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The Problem of Primary Megalo-Ureter
THE JOURNAL OF UROLOGY
Vol. 72, No. 2, August 1954 Printed in U.S.A.
THE PROBLEM OF PRIMARY MEGALO-URETER REED M. NESBIT
AND
JOHN F. WITHYCOMBE
From the Section of Urology, Department of Surgery, University of Michigan, Ann Arbor, Mich.
In recent years congenital anomalies of the urinary tract in children are being recognized and reported in the literature in increasing numbers. This has resulted to a great extent from the wider recognition of the principle that a persistent urinary tract infection calls for detailed examination. Among these abnormalities dilatation of the ureter, unilateral or bilateral, is no longer a rarity. Campbell1 has classified such dilatations into two groups, primary and secondary. A diagnosis of primary megalo-ureter should be confined to those cases in which no mechanical obstruction can be found to account for the ureteral dilatation. The term megalo-ureter was first used by Caulk2 in 1923 to describe such a deformity in a case in which no obstructive lesion was demonstrated and in which the ureteral orifices appeared normal on cystoscopic examination. Prior to this, similar ureteral dilatation without apparent cause had been noted by other observers (Saintu3 1896, Fortescue-Brickdale4 1905, and others). The purpose of this paper is to review the results of some methods of treatment used for this condition in the past, and to consider briefly whether the operative procedures have yielded significant clinical benefits. It would be tempting also to discuss the etiology of megalo-ureter, but with the evidence available in the cases presented here, any conclusion reached would be largely speculative. Before making a diagnosis of primary megalo-ureter it is well to remember its rarity. Such a diagnosis was made in only 4 patients admitted to University Hospital since 1935: two further cases have been excluded from the present study owing to inadequate record of bladder function. Similarly, Campbell5 could only find two cases of primary megalo-ureter among several hundred cases of dilatation of the ureter. To establish the diagnosis two criteria must be fulfilled: 1.
DILATATION OF THE URETER
Ureteral dilatation may be demonstrated by excretory or retrograde pyelography, or by cystogra~ if reflux of urine from bladder to affected ureter is present. The value of al delayed or voiding cystogram is emphasized, for in some cases no sign of reflux is found in early films but is only observed in those made after an interval of one-half hour or an hour (Stewart 6). Presented to the New York Section of the American Urological Association, April 22, 1953. 1 Campbell, M.: Clinical Pediatric Urology. Philadelphia: W. B. Saunders Co., 1951. 2 Caulk, J. R.: The importance of the ureterovesical valve. J. Urol., 9: 315, 1923. 3 Saintu, 0.: Note sur un cas de retention d'urine chez le foetus avec permeabilites du canal de l'urethre, J. de Med. de Paris, 8: 332, 1896. 4 Fortescue-Brickdale, J.M.: A note on congenital dilatation of the ureters. Bristol Med. Chir. J., 23: 231, 1905. 5 Campbell, M.: Primary megalo-ureter, J. Urol.., 68: 584, 1952. 6 Stewart, C. M.: Delayed cystograms. J. Urol., 70: 588, 1953. 162
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The diameter of the ureter is increased; this may be unilateral or bilateral. In the present study it has been noted that the circumferential dilatation is not accompanied by commensurate increase in length, and kinking of the ureter is not a marked feature of these cases. A similar observation has been made by others (Campbell, 5 Hepler7, Wayman 8), and Hinman9 has considered multiple angulation to be indicative of an obstructive etiology. The renal pelvis and calyces of these patients do not show the degree of dilatation which might be expected in the presence of such ureteral deformity. 2.
ABSENCE OF OBSTRUCTION
Obstruction in the course of the lower urinary tract must be excluded. The more gross types of obstructive lesion at the lower end of the ureter or at the bladder neck should present no difficulty in demonstration. But exclusion of obstruction at the bladder level cannot be regarded as certain without careful assessment of vesical function by cystometric examination and estimation of residual urine. Bladder dysfunction due to neurogenic disturbances may be reflected in the ureter, and many reported cases of so-called primary megaloureter would properly be excluded from this group if such full investigation had been carried out. It is an accepted fact that long standing ureteral infection can produce some degree of dilatation of the ureter. With this knowledge it would be desirable, before establishing a diagnosis of primary megalo-ureter, to exclude infection as a possible etiological factor. In the present series of cases, however, infection is an invariable accompaniment of the stasis associated with ureteral dilatation. For this reason it is felt that cases with infection should not be excluded from this category if the criteria mentioned above are fulfilled. Some observers on this subject have stated that additional criteria are necessary to confirm the diagnosis of primary megalo-ureter. Campbell considers that vesico-ureteral reflux with a relaxed immobile ureteral orifice is a characteristic finding in this condition. Although reflux may be present, it appears not to be invariably the case; reflux occurred in only one of the 4 patients presented here (case 1). Indeed its absence tends to confirm a diagnosis of primary ureteral dilatation provided that an obstructive lesion of the lower ureter has been excluded. Also, on cystoscopy we are impressed with the normal appearance of the ureteral opening in these cases and have observed patulous orifices in only one case. CASE REPORTS
Case 1. An 11 year old girl, S. P., was first seen in August 1950. Her mother gave a history that the child was well until two years old when she had a convulsion accompanied by temperature of 102F. During the course of illness, which lasted a few days, her doctor found that she had a urinary tract infection which 7 Hepler, A. B.: Non-obstructive dilatations of upper urinary tract in children. J. A. M. A., 109: 1602, 1937. 8 Wayman, T. B.: Surgical treatment of megalo-ureter. J. Urol., 61: 883, 1949. 9 Hinman, F.: Obstructive hydroureteral angularity with hydronephrosis in children. Arch. Surg., 18: 21, 1929.
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responded promptly to treatment with a sulfonamide preparation. This was the first attack of many similar episodes which ·occurred at intervals of three to five months and all were accompanied by the presence of pus cells and organisms in the urine. Since the age of eight it had become increasingly difficult to control the infections and attacks had become prolonged. Her mother stated that she appeared to have no difficulty in passing urine at any time. The patient was a healthy looking girl of normal size and weight and no gross abnormality was found on physical examination. She voided urine with good force although 55 cc residual urine was present following micturition and this showed 10 to 15 white blood cells and rod shaped organisms when examined microscopically. Renal function tests were within normal limits. A cystometrograph was performed at this time and although there was large bladder capacity (400 cc) the shape of the curve was normal. Panendoscopy and cystoscopy (August 16, 1950) revealed a normal bladder with no trabeculationand no vesical neck obstruction. Both ureteral orifices were patulous and were easily catheterized; on retrograde injection of dye moderate increase in ureteral diameter was noted. A cystogram revealed the presence of bilateral ureteral reflux. At operation on August 18, 1950, the left ureter was exposed throughout its length by a left pararectal incision. It was found to be dilated to three times its normal size but showed active peristalsis on stimulation. The dilatation continued to the point where the ureter entered the bladder. The caliber of the ureter was reduced throughout its length by removal of a strip comprising approximately two thirds of its circumference as described by Crabtree and also used by Wayman. The lower end of the ureter was then re-implanted into the bladder by a fish-mouth technique. The operation was completed by suprapubic cystotomy. The patient made a good recovery from operation and in view of the ureteral reflux her cystotomy drainage was maintained to insure continuous and complete bladder drainage. However, repeated episodes of urinary tract infection occurred which could be controlled by various antibiotic agents. A cystogram made on October 31, 1950, showed that ureteral reflux persisted bilaterally. Three months after operation, following a trial of voiding with the suprapubic tube clamped, only a few cubic centimeters of residual urine remained in the bladder and her suprapubic drainage tube was removed. The removal of the suprapubic tube appeared to lessen the frequency of attacks of urinary infection, and a cystogram made one year later demonstrated diminution in reflux on the right side but it was still present on the left. Since this time she has continued to make very satisfactory progress with only one attack of urinary infection during the the past year and recent excretory urograms give evidence of good renal function with no hydronephrosis. Commentary on case 1: This was the only case of the series in which ureteral reflux was demonstreated preoperatively.· It is significant that she was found to carry residual urine of 50-100 cc although she was observed to void with an uninterrupted and forceful stream with apparent complete emptying of the bladder. In view of the normal vesical function it was assumed that this amount
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of residual urine did in fact represent the volume of reflux. Crabtree10 has reported a similar case in ·which incompetence of the ureteral valves allowed reflux of urine during voiding. In this case a period of 3 months' vesical drainage by cystotomy did not diminish reflux nor did it improve the degree of megalo-ureter on either side. It is noteworthy that following removal of the suprapubic drainage tube her pyrexia subsided and urinary infection markedly improved. A cystogram made 13 months after operation revealed only minimal reflux into the lower third of the ureter on the right but was still present on the opposite side which had been treated surgically. Although the left ureter was poorly visualized in this cystogram the x-ray suggested that the left ureter was in fact as dilated as before operation. The last excretory urogram made in August 1952 (two years after operation) shows good renal function on both sides with no evidence of hydronephrosis or calyceal dilatation. This fact coupled with the satisfactory clinical progress that the child is making is strong evidence that little benefit was derived from operation. It would be interesting to know the degree of ureteral reflux which may now be present, but the mother is reluctant to bring her child to the hospital for this purpose as she is making such excellent progress. Case 2. J. 0., a girl, was brought to University Hospital in July 1950, when 4 years old. She had been ·well until the age of 18 months when her mother noticed that she had pain on urination. At this time her doctor found pus cells in the urine. Since this first attack she had had four episodes of pyrexia accompanied by frequency of micturition every one to two hours and an infected urine. At no time was there a history of flank pain or tenderness on palpation in the renal areas. Physical examination ·was negative and tests sho-wed satisfactory renal function (blood urea nitrogen 16 mg. per cent; phenolsulfonphthalein excretion 48 per cent in 2 hours). An excretory urogram revealed a severe degree of bilateral ureteral dilatation with minimal hydronephrosis on the left. No evidence of ureteral reflux was demonstrated in a cystogram. At operation on July 28, 1950 the right ureter was found to be approximately 2 cm. in diameter but showed good peristalsis. The dilatation extended from the kidney to a point approximately one inch from the bladder. At this point the ureter was of normal size and through this narrowed portion a No. 6 ureteral catheter was passed with ease into the bladder. It was therefore felt that obstruction at the lower end of the ureter could be confidently excluded. The ureter was detached from the bladder at the ureterovesical junction and this narrower portion excised. Approximately one-third of the diameter of the ureter was resected throughout its length and re-implanted into the bladder by an elliptical anastomosis at a point above and to the right of the previous ureteral opening, The ureter was drained by ureterostomy and a cystotomy tube was left in situ suprapubically. A cystogram made 3 months after this operation now showed reflux on the operated side. On October 9, 1950, at a second operation, exposure of the left ureter shmved 1
° Crabtree, E.G.: Plastic operation for the relief of megalo-mCJter. Trans. Amer. Assoc.
G, TJ Snrg., 30: 311, 1937.
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similar findings to those on the right side. Again no evidence of obstruction could be demonstrated at the lower end of the ureter and approximately 4 inches of the lower ureter were resected and the free end re-implanted into the bladder by elliptical anastomosis. On this side no longitudinal segmental resection was performed. A cystogram made one month following this procedure now revealed that reflux was present bilaterally. The child made satisfactory progress following these operations and 2 months after the second operation the cystotomy tube was removed and the suprapubic fistula allowed to close. At this point severe episodes of pyrexia occurred and could only be controlled by sustained catheter drainage. From then until the present time removal of the indwelling catheter has invariably been accompanied by a recurrence of these attacks of pyrexia and flank pain. A recent excretory urogram (fig. 1, A) showed satisfactory function although ureteral dilatation persists and on cystogram (fig. 1, B) it is seen that she has a severe degree of megalo-ureter and hydronephrosis. At no time during the course of this patient's illness and treatment have renal function tests revealed any gross deviation from normal. Commentary on case 2: In this case, although the dilatation of right ureter appeared to be initially improved by operation, the final result and persistence of megalo-ureter show that surgery did little to benefit the child. In fact, ureteral reflux which was not present in the original x-rays appeared in cystograms made after operation. It is significant that continuous bladder drainage produced no improvement in her ureteral dilatation. In spite, however, of these abnormalities and a urinary infection from which she is seldom free, the child remains surprisingly active and healthy; this fact is reflected in the comparatively normal renal function tests. This case also illustrates the value of a cystogram in demonstrating the true degree of ureteral dilatation. The excretory pyelogram (fig. 1, A) does not suggest the gross megalo-ureters which in fact exist, but which are dramatically revealed in a cystogram made shortly afterwards (fig. 1, B). Case 3. A 4 year old girl, L. A., was adinitted to hospital in March 1952. For
Fm. 1. Case 2. A, excretory urogram and B, cystogram 2 years after operation showing recurrence of dilatation of right ureter. Cystogram reveals true degree of ureteral dilatation which is not demonstrated in excretory urogram made 2 days previously.
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two and a half years she had suffered from recent episodes of high fever, frequency and pain on micturition. During each of these attacks her urine was found to contain pus cells and bacteria, and although initially the infection responded rapidly to treatment with sulfa drugs it had recently become refractory to therapy. At no time had there been any difficulty in initiating micturition. On admission, physical examination was negative and she was seen to void with a good stream. A catheter specimen of urine examined microscopically showed 5 pus cells per high power field, and numerous bacilli which proved on culture to be E. coli. The blood urea nitrogen was 17 .5 mg. per cent, the plasma CO 2 combining power 38 vols. per cent, and serum chlorides were 103 m/Eq. per liter. Excretory urograms revealed dilatation of both ureters, with some degree of hydronephrosis on the left. The calyces, however, were sharply outlined ,vith no loss of "cupping." A cystogram showed no evidence of reflux. A normal cystometrograph and absence of residual urine after voiding suggested good bladder function. On cystoscopy and panendoscopy the bladder appeared normal, with an adequate vesical neck outlet. No ureterocele or other obstruction was seen at either ureteral orifice, through which No. 5 catheters could be passed with ease. At operation on March 31, 1952, the lower third of the left ureter was exposed extraperitoneally by a transverse lower abdominal incision. The ureter was approximately 2 cm. in diameter throughout its course until, at a point 3 cm. from the bladder, the dilatation ceased and the remaining portion of the ureter appeared to be of normal size. Active peristalsis was noted in the dilated portion of the ureter. The ureter was divided at its junction with the bladder and the narrowed section removed, together with 3-4 cm. of the dilated portion. The remaining ureter was re-implanted into the bladder at a point higher on the lateral wall, by elliptical anastomosis. A pathological report of the removed portion read as follows: "Dilatation of the ureter ·with hypertrophy of muscularis and heavy focal collections of lymphocytes in the muscularis." The patient made a good recovery from operation, but convalescence was complicated by attacks of high temperature and pain and tenderness in the left costovertebral angle. Vigorous therapy with antibiotic drugs during the next 3 months was required to control these episodes of infection but her flank pain became progressively more severe. A cystogram made at this time revealed reflux of urine on the side of operation, and it was believed that these symptoms were due to an ascending pyelonephritis. During July 1952 she had persistent pyrexia, her general condition deteriorated and the child became pale and listless. Although studies showed good renal function, urgent treatment was considered necessary to prevent severe renal damage and possible nephrectomy. Accordingly, at a second operation on August 11, 1952, the left ureter was excised in its entirety, and replaced by an isolated segment of ileum as reported by McLean and Fais 11 following its experimental use in dogs. In view of the recognized association of megacolon and ureteral dilatation this procedure ·was 11 McLean, D. W. and Fais, 0. G.: The use of segments of small intestine as ureters. J. UroL, 68: 190, 1952.
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FIG. 2. Case 3. A, injection of radio-opaque dye through nephrostomy tube 3 weeks after replacement of left ureter by isolated loop of ileum. B, cystogram demonstrating reflux up ileal loop. C, excretory urogram 4 months following use of ileal loop to replace left ureter.
undertaken after x-ray investigation had excluded any intestinal abnormality. At a point about 18 inches from the ileocaecal valve a loop of ileum and mesentery was isolated. This loop was swung across in front of the colon and anastomosed to the renal pelvis and bladder, after the removal of the affected ureter. Active peristalsis was again observed during the manipulation of the ureter. The operation was completed by the insertion of a nephrostomy drainage tube. Following this surgery the patient's general condition improved steadily and although her urine remained infected she became asymptomatic and the pain and tenderness in the left costovertebral angle subsided. During the first few weeks the urine contained varying amounts of mucus from the transplanted intestine but this gradually subsided and is now completely absent. Two weeks after operation radio-opaque dye injected through the nephrostomy tube and observed during fluoroscopic screening was seen to pass rapidly from renal pelvis to bladder (fig. 2, A). A cystogram also made at this time showed that reflux occurred up the intestinal loop (fig. 2, B). However, as drainage from the renal pelvis was so efficient the nephrostomy tube was removed 21 days after operation and the wound healed rapidly. The initial satisfactory progress that this child made has been maintained and when last seen 4 months after operation her urine contained only a few pus cells with an occasional bacillus when exainined microscopically. Commentary on case 3: Several writers on this subject (MacMyn12 , Hurst and Gaymer-Jones18 , Swenson and associates14 and Lewis and Kimbrough15) have drawn comparisons between primary megalo-ureter and congenital megacolon, 12 MacMyn, D. J.: On dilatation of the ureters and hydronephrosis in childhood. Brit. J. Urol., 1: 150, 1929. 13 Hurst, A. F. and Gaymer-Jones, J.: A case of megalo-ureter due to achalasia of the ureterovesical sphincter. Brit. J. Urol., 3: 43, 1931. 14 Swenson, 0., MacMahon, H. E., Jaques, W. E. and Campbell, J. S. A new concept of the etiology of megaloureters. New Eng. J. Med., 246: 41, 1952. 16 Lewis, E. L. and Kimbrough, J.C.: Megalo-ureter: New concept in treatment. South. Med. J., 45: 171, 1952.
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Frn. 3. Case 4. Retrograde pyelograms (1931) showing bilateral megalo-ureter.
and indeed the two conditions are cometimes co-existent (Moore and Lawrence 16 ). In this case and in case 2 it was noted at operation that the dilated portion of ureter had inherent contractibility when stimulated and terminated from 2 to 4 cm. from the ureterovesical junction, these lower few centimeters of ureter being of normal size. Such an appearance certainly seems to suggest an analogy to the dilated and hypertrophic colon proximal to a narrow section of bowel vvhich Swenson and others 17 , 18 have shown to be devoid of parasympathetic nerve supply in congenital megacolon. Kimbrough 15 reports encouragingly on the results of resection of this normal appearing segment of ureter and vesical re-implantation of the dilated ureter. It has been our experience, however, that such an operation produced no improvement in the degree of megalo-ureter in the two cases in which it was employed. In this case excision of the narrower portion of ureter and re-implantation into the bladder allowed ureteral reflux of urine which had not been present prior to operation. This appeared to initiate a series of severe episodes of ascending infection and pyelonephritis. It is possible that such reflux might be prevented by allowing a short segment of ureter to lie free in the bladder as practiced by Kimbrough who considers that such a procedure is helpful in preventing this complication. The use of an isolated loop of intestine to replace the ureter undoubtedly improved the child's condition symptomatically and the recurrent episodes of pyelonephritis ceased. Up to the present time the result of this operation appears very satisfactory, but a longer period of observation will be necessary before final evaluation of such a procedure can be made. It may be pertinent to remark on the possibilities of such an operation in the treatment of other conditions in which replacement of a ureter is necessary. 16 lVIoore, T. C. and L11wrence, E. A.: Congenital malformation of the rectum and anus. Surg. Gynec. & Obst., 95: 281, 1952. 17 Swanson, 0., Rheinlander, H. F. and Diamond, I.: Hirschsprung's disease: N cw concept of etiology. New Eng. J. Med., 241: 551, 1949. 18 Bodian, M. and Stephens, F. D.: Hirschsprung's disease: A new concept. Proc. Roy. Soc. Med., 42: 225, 1949.
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Case 4. M. E., an unmarried 33 year old woman, has been observed at University Hospital since she was nine, when her mother stated that she had had episodes of fever accompanied by flank pain since the age of two. Cystoscopy revealed an inflamed but otherwise normal appearing right ureteral orifice and a normal left ureteral orifice. Catheterization of both ureters was easily performed and there was no evidence of obstruction. The specimens of urine obtained from the ureters were heavily loaded with pus cells and bacilli. Pyeloureterograms (fig. 3, A and B) made at this time revealed bilateral ureteral dilatation but the renal calyceal systems did not show a commensurate degree of defonnity although hydronephrosis was present. At intervals for the next 6 years lavage of both ureters was carried out and with this treatment she remained in good health and remarkably free from symptoms, and the intervals during which the bladder urine was free from infection became increasingly longer.
Fm. 4. Case 4. Retrograde pyelograms (1948). In spite of persistence of bilateral megaloureter, patient's renal function remains good, she has uninfected urine and is leading an active life. No operation was performed.
In 1935, however, when the patient was aged 15, severe urinary tract infection recurred accompanied by bilateral flank pain radiating to the lower abdomen. It was noted that these bouts of infection coincided with her menstrual periods. Owing to the increasing severity of the attacks and their persistent association with menstruation, an x-ray sterilization was considered advisable. This produced a dramatic amelioration of her urinary symptoms. The improvement was maintained and she was well until 1948 when menstruation re-commenced and pain recurred, to be relieved once again when x-ray therapy terIninated her periods. Since this time she has remained entirely free from symptoms and has led an active and healthy life as a teacher. It is noteworthy that her urinary tract infection was promptly cleared on the institution of treatment with sulfonamide drugs, and has not returned. Her ureterograms made at intervals since 1929 show that the degree of ureteral dilatation has not materially changed, nor has there been evidence of increasing hydronephrosis (fig. 4). Recent renal function tests show that the phenolsulfonphthalein clearance was 58 per cent in 2 hours.
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Commentary on case 4: The satisfactory result in this case from conservative management adds weight to the doubts cast on the value of any surgical interference in these cases. It must be noted again, however, that the dilatation of her ureters has persisted unchanged throughout the course of our observation. A further point of interest in this case is the manner in -which the infection of the urine seemed to be closely associated -with menstruation and -was cleared by an artificial menopause. Such an association may favor the possibility of an hormonal factor in the etiology of this condition. In this respect also the anatomical relationship of the uterine artery to the lower end of the ureter must not be forgotten. DISCUSSION
At the present time the many theories of the cause of primary megalo-ureter are all largely conjectural. With so little understood about the etiology it is not surprising that varied surgical approaches to the problem have been attempted. It had been believed in the past that suprapubic cystostomy alone had, in some instances, resulted in decrease in the size of the ureters. In the light of present knowledge, however, it is probable that those cases in which improvement has been noted, -were, in fact, not true primary megalo-ureters, but cases in which faulty vesical function was present. Neither supra pubic cystostomy nor continuous bladder drainage by catheter has resulted in diminution of ureteral dilatation in any of the cases reported here. Our present investigation has sought an answer to the question of whether the operative procedures in these cases have yielded significant clinical benefits. Operation in all 3 cases was performed in an effort to alleviate the following conditions: gross bilateral ureteral dilatation, infection in the urine, and episodes of sepsis. All three of the cases following operation have shown persistence of the ureteral dilatation, and have continued to have infection of the urine. Based on the stated criteria one is forced to conclude that results hoped for have not been attained. Compared to these 3 cases the other patient in whom no operation was performed also has dilated ureters, but she is clinically well and has been free from infection for nearly ten years. It appears that she has fared better than the others. Our present opinion regarding the management of such cases would be this: the clinician who faces any problem of this sort must focus his attention on excluding evidence of obstructive uropathy which might be amenable to surgical correction. It is only -when all such factors are found to be lacking that a diagnosis of primary megalo-ureter can be established. It seems that renal function remains surprisingly good in these cases, and that the prognosis need not be as pessimistic as the degree of ureteral dilatation would at first suggest. Perhaps in this particular type of case it might be better to focus our therapeutic efforts along conservative antibacterial avenues and be less concerned with correction of ureteral dilatation.
Vol. 72, No. 2, August 1954 Printed in U.S.A.
THE PROBLEM OF PRIMARY MEGALO-URETER REED M. NESBIT
AND
JOHN F. WITHYCOMBE
From the Section of Urology, Department of Surgery, University of Michigan, Ann Arbor, Mich.
In recent years congenital anomalies of the urinary tract in children are being recognized and reported in the literature in increasing numbers. This has resulted to a great extent from the wider recognition of the principle that a persistent urinary tract infection calls for detailed examination. Among these abnormalities dilatation of the ureter, unilateral or bilateral, is no longer a rarity. Campbell1 has classified such dilatations into two groups, primary and secondary. A diagnosis of primary megalo-ureter should be confined to those cases in which no mechanical obstruction can be found to account for the ureteral dilatation. The term megalo-ureter was first used by Caulk2 in 1923 to describe such a deformity in a case in which no obstructive lesion was demonstrated and in which the ureteral orifices appeared normal on cystoscopic examination. Prior to this, similar ureteral dilatation without apparent cause had been noted by other observers (Saintu3 1896, Fortescue-Brickdale4 1905, and others). The purpose of this paper is to review the results of some methods of treatment used for this condition in the past, and to consider briefly whether the operative procedures have yielded significant clinical benefits. It would be tempting also to discuss the etiology of megalo-ureter, but with the evidence available in the cases presented here, any conclusion reached would be largely speculative. Before making a diagnosis of primary megalo-ureter it is well to remember its rarity. Such a diagnosis was made in only 4 patients admitted to University Hospital since 1935: two further cases have been excluded from the present study owing to inadequate record of bladder function. Similarly, Campbell5 could only find two cases of primary megalo-ureter among several hundred cases of dilatation of the ureter. To establish the diagnosis two criteria must be fulfilled: 1.
DILATATION OF THE URETER
Ureteral dilatation may be demonstrated by excretory or retrograde pyelography, or by cystogra~ if reflux of urine from bladder to affected ureter is present. The value of al delayed or voiding cystogram is emphasized, for in some cases no sign of reflux is found in early films but is only observed in those made after an interval of one-half hour or an hour (Stewart 6). Presented to the New York Section of the American Urological Association, April 22, 1953. 1 Campbell, M.: Clinical Pediatric Urology. Philadelphia: W. B. Saunders Co., 1951. 2 Caulk, J. R.: The importance of the ureterovesical valve. J. Urol., 9: 315, 1923. 3 Saintu, 0.: Note sur un cas de retention d'urine chez le foetus avec permeabilites du canal de l'urethre, J. de Med. de Paris, 8: 332, 1896. 4 Fortescue-Brickdale, J.M.: A note on congenital dilatation of the ureters. Bristol Med. Chir. J., 23: 231, 1905. 5 Campbell, M.: Primary megalo-ureter, J. Urol.., 68: 584, 1952. 6 Stewart, C. M.: Delayed cystograms. J. Urol., 70: 588, 1953. 162
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The diameter of the ureter is increased; this may be unilateral or bilateral. In the present study it has been noted that the circumferential dilatation is not accompanied by commensurate increase in length, and kinking of the ureter is not a marked feature of these cases. A similar observation has been made by others (Campbell, 5 Hepler7, Wayman 8), and Hinman9 has considered multiple angulation to be indicative of an obstructive etiology. The renal pelvis and calyces of these patients do not show the degree of dilatation which might be expected in the presence of such ureteral deformity. 2.
ABSENCE OF OBSTRUCTION
Obstruction in the course of the lower urinary tract must be excluded. The more gross types of obstructive lesion at the lower end of the ureter or at the bladder neck should present no difficulty in demonstration. But exclusion of obstruction at the bladder level cannot be regarded as certain without careful assessment of vesical function by cystometric examination and estimation of residual urine. Bladder dysfunction due to neurogenic disturbances may be reflected in the ureter, and many reported cases of so-called primary megaloureter would properly be excluded from this group if such full investigation had been carried out. It is an accepted fact that long standing ureteral infection can produce some degree of dilatation of the ureter. With this knowledge it would be desirable, before establishing a diagnosis of primary megalo-ureter, to exclude infection as a possible etiological factor. In the present series of cases, however, infection is an invariable accompaniment of the stasis associated with ureteral dilatation. For this reason it is felt that cases with infection should not be excluded from this category if the criteria mentioned above are fulfilled. Some observers on this subject have stated that additional criteria are necessary to confirm the diagnosis of primary megalo-ureter. Campbell considers that vesico-ureteral reflux with a relaxed immobile ureteral orifice is a characteristic finding in this condition. Although reflux may be present, it appears not to be invariably the case; reflux occurred in only one of the 4 patients presented here (case 1). Indeed its absence tends to confirm a diagnosis of primary ureteral dilatation provided that an obstructive lesion of the lower ureter has been excluded. Also, on cystoscopy we are impressed with the normal appearance of the ureteral opening in these cases and have observed patulous orifices in only one case. CASE REPORTS
Case 1. An 11 year old girl, S. P., was first seen in August 1950. Her mother gave a history that the child was well until two years old when she had a convulsion accompanied by temperature of 102F. During the course of illness, which lasted a few days, her doctor found that she had a urinary tract infection which 7 Hepler, A. B.: Non-obstructive dilatations of upper urinary tract in children. J. A. M. A., 109: 1602, 1937. 8 Wayman, T. B.: Surgical treatment of megalo-ureter. J. Urol., 61: 883, 1949. 9 Hinman, F.: Obstructive hydroureteral angularity with hydronephrosis in children. Arch. Surg., 18: 21, 1929.
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responded promptly to treatment with a sulfonamide preparation. This was the first attack of many similar episodes which ·occurred at intervals of three to five months and all were accompanied by the presence of pus cells and organisms in the urine. Since the age of eight it had become increasingly difficult to control the infections and attacks had become prolonged. Her mother stated that she appeared to have no difficulty in passing urine at any time. The patient was a healthy looking girl of normal size and weight and no gross abnormality was found on physical examination. She voided urine with good force although 55 cc residual urine was present following micturition and this showed 10 to 15 white blood cells and rod shaped organisms when examined microscopically. Renal function tests were within normal limits. A cystometrograph was performed at this time and although there was large bladder capacity (400 cc) the shape of the curve was normal. Panendoscopy and cystoscopy (August 16, 1950) revealed a normal bladder with no trabeculationand no vesical neck obstruction. Both ureteral orifices were patulous and were easily catheterized; on retrograde injection of dye moderate increase in ureteral diameter was noted. A cystogram revealed the presence of bilateral ureteral reflux. At operation on August 18, 1950, the left ureter was exposed throughout its length by a left pararectal incision. It was found to be dilated to three times its normal size but showed active peristalsis on stimulation. The dilatation continued to the point where the ureter entered the bladder. The caliber of the ureter was reduced throughout its length by removal of a strip comprising approximately two thirds of its circumference as described by Crabtree and also used by Wayman. The lower end of the ureter was then re-implanted into the bladder by a fish-mouth technique. The operation was completed by suprapubic cystotomy. The patient made a good recovery from operation and in view of the ureteral reflux her cystotomy drainage was maintained to insure continuous and complete bladder drainage. However, repeated episodes of urinary tract infection occurred which could be controlled by various antibiotic agents. A cystogram made on October 31, 1950, showed that ureteral reflux persisted bilaterally. Three months after operation, following a trial of voiding with the suprapubic tube clamped, only a few cubic centimeters of residual urine remained in the bladder and her suprapubic drainage tube was removed. The removal of the suprapubic tube appeared to lessen the frequency of attacks of urinary infection, and a cystogram made one year later demonstrated diminution in reflux on the right side but it was still present on the left. Since this time she has continued to make very satisfactory progress with only one attack of urinary infection during the the past year and recent excretory urograms give evidence of good renal function with no hydronephrosis. Commentary on case 1: This was the only case of the series in which ureteral reflux was demonstreated preoperatively.· It is significant that she was found to carry residual urine of 50-100 cc although she was observed to void with an uninterrupted and forceful stream with apparent complete emptying of the bladder. In view of the normal vesical function it was assumed that this amount
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of residual urine did in fact represent the volume of reflux. Crabtree10 has reported a similar case in ·which incompetence of the ureteral valves allowed reflux of urine during voiding. In this case a period of 3 months' vesical drainage by cystotomy did not diminish reflux nor did it improve the degree of megalo-ureter on either side. It is noteworthy that following removal of the suprapubic drainage tube her pyrexia subsided and urinary infection markedly improved. A cystogram made 13 months after operation revealed only minimal reflux into the lower third of the ureter on the right but was still present on the opposite side which had been treated surgically. Although the left ureter was poorly visualized in this cystogram the x-ray suggested that the left ureter was in fact as dilated as before operation. The last excretory urogram made in August 1952 (two years after operation) shows good renal function on both sides with no evidence of hydronephrosis or calyceal dilatation. This fact coupled with the satisfactory clinical progress that the child is making is strong evidence that little benefit was derived from operation. It would be interesting to know the degree of ureteral reflux which may now be present, but the mother is reluctant to bring her child to the hospital for this purpose as she is making such excellent progress. Case 2. J. 0., a girl, was brought to University Hospital in July 1950, when 4 years old. She had been ·well until the age of 18 months when her mother noticed that she had pain on urination. At this time her doctor found pus cells in the urine. Since this first attack she had had four episodes of pyrexia accompanied by frequency of micturition every one to two hours and an infected urine. At no time was there a history of flank pain or tenderness on palpation in the renal areas. Physical examination ·was negative and tests sho-wed satisfactory renal function (blood urea nitrogen 16 mg. per cent; phenolsulfonphthalein excretion 48 per cent in 2 hours). An excretory urogram revealed a severe degree of bilateral ureteral dilatation with minimal hydronephrosis on the left. No evidence of ureteral reflux was demonstrated in a cystogram. At operation on July 28, 1950 the right ureter was found to be approximately 2 cm. in diameter but showed good peristalsis. The dilatation extended from the kidney to a point approximately one inch from the bladder. At this point the ureter was of normal size and through this narrowed portion a No. 6 ureteral catheter was passed with ease into the bladder. It was therefore felt that obstruction at the lower end of the ureter could be confidently excluded. The ureter was detached from the bladder at the ureterovesical junction and this narrower portion excised. Approximately one-third of the diameter of the ureter was resected throughout its length and re-implanted into the bladder by an elliptical anastomosis at a point above and to the right of the previous ureteral opening, The ureter was drained by ureterostomy and a cystotomy tube was left in situ suprapubically. A cystogram made 3 months after this operation now showed reflux on the operated side. On October 9, 1950, at a second operation, exposure of the left ureter shmved 1
° Crabtree, E.G.: Plastic operation for the relief of megalo-mCJter. Trans. Amer. Assoc.
G, TJ Snrg., 30: 311, 1937.
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similar findings to those on the right side. Again no evidence of obstruction could be demonstrated at the lower end of the ureter and approximately 4 inches of the lower ureter were resected and the free end re-implanted into the bladder by elliptical anastomosis. On this side no longitudinal segmental resection was performed. A cystogram made one month following this procedure now revealed that reflux was present bilaterally. The child made satisfactory progress following these operations and 2 months after the second operation the cystotomy tube was removed and the suprapubic fistula allowed to close. At this point severe episodes of pyrexia occurred and could only be controlled by sustained catheter drainage. From then until the present time removal of the indwelling catheter has invariably been accompanied by a recurrence of these attacks of pyrexia and flank pain. A recent excretory urogram (fig. 1, A) showed satisfactory function although ureteral dilatation persists and on cystogram (fig. 1, B) it is seen that she has a severe degree of megalo-ureter and hydronephrosis. At no time during the course of this patient's illness and treatment have renal function tests revealed any gross deviation from normal. Commentary on case 2: In this case, although the dilatation of right ureter appeared to be initially improved by operation, the final result and persistence of megalo-ureter show that surgery did little to benefit the child. In fact, ureteral reflux which was not present in the original x-rays appeared in cystograms made after operation. It is significant that continuous bladder drainage produced no improvement in her ureteral dilatation. In spite, however, of these abnormalities and a urinary infection from which she is seldom free, the child remains surprisingly active and healthy; this fact is reflected in the comparatively normal renal function tests. This case also illustrates the value of a cystogram in demonstrating the true degree of ureteral dilatation. The excretory pyelogram (fig. 1, A) does not suggest the gross megalo-ureters which in fact exist, but which are dramatically revealed in a cystogram made shortly afterwards (fig. 1, B). Case 3. A 4 year old girl, L. A., was adinitted to hospital in March 1952. For
Fm. 1. Case 2. A, excretory urogram and B, cystogram 2 years after operation showing recurrence of dilatation of right ureter. Cystogram reveals true degree of ureteral dilatation which is not demonstrated in excretory urogram made 2 days previously.
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two and a half years she had suffered from recent episodes of high fever, frequency and pain on micturition. During each of these attacks her urine was found to contain pus cells and bacteria, and although initially the infection responded rapidly to treatment with sulfa drugs it had recently become refractory to therapy. At no time had there been any difficulty in initiating micturition. On admission, physical examination was negative and she was seen to void with a good stream. A catheter specimen of urine examined microscopically showed 5 pus cells per high power field, and numerous bacilli which proved on culture to be E. coli. The blood urea nitrogen was 17 .5 mg. per cent, the plasma CO 2 combining power 38 vols. per cent, and serum chlorides were 103 m/Eq. per liter. Excretory urograms revealed dilatation of both ureters, with some degree of hydronephrosis on the left. The calyces, however, were sharply outlined ,vith no loss of "cupping." A cystogram showed no evidence of reflux. A normal cystometrograph and absence of residual urine after voiding suggested good bladder function. On cystoscopy and panendoscopy the bladder appeared normal, with an adequate vesical neck outlet. No ureterocele or other obstruction was seen at either ureteral orifice, through which No. 5 catheters could be passed with ease. At operation on March 31, 1952, the lower third of the left ureter was exposed extraperitoneally by a transverse lower abdominal incision. The ureter was approximately 2 cm. in diameter throughout its course until, at a point 3 cm. from the bladder, the dilatation ceased and the remaining portion of the ureter appeared to be of normal size. Active peristalsis was noted in the dilated portion of the ureter. The ureter was divided at its junction with the bladder and the narrowed section removed, together with 3-4 cm. of the dilated portion. The remaining ureter was re-implanted into the bladder at a point higher on the lateral wall, by elliptical anastomosis. A pathological report of the removed portion read as follows: "Dilatation of the ureter ·with hypertrophy of muscularis and heavy focal collections of lymphocytes in the muscularis." The patient made a good recovery from operation, but convalescence was complicated by attacks of high temperature and pain and tenderness in the left costovertebral angle. Vigorous therapy with antibiotic drugs during the next 3 months was required to control these episodes of infection but her flank pain became progressively more severe. A cystogram made at this time revealed reflux of urine on the side of operation, and it was believed that these symptoms were due to an ascending pyelonephritis. During July 1952 she had persistent pyrexia, her general condition deteriorated and the child became pale and listless. Although studies showed good renal function, urgent treatment was considered necessary to prevent severe renal damage and possible nephrectomy. Accordingly, at a second operation on August 11, 1952, the left ureter was excised in its entirety, and replaced by an isolated segment of ileum as reported by McLean and Fais 11 following its experimental use in dogs. In view of the recognized association of megacolon and ureteral dilatation this procedure ·was 11 McLean, D. W. and Fais, 0. G.: The use of segments of small intestine as ureters. J. UroL, 68: 190, 1952.
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FIG. 2. Case 3. A, injection of radio-opaque dye through nephrostomy tube 3 weeks after replacement of left ureter by isolated loop of ileum. B, cystogram demonstrating reflux up ileal loop. C, excretory urogram 4 months following use of ileal loop to replace left ureter.
undertaken after x-ray investigation had excluded any intestinal abnormality. At a point about 18 inches from the ileocaecal valve a loop of ileum and mesentery was isolated. This loop was swung across in front of the colon and anastomosed to the renal pelvis and bladder, after the removal of the affected ureter. Active peristalsis was again observed during the manipulation of the ureter. The operation was completed by the insertion of a nephrostomy drainage tube. Following this surgery the patient's general condition improved steadily and although her urine remained infected she became asymptomatic and the pain and tenderness in the left costovertebral angle subsided. During the first few weeks the urine contained varying amounts of mucus from the transplanted intestine but this gradually subsided and is now completely absent. Two weeks after operation radio-opaque dye injected through the nephrostomy tube and observed during fluoroscopic screening was seen to pass rapidly from renal pelvis to bladder (fig. 2, A). A cystogram also made at this time showed that reflux occurred up the intestinal loop (fig. 2, B). However, as drainage from the renal pelvis was so efficient the nephrostomy tube was removed 21 days after operation and the wound healed rapidly. The initial satisfactory progress that this child made has been maintained and when last seen 4 months after operation her urine contained only a few pus cells with an occasional bacillus when exainined microscopically. Commentary on case 3: Several writers on this subject (MacMyn12 , Hurst and Gaymer-Jones18 , Swenson and associates14 and Lewis and Kimbrough15) have drawn comparisons between primary megalo-ureter and congenital megacolon, 12 MacMyn, D. J.: On dilatation of the ureters and hydronephrosis in childhood. Brit. J. Urol., 1: 150, 1929. 13 Hurst, A. F. and Gaymer-Jones, J.: A case of megalo-ureter due to achalasia of the ureterovesical sphincter. Brit. J. Urol., 3: 43, 1931. 14 Swenson, 0., MacMahon, H. E., Jaques, W. E. and Campbell, J. S. A new concept of the etiology of megaloureters. New Eng. J. Med., 246: 41, 1952. 16 Lewis, E. L. and Kimbrough, J.C.: Megalo-ureter: New concept in treatment. South. Med. J., 45: 171, 1952.
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Frn. 3. Case 4. Retrograde pyelograms (1931) showing bilateral megalo-ureter.
and indeed the two conditions are cometimes co-existent (Moore and Lawrence 16 ). In this case and in case 2 it was noted at operation that the dilated portion of ureter had inherent contractibility when stimulated and terminated from 2 to 4 cm. from the ureterovesical junction, these lower few centimeters of ureter being of normal size. Such an appearance certainly seems to suggest an analogy to the dilated and hypertrophic colon proximal to a narrow section of bowel vvhich Swenson and others 17 , 18 have shown to be devoid of parasympathetic nerve supply in congenital megacolon. Kimbrough 15 reports encouragingly on the results of resection of this normal appearing segment of ureter and vesical re-implantation of the dilated ureter. It has been our experience, however, that such an operation produced no improvement in the degree of megalo-ureter in the two cases in which it was employed. In this case excision of the narrower portion of ureter and re-implantation into the bladder allowed ureteral reflux of urine which had not been present prior to operation. This appeared to initiate a series of severe episodes of ascending infection and pyelonephritis. It is possible that such reflux might be prevented by allowing a short segment of ureter to lie free in the bladder as practiced by Kimbrough who considers that such a procedure is helpful in preventing this complication. The use of an isolated loop of intestine to replace the ureter undoubtedly improved the child's condition symptomatically and the recurrent episodes of pyelonephritis ceased. Up to the present time the result of this operation appears very satisfactory, but a longer period of observation will be necessary before final evaluation of such a procedure can be made. It may be pertinent to remark on the possibilities of such an operation in the treatment of other conditions in which replacement of a ureter is necessary. 16 lVIoore, T. C. and L11wrence, E. A.: Congenital malformation of the rectum and anus. Surg. Gynec. & Obst., 95: 281, 1952. 17 Swanson, 0., Rheinlander, H. F. and Diamond, I.: Hirschsprung's disease: N cw concept of etiology. New Eng. J. Med., 241: 551, 1949. 18 Bodian, M. and Stephens, F. D.: Hirschsprung's disease: A new concept. Proc. Roy. Soc. Med., 42: 225, 1949.
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Case 4. M. E., an unmarried 33 year old woman, has been observed at University Hospital since she was nine, when her mother stated that she had had episodes of fever accompanied by flank pain since the age of two. Cystoscopy revealed an inflamed but otherwise normal appearing right ureteral orifice and a normal left ureteral orifice. Catheterization of both ureters was easily performed and there was no evidence of obstruction. The specimens of urine obtained from the ureters were heavily loaded with pus cells and bacilli. Pyeloureterograms (fig. 3, A and B) made at this time revealed bilateral ureteral dilatation but the renal calyceal systems did not show a commensurate degree of defonnity although hydronephrosis was present. At intervals for the next 6 years lavage of both ureters was carried out and with this treatment she remained in good health and remarkably free from symptoms, and the intervals during which the bladder urine was free from infection became increasingly longer.
Fm. 4. Case 4. Retrograde pyelograms (1948). In spite of persistence of bilateral megaloureter, patient's renal function remains good, she has uninfected urine and is leading an active life. No operation was performed.
In 1935, however, when the patient was aged 15, severe urinary tract infection recurred accompanied by bilateral flank pain radiating to the lower abdomen. It was noted that these bouts of infection coincided with her menstrual periods. Owing to the increasing severity of the attacks and their persistent association with menstruation, an x-ray sterilization was considered advisable. This produced a dramatic amelioration of her urinary symptoms. The improvement was maintained and she was well until 1948 when menstruation re-commenced and pain recurred, to be relieved once again when x-ray therapy terIninated her periods. Since this time she has remained entirely free from symptoms and has led an active and healthy life as a teacher. It is noteworthy that her urinary tract infection was promptly cleared on the institution of treatment with sulfonamide drugs, and has not returned. Her ureterograms made at intervals since 1929 show that the degree of ureteral dilatation has not materially changed, nor has there been evidence of increasing hydronephrosis (fig. 4). Recent renal function tests show that the phenolsulfonphthalein clearance was 58 per cent in 2 hours.
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Commentary on case 4: The satisfactory result in this case from conservative management adds weight to the doubts cast on the value of any surgical interference in these cases. It must be noted again, however, that the dilatation of her ureters has persisted unchanged throughout the course of our observation. A further point of interest in this case is the manner in -which the infection of the urine seemed to be closely associated -with menstruation and -was cleared by an artificial menopause. Such an association may favor the possibility of an hormonal factor in the etiology of this condition. In this respect also the anatomical relationship of the uterine artery to the lower end of the ureter must not be forgotten. DISCUSSION
At the present time the many theories of the cause of primary megalo-ureter are all largely conjectural. With so little understood about the etiology it is not surprising that varied surgical approaches to the problem have been attempted. It had been believed in the past that suprapubic cystostomy alone had, in some instances, resulted in decrease in the size of the ureters. In the light of present knowledge, however, it is probable that those cases in which improvement has been noted, -were, in fact, not true primary megalo-ureters, but cases in which faulty vesical function was present. Neither supra pubic cystostomy nor continuous bladder drainage by catheter has resulted in diminution of ureteral dilatation in any of the cases reported here. Our present investigation has sought an answer to the question of whether the operative procedures in these cases have yielded significant clinical benefits. Operation in all 3 cases was performed in an effort to alleviate the following conditions: gross bilateral ureteral dilatation, infection in the urine, and episodes of sepsis. All three of the cases following operation have shown persistence of the ureteral dilatation, and have continued to have infection of the urine. Based on the stated criteria one is forced to conclude that results hoped for have not been attained. Compared to these 3 cases the other patient in whom no operation was performed also has dilated ureters, but she is clinically well and has been free from infection for nearly ten years. It appears that she has fared better than the others. Our present opinion regarding the management of such cases would be this: the clinician who faces any problem of this sort must focus his attention on excluding evidence of obstructive uropathy which might be amenable to surgical correction. It is only -when all such factors are found to be lacking that a diagnosis of primary megalo-ureter can be established. It seems that renal function remains surprisingly good in these cases, and that the prognosis need not be as pessimistic as the degree of ureteral dilatation would at first suggest. Perhaps in this particular type of case it might be better to focus our therapeutic efforts along conservative antibacterial avenues and be less concerned with correction of ureteral dilatation.