THE JOURNAL OF UROLOGY
Vol. 74, No. 5, November 1955 Printed in U.S.A.
VESICOURETERAL REFLUX IN CHILDREN JOHN A. HUTCH, RAYMOND G. BUNGE
RUBIN H. FLOCKS
In 1951 an operative procedure designed to correct vesicoureteral reflux in paraplegic patients was described by one of us. 1 A question was raised as to the applicability of this operation to the correction of the reflux encountered in children. In an effort to answer this question our study was undertaken. It includes 8 children each of whom had persistent vesicoureteral reflux, hydroureter and hydronephrosis to varying degrees, and clinical symptoms consisting for the most part of recurring episodes of urinary tract infection and kidney pain. In all, 14 ureters were subjected to the operation. All but one of the cases has been followe:l from three to four years. The operation has been described elsewhere.1 Briefly it is an attempt to increase the length of the intravesical segment of the ureter. It is accomplished by dissecting the intramural ureter from its attachments to the bladder wall except at the trigone. After this has been done a 2 cm. segment of ureter is pulled into the bladder and the defect in the bladder wall created by the dissection of the intramural ureter is sutured under the newly created intravesical ureter. CASE REPORTS
Case 1. J. H., a 9-year-old girl, was born with a meningomyocele. At the age of 11 months she had many white blood cells in her urine and was already showing left hydronephrosis and reflux up the dilated left ureter. The meningomyelocele was removed surgically at the State University of Iowa Hospitals in 1946. She was seen in February 1950, on the urology service because of pyuria, chills and fever. Her examination revealed hydronephrosis, hydroureter, calyectasis and reflux bilaterally. On July 27, 1951, a plastic operation was performed on the left ureterovesical junction. A checkup examination on February 22, 1952, seven months postoperatively, revealed that she had been clinically well since her operation except for two episodes of chills and fever, each of which was controlled easily by gantrisin. Her cystogram demonstrated reflux up the right ureter but the reflux of the left ureter was no longer present. Excretory urograms revealed excellent function in 5 minutes bilaterally and the films were essentially unchanged as compared with the preoperative excretory urograms. This child has been carefully followed at 6-month intervals during the ensuing 3½ years. Repeated delayed cystograms have failed to demonstrate any reflux up the left ureter. Excretory urography on March 7, 1955 revealed excellent function of the left kidney in 5 minutes and appeared essentially identical with the films taken 7 months postoperatively. Clinically, the child has done well. A marked reduction has resulted in the episodes of chills and fever and those that have occurred have been less severe than before the operation. See figure 1. Read at annual meeting, American Urological Association, Los Angeles, Calif. May 16-19, 1955. 1 Hutch, J. A.: Vesicoureteral reflux in paraplegics. J. Urol., 68: 457, 1952. 607
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FIG. 1. Case 1. A, preoperative excretory urogram. B, preoperative cystogram. C, excretory urogram 7 months postoperatively. D, cystogram 7 months postoperatively.
The fate of the unoperated right ureter has not been good. Reflux has contiirned into this ureter and progressive dilatation has occurred. Recently it became necessary to do a plastic operation at the right ureterovesical junction in an effort to prevent further deterioration of the right kidney. While this operation stopped the reflux up the right ureter, the function of the right kidney re-
mains poor, the ureter and the renal pelvis remain dilated and emptying from the right ureter is slow. Case 2. S. L., a 3}:i-year-old boy, was born with a mf:ningomyelocele. _-\t the age of 13 month1:, it was removed surgically in the State UniYersity of Imm Ho,8pitals. He had neurological disturbance in his right foot and ,vore a brace. T.' rologically, this patient had incontinence of urine and repeated episodes of chill,c;, feyer, pyuria and left tlank pain. His rectal tone was zero and his foce8 had to he manually extracted. Cystograms revealed complete left reflux ·with hydronretcr hydronephrosit' and calyectasis. Excretory urograrns showed an essentially norm.al right upper urinary tract except for a right re-duplicated ureter. Ou the left, no diodrast wa,'3 seen until 15 minutes after injection and it appeared in puddleE outlining the calyces. A left vesicoureteral plasty was done on August 2°~, 1051. A checkup examination on November 26, 1951 (three months postoperatively) lY\'Calcd that the boy had been improved clinically. Since his operation he had had no rnore chills or fever or abdominal pains. His cystograrn re,,ealed no reflux up either ureter. Excretory urography demonstrated good function hilaterally in 5 minutes ,,,ith a definite improvement in the loft kidney to a point IYhere normal calyceal cupping can be seen. This child has bem1 followed carefully since operation. Delayed cystogram, have failed to reveal any recurrence of the left reflux. Repeated excretory urograms have been normal. The chills and fever and pain in the leH flank luwe disappeared and according to his father, the only symptom remaining is the' m·inary incontinence. See figure 2. Case 3. lVL C., a 9-year-old girl, \ms born with a mcningomyelocele. She 1rns first seen at the State 1h1iversity of Iowa Hospitals in 1948, at IYhich tirne hicr right kidney was nonfunctioning. Severe hydroureter and hydronephrosis wen, present and reflux occurred up the right ureter. The left kidney had good func· tion and appeared uorn1al by excretory urography. The right kidrn~y was n> mo\'ed. She has been followed carefully since and has had left flank pain, especially 1Yhen voiding. She is incontinent of urine and has marked pyuria with qccasional chills and fever. In November 1951, excretory urograms reyealed good function of the solitary left kidney with mild dilatation of the renal peh·is. Cystograrns rffrnaled reflux up the stump of the right ureter and complete left reflux. A plastic operation was done on the left ureterovesical junction on Xovcrnber I;;, HJ51. Postoperatively the patient did well and 2 weeks later the reflux ,rn.s nu longer present.. Excretory urography revealed excellent function in ,j minutes, hut, calyectasis and hydronephrosis were more marked than preopernti,-ely Followup examinations failed to show any recurrence of the reflux but ff,'.eretory urography demonstrated a slow dilatation of the remaining kidney. T,Yn and a half years postoperatively it was necessary to do nephrm,iomy to presen'e this patient's life. See figure :3. C'ase 4. K. IL, a 6-year-old white girl, was a difficult foot, presentation at birth and v.;ac, delivered by cesarian section. Immediately after birth a deformit:v of the left foot waR noted and treatment begun in the orthopedic department of St.ate 1Jniversit:v of Iowa Hospitals. Bowel and bladder control never de1·eloped.
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FrG. 2. Case 2. A, preoperative excretory urogram. No contrast medium seen on 5-minute film on left side. In 15 minutes dye appeared in puddles in region of left kidney, as is outlined. B, preoperative cystogram. C, excretory urogram 3 months postoperatively. Function present in 5 minutes and calyceal cupping has returned. D, cystogram made 3 months postoperatively.
At the age of four, examination in another hospital revealed bilateral hydroureter, hydronephrosis and ureteral reflux. Through the patient's life, episodes of chills and fever and bilateral flank pain have occurred on an average of once every two months. These have been controlled with chloromycetin. Physical examination revealed atrophy of the left foot, no anal sphincter tone and constant dribbling of urine. Cystoscopically, a saccule was demonstrated at each lateral boundary of the trigone and the respective intramural ureter passed
V 1':SICOT;RJD'I'ERA L RJDFLUX
FrG. ;j_ Ca~e 3. A pn•.oporativA excretor 0- urogram. B, preoperntive cystogram showing rnfiux into stump right ureter aml complet0 left reflux. C, postoperative! cxc-r0to1·y 11.rogram sh01rn inercnsecl dilatn1ion of left kidnc 0-. Dilatation slowl)- prngre.ssecl and uophrn,-
t,omy necc,ssarc· 2Lz )'earn later. D, post-operative Co'Stogram,
along the floor of each ,:;un·ule. Excretmy urography ,:;ho1\·ed good fnnction hiclemlaLernlly \\-ith marked bilateral hydronephro,:;is aud culyectaHicJ. (m/:ltrnted severe bilateral urcteral reflux. On August 10, 1951, a Yesicometcral phtc1ty wa,:; done 011 the rig;ht side.
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Fm. 4. Case 4. A, preoperative excretory urogram. B, preoperative cystogram. C, excretory urogram 2½ years after plastic operation on right ureterovesical junction and 1½ years after similar operation at left ureterovesical junction.
Fm. 5. Case 4. Cystogram made at time described in figure 4, C
A cystogram made 3 weeks postoperatively revealed reflux on the left, but none on the right. The excretory urogram was unchanged from the preoperative one. Followup examinations were so satisfactory that a vesicoureteral plasty was done on the left 1 year later. She continued to do well and her examination on March 4, 1954 (two and a half years postoperatively on the right and 1½ years postoperatively on the left) revealed no reflux into either ureter. The excretory urograms were quite satisfactory and were improved over the preoperative ones. Clinically, the patient was enjoying the best health of her life, according to her mother. Her urine was free of infection. We were quite encouraged at this point.
Howen,r, examination G mollths later showed an increase in dilatation of thti upper urinary tract bilaterally. Examination in February 1955 showed the dilatation to be progressing. At 110 time has she shown any postoperative reflux. See figures 4 and 5 . Case 5. P. P., a 3-year-old girl, was admitted to the State University of Iowa Hospitals with a histoey of repeated episodes of chills, fever and pyuria since birth. Physical examination, including neurological examination, was negative. Excretory urograms demonstrated good function bilaterally and complete reduplication of both upper urinary tracts. No function could be seen in the upper segment of the left kidney. Cystography revealed complete ureteral reflux into all four ureters and renal pel ves. The reflux was most marked in the upper seg-· ments. On cystoscopic examination no ureteral orifice:,: could be seen, but a large saccule ,vas present at each lateral boundary of the trigone. On November 1, 1951, a vet:1icoureteral plasty was done on each ureterovesical junction. When the bladder was opened, two saccules large enough to admit the distal phalanx of the little finger ,rnre found at each lateral boundary of the trigone. The lower ureter on each side was found in the depth of each saccule. The upper ureter bilaterally opened into the roof of its respective saccule. On each side, the intranrnral ureters were dissected free of the bladder wall and a short segment of both meters drawn into the bladder. The bladder wall was closed carefully under these newly created intravcsical ureters. Postoperatively, the patient did well and when checked 3}"2 montfoi later, there was no ureteral reflux by cystography. The excretory urograms were improYed ,vhen compared with the preoperative films. Clinically, the patient has had no chills or fever since her operation. She has been carefully checked since her operation and never has demonstrated reflux into any of her four ureters. The pyelograms have improved progressively and except for the upper segment on her left (which has never shown function) the pyelograms are normal. Clinically, she has been greatly improved but does have occasional urinary tract infection which requires treatment. Her last check-up examination was :;\farch 1955, three and one half years postoperatively. See figures t1 and 7. Case 6. M. M_, a ~l-year-old girl, was admitted to the State University of Iowa Hospitals because of severe attacks of chills and fe\-er which had occurred on an average of every 2 1veeks for the preceding 6 months_ Associated marked pyuria and bilateral flank pain had been noted_ Physical examination was negative and there \\-as no neurologie lesion demonstrable. Excretory urograms revealed excellent function bilaterally, and mild bilateral calyectasis, hydroureter a,nd complete re-duplication of the left ureter and pelvis_ Cystograms revealed com plete bilateral ureteral reflux. On September 21, 19,51, a right vesicoureteral plasty waE> performed This patient haE:' been carefully followed for 3Yz years. The reflux has bec,n offectirnly stopped althongh a slight tendency to reflux still persists. Her excre-· tory urograms are normal and have shown a definite improvement over the preopPrati-:e one;c;. Clinieallr, she is symptorn free. See figure 8.
Fm. 6. Case 5. A, preoperative excretory urogram. B, preoperative cystogram. Complete cystogram reveals reflux into all 4 ureters and renal segments.
Fm. 7. Case 5. A, excretory urogram 3~1i" months after bilateral plastic operation in which all ureteral segments were transplanted. B, cystogram made 3½ months postoperatively. C, excretory urogram made 3~1i" years postoperatively. D, cystogram 3>1i° yearn postoperatively. 614
FrG. 8. Case 6. A, preoperative excretory urogrmn. B, preoperative cy·stogrnm C. po,s/;opcra.tivt' excretor~· urogrmn. D, postoperative cystograrn. ~ote tlrnt reflux has stopped on hoth sides in spi1P of fa.ct thal operation wa.s done onlr on right side. Suhsequent, ex:uninn hons h:i.ve ,shown occa,sional reflux bilaterally.
HUTCH, BUNGE AND FLOCKS
Fm. 9. Case 7. A, preoperative excretory urogram. Right kidney nonfunctioning throughout entire examination, B, preoperative cystogram. C, excretory urogram 2 years postoperatively. D, cystogram 2 years postoperatively.
FrG, 10, Case 8, ti, preoperative excretory urogrnm. B, preoperative cystogran1. Note snccule a( right nreti,rovesical junction. C, post.operative excretory urogram. D, postopern, t.ive cystogranL
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Case 7. D. K., a girl aged 2, began to have recurring episodes of chills and fever and pyuria at age of 5 months. Her physical examination was negative including the neurologic examination. In February 1952, when the patient was 1 year old, a cystogram revealed right ureteral reflux and a bladder neck resection was done. The patient did not do well and a second bladder neck resection was done. The patient continued to have pus in her urine and chills and fever when she was taken off gantrisin. Pain developed also in the right upper abdomen. Physical examination ,ms essentially normal. Delayed cystograms revealed bilateral ureteral reflux. Intravenous pyelograms revealed a nonfunctioning right kidney and a dilated, tortuous left ureter. The urine was chemically negative and microscopically showed numerous pus cells. On February 5, 1953, a bilateral ureterovesical plasty was done. The postoperative course was good. The pyuria and pain in the right flank disappeared and the episodes of chills and fever ceased. Several delayed cystograms done postoperatively have failed to reveal any recurrence of the reflux. The patient has also had several excretory urograms which revealed prompt bilateral function, a normal left kidney and marked improYement in the right kidney. See figure 9. Case 8. A HJ-year-old -white man was seen on the urologic service at Park's Air Force Base, California because of pyuria and pain in the right flank. The pain had been present off and on for several years; no satisfactory diagnosis had been made. Excretory urograms revealed prompt bilateral function, both kidneys appearing essentially normal except for some dilatation in the lower portion of the right ureter. A cystogram revealed right vesicoureteral reflux and a large saccule or diverticulum on the right side of the bladder wall at the point where the ureter entered the bladder. Cystoscopic examination reveale:l that the right ureteral orifice was situated in the depth of a large diverticulum. In September 1954 a right vesicoureteral plasty was done. The postoperative course was good. Following the operation the pain in the right flank has completely disappeared and the urine has remained consi8tently free of pus. Excretory urograms are essentially normal and the dilatation present in the lm,,er portion of the right ureter has disappeared. Delayed cystograms fail to reveal any evidence of reflux. See figure 10. DISCUSSION
It is our belief that the ability of the normal urinary tract to resist vesicoureteral reflux rests in the ureterovesical junction and is a co-ordinated and cooperative effort of the intravesical ureter and the muscles of the bladder wall through which it passes. Two distinct types of action occur at the ureterovesical junction which are designed to prevent the regurgitation of bladder contents up the ureter. The first of these is a primary function of the bladder muscle which lies underneath and supports the intravesical ureter. As the bladder fills and the intravesical pressure increases these muscles stretch and carry the intravesical ureter into a more oblique position as it passes through the bladder wall. The roof of the intravesical ureter is then compressed against its floor between the pressure of the bladder contents and the firm bladder muscles behind it. Thus the relationship bet,rnen the bladder wall and the intravesical ureter is constantly
changing as the bladder fills and empties. While this activity is basically a function of the detrusor fibers underneath the ureter it is dependent upon the collapsibility of the intravesical ureter for its success in the prevention of reflux. The second of these activities of the ureterovesical junction designed to prevent reflux is a primary function of the intravesical ureter. Immediately following the spurt of urine through the ureteral orifice the intravesical ureter and the lateral border of the trigone are pulled sharply upward carrying the ureteral orifice with it. This must be the result of contraction of the longitudinal fibers of the intravesical ureter. The lumen of the intravesical ureter is actively occluded by the contraction of its walls. Also it is possible that this activity bends or angulates the intravesical ureter over the edge of the bladder muscles upon which it lies. This defense against reflux is a valuable one as it occurs at a time when the ureter is very vulnerable to reflux, viz., immediately after the ureter has emptied its contents into the bladder. For the sake of completeness a third possible defense against reflux must be discussed. This is theoretical and based on the assumption that W esson 2 and Young and W esson 3 are correct when they suggest that contraction of the trigone helps to open the internal urinary sphincter during micturition. When one considers that the fibers of the trigone sweep over the posterior lip of the bladder neck to insert around the verumontanum it becomes apparent that the trigone is admirably placed anatomically to do just that. During voiding the intravesical pressure rises rapidly to as high as 150 cc of water. The susceptibility to reflux is great at this time. However, if the trigone is contracting at this moment the ureters would be pulled downward since they are continuous with the lateral borders of the trigone and the length of the intravesical segment of the ureters would be increased. That such an increase in the length of the intravesical segment of the ureter could serve as a defense against reflux is supported by Gruber. 4 He found that in species which are very susceptible to reflux (rabbits, cats and dogs) the trigone was poorly developed and the intravesical ureter was short, where as in humans and other species where reflux is rare, the trigoue is well developed and the intravesical ureter is long. Based on the foregoing ideas we have come to think of our defenses against reflux as a dynamic relationship between the bladder wall on one hand and the intravesical ureter and trigone on the other hand. It is a constantly changing fluid type of relationship which automatically adjusts to meet varying conditions within the bladder and ureter. Any disease which destroys this relationship or alters the adaptability of one or both of the structures involved may result in vesicoureteral reflux. Diseases which cause bladder trabeculation are frequently complicated by reflux. These would include spastic neurogenic bladders secondary to cord injury or disease and diseases which cause urinary obstruction at or below the bladder neck. Here the changes at the ureterovesical junction can be clearly visualized cystoscopically or by cystogram. In certain other conditions 2 Wesson, M. B.: Anatomical, embryological and physiological studies on trigone and of neck of bladder. J. Urol., 4: 279-307, 1920. 3 Young, H. H. and Wesson, JV[. B.: Anatomy and surgery of trigone. Arch. Surg., 3: 1-37, 1921. 4 Gruber, C. M.: J. Urol., 21: 567, 1929.
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in which the bladder wall becomes very thin there is insufficient muscle behind the ureter to support it in an intravesical position. This is probably the explanation of the reflux in the meningomyelocele cases. In certain other cases the explanation for the reflux must lie in the faulty development of the ureteral bud. It is noted that three of our cases had complete ureteral reduplication, one bilateral. No discussion of reflux is complete without some mention of the part it plays in the dilatation of the upper urinary tract. It is recognized that reflux is often present in cases which have functional obstruction at the ureterovesical junction. The additional work load placed on the ureter by the reflux could account for the dilatation of the ureter but often the dilated ureter exists alone and no reflux can be demonstrated to account for it. In addition to preventing reflux the intravesical ureter must also allow ureteral urine to pass through it unobstructed. Perhaps these changes discussed above which destroy the capacity of the ureterovesical junction to resist reflux also cause it to fail in this second function and may result in a functional obstruction as well as in reflux. There is some clinical evidence to support this idea. 5 The relationship between vesicoureteral reflux and nonobstructive dilatation of the upper urinary tract is a close one and it may be that the ureterovesical junction is the key to both problems. SUMMARY AND CONCLUSION
After observing the clinical and radiological course of these patients for almost four years we feel justified in making some conclusions. First, the operation effectively stops reflux. All patients included in this study had persistent, severe reflux preoperatively. Postoperatively, they were subjected to the most rigid testing we could devise, namely, the delayed cystogram consisting of 3 to 4 films over a period of one to two hours. Most of these patients have had two to three such examinations each year since their surgery. In spite of this only two of the fourteen ureters involved have shown any tendency to reflux. Clinically, the improvement has been equally gratifying. Without exception each patient has either been cured of symptoms or has experienced a reduction in the frequency or severity of symptoms. Of maximal importance in the evaluation of any procedure designed to correct reflux is its effect upon the upper urinary tract as judged pyelographically. In five of the eight cases the pyelogram has been improved and is today normal or nearly normal. In two cases pyelographic improvement was noted for two and a half years postoperatively but further dilatation has been occurring in the last year and a half. One kidney was damaged by the operative procedure and required nephrostomy drainage two and one half years postoperatively. All of the poor results were in the meningomyelocele group. Our overall experience with this procedure has been quite gratifying and we believe it will earn a place in the treatment of reflux.
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Hutch, J. A.: Nonobstructive dilatation of upper urinary tract. J. Urol., 71: 412, 1954.