Megaureter

Evaluation and management of megaureter

1. Me g aurete r Dr. Faheem ul Hassan Fellow Pediatric Urology Dr. Gowhar Mufti Assist. Professor Pediatric & Neonatal Surgery

2. Megaureter Megaureter is synonymous with a dilated ureter, or hydroureter . By definition, a megaureter is a ureter >8 mm in diameter. The megaureter was classified as primary , referring to a lesion intrinsic to the ureter, and secondary, denoting a reaction of the ureter to a process elsewhere .

3. Anatomy In order to understand pathophysiology, it is important to have a framework of normal anatomy . The ureter is divided into three distinct regions the ureteropelvic junction the middle spindle the ureterovesical junction .

4. Anatomy The ureterovesical junction is subsequently divided into the juxtavesical ureter and terminal ureter. The terminal ureter then separates into intramural and submucosal segments. intramural submucosal

5. Anatomy The ureter is enclosed in a loose, ill-defined sheath within the retroperitoneum. This sheath forms a protective barrier for neoplastic or inflammatory retroperitoneal processes .

6. Anatomy Proximally , the ureteral sheath and adventitia become continuous with the renal pelvis . Distally , the sheath and adventitia join to form Waldeyer’s sheath, which extends into the bladder & trigone

7. Anatomy The ureter consists of three layers: adventitia , muscularis, and mucosa.

8. Anatomy The adventitia is composed of collagen loosely attached to the underlying muscularis, allowing for free peristaltic activity.

9. Anatomy The muscularis is arranged in three layers The inner muscle bundles are arranged longitudinally , the middle circumferentially , and the outer longitudinally . In intramural region all the muscle fibers are placed longitudinally .

10. Anatomy The mucosa consists of multiple layers of transitional epithelium lying directly on the lamina propria

11. Anatomy The proximal ureter is vascularized predominantly by an artery originating from the renal artery. The middle spindle receives a branch from the aorta and gonadal artery. The distal ureter is supported by arteries from the internal iliac, superior and inferior vesical arteries . A periureteral arterial plexus courses the full extent of the ureter through the adventitia.

12. Anatomy

13. Classification The dilated ureter or MGU can be classified into one of four groups based on the cause of the dilatation: (1) refluxing (2) obstructed (3) nonrefluxing and nonobstructed (4) both refluxing and obstructed

14. Classification

15. Pathophysiology The common finding is an abundance of connective tissue in the abnormal ureter Lee et al. demonstrated altered collagen to smooth muscle ratio in megaureters is Collagen to smooth muscle ratio is 0.52 in normal ureters, 0.78 in obstructed and 1.99 in refluxing megaureters.

16. Pathophysiology Other studies have demonstrated that smooth muscle cells in these ureters produce an abnormally elevated amount of collagen. The muscles in these ureteral segments have also been shown to respond abnormally to neurotransmitters , emphasizing the anomalous behavior of these cells

17. Obstructed megaureter

18. Primary Obstructed megaureter The primary obstructed megaureter has generated the greatest interest and investigation . The primary obstructed megaureter has been reported in approximately 25 % of children with obstructive uropathy.

19. Primary Obstructed megaureter It is bilateral in 25 % Four times more often in boys The left ureter is more frequently affected Contralateral kidney may be dysplastic or obstructed in 10–15% of children

20. Primary Obstructed megaureter Endoscopically, the obstructed ureteral orifice can have a normal appearance and insert appropriately on the trigone. Caulk and Swensen et al proposed that the obstructed megaureter was similar to the megacolon seen in Hirschsprung’s disease. However , this proposition has been refuted based on histologic evidence showing presence of ganglia

21. Primary Obstructed megaureter Primary obstructive megaureter is considered a functional obstruction. There is thought to be an aperistaltic (adynamic ) segment in the ureter, leading to a lack of propagation of the ureteral peristalsis This distal segment has been found to contain increased levels of collagen type I and III (predominantly type I ).

22. Primary Obstructed megaureter This increased fibrosis is implicated in the disruption of intercellular communications which leads to uretero - arrhythmias and obstruction. Some scientists have shown evidence of atrophy of the inner longitudinal muscles in these ureteral segments (the longitudinal muscles are the ones that transmit peristalsis) and hypertrophy of outer circular muscle, leading to obstruction

23. Primary Obstructed megaureter The fact that many obstructive megaureters resolve with times has pushed many to define a maturational cause of obstructive megaureters The renal urine production begins slightly prematurely , before the ureter is fully cannulated at its caudal end, leading to hydroureter. The full canalization of the mature ureter could then explain the resolution of the obstructive appearance of the ureter.

24. Primary Obstructed megaureter Another maturational theory is that the obstruction represents a developmental evolution of the distal ureter from a single, circular muscle layer to the double layer (circular and longitudinal) of the child. Other histologic findings include distal ureteral segments with no muscle tissue present , but simply a fibrotic, static terminal end.

25. Primary Obstructed megaureter Yet others have documented distal ureteral segments with an abnormal muscle that is excessively responsive to non-adrenergic stimulus, leading to almost tonic contraction. The proximal, dilated ureteral segment has also been found to be composed of altered connective tissue, and this fibrosis and the dilation itself can lead to uretero arrhythmias and poor peristaltic wave transmission .

26. Primary Obstructed megaureter The infant collecting system is very pliable and this dilation allows for the dampening of pressure, allowing the kidneys to produce urine into a collecting system at close to physiologic pressures.

27. Primary Obstructed megaureter other anatomic causes that can lead to a similar clinical scenario are congenital distal ureteral strictures and distal ureteral valves

28. Secondary Obstructive Megaureter Secondary obstructive megaureter represents an obstructive process secondary to elevated intravesical pressure of some other cause. Common causes include spinal dysraphism and neurogenic bladder (which may elevate detrusor pressure to over 40 cm H2O, causing a physiologic obstruction and hydronephrosis) Non-neurogenic voiding dysfunction

29. Secondary Obstructive Megaureter Other causes of secondary Obstructive megaureter are Ureterocele ectopic ureter bladder diverticula periureteral fibrosis infravesical obstruction like Posterior urethral valves and external compression by retroperitoneal tumor, masses, or aberrant vessels

30. Refluxing Megaureter

31. Primary & Secondary Refluxing Megaureter Refluxing megaureters simply represent a refluxing ureter that is dilated. The refluxing megaureter is endoscopically characterized by a gaping lateral ureteral orifice. Bladder filling and cyclic voiding can transmit pressure into the ureter, resulting in mechanical enlargement

32. Primary & Secondary Refluxing Megaureter

33. Primary & Secondary Refluxing Megaureter The causes may be short intravesical and submucosal tunnel. Increased type III collagen periureteral diverticula megacystis megaureter syndrome Prune Belly syndrome

34. Refluxing Megaureter of PBS Ureters are elongated, tortuous, and dilated Ureteral orifices are lateral, golf hole in appearance, and frequently associated with diverticulum. The distal ureter is characterized by asymmetric ectasia and is more often involved than the proximal ureter.

35. Refluxing Megaureter of PBS Secondary obstruction may occur from kinking and folding of the redundant ureter. Primary obstruction has been reported at the ureterovesical junction in a select group. Histologically, there is an increase in fibrous tissue at the expense of normally developed ureteric muscle.

36. Primary & Secondary Refluxing Megaureter

37. Non- obstructing Non-Refluxing Megaureter

38. The non-refluxing non-obstructed megaureter is most often encountered in the neonate with the antenatal diagnosis of hydronephrosis. The fetus makes larger volumes of urine compared to the infant, and if this diuresis precedes the natural canalization of the distal ureter, a megaureter may develop (maturational delay hypothesis).

39. Non- obstructing Non-Refluxing Megaureter The cases of nonobstructive and nonrefluxing megaureter due to a cause unrelated to ureteral anatomy are termed secondary. It is in this category dilation occurs due to high fetal urine output (diabetes insipidus or mellitus, sickle cell nephropathy). increased compliance of fetal ureter due to elevated collagen type II,

40. Non- obstructing Non-Refluxing Megaureter partial or transient obstruction during development due to ureteral folds or delay in normal peristalsis urinary tract infections can lead to temporary ureteral dilation due to the presence of bacterial endotoxins that can inhibit peristalsis

41. Non- obstructing Non-Refluxing Megaureter McLellan et al reported resolution of the non-refluxing megaureter in the majority of children, with the time to resolution based on the initial grade of hydronephrosis. Children with grades 1–3 hydronephrosis resolved at a median age of 13-35 months and children with grade 4 and 5 hydronephrosis resolved at a median age of 48 months.

42. Obstructed Refluxing Megaureter

43. Obstructed Refluxing Megaureter The refluxing obstructed megaureter results from ectopic insertion of the ureteral orifice in the region of the bladder neck. During bladder filling, the bladder neck is closed , acting as a distal obstruction. With voiding, the bladder neck opens and allows for reflux. A cyclic voiding cystourethrogram may be required for diagnosis in suspected cases.

44. Diagnosis The routine use of fetal sonography has dramatically increased the diagnosis of the megaureter. Cases detected later in life often present with urinary tract infection, hematuria, and/or pain

45. Diagnosis With routine fetal sonography the megaureter is noted to occur in 23% of asymptomatic neonates , surpassed only by hydronephrosis, which is seen in 41%. The increased incidence of the megaureter can be explained by a more liberal use of fetal sonography and improved technology.

46. Diagnosis An unknown percentage of infants with asymptomatic megaureter will subsequently develop symptoms. This places a greater burden on imaging technology and our clinical ability

47. Ultrasonography Ultrasonography is the primary & initial imaging modality in the assessment of megaureter. Evaluating the size, shape, tortuosity, and bulbar appearance of the ureter & pelvis can often give the impression of an obstructive process.

48. Ultrasonography Ultrasonography is a simple & safe study that can provide important information on Renal size Parenchymal thickness Echogenicity , and architecture Renal pelvis and ureteral dilation and Bladder wall thickness

49. Ultrasonography The course of the ureter may be traced from the renal pelvis to its distal insertion The ureter may enter an obstructed ureterocele or and in an ectopic location within the bladder neck or posterior urethra

50. Ultrasonography An obstructed distal segment may be recognized when a peristaltic wave of urine abruptly stops and rebounds into the dilated proximal ureter The echogenicity of the kidney is a helpful parameter used to distinguish between and obstructive and a non-obstructive process, with increased echogenicity supporting obstruction

51. Ultrasonography A renal resistance index (RI) >0.70 has been suggested to correlate with obstruction. It is important to remember that grey-scale ultrasonography is only descriptive and provides no details on renal function or drainag e

52. Ultrasonography

53. Voiding cystourethrography If renal pelvis or ureteral dilation is observed on ultrasonography, a voiding cystourethrogram is needed to rule out reflux This also allows for the complete anatomic evaluation of the bladder and urethra

54. Voiding cystourethrography

55. Voiding cystourethrography The cyclic voiding cystourethrogram is beneficial when an ectopic, sphincteric ureter is suspected. In this scenario, the ureter can be obstructed when the bladder is at rest and refluxes only during the voiding phase.

56. IVU Excretory urography is waning as a diagnostic modality in the evaluation of pediatric uropathy because only limited information is gained. Stool, bowel gas, and immaturity of the neonatal kidney limit its utility . On a rare occasion, excretory urography may play a role when anatomic definition is required.

57. Renography Presently the most commonly used tool for the evaluation of obstructive nephropathy is the diuretic renogram Two most commonly used radiotracers for renography are Technetium Tc 99 DTPA (diethylene triaminepenta -acetic acid) and Tc 99 MAG3 (mercaptoacetyltriglycine)

58. Renography DTPA is a glomerular agent and provides limited information during the first month of life because of a low neonatal GFR MAG3 is extracted by the kidney and dependent on effective renal plasma flow not GFR. It is important to have a separate activity curve generated for the kidney and the ureter when assessing for an obstructive pattern.

59. Renography Obtaining activity curves over the ureter will help confirm distal ureteral obstruction. Variables involved in diuretic renography that can influence study findings are Tracer dosing Timing of diuretic administration Patient hydration and Determination of the study areas of interest

60. Renography The well-tempered renogram has three important components: 1; 10–15 ml/kg crystalloid hydration prior to the study, 2: 1 mg/kg of Lasix administered at the peak of tracer accumulation in the kidneys (plateau), and 3; a catheter in place during the entire study

61. Renography Range of t½ values associated with obstructed or unobstructed collecting systems <10 m in unobstructed 10–20 min equivocal >20 min obstructed However, in cases of megaureter, the dilated collecting system can have such a large capacity that the drainage of the radiotracer is delayed despite the absence of true obstruction

62. Renography Attempts to improve renography include the F-15 method, in which Lasix is given 15 min before tracer dosing This method is thought to decrease false-positive studies in children with dilated or poorly functioning systems,

63. Renography Historically, a Whitaker’s test was used in cases of hydronephrosis to rule out obstruction using pressure/flow measurement; however, it is rarely used now due to the invasive nature.

64. Magnetic resonance urography (MRU) Magnetic resonance urography (MRU) may play a future role in the evaluation of the megaureter This imaging modality may become the anatomic study of choice, particularly when renal compromise is present.

65. Cystoscopy Obstructing— normal orifice Refluxing – wide ureteric orifice

66. Management Therapeutic intervention of the megaureter is dependent on accurate classification. Secondary causes of a megaureter justify treatment of the primary problem, whether it is due to a neurogenic bladder, posterior urethral membrane, ureterocele, diabetes insipidus, or a retroperitoneal process.

67. Refluxing megaureter There is growing evidence that operative intervention is not required in all neonates with refluxing megaureters , especially when identified during the work-up of asymptomatic antenatal hydronephrosis.

68. Refluxing megaureter High-grade VUR in neonates occurs more often in males than females, and improvement can occur during the first year of life. There is little reason to proceed with early intervention, particularly when an infant has remained symptom-free on prophylactic medical management .

69. Refluxing megaureter Surgery is only considered for persistent high-grade reflux in older children (especially with recurrent pyelonephritis ) and in infants that have failed medical management . As the complication rate for ureteroneocystostomy is high when performed in children under the age of 1 year, cutaneous ureterostomy or vesicostomy may be used as a temporizing measure in infants requiring surgical intervention

70. Refluxing megaureter Megacystis–megaureter occurs in approximately 80% of boys diagnosed antenatally with bilateral reflux and found to have renal impairment It is a large-capacity, thin-walled bladder with massive primary vesicoureteral reflux . megacystis–megaureter does not appear to be due to bladder outlet obstruction.

71. Refluxing megaureter There is progressive upper tract HUN and bladder enlargement as a result of recurrent cycling of urine into the upper tract Double voiding can temporize this process in children who are toilet trained

72. Refluxing megaureter Intermittent bladder catheterization can be an effective technique of eliminating residual urine in neonates who are not toilet trained Ultimately, children with a megacystis–megaureter are best served by operative correction of the reflux.

73. Obstructed megaureter Fetal sonography has identified a substantial number of neonates with an obstructed megaureter, many of whom will not have clinical symptoms Medical management, based on prophylactic antibiotics and watchful waiting, allows for potential spontaneous regression of the obstructed megaureter.

74. Obstructed megaureter Renal parenchymal thickness and function must be objectively followed with sonography and renography in order to identify renal compromise . Repair of the infant megaureter is technically feasible but remains a challenge even in experienced hands .

75. Obstructed megaureter Secondary operative procedures have been reported as high as 10% when correcting an obstructed megaureter in an infant <8 months of age . It is best to delay the repair until the child is older than 12 months of age

76. Obstructed megaureter Occasionally, a neonate with an obstructed megaureter will present with severe renal compromise. In this situation, a distal cutaneous ureterostomy can provide temporary relief, adequately draining the upper urinary tract and decreasing the risk of infection.

77. Non-refluxing, non-obstructed megaureter Approximately 6–10% of neonates diagnosed with fetal sonography will have a non-refluxing non-obstructed megaureter. A functional study is required to confirm adequate ureteral drainage .

78. Non-refluxing, non-obstructed megaureter The initial medical management will be prophylactic antibiotics. Children with a non-refluxing non-obstructed megaureter maintain normal renal function and the megaureter often reverts to normal

79. Obstructed refluxing megaureter The obstructed refluxing megaureter occurs as a result of either a laterally positioned aperistaltic distal segment or ectopic insertion of the ureter into the bladder neck. Although the condition is not an emergency, operative correction is required in order to diminish the risk of upper urinary tract deterioration

80. Secondary Refluxing Secondary reflux must be treated by addressing the cause of elevated intravesical pressure Reflux in children with posterior urethral valves is treated by valve ablation and proper bladder management

81. Secondary Refluxing Neurogenic bladders with elevated DLPP (>40 cm H2O) must be treated with a combination of Medical therapy (i.e., anticholinergic medication) Clean intermittent catheterization and Surgery , if necessary

82. Secondary Refluxing or Obstructive Megaureter Prune Belly and diabetes insipidus can be managed with observation, presuming the appropriate medical therapy

83. General principles of treatment No surgery should be performed as long as renal function is not significantly affected and Urinary tract infections are not a major issue Instead, antibiotic suppression with close observation is all that is required. surgical repair is warranted between 1 and 2 years of age if the condition is worsening

84. General principles of treatment In certain rare cases, early intervention in the form of ureterostomy and vesicostomy becomes necessary In terms of forming algorithms of treatment, no good parameters dictate the children that will resolve and those that will worsen . In general, over 70% of cases resolve over 2 years of follow-up .

85. Indications of surgical treatment Primary obstructive megaureter Poor function (<35-40%) A severely scarred kidney Recurrent Febrile UTI Decreasing function on serial studies Failure to improve after a reasonable period of observation Solitary kidney---treat aggressively

86. Operative approach Temporary diversion A percutaneous nephrostomy is helpful when rapid drainage is required. small nephrostomy tubes are difficult to maintain longer than a few weeks. When prolonged drainage is required, a distal ureterostomy is appropriate. A pyelostomy results in unnecessary proximal diversion when the pathology exists at the bladder level.

87. Temporary diversion A cutaneous ureterostomy carries minimal morbidity, allows for rapid continuous decompression , and can often be performed in the outpatient setting It may be used for the severely obstructed neonatal megaureter.

88. Definitive reconstruction Definitive urinary reconstruction can be either intravesical, extravesical , or combined . Straightening and tapering the ureter without devascularization is required. The functional ability of the ureter to transmit urine is inversely related to the size of the megaureter.

89. Definitive reconstruction The ureter is tapered to achieve a 4–5:1 ratio of tunnel length to ureteral diameter necessary for an antirefluxing repair. Tapering should be gradual to prevent a sharp gradient, which can act as a pseudo-obstruction. Commonly used Tailoring techniques include ureteral imbrication and formal ureteral excision

90. Imbrication Ureteral imbrication is appropriate for marginally dilated ureters. Two common imbricating techniques are the Starr and Kalicinski plications .

91. Imbrication

92. Imbrication

93. Imbrication Advantages of Imbrication Preservation of the blood supply , Minimal risk of urinary leak , and Infrequent obstruction Disadvantage Adds unwanted bulk, making the ureter difficult to reimplant

94. Excisional tapering Formal excisional tapering of the ureter is required for extremely bulky ureters or a bilateral process A ureteral stent can be placed: To decrease urinary extravasation To provide a scaffold for the ureter to conform to To prevent kinking To bypass the tapered region, which initially may act as an obstruction due to edema

95. Excisional tapering

96. Excisional tapering In most situations, only the portion of the ureter which is going to be placed within the bladder and 1 or 2 cm beyond needs to be tapered. There should be a gentle transition from the ureteral hiatus at the bladder to the non-tapered ureter

97. Postoperative management The stent can be removed 3–7 days after imbrication, and 7–14 days following an excisional repair Ureterograms at the time of stent removal are not necessary Administration of a broadspectrum antibiotic prior to removing a stent decreases the possibility of urosepsis

98. Postoperative management Postoperative ureteral edema can persist for 6 weeks. Imaging studies, either sonography or renal scintigraphy , should be avoided during that time.

99. Postoperative management initial images on sonography may show increased hydronephrosis and hydroureter when compared with preoperative sonographic imaging, due to; Compliant proximal ureter and Relative resistance to flow through the tapered segment.

100. Postoperative management A 6-week postoperative ultrasound, showing hydronephrosis (left) and a hydroureter (right). The preoperative ultrasound was normal.

101. Postoperative management A 3-month postoperative ultrasound. The hydronephrosis (left) and hydroureter (right) has resolved.

102. Postoperative management A postoperative voiding cystourethrogram at 6 months is performed to confirm the absence of vesicoureteral reflux. Prophylactic antibiotics can be discontinued with resolution of the reflux .

103. Outcome Procedure Successful outcome Imbrication 93-95% Excisional tapering 74-90% Non-tapered uretero-neocystostomy Less success more complications and morbidity

104. Complications The two most common complications are obstruction and persisting reflux. inherent ureteral characteristics and bladder dysfunction affect a successful outcome Increased collagen deposition and altered smooth muscle may be the etiology for a higher rate of persisting vesicoureteral reflux following repair

105. Complications Postoperative edema can lead to obstruction which might take 2–3 weeks. it may require temporary percutaneous nephrostomy Transient mild reflux noted at 6 months can resolve with further time. Reflux persisting greater than 3 years is unlikely to improve

106. I have a perfect cure of sore throat; cut it T h a n k Y o u

107. Index case 12 years male child Operated case of 1; Meatotomy 5 Aug 2005 2; Chordee correction 28 jan 2008 3; Residual Chordee correction 30 Jan 2008 Urethroplasty by modified Bracka 18 Aug 2009

108. Index case On 5 Jan 2015 patient presented with pain left flank with poor urinary stream USG : B/L HUN with significant PVRU (160ml) and thickened and trabeculatd bladder. DTPA LEFT RIGHT SPLIT FUNCTION 27.9 72.1 GFR 49.2 72.8

109. Index case MCU was normal

110. Index case IVP B/L HDN Rt. Ureter visualised Lt ureter not visualised (secondary PUJO) B/L ureters grossly dilated

111. Index case Cystoscopy Jan 2015 Normal caliber anterior and posterior urethra, no evidence of PUV, small mucosal fold in anterior urethra non-obstructing AH pyeloplasty Jan 2015 Kidney hydronephrotic with intrarenal pelvis Dilated ureter

112. Index case Uroflometry : normal study USG 9 Dec 2015 Rt. Kidney GII-III HDN Lt. Kidney GIII-IV HDN B/L ureters grossly dilated PVRU 22 ml

113. Index case IVU in Aug 2015 showing b/l GR III_IV HDN with hydroureter

114. Index case DMSA; Normal tracer uptake in both kidneys. A wedge shaped cortical defect is seen in Lt. Kidney EBC- 360 ml PVRU- 22 ml Calculated GFR- 132

115. Index case Presently patient is assymptomatic No history of Thin stream Dysurea Incontinence Urgency Constipation Fever & pain

116. Index case Abdomen is soft Coronal hypospadias Anal tone is normal

117. Index case Abdomen is soft Coronal hypospadias Anal tone is normal