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Posterior urethral valves in children: a review of 28 cases in Yaounde, Cameroon( Télécharger le fichier original )par Andreas TEHJI CHIABI Université of Yaounde I - Specialist Diploma in Clinical Sciences, Option Paediatrics 0000 |
REPUBLIC OF CAMEROON REPUBLIQUE DU CAMEROUN Peace - Work - Fatherland Paix - Travail - Patrie FACULTY OF MEDICINE AND BIOMEDICAL SCIENCES DEPARTMENT OF PAEDIATRICS POSTERIOR URETHRAL VALVES IN CHILDREN: A review of 28 cases in Yaounde, Cameroon Thesis Submitted in Partial Fulfilment for
the By DIRECTOR CO-DIRECTORS Prof. ZOUNG KANYI Jimmy Dr. FRU ANGWAFO III Dr. Prof. ABENA OBAMA Marie Thérèse 1 POSTERIOR URETHRAL VALVES IN CHILDREN: A review of 28 cases in Yaounde TABLE OF CONTENTS PAGE DEDICATIONS 2 ACKNOWLEDGEMENTS 3 LIST OF PERSONNEL FMBS . .5 LIST OF ABBREVLATIONS 10 RESUME .. 12 SUMMARY . .17 CHAPTER I : I NTRODUCTION .. 21 CHAPTER II : OBJECTIVES 24 REVIEW OF LITERATURE 26 CHAPTER III : Anatomy of the normal urethra 27 Embryology of the urinary system .27 Embryogenesis of posterior urethral valves 35 Classification of posterior urethral valves .35 Patho-physiological changes induced by posterior III -- A
M ATERIALS AND METHODS 42 R ESULTS .45 D ISCUSSION .66 C ONCLUSIONS AND RECOMMENDATIONS ......78 B IBLIOGRAPHY 81 APPENDIX 91 2
DEDICATIONS
To The ALMIGHTY GOD: I pray you continue to help and guide me in my daily and professional activities so that the future be brighter and life more worthwhile. To my Family: My wife - Ema, my sons - Edmond and Roland. Thanks for the perseverance and may we hope for brighter days in the nearest future. To my mum - NDISI Tabitha, late Dad CHIABI David, Uncle NGONG Mathias and all my brothers and sisters. This work is entirely the fruit of your sacrifice To all children with posterior urethral valves. I love you and I promise to take special care of you 3
ACKNOWLEDGEMENTS
To Dr ANGWAFO III Thanks for encouraging me to do this work despite all the difficulties I had. You have made me learn and understand a bit of Paediatric Urology. Thanks for everything. To Dr ABENA OBAMA Marie Thérèse Thanks for accepting to supervise this work. I highly appreciate the advice and encouragement you gave me. All through my residency you had been like a mother to me. To Prof ZOUNG KANYI Jimmy Thanks for accepting to supervise this work despite your tight schedule. Thanks very much indeed. Thanks to all my teachers who moulded me up into a Paediatrician, especially Prof TETANYE EKOE, Dr ABENA OBAMA, Dr DOUMBE Pierre, Dr KAGO Innocent, Dr MBONDA Elie, Dr TCHOKOTEU Pierre Fernand, Dr TIETCHE Felix, Dr MONEBENIMP Francisca, Dr ONDOA MEKONGO Martin, Dr YAP John, Dr NSANGOU Innoussa. I hope to apply all the technical skills you taught me in examining and treating my patients. Special thanks to Dr TCHOKOTEU Pierre Fernand and Dr ENGOUDOU née Douala MOUTENG Valentine of the General Hospital. My first staggering steps in Paediatrics were with you when I was still premature. You encouraged me to go on. Thanks to Dr KAMDEM Annie and husband Mr Jean Paul KAMDEM, Dr Amos KAMDEM. Thanks for all the material and moral support you gave me in the most difficult moments of my life. I pray our friendship blossom as the morning roses. Thanks to my friends Mr EYÀA Jean Dominique, Mr KAMTO Victor, Mr KEUKAM Justin, Mr TCHOUGA Phillipe, Mr NANKAM Bernard, Mr KEMAJOU Augustin. You were close to me in very trying moments of my career. Accept my sincere thanks 4
Thanks to my long time friends Dr TAKOU Virgine, Dr BIBEE MAYI, Dr TSIAGADIGUI Jean Gustave, Dr MBANGTANG Celestine (University of Zimbabwe), Dr NYOM Elizabeth (FMBS). It has been very rough but worth the while. Thanks to Mr and Mrs Leo ANGUO for the material and moral support. Finally, sincere thanks to Miss Evelyn BANINLA and Mr MBUYONGHA Nico for sparing their time to type and arrange this work. 5
LISTE DU PERSONNEL I PERSONNEL ADMINISTRATIF 1 SOSSO Maurice Doyen. 2 NGU BLACKETT Kathleen Vice-Doyen Chargée des Affaires Académiques et de la Coopération. 3 BENGONO née CISSE TOURE Vice-Doyen Chargée de la Scolarité et des Statistiques. 4 NDUMBE Peter Vice-Doyen Chargée de la Recherche. S EWOLO NOMO DAF 6 MBARGA BEKONO Chef de Service Financier 7 ABENA Marie- Thérèse Chef de Service de Stage S DONGMO Louis Chef de Service de Programmes 9 BOUMSONG Vincent Bibliothécaire en Chef II PERSONNEL ENSEIGNANT a) PROFESSEURS 1 ABONDO Antoine Anatomie Pathologique 2 EDZOA Titus Chirurgie Générale 3 EIMO MALONGA Elisée Chirurgie Générale 4 HAGBE Paul Médecine Interne / Cardiologie 5 KAPTUE NOCHE Lazare Hématologie 6 LANTUM NONI Daniel Santé Publique 7 MAKANG MA MBOG Mathias Neuropsychiatrie S MBEDE Joseph Pédiatrie 9 NGU BLACKETT Kathleen Médecine Interne / Cardiologie 10 NGU LIFANJI Jacob Médecine Interne /Néphrologie 11 NKOULOU Hubert Pédiatrie 12 OBOUNOU AKONG Dominique Anatomie Humaine 13 ZOUNG KANYI Jimmy Chirurgie/Urologie 6
c) CHARGES DE COURS 1 ABENA OBAMA Marie-Thérèse Pédiatrie 2 ABOLO MBENTI Louis Chirurgie Générale 3 AFANE ELA Anatole Anesthésie - Réanimation 4 AFANE ZE Emmanuel Médecine Interne / Pneumologie 5 ANGWAFO III FRU Chirurgie / Urologie 7
48 WAMBA TEMGOUA Maurice Gynécologie-Obstétrique 49 YOMI Jean Radiologie / Radiothérapie d) ASSISTANTS
9
e) CYCLE DES ETUDES SUPERIEURES EN SOINS INFIRMIERES (CESSI) 1 MBONDA Elie 2 BOLANGA Elise (Mme) 3 NGUEMATCHA Julienne 4 ASSOMOU MBA Lydienne 5 NOUMSI André 6 OUSMANOU NASSOURO 7 OMOLOKO Cécile 8 KAMTA Charles 10
ABBREVIATIONS BUN Blood Urea Nitrogen CBC Complete Blood Count DMSA Dimercapto -- Succinic Acid FG Filtration Glomerulaire GFR Glomerular Filtration Rate IVP Intra Venous Pyelography IVSD Intra-Ventricular Septal Defect K+ Potassium NCHS National Centre for Health Statistics PUV Posterior Urethral Valves RBC Red Blood Count TUR Trans-Urethral Resection UPJ Uretero - Pelvic Junction UTI Urinary Tract Infection UVI Urographie Intraveineuse V Vesicostomy VCUG Voiding Cystourethrogram VUR Vesico - Ureteral Reflux WBC White Blood Count 11
«Posterior urethral valves is a heterogeneous disorder with a sequelae ranging from voiding dysfunction without renal impairment to early onset of renal failure and death» DENES et al 1997 (1) « the picture as usually described is but one end of a spectrum and there are many less severe and dramatic cases which escape recognition» HENDREN 1971 (2) 12
RESUME 13
Nous avons étudié 28 cas d'enfants traités ou suivis pour valves de l'urètre postérieure du ler Janvier 1985 au 31 Décembre 1996 au CHU, à l'Hôpital Central et à l'Hôpital Général de Yaoundé.' Nos objectifs ont été d'étudier les aspects épidémiologiques des valves de l'urètre postérieure à Yaoundé, de décrire la présentation c1inique, les procédures diagnostiques et le devenir post-chirurgical en termes de fonction rénale, de croissance et d'anornalies urinaires chez ces enfants L'étude a comporté 2 phases: une rétrospective transversale et l'autre prospective longitudinale descriptive, durant lesquelles nous avons étudié les données cliniques (anamnèse, procédures diagnostiques, traitement et suivi). Ce suivi comportait la surveillance clinique du jet urinaire, du poids, de la taille, des complications post-opératoires, de l'urée et la créatinine sanguine, ainsi que de l'uroculture. L'âge des patients à la première consultation après le début des symptômes variait entre 1 jour et 8 ans (moyenne 1,6 ans). L'age des patients au moment du diagnostic variait entre 9 jours et 13 ans (moyenne 2.9 ans). L'intervalle moyen entre l'âge à la première consultation et l'âge au moment du diagnostic était de 9.7 mois. Le diagnostic des valves a été fait par échographie chez 3 patients (sur la base de l'hydronéphrose bilatérale, vessie de lutte et dilatation de l'urètre postérieure). Chez les 25 patients restants le diagnostic a été fait à la fois par l'échographie et par la cystographie mictionnelle Considérant l'âge des patients au moment du diagnostic, ceux-ci ont été' divisés en trois groupes : Groupe I : (âge inférieur à 1 mois au moment du diagnostic): 5 patients. Groupe II (âge compris entre 1 mois et 12 mois): 9 patients. Groupe III: (âge supérieur à 12 mois au moment du diagnostic): 14 patients. Dans les antécédents, on note le plus souvent des infections urinaires à répétition (50%), une hypertension artérielle chez 7% des patients (en insuffisance rénale terminale). Les symptômes urinaires les plus fréquemment retrouvés sont la miction « goutte-à-goutte » (60.7%), dysurie (54%) et rétention urinaire (25%). Les symptômes 14
extra-urinaires les plus fréquents sont la fièvre (25%) et 'un retard de croissance (25%). Les principaux signes physiques sont: hernies ombilicales (21%) et distensions vésicales (10.7%). Une ascite urinaire est retrouvée chez 2 patients. Nous avons pu avoir les résultats d'uroculture chez 19 de nos patients: 12 étaient stériles; chez les 7 autres, les germes retrouvés étaient des bactéries Gram-négatif: E. coli (26%), Pseudomonas aeroginosa (11 %), Moraxella (11%), Klebsiella pneumoniae (11 %), Enterobacter aerogenes (5 %) et Proteus mirabilis (5%). La fonction rénale au moment du diagnostic a été appréciée par le calcul de la filtration glomérulaire (F.G) (à partir de la formule de COCKCROFT) Elle était très altérée avec une F.G à 5ml/min/ 1.73m2 dans le Groupe I, à 14ml/min/1.73m2 dans le Groupe II et 19m1/min/l.73m2 dans le Groupe III. Cependant, 12 patients seulement ont été revus pour évaluation dans la phase prospective et parmi eux, 9 patients seulement ont fait les tests de fonction rénale. Nous avons comparé la F.G au moment du diagnostic et a l'évaluation finale chez ces 9 patients. On a noté une amélioration de la fonction rénale chez 6 patients (66,7%) avec une augmentation de la F.G. moyenne passant de 23.7m1/min/1 73m2 à 58,8ml/min/1.73m2. Chez 2 patients (22%), on a noté une détérioration de a fonction rénale avec une F.G moyenne passant de 53,5m1/min/1,73m2 à 33ml/min/1.73m2. Chez 2 patients, la F.G est restée stable à 15ml/min/1,73m2 Une analyse comparative du poids (au moment du diagnostic et de l'évaluation finale) a également été faite chez 9 patients. Ces poids ont été reportés sur les courbes de croissance de la NCHS (National Center for Health Statistics). Au moment du diagnostic, 8 de ces 9 patients avaient un retard de croissance inférieur au 50ème percentile. A l'évaluation finale nous avons noté une amélioration de La croissance chez 5 patients mais seulement 2 sont passés au dessus de 50ème percentile. L'urographie intraveineuse (UIV) a été faite chez 6 patients et a montré une uretèro -hydronéphrose bilatérale chez 5 patients (83%), un retard de sécrétion chez 1 patient (17%) et un rein gauche muet chez 1 patient 17%. La scintigraphie a été faite chez 2 patients et chez l'un d'eux, il y avait une forte suspicion de dysplasie rénale 15
L'exploration urodynamique de la vessie a été faite chez 2 patients et a montré une réduction de la compliance vésicale chez l'un des patients En ce qui concerne le traitement, 26 patients ont subi une intervention chirurgicale les 2 patients restants ayant été perdus de vue après le diagnostic. Vingt patients ont eu une ablation endoscopique des valves, 4 une vesicostomie de Blocksom, 3 une cystostomie et 2 une ablation par sonde. Les interventions chirurgicale secondaires ont été: urétéroplastie (3), nephrostomie (4), circoncisions (4), urétérostomie (4), diverticulectomie (5) et urétérostomie pour sténose urétrale secondaire a une ablation par sonde (6). Lors de l'évaluation finale, nous avons noté 6 décès (21%), 10 perdus de vue (36%) et 12 revus à la phase prospective de l'étude. Les causes de décès ont été : septicémie 3 cas (50%), syndrome de levée d'obstacle, 2 cas (33%) et insuffisance rénale chronique, 1 cas (17%). A la fin de l'étude, nous arrivons à la conclusion que les valves de l'urètre postérieure sont diagnostiquées tardivement au Cameroun, quand l'insuffisance rénale et le retard de croissance sont déjà avancés. Le suivi des ces patients est insuffisant principalement parce que cette pathologie aussi bien que ses répercussions sur la fonction rénale et la croissance ne sont pas bien comprises. Ainsi nous recommandons que
Le jet urinaire des enfants soit évalué cliniquement lors de consultations Toute infection urinaire chez l'enfant soit correctement investiguée (surtout à l'échographie) car elle peut être la première manifestation des valves de l'urètre postérieur ou d'une autre uropathie obstructive. Les complications des valves de l'urètre postérieur et leur prise en charge soient bien connues. Un effort soit fait par les obstétriciens, les pédiatres et les radiologues afin qu'un diagnostic précoce, puisse être posé pour qu'une prise en charge adéquate soit instituée dans les plus brefs délais. 16
SUMMARY 17
We reviewed the files of 28 children treated or followed up for posterior urethral valves (PUV) from 1st January 1985 to the 31st of December 1996 in the University Teaching Hospital, Central Hospital and the General Hospital in Yaoundé. Our specific objectives were to review the epidemiological aspects of PUV in Yaoundé, assess the clinical presentation, diagnostic procedures and outcome following surgery in terms of renal function, patient growth and urinary abnormalities. The study was a retrospective cross-sectional and a prospective longitudinal descriptive review of clinical data, during which the history diagnostic procedures, treatment and follow-up parameters were noted; (stream, weight, height, BUN, creatinine, urine cultures and post - operative complications). The mean age of the patients at diagnosis was 2.9 years (range 9 days to 13 years) and the mean age at first consultation after onset of symptoms was 1.6 years (range 1 day to 8 years). The mean interval between age of first consultation and age at diagnosis was 9.7 months. The diagnosis of PUV was made on ultrasound in 3 patients on the basis of bilateral uretero - hydronephrosis, thick - wall trabeculated bladder and a dilated posterior urethra. In the remaining 25, diagnosis was made on both ultrasound and voiding cystourethrograms. Considering the age of diagnosis, the patients were divided into three groups: Group I (age of diagnosis less than 1 month) 5 patients; Group II (1 month -12 months) 9 patients and Group III (age greater than 12 months) 14 patients. The past history showed mostly recurrent urinary tract infection (UTI) in 50% of the patients and hypertension in 7% of the patients who had end-stage renal failure. The most frequent urinary symptoms were dribbling (60.7%), dysuria (54%) and urine retention (25%) whereas the most frequent non-urinary symptoms were fever (25%) and failure to thrive (25%). The main physical findings were umbilical hernias (21%) and bladder distension (10.7%), urinary ascitis was present in 2 patients (7%). Results of urine cultures were available in 9 patients, 12 were sterile Pathogens cultured in 7 patients were gram negative bacteria: E. coli (26%) Pseudomonas aeroginosa (11%), Moraxella (11%), Kiebsiella pneumoniae (11%), Enterobacter aerogenes (5%), and Proteus mirabilis (5%). 18
Renal function at diagnosis , assessed from the Glomerular-Filtration Rate (GFR) (calculated from COCKCROFT'S FORMULA ) was markedly impaired with a GFR at 5 ml/min/1.73m2 in Group I, 14m1/min/1.73m2 in Group II and 19 ml/min/1.73m2 in Group III. However, 12 patients turned up for evaluation in the prospective phase of the study and only 9 could do renal function tests. We compared the GFR at diagnosis and at final evaluation in these 9 patients. 6 (66.7%) had improved renal function with a mean GFR increasing from 23.7 ml/min/l.73m2 to 58.8 ml/min/1.75m2. 2 (22%) had deteriorated renal function with a mean GFR dropping from 53.5 ml/min to 33 rnl/min/l.73m2 whereas in 2 the GFR remained stable, at 15m1/min/l.73m2. Comparative weight analysis (at diagnosis and at final follow-up) was also done in the same 9 patients. The weights were plotted onto NCHS (National Centre for Health Statistics) growth charts. At diagnosis 8 of the 9 patients (88.9%) had growth retardation with weights below the 50th percentile. At final evaluation 5 patients had improved growth, but only 2 had gone above the 50th percentile. Intravenous pyelography (IVP) was done in 6 patients and it showed bilateral uretero-hydronephrosis in 5 (83%), late secretion in 1(17%) and a non-functioning left kidney in 1(17%). Scintigraphy was done in 2 patients and in 1 there was a strong suspicion of dysplastic kidneys. Bladder urodynamic studies were undertaken in 2 patients and reduced bladder compliance was noted in 1. Concerning treatment 26 patients underwent surgery. 2 were lost to follow up after diagnosis. 20 patients underwent endoscopic valve ablations, 4 Blocksom vesicostomies, 3 cystostomies and 2 catheter ablations. Secondary procedures performed were: ureterosplasty (3), nephrostomy (4), circumcisions (4), ureterostomy (4), diverticulectomy (5) and urethrostomy [for meatal stenosis following catheter ablations] (6). At final evaluation we noted 6 deaths (21%). 10 lost to follow-up (36%) and 12 reassessed. Causes of the deaths were septicemia: 3 cases (50%), post-obstructive diuresis: 2 cases (33 %) and chronic renal failure: 1 case (17%). 8 cases of incontinence were noted in the whole series. At the end of the study we arrived at the conclusions that PUV in Cameroon are 19
still diagnosed very late with renal impairment and growth retardation already advanced. Follow-up of these patients is inadequate mainly because the pathology is not well understood as well as its repercussions on renal function and growth. We thus recommend that:
The urinary stream of children be clinically evaluated in routine consultations. Any urinary tract infection in a child be adequately investigated (especially with ultrasound) as it might be the first manifestation of PUV or any other obstructive uropathy. The complications of PUV and their management be well known An effort be made by obstetricians, paediatricians and radiologists in making early diagnosis so that appropriate management be started as soon as possible. 20
INTRODUCTION 21
Posterior Urethral Valves (PUV) are congenital membranous recesses in the posterior urethra in males (7). They are the most common cause of lower urinary tract obstruction in male infants (7,8,9,10,11,12, 13,14,15,16,19). The incidence of PUV is reported to be 1 in 8000 live births according to CASALE A.J. cited in (10) and 1 in 25 000 live births according to ATWEL J.D. (4). The incidence in Oman is reported to be 1 in 2375 new-born males (16) which is considerably higher than any previously reported series. This was associated with an increased rate of consanguinity but there was no clear pattern of inheritance. In Yaoundé, they constitute the second cause of obstructive uropathies (1 3.3%) after uretero-pelvic junction obstruction (14.6%) according to NNOMZO'O (62) whereas it represents 15.22% of all uropathies in children in Côte d'Ivoire (18). In infants especially neonates, the clinical presentation may be atypical in the form of diarrhoea, vomiting, fever, convulsions, abdominal masses (hydronephrotic kidneys, distended bladder, foetal or neonatal urinary ascitis with retroperitoneal urinomas), failure to thrive or even sepsis (11, 13, 19, 20, 22). Some new-borns who present an unexpected respiratory distress syndrome and/or an unexplained pneumothorax or pneumomediastinum, may be found to have obstructive uropathy - usually posterior urethral valves and pulmonary hypoplasia (8, 11). In older boys, the presenting symptoms are usually recurrent urinary tract infections and dribbling or straining to urinate (8, 11, 20, 21, 22). In small infants, the condition may be so advanced when first seen, that renal failure secondary to gross bilateral hydroureters and hydronephrosis dominates the clinical picture (22). Clinical suspicion may be missed especially in neonates because of the non-urological symptomatology. The long-term consequences of such obstruction including impaired renal function and infection, remain serious problems for these patients despite newer methods of diagnosis and treatment (13). Because of the threat of premature death, early diagnosis and appropriate management are imperative. All infants or older children with urinary tract infections or abnormal voiding stream should benefit from 22
appropriate radiological investigations. Renal dysplasia and renal failure are the primary causes of death in neonates with PUV who survive initial pulmonary problems (23). According to CHURCHILL B.M. (24) the treatment of PUV is now in its fourth major phase. The first phase was recognition of the entity. The second was treatment but in which the mortality rate, particularly in neonates in the first month was almost 50 percent in most major series. The third phase consisted of markedly improved survival rates, in which the mortality rate in most tertiary paediatric urology centres was less than 10 percent. In the fourth phase the challenge after having kept these children alive is to get optimal renal function, so that optimal growth and the late complications of dialysis and transplantation are avoided. It is in this light that we reviewed the files of 28 patients with PUV followed up in the University Teaching Hospital, Central Hospital and the General Hospital in Yaoundé over an 11 year period (1st January 1985 to 31st December 1996) to assess the diagnostic methodology and outcome. To the best of our knowledge, no study has been done with these objectives in Cameroon. We hope to come out with pertinent findings and recommendations which will help physicians make early diagnosis and institute appropriate management thus avoiding long-term renal compromise and death from this disorder. 23
OBJECTIVES 24
* To review the epidemiological aspects of PIN in Yaoundé. * To assess the clinical presentation of PIN in Yaoundé. * To appraise the diagnostic procedures. * To assess the outcome of the patients following surgery (in terms of renal function, patient growth, urinary tract abnormalities, dialysis and transplantation). 25
REVIEW OF LITERATURE 26
Functionally, the urogenital system can be divided into two entirely different components (1) The urinary system and (2) the genital system. Embryologically and anatomically however, they are intimately interwoven Both develop from a common mesodermal ridge along the posterior wall of the abdominal cavity, and the excretory ducts of both systems, initially enter a common cavity, the cloaca. With further development, the overlapping of the two Systems is particularly evident in the male. The primitive excretory duct first functions as a urinary duct but later is transformed into the main genital duct Moreover , in the adult the urinary as well as the genital organs discharge urine and semen through a common duct, the penile urethra. 27
1.1 THE KIDNEY SYSTEMS Three different, slightly overlapping kidneys are formed during intra -uterine life in man: the PRONEPHROS, the MESONEPHROS, and METANEPHROS or permanent kidney. PRONEPHROS: In the human embryo the pronephros is represented by a 7 to 10 solid cell groups in the cervical region ( Fig. 3B) The first formed vestigial nephrotomes regress before the last ones are formed, and at the end of the fourth week all indications of the pronephric system have disappeared. *MESONEPHROS: During regression of the pronephric system, the first excretory tubules of the mesonephros appear. They lengthen rapidly, form an «S» - shaped loop, and acquire a glomerulus at their medial extremity. Here the tubule forms the Bowman's capsule.
Fig. 1 Diagrammatic representation of the male genital system. The midline structures are shown in a sagittal section; bilateral structures, such as testis, epididymis, vas deferens, and seminal vesicle, are depicted intact. (From Bloom/Fawcett 28
(6)) Fig. 2 The normal urethra (from Baunin et al (5)) The capsule and glomerulus form together a mesonephric (renal) corpuscle - At the opposite end the tubule enters the longitudinal collecting duct known as the mesonephric or Wolfian duct (fig 3). In the middle of the second month, the mesonephros forms a large ovoid organ on each side of the midline. Since the developing gonad is located on its medial side the ridge formed by both organs is known as the urogenital ridge. While the caudal tubules are still differentiating the cranial tubules and glomeruli show degenerative changes and by the end of the second month, the majority has disappeared. A few of the caudal tubules and the mesonephric duct however persist in the male but disappear in the female. Although great resemblances in ultra structure exist between the mesonephros and metanephros, functional activity of the mesonephros has not been demonstrated in the human embryo. *METANEPHROS OR PERMANENT KIDNEY: The third urinary organ, the metanephros or permanent kidney appears in the fifth week. Its excretory units develop from the metanephric mesoderm (fig 4) in the same manner as in the mesonephric system. 29
THE COLLECTING SYSTEM The collecting ducts of the permanent kidneys develop from the ureteric bud, an outgrowth of mesonephric duct close to its entrance into the cloaca (fig 4). The bud penetrates the metanephric tissue, which, as a cap is moulded over its distal end (Fig. 4) Subsequently the bud dilates forming the primitive renal pelvis; simultaneously it splits into a caudal portion, the future major calyces. Each calyx, while penetrating into the metanephric tissue, forms two new buds. These buds continue to subdivide until 12 or more generations of the tubules have been formed. While at the periphery more tubules are formed until the end of the fifth month, the tubules of the second order enlarge and absorb those of the third and fourth generations, thus forming the minor calyces of the renal pelvis. During further development, the collecting tubules of the fifth and successive generations elongate considerably and converge on the minor calyx, thereby forming the renal pyramid. Hence , the ureteric bud gives rise to the ureter, renal pelvis, the major and minor calyces and approximately one to three million collecting tubules. THE EXCRETORY SYSTEM Each newly formed collecting tubule is covered at its distal end by a so-called metanephric tissue cap. Under the inductive influence of the tubule cells of the tissue cap form small vesicles, the renal vesicles which in turn give rise to small tubules. These tubules form the nephrons or excretory units. The proximal end of the nephron forms the Bowman's capsule of the renal glomerulus. The distal end forms an open connection with one of the collecting tubules, thus establishing a passageway from the glomerulus to the collecting unit. Continuous lengthening of the excretory tubule results in the formation of the proximal convoluted tubule, the loop of Henle, and the distal convoluted tubule. 30
EMBRYOLOGY OF THE UROGENITAL SYSTEM (FROM LANGMAN (49)
Fig.3a Schematic transverse sections through embryos at various stages of development to show the formation of the nephric tubule. A, At 21 days; B, at 25 days. Note the formation Of the external and internal glomeruli, and the open connection between the coelomic cavity and the nephric tubule (modified after Heuser).
Fig. 3b A, Schematic diagram showing the relation of the intermediate mesoderm of the pronephric, mesonephric, and metanephric systems. In the cervical and upper thoracic regions the intermediate mesoderm is segmented; in the lower thoracic, lumbar, and sacral regions it forms a solid, unsegmented mass of tissue, the nephrogenic cord. Note the longitudinal collecting duct, initially formed by the pronephros but later taken over by the mesonephros. B, Schematic representation of the excretory tubules of the pronephric and mesonephric systems in a five-week-old embryo. Note the remnant of the pronephric excretory tubules and longitudinal collecting duct. 31
Fig 4 Schematic drawing to show the relationship of the hindgut and cloaca at the end of the fifth week. The ureteric bud begins metanephric mesoderm or blastema.
Fig. 5: Diagrams showing the division of the cloaca into the urogenital sinus and anorectal canal. Note that the mesonephric duct is gradually absorbed into the wall of the urogenital sinus and that the ureters enter separately. A, End of the fifth week; B, seven weeks; C, eight weeks. 32
Fig 6 A, Development of the urogenital sinus into the urinary bladder, the pelvic part of the urogenital sinus, and the definitive urogenital sinus. B, In the male the definitive urogenital sinus develops into the penile urethra. The prostate gland is formed by outbuddings of the urethra, while the seminal vesicles are formed by an outbudding of the ductus deferens.
Fig 7 Dorsal view of the bladder to show the relationship of the ureters and mesonephric ducts during development. Initially the ureter is formed by an outgrowth of the mesonephric duct, but with time it obtains a separate entrance into the urinary bladder. Note the trigone of the bladder formed by incorporation of the mesonephric ducts. 33
Hence the kidney develops from two different sources (1) the matanephric mesoderm which provides the excretory units and (2) the ureteric bud which gives rise to the collecting system. 1-2 BLADDER AND URETHRA During the fourth to seventh week of development, the uro-urectal septum divides the cloaca into the ano-rectal canal, and the primitive urogenital sinus (Fig.5). The cloacal membrane itself is then divided into the urogenital membrane, anteriorly, and the anal membrane, posteriorly (Fig.5C). Three portions of the primitive urogenital sinus can be distinguished: (1) the upper and largest part is the urinary bladder (Fig. 6A). Initially the bladder is continuous with the allantois, but when the lumen of the allantois is obliterated, a thick fibrous cord, the urachus remains, connecting the apex of the bladder with the umbilicus. In the adult, the ligament is known as the median umbilical ligament; (2) A rather narrow canal, the pelvic part of the urogenital sinus; which in the male gives rise to the prostatic and membranous parts of the urethra; (3) the definitive urogenital sinus, also known as the phallic part of the urogenital sinus. It is considerably flattened from side to side and is separated from the outside by the urogenital membrane. During division of the cloaca, the caudal portions of the mesonephric ducts are gradually absorbed into the wall of the urinary bladder (Fig.7). Consequently the ureters, initially outbuddings of the mesonephric ducts, enter the bladder separately (Fig.7B). As a result of the ascent of the kidneys, the orifices of the ureters move further cranial; those of the mesonephric ducts more close together to enter the prostatic urethra and in the male, become the ejaculatory ducts (Fig.7C, D). Since both the mesonephric ducts and the ureters are of mesodermal origin, the mucosa of the bladder formed by incorporation of the ducts, the trigone of the bladder is of mesodermal origin. The remaining part of the bladder is derived from the urogenital sinus and is endodermal in origin. With time, the mesodermal lining of the trigone is replaced by endodermal epithelium so that finally the inside of the bladder is completely lined with epithelium of endodermal origin. 34
The epithelium of the male and female urethra is of endodermal origin, while the surrounding connective and smooth muscle tissue are derived from the splanchnic mesoderm. At the end of the third month, the epithelium of the prostatic urethra begins to proliferate and forms a number of outbuddings which penetrate the surrounding mesenchyme. In the male, these buds form the prostatic gland (Fig.6 B). In the female, the cranial part of the urethra gives rise to the urethral and paraurethral glands. C. EMBRYOGENESIS OF POSTERIOR URETHRAL VALVES (11,13) Currently, the most accepted view is that type I valves arise from the urethrovaginal folds which become the plicae colliculi in the course of development. The origin of the urethrovaginal folds is a matter of dispute. Some authors believe that these folds represent the fibrous track left behind by the Wolfian ducts as they migrate posteriorly and medially around the wall of the urogenital sinus until they meet the paramesonephric duct at the müllerian tubercle in the middling, whereas others think they represent the anterior potion of the hymenal ring and thus would be müllerian derivatives. However abnormal formation or regression of these plicae colliculi may be involved in the genesis of typical PUV which are exaggerations of the normal folds. Type III membranes may be variable in origin. Some may represent type I valves with marked anterior fusion, whereas others may represent incomplete disappearance of the urogenital membrane. A genetic component has been postulated from occasional observations of PUV in twin and no-twin siblings (8, 11, 27, and 16). But the genetic factors in the pathogenesis of PUV are poorly understood. PUV have also been described to be associated with other chromosomal abnormalities ad Down's Syndrome (19, 26). 35
D. CLASSIFICATION OF POSTERIOR URETHRAL VALVESLANGENBECK in 1802 is credited with the first description of PUV, but in 1919 YOUNG H.H, FRONTZ W.A and BALDWIN J.C. reported 36 cases, 12 from a personal series and a further 24 from the world literature (cited by DINNEEN and Duffy in 10). YOUNG et al described 3 types of valves -Fig.8 (cited in 28, 29, 30, 11, 12, 2, 13, and 31) Type I: It is a bicuspid valve that originates just distal to the verumontanum on the floor of the posterior urethra and diverges distally in an antero-lateral orientation to fuse anteriorly in the midline at the twelve o'clock position at the anterior wall just proximal to the membranes urethra. The appearance endoscopically is that of two membranes, paired in a manner similar to the vocal cords, fused anteriorly. The fusion creates a valve which obstructs the outflow of urine while allowing the retrograde passage of catheters or irrigating fluid 95% of PUV are Type I, with variations in leaflet thickness and in the degree of coalescence at the twelve o'clock position. The resulting obstruction consists of filmy membranes which are easily disrupted, or at worst, a thickened tissue with a small inferior opening. This type corresponds to the "Spinnaker Sail" appearance. Type II: They are a series of folds that run between the verumontanum and the bladder neck and probably are non-obstructive. Type III: They are obstructing diaphragms with a central opening, located in the membranous urethra. They do not have a typical attachment to the inferior portion of the verumontanum and are of a different embryological origin. There are two subgroups: IIIa. - below the verumontanum; and IIIb above the verumontanum. 36
BASIC TYPES OF POSTERIOR URETHRAL VALVES (FROM GARRY S.H. (30))
The YOUNG's classification however, developed largely on the basis of autopsy dissection before the advent of endoscopy, has some inaccuracies and does not correspond well to modern ideas of the normal anatomy and embryology of this region (11). 37
The three types of valves described in YOUNG's series had undergone urethral manipulation before assessment and so this classification has been criticized (10). This misconception appears to result from post-mortem dissections from the anterior approach, cutting through the fused anterior portion of a structure that modern endoscopic studies reveal is actually a diaphragm with a lumen, making it appear as if there were two leaflets instead of a membrane (11). In a similar fashion, there are superficial fibroelastic bundles that pass upward and laterally towards the base of the bladder. These are the structures that YOUNG et al thought correspond to Type II valves. Although they are occasionally quite prominent, most authors agree that these structures are almost never obstructive (11). Current endoscopic evidence (29, 30, 11) dismiss the existence of Type II valves. According to DEWAN (29), the acceptance of a single basic morphology for the posterior urethral pathology suggests that there is only one embryological process, which is probably a persistence of the normal attachment of the verumontanum to the posterior urethra. He has thus proposed a nomenclature for valves different from YOUNG's classification. The type III valve which is a more distal bulbar obstructing membrane with a central hole may well constitute a persistence of the urogenital diaphragm and referred to as COBB's COLLAR, whereas the term COPUM (Congenital Obstructive Posterior Urethral Membrane) may be appropriate for the posterior urethral valves (Type I). E. PATHOPHYSIOLOGIC CHANGES INDUCED BY PUV ON THE URO- GENITAL TRACT(32, 10, 11, 33, 64, 17, 35, 36) i. Urethral Changes Proximal to the obstruction, the urethral dilates and balloons. A proximal diverticulum may develop and dilatation and gaping of the prostatic and ejaculation ducts may occur. PUV have been mentioned as a possible cause of urethro-ejaculatory reflux of infected or sterile urine (with possibility of bilateral obstruction of the genital 38
tract) and presumed to be a possible cause of acute epididymitis and infertility. Under normal circumstances, the reflux of urine into the male genital tract is impossible. The anti-reflux mechanism is effected by the oblique passage of the ejaculatory duct through the thick prostatic tissue. This mechanism might be rendered incompetent by the extreme attenuation of the foetal prostatic tissue consequent upon excessive dilatation of the obstructed prostatic urethra. It should be noted that the foetal kidneys start producing urine during the third month of gestation would prevent the growth of the prostate; early urethral obstruction would prevent the growth of the prostrate and the development of a competent anti-reflux mechanism. Infertility could also result from retrograde ejaculations following surgery on the bladder neck. ii. Vesical Changes Early, the detrusor and trigonal thickening and hypertrophy compensate for the outlet obstruction and lead to complete bladder emptying. This change leads to progressive development of the bladder trabeculation, cellules then diverticula. Beyond a certain phase, bladder decompensation occurs and is characterized by the above changes, pins variable amounts of residual urine. Trigonal hypertrophy leads to secondary ureteral obstruction due to increased resistance to flow through the intravesical ureter. With the detrusor decompensation and residual urine accumulation, there is stretching of the hypertrophied trigone, which increases ureteral obstruction. This is the mechanism of back pressure on the kidneys in the presence of vesical outlet obstruction, while the uretero-vesical junction maintains its competence. Catheter drainage of the bladder relieves trigonal stretch and improves drainage from the upper tract. A very late change with persistent obstruction (more frequently encountered with neurogenic dysfunction) is decompensation of the uretero-vesical junction, leading to reflux, which aggravates the back pressure in the upper tract by exposing it to abnormally high intravesical pressure, in addition to favouring (the onset or persistence ) of urinary tract infection. Should ureteral obstruction be unilateral a compensatory hypertrophy of the contralateral kidney will develop. Total renal function therefore remains normal. 39
Bladder diverticula and unilateral vesicoureteral reflux may serve as 'popoff' mechanisms to buffer high pressures in the urinary tract. Patients with PUV may also develop valve bladders, which are thick walled, poorly compliant and often with high resting pressures even at small urine volumes. It is this high bladder pressure that is so damaging to the urinary tract. Bladder dysfunction (unstable, poorly compliant and over distended bladders which are variations of the same basic urodynamic pattern) that changes with time towards decompensation is clearly a contributory factor to urinary incontinence.
The renal pelvis and calyces being subjected to progressively increasing volumes of retained urine progressively distend. The pelvis first shows evidence of hyperactivity and hypertrophy and then progressive dilatation and atony. The calyces show the same changes to a variable degree depending on whether the renal pelvis is intra or extra-renal. In the latter, the calyceal dilatation may be minimal in spite of marked pelvic dilatation. In the intra -renal pelvis, calyceal dilatation and renal parenchymal damage are maximum. The successive phases seen with obstruction are rounding of the fornices, followed by flattening of the papillae and finally clubbing of the minor calyces. In neonates and infants there may be extravasation of urine at the level of the renal pelvis or the ureterovesical junction with formation of urinary ascitis and perirenal 40
and retroperitoneal urinomas resulting in abdominal distension v. Renal Parenchymal changes Since urine formation begins between the ninth and twelfth weeks of gestation corresponding to the formation of the inner cortical nephrons in the centrifugally developing kidney , obstruction to urinary outflow could increase hydrostatic pressure and thus affect the environment of the foetal kidney during the very early phases of morphogenesis, resulting in hypoplastic or dysplastic renal development in addition to simple hydronephrosis whereas obstruction late in gestation may produce simple hydronephrosis It should be noted that nephron differentiation occurs up to the thirty-second week of gestation. With progressive pelvicalyceal distension, there is parenchymal compression against the renal capsule. This, plus the more important factor of compression of the arcuate vessels as a result of the expanding distended calyces results in a marked drop in renal blood flow. This phenomenon leads to progressive parenchymal compression and ischemic atrophy. Lateral groups of nephrons are affected more than central ones, leading to patchy atrophy with variable degree of severity. The glomeruli and proximal convoluted tubules suffer most, of this ischemia. Associated with the increased intrapelvic pressure there is progressive dilatation of the collecting and distal tubules with compression and atrophy of tubular cells. Whereas dilation of the calices and the thinness of the parenchyma my be explained on the bases of atrophy from back pressure of obstruction and reflux, the etiology of variants such as asymmetrical kidney morphologies, the occurrence of near normal renal parenchyma in some kidneys exhibiting all the ureteral and caliceal stigmas of severe obstruction and dysplasia, is not the same. HENNEBERY and STEPHENS (37) have clearly demonstrated that these variants may be due to ectopic origins of the ureteral buds from the most caudal part of the Wolfian duct, which leads to induction of defective or sparse mesenchyme of the tail end of the nephrogenic cord with resultant dysplasia and hypoplasia, respectively. The key to the potential quality of the renal parenchyma is the ureteral orifice. This is the "bud theory" of the renal morphology 41
42
MATERIALS AND METHODS 43
Consent was obtained from all the parents before admission into the study. Explanations as to the innocuity of the study were given as well as benefits incurred from regular follow-up after surgery to avoid short and long-term complications. 44
6. DATA ANALYSIS The data collected was analysed in a computer (type NCR) using the Epi-lnfo medical software. 45
RESULTS 46
Table 1: CLASSIFICATION OF ALL THE PATIENTS ACCORDING TO AGE AT DIAGNOSIS
Table 2: PAST HISTORY
*glucose 6 phosphate dehydrogenase deficiency **intra ventricular septal defect 47
Table 3: PRESENTING COMPLAINTS AT DIAGNOSIS ACCORDING TO AGE GROUPS (N=28)
48
Table 4: MAIN PHYSICAL FINDINGS AT DIAGNOSIS ACCORDING TO AGE GROUPS (N=28)
Table 5: BIOLOGIC INVESTIGATIONS AT DIAGNOSIS
49
Table 6: GLOMERULAR FILTRATION RATES AT DIAGNOSIS
GFR (ml / min / 1.73m2) was calculated from COCKCROFT'S formula:
Table 7: RESULTS OF URINE CULTURE AT DIAGNOSIS (N = 12)
Urine cultures were available in 19 patients. In 12 they were positive of the above pathogens and sterile in 7. One patient had both a klebsiella pnuemoniae and Proteus mirabilis infection. 50
Table 8: MAIN ULTRA SONOGRAPHIC FINDINGS AT DIAGNOSIS (N = 18)
Other associated findings: + Bilateral renal cortical atrophy in 3 (17%) + Bilateral renal antrophy in 1 (6%) + Bilateral renal parenchyma atrophy and megaureters in 1 (6%) + Megaureters with the left ectopic (6%) Table 9: MAIN VOIDING CYSTOURETHROGRAM FINDINGS AT DIAGNOSIS (N = 18)
VUR was bilateral in 4 patients and on the right in 1 patient. Large urine residual volumes were present in 2 patients. Hutch's diverticulum was noted in 2. Table 10: IVP FINDINGS AT DIAGNOSIS (N = 6)
51
52
Voiding cystourethrogram of a 9 day old child showing a large trabeculated bladder, dilated posterior urethra and a filling defect at the posterior urethra indicating a PUV.
53
A 3 months old with a multidiverticular bladder and a dilated posterior urethra Control cysto urethrogram in an 8 year old boy following resection of PUV at the age of 2 years showing a normal bladder wall and posterior urethra. 4
Table 11: SCINTIGRAPHY (N = 2)
NB There was a strong suspicion of dysplasia in the patient with bilateral atrophy. Table 12: URODYNAMIC STUDIES (N = 2)
Table 13: SURGICAL TREATMENT (N = 25)
2 patients were lost to follow-up after diagnosis and didn't undergo and surgery. One patient with terminal renal failure underwent ureterostomy in France but was lost to follow-up. 22 patients underwent surgery in Cameroon, 1 in Britain and 1 in France. 5 Patients did not have endoscopic resection. 4 in the vesicostomy group (2 died and 2 pending by the end of the study) and 1 in the catheter ablation group. 55
Table 14: SECONDARY PROCEDURES IN 11 PATIENTS (N=15)
Table 15: OUTCOME OF THE 28 PATIENTS
Table 16: CAUSES OF DEATHS
1 case of septicaemia was associated with congestive heart failure. 56
Table 17: EVALUATION OF RENAL FUNCTION AND WEIGHTS AT DIAGNOSIS AND AT FINAL FOLLOW-UP PRE-OPERATIVELY:
POST-OPERATIVELY(at end of follow-up):
= 140 -age (yrs) X weight (kg) 72 x Creatinine (mg %) GFR was calculated from COCKCROFT'S formula* GFR (ml/min/1.73m2) Normal values: New born (day 1) - 5-50 ml/min/1.73m2 (mean 18 ml/min/1.73m2) (day 6) * 15 - 90 ml/min/1.73m2 (mean 36 ml/min/1.73m2) Older children and adults (levels reached at 6 months * Males: 85 - 125 ml/min/1.73m2 * Females: 75 - 115 ml/min/1.73m2 > Nephron 16: - 31 -71, 1976 57
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DISCUSSION 67
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