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Ureteral reflux in pediatric patients
Ureteral Refiux in Pediatric Patients NEIL R. FEINS, MD, Boston, Massachusetts ROBERT M. SCHLESINGER, MD, Boston, Massachusetts JOHN O’CONNOR, MD, Boston, Massachusetts ROBERT P. YOUNNES, MD, Boston, Massachusetts
The question of refluxing ureters in pediatric patients represents a true controversy. Much energy and time has been spent in trying to determine the etiology, pathogenesis, and the proper mode of treatment for this problem. Accepted authorities with long-term experience find it difficult to agree on the treatment of refluxing ureters. The following material will attempt to present the significant accepted ideas involved in reflux and the manner in which our group interprets these findings in the clinical care of infants and children. The finding of ureteral reflux in man is abnormal. The ability of the ureterovesical junction in normal subjects to prevent reflux was first alluded to by Young [1] in 1898 when he failed to produce reflux in human cadavers. Galen [Z] in 150 AD could not induce reflux in dog bladders by pressure technics. Other have subsequently shown that in a significant number of dogs reflux will occur if the level of intravesical pressure is markedly elevated [3-51. Eisendrath, Katz, and Glasser [6] in 1925 reported that reflux was not a normal event in man. In two series in 1957 of one hundred cystograms taken in children reflux was not exhibited [7,8]. A study made by Lich, Howerton, and Goode [.9] of twenty-six infants, all less than two days of age, revealed no reflux present. Fifty symptomless children ranging in age from 10 to 180 days examined cystographically had negative results [IO]. With this fund of information gathered from clinical investigation, it can safely be assumed that any reflux seen in children is abnormal. Causes
of Reflux
The causes of ureteral reflux are multiple. It is commonly believed that a derangement of the norFrom the Departments Pediatrics, Boston City Boston. Massachusetts.
Volume
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of Pediatric Surgery. Urology, Radiology, and Hospital, Boston University School of Medicine,
1971
ma1 anatomic relationship of the ureterovesical junction, either primary or secondary, is usually present. Anatomic drawings by Leonardo Da Vinci demonstrated the oblique course of the ureter through the bladder wall [11]. The obliquity of the path of the ureter through the bladder wall, with the formation of a flap valve, has been given much credit for preventing reflux. Middleton [12] emphasized the importance of the length of the intravesical ureter. He found that normal ureters had a ratio of length to diameter of 6.7: 1.0, and that in cases of reflux the ratio was 0.75:l.O. Thus, rising pressures and tensions in the bladder wall compress the submucosal and intravesical ureter, preventing reflux. The proper fixation of the ureter to the trigone with sufficient musculature allows trigone contraction to pull the ureteral meatus and narrow the ureter, thus contributing to competence [13,16]. Ureteral peristalsis also plays a role in inhibiting reflux. The prevention of reflux in the normal subject is probably due to more than one anatomic factor. These mechanisms working concomitantly with an intact neurologic system inhibit reflux of urine in a retrograde manner. Abnormalities related to these mechanisms that result in reflux are thought to be congenital and cause what is referred to as primary reflux. (Figures 1 and 2.) However, in children reflux is a dynamic process and with their subsequent growth, and the lengthening of the ureter, reflux may cease spontaneously. Secondary reflux has its various bases. The mechanical blockage of the urethra by posterior valves is an ever-increasing cause of reflux in male infants and children. (Figures 3 and 4.) Ectopically placed ureters (Figures 5 and 6) and ureteroceles (Figure 7) can be responsible for reflux. The place of bladder neck (outlet) obstruction
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Figure 1. Case I: three month 012 male infant with primary reflux. A film taken after a voiding cystourethrogram shows contrast material in the bladder and a markedly dilated and tortuous left megaureter. Calyectasis is present, but there was preservation of normal renal parenchyma on intravenous pyelogram.
Figure 2. Case I. follow-up intravenous pyelogram three months after left ureteroplasty and reimplantation. Note the considerable improvement in the dilatation of the ureter and calyectas,is. The ureter is shown to advantage on this oblique film. A voiding cystourethrogram showed no evidence of reflux.
as a cause of reflux is an area of much controversy. Many surgeons have routinely performed a Y-V plasty of the “obstructing” bladder neck for reflux with varying reported success. This procedure has recently fallen into disfavor, and Johnston [15] has stated that surgery to the vesical neck is unnecessary for the operative cure of reflux and could actually be dangerous. Meatal stenosis in male children can be a cause of secondary reflux. The pathologic significance of this finding in girls with urinary tract infection and reflux remains unclear [1S]. Urinary tract infections are an important cause of reflux. (Figure 8.) It has long been thought that infection readily superimposed on an abnormal urinary tract can cause reflux. The mechanism probably manifests itself by causing inflammation, edema, and subsequent scarring of the ureterovesical junction. Shopner [17] believes that blood-borne sepsis in children six months or younger with normal anatomic urinary tracts is responsible for causing ileus, reflux, and nonobstructive hydronephrosis. If infection continues, the child can go on to develop severe chronic changes designated as bladder neck obstruction and megacystis. Thus, infection may be considered a primary rather than a secon-
dary cause superimposed on factors such as obstruction and anomalies. It seems evident that competence of the ureterovesical junction can be altered by infection. As a result, the ureteral orifices lose their normal configuration, gape widely, move superiolaterally, and fade into an indistinct weak trigone [18]. Inhibiting infection, spasm, and inflammation is important not only in controlling the aforementioned changes, but also in preventing significant incompetence from developing in the growing child. The fine network of muscle at the distal end of the ureter can be damaged by infection with resulting thinning and weakness. This situation appears to be reversible if the infection can be controlled. Neurogenic bladder is readily acknowledged as a cause of reflux. The severity of the reflux and other associated anatomic abnormalities are dependent upon the level and extent of the spinal cord lesion. The most common etiology of the neuropathic bladder is menigomyelocele with lumbosacral spinabifida. When myelodysplasia is present, it is not always easy to predict which patients will develop the classic large dilated ureters with a sacculated, hypertonic bladder. Vesical dysfunction may vary according to subtle involvement of the neurologic pathways, and superim-
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History and Physical Examination. In the child with a history compatible with acute pyelonephritis, the presence of ureterovesical reflux may
be suggested since 26.4 per cent of children in a review of one hundred patients with pyelonephritis showed reflux [21]. Similarly, a history of persistent chronic urinary tract infection in a child of any age, in spite of repetitive courses of antimicrobial therapy, is suggestive of an anatomic abnormality of the urinary tract with secondary reflux. A history of “failure to thrive,” obscure abdominal pain, especially on voiding, flank masses resulting from secondary hydronephrosis, or enuresis may all indicate chronic urinary tract infection with reflux. Since the clinical evidence of reflux results from damage to renal tissue, the specifics of physical examination must be oriented to a detection of those changes as well as to any manifestations of distal urinary tract obstruction. When feasible, the voiding of the patient must be observed. Patients with sustained hypertension should be investigated for reflux, since blood pressure elevation is occasionally the only evidence of healed parenchymal disease [22]. However, the relationship of chronic pyelonephritis and hypertension is thought by some to be so variable that the clinical association may be only by chance or
Figure 3. Case II: eighteen month old male child who presented with gram-negative sepsis and urinary tract infection. This voiding cystourethrogram shows marked dilatation of the posterior urethra with filamentous urethral valves at the junction of the prostatic and bulbous portions. The arrow demonstrates the filamentous urethral valves coursing back toward the verumontanum; the superior arrows demonstrate secondary hypertrophy of the bladder neck. The penile urethra is markedly diminished in caliber and the patient voided very slowly.
Figure 4. Case II. A postvoiding film shows massive reflux on the right side in the patient with urethra/ valves demonstrated in Figure 3. There is marked trabeculation of the bladder and multiple small diverticula are present. No reflux was seen on the left side but massive hydronephrosis was demonstrated on delayed films of an intravenous pyelogram.
posed infections may further alter the clinical presentation of the patient’s problems. Recently, the problem of subclinical neurogenic bladder in children has been brought into focus [19]. There may be bladder dysfunction present on the basis of only suggestive signs of myelodysplasia. These may be spina bifida occulta, sacral deformities, sensory changes in the saddle area, and club foot. Sacral agenesis will have significant effect on normal bladder function since in many such cases the lack of the sacral nerve roots corresponds to the vertebral deficit. Certain iatrogenic causes of reflux must be mentioned. Ureterocelectomy can substitute a refluxing ureter for a previously partially obstructed ureter. Ureteral meatotomy can also be responsible for producing reflux. Errors in previous ureteral reimplantation procedures can cause reflux problems, as can transurethral resection of the prostate [ 201. Diagnosis
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Figure 5. Case 111:three year old male child with urinary tract infection.. Sequential frames of the voiding cystourethrogram labeled A, 6, C and D demonstrate abnormal implantation of the upper pole ureter of a double collecting system into the region of the internal sphincter and prostatic portion of the urethra. This is demonstrated well on A and as the bladder empties, the site of connection between the dilated distal ureter and the posterior urethra is well demonstrated (arrows). C and D show persistence of the contrast material in the dilated upper pole ureter. This will not drain well due to the closure of the internal and external sphincters.
the hypertension may be the primary disease [23]. In the evaluation of reflux, the usual careful physical examination is mandatory. Unfortunately, there are few specific physical findings related to reflux. In acute pyelonephritis physical examination reveals an obviously ill child, with flank or costovertebral angle tenderness and significant hyperpyrexia; nausea and vomiting may be part of the clinical picture. In the majority of cases the clinical presentation and associated physical findings are less dramatic. The patient with hydronephrosis secondary to reflux may present a flank mass that will be transilluminated. Palpation and percussion of the suprapubic region may disclose a chronically distended bladder, suggesting either anatomic or neurologic obstruction. In such cases a careful examination of the sacral area for obvious bone defects, midline “dimples,” or other cutaneous manifestations of underlying neurologic abnormalities is in order. A careful examination of the genital area requires, in the male, inspection
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Figure 6. Case Ill. Postvoiding film demonstrates dilatation of the upper pole collecting system due to reflux through the abnormally implanted ureter noted on the spot films in Figure 5. The lower pole collecting system and right kidney were normal on intravenous pyelography. The residual urine in the bladder is partially the result of drainage from the upper system at the terminus of voiding.
of the penis for phimosis, and obvious meatal stenosis, both causes of urethral obstruction. The bulbocavernosus reflex should be elicited. In the female it is important to note whether the labia minora are fused, and, if possible, to determine whether the hymen is imperforate. Finally, a careful neurologic examination evaluating the motor and sensory modalities, especially of the lumbar and sacral outflow tracts, is made. Laboratory Studies. Alterations in both the hemogram and usual serum chemistries are looked for ; on clinical assay of renal function the twentyfour hour creatinine clearance appears to decrease prior to increases in blood urea nitrogen or serum creatinine [24]. Urine for analysis may be obtained, along with a sample for culture, at the time of testing for postvoid residual. This may be accomplished by the passage of a urethral catheter, or in infants or young children by suprapubic tap [25]. A portion of the residual volume may represent refluxed urine that has returned to the bladder after voiding.
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The finding of sterile urine does not rule out the presence of clinically important reflux, since sterile reflux does occur and can lead to deterioration of renal function [26]. Radiogruphg. Usually the intravenous pyelogram is considered the first radiographic test to be performed in the evaluation of the urinary tract, yet not uncommonly an intravenous pyelogram will suggest little of the ureteropyelectasis that is the hallmark of reflux. By contrast, cystograms will demonstrate significant degrees of ureteral decompensation [27]. Probably, a normal excretory urogram is not sufficient evidence of a normal urinary tract in a child. The number of positive findings is significantly increased by the use of cystourethrograms, and one author believes that in children suspected of having reflux the most important examination to be performed is [28]. voiding cystourethrography Nevertheless, the changes that are seen on in-
travenous pyelography can be used as a guide to the severity of the reflux and, in turn, the severity of the reflux seems to have some value in predicting the outcome of conservative therapy. The findings are graded as follows: grade I: normal urethropyelogram with no dilatation ; grade II : minimal dilatation of ureter and collecting system ; grade III: marked dilatation of ureter and collecting system with parenchymal damage; grade IV: marked dilatation and tortuosity with hydronephrosis, calyceal blunting, and loss of parenchyma. In one series in which this method of grading was used, 70 per cent of the cases of grade I and 46 per cent of those of grade II reflux cleared spontaneously; no patients with grade III or grade IV had cessation of reflux without surgery [29]. The intravenous pyelogram serves to evaluate the anatomic and excretory status of the kidney and ureter; it is difficult to evaluate lower urinary tract disease with this technic. If the blood
Case VI: two month old female infant with urinary Intravenous pyelogram demonstrated an incomplete and dilated lower pole collecting system on the left side. This postvoiding film taken after voiding cystourethrography demonstrates reflux in the lower pole segment of a duplicated collecting system. The filling defect in the b/adder is an ectopic ureterocele at the lower end of the ureter draining the upper pole segment. Reflux is usually noted in the uninvolved lower ureter when an ectopic ureterocele is present with double ureters. The ureterocele is usually related to the upper collecting system and refiux is unusual in the upper segment. The patient was treated by resection of the upper pole collecting system and ureteroceie with a modified Poiitano-Leadbetter reimplantation of the ureter to the lower poles.
Figure 8. Case V: nine year old girl who presented with urinary tract infection followed by a course of conservative antibiotic therapy. Postvoiding film after a voiding cystourethrogram shows persistence of reflux. There is moderate calyectasis and focal scarring in both kidneys. The left kidney is much smaller than the right. This patient was surgically managed with bilateral Leadbetter-Politano reimplantations of both ureters.
Figure 7.
tract infection.
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urea nitrogen is over 40 then high dose or socalled infusion intravenous pyelography is required. The changes of reflux may be seen and may be interpreted as simply chronic pyelonephritis [SO]. Pyelonephritis may be unrelated to reflux ; when intravenous pyelography shows associated hydronephrosis or hydroureter, the existence of reflux is a greater possibility. With severe or chronic reflux secondary ureterovesical or ureteropelvic strictures may occur. Cystography. The standard type of static voiding cystourethrogram may well demonstrate the presence of urethral reflux and the associated lower tract obstructions that produce it. Cine technics are considered to be advantageous over the standard method, since the constant monitoring of the urethrovesical junction that this method provides allows for the demonstration of transient reflux [S1]. However, a comparison of the incidence of reflux demonstrated by both static and tine technics demonstrated ureterovesical incompetence in 80 per cent of cases with tine technic and in 76 per cent in which standard methods were used. The inference was that tine studies were not necessary, and that the hazards of increased radiation exposure outweighed the small percentage increase in demonstrable reflux [&Z]. For standardization of the static cystogram technic, it may be performed under cystometric control. Endoscopy. Endoscopic examination is a necessary part of the evaluation of any child with continued reflux. Careful study of the entire urethra will reveal any evidence of intraluminal obstruction. Special attention should be paid to the area adjacent to the verumontanum if there is a question of posterior valves; pressure of an assistant’s hand applied to the patient’s abdomen, with the panendoscope in place, will cause “valves” to balloon out, thus increasing their visualization. The bladder neck area must be carefully inspected for contracture or stricture. A prominent “median bar” may represent primary contracture, but in a bladder showing generalized trabeculations this may represent the local changes of generalized detrussor hypertrophy. Endoscopic evaluation of the position and contour of the urethral orifices correlates well with the presence of reflux. The more laterosuperior the orifice is noted from its normal position (graded from A to C) and the more the orifice contour changes from “cone” to gaping opening (graded from 0 to 3), the higher the percentage of
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demonstrable reflux. Those orifices graded “0” or “1” had a 90 per cent and 70 per cent chance, respectively, of ceasing reflux with conservative treatment; the more abnormal contours required surgery [ 331. Treatment
In the treatment of primary reflux there is no unanimity of opinion. Many clinicians believe that there is no treatment which brings adequate results; some believe that only medical treatment is indicated, whereas others think that surgical revision of the bladder neck is the procedure of choice. As it becomes evident that reflux is not normal, more surgeons are prone to modify the primary type of abnormal ureterovesical junction. Reflux is not an “all or nothing” phenomenon and various factors can be present which alter the findings at sequential examinations. It appears that the main factor influencing the development of reflux on a marginally competent valve is infection. Renal atrophy occurred only in the presence of infection and was never observed in cases of sterile reflux in a series observed by Lyon et al [34]. Interestingly, Rolleston, Shannon, and Utley [.%%Istated that the hydrodynamic effect of sterile vesicoureteric reflux is an important factor in producing renal damage in the prenatal and neonatal period. Lyon et al [84] believe that there is no support for the theory of maturation of the muscularly deficient ureterotrigonal unit. The marginally incompetent ureterovesical junction may become competent by control of infection and urethral dilatation. Those junctions that inherently lack significant musculature for competence and fixation will not overcome the deficit by the natural growth process. Lyon, Marshall, and Tanagho [33] classified the position and configuration of the ureteral orifice, and believed that the ureteral orifice controls valvular competency ; their categories give guidelines of expected response to conservative management. Children with reflux resulting from a short tunnel with decreased trigonal support, as well as serious deformities of the orifice contour and position, will need serious surgical consideration. Tanagho [35] operated on seventy-two patients for primary reflux and consistently found muscular deficiency of the intravesical ureter. The deficiency corresponded with the endoscopic appearance of the ureteral orifice abnormality as well as the degree and severity of reflux. Bridge and Roe [29] also have designated a grad-
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ing system for ureterovesical reflux based on degree of dilatation of the ureter and collecting system as seen on the voiding cystourethrogram and intravenous pyelogram. These grades serve as a guideline to treatment and prognosis. In all arbitrary guidelines there will be patients on the middle ground for whom the conservative or surgical treatment must be based on clinical impression and follow-up study. The patient with primary reflux with gaping lateral ureteral orifices, dilated ureters, distended pelves, and possible loss of renal parenchyma with superimposed infection will need surgical treatment. Hutch [36] in 1952 has been credited with the first organized attempt to surgically prevent reflux. Many procedures have been attempted subsequently but it appears that the operative technic devised by Politano and Leadbetter [ST] is the most widely used. This procedure is performed intravesically with a safe and straightforward method. Most reports reveal cessation of reflux in 90 to 96 per cent with the use of this procedure. The excellent results of Hendren [38] et al using this technic attest to the low risk and high success of this operation. The problem of megaureter caused by massive reflux had been neglected. Many physicians thought that there was no surgical treatment for this precarious condition. In 1969 Hendren [39] reported his results after direct operative repair with longitudinal resection of the large ureter, tunneling, and reimplantation. He described restoration of ureteral function and improvement in kidney drainage. This disclosure has added much to resolving a difficult problem. (Figures 1 and 2.) Duplicated ureters are prone to reflux because of abnormalities of the ureteral vesical junction [40]. A successful management of this problem appears to be reimplantation of both ureters as a single unit, with the common sheath left intact. Ectopic ureteral orifices, especially those opening into the proximal urethra, are associated with significant reflux and damage to those renal units drained by the ureter. (Figures 5 and 6.) The surgical procedure to be performed is dictated by the degree of damage. If significant, the tissue and ureter are excised ; if reasonable function remains, reimplantation is performed. If the ectopic ureter is associated with ureteral duplication and good function is noted in the refluxing segment, then the ectopic ureter is resected and the remaining ureter is reimplanted if necessary and pyelopyelostomy is carried out. Hutch and Chisholm [42] devised an antireflux operation for ureterocele. The ureterocele is excised and the ureter is reimplanted in the man-
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ner of Politano and Leadbetter. An ectopic ureterocele with double ureters is best handled by ureterocelectomy. The further management is then subject to the same considerations as for the simple ectopic duplicated ureter without ureterocele. The treatment of reflux secondary to obstruction seems to have a clear enough objective; improvement is to be expected if the obstructing lesion is removed and if proximal damage from dilatation and infection is reversible. Meatal stenosis in male children is easily diagnosed and treated with consistent results. Most believe that distal urethral stenosis in girls contributes to the development of urinary tract infection and subsequent reflux. It would appear that, combined with drug therapy, meatotomy has not influenced the recurrence rate or symptomatology in a series of urinary tract infections in girls [16]. If significant reflux is present, this will probably need surgical attention. There are no strict criteria for the diagnosis of bladder neck, or vesical outlet, obstruction. Many physicians believe that children of either sex with primary reflux and infection have some degree of bladder neck obstruction requiring dilatation. Hendren [39] routinely performs a Y-V plasty with antireflux procedures. Stephens and Lenaghan [42] believe that surgery to the vesical neck is unnecessary for operative cure of reflux. It has been stated that Y-V plasty can be responsible for retrograde ejaculation and sterility in males and varying incidence of incontinence in females. Recently, a study revealed no incidence of retrograde ejaculation in patients who had undergone Y-V plasty [43]. In the past Y-V plasty of the bladder neck frequently was performed; at the present time this procedure is carried out infrequently for reflux. Harrow, Sloane, and Witus [44] state that a good stream in absence of a trabeculated bladder and no residual urine is sufficient evidence that bladder neck obstruction is absent ; cystometry seems to be of little help in the diagnosis. Therefore, it seems that the diagnosis of bladder neck obstruction should be certain before surgery is carried out. The use of extended antimicrobic therapy may be successful in treatment of reflux in doubtful cases of bladder neck obstruction. Iatrogenic cause of reflux usually requires corrective surgical procedures. Ureteral meatotomy followed by reflux will need reimplantation. Ureterocelectomy frequently results in a refluxing ureter, necessitating reimplantation of the ureter. Transurethral resections may be followed by reflux
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as a result of inadvertent removal of excessive amounts of trigone, Correction of this situation requires reimplantation of the affected ureters. Faulty reimplantation is the most common iatrogenie cause of reflux. Correction of reflux in the abnormal ureter may eventually precipitate the appearance of reflux in the contralateral side [45]. Urinary tract infection is an accepted cause of ureteral reflux. Sommer and Roberts [4S] were able to cause reflux in dogs after intravesical implantation of paraffin contaminated with bacteria. Reflux has been seen in acute cystistis and associated with pyelonephritis of pregnancy. It remains to be proved that primary reflux in children can be due to urinary tract infection alone. It is not difficult to comprehend any situation of primary or secondary reflux being made more severe by superimposed infection. The manner in which infection causes renal damage appears to be by pyelotubular backflow ; this can be seen in voiding cystourethrograms taken in patients with preexisting bladder infection. Treatment of vesicoureteral reflux due to infection is best begun in a conservative manner. The following is the management protocol for the Urinary Tract Infection Clinic : I. Initial Infection 1. History 2. Physical examination including blood pressure, height, weight, head circumference 3. Complete blood count 4. Urinalysis, gram stain of unspun urine for organisms (performed by laboratory technician or house officer) 5. Clean voided specimen three times or bladder tap/sterile catheterization ; sensitivities 6. Blood urea nitrogen, creatinine, creatinine clearance 7. Therapy with Gantrisin@ 100-200 mg/kgday, four times a day for two weeks 8. Follow-up clean voided specimen within forty-eight hours after initiation or therapy if clinical status has improved and urine is sterile; then Gantrisin will be continued for full course of fourteen days. If there is no improvement of clinical status and the urine is not sterile, then an antibiotic is chosen in light of sensitivity studies performed on the organism. II, Follow-up investigation of initial infection (performed within six weeks of initiation of therapy)
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1. Intravenous pyelography, voiding urethrogram 2. Urine-concentrating ability
cysto-
III. Follow-up screening of those with bacteriologic cure : 1. Clean voided specimen to be taken: (1) every month for three months, then, (2) every three months for six months, then, (3) every six months for one year, then, (4) every year IV. Management of reinfection 1. Treatment with antibiotics according to sensitivity studies 2. In the event of a fourth successive urinary tract infection, the patient will be placed on long-term antimicrobial supression therapy after treatment and cure of the recurrence with appropriate antibiotics. The following drugs will be used for long term suppression : (a) mandelamine 2 gm/M2/day three or four times daily methionine 8 gm/H2/day three or four times daily for urine acidification below pH 5.5 ; or (b) absorbic acid 0.5 gm three or four times daily ; the dosage of ascorbic acid may be doubled or tripled to achieve sufficient urine acidification 3. Long-term suppression therapy will be carried out for at least six months to one year 4. On termination of long-term suppression therapy and with bacteriologic cure, the patient will be screened according to the foregoing screening schedule V. Long-term follow-up of : 1. Bacteriologically cured patients (a) routine screening for reinfection according to aforementioned schedule (b) intercurrent history, physical, routine growth and development measures, and blood pressure measurements on each routine visit (cl other studies as indicated 2. Patients with recurrent infection and those on long-term suppression therapy (a) Intercurrent history and physical on each return visit (a) Periodic complete blood count, blood urea nitrogen, creatinine, urine concentration ability, intravenous pyelogram and creatinine clearance
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This form of management will identify the patient with reflux and permit treatment to begin. Forbes, Drummond, and Vogrady [16] report recurrence rate of infection to be 24 per cent, and the rate was six times as high in patients with radiologically observed abnormalities. About 35 per cent of children with recurrent infection will have ureterovesical reflux. It is significant that in Lyons’ series [33] all the children who ceased to have reflux while on medical therapy did so in less than two years. In many patients in whom infection is controlled competence of the ureterovesical junction will be regained. There is little need for hasty surgical intervention; it must be borne in mind, however, that a slow, insidious infectious process can destroy kidneys, and in one group half of the patients with recurrent infection were asymptomatic. Conservative treatment of patients with reflux must be carried out aggressively and with extreme vigor, utilizing specific long-term antimicrobial therapy, combined with frequent voidings. The patient with continued bouts of recurrent pyelonephritis, radiographic changes in the kidneys, and grossly abnormal ureteral orifices, will probably develop progressive parenchymal damage unless antireflux surgery is carried out. The procedure of choice in reflux due to infection is the Politano-Leadbetter [37] operation. The success of this procedure is undisputed in preventing reflux and protecting renal function in more than 90 per cent of patients. In the series of Govan and Palmer [47] only 7 per cent of children had symptoms after surgery. They also found that the children operated upon had the same incidence of recurrent bladder infection as did children with bacilluria without reflux. It appears that correction of reflux protects renal tissue in uncomplicated bladder infection [48]. Scott [49] advises operation in carefully selected cases and reports 98 per cent successful elimination of reflux. He reports that 69 per cent of his patients had none or only one urinary infection in two years and 17 per cent had three or more relapses, with the proportionately greater number of relapses occuring in girls. The fact that 25 per cent of children with successful antireflux surgery have recurrent infection is not too disappointing in light of the relapse rate of about 25 per cent in children who have urinary tract infection unassociated with abnormalities correctable by surgery. Thus, it can be stated that antireflux procedures have an important place in the treatment of selected children with urinary tract infection and ureteral reflux.
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The treatment of reflux in patients suffering from neurologic deficit, as seen in myelomingocele, requires the surgeon to be on guard for early renal changes. It must be understood that some of these children have associated abnormalities of the urinary tract which may be the cause of the reflux and amenable to corrective surgery. The guidelines of treatment require close observation of these patients and prevention and/or early treatment of infection. Suprapubic expression of residual urine is a valuable tool to keep the bladder empty but is not without danger in the patient who has reflux. The use of prophylatic drugs does not meet universal approval but most physicians use them. An early in-depth work-up must be carried out and repeated in an attempt to discover changes in the upper tracts. Once there is evidence of renal compromise, certain procedures may be of help. Usually the immediate cause is inadequate bladder emptying with increased pressure and superimposed infection. Surgically these patients can have their bladder outlet widened either by transurethral resection or a Y-V plasty. The pudendal neurectomy could conceivably be of help if external sphincter obstruction is present. The Y-V plasty will help some of these patients but the chances of improvement will be small in those children in whom upper urinary tract damage, bladder trabeculation, and significant infection have developed. The patient with severe infections, reflux, evidence of upper tract disease, and who is refractory to more conservative therapy, needs supravesical diversion for protection of renal function. Conclusion
The treatment of reflux as described in textbooks and the recent literature remains vague. There are many one-sided arguments for specific modalities of treatment with results at best doubtful since the lack of comparable groups makes interpretation of the final outcome difficult. Contradictions are almost the rule in pediatric and urologic literature as various fads become unfashionable, and new therapeutic technics are introduced. To decrease the amount of confusion and to allow for ongoing enlightened constructive criticism of the various regimens it is our belief that a multidisciplinary group become established. Our group consists of a pediatric surgeon, a urologist with a keen interest in pediatric urology, a pediatric radiologist, and a pediatrician whose main interest
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is in renal infections and who has established a urinary tract infection clinic. All children with urinary tract infections are seen in the clinic and followed up by members of the group. The patients are evaluated from various viewpoints and plans of treatment and follow-up are established. A multidisciplinary approach appears to be the most reasonable method of solving the controversial problem of ureteral reflux in children.
24. 25.
26.
27. 28. 29.
References 1. Young HH: Hydraulic pressure in urologic practice. Johns Hookins HOSDBull. 9: 100. 1898. 2. Polk HC Jr: Notes on Galenic urology. Ural Surgery 15: 2, 1965. 3. Levin L, Goldschmidt H: Study on the relationships be. tween bladder, ureters, and kidneys. Arch Path Anat 134: 33, 1893. 4. Courtade D, Guyon JF: On reflux of vesical contents into the ureters. Comp Rend Sot 8iol46: 556, 1894. 5. Graves RC, Davidoff LU: Studies on the ureter and bladder. J Ural 10: 184, 1923. 6. Eisendrath DN, Katz H, Glasser JM: Bladder reflux. JAMA 85: 1121,1925. 7. Kjillberg SR, Ericsson NO, Ruhde V: The Lower Urinary Tract in Childhood; Chicago, Yearbook Medical Publishers, 1957. 8. Jones BW, Headstream JW: Vesicoureteral reflux in children. Trans So Cent Sect AUA. D 44. 1957. 9. Lich R Jr, Howerton LW, Goode ‘LA: The ureterovesical junction of the newborn. J Ural 92: 436, 1964. 10. lannaccone G, Panzironi PE: Ureteral reflux in normal infants. Acta Radio1 44: 451, 1956. 11. Belt E: Leonardo the Anatomist. Lawrence, Kansas, The University of Kansas, 1955. 12: Middelton RD (1959): Cited by McGovern et al, J Ural 83: 122, 1960. 13. Tanagho EA, Hutch JA: Primary reflux. J Ural 93: 158, 1965. 14. Tanagho EA, Hutch JA, Meyers FH, Rambo UN Jr: Primary vesicoureteral reflux: experimental studies of its etiology. J Ural 93: 165, 1965. 15. Johnston JH: Reflux treated by ureteric reimplantation. J Pediat Surg 1: 145, 1966. 16. Forbes PA, Drummond KN, Vogrady MB: Initial urinary tract infections. J Pediat 75: 187, 1969. 17. Shopner LE: Urinary tract pathology with sepsis. Amer J Roentgenof 108: 632,197O. 18. Tenagho EA, Guthrie TH, Lyon RP: The intravesical ureter in primary reflux. J Ural 101: 824, 1969. 19. Dorfman LE, Bailey J, Smith JP: Subclinical neurogenic bladder in children. J Ural 101: 48, 1969. 20. Samellas W, Herberman H: Vesicoureteral reflux following electroresection of the prostate or of bladder tumor. J Ural 96: 174, 1966. 21. Campbell’s Urology, 3rd ed, p 849. (Harrison and Campbell, ed). Philadelphia, Saunders, 1971. 22. King SE: Diastolic hypertension and chronic proteinuria. Amer J Cardiol9: 669, 1962. 23. Shapiro AP: Experimental pyelonephritis and hyperten-
30. 31.
32.
32.
34. 35. 36. 37.
38. 39. 40. 41. 42.
43. 44.
45.
46. 47.
48.
49.
sion: implications for the clinical problem. Ann Intern Med 59: 37,1963. Smith HL, Martin JW: Infections of the urinary tract. Med Clin N Amer 50: 1127, 1966. Edelman CM Jr: Urinary tract infection in childhood. Report of the First Ross Roundtable, 1969. Ross Laboratories, Columbus, Ohio, p 28. Rolleston GL, Shannon FT, Utley WLF: Relationship of infantile vesioureteric reflux to renal damage. Brit Med J 1: 463, 1970. Hudson CJ: The radiologic diagnosis of pyelonephritis. Proc Roy Sot Med 52: 669, 1969. Emmett JL, Witten DM: Clinical Urography, 3rd ed. Philadelphia, Saunders, 1971. Bridge RA, Roe CW: The grading of vesicoureteral reflux: guide to therapy. J Ural 101: 821, 1969. St. Martin ECCampbell JH, Pasquier CM: Cystography in childhood. J Ural 75: 151, 1956. Weber AL, Weglmann WF: Evaluation of ureterovesical reflux by intravenous pyelography and cinecystography. Radiology 87: 489, 1966. Smith AN: Comparison of standard and tine cystography for detecting vesico-ureteral reflux. J Ural 96: 49, 1966. Smith AN: Comparison of standard and tine cystography its configuration and competency. J Urof 102: 504, 1969. Tanagho EA. Guthrie TH, Lyon RP: The intravesical ureter in primary reflux. J Ural 101: 824, 1969. Lyon RP, Marshall PS, Tanagho EA: The theory of maturation: a critique. J Urol 103: 795, 1970. Hutch JA: Vesicoureteral reflux in the paraplegic: cause and correction. J Urol68: 457, 1952. Politano VA, Leadbetter WF: An operation technique for correction of vesicoureteral reflux. J Urol 79: 932, 1958. Hendren WH: Ureteral reimplantation in children. J Pediat Surg 3: 649, 1968. Hendren WH: Operative repair of megaureter in children. J Ural 101: 491, 1969. Ambrose SS, Nicholson WP: Ureteral reflux in duplicated ureters. J Ural 92: 439, 1964. Hutch JA, Chisholm ER: Surgical repair of ureterocele. J Urol96: 445, 1966. Stephens FD, Lenaghan D: Congenital Malformation of the Rectum, Anus and Genito-urinary tracts, p 132. Edinburgh, Livingstone, 1938. Koraitum M, Al-Ghorab M: Normal ejaculation after Y-V urethroplasty. Brit J Ural 42: 410, 1970. Harrow BR, Sloane JA, Witus WS: A critical examination of bladder neck obstruction in children. J Ural 98: 613,1967. Fortunoff S: Reflux ureter: does it protect the opposite kidney from excessive bladder pressure? Amer J Dis Child 151: 393,1964. Sommer JL. Roberts JA: Ureteral reflux resulting from chronic infection in dogs. J Urol 95: 502, 1966. Govan DE, Palmer JM: Urinary tract infections in children: Influence of successful anti-reflux operations in morbiditv from infection. Pediatrics 44: 677. 1969. Corriere JN-Jr, Kuhl DE, Murphy JJ: The use of 99 Tc labeled sulphur colloid to study particle dynamics in the urinary tract: vesicoureteral reflux. Invest Ural 4: 570, 1967. Scott JES: Results of anti-reflux surgery. Lancet, p 68, 1969.
End of Symposium Papers
362
The Amsrkw~
Journal
of Sut~ery
The question of refluxing ureters in pediatric patients represents a true controversy. Much energy and time has been spent in trying to determine the etiology, pathogenesis, and the proper mode of treatment for this problem. Accepted authorities with long-term experience find it difficult to agree on the treatment of refluxing ureters. The following material will attempt to present the significant accepted ideas involved in reflux and the manner in which our group interprets these findings in the clinical care of infants and children. The finding of ureteral reflux in man is abnormal. The ability of the ureterovesical junction in normal subjects to prevent reflux was first alluded to by Young [1] in 1898 when he failed to produce reflux in human cadavers. Galen [Z] in 150 AD could not induce reflux in dog bladders by pressure technics. Other have subsequently shown that in a significant number of dogs reflux will occur if the level of intravesical pressure is markedly elevated [3-51. Eisendrath, Katz, and Glasser [6] in 1925 reported that reflux was not a normal event in man. In two series in 1957 of one hundred cystograms taken in children reflux was not exhibited [7,8]. A study made by Lich, Howerton, and Goode [.9] of twenty-six infants, all less than two days of age, revealed no reflux present. Fifty symptomless children ranging in age from 10 to 180 days examined cystographically had negative results [IO]. With this fund of information gathered from clinical investigation, it can safely be assumed that any reflux seen in children is abnormal. Causes
of Reflux
The causes of ureteral reflux are multiple. It is commonly believed that a derangement of the norFrom the Departments Pediatrics, Boston City Boston. Massachusetts.
Volume
122,
September
of Pediatric Surgery. Urology, Radiology, and Hospital, Boston University School of Medicine,
1971
ma1 anatomic relationship of the ureterovesical junction, either primary or secondary, is usually present. Anatomic drawings by Leonardo Da Vinci demonstrated the oblique course of the ureter through the bladder wall [11]. The obliquity of the path of the ureter through the bladder wall, with the formation of a flap valve, has been given much credit for preventing reflux. Middleton [12] emphasized the importance of the length of the intravesical ureter. He found that normal ureters had a ratio of length to diameter of 6.7: 1.0, and that in cases of reflux the ratio was 0.75:l.O. Thus, rising pressures and tensions in the bladder wall compress the submucosal and intravesical ureter, preventing reflux. The proper fixation of the ureter to the trigone with sufficient musculature allows trigone contraction to pull the ureteral meatus and narrow the ureter, thus contributing to competence [13,16]. Ureteral peristalsis also plays a role in inhibiting reflux. The prevention of reflux in the normal subject is probably due to more than one anatomic factor. These mechanisms working concomitantly with an intact neurologic system inhibit reflux of urine in a retrograde manner. Abnormalities related to these mechanisms that result in reflux are thought to be congenital and cause what is referred to as primary reflux. (Figures 1 and 2.) However, in children reflux is a dynamic process and with their subsequent growth, and the lengthening of the ureter, reflux may cease spontaneously. Secondary reflux has its various bases. The mechanical blockage of the urethra by posterior valves is an ever-increasing cause of reflux in male infants and children. (Figures 3 and 4.) Ectopically placed ureters (Figures 5 and 6) and ureteroceles (Figure 7) can be responsible for reflux. The place of bladder neck (outlet) obstruction
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Figure 1. Case I: three month 012 male infant with primary reflux. A film taken after a voiding cystourethrogram shows contrast material in the bladder and a markedly dilated and tortuous left megaureter. Calyectasis is present, but there was preservation of normal renal parenchyma on intravenous pyelogram.
Figure 2. Case I. follow-up intravenous pyelogram three months after left ureteroplasty and reimplantation. Note the considerable improvement in the dilatation of the ureter and calyectas,is. The ureter is shown to advantage on this oblique film. A voiding cystourethrogram showed no evidence of reflux.
as a cause of reflux is an area of much controversy. Many surgeons have routinely performed a Y-V plasty of the “obstructing” bladder neck for reflux with varying reported success. This procedure has recently fallen into disfavor, and Johnston [15] has stated that surgery to the vesical neck is unnecessary for the operative cure of reflux and could actually be dangerous. Meatal stenosis in male children can be a cause of secondary reflux. The pathologic significance of this finding in girls with urinary tract infection and reflux remains unclear [1S]. Urinary tract infections are an important cause of reflux. (Figure 8.) It has long been thought that infection readily superimposed on an abnormal urinary tract can cause reflux. The mechanism probably manifests itself by causing inflammation, edema, and subsequent scarring of the ureterovesical junction. Shopner [17] believes that blood-borne sepsis in children six months or younger with normal anatomic urinary tracts is responsible for causing ileus, reflux, and nonobstructive hydronephrosis. If infection continues, the child can go on to develop severe chronic changes designated as bladder neck obstruction and megacystis. Thus, infection may be considered a primary rather than a secon-
dary cause superimposed on factors such as obstruction and anomalies. It seems evident that competence of the ureterovesical junction can be altered by infection. As a result, the ureteral orifices lose their normal configuration, gape widely, move superiolaterally, and fade into an indistinct weak trigone [18]. Inhibiting infection, spasm, and inflammation is important not only in controlling the aforementioned changes, but also in preventing significant incompetence from developing in the growing child. The fine network of muscle at the distal end of the ureter can be damaged by infection with resulting thinning and weakness. This situation appears to be reversible if the infection can be controlled. Neurogenic bladder is readily acknowledged as a cause of reflux. The severity of the reflux and other associated anatomic abnormalities are dependent upon the level and extent of the spinal cord lesion. The most common etiology of the neuropathic bladder is menigomyelocele with lumbosacral spinabifida. When myelodysplasia is present, it is not always easy to predict which patients will develop the classic large dilated ureters with a sacculated, hypertonic bladder. Vesical dysfunction may vary according to subtle involvement of the neurologic pathways, and superim-
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The American
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of Surgery
Ureteral
Reflux
in Pediatric
Patients
History and Physical Examination. In the child with a history compatible with acute pyelonephritis, the presence of ureterovesical reflux may
be suggested since 26.4 per cent of children in a review of one hundred patients with pyelonephritis showed reflux [21]. Similarly, a history of persistent chronic urinary tract infection in a child of any age, in spite of repetitive courses of antimicrobial therapy, is suggestive of an anatomic abnormality of the urinary tract with secondary reflux. A history of “failure to thrive,” obscure abdominal pain, especially on voiding, flank masses resulting from secondary hydronephrosis, or enuresis may all indicate chronic urinary tract infection with reflux. Since the clinical evidence of reflux results from damage to renal tissue, the specifics of physical examination must be oriented to a detection of those changes as well as to any manifestations of distal urinary tract obstruction. When feasible, the voiding of the patient must be observed. Patients with sustained hypertension should be investigated for reflux, since blood pressure elevation is occasionally the only evidence of healed parenchymal disease [22]. However, the relationship of chronic pyelonephritis and hypertension is thought by some to be so variable that the clinical association may be only by chance or
Figure 3. Case II: eighteen month old male child who presented with gram-negative sepsis and urinary tract infection. This voiding cystourethrogram shows marked dilatation of the posterior urethra with filamentous urethral valves at the junction of the prostatic and bulbous portions. The arrow demonstrates the filamentous urethral valves coursing back toward the verumontanum; the superior arrows demonstrate secondary hypertrophy of the bladder neck. The penile urethra is markedly diminished in caliber and the patient voided very slowly.
Figure 4. Case II. A postvoiding film shows massive reflux on the right side in the patient with urethra/ valves demonstrated in Figure 3. There is marked trabeculation of the bladder and multiple small diverticula are present. No reflux was seen on the left side but massive hydronephrosis was demonstrated on delayed films of an intravenous pyelogram.
posed infections may further alter the clinical presentation of the patient’s problems. Recently, the problem of subclinical neurogenic bladder in children has been brought into focus [19]. There may be bladder dysfunction present on the basis of only suggestive signs of myelodysplasia. These may be spina bifida occulta, sacral deformities, sensory changes in the saddle area, and club foot. Sacral agenesis will have significant effect on normal bladder function since in many such cases the lack of the sacral nerve roots corresponds to the vertebral deficit. Certain iatrogenic causes of reflux must be mentioned. Ureterocelectomy can substitute a refluxing ureter for a previously partially obstructed ureter. Ureteral meatotomy can also be responsible for producing reflux. Errors in previous ureteral reimplantation procedures can cause reflux problems, as can transurethral resection of the prostate [ 201. Diagnosis
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Figure 5. Case 111:three year old male child with urinary tract infection.. Sequential frames of the voiding cystourethrogram labeled A, 6, C and D demonstrate abnormal implantation of the upper pole ureter of a double collecting system into the region of the internal sphincter and prostatic portion of the urethra. This is demonstrated well on A and as the bladder empties, the site of connection between the dilated distal ureter and the posterior urethra is well demonstrated (arrows). C and D show persistence of the contrast material in the dilated upper pole ureter. This will not drain well due to the closure of the internal and external sphincters.
the hypertension may be the primary disease [23]. In the evaluation of reflux, the usual careful physical examination is mandatory. Unfortunately, there are few specific physical findings related to reflux. In acute pyelonephritis physical examination reveals an obviously ill child, with flank or costovertebral angle tenderness and significant hyperpyrexia; nausea and vomiting may be part of the clinical picture. In the majority of cases the clinical presentation and associated physical findings are less dramatic. The patient with hydronephrosis secondary to reflux may present a flank mass that will be transilluminated. Palpation and percussion of the suprapubic region may disclose a chronically distended bladder, suggesting either anatomic or neurologic obstruction. In such cases a careful examination of the sacral area for obvious bone defects, midline “dimples,” or other cutaneous manifestations of underlying neurologic abnormalities is in order. A careful examination of the genital area requires, in the male, inspection
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Figure 6. Case Ill. Postvoiding film demonstrates dilatation of the upper pole collecting system due to reflux through the abnormally implanted ureter noted on the spot films in Figure 5. The lower pole collecting system and right kidney were normal on intravenous pyelography. The residual urine in the bladder is partially the result of drainage from the upper system at the terminus of voiding.
of the penis for phimosis, and obvious meatal stenosis, both causes of urethral obstruction. The bulbocavernosus reflex should be elicited. In the female it is important to note whether the labia minora are fused, and, if possible, to determine whether the hymen is imperforate. Finally, a careful neurologic examination evaluating the motor and sensory modalities, especially of the lumbar and sacral outflow tracts, is made. Laboratory Studies. Alterations in both the hemogram and usual serum chemistries are looked for ; on clinical assay of renal function the twentyfour hour creatinine clearance appears to decrease prior to increases in blood urea nitrogen or serum creatinine [24]. Urine for analysis may be obtained, along with a sample for culture, at the time of testing for postvoid residual. This may be accomplished by the passage of a urethral catheter, or in infants or young children by suprapubic tap [25]. A portion of the residual volume may represent refluxed urine that has returned to the bladder after voiding.
The
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of
Surgery
Ureteraf Reflux in Pediatric
Patients
The finding of sterile urine does not rule out the presence of clinically important reflux, since sterile reflux does occur and can lead to deterioration of renal function [26]. Radiogruphg. Usually the intravenous pyelogram is considered the first radiographic test to be performed in the evaluation of the urinary tract, yet not uncommonly an intravenous pyelogram will suggest little of the ureteropyelectasis that is the hallmark of reflux. By contrast, cystograms will demonstrate significant degrees of ureteral decompensation [27]. Probably, a normal excretory urogram is not sufficient evidence of a normal urinary tract in a child. The number of positive findings is significantly increased by the use of cystourethrograms, and one author believes that in children suspected of having reflux the most important examination to be performed is [28]. voiding cystourethrography Nevertheless, the changes that are seen on in-
travenous pyelography can be used as a guide to the severity of the reflux and, in turn, the severity of the reflux seems to have some value in predicting the outcome of conservative therapy. The findings are graded as follows: grade I: normal urethropyelogram with no dilatation ; grade II : minimal dilatation of ureter and collecting system ; grade III: marked dilatation of ureter and collecting system with parenchymal damage; grade IV: marked dilatation and tortuosity with hydronephrosis, calyceal blunting, and loss of parenchyma. In one series in which this method of grading was used, 70 per cent of the cases of grade I and 46 per cent of those of grade II reflux cleared spontaneously; no patients with grade III or grade IV had cessation of reflux without surgery [29]. The intravenous pyelogram serves to evaluate the anatomic and excretory status of the kidney and ureter; it is difficult to evaluate lower urinary tract disease with this technic. If the blood
Case VI: two month old female infant with urinary Intravenous pyelogram demonstrated an incomplete and dilated lower pole collecting system on the left side. This postvoiding film taken after voiding cystourethrography demonstrates reflux in the lower pole segment of a duplicated collecting system. The filling defect in the b/adder is an ectopic ureterocele at the lower end of the ureter draining the upper pole segment. Reflux is usually noted in the uninvolved lower ureter when an ectopic ureterocele is present with double ureters. The ureterocele is usually related to the upper collecting system and refiux is unusual in the upper segment. The patient was treated by resection of the upper pole collecting system and ureteroceie with a modified Poiitano-Leadbetter reimplantation of the ureter to the lower poles.
Figure 8. Case V: nine year old girl who presented with urinary tract infection followed by a course of conservative antibiotic therapy. Postvoiding film after a voiding cystourethrogram shows persistence of reflux. There is moderate calyectasis and focal scarring in both kidneys. The left kidney is much smaller than the right. This patient was surgically managed with bilateral Leadbetter-Politano reimplantations of both ureters.
Figure 7.
tract infection.
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1971
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urea nitrogen is over 40 then high dose or socalled infusion intravenous pyelography is required. The changes of reflux may be seen and may be interpreted as simply chronic pyelonephritis [SO]. Pyelonephritis may be unrelated to reflux ; when intravenous pyelography shows associated hydronephrosis or hydroureter, the existence of reflux is a greater possibility. With severe or chronic reflux secondary ureterovesical or ureteropelvic strictures may occur. Cystography. The standard type of static voiding cystourethrogram may well demonstrate the presence of urethral reflux and the associated lower tract obstructions that produce it. Cine technics are considered to be advantageous over the standard method, since the constant monitoring of the urethrovesical junction that this method provides allows for the demonstration of transient reflux [S1]. However, a comparison of the incidence of reflux demonstrated by both static and tine technics demonstrated ureterovesical incompetence in 80 per cent of cases with tine technic and in 76 per cent in which standard methods were used. The inference was that tine studies were not necessary, and that the hazards of increased radiation exposure outweighed the small percentage increase in demonstrable reflux [&Z]. For standardization of the static cystogram technic, it may be performed under cystometric control. Endoscopy. Endoscopic examination is a necessary part of the evaluation of any child with continued reflux. Careful study of the entire urethra will reveal any evidence of intraluminal obstruction. Special attention should be paid to the area adjacent to the verumontanum if there is a question of posterior valves; pressure of an assistant’s hand applied to the patient’s abdomen, with the panendoscope in place, will cause “valves” to balloon out, thus increasing their visualization. The bladder neck area must be carefully inspected for contracture or stricture. A prominent “median bar” may represent primary contracture, but in a bladder showing generalized trabeculations this may represent the local changes of generalized detrussor hypertrophy. Endoscopic evaluation of the position and contour of the urethral orifices correlates well with the presence of reflux. The more laterosuperior the orifice is noted from its normal position (graded from A to C) and the more the orifice contour changes from “cone” to gaping opening (graded from 0 to 3), the higher the percentage of
358
demonstrable reflux. Those orifices graded “0” or “1” had a 90 per cent and 70 per cent chance, respectively, of ceasing reflux with conservative treatment; the more abnormal contours required surgery [ 331. Treatment
In the treatment of primary reflux there is no unanimity of opinion. Many clinicians believe that there is no treatment which brings adequate results; some believe that only medical treatment is indicated, whereas others think that surgical revision of the bladder neck is the procedure of choice. As it becomes evident that reflux is not normal, more surgeons are prone to modify the primary type of abnormal ureterovesical junction. Reflux is not an “all or nothing” phenomenon and various factors can be present which alter the findings at sequential examinations. It appears that the main factor influencing the development of reflux on a marginally competent valve is infection. Renal atrophy occurred only in the presence of infection and was never observed in cases of sterile reflux in a series observed by Lyon et al [34]. Interestingly, Rolleston, Shannon, and Utley [.%%Istated that the hydrodynamic effect of sterile vesicoureteric reflux is an important factor in producing renal damage in the prenatal and neonatal period. Lyon et al [84] believe that there is no support for the theory of maturation of the muscularly deficient ureterotrigonal unit. The marginally incompetent ureterovesical junction may become competent by control of infection and urethral dilatation. Those junctions that inherently lack significant musculature for competence and fixation will not overcome the deficit by the natural growth process. Lyon, Marshall, and Tanagho [33] classified the position and configuration of the ureteral orifice, and believed that the ureteral orifice controls valvular competency ; their categories give guidelines of expected response to conservative management. Children with reflux resulting from a short tunnel with decreased trigonal support, as well as serious deformities of the orifice contour and position, will need serious surgical consideration. Tanagho [35] operated on seventy-two patients for primary reflux and consistently found muscular deficiency of the intravesical ureter. The deficiency corresponded with the endoscopic appearance of the ureteral orifice abnormality as well as the degree and severity of reflux. Bridge and Roe [29] also have designated a grad-
Ths
American
Journal
of
Sumwy
Ureteral
ing system for ureterovesical reflux based on degree of dilatation of the ureter and collecting system as seen on the voiding cystourethrogram and intravenous pyelogram. These grades serve as a guideline to treatment and prognosis. In all arbitrary guidelines there will be patients on the middle ground for whom the conservative or surgical treatment must be based on clinical impression and follow-up study. The patient with primary reflux with gaping lateral ureteral orifices, dilated ureters, distended pelves, and possible loss of renal parenchyma with superimposed infection will need surgical treatment. Hutch [36] in 1952 has been credited with the first organized attempt to surgically prevent reflux. Many procedures have been attempted subsequently but it appears that the operative technic devised by Politano and Leadbetter [ST] is the most widely used. This procedure is performed intravesically with a safe and straightforward method. Most reports reveal cessation of reflux in 90 to 96 per cent with the use of this procedure. The excellent results of Hendren [38] et al using this technic attest to the low risk and high success of this operation. The problem of megaureter caused by massive reflux had been neglected. Many physicians thought that there was no surgical treatment for this precarious condition. In 1969 Hendren [39] reported his results after direct operative repair with longitudinal resection of the large ureter, tunneling, and reimplantation. He described restoration of ureteral function and improvement in kidney drainage. This disclosure has added much to resolving a difficult problem. (Figures 1 and 2.) Duplicated ureters are prone to reflux because of abnormalities of the ureteral vesical junction [40]. A successful management of this problem appears to be reimplantation of both ureters as a single unit, with the common sheath left intact. Ectopic ureteral orifices, especially those opening into the proximal urethra, are associated with significant reflux and damage to those renal units drained by the ureter. (Figures 5 and 6.) The surgical procedure to be performed is dictated by the degree of damage. If significant, the tissue and ureter are excised ; if reasonable function remains, reimplantation is performed. If the ectopic ureter is associated with ureteral duplication and good function is noted in the refluxing segment, then the ectopic ureter is resected and the remaining ureter is reimplanted if necessary and pyelopyelostomy is carried out. Hutch and Chisholm [42] devised an antireflux operation for ureterocele. The ureterocele is excised and the ureter is reimplanted in the man-
Volume 122, September 1971
Reflux
in Pediatric
Patients
ner of Politano and Leadbetter. An ectopic ureterocele with double ureters is best handled by ureterocelectomy. The further management is then subject to the same considerations as for the simple ectopic duplicated ureter without ureterocele. The treatment of reflux secondary to obstruction seems to have a clear enough objective; improvement is to be expected if the obstructing lesion is removed and if proximal damage from dilatation and infection is reversible. Meatal stenosis in male children is easily diagnosed and treated with consistent results. Most believe that distal urethral stenosis in girls contributes to the development of urinary tract infection and subsequent reflux. It would appear that, combined with drug therapy, meatotomy has not influenced the recurrence rate or symptomatology in a series of urinary tract infections in girls [16]. If significant reflux is present, this will probably need surgical attention. There are no strict criteria for the diagnosis of bladder neck, or vesical outlet, obstruction. Many physicians believe that children of either sex with primary reflux and infection have some degree of bladder neck obstruction requiring dilatation. Hendren [39] routinely performs a Y-V plasty with antireflux procedures. Stephens and Lenaghan [42] believe that surgery to the vesical neck is unnecessary for operative cure of reflux. It has been stated that Y-V plasty can be responsible for retrograde ejaculation and sterility in males and varying incidence of incontinence in females. Recently, a study revealed no incidence of retrograde ejaculation in patients who had undergone Y-V plasty [43]. In the past Y-V plasty of the bladder neck frequently was performed; at the present time this procedure is carried out infrequently for reflux. Harrow, Sloane, and Witus [44] state that a good stream in absence of a trabeculated bladder and no residual urine is sufficient evidence that bladder neck obstruction is absent ; cystometry seems to be of little help in the diagnosis. Therefore, it seems that the diagnosis of bladder neck obstruction should be certain before surgery is carried out. The use of extended antimicrobic therapy may be successful in treatment of reflux in doubtful cases of bladder neck obstruction. Iatrogenic cause of reflux usually requires corrective surgical procedures. Ureteral meatotomy followed by reflux will need reimplantation. Ureterocelectomy frequently results in a refluxing ureter, necessitating reimplantation of the ureter. Transurethral resections may be followed by reflux
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as a result of inadvertent removal of excessive amounts of trigone, Correction of this situation requires reimplantation of the affected ureters. Faulty reimplantation is the most common iatrogenie cause of reflux. Correction of reflux in the abnormal ureter may eventually precipitate the appearance of reflux in the contralateral side [45]. Urinary tract infection is an accepted cause of ureteral reflux. Sommer and Roberts [4S] were able to cause reflux in dogs after intravesical implantation of paraffin contaminated with bacteria. Reflux has been seen in acute cystistis and associated with pyelonephritis of pregnancy. It remains to be proved that primary reflux in children can be due to urinary tract infection alone. It is not difficult to comprehend any situation of primary or secondary reflux being made more severe by superimposed infection. The manner in which infection causes renal damage appears to be by pyelotubular backflow ; this can be seen in voiding cystourethrograms taken in patients with preexisting bladder infection. Treatment of vesicoureteral reflux due to infection is best begun in a conservative manner. The following is the management protocol for the Urinary Tract Infection Clinic : I. Initial Infection 1. History 2. Physical examination including blood pressure, height, weight, head circumference 3. Complete blood count 4. Urinalysis, gram stain of unspun urine for organisms (performed by laboratory technician or house officer) 5. Clean voided specimen three times or bladder tap/sterile catheterization ; sensitivities 6. Blood urea nitrogen, creatinine, creatinine clearance 7. Therapy with Gantrisin@ 100-200 mg/kgday, four times a day for two weeks 8. Follow-up clean voided specimen within forty-eight hours after initiation or therapy if clinical status has improved and urine is sterile; then Gantrisin will be continued for full course of fourteen days. If there is no improvement of clinical status and the urine is not sterile, then an antibiotic is chosen in light of sensitivity studies performed on the organism. II, Follow-up investigation of initial infection (performed within six weeks of initiation of therapy)
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1. Intravenous pyelography, voiding urethrogram 2. Urine-concentrating ability
cysto-
III. Follow-up screening of those with bacteriologic cure : 1. Clean voided specimen to be taken: (1) every month for three months, then, (2) every three months for six months, then, (3) every six months for one year, then, (4) every year IV. Management of reinfection 1. Treatment with antibiotics according to sensitivity studies 2. In the event of a fourth successive urinary tract infection, the patient will be placed on long-term antimicrobial supression therapy after treatment and cure of the recurrence with appropriate antibiotics. The following drugs will be used for long term suppression : (a) mandelamine 2 gm/M2/day three or four times daily methionine 8 gm/H2/day three or four times daily for urine acidification below pH 5.5 ; or (b) absorbic acid 0.5 gm three or four times daily ; the dosage of ascorbic acid may be doubled or tripled to achieve sufficient urine acidification 3. Long-term suppression therapy will be carried out for at least six months to one year 4. On termination of long-term suppression therapy and with bacteriologic cure, the patient will be screened according to the foregoing screening schedule V. Long-term follow-up of : 1. Bacteriologically cured patients (a) routine screening for reinfection according to aforementioned schedule (b) intercurrent history, physical, routine growth and development measures, and blood pressure measurements on each routine visit (cl other studies as indicated 2. Patients with recurrent infection and those on long-term suppression therapy (a) Intercurrent history and physical on each return visit (a) Periodic complete blood count, blood urea nitrogen, creatinine, urine concentration ability, intravenous pyelogram and creatinine clearance
The
Americrn
Journal
of
Swgery
Ureteral
This form of management will identify the patient with reflux and permit treatment to begin. Forbes, Drummond, and Vogrady [16] report recurrence rate of infection to be 24 per cent, and the rate was six times as high in patients with radiologically observed abnormalities. About 35 per cent of children with recurrent infection will have ureterovesical reflux. It is significant that in Lyons’ series [33] all the children who ceased to have reflux while on medical therapy did so in less than two years. In many patients in whom infection is controlled competence of the ureterovesical junction will be regained. There is little need for hasty surgical intervention; it must be borne in mind, however, that a slow, insidious infectious process can destroy kidneys, and in one group half of the patients with recurrent infection were asymptomatic. Conservative treatment of patients with reflux must be carried out aggressively and with extreme vigor, utilizing specific long-term antimicrobial therapy, combined with frequent voidings. The patient with continued bouts of recurrent pyelonephritis, radiographic changes in the kidneys, and grossly abnormal ureteral orifices, will probably develop progressive parenchymal damage unless antireflux surgery is carried out. The procedure of choice in reflux due to infection is the Politano-Leadbetter [37] operation. The success of this procedure is undisputed in preventing reflux and protecting renal function in more than 90 per cent of patients. In the series of Govan and Palmer [47] only 7 per cent of children had symptoms after surgery. They also found that the children operated upon had the same incidence of recurrent bladder infection as did children with bacilluria without reflux. It appears that correction of reflux protects renal tissue in uncomplicated bladder infection [48]. Scott [49] advises operation in carefully selected cases and reports 98 per cent successful elimination of reflux. He reports that 69 per cent of his patients had none or only one urinary infection in two years and 17 per cent had three or more relapses, with the proportionately greater number of relapses occuring in girls. The fact that 25 per cent of children with successful antireflux surgery have recurrent infection is not too disappointing in light of the relapse rate of about 25 per cent in children who have urinary tract infection unassociated with abnormalities correctable by surgery. Thus, it can be stated that antireflux procedures have an important place in the treatment of selected children with urinary tract infection and ureteral reflux.
Volume
122,
September
1971
Reflux
in Pediatric
Patients
The treatment of reflux in patients suffering from neurologic deficit, as seen in myelomingocele, requires the surgeon to be on guard for early renal changes. It must be understood that some of these children have associated abnormalities of the urinary tract which may be the cause of the reflux and amenable to corrective surgery. The guidelines of treatment require close observation of these patients and prevention and/or early treatment of infection. Suprapubic expression of residual urine is a valuable tool to keep the bladder empty but is not without danger in the patient who has reflux. The use of prophylatic drugs does not meet universal approval but most physicians use them. An early in-depth work-up must be carried out and repeated in an attempt to discover changes in the upper tracts. Once there is evidence of renal compromise, certain procedures may be of help. Usually the immediate cause is inadequate bladder emptying with increased pressure and superimposed infection. Surgically these patients can have their bladder outlet widened either by transurethral resection or a Y-V plasty. The pudendal neurectomy could conceivably be of help if external sphincter obstruction is present. The Y-V plasty will help some of these patients but the chances of improvement will be small in those children in whom upper urinary tract damage, bladder trabeculation, and significant infection have developed. The patient with severe infections, reflux, evidence of upper tract disease, and who is refractory to more conservative therapy, needs supravesical diversion for protection of renal function. Conclusion
The treatment of reflux as described in textbooks and the recent literature remains vague. There are many one-sided arguments for specific modalities of treatment with results at best doubtful since the lack of comparable groups makes interpretation of the final outcome difficult. Contradictions are almost the rule in pediatric and urologic literature as various fads become unfashionable, and new therapeutic technics are introduced. To decrease the amount of confusion and to allow for ongoing enlightened constructive criticism of the various regimens it is our belief that a multidisciplinary group become established. Our group consists of a pediatric surgeon, a urologist with a keen interest in pediatric urology, a pediatric radiologist, and a pediatrician whose main interest
361
Feins et al
is in renal infections and who has established a urinary tract infection clinic. All children with urinary tract infections are seen in the clinic and followed up by members of the group. The patients are evaluated from various viewpoints and plans of treatment and follow-up are established. A multidisciplinary approach appears to be the most reasonable method of solving the controversial problem of ureteral reflux in children.
24. 25.
26.
27. 28. 29.
References 1. Young HH: Hydraulic pressure in urologic practice. Johns Hookins HOSDBull. 9: 100. 1898. 2. Polk HC Jr: Notes on Galenic urology. Ural Surgery 15: 2, 1965. 3. Levin L, Goldschmidt H: Study on the relationships be. tween bladder, ureters, and kidneys. Arch Path Anat 134: 33, 1893. 4. Courtade D, Guyon JF: On reflux of vesical contents into the ureters. Comp Rend Sot 8iol46: 556, 1894. 5. Graves RC, Davidoff LU: Studies on the ureter and bladder. J Ural 10: 184, 1923. 6. Eisendrath DN, Katz H, Glasser JM: Bladder reflux. JAMA 85: 1121,1925. 7. Kjillberg SR, Ericsson NO, Ruhde V: The Lower Urinary Tract in Childhood; Chicago, Yearbook Medical Publishers, 1957. 8. Jones BW, Headstream JW: Vesicoureteral reflux in children. Trans So Cent Sect AUA. D 44. 1957. 9. Lich R Jr, Howerton LW, Goode ‘LA: The ureterovesical junction of the newborn. J Ural 92: 436, 1964. 10. lannaccone G, Panzironi PE: Ureteral reflux in normal infants. Acta Radio1 44: 451, 1956. 11. Belt E: Leonardo the Anatomist. Lawrence, Kansas, The University of Kansas, 1955. 12: Middelton RD (1959): Cited by McGovern et al, J Ural 83: 122, 1960. 13. Tanagho EA, Hutch JA: Primary reflux. J Ural 93: 158, 1965. 14. Tanagho EA, Hutch JA, Meyers FH, Rambo UN Jr: Primary vesicoureteral reflux: experimental studies of its etiology. J Ural 93: 165, 1965. 15. Johnston JH: Reflux treated by ureteric reimplantation. J Pediat Surg 1: 145, 1966. 16. Forbes PA, Drummond KN, Vogrady MB: Initial urinary tract infections. J Pediat 75: 187, 1969. 17. Shopner LE: Urinary tract pathology with sepsis. Amer J Roentgenof 108: 632,197O. 18. Tenagho EA, Guthrie TH, Lyon RP: The intravesical ureter in primary reflux. J Ural 101: 824, 1969. 19. Dorfman LE, Bailey J, Smith JP: Subclinical neurogenic bladder in children. J Ural 101: 48, 1969. 20. Samellas W, Herberman H: Vesicoureteral reflux following electroresection of the prostate or of bladder tumor. J Ural 96: 174, 1966. 21. Campbell’s Urology, 3rd ed, p 849. (Harrison and Campbell, ed). Philadelphia, Saunders, 1971. 22. King SE: Diastolic hypertension and chronic proteinuria. Amer J Cardiol9: 669, 1962. 23. Shapiro AP: Experimental pyelonephritis and hyperten-
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End of Symposium Papers
362
The Amsrkw~
Journal
of Sut~ery