingfistula repair is much debated and the success ratein those diverted or left undiverted seems verysimilar in most series. Therefore, unless there issome doubt about postoperative voiding it ispossible to perform a fistula repair without drain-ing the bladder.

Meatal stenosisMeatal stenosis results from either ischaemia ofglans flaps or an inadequately mobilised glanswrap. It can present with difficulty voiding, anarrowed urinary stream, spraying or, in somepatients, with urinary tract infections secondary toincomplete bladder emptying. Meatal stenosis canbe treated initially with gentle dilatation of themeatus. Although this can be accomplished as anoutpatient procedure using a fine-tipped catheterin minor degrees of stenosis, dilatation undergeneral anaesthesia is required for moderate orsevere degrees of stenosis. When dilatation alonewill not suffice, formal meatotomy is a simpleprocedure that is generally successful.

Hypospadias 229


Urethral stenosisUrethral stenosis is a rare problem with modernprocedures, which avoid a circular anastomosis.Although strictures can occur at any point alongthe urethroplasty, they most commonly occur atthe distal and proximal ends of the neourethra.Distal stenosis is often associated with a fistula andcan usually be treated with regular dilatation but insevere cases a formal surgical repair is necessary.Proximal stenosis is a serious complication which,if severe, often requires complete reconstruction ofthe urethra.

Persistent chordeeThe persistence of penile chordee after hypospa-dias repair is usually due to inadequate correctionat the time of the original repair. In rare cases,however, it may be the consequence of postopera-tive fibrosis. This complication is easier toavoid – by a good repair and confirmation ofcorrection with an intraoperative artificial erectiontest – than to treat. In the correction of persistentchordee it is first necessary to deglove the peniscompletely to exclude skin tethering as the cause.If true chordee is found to be present after thismanoeuvre, dorsal plication of the tunica albu-ginea is usually sufficient to correct it.

Balanitis xerotica obliteransThis rare complication caused by chronic inflam-mation and fibrosis of the glans and meatus resultsin scarring and meatal stenosis. Topical steroidshelp in some patients, but the majority require aformal meatoplasty to correct the stenosis.

Hairy urethraThe presence of hairs within the lumen of theneourethra is a consequence of using hair-bearingskin for the urethroplasty. Its significance liesprincipally in the potential for hairs to act as anidus for the formation of urethral calculi. This islargely a historical complication that has beenovercome by the introduction of operations utilis-ing non-hair-bearing skin. For patients with a hairy

urethra causing symptoms the only effectiveoption is a repeat non-hair-bearing urethroplasty.

UrethrocoeleThis term refers to a dilated, ‘baggy’ section ofneourethra, often resulting from distal obstructionthat gives rise to ‘back pressure’ distension of theproximal neourethra. It may also be secondary toan absence or deficiency of supportive corpusspongiosum tissue. A urethrocoele can present witha poor urinary stream, postvoid dribbling, urinarytract infections, swelling of the ventral aspect of thepenis at the time of voiding and urethral calculisecondary to stasis. Surgical treatment requiresexcision of the redundant urethral tissue and treat-ment of any distal stenosis as necessary.

Key points

• Despite advances in technique,instrumentation and aftercare, thecorrection of hypospadias remains one of the most technically challengingaspects of paediatric urology.

• There is no place for the ‘occasional’hypospadias surgeon, even in thecorrection of so-called ‘minor’hypospadias. Surgeons should have adetailed understanding of the variousconcepts and surgical techniques andmaintain a clinical workload that issufficient to obtain consistently goodresults.

• Preservation of the urethral plate is the keystone of modern single-stageprocedures; however, there has been arecent revival of the two-stage free flaptechnique for more complex patients.

• With improving functional results thechallenge is now to obtain the optimalcosmetic result to provide patients with a penis of normal appearanceregardless of the severity of the original abnormality.



Further reading

Baskin LS. Hypospadias In: Stringer MD, Oldham KT,Mouriquand PDE (eds). Paediatric Surgery and Urology:Long-Term Outcomes. Cambridge: Cambridge UniversityPress, 2006: 611–620

Bracka A. Hypospadias repair: the two-stage alternative.Br J Urol 1995; 76 (Suppl 3): 31–41

Mouriquand PDE, Persad R, Sharma S. Hypospadiasrepair: current principles and procedures. Br J Urol1995; 76(Suppl 3): 9–22

Mureau MA, Slijper M, Slob AK, Verhulst FC. Psychoso-cial functioning of children, adolescents, and adults

following hypospadias surgery: a comparative study.J Pediatr Psychol 1997; 22: 371–387

Redman JF. Results of undiverted simple closure of51 urethrocutaneous fistulae in boys. Urology 1993;41: 369–371

Smith ED. The history of hypospadias. Pediatr Surg Int1997; 12: 81–85

Thomas DFM. Hypospadiology: science and surgery.BJU Int 2004; 93: 470–473

Wilcox D, Snodgrass W. Long-term outcome followinghypospadias repair. World J Urol 2006; 24(3): 240–243

Hypospadias 231



The prepuce

Kim AR Hutton

Introduction

The history of circumcision has been welldocumented, with evidence of the practice datingback to ancient Egypt during the Sixth Dynasty of the Old Kingdom (2345–2181 BC). Althoughapproximately one-third of English boys under-went ‘routine’ circumcision in infancy in the1930s, this number has since dwindled to negligi-ble proportions. In the UK, circumcision for non-medical reasons is now virtually confined to thosefaiths in which ritual circumcision is required tocomply with religious beliefs. By contrast, newborncircumcision remains culturally entrenched,regardless of religious faith in the United States,although the legitimacy of this practice is beingincreasingly challenged. The number of ‘medical’circumcisions in children performed in the UK’sNational Health Service (NHS) has declinedprogressively over the last three decades. Forexample, whereas NHS data for England recordedthat 18 500 circumcisions were performed in boysaged 0–16 in 1994/1995, the figure fell over theensuing decade to 10 000 in 2004/2005. Thisstriking reduction in the number of circumcisionsoccurred almost entirely in district general hospi-tals and almost certainly reflects fewer unnecessarycircumcisions being undertaken by adult surgeons.

An understanding of the valid medical indica-tions for circumcision (or alternative procedures)

calls for a knowledge of preputial developmentbefore and after birth, and of preputial pathology.

Development and function of the prepuce

PrenatallyFirst appearing at 8 weeks’ gestation as a ridge ofthickened epithelium, the prepuce grows forwardover the developing glans so that preputialconstruction is complete by 16 weeks’ gestation. At this stage, however, the epithelia lining theprepuce and surfacing the glans are contiguous,with no plane of separation between them, so that‘preputial adhesions’ represent a feature of normaldevelopment, not a pathological process. Sponta-neous separation, commencing late in gestationand usually proceeding proximally, occurs bydesquamation, with areas of cell nests degeneratingto form a series of spaces that ultimately enlargeand coalesce to form a continuous preputial sac.

PostnatallyPreputial separation after birth proceeds at a ratevarying from one individual to another and isuninfluenced by environmental or genetic factors:even at 5 years of age some degree of preputialadherence persists in upwards of 70% of boys. This

17

Topics coveredDevelopment and function of the prepucePreputial disorders and abnormalities

Pathological phimosisBalanoposthitisParaphimosis, preputial cysts, megaprepuce

CircumcisionAlternatives to circumcision

Topical steroidsPreputioplasty


process may be accompanied by mild inflammatoryepisodes, possibly due to infection of retainedsmegma. At birth the prepuce is almost alwaysnon-retractable and usually remains so for avariable period thereafter, during which timeattempted retraction results in the appearance of ablanched and apparently constricting ring of skinproximal to the preputial meatus (Figure 17.1).Viewed end-on, the preputial orifice is supple andunscarred, with an opening likened to a flower asthe foreskin is pulled back (Figure 17.2).

Although normal, developmental, non-retractil-ity of the foreskin is often termed ‘phimosis’(Ψιμoσισ ‘muzzling’ in Greek). This is misleadingas it implies the existence of pathology when inreality there is none. ‘Non-retractile foreskin’or ‘physiological phimosis’ are thus more appro-priate terms.

In younger boys the natural history of non-retractile foreskin and preputial adhesions wasdocumented by Gairdner in 1949and in older boysby Øster in 1968. Their findings, summarised inFigure 17.3, show unequivocally that the foreskin,if left alone, becomes fully and easily retractable byphysical maturity in all but a tiny minority of boys(probably around 1%).

‘Ballooning’ of the foreskin during micturition isa common phenomenon in the period of early

childhood when the foreskin is still non-retractile,but when substantial preputial separation has takenplace. Typically occurring between 2 and 4 years ofage ballooning calls for no treatment as it is bothtransient and self-limiting, resolving as the prepucebecomes more retractable. Concerned parents canbe confidently reassured that neither non-retractil-ity nor ballooning are indicative of obstructedvoiding, as non-invasive studies have establishedthat urine flow rates (Figure 17.4), postvoid resid-ual bladder volumes and bladder wall thickness areunaffected by physiological phimosis.


Figure 17.1 Developmentally non-retractile foreskin:attempted retraction reveals an apparent constrictionring a few millimetres proximal to the preputial orifice.

Figure 17.2 Developmentally non-retractile foreskin:on attempted retraction, the preputial orifice opens asa flower with a moist, supple and unscarred appear-ance to the pouting inner preputial mucosa.

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Preputial function

Although the prepuce serves no essential physio-logical function, it is not wholly without purpose.In the first instance, the foreskin typically remainsnon-retractable prior to toilet training, thereby –perhaps coincidentally, perhaps not – protectingthe glans penis and its meatus from ammoniacalinflammation and hence meatal ulceration orsubsequent stenosis.

The other consideration is that of sexual satis-faction. In contrast to the glans, which is inner-vated principally by free nerve endings mediatingpoorly localised sensations, the prepuce has a richsomatosensory innervation forming an importantcomponent of the normal complement of penileerogenous tissue. Amputation neuromas mayfollow circumcision. Moreover, this procedure notonly removes some 30% of the penile skin, plusthe greater part of the muscular component of thedartos layer, but also leaves the surface of the glansto undergo keratinisation. However, because of thehighly subjective nature of sexual pleasure it isimpossible to draw meaningful comparisonsbetween the circumcised and the uncircumcisedstate other than on a purely anecdotal basis.

Preputial disorders andabnormalities

Balanitis xerotica obliteransTrue pathological phimosis with scarring of thepreputial orifice (Figures 17.5 and 17.6) is causedby the chronic cicatrising skin condition balanitisxerotica obliterans (BXO). The disease process is histologically identical to lichen sclerosis etatrophicus of the vulva and affects the prepuce,glans and occasionally the urethra. Histologicalfindings are characterised by the following features –hyperkeratosis with follicular plugging, atrophy ofthe stratum spinosum Malphigi with hydropicdegeneration of basal cells, lymphoedema, hyali-nosis, homogenisation of collagen in the dermisand an associated band-like chronic inflammatorycell infiltrate (Figure 17.7). The disorder typicallypresents with irritation, local infection, dysuria,bleeding, secondary non-retractability of theforeskin or a deteriorating urinary stream. On rareoccasions it can progress to the point of presentingwith acute urinary retention or secondary diurnalor nocturnal enuresis resulting from chronic outflowobstruction.

The prepuce 235

Figure 17.4 Uroflow age-related nomograms plotted with the Qmax and voided volume data for 32 boys withphysiological phimosis: (a) nomogram for 3–7 year olds; (b) nomogram for 8–12 year olds. The blue diamondsrepresent flow data from patients with, and pink circles from boys without, ballooning of the foreskin. The twogroups have a similar distribution of flow rate values and all points are within the normal range. (Reprinted withpermission.)

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Ultrasonography in cases with obstructivesymptoms may disclose thickening of the bladderwall and/or significant residual urine, althoughonly very rarely secondary dilatation of the upperrenal tracts.

BXO is rare under the age of 5 years old, with apeak incidence in boys aged 9–11 years old (76%),and is estimated to have affected 0.6% of boys bytheir 15th birthday. Glanular involvement occursin 49% of cases, although the meatus is affected inonly a small proportion.

The aetiology of BXO is unknown, with nofamilial predisposition, or any identifiable causativebacterial or viral agent. There is no association

with puberty and, contrary to widespread belief,BXO does not result from recurrent balanoposthi-tis (Figure 17.8).

The preferred treatment is circumcision: indeed,pathological phimosis constitutes the onlyabsolute indication for this procedure in boys.Preputioplasty is not an option as the continuinginflammatory process results in recurrent stenosisof the preputial orifice. Glanular involvementnearly always resolves following circumcision.However, meatal involvement calls for simultane-ous meatotomy or meatoplasty in approximately5% of cases and postoperative application oftopical steroid creams may lessen the risk of subse-quent restenosis. Parents should be notified of therisk of recurrent meatal stenosis and follow-up isalso advisable for this reason.

In boys presenting with milder forms of BXO,the application of a potent topical steroid (e.g.0.05% mometasone furoate, 0.05% clobetasolpropionate or 0.05% betamethasone cream) mayameliorate local symptoms and result in animprovement in the appearances of the foreskin.But while this approach may afford symptomaticrelief, it is rarely curative and delays rather thanavoids the need for circumcision. Misguidedattempts to persist with medical managementdespite progressive BXO carry the risk that the


Figure 17.5 Pathological phimosis due to balanitisxerotica obliterans. Characteristic pallor, scarring andstenosis of the prepuce.

Figure 17.6 BXO, extensive glanular involvementand meatal stenosis.

Figure 17.7 Characteristic histological features ofBXO, including an acellular band/layer between theepithelium and deeper dermis and a band-like chronicinflammatory cell infiltrate.


partially treated sclerotic process may extend toinvolve the meatus and distal urethra.

In adults there is an association between BXO andpenile cancer (28% of patients with penile malig-nancy have BXO), although a specific causal relation-ship is uncertain. The relevance of this association topaediatric patients is unknown since there are no datadocumenting the long-term outcome for boys withBXO followed into adulthood.

Acute balanoposthitis

In its full-blown form, acute balanoposthitisconsists of purulent, pyogenic, infection of theentire preputial sac. Typically this is accompaniedby purulent discharge and overlying oedema ofthe prepuce that may, on occasion, spread toinvolve the skin of the entire penile shaft. In the lesser severe forms of the condition, moreproperly termed posthitis, the inflammatory

process is limited to the preputial orifice and theouter reaches of the lining of the foreskin, result-ing in localised erythema and oedema, along withcorresponding irritation, but not purulentdischarge. Dysuria is a common complaint andminor bleeding from the preputial orifice mayalso occur. Urinary infection is the only dif-ferential diagnosis and may be distinguished from balanoposthitis by the absence of preputialsymptoms and signs.

Balanoposthitis is comparatively infrequentprior to toilet training, perhaps because ammoniainhibits the growth of pathogens. Commoncausative organisms are Staphylococcus aureus,Escherichia coli and Proteus spp., although in a thirdof cases the preputial discharge is sterile on culture.Balanoposthitis occurring when the prepuce isfully and easily retractable should arouse suspicionin older boys, as it may be the presenting featureof diabetes mellitus.

The prepuce 237

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Figure 17.8 Age distributions of pathological phimosis (orange) and of balanoposthitis (purple) (UrologyDepartment, Alder Hey Children’s Hospital, 1984–99).


Treatment comprises antibiotic therapy foracute episodes, where indicated, and attention tohygiene. Beyond the acute episode, therapeuticintervention should be restricted to boys whosuffer recurrent episodes. Because the complaint is typically associated with complete or partial non-retractility of the foreskin, preputioplasty or preputiolysis (according to individual circum-stances) should be considered as surgical alterna-tives to circumcision. Topical steroid creamsrepresent another option.

Schönlein–Henoch purpurainvolving the penisThe preputial and penile swelling and oedemasometimes associated with this condition may beconfused with balanoposthitis if these featuresappear before the characteristic purpuric rash onthe legs, lower abdomen and buttocks. Like-wise, idiopathic scrotal oedema can occasionallyextend up from the perineum to involve the penileshaft, although this is unlikely to cause diagnosticuncertainty.

ParaphimosisThis is a rare condition in boys which is related tomanipulations of the foreskin and a failure to drawthe prepuce forward again following retraction,with resultant congestion and oedema of theprepuce and glans (Figure 17.9). Often the boy has been encouraged to retract the foreskin forphysiological phimosis by parents or medical staff. Iatrogenic paraphimosis can occur follow-ing catheterisation if the foreskin is not reduced.Paraphimosis does not signify underlying foreskindisease and an isolated episode is not an indicationfor circumcision. It is only seldom necessary toresort to a dorsal slit and in most instances reduc-tion can be achieved by reducing the preputialoedema by manual compression, multiple needlepuncture or topical cooling then drawing theforeskin forwards over the glans employing EMLAcream as a topical local anaesthetic. Recurrentepisodes are exceptional and constitute the onlyindication for circumcision with this complaint.

Preputial cysts and adhesionsDepending on age, preputial adhesions are anormal phenomenon and resolve spontaneouslythrough childhood, as described by Gairdner in1949.Some boys present with one or more yellow-ish lumps on the penis that are often diagnosed bythe general practitioner as sebaceous cysts orlipoma of the penile shaft. Invariably, on outpa-tient assessment, these prove to be collections ofretained smegma trapped by surroundingpreputial adhesions (Figure 17.10). Reassurance isall that is required, as the smegma is released whenthe adhesions lyse spontaneously over time.

There is a very limited role for the surgicalrelease of preputial adhesions in the managementof recurrent balanoposthitis and such patients maybe better served with a circumcision or preputio-plasty (see later). Occasional examples are seen oftrue retention cysts of the prepuce. Localisedretention cysts can be enucleated, but more diffuselesions call for circumcision.

Congenital megaprepuceThis rare condition has only recently receivedrecognition as an entity in its own right and it ispossible that it represents a genuinely newpathology. On cursory inspection it resembles aburied penis, but closer examination reveals an


Figure 17.9 Paraphimosis. There is oedema of theforeskin and glans due to a constriction ring at thesubcoronal level.


enormously capacious preputial sac, engulfing thewhole penile shaft and upper scrotum (promptingthe term ‘preputial bladder’). Urine dribbles moreor less continuously from the preputial orifice and,although the capacious urine-filled sac can bereadily emptied by compression, there is never anormal urinary stream. Almost nothing is knownof the natural history of the deformity and whetheror not it tends to improve over time, since surgeryis usually undertaken because of functional andcosmetic concerns (Figure 17.11). The correctionof congenital megaprepuce can be a significanttechnical challenge and considerable experience isrequired to achieve a good cosmetic result. Themain problems stem from a deficiency of penile

shaft skin, an absence of defined penopubic andpenoscrotal angles and a marked excess of innerpreputial ‘mucosa’. Various reconstructive proce-dures have been described which result in acircumcised penis. Revision surgery is not uncom-mon for redundant penile skin or recurrence of theburied appearance.

Circumcision

Religious circumcisionThe ethical issues surrounding religious circumci-sion are beyond the scope of this chapter butcentre principally on concerns that scarcely anyboys being submitted to the procedure are in aposition to give informed consent. Althoughthere is some variation between different areas ofthe UK, religious circumcision is not generallyfunded within NHS hospitals. However, in somecities with a large Muslim population, circumci-sion services are provided under the auspices oflocal NHS organisations. Religious circumcisionsin the Muslim faith are otherwise undertaken inthe community by general practitioners and othermedically qualified practitioners and in theJewish community by mohels – trained circum-cisers who may or may not be medically qualified.

‘Routine’ circumcisionMost medical arguments previously advanced injustification of newborn circumcision, including areduced risk of venereal disease or carcinoma of the penis for the patient, or of carcinoma of thecervix in a prospective spouse, have largely beendiscounted. However, there is now good evidencefrom recent randomised trials in sub-SaharanAfrica that circumcised adults are relativelyprotected from infection by the human immuno-deficiency virus (HIV). Thus routine circumcisionmay become an important healthcare measure indeveloping countries with a high prevalence ofHIV infection.

Otherwise, the only other possible justificationrelates to the risk of urinary tract infection (UTI).

The prepuce 239

Figure 17.10 Smegma retention ‘cyst’. The mobile,subcutaneous, firm lump at the coronal level has ayellowish appearance and is often misdiagnosed inprimary care as a dermoid cyst or lipoma.


It has long been recognised that during the first yearof life UTI occurs more frequently in boys than ingirls and, moreover, that the risk of a UTI is six toten times higher in uncircumcised boys. Neverthe-less, the absolute incidence of UTI is low, and it hasbeen calculated from a systematic review ofrandomised trials and observational studies that thenumber needed-to-treat to prevent one UTI innormal boys is 111. Routine neonatal circumcisionis clearly not justified as a routine prophylactic

measure on this basis. However, there is morepersuasive evidence that circumcision is beneficial inreducing the risk of UTI in male infants with predis-posing urinary pathology, such as vesicoureteric refluxor urinary dilatation resulting from congenitalurethral obstruction. In boys with recurrent UTI orhigh-grade vesicoureteric reflux, the risk of UTIrecurrence is 10% and 30% and the numbersneeded-to-treat are much less at 11 and 4, respec-tively. However, performing circumcision at the


Figure 17.11 Congenital megaprepuce. This seriesof photographs shows the distended state where thepenile shaft is no longer visible, being surrounded byurine collecting within the dilated subcutaneouspreputial sac (a), manual expression of the megapre-puce producing a stream from the retained urine (b)and the decompressed more normal appearance priorto a modified circumcision (c).

(a)

(b)

(c)


time of antireflux surgery does not reduce furtherthe incidence of postoperative UTI.

Circumcision for medicalindicationsThe principal indications cited for medicalcircumcision in the UK are ‘phimosis’ andbalanoposthitis. In Scandinavian countriesapproximately 2% of boys are circumcised formedical reasons and although the percentage hashistorically been considerably higher in the UKthe percentage has almost fallen to the Scandina-vian level over the last decade, currently standingat around 3% for boys aged 0–16 years old.Nevertheless, it is almost certainly the case thatunnecessary circumcisions are still beingperformed, particularly for physiological phimosisin boys under 5 years old (an age at which BXO isvirtually unheard of and non-retractility of thehealthy prepuce is the norm).

Contraindications tocircumcisionAll parents of boys with hypospadias, as well asthose with epispadias or ambiguous genitalia,should be advised not to have their son circum-cised as the foreskin may be required for recon-structive purposes. Special considerations relatingto buried penis are outlined below. A familyhistory of bleeding disorder is a relative contraindi-cation to circumcision. In this context, excessivepostoperative haemorrhage after circumcision maybe the first manifestation of a bleeding disordersuch as factor VIII deficiency.

Surgical aspects

The techniques employed for neonatal circumcisionwill not be considered here. Circumcisionperformed for genuine medical indications shouldbe undertaken as a formal surgical procedure undergeneral anaesthesia, with additional local anaesthe-sia (caudal or penile block) to provide postoperative

analgesia. The details of technique are a matter ofindividual surgical preference, but the followinggeneral points should be observed:

• Care should be taken to ensure that the prepuceis completely separated from the underlyingglans and coronal sulcus prior to circumcision.Failure to do so may result in the formation ofpersistent skin bridges between the glans andthe penile skin.

• The outer and inner layers of preputial skinshould be excised separately and trimmedfurther if necessary to ensure the best cosmeticresult. For this purpose some surgeons delin-eate the planned incisions with a marking pen.Failure to excise sufficient of the outer layermay leave redundant penile skin, resulting in anunsatisfactory cosmetic outcome (incompletecircumcision) and a requirement for secondarysurgical revision.

• Conversely, removal of too much skin mayleave insufficient to cover the penile shaft. Thisrisk is greatest in boys with so-called ‘buriedpenis’, in whom even a standard circumcisionmay result in a denuded penile shaft and arequirement for skin grafting. A modifiedtechnique is required in such cases, to redis-tribute rather than remove preputial skin.

• Careful attention to haemostasis is importantto minimise the risk of postoperative haemor-rhage. Bipolar diathermy is more effective thanligation of individual vessels. Laser circumci-sion has been shown to have a low risk ofpostoperative haemorrhage.

• Sutures chosen for skin closure (e.g. VicrylRapide) should be rapidly absorbed to reducethe incidence of suture tract formation,whereas some surgeons employ subcuticularsutures to minimise this risk. The use of tissueglues instead of sutures is well documentedin sizeable series and has been claimed toreduce operative times and improve cosmeticappearances.

The choice of postoperative dressing (if any) is alsoa matter of individual preference. Many surgeons

The prepuce 241


avoid dressings because of the distress caused bytheir removal.

Complications of circumcision

Parents should be made aware that there is anappreciable incidence of postoperative distress andmorbidity following circumcision. Early complica-tions include urinary retention and haemorrhage.The former can be prevented by adequate analge-sia or intraoperative local block with levobupiva-caine. As a rule, any subsequent difficulty withmicturition can be relieved by sitting the boy in awarm bath and allowing him to urinate in thewater, while on occasion oral diazepam can suffi-ciently relax the urethral sphincter to avoid a full-blown episode of acute retention. Haemorrhage ofsufficient severity to necessitate early reoperation isreported to occur in 2–5% of boys. The mostcommon postoperative problem is encrustation,scabbing and infection of the exposed glans.Meatal stenosis occurs in a small proportion aftercircumcision. Major complications such as severesepsis, urethral fistula, injury to the glans andpartial penile amputations are virtually confined toreligious circumcisions performed in the commu-nity (Figures 17.12 and 17.13).

Alternatives to circumcision

These are designed not to treat pathologicalphimosis due to BXO but rather to render anormal foreskin fully retractable at an earlier agethan would otherwise have been the case.Although such intervention is often well worth-while for boys troubled by localised symptoms or recurrent balanoposthitis, it is not justifiablesimply as a response to parental pressureprompted by concerns about non-retractility ofthe foreskin or ‘ballooning’. Reassurance andan explanation of the natural history of the healthynon-retractile foreskin should be employed inthis situation.

Topical steroidsThere are now many retrospective and prospectivestudies unequivocally demonstrating that a rangeof steroid creams can alter the characteristics ofthe foreskin, rendering it retractable earlier thanwould naturally have been the case. Postulatedmodes of action relate to the anti-inflammatoryand antiproliferative properties of topical steroids.There may also be effects on extracellular matrixcomposition.

Although the literature consists largely of obser-vational and uncontrolled studies, it does include atleast eight controlled studies – indicating that thebeneficial effect is genuinely attributable to thesteroid component, not simply a non-specificphysical effect of the cream or ointment. Unfortu-nately the entry criteria into these studies areusually poorly defined and the extent, if any, towhich they included cases of early BXO is unclear.It is difficult to escape the impression, however,


Figure 17.12 Complication of circumcision. Childadmitted to hospital following religious circumcision.Excoriation and infection of the glans.


that the favourable results reported by these studieswere obtained predominantly in boys with healthynon-retractile foreskins. Various different steroidpreparations have been used (including 0.05%betamethasone cream, 0.05% clobetasol propi-onate cream and 0.02% triamcinolone acetonidecream), usually with a twice daily application for4–8 weeks and a repeat course if initial results areunsatisfactory. Although ‘success rates’ of 70–95%have been reported, ‘success’ is often loosely (andsubjectively) defined, with some authors regardingit as full retraction whereas others extend the defini-tion of ‘success’ to encompass partial responders orboys with retractability deemed ‘appropriate forage’ following treatment. Application of the steroid

cream must be combined with regular attempts atretraction of the prepuce to achieve success. Oneconsistent finding to emerge from all the studies isthat this form of treatment is safe and free ofcomplications.

PreputioplastyIn boys where intervention is felt necessary fora tight non-retractile foreskin, a preputioplastymay be a sensible option allowing foreskin preser-vation. Performed under general anaesthetic,this consists of incising the ‘constriction ring’apparent on retracting the foreskin and closing theincision transversely with interrupted sutures

The prepuce 243

Figure 17.13 (a) Iatrogenic buried penis due to scarring and occlusion of the residual skin following ritualcircumcision. (b) Appearances following surgical release and revision of circumcision.

(a) (b)


(Figure 17.14). A single incision has a tendency toleave an initial cleft-like deformity, resembling alimited dorsal slit, although this improves withtime. For this reason various modifications havebeen described using multiple incisions or Y-Vplasties. The procedure is contraindicated in thepresence of BXO and success depends on early andfrequent retraction of the prepuce postoperatively

once oedema and pain have settled. It is agood alternative to circumcision when used selec-tively, ideally in older boys who are able tocooperate with the postoperative regimen ofregular retraction.

Key points

• Although the foreskin is almost alwaysunretractable at birth, it spontaneouslybecomes fully and easily retractable in approximately 99% of boys by 16 years of age.

• Conservative treatment of thenon-retractable foreskin involveseducating the parents on thenatural fate of the foreskin.

• Effective alternative treatments forthe non-retractable foreskin includethe use of topical steroid therapyand, on occasion, preputioplasty.

• Surgical intervention forbalanoposthitis can reasonablybe considered for boys troubled byrecurrent episodes and may take theform of preputioplasty and/orpreputiolysis rather thancircumcision.

• Pathological phimosis due tobalanitis xerotica obliterans affectsonly 0.6% of boys and is rareunder the age of 5.

• Balanitis xerotica obliterans isthe one absolute indication forcircumcision.

Further reading

Babu R, Harrison SK, Hutton KA. Ballooning of theforeskin and physiological phimosis: is there any objec-tive evidence of obstructed voiding? BJU Int 2004; 94:384–387

Bailey RC, Moses S, Parker CB et al. Male circumcisionfor HIV prevention in young men in Kisumu, Kenya:


Figure 17.14 Technique of preputioplasty. (a)Adhesions divided, prepuce retracted. (b) Constrictingring incised and (c, d) incision closed transversely. (e)‘Dorsal slit’ appearance on completion of the proce-dure evolves into normal retractile prepuce (f) if retrac-tion is undertaken regularly in the ensuing weeks.

(a) (b)

(c) (d)

(e) (f)


a randomised controlled trial. Lancet 2007; 369:643–656

Cuckow PM, Rix G, Mouriquand PD. Preputial plasty: agood alternative to circumcision. J Pediatr Surg 1994;29: 561–563

Gairdner D. The fate of the foreskin. A study of circumci-sion. BMJ 1949; 2: 1433–1437

∅ster J. The further fate of the foreskin. Arch Dis Child1968; 43: 200–203

Rickwood AMK, Hemalatha V, Batcup G, Spitz L. Phimo-sis in boys. Br J Urol 1980; 52: 147–150

Singh-Grewal D, Macdessi J, Craig J. Circumcision for theprevention of urinary tract infection in boys: a systematic

review of randomised trials and observational studies.Arch Dis Child 2005; 90: 853–858

Subramaniam R, Jacobsen AS. Sutureless circumcision: aprospective randomised controlled study. Pediatr SurgInt 2004; 20: 783–785

Summerton DJ, McNally J, Denny AJ, Malone PS.Congenital megaprepuce: an emerging condition –how to recognize and treat it. BJU Int 2000; 86:519–522

Yang SS, Tsai YC, Wu CC, Liu SP, Wang CC. Highly potentand moderately potent topical steroids are effective intreating phimosis: a prospective randomised study.J Urol 2005; 173: 1361–1363

The prepuce 245



Testis, hydrocoele andvaricocoele

Nicholas P Madden

Introduction

Orchidopexy and operations for hydrocoele (so-called ‘groin surgery’) are among the commonestelective surgical procedures of childhood, and themanagement of varicocoele is increasingly enteringthe sphere of paediatric urological practice. Despitethe frequency of these conditions, several impor-tant aspects of the long-term functional outcome oforchidopexy and the treatment of varicocoeleremain unresolved. The reasons lie partly in thelengthy interval between intervention and outcome(plus the difficulty of devising reliable prospectivestudies) and partly in the problems inherent inmeasuring fertility. The embryological basis ofcryptorchidism and hydrocoele, the normal mecha-nism of testicular descent and the role of theprocessus vaginalis are described in Chapter 1.

The well-documented phenomenon of second-ary testicular ascent is addressed below under theseparate heading ‘Ascending testis’. For ease ofunderstanding throughout this chapter, the terms‘cryptorchidism’ and ‘undescended testis’ will referto congenital maldescent.

Incidence

The incidence of cryptorchidism appears to beincreasing. An authoritative study in the 1950sput the figure at 0.8% at 1 year of age, whereas

subsequent work in the 1980s based on similarcriteria documented an incidence, of 1.55%. Hospi-tal discharge data collected in England in the early1990s indicated that at that time the orchidopexyrate for boys in England and Wales was considerablyhigher than either of these estimates of incidence, atapproximately 3%. Over the period 1994–2004,however, the orchidopexy rate in England fell by athird, the most plausible explanation being a reduc-tion in the number of inappropriate proceduresperformed on retractile testes. The calculations arenow further complicated by the acceptance of thewell-documented phenomenon of secondary testic-ular ascent. In summary, the best current estimate ofthe incidence of testicular maldescent (both congen-ital and acquired) is probably of the order 1.5–2%.

In boys born at term the testis should be in thescrotum and, where it is not, spontaneous descentthereafter is comparatively unusual. By contrast,premature infants have a significantly higherincidence of undescended testes, and in these infantsspontaneous testicular descent frequently occursduring the first 3 months of life (Table 18.1).

Pathology

Congenitally undescended testes develop progres-sive histological changes during the first few yearsof life, with defective transformation of gonocytesand loss of germ cells. These changes are most

18

Topics coveredUndescended testis

EpidemiologyImpalpable testis, retractile testis, ascending testis Fertility, malignancy

HydrocoeleVaricocoele


apparent from 2 years of age onwards. In gonadsnot brought into the scrotum, this histologicalpicture progresses to one in which there iscomplete loss of germ cells (so-called ‘Sertoli cellonly’ appearances). Seminiferous tissue accountsfor the bulk of testicular volume and its loss there-fore results in atrophy of the testis and azoosper-mia. Eventually, carcinoma in situ may supervene,being present in up to 25% of testes retained inan intra-abdominal position into adult life. Thehistological changes observed in cryptorchidismprobably represent the outcome of a combina-tion of temperature-related damage, pituitary–gonadal dysfunction and underlying dysplasia.Undescended testes are also associated with anappreciable incidence of coexisting congenitalabnormalities of the epididymis and vas which, intheir own right, may further contribute to impairedfertility in later life.

It should be noted that congenitally maldescendedtestes are almost always associated with a completelypatent processus vaginalis or, occasionally, a frankinguinal hernia. However, genuinely ectopic testesrepresent an exception to this rule, as these gonadshave descended fully but to the wrong site.

Testicular dysgenesis syndrome has been proposedas a unifying concept to explain the associationbetween undescended testes, testicular malignancy,reduced fertility and hypospadias. The limited biopsydata relating to ascending testes reveals similar histo-logical changes to those associated with congenitallyundescended testes retained into later childhood. Ifconfirmed by further studies, this would providefurther evidence of the role of elevated temperatureas a major factor in degenerative damage.

Classification

Because of the implications for clinical manage-ment, the most practical distinction lies betweenthe palpable and the impalpable testis.

The anatomical classification of undescendedtestis can be further subdivided into maldescendedtestes, lying somewhere along the normal line ofdescent, and ectopic testes lying outside that line.Ectopic gonads are most commonly encounteredin the perineum, lateral to the scrotum (Figure18.1), occasionally in the thigh, and exceptionally,as crossed ectopia, in the contralateral hemiscro-tum. Although undescended testes are often to befound within the ‘superficial inguinal pouch’, thislocation is no longer considered to be ‘ectopic’.

Presentation

In the UK, undescended testes are most frequentlydiagnosed during the course of the examinationroutinely performed in all newborns. If at thisstage the testis is not in the scrotum, its positionshould be reassessed at 3 months of age (or 52weeks postconceptual age in premature infants). Itshould be noted that at birth, and for the first3 months of life, the cremasteric reflex is absent, sothat the true location of the gonad is easier to


Table 18.1 Incidence of undescended testis inlow birthweight premature infants

Incidence of undescended testis (%)

Birthweight (g) At birth At 3 months

<2000 45.4 7.72000–2499 13.4 2.5>2500 3.8 1.4

Figure 18.1 Right ectopic testis. Empty right hemi-scrotum, and a visible swelling (ectopic testis) in theperineum lateral to the scrotum.


assess than at other times in infancy and childhood.Testicular maldescent is also sometimes identifiedfor the first time during routine developmentalassessments at 6–8 months of age, or during subse-quent school medical examinations.

The right testis is more commonly undescendedthan the left, and in approximately 25% of cases ofcryptorchidism the condition is bilateral.

Older boys referred with ‘undescended testis’more commonly prove to have a retractile orascending gonad. The term ‘retractile testis’ shouldbe confined to those where the testis, whereversited initially, can nevertheless be brought fully tothe floor of the scrotum without tension on thespermatic cord. It is important to note that acremasteric reflex can sometimes also be elicited incongenitally maldescended testes, and hence thedistinction between maldescent and retractility isnot always so clear-cut as was once believed.

History

History is straightforward if referral is made directlyfrom a maternity unit. When boys are referred at anylater stage the information recorded in the neonatalnotes regarding the location of the testes at birth canbe helpful. However, these findings are not alwaysreliable and in most instances this information islacking, and so the history assumes importance.Occasionally, transient testicular descent has beenobserved, typically during a warm bath, in which casethe diagnosis is almost certainly one of retractile testis.In the absence of such a history the parents should beasked whether the possibility of testicular maldescentwas mentioned at birth, at subsequent routine checksduring infancy or, in older boys, at any school medicalexamination. If the answer to these questions is ‘no’,there is strong presumptive evidence that the testiswas, at some stage, fully descended.

Examination

Examination begins with scrotal inspection. Notinfrequently, both gonads are to be seen at the base

of the scrotum, in which case the diagnosis isevidently one of retractile testis. Sometimes there isobvious asymmetry of the scrotum, whereas in otherinstances, where bilateral maldescent is suspected,the scrotum appears to be ‘small’. However, becausethe scrotal skin is highly sensitive to external temper-ature, a ‘small’ scrotum, or one exhibiting asymme-try, cannot be taken as reliable evidence of truetesticular maldescent. The examiner’s hands mustnot be cold and examination should be conducted ina relaxed, warm environment. Palpation may be facil-itated by the application of talcum powder tominimise friction between the examiner’s hands andthe patient’s skin. Starting laterally to the right inter-nal ring, the left hand moves down the inguinalcanal, ‘milking’ the testis towards the scrotum. Oncethe left hand reaches the pubic tubercle, the righthand is employed to locate the testis and to draw itdownwards towards the scrotum.

A testis which can be readily manipulated fromthe groin to the floor of the scrotum, and whichremains there, is evidently ‘retractile’ and, as such,normal (Figure 18.2). In other instances, althoughthe testis can be brought to the base of the scrotum,this is only with some difficulty and is followed byimmediate ascent once traction is released, a situa-tion commonly termed ‘high retractile testis’.

Thickening of the spermatic cord may be indica-tive of a persistent processus vaginalis, and veryoccasionally – usually in infants – there is aninguinal hernia. Care should be taken not tooverlook ectopic gonads, which are most oftento be found in the perineum immediately lateral tothe scrotum. Where one testis is impalpable,hypertrophy of the contralateral testis (see below)suggests that the impalpable gonad is absent,although this finding is not sufficiently reliable toavoid the need for laparoscopy.

Management

Hormonal treatmentAlthough success rates in excess of 50% have beenreported in uncontrolled studies, these almost

Testis, hydrocoele and varicocoele 249


certainly reflect the inclusion of boys with retractiletestes. When subjected to a double-blind placebocross-over trial it was demonstrated conclusively thathormone therapy is ineffective in treating congeni-tally undescended testes. Nonetheless, hormonalmanipulation does have its uses, sometimes whenadministered preoperatively to facilitate a potentiallydifficult orchidopexy, and otherwise to distinguishbetween true maldescent and ‘high retractile testis’.

Hormonal treatment may consist of a 3-weekcourse of intranasal luteinising hormone-releasinghormone administered four to six times dailyor, more commonly, of human chorionicgonadotrophin given by intramuscular injectiononce or twice weekly for the same period.

SurgeryPalpable undescended testis

Standard single-stage orchidopexy is usuallyundertaken as a day-case procedure, ideally at some

stage between 9 and 24 months of age. In experi-enced hands, the incidence of testicular atrophyfollowing orchidopexy before 2 years of age is nogreater than when the procedure is undertaken ata later stage.

Impalpable testis

Some 10–20% of undescended testes are impalpa-ble. Before embarking upon definitive surgery, it isnecessary to establish whether the testis is absent(anorchia), is intra-abdominal, or is represented byan atrophic nubbin of tissue within the inguinalcanal. In approximately 40% of cases of ‘impalpa-ble testis’ the gonad lies intra-abdominally; in 30%it has ‘vanished’, with vas and vessels ending blindlydeep to the internal inguinal ring; in 20% the vasand vessels end blindly within the inguinal canal;and in 10% the testis is normal but concealedwithin the inguinal canal.

Ultrasound is unreliable in distinguishing betweenanorchia and intra-abdominal testis, giving bothfalse-positive and false-negative findings, but it issometimes helpful in visualising a testis within theinguinal canal. Magnetic resonance imaging (MRI)is also unhelpful alone, although more reliable whencombined with angiography, but this requires ageneral anaesthetic.

Consequently, laparoscopy remains the investi-gation of first choice in cases of impalpable testis,being both highly reliable and providing positiveguidance for further management. In this regard,there are five possible laparoscopic findings:

• Testis lying adjacent to the internal inguinalring – such gonads are usually amenable to asingle-stage orchidopexy using a conventionalor a preperitoneal approach. An experiencedlaparoscopist may be able to manipulate thetestis towards the inguinal canal so as to assessthe feasibility of a single-stage procedure.

• Testis located on the posterior abdominalwall or ectopically within the pelvis (Figure18.3) – this calls for a decision as to whether toremove the gonad (either laparoscopically or asan open procedure) or whether to embark uponorchidopexy. Here the options lie between open


Figure 18.2 True retractile testis, brought easily tothe floor of the scrotum without undue traction.


or laparoscopically assisted orchidopexy, aseither a single or a staged procedure.

• Failure to visualise blind-ending vesselsor testis – in this rare situation, a limitedlaparotomy is indicated in view of the high riskof subsequent malignancy associated with anundetected intra-abdominal testes left in situ.

• Vas and vessels ending blindly together at orabove the internal ring – such ‘vanished’ testespresumably result from intrauterine torsion andno further exploration is required.

• Vas and vessels seen entering the inguinalcanal – here it is impossible to be certainwhether the canal contains a normal testis or an

atrophic nubbin of testicular tissue. Opinionvaries on whether inguinal exploration is stillmandatory in this situation. Alternatively it hasbeen suggested that inguinal exploration isunnecessary if a nubbin is palpable and thecontralateral testis is hypertrophied (>1.8 cmpolar length or 2 ml in volume).

The last two situations are examples of testicularregression syndrome. Histological examination ofthe remnant shows a vascularised fibrous nodulewith calcification, haemosiderin or spermatic cordelements. More extreme examples of this syndromecan present as disorders of sex development.


Figure 18.3 (a,b) Intra-abdominal testis and vasviewed laparoscopically. (c) Intra-abdominal testislying above the entry to the inguinal canal.

(a) (b)

(c)


Bilateral impalpable testes

Determination of karyotype is always worthwhilein this situation, looking for sex chromosomemosaicism or for chromosomal aberrations suchas the Prader–Willi syndrome. A human chorionicgonadotrophin stimulation test may be undertakento determine the presence or otherwise offunctioning testicular tissue. However, although apositive result is encouraging for the parents, anegative result does not obviate the need forlaparoscopy.

Orchidopexy – surgicalconsiderations

For a detailed account of standard orchidopexy for apalpable testis, the reader is referred to one of thetextbooks of operative paediatric surgery or urologylisted under Further reading. In cases of true congen-ital maldescent the crucial step is clean separation

of the patent processus vaginalis from the cordstructures so as to facilitate full mobilisation of thetesticular vessels, extended retroperitoneally ifnecessary (Figure 18.4).

In the absence of a patent processus vaginalis,orchidopexy is usually straightforward, with thegonad coming readily to the scrotum followingseparation of the cremasteric coverings from thecord structures.

More specialised techniques are required for testeslying high within the inguinal canal or within theabdomen: these options are listed below.

Preperitoneal approach (Jones)

A skin incision at or slightly higher than for astandard inguinal approach is employed and theoblique abdominal muscles are split to gain access tothe peritoneum above the inguinal canal. Thereafter,the testis is mobilised transperitoneally and is passedto the scrotum through the inguinal canal or, if


Figure 18.4 Conventional inguinal orchidopexy. (a) Intraoperative photograph. (b) Diagrammatic representa-tion illustrating mobilisation of cord structures from the processus vaginalis.

(a) (b)


necessary, more directly through the posterior wall ofthe canal medial to the inferior epigastric vessels.

Fowler–Stephens procedure(Figure 18.5)

With intra-abdominal testes, failure to mobilisethe gonad to the scrotum is usually the result ofinadequate length of the testicular vessels rather thanof the vas deferens. The existence of a collateral bloodsupply to the testis via the artery to the vas represents

the rationale for this procedure, and the results arebetter when it is conducted in two stages. At the firststage, undertaken either via an open approach orlaparoscopically, the testicular vessels are isolated anddivided, taking care not to disturb the vas and itsimportant collateral vessels. The second stage isundertaken 6 months later, when this collateralsupply has become more robust following ligation ofthe testicular vessels. The testis and vas are mobilised,along with a broad strip of overlying peritoneum,and brought transinguinally to the scrotum. Thismay be undertaken as an entirely open procedure orwith laparoscopic assistance.

Microvascular orchidopexy

This procedure is appropriate for intra-abdominaltestes, especially if the vas is too short for aFowler–Stephens procedure or, rarely, if the vas isabsent. The testicular vessels are mobilised anddivided as high as possible, following which testisand vas are brought to the scrotum and the testic-ular vessels are anastomosed to the inferior epigas-tric vessels in the inguinal canal (Figure 18.6).

Laparoscopically assisted orchidopexy(Figure 18.7)

The intraperitoneal pedicle of testicular vessels isextensively mobilised laparoscopically, and whensufficient length has been obtained the testis isplaced in the scrotum by either an open inguinalapproach or an entirely laparoscopic procedure.

Difficult situationsEven an experienced surgeon may occasionallyoperate for what is thought to be a palpable testis,only to find – having opened the inguinal canal –that it is empty. This situation should not bemanaged by exploring retroperitoneally. First, ifthere is a patent processus vaginalis, this should beopened, and usually the ‘emergent’ testis will beeasily delivered into the inguinal canal and astandard single-stage orchidopexy should be achiev-able, although there may be some tension when thetestis is placed in the scrotum. If the testis is not


Figure 18.5 Fowler–Stephens orchidopexy. (a)Stage I, testicular vessels ligated or clipped in conti-nuity. (b) Stage II, collateral vascularisation of thetestis via the artery to the vas. After 6 months thetestis is mobilised on the vas and a strip of surround-ing peritoneum and brought to the scrotum by themost direct route.

(a)

(b)


found by this approach, a preperitoneal (Jonesapproach – see above) should be used; this can easilybe achieved through the same skin incision.

Management of retractile testisIn clear-cut cases parents may be reassured thatretractile testes are common, particularly betweenthe ages of 3 and 7 years, and that surgical inter-vention is rarely required. Moreover, one study hasshown that men with bilateral retractile testesduring childhood subsequently have normal testic-ular volume and fertility.

It is not possible to be so confident where thediagnosis lies between ‘high retractile testis’ and

true congenital maldescent. In these circumstancesthe history may be more informative than theexamination. Where any doubt exists, regularannual reassessment should be undertaken, and theparents should be advised that the need for surgerycannot be discounted.

If, during follow-up, it becomes apparent that a‘high retractile testis’ is assuming an increasinglyabnormal position, hormonal manipulation may beconsidered as both a diagnostic and a therapeutictrial. In practice, orchidopexy is generally favoured asthe primary treatment of choice. In such cases it maybe possible to perform this via a scrotal approach.Mobilisation of the cord structures, division of theremnant of the processus and complete separation


Figure 18.6 Microvascular orchidopexy. Testicularartery and single vein anastomosed to inferior epigas-tric vessels (or branches).

Figure 18.7 Laparoscopic or laparoscopically assistedorchidopexy. Extensive intraperitoneal mobilisation oftesticular vessels enables the testis to be brought downto the scrotum with its vascular pedicle intact.


from the overlying cremasteric coverings is usuallysufficient to allow the testis to be positioned satisfac-torily in the scrotum.

Ascending testis

The concept of secondary ascent is now welldocumented by a number of credible studiesdating from the 1980s, with recent reportssuggesting that this phenomenon accounts for arelatively high percentage of boys undergoingorchidopexy in later childhood and up to 20% ofall orchidopexies.

The aetiology of the condition is unknown,although obliteration of a patent processusvaginalis with contraction of the remnant has beenadvanced as a possible cause. A history of retractil-ity has been identified as another contributoryfactor. In almost all series of ‘secondary testicularascent’ orchidopexy was undertaken prior topuberty, so that it is impossible to be sure whetheror not spontaneous descent would ultimately haveoccurred. However, in one large study reportedfrom the Netherlands approximately 20% ofascending testes failed to revert to the scrotumat puberty. In view of some histological datasuggesting that ascending testes are prone tosimilar degenerative changes to those found inundescended testes, there is a risk that thoseascending testes which do return spontaneously tothe scrotum may nevertheless have sustaineddamage during the period spent at a highertemperature in the groin. Further research isneeded, but in the light of the limited availableevidence, orchidopexy is the preferred treatment ofascending testes.

Complications of orchidopexy

The principal complications are postoperativetesticular atrophy, injury to the vas and reascent ofthe testis. Among a total of 8425 procedures in64 published studies, the failure rate, including

atrophy, was 8% when the testis lay beyond theexternal inguinal ring, 13% when the testis waswithin the inguinal canal, and in the case of intra-abdominal testes 16% for microvascular proce-dures and 27% for two-stage Fowler–Stephensprocedures. A 5% incidence of testicular atrophyfollowing inguinal orchidopexy reported from onespecialist paediatric surgical centre in the UK isprobably representative of current practice.

However, atrophy is not an ‘all or none’phenomenon and partial degrees of atrophy areprobably more common than is generallyrecognised.

The incidence of injury to the vas is more diffi-cult to determine, and although a figure of 1–2%is sometimes cited the true incidence is probablyhigher, as direct injury may go unnoticed orunreported. Postischaemic obliteration of the vasresulting from intraoperative damage to thedelicate blood supply is likely to remain unrecog-nised except in individuals who undergo explo-ration or vasography in later life.

Long-term follow-up studies following prepu-bertal orchidopexy indicate that testicular volumeis ultimately influenced by the initial position ofthe gonad, but not by the age at which the surgerywas performed.

Long-term outcomes oforchidopexy

FertilityAssessment of fertility is inexact, as almost all long-term studies have been retrospective, with thelimitations inherent in such studies. In addition,the ability to father children does not consistentlycorrelate with parameters of semen quality.

Although there is considerable variation in theresults reported by different series, there is agree-ment that the prognosis for fertility is better whenjudged by paternity than by semen analysis.Moreover, all published series show that men witha history of unilateral undescended testis have



significantly better prospects of fertility than thosewith a history of bilateral undescended testes,regardless of how fertility is measured (Table 18.2).Indeed, one of the largest long-term studies foundthat the eventual paternity rates of men with ahistory of unilateral undescended testis were onlymarginally less than that for the normal popula-tion. However, men with a history of unilateralcryptorchidisim do demonstrate some degree ofsubfertility, as evidenced by the fact that 11% ofthose attempting paternity fail to achieve concep-tion within 12 months, compared with only 5% ofcontrols. Figures for both semen analysis andpaternity are based upon men who underwentorchidopexy comparatively late in childhood. Itseems reasonable to anticipate an improvement infertility as a consequence of the recent trendtoward earlier orchidopexy before the age of 2years. Some evidence is emerging to this effect, butit will be some time before the presumed benefit ofearlier orchidopexy can be confirmed by reliablelong-term data.

The published evidence can be summarisedbriefly as follows:

• The long-term prognosis for fertility is betterwhen judged by paternity than semen analysis.

• Published series report paternity rates in therange 80–90% for men with a history ofunilateral undescended testis (percentage ofmen with normal semen analysis 55–95%).

• Published series report paternity rates in therange 45–65% for men with a history of bilat-eral undescended testes (percentage of menwith normal semen analysis 25–30%).

• The evidence of biopsy studies supported bylimited clinical data indicate that the prospectsof fertility are enhanced by early orchidopexy(under 2 years of age).

• Testes arrested in a higher position of maldes-cent have a poorer prognosis for fertility.

• Ascending testes (secondary maldescent) sharesimilar histological features to congenitallyundescended testes and the impact on fertilitymay be comparable.

MalignancyMen with a history of cryptorchidism are undoubt-edly at increased risk of testicular malignancy. Alarge case–control study in the UK put the relativerisk at 3.8 times greater than normal when orchi-dopexy had been performed after 9 years of age.However, the relative risk was not found to besignificantly increased if the procedure was under-taken before that age. Other studies based onrecent figures for the incidence of testicular cancerand cryptorchidism have generally placed theincreased relative risk at between 5 and 10 timesgreater than that for the normal population. Thelifetime risk of developing cancer in an undescendedtestis has been calculated to lie in the order of 1 in


Table 18.2 Fertility (paternity) of men with a previous history of undescended testis (UDT)

Paternity rate of Paternity rate Authors Number of patients unilateral UDT (%) of bilateral UDT (%)

Gilhooly et al 145 80 48Kumar et al 56 84 60Lee 467 88 59Lee and Coughlin 408 90 65

Reviewed by Hutson (2006) see Further reading.


100, compared with 1 in 500 in the population atlarge. However, this risk is somewhat less if malde-scent is unilateral, and correspondingly somewhatgreater if bilateral.

In adults the incidence of carcinoma in situ, aprecursor of invasive malignancy, is strongly linkedto the anatomical position of the testis, beingfound in 25% of gonads retained intra-abdomi-nally into adult life. This and other evidencesuggests that the original position of the testis maybe a factor influencing the long-term risk of malig-nancy. During the first year of life undescendedtestes develop Leydig cell hypoplasia and delayeddisappearance of gonocytes. There is some evidencethat these gonocytes may degenerate into carci-noma in situ cells, thus providing further justifica-tion for the trend towards earlier orchidopexy inthe belief that this will be accompanied by a reduc-tion in the risk of malignancy.

Regardless of the age at which orchidopexy hasbeen performed, men who have undergone theprocedure should be encouraged to practise testic-ular self-examination.

Testicular microcalcification

This disorder, which is characterised by the presenceof multiple small echogenic foci of calcification(Figure 18.8), has come to light as a result of theintroduction of testicular ultrasound as a screeningtool in adult urology. Two studies of healthy militarypersonnel found prevalences of 2.4 and 5.6%, withmarked differences between racial groups. Testicularultrasound is performed far less frequently inchildren and adolescents but, nevertheless, cases oftesticular microcalcification are being identified.Although it had been suggested that microcalcifica-tion might serve as a potential marker of premalig-nancy, this probably applies only when the findingis associated with other recognised risk factors, suchas cryptorchidism, infertility, testicular asymmetryor atrophy. Increasingly, the evidence suggests thatasymptomatic microcalcification is an innocentincidental finding in the majority of individuals and

that prolonged ultrasound surveillance is notrequired unless other risk factors are present. Inadolescents and young adults there is certainly noevidence to support testicular biopsy on the basis ofthis ultrasound finding.

Hydrocoele

With few exceptions, hydrocoeles in boys sharea common underlying aetiology with indirectinguinal hernias: namely, failure of closure of thepatent processus vaginalis following descent of thetestis – see Chapter 1 (Figure 18.9). The differencebetween the two conditions lies in the diameter ofthe processus, which in communicating hydro-coeles is narrow and allows no more than thepassage of intraperitoneal fluid (Figure 18.10).Non-communicating hydrocoeles are very rare inboys and occur principally around or after the timeof puberty (Figure 18.11).

Communicating hydrocoeles are common innewborn males, with an incidence of 2–5%.Upwards of 90% of these congenital lesionsresolve during the first year of life as a result ofspontaneous closure of the processus. A hydro-coele, associated with a patent processus vaginalis,may present at some time later during childhood,although usually before the age of 5 years.


Figure 18.8 Testicular microcalcification. Ultrasoundimage demonstrating characteristic appearances.


PresentationMost hydrocoeles present as a painless scrotalswelling which may vary in size throughout theday, being comparatively small first thing inthe morning and enlarging during the course ofthe day. Sometimes hydrocoeles develop follow-ing the insertion of a ventriculoperitoneal shuntfor hydrocephalus, whereas others present acutelyin association with a viral illness. Although rare,it should always be remembered that hydrocoelesmay be a secondary phenomenon associated withtesticular tumours or omentum incarcerated in ahernial sac.

Encysted hydrocoeles of the cord typicallypresent as a painless swelling in the groin and,being ‘irreducible’, are apt to be confused with anincarcerated inguinal hernia.

ExaminationThe principal differential diagnosis is one of aninguinoscrotal hernia, the latter being reduciblewhereas hydrocoeles are not. Transillumination, theclassic physical sign of a hydrocoele, is not reliably


Figure 18.9 Anatomical classification of hydrocoele.(a) Communicating hydrocoele. (b) Hydrocoele of thecord (‘encysted hydrocoele’). (c) Non-communicatinghydrocoele.

Figure 18.10 Congenital (communicating) hydro-coele.

Figure 18.11 A 14-year-old boy presenting with1-year history of increasing scrotal swelling. Non-communicating ‘adult type’ hydrocoele managed byscrotal approach and plicating hydrocoele sac.

(a) (b) (c)



diagnostic as a scrotal hernia in infancy will alsotransilluminate in bright light. However, hydro-coeles impart a blue colour to the scrotum on inspec-tion; in addition, hydrocoeles are mobile, whereasirreducible hernias are not. A hydrocoele of the cordis distinguished from an irreducible inguinal hernia,which does not extend to the scrotum, in thatdownward traction on the testis causes a correspon-ding movement in the hydrocoele.

Although investigation is usually unnecessary,ultrasonography is helpful whenever there is anysuspicion of testicular tumour or incarceratedhernia.

ManagementCongenital hydrocoeles should be managedconservatively, as almost all will resolve sponta-neously during the first 12 months of life.

Surgical intervention is indicated for congenitalhydrocoeles that persists beyond 1 year of age, andfor those appearing for the first time in later child-hood. Hydrocoeles of the cord are rarely present atbirth and can present acutely. If the diagnosis isuncertain the combination of clinical examination(see above) and ultrasound may avoid unnecessaryemergency operation.

Operative techniqueThe operation for communicating hydrocoeles isthe same as for indirect inguinal hernia. Througha short skin-crease incision in the groin thespermatic cord is delivered, with or without openingthe inguinal canal according to the surgeon’spreference. The patent processus vaginalis isisolated from the testicular vessels and vas, tracedback to its junction with the peritoneal cavity, andtransfixed, ligated and divided at this point. Thehydrocoele sac is then drained by incising the distalportion of the processus, or by percutaneousneedle aspiration of the sac.

If the processus appears to be very narrow orof doubtful patency, suggesting a probable non-communicating variant, it is prudent to combinethe groin procedure with a scrotal procedure to

open, drain and evert the hydrocoele sac ratherthan run the risk of recurrence.

Varicocoele

Although the significance of varicocoeles liesprincipally in their association with subfertility,there is considerable variation in both the clinicalcharacteristics of these lesions and their impact, ifany, upon fertility. Opinion therefore remainsdivided on the indications for surgical interventionin childhood or adolescence. There is also debateas to the preferred surgical technique.

IncidenceVaricocoeles can be demonstrated in 6% of 10-year-old boys and 15% of 13 year olds, the latterfigure being comparable to the prevalence amongadult males generally. Among the male partnersof infertile couples, the incidence of varicocoeleis 30%.

AetiologyThe tortuosity and dilatation of the veins of thepampiniform plexus is the result of incompe-tence of the valvular mechanism that normallyprotects the spermatic veins from the hydrostaticpressure of the column of venous blood trans-mitted from the great veins. The fact that morethan 90% of varicocoeles are left-sided reflectsdifferences in venous anatomy, with the lefttesticular vein draining into the renal vein,whereas the right testicular vein drains into thevena cava. Several patterns of abnormal venousanatomy predisposing to varicocoele formationhave been described:

• absence of valves within an otherwise normalsingle testicular vein

• anomalous venous drainage, for example betweentesticular and retroperitoneal veins

• bifurcation of the left renal vein, with an abnor-mal point of entry of the spermatic veins.


Although renal tumours account for less than 1%of varicocoeles during childhood, this possibilityshould never be overlooked.

PathologyStudies involving the application of heat-sensitivestrips to the scrotal skin have confirmed that thepresence of a varicocoele elevates the temperatureof the scrotal contents, leading to loss of thenormal temperature differential necessary forspermatogenesis. The role, if any, of venouspressure-related damage to the testis is more diffi-cult to assess. Testicular biopsies in the presence ofa varicocoele show reduced spermatogonia,seminiferous tubal atrophy, endothelial cell prolif-eration and Leydig cell abnormalities. When foundin patients under 18 years of age the changes arepotentially reversible, but the more extensive histo-logical changes found in older men are not – anobservation that argues in favour of treating vari-cocoeles during adolescence rather than later.

ClassificationThe classification devised by Hudson is widelyemployed:

• Subclinical: neither palpable nor visible, butdemonstrable by Doppler ultrasound.

• Grade I: palpable only on Valsalva manoeuvre.• Grade II: palpable at rest but not visible.• Grade III: visible and palpable at rest.

PresentationVaricocoeles may be detected during the course ofroutine medical examination or may presentsymptomatically, either as a scrotal swelling, classi-cally likened to a ‘bag of worms’, or by a draggingsensation within the scrotum, which is often worseduring hot weather (Figure 18.12).

Diagnosis and investigationThe patient should be examined both lying and,more importantly, standing, the latter both with and

without a Valsalva manoeuvre. Testicular size andvolume should be assessed. The traditional methodusing a Prader orchiometer or callipers is prone toconsiderable observer variation. Ultrasound assess-ment of testicular volume is more reliable and canbe combined with an abdominal ultrasound scan toexclude a renal tumour.

Indications for treatmentThe presence of symptoms is generally accepted asan indication for surgical intervention, as is impair-ment of testicular growth. Among adolescent boyswith asymptomatic lesions, however, the issue of‘prophylactic’ intervention is altogether morecontroversial. The arguments in favour of inter-vention can be summarised as follows:


Figure 18.12 Grade III varicocoele. Visibly distendedcremasteric veins (‘bag of worms’).



• Persistence of an untreated varicocoele intoadult life leads to a demonstrable reduction intesticular volume, and there is evidence thatsurgical correction may partly reverse thisprocess, leading to some degree of subsequent‘catch-up growth’.

• The incidence of varicocoele among men inves-tigated for infertility is higher than in the malepopulation at large.

• Some studies have found an improvement insemen quality and pregnancy rates followingtreatment of varicocoele in subfertile men.

Arguments against prophylactic intervention inadolescence are:

• Varicocoeles exist in some 15% of adult males,most of whom, as judged by paternity, havenormal fertility.

• Although a link exists between varicocoele andinfertility or subfertility, there is no consistentcorrelation between the presence or size of thelesion and semen quality or fertility.

Only time will ultimately resolve this controversy,but the present tendency is to advise ‘prophylactic’intervention in the case of the larger, grade III,lesions, particularly if there is testicular asymmetrywith a discrepancy in testicular volume of >20%.From the mid teens onwards the decision on whetherto proceed to surgical correction of grade IIIvaricoceles can also be guided by semen analysis.

Treatment options (Figure 18.13)Embolisation

Embolisation may be carried out under sedation,although a general anaesthetic is usually used forprepubertal boys. A catheter introduced via theright femoral or internal jugular vein is screenedinto the left renal vein and thence into thespermatic vein. Venography is performed toidentify collaterals. Embolisation is undertakenusing coils inserted into the testicular vein or, lessoften, by the injection of a sclerosant.

Surgical ligation

Using the inguinal approach (Ivanissevich), theinternal inguinal ring is exposed via the inguinalcanal; the spermatic vein is exposed deep to thetransversalis fascia and divided at this level.

Using the high approach (Palomo), a shorttransverse incision is performed lateral to theinternal inguinal ring. The testicular vessels are

4

3

2

1

Figure 18.13 Varicocoele treatment options. (1)Surgical ligation of individual veins, inguinal approach.(2) Surgical ligation of veins and artery, highapproach. (3) Laparoscopic clipping, all vessels orselective ‘artery sparing’. (4) Embolisation.



identified extraperitoneally above the point theydiverge from the vas deferens. In Palomo’s descrip-tion, the testicular artery, vein and lymphatics areligated and divided together but many surgeonsligate only the veins.

Microvascular procedures are nowadayssometimes performed for local ligation of varico-coeles. Although usually undertaken beyond theexternal inguinal ring, in prepubertal boys, thedissection is better performed within the inguinalcanal. Magnification is employed and papaverineand intraoperative ultrasound are helpful in identi-fying and preserving the arteries. Care is takento preserve the testicular and cremasteric arteries,the vas deferens and its artery, and also thelymphatics, as preservation of the lymphatics isbelieved to minimise the incidence of postopera-tive hydrocoele.

Other direct approaches to the dilated veinsdistal to the internal ring carry an unacceptablyhigh risk of testicular atrophy and should beavoided.

With laparoscopic ligation three ports are placedand the testicular vessels identified. The veins caneither be dissected and divided alone or clippedand ligated en bloc, along with the artery, as in thePalomo technique. This approach also allows easyidentification and division of any abnormal veins,and is also especially applicable to the rare case ofbilateral varicocoele. As with open techniques,lymphatic vessels should be preserved as far aspossible in order to reduce the risk of postopera-tive hydrocele; this can be facilitated by injectingmethylene blue into the scotum preoperatively,demonstrating the lymphatics more clearly atoperation.

Complications and outcomeThe fact that several surgical techniques continueto be employed for treating varicocoeles indicatethat no single technique gives consistently satisfac-tory results. The failure rate for all procedures is upto 20%, although this figure appears to be ratherlower when the testicular artery, as well as theveins, is occluded. The incidence of complications,

notably hydrocoele and testicular atrophy, is in theregion of 5%. Almost all published results relateprincipally to adult men, and there is insufficientinformation relating specifically to boys andadolescents from which to draw meaningfulconclusions about the best form of treatment inthis age group.

Improved fertility has been documented insubfertile men following varicocoele ligation,although these represent only a minority of all menwith varicocoeles. Whether prophylactic treatmentof asymptomatic varicocoeles in adolescents isbeneficial for fertility has yet to be ascertained.

Key points

• The optimal age for orchidopexyremains uncertain. Paediatricurologists and paediatric surgeonsfavour the second year of life. Fornon-specialist surgeons it may bereasonable to defer orchidopexyuntil 3–4 years of age.

• The risk of testicular atrophy shouldbe specifically discussed withparents when obtaining consent fororchidopexy.

• Laparoscopy is the investigation ofchoice for impalpable testes.

• In infants a clear diagnostic distinctionmust be made between an inguinalhernia (which requires prompt surgicalintervention in this age group) and acommunicating hydrocoele (whichgenerally resolves as a result ofspontaneous closure of the patentprocessus vaginalis in the first yearof life).

• The available evidence suggests thattreatment of varicocoeles in adolescenceshould be limited to boys with grade IIIvaricocoeles, symptoms and/or evidenceof impaired testicular growth.



Further reading

Barthold JS, Redman JF. Congenital anomalies of the testisand scrotum. In: Whitfield HN, Hendry WF, Kirby RS,Duckett JW (eds). Textbook of Genitourinary Surgery.Oxford: Blackwell Science, 1998; 254–260

Dagash H, MacKinnon EA. Testicular microlithiasis: whatdoes it mean clinically? Br J Urol Intl 2007; 99:157–160

Hendry WF. Testicular, epididymal and vasal injuries. Br JUrol Int 2000; 86: 344–348

Hutson JM. Undescended testes. In: Stringer MD, OldhamKT, Mouriquand PDE (eds). Paediatric Surgery andUrology: Long-Term Outcomes. Cambridge: CambridgeUniversity Press, 2006: 652–663

Hutson JM. Orchidopexy. In: Spitz L, Coran AG (eds).Operative Pediatric Surgery. London: Hodder Arnold,2006: 861–869



The acute scrotum

David FM Thomas

Introduction

Acute scrotal pathology represents one of the fewreal emergencies encountered in paediatric urologi-cal practice. Testicular torsion accounts for 80–90%of cases of ‘acute scrotum’ in teenage boys and inview of the high probability of torsion in this agegroup immediate surgical exploration should beundertaken unless there is compelling evidence of analternative diagnosis. By contrast, the differential

diagnosis is more varied in prepubertal boys, but itis nevertheless important to recognise that testiculartorsion figures prominently as a cause of acutescrotal pathology across the entire paediatric agerange. Surgical intervention can sometimes beavoided if a reliable alternative diagnosis, such astorsion of a testicular appendage, can be establishedrapidly, but it is generally wiser to observe the time-honoured adage: ‘Whenever doubt exists, it is saferto explore.’

19

Topics coveredEpidemiologyDiagnostic features, symptoms and signsTorsion of the testis

Torsion of testicular appendageEpididymo-orchitisIdiopathic scrotal oedemaOther acute scrotal pathology

16

14

12

10

8

6

4

2

01 3 5 7 9 11 13

Age (years)15 17 19 21 23 25

Testicular torsion

Torsion of appendage

Other acute scrotalpathology and negativesurgical exploration

Figure 19.1 The relative frequencyof different causes of acute scrotalpathology at different ages in child-hood and early adult life (Ben-Chaim J,Leibovitch I, Ramon J et al – see‘Further reading’).


Epidemiology

The relative frequency of the various causes ofthe ‘acute scrotum’ in the different age groups isillustrated in Figure 19.1. Between the ages of13 and 21 years, testicular torsion accounts fornearly 90% of acutely presenting scrotal symptoms.However, in prepubertal boys torsion of a testicularappendage (hydatid of Morgagni) is more common,accounting for 45–50% of cases. Testicular torsion,nevertheless, accounts for approximately 35% ofacutely presenting scrotal symptoms before puberty,with epididymo-orchitis, idiopathic scrotal oedema,acute hydrocoele and Henoch-Schönlein vasculitisconstituting the remaining 15–20%.

Diagnosis

Clinical featuresThe differential diagnosis of the acute scrotumand the relative importance of the differentpathologies in pre- and postpubertal boys inone sizeable series are detailed in Table 19.1.Although the diagnosis should be straightforwardin the presence of a characteristic history anddistinctive physical findings it should be notedthat fewer than 50% of cases present with theclassic ‘full house’ of signs and symptoms described

in undergraduate textbooks. Frequently thehistory is less specific and examination simplyreveals a swollen, reddened tender scrotum. Inother instances the history or initial findings maybe frankly misleading.

• Contrary to some textbook descriptions, painis not always a prominent feature of testiculartorsion and, indeed, in infants and youngchildren pain may be virtually absent untilchanges secondary to established testicularinfarction are apparent.

• Pain arising from a right-sided testicular torsionmay radiate to the right iliac fossa, mimickingappendicitis.

• Examination of the scrotal contents should beroutinely included as part of the clinical exami-nation of any child or adolescent presentingwith lower abdominal pain of sudden onset.

• Oedema and erythema of the scrotal skin arenot apparent in the first few hours of testiculartorsion. Absence of these physical signs shouldnot be allowed to delay surgical exploration.

• The pathognomonic ‘blue dot sign’ associatedwith torsion of a testicular appendage (hydatid ofMorgagni) is present in fewer than 20% of cases.

• Urinary symptoms (frequency, dysuria), whichcan sometimes feature in the clinical picture oftesticular torsion, may be wrongly attributed tourinary infection and epididymo-orchitis.


0–12 years 13–21 years

Diagnosis n % n %

Torsion of testis 24 34 72 86Torsion of appendix 33 47 8 9Negative exploration 8 11 4 5Epididymitis 3 4Acute scrotal oedema 1 2Acute haematocoele 1 2Total 70 100 84 100

Table 19.1 Relative frequency of different causes of ‘acute scrotum’ in 154 cases


Diagnostic imagingColour Doppler ultrasound

Colour Doppler ultrasound provides simultaneousreal-time anatomical imaging of the scrotal con-tents together with colour-encoded characteristicsof blood flow. Perfusion of the testis is absent ordramatically reduced in testicular torsion. Draw-backs include operator dependency, limited out-of-hours availability and falsely reassuring findings inearly or intermittent torsion.

Radionuclide testicularscanning (RTS)

This investigation – in which pertechnetatelabelled with technetium-99m (99mTC) is injectedintravenously – is now rarely undertaken and is oflargely historical interest. Testicular torsion is

characterised by a central ‘cold’ area of poorisotope uptake, corresponding to the ischaemictestis, surrounded by a halo of vascular activity inhyperaemic scrotal tissue.

The role of diagnostic imaging, notably colourDoppler ultrasound, is largely confined to prepu-bertal boys in whom testicular torsion is thoughtto have been excluded on clinical grounds butwhere further confirmation is sought.

Testicular torsion

Although the peak incidence lies between the agesof 14 and 16 years (see Figure 19.1), the occur-rence of torsion has been described across theentire age range extending from the neonatalperiod through to late adult life. NHS (NationalHealth Service) hospital data for England indicate

The acute scrotum 267

Figure 19.2 (a) Intravaginal torsion. ‘Bell-clapper’ testis suspended on an abnormally long leash of vessels(mesorchium) within the tunica vaginalis. (b) Undue mobility of the testis predisposes to torsion around the axisof the spermatic cord.

(a) (b)


that approximately 1000 boys aged 0–16 yearsundergo emergency scrotal exploration each year.Unfortunately, no information is available onoperative findings or outcome. The left testis isaffected more commonly than the right. Predis-posing factors may include cold weather (precipi-tating activity of the cremasteric muscle) andtesticular trauma. Maldescended testes account for2–5% of cases.

AetiologyNeonatal or intrauterine testicular torsion is of theextravaginal pattern, in which the testis and cover-ings twist in their entirety within the scrotum.In contrast, testicular torsion in all other agegroups is generally intravaginal, i.e. the testistwists within the confines of the tunica vaginalis.It is generally accepted that an anatomical varianttermed the ‘bell clapper’ testis, with a long mesen-tery-like leash of vessels (mesorchium), pre-disposes to torsion by permitting an abnormallymobile testis to twist around the axis of thespermatic cord (Figure 19.2). Although a rotationaltwist of 360–720° is commonly encountered at thetime of surgical exploration, the degree of rotationrequired to produce testicular ischaemia is poorlydocumented.

Experimental studies, coupled with the findingsof a limited number of clinical follow-up studies,indicate that the only prospect of salvaging a fullyviable testis lies in restoring blood supply to thetestis within 4–6 hours of the onset of ischaemia.However, it is too simplistic to regard atrophy asan ‘all or none’ phenomenon, and partial degreesof atrophy can occur even when exploration isundertaken in less than 6 hours. Atrophy ofvarying severity is virtually inevitable when surgi-cal exploration is delayed by 6–8 hours after theonset of symptoms and ischaemic necrosis andatrophy are the rule after 8–10 hours.

PresentationUnilateral scrotal pain and swelling of acute onsetare the pathognomonic features of testicular torsion,but the clinical picture is variable and fewer than


Figure 19.3 (a) Deceptively painless presentation oftesticular torsion in an infant with a 3-day history ofminimal symptoms. Discoloration of the scrotumprompted his parents to seek medical advice. (b)Prompt surgical exploration nevertheless revealed anecrotic testis.

(a)

(b)


50% of cases present with a classic ‘full house’ ofhistory and clinical findings. Pain is often referred tothe groin or lower abdomen, and vomiting is afeature of approximately 40% of cases. The poten-tially misleading painless form of presentation isencountered more frequently in younger children(Figure 19.3) but may also give rise to diagnosticconfusion in the postpubertal age group.

ManagementExternal non-operative detorsion in the emergencydepartment has been advocated, but although thismay have a place in young adults it is not generallyfeasible in children.

Urgent surgical exploration is the keystone ofmanagement. Following exposure of the testis via ascrotal incision, the spermatic cord is untwisted andtesticular viability assessed. Factors influencing the

decision to conserve or remove the testis include theduration of the history, the appearance of the testisand arterial bleeding on incising the tunica albuginea(Figure 19.4). Surgical optimism (or wishful think-ing) is often misplaced and unless the testis is clearlyviable it is preferable to err in favour of orchidectomy(assuming the contralateral testis is healthy). Whenexploration has been undertaken within the first fewhours and the testis is clearly viable it should be fixedto prevent recurrent torsion. Regardless of theoutcome on the affected side, fixation of thecontralateral testis is mandatory in view of the bilat-eral nature of the anatomy predisposing to torsion.

Technical aspects of fixation

Via a scrotal incision, the tunica vaginalis is openedand the testis anchored to the scrotal wall usingtwo or three non-absorbable sutures, e.g. 4/0 or


Figure 19.4 (a) Characteristic appearances of early torsion (3-hour history). The right testis is tender, mildlyswollen and lies in an elevated position within the scrotum. (b) This testis was judged to be viable in view of theshort history and operative findings indicating good return of perfusion following detorsion.

(a) (b)


5/0 Prolene (polypropylene), placed at the upperand lower poles of the testis and midzone. Cases offurther torsion despite fixation have been reportedfollowing the use of catgut sutures. Suturelessfixation performed by placing the testis withina dartos pouch has been advocated by somesurgeons on the basis of experimental evidence.However, this method cannot be guaranteed inclinical practice since the occurrence of torsiondespite previous dartos pouch orchidopexy forcryptorchidism has been reported.

Although it has been suggested that puncture of thetunica albuginea by fixation sutures carries a risk ofstimulating antisperm antibody production, there isno evidence to substantiate this hypothetical risk inprepubertal boys. By contrast, the presence of circu-lating autoantibodies has been demonstrated in aproportion of men following postpubertal torsion.The significance of this finding, and its relevance tofertility in these circumstances, remains uncertain.Moreover, it is not possible to determine theextent to which this finding might result from a breachin the blood/testis barrier sustained during suturefixation or, as seems more likely, exposure of antigensduring detorsion or removal of the ischaemic testis.

In summary, the well-documented risks ofrecurrent or asynchronous contralateral torsionoutweigh the theoretical risk of autoantibodyformation. The recommended technique offixation therefore consists of exposure of thetestis and placement of three non-absorbablesutures between the tunica albuginea and thescrotal wall.

Implantation of a testicular prosthesis is anoption available to young men following unilateralorchidectomy or testicular atrophy, but because ofthe risk of infection this should be a subsequentelective procedure via an inguinal incision, ratherthan at the time of acute surgical exploration.

PrognosisFertility

Follow-up studies in adults have revealed thatsemen quality is significantly reduced followingunilateral torsion in adolescence. In one such study

semen quality was reduced in 50% of men, and inanother study of 36 patients only 16% had normalparameters of semen quality on follow-up. Themechanism is unclear, but possibilities includeantisperm antibodies and pre-existing abnormali-ties of the spermatogenic tissue in the ‘healthy’contralateral testis. Toxic free radicals released intothe circulation as part of a reperfusion injury to theischaemic testis at the time of exploration have alsobeen implicated by some experimental studies.Follow-up studies have tended to rely upon param-eters of semen quality as the measure of fertilitybut whether this is actually reflected in impairedrates of paternity is largely unknown.

Very little information exists on the prognosisfor fertility following torsion in prepubertal boys,but the limited clinical data and some experimen-tal evidence suggest that it does not have the samepotential impact on fertility as torsion in adoles-cents and young adults.

Endocrine function

In contrast to the impaired spermatogenesis,endocrine function is unaffected and uniformlynormal plasma levels of testosterone have beendocumented following unilateral torsion (regard-less of the outcome for the twisted testis). Folliclestimulating hormone (FSH) levels may beelevated, reflecting impaired spermatogenesis inthese patients.

The elective implantation of a testicular prosthe-sis should be offered patients who have undergoneorchidectomy or in whom the salvaged testis hasdeveloped significant atrophy resulting in anobvious discrepancy in size. Ideally, implantationshould be deferred until the mid teens to permitthe use of an adult-sized prosthesis which bestmatches the volume of the contralateral testis(Figure 19.5).

Neonatal torsion

More strictly, neonatal torsion should be termedintrauterine or ‘perinatal’ torsion, since with veryrare exceptions the event dates from the late stages



of intrauterine life. Indeed, cases of intrauterinetesticular torsion have been documented on prena-tal ultrasound. Typically, the surgeon is called to the

postnatal ward to see an infant with scrotal discol-oration and an indurated testis. In these circum-stances the prospects of salvaging a viable testis areeffectively zero. Reviewing the outcome of torsionin 30 neonates presenting over a 20-year period,Burge did not encounter a single viable testis. Thealmost invariably disappointing findings at surgicalexploration, coupled with the belief that extravagi-nal torsion does carry the same risk to the contralat-eral testis, prompted a shift in policy.

As a result, many centres moved to conservativemanagement of neonatal torsion, with regularultrasound follow-up to monitor the process oftesticular atrophy. One risk associated with non-operative management lies in the remote possibil-ity of failing to recognise a congenital testiculartumour masquerading as ‘neonatal’ testicular torsion.If the ultrasound appearances are in any way suspi-cious, or the indurated testis fails to involute,surgical exploration and orchidectomy should beperformed.

The assumption that torsion in the neonatalperiod does not carry a comparable risk of torsionto the contralateral testis as in other age groups isbeing challenged by recent reports suggesting thatsynchronous and asynchronous bilateral neonataltorsion is not as rare an event as was previouslybelieved. Opinion may therefore swing back infavour of exploration and contralateral fixation.

Torsion of testicularappendage (hydatid ofMorgagni)

Although children of any age can be affected, thepeak incidence is between 10 and 12 years. Inprepubertal boys torsion of a testicular appendageoccurs more frequently than torsion of the testisitself (see Table 19.1).

PresentationAlthough pain is the usual presenting symptom, itis typically less severe and more gradual in onsetthan that of testicular torsion. However, the two


Figure 19.5 (a) Silicone gel testicular prosthesis.This is inserted via an inguinal incision and positionedin the most dependent part of the scrotum by invert-ing the scrotum and placing an anchoring suture in thereinforced disc at the lower pole of the prosthesis.(b) Postoperative appearances.

(a)

(b)


conditions cannot always be distinguished reliablyon clinical grounds, particularly in youngerchildren. Haemorrhagic infarction of the hydatidof Morgagni, visible as a localised area of discol-oration at the upper pole of the testis (‘blue dotsign’), is pathognomonic of the condition but isonly present in a minority of cases. Similarly,whereas examination may reveal tenderness con-fined to an indurated nodule, more generalisedtenderness is often present and accompanied byoedema and erythema of the hemiscrotum.

DiagnosisThe clinical features may be sufficiently distinctiveto enable an experienced clinician to make a firmdiagnosis. Colour Doppler ultrasound can provideadditional confirmation.

ManagementSurgical intervention is indicated when testiculartorsion cannot be excluded or when discomfort issevere. Treatment consists of simple excision ofthe infarcted hydatid of Morgagni. Prophylacticexcision of the contralateral testicular appendage isnot necessary. In cases where an unequivocal clini-cal diagnosis has been made, and where the painis mild or resolving, conservative management isappropriate.

Epididymo-orchitis

AetiologyBacterial infection of the epididymis progressingto involve the testis occurs as a result of retrogradebacterial colonisation via the ejaculatory ductsand vas deferens. Vasal reflux of infected urine isusually present. Epididymo-orchitis (particularlywhen recurrent) may be linked to an underlyingurological condition such as neuropathic bladder,persistent müllerian remnant (‘prostatic utricle’,‘vagina masculina’) or ectopic ureter. However, italso occurs in infants with urinary infection associatedwith low-grade vesicoureteric reflux, or urinary

infection for which there is no identifiable predis-posing cause.

PresentationScrotal pain may be accompanied by evidence ofurinary infection, e.g. dysuria or offensive urine.Examination typically reveals marked scrotalerythema and tenderness, and induration of thetestis, often accompanied by fever and systemicupset.

DiagnosisIn boys of all ages testicular torsion is considerablymore common than epididymo-orchitis, and thisdiagnosis should therefore be viewed with suspi-cion. Moreover, epididymo-orchitis cannot alwaysbe reliably distinguished from testicular torsion onclinical grounds alone. For these reasons surgicalexploration should be performed, unless the child isknown to have a predisposing urological abnor-mality and the clinical features point stronglyto epidiymo-orchitis. Confirmatory investigationsinclude:

• urine microscopy – pyuria, bacteriuria andpositive urine culture

• Doppler ultrasound – hyperaemia and increasedvascularity.

ManagementSurgical

Surgical intervention is indicated:

• to exclude the diagnosis of testicular torsion• to drain a scrotal or testicular abscess.

In cases of recurrent symptomatic epididymo-orchitis it may be necessary to consider vasectomyif the underlying urological abnormality is notamenable to surgical correction.

Excision of a large müllerian remnant haspreviously been performed using a transvesical,transtrigonal approach, but laparoscopic excisionhas been reported more recently. Little is known of




the late outcome for fertility following these proce-dures but risk of vasal injury is likely to be high.

Medical

Non-operative management comprises analgesia(epididymo-orchitis is an acutely painful condition)and an intravenous antibiotic, e.g. gentamicin orciprofloxacin, pending the result of urine culture.Antibiotic treatment should be instituted postopera-tively when the condition is discovered at exploration.

PrognosisThe fate of the testis cannot be reliably assesseduntil all the induration has resolved, which isgenerally a matter of several months. Following anisolated and promptly treated episode in a childwithout underlying urological abnormalities, theprognosis is generally good. However, after recur-rent attacks of epididymo-orchitis varying degreesof testicular atrophy supervene.

Idiopathic scrotal oedema

This condition is virtually confined to the prepu-bertal age group, with a peak incidence betweenthe ages of 5 and 6 years.

AetiologyAlthough the condition is genuinely idiopathic, theassociation with anal pathology and the occasionalfinding of erythema extending from the perineumhas been interpreted as evidence of reactive oedemasecondary to localised lymphangitis.

PresentationThe clinical picture is characterised by markedoedema of the scrotum, which is usually unilateral indistribution but which may occur bilaterally and mayalso extend upwards to involve the subcutaneoustissues of the inguinal region (Figure 19.6). Pain isminimal or absent. The diagnosis presents fewproblems to those acquainted with the condition.

ManagementThe swelling settles spontaneously, usually within24–48 hours. Antihistamines or antibiotics are some-times prescribed but there is no evidence of benefit,and in general no specific treatment is required.

Other acute scrotal conditions

Incarcerated herniaIn infancy, scrotal swelling may be the most strikingvisible manifestation of an inguinoscrotal hernia.Palpation will distinguish between an inguinoscrotalhernia (which extends from the inguinal region tothe scrotum) and true intrascrotal pathology.

Acute hydrocoeleA tense, rapidly developing hydrocoele can giverise to diagnostic uncertainty. However, acute

Figure 19.6 Idiopathic scrotal oedema.



hydrocoeles are rarely painful (unless associatedwith underlying pathology of the testis). Transillu-mination confirms the diagnosis.

Henoch–Schönlein vasculitisInvolvement of the testis, giving rise to tenderness,swelling and scrotal discoloration, is a well-documented complication of Henoch–Schönleinvasculitis. The presence of a purpuric rash shouldgive the clue to the diagnosis and thus avert unnec-essary surgical intervention.

Key points

• Torsion of the testis accounts for 90%of acutely presenting scrotalsymptoms in postpubertal boys andadolescents. Urgent surgicalexploration is mandatory unless thereis compelling evidence of analternative diagnosis.

• Regardless of the outcome onthe affected side, it is mandatoryto perform prophylactic open suturefixation of the contralateral testis.

• The recommended technique forfixation of the testis consists ofopening the tunica vaginalis andplacing three non-absorbable suturesbetween the tunica albuginea andscrotal wall.

• Most cases of so-called ‘neonatal’torsion have actually occurred inutero and the affected testis is almostinvariably non-viable.

• Torsion of a testicular appendage(hydatid of Morgagni) in a prepubertalboy can be managed conservativelyprovided a confident diagnosis hasbeen made by an experiencedclinician.

• Epididymo-orchitis is uncommon inchildhood and, if proven, alwaysmerits investigation of theurinary tract.

Further reading

Baglaj M, Carachi R. Neonatal bilateral testicular torsion: aplea for emergency exploration. J Urol 2007; 177(6):2296–2299

Bartsch G, Frank S, Marbeger J, Mikuz G. Testiculartorsion: late results with special regard to fertility andendocrine function. J Urol 1980; 124: 375–378

Ben-Chaim J, Pinthus JH. Testicular torsion. EuropeanBoard of Urology Update Series 1998; 7: 39–44

Ben-Chaim J, Leibovitch I, Ramon J et al. Etiology of acutescrotum at surgical exploration in children, adolescentsand adults. Eur Urol 1992; 21: 45–47

Burge DM. Neonatal testicular torsion and infarction:aetiology and management. Br J Urol 1987; 59: 70–73

Nour S, MacKinnon AE. Acute scrotal swelling in children.J Roy Coll Surg Edin 1991; 36: 392–394

Puri P, Barton D, O’Donnell B. Prepubertal testicular torsion:subsequent fertility. J Pediatr Surg 1985; 20: 598–601


Disorders of sex development

Henri Lottman and David FM Thomas

Introduction

The nomenclature used to describe and classify thisimportant group of disorders has undergoneextensive revision since the first edition of thisbook was published. The changes adopted in thischapter reflect the recommendations of an interna-tional consensus conference on intersex held underthe auspices of the North American and EuropeanSocieties for Paediatric Endocrinology in 2006.

Wherever possible, potentially pejorative termshave been replaced. For example ‘intersex’ and‘true hermaphroditism’ are now referred to as‘disorders of sex development (DSD)’ and ‘ovotes-ticular DSD’, respectively. The old and newnomenclature are summarised in Table 20.1.

Because the acceptance and usage of the newterminology is likely to be a gradual process, theestablished terminology will also be includedthroughout this chapter, where it will appear asitalicised text.

Disorders of sex development originate fromthe following underlying mechanisms:

• chromosomal defects (chromosomal DSD)• abnormalities of gonadal development (gonadal

DSD)• defects in the synthesis of sex hormones or

relevant receptor (phenotypic/anatomical DSD).

Those aspects of sexual development which relateto behaviour and gender identity are less well

understood and some areas, such as the concept ofthe ‘male’ or ‘female’ brain, remain highly contro-versial. The determinants of gender-related behav-iour include neuroendocrine factors (notably theeffects of testosterone on the developing brain)and complex sociocultural influences. Althoughsome reference will be made to these importantcomponents of gender identity, a more detailedconsideration of the psychological and behaviouralmanifestations of disorders of sex development islargely beyond the scope of this chapter.

A newborn infant with ambiguous genitaliapresents the clinician with a rare and potentiallyurgent diagnostic problem. Congenital adrenalhyperplasia (CAH), numerically the most impor-tant condition, is associated with disorders ofadrenal metabolism that may pose a threat tothe survival of the affected infant. Even when theunderlying condition does not carry this risk, itis important to investigate every infant with

20

Topics coveredEmbryological differentiation – normal andabnormalClassification of disorders of sex development(DSD)

InvestigationGender assignmentSurgical management of DSD Gynaecological disorders of childhood andadolescence

Table 20.1 Revised nomenclature

Previous Proposed

Intersex DSDMale pseudohermaphrodite 46XY DSDFemale pseudohermaphrodite 46XX DSDTrue hermaphrodite Ovotesticular DSDMixed gonadal dysgenesis Mixed gonadal

dysgenesis (MGD)(unchanged)


ambiguous genitalia without delay. This is bestachieved by involving a specialised multidiscipli-nary team comprising a paediatric endocrinologist,urologist, radiologist, biochemist and geneticist.Transfer to a specialist centre may be required if therelevant specialist expertise is not available locally.

Parents should be advised against registering thebirth of a child with ambiguous genitalia until thediagnosis has been established and agreementreached on the assignment of gender.

Although the overall incidence of disorders of sexdevelopment is low, it is subject to geographicalvariation in population genetics: for example, thereis a relatively high incidence of true hermaphroditism(ovotesticular DSD) in South Africa and of 5α-reductase deficiency in the Dominican Republic.

Normal sexual differentiation

A knowledge of the embryological development ofthe internal and external genital tracts is essentialin understanding disorders of sex development(intersex states). The embryology of the genitaltracts has already been considered in Chapter 1 butthe key elements are summarised again as follows:

1. The precursors of the gonads, genital ducts andexternal genitalia are present in an identicalundifferentiated state in both 46XX and 46XYembryos until around the 6th week of gestation.

2. The genital tract of the embryo and fetus isgenetically programmed to develop by aprocess of passive differentiation down a femalephenotypic pathway, unless positively switchedinto a pattern of male phenotypic differentia-tion by the influence of certain genetic andendocrine factors.

3. With the exception of those disorders charac-terised by the presence of both testicular andovarian gonadal tissue (i.e. true hermaphro-ditism or ovotesticular DSD), disorders of sexdevelopment fall into two broad categories:

• inappropriate virilisation of a 46XX fetusas a result of intrauterine exposure to

virilising agents (46XX DSD or femalepseudohermaphroditism)

• incomplete virilisation of a 46XY fetus(46XY DSD or male pseudohermaphroditism).

Differentiation of the malegenital tractTestis

Differentiation of the testis commences at around6 weeks, when the gonadal primordium situated atthe anterior aspect of the mesonephros is colonisedby extraembryonic primordial germ cells. Theprocess of differentiation is initiated during the 7thweek, when the pre-Sertoli cells aggregate to formthe seminiferous tubules secreting the glycoproteinmüllerian inhibitory substance (MIS). Leydig cellsappear at around 8–9 weeks, increasing until12–14 weeks, when their number remains stableuntil 24 weeks before declining. At birth the testiscontains relatively few Leydig cells, a state thatpersists until puberty, when there is proliferation ofLeydig cells within the pubertal testis.

Internal genitalia

In the undifferentiated state the genital ducts of bothXX and XY embryos comprise the mesonephric(wolffian) and paramesonephric (müllerian) ducts.Regression of the müllerian ducts in the male beginsat 8 weeks in response to MIS and is complete by10–12 weeks. Under the influence of androgenssecreted by the fetal testis each mesonephric ductdevelops into epididymis, vas deferens and seminalvesicle. The prostatic bud develops around the distalend of the mesonephric ducts at approximately11–13 weeks. The prostatic utricule forms at thejunction of the paired mesonephric ducts and theurogenital sinus (Figure 20.1).

External genitalia

The undifferentiated state of the external genitaliain both XX and XY embryos comprises a genitaltubercle, and a urogenital groove surrounded byurethral folds and labioscrotal swellings. Without



androgenic stimulation the external genitalia of anXY fetus would be destined to retain these featuresand hence develop into the external genitalia ofa female phenotype. Conversely, when exposedto circulating androgens the genital tubercleelongates and the urethral folds fuse over theurethral groove to create the penile urethrasurrounded by the corpus spongiosus. Meanwhile,the genital swellings fuse posteriorly to form thescrotum. Male anatomical differentiation is essen-tially complete by the 13th week of gestation,except for testicular descent (see Chapter 1) and

further penile growth and development, whichcontinues from 20 weeks to term.

Differentiation of the femalegenital tractOvary

Differentiation is triggered around the 6th week ofgestation by the interaction of the primordial germcells and the mesenchymal tissue of the genitalridge. Oogonia enter the meiotic phase at 12–13weeks, and all the germ cells have entered themeiotic prophase by 7 months. The oocytes thenremain in a state of arrested division until the onsetof puberty. From the 12th week of gestation thefetal granulosa cells produce oestrogens.

Internal genitalia

The mesonephric ducts undergo spontaneousdegeneration at around 10 weeks, while theparamesonephric ducts develop into the fallopiantubes, the uterus and the upper vagina. The lowervagina is derived from urogenital sinus. Separationof the urethra and vagina results from downgrowthtowards the perineum of the junction of the pairedparamesonephric ducts and urogenital sinus at thelevel of the sinovaginal bulb (Figure 20.2).

External genitalia

Differentiation of the genitalia into the female pheno-type occurs without any known requirement forendocrine stimulation, and begins with the formationof a dorsal commissure between the labioscrotalswellings. The genital tubercle persists as the clitoris,and the urethral folds become the labia minora andthe labioscrotal swellings the labia majora.

The role ofsex-determining genesDetermination of sexual differentiation in mammalianspecies is governed primarily by the presence ofgenes located on the Y chromosome. Of these, byfar the most important is the testis-determininggene, which is located at the distal part of the short

Disorders of sex development 277

46XY

46XY

46XY

MIS

Testosterone

46XY

Figure 20.1 Normal male development. (a) Undiffer-entiated state. (b) Regression of paramesonephricducts (red) under the influence of MIS, and persistenceof mesonephric ducts (blue) in response to localisedtestosterone secretion by the fetal testis. Virilisation ofexternal genitalia by circulating androgens.

(a)

(b)


arm of the Y chromosome and has been namedSRY (sex-determining region Y). Although theSRY gene is ultimately responsible for initiatingtesticular differentiation, many downstream geneslocated on the sex chromosomes and autosomesare also involved in the complex sequence of subse-quent events contributing to the embryologicaldevelopment of the genital tracts.

It had been thought that in the absence of the Ychromosome the gonad adopts a default pattern ofdifferentiation to form an ovary. Evidence is

emerging, however, that this is not an entirelypassive process and that normal ovarian differenti-ation is dependent on the presence of the paired Xchromosomes. In particular, survival of the germcells requires the presence of two X chromosomes.In 45X female patients (Turner syndrome) theovaries degenerate into fibrous streaks containingno surviving germ cells.

Phenotypic sex differentiationExperimental studies conducted by Jost and Jossoin animals such as the rabbit and rat have provideda detailed picture of the endocrine factors impli-cated in male sex differentiation.

As already indicated, müllerian inhibitorysubstance and androgens play key roles which aresummarised below.

Müllerian inhibitory substance

Produced within the testis by the Sertoli cells, MISis a glycopeptide that induces resorption of themüllerian (paramesonephric) ducts, stimulates theLeydig cells and is implicated in the initial phase oftesticular descent. The genes coding for MIS andits receptor have been mapped on chomosomes 19and 12, respectively.

Testosterone anddihydrotestosterone

Testosterone, secreted by the Leydig cells of theembryonic testis, is responsible for maintenanceof the mesonephric ducts and virilisation of theurogenital sinus and external genitalia. Theproduction of testosterone by the fetal testis isdetectable at 9 weeks, with a peak around 15–18weeks and then a sharp fall. Testosterone isreleased into the bloodstream, enters target cellsand is converted to dihydrotestosterone (DHT)by the enzyme 5α-reductase. DHT binds toandrogen receptors with a greater affinity thandoes testosterone. The androgen receptors arecoded by genes located on the X chromosome.A local source of androgen is essential formesonephric duct development, which does not


46XX

46XX

46XX

46XX

Figure 20.2 Normal female development. (a) Undif-ferentiated state. (b) Persistence of paramesonephricduct derivatives (no exposure to MIS). Spontaneousregression of mesonephric ducts. Passive differentionof external genitalia to female phenotype.

(a)

(b)


occur if testosterone is supplied only via theperipheral circulation, as in 46XX DSD (femalepseudohermaphroditism) due to adrenal hyperpla-sia. The fetus is exposed to high levels of maternaland intrinsic gonadotrophins, and also to oestro-gens of fetal and maternal origin. Their role insexual differentiation is poorly understood.

Classification of disorders ofsex development

As indicated above, disorders of sex developmentmay have their origins in chromosomal defects,abnormalities of gonadal development or impairedendocrine function due to deficient sex hormonesynthesis or receptor activity.

Despite full investigation, the cause cannot beestablished in some patients. This is particularlytrue in individuals whose ambiguous genital stateis accompanied by the presence of a Y chromo-some. Such cases presumably represent a defectivecomponent of sexual differentiation that has yet tobe identified.

The most commonly encountered forms ofDSD are:

• 46XX DSD – virilisation of a 46XX female(previously termed female pseudohermaphro-ditism). The majority of these patients haveCAH.

• 46XY DSD – inadequate virilisation of a 46XYmale (previously termed male pseudohermaphro-ditism). In contrast to 46XX DSD, there areseveral different causes, and in approximately50% of cases no definitive diagnosis can beestablished.

• Gonadal dysgenesis – a spectrum of gonadaland genital abnormalities associated withabsence of one of the pair of sex chromosomes,e.g. 45X, 45X/46XY, and often present in mosaicform (see Chapter 1).

• Ovotesticular DSD (previously termed truehermaphroditism) – both ovarian and testiculartissue are present in the same individual. Thegenotype and phenotype are variable.

46XX DSD (femalepseudohermaphroditism)Children with this group of abnormalities consistalmost entirely of 46XX females whose externalgenitalia have been virilised by intrauterine exposureto androgens at a critical phase in differentiation(Figure 20.3). Affected individuals have ambigu-ous external genitalia but their ovaries and internalgenitalia (fallopian tubes, uterus, upper vagina) arenormal.


Adrenalglands

AdrenalsACTH

46XX

46XX

46XX

46XX

Testosterone

Testosterone

Figure 20.3 Congenital adrenal hyperplasia. (a) Undif-ferentiated state. (b) Persistence of paramesonephricduct derivatives (no exposure to MIS). Regression ofmesonephric ducts (no localised secretion of testo-sterone by the gonad–ovary). Virilisation of externalgenitalia caused by circulating adrenal-derivedtestosterone.

(a)

(b)


Congenital adrenal hyperplasia

CAH is not only the most common cause of 46XXDSD (female pseudohermaphroditism) but alsoaccounts for approximately 85% of all infants withambiguous genitalia in Western countries. Thedisorder can arise as a result of one of threeenzymatic defects occurring at different points onthe biosynthetic pathways for the production ofcortisol and aldosterone in the adrenal gland. Allthree defects prompt overproduction of adreno-corticotrophic hormone (ACTH), which in turnstimulates overproduction of androgenic precur-sors by the adrenals (Figure 20.4).

21-Hydroxylase deficiency is the mostcommon form of CAH (estimated incidence1:15 000 births) and is an autosomal recessivedisorder associated with a mutation of a genelocated on chromosome 6. The diagnostic featureis elevation of plasma 17α-hydroxyprogesterone.Prenatal diagnosis is possible and treatment has

been described using dexamethasone to suppressthe fetal pituitary–adrenal axis from the 9th to the17th weeks of gestation. Fifty per cent of cases arecomplicated by a salt-losing state which may posea potentially life-threatening neonatal emergency.Management comprises gluco- and mineralocorti-coid replacement therapy, female gender assign-ment and consideration of feminising genitoplasty.

11ββ-Hydroxylase deficiency is a rare cause ofCAH associated with severe virilisation andleading to salt retention and potassium loss with,in some instances, hypoglycaemia and impairedstress response. The diagnosis is based on theelevation of plasma levels of 11-deoxycortisol.Prenatal diagnosis is feasible in the siblings and theoffspring of affected individuals. Sex determina-tion and a range of genetic studies with geneprobes for CAH can be performed on fetal cellsobtained by chorionic villus sampling or amnio-centesis. In addition, the external genitalia of a46XX fetus can be assessed with ultrasound for


Cholesterol

Pregnenolone 17-OH-pregnenolone Dehydroepiandrosterone

4-androstenedione

3βHSD

(11βOH)

(21-OH)

17-OH-progesterone

11-deoxycortisol

Cortisol

Progesterone

Deoxycorticosterone

Corticosterone

18-OH-corticosterone

Aldosterone

Figure 20.4 Congenital adrenal hyperplasia. Sites of enzyme block in metabolic pathway.


evidence of virilisation. Prenatal treatment hasbeen reported, consisting of the administration ofdexamethasone as for the 21-hydroxylase deficiencyform of CAH.

3ββ-Hydroxysteroid dehydrogenase deficiencyis the rarest form of CAH. Virilisation is of moder-ate severity, but salt loss and hyponatraemiaare severe. Plasma dehydroepiandrosterone, 17-hydroxypregnenolone and ACTH are elevated.The management is similar to that for 21-hydroxy-lase deficiency.

Aromatase deficiency

This oestrogen synthetase enzyme is present inparticularly high concentrations in the placentaand is involved in the synthesis of oestrogens fromandrogenic precursors. Deficiency of this enzymeresults in an accumulation of androgens and conse-quent fetal virilisation.

Virilisation by androgens ofmaternal origin

This is a rare cause of 46XX DSD, with possiblecauses which include androgen-secreting tumoursof the adrenal or ovary and maternal treatmentwith progestational agents. Examples of virilisinganomalies of the female external genitalia whichhave a teratogenic rather than an endocrine aetiol-ogy include isolated clitoral hypertrophy andabnormalities associated with urogenital sinus andcloacal anomalies.

46XY DSD (malepseudohermaphroditism) In this group of disorders, 46XY male infantsexhibit varying degrees of inadequate virilisationwhich can be ascribed either to defects in androgenproduction or metabolism or to abnormalities ofreceptor sensitivity in the target tissues.

Defects of testosterone production

These may be the outcome of rare testicular abnor-malities such as testicular dysgenesis or Leydig cell

aplasia. Alternatively, the testes may be morpho-logically normal but the production of testosteroneis impaired by an enzymatic block in the biosyn-thetic pathway.

Defects of testosterone metabolism

The enzyme 5α-reductase is responsible forconverting testosterone to the more potent andro-gen dihydrotestosterone. 5α-Reductase deficiencyis responsible for a particular pattern of virilisationdefects found in inbred communities in theDominican Republic, and, rarely, in certain otherparts of the world.

Defects of receptor sensitivity

Failure of virilisation can occur despite thepresence of normal or elevated levels of testos-terone and/or dihydrotestosterone if the targettissues are resistant to androgens.

Androgen insensitivity syndrome (AIS) is inher-ited as an X-linked recessive disorder associatedwith a mutation on the long arm of the X chromo-some. In the complete form (CAIS; previouslytermed testicular feminisation syndrome), the exter-nal genitalia are phenotypically female. In contrast,the internal genitalia have differentiated normallydown a male pathway in response to MIS secretedby the fetal testis. Typically the condition is discov-ered during the investigation of primary amenor-rhoea, or following the discovery of a testis duringhernia surgery in a girl. Partial androgen insensitiv-ity (PAIS) has a broad phenotypic spectrumcharacterised by impaired virilisation of varyingseverity.

Abnormalities of MIS activity

Deficiency of MIS or a target receptor defectwhich renders the internal genitalia insensitive toMIS is characterised by a combination of normallymasculinised external genitalia and varying degreesof persistence of internal müllerian structures(vestigial uterus, tubes, upper vagina) (Figure 20.5).The condition usually comes to light during asurgical procedure for cryptorchidism or inguinal



hernia. The diagnosis is confirmed by measuringcirculating MIS, which is low in cases due toimpaired synthesis of MIS and high in those casesdue to mutation of the gene encoding for the MISreceptor.

Idiopathic 46XY DSD (malepseudohermaphroditism)

In up to 50% of cases no genetic or hormonalabnormality is identifiable. In such instances themalformation of the genitalia may be attributed toteratogenic factors, to mutations in yet unknowngenes or to genes acting downstream of androgenor MIS receptors.

Gonadal dysgenesisDysgenesis is a term applied to a fundamentalabnormality of gonadal development in which thedegenerate testis or ovary persists as a non-functioning ‘streak’ gonad. In a 46XY fetus thefailure of the dysgenetic testes to produce testos-terone and müllerian inhibiting substance results inan entirely female phenotype. Partial gonadaldysgenesis may be unilateral or bilateral, and sogives rise to varying degrees of sexual ambiguity.

Mixed gonadal dysgenesis is most commonlythe result of 45X/46XY mosaicism. A mixedgonadal phenotype ensues: for example, an inguinaltestis (with limited endocrine function) on one

side accompanied by a contralateral dysgeneticstreak gonad with persistent müllerian derivatives.The external genital phenotype is also variable and,although predominantly female, may, in someinstances, be sufficiently virilised to permit rearingas a male (Figure 20.6).

Ovarian dysgenesis (Turner syndrome, 45X or45X/46XX mosaicism) does not result in sexual


Figure 20.5 Laparotomy findings in a case of MISdeficiency. Intra-abdominal testis, persistence ofparamesonephric duct structures – vestigial fallopiantubes and uterus.

45X/46XY

45X/46XY

45X/46XY

Testosterone

MISStreakgonad

45X/46XY

Figure 20.6 Gonadal dysgenesis. (a) Undifferenti-ated state. (b) Varying embryological patterns andphenotypes. For example, non-functional streakgonad with persistence of paramesonephric struc-tures (left). Mosaicism, right gonad, with male internalgenital tract owing to presence of Y chromosome andMIS and testosterone production. Incomplete externalvirilisation.

(a)

(b)


ambiguity, since no tissue containing a Y chromo-some is present. Streak or dysgenetic gonads carrya significantly increased risk of malignant change.

Ovotesticular DSD (truehermaphroditism)This is a variant of gonadal dysgenesis in which theindividual possesses both testicular and ovariantissue, either in separate gonads or coexisting inthe same gonad as an ovotestis.

The genitalia are invariably ambiguous. Severalkaryotypes have been documented, including46XX/46XY, 46XX and 46XY. The diagnosis issuggested by exclusion of other causes of DSD andis confirmed by macroscopic and microscopicexamination of the gonads. The choice of sex ofrearing may raise difficulties. In case of femalerearing, spontaneous puberty may occur and evenpregnancy; in case of male rearing, pubertal devel-opment may require sex hormone therapy andthere is a significant risk of gonadal malignancy.

Investigation of disorders ofsex development

In the newborn period the aims are twofold:

• To recognise any life-threatening underlyingmetabolic disorder (notably congenital adrenalhyperplasia).

• To establish a precise diagnosis so as to permitan informed decision on gender assignment.Legal registration of the birth should not beperformed until such investigation is complete.

Clinical evaluationDetails of the history should include an enquiryabout siblings and other family members anddetails of the pregnancy.

Examination of the newborn should focus on:

• Appearances of the external genitalia, assess-ment of the degree of virilisation and the

presence of pigmentation (favouring a diagno-sis of CAH) (Figure 20.7).


Figure 20.7 Two examples of ambiguous genitaliain 46XX newborn infants with CAH. (a) Ambiguousgenitalia in a newborn infant. Severe hypospadiasaccompanied by an empty scrotum. (b) Appearancewhich might be mistaken for proximal hypospadias ina male infant. In this situation, however, the absenceof palpable gonads should always signal the need forurgent investigation to identify possible CAH.

(a)

(b)


• The presence or absence of palpable gonads.• The presence of any coexisting abnormalities

outside the genital system (which are indicativeof a probable teratogenic aetiology).

Laboratory investigationsIn addition to routine initial investigations(karyotype, 17-hydroxyprogesterone and plasmaelectrolytes), more detailed evaluation may includeplasma testosterone, basal level and following hCG(human chorionic gonadotrophin) stimulation,steroid assay, e.g. 11-deoxycortisol, MIS levels,DNA analysis to look for specific gene mutations,and studies of binding capacity and androgenreceptor activity in genital skin fibroblasts.

Diagnostic imagingUltrasound is aimed at identifying gonads and/ora uterus within the pelvis. An enlarged müllerianremnant can often be visualised in the undervir-ilised male (Figure 20.8).

A genitogram (also termed a ‘sinogram’) is acontrast study performed via a catheter introducedinto the urethra, vagina or the opening of acommon urogenital sinus. It demonstrates theanatomy of the urogenital sinus and the junctionof the vagina/müllerian structure and lowerurinary tract (Figure 20.9). This information is of

value when planning the surgical approach togenital reconstruction. In addition, it may bepossible to visualise the uterine cervix, uterinecanal, fallopian tube(s) or vas deferens.

Magnetic resonance imaging (MRI) is proving tobe a very valuable diagnostic tool for elucidatingpelvic anatomy in older children but its use in infantsis somewhat limited by technical factors and by theneed for general anaesthesia to prevent movementduring the duration of the study (see Chapter 3).

Surgical investigationsIn addition to the information yielded by non-invasive investigations, diagnostic surgical inter-vention is often required in the form of:

• endoscopy of the lower urinary and genitaltracts (cystourethroscopy and vaginoscopy)

• laparoscopy to identify internal structures(uterus, tubes, gonads)

• in some cases the information needed to establishthe diagnosis and guide management will requirepelvic laparotomy and biopsy of the gonads.

Diagnostic features of disordersof sex development Where the abnormal physical findings are confinedto ambiguous genitalia and impalpable gonadsthe diagnosis is most likely to be congenitaladrenal hyperplasia. An elevated plasma level of17-hydroxyprogesterone associated with positivevisualisation of a uterus and ovaries on ultrasoundis confirmatory. Although an emergency buccalsmear for sex chromatin determination (positive inthe case of CAH) can also be performed, moderntechniques of karyotyping are preferable and willprovide rapid authoritative confirmation of anXX genotype within 48–72 hours. A contrastgenitogram will define the level of confluence ofthe vagina with the urogenital sinus.

The finding of palpable gonads in conjunctionwith an abnormal sex chromosome karyotype(typically 45X/46XY) points to a diagnosis ofmixed gonadal dysgenesis or some formof ovotesticular DSD (true hermaphroditism)


Figure 20.8 Pelvic ultrasound. Transverse view illus-trating the bladder (top) and dilated müllerian struc-ture lying posteriorly.


(e.g. 46XX/46XY). A normal male karyotype(46XY) is suggestive of (PAIS).

The presence of müllerian structures (uterus,fallopian tubes) indicates a lack of MIS consistentwith a diagnosis of gonadal dysgenesis or ovotes-ticular DSD. MIS deficiency or MIS receptordefect in a 46XY patient is not associated withambiguous genitalia. The absence of müllerianstructures in an infant with genital ambiguityprovides evidence of MIS activity and points to adiagnosis of 46XY DSD (male pseudohermaphro-ditism) due to androgen insensitivity or, rarely, ablock in testosterone synthesis.

Gender assignmentThis is the defining step in management of a childwith a disorder of sex development. The decisionon the sex of rearing should be delayed until aprecise diagnosis has been established and thelikely functional potential of the genitalia has beenadequately assessed. This may take some time,particularly when it is necessary to await theoutcome of hCG tests or assessment of the poten-tial for penile development in response to andro-gen stimulation.

Advice on gender should be carefully consideredbefore it is communicated sympathetically to theparents by the key members of the multidisciplinaryteam. At that time, the plan of further managementshould be set out as precisely as possible. Once adecision on gender has been agreed it is vital thatno uncertainty should persist about the sex ofrearing of the child (e.g. ambiguous first namesshould be avoided).

Although management may have to be individ-ualised according to the particular features of eachcase, the following broad generalisations apply tothe more common categories of DSD anomalies:

• 46XX DSD (female pseudohermaphroditism) –these patients are mostly virilised females withCAH who have normal female internalgenitalia, normal ovaries and a normal expecta-tion for fertility. Female sex of rearing is invari-ably advised, and only in the most exceptionalcircumstances (e.g. late presentation with estab-lished male identity) would it be appropriate toconsider male gender assignment.

• 46XY DSD (male pseudohermaphroditism) –female gender assignment is generally advisedwhere the external genitalia are predominantly


Figure 20.9 Contrast sinogram (genitogram). (a) Injection of contrast through a catheter positioned too low inthe urethra/urogenital sinus may fail to fill the müllerian structure. (b,c) Visualisation of müllerian structure inrelation to the lower urinary tract.

(a) (c)(b)


or entirely female and there is no realisticprospect of constructing a functional phallus.The presence of androgen insensitivity greatlystrengthens the case for female sex of rearing. Bycontrast, where there is a significantly malephenotype and where a positive stimulation testindicates responsiveness to androgens, malegender assignment is preferable. Typically thephenotype in such cases is characterised bysevere hypospadias and bilateral cryptorchidism.

• Mixed gonadal dysgenesis and ovotesticularDSD (true hermaphroditism) – in both conditionsthe sex of rearing depends on the phenotype(notably the size of the phallus) and upon thepotential for androgen production as revealed bystimulation tests. In practice, female assignment isusually judged the better option, but a male sex ofrearing may be considered appropriate if thephallus is amenable to reconstruction and function-ing gonadal tissue is predominantly testicular.

• Müllerian inhibitory substance deficiency orreceptor insensitivity – with the exception ofbilateral cryptorchidism and the persistence ofsome internal müllerian remnants, the phenotypeis male. Affected individuals are reared as males.

Cultural considerations may impinge upon thedecision regarding sex of rearing. For example, insome situations parents and their medical advisersmay believe it is better for a highly virilised child with46XX DSD (female pseudohermaphroditism) to beraised as a male. In some societies an affected individ-ual may find it easier to lead an independent adult lifeas an undervirilised male than as a sterile female.

Surgical managementOnce the sex of rearing has been determined withthe parents, appropriate surgical correction of thegenital abnormalities should be planned, with thetiming being dependent on the nature and severityof the genital abnormality and the preference ofthe surgeon. The indications for feminising genito-plasty and the nature and timing of surgical inter-vention have generated considerable controversyin recent years. Where there is agreement between

parents and clinicians that feminising genitoplastyis in the child’s best interests this should, ideally, beundertaken during the first 6 months of life. Theoptimum timing for masculinising genitoplasty isbetween the ages of 6 and 18 months.

The steps in masculinising genitoplastycomprise:

• Hormonal treatment with testosterone prepa-rations to stimulate phallic enlargement.

• Excision of müllerian structures.• Phalloplasty – surgical reconstruction of the

severe hypospadias combines correction ofchordee to achieve a straight penis and urethro-plasty to create an orthotopic meatus. In addition,transposition of scrotal skin may be required toovercome the ‘buried’ phallus and to improve theoverall cosmetic appearances of the genitalia. Atwo-stage phallic reconstruction is favoured bymost paediatric urologists (see Chapter 16).

• Orchidopexy is frequently required.

The key steps involved in feminising genitoplastyinclude:

• Clitoroplasty to reduce the size of the glansand shaft, which is achieved by combiningexcision of corporeal erectile tissue with preserva-tion of the neurovascular bundles aimed atpreserving normal sensation of the glans (Figure20.10). Long-term follow-up studies have unfor-tunately demonstrated significant morbidity andsensory denervation following clitoroplasty inchildhood. Some patient groups stronglyadvocate deferring any surgery until the affectedindividual is competent to provide informedconsent. However, this approach represents alargely untested hypothesis and little, if anything,is known about the psychological impact on thechild and parents of rearing a girl with a promi-nently enlarged phallus resembling a penis. Theweight of professional opinion therefore stillfavours undertaking a careful clitoral reduction ingirls with prominent phallic enlargement.

• Vaginoplasty and labioplasty, which is surgeryto separate the vagina and urethra from the



common urogenital sinus and create twoseparate perineal orifices (Figure 20.11). Theintroitus and vagina should be adequate topermit normal menstruation and intercourse inadult life. Flaps of ‘scrotalised’ skin arefashioned so as to create as far as possiblenormal labial appearances (Figure 20.12).Vaginoplasty may be technically challenging incases when the vagina opens high in the urogen-ital sinus. A number of surgical techniques havebeen advocated to overcome this problem,including perineal, abdominal or anterior sagit-tal transanorectal approaches (ASTRA).

Whereas it is reasonable to correct low confluenceforms of urogenital sinus at the time of clitoro-plasty, it may be preferable to defer surgical correc-tion of the ‘high’ vagina until the menarche and thesubsequent onset of sexual activity. This timingpermits genuinely informed consent. Moreover, thetissues are more robust and amenable to reconstruc-tive use and there is some evidence that the relative

anatomy of the ‘high’ vagina changes during thecourse of childhood and early adolescence, makingit more accessible to perineal exposure. Finally, ifpostoperative dilatation is required (which is oftenthe case), this is much better undertaken by amotivated young woman herself than beingperformed on an apprehensive child. Long-termfollow-up studies of feminising genitoplastyperformed in childhood have reported a highincidence of vaginal stenosis, necessitating someform of further revision (Figure 20.13).

In the alternative technique of total urogenitalmobilisation (TUM) the urogenital sinus, urethraand vagina are mobilised as a single unit, which isthen brought down towards the perineum. Theurethra and vagina are exteriorised and some of thetissue derived from the common urogenital sinusis refashioned to contribute to the reconstructed


Figure 20.10 Feminising genitoplasty: clitoroplasty.(a) Exposure of the corpora and neurovascularbundles. (b) Mobilisation of the neurovascularbundles. (c) Resection of erectile tissue (the corporealbodies).

Figure 20.11 Feminising genitoplasty: vaginoplasty.(a) Lines of incision. (b) Exposure of low-lying vagina.(c) Exposure of high vagina. (d) Completed vagino-plasty and labioplasty.

(a)

(b) (c)

(a)

(b)(c)

(d)


introitus. The long-term results have yet to be fullyassessed and concerns have been expressed aboutthe possible risk of sphincteric weakness and stressincontinence.

CAH is the most common indication forfeminising genitoplasty. In conditions not associ-ated with external virilisation and where the vaginais absent or grossly atretic, it is generally agreed thatvaginoplasty should be deferred until after puberty.

Gonadal management• 46XX DSD (female pseudohermaphroditism): the

ovaries are normal and no specific treatment isrequired.

• 46XY DSD (male pseudohermaphroditism):where female gender is assigned (as in completeandrogen insensitivity), the testes should beremoved, although whether this should beperformed in infancy, childhood or afterpuberty remains a subject of debate. Where it isdecided to rear an affected individual as a male,orchidopexy is performed to bring the testes tothe scrotum.

• Mixed gonadal dysgenesis and ovotesticularDSD (true hermaphroditism): gonadal biopsymay be required to define the nature and distri-bution of the different gonadal tissues. Streak(dysgenetic) gonads are excised, whereas gonadaltissue concordant with the sex of rearing isconserved. Sex hormone replacement therapymay be needed at and after puberty.

In view of the high risk of malignancy afterpuberty any retained testicular tissue should beplaced surgically within the scrotum to facilitatecareful monitoring. This is particularly importantin cases of gonadal dysgenesis or ovotesticularDSD. Lifelong follow-up is required, involvingtesticular self-palpation, ultrasound and, eventu-ally, postpubertal testicular biopsy for evidence ofcarcinoma in situ.

Persistent müllerian remnant(prostatic utricle)This is predominantly a feature of impaired virili-sation, with proximal hypospadias or DSDaccounting for more than 90% of cases. At one endof the spectrum, the müllerian remnant consists oflittle more than a slightly enlarged prostatic utricle,whereas more severe cases may comprise apseudovagina (vagina masculina), accompanied bya rudimentary uterus and fallopian tubes.

In many instances the anomaly is identified duringthe investigation of ambiguous genitalia or, for


Figure 20.12 (a) CAH. Preoperative appearances ofvirilised external genitalia prior to feminising genito-plasty. (b) Appearance following labioplasty.

(a)

(b)



example, when it interferes with bladder catheterisationduring hypospadias repair. Symptomatic presentationincludes infection (e.g. epididymo-orchitis due toassociated vasal reflux), stone formation within thestagnant urine in the prostatic utricle, postvoiddribbling, obstructed voiding and haemospermia. Insuch cases, diagnosis is by contrast radiology, ultra-sound and MRI. Small asymptomatic müllerianremnants are managed conservatively. Where treat-ment is indicated the options include endoscopicincision or deroofing or formal excision. In the past,this was performed via a transvesical approach,employing a midline trigonal incision to expose andexcise the distended müllerian remnants. More recently,however, laparoscopic excision has been reported.

Gynaecological disordersof childhood

Symptoms relating to the external genitalia ofprepubertal girls are common and often generateconsiderable parental anxiety. A balanced approachis required to avoid causing unnecessary distress byoverinvestigating healthy children while recognis-ing those clinical features that may denote moresignificant pathology.

‘Vulvovaginitis’The term vulvitis is strictly more accurate in mostcases, as true vaginitis is rare in childhood, whereas

Figure 20.13 Postpubertal outcome of feminising genitoplasty for the correction of virilisation associated withcongenital adrenal hyperplasia. Single-stage feminising genitoplasty previously undertaken in the first year of life. (a)External cosmetic outcome satisfactory, with no visible phallic hypertrophy and normal appearance of labia createdfrom ‘scrotalised’ skin. (b) Retraction of the labia reveals introital scarring, requiring introitoplasty to permit normal,comfortable intercourse.

(a) (b)



non-specific inflammation of the non-oestro-genised prepubertal skin of the intoitus and vulvais very common. Irritation and itching are thedominant symptoms, accompanied by localiseddysuria and slight discharge.

Parents tend to interpret the symptoms of vulvi-tis as evidence of ‘cystitis’ or of urinary infection.

It is therefore important to enquire specificallyabout those aspects of the history, such asfrequency, fever, suprapubic or loin pain, whichhelp to distinguish genuine urinary infection fromlocalised vulvitis (although the two diagnoses maysometimes coexist).

Hyperaemia of the vulval skin may be apparentif there is florid active inflammation, but examina-tion generally reveals normal external genitalia.

Treatment is aimed at correcting any identifiablepredisposing causes, such as poor perineal hygiene,tight-fitting clothes and threadworm infestation.Antibiotic treatment is often effective andmay be justified on an occasional short-term basiswhere symptoms are severe (although cultureswabs generally reveal a mixed growth of perinealcommensal flora).

Longer-term antibiotic usage should beavoided. Similarly, the use of antimicrobialpessaries is inappropriate in children. Unfortu-nately, some girls continue to experience trouble-some episodes of symptomatic non-specificvulvitis despite a range of simple preventativemeasures. Reassurance and an explanation of theaetiology and self-limiting nature of the conditionis often helpful in allaying parental anxiety.

Labial adhesionsLabial adhesions are inflammatory in aetiologyand are a consequence of vulvitis. The conditionpresents most commonly between the ages of 2and 6 years. Gentle separation of the labia majorareveals flimsy midline fusion of the labia minoraoccluding part or most of the introitus.

In time, labial adhesions always resolve sponta-neously. However, active measures to separate theadhesions may be indicated if anxious parents seek

positive reassurance that their daughter’s genitaliaare normal. Active intervention is also justified ifocclusion of the introitus by labial adhesionsresults in dribbling of urine which has pooled inthe vagina (Figure 20.14).

The simplest treatment comprises a 7–10-daycourse of an oestrogen or topical steroid creamapplied to the area of adhesions. Alternatively,where it is thought justifiable to intervene surgi-cally, the adherent labia are separated with a probeor pair of artery forceps under general anaesthesia.Parents should be warned that recurrent adhesionsare not uncommon.

Vaginal dischargeA copious or purulent vaginal discharge is uncom-mon and should be investigated. Possible causesinclude a vaginal foreign body, specific bacterialinfections and perineal ectopic ureter. Althoughvaginal rhabdomyosarcoma typically presentswith a bloody discharge, this is not always thecase. Depending upon the clinical picture, initialinvestigation generally includes ultrasoundimaging of the pelvis and urinary tract and exami-nation under anaesthesia. The possibility of sexualabuse and sexually transmitted infection should beconsidered and the relevant bacteriological exami-nations performed (i.e. for Neisseria gonorrhoeae)at the time of the examination under anaesthesia.

Vaginal bleedingAlthough inflammation of the vulval region mayoccasionally be associated with slight spotting ofblood on the underclothes, the passage of frankblood or a bloodstained vaginal discharge is poten-tially an ominous sign demanding prompt investi-gation at a specialist centre.

Rhabdomyosarcoma of the vagina (sarcomabotryoides) is a tumour of infancy and early child-hood, whereas uterine rhabdomyosarcomas occurfrom the teens onward. Other causes of vaginalbleeding include trauma, foreign body, vascularmalformations and precocious puberty.



Congenital anomaliesof the vagina

In girls with imperforate hymen the vagina isobstructed but otherwise embryologically normal.Accumulation of secretions within the obstructedvagina and/or uterus (hydrocolpos or hydrometro-colpos) characteristically presents clinically as abulging introital mass in the newborn period, or asprimary amenorrhoea (or occasionally urinaryretention) in pubertal or postpubertal girls.Nowadays the distended vaginal and/or uterinemass may be detected on prenatal ultrasound. Treat-ment comprises incision of the hymenal membrane.

Mayer–Rokitansky–Küster–Hauser syndromeis characterised by müllerian aplasia. Associated

renal anomalies and abnormalities of the skeletalsystem occur in 10–40% of patients. A familialrecurrence rate of 1–2% has been reported and thedisorder is thought to be polygenic in aetiology.The spectrum of müllerian anomalies is broad,encompassing conditions such as transversevaginal septum, vaginal agenesis (complete orpartial), absence of the vagina and uterus withrudimentary uterine horns, bicornuate uterus(sharing a common cervix) and uterus didelphys.

The syndrome characteristically presents in earlyadolescence with primary amenorrhea. In theabsence of normal uterine/endometrial tissue,menstruation does not occur and the primaryamenorrhea is otherwise asymptomatic. In caseswhere uterine tissue is present which responds to

Figure 20.14 (a) Separation under general anaesthesia of extensive labial adhesions causing introital occlu-sion and postvoid dribbling. (b) Normal appearance of external genitalia confirmed following separation ofadhesions.

(a) (b)



cyclical oestrogenic stimulation, obstructed menstru-ation gives rise to cyclical abdominal pain and, ifundiagnosed, an abdominal mass. Alternatively,primary amenorrhoea may be associated with retro-grade menstruation, endometriosis and pelvic pain.

Management should ideally be undertaken by aspecialist adolescent gynaecologist. Thin vaginalseptae can be excised to create continuity betweenthe vagina on either side of the obstruction. Moreextensive septae or localised atretic segments are moredifficult to treat and complex surgery is required to‘bridge the gap’. Longitudinal septae are manifesta-tions of duplication anomalies, which may alsoinclude obstruction in one limb of a bicornuate uterus.Excision of the obstructed hemiuterus is undertaken inconjunction with excision of the septum.

Techniques for vaginal replacement include asplit skin graft reconfigured as a vaginal pouchover a mould or substitution with a segment ofcolon or ileum which is mobilized on its vascularpedicle and brought down to the perineum usinga combined abdominoperineal approach. Problemscan include mucus discharge and diversion colitis.

Ovarian pathologyStreak gonads and ovarian dysgenesis are consideredabove. Unilateral ovarian agenesis may be associatedwith unilateral renal agenesis as an isolated anomaly,or as part of a more complex manifestation of theMayer–Rokitansky–Küster–Hauser syndrome.

Ovarian cysts in infants and young girls aregenerally benign follicular cysts. Small to medium-sized cysts (5 cm in diameter) detected incidentallyon pre- or postnatal ultrasound can be managedexpectantly and monitored with ultrasound.The management of larger, asymptomatic cysts iscontroversial, with the rationale for surgery hingingon diagnostic uncertainty and the risk of torsion.

The classification of ovarian tumours in childrenis beyond the scope of this book. Benign teratomais the most common pathology, although malig-nancy can arise in any of the cell lines of which theteratoma is composed. Some patients presentacutely with torsion of the bulky ovarian mass(Figure 20.15).

Key points

• By international consensus, theterminology used to classify thesedisorders has recently undergonerevision, with potentially pejorativeterms such as ‘intersex’ and ‘truehermaphroditism’ being replaced by‘disorders of sex development (DSD)’and ‘ovotesticular DSD’, respectively.

• The management of children withDSD should be concentrated in thehands of specialised multidisciplinaryteams working in collaboration withlocal paediatricians andprimary care physicians.

• Errors in diagnosis or earlymanagement can have disastrous andlifelong consequences for affectedindividuals and their families. Gendershould not be assigned until a firmdiagnosis has been established anda clear plan of management defined.

• Congenital adrenal hyperplasia(CAH) is the most common causeof ambiguous genitalia in WesternEurope, accounting for approximately80–85% of cases. Affected individualsare almost invariably reared as

Figure 20.15 Torsion of a large (benign) ovariancyst.



females. Salt-losing forms of thecondition are potentially life-threatening unless recognised early.

• Gonadal dysgenesis (associated withdiffering patterns of sex chromosomeabnormalities) represents thesecond largest group. Sex of rearingand surgical management areindividualised according to thephenotype and the potential forsexual function.

• Mild inflammatory vulvitis and labialadhesions are common in young girls.Simple measures are generally helpfulbut there is no uniformly effectivetreatment. Other gynaecologicalsymptoms in this age group areuncommon and merit specialist referralfor further investigation.

Further reading

Aaronson IA. Sexual differentiation and intersexuality. In:Bellman AB, King GLR, Kramer SA (eds). ClinicalPaediatric Urology. London: Martin Dunitz, 2002:995–1060

Balen AH, Creighton SM, Davies MC et al. Paediatric andAdolescent Gynaecology: A Multidisciplinary Approach.Cambridge: Cambridge University Press, 2004

Houk CP, Hughes IA, Ahmed SF et al. Summary ofconsensus statement on intersex disorders. InternationalIntersex Consensus Conference. Pediatrics 2006; 118(2):753–757

Minto CL, Liao LM, Woodhouse CR et al. The effect ofclitoral surgery on sexual outcome in individuals whohave intersex conditions with ambiguous genitalia: across-sectional study. Lancet 2003; 361: 1252–1257

The Management of Ambiguous Genitalia. Proceedings ofa symposium. Lyon, France, April 2003. BJU Int 2004;93 (Suppl 3): 1–66

Woodhouse CRJ. Genitoplasty in exstrophy and epispadias.In: Stringer MD, Oldham KT, Mouriquand PDE (eds).Paediatric Surgery and Urology: Long-Term Outcomes.Cambridge: Cambridge University Press, 2006: 583–594



Genitourinary malignancies

Patrick G Duffy and Neil J Sebire

Renal tumours

IntroductionNephroblastoma (Wilms’ tumour) accounts formore than 90% of malignant renal tumoursencountered in children and, since the presentationof renal malignancies is broadly similar in thisage group, this chapter will focus primarily onnephroblastoma.

With an incidence of 7 per million children peryear, nephroblastoma accounts for 6–7% of all child-hood cancers, and approximately 100 cases in theUK a year. Although Jessop performed the firstnephrectomy in 1877, the tumour is named afterMax Wilms, who described a group of children withthis malignancy in 1889. Radiation treatment wasoriginally described in 1915, but the prognosiswas much improved following the introduction ofactinomycin as a chemotherapeutic agent in 1995.

The current 5-year survival rate of greater than90% has been achieved by the judicious use ofsurgery, chemotherapy and radiotherapy. Suchprogress is the result of collaborative national andinternational clinical trials, including the NationalWilms’ Tumor Study (NWTS) in the UnitedStates, the UK Wilms’ Tumour Studies (UKWs)and the International Society of PaediatricOncology (SIOP) trials. Currently, trials in theUnited States and Europe differ mainly in theinitial management of the patient, and hencethe trials are examining slightly different issues. Ingeneral, in the United States, children with renaltumours undergo primary nephrectomy followed

by chemotherapy, whereas in the UK and Europe,the initial management is biopsy and preoperativechemotherapy followed by interval surgery.

Epidemiology/aetiologyNephroblastoma is by far the most common renalneoplasm of childhood, although other entitiesexist (Table 21.1). In the older literature, many ofthese other lesions, which are now recognised asseparate entities, were classified as favourable orunfavourable variants of Wilms’ tumour, examplesbeing clear cell sarcoma of the kidney (CCSK) andrenal rhabdoid tumour (RRT), both of which werepreviously categorised as unfavourable histologypatterns of Wilms’ tumour.

The prevalence of Wilms’ tumour is 50% higheramong Afro-Caribbean children than children ofother races. Although the tumour usually occurssporadically, a number of syndromes are knownto predispose to the development of this malig-nancy (Table 21.2). Nephroblastoma may alsooccur in association with aniridia, hemihypertro-phy, cryptorchidism and hypospadias.

At least three genes are linked to Wilms’ tumour.Located on chromosomes 11p13, 11p15 and 16q,they are found mainly in children with the predis-position syndromes. Specific gene mutations arefound only in around 10% of sporadic Wilms’tumours (sporadic tumours account for 90%of cases).

The peak age of presentation of sporadic Wilms’tumour is 3–4 years of age, but children with bilat-eral disease (5%), or a predisposition syndrome,

21

Topics coveredPaediatric renal tumours (Wilms’ tumour)

RhabdomyosarcomaPaediatric testicular tumours


usually present at younger ages. Mesoblasticnephroma is a tumour that is essentially confinedto infants under 1 year of age.

PresentationNephroblastoma is the most common solidabdominal tumour of childhood and typicallypresents as a painless abdominal mass in an other-wise well child (Table 21.3). Pain is uncommonand usually results from bleeding into the tumour.Haematuria occurs in 10–15% of cases. Tumourrupture may result from minor trauma and so leadto presentation with an acute abdomen. A leftvaricocoele sometimes occurs in association withunusually large tumours. Hypertension is moreoften seen in mesoblastic nephroma.

Symptoms of metastatic spread are rare. Thediagnosis of a solid renal tumour can be madesolely on ultrasound in most instances, althoughoccasionally the appearances are mimicked byxanthogranulomatous pyelonephritis, a chronicinflammatory reaction within the kidney usuallyassociated with renal calculi (see Chapter 11). Thislatter condition also presents with a large renalmass, typically with a long-standing history oflistlessness and with a finding of anaemia.

InvestigationsThe routine tests for malignancy are performed(Table 21.4). Specific features to be assessed byultrasound are extension of the tumour into therenal vein or inferior vena cava, and the bloodlakes characteristic of bleeding into the tumour.Computed tomography (CT) scanning clearlydemonstrates the renal origin of the tumour, aswell as the anatomy of the opposite kidney, andcontributes to assessment of tumour within theinferior vena cava, which, if detected, should betreated by chemotherapy prior to surgery. Althoughuseful for planning surgery and assessing tumoursize, such imaging techniques are not especiallyaccurate in distinguishing Wilms’ tumour from theother less common renal tumours of childhood.Proteinuria may be indicative of Denys–Drashsyndrome, with concomitant increased risk ofbilateral disease. Wilms’ tumour may occasionallymanufacture anti-von Willebrand’s factor, leading toa bleeding disorder. The presence of elevated VMA


Table 21.1 Classification of childhood renaltumours

Benign Malignant

Mesoblastic nephroma Wilms’ tumour(<1 year of age)

Cystic nephroma Clear cell sarcoma(bone secondaries)

Angiomyolipoma Rhabdoid tumour(bone/brainsecondaries)

Haemangioma/ Neuroblastoma (usuallylymphangioma retroperitoneal)

Table 21.2 Syndromes predisposing to Wilms’tumour

Denys–Drash Renal disease(glomerulosclerosis/malepseudohermaphrodite)

WAGR Wilms’, aniridia,genitourinarymalformation,mental retardation

Beckwith– Macroglossia,Wiedemann omphalocoele,

visceromegaly

Table 21.3 Differential diagnosis – childhoodabdominal mass

Benign Malignant

Xanthogranulomatous Nephroblastomapyelonephritis

Large hydronephrosis NeuroblastomaRenal cysts Hepatic tumourSplenomegaly Soft tissue sarcomaBowel duplication


(vanillylmandelic acid) in the urine raises the possi-bility of neuroblastoma, a retroperitoneal tumourusually of non-renal origin.

Treatment• Biopsy/chemotherapy• Surgery• Chemotherapy/radiotherapy.

Management of these lesions in the UK usuallyconsists of initial biopsy and chemotherapy followed

by surgery, with further chemotherapy and/or radiotherapy according to the histopathologicalfeatures of the resected tumour. By contrast, thepolicy in the United States is to proceed to primarynephrectomy with the aim of removing the malig-nant tissue as soon as possible following diagnosis.In most of Europe, preoperative chemotherapy isadministered in order to reduce the tumour burdenand induce chemotherapy-associated shrinkageof the primary tumour to maximise the chance ofcomplete resection.

Genitourinary malignancies 297

Table 21.4 Investigations for suspected Wilms’ tumour

Abdominal ultrasound – to include renal vein and inferior vena cava Chest X-ray – anteroposterior (AP) and lateralCT scan – abdomen and lungsUrinalysis – protein, vanillylmandelic acidBrain/bone scan – clear cell sarcoma and rhabdoid tumours onlyBlood count – to include partial thromboplastin time

Stage I Stage II Stage III Stage IV Stage V

Figure 21.1 Staging of Wilms’ tumour. Stage I: tumour confined to the kidney and completely excised macro-and microscopically. Stage II: tumour extending beyond the kidney but completely excised macro- and micro-scopically. Tumour rupture and spill confined to flank. Stage III: tumour (a) invading adjacent tissues andincompletely excised; (b) incompletely resected because of local invasion; (c) positive lymph nodes; (d) tumourspill not confined to the flank. Stage IV: metastatic disease (usually pulmonary). Stage V: bilateral Wilms’ tumours.


In the UK, an initial image-guided needlebiopsy is carried out for diagnosis, with the ration-ale that high-risk tumours, such as clear cell sarcomaof kidney, renal rhabdoid tumour and anaplasticWilms’ tumour, are treated with more intensivechemotherapeutic regimens from the outset. Inaddition, the other rare entities such as intrarenalneuroblastoma and primitive neuroectodermal tumourcan be appropriately treated.

Definitive treatment is determined by tumourstaging (Figure 21.1) based on both clinicaland imaging assessment, and histopathologicalfindings at surgical excision (Figure 21.2a,b). Inunilateral disease, which accounts for 90% of

cases, surgery consists of removing the tumourand kidney intact, inspecting the contralateralkidney, and sampling lymph nodes. If tumourshrinkage is sufficient and the site of tumour isfavourable, nephron-sparing partial nephrectomymay be an option.

The procedure is performed via a large trans-verse abdominal incision so as to expose bothkidneys and to allow easy access to the inferiorvena cava (Figure 21.3a). After ensuring that notumour is present in the contralateral kidney, thesequence of surgical steps comprises mobilisationof the colon (Figure 21.3b), identification of themajor vessels (i.e. the aorta, inferior vena cava, renalartery and vein), ligation of the renal vessels afterchecking for tumour in the renal vein or inferiorvena cava (Figure 21.3c,d) and removal of thekidney and tumour without rupture (Figure 21.3e).All cases receive chemotherapy usually employingvincristine, actinomycin D and doxorubicin (Table21.5). Radiotherapy is used to treat gross abdom-inal disease and lung secondaries that have notfully responded to chemotherapy and may also beindicated for local control in stage III tumours.

Complex simultaneous cardiac surgery is occasion-ally required for cases where inferior vena cava tumourextension has not responded to chemotherapy.


Table 21.5 Example of conventional 'standard'chemotherapy regimens

Stage Peri-operative PeriodTreatment

I VA 10 weeksII VA +/− D 6 monthsIII VA +/− D +/− RT 1 yearIV VCyCD +/− RT 1 year

V = Vincristine; A = ActinomycinD;D = Doxorubicin; Cy = Cyclophosphamide;C = Carboplatin; RT = Radiotherapy.

Current chemotherapy regimens are moresophisticated, being tailored to individualstaging, histology and other clinical features.A more detailed account is, however, beyondthe scope of this chapter

Figure 21.2 (a) Nephrectomy specimen stage IIWilms’ tumour. Localised penetration of renal capsulewith some tumour extension. Full macroscopic andhistological clearance achieved. (b) A nephrectomyspecimen from a patient with a Wilms’ tumour. Therenal capsule is intact and there was obvious tumourextension into the renal vein and inferior vena cava.

(a)

(b)



Figure 21.3 Operative procedure: see text for details.

(a)

(b)

(c)

(d)

(e)


HistopathologyOn histopathology, Wilms’ tumour has a charac-teristic triphasic appearance comprising elementsreminiscent of the developing kidney, includingimmature and poorly differentiated blastema,epithelial elements forming tubules, and avariable stromal component (Figure 21.4). Caseswith unfavourable histology represent only around10% of cases but account for 60% of tumour-related deaths. Categories of unfavourable histologyinclude nephroblastoma with anaplasia, blastemal-type nephroblastoma, and clear cell sarcoma of kidneyor renal rhabdoid tumour (Figure 21.5).

Further management of the patient is deter-mined by the histopathological findings of thetumour at nephrectomy following initial chemother-apy. Following histopathological examination,tumours are classified according to the SIOP WT2001 protocol into low-risk, intermediate-risk andhigh-risk groups.

NephroblastomatosisThis uncommon tumour-like condition is charac-terised by foci of immature elements reminiscentof the developing kidney – with no pseudocapsule.These features are assumed to be precursor lesions

for the development of Wilms’ tumour andare noted in almost all cases of bilateralWilms’ tumour. They are also present in a minorityof tumour specimens removed for unilateralWilms’ tumour, although the significance remainsuncertain (Figure 21.6). Rarely, there may bemassive bilateral renal enlargement due to exten-sive involvement with nephroblastomatosis.

Bilateral Wilms’ tumour• Biopsy• Chemotherapy• Radiotherapy.

Bilateral disease is managed initially by biopsies(open or trucut) of both kidneys, followed bychemotherapy intended to minimise the extent ofsubsequent surgery. Fundamental to the latter ispreservation of functional renal tissue while at thesame time excising all tumour, if necessary employ-ing an extracorporeal technique. In predispositionsyndromes (e.g. Denys–Drash syndrome), whereboth kidneys inevitably become involved, bilateralnephrectomy is followed by haemo- or peritoneal


TubulesBlastema

Stroma

Figure 21.4 Triphasic nephroblastoma. Photomicro-graph of a core biopsy from a 3-year-old child with aunilateral renal mass showing the characteristictriphasic histological features of Wilms’ tumour.

Figure 21.5 Renal rhabdoid tumour. High-powerphotomicrograph of a 2-year-old child with a unilateralrenal mass, which on biopsy was diagnosed as arenal rhabdoid tumour. There is a sheet-like tumourinfiltrate, and many cells have characteristic pink intra-cytoplasmic inclusions, which give rise to the namerhabdoid tumour (although this tumour is completelyunrelated to rhabdomyosarcoma).


dialysis. Renal transplantation may then be under-taken in the event of 2-year disease-free survival.

These management strategies for unilateral andbilateral disease are derived from the UK trials.Other regimens employed elsewhere incorporatethe same basic principles but have subtly differentbalances in the burdens of chemotherapy andradiotherapy. The European and UK regimens, forexample, achieve similar results using less radio-therapy but more chemotherapy. Vincristine anddoxorubicin are administered preoperatively to reducethe risk of tumour rupture and the need for subse-quent radiotherapy, and whole lung radiation isnot routine for stage IV disease. Renal bed irradi-ation is omitted in cases where local lymph nodesare disease-free and, although the local relapse rateis higher, this is not at the expense of survival rates,possibly because tumour histology is downgradedby preoperative chemotherapy.

Survival rates are good for patients withfavourable histology Wilms’ tumour (Table 21.6),but less so in high-risk tumours (Table 21.7).Although improved outcomes have been achievedin patients with high-risk disease, these tumours

still carry a poor prognosis, especially clear cellsarcoma of the kidney and renal rhabdoid tumour.

In the event of relapse, approximately 50% ofpatients are still curable, principally those withsubdiaphragmatic relapse and those who, althoughtreated by chemotherapy, have received no previ-ous abdominal radiotherapy.

Although Wilms’ tumour currently carries anexcellent prognosis, the challenge for the future isto maintain these outcomes while at the same timereducing the morbidity inherent in adjuvantchemotherapy and radiotherapy.

Rhabdomyosarcoma

IntroductionRhabdomyosarcoma, which occurs principallyduring childhood, arises from undifferentiatedmesenchyme. As this is the origin of skeletalmuscle, differentiation towards tissue resemblingmature muscle is a common histological character-istic. Rhabdomyosarcoma is rare, accounting for


Figure 21.6 Nephrogenic rests. Low-power photomi-crograph of a nephrectomy specimen showing thepresence of nephroblastomatosis, in which there is anabnormal area of immature epithelial tubular structuresin a subcapsular location.

Table 21.6 Wilms’ tumour (favourable histology) –5-year survival rates

Stage 5-year survival (%)

I/II > 90III 80–85IV 60–80V (bilateral) 70–80

Table 21.7 Malignant renal tumours ofunfavourable histology – 5-year survival rates

Tumour type Survival (%)

Anaplastic nephroblastoma 60Clear cell sarcoma of kidney 70–80Rhabdoid tumour 20


10–15% of solid malignant tumours of childhood.It affects around 1 in 2 million people annually,with a male preponderance and an increasedincidence among Afro-Caribbeans. Although itoccurs throughout the body, one-third of tumoursarise in the genitourinary tract, in the bladder,particularly the base, or in the prostate, vagina,uterus, or paratesticular region.

PathologyThere are two main categories within the histolog-ical classification of rhabdomyosarcoma: embry-onal and alveolar. The majority of cases occurringin the genitourinary tract are of the embryonalsubtype, typically with a botryoid configuration(Figure 21.7). In girls the tumour classicallypresents as a grape-like mass protruding from thevagina. Paratesticular rhabdomyosarcomas accountfor approximately 10% of solid scrotal mass lesionsin childhood and usually demonstrate a character-istic spindle cell histology. They are believed to bea subtype of embryonal rhabdomyosarcoma.

The characteristic feature is early differentiationtowards skeletal muscle phenotype, which maybe manifest as eosinophilic cytoplasm with cross-striations indicative of rhabdomyoblasts. However,the majority of cells may simply appear as immaturemesenchymal cells within a loose stromal background.A range of immunohistochemical markers are used

to demonstrate the presence of differentiationtowards a skeletal muscle phenotype, includingdesmin and myogenin, and the introduction ofthese markers has significantly improved thediagnostic accuracy of these entities. Alveolarrhabdosarcoma is now recognised as a sub typewith an unfavourable prognosis and increasedrisk of metastatic disease. Definitive diagnosis,especially on a small biopsy, often requires molec-ular detection of the characteristic PAX-FKHRgene fusion transcript, using fluorescence in-situhybridisation (FISH) or reverse transcriptasepolymerase chain reaction (RT-PCR).

The tumour disseminates principally by localinvasion, and less often by lymphatic spread (20%)or by distant metastasis (10%).

Clinical presentationClinical presentation includes:

• urinary symptoms, e.g. urgency/frequency• abdominal pain and/or mass• protruding botryoid vaginal mass.

Rhabdomyosarcoma may occur at any time duringchildhood, although the uterine form is confinedalmost exclusively to adolescence. Paratesticulartumours arise both in pre- and postpubertal boys.

Tumours at the most common sites (the bladderbase and prostate) give rise to urinary frequency,urgency or retention, and similarly tumours of genitalorigin if forming a pelvic mass. Lesions obstructingthe urinary tract may lead to hypertension or tosymptoms of renal failure (Figure 21.8). Haematuriais rare. Vaginal neoplasms may cause correspondinglysited pain or may present as a protruding botryoidmass. Examination typically reveals a lower abdomi-nal mass or a distended bladder.

InvestigationRoutine initial investigations comprise chest X-ray,pelvic and urinary tract ultrasonography, cross-sectional imaging (CT; Figure 21.9) or magneticresonance imaging (MRI) of the pelvis and chest,


Figure 21.7 Macroscopic appearances of bladderrhabdomyosarcoma in cystectomy specimen.



radioisotope bone scintigraphy and bone marrowaspiration. Renal function should be assessed ifthere is evidence of upper tract dilatation.

Although the imaging studies are usually diag-nostic, specific histological assessment is mandatoryprior to treatment. The necessary biopsy tissuemay be obtained percutaneously, transurethrallyor by open surgery according to circumstances.Endoscopic examination is a further prerequisite inmost instances.

Management• Biopsy• Chemotherapy and/or radiotherapy• Organ-sparing surgery.

Management is determined by considerations ofhistology, anatomy and local or distant spread.Except in rare instances where tumours at afavourable site (e.g. the bladder dome) can bedealt with by excision biopsy, initial treatmentis chemotherapy, which is followed by surgery

preserving, if at all possible, the organ of origin.Chemotherapy regimens involve vincristine, actino-mycin D, cyclophosphamide and ifosfamide invarious combinations. Radiotherapy, either as anexternal beam or as a radioactive iridium wireinserted into the urethra or vagina, is employed totreat microscopic disease following surgery or,rarely, as the principal form of treatment in caseswhere adequate tumour control cannot beachieved without major ablative surgery.

Surgery may take the form of partial cystectomy,submucosal resection of intravesical lesions, orexcision of tumour masses adherent to bladderor prostate. Total cystectomy, with or withouturethrectomy, represents a salvage procedure to beused only in cases with intravesical, bladder baseor prostatic recurrence following chemotherapy,radiotherapy and previous conservative surgery.

PrognosisThe evolution during the last 20 years of multimodaltherapies based on collaborative international trialshas achieved 70–80% 5-year survival rates. Nonethe-less, although such success is achievable while retain-ing the bladder in some two-thirds of cases, this isnot without cost, particularly in respect of persistenturinary frequency and incontinence.

Figure 21.8 Micturating cystourethrogram demon-strating a lobulated filling defect (rhabdomyosarcoma)in the bladder of a 14-month-old child who hadpresented in renal failure owing to bladder outletobstruction.

Figure 21.9 CT scan of the pelvis in a child withrhabdomyosarcoma presenting with an abdominalmass (distended bladder).



The major challenge for the future lies inimproving survival rates while at the same timereducing morbidity, both generally and in relationto local sequelae.

Testicular tumours

The incidence of testicular malignancies in thepaediatric age group is in the range 0.5–2 per100 000. They are conveniently categorisedaccording to the usual age at the presentation.Testicular tumours in this age group do not tendto metastasise and mostly come to light as a

painless scrotal swelling, sometimes in associationwith a (usually small) secondary hydrocoele.

Germ cell tumoursYolk sac tumours

With few exceptions presentation is before 2 yearsof age, and in most cases treatment amounts to nomore than excision of the affected testis afterclamping the cord via an inguinal approach.α-Fetoprotein is a sensitive marker of this tumourand, if serum levels do not return to normalfollowing orchidectomy, metastatic spread is likely.This may be confirmed by chest X-ray or CT scan.

Figure 21.10 (a) Paratesticular rhabdomyosarcoma presenting as a solid testicular swelling. (b) Operativefindings in the patient in (a). As in adults, exploration and orchidectomy should be performed via an inguinalapproach and not by a scrotal incision.

(a) (b)



The occurrence of metastases is seen in only 13%of cases and is generally treatable by chemotherapy.

Teratoma

The second most common testicular neoplasm ofchildhood, teratoma principally affects the veryyoung, 18 months being the mean age at presen-tation. Orchidectomy is curative, as metastaticdisease does not occur in prepubertal boys.

Other testicular tumoursSex cord stromal tumours

Leydig and Sertoli cell tumours usually presentbetween 5 and 10 years of age. In contrast, juvenilegranulosa cell tumours present at birth. Secondarytumours of the testis in prepubertal boysare almost always associated with lymphoma orleukaemia; 4% of such patients are affected.

Germ cell tumours and testicularmaldescentApproximately 10% of germ cell tumours in adultsarise in undescended testes, the higher the locationof the gonad the greater being the risk. Theevidence remains somewhat contradictory onwhether the risk is reduced by orchidopexy, and, ifso, by its timing (see Chapter 18). The contralat-eral gonad is also at enhanced risk of malignancy.

ParatesticularrhabdomyosarcomaThese tumours account for 10% of solid scrotal masslesions in childhood. Presentation is with a discretetesticular lump, often in association with a smallsecondary hydrocoele (Figure 21.10a,b). Investiga-tion and treatment are approached in a similarfashion to that already described for rhabdomyosar-coma in other anatomical sites. The reported 3-yearsurvival rate is in the order of 90%.

Key points

• Wilms’ tumour now has an excellentprognosis, with treatment based on acombination of surgery, chemotherapyand, in some cases, radiotherapy. Thechallenge for the future is to maintainexcellent survival figures while reducingthe morbidity related to intensivetreatment regimens.

• Rhabdomyosarcoma is a raremalignancy managed by chemotherapy,radiotherapy and organ-sparing surgeryinsofar as this is feasible. The difficultylies in balancing the desirability oflocalised excision which preserves anintact bladder and urethral sphincteragainst the risk of local recurrence ofan aggressively malignant tumour.Where the tumour is totally excisedthe long-term prognosis is good.

• Most childhood testicular malignanciescan be managed by orchidectomy andclose follow-up.

Further reading

Atra A, Ward HC, Aitken K et al. Conservative surgery inmultimodal therapy for pelvic rhabdomyosarcoma inchildren. Br J Cancer 1994; 70: 1004–1008

Beckwith JB, Kiviat NB, Bonadiot JF. Nephrogenic rests,nephroblastomatosis and the pathogenesis of Wilms’tumour. Paediatr Nephrol 1990; 10: 1–36

Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Tumours ofthe urinary system and male genital organs. WorldHealth Organisation Classification of Tumours. Lyon:IARC Press, 2004

Murphy WM, Grignon DJ, Perlman EJ. Tumors of thekidney, bladder, and related urinary structures. AFIPAtlas of Tumor Pathology, Series 4. Washington, DC:Armed Forces Institute of Pathology, 2004



Urogenital trauma

David FM Thomas

Introduction

Although minor injuries to the genitourinarytract are relatively common in childhood, majortrauma is fortunately rare and, with the exceptionof isolated blunt renal trauma, tends to occur inconjunction with other injuries. Penetrating injuriesresulting from gunshot or stab wounds of the typeencountered by paediatric urologists in the UnitedStates are exceptionally rare in Western Europe,where the overwhelming majority of injuries tothe urogenital tract in children result from bluntinjury.

Although the general principles of the manage-ment of urological injuries in children followbroadly similar lines to those in adults, the overallmanagement of the injured child demands special-ist paediatric expertise and the input of a numberof relevant disciplines.

The organisation of trauma services for childrenis beyond the scope of this book, but it is gener-ally accepted that children with multiple traumainvolving the urinary tract should be transferred toa specialist regional centre once their initial condi-tion has been stabilised. Trauma of a minor nature,however, can generally be managed locally, withadvice being sought from a specialist paediatricurologist where appropriate.

Although isolated genital injuries often havean innocent explanation, the possibility ofsexual abuse, particularly in girls, should neverbe overlooked, and the early involvement of a

paediatrician with appropriate expertise should besought, particularly as forensic samples may berequired.

Renal trauma

In childhood, the kidney is more susceptibleto blunt trauma because it lacks the degree ofprotection afforded to the adult kidney bythe bulk of surrounding perirenal fascia andoverlying muscle. In addition, the ribs are lesswell ossified in childhood and the kidney ismore vulnerable because it occupies a relativelylarger space within the retroperitoneum. Althoughabnormalities such as pelviureteric junction(PUJ) obstruction render the kidney moresusceptible to injury (sometimes of a seeminglytrivial nature), pre-existing pathology is acontributory factor in fewer than 10% of cases ofblunt renal trauma (Figure 22.1).

Data collected by the US National PediatricTrauma Registry recorded renal injuries inapproximately 2% of 49 651 paediatric traumacases. The average age of children sustaining arenal injury was 10.6 years, with boys outnum-bering girls by a ratio of almost 2:1. In this largeseries of renal injuries, there were no reports ofinjury to a solitary kidney. The causes of renalinjury included road traffic accidents, cycling anda range of sporting activities – notably Americanfootball.

22

Topics coveredRenal traumaUreteric injuries

Bladder injuriesUrethral injuriesInjuries to the external genitalia


PresentationIsolated renal trauma most commonly results froma sporting or playground injury. In children theextent of the renal injury may not correlate closelywith the apparent severity of the trauma, andseemingly insignificant injuries can be associatedwith deceptively severe renal damage. Moreover,children have the capacity to sustain significantblood loss before developing hypotension andother manifestations of hypovolaemia. The present-ing clinical features of renal trauma typicallyinclude haematuria, loin pain and tenderness, anexpanding perirenal mass, and external evidence ofinjury such as bruising or abrasions.

In children with multiple injuries the renal injurymay sometimes dominate the clinical picture, butis often overshadowed by coexisting visceralinjuries such as liver, splenic or duodenal rupture(Figure 22.2). In these circumstances it is notuncommon for renal contusion or laceration to beidentified during the course of abdominal or initial

assessment with computed tomography (CT)scanning.

InvestigationsAll children with suspected renal injury should beadmitted for observation and monitoring of vitalsigns. Laboratory tests include urine microscopy, fullblood count and haematocrit. Renal trauma is almostinvariably accompanied by haematuria, but it shouldbe noted that the severity of the haematuria does notcorrelate well with the extent of the renal injury.


Figure 22.1 A 12-year-old boy was admitted withrenal trauma after receiving a seemingly trivial blow tothe abomen while at school. The CT scan demon-strates extensive extravasation and blood clot withinthe dilated left renal pelvis. Exploration confirmedrupture of the renal pelvis associated with pre-existingpelviureteric junction obstruction. There was full recov-ery and preservation of normal differential functionfollowing repair of the renal pelvis and pyeloplasty.

Figure 22.2 CT scan with contrast. Two imagesdemonstrating transection of the upper pole of theright kidney in an 18-month-old child. Seatbelt injurysustained in road traffic accident. An associatedduodenal rupture was managed by laparotomy but therenal injury was treated conservatively.


Imaging

In view of the vulnerability of the kidney inchildren and the potentially deceptive clinicalpicture in this age group, renal imaging is manda-tory in the presence of haematuria or a suspectedrenal injury. The pattern and extent of imaging,however, may be determined by the overall clinicalcondition and the availability of imaging modali-ties. Children with clinical or radiological evidenceof a significant renal injury, haemodynamic insta-bility, or evidence of coexisting injuries should betransferred to a specialist centre.

Computed tomography with contrast is theimaging modality of choice, particularly wherethere is any suspicion of coexisting abdominalvisceral trauma. CT is now available in all majorpaediatric centres and most larger district generalhospitals. It permits grading of the renal injury andan assessment of renal perfusion (Figure 22.3).Further CT scans may be required to monitor thecourse of the injury and to guide any decision onpossible surgical intervention.

Ultrasound is a reasonable first-line investigationin a child who is clinically stable and who is thoughtto have sustained only minor renal trauma. However,appearances in the initial phase following injury canappear misleadingly normal. If ultrasound revealsevidence of renal trauma, a CT scan is always advis-able to permit a more detailed functional assessment.Although the intravenous urogram (IVU) has been

largely superseded by CT, it remains a useful investi-gation where CT is not readily available. UnlikeCT, however, the IVU provides no additional infor-mation on possible injury to other abdominalviscera. Arteriography has likewise been largelyreplaced by CT scanning, and in any event is of littlepractical value as the prospects of salvaging renalfunction by revascularisation in avulsion injuries areremote. The interval between devascularisation andeven the most prompt surgical intervention invari-ably exceeds the warm ischaemic time of devitalisedrenal parenchyma.

ManagementThe broader aspects of trauma management inchildren are beyond the scope of this chapter.However, the guiding principles can be defined asfollows:

• All children with a suspected or proven diagno-sis of renal trauma (even if seemingly trivial)should be admitted for observation, monitoringof vital signs and imaging.

• Blunt renal trauma should generally bemanaged conservatively, but in cases of majorrenal trauma the possible indications for surgi-cal intervention should be actively reviewed atregular intervals. Conservative managementof moderate to major renal trauma comprisesactive monitoring of vital signs, correction of

Urogenital trauma 309

I II III IV V

Figure 22.3 Grading of renal trauma. Grade I, renal contusion. Grade II, parenchymal laceration not extend-ing into collecting system. Grade III, parenchymal laceration involving collecting system, perirenal haematomaand extravasation. Grade IV, extensive laceration/parenchymal avulsion injury. Grade V, shattered kidney and/oravulsion of vascular pedicle.


hypovolaemia (with blood if necessary), andreimaging with ultrasound and further CTor other modalities where indicated. Minorinjuries require inpatient observation until frankhaematuria has resolved.

Indications for surgical intervention arerelative rather than absolute and include:

• Haemorrhage resulting in haemodynamicinstability, particularly if accompanied byan expanding retroperitoneal haematoma orhaemoperitoneum.

• Urinary extravasation: a minor or moderatedegree of urinary extravasation is not uncommonand does not, in itself, amount to an indicationfor surgical exploration. Localised collectionscan be aspirated or drained percutaneously (Figure22.4a,b). In one series of 374 paediatric renalinjuries, even relatively severe (grade IV) injurieswere successfully managed non-operatively in41% of children. Surgical exploration, however,may be warranted if the renal parenchyma is largelyintact and there is evidence of a pelvic tear oravulsion of the ureter.

• ‘Shattered kidney’ (grade V injury): even ifhaemodynamic stability can be achieved,removal of a non-functioning ‘shattered’ kidneymay be justified to hasten recovery and reducethe risk of complications. If there are no otherintra-abdominal injuries, exploration can bedeferred for a few days rather than undertakenacutely. In the presence of other intra-abdomi-nal injuries requiring laparotomy, a ‘shattered’kidney should be removed at the same time.

• Vascular injuries: the prospects of successfulrevascularisation are minimal in view of therelatively short warm ischaemic time of thekidney. Nevertheless, an attempt at revascularisa-tion might be justifiable in the rare event of devas-cularisation of a solitary kidney or bilateral injury.

Technical considerations

The kidney should be explored transperitoneally viaa midline or upper transverse incision, depending

on the age of the child. Laparotomy provides anopportunity to examine the other intra-abdominalviscera for injury and provides better access forvascular control. Prior to exposure of the kidney,the renal artery and vein(s) are identified by theirrespective points of origin on the aorta and inferiorvena cava, and vascular control is achieved bypassing vascular slings around the vessels to permittemporary occlusion if required.


Figure 22.4 (a) Ultrasound scan demonstrating theavulsed lower pole of the right kidney lying free in alarge perirenal urinary collection. (b) Pigtail catheterinserted percutaneously to drain an enlarging urinarycollection despite 6 days of conservative manage-ment. IVU demonstrating leakage of contrast fromthe severed lower pole calyx. In this case surgicalexploration was required some days later to closethe leaking calyx and remove the necrotic, avulsedlower pole.

(a)

(b)


The nature and extent of the surgical procedureis determined by the operative findings and mayinclude, for example, repair of a parenchymal lacer-ation with closure of any associated collectingsystem defect, repair of a pelvic tear, or reanasto-mosis of an avulsed ureter, or debridement andpartial nephrectomy. When renal salvage is notfeasible or is not justified by the amount of resid-ual functioning renal tissue, nephrectomy is under-taken. However, it is crucially important to havepreviously obtained positive confirmation that anormal functioning contralateral kidney is presentbefore proceeding with nephrectomy.

OutcomeEarly complications include urinoma, infectionand abscess formation. Secondary haematuria isnot uncommon within the first few weeks of theinjury, but is rarely of sufficient severity to requireactive intervention. Follow-up imaging comprises

ultrasound and DMSA (dimercaptosuccinic acid),which is best deferred for 2–3 months after the injury(Figure 22.5). Hypertension is the principal long-term complication, although the true incidence isdifficult to assess because of the lack of reliable long-term data. The overall risk of renal-related hyperten-sion following childhood renal trauma is thought tobe low – probably around 2–3% – but the relativerisk is likely to be greater when a significant bulk ofdevascularised tissue has been left in situ. There issome evidence that if hypertension is going to occur,the risk is greatest in the first 2 years following injury.Nevertheless an annual lifelong check of bloodpressure is advisable for individuals who havesustained significant parenchymal injuries.

What advice should be given to the parentsof a child with a solitary kidney? Parents oftenreceive differing advice, with little consistency inthe recommendations regarding contact sports.Insofar as it is possible to provide evidence-basedadvice (e.g. from the findings of the US TraumaCenter Study) the statistical risk to a solitarykidney appears to be extremely low. There appearsto be little objective justification for limiting thequality of life of children and young people byimposing constraints on normal sporting activities.

Ureteric injuries

Injuries to the ureter are very rare in children and aremore likely to be iatrogenic than traumatic in aetiol-ogy. Management is individualised according tothe nature and level of the injury. Options includespatulation and end-to-end anastomosis over anindwelling JJ stent; mobilisation of the kidney;nephropexy; and pyeloureterostomy for proximalureteric injuries. Psoas hitch and ureteric reimplanta-tion may be feasible for injuries to the distal ureter.

Bladder injuries

Penetrating injuries of the bladder are exceedinglyrare in children and when they do occur are usually


Figure 22.5 DMSA scintigraphy 4 months afterrenal injury (CT demonstrating right upper poletransection in the patient illustrated in Figure 22.2).DMSA shows complete loss of function in the devas-cularised lower pole. Differential function right kidney21%, left kidney 79%.


iatrogenic in origin, for example inadvertent damageto the bladder wall during herniotomy. Blunt injuriesare similarly rare in this age group and, when theyoccur, are almost invariably the result of motorvehicle accidents. Spontaneous rupture of the bladderis a recognised and potentially lethal complication ofenterocystoplasty, and has also occurred followingimpaction of a calculus at the bladder neck.

Bladder injuries are traditionally classified accord-ing to whether urinary extravasation is confinedto the perivesical space (extraperitoneal rupture) orwhether there is free leakage of urine into theperitoneum (intraperitoneal bladder rupture).

The presentation of bladder injuries dependson the circumstances in which they have beensustained – for example, iatrogenic bladder perfora-tion during cystoscopy is either recognised during thecourse of the procedure or becomes apparent as asuprapubic swelling arising out of the pelvis in caseswhere a catheter has not been left in the bladderpostoperatively. Iatrogenic damage to the bladderduring herniotomy may be apparent as urinaryleakage from the skin incision. Seatbelt injuriespresent with pain, and major injuries associated withpelvic fractures should be identified during the courseof initial evaluation for major trauma. Whenevercircumstances permit, the diagnosis should beconfirmed by urethral catheterisation and contrastcystography.

ManagementEndoscopic extraperitoneal perforation can usuallybe managed by a period of continuous catheterdrainage, but it is advisable to undertake formalrepair of any other iatrogenic bladder perforationincurred for example during herniotomy or appen-dicectomy. Intraperitoneal bladder rupture demandsprompt surgical exploration, closure of the bladderdefect and, where possible, closure of the overlyingperitoneum. Following repair of any bladderinjury, continuous postoperative bladder drainagevia a urethral or suprapubic catheter should bemaintained for a number of days.

The possible diagnosis of bladder perforation orspontaneous rupture should always be actively

considered in any patient with a history of bladderaugmentation, who subsequently presents withabdominal pain, distension or unexplained systemicill health and metabolic disturbance.

Urethral injuries

Urethral injuries are generally confined to the maleurethra. Three broad mechanisms of injury can beidentified:

• Perineal blunt trauma, typically ‘stride’ or‘straddle’ injuries to the bulbar urethra.

• Injuries to the posterior and membranousurethra associated with pelvic fractures (usuallyroad traffic accidents in children).

• Urethral damage resulting from instrumenta-tion or prolonged urethral catheterisation.

Presentation

Blunt trauma – ‘straddle injuries’

Children generally present with a history of atraumatic episode and evidence of perineal bruis-ing. Depending on the severity of the injury,the clinical picture may also include urethral bleed-ing, haematuria or painful urinary retention withbladder distension. Imaging is not usually contrib-utory in the acute phase, although it is advisableto perform an ultrasound scan (and plain X-rayif bony injury is suspected). Ascending contrasturethrography or attempted catheterisation andcystography are not usually tolerated in youngerchildren, but an ascending urethrogram may befeasible in an older boy or adolescent.

ManagementChildren with suspected or proven urethral injuriesshould be admitted for observation until the initialdiscomfort has settled and voiding has been re-established. Where there is evidence of a moresevere injury, particularly associated with retentionor anuria, the initial management is aimed at



establishing bladder drainage and evaluating theseverity of the urethral injury.

If the child does not pass urine despite analgesia,the safest course of action is percutaneous insertionof a suprapubic catheter under general anaesthesia.Urethral catheterisation or urethroscopy may beconsidered, provided these manoeuvres are under-taken cautiously by an experienced paediatric urolo-gist. However, injudicious attempts at catheterisationor traumatic urethroscopy should be avoided, as thismay compound the urethral damage.

After a period of drainage of several days’duration, the urethra is then visualised by contrastdescending cystography (and, ideally, an ascendingurethrogram). If there is no evidence of extravasa-tion or disruption, the suprapubic catheter can beclamped and normal urethral voiding re-established.More severe injuries of the bulbar urethra are bestmanaged by a sustained period of suprapubic diver-sion, followed by urethroplasty (see below).

Pelvic fractures

The possibility of injury or disruption of the poste-rior and/or membranous urethra should be activelyconsidered in any child with a pelvic fracture. As inadults, management of these injuries is controver-sial, the options comprising:

• prolonged suprapubic drainage followed byelective urethroplasty or

• open exploration, debridement and attemptedre-alignment approximation of the urethra overa catheter once the initial effects of the injuryhave subsided, e.g. after 7–14 days.

Post-traumatic urethral stricture

The treatment options are summarised in Figure 22.6and consist of the following procedures:

Optical urethrotomy (Figure 22.6a)

This procedure is best suited to short, diaphragm-like strictures. Using a ‘cold knife’ blade mountedon a paediatric or neonatal resectoscope with a 0°or 5° end-viewing lens, the stricture is visualised,

and if necessary a ureteric catheter passed throughthe central lumen to enable the blade to bepositioned accurately. The stricture is then incisedunder vision with radial cuts. A silicone catheter isleft in situ for 48–72 hours postoperatively.

Although optical urethrotomy can be repeated,it is unlikely to prove curative if the stricture recursdespite two or three episodes of treatment.

Urethroplasty

The length and severity of the stricture is delin-eated preoperatively by a combination of cystogra-phy and urethrography, and by instrumentation atthe time of surgery. A perineal approach usuallygives adequate exposure, but an abdominoperinealor transpubic approach may be required for stric-tures resulting from pelvic fracture injuries. Thetechniques of choice in children comprise:

• excision of the strictured urethral segment,mobilisation of the urethra and end-to-endanastomosis (Figure 22.6b)

• incision (‘laying open’) of the stricture andonlay grafting, ideally with a free graft of buccal‘mucosa’, or alternatively with a pedicled or freeskin graft (Figure 22.6c).

The surgical management of urethral stricturesshould only be undertaken by paediatric or recon-structive urologists with extensive experience ofurethral reconstructive surgery.

Genital injuries

Genital injuries are uncommon but typically resultfrom playground injuries or animal bites. Scrotallacerations and severe blunt scrotal trauma shouldbe explored under general anaesthesia to permitdebridement and inspection of the testis. When atesticular injury is identified, devitalised tissue isexcised, the tunica albuginea repaired, and thescrotum then closed in layers, with attention tohaemostasis. Intravenous broad-spectrum antibioticsshould be administered for 48 hours postoperatively.



Penile injuries should be managed according totheir site and severity. The possibility of sexualabuse should not be overlooked.

Injuries to the female external genitalia, suchas stride or straddle injuries, may result in bruisingand superficial laceration of the perineum andexternal genitalia. A short period of suprapubic or

urethral catheter drainage may be required insevere cases until the initial early oedema andbruising have resolved. Long-term complicationssuch as strictures are not encountered in girls, asthe female urethra is less anatomically vulnerablethan in the male. Sexual abuse (rape or attemptedrape) is a serious cause of genital injury in girls,


(a)

(b1)

(b2)

(b3)

(c1)

(c2)

(c3)

Figure 22.6 Urethral stricture: treatment options. (a) Optical urethrotomy. Best suited to short, well circum-scribed strictures. Stricture incised with radial cuts using a cold knife blade mounted on a paediatric resecto-scope. (b) 1 Perineal exposure of the bulbar urethra; 2 excision of the strictured segment, mobilisation of healthyurethra; 3 end-to-end primary anastomotic urethroplasty over a silicone catheter. (c) 1 Perineal exposure of thestrictured bulbar urethra; 2 incision to lay open strictured segment (‘stricturotomy’) extended into adjacent healthyurethra; 3 onlay graft of buccal mucosa sutured into the defect.


and for this reason the circumstances of the injuryshould always be actively investigated in any girlpresenting with unexplained genital trauma.

Key points

• Potentially serious renal trauma canoccur after seemingly insignificantinjury. All children with suspectedrenal trauma should be admitted forobservation, imaging and evaluation.

• Most renal injuries can be managedconservatively, but in cases of severerenal trauma the indications forpossible surgical intervention shouldbe actively reviewed at regularintervals.

• The (limited) available evidenceindicates that the risk of significantinjury to a solitary kidney is extremelylow and does not justify constraintson normal sporting and leisureactivities in childhood.

• The surgical management ofpost-traumatic urethral strictures

should only be undertaken by anexperienced paediatric orreconstructive urologist.

• The possibility of sexual abuse shouldalways be considered in any childpresenting with an injury to the externalgenitalia.

Further reading

Brown SL, Elder JS, Spirnak JP. Are pediatric patients moresusceptible to major renal injury from blunt trauma?J Urol 1998; 160: 138–140

Connor JP, Hensle TW. Trauma to the urinary tract.In: O’Donnell B, Koff SA (eds). Pediatric Urology,3rd edn. Oxford: Butterworth-Heinemann, 1997:696–708

Johnson B, Cristensen C, Dirusso S, Choudhury M, FrancoI. A need for re-evaluation of sports participationrecommendations for children with a solitary kidney.J Urol 2005; 174(2): 686–689

Kardar AH, Sundin T, Ahmed S. Delayed management ofposterior urethral disruption in children. Br J Urol1995; 75: 543–547

McAninch JW, Safir MH. Genitourinary trauma. In: WeissRM, George NJR, O’Reilly PH (eds). ComprehensiveUrology. London: Mosby, 2001: 637–650




Laparoscopic paediatric urology

Imran Mushtaq

Introduction

Laparoscopic skills are now essential ‘tools of thetrade’ for both paediatric surgeons and paediatricurologists. The benefits of minimally invasivesurgery, coupled with parental awareness anddemand, have led to its increasing popularity inrecent years. Diagnostic laparoscopy forcryptorchidism was first described in 1976 byCortesi and rapidly became an establishedtechnique. By contrast, therapeutic laparoscopywas slow to evolve and it was not until 1990 thatClayman performed the first transperitoneallaparoscopic nephrectomy. Two years later, in1992, Gaur described the first retroperitoneo-scopic nephrectomy.

Benefits and drawbacks

The benefits of laparoscopic surgery to children arewell known and include reduced postoperativepain, increased postoperative comfort, reducedhospital stay, quicker return to normal activities,improved cosmesis and reduced wound complica-tions. Although very few randomised controlledstudies have been performed to demonstrate theseadvantages, there is sufficient evidence in the liter-ature to support the philosophy of minimallyinvasive surgery. The relatively smaller size of the

paediatric patient provides the surgeon with theunique advantage of being able to access both theupper (kidney) and lower (ureter) urinary tractthrough the same port sites. This advantageapplies to both the transperitoneal and retroperi-toneoscopic approaches, although the puristswould prefer the transperitoneal route for access tothe very distal ureter. Laparoscopy also providessuperior access to the pelvis when dealing withmüllerian duct remnants, intra-abdominal testesand cloacal anomalies as examples.

Clearly there are drawbacks to every surgicalapproach and there are some that are unique to thepaediatric population. Paediatric surgeons andurologists have to deal with a very wide spectrumof disease, covering congenital anomalies, benigntumours and malignant conditions, and in additionwith the variation in age (neonates to adolescents)and size of the patients. We therefore need to beadaptable to deal with the different situations wemay find ourselves having to manage. There are, ofcourse, the technical difficulties of operating in arelatively small space, and this is particularly thecase with the retroperitoneoscopic approach.However, recent advances in camera technologyand instrumentation have overcome the majority ofthese limitations. Finally, the financial costs ofcertain forms of treatment will have a bearing ontheir acceptance. This can be measured in the adultpopulation as loss of earnings or time to return to

23

Topics coveredBenefits and limitations of laparoscopic surgery inchildrenPatient selectionFundamentals of technique

Procedures, indications and outcomesNephrectomyHeminephrectomyPyeloplasty (including robotic pyeloplasty) AdrenalectomyOthers


normal activities (particularly their employment inthe case of adults). In the paediatric population, theeconomic advantages of a reduced duration ofhospital stay are less obvious.

When laparoscopic surgery was first introduced,it was perceived to carry a greater risk of compli-cations, and it is the case that there are somecomplications that are unique to laparoscopicsurgery. However, retrospective reviews, randomisedcontrolled studies and multicentre trials havereassured the surgical community that laparoscopicsurgery can be as safe as open surgery. Complica-tions of laparoscopic surgery in children are similarto those in adults. However, the smaller workingspace combined with the relatively larger size ofthe liver, spleen and bladder mean that the inser-tion of trocars and instrumentation must always beperformed under direct vision. The use of a Veresneedle to establish pneumoperitoneum is routinein adult practice but is nevertheless associated withsome degree of morbidity. In the paediatricpopulation the most common complication associ-ated with its use is extraperitoneal insufflation andsurgical emphysema. The close proximity of theintra-abdominal organs, bowel and major vesselsplaces them at risk of iatrogenic injury with theVeres needle. For these reasons the open Hassontechnique is the method of choice to establishpneumoperitoneum in children.

Patient selection

The principal urological indications for minimallyinvasive surgery in children are as follows:

• nephrectomy• partial nephrectomy• pyeloplasty• adrenalectomy • renal cyst excision/marsupialisation• pyelolithotomy and ureterolithotomy• ureteric stumpectomy after partial nephrectomy• ureteric reimplantation• impalpable testis• varicocoele

• disorders of sex development (gonadalbiopsy/excision)

• müllerian remnants• ovarian disorders.

Contraindications The majority of conditions encountered in paedi-atric urological practice are either congenital inorigin or, if acquired, are of a benign nature; as such,these conditions are all generally suitable for alaparoscopic approach. The role of laparoscopy inthe management of malignant tumours in childrenis yet to be defined, and certainly for Wilms’nephrectomy it is currently not recommended. Inthe case of malignant adrenal tumours the recom-mendations from the oncological groups still favouropen surgery. However, there are already somereports in the literature describing successful laparo-scopic surgery for malignant adrenal tumours.

Absolute contraindications include:

• significant comorbidity (e.g. cardiac, respira-tory disease)

• uncorrectable coagulopathies• sepsis.

Fundamentals of technique

AnaesthesiaAnaesthesia for minimally invasive surgery proceduresin children requires endotracheal intubation and theuse of volatile and/or intravenous anaesthetic agents.In some cases, such as retroperitoneoscopic surgeryfor example, the use of a reinforced endotracheal tubemay be advisable. Respiration in infants and youngchildren is primarily diaphragmatic in origin. Abdom-inal insufflation during transperitoneal surgerymay compromise diaphragmatic excursion and forthis reason insufflation pressures should be kept<10 mmHg in children under 10 kg and <12 mmHgin larger children. When performing retroperitoneo-scopic surgery with the patient in the prone position,the chest and pelvis should be kept raised to allow theabdomen to be free of the operating table.



Children are at significant risk of developinghypothermia during laparoscopic surgery, especiallywith prolonged operating times and a high gasflow. Therefore, the use of warming blankets andpadded cotton wool is recommended for all cases.

Most paediatric anaesthetists now routinelyrecommend pre-emptive analgesia. This can beprovided by means of the instillation of analgesicagents into the caudal space, by means of anindwelling epidural catheter or by means of instil-lation of local anaesthetic drugs into the site of theincision(s). A ‘top-up’ at the end of a prolongedprocedure should be considered, provided themaximal administrable dose is not exceeded.

InstrumentationRecent advances in digital video technology andinstrumentation now allow a wide spectrum ofurological conditions to be managed using minimallyinvasive techniques. Laparoscopic instruments areavailable in 2, 3 and 5 mm sizes, although the 5 mminstruments remain the most popular for general use.The use of a 5 mm 30° laparoscope provides optimumvisualisation for most procedures. The Hassoncannula, which is used for the initial access, is avail-able in 5 mm and 10 mm sizes. For diagnostic andreconstructive procedures (e.g. pyeloplasty), the 5mmcannula is sufficient. However, a 10 mm cannula isrequired when use of an Endopouch retrieval deviceis expected for specimen extraction.

A wide assortment of instrument trocars arenow available, both reusable and disposable.Bladeless trocars are generally safer for use inchildren, where the abdominal wall is morecompliant and less muscular.

AccessThere are two methods available to access theperitoneum: the blind technique and the open(Hasson) technique. The blind technique involvesinsertion of a Veres needle adjacent to the umbili-cus through all layers of the abdominal wall intothe peritoneal cavity. Entry into the peritonealcavity is confirmed by dropping a small amount ofsaline into the open end of the Veres needle.

The open Hasson technique is the preferredapproach for access to the peritoneum in children,for reasons already outlined above. A stab incision ismade in the supraumbilical skin crease, and isenlarged along Langer’s line by inserting andopening the jaws of an artery forceps. The underly-ing linea alba is grasped and opened transverselywith scissors or a scalpel. The peritoneum is graspedand opened in a similar manner. The Hasson cannulais introduced into the peritoneal cavity, keeping thecone of the cannula snug against the skin incision.The cannula is secured in place with a suture throughthe skin (Figure 23.1). For retroperitoneoscopicprocedures a blunt approach is used to access theretroperitoneum and this is described below in thenephrectomy subsection of this chapter.

Current indications forminimally invasive surgery inpaediatric urology

Laparoscopic nephrectomyOver the last decade, the minimally invasive approachfor the treatment of benign renal conditions hasgained great popularity. Laparoscopic nephrectomy

Laparoscopic paediatric urology 319

Figure 23.1 Port placement for a transperitoneallaparoscopic nephrectomy. The camera (Hasson) portis placed in a periumbilical position in an openmanner, with the cone securely against the incision toprevent loss of pneumoperitoneum.


and nephroureterectomy are now standard proce-dures in centres where this expertise is available.Laparoscopic heminephrectomy, however, is still notwidely practised despite the publication of compara-ble results to the open technique.

The retroperitoneoscopic approach, initiallydescribed by Gaur, is now the approach to thekidney favoured by most paediatric urologists. Itavoids colonic mobilisation, the risk of injury tohollow viscera and the potential risk of adhesionformation. However, the reversed orientation of thekidney and hilum with the patient in a semiprone orprone position, combined with the comparativelysmaller working space, may make this approachdifficult to master. The transperitoneal route has theadvantage of a larger working space and may bepreferred if the surgeon is relatively inexperienced orwhen there has been previous renal surgery. Regard-less of the approach utilised, the benefits to the childin terms of a faster postoperative recovery andimproved cosmesis are without question.

Indications

Laparoscopic nephrectomy or nephroureterec-tomy is indicated in the following situations:

• congenital dysplastic kidneys• multicystic dysplastic kidneys, which, on

follow-up, have failed to involute or are associ-ated with systemic hypertension

• pelviureteric junction (PUJ) obstruction withloss of function

• reflux-associated nephropathy• intractable protein loss associated with congen-

ital nephrotic syndrome • pretransplant in children with focal segmental

glomerulosclerosis.

Operative technique forretroperitoneoscopic nephrectomy

The theatre layout for a retroperitoneoscopicnephrectomy is shown in Figure 23.2. The patientis positioned prone, with the chest and pelvis raisedto allow the abdomen to be free. Pressure points areprotected in an appropriate manner (Figure 23.3).

Topographic landmarks and anticipated port sitesare marked as shown in Figure 23.4. A 5 mm trans-verse incision is made midway between the iliaccrest and the tip of the 12th rib, just lateral to theouter border of the sacrospinalis muscle. Throughthis incision, a small area of the retroperitoneum isdissected bluntly with artery forceps to allow theinsertion and inflation of a balloon to create theretroperitoneal working space.

A Hasson cannula is inserted into the port site,followed by insufflation of the retroperitoneumwith CO2 to a pressure of 10–12 mmHg. Aninstrument port is placed under direct vision belowthe tip of the 11th/12th ribs and above the iliaccrest. A second instrument port can be placedthrough the paravertebral muscles if required.

Gerota’s fascia is incised in a cruciate manner toenter the perinephric space. The kidney is dissectedon its posteromedial aspect to expose the hilarvessels: these are individually displayed and dividedbetween haemoclips or with a harmonic scalpel.The ureter should be traced inferiorly as far asnecessary and divided. In children with ipsilateral


AV N

I

P

A S

Figure 23.2 Theatre layout for left retroperitoneo-scopic nephrectomy, with patient (P) in prone position:monitor and stack system (AV), theatre nurse (N),operating surgeon (S), assistant (A) and instrumenttable (I).


vesicoureteric reflux, the ureter should be ligatedor the bladder drained with a urethral catheter for48 hours.

Small kidneys can be removed directly via thecamera port, whereas larger specimens may requireentrapment in an Endopouch retrieval device andpiecemeal removal.

Results

A recent study from Scotland compared the resultsof laparoscopic and open nephrectomy in children.It was found that a laparoscopic nephrectomy maytake longer to perform, but that the children sufferless postoperative pain and have a shorter durationof hospital stay. Furthermore, they found thatthose children who had a retroperitoneoscopicnephrectomy made an even faster recovery. Thetechnique of retroperitoneoscopic nephrectomy isnow well established and has been shown to beapplicable to all age groups, with a low conversion(<3%) and complication rate. The technique hasbeen adapted to the management of children whohave end-stage renal disease and who require bilat-eral native kidney nephrectomy. As the peritoneumcan be maintained intact, it allows for immediate

postoperative peritoneal dialysis. This approachhas been utilised in the management of 20 childrenin the author’s institution. One child requiredconversion to open and 17 children were estab-lished on peritoneal dialysis immediately aftersurgery. The technique continues to evolve and arecent development is the SIMPL (single instru-ment port laparoscopic) nephrectomy, which is amodification of the posterior prone retroperito-neoscopic nephrectomy. The entire procedure canbe performed through a single instrument portwithout compromising safety and operative time.It has been used in the author’s centre in themanagement of 80 children, ranging from 1month to 18 years of age. The average operativetime is 60 minutes and there have been no compli-cations or conversions.

Laparoscopic heminephrectomyThe first laparoscopic heminephrectomy wasperformed in 1992 by the transperitonealroute. Two years later, Gill performed the firstretroperitoneoscopic heminephrectomy. Despitethe unquestionable benefits of the laparoscopic


Figure 23.3 Patient positioned for right retroperito-neoscopic nephrectomy. The chest and pelvis areraised to allow the abdomen to lie in a dependentmanner. The pressure points (face, arms, knees andtoes) are protected with gel pads.

11th rib12th rib

Lateral borderof sacrospinalisIliac crest

Instrumentport site

Cameraport site

Figure 23.4 Schematic representation of portposition. A second instrument port can be placedthrough the sacrospinalis muscle in a position medialto the camera port site.


approach for nephrectomy in children, laparo-scopic heminephrectomy has not yet gainedwidespread popularity. The difficulty of achievingnear total ureterectomy, coupled with the sugges-tion of higher complication rates, is perhaps thereason why. Current results in children arediscussed later in this chapter.

Indications

The indications for a laparoscopic heminephrectomyare similar to those for standard open heminephrec-tomy and include the following conditions:

• Renal duplication anomalies. Upper poleheminephrectomy is performed most commonly,typically in cases characterised by dilatation of apoorly functioning upper pole and dilated upperpole ureter.

• Renal duplication in girls with ectopic insertionof upper moiety ureter with urinary inconti-nence and poorly functioning upper pole.

• Lower pole heminephrectomy is performed incases of reflux-associated nephropathy with lossof lower pole function or rarely in cases of lowermoiety PUJ obstruction with loss of function.

Caution should be exercised when considering alaparoscopic heminephrectomy in a child with ahistory of recurrent or recent upper urinary tractinfection(s). In this situation it is not uncommon toencounter dense adhesions between the kidney, theureter and the peritoneum which may make dissec-tion difficult and blood loss excessive. In such cases,an open approach may be more suitable.

Operative technique forretroperitoneoscopicheminephrectomy

The steps for surgical access to the kidney are thesame for a retroperitoneoscopic heminephrectomyas they are for a retroperitoneoscopic nephrectomy.In particular, the position of the patient and theport sites are identical. Once the kidney is located,it is mandatory to visualise both the upper andlower moiety ureters to confirm the anatomy and

provide a guide to the vascular supply. The vesselssupplying the affected moiety are selectively identi-fied and divided and the ureter from the affectedmoiety is separated from the ureter to be preservedand divided. The proximal stump of the ureter canbe used to expose the anteromedial surface andany additional vessels supplying the affectedmoiety. Blanching of the parenchyma secondary tohypoperfusion will delineate the portion of renalparenchyma that needs to be resected. Transectionof the parenchyma between the two moieties canbe performed with monopolar diathermy,harmonic scalpel or with the use of an endoloop toconstrict the parenchyma (Figure 23.5).

The distal ureteric stump should be removed asfar down into the bony pelvis as possible, takingcare to visualise and protect the ureter draining theunaffected moiety.

Results

Laparoscopic heminephrectomy has only beenintroduced recently and is still limited to arelatively small number of centres. For this reason,very little has yet been documented regarding theefficacy, complications and long-term outcomes ofthis approach. Recently a group from Miamireported a 10% serious complication rate and agroup from Toronto a 14% complication rate(consisting mainly of urinary leakage from theremaining kidney tissue at the resection margin).In our own centre we prefer the use on anendoloop to constrict or ‘cinch’ the parenchyma,which significantly reduces the risk of urine leak.In a retrospective review of 54 successive retro-peritoneoscopic heminephrectomies performedbetween 2001 and 2005 in our centre, no case ofpostoperative urine leak was encountered.

Laparoscopic pyeloplastyLaparoscopic pyeloplasty in adults has been shownto be an effective modality for the treatmentof PUJ obstruction. Its use in the paediatricpopulation was first described in 1995, and it hasnow become an established technique in the



management of older children with PUJ obstruc-tion. Recent reports suggest that it is also feasiblein infants and smaller children, where the clinicalbenefits of a laparoscopic approach would bemarginal.

Indications

Indications for laparoscopic pyeloplasty are similarto those for open pyeloplasty and comprise:

• symptomatic PUJ obstruction • worsening hydronephrosis on serial imaging• anteroposterior (AP) diameter >20 mm with

calyceal dilatation and renal function <40%• AP diameter >30 mm with calyceal dilatation.

Contraindications for laparoscopic pyeloplastymay include a small extrarenal pelvis, prior renalsurgery and anatomical variants, such as a horse-shoe kidney.

In our own institution we offer laparoscopicpyeloplasty to children >6 years old who fulfil theabove criteria for surgery. From a clinicalviewpoint, it is the older children and adolescentswho are most likely to benefit from a minimallyinvasive approach, both in terms of postoperativepain and improved cosmesis.

Operative technique forlaparoscopic pyeloplasty

Laparoscopic pyeloplasty can be performed via thetransperitoneal or the retroperitoneal route. Bothapproaches are well described, with no particularadvantages of one over the other, although in ourown centre we prefer the transperitoneal routesince it provides a relatively large working spacefor intracorporeal suturing. This technique isdescribed below.

The patient is positioned in a lateral decubitusposition with the affected kidney uppermost. Thecamera port is placed using the open Hassontechnique in the region of the umbilicus, and issecured in place with a skin suture. Two workingports are inserted under direct vision: one under thecostal margin and the other in the ipsilateral iliac


Figure 23.5 Intraoperative images of retroperito-neoscopic left upper pole heminephrectomy. (a) Theupper pole vessels are selectively ligated and divided.(b) Blanching of the affected moiety occurs. (c) Theaffected moiety is removed with the use of anendoloop to constrict the parenchyma.

(a)

(b)

(c)


fossa. The kidney can be identified either by reflect-ing the colon medially or through a transmesentericwindow. It can often help to identify the ureter firstand then trace this cranially towards the hilum ofthe kidney. Once the PUJ has been identified anddisplayed, the renal pelvis is stabilised with a ‘hitchstitch’ through the abdominal wall. The renal pelvisis then dismembered from the ureter and a portionmay be excised. The ureter is spatulated and theanastomosis is commenced by securing the tail ofthe spatulation to the inferior border of the dividededge of the renal pelvis (Figure 23.6). The poste-rior wall of the anastomosis is performed witha continuous absorbable suture. An antegradesilicone double J stent is placed across the anasto-mosis over a guidewire and the remainder of theanastomosis is completed with a further continuousabsorbable suture. A urethral catheter should be leftin situ for a minimum period of 48 hours or untilthe patient is fully mobile. The stent is removedcystoscopically after a period of 4 weeks.

Results

In experienced hands the technique of laparoscopicpyeloplasty provides comparable results to thoseobtained with the open technique. In a consecutiveseries of 170 procedures in adults, one UK group

reported a success rate of 96% at a median follow-up of 12 months. A similar success rate of 96%was reported in a cohort of 46 paediatric patientsfrom Hanover, Germany. Recent reports havedocumented the feasibility of laparoscopic pyelo-plasty in children <2 years of age, in children withhorseshoe kidneys as well as in children with duplexkidneys with associated PUJ obstruction. It is becom-ing increasingly reasonable to assert that laparoscopicpyeloplasty is the gold standard in the managementof PUJ obstruction in older children and adolescents.

Recent innovations inpelviureteric junction obstructionRecently there have been two developments relat-ing to the minimally invasive management of childrenwith PUJ obstruction: first, the introduction ofrobotic-assisted laparoscopic pyeloplasty; second,the development of the laparoscopic ‘vascularhitch’ operation for children with symptomaticPUJ obstruction secondary to lower pole accessoryvessels.

Robotic pyeloplasty

The introduction of the da Vinci system enablingprecise laparoscopic manipulations has openedthe door for a whole range of intracorporealreconstructive procedures. Robotically assistedpyeloplasty in children has been one of the firstapplications, with encouraging early results. Theadvantages of the da Vinci system include a magni-fied three-dimensional view of the operative field,wrist-like movements of the instrument tips with6° of freedom of movement and the elimination ofhand tremor (Figure 23.7). A major disadvantageof the da Vinci system is the lack of tactilefeedback, which requires the operator to rely to afar greater extent on visual cues. Another disad-vantage of the system is the large capital outlay andthe ongoing costs of consumables. Despite thesedrawbacks, the da Vinci system has already secureda place in modern paediatric surgery and urology.

The group from Boston Children’s Hospitalcompared an age-matched cohort of 33 children


Figure 23.6 Intraoperative view of laparoscopic leftpyeloplasty. The renal pelvis is stabilised with a ‘hitchstitch’ through the lateral abdominal wall (top rightcorner). An antegrade double J stent is placed acrossthe anastomosis over a guidewire.


undergoing open or robotic-assisted laparoscopicpyeloplasty. The average age in each group wasaround 7 years old. The robotic-assisted surgeryhad advantages in terms of reduced hospital stayand narcotic analgesic requirements, with operativetimes approaching those for open surgery. A morerecent report from a group in California showedsimilar findings, whereas a group from Philadelphiasuccessfully performed robotic-assisted laparoscopicpyeloplasty in 9 infants with ages ranging between3 and 8 months. Clearly, robotic-assisted surgeryhas a place in the paediatric population and thechallenge is to identify the correct balance betweencost, ethics and clinical benefit.

Laparoscopic ‘vascular hitch’

In children with antenatally detected PUJ obstruc-tion, lower pole crossing vessels are a rare finding,being present in only 6–11% of cases. By contrast,lower pole crossing vessels are a feature of 50–60%of cases of PUJ obstruction in older children –particularly in those who present with pain.

When crossing vessels are identified duringpyeloplasty, the usual approach is to transposethem posterior to the ureteropelvic anastomosis.

The aetiological relationship between crossingrenal vessels and PUJ obstruction remains contro-versial, with opinion divided over whether cross-ing vessels are incidental, aggravating or causativefactors. A causative role for crossing vessels maybe suggested by the direct intraoperative exami-nation of the PUJ: if dissection of crossing vesselsaway from the PUJ appears to relieve obstruction,and there is no evidence of intrinsic obstruction,then it is probable that the vessels are the solecause of the obstruction and symptoms. In suchcases, transposing the vessels superiorly withoutperforming a dismembered pyeloplasty may becurative. Pesce et al reported a successful outcomein 60/61 children treated with vessel transpositionalone, and Meng and Stoller reported success in9/9 adults treated with laparoscopic vessel trans-position. At our institution, laparoscopic vesseltransposition is offered to children with a clinicalpresentation suggestive of intermittent obstruction


Figure 23.7 The da Vinci system. (a) The da Vincihas three main components: the surgeon’s console;the AV stack system; and the surgical cart. (b) Therobotic instruments are attached to the arms ofthe surgical cart and inserted into the patient. (c) Thearticulation at the tip of the instruments provides 6° offreedom of movement.

(a)

(b)

(c)


and crossing vessels at laparoscopy, providedintraoperative inspection of the PUJ reveals noevidence of intrinsic obstruction. We routinelyperform preoperative magnetic resonance angiog-raphy (MRA) to demonstrate the presence ofcrossing vessels (Figure 23.8). The procedureitself is performed in a transperitoneal manner,similar to a laparoscopic pyeloplasty. The crossingvessels are dissected away from the PUJ, which iscarefully examined for evidence of intrinsicobstruction following an intravenous fluid bolus.Provided there is no evidence of intrinsic obstruc-tion, the vessels are sutured superiorly away fromthe PUJ, typically by fixation into a tunnel createdfrom the anterior wall of the dilated renal pelvis.This procedure offers the advantage of not incis-ing the upper urinary tract, and is a considerablyshorter procedure than laparoscopic pyeloplasty.To date we have performed the laparoscopicvascular ‘hitch’ in 20 children between 5 and17 years of age. With one exception, all patientsexperienced immediate resolution of symptoms,with a reduction in the degree of hydronephrosisand improved drainage parameters on follow-up imaging. One child developed recurrentsymptoms within a short interval and required alaparoscopic dismembered pyeloplasty. Laparo-scopic vascular ‘hitch’ is an alternative procedurein a select group of children who have sympto-matic PUJ obstruction due to crossing renalvessels.

Laparoscopic adrenalectomyLaparoscopic adrenalectomy is now considered bymany to be the standard of care for surgical excisionof the adrenal gland. Since the initial report oflaparoscopic adrenalectomy in 1992, it has evolvedinto a feasible and reproducible minimally invasiveprocedure for both benign and malignant adrenaltumours. Both the transperitoneal and retroperito-neoscopic approaches are well described. Althoughthe transperitoneal approach is used more widely,the retroperitoneoscopic approach offers distinctadvantages that make it a valuable alternative routeto the adrenal gland.

Indications

Laparoscopic adrenalectomy is indicated for thefollowing conditions:

• phaeochromocytoma• adrenal adenoma• ACTH (adrenocorticotrophic hormone)-

dependent Cushing’s syndrome• neuroblastoma.

Contraindications to a laparoscopic approachinclude previous renal surgery, large tumours>8 cm in diameter, coagulation disorders and inchildren with known adrenal carcinoma.

Preoperative work-up

A detailed ultrasound of the adrenal glandsprovides information relating to the location andsize of the mass, and whether it is cystic or solid.CT is also a very valuable modality (Figure 23.9).In some cases, typically ‘central’ Cushing’s syndrome,there is bilateral diffuse enlargement of the adrenalglands without a focal lesion. In addition to visual-ising the adrenal lesion itself, it is also essentialto determine if there is intravascular extensioninto the adrenal vein and inferior vena cava. This


Figure 23.8 Magnetic resonance angiogram. Three-dimensional image reconstruction demonstratesanatomy of the collecting system and the renal vascu-lature. The lower pole crossing artery overlies theregion of PUJ, indicating a possible aetiologicalrelationship in intermittent PUJ obstruction.


information serves as a guide to the suitability of alaparoscopic approach and also for planning thesafest approach for specimen retrieval, e.g.Endopouch, cyst aspiration, etc.

All hypertensive patients with a phaeochromo-cytoma require preoperative preparation with theadministration of phenoxybenzamine for 7 daysprior to surgery. In addition, the administration ofβ-blockers (propranolol) can decrease the risk oftachyarrhythmias, but should not be given withoutprior α-blockade.

Operative technique forretroperitoneoscopic adrenalectomy

The operative strategy is based on complete dissec-tion of the adrenal gland outside the surroundingadipose tissue. This minimises bleeding, which canoccur with dissection on the surface of the gland.Left adrenalectomy is more difficult than a rightadrenalectomy due to the absence of clear landmarks

such as the vena cava, coupled with the smaller sizeof the gland and adrenal vein. The key to success isstarting the dissection on the medial aspect in orderto identify and ligate the vessels at an early stage inthe operation.

The patient is positioned fully prone in a similarmanner to a retroperitoneoscopic nephrectomy.The same landmarks and access technique are usedto enter the retroperitoneum.

The kidney is dissected first, commencing atthe apex and along the medial aspect to exposethe posterolateral aspect of the kidney. The lateraland inferior attachments are not divided as theyhelp to anchor the kidney in position and aid inexposure of the upper pole. The inferior marginof the adrenal gland can be visualised at thesuperomedial border of the kidney. The arterialblood supply is identified first and divided. Theadrenal vein on the left side is less prominent thanon the right and thus is less easily identified. Onthe right side, the adrenal vein is short and entersdirectly into the vena cava. Once identified, theadrenal vein should be divided between clips, toavoid thermal injury to the vena cava. The glandis fully mobilised and freed of all attachments,placed within an endobag and removed throughthe camera port incision.

There is little doubt that laparoscopic adrenal-ectomy is a safe and effective procedure in bothadults and children. Controversy exists, however,on whether the transperitoneal or retroperitoneo-scopic approach is preferable. A recent publicationfrom Germany describes more than 560 laparoscopicadrenalectomies, of which 520 were performedretroperitoneoscopically. They reported lowconversion (<2%) and major complication (<2%)rates with this approach. Similar studies are lackingin the paediatric age group, with most centresreporting their individual experiences and prefer-ences based upon relatively small numbers ofpatients. In the author’s institution, eightretroperitoneoscopic adrenalectomies have beenperformed in seven patients, including one bilat-eral synchronous adrenalectomy. Diagnosesincluded adrenal cyst, cystic phaeochromocytoma,adrenal cortical tumour and ACTH-dependent


Figure 23.9 CT scan showing left cystic phaeochro-mocytoma in an 8-year-old male child.


Cushing’s syndrome. The technique providedexcellent intraoperative haemodynamic stabilityand all lesions were completely excised. In experi-enced hands, laparoscopic adrenalectomy is a safeprocedure in children, utilising either the transperi-toneal or the retroperitoneoscopic route.

Other techniquesLaparoscopic ureteric reimplantation

The gold standard for antireflux surgery remains theCohen cross-trigonal reimplantation, with successrates of 96%. The Lich–Gregoir extravesical reimplan-tation does not require cystotomy and has successrates approaching 90%, although there are concernssurrounding postoperative voiding dysfunction.

Various surgical techniques have been described forthe endoscopic correction of reflux using suburetericinjection of a variety of substances (see Chapter 5).Unfortunately, many patients require more than oneinjection, particularly for high-grade reflux.

Recently, a new approach has been described forthe surgical management of reflux which consists ofendoscopic intravesical reimplantation using theCohen technique. Since the bladder is a naturallyoccurring cavity, it can be insufflated with CO2 tocreate a pneumovesicum. The refluxing ureter ismobilised in a similar manner to the open techniqueand is then positioned in a cross-trigonal submucosaltunnel. Preliminary results in 16 children have shownthat this is a safe and effective technique, with resultscomparable to the open operation. Apart from thecosmetic advantages, it is claimed that patientsexperience less postoperative bladder spasms and canbe discharged on the day after surgery.

Laparoscopy in disorders ofsex development

Laparoscopy can play a valuable role in the investi-gation and management of children with disordersof sex development (DSD). It allows direct visual-isation of the internal genital anatomy including theuterus, müllerian duct remnants, gonads and vasadeferentia. Laparoscopy also provides an opportu-nity to perform gonadal biopsies where indicatedand to remove dysgenetic gonads or gonads which

are discordant with the sex of rearing (see Chapter20). Symptomatic müllerian duct remnants can beevaluated and removed with relative ease. Access tothe depths of the male pelvis can be challengingwith open techniques, with restricted visualisationof the seminal vesicles, ureters and vasa. The laparo-scopic approach provides a magnified view of thesestructures, which can therefore be meticulouslyseparated and preserved.

Laparoscopic cystolithotomy

Stone formation is a well-documented and relativelycommon complication of bladder augmentation.When stones occur, the key to preventing theirrecurrence is to minimise stone fragmentationduring removal. This usually mandates the useof open cystolithotomy rather than in situlithotripsy. An alternative approach is to removethe stones without intravesical fragmentation usingan Endopouch retrieval device. A laparoscopeis inserted via a small 10 mm suprapubic cystotomy.Under direct laparoscopic vision, a second 5 mmtrocar is placed into the augmented bladder. Thelaparoscope is moved to this trocar and a 10 mmEndopouch is inserted into the bladder via the10 mm cystotomy. The stones are captured withinthe Endopouch and removed either intact or byfragmentation within the pouch. The suprapubiccystotomy should be closed with an absorbablesuture and the bladder drained for 1 week beforerecommencing intermittent catheterisation.

Key points

• Minimally invasive alternatives toconventional open urologicalprocedures are increasinglyavailable in most paediatric urologycentres. Examples of procedures arenephrectomy, heminephrectomy,pyeloplasty and adrenalectomy.

• The relatively small size of paediatricpatients permits access to both the




upper and lower urinary tract throughthe same ports. Both thetransperitoneal and retroperitoneo-scopic approaches are utilised inchildren, although the retroperitoneo-scopic technique is increasinglyfavoured for renal procedures.

• Laparoscopic pyeloplasty remainsa technically challenging procedure,which at present is generally bettersuited to older children andadolescents. The advent of robotictechnology has made some aspects ofthe operation simpler.

• The advent of minimally invasivetechniques has provided a newinsight into disease processes,allowing the emergence of noveloperations such as laparoscopicvascular hitch for intermittent PUJobstruction due to crossing vessels.The technical boundaries of what canbe achieved are being constantlyextended, e.g. with the recentdevelopment of pneumovesicoscopicureteric reimplantation.

Further reading

Cascio S, Tien A, Chee W, Tan HL. Laparoscopic dismem-bered pyeloplasty in children younger than 2 years.J Urol 2007; 177: 335–338

Garg S, Gundeti M, Mushtaq I. The single instrument portlaparoscopic (SIMPL) nephrectomy. J Pediatr Urol2006; 3: 194–196

Gaur DD. Retroperitoneoscopy: the balloon technique.Ann R Coll Surg Engl 1994; 76: 259–263

Godbole P, Mushtaq I, Wilcox DT, Duffy PG. Laparoscopictransposition of lower pole vessels – the ‘vascular hitch’:an alternative to dismembered pyeloplasty for pelvi-ureteric junction obstruction in children. J Pediatr Urol2006; 4: 285–289

Gundeti MS, Taghizaedh A, Mushtaq I. Bilateral synchro-nous posterior prone retroperitoneoscopic nephrec-tomy with simultaneous peritoneal dialysis: a newmanagement for end-stage renal disease in children.BJU Int 2007; 99: 904–906

Lee RS, Retik AB, Borer JG, Peters CA. Pediatric robotassisted laparoscopic dismembered pyeloplasty: compari-son with a cohort of open surgery. J Urol 2006; 175:683–688

López PJ, Pierro A, Curry J, Mushtaq I. Retroperitoneo-scopic adrenalectomy: an early institutional experience.J Pediatr Urol 2007; 3: 96–99

Moon DA, El-Shazly MA, Chang CM, Gianduzzo TR,Eden CG. Laparoscopic pyeloplasty: evolution of a newgold standard. Urology 2006; 67: 932–936

Mushtaq I, Haleblian G. Laparoscopic heminephrectomy ininfants and children: first 54 cases. J Pediatr Urol 2007;3: 100–103

Smaldone MC, Sweeney DD, Ost MC, Docimo SG.Laparoscopy in paediatric urology: present status. BJUInt 2007; 100: 143–150

Walz MK, Alesina PF, Wenger FA et al. Posterior retroperi-toneoscopic adrenalectomy – results of 560 proceduresin 520 patients. Surgery 2006; 140: 943–948

Yeung CK, Sihoe JD, Borzi PA. Endoscopic cross-trigonalureteral reimplantation under carbon dioxide bladderinsufflation: a novel technique. J Endourol 2005; 19:295–299



Adolescent urology

Christopher RJ Woodhouse

Introduction

The major anomalies of the genitourinary tract arenow reconstructed in infancy and from the paedi-atric point of view the results are good. However,they leave a legacy of potential morbidity inadolescence and adult life. Many problems arepredominantly medical or psychosocial rather thansurgical in nature and it is essential to adopt aholistic approach to long-term care. Close collab-oration between paediatric and adolescent or adulturologists is also important to ensure continuity offollow-up and specialist care.

Renal function

The renal damage associated with many of thecongenital urological anomalies dates from foetallife and despite correction of the structuralanomaly, such as a posterior urethral valve, shortlyafter birth (or even in utero) hypertension andrenal failure may supervene in later life. Monitor-ing of renal function is therefore an integral part ofadolescent care – with blood pressure measure-ment, plasma creatinine and testing for proteinuriaforming an essential part of the annual review.

Patients who reach adolescence with a glomerularfiltration rate (GFR) of less than 40 ml/min/1.73 m2

are at a substantial risk of progressing to end-stage

renal failure within 16 years (Figure 24.1). Thedownward progress can, however, be delayed withrigorous control of proteinuria and blood pressurethrough the use of angiotensin-conversion enzymeinhibitors (ACEIs).

Hyperperfusion injury of the surviving nephronsis the mechanism which is generally responsiblefor this late decline in renal function, but it isimportant not to overlook the additional contri-bution of high-pressure bladder dysfunction,particularly in boys with a history of posteriorurethral valves (PUV).

24

Topics coveredVesicoureteric refluxBladder exstrophyFemale genital reconstructionHypospadias

Posterior urethral valvesPrune-belly syndromeEnterocystoplastySpina bifidaFertility

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Figure 24.1 Percentage of patients survivingwithout dialysis/transplantation by initial GFR (ml/min)corrected to 1.73 m2. Time zero was at entry intoadolescent follow-up around puberty.



Four groups of adults must be considered:

1. Adults whose vesicoureteric reflux (VUR)has either ceased or been corrected in child-hood. If there is no renal damage no follow-upis necessary.

2. Adults whose VUR has ceased or beencorrected in childhood but in whom refluxnephropathy is present. These patients needlifelong follow-up. By the age of 18 years 11%of those with unilateral scarring and 18%of those with bilateral scars have developedhypertension, a figure rising to 23% at 27years. If the renal damage is sufficiently severeto reduce the GFR below 40 ml/min/1.73 m2,late renal failure may be inevitable.

3. Reflux persisting from childhood beyondpuberty. There is no consensus on manage-ment, but it is has been the author’s practice torecommend surgical reimplantation in femalessince reflux nephropathy may be acquired inpregnancy. However, it has been reported thatwomen who have previously undergonereimplantation are at greater risk of urinaryinfection in pregnancy than any other group.Whether this is because their urinary tractswere the most damaged originally, or becauseof some consequence of reimplantation isunknown. In asymptomatic males there seemsto be no indication for surgery in the absenceof bladder outflow obstruction.

4. Adults presenting for the first time withvesicoureteric reflux. Because most are sympto-matic, surgical treatment (either endoscopic oropen) is indicated.

Bladder exstrophy

Most children with exstrophy have an isolatedanomaly and generally grow up very well, being bothintelligent and well motivated. Despite the excellentresults of bladder reconstruction reported from

major centres, there remains a lingering suspicionthat early diversion is also an acceptable form ofmanagement and one with a lower complicationrate. Certainly, reconstruction should only be under-taken by surgeons with very wide experience. Forthis reason, and because of the declining number ofnew cases, the surgical management of bladderexstrophy is now concentrated in two supraregionalcentres in England and Wales.

The reconstructed bladder may not be durableinto adulthood. Historically, only 23% of exstro-phy patients who underwent bladder reconstruc-tion in childhood progressed into adult lifewithout the need for urinary diversion. Of thosewhose bladder reconstruction did survive beyondchildhood, 60% required further reconstruction inadolescence or early adult life.

The risk of developing bladder cancer at a youngage is greatly increased in exstrophy patients, withan incidence which is 645 times greater than thatof the normal population by the age of 40 years.Most reported cases have occurred in bladderswhich were defunctioned by urinary diversion inchildhood and it is possible that the risk of malig-nancy will be lower in patients with a functioningreconstructed bladder.

Genital reconstruction inexstrophyMales

The penis in exstrophy is short but of normalcalibre. An intrinsic component of the deformity istight dorsal chordee which, if uncorrected duringinfancy, will prevent penetrative sexual intercourse(Figure 24.2). In adults the deformity is investi-gated by artificial erection, infusing both corporawith saline. Minor defects may be corrected by aventral Nesbit’s procedure, whereas severe peniledeformity requires more extensive correction by aCantwell–Ransley operation.

Females

The vagina is short and lies in a more horizontalplane than normal. The labia are located on the



anterior abdominal wall, the introitus is narrowedand the clitoris bifid (Figure 24.3). Although thelabia cannot be repositioned, the overall abnor-mality can be disguised and patients can havenormal sexual function. Fertility is unaffected,but uterine prolapse (procidentia) can be particu-larly troublesome for up to 50% of women.When one parent has bladder exstrophy the riskof exstrophy or epispadias in their offspring isapproximately 1:70.

Female genital reconstructionof ambiguous genitalia

The timing and nature of female genital recon-struction for conditions such as congenital adrenalhyperplasia is a source of growing controversy.Historically, very few studies have attempted todocument the long-term functional and psycho-logical outcome of feminising genitoplasty andvaginoplasty performed in childhood. However,evidence is accumulating from recent follow-upstudies which challenges some of the assumptionsunderpinning the current approach to femalegenital reconstruction, particularly the belief thatone-stage surgery in childhood will suffice. It isincreasingly clear that the majority of youngwomen will require further vaginal surgery,ranging from simple introital revision to complexvaginoplasty, to permit normal comfortable inter-course (Figure 24.4). Furthermore, impairedclitoral sensation is not uncommon. Continuity offollow-up from childhood into early adulthood isessential, with further care being undertaken in acentre specialising in adolescent gynaecology toensure access to relevant specialist expertise andappropriate psychological support.

Hypospadias

There are so many operations for the repair ofhypospadias that the non-specialist may despair ofever understanding even the basic techniques. Byadult life, however, most patients have experienced asatisfactory repair, at least by the standards of thesurgeon. Surgeons tend to view their own results inan overoptimistic light, sometimes with glowingreports of straight erections and normal urine streamin 100% of cases. When viewed more objectively, thelate results are less impressive and up to 50% of menexperience a poor functional or cosmetic outcome.

Patients themselves are less easily satisfied thantheir surgeons, with dissatisfaction centering onsome of those aspects of hypospadias that are leasteasy to correct such as penile and glans size and theabsence of a normal prepuce.

Adolescent urology 333

Figure 24.2 Clinical photograph of an epispadiacpenis showing dorsal chordee and retraction into therecessed mons area.

Clitoris

Labia minora

Introitus

Figure 24.3 Female perineum in exstrophy.


There is little consensus on the effect of hypospa-dias on sexual development, one problem being thattoday’s adults underwent correction of theirhypospadias using techniques that are now outdated.

If there are gross persistent anomalies, especiallychordee, intercourse may be impossible (Figure 24.5).With lesser anomalies, particularly of a cosmeticvariety, sexual debut and intercourse may be nearlynormal. When compared to boys operated forhernia or for phimosis, there are no differences inthe development of standard sexual milestones.Reduced semen quality has been reported in up to50% of men, although this does not appear to beaccompanied by a corresponding increase in theincidence of infertility.

Following repair of penoscrotal or perinealhypospadias (which has often presented initially asambiguous genitalia) intercourse is possible butejaculation is poor and infertility is common.

Posterior urethral valves

Bladder functionIt is essential to understand that the main long-term consequences of PUV occur because ofdamage to the bladder caused by the period ofobstructed voiding in utero and in the neonatalperiod before the obstruction is relieved by valve


Figure 24.4 Postpubertal outcome of feminising genitoplasty for the correction of virilisation associated withcongenital adrenal hyperplasia. Single-stage feminising genitoplasty previously undertaken in the first year of life.(a) External cosmetic outcome satisfactory, with no visible phallic hypertrophy and normal appearance of labiacreated from ‘scrotalised’ skin. (b) Retraction of the labia reveals introital scarring, requiring introitoplasty to permitnormal, comfortable intercourse.

(a) (b)


resection. The pattern of bladder dysfunction ischaracterised by poor compliance, detrusorinstability and reduced functional capacity (the‘valve bladder’). In adulthood, the pattern maychange to one of chronic retention, often withhigh pressure.

Although bladder dysfunction does not occur inall boys with a history of posterior urethral valves,the potential is always present and may not bemanifest until adolescence or early adult life. Thesymptoms will be familiar to all urologists asfrequency, urgency and incontinence. What maynot be recognised is the relentless effect of bladderdysfunction on the kidneys.

Renal functionThe progressive nature of renal failure in PUVboys has been recognised for many years. A studypublished in 1988 reported the incidence of renalfailure as 23% at 10 years, 30% at 16 years and43% at 30 years. In spite of improvements inmanagement and a greater understanding of thepathophysiology of the valve bladder, the figureshave not greatly improved, with an incidence of18%, 32% and 36% at comparable ages, reportedin 2005. It is important to note that normal levelsof serum creatinine at the beginning of puberty donot guarantee that the plasma creatinine will stillbe normal at the end of puberty.

Apart from the renal damage dating from theperiod of unrelieved obstruction before the valveresection, further ongoing damage is caused by thepoorly compliant bladder. Upper tract obstructioncauses damage to the medulla, resulting in renaltubular concentration defects and consequentpolyuria. There are, therefore, more bladder fillingcycles in a day so that longer periods are spent withdangerously high bladder storage pressures, thuscreating a vicious cycle of worsening renal damage.

Significant prognostic factors indicatingpoor long-term outcome include:

• diagnosis before the age of 1 year (includingprenatal diagnosis)

• diurnal incontinence persisting after 5 years of age• persistent bilateral reflux• polyuria.

Recent work has suggested that the risk of renalfailure can be averted or reduced by aggressivebladder management with anticholinergics, self-catheterisation and clam cystoplasty.

EjaculationLike the bladder, the prostate is damaged by backpressure before the valve is resected. This may lead toabnormal semen and poor ejaculation in up to 50%of patients. The seminal abnormality is characterisedby lack of liquefaction, low sperm count, poor motil-ity and high pH (up to 9.5). The effect on fertility isunknown but up to a third of patients appear to havesome difficulty in achieving paternity. The dilatedposterior urethra means that inadequate pressure isestablished at the beginning of orgasm, resulting inless forceful (or absent) ejaculation.

TransplantationA bladder which has contributed to the destruction ofthe two native kidneys and caused end-stage renalfailure is likely to do the same to a transplantedkidney. In the past, the published 5-year graft survivalin PUV patients was approximately 50% lower thanin all other recipients. However, current 5-year graftsurvivals figures are comparable, although PUV


Figure 24.5 Clinical photograph of a patient withpersistent chordee following repair of hypospadias inchildhood.


transplant patients have more infections and higherlevels of plasma creatinine than other transplantpatients, especially from 7 years onwards. It is essen-tial to correct any bladder abnormalities, by augmen-tation if necessary, before renal transplantation.

Prune-belly syndrome

Prune-belly syndrome is now very rare, at least inthe UK. The most likely explanation is that affectedpregnancies are being terminated. However, theimproved survival that was seen from the 1960sonwards has left a group of adults who have grownup very well.

There are three components to the syndrome(Figure 24.6):

• bilateral undescended testes• absence of the muscle of the anterior abdominal

wall• variable functional and anatomical anomalies of

the urinary tract.

Although each of these components has the poten-tial to affect long-term development, prune-belly patients generally grow well and tend to betall. Other, associated anomalies, notably skeletal,have been described, but with the exception ofkyphoscoliosis are seldom of great consequence.

Undescended testesIn the 1950s and 1960s it was believed that thetestes were so intrinsically abnormal that there waslittle prospect of fertility. Likewise it was incorrectlythought that the testes were too dysplastic to carryany appreciable risk of malignancy. Men with prune-belly syndrome were thought to be sterile and testic-ular biopsies showed Sertoli cells only. Orchdiopexywas, therefore, delayed either until a major recon-struction was performed or until late childhood. Ithas now become apparent that some germ cells arepresent and so the outlook is not so bleak. Therehave been reports of sperm in the semen. At leastone pregnancy has been achieved using intracyto-plasmic sperm injection (ICSI), which resulted intwins, one of whom was normal but the other hadmultiple anomalies. There have also been threereported cases of germ cell neoplasia.

Endocrine function is usually adequate toproduce virilisation and maintain masculinity butonly at the price of high pituitary drive. Serumtestosterone levels in adulthood are usually in thenormal range but serum luteinising hormone(LH) levels are two or three times normal.

The abdominal wallThe literature on the value of abdominal wallreconstruction during childhood is contradictory(Figure 24.7). Although it is certainly possible toimprove the wrinkled appearance of the skin, it isdoubtful whether there is any long-term benefit.Tightening of the skin is very unlikely to result insustained improvement without the necessaryunderlying muscular or fascial support.

In adult life the abdomen is protuberant, resem-bling a premature ‘pot belly’. However, there is nofunctional problem other than an inability to sit up


Figure 24.6 Characteristic appearance of the abdom-inal wall in a newborn infant with prune-belly syndrome.


directly from the lying position. Patients in theauthor’s practice are physically fully active andinclude a long distance cyclist and a mountaineer.

The kidneysThe long-term function of the kidneys is dependenton the degree of development in utero (severity ofany renal dysplasia) and the management of urinarytract abnormalities in childhood. By the time adultlife is reached, however, renal function has usuallystabilised. In a cohort of adult patients in the author’spractice who underwent minimal surgery in child-hood, 17 out of 21 patients have normal renal

function, with a mean GFR of 85 ml/min/1.73 m2

at a mean age of 24 years. Four are in end-stage renalfailure and another four are hypertensive. Early,major reconstruction was only performed in boyswith significant renal impairment at birth. In thisgroup, the prognosis has been worse and amongstthe eight patients who have reached adulthood fiveare in end-stage renal failure.

Satisfactory bladder function is generallymaintained, although cystitis may occur andshould always be investigated, particularly to lookfor residual urine after voiding. If this problem isidentified, it is most important to look for possibleoutflow obstruction, either at the level of theurethra or the bladder neck. Bladder outflowobstruction is a more likely cause of progressiveupper tract dilatation than upper tract obstruction.

Enterocystoplasty

All urinary reservoirs made of intestine have thesame basic long-term problems. Hyperchloraemicacidosis occurs in up to 14% of patients thoughmany more may have a metabolic acidosis withrespiratory compensation. Anaemia occurs in 8%.Vitamin B12 deficiency is a risk after 5 yearsespecially if terminal ileum is used. Reservoirstones occur in 12–15% of patients. Risk factorsinclude infection, need for self-catheterisation andretained mucus. Recent work has suggested thatthere may be metabolic abnormalities in somepatients with enterocystoplasty that predispose tostone formation.

The incidence of malignancy in patients withureterosigmoidostomies is 22% after a mean inter-val of 20 years. The interaction of urine and faecalbacteria in the sigmoid has been shown to result inthe presence of nitrosamine and other knowncarcinogens. Although low concentrations of suchurinary carcinogens have also been identified inbladders following enterocystoplasty, the overallrisk of malignancy is likely to be lower. One recentstudy found a 3.8% incidence of bladder malig-nancy in a large cohort of enterocystoplasty patientsfollowed for 20–25 years. Patients who undergo


Figure 24.7 Clinical photograph of an adult withprune-belly syndrome. Note the ‘pot-belly’. Pectuscavus, a common anomaly in prune-belly syndrome,is also present.


enterocystoplasty in childhood require careful long-term follow-up into adult life, with protocols whichshould include periodic cystoscopy.

Spina bifida – social andsexual development

In spite of great advances in management of babiesborn with spina bifida, the long-term problems arelegion. Approximately 20% of babies die in thefirst year of life. There is then a period of stabilitybefore a second wave of deaths occurs from aboutpuberty. By the age of 35 years only about 45% ofpatients are still alive (Figure 24.8). Cardiovascu-lar and pulmonary diseases are the commonestcauses of adult death. About 10% of adolescentsare unfit for major surgery, which makes it essen-tial that reconstructive surgery is completed inchildhood. Few if any of the problems experiencedby spina bifida patients improve with the passageof time.

Patients with spina bifida have a spectrum ofdisabilities, ranging from virtual normality to wheel-chair dependence and poor intelligence. Duringchildhood a heavy burden falls upon the parents, butindependent self-care should always be the long-termobjective. Achieving this goal depends on:

• adaptation of daily living to permit self-sufficiency in tasks such as dressing, washingand performing routine household chores

• bowel and bladder management• sexual education• general education.

The urologist has a role in all these aspects ofdevelopment.

Daily livingParents tend to be overprotective. Only 15%of spina bifida patients undertake the same house-hold chores as their normal siblings and 16% do noteven acquire a basic level of self-sufficiency. Twenty-eight per cent of females are not taught hygenicmanagement of menstruation. Up to 46% of

individuals with spina bifida develop pressure soresat some time.

Bowel management Even the mildest neurological deficit leads toincompetence of the anal sphincter. Faecal conti-nence is usually dependent on acquiring a patternof ‘controlled constipation’. The concept of theMalone antegrade continence enema (MACE) hasbeen an important advance in the management ofthe neuropathic bowel.

Bladder controlOnly a small percentage of individuals are conti-nent without the use of clean intermittentcatheterisation, which in many cases is in additionto reconstructive procedures. It is most importantthat surgery required to establish continence iscompleted before puberty, as the natural tendencyis for continence to deteriorate rather than toimprove. Very few adults with spina bifida,especially females, can learn urethral self-catheter-isation if not taught in childhood. Moreover,about 10% of wheelchair-bound patients becomeunfit for radical surgery in adulthood because ofinadequate respiratory reserve.

Sexual development – femalesThe impact of spina bifida on sexual function isclosely related to the level of the spinal cord lesionand the severity of the associated neuropathicbladder. Most females whose neurological


1 7 14 21 28 35

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Figure 24.8 Survival curve for all patients born withspina bifida.


impairment is below L2 are normal, as are mostof those who are continent of urine. In contrast,only about 20% of women with higher levels ofcord damage or with urinary incontinence experi-ence normal sexual function. Nevertheless, two-thirds form steady sexual relationships, regardlessof the degree of handicap or continence. Pregnan-cies are difficult, with high rates of urinary infec-tion and deterioration in bladder function. Theoverall risk of neural tube defect among offspringis 1:23 (1:50 for sons and 1:13 for daughters)though it can be significantly reduced by folicacid supplements for 3 months prior to concep-tion. Few spina bifida patients will accept antena-tal screening and termination of affectedpregnancies.

Sexual development – malesMales with intact sacral reflexes and urinary conti-nence are potent. Of those with absent sacralreflexes, 64% of those whose primary neurologicallevel is below D10 are potent, but the figure fallsto 14% in men with higher neurological levels.There is doubt about the true sexual nature of sucherections. Sildenafil (Viagra) may be helpful intreating erectile dysfunction in some cases. Semencan be obtained from impotent men by electroe-jaculation, but analysis reveals azoospermia.Despite these drawbacks 60% of adult males withspina bifida have a regular sexual partner regardlessof their degree of mobility or continence.

General education and socialadaptationRisk factors for poor social outcome are:

• mental handicap• poor manual dexterity• inappropriate schooling• overprotective parents.

The latter two factors can be overcome if they arerecognised and if appropriate support is provided.The presence of neuropathic bladder and bowel andthe overall level of neurological deficit (excluding

intellectual impairment) have little direct bearingon educational potential and social integration.

Fertility and pregnancy:general considerations

Most genitourinary anomalies have the potentialto cause sexual and reproductive problems inadolescence, with spina bifida, bladder exstrophyand posterior urethral valve patients being atparticular risk. Many others require reconstructionto allow sexual normality.

Many anomalies also affect fertility and pregnancyand while advances in reproductive technology haveimproved matters very considerably they are never-theless accompanied by stress and expense.

Poor male fertility is a feature of adults withbladder exstrophy, prune-belly syndrome, renalfailure, disorders of sexual differentiation (DSD)and spina bifida. Boys born with a unilateralundescended testis (UDT) probably have normalprospects of fertility. Those with bilateral UDTsuccessfully operated in childhood have about a50% chance of fathering a child.

Reduced fertility is seen in women with chronicrenal failure, DSD (including congenital adrenalhyperplasia) and anomalies of uterine develop-ment. There is a specific problem in confirmingpregnancy in women whose urine is stored withinan intestinal reservoir; the standard human chori-onic gonadotrophin (hCG) antibody (blue line)urine test is commonly positive in the absence ofpregnancy.

Pregnancy itself is associated with particularproblems in women with spina bifida, entero-cystoplasty, reimplanted ureters and bladderexstrophy. Almost all of the problems encounteredin pregnancy resolve after delivery. Women shouldalways be advised of such problems but few will bedeterred from having a baby. However, womenwith a GFR below 50 ml/min/1.73 m2 and adiastolic blood pressure (untreated) above 90 mmHgare notable exceptions and pregnancy carries verysignificant risks of irreversible deterioration.Between one-third and two-thirds of women with




this degree of renal impairment will be precipitatedinto end-stage renal failure during pregnancy.About 20% will be left with worse hypertensionand 20% with worse proteinuria after delivery.

Key points

• Individuals with evidence of renalscarring (reflux nephropathy) shouldundergo lifetime measurement ofblood pressure. Closer monitoring isrequired for those with severescarring who are at risk ofrenal impairment.

• Approximately one-third of boyswith posterior urethral valvesare destined for renal failure bythe time of adolescence oradult life.

• The incidence of new cases ofprune-belly syndrome has fallendramatically following theintroduction of antenatalscreening.

• Enterocystoplasty may beassociated with stones andmetabolic disturbances. The fullextent of the risk of malignancy inreconstructed bladders may not beapparent for some decades.

• Measures needed to restore urinarycontinence in patients with spinabifida should be commenced duringchildhood and completed beforeadulthood.

• Congenital urinary tractmalformations can have a major

long-term impact on fertility.Advances in in vitro fertilisationand improved obstetric care may,however, offer the prospect offertility to some of those whowould previously have beendenied parenthood.

Further reading

Baskin LS. Hypospadias. In: Stringer MD, Oldham KT,Mouriquand PDE (eds). Paediatric Surgery and Urology:Long-Term Outcomes. Cambridge: Cambridge UniversityPress, 2006: 611–620

Holmdahl G, Sillen U. Boys with posterior urethral valves:outcome concerning renal function, bladder functionand paternity at ages 31 to 44. J Urol 2005; 174:1031–1034

Mansfield JT, Snow BW, Cartwright PC, Wadsworth K.Complications of pregnancy in women after reimplan-tation for vesicoureteric reflux. J Urol 1995; 154:787–790

Mathews R, Gan M, Gearhart JP. Urogynecological andobstetric issues in women with the exstrophy–epispadiascomplex. BJU Int 2003; 91: 845–849

Neild GH, Thomson G, Nitsch D et al. Renal outcome inadults with renal insufficiency and irregular asymmetrickidneys. BMC Nephrol 2004; 5: 12–22

Patil KK, Duffy PG, Woodhouse CRJ, Ransley PG. Long-term outcome of Fowler–Stephens orchiopexy in boyswith prune-belly syndrome. J Urol 2004; 171: 1666–1669

Woodhouse CRJ. Long-Term Paediatric Urology. Oxford:Blackwell Scientific, 1991

Woodhouse CRJ. Myelomeningocoele in young adults.BJU Int 2005; 95: 223–230

Woodhouse CRJ. Genitoplasty in exstrophy and epispadias.In: Stringer MD, Oldham KT, Mouriquand PDE (eds).Paediatric Surgery and Urology: Long-Term Outcomes.Cambridge: Cambridge University Press, 2006:583–594

Woodhouse CRJ, Christie D. Nonsurgical factors in thesuccess of hypospadias repair. BJU Int 2005; 96: 22–27


Children and young people asurological patients

David FM Thomas

Introduction

Surgeons who care for children and young peoplemust demonstrate professional skills and attitudeswhich differ considerably from those employed inadult urological practice. One of the most obviousdifferences between paediatric and adult practice isthe extent to which the surgeon’s responsibilitiesextend beyond the individual patient to theirparents and family. Communicating effectivelywith parents and children who range in age fromtoddlers through to young adults calls for empathy,patience and a varied range of communicationskills. A report by the Healthcare Commissionnoted, however, that only 7–9% of surgeons andanaesthetists caring for children had received anyrelevant communication skills training.

Faced with the additional complexities inherentin treating children (and their anxious parents) itis perhaps understandable that many surgeonschoose to confine their consultant practice toadults. But those who do opt for a mixed adult andpaediatric practice and those who specialize inpaediatric urology or paediatric surgery know thatno other age group of patients is more rewardingto treat.

The aims of this brief chapter are to highlight themost important differences between adults andchildren as urological patients, to review theevidence on the impact of surgery and hospitalisa-tion in the paediatric age group and to consider the

implications for the provision of urological services.The chapter concludes by looking at the importantissues surrounding decision-making, competenceand informed consent.

History taking andexamination: practicalconsiderations

Whether in the ward or outpatient clinic it isimportant to establish the relationship of theadults to the child at the time of the first meeting.In some circumstances this may be particularlyimportant in order to clarify who has responsibil-ity (‘competence’ in legal terminology) to provideconsent on behalf of the child. Confidence andtrust are not conferred automatically, particularlywhen parents are anxious and acutely concernedfor the welfare of their child. For this reason it isessential that the surgeons introduce themselves,explaining their role in the team and outlining thepurpose of the consultation in relation to thepossible sequence of events in the child’s treat-ment. The initial priority is to establish a profes-sional working relationship with the parents and toshare information honestly with them in order toarrive at a course of action which all parties believeis in the best interests of the child. This processmay involve other health professionals and, possi-bly, other family members.

25

Topics covered Psychological aspects of surgical treatment in children Timing of surgery

‘Child friendly’ facilities Adolescents Consent for surgery


When taking the history from the parents, it ishelpful to try and uncover any unspoken concerns.For example, the completely innocent swellingwhich results from a collection of smegma trappedbetween the prepuce and glans may neverthelessraise the spectre of cancer in the minds of someparents. Obtaining a careful history from theparents can sometimes be the only means of estab-lishing the diagnosis of an inguinal hernia sincethis may not be clinically apparent, even as a coughimpulse, when the child is examined in the outpa-tient clinic. In toddlers and younger children thehistory will inevitably be obtained primarily fromthe parents, but, beyond this age, the informationprovided by the child can also make a very impor-tant contribution to the correct diagnosis. Forexample, in the assessment of daytime wetting,tactful questioning of the child herself mayuncover the fact that the child spends the entireday at school without visiting the toilet, a patternwhich strongly predisposes to dysfunctional voiding.Information volunteered by the child regardingvoiding habits at school often comes as a consid-erable surprise to the child’s parents.

The physical examination should always beundertaken with respect for the privacy of the childand in the presence of a parent or chaperon. Timespent putting the child at ease is usually wellrewarded – as are a gentle approach and respect forthe adage ‘warm smile and warm hands!’

Hospitalisation

The psychological impact of hospitalisation onyoung children has been well documented by anumber of important studies. Typically this ischaracterised by an acute reaction of stress, anxietyand behavioural disturbance. The stress created bythe strange and potentially threatening environ-ment of a hospital ward is compounded if infantsare separated from their parents. Behaviouraldisturbance after discharge from hospital is alsorelatively common, particularly in children under5 years of age. Long-term studies have demonstrated

that psychological morbidity is increased by hospi-talisation that exceeds 1 week in duration and byrepeated admissions. Moreover, prolonged orrepeated hospitalisation in the early years has beenshown to lead to reduced educational attainmentin later childhood.

The following measures can help to minimisethe harmful effects of hospitalisation on behaviourand emotional development:

• Wherever possible, routine urological proce-dures of a minor or intermediate nature shouldbe performed as day cases.

• There should be no restrictions to parentalaccess. For day-case procedures, parents shouldaccompany their child to the anaesthetic roomand be available in the recovery area after theinitial stages of recovery.

• Children should always be admitted to desig-nated childrens wards. Under no circumstancesshould children be admitted to adult wards.Facilities for play should be provided.

• Facilities for schooling should also be availablefor children requiring longer periods ofhospitalisation.

Timing of surgery

In the first few months of life, separation from theparent does not appear to have the same impact onsubsequent emotional development as separationat a later stage in development. By 6 months,however, babies form stronger attachments tocertain adults, particularly their mother. Separationdistress becomes apparent at around 6 months andis maximal in the second year of life. By 2 years ofage, self-awareness is well established and childrenbecome conscious of gender differences; it is alsoaround this age that children develop the capacityto acquire memories of painful or distressingevents. By 4–5 years of age, however, children aremore receptive to simple explanations of what theymay encounter in hospital and can be persuaded toaccept periods of separation from their parents.



Current paediatric urological thinking thereforefavours the complete surgical correction of mostcongenital genitourinary anomalies in the first yearor two of life, when the experience of hospitalisationis less likely to result in distressing memories andsubsequent behavioural and emotional disturbance.In this context the timing of corrective surgery forhypospadias has been the subject of a number ofstudies. Some earlier studies identified a degree oflate psychological morbidity in men who had under-gone correction of hypospadias in childhood.(However it should be noted that the techniques inquestion are now outdated.) By contrast, thefindings of more recent studies have been broadlyreassuring: for example, one recent study found nosignificant differences in psychosocial outcomesbetween individuals who had undergone hypospa-dias repair and a cohort of age-matched controls.Another study found that the incidence of emotionaland behavioural disturbance was not significantlydifferent from normal, unless the hypospadiassurgery had resulted in repeated hospitalisation. Afurther study comparing adults who had beentreated for hypospadias with adults who had under-gone inguinal hernia operations at a comparable agein childhood found no differences in psychologicalparameters between the two groups.

By contrast to the low risk of late psychologicalsequelae arising from a single procedure in child-hood, chronic conditions, repeated hospitalisationand numerous surgical interventions are associatedwith a far more significant burden of late psycholog-ical morbidity and mental health problems. For thisreason the provision of specialised psychologicalsupport should be available from an early age foryoung patients with chronic renal failure, disordersof sex development and other serious urologicaldisorders requiring ongoing or long-term treatment.

The practical implications include the following:

• Children requiring surgery that is likely to bean isolated event such as orchidopexy or single-stage hypospadias repair should, ideally, beoperated upon between 6 and 18 months ofage. Every effort should be made to limit the

period of hospitalisation, ideally by day-casesurgery whenever possible.

• Complex reconstruction requiring repeated orstaged procedures should be completed by18–24 months of age whenever this can beachieved without compromising the long-termoutcome. If further surgery is required, thisshould be planned for later childhood andsurgery should be avoided between the ages of2 years and 6 years.

• The timing of procedures which are dependentupon cooperation and self-management by thepatient (e.g. intermittent self-catheterisation ofa catheterisable stoma) should be determinedby a number of factors, including the emotionalmaturity and motivation of the young patientand the level of support available within thefamily and school.

• Certain procedures such as complex vaginoplastyor vaginal substitution should be deferred untilthe patient reaches adolescence or early adult-hood when she can give genuinely informedconsent herself and can cooperate with postoper-ative management such as vaginal dilatation.

Importance of the ‘childfriendly’ environment

The needs of children and their families are bestmet within the environment of a dedicatedchildren’s hospital. Nevertheless, considerableprogress has been made in recent years in creating‘child friendly’ facilities within non-specialistdistrict general hospitals. The recommendations ofa number of different professional bodies havebeen instrumental in setting standards:

• Outpatient activity should be organised insuch a way that children are seen in desig-nated surgical clinics held in a paediatricoutpatient environment rather than in mixedclinics devoted primarily to adults. If thiscannot be achieved, a segregated area suitablyfurnished for children should be provided.

Children and young people as urological patients 343


• The majority of routine urological proceduresin children can be performed on a day-casebasis. Wherever possible, elective paediatriccases should be concentrated in separatedesignated paediatric operating lists. Wherethis cannot be achieved, childrens’ operationsshould be grouped together at the beginning ofthe theatre list to avoid the need for anovernight hospital stay. A survey published bythe Healthcare Commission in 2007 foundthat 79% of elective general surgery in childrenwas performed on child-only theatre lists,although the figure was considerably lower forear, nose, and throat surgery.

Multidisciplinary team

Paediatric urology nurse specialists, who are basedpredominantly in specialist centres, make an invalu-able contribution to the overall provision of a high-quality service for children, young people and theirparents. Examples of their roles include teachingself-catheterisation and providing ongoing supportin the home and community setting for youngpeople with severe bladder dysfunction, liaisingwith schools and practice nurses and performingurodynamics. Their varied roles also encompasspreoperative counselling and postoperative outreachcare following more routine procedures such ashypospadias surgery. Skilled inpatient nursing careis also important to ensure optimal management oftubes and catheters. The sympathetic approach andexperience of the inpatient nursing team is also veryimportant in alleviating the apprehension whichcommonly surrounds procedures such as catheterand drain removal. Effective teamwork is one of thehallmarks of a successful paediatric urological unit.

Young people and adolescents

The needs of this emotionally vulnerable age grouphave been inadequately recognised in the past andthere is little doubt that many young people have

been disadvantaged by the arbitrary division intopaediatric and adult services. The importance ofimproving services for young people as they growinto adulthood was identified as one of the priori-ties of the UK Government’s National ServiceFramework for children and young people. Desig-nated adolescent units are already provided in somehospitals – predominantly specialist units, butcurrently these are very much the exception ratherthan the rule. Although most young people at theupper age limit of childhood (typically defined inmost non-specialist hospitals as the 16th birthday)can be safely treated in either an adult or children’senvironment, they should ideally be offered thechoice. The delivery of safe clinical care is not thesole priority, and far more effort is needed to createhospital environments tailored to the psychologicaland emotional needs of this age group.

Children and young people with serious urologicalabnormalities are now surviving into adult life, witha requirement for ongoing long-term specialist care.The transition from paediatric- to adult-orientedhealth services has been poorly managed in the past,with the risk of loss of follow-up and consequentmorbidity and mortality. Where possible, the transi-tion from the care of a paediatric specialist to anadolescent or adult urologist should be managedas a process of transition rather than a ‘one-off ’transfer of care. For young patients with complexdisorders and disabilities, the transition will alsoencompass other important aspects of multidiscipli-nary care: e.g. transfer from paediatric to adultnephrologists, psychologists and endocrinologists.

Consent

The legal issues surrounding consent in childrenand young people are complex and largely beyondthe scope of this short chapter. The followingsummary is intended as a guide rather than adetailed account of current position in English Law.

For children between the ages 0 and 16 years oldlegal ‘competence’ to provide consent ultimatelyrests with the adult(s) with ‘parental responsibility’.



In practice the legally competent adults are usuallythe child’s parents. Although the legal requirementplaced on the doctor is limited to obtaining consentfrom one person with parental responsibility, it isclearly preferable to involve both parents in thedecision-making process. It should be noted,however, that in some circumstances the law recog-nises that young people under the age of 16 dohave the capacity to provide consent without theinvolvement of their parents (based on the Gillickcourt ruling).

The legal position regarding those with‘parental responsibility’, as defined by theChildren Act 1989, is as follows:

• The child’s parents automatically haveresponsibility if they were married to eachother at the time of birth.

• The child’s mother (but not the father)automatically has legal responsibility if theparents were not married at the time ofbirth. However, this consideration does notapply if the father subsequently acquiredparental responsibility through the courtsor a parental responsibility agreement – orif the couple subsequently marry.

In some circumstances parental responsibility maybe assigned to:

• A legally appointed guardian who has beenappointed either by a court or by a parentwith parental responsibility subject to theirown death.

• A representative of a local authority desig-nated in a Care Order.

Children who have reached the age of 16 yearsold are presumed, in law, to be competent to giveconsent for their own surgical treatment and, assuch, can be regarded, in most respects, as adults.Nevertheless, it is clearly good practice to involveparents in the decision-making process and toencourage young people with legal competence(ages 16 and 17) to provide their consent after

discussion with their parents. The position is morecomplicated if someone of this age refuses treatment,but in general this request should be respected. Life-threatening illnesses are a possible exception.

Although the ultimate responsibility for provid-ing consent for children under the age of 16years old rests with the person with parentalresponsibility, the surgeon is also obliged to obtainthe consent of the young patient insofar as this isfeasible. Clearly, the extent of the child’s involve-ment is dependent upon their level of understand-ing and emotional maturity. The informationprovided and the degree of detail, particularlyrelating to possible complications and adverseevents, should be modified accordingly.

On the one hand, it is important to maintainreassurance and to avoid frightening the child byvolunteering potentially distressing information;on the other hand, the child is owed a simple andhonest account of what to anticipate postopera-tively. A misleadingly bland or inaccurate assurancethat it ‘will not hurt’ will undermine the child’sconfidence and trust in the doctors and nursingteam if it proves to be untrue.

Young people who have reached the age of 18years old are adults and, as such, have soleresponsibility for their own decisions providedthey have the capacity. Incapacitated adults andyounger patients aged 16 or 17 years old may betreated in a variety of circumstances on the basis ofother people’s assessment.

Obtaining informed consent is a process ratherthan a ‘one-off ’ event documented by a signatureon a surgical consent form. Before arriving at thepoint at which the consent form is signed, theinformation provided to parents (and youngpatient, if appropriate) during outpatient consulta-tions or ward rounds should include the indica-tions for surgery and an outline of possible risksand complications. The person giving consentmust be competent to do so (see above), shouldhave been provided with sufficient informationand should not be subjected to pressure or duress.

The person obtaining consent should, ideally,be the surgeon who will be responsible for



performing the operation. When this is not possi-ble, the consent should be obtained by someonewho is capable of performing the procedure inquestion. It is not acceptable for a surgeon todelegate responsibility for obtaining consent for amajor or risky operation to a junior trainee.

Although there is some variation in wording andlayout, most National Health Service (NHS)hospitals employ a standardised consent form.‘Procedure specific’ consent forms which weredevised for some specialties have not been widelyadopted within the NHS because of legal concerns,whereas, patient (or parent) information sheets arebeing used increasingly and are seen as a valuablecontribution to the consent process.

The introduction of new interventional proce-dures into surgical practice is now more formallyregulated than in the past and mechanisms forassessment and peer review are now in place withinthe NHS. An individual surgeon planning toadopt a new operation which has been developedelsewhere must be able to demonstrate that he orshe has received the appropriate training. Surgeonsare also under an ethical and legal obligation toprovide parents with an honest and balancedassessment of the perceived benefits and risks ofany innovative procedure, together with informa-tion on their experience and results.

Occasionally, during the course of an operation,it may become apparent that an additional proce-dure is required for which consent has not beenobtained. In this situation, the surgeon is under alegal obligation to obtain further consent for theadditional procedure. Indeed, the surgeon is onlypermitted to proceed to perform the additionalprocedure if the failure to do so would result indeath or irreversible harm. NHS consent formsgenerally include consent for photography andthe use of diagnostic images when this forms partof the child’s management and for the purposes ofteaching and research, providing the child cannotbe recognised. However, specific consent must besought if the child can be recognised or identified

in any material intended for teaching or research.Likewise, additional consent must be sought ifclinical photographs are intended for publication,even if the child cannot be recognised.

Key points

• The professional relationshipbetween surgeons and children andparents requires a different set ofcommunication skills and professionalattitudes to those employed in adultsurgical practice.

• The psychological impact ofhospitalisation in early childhoodis well documented. Whereverpossible, elective urologicalprocedures should be performed asday cases.

• Isolated procedures such ashypospadias repair or orchidopexyshould ideally be undertakenbetween 6 and 18 months of ageand staged reconstructive surgerycompleted before 18–24 months.

• The needs of adolescents inhospital have been inadequatelyrecognized and greater effort isneeded to create hospitalenvironments better suited tothis age group.

• Although legal responsibility forconsent in children under16 years old ultimately rests withthose who have parental responsibility,surgeons have a responsibility toinvolve young patients in the consentprocess and obtain their consent,insofar as this is feasible accordingto age and capacity.



Further reading

Department of Health. www.doh.gov.uk/consentLissauer T. History and examination, care of the sick child. In

Lissauer T, Clayden G (eds). Illustrated Textbook ofPaediatrics, 3rd edn. London: Elsevier, 2007: 9–22

Ludman L. Psychological aspects of paediatric surgery. In:Stringer MD, Oldham KT, Mouriquand PDE (eds).

Paediatric Surgery and Urology: Long-Term Outcomes.Cambridge: Cambridge University Press, 2006: 54–64

Sandberg DE, Meyer-Bahlburg HF, Hensle TW et al. Psychoso-cial adaptation of middle childhood boys with hypospadiasafter genital surgery. J Paediatr Psychol 2001; 26: 465–475

Surgery for children: delivering a first class service. Reportof the Children’s Surgical Forum. London: RoyalCollege of Surgeons of England, 2007




Appendix I Self-assessment section: Questions

Introduction

This section is intended to provide readers with anopportunity to test their understanding of thecontent of individual chapters by answering aseries of multiple choice questions (MCQs).

• All questions have been set using the ‘single bestanswer’ or ‘single correct answer’ format. Thistype of question is now widely used for testingfactual knowledge in postgraduate examina-tions, including the Intercollegiate examina-tions in Urology and Paediatric Surgery (FRCS(Urol) and FRCS (Paed)), the in-service exami-nation of the European Academy of PaediatricUrology and the Fellowship of the EuropeanBoard of Urology. This MCQ format is alsowidely used for postgraduate assessment inNorth America.

• Five answers are provided after each question –of which only one answer is correct. There is nonegative marking for incorrect answers.

• All the information needed for the reader toanswer the MCQs correctly is provided withinthe relevant chapter.

• Where percentages are quoted (for example, toincidence, complication rates etc), the “correct”answer is the figure quoted in the chapter. It isrecognised that there is sometimes considerablevariation in quoted incidences of differentconditions in the published literature. However,the authors have, as far as possible, cited figures

for incidence, complication rates, etc, which areevidence-based and derived from a range ofsources.

Chapter 1: Embryology

1 Which of the following mechanisms is prima-rily responsible for initiating early developmentof the kidney?

a) Differentiation of the pronephrosb) Interaction between the mesonephric ducts

and metanephrosc) Intraction between the ureteric bud and the

mesonephrosd) Interaction between the paramesonephric

ducts and metanephrose) Interaction between the ureteric bud and

metanephros

2 Which of the following is a recognised functionof Mullerian Inhibitory Substance (MIS)?

a) Causes regression of the mesonephric ducts b) Causes regression of the paramesonephric

ducts c) Converts testosterone to dihydrotestos-

terone d) Stimulates the second phase of testicular

descente) None of the above

Appendix-I Thomas-8043.qxd 2/29/2008 7:16 PM Page 349

3 Which of the following statements does notapply to the paramesonephric ducts?

a) They are present from the 6th week ofgestation

b) They give rise to the fallopian tubes, uterusand upper vagina

c) They regress in response to exposure tofoetal MIS

d) Their development is dependent uponexposure to foetal oestrogens

e) They may persist in some individuals with a46XY karyotype

4 Which of the following common conditionshave been shown to be linked to single genemutations?

a) Polycystic kidney disease b) Vesico ureteric reflux c) Hypospadiasd) Ureteric duplicatione) All of the above

5 Klinefelter’s syndrome is most commonly associ-ated with which of the following karyotypes?

a) 46XYb) 47XYYc) 45Yd) 47XXYe) 45X

Chapter 2: Renal Physiologyand Renal Failure

1 Which of the following patterns of physiologi-cal disturbance is most commonly encounteredin neonates?

a) Metabolic alkalosisb) Respiratory alkalosis c) Compensatory hypernatraemia d) Dilutional hyponatraemiae) Compensatory hypokalaemia

2 Which of the following statements is mostapplicable to renal osteodystrophy in childrenwith chronic renal disease?

a) It presents at an early stage with severespinal pain

b) The presentation is often non-specific andmay go unnoticed

c) Soft tissue calcification is more common inchildren than adults

d) Secondary hypoparathyroidism is found in70-90% of patients

e) Skeletal deformity does not occur inchildren

3 Which of the following statements bestdescribes the use of Erythropoietin in childrenwith chronic renal failure or end stage renaldisease?

a) It is usually administered orally b) It is usually administered subcutaneously c) Dosage is increased until a target haemo-

globin of 14.5g/dl is achievedd) Cardiac failure due to polycythemia has

been reported in 5–10% of casese) Erythropoietin treatment avoids the need

for iron supplements

4 Which of the following is the commonest causeof graft loss following renal transplantation inchildren?

a) Acute rejection b) Renal vascular thrombosis. c) Complications of immunosuppressant

medicationd) Chronic rejection e) Recurrence of primary disease

Appendix I350


5 A 6 month old child has a plasma creatinine of180 µm mol/L. At what age is the developmentof end stage renal failure most likely?

a) 12–18 months b) 2–5 years c) 5–10 years d) Older than 10 years e) Never – good long term prognosis for renal

function

Chapter 3: Diagnostic Imaging

1 Which of the following statements best describesindirect isotope cystography in children?

a) Uses intravenous I131mercapto-acetyltriglycineb) Uses intravenous Tc99m dimercapto-succinic

acidc) Uses intravenous Tc99m mercapto-acetyl-

triglycined) Is more sensitive than MCUG for the detec-

tion of Grades I and II VURe) Is equally suitable for children of all ages.

2 On initial postnatal ultrasound, which of thefollowing measurements of renal pelvic AnteroPosterior diameter denotes the presence ofclinically significant pathology?

a) Any degree of renal pelvic dilatation b) Renal pelvic AP diameter 5mmc) Renal pelvic AP diameter 7 mm d) Renal pelvic AP diameter 10 mme) None of the above

3 Which of the following statements bestdescribes the use of ultrasonography in theevaluation of the urinary tract in children?

a) The bladder should be empty to facilitatevisualisation of ureteroceles

b) Ultrasound is a sensitive modality fordetecting minor renal scarring in infants

c) Ultrasound is a sensitive modality for visual-ising non-dilated ureters in children

d) Ultrasound is a sensitive modality for visual-ising calculi in children

e) Ultrasound is a sensitive modality fordetecting grades I to III VUR in children

4 Which of the following statements mostaccurately describes the role of MRI in children?

a) MRI is inferior to plain X-ray for the inves-tigation of spinal dysraphism

b) T2-weighted images provide better anatomicaldetail than T1-weighted images

c) Modern MRI scanners no longer requiresedation or anaesthesia in infants or youngchildren

d) MRI is the cross-sectional imaging techniqueof choice in acute abdominal trauma

e) MRI can be used to visualise ‘crossingvessels’ associated with PUJ obstruction

5 By what approximate factor does the radiationdose from a combined abdominal and pelvicCT examination exceed the radiation dose of achest ray?

a) 5 to 10 times higher radiation dose b) 50 to 70 times higher radiation dose c) 200 to 300 times higher radiation dose d) 500 to 600 times higher radiation dose e) None of the above

Appendix I 351


Chapter 4: Urinary TractInfection

1 A 7 year old girl is admitted acutely with atemperature of 39.5 C and left loin pain. Whatis the most appropriate method of collectingurine to confirm the presumed diagnosis ofpyelonephritis?

a) Suprapubic puncture b) Clean catch mid-stream specimen c) Catheter urine specimen d) Adhesive collection bag applied to the genitalia e) Percutaneous renal aspiration

2 According to the 2007 NICE guidelines whichof the following is not regarded as a feature of‘atypical’ urinary infection meriting furtherinvestigation?

a) Family history of vesico ureteric reflux b) Palpable bladder c) Infection with an organism other than

E.Colid) Failure to respond to appropriate antibiotics

within 24 hours e) Elevated plasma creatinine

3 A 4 year old girl presents with symptoms ofdysuria, urgency and ‘smelly’ urine but is other-wise well. A urine dipstick test is negative forleucocyte esterase negative but positive fornitrite. According to the 2007 NICE guidelineswhat action should be taken next?

a) Send urine sample for microscopy andculture but await result before commencingantibiotics

b) Commence antibiotic treatment. It is notnecessary to send urine for microscopy andculture

c) Do not commence antibiotics and do notsend urine for microscopy and culture

d) Advise increased oral fluid intake and repeatdipstick test in 48 hours

e) Commence antibiotic treatment and sendurine for culture

4 Which of the following is regarded as diagnos-tic of infection in a clean catch mid-streamspecimen of urine?

a) Pure growth of >107 bacterial colonyforming units (CFU) per ml

b) Mixed growth of >107 bacterial colonyforming units (CFU) per ml

c) Pure growth of >102 bacterial colonyforming units (CFU) per ml if pyuria is alsopresent

d) Pure growth of >104 bacterial colonyforming units (CFU) per ml if nitritespositive on dipstick

e) Pure growth of >105 bacterial colonyforming units (CFU ) per ml

5 A 6 month old male infant has made a full recov-ery following a non-specific febrile illness whichproved to be a urinary infection. Ultrasounddemonstrates bilateral upper tract dilatation(collecting systems and ureters). Which of thefollowing is the most appropriate next investi-gation?

a) Intravenous urogram (IVU)b) Micturating cystourethrogram (MCUG)c) Indirect MAG3 isotope cystogram d) Direct MAG3 isotope cystogram e) MRI

Chapter 5: VesicouretericReflux

1 The injectable implant material Deflux consistsof which of the following materials?

a) Dextranomer/hyaluronic acid copolymer b) Polytetrafluoroethylene (PTFE) c) Polydimethylsiloxan (PDMS) d) Deactivated bovine collagen e) Deactivated bovine collagen/hyaluronic acid

copolymer

Appendix I352


2 Which of the following statements best describesthe familial basis of vesico-ureteric reflux?

a) VUR can be demonstrated in 70-80% ofsiblings of children with known VUR

b) VUR can be demonstrated in 30-40% ofsiblings of children with known VUR

c) VUR can be demonstrated in 10-20% ofthe offspring of parents with known VUR

d) 40–45% of children with non-syndromicVUR have an associated mutation of thePAX2 gene

e) None of the above

3 In the United Kingdom approximately whatpercentage of cases of end stage renal failure inchildren and young people are due to refluxnephropathy?

a) 5–10%b) 10–15%c) 20–25%d) 40–50% e) 50–60%

4 Which of the following statements bestdescribes the Cohen technique of uretericreimplantation?

a) It is an extravesical procedure b) The overall success rate for the complete

correction of VUR is 80-85% c) It is the operation of choice when

reimplanting grossly dilated mega uretersd) The submucosal tunnel length should be

4 or 5 times greater than the uretericdiameter

e) All of the above

5 Which of the following statements most accuratelydescribes the aetiology of reflux nephropathy?

a) Focal scarring seen on DMSA is more likelyto be due to infective damage than congen-ital dysplasia

b) Ongoing reflux of sterile urine results inprogressive renal scarring

c) Asymptomatic bacteruria can result in renalscarring

d) The maximum risk of scarring occurs withthe second and subsequent urinary tractinfections


Chapter 6: Upper TractObstruction

1 Unilateral upper tract dilatation has beendetected antenatally in a male infant. Postnatalimaging is as follows: Ultrasound ureteric dilata-tion (diameter 1.1cm) and pelvicaliceal dilatationwith a renal pelvic AP diameter of 1.3cm. MAG3at 6 weeks – ipsilateral differential function 49%,minimal washout with diuretic (type 3 B curve).MCUG - no reflux, normal bladder and urethra.Which of the following would be the mostappropriate management in this case?

a) Cutaneous ureterostomy b) Leadbetter Politano ureteric reimplantation c) Cohen ureteric reimplantation d) Percutaneous nephrostomy e) Antibiotic prophylaxis, follow up ultrasound

at 6 months

Appendix I 353


2 Which of the following statements bestdescribes pyeloplasty in children?

a) The Anderson-Hines pyeloplasty is nolonger the operation of choice

b) The overall long-term success rate of openpyeloplasty is greater than 95%

c) Randomised controlled studies have shownthat the use of JJ stents significantly reducesthe risk of post-operative complications

d) The lumbotomy incision offers greater flexi-bility to deal with unexpected operativefindings


3 A 6 year old girl is referred following an episodeof left abdominal/loin pain which has nowresolved. Ultrasound demonstrates moderatedilatation of the pelvis (AP Diameter 30mm)and calyces. Which of the following would bethe most appropriate next investigation?

a) Intravenous urogram b) 99mTc MAG3 isotope renogram c) Micturating cystourethrogram d) CT scan e) Antegrade pyelogram

4 Which of the following statements bestdescribes the aetiology of pelviureteric junctionobstruction?

a) It has a familial basis in 30-35% of casesb) It is inherited as an autosomal recessive

condition in 10-15% of casesc) Aberrant ‘crossing vessels’ are present in 30-

35% of infants with prenatally detected PUJobstruction

d) It occurs more commonly in boys than girlsby a ratio of 3:1

e) It affects the left kidney more commonlythan the right by a ratio of 2:1

5 Which of the following statements bestdescribes the use of MAG3 (Mercaptoacetyl-triglycine) for the investigation of upper tractobstruction?

a) Imaging is commenced approximately 3hours after injection

b) The radio pharmaceutical agent is I131

MAG3 c) MAG3 is more sensitive than MR urogra-

phy for quantifying differential renalfunction

d) Obstruction can be reliably diagnosed fromdrainage curve data in the first month of life

e) Measurement of Glomerular Filtration ratecan be combined with imaging

Chapter 7: Duplicationanomalies, ureteroceles andectopic ureters

1 According to the Meyer-Weigart Law,

a) the ureter draining the upper renal polealways enters the urinary tract below thebladder neck in females

b) the ureter draining the upper renal polealways joins the ejaculatory ducts in males

c) the upper and lower pole ureters may bothdrain into the bladder

d) the ureter draining the lower pole enters theurinary tract in a more cephalid positionthan the ureter draining the upper renal pole

e) the ureter draining the lower renal poledrains ectopically into the vagina in 10-15%of cases

Appendix I354


2 During investigation of urinary tract infectiona 4 year old boy is found to have a unilateralright-sided single system (orthotopic) urete-rocele. A MAG3 study demonstrates obstruc-tion with 32% differential function in theaffected kidney. Which of the following wouldbe the most appropriate management in thiscase?

a) Endoscopic incision b) Heminephroureterectomy c) Vesicostomy d) Trans-uretero ureterostomy e) Pyelopyelostomy

3 What is the autopsy incidence of upper tractduplication in the general population?

a) 0.0–0.1% b) 0.5–1%c) 1.5–2.5%d) 2.5–5%e) 5–10%

4 A 7 year old girl is referred with wetting.Although the history is suggestive of a possiblediagnosis of duplex kidney with ectopic ureterthe ultrasound findings are normal. Which ofthe following investigations should be under-taken next to pursue the presumptive diagnosisfurther?

a) IVU b) MRIc) 99m Tc MAG3 scan. d) Laparoscopy e) Careful examination of the perineum under

anaesthesia

5 Which of the following statements bestdescribes the occurrence and managementof vesico-ureteric reflux (VUR ) in duplexsystems

a) VUR typically affects the lower pole ureterin cases of complete duplication

b) VUR typically affects the upper pole ureterin cases of complete duplication

c) VUR in duplex systems is more likely toresolve spontaneously than VUR in singlesystems

d) VUR should never be managed by uretericreimplantation

e) Endoscopic correction of VUR is moresuccessful in duplex ureters than singleureters.

Chapter 8: Posterior urethralvalves and other urethralabnormalities

1 Which of the following is not a recognisedpredictor of long term renal impairment?

a) Maternal oligohydramniosb) Proteinuria c) Clinical presentation after 7 years of age d) Bilateral vesico ureteric reflux e) Impaired daytime urinary continence after

the age of 5 years

Appendix I 355


2 A 3.5kg term infant is born with an antenataldiagnosis of posterior urethral valves which isconfirmed postnatally on MCUG. His plasmacreatinine on the second day of life is 46mmol/L.Which of the following would be the mostappropriate form of intervention at this stage?

a) Vesicostomy b) Endoscopic valve ablation c) Bilateral nephrostomiesd) Bilateral loop ureterostomies e) Bilateral end ureterostomies

3 In the United Kingdom approximately whatpercentage of boys with posterior urethralvalves are currently diagnosed antenatally?

a) 10-20%b) 20-30%c) 40-50%d) 60-70%e) >80%

4 Which of the following statements bestdescribes the current status of vesico amnioticshunting for foetuses with prenatally detectedposterior urethral valves?

a) The long term benefits of shunting havebeen confirmed by the United Kingdom’sPLUTO trial

b) Shunting has been shown to reverse renaldysplasia providing it is performed before16 weeks gestation

c) Shunting may increase the severity ofpulmonary hypoplasia

d) Shunting may reduce the severity ofpulmonary hypoplasia

e) The long term results of intra uterine valveablation are superior to vesico amnioticshunting

5 An 11 year old boy is referred with a 4 monthhistory of dysuria and occasional spotting ofblood from the urethral meatus. The most likelydiagnosis is

a) Cobbs collar b) posterior urethral polypc) urethral calculus d) urethritis e) rhabdomyosarcoma involving the posterior

urethra

Chapter 9: Cystic renaldisease

1 Which of the following statements bestdescribes the features of autosomal recessivepolycystic kidney disease?

a) The kidneys typically appear small andcystic on antenatal ultrasound

b) This form of polycystic disease may beassociated with maternal oligohydramnios

c) The disorder typically presents with hyper-tension, abdominal pain, abdominal mass,etc, in late childhood or adult life

d) Mutations of the PK2 gene are present in85-90% of cases

e) Percutaneous cyst drainage reduces theincidence of pain and infection

2 Which of the following statements mostaccurately describes the inheritance of multicys-tic dysplastic kidney (MCDK)?

a) MCDK is most commonly inherited as anautosomal recessive disorder

b) MCDK is most commonly inherited as anX-linked recessive disorder

c) MCDK is most commonly inherited as anautosomal dominant disorder

d) MCDK is associated with mutation of the PK1gene on chromosome 16 in 65-70% of cases

e) MCDK is most commonly a sporadicanomaly

Appendix I356


3 What percentage of adults on end stage renalreplacement programmes have autosomaldominant polycystic kidney disease? a) 1–5%b) 5–10%c) 15–20%d) 20–25%e) 25–30%

4 A female infant has an antenatally detectedunilateral MCDK. Her contralateral kidney isnormal and she is otherwise healthy. What isher approximate life time risk of developing aWilms tumour in the MCDK?

a) Less than 0.1%b) 0.5–1%c) 1–1.5%d) 1.5–2%e) Greater than 2%

5 Postnatal ultrasound in a newborn infantreveals findings consistent with a diagnosis ofunilateral multicystic dysplastic kidney. Whichof the following would be the most appropriatenext investigation?

a) 99mTC DMSA scanb) IVU c) Measurement of glomerular filtration rate

(GFR) d) CT scan e) MRI

Chapter 10: Prenatal Diagnosis

1 At what stage in gestation is routine antenatalultrasound screening for foetal anomalies(including the genitourinary tract) mostcommonly performed in the United Kingdom?

a) 10 to 12 weeks b) 12 to 14 weeks c) 15 to 20 weeks d) 20 to 25 weeks e) 25 to 30 weeks

2 Which of the following antenatal ultrasoundfindings would not routinely merit a routine apostnatal MCUG?

a) Duplex kidney b) Thick walled bladder c) Unilateral pelvicaliceal dilatation (AP diame-

ter renal pelvis 25 mm) without uretericdilatation

d) Unilateral pelvicaliceal dilatation AP diame-ter renal pelvis 25mm with ureteric dilatation

e) Bilateral upper tract dilatation in a male infant

3 At 20 weeks gestation dilatation of the left renalpelvis and calyces (AP diameter renal pelvis of16mm) is identified in a male foetus. The rightkidney is normal. What would be the mostappropriate advice to the parents regardingmanagement at this stage in the pregnancy?

a) Termination of pregnancy b) Ultrasound guided nephrostomy to decom-

press the left kidney c) Fetoscopic pyeloplasty d) No intervention, re scan in the third

trimester e) Elective pre term delivery at 34 to 36 weeks

followed by urgent neonatal pyeloplasty

4 Which of the following is not regarded as apredictor of poor outcome for renal function ina foetus with outflow obstruction?

a) Foetal plasma creatinine greater than150µmol/L

b) Oligyhydramniosc) Foetal urinary sodium greater than

100mEq/L after 20m weeks gestation d) Increased levels of urinary beta 2

microglobulin e) Elevated urinary calcium (greater than

1.2mmol/L)

Appendix I 357


5 Approximately what percentage of newborninfants with a prenatally diagnosed urinary tractabnormality are also found to have relevantclinical signs on neonatal examination?

a) <5% b) 5–10%c) 10–15%d) 15–20%e) > 20%

Chapter 11: Stone disease inchildren

1 A 9 year old boy presents with a 1.1cm stone inthe distal left ureter. There is moderate dilata-tion of the ureter and collecting systems onultrasound. He is pain free but the appearanceson further imaging after two weeks areunchanged. Which of the following is now theoptimal management of this young patient?

a) External shockwave lithotripsy (ESWL)b) Conservative – re-assess with further imaging

after two months c) Open ureterolithotomyd) Basket extraction e) Ureteroscopy and laser lithotripsy

2 Which of the following statements bestdescribes the role of percutaneous nephro litho-tomy (PCNL) in children?

a) PCNL can be employed safely and effec-tively in all age groups of children

b) PCNL can be performed without anaesthe-sia in older children

c) Stones are most commonly disintegratedwith an ultrasound probe

d) Stones are most commonly extracted intactfrom the kidney using a modified stone basket

e) Renal cooling is undertaken to minimise therisk of parenchymal damage

3 A 10 year old girl is referred with a provisionaldiagnosis of xanthopyelonephritis? Which of thefollowing features of her presentation and inves-tigation is not consistent with this diagnosis?

a) Differential function 28% on DMSA scan b) Elevated ESRc) Weight loss d) Haemoglobin 8.5g/dle) Palpable mass

4 Which of the following is the most commoncause of metabolic stones in children?

a) Hyperoxaluriab) Cystinosisc) Hypercalcuria d) Uric acidaemia e) Xanthine oxidase deficiency

5 A 2 year old boy presents with haematuria. Anultrasound scan on admission demonstrates a‘staghorn’ calculus in the left kidney. Urineculture is positive. What is the most likelyinfecting organism in this case?

a) E.Colib) Strep faecalisc) Enterococcusd) Staph aureuse) Proteus

Chapter 12: Urinaryincontinence

1 During the process of normal voiding, detrusorcontraction is initiated in response to stimula-tion via which of the following pathways?

a) Voluntary somatic S2 -4 pathways b) Parasympathetic S 2 to 4 pathways c) T 10 to 12 lumbar sympathetic pathways d) T 10 to 12 lumbar parasympathetic pathways e) None of the above

Appendix I358


2 A 6 year old girl is referred with a history ofdiurnal and nocturnal incontinence. She cameout of nappies at 2 ½ years of age and was dryduring the daytime (but not at night), untilaround 3 years of age. Since then, she has beenwetting on an almost daily basis. Which of thefollowing is the most likely diagnosis basedupon this history?

a) Occult spinal dysraphism b) Sacral agenesis c) Dysfunctional voiding d) Pelvic floor weakness (stress incontinence) e) Ectopic ureter

3 A 7 year old boy is referred with a lifelonghistory of nocturnal enuresis. He wets the bedvirtually every night but has been consistentlydry during the daytime since the age of three.Physical examination is normal. Which of thefollowing would be the most appropriate?

a) Ultrasound scan with pre and post voidbladder views

b) Early morning urine osmolality c) Urodynamics d) Spinal x-ray e) Reassurance, no investigation

4 A 12 year old girl is referred with a history ofincontinence which is confined to occasionswhen she is laughing and joking with friends.She is dry at other times. Which of the follow-ing forms of treatment would have the highestchance of providing symptomatic relief in thispatient?

a) Pelvic floor exercises b) Methylphedinate c) Oxybutinin d) Tolterodine e) Desmopressin

5 Which of the following anatomical causes ofurinary incontinence in girls is least likelyto be detected on visual examination of theperineum?

a) Congenital cloacal anomaly b) Urogenital sinus anomaly c) Primary epispadias d) Ectopic ureter e) Labial adhesions

Chapter 13: Neuropathicbladder

1 ‘Intermediate’ neuropathic bladder dysfunction ischaracterised by detrusor hyperreflexia combinedwith partial sphincteric incontinence. Whatpercentage of children with myelomeningoceleexhibit intermediate neuropathic dysfunction?

a) 15–25%b) 25–35%c) 35–45%d) 55–65%e) 65–75%

2 Which of the following structures is usually used tocreate the Monti continent catheterisable conduit? a) Ileumb) Caecum c) Colon d) Appendixe) Rectus sheath

3 Using the formula provided in the chapter,what is the calculated functional bladder capac-ity of a normal 6 year old child?

a) 110 to 130mlb) 160 to 180mlc) 200 to 220mld) 260 to 280mle) 310 to 370ml

Appendix I 359


4 Which of the following is not a recognised formof treatment for reduced bladder capacityassociated with detrusor over activity?

a) Ileocystoplasty b) Botulinum toxin Ac) Sigmoid colocystoplasty d) Alpha agonist medication e) Anti cholinergic medication

5 What is now the most common cause of neuro-pathic bladder in children?

a) Spinal injury b) Occult spinal dysraphism c) Transverse myelitis d) Sacral agenesise) Myelomeningocele

Chapter 14: The urinary tractin anorectal malformations,multisystem disorders andsyndromes

1 What percentage of children with anorectalmalformations have co-existing anomalies ofthe urinary tract?

a) 15–25%b) 25–35%c) 35–45%d) 45–55%e) 55–65%

2 A newborn male infant has a low anorectalanomaly. What imaging modality is currentlyrecommended for initial imaging of his spine?

a) MRIb) CT c) Spinal x-ray and ultrasound d) Bone scan e) Contrast myelography

3 Which of the following is not a recognisedfeature of the VACTERL association?

a) Vertebral anomalies b) Anorectal anomalies c) Eye anomalies (coloboma) d) Renal anomalies e) Limb anomalies

4 A healthy newborn female infant is born witha presumed diagnosis of unilateral renalagenesis – based on antenatal ultrasound. Onlyone (normal) kidney is seen on the postnatalultrasound scan. What investigation (if any) isindicated next?

a) None. The diagnosis of renal agenesis hadbeen confirmed on two ultrasound scans

b) MRIc) CTd) Laparoscopy e) DMSA scan

5 Which of the following statements does notapply to horseshoe kidneys?

a) Horseshoe kidney is well visualised onDMSA renography

b) Horseshoe kidney occurs more commonlyin children with Turners Syndrome

c) The autopsy incidence of horseshoe kidneyis reported to lie between 1:400 and 1:1800

d) 35–45% of horseshoe kidneys are associatedwith fusion of the upper pole renalparenchyma

e) Horseshoe kidney is associated with anincreased incidence of PUJ obstruction

Appendix I360


Chapter 15: Bladder exstrophyand epispadias

1 The incidence of bladder exstrophy is approxi-mately:

a) One in 5000 live births b) One in 25 000 live births c) One in 50 000 live births d) One in 150 000 live births e) One in 300 000 live births

2 Which of the following is not a common featureof primary epispadias?

a) Sphincteric weaknessb) Pubic diastasis c) Normal calibre ureteric orifices d) Urethra sited on the dorsal aspect of the penis e) Anterior ectopic anus.

3 A 3.5kg male infant with classic bladder exstro-phy is transferred to a specialist centre at 6hours of age. He is otherwise well with noevidence of cardiac or other anomalies. What isnow the optimal management of this infant?

a) Primary closure with pelvic osteotomy inthe first 48 hours of life

b) Primary closure without pelvic osteotomyin the first 48 hours of life

c) Parental nutrition for one month followedby closure with pelvic osteotomies.

d) Temporary urinary diversion with ureteros-tomies following by primary closure andundiversion at 6 months

e) Delayed closure with augmentation cysto-plasty at 12 months.

4 Which of the following anomalies are associ-ated with cloacal exstrophy?

a) Sacral agenesis in 30- 40% of cases b) Renal anomalies in 15-25% of cases c) Skeletal abnormalities affecting the pelvis

and lower limbs in 10-20% of cases. d) Small bowel defects in 60-70% of cases e) All of the above

5 Which of the following statements best describesthe features of primary epispadias in girls?

a) Normal continence occurs spontaneously in85% of cases by 7 years of age

b) Sphincter weakness incontinence is invari-ably present

c) The external genitalia are usually normald) The clitoris is usually absent e) The overall chances of achieving pregnancy

are less that 10%

Chapter 16: Hypospadias

1 Which of the following statements is mostapplicable to the Mega Meatus Intact Prepuce(MIP) variant of hypospadias?

a) The MIP variant is usually detected onroutine neonatal examination

b) Circumcision is sufficient to create a satis-factory cosmetic appearance

c) The MAGPI procedure is the operation ofchoice for correcting the MIP variant

d) The MAGPI procedure is unsuited to thecorrection of the MIP variant


2 What is the overall incidence of co-existing upperurinary tract anomalies in boys with hypospadias?

a) 1–5%b) 5–10%c) 10–15%d) 15–20%e) 20–25%

3 Which of the following graft materials is mostwidely used in the first stage of a two stagerepair of proximal hypospadias?

a) Post auricular skin b) Buccal skin c) Bladder mucosad) Porcine dermise) Inner preputial skin

Appendix I 361


4 Which of the following statements best describesthe aetiology and epidemiology of hypospadias?

a) The incidence is increased in low birth-weight infants

b) The incidence is increased in the offspringof older mothers

c) The overall incidence of male first degreerelatives is 5-20%

d) Hypospadias is more common in monozy-gotic twins

e) All of the above

5 A healthy infant is referred with hypospadias.The urethral meatus is located at the junction ofthe proximal two thirds and distal one thirdof the penile shaft and there is no evidence ofchordee. What type of operative repair iscurrently favoured by most paediatric urologistsfor this type of hypospadias?

a) Two stage repair b) Buccal mucosa graftc) Onlay island flapd) Meatal advancement and glanluloplasty

(MAGPI)e) Tubularised incised plate repair (Snodgrass)

Chapter 17: The prepuce

1 Which of the following statements bestdescribes the aetiology and management ofbalanitis xerotica obliterans (BXO) in children?

a) BXO carries a 1-3% risk of penile carcinomabefore the age of 20 years

b) Treatment with topical steroids avoids theneed for surgery in 80-85% of cases

c) Preputioplasty is preferable to circumcisionfor the treatment of BXO in boys over 10years of age

d) Glans involvement is present in 5-7% ofcases

e) BXO is rare in children under 5 years of age

2 The parents of a 4 year old boy are concernedbecause they have observed obvious ballooningof his prepuce during micturition. Which of thefollowing is most applicable in this case?

a) The ballooning probably denotes thepresence of BXO

b) Measurement of his urine flow rate is likelyto show a significant reduction

c) The most likely diagnosis is congenitalmega prepuce

d) The parents can be reassured that balloon-ing is a self-limiting phenomenon of nopathological significance

e) The presence of ballooning is a strongindication for circumcision

3 Which of the following statements bestdescribes the features of congenital megaprepuce?

a) The condition is characterised by an exces-sively long, redundant prepuce

b) The overall appearances may resemble a‘buried’ penis

c) Circumcision usually gives satisfactorycosmetic results

d) Any male siblings will also have a 1:4chance of being born with this condition

e) Any male siblings will also have a 10-15%chance of being born with this condition

4 Which of the following statements is mostapplicable to preputioplasty?

a) Preputioplasy can be used as an effectivealternative to circumcision in 70-80% ofboys with BXO

b) Retraction of the prepuce should be avoidedfor three to six months after the procedure

c) Regular retraction of the prepuce shouldbe advised in the early post-operativeperiod

d) Preputioplasty is equally successful in all agegroups


Appendix I362


5 A 5 year old boy is referred with a non-retractile prepuce. The prepuce is healthy butcannot be retracted beyond the tip of the glansbecause of preputial adhesions. What manage-ment should be advised?

a) Reassurance, see again only if symptoms arise b) Circumcision c) Preputioplasty d) Surgical release of adhesions under general

anaesthesia e) Surgical release of adhesions under general

anaesthesia if the prepuce is still partiallyadherent to the glans at 6-7 years of age

Chapter 18: Testis, hydroceleand varicocele

1 A 17 year old patient presents for the first timewith a small palpable testis in the inguinalregion. Orchidectomy is performed. The histo-logical appearances of these testis are mostlikely to show:

a) Germ cell hyperplasia b) ‘Sertoli cell only’ appearances c) Normal appearances d) Well-differentiated seminoma e) Leydig cell hyperplasia

2 A three year old boy is referred with a unilateralimpalpable testis. The most reliable meansof confirming the presence or absence of thetestis is:

a) Abdominal ultrasonography b) MRIc) CT scan d) Retrograde venographye) Laparoscopy

3 A 2 ½ year old boy presents with a lax left sidedscrotal swelling which can be transilluminated.The clinical findings are those of a hydrocele.Which of the following statements bestdescribes the clinical features and managementin this patient?

a) The hydrocele is most likely to be of thenon-communicating variety

b) There is a 90% probability of spontaneousresolution in the next 12 months

c) The hydrocele should be aspirated andre-assessed after 6 months

d) Inguinal ligation of the processus vaginaliswould be the most appropriate operativeprocedure

e) A Jaboulay operation would be the mostappropriate operative procedure

4 An 11 year old boy presents with a painlessgrade III left sided varicocele. What adviceshould be given to his parents?

a) Infertility is inevitable unless some form ofintervention is undertaken

b) Treatment of the varicocele is likely to carrya 50% failure rate regardless of the mode oftreatment

c) A CT renal scan should be performed inview of the 2% risk of Wilms tumour

d) An ultrasound scan of the testes and kidneysis all that is required at this stage

e) A semen sample should be analysed beforedetermining further management

Appendix I 363


5 Testicular ultrasound in a 14 year old boydemonstrates bilateral microcalcification. Thisis essentially an incidental finding following asporting injury. What action should be advisedin the light of these findings?

a) Reassurance, no further follow up unlesssymptomatic

b) Urgent testicular biopsyc) Testicular biopsy around the age of 19 or 20

years d) Bilateral prophylactic testicular fixation in

view of the high risk of testicular torsion e) Six monthly ultrasound review for 5 years

with annual ultrasound examination there-after

Chapter 19: The acute scrotum

1 Scrotal exploration is being performed in a 14year old boy for a presumed diagnosis of righttesticular torsion. He has a 10 hour history ofsymptoms. The diagnosis is confirmed butdespite detorsion, the testis remains dark bluein colour with no evidence of perfusion. Whataction should the surgeon take?

a) Right orchidectomy. Defer fixation of theleft testis until a second operation in view ofthe risk of infection

b) Right orchidectomy combined with simul-taneous fixation of the left testis within adartos pouch

c) Right orchidectomy combined with simul-taneous fixation of the left testis withprolene sutures

d) Leave the right testis in situ (in the hope itmay contribute to endocrine function).Simultaneous suture fixation of the left testis

e) Right orchidectomy and implantation ofsilicone gel prosthesis, simultaneous suturefixation of the left testis

2 A 5 year old boy presents with diffuse swellinginvolving both sides of the scrotum He isafebrile and has only minimal discomfort. Whataction should be taken next?

a) Urgent surgical exploration to exclude anatypical presentation of bilateral synchro-nous testicular torsion

b) Commence intravenous antibiotics c) Full blood count, platelet count and plasma

viscosity d) Oral Prednisilone e) No specific treatment

3 A 13 year old boy presents with severe rightiliac fossa pain of sudden onset. No abnormal-ity if detected on abdominal palpation. Hisright testis is moderately tender but there is noerythema of the overlying scrotal skin. Howshould he be investigated and managed?

a) Scrotal ultrasound b) Admit for observation, re-assess clinical

findings after 4 hours c) Doppler ultrasound d) Radionuclide scan e) No investigation, proceed directly to surgi-

cal exploration

4 A 17 year old patient with testicular torsion hasundergone unilateral orchidectomy for a non-viable testis. What advice should be given inresponse to questions regarding the prognosisfor endocrine function and fertility?

a) Reassurance that semen quality will beunaffected

b) Testosterone levels should be checkedannually since endocrine replacement treat-ment may be required

c) Semen quality is likely to be impaired but itis not possible to predict the extent to whichthis might affect paternity

d) Semen quality is likely to be impaired andavailable evidence indicates that infertility isinevitable


Appendix I364


5 Which of the following statements does notapply to torsion of the Hydatid of Morgagni?

a) The ‘blue dot’ sign is present in 50-60% ofcases

b) The peak incidence is between 10 and 12years of age

c) It can usually be diagnosed on clinicalgrounds

d) The pain is usually more gradual in onsetthan testicular torsion.

e) Conservative management can be safelyconsidered if symptoms are mild or resolving

Chapter 20: Disorders of SexDevelopment

1 Which is the commonest disorder of sex devel-opment encountered in Europe and NorthAmerica?

a) Ovotesticular DSD b) 5 Alpha reductase deficiency c) 46XX DSD due to congenital adrenal

hyperplasiad) Mixed gonadal dysgenesis e) 46XY DSD (male pseudo hermaphroditism)

2 Which of the following statements bestdescribes the features of children with Turner’sSyndrome?

a) Clitoral hypertrophy is present in 80-90%of patients

b) Normal ovarian tissue is present in 55-75%of patients

c) The lifetime risk of gonadal malignancy issignificantly increased

d) The lifetime risk of gonadal malignancy isnot significantly increased

e) The diagnosis is most commonly madeduring investigation of ambiguous genitaliain infancy

3 Which of the following statements bestdescribes the aetiology and epidemiology ofcongenital adrenal hyperplasia (CAH)?

a) CAH accounts for 20-25% of all infantswith ambiguous genitalia

b) The most common underlying endocrinedefect is 11 Beta hydroxylase deficiency

c) CAH is an autosomal dominant disorderwith variable expression

d) CAH is an X linked recessive disordere) CAH is an autosomal recessive disorder

4 As a consequence of the findings during ahernia operation, Sarah, aged 5, is diagnosedwith complete androgen insensitivity syndrome.Which of the following statements bestdescribes the other features of her phenotypeand genotype?

a) The most likely karyotype is 47XXYb) The most likely karyotype is 46XYc) The most likely karyotype is 47XYY d) The gonads identified in the hernial sacs are

most like to be dysgenetic streak gonadse) The internal genitalia are most likely to

comprise a vestigial uterus and fallopiantubes.

5 Which disorder of sex development is charac-terised by an elevated plasma level of 17 OHprogesterone?

a) Mixed gonadal dysgenesisb) Ovotesticular DSD (true hermaphroditism) c) 46XY DSD (male pseudohermaphroditism)d) Mullarian inhibitory substance receptor

insensitivity e) 46XX DSD (female pseudohermaphro-

ditism) due to congenital adrenal hyperplasia

Appendix I 365


Chapter 21: GenitourinaryMalignancies

1 Which of the following statements mostaccurately refers to the epidemiology andaetiology of rhabdomyosarcoma? a) This tumour accounts for 40-50% of all

solid tumours in childhood b) This tumour accounts for approximately

30% of all tumours of the genito urinarytract in childhood

c) Approximately one third of all rhabdomyosar-comas in children arise within the genitourinary tract

d) This tumour is less common in children ofAfro Caribbean origin.

e) Girls are affected more commonly than boys

2 A 2 year old boy presents with urinary retentionand haematuria. Initial ultrasound demonstratesa polypoid mass in the region of the trigoneand bladder neck. Both upper tracts are normal.Which of the following would not be routinelyincluded in the diagnostic protocol for thischild?

a) Cystoscopyb) Biopsyc) CT scan d) Bone scan e) Glomerular Filtration Rate (GFR)

3 What is the approximate current overall 5 yearsurvival rate for children with nephroblastoma(Wilms tumour)?

a) 20–30% b) 40–50% c) 50–60% d) 80–90% e) >90%

4 In the United Kingdom and Europe, which ofthe following is currently the most commonlyused sequence of treatment modalities forWilms tumour?

a) Nephrectomy followed by post operativeradiotherapy

b) Nephrectomy followed by post operativechemotherapy and radiotherapy

c) Nephrectomy followed by post operativechemotherapy

d) Biopsy, pre-operative radiotherapy followedby nephrectomy

e) Biopsy, pre-operative chemotherapy followedby nephrectomy

5 Which of the following is not a feature ofBeckwith-Weidemann Syndrome?

a) Macroglossia b) Anidiridia c) Wilms tumourd) Omphalocoelee) Visceromegaly

Chapter 22: Urogenital trauma

1 A 6 year old boy has been brought to theaccident and emergency department followinga fall from a playground swing. He is haemo-dynamically stable but is tender in the left upperquadrant. His urine contains +++ blood ondipstick testing. Ultrasound in the A&E depart-ment demonstrates haematoma in the region ofthe upper pole of the left kidney. Which of thefollowing (if any) would be most appropriatefollowing admission to the paediatric ward?

a) Urgent DMSA scan b) Repeat ultrasound scan after 48 hours c) Intravenous urogram d) CT scan e) No further imaging required if clinical

condition remains stable.

Appendix I366


2 What is the estimated risk of hypertensionassociated with a renal injury in childhood? a) Less than 5% b) 5–10% c) 10–15%d) 15–20% e) 20–25%

3 Which of the following procedures would bethe most appropriate surgical management of a0.5 cm length post-traumatic urethral stricturein the bulbar urethra of a 10 year old boy?

a) Laying open the stricture and two stageurethroplasty with buccal skin

b) Laying open the stricture and two stageurethroplasty with post auricular skin

c) Excision of stricture and substitutionurethroplasty with vascularised preputial skin

d) Excision of stricture and end to end urethralanastomosis

e) Transpubic sphincterotomy

4 A 7 year old girl with a blunt renal injury to theright kidney is assessed with ultrasound and CT.Imaging reveals a laceration of the renalparenchyma extending across most of the lowerpole of the right kidney accompanied by peri-renalhaematoma and urinary extravasation. Whatgrade of renal injury do these findings represent?

a) Grade I b) Grade II c) Grade III d) Grade IV e) Grade V

5 A 2 ½ year old girl is brought by her mother tothe accident and emergency department follow-ing an accident which occurred whilst beinglooked after overnight by a neighbour. No onesaw the accident occur. Examination revealsbruising of the perineum and labia, contusionof the introitis and a superficial laceration of thevaginal mucosa. What measures should betaken next?

a) Admit to hospital, proceed to urgentcystoscopy

b) Admit to hospital. Contact the duty paedia-trician to investigate the circumstances ofthe injury

c) Prescribe antibiotic cream and regular baths.Arrange further review in the outpatientclinic in 2 days

d) Prescribe oral antibiotics and regular baths.Arrange further review in the outpatientclinic in 2 days

e) Reassure, no antibiotics prescribed butadvise regular baths. No arrangement forfollow up

Chapter 23: Laparoscopicpaediatric urology

1. Which of the following statements bestdescribes the use of laparoscopic pyeloplasty forPUJ obstruction in children?

a) The first series of laparoscopic pyeloplastiesin children was reported in 1990

b) Non-dismembered pyeloplasty is usuallyperformed for cases of PUJ obstructionwithout crossing vessels

c) Laparoscopic pyeloplasty can be performedby a retro peritoneal approach in children

d) Laparoscopic pyeloplasty cannot be performedby a retro peritoneal approach in children

e) Robotic laparoscopic pyeloplasty cannot beperformed safely in children

Appendix I 367


2 Which of the following is not regarded as anabsolute contra indication to laparoscopicadrenalectomy in children?

a) Phaeochromocytoma b) Cardiac failure due to severe congenital

heart disease c) Respiratory insufficiency due to cystic fibrosis d) Uncorrectable coagulopathy e) Systemic sepsis

3 What is the optimal insufflation pressure forlaparoscopic procedures in children whoseweight is the range 10–20kg?

a) <12 mmHgb) 15–17 mmHg c) 17–19 mmHgd) 21–23 mmHge) 23–25 mmHg

4 Which of the following is not a well recognisedindication for laparoscopic nephrectomy?

a) Dysplastic kidney associated with hypertension b) Non-functioning hydronephrotic kidney c) Severe reflux nephropathy with hypertension d) Stage I or Stage II Wilms Tumour e) Intractable protein loss associated with

nephrotic syndrome

5. What was the first laparoscopic procedure to gainwidespread acceptance in paediatric Urology?

a) Laparoscopic nephrectomy b) Diagnostic laparoscopy for impalpable testes c) Laparoscopic pyeloplasty d) Laparoscopic excision of mullarian remnants e) Laparoscopic hemi nephrectomy

Chapter 24: Adolescenturology

1 What is the most common cause of death inadult spina bifida patients?

a) Renal failure b) Uncontrolled hydrocephalus c) Bladder cancer d) Cardiovascular and respiratory disease e) Suicide

2 What is the approximate risk of malignancyassociated with enterocystoplasty after a latencyperiod of 20–25 years?

a) 2–5%b) 5–7%c) 7–10%d) 10–12%e) 12–15%

3 Which of the following is not a well recognisedfeature of Prune Belly Syndrome?

a) Renovascular malformationsb) Bilateral undescended testesc) Absent abdominal wall musculature d) Kyphoscoliosise) Urinary tract dilatation

4 Which of the following statements best describesthe prognosis for sexual and reproductivefunction in female bladder exstrophy patients?

a) Substitution vaginoplasty is usually requiredto permit normal intercourse

b) Uterine prolapse occurs in up to 50% ofwomen

c) Fewer than 15% of women with a history ofbladder exstrophy can achieve pregnancy

d) Sensory function is usually impaired as aresult of clitoral agenesis

e) Infertility is inevitable because of the associ-ation between bladder exstrophy and uterineagenesis

Appendix I368


5 Which of the following is a well documentedprognostic indicator of long term renalimpairment in patients with posterior urethralvalves?

a) GFR 65 mls/min/1.73m2 at 8 yearsof age

b) Daytime incontinence after 5 years of age c) Diagnosis after 5 years of age d) Non refluxing upper tracts e) High urine osmolality

Chapter 25: Children andyoung people as urologicalpatients

1 In the United Kingdom, which of the follow-ing adults do not have parental responsibility(defined by the 1989 Children Act) toprovide consent for a child to undergosurgery?

a) The child’s mother regardless of marriagestatus

b) The child’s father regardless of marriage status c) The child’s father if the parents were

married at the time of birth or marriedsubsequently.

d) A legally appointed guardian e) A local Authority representative designated

in a Care Order

2 At what age do young patients have sole legalresponsibility to consent to treatment or torefuse it?

a) 15 years b) 16 years c) 17 years d) 18 years e) 21 years

3 If the operating surgeon is unable to obtainconsent for a major procedure in person, whichof the following should obtain consent onhis/her behalf?

a) Any qualified doctor b) Any surgical trainee of the specialist regis-

trar gradec) A surgeon who has observed the procedure

in questiond) A surgeon who is capable of performing the

procedure in question e) A nurse specialist

4 At what age do children typically develop self-awareness and become conscious of genderdifferences?

a) 6 months b) 12 months c) 2 years d) 4 years e) 7 years

Appendix I 369



Appendix II Self-assessment section: Answers

Chapter 1 Embryology

Question 1 eQuestion 2 bQuestion 3 dQuestion 4 aQuestion 5 d

Question 4 Comment: Although conditions such asvesico ureteric reflux, hypospadias and ureteric duplicationhave a well documented familial basis, attempts to impli-cate individual gene mutations have been unfruitful andit is generally believed that they result from the interactionof multiple genes. By contrast, specific mutations havebeen identified in autosomal dominant polycystic kidneydisease – see Chapter 9: Cystic renal disease.

Chapter 2 Renal physiology and renal failure

Question 1 dQuestion 2 bQuestion 3 bQuestion 4 dQuestion 5 d

Question 1 Comment: Hyponatremia (plasmasodium less than 130mmol/L), due to water retentionand sodium depletion is a common feature of sick andpremature newborn infants. Monitoring of sodiumand fluid balance in such infants is particularly impor-tant in the early weeks of life.

Chapter 3 Diagnostic imaging

Question 1 cQuestion 2 eQuestion 3 dQuestion 4 eQuestion 5 c

Question 2 Comment: A renal pelvic AP diameterof greater than 10mm is regarded as abnormal but isnot necessarily indicative of clinically significantpathology.

Chapter 4 Urinary Tract Infection

Question 1 bQuestion 2 dQuestion 3 eQuestion 4 eQuestion 5 b

Question 1 Comment: A child of this age should beable to cooperate in the correction of a ‘clean catch’midstream sample – the least invasive, reliable methodof collecting an uncontaminated specimen.

Question 3 Comment: Leucocyte esterase negative,nitrite positive. This finding represents presumptiveevidence of UTI. The NICE guidelines recommendthat antibiotic treatment should be commenced and aurine sample sent for culture.

Appendix-II Thomas-8043.qxd 2/29/2008 7:16 PM Page 371

Chapter 5 Vesico ureteric reflux

Question 1 aQuestion 2 bQuestion 3 cQuestion 4 dQuestion 5 a

Chapter 6 Upper tract obstruction

Question 1 eQuestion 2 bQuestion 3 bQuestion 4 eQuestion 5 c

Question 1 Comment: The imaging points to adiagnosis of obstructed megaureter with good preserva-tion of function. In the majority of cases the naturalhistory is one of gradual spontaneous resolution. In thiscase, conservative management would be more appro-priate than any form of surgical intervention at thisstage.

Chapter 7 Duplication anomalies, ureterocelesand ectopic ureters

Question 1 cQuestion 2 aQuestion 3 bQuestion 4 bQuestion 5 a

Chapter 8 Posterior urethral valves and otherurethral abnormalities

Question 1 cQuestion 2 bQuestion 3 eQuestion 4 dQuestion 5 d

Chapter 9 Cystic renal disease

Question 1 bQuestion 2 eQuestion 3 bQuestion 4 aQuestion 5 a

Chapter 10 Prenatal diagnosis

Question 1 cQuestion 2 cQuestion 3 dQuestion 4 aQuestion 5 a

Question 4 Comment: Plasma creatinine is not ameaningful measure of renal function in the foetus,since creatinine crosses the placental barrier. Even iffoetal plasma creatinine could be measured, a value ofgreater than 150mmol/L would raise concern aboutrenal impairment in the mother but tell us nothinguseful about renal function in the foetus.

Chapter 11 Stone disease in children

Question 1 eQuestion 2 cQuestion 3 aQuestion 4 cQuestion 5 e

Chapter 12 Urinary incontinence

Question 1 bQuestion 2 cQuestion 3 eQuestion 4 bQuestion 5 d

Question 3 Comment: This boy has monosympomaticnocturnal enuresis. In the absence of daytime wettingor any other unusual features the yield from investiga-tion is minimal and the parents can be reassured thathe will become dry.

Question 4 Comment: Giggle incontinence is a rarebut distinctive disorder. Treatment with anticholinergicsis usually unhelpful, but Methylphedinate (Ritalin) cansometimes be dramatically effective.

Chapter 13 Neuropathic bladder

Question 1 dQuestion 2 aQuestion 3 cQuestion 4 dQuestion 5 e

Appendix II372


Chapter 14 The Urinary tract in anorectalmalformations, multisystem disorders andsyndromes

Question 1 eQuestion 2 cQuestion 3 cQuestion 4 eQuestion 5 d

Question 4 Comment: A pelvic kidney can be missedon ultrasound. A DMSA scan is indicated to identifyany ectopic function in renal tissue principally to lookfor a pelvic kidney.

Chapter 15 Bladder exstrophy and epispadias

Question 1 cQuestion 2 eQuestion 3 bQuestion 4 dQuestion 5 b

Chapter 16 Hypospadias

Question 1 dQuestion 2 aQuestion 3 eQuestion 4 eQuestion 5 e

Chapter 17 The prepuce

Question 1 eQuestion 2 dQuestion 3 bQuestion 4 cQuestion 5 a

Chapter 18 Testis, hydrocele and varicocele

Question 1 bQuestion 2 eQuestion 3 dQuestion 4 dQuestion 5 a

Question 3 Comment: Surgery is not necessarilyindicated at this stage but if it is decided to operate thecorrect procedure for a presumed communicatinghydrocele is ligation of the processus vaginalis.

Chapter 19 The acute scrotum

Question 1 cQuestion 2 eQuestion 3 eQuestion 4 cQuestion 5 a

Question 2 Comment: The diagnosis is idiopathicscrotal oedema for which no specific treatment is required.

Chapter 20 Disorders of sex development

Question 1 cQuestion 2 cQuestion 3 eQuestion 4 bQuestion 5 e

Chapter 21 Genitourinary malignancies

Question 1 cQuestion 2 eQuestion 3 eQuestion 4 eQuestion 5 b

Chapter 22 Urogenital trauma

Question 1 dQuestion 2 aQuestion 3 dQuestion 4 cQuestion 5 b

Chapter 23 Laparoscopic paediatric urology

Question 1 cQuestion 2 aQuestion 3 aQuestion 4 dQuestion 5 b

Chapter 24 Adolescent urology

Question 1 dQuestion 2 aQuestion 3 aQuestion 4 bQuestion 5 b

Appendix II 373


Chapter 25 Children and young people asurological patients

Question 1 bQuestion 2 dQuestion 3 dQuestion 4 c

Question 1 Comment: The child’s father is notautomatically deemed to be competent to provideconsent unless he was married to the mother at the timeof the child’s birth or they married subsequently.

Appendix II374


Index

abdominal mass 81calculi and 146as indication for ultrasound 29pelvic 29

abdominal migraine 89abdominal X-ray 25, 41, 146–7acid–base balance 17, 115acoustic shadow 146, 147acute scrotum 265–74

clinical features 266diagnosis 266–7epidemiology 266

adenoma, adrenal 326adenosine, intrarenal 16adolescents

needs of 344urology 331–40

adrenal adenoma 326adrenocorticotrophic hormone (ACTH) 280adrenocorticotrophic hormone (ACTH)-dependent

Cushing’s syndrome 326, 327–8AGTR2 gene 59ambiguous genitalia, female genital reconstruction of 333aminoglycoside in pyelonephritis 52amputation neuromas 235anaemia

Fanconi’s 195treatment of 22

Anderson–Hynes dismembered pyeloplasty 83–4androgen insensitivity syndrome (AIS) 12, 281aneurysms, cerebral 123angiomyolipoma 296angiotensin-conversion enzyme inhibitors (ACEIs) 331anorectal anomalies 189–94

aetiology 189associated anomalies 191classification 189–92cloacal anomalies 194incidence 189lower urinary tract dysfunction 192–4surgical management of 193syndromes and associations involving

the urinary tract 194–5

urological complications 193–4urological investigation 193

anorexia 18antegrade continence enema (ACE) 186–7antegrade pyelography 41–2, 77antibiotics

hypospadias 227prenatal diagnosis 138pyelonephritis 52, 54urinary incontinence 167vesicoureteric reflux 65, 67, 72in vulvovaginitis 290

anti-Müllerian hormone (AMH) see Müllerian inhibitingsubstance (MIS)

appendicitis 49arteriography 41atrial natriuretic peptide 16attention-deficit hyperactivity disorder (ADHD) 165, 167augmentation cystoplasty 117augmentation with tissue-engineered neobladder 182–3autoaugmentation 181

plus demucosalised enterocystoplasty 182

balanitis 49, 146balanitis xerotica obliterans 163, 228, 230, 235–7

aetiology 236treatment 236–7

balanoposthitis, acute 237–8, 241Beckwith–Wiedemann 296bell-clapper testis 267, 268bicornuate uterus 12, 194, 195bifid scrotum 191bifid system 76biliary dysgenesis 122bipolar diathermy 227bladder, acontractile 174, 176bladder control, development of 157–8bladder diverticulum 116bladder exstrophy 8, 138

in adolescents 332–3antenatal diagnosis 201classic 201–7continence outcomes 206–7

Index Thomas-8043.qxd 2/29/2008 7:17 PM Page 375

continence surgery 204–6embryology and anatomy 199–200grading system for continence 206incontinence an 163initial neonatal management and primary closure 202–4late outcomes 207pelvic osteotomy 204presentation and clinical features 201–2surgical technique 202–4

bladder injuries 311–12bladder neck

closure 184–5suspension and slings 184

bladder outflow obstruction 163, 176–7bladder volume 26‘blue dot sign’ 266Botulinum toxin A 166, 180buried penis 241

caecoureterocoele 95CAH 288calcium acetate 21calcium calculi 145calcium carbonate 21calcium-containing agents 21calculi 143–55

bladder 28, 143, 151, 153clinical presentation 146complications 153–4diagnosis 146–9evaluation 147–8incidence and epidemiology 143infective 144, 154kidney 26, 27, 28, 149, 152metabolic 145, 154minimally invasive treatment 152–3, 153–4open stone surgery 149–52, 153passage of stone material per urethram 146pathology/aetiology 143–6recurrence 154screening 146–7, 148staghorn 27, 144, 149, 154ureter 149–50urethral 28, 151–2urinary 26–9

Cantwell–Ransley epispadias repair 210, 332cerebral aneurysms 123CHARGE association 194–5child friendly environment 343–4chordee, penile 213, 332

correction of 215–16persistent 230without hypospadias 225

chorionic villus sampling 136chromosomal abnormalities 1–2chronic renal failure (CRF) 17–22

anaemia, treatment of 22assessment of therapy 22clinical manifestations 19–21growth and development 18–22

growth failure, treatment of 22measurement 17–18renal replacement therapy 22–4sodium chloride and bicarbonate 22

circumcision 233, 239–41alternatives 242–4in balanitis xerotica obliterans 236complications 242contraindications 241medical indications 241religious 239, 242routine 239–41surgical aspects 241–2neonatal 45, 117vesicouretic reflux 69–70

clam-patch cystoplasty 180, 181clean intermittent self-catheterisation (CISC) 171, 172, 173,

178, 179, 180, 183clear cell sarcoma of the kidney (CCSK) 295, 298clitoral hypertrophy 192clitoroplasty 286cloacal exstrophy 138, 200, 207–9

associated anomalies 208continence and long-term outcomes 209gender of rearing 208initial outcomes 208initial presentation and management 207–8

cloacal malformations 192Cobb’s collar 119Cohen technique of ureteric reimplantation 69, 328colour Doppler ultrasound 74, 267communicating hydrocoele 258computed tomography (CT) 25, 40–1

calculi 148unenhanced spiral 147

conduit urinary diversion 185–6congenital adrenal hyperplasia (CAH) 12, 275, 284congenital obstructive posterior urethral membrane

(COPUM) 109congenital short urethra 163conjoined twins 195consent 344–6constipation 54

urinary incontinence 163, 165vesicoureteric reflux 65

continuous ambulatory peritoneal dialysis (CAPD) 23continuous cycling peritoneal dialysis (CCPD) 22–3contractile bladder 174cord lesions, acquired 173cordocentesis 136corpus callosum, agenesis of 197counselling 135Cowper’s gland cysts (syringocoele) 118creatinine 15creatinine clearance 18cross-sectional imaging 36–41cryptic duplication 99, 100cryptorchidism 4, 12–13

classification 248examination 249

Index376


history 249incidence 247management 249–55

difficult situations 253–4hormonal treatment 249–50surgery 250–3

pathology 247–8presentation 248–9

Cushing’s syndrome, adrenocorticotrophic hormone(ACTH)-dependent 326, 327–8

cutaneous vesicostomy 185cyst

hepatic 123ovarian 292preputial 238simple (solitary) renal 129–30smegma retention 238, 239

cystic anomalies 6cystic fibrosis 145, 164cystic nephroma see multilocular renal cystcystic renal disease 121–30cystine calculi 144, 145cystitis, haemorrhagic 48cystolithotomy 151cystoplasty, augmentation 180–3cystoscopy 100cystourethroscopy 162, 284

da Vinci system 324, 325deferred voiding 167Denys–Drash syndrome 296, 300desmopressin 169detrusor

non-compliance 180overactivity 180

detrusor-sphincteric dyssynergia 161, 165, 167, 174detrusor-sphincteric synergia 157, 165diabetes inspidus 159diabetes mellitus 159, 237diagnostic imaging 25–42dietary manipulation 21diethylenetriamine pentaacetic acid (DTPA) isotope 35–6, 75dihydrotestosterone 10, 12, 278–9dimercaptosuccinic acid (DMSA) scintigraphy 25,

31–6, 51, 179calculi 147DMSA isotope 62, 78, 81, 116, 139dynamic renography (MAG3 and DTPA) 35–6ectopic ureter 98–9technique 32–4vesicouretic reflux 63

direct radionuclide cystography (DIC) 31disorders of sex development (DSD) 12, 214, 275–93

classification of 279clinical evaluation 283–4diagnostic features 284–5diagnostic imaging 284gender assignment 285–6gonadal management 288–9investigation of 283–9

laboratory investigations 284ovarian pathology 292persistent Müllerian remnant (prostatic utricle) 288–9surgical investigations 284surgical management 286–8

diurnal urinary frequency of childhood 166–7diurnal urinary incontinence, functional 164–8Down syndrome (trisomy 21) 1, 2

anorectal anomalies 189ultrasound 134

Duplay procedure 217duplex kidney 76, 98duplex-system ureteroceles 95, 98, 103duplication anomalies 93–105, 161

classification 93clinical presentation 97–8embryology 93–4incidence 96–7pathology 95

dynamic renography 148dynamic sphincteric obstruction 174dysfunctional voiding 165dyssynergia 164

ectopic kidney see renal ectopiaectopic ureter

bilateral single 106–7incidence 96infrasphincteric 97–8, 104investigations 98–101ipsilateral 195management 101–5suprasphincteric 97, 104

ectopic ureterocoele 95ectopic urinary orifice 160Edwards’ syndrome (trisomy 18) 1, 2ejaculation 335electromyography 173embryogenesis 3–4, 3embryology 1–13

lower urinary tract 7–8upper urinary tract 4–6

encysted hydrocele 258endopyelotomy and balloon dilatation

in pelviureteric junction (PUJ) obstruction 86endoscopic reimplantation 69endoscopic ureterocoele incision 101–2endoscopic urethral sphincterotomy 185endoscopic valve ablation 114endoscopy of vesicouretic reflux 66–8end-stage renal disease (ESRD) 17, 26Enterobacter 45enterocystoplasty 117, 180–1

calculi and 145complications of 182long-term outcome 337–8

enuresis alarm 169ephrin B gene 189epididymo-orchitis 48–9, 97, 207, 266, 272–3epispadias 8, 209–10

Index 377


girls 210glanular 200males 210management 210outcome 210penile 201penopubic 201presentation 209–10primary 159, 160, 163, 200–1pubic 201urinary incontinence and 163

Escherichia coli 45in balanitis xerotica obliterans 237in reflux nephropathy 60in urinary tract infection 44, 45

external shockwave lithotripsy (ESWL) 143,147–8, 149, 152, 154

factor VIII deficiency 241Fanconi’s anaemia 195feed and wrap technique 38feminising genitoplasty 286fertility 339–40

bladder exstrophy 207orchidopexy 255–6testicular torsion 270

fetal intervention 135–6fetal urine sampling 136fir-tree bladder 167fistulae 229fluorescent in situ hybridisation (FISH) 2, 302focal segmental glomerulosclerosis 17Fowler–Stephens procedure 253‘functional obstruction’, idiopathic 80

gamete intrafallopian transfer (GIFT) 4gametogenesis 1gastroschisis 201genetic basis of genitourinary tract malformations 1–2genital anomalies 191–2genital injuries 313–15genital reconstruction

in bladder exstrophy 332–3genitalia/genital tracts 8–13

clinical considerations 11–13female 8–9

external 9, 12, 314internal 8–9, 11–12

male 9–11external 10, 11, 12–13internal 12testis 10–11

genitogram 284genitourinary fistulae 44genitourinary malignancies 295–305germ cell tumours 304–5giggle incontinence 167glanular epispadias 200glomerular filtration rate (GFR) 15, 16, 17–18, 36, 61, 75

gonadal dysgenesis 279mixed 282, 284, 286, 288ovarian 282–3

growth pattern 19

haemangioma 296haematocolpos 163haematoma in hypospadias 228haematuria 81

calculi 146haemodialysis, chronic 23haemorrhage in hypospadias 228haemorrhagic cystitis 48Heineke–Mikulicz procedure 210heminephrectomy, upper pole 102, 103–4heminephroureterctomy 104Henoch–Schonlein vasculitis 266, 274hepatic cysts 123hernia

incarcerated 273inguinal 249, 258

Hinman’s syndrome 168history taking 341–2

neuropathic bladder 177–8HIV infection, circumcision and 239holmium laser 152horseshoe kidney 6, 32, 37, 39, 79, 195–6hospitalisation 342hydrocephalus 171, 172hydrocoele 247, 257–9

acute 266, 273–4communicating 258encysted 258examination 258–9management 259non-communication 258operative technique 259presentation 258

hydrocolpos 163hydronephrosis 26, 29, 33, 7311β-hydroxylase deficiency 280–121–hydroxylase deficiency 280, 2813β-hydroxysteroid dehydrogenase 281hypercalcaemia 21hypernatraemia

early-onset 16late-onset 16

hyperoxaluria 145hyperparathyroidism, secondary 21hypertension

in multicystic dysplastic kidney 126–7renal 62

hyponatraemia 16hypoplastic–dysplastic kidneys 17hypospadias 2, 12–13, 191, 213–30

aetiology/incidence 213–14classification 214–15complications 228–30history 213

Index378


in adolescents 333–4intersex and associated anomalies 214outcome 2227–8surgical principles 215–25, 226–7

hypospadias cripples 215, 216hypospadias fistula 229

imipramine 167, 169impalpable testis 250–1

bilateral 252imperforate hymen 160, 291implant materials 66in vitro fertilisation (IVF) 4incarcerated hernia 273inflatable periurethral constrictor 183–4inguinal hernia 249, 258intermediate bladder dysfunction 175intersex see disorders of sex developmentinterventional techniques 41–2intracytoplasmic sperm injection (ICSI) 4, 336intraluminal fibroepithelial polyps 80intraluminal obstruction 80intrarenal reflux (IRR) 57intravenous urography (IVU) 25, 41, 62, 64, 76, 147–8

ectopic ureter 99isotope imaging 139isotope renography 75, 88

JJ stent, in-dwelling 84Jones preperitoneal procedure 252–3

Kalicinski plication 91Kallmann’s syndrome 2karyotype 136Kelly operation 205–6, 208, 210keyhole sign 111kidney, abnormal migration and fusion 195–7Klebsiella infection 45, 144Klinefelter’s syndrome (47XXY) 1knock out deletion 3Koyanagi procedure 225kyphoscoliosis 172

labia minora, fused 160labial adhesions 159, 163, 290labioplasty 286–7laparoscopic adrenalectomy 326–8laparoscopic cystolithotomy 328laparoscopic heminephrectomy 321–2laparoscopic nephrectomy 319–21laparoscopic paediatric urology 317–29

access 319anaesthesia 318–19benefits and drawbacks 317–18instrumentation 319patient selection 318technique 318–19

laparoscopic pyeloplasty 322–4in pelviureteric junction (PUJ) obstruction 85–6

laparoscopic ureteric reimplantation 328laparoscopic vascular hitch 325–6laparoscopically assisted orchidopexy 253, 254laparoscopy in disorders of sex development 284, 328lazy bladder 167Leydig tumours 305lichen sclerosis et atrophicus of the vulva 235Lich–Gregoir technique 69, 70, 328Lima cuff urethral constrictor 184lipoma, lumbosacral 172lower pole dysplasia 105lower pole reflux 104–5lumbosacral lipoma 172lymphangioma 296

MAG3 dynamic stress renography 25MAG3 isotope 35–6, 51, 64, 75, 78, 81, 83, 116, 139magnetic resonance angiography 38, 40magnetic resonance imaging (MRI) 25, 37–40, 162

in children 38ectopic ureter 100–1techniques and indications 38–40, 39–40upper urinary tract obstruction 76–7urinary incontinence 162

magnetic resonance urography 39, 162MAGPI procedure 218, 222, 228malnutrition 18–19Malone antegrade continence

enema (MACE) 338Marshall–Marchetti bladder neck suspension 184masculising genitoplasty 286Mathieu procedure 221, 223, 228Mayer–Rokitansky–Küster–Hauser

syndrome 195, 291–2meatal stenosis 159, 163, 229meatal-based flap (Mathieu procedure) 221, 223, 228megacystis–microcolon intestinal

hypoperistalsis syndrome 111megalourethra 118megameatus intact prepuce 225, 226megaprepuce. congenital 238–9, 240megaureter

non-refluxing, non-obstructed 87obstructed 87–8

alternatives to open surgery infirst year of life 90

investigations 88management 88–90prenatally detected 88–90presentationsurgery 90–1

mercaptoacetyltriglycine (MAG3) see MAG3mesoblastic nephroma 296metastases as indication for ultrasound 29methylene blue test 162

ectopic ureter 100Meyer–Weigart law 8, 94microvascular orchidopexy 253micturating cystography 148, 179

Index 379


micturating cystourethrography (MCUG; voidingcystourethrogram; VCUG)) 25, 29–31, 34–5, 138–9

ectopic ureter 99indirect 64isotope cystography 31mulicystic dysplastic kidney (MCDK) 126posterior urethral valves 112technique 29–31upper tract obstruction 88urinary tract infection 51vesicoureteric reflux 62–4

midstream urine (MSU) 45–6, 65milk

formula 18–19human 18

Mitchell approach 204Mitrofanoff procedure 107, 117, 151, 171,

173, 184, 185, 186mixed gonadal dysgenesis 282, 284, 286, 288monopolar diathermy 227monosomy 1Monti tube 185mosaicism 2Müllerian inhibiting substance (MIS) 9, 10, 276, 278

deficiency 12, 286multicystic dysplastic kidney (MCDK) 5, 6, 78, 121, 124–8

aetiology/embryology 124bilateral 136complications 126–7diagnosis 126incidence 124malignant potential 127management 127–8natural history 126other complications 127pathology 124–5presentation 125

multidisciplinary team 344multilocular cystic nephroma, benign

see multilocular renal cystmultilocular renal cyst 128–9, 296myelomeningocoele 171–2, 201

Neisseria gonorrhoeae 290nephrectomy

ectopic ureter 103in pelviureteric junction (PUJ) obstruction 86–7retroperitoneoscopic 320–1SIMPL (single instrument port laparoscopic)

nephrectomy 321nephro stent 84nephroblastoma 39, 295nephrocalcinosis 26, 28, 144, 145nephrogenesis 4–5, 15nephrolithiasis 144nephroma, mesoblastic 296nephroureterectomy 71Nesbit’s procedure 216, 332neuroblastoma see Wilms’ tumour

neuromas, amputation 235neuropathic bladder 171–87

aetiology 171–3bowel management 187–8classification 173–5incomplete cord lesions 175investigations 179management 179–87management in neonates and infants 187management of the severely disabled 187neonatal assessment 179pathophysiology 173–7patient assessment 177–9secondary upper renal tract complications 175–7sphincteric incompetence 180surgery for impaired/high-pressure

bladder capacity 180–5NICE guidelines 43, 46, 47, 51–4nocturnal enuresis, primary monosymptomatic 168–9non-communication hydrocoele 258non-disjunction 1non-neuropathic neuropathic bladder 167–8non-retractile foreskin see phimosis

obstructive uropathy 17oligohydramnios 6, 15onlay island flap procedure 221–5open (Hasson) technique 319open pyeloplasty in pelviureteric junction

(PUJ) obstruction 84, 85–6open ureterolithotomy 153optical urethrotomy 313orchidopexy 247, 252, 286

complications 255fertility 255–6long-term outcomes 255–7malignancy 256–7

osteodystrophy, renal 19–20, 21ovarian cysts 292ovary 277overactive bladder 164–6aetiology 164ameliorative measures 165Botulinum toxin A 166clinical features 164–5cognitive bladder retraining 166detrusor antispasmodics 166investigation 165management 165neuromodulation 166prognosis 165simple bladder retraining 165–6ovotesticular DSD (true hermaphroditism) 275, 276, 279,

283, 284–5oxalate calculi 145oxybutynin 180

in giggle incontinence 167in nocturnal enuresis 169in urinary incontinence 166

Index380


pain calculi and 146in pelviureteric junction (PUJ) obstruction 81

Palomo technique 262palpable undescended testis 250paraphimosis 238paratesticular rhabdomyosarcoma 305parathyroid hormone (PTH) 19partial androgen insensitivity (PAIS) 281, 285Patau syndrome (trisomy 13) 1, 2patent processus vaginalis 257patent urachus 7PAX2 gene 2, 59pedicle flaps 221, 228pelvic fractures 313pelvic kidney 6, 195pelvic laparotomy 284pelvic tumours 163pelviureteric junction (PUJ) obstruction 42, 73, 78–87, 98,

105, 307, 324–6aetiology 79investigation 81–2laparoscopic vascular hitch 325–6management 82–6natural history 81pathology 79presentation 81robotic pyeloplasty 324–5variants 79–81

penile injuries 314percutaneous nephrolithotomy (PNCL) 147, 152, 154percutaneous nephrostomy 42

in pelviureteric junction (PUJ) obstruction 86perinephric urinoma 116peritoneal dialysis (PD) 22, 23periurethral bulking agents 184persistent processus vaginalis 249persistent reflux 104–5Pfannenstiel incision 150phaeochromocytoma 326, 327phalloplasty 286phenotypic sex differentiation 278–9phimosis 159, 234, 241phosphate-binding agents 21Pippi Salle procedure 184, 185PKD1 gene 123PKD2 gene 123PKHD1 gene 122PLUTO trial 113Politano–Leadbetter reimplantation 69, 71, 91polycystic kidney/renal disease 33, 121

autosomal recessive (ARPKD) 121, 122–3autosomal dominant (ADPKD) 2, 121, 123–4

polymerase chain reaction (PCR) 2pop-off phenomenon 116posterior urethral valves (PUV) 331posttraumatic urethral stricture 313potassium balance 16–17Potter’ syndrome 111

Potter’s facies 122Prader–Willi syndrome 252pregnancy 339–40pregnancy, termination of 137–8

posterior urethral valves 113prenatal diagnosis of uropathy 137–8prune-belly syndrome 138

prenatal diagnosis 133–42diagnostic pathways 139incidence 134–5management 135–9

postnatal 138–9prenatal 135–8

obstetric ultrasound 134prepuce 233–44

development and function 233–4disorders and abnormalities 235–9function 235

preputial adhesions 233, 238preputial bladder 239preputial cysts 238preputial flap (onlay island flap

procedure) 221–5, 228preputioplasty 243–4pressure/flow studies 75–6primary megaureter 73prostaglandins 16prostatic utricle 272Proteus 48, 144, 146

in balanitis xerotica obliterans 237in urinary tract infection 45

prune-belly syndrome 111, 336–7abdominal wall 336–7kidneys 337termination 138undescended testes (cryptorchidism) 191, 336

pseudohermaphroditism, female(46XX DSD) 276, 279–81, 285, 286, 288

aromatase deficiency 281congenital adrenal hyperplasia 280–1virilisation by androgens of maternal origin 281

pseudohermaphroditism, male (46XY DSD)276, 279, 281–2, 285–6, 288

abnormalities of MIS activity 281–2idiopathic 282

Pseudomonas 45, 144psoas hitch 91psychosexual outcome (hypospadias) 228pubic epispadas 201pulmonary hypoplasia 6pulse dye laser 152pyelectasis 139–41pyelonephritis 26, 32, 62pyeloplasty, indications for 83pyelopyelostomy 102, 104

radionuclide testicular scanning (RTS) 267receptor sensitivity, defects of 281reciprocal induction 4–5

Index 381


recombinant human erythroipoietin (r-Hu EPO) 22recommended dietary allowance (RDA) 19redo surgery 2255α-reductase 10, 2785α-reductase deficiency 276, 281reflux nephropathy 17, 60–2

aetiology 60–1clinical significance 61–2

refluxing megaureter 87refluxing stump 71refluxing ureterostomy 114–15renal agenesis 134

bilateral 136embryology 5unilateral 106

renal ascent and fusion 6–7renal biopsy 42renal coloboma syndrome 2renal dysplasia 5, 22renal ectopia (ectopic kidneys) 134, 195–7

crossed 6, 196–7simple 195

renal function in adolescents 331renal impairment 17renal insufficiency 62renal physiology 15–17renal rhabdoid tumour (RRT) 295, 298renal scarring 51, 57renal transplantation 23–4renal trauma 307–11

imaging 309as indication for ultrasound 29, 33investigations 308–9management 309–11outcome 311presentation 308

renal tubular reabsorption disorder 145renal tumours 295–301

epidemiology/aetiology 295–6histopathology 300investigations 296–7nephroblastomatosis 300presentation 296treatment 297–9

renin–angiotensin system 16renocystography, indirect MAG3 31renogram curves 75renography, isotope 75resistive index 74–5retractile testis 249, 254–5retrocaval ureter 80, 195retrograde pyelography 77retroperitoneoscopic adrenalectomy 327–8retroperitoneoscopic heminephrectomy 322retroperitoneoscopic nephrectomy 320–1reverse transcriptase polymerase chain reaction (RT-PCR) 302rhabdomyosarcoma 290, 301–4

clinical presentation 302investigation 302–3

management 303paratesticular 305pathology 302prognosis 303–4

rickets, vitamin-D deficient 20robotic pyeloplasty 86, 324–5Rokitansky syndrome 12

sacral agenesis 160, 172–3sacral cord lesions 174sagittal anorectoplasty, posterior 193, 194salvage surgery 225sarcoma botyroides 290Schönlein–Henoch purpura 238scrotal oedema, idiopathic 266, 273secondary hyperparathyroidism 20secondary pelviureteric junction obstruction 62, 80–1sensory urgency 166septate vagina 194Sertoli cell tumours 305sex cord stromal tumours 305sex-determining genes 277–8sexual differentiation, normal 276–9

female genital tract 277male genital tract 276–7phenotypic 278–9

shattered kidney 310sibling screening 64SIMPL (single instrument port laparoscopic) nephrectomy

321simple (solitary) renal cyst 129–30single-system ectopic ureter 106single vaginal ectopic ureter 106smegma retention cyst 238, 239Snodgrass repair 216–17, 227sodium balance 16Sonic hedgehog gene 189sphincter-enhancement procedures 183spina bifida 4, 171

bladder control 33bowel management 338daily living 338general education and social adaptation 339sexual development

females 338–9males 339

social development 338–9termination 138

spinal anomalies 192spinal neurological disease 162spinal X-ray 162spindle duplications 118SRY gene 8, 9, 278staccato voiding 165staged reconstruction (bladder exstrophy) 204Staphyloccosus aureus in balanitis xerotica obliterans 237Starr technique 69, 90static renography see dimercaptosuccinic

acid (DMSA) scintigraphy

Index382


static sphincteric obstruction 174–5Stephen’s hypothesis 94STING procedure 67, 105stone basket 150stone disease see calculi‘straddle injuries’ 312stress incontinence 163–4supernumerary kidney 195suprapubic needle aspiration 46suprasacral cord lesions 174supravesical diversion 114surgery, timing of 342–3syringocoele 29, 118, 163

talipes 122teratoma 305testes

ascending 255undescended 191, 336

testicular agenesis 13testicular cancer 256testicular dysgenesis syndrome 248testicular feminisation syndrome (CAIS) 281testicular maldescent 305testicular microcalcification 257testicular regression syndrome 251testicular torsion 266, 267–70

aetiology 268endocrine function 270fertility 270management 269–70neonatal torsion (intrauterine or ‘perinatal’) 270–1presentation 268–9prognosis 270

testicular tumours 304–5testis 276testosterone 10, 278–9

metabolism defects 281production defects 281

tethered cord syndrome 192tolterodine 180topical steroids as alternative to circumcision 242–3torsion of testicular appendage (hydatid of Morgagni) 271–8total urogenital mobilisation (TUM) 287–8transcutaneous electric nerve stimulation (TENS) 166transitional nephrology 75translocation 1transplantation 335–6transureteroureterostomy (TUU) 71transverse vaginal septum 12triphasic nephroblastoma 300trisomy 13 (Patau syndrome) 1, 2trisomy 18 (Edwards’ syndrome) 1, 2trisomy 21 see Down’s syndrometrue hermaphroditism (ovotesticular disorders of sex

development) 275, 276, 279, 283, 284–5true retention cysts 238tubularisation of the urethral plate 227Turner syndrome (45X) 1–2, 4, 8, 196, 278

two-stage repair (hypospadias) 227–8two-stage repair 218, 219–21

ultrasound (US) 25–9advantages 25assessment of upper urinary tract 26calculi 146Doppler 29ectopic ureter 98indications 26–9limitations 26measurements in lower urinary tract 26neuropathic bladder 179obstructed megaureter 88overactive bladder 165postnatal 138prenatal 81renal cystic disease 29, 32–3scanning technique 26upper urinary tract obstruction 74urinary incontinence 162urinary tract infection 26, 50–1vesicouretic reflux 62–3

uncomplicated urgency 165undescended testes 191, 336unenhanced spiral CT 147UP3 gene 59upper pole heminephrectomy 102, 103–4upper urinary tract

duplication 2, 29obstruction 73–92

pathophysiology 73–4investigation 74–7diagnostic pathway 77–8

ureterectomy 103–4ureteric duplication 8, 58ureteric ectopia 98ureteric folds 79ureteric injuries 311ureteric reimplantation 68–9ureterocalicostomy 86, 87ureterocoele 26, 95, 96

duplex-system 95, 97, 98, 101, 103excision and reimplantation 102–4MCUG 29, 35single-system 105–6

ureterocystoplasty 117, 181, 182ureterolitotomy 150ureteroscopy 150urethra

congenital short 163hairy 230injuries 312–13

urethral advancement 228urethral atresia 111urethral catheterisation 46urethral diverticulum 118urethral duplications 118urethral ectopic ureter, unilateral 106

Index 383


urethral plate tubularisation 216–18urethral polyps, posterior 118urethral repositioning 218–20urethral stenosis 230urethral strictures 118–19, 163urethral valves

anterior 117–18posterior 4, 109–17, 163

in adolescents 334–6anatomy 109–10bladder function 334–5ejaculation 335investigations 111–12pathophysiology 110presentation 110–11prognosis 115–16renal function 335transplantation 335–6treatment 113–15

urethritis 48, 119urethrocoele 230urethroplasty 216–25, 313

chordee without hypospadias 225MAGPI procedure 218, 222meatal-based flap (Mathieu procedure) 221, 223megameatus intact prepuce 225, 226pedical flaps 221preputial flap (onlay island flap procedure) 221–5salvage or redo surgery 225two-stage repair 218, 219–21urethral repositioning 218–20

urge syndrome 165uric acid calculi 145urinary ascites 116urinary flowmeter 162urinary incontinence 157–69

development of bladder control 157–8functional diurnal 164–8investigations 161–2organic 162–4patient assessment 158–62

urinary infectionincontinence and 162calculi 146

urinary sphincter, artificial 183urinary tract anomalies 191urinary tract infection 26, 43–55, 62, 81

age-related incidence 44anatomical abnormalities 45circumcision and 239–41clinical features 47–9

children aged 2 years and older 49lower tract infection 47–8neonates and infants 49upper tract infection (pyelonephritis) 48

clinical presentation 47–9diagnosis 47–9diagnostic imaging 49–52epidemiology 43–4

history and examination 47host susceptibility 45incidence 43laboratory diagnosis 45–7management 52–4

conservative measures 54initial 52–4longer-term 54

neuropathic bladder 176organisms 44–5pathogenesis 44–5, 44urinary stasis 45

urine collection 45–6urine collection bags, adhesive 46urine collection pads 46urine culture 47, 162urine dipsticks 46urine microscopy 46, 47urine storage and transport 46urine surveillance 65urinomas 115, 116urodynamic examination 162

overactive bladder 165urogenital sinus anomaly 160, 163urogenital trauma 307–15urolithiasis 145urovaginal confluence 163uterine duplications 192

VACTERL association 78, 191, 194, 197vagina

absence of 195congenital anomalies 291–2

vagina masculina 272vaginal bleeding 290vaginal discharge 290vaginal duplications 192vaginal septae 192vaginoplasty 286–7vaginoscopy 284valves, bladder 335varicocoele 247, 259–62

aetiology 259–60bag of worms 260classification 260complications and outcome 262diagnosis and investigation 260embolisation 261incidence 259indications for treatment 260–1pathology 260presentation 260surgical ligation 261–2treatment options 261–2

VATERL see VACTERL associationvenography 41vesicoamniotic shunting 136–7vesicointestinal fistulae 44vesicostomy 70, 114

Index384


vesicoureteric junction obstruction 73, 87–91vesicoureteric reflux 2, 57–72, 191

in adolescents 332aetiology 57–8asymptomatic presentation 62classification 58–9duplication 98ectopic ureter 104gender differences 60incidence and genetic factors 59–60investigations 62–4management 64–72

circumcision 69–70conservative or ‘medical’ 65–6, 71–2endoscopic correction 66–8endoscopic reimplantation 69nephroureterectomy 71secondary VUR 71surgical intervention 66, 71–2transureteroureerostomy (TUU) 71ureteric reimplantation 68–9vesicostomy 70

neuropathic bladder 176presentation 62primary 58secondary 58symptomatic presentation 62urinary tract infection 45voiding dysfunction 58–9

vesicouretic reflux (VCR)videocystometry 173videourodynamics 64

Vincent’s curtsey sign 164vitamin D deficiency 20, 21vitamin D synthesis 19vitamin D therapy 21–2vitamin K 202vulvovaginitis 49, 289–90VURD syndrome 116

WAGR 296water metabolism 16wide bladder neck anomaly 163–4

bilateral 300–1predisposition syndromes 295, 296staging 297survival rates 301treatment 298

Wilms’ tumour (nephroblastoma) 1, 39, 127, 128, 146, 295,326

intrarenal 298Wolf–Hirschorn syndrome 2wound infections in hypospadias 229

xanthine calculi 144, 145xanthogranulomatous pyelonephritis 144, 146, 154, 296X-ray

abdominal (AXR) 25, 41, 146–7spinal 162

Y duplications 118yolk sac tumours 304–5

zygote intrafallopian transfer (ZIFT) 4

Index 385



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PAEDIATRICUROLOGYESSENTIALSOF

This excellent and superbly illustrated text provides surgical trainees and non-specialists with an updated andextensively revised account of the urological disorders of childhood. The second edition reflects the manyadvances and innovations in paediatric urology since the first edition was published in 2002 and incorporatessuggestions and feedback from readers and reviewers of the first edition of Essentials of Paediatric Urology.There are new chapters such as “Minimally invasive paediatric urology”, which covers the innovative andrapidly advancing contribution made by laparoscopic surgery to effective patient care and "The Child as aPatient", which highlights the important differences of approach to caring for children and adults and providesclarification of the legal and ethical issues surrounding consent. There is also a new multiple choice questionchapter with cross-references to the text, as requested by many readers of the first edition, thus providing anaide-memoire for those undergoing speciality examinations.

This popular text was never intended to duplicate the large reference books written primarily for specialists.Instead it fulfils a unique role as the only textbook of paediatric urology written primarily for trainees andthose practising adult urology, paediatric surgery and paediatric urology. The second edition continues tomeet this need as well as providing a ready source of reference for non-specialists including paediatriciansand nurses. Like the first edition, the second is accessible and concise with a visual format characterised byextensive use of colour illustrations, flow charts and diagrams.

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Essential of paediatric urology