Megacystis

Distended thick-walled bladder usually associated with bilateral hydro-ureteronephrosis or cystic dysplastic kidneys.

1/2000–4000 newborns.

A dilated bladder may be due to obstructive or non-obstructive conditions. The first group comprises posterior urethral valves (PUV), typical of male fetuses, urethral steno-atresia, and persistent cloaca (mainly female). In the second group, the bladder dilatation is not due to obstruction but rather to abnormalities of the vesical tone, frequently related to neurologic or genetic (e.g., megacystis microcolon intestinal hypoperistalsis syndrome, MMIH) disorders.

Early and complete obstruction (urethral atresia, and complete posterior urethral valves) may result in conspicuous dilatation of the bladder, with elevation of the diaphragm and distension and thinning of the fetal abdominal wall. The association of megacystis with deficit of abdominal wall muscles, and cryptorchidism is typical of the clinical condition known as prune belly syndrome, which can occur as a primary lesion due to an aberration of mesenchymal development between the 6th and 10th weeks of gestation, or be secondary to various causes, with urethral obstruction being the most common.^1,2

The increased intravesical pressure present in megacystis, commonly leads to vesicoureteral reflux and consequent hydro-ureteronephrosis. The increased intrarenal pressure leads to a dilatation of the collecting system and impairing, by compression, the blood flow to the proximal renal tubules. The consequent parenchymal damage results in a loss of proteins, which are no longer reabsorbed, in the fetal urine. Sometimes, the vesicoureteral reflux resulting from the obstruction may cause massive unilateral hydronephrosis that can totally destroy the kidney, decompressing the contralateral kidney, which may only show moderate hydronephrosis. The extremely high intraluminal pressures may also lead to rupture of the bladder; in this case, urinous ascites and decompression of the collecting system occur. However, in most of cases, the end stage effects of early gestation high grade bladder outlet obstruction is cystic renal dysplasia.

The etiology is unknown for most of these conditions. PUV may result from failure of complete disintegration of the urogenital membrane, leaving membranous tissue within the posterior urethra.³ The etiology is probably variable, as PUV occurs in a number of disorders with multiple congenital anomalies.

Urethral atresia and agenesis result from damage or failure of formation of the urethra. The defect could involve any part of the urethra, and is most common in males, probably due to the complexity of the embryologic origin of the male urethra.

Persistent cloaca is a complex embryological anomaly characterized by a common opening for the rectum, vagina and urinary tract.³ It results from abnormal formation of the urorectal septum.

In MMIH syndrome, myogenic and neurogenic influences have been proposed.

PUV appears like a diaphragmatic membrane with a small eccentric opening situated within the posterior urethra. This is a simple mucosal membrane with a small amount of fibrous stroma. A fusiform dilatation of the prostatic urethra occurs between the obstructing membrane and the bladder neck4

In persistent cloaca a confluence of the bladder, proximal uretra, upper 2/3 of the vagina, and rectum, with connection to the perineum through a single common channel, is present. In more than 50% of cases there is hydrocolpos which can compress the trigone of bladder, with resulting bladder outlet obstruction and consequent megacystis. Intestinal obstruction is usually associated.

In MMIH syndrome the pathologic findings vary considerably and include changes in the neural tissue and muscle within the bowel wall. Macroscopically there is a dilated thick-walled bladder that is non-obstructed, functional small bowel obstruction and malrotated microcolon.⁴

PUV has been found in association with other anomalies in up to 43% of cases, mainly cardiac anomalies, anal atresia, VATER syndrome and vescicoureteric fistula 3.

Urethral atresia can be associated with multiple abnormalities in 52% to 66% of cases, but the diagnosis is usually difficult due to the oligo/anhydramnios. Abnormalities often associated with urethral atresia include cardiac defects, diaphragmatic hernia, anal atresia, esophageal atresia, unilateral renal agenesis, polydactyly, cleft lip and palate and VATER syndrome. An association with chromosomal defects in particular trisomy 13, 18 and 21 has been reported4

Multiple associated anomalies are present with persistent cloaca, including upper urinary tract obstruction and ectopic kidneys. Uterine and vaginal duplication, esophageal and duodenal atresia, myelomeningocele and congenital heart defects have been also reported.

MMIH has been found in association with omphalocele, cardiac defects and cleft palate.

Urethral atresia mainly represents a sporadic condition, and the recurrence risk is therefore low.

The pattern of inheritance is unclear for PUV, with both autosomal recessive and autosomal dominant modes suggested. The overall recurrence risk for isolated PUV is around 2-6%.⁵

Persistent cloaca represents a sporadic condition, with no increased risk of recurrence.

MMIH syndrome is an autosomal recessive condition with a consequent 25% risk of recurrence.⁴

Ultrasound diagnosis of lower urinary tract obstruction is mainly based on visualization of a dilated bladder with thick and hyperechoic walls, usually associated with bilateral hydro-ureteronephrosis.⁶ The bladder wall is considered thickened if it measures more than 2 mm. Proximal urethral distensionmay be also evident (“keyhole sign”). Although it was reported that the “keyhole sign” represents the appearance of a dilated bladder and distended posterior urethra and it is typical of PUV, in a recent case series⁷ it was present in only 45% of PUV cases and in more than 25% of cases of lower urinary obstruction with other etiologies.

However, the ultrasound picture depends on the degree and duration of the obstruction. In the case of incomplete obstruction, as in some cases of posterior urethral valves, the amniotic fluid is normal or slightly decreased and hydro-ureteronephrosis is present. On the contrary, in cases of complete posterior urethral valves, or of urethral atresia, an early and long lasting obstruction can lead to early and severe back pressure damage resulting in cystic renal dysplasia ( Potter type IV) with complete loss of renal function. As a result, the production of urine is extremely reduced. In this case, the sonographic findings consists of small and hyperechoic kidneys, sometimes with small pericortical cysts, and oligohydramnios. In this regard, it must be underlined that the lack of amniotic fluid could be noted after 14–16 weeks of gestation, when its production mainly depends on the fetal renal function. In a meta-analysis of infants with lower urinary tract obstruction, hyperecoic kidneys and cortical cysts were the most predictive parameters of poor renal function with a specificity of 84% and sensitivity of 57%.⁸ Oligohydramnios was also associated with poor prognosis.⁸

In the first trimester of gestation, the early and severe obstruction, such as in case of urethral atresia, is responsible for a severe dilatation of the bladder, which frequently occupies the whole abdomen.

In the case of persistent cloaca, megacystis is usually associated with hydrometrocolpos and obstructed bowel.

As already mentioned, it should be noted that megacystis can be also associated with non-obstructive disorders, often in the context of genetic syndromes, as in case of the MMIH syndrome, in which the amount of amniotic fluid is usually increased and dilatation of the stomach is frequently present.

PUV must be differentiated from severe vesico-ureteral reflux: bladder dilatation and hydro-ureteronephrosis may be present in both; however, posterior urethral valves are usually associated with thickened bladder walls and dilatation of the proximal urethra, which are absent in vesico-ureteral reflux.

An enlarged bladder detected at ultrasound may simply be a transient phase in the normal voiding cycle, or, if persistent and/or severe, it may be secondary to reflux or obstructive, neurogenic, or myopathic causes. A correct diagnosis, therefore, requires longitudinal observation.

It has been reported that, If mild to moderate vesical dilatation is present as early as the 10th–14th week, with a longitudinal bladder diameter of 7–15 mm, 23.6% of the fetuses have a chromosomal anomaly.⁹ However, if the karyotype is normal, spontaneous resolution of the megacystis occurs in about 90% of cases. If the longitudinal diameter of the bladder is greater than 15 mm, the risk of aneuploidy is about 11,4%, and in the chromosomally normal group, the condition is usually associated with progressive obstructive uropathy.⁹

If the lesion is isolated and the amount of amniotic fluid is within the normal range, the prognosis may be favourable; if, on the other hand, oligohydramnios is already present before the 24th week of gestation and the kidneys are hyperechoic (with or without cysts), the prognosis is unfavourable. Mortality is high when associated extra-renal anomalies are present. In case of PUV, although occasional spontaneous remission before birth is possible, however the prognosis is usually severe. Long term complications include recurrent urinary tract infection, persistent vescicoureteral reflux and hydronephrosis, bladder dysfunction and renal insufficiency.^3,7

The prognosis is usually poor in case of urethral atresia, with most babies dying in the neonatal period because of pulmonary hypoplasia. The development of vesico-cutaneous fistula can decompress the urinary tract and lead to neonatal survival. Those babies who do survive the neonatal period usually develop end-stage renal failure requiring dialysis or transplantation and major reconstructive surgery.³ The prognosis is also poor in cases of MMIH syndrome.³

Ultrasound monitoring of fetuses with lower urinary obstruction, together with the study of animal models, has expanded the understanding of the natural history of this disease, and has allowed the definition of some general diagnostic criteria and algorithms for pre- and postnatal management of such patients. However, several aspects of the physiopathology of fetal obstructive uropathies remain unresolved, which in turn limits both diagnostic and therapeutic approaches. The first crucial point is the inability of the sonographic examination to fully define the extent and severity of parenchymal damage and to forecast its outcome at the time of initial diagnosis, with the possible exception of the most severe forms of renal cystic dysplasia, associated with severe oligohydramnios.

The technical feasibility of in utero vesico-amniotic shunting, to be performed in selected cases to relieve prenatal urinary tract obstruction, has led to research into sensitive biochemical markers that might accurately reflect the residual fetal renal function. Unfortunately, in a significant number of cases, this approach has been unsuccessful, for a number of reasons. First, the biochemical function of the fetal kidney is only partially known, and depends largely on gestational age. Then, the fetal blood or urine concentration of any putative biochemical marker of renal function is strongly influenced by its transplacental passage. Lastly, with the limitations cited above, it appears difficultly feasible to define cut-off values that can reliably forecast the progression of renal damage, and select patients for intrauterine interventions.

Based on the available evidence, it is reasonable to adopt the following algorithm for the management: after the US detection of megacystis it is important to perform a detailed anatomic scan in order to exclude the presence of associated anomalies and offer karyotyping. Once the association with other significant anomalies (including chromosomal abnormalities) has been excluded, and if the amniotic fluid is normal, a conservative ultrasound follow-up is required, with surgical correction usually being postponed until birth.

The sonographic recognition of associated hyperecoic kidneys with or without cortical cysts, suggesting renal dysplasia, is a sign of an unfavourable outcome. Nevertheless, renal function should be explored with more invasive procedures.¹ With the already mentioned limits, it is relatively possible to assess renal function in utero carrying out vesicocentesis. Vesicocentesis is usually performed three times at 48-72-hour intervals. Depending on the results, the fetus can be assigned to either a good or poor prognostic group10,11.Normally, fetal urine is hypotonic; isotonic urine indicates renal tubular damage. For these reasons indicators of poor prognosis are : Na > 100 mg/dL, Cl> 90 mg/dL, Ca > 8mg/dL, ß2-microglobulin > 5mg/L, Osm > 210mg/dL, total protein > 40mg/dL1. Fetuses assigned to the good prognostic group, after exclusion of associated anomalies, including the chromosomal ones, are candidates for in utero surgery (placement of a vesico-amniotic shunt, cystoscopy with ablation of the posterior urethral valve, etc.). Conversely, if sonographic and biochemical findings indicate an unfavorable outcome, then termination of pregnancy may be an option, where legally allowed.

The outcome for fetuses with urethral valves that have been shunted is difficult to evaluate due to the small numbers of cases in the literature. This procedure carriers potential maternal and fetal risks (including chorioamniotitis, shunt malplacement, anterior abdominal wall defects, preterm labor, and fetal demise)¹² and it has not been yet validated by randomized trials. Part of the reported poor outcomes is related to inaccurate patient selection for such therapy, especially considering the heterogeneity of the underlying pathologies, each one associated to different outcomes.^13,14 A recent review shows that prenatal bladder drainage improves perinatal survival compared with no treatment, but may confer a high residual risk of poor postnatal renal function.¹⁵ Recently percutaneous fetal cystoscopy has been proposed for differential diagnosis between PUV and urethral atresia, and potential in utero treatment of the former.^12,16 The use of fetal cystoscopy as a diagnostic and therapeutic intervention needs to be validated.

1. Paladini D, Volpe P. Ultrasound of Congenital Fetal Anomalies. Informa Healthcare, 2007

2. Woods AG, Brandon DH, Prune belly syndrome: a focused physical assessment. Adv Neonatal Care 2007; 7: 132-143.

3. Evans JA. Urinary tract. In: Stevenson RE, Hall JG. Human Malformations and Related Anomalies, second edition. Oxford. Oxford University Press. 2006: 1161-90.

4. Twining P. Genitourinary Malformation. In: Nyberg DA, McGahan JP, Pretorius DH, Pilu G (eds): Diagnostic Imaging of Fetal Anomalies. Lippincott Williams & Wilkins, Philadelphia, 2003: 610-14.

5. Rajab A, Freeman NV, Patton M. The frequency of posterior urethral valves in Oman. Br J Urol 1996;77:900

6. Chapman T. Fetal genitourinary imaging. Pediatr Radiol. 2012 Jan; 42 Suppl 1:S115-23.

7. Bernardes LS, Aksnes G, Saada J et al. Keyhole sign: how specific is it for the diagnosis of posterior urethral valves? Ultrasound Obstet Gynecol 2009; 34: 419-23

8. Morris RK, Malin GK, Khan KS et al. Antenatal ultrasound to predict postnatal renal function in congenital lower urinary tract obstruction: systematic review of test accuracy. Br J Obstet Gynecol 2009; 116:1290-99

9. Liao AW, Sebire NJ, Geerts L, et al. Megacystis at 10-14 weeks of gestation. Chromosomal defects and outcome according to bladder length. Ultrasound Obstet Gynecol 2003; 21:338-341

10. Nicolaides KH, Cheng HH, Snijders RJ, Moniz CF. Fetal urine biochemistry in the assessment of obstructive uropathy. Am J Obstet Gynecol. 1992;166(3):932-7

11. Lun A, Lenz F, Priem F, Brux B, Gross J, Bollmann R, Hartung J, Bartho S, Kirchmaier F, Reisinger I. Biochemical diagnosis in prenatal uropathy Clin Biochem. 1994 Aug;27(4):283-7.

12. Irwin BH, Vane DW. Complications of intrauterine intervention for treatment of fetal obstructive uropathy. Urology. 2000 May 1;55(5):774.

13. Morris RK, Ruano R, Kilby MD. Effectiveness of fetal cystoscopy as a diagnostic and therapeutic intervention for lower urinary tract obstruction: a systematic review. Ultrasound Obstet Gynecol. 2011 Jun;37(6):629-37.

14. Morris RK, Kilby MD. An overview of the literature on congenital lower urinary tract obstruction and introduction to the PLUTO trial: percutaneous shunting in lower urinary tract obstruction. Aust N Z J Obstet Gynaecol. 2009 Feb;49(1):6-10.

15. Morris RK, Malin GL, Khan KS, Kilby MD. Systematic review of the effectiveness of antenatal intervention for the treatment of congenital lower urinary tract obstruction BJOG. 2010 Mar;117(4):382-90.

16. Welsh A, Agarwal S, Kumar S, Smith RP, Fisk NM. Fetal cystoscopy in the management of fetal obstructive uropathy: experience in a single European centre.Prenat Diagn. 2003 Dec 30;23(13):1033-41.

This article should be cited as: Paolo Volpe, Brunella Muto, Valentina De Robertis Megacystis, Visual Encyclopedia of Ultrasound in Obstetrics and Gynecology, www.VISUOG.org, 30 March, 2013.

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