Development of posterior urethral valves-current concepts-Prof. P Venugopal

 Development of Posterior Urethral valves - Current Concepts Prof. P. Venugopal Posterior urethral valve (PUV) is a common cause of lower urinary tract obstruction in male infants and the most common congenital cause of bilateral renal obstruction. PUV continues to be a significant cause of morbidity, mortality and ongoing renal damage in infants and children. The incidence of PUV is estimated to be 1 in 5000 to 8000 male births. But it may be more common if foetal demise is taken into consideration. With the advent of Foetal Ultrasound more cases are being detected antenatally enabling prompt treatment to be instituted early. This has resulted in successful treatment in considerable number of children. But if one were to consider renal failure with progression to ESRD, PUV still stands out a a prominent cause. In the past till 1950, the success of treatment for PUV was dismal with near 100% mortality. Many considered most of these children as having Bladder Neck stenosis and the post urethral dilatation evidenced on VCUG as post stenotic dilatation. Many of these unfortunates underwent bladder neck excision till Hutch commented that the virginity of the bladder neck should not be sacrificed. Subsequently many open procedures were devised to ablate the inaccessible location of the valve. Using ENT Bivalve Speculum and use of plastic surgery hooks were one of them. Upper tract urinary diversion of some type (there were several), in those who had evidence of renal failure and most presented with renal failure was routine. Cutaneous vesicostomy became a procedure of choice for some time. Primary valve fulguration was not considered as no endoscopes available at that time were suitable. With miniaturization of scopes as we have today, with better understanding of neonatal care and better understanding of pathophysiology, our treatment regimes for initial management changed dramatically. But in a country like India, we still do come across children with PUV in a state of renal failure where an initial upper tract diversion may be required. MacKinnon (2005) in an article on the value of high diversion for PUV summed up by stating ‘where there is gross upper tract dilatation, consideration need be given to temporary diversion to allow recovery of renal function and elimination of infection’. He further adds ‘Western literature is strongly against diversion. Countries not having highly developed medical facilities encounter more complicated cases and in them it may be necessary to consider even initial diversion’. The commonest investigation used for diagnosis of PUV apart from Ultrasound postnatally is VCUG, Radiopharmaceuticals and scopy. Abdolmohammed Kajbafzadeh (2005) tracing the VCUG images found 12 variations. Embryology of Male Urethra To understand the development of PUV, it is essential to know the embryology of male urethra briefly. It is easier to quote from Terry Levin’s article published in 2007, Paediatric Radiology as it is succinct and brief. Between weeks four and five of foetal life, the cloaca is separated from the amniotic cavity by the cloacal membrane (Krishnan A, Basin L et al 2006). The cloaca is divided into the urogenital sinus and the hindgut by the urorectal septum, which descends in a rostral-to-caudal fashion (Figure 1). The urogenital sinus is the precursor of the bladder and posterior urethra. The urorectal septum is formed by proliferation, migration and fusion of mesodermal folds that arise from the lateral walls of the cloaca. When the urorectal septum reaches the caudal aspect of the cloaca, the cloacal folds, which lie on the dorsal portion of the cloacal membrane, fuse to form the rudimentary perineum. The cloacal membrane subsequently undergoes disruption such that the hindgut and phallic cloaca open separately to the exterior, divided by the urorectal septum (Fig. 2). The most caudal aspect of the cloaca (phallic cloaca) extends distally through the developing genital tubercle. Proliferation of rostral mesoderm of the genital tubercle displaces the cloaca so that it lies on the caudal aspect of the developing glans (Fig. 3). Failure of this step results in epispadias. The endodermal lining of the phallic cloaca appose to form the urethral plate. Portions of the cloacal membrane also contribute to the urethral plate (Fig. 4). 1. Embryologic development of the male genitourinary tract. The cloaca is divided into the urogenital sinus (precursor of the bladder and posterior urethra) and the hindgut by the urorectal septum. 2. The urorectal septum continues to descend and the cloacal membrane undergoes disruption. The hindgut and phallic cloaca now open separately to the exterior. 3. The phallic cloaca extends distally through the developing genital tubercle. Proliferation of rostral mesoderm of the genital tubercle displaces the cloaca so that it lies on the caudal aspect of the developing glans. 4. Median cleavage of the urethral plate occurs. The urethral plate forms the deep and lateral walls of the proximal urethra. The phallic cloaca opens to the exterior at the base of the glans. There is considerable controversy as regards urethral groove along the undersurface of the genital tubercle. van der Putte et al (2003) found no evidence of a groove or of fusion of folds on the undersurface of the genital tubercle. According to them, the urorectal septum, which divides the cloaca and forms the perineum, extends ventral ward by intrinsic growth, pushing the urogenital opening distally to form the penile urethra. History of PUV 1717 – Morgagni first described obstruction of the posterior urethra. 1802 – Langenbeck in his monogram on stone disease mentioned this condition. 1832 – Velpaeu coined the term ‘valves’ because the folds in posterior urethra resembled cardiac valves. 1840 – Budd and 1847 Bednar described the valves as the valves seen in Venous system and considered the reverse placement as cause of obstruction. 1911 – Lederer concluded that the abnormality was a ‘semi circular diaphragmatic obstruction below the verumontanum’ in autopsy study. 1914 – Lowsley found the entire structure is more or less dome shaped and said that the term ‘diaphragm’ more appropriate. 1919 – Hugh Hampton Young published his article on 12 cases he studied. His description was well accepted and only recently the description was questioned. Even today students of PUV attach much importance for his description. In 1929 he modified his classification to add additional features. Taken from Paddy Dewan’s article of 2006 His original description of 1919 and the modified version of 1929. He was the first to use Scopy for the diagnosis of PUV. In 1919, Young proposed a classification system consisting of three types of valves. Type I valves (the most common) arise from the verumontanum and extend distally to attach to the lateral walls of the urethra as two leaflets (type I a) or as a unicuspid leaflet (type I b). Type II valves extend proximally from the verumontanum to the bladder neck. The existence of Young’s type II valves is debated (Manzoni and Valentini 2002). Ttype III valves represent a diaphragm attached to the circumference of the urethra with a central hole, distal (type III a) or proximal (type III b) to the verumontanum. 1961 – Presman presented his autopsy finding on infants not instrumented and found the offending lesion was a membrane with a pinhole opening. 1969 – Robertson and Hynes found an obliquely lying diaphragm below the verumontanum with a slit like opening posteriorly. 1977 - Parkkulainen supported the membrane theory using cystoscopic evidence. 1992 – Paddy Dewan proposed a new terminology for this complex obstructive lesion and the importance of this will be discussed later. Embryology – Various concepts The embryologic defect leading to the development of PUV is not known. Various concepts have been proposed. Though Morgagni in 1717 described the existence of valve like structure in the posterior urethra he did not give it any importance it was due. Tolmatschew (1870) described the valves discovered in autopsy specimens as ‘overgrowths of the normally present anatomical folds and ridges in the urethra’. He was the first to postulate an embryological theory of PUV development. Bazy (1903) disagreed with these theories and claimed that the site of PUVs corresponded to the site of the urogenital membrane that separated the anterior and posterior urethra during development. He believed that it was the persistence of this membrane that led to the pathological condition of PUVs. Wilckens (1910) claimed that PUVs were remnants of the cloacal membrane that had been left as the cloaca divided into the urogenital sinus, perineum and rectum. Lowsley (1914) was the first to offer a theory of PUV development based on microscopic examination. He noted that these valves came from the same connective tissue sheath encasing the ejaculatory ducts except these fibers attached to the entire circumference of the urethra, creating almost total obstruction of the urethra proximal to the valve. Understanding the Wolffian origin of the ejaculatory ducts, Lowsley proposed that PUVs were due to an anomaly of Wolffian or Müllerian duct origin. Lowsley was the first to study and mention that the membrane had stratified squamous epithelium, differentiating it from the usual transitional epithelium of the prostatic urethra. The valves were primarily composed of dense connective tissue fibers and interspersed smooth muscle fibers, possibly suggesting a mesodermal origin. Watson (1918) provided his theory of PUVs. During week 14 there was evidence that the surface epithelium above the developing glands of the colliculus seminalis underwent notable proliferation, filling the space between the verumontanum and the roof of the urethra. During this time the mucosal lining of the colliculus was histologically continuous with the lining of the roof of the urethra. Watson surmised that PUV formation occurred when this growth and attachment of the verumontanum to the roof of the urethra persisted during this time of surface epithelial proliferation. He was unknowingly making a reference to Apoptosis. This is the accepted view of Paddy Dewan from subsequent studies. Young et al (1919) attempted to unify several of these theories, perhaps because they believed that no single view explained the development of all types of PUVs. To sum up the embryogenesis as it was understood at that time Campbell in 1932 mentioned the various theories existing in nut shell and remain unchanged and used even today. But it should be realized that none of these theories has been, however, complete and descriptive of the entire pathology of the urethral valve. 1. Hypertrophy of the urethral mucosal folds, proposed by Tolmatschew in 1870 2. Bazy's theory, the persistence and continuation of the urogenital membrane, proposed in 1903 3. Abnormal development of the Wolffian or Mullerian duct, proposed by Lowsley in 1914 4. Fusion of the colliculus seminalis or the posterior urethral roof epithelium, proposed by Watson in 1918. Further concepts were proposed subsequently Stephens (1955) looking at VCUG as well as macroscopic and microscopic analysis of the posterior urethra in normal fetuses and cases suspicious for PUVs made several astute observations during a detailed gross anatomical description of the urethra and the ‘inferior crest’ with its distally diverging fins in the urethra. This was reproducibly seen as a ‘straight tapering ridge arising from the lower end of the verumontanum, diverging laterally into 2 to 4 fins and disappearing distal at the level of the perineal membrane’. Stephens also noted that in the majority of patients with PUVs the inferior crest was shortened or totally absent. In normal infants in some these fins may be shortened but never absent. With this Stephens concluded that PUVs were a result of abnormal integration of the Wolffian ducts into the urethra, causing an abnormally obstructing membrane that would normally be seen as non-obstructing “fins” radiating distal from the verumontanum in the un-afflicted infant. His contribution is undeniable in supporting the theory of Lowsley of PUVs with careful autopsy dissection and keen embryological observations. But all was not well for the Wolffian Theory proposed by Lowsley and supported by Stephens. Williams and Eckstein (1965) examined 104 cases of PUVs and supported the theory of Tolmatschew that valves represented an exaggeration of normal folds first seen in the urethra at the 50 mm stage, which grow to their maximum dimensions by the 100 mm stage. They believed that these ridges bore no relation whatsoever to Wolffian duct structures. In studies subsequently the Wolffian Theory regained its position. The very concept of naming this condition as posterior urethral valves was questioned. Studies showed that these were not valves but represented a membrane in the posterior urethra. Though Presman (1961) found the offending lesion as a membrane with a pinhole opening, credit goes to Robertson and Hynes (1969) for clarifying the concept of membrane as against they being valves. They consistently observed an obliquely oriented diaphragm extending from the verumontanum to the urethral roof. The bicuspid appearance was due to defective dissection of the anterior urethral valve employed by other workers. They opined that the valvular structure instead of what was truly a single membrane. The cloaca separates into the urogenital sinus and the rectum sometime between weeks 4 and 6 of gestation, and the urogenital sinus gives rise to the bladder and posterior urethra. The Wolffian ducts fuse early with the cloaca at week 4 of gestation. The study of Robertson and Hayes suggests that, as the connective tissue sheath of the ejaculatory ducts pierces the lumen of the urethra, it heaps up the transitional epithelium of the posterior urethra. Histologically this study as well as that of Lowsley supported the hypothesis of an extra-urethral or Wolffian origin of PUVs. Current Terminology and Justification With all the current views expressed succinctly by various recent workers, have we been calling the condition by a wrong terminology which still will remain entrenched in our minds irrespective of the fact that the condition should get another terminology. Credit should go to Paddy Dewan, whose persistent studies from early 1990 (publications in 1992, 1994, 1995,1997and 2006) has lead us to call this condition collectively as Congenital Obstructive Posterior Urethral Membrane (CPOUM). He demonstrated by performing Videoendoscopic studies the presence of the membrane and not valves. He opined that most of the lesions seen were originally unicuspid and not bicuspid as described. Robertson and Hynes from proper dissection of posterior urethra had arrived at a similar conclusion. Both opined that the membrane ran down from verumontanum obliquely to the urethral roof with a hole of varying sizes placed near the verumontanum. This Dewan opined was the reason for various presentations from mild to severe obstruction. The endoscopic appearance of severe obstructing membrane with posterior defect connecting to the verumontanum (Paddy Dewan, 2006). They also claimed that the types 1 and 3 valves of Young et al were in fact the same with either being mistaken for the other during endoscopy based on the angle of visualization, flow, suprapubic pressure and prior urethral instrumentation including catheter placement. COPUM Type 3 Catheter splitting COPUM Type 1 Catheter Slitting Paddy Dewan believes that there are only 2 distinct entities with 2 distinct embryological origins causing obstruction in the posterior urethra, namely COPUM and Cobb’s collar (Moorman’s Ring). The distinction between COPUM and Cobb’s Collar should be made from their lie in relation to Verumontanum. COPUM is oblique and has intimate attachment to the Verumontanum while the later, Cobb’s collar, is independent in its relationship with Verumontanum and is seen a s a transverse membrane unrelated to the urethral sphincter. Cobb’s collar is more often missed unless it produces urinary problems. In many cases of Nocturnal Enuresis this condition has been observed (Mikio Sugimoto et al 2005). Watson’s theory for embryogenesis was considered the most appropriate for COPUM and persistence of the urogenital membrane for Cobb’s collar. Cobb’s Collar Radiological and Endoscopic Thus at present the very terminology, however close it is to our hearts, is being questioned and the term COPUM and Cobb’s collar be used to describe these conditions depending on their lie as explained. It may be difficult for such a change (as is seen with the terminology, BPH) with our using the terminology PUV for such a long time. Considerable studies are being carried out in the molecular and genetic aspects of development of Wolffian ducts in Ureterogenesis and in the development of Lower urinary tract. May be soon we may have a different concepts in our understanding of COPUM (PUV) based on these studies. It may refute or agree with the present concept of COPUM. Nothing is static as we have seen with the development of COPUM/PUV. We have to wait till this end patiently.

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  • Dr. Anil Takvani
    Dr. Anil Takvani
    26 Jun 2020 05:44:54 PM

    Dear All,

    I have posted an excellent write up on development of posterior urethral valve-Current concepts received from Prof. P Venugopal as a separate thread.
    Attached document is a complete article. 
    Thanks Sir

  • Uday Sankar Chatterjee
    Uday Sankar Chatterjee
    03 Jul 2020 08:05:22 PM

    Thanks to Venugopal Sir, for valuable post on PUV...

    We are very much interested to find out the factors cause upstaging and end staging of CKD  i.e. ESRF: incidence of which is ~25-50%.

    In our study… along with review of literature, we opine that actual cause of obstruction of posterior urethra is presumed to be due to RSS (Rhabdo Sphincter Spasm). Cusp of PU valve, particularly in Neonate, only amplify the obstruction.

        RSS presumed to be due to delayed coordination between autonomic and somatic Nv system; approximates NNB.

       RSS usually cause detrusor hypertrophy. So sequels to BNO, UVJO and to upstaging of CKD.

    That's why even after meticulous and complete fulguration,  progress of stages of CKD might not abate.

    We have suggested the necessary investigations and procedure for prevention of upstaging and end staging,  in our article in press (already posted in this forum)
    Please go through and give your valuable opinion.

  • Uday Sankar Chatterjee
    Uday Sankar Chatterjee
    03 Jul 2020 08:32:59 PM


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