Kidiu'v lntcrnaiio,wl Vol. 20 (/98/) pp 695—699 Etiology and pathogenesis of the prune belly syndrome EBERHARD STRAUB and JURGEN SPRANGER (/,iI/ren's Hospital, Uni'ersitv of Molar, Ma/ar, Germany The congenital triad of abdominal muscle deficiency, severe urinary tract abnormality, and cryptorchidism forms a rare hut well-defined clinical condition popularly known as the "prune belly syndrome" (PBS) 11—101. The term "prune belly" is descriptive of the characteristic wizened, dried-plum appear- ance in the newborn and young infant (Fig. I). The peculiar and, in "classical" cases, pathognomonic aspect of the thin, trans- parent, redundant abdominal skin, which is loose rather than stretched, nestling to the wobbly intestines at birth, becomes less marked with advancing age. With age, the wrinkles flatten out as the subcutaneous fat and intraabdominal content in- crease, expanding further the flaring and floppy flanks and the paunch. In addition to the therapeutic challenge presented by the PBS, its etiology and pathogenesis have been controversial. Earlier studies suggested a mesenchymal developmental arrest during the 6th to 7th week of gestation leading to coordinated defects of dependent structures [II, 121. Recently, an old hypothesis has been resurrected and extend- ed 113—151. It explains the morphologic characteristics of the PBS as sequelae of' an intrauterine distension of the abdomen, usually by enlargement of' the bladder due to an obstruction of the proximal urethra 116—191. Operative removal of the ob- structing tissue such as an urethral valve would under these circumstances be a logical measure in the affected newborn or infant. Our personal experience with 14 patients with PBS and a critical analysis of the literature do not support the hypothesis of a secondary pathogenetic sequence arising from a primary obstructive uropathy. PBS and the "urethral obstruction mal- formation complex" 114] are different conditions, which can he separated by clinical, radiographic, endoscopic, and histologic evaluation. This distinction determines the choice of the most effective form of therapy. Patients The clinical features of our patients, 12 males and 2 females;, are summarized in Tables I and 2. The typically ectatic, extremely elongated, and tortuous ureters were present in 13 patients. All of these patients had hypoplastic or dysplastic kidneys and an enlarged bladder with considerable amounts cf residual urine. In the 6 patients with dilatation of the collecting system, the "hydronephrosis" was less pronounced than would be expected in view of the massiveness of the megaureters (Fig. 2). The boys in this group showed an extraordinary bulge in the proximal urethra, associated with an abnormally small or absent prostate (Fig. 3). The increased width of the proximal urethra was somewhat less distinct in the 2 girls. Appropriate radiographic investigations and cystoscopic examination re- vealed some type of urethral stenosis in only 4 patients (exclu- sively males). Six boys displayed visible (partial) agenesis of the abdominal wall musculature, corresponding to the "classical" PBS. In 7 children, including the 2 girls, hypoplasia and/or dysplasia of the abdominal musculature was confirmed by muscle biopsies, demonstrating a reduced number of partially broadened muscle fibres with loss of' coherence of the Z hands. clumping of glycogen granules, and mitochondrial abnormali- ties on electron microscopic studies, described in the literature as the "embryonal type" [5, II, 20, 21]. Bilateral cryptorchi- dism was recognized in 8 of the 12 boys. Of particular interest is patient 7, a 3-year-old boy with a classical prune belly and bilateral cryptorchidism but with a normal urinary tract (Figs. 4 and 5). Discussion In the past, the question of whether the uropathy in the PBS is of an obstructive nature has been the subject of vehement debate among urologists [9—lI, 16—18, 22—34]. The issue, how- ever, was considered settled 19, 10, 24—27, 29—331 until the surprising renaissance in the pediatric literature of the hypothe- sis that both the muscular abdominal wall defect and the intraabdominal retention of the testes were produced by urinary tract distension [13--l5, 19]. The modern concept is based on growing experience with technically improved endoscopes, which have disclosed clearly that the abrupt transition from the extremely wide prostatic to the distal portion of the urethra is caused not by a real valve or other cause of narrowing, hut rather by agenesis or hypoplasia of the prostate 19. 10. 2 1—27. 29, 31, 33, 34]. The latter phenomenon is, in fact, confined almost entirely to the PBS and could hardly be related to any infravesical obstruction because, despite voluminous residual urine, the intravesical fluid pressure is abnormally low in PBS [30, 311. In addition, the phenomenon does not occur in cases of isolated urethral valve. Close analysis of radiographs ol' this region reveals unequivocal differences from pictures seen in "mechanical" urethral obstruction [9, 10, 22—27, 33, 34]. The caliber of the urethra at the level of the verumontanum usually is normal; also saccular diverticula and/or absence of a corpus 695 Received for publication April l. 1981 0085-2538/8 1/0020-0695 $01 .00 © 1981 by the International Society of Nephrology brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Elsevier - Publisher Connector
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Etiology and pathogenesis of the prune belly syndromeKidiu'v lntcrnaiio,wl Vol. 20 (/98/) pp 695—699
Etiology and pathogenesis of the prune belly syndrome EBERHARD STRAUB and JURGEN SPRANGER
(/,iI/ren's Hospital, Uni'ersitv of Molar, Ma/ar, Germany
The congenital triad of abdominal muscle deficiency, severe urinary tract abnormality, and cryptorchidism forms a rare hut well-defined clinical condition popularly known as the "prune belly syndrome" (PBS) 11—101. The term "prune belly" is descriptive of the characteristic wizened, dried-plum appear- ance in the newborn and young infant (Fig. I). The peculiar and, in "classical" cases, pathognomonic aspect of the thin, trans- parent, redundant abdominal skin, which is loose rather than stretched, nestling to the wobbly intestines at birth, becomes less marked with advancing age. With age, the wrinkles flatten out as the subcutaneous fat and intraabdominal content in- crease, expanding further the flaring and floppy flanks and the paunch.
In addition to the therapeutic challenge presented by the PBS, its etiology and pathogenesis have been controversial. Earlier studies suggested a mesenchymal developmental arrest during the 6th to 7th week of gestation leading to coordinated defects of dependent structures [II, 121.
Recently, an old hypothesis has been resurrected and extend- ed 113—151. It explains the morphologic characteristics of the PBS as sequelae of' an intrauterine distension of the abdomen, usually by enlargement of' the bladder due to an obstruction of the proximal urethra 116—191. Operative removal of the ob- structing tissue such as an urethral valve would under these circumstances be a logical measure in the affected newborn or infant.
Our personal experience with 14 patients with PBS and a critical analysis of the literature do not support the hypothesis of a secondary pathogenetic sequence arising from a primary obstructive uropathy. PBS and the "urethral obstruction mal- formation complex" 114] are different conditions, which can he separated by clinical, radiographic, endoscopic, and histologic evaluation. This distinction determines the choice of the most effective form of therapy.
Patients
The clinical features of our patients, 12 males and 2 females;, are summarized in Tables I and 2. The typically ectatic, extremely elongated, and tortuous ureters were present in 13 patients. All of these patients had hypoplastic or dysplastic kidneys and an enlarged bladder with considerable amounts cf residual urine. In the 6 patients with dilatation of the collecting system, the "hydronephrosis" was less pronounced than would be expected in view of the massiveness of the megaureters (Fig. 2). The boys in this group showed an extraordinary bulge in the proximal urethra, associated with an abnormally small or absent prostate (Fig. 3). The increased width of the proximal
urethra was somewhat less distinct in the 2 girls. Appropriate radiographic investigations and cystoscopic examination re- vealed some type of urethral stenosis in only 4 patients (exclu- sively males). Six boys displayed visible (partial) agenesis of the abdominal wall musculature, corresponding to the "classical" PBS. In 7 children, including the 2 girls, hypoplasia and/or dysplasia of the abdominal musculature was confirmed by muscle biopsies, demonstrating a reduced number of partially broadened muscle fibres with loss of' coherence of the Z hands. clumping of glycogen granules, and mitochondrial abnormali- ties on electron microscopic studies, described in the literature as the "embryonal type" [5, II, 20, 21]. Bilateral cryptorchi- dism was recognized in 8 of the 12 boys. Of particular interest is patient 7, a 3-year-old boy with a classical prune belly and bilateral cryptorchidism but with a normal urinary tract (Figs. 4 and 5).
Discussion
In the past, the question of whether the uropathy in the PBS is of an obstructive nature has been the subject of vehement debate among urologists [9—lI, 16—18, 22—34]. The issue, how- ever, was considered settled 19, 10, 24—27, 29—331 until the surprising renaissance in the pediatric literature of the hypothe- sis that both the muscular abdominal wall defect and the intraabdominal retention of the testes were produced by urinary tract distension [13--l5, 19]. The modern concept is based on growing experience with technically improved endoscopes, which have disclosed clearly that the abrupt transition from the extremely wide prostatic to the distal portion of the urethra is caused not by a real valve or other cause of narrowing, hut rather by agenesis or hypoplasia of the prostate 19. 10. 2 1—27. 29, 31, 33, 34]. The latter phenomenon is, in fact, confined almost entirely to the PBS and could hardly be related to any infravesical obstruction because, despite voluminous residual urine, the intravesical fluid pressure is abnormally low in PBS [30, 311. In addition, the phenomenon does not occur in cases of isolated urethral valve. Close analysis of radiographs ol' this region reveals unequivocal differences from pictures seen in "mechanical" urethral obstruction [9, 10, 22—27, 33, 34]. The caliber of the urethra at the level of the verumontanum usually is normal; also saccular diverticula and/or absence of a corpus
695
Received for publication April l. 1981
0085-2538/8 1/0020-0695 $01 .00 © 1981 by the International Society of Nephrology
brought to you by COREView metadata, citation and similar papers at core.ac.uk
provided by Elsevier - Publisher Connector
Fig. 2. Intravenous urogram in a patient with the prune belly syndro,ne, demonstrating the characteristic elongation and tortuosity of the ureters without hydronephrosis.'
Fig. 1. Prune belly aspect still recognizable at the age qf /0 months
Fig. 4. Abdominal aspect of patient no. 7 at 3 years of age. The Fig. 3. Urethrogram in a patient with the prune belly syndrome. There characteristic wrinkles that contribute to the wizened, dried plum is an extreme ectasia of the proximal urethra (agenesis of the prostate) appearance, present during the first months of life have flattened out. but no real obstruction. Note the bilateral cryptorchidism and agenesis of the inguinal canal.
I
Prune he/fr svndrwne
Table 1. Characteristics of patients with prune belly snydrome (PBS) or obstructive uropathy
Partial agenesis or hypoplasia of abdom. wall musculature Cryptorchidism Abnormalities of the inguinal canal Agenesis or hypoplasia of the prostate Extreme tortuosity of the massive megaureters Dysplastic (or almost normal) kidneys Reduced ureteral fluid pressure Reduced intravesical micturation pressure (Gross) hydronephosis Increased ureteral fluid pressure Increased intravesical micturation pressure
Table 2. Clinical features of our patients
I 2 3 4
+ + + + + + + + — +
— + —
— + — — + —
spongiosum (but no meatal stenosis) are frequently observed distal to the "false," counterfeit obstruction 110, 24—28, 31, 341. Real stenotic alterations or valves of the posterior urethra are the exception in PBS [10, 191; they were diagnosed in only 4 of our patients. Thus, PBS can occur in association with clear-cut urethral obstruction, but this combination is not a causal one. Hence, most cases of congenital urethral obstruction will have abdominal swelling but not a prune belly. Patients with urethral atresia are stillborn or die shortly after birth and may present with various symptoms of the Potter (renal agenesis) syndrome [19, 341.
The reduced intravesical fluid pressure in PBS [II. 23, 31J differs distinctly from the increased values measured in obstruc- tive uropathy. The bladder wall shows no muscular hypertro- phy or trabeculation [9, 10, 24—28, 31, 341; its augmented thickness results from hyaline-rich deposits [II, 20, 281. Ac- cording to all surveys, and in contrast to the situation in
obstructive uropathy. the dome of the bladder is quite often capped with a urachal process or diverticulum. and a patent, eventually huge, urachal cyst may be detected in PBS.
Numerous other findings in the PBS are not explained by the assumption of a primary obstructive lesion of the urinary tract. The muscle deficiency in PBS only rarely affects the entire abdominal wall, and it may be unilateral or assymmetric [9. 10. 34, 35]. In PBS with agenesis of the abdominal musculature there is no histologic sign of an aponeurotic layer that might represent atrophied muscles [9] as one would expect if the defect were due to degeneration following abdominal disten- sion. The type of abdominal wall defect usually present in PBS is an infrequent feature in proven congenital obstructive uro- pathy. Conversely, the characteristic abdominal muscle agenesis or ("embryonal") hypoplasia in PBS may be manifest with normal urinary tracts, as in our patient 7 and in a few females in the literature [9, 10, 34. 35]. On the other hand, typical PBS
PBS Obstructive uropathy
+ + + -F — + -1- — -F-
7 8 9 10 II 12 13 14
6 4 4 Vt- 3 8 6 4 4 I 5 /I2+ M M M M M M M M M M F F + + + + — + + -F- + + + +
Age, rear,s Sex Characteristic PBS uropathy (ectasia &
extreme elongation/tortuosity of ureters) Renal dysplasia and/or hypoplasia Dilatation of the collecting system Vesicoureteral/renal reflux (uni or bilat.) Communicating urachal cyst "Megacystis" (residual urine) Moderate trabeculation of the bladder Extreme and pathognom. (!) dilatation of the
prox. urethra )absence/hypopl. of prostate) Marked dilatation of the prox. urethra Normal urethra Urethral stenosis (valve?) Normal urinary tract Chron. recurr. urinary tract infection Irreversible uremic syndrome Mild or (partly) reversed renal insuffic.
improvement of kidney function by therapy Partial abdominal muscle agenesis
("classical" dried plum appearance) Abdominal muscle drsp/usiu/hvpop/usia
(verification h biopsy: "incomplete" PBS) Cryptorchidism (bilateral)
— +
— + + + + + + + * +
— + + + + +
— + + — + —
+ — + — — + + —
— -- — + — —
+ + + + + + — + + + + + + +
+ + - + + + + -- — +
— + + + + + + +
+ —
698 Straub and Spranger
Fig. 5. Intravenous urogram showing a normal urinary tract (patient no. 7).
uropathy may be associated with a normal abdominal wall [10, 24, 25, 351.
The morphology of upper urinary tract abnormalities in PBS differs decisively from the well-known form in obstructive uropathy. The kidneys are nearly normal or, much more often there are histologic features of a primary dysplasia with depos- its of cartilage, tubular irregularities, cystic areas, and strikingly pronounced vascularization. In contrast, the "hydronephrotic" rarefaction of a kidney dilated by obstruction and high intralu- minal pressure is not seen [10, II, 21, 23, 35, 36]. The calyces are elongated, have a bizarre configuration, and are mostly reduced in number [9, 10, 21, 25—30, 32, 341. Obstructive uropathy does not initiate the grotesque tortuosity of the ureters of PBS with grossly enlarged and relatively "normal" segments alternating [10, 24—27, 34]. The smooth muscles in PBS are replaced to a great extent by fibrous tissue [II, 23], whereas congenitally obstructed ureters show muscular hyperplasia.
In this context, the paucity and dysplasia of the nerve plexus and the irregularities of the Schwann cells [371 may have pathogenetic significance in the atony of the ureters and the ensuing insufficiency of urine transport in PBS. Even in cases of PBS with enormous ureteral (and vesical) distension, the intra- luminal fluid pressure is low rather than elevated as in obstruc- tive uropathy [10, II, 23, 30, 31].
Statements such as "testicular descent would be blocked by distension of the bladder" [131 and "cryptorchidism . . . ap- pears to be secondary to the massively dilated bladder obstruct- ing descent of the testes" in PBS [14] are refuted by the fact that the gonads are usually descended in severe megacystis due to congenital infravesical obstruction and sometimes in the pres- ence of PBS-associated enlargement of the (hypotonic) bladder
(see Refs. 1, 8, 16, 17, 35, and our patient 3). Megacystis could not be responsible for either the agenesis or dysplasia and/or abnormal location of the inguinal canal [6, 9, 10, 32, 38] or for the typical position of the testes at the high posterior abdominal wall in PBS [9, 10, 34].
Finally, the clinical course of PBS differs in many ways, usually unfavorably, from that in obstructive uropathy. Several authors have reported excellent results in preserving and im- proving renal function in PBS by extensive surgical reconstruc- tion (tapering and reimplantation of the eventually refluxing ureters, urethrotomy, abdominal wall plication) [16—18, 29, 39— 421. But, the majority of urologists now have arrived at a far more tentative position or even a "hands-off philosophy" [10]. They advise utmost caution in attempting to alter the urody- namics and the course of events in PBS by operative manage- ment, including drainage measures by nephrostomy, cutaneous ureterostomy or cystostomy (except for the emergency situa- tion or the rare patient with real obstruction) [9, 10, 31, 32, 34, 38, 43, 44]. The almost consistently disappointing long-term outcome of more or less aggressive operative procedures proba- bly is due to the resistance to therapy of the primary atony with ineffective peristalsis of the ureters and bladder and ensuing persistent urinary stasis. Because intraluminal fluid pressure is not increased in PBS (for the same pathophysiologic reasons), the threat of pressure-induced renal tissue deterioration by itself does not constitute an indication for surgical intervention. Conservative treatment will maintain renal function even better if bacterial infection is kept under control, because tonicity and peristalsis of the urinary tract structures have a tendency to improve spontaneously [10, 23, 29, 32, 38, 43—45].
These practical aspects alone should lead to the abandonment of the concept of PBS as a multiple anomaly syndrome second- ary to lower urinary tract obstruction. The bulk of other evidence precludes the idea of urethral obstruction as the cause of the PBS [14] and favors the concept of it being a generalized developmental abnormality [46, 47] in which the individual manifestations of the PBS are independent results of a disturbed inductor/organizer cell-cell interaction during early embryogen- esis. The "developmental abnormality" is thought to represent an area of segmenting mesoderm lateral to the notochord from which multiple structures including kidneys, genitourinary tract, and abdominal wall originate [48]. The cause and nature of the generalized disturbance are unknown.
Summary. The hypothesis explaining the characteristics of the prune belly syndrome (congenital partial absense of the abdominal wall musculature, severe urinary tract abnormali- ties, and cryptorchidism) as sequelae of a primary obstructive uropathy is supported neither by evidence from the literature nor by our own observations. Critical analysis of the known facts favors the concept of a developmental field complex in which the various manifestations of the prune belly syndrome are produced by an early mesodermal defect.
Reprint requests to Prqf. ES t,auh, Children's Hospital. Stiidtisches Krankenhaus Hoechst, Gotenstral3e 6—8, 6230 F,'ankfurt a rn. 80. Ge,'— many
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Etiology and pathogenesis of the prune belly syndrome EBERHARD STRAUB and JURGEN SPRANGER
(/,iI/ren's Hospital, Uni'ersitv of Molar, Ma/ar, Germany
The congenital triad of abdominal muscle deficiency, severe urinary tract abnormality, and cryptorchidism forms a rare hut well-defined clinical condition popularly known as the "prune belly syndrome" (PBS) 11—101. The term "prune belly" is descriptive of the characteristic wizened, dried-plum appear- ance in the newborn and young infant (Fig. I). The peculiar and, in "classical" cases, pathognomonic aspect of the thin, trans- parent, redundant abdominal skin, which is loose rather than stretched, nestling to the wobbly intestines at birth, becomes less marked with advancing age. With age, the wrinkles flatten out as the subcutaneous fat and intraabdominal content in- crease, expanding further the flaring and floppy flanks and the paunch.
In addition to the therapeutic challenge presented by the PBS, its etiology and pathogenesis have been controversial. Earlier studies suggested a mesenchymal developmental arrest during the 6th to 7th week of gestation leading to coordinated defects of dependent structures [II, 121.
Recently, an old hypothesis has been resurrected and extend- ed 113—151. It explains the morphologic characteristics of the PBS as sequelae of' an intrauterine distension of the abdomen, usually by enlargement of' the bladder due to an obstruction of the proximal urethra 116—191. Operative removal of the ob- structing tissue such as an urethral valve would under these circumstances be a logical measure in the affected newborn or infant.
Our personal experience with 14 patients with PBS and a critical analysis of the literature do not support the hypothesis of a secondary pathogenetic sequence arising from a primary obstructive uropathy. PBS and the "urethral obstruction mal- formation complex" 114] are different conditions, which can he separated by clinical, radiographic, endoscopic, and histologic evaluation. This distinction determines the choice of the most effective form of therapy.
Patients
The clinical features of our patients, 12 males and 2 females;, are summarized in Tables I and 2. The typically ectatic, extremely elongated, and tortuous ureters were present in 13 patients. All of these patients had hypoplastic or dysplastic kidneys and an enlarged bladder with considerable amounts cf residual urine. In the 6 patients with dilatation of the collecting system, the "hydronephrosis" was less pronounced than would be expected in view of the massiveness of the megaureters (Fig. 2). The boys in this group showed an extraordinary bulge in the proximal urethra, associated with an abnormally small or absent prostate (Fig. 3). The increased width of the proximal
urethra was somewhat less distinct in the 2 girls. Appropriate radiographic investigations and cystoscopic examination re- vealed some type of urethral stenosis in only 4 patients (exclu- sively males). Six boys displayed visible (partial) agenesis of the abdominal wall musculature, corresponding to the "classical" PBS. In 7 children, including the 2 girls, hypoplasia and/or dysplasia of the abdominal musculature was confirmed by muscle biopsies, demonstrating a reduced number of partially broadened muscle fibres with loss of' coherence of the Z hands. clumping of glycogen granules, and mitochondrial abnormali- ties on electron microscopic studies, described in the literature as the "embryonal type" [5, II, 20, 21]. Bilateral cryptorchi- dism was recognized in 8 of the 12 boys. Of particular interest is patient 7, a 3-year-old boy with a classical prune belly and bilateral cryptorchidism but with a normal urinary tract (Figs. 4 and 5).
Discussion
In the past, the question of whether the uropathy in the PBS is of an obstructive nature has been the subject of vehement debate among urologists [9—lI, 16—18, 22—34]. The issue, how- ever, was considered settled 19, 10, 24—27, 29—331 until the surprising renaissance in the pediatric literature of the hypothe- sis that both the muscular abdominal wall defect and the intraabdominal retention of the testes were produced by urinary tract distension [13--l5, 19]. The modern concept is based on growing experience with technically improved endoscopes, which have disclosed clearly that the abrupt transition from the extremely wide prostatic to the distal portion of the urethra is caused not by a real valve or other cause of narrowing, hut rather by agenesis or hypoplasia of the prostate 19. 10. 2 1—27. 29, 31, 33, 34]. The latter phenomenon is, in fact, confined almost entirely to the PBS and could hardly be related to any infravesical obstruction because, despite voluminous residual urine, the intravesical fluid pressure is abnormally low in PBS [30, 311. In addition, the phenomenon does not occur in cases of isolated urethral valve. Close analysis of radiographs ol' this region reveals unequivocal differences from pictures seen in "mechanical" urethral obstruction [9, 10, 22—27, 33, 34]. The caliber of the urethra at the level of the verumontanum usually is normal; also saccular diverticula and/or absence of a corpus
695
Received for publication April l. 1981
0085-2538/8 1/0020-0695 $01 .00 © 1981 by the International Society of Nephrology
brought to you by COREView metadata, citation and similar papers at core.ac.uk
provided by Elsevier - Publisher Connector
Fig. 2. Intravenous urogram in a patient with the prune belly syndro,ne, demonstrating the characteristic elongation and tortuosity of the ureters without hydronephrosis.'
Fig. 1. Prune belly aspect still recognizable at the age qf /0 months
Fig. 4. Abdominal aspect of patient no. 7 at 3 years of age. The Fig. 3. Urethrogram in a patient with the prune belly syndrome. There characteristic wrinkles that contribute to the wizened, dried plum is an extreme ectasia of the proximal urethra (agenesis of the prostate) appearance, present during the first months of life have flattened out. but no real obstruction. Note the bilateral cryptorchidism and agenesis of the inguinal canal.
I
Prune he/fr svndrwne
Table 1. Characteristics of patients with prune belly snydrome (PBS) or obstructive uropathy
Partial agenesis or hypoplasia of abdom. wall musculature Cryptorchidism Abnormalities of the inguinal canal Agenesis or hypoplasia of the prostate Extreme tortuosity of the massive megaureters Dysplastic (or almost normal) kidneys Reduced ureteral fluid pressure Reduced intravesical micturation pressure (Gross) hydronephosis Increased ureteral fluid pressure Increased intravesical micturation pressure
Table 2. Clinical features of our patients
I 2 3 4
+ + + + + + + + — +
— + —
— + — — + —
spongiosum (but no meatal stenosis) are frequently observed distal to the "false," counterfeit obstruction 110, 24—28, 31, 341. Real stenotic alterations or valves of the posterior urethra are the exception in PBS [10, 191; they were diagnosed in only 4 of our patients. Thus, PBS can occur in association with clear-cut urethral obstruction, but this combination is not a causal one. Hence, most cases of congenital urethral obstruction will have abdominal swelling but not a prune belly. Patients with urethral atresia are stillborn or die shortly after birth and may present with various symptoms of the Potter (renal agenesis) syndrome [19, 341.
The reduced intravesical fluid pressure in PBS [II. 23, 31J differs distinctly from the increased values measured in obstruc- tive uropathy. The bladder wall shows no muscular hypertro- phy or trabeculation [9, 10, 24—28, 31, 341; its augmented thickness results from hyaline-rich deposits [II, 20, 281. Ac- cording to all surveys, and in contrast to the situation in
obstructive uropathy. the dome of the bladder is quite often capped with a urachal process or diverticulum. and a patent, eventually huge, urachal cyst may be detected in PBS.
Numerous other findings in the PBS are not explained by the assumption of a primary obstructive lesion of the urinary tract. The muscle deficiency in PBS only rarely affects the entire abdominal wall, and it may be unilateral or assymmetric [9. 10. 34, 35]. In PBS with agenesis of the abdominal musculature there is no histologic sign of an aponeurotic layer that might represent atrophied muscles [9] as one would expect if the defect were due to degeneration following abdominal disten- sion. The type of abdominal wall defect usually present in PBS is an infrequent feature in proven congenital obstructive uro- pathy. Conversely, the characteristic abdominal muscle agenesis or ("embryonal") hypoplasia in PBS may be manifest with normal urinary tracts, as in our patient 7 and in a few females in the literature [9, 10, 34. 35]. On the other hand, typical PBS
PBS Obstructive uropathy
+ + + -F — + -1- — -F-
7 8 9 10 II 12 13 14
6 4 4 Vt- 3 8 6 4 4 I 5 /I2+ M M M M M M M M M M F F + + + + — + + -F- + + + +
Age, rear,s Sex Characteristic PBS uropathy (ectasia &
extreme elongation/tortuosity of ureters) Renal dysplasia and/or hypoplasia Dilatation of the collecting system Vesicoureteral/renal reflux (uni or bilat.) Communicating urachal cyst "Megacystis" (residual urine) Moderate trabeculation of the bladder Extreme and pathognom. (!) dilatation of the
prox. urethra )absence/hypopl. of prostate) Marked dilatation of the prox. urethra Normal urethra Urethral stenosis (valve?) Normal urinary tract Chron. recurr. urinary tract infection Irreversible uremic syndrome Mild or (partly) reversed renal insuffic.
improvement of kidney function by therapy Partial abdominal muscle agenesis
("classical" dried plum appearance) Abdominal muscle drsp/usiu/hvpop/usia
(verification h biopsy: "incomplete" PBS) Cryptorchidism (bilateral)
— +
— + + + + + + + * +
— + + + + +
— + + — + —
+ — + — — + + —
— -- — + — —
+ + + + + + — + + + + + + +
+ + - + + + + -- — +
— + + + + + + +
+ —
698 Straub and Spranger
Fig. 5. Intravenous urogram showing a normal urinary tract (patient no. 7).
uropathy may be associated with a normal abdominal wall [10, 24, 25, 351.
The morphology of upper urinary tract abnormalities in PBS differs decisively from the well-known form in obstructive uropathy. The kidneys are nearly normal or, much more often there are histologic features of a primary dysplasia with depos- its of cartilage, tubular irregularities, cystic areas, and strikingly pronounced vascularization. In contrast, the "hydronephrotic" rarefaction of a kidney dilated by obstruction and high intralu- minal pressure is not seen [10, II, 21, 23, 35, 36]. The calyces are elongated, have a bizarre configuration, and are mostly reduced in number [9, 10, 21, 25—30, 32, 341. Obstructive uropathy does not initiate the grotesque tortuosity of the ureters of PBS with grossly enlarged and relatively "normal" segments alternating [10, 24—27, 34]. The smooth muscles in PBS are replaced to a great extent by fibrous tissue [II, 23], whereas congenitally obstructed ureters show muscular hyperplasia.
In this context, the paucity and dysplasia of the nerve plexus and the irregularities of the Schwann cells [371 may have pathogenetic significance in the atony of the ureters and the ensuing insufficiency of urine transport in PBS. Even in cases of PBS with enormous ureteral (and vesical) distension, the intra- luminal fluid pressure is low rather than elevated as in obstruc- tive uropathy [10, II, 23, 30, 31].
Statements such as "testicular descent would be blocked by distension of the bladder" [131 and "cryptorchidism . . . ap- pears to be secondary to the massively dilated bladder obstruct- ing descent of the testes" in PBS [14] are refuted by the fact that the gonads are usually descended in severe megacystis due to congenital infravesical obstruction and sometimes in the pres- ence of PBS-associated enlargement of the (hypotonic) bladder
(see Refs. 1, 8, 16, 17, 35, and our patient 3). Megacystis could not be responsible for either the agenesis or dysplasia and/or abnormal location of the inguinal canal [6, 9, 10, 32, 38] or for the typical position of the testes at the high posterior abdominal wall in PBS [9, 10, 34].
Finally, the clinical course of PBS differs in many ways, usually unfavorably, from that in obstructive uropathy. Several authors have reported excellent results in preserving and im- proving renal function in PBS by extensive surgical reconstruc- tion (tapering and reimplantation of the eventually refluxing ureters, urethrotomy, abdominal wall plication) [16—18, 29, 39— 421. But, the majority of urologists now have arrived at a far more tentative position or even a "hands-off philosophy" [10]. They advise utmost caution in attempting to alter the urody- namics and the course of events in PBS by operative manage- ment, including drainage measures by nephrostomy, cutaneous ureterostomy or cystostomy (except for the emergency situa- tion or the rare patient with real obstruction) [9, 10, 31, 32, 34, 38, 43, 44]. The almost consistently disappointing long-term outcome of more or less aggressive operative procedures proba- bly is due to the resistance to therapy of the primary atony with ineffective peristalsis of the ureters and bladder and ensuing persistent urinary stasis. Because intraluminal fluid pressure is not increased in PBS (for the same pathophysiologic reasons), the threat of pressure-induced renal tissue deterioration by itself does not constitute an indication for surgical intervention. Conservative treatment will maintain renal function even better if bacterial infection is kept under control, because tonicity and peristalsis of the urinary tract structures have a tendency to improve spontaneously [10, 23, 29, 32, 38, 43—45].
These practical aspects alone should lead to the abandonment of the concept of PBS as a multiple anomaly syndrome second- ary to lower urinary tract obstruction. The bulk of other evidence precludes the idea of urethral obstruction as the cause of the PBS [14] and favors the concept of it being a generalized developmental abnormality [46, 47] in which the individual manifestations of the PBS are independent results of a disturbed inductor/organizer cell-cell interaction during early embryogen- esis. The "developmental abnormality" is thought to represent an area of segmenting mesoderm lateral to the notochord from which multiple structures including kidneys, genitourinary tract, and abdominal wall originate [48]. The cause and nature of the generalized disturbance are unknown.
Summary. The hypothesis explaining the characteristics of the prune belly syndrome (congenital partial absense of the abdominal wall musculature, severe urinary tract abnormali- ties, and cryptorchidism) as sequelae of a primary obstructive uropathy is supported neither by evidence from the literature nor by our own observations. Critical analysis of the known facts favors the concept of a developmental field complex in which the various manifestations of the prune belly syndrome are produced by an early mesodermal defect.
Reprint requests to Prqf. ES t,auh, Children's Hospital. Stiidtisches Krankenhaus Hoechst, Gotenstral3e 6—8, 6230 F,'ankfurt a rn. 80. Ge,'— many
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