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Vesico-Ureteral Reflux Report of Case Cured by Operation1
VESICO-URETERAL REFLUX REPORT OF CASE CURED BY OPERATION 1
MAJOR GEORGE C. PRATHER (MC), AUS
From Ashford General Hospital, West Virginia
The existence and mechanism of vesico-ureteral reflux or regurgitation have been studied for many years and to some extent remain matters of urological controversy. Apparent discrepancies involving clinical observations, as well as experimental work in animals have prevented complete agreement regarding the subject. The purpose of this paper is to present a brief review of this topic before describing a case report which appears pertinent. One point for debate is whether or not vesico-ureteral reflux occurs in patients who have no abnormality of the bladder or ureteral orifices. Let us see what some of the present standard urological texts say about this. Hinman 2 states: "The bladder of cadavers can be filled to bursting without a drop flowing back into the ureters." Campbell3 says: "Reflux in normal bladders has been alleged to result from an increased intracystic pressure caused by contractions of the bladder simultaneous with the opening of the ureteral orifice by urinary ejaculation. This contention lacks pyeloscopic proof." Randall and Campbell4 have written: "Ureteral regurgitation does not occur in the normal patient." Keyes and Ferguson5 say "Ureteral reflux is exceptional." Eisendrath and Rolnick6 do not discuss the problem in their textbook. Lowsley and Kirwin 7 have written: "Investigators differ in their opinions as to whether or not it is possible for vesicoureteral reflux to occur under normal conditions. Although vesico-ureteral reflux is much more frequent in pathological than in normal conditions, it has been cystographically demonstrated in normal persons, both children and adults, in numerous instances." No explanation or qualification is made by the latter authors regarding whether the normal individuals were anesthethized or not. Thus, of the texts immediately available, only Lowsley and Kirwin state without reservation that vesico-ureteral reflux occurs in normal persons. I cannot personally contribute data on this question but mention the quoted statements to summarize current opinion regarding this subject. For those who may assemble future clinical data on this matter, it will help to clarify the question if it is 1 Read before the Mid-Atlantic Section, American Urological Association, Roanoke, Va., March 11, 1944. 2 Hinman, Frank: The Principles and Practice of Urology. Philadelphia: W. B. Saunders Co., 1935, p. 232. 3 Campbell, Meredith F.: Pediatric Urology. New York: The Macmillan Co., 1937, vol. 2, p. 259. 4 Randall, A., and Campbell, E.: Modern Urology, edited by Cabot. Philadelphia: Lea & Febiger, 1936, 3rd ed. Vol. 2, p. 260. 5 Keyes, E., and Ferguson, R.: Urology, 6th Ed. D. Appleton-Century Co., New York, 1938, p. 134. 6 Eisendrath, D ., and Rolnick, H.: Urology. Philadelphia: J. R. Lippincott Co., 1938, 4th ed. 7 Lowsley, 0., and Kirwin, J.: Clinical Urology. Baltimore: Williams & Wilkins Co., 1940, vol. 2, p. 1158. 437
438
GEORGE C. PRATHER
specifically stated ,vhether or not the patient's examination was done under anesthesia. Inasmuch as majority opinion believes vesico-ureteral reflux in the normal indivifual is exceptional if it does exist, remarks concerning the anatomical features of the ureteral orifice continue to be of interest. Although most authors have given Charles Bell 8 credit for the original description of the continuance of ureteral musculature into the trigone and prostatic urethra, close scrutiny of Bell's paper "Account of the muscles of the ureters" fails to disclose opinion of that nature. Bell did describe "2 strong fleshy columns, which descend from the orifices of the ureters toward the orifice of the bladder: they unite and run towards the prostate gland.'' His reason for declaring these structures as muscle appear to be the statement "the variety which we find in their length according with the degree of contraction of the bladder, proves their muscularity." I believe Bell considered these structures (now known as Bell's muscles) to be distinct from and not continuous with the muscular wall of the ureter. However, in 1856, Ellis 9 demonstrated that the longitudinal muscle fibres of the ureter "pierce the outer and middle strata of the flesh wall of the bladder and the fibres are directed obliquely downwards over the 'triangular space' to the sub-mucous stratum of the urethra." The sketches which accompany his paper leave no doubt about this opinion. Thus Ellis deserves credit for calling attention to the distal insertion of ureteral musculature in the region of the prostatic urethra. In 1920 after making an anatomical study of the trigone Wesson10 stated: "In the trigonal region are the 2 muscle layers of the bladder wall, the longitudinal and the internal circular, and superimposed upon these is the submucous or trigonal muscle, which is an expansion of the longitudinal muscle layers of the ureters and tleir sheaths extending downward and passing into the urethra." A year later these studies were elaborated upon and correlated with clinical material by Young and Wesson11 • They described pathological conditions of the trigone which had been treated surgically ·with excellent results. Gruber12 states: "Definite bands of muscle tissue pass from both ureterovesical valves into the urethra. The uretero-vesical valve or intravesical ureter is considerably thicker than those found in most experimental animals but is composed as are the others of a few longitudinal muscle fibres, a few elastic fibres and a large amount of white fibrous connective tissue covered on one side by the intravesical ureteral mucosa and on the other side by the mucosa of the bladder." A diagramatic sketch of the vesico-ureteral junction is shown in figure 1. 8 Bell, Charles: Account of the muscles of the ureters and their effects. Medico-Chirurg. Trans. London, 3: 171, 1812. 9 Ellis, G. W.: An account of the arrangement of the muscular substance in the urinary and certain of the generative organs of the human body. Medico-Chirurg. Trans. London, 39: 327, 1856. 10 Wesson, M. B.: Anatomical, embryological and physiological studies of the trigone and neck of the bladder. J. Urol., 4: 279, 1920. 11 Young, H. H., and Wesson, M. B.: The anatomy and surgery of the trigone. Arch. Surg., 3: 1, 1921. 12 Gruber, C. M.: A Comparative study of the intra-vesical ureters (uretero-vesica valves) in man and experimental animals. J. Urol., 21: 567, 1929.
VESICO-URETERAL REFLUX
439
The early animal experiments of Guyon, and Lewin and Goldschmidt were reviewed by Young13 in 1898. These investigators concluded that whik a small amount of fluid injected slowly into the bladder may bring about ureteral reflux, a large amount injected rapidly cannot enter the ureter. Young also carried out experiments in cadavers and in a dog using gentian violet under great pressure and proved that there was no reflux. From these experiments and continued clinical observations Young14 concluded that forcibly filling the bladder quickly was not conducive to reflux and therefore a safe method of dilating a contracted bladder. From observation in experimental animals Graves and Davidoff15 concluded that regurgitation "depends primarily upon sustained tonus of bladder muscula-
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Fm. 1. Diagrammatic section uretero-vesical valve
ture as it actively resists distention." They believed that the "lesser incidence of regurgitation in dogs as compared with rabbits and cats is due, not to difference in the structure of the uretero-vesical junction, ... but to failure of the bladder contraction to be sustained in the presence of continually increasing distention." However when Graves and Davidoff16 transplanted ureters directly into the bladder with no attempt to reproduce the normal valve like uretero-vesical junction, reflux into the transplanted ureters occurred with only one-third the 13 Young, H. H.: Hydraulic pressure in genito-urinary practice, especially in contracture of the bladder. Johns Hopkins Hosp. Bull., May, 1898. 14 Young, H. H. Personal communication. 15 Graves, R. C., and Davidoff, L. M. Studies on the bladder and ureters with special reference to regurgitation of vesical contents. J. Urol., 14: 1, 1925. 16 Graves, R. C., and Davidoff, L. M.: Studies on the ureter and bladder with special reference to regurgitation of vesical contents. J. Urol., 10: 185, 1923.
440
GEORGE C. PRATHER
amount of fluid necessary to produce reflux in those with obliquely transplanted ureters. These facts appear somewhat contradictory to the conclusions of these authors although it must be admitted that the studies of transplanted ureters was only a minor part of their extensive studies on vesico-ureteral reflux. By a comparative study of the uretero-vesical valves in experimental animals Gruber demonstrated probable reasons for the wide variation of the incidence of vesico-ureteral reflux in various animals and man. After removing the trigone, bladder base and lower ureters and allowing them to become fixed in formalin in a normal position, Gruber made measurements, drawings and histological sections of specimens from rabbits, pigs, dogs, monkeys, baboon, ape and human beings pc.~c<1.rit
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Fm. 2. The above chart has been compiled from data published by Gruber, and Graves and Davidoff. The incidence of reflux in normal human and in the pig is very small if it exists at all.
In rabbits Graves and Davidoff16 had reported an incidence of reflux in over 80 per cent. In rabbits Gruber found the intravesical ureters or valve flaps were short and had an average length of about 4mm. In cats Graves and Davidoff15 had reported the incidence of reflux as 62.5 per cent and Gruber found the average length of intravesical ureter to be 4 mm. In dogs Graves and Davidoff15 had found the incidence of reflux to be 27 per cent. Gruber described an average length of intravesical ureter as 9 mm. in dogs. In the pig Gruber states the uretero-vesical valve is competent. Here the average length of the intravesical ureter was found to be 15 mm. He also found that the length of the intravesical ureters in 15 human specimens varied from 5 to 26 mm. No average length was given. It will be seen in figure 2 that combined data from the studies by Gruber,
VESICO-URETERAL REFLUX
441
and Graves and Davidoff indicate that the incidence of reflux may be to some extent inversely proportional to the length of the intravesical ureter. Other factors which may influence reflux were noted by Gruber. In the rabbit, where there is a high incidence of reflux, the trigone and Bell's muscle was very poorly developed, but in the male cat in which there is also frequent reflux experimentally Bell's muscle was wen· developed. In pigs the trigone and Bell's muscle are said to be well developed. The same is true in man. Thus it might be inferred that the presence of reflux is also partially dependent on the lack of the development of the trigone. However in the cat and dog in which the incidence of reflux is relatively high, Bell's muscle is said to be a prominent feature. Perhaps it is logical therefore to place most importance on the length and condition of the intravesical ureter as the factor which prevents reflux. Summarizing the data on this subject available to me it would appear reasonable to assume that for reflux to occur it is necessary to have sustained tonus of bladder musculature as it resists distention, and that the anatomical features of the uretero-vesical junction (principally the length and condition of the intravesical ureter) govern the frequency or incidence of vesico-ureteral regurgitation. The oblique course of the intramural ureter probably provides an additional measure of protection. There is universal agreement that no sphincter exists at the uretero-vesical junction. In contrast to the normal it is well known that vesico-ureteral reflux is not uncommon when there is distortion of the uretero-vesical valve (intravesical ureter). Sampson17 was well aware of this fact 40 years ago. Distortion may be caused by an inflammatory process, malignancy, or mechanical influence from changes in the bladder, trigone, or bladder neck and thus allow the valve to become incompetent, Bumpus 18 reviewed 1036 cystograms in patients with various types of urinary tract pathology and found reflux into one or both ureters occurred in 8.59 per cent. Since there is both experimental1 9 and clinical evidence that an incompetent valve permits direct ascending infection and if continued over a long period of time produces a hydrometer it behooves us to attempt to remedy this abnormality when found in clinical practice. An opportunity of this type recently presented itself in a soldier at the Ashford General Hospital. Several factors will be evident as the possible cause of vesico-ureteral reflux in this patient and since at least two factors were removed it will be difficult to say which was the most important. The case report of the soldier follows. CASE REPORT
A soldier entered the Ashford General Hospital September 29, 1943. On February 16, 1943, near Algiers, a command car in which he was riding overturned. The patient sustained a fracture of the pelvis, an incomplete dislocation 17 Sampson, J. A.: Ascending renal infection; with special reference to the reflux of urine from the bladder into the ureters as an etiological factor in its causation and maintenance. Johns Hopkins Hosp. Bull., Dec., 1903. 18 Bumpus, R. C.: Urinary reflux. J. Urol., 12: 341, 1924. 19 Gruber, C. M.: The function of the uretero-vesical valve and the experimental production of hydroureters without obstruction. J. Urol., 23: 161, 1930.
442
GEORGE C. PRATHER
of the left sacro iliac joint, an intraperitoneal rupture of the bladder, an incomplete rupture of the posterior urethra and a Colles fractt1re of the right forearm. Suprapubic cystotomy with splinting of the posterior urethra by catheter was performed immediately at a British general hospital. The suprapubic tube remained in place 45 days. After removal of the suprapubic tube, the suprapubic wound soon healed and the urethral catheter was removed. Shortly afterward the patient passed a small calculus per urethram. This was followed by a spontaneous opening of the suprapubic incision and drainage of urine but the wound healed without the aid of urethral drainage. Again the patient passed small stones and had a temporary recurrence of leakage of urine from the suprapubic wound. Cystoscopy revealed a bladder calculus. The pelvic fracture had been first treated with traction, later with a body cast. On August 5, 1943, the patient was transferred to an evacuation hospital where cystoscopy disclosed marked cystitis, a large bladder calculus and a bladder capacity of 125-150 cc. Urinalysis showed 4+ albumin, no sugar, with the
Fm. 3. An x-ray of the pelvis at an overseas general hospital demonstrates the bladder stone and fracture of pelvis (6 months after injury).
sediment containing many pus cells. An intravenous urogram is reported to have shown normal kidneys and a contracted irregular bladder containing a calculus 2. 7 cm. by 2.2 cm. On August 12, 1943, at a general hospital, litholapaxy under intravenous anesthesia was unsuccessful. An x-ray of the pelvis as of about that date is shown in figure 3. The patient was then transferred to the Zone of the Interior and when admitted to Ashford General Hospital complained of diurnal and nocturnal urinary frequency, difficulty with urination, and dysuria. It was necessary for him to lie down or set well forward and strain severely to void. Physical examination was normal except for a slightly tender lower abdominal nidline scar and hypalgesia over a rectangular area on the lateral aspect of the left thigh at the level of the buttocks. Blood cell counts were normal. Blood serology was negative. The urine showed 2 albumin, no sugar, and many pus cells in the centrifuged sediment. Urine culture revealed an overgrowth of B. proteus vulgaris. Blood urea nitrogen was 11.5 mg.
+
VESICO-URETERAL REFLUX
443
On October 1, 1943, a urethrogram was done with 25 cc. of Lipiodol to disclose any changes in the posterior urethra, secondary to fracture of the pelvis. This demonstrated an irregular stricture in the posterior urethra and a small bladder with reflux up both ureters, each of ,vhich showed moderate dilation (fig. 4). The following day a plain x-ray of the urinary tract and intravenous urography revealed a small amount of Lipiodol in the lower calyce3 of both kidneys, moderate bilateral pyelectasis and some delay in the excretion of the dye (figs. 5 and 6). The patient was instructed to lie with his head and trunk lmver than his hips for 20 minutes, twice each day, in an attempt to drain the iodized oil from the calyces. A plain x-ray film of the urinary tract 6 days later (October 7, 1943) indicated that all Lipiodol had disapp2ared from the kidneys (fig. 7). On October 8, 1943, suprapubic cystolithotomy was performed under spinal
Fm. 4. Urethrogram shows an irregularity of the prostatic urethra, with refl.ux up both -0f the dilated ureters. The bladder calculus is visible in 1 side of the bladder.
anesthesia. In order to avoid distending the bladder with fluid when vesicoureteral reflux was known to exist a Foley catheter with balloon was passed to the bladder and distended to 45 cc in order to facilitate the cystotomy. The bladder was found to be of the hour glass type with a transverse fibrous .septum on the posterior bladder wall which apparently confined the calculus to the distal or trigonal segment of the bladder (fig. 8). It was thought that this septum was probably secondary to the surgical closure of the old intraperitoneal rupture and that by distortion of the ureteric regions it might be responsible for reflux up the ureters. After removal of the bladder calculus the transverse band was bisected with scissors allmving the bladder to become one compartment. The bladder was closed around a Ko. 32 F. Malecot catheter and the prevesical .space drained with rubber tissue. Convalescence was uneventful. The suprapubic catheter was removed 10 days after operation and the patient placed on urethral drainage for a period of 11 days. During this period the patient received 2 gm. of sulfadiazine each day. Following removal of the urethral catheter the patient voided easily and comfortably in large amounts, There was no rise in temperature.
Fm. 5. A plain x-ray film of the urinary tract the day after the urethrogram discloses lipiodol in the lower calyces of both kidneys, more in the right than in the left. Some material remains in tissue adjacent to the prostatic urethra.
Fm. 6. Intravenous urogram demonstrates moderate pyelectasis in both kidneys. cretion of the dye was delayed. 444
Ex-
Fm. 7. A plain x-ray of the urinary tract after 6 days of postural drainage shows no remaining lipidodol in either kidney. The bladder calculus has increased in size in 2 months (compare with figure 3).
Fm. 8. Diagrammatic sketch of findings at operation which disclosed a transverse fibrous band partially dividing the bladder into 2 compartments. 445
446
GEORGE C. PRATHER
FIG. 9. Urethrogram with Lipiodol 33 days after operation. No reflux is evident. prostatic urethra is smoother and the bladder shadow much less deformed.
The
FIG.10 Frn.11 FIG. 10. Intravenous urogram about 5 weeks after operation shows imporved condition of kidneys. FIG. 11. Intravenous urogram about 3-months after operation. Kidneys appear normal and bladder shadow satisfactory. The lower right ureter is visible.
VESICO-URETERAL REFLUX
447
On November 12, 1943, for further data of the urethra and bladder and for a decision as to the prognosis, a urethrogram was done using the same quantity and substance as previously employed. The stricture of the posterior urethra was still evident, but no vesico-ureteral reflux occurred (fig. 9). Intravenous urograms on November 18, 1943 (fig. 10), about 5 weeks after operation showed remarkable improvement in the pyelectasis. Urine culture at this time revealed a growth of a urea splitting staphylococcus organism even though the urinary pH was found to be 5.8. Calcium mandelate and acidification was used for 8 days at the end of which time the urinary sediment contained 8-10 leukocytes per high dry field. The patient then enjoyed a 30 day convalescent furlough and returned to hospital on Janyary 6, 1944. The urine did not show a positive albumin test but culture revealed a growth of B. proteus vulgaris and Staphylococcus aureus. Sulfathiazole improved the urinary picture and further intravenous urography (fig. 11) demonstrated essentially normal pyelograms. On January 17, 1944 the urine contained only scattered leukocytes and urine culture was reported as showing only 1 colony of Staphylococcus aureus. The patient was discharged to a limited type of military duty. In the case report just described there would appear to be 3 possible factors producing the vesico-ureteral reflux. Mechanical distortion of the ureterovesical junction by the transverse band in the bladder does not appear improbable. An inflammatory change due to cystitis is a possibility. Inflammatory changes secondary to the irritation of the confined calculus also merits consideration. The mechanical factor and the stone were removed prior to the second urethrogram, and it is difficult to state which of these most important. It will be realized that correction of one factor at a time did not appear feasible. The excellent result in this patient with recovery from pyelectasis should stimulate further interest in the mechanisms of vesico-ureteral reflux and the possibility of correcting the condition in certain instances.
MAJOR GEORGE C. PRATHER (MC), AUS
From Ashford General Hospital, West Virginia
The existence and mechanism of vesico-ureteral reflux or regurgitation have been studied for many years and to some extent remain matters of urological controversy. Apparent discrepancies involving clinical observations, as well as experimental work in animals have prevented complete agreement regarding the subject. The purpose of this paper is to present a brief review of this topic before describing a case report which appears pertinent. One point for debate is whether or not vesico-ureteral reflux occurs in patients who have no abnormality of the bladder or ureteral orifices. Let us see what some of the present standard urological texts say about this. Hinman 2 states: "The bladder of cadavers can be filled to bursting without a drop flowing back into the ureters." Campbell3 says: "Reflux in normal bladders has been alleged to result from an increased intracystic pressure caused by contractions of the bladder simultaneous with the opening of the ureteral orifice by urinary ejaculation. This contention lacks pyeloscopic proof." Randall and Campbell4 have written: "Ureteral regurgitation does not occur in the normal patient." Keyes and Ferguson5 say "Ureteral reflux is exceptional." Eisendrath and Rolnick6 do not discuss the problem in their textbook. Lowsley and Kirwin 7 have written: "Investigators differ in their opinions as to whether or not it is possible for vesicoureteral reflux to occur under normal conditions. Although vesico-ureteral reflux is much more frequent in pathological than in normal conditions, it has been cystographically demonstrated in normal persons, both children and adults, in numerous instances." No explanation or qualification is made by the latter authors regarding whether the normal individuals were anesthethized or not. Thus, of the texts immediately available, only Lowsley and Kirwin state without reservation that vesico-ureteral reflux occurs in normal persons. I cannot personally contribute data on this question but mention the quoted statements to summarize current opinion regarding this subject. For those who may assemble future clinical data on this matter, it will help to clarify the question if it is 1 Read before the Mid-Atlantic Section, American Urological Association, Roanoke, Va., March 11, 1944. 2 Hinman, Frank: The Principles and Practice of Urology. Philadelphia: W. B. Saunders Co., 1935, p. 232. 3 Campbell, Meredith F.: Pediatric Urology. New York: The Macmillan Co., 1937, vol. 2, p. 259. 4 Randall, A., and Campbell, E.: Modern Urology, edited by Cabot. Philadelphia: Lea & Febiger, 1936, 3rd ed. Vol. 2, p. 260. 5 Keyes, E., and Ferguson, R.: Urology, 6th Ed. D. Appleton-Century Co., New York, 1938, p. 134. 6 Eisendrath, D ., and Rolnick, H.: Urology. Philadelphia: J. R. Lippincott Co., 1938, 4th ed. 7 Lowsley, 0., and Kirwin, J.: Clinical Urology. Baltimore: Williams & Wilkins Co., 1940, vol. 2, p. 1158. 437
438
GEORGE C. PRATHER
specifically stated ,vhether or not the patient's examination was done under anesthesia. Inasmuch as majority opinion believes vesico-ureteral reflux in the normal indivifual is exceptional if it does exist, remarks concerning the anatomical features of the ureteral orifice continue to be of interest. Although most authors have given Charles Bell 8 credit for the original description of the continuance of ureteral musculature into the trigone and prostatic urethra, close scrutiny of Bell's paper "Account of the muscles of the ureters" fails to disclose opinion of that nature. Bell did describe "2 strong fleshy columns, which descend from the orifices of the ureters toward the orifice of the bladder: they unite and run towards the prostate gland.'' His reason for declaring these structures as muscle appear to be the statement "the variety which we find in their length according with the degree of contraction of the bladder, proves their muscularity." I believe Bell considered these structures (now known as Bell's muscles) to be distinct from and not continuous with the muscular wall of the ureter. However, in 1856, Ellis 9 demonstrated that the longitudinal muscle fibres of the ureter "pierce the outer and middle strata of the flesh wall of the bladder and the fibres are directed obliquely downwards over the 'triangular space' to the sub-mucous stratum of the urethra." The sketches which accompany his paper leave no doubt about this opinion. Thus Ellis deserves credit for calling attention to the distal insertion of ureteral musculature in the region of the prostatic urethra. In 1920 after making an anatomical study of the trigone Wesson10 stated: "In the trigonal region are the 2 muscle layers of the bladder wall, the longitudinal and the internal circular, and superimposed upon these is the submucous or trigonal muscle, which is an expansion of the longitudinal muscle layers of the ureters and tleir sheaths extending downward and passing into the urethra." A year later these studies were elaborated upon and correlated with clinical material by Young and Wesson11 • They described pathological conditions of the trigone which had been treated surgically ·with excellent results. Gruber12 states: "Definite bands of muscle tissue pass from both ureterovesical valves into the urethra. The uretero-vesical valve or intravesical ureter is considerably thicker than those found in most experimental animals but is composed as are the others of a few longitudinal muscle fibres, a few elastic fibres and a large amount of white fibrous connective tissue covered on one side by the intravesical ureteral mucosa and on the other side by the mucosa of the bladder." A diagramatic sketch of the vesico-ureteral junction is shown in figure 1. 8 Bell, Charles: Account of the muscles of the ureters and their effects. Medico-Chirurg. Trans. London, 3: 171, 1812. 9 Ellis, G. W.: An account of the arrangement of the muscular substance in the urinary and certain of the generative organs of the human body. Medico-Chirurg. Trans. London, 39: 327, 1856. 10 Wesson, M. B.: Anatomical, embryological and physiological studies of the trigone and neck of the bladder. J. Urol., 4: 279, 1920. 11 Young, H. H., and Wesson, M. B.: The anatomy and surgery of the trigone. Arch. Surg., 3: 1, 1921. 12 Gruber, C. M.: A Comparative study of the intra-vesical ureters (uretero-vesica valves) in man and experimental animals. J. Urol., 21: 567, 1929.
VESICO-URETERAL REFLUX
439
The early animal experiments of Guyon, and Lewin and Goldschmidt were reviewed by Young13 in 1898. These investigators concluded that whik a small amount of fluid injected slowly into the bladder may bring about ureteral reflux, a large amount injected rapidly cannot enter the ureter. Young also carried out experiments in cadavers and in a dog using gentian violet under great pressure and proved that there was no reflux. From these experiments and continued clinical observations Young14 concluded that forcibly filling the bladder quickly was not conducive to reflux and therefore a safe method of dilating a contracted bladder. From observation in experimental animals Graves and Davidoff15 concluded that regurgitation "depends primarily upon sustained tonus of bladder muscula-
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ture as it actively resists distention." They believed that the "lesser incidence of regurgitation in dogs as compared with rabbits and cats is due, not to difference in the structure of the uretero-vesical junction, ... but to failure of the bladder contraction to be sustained in the presence of continually increasing distention." However when Graves and Davidoff16 transplanted ureters directly into the bladder with no attempt to reproduce the normal valve like uretero-vesical junction, reflux into the transplanted ureters occurred with only one-third the 13 Young, H. H.: Hydraulic pressure in genito-urinary practice, especially in contracture of the bladder. Johns Hopkins Hosp. Bull., May, 1898. 14 Young, H. H. Personal communication. 15 Graves, R. C., and Davidoff, L. M. Studies on the bladder and ureters with special reference to regurgitation of vesical contents. J. Urol., 14: 1, 1925. 16 Graves, R. C., and Davidoff, L. M.: Studies on the ureter and bladder with special reference to regurgitation of vesical contents. J. Urol., 10: 185, 1923.
440
GEORGE C. PRATHER
amount of fluid necessary to produce reflux in those with obliquely transplanted ureters. These facts appear somewhat contradictory to the conclusions of these authors although it must be admitted that the studies of transplanted ureters was only a minor part of their extensive studies on vesico-ureteral reflux. By a comparative study of the uretero-vesical valves in experimental animals Gruber demonstrated probable reasons for the wide variation of the incidence of vesico-ureteral reflux in various animals and man. After removing the trigone, bladder base and lower ureters and allowing them to become fixed in formalin in a normal position, Gruber made measurements, drawings and histological sections of specimens from rabbits, pigs, dogs, monkeys, baboon, ape and human beings pc.~c<1.rit
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Fm. 2. The above chart has been compiled from data published by Gruber, and Graves and Davidoff. The incidence of reflux in normal human and in the pig is very small if it exists at all.
In rabbits Graves and Davidoff16 had reported an incidence of reflux in over 80 per cent. In rabbits Gruber found the intravesical ureters or valve flaps were short and had an average length of about 4mm. In cats Graves and Davidoff15 had reported the incidence of reflux as 62.5 per cent and Gruber found the average length of intravesical ureter to be 4 mm. In dogs Graves and Davidoff15 had found the incidence of reflux to be 27 per cent. Gruber described an average length of intravesical ureter as 9 mm. in dogs. In the pig Gruber states the uretero-vesical valve is competent. Here the average length of the intravesical ureter was found to be 15 mm. He also found that the length of the intravesical ureters in 15 human specimens varied from 5 to 26 mm. No average length was given. It will be seen in figure 2 that combined data from the studies by Gruber,
VESICO-URETERAL REFLUX
441
and Graves and Davidoff indicate that the incidence of reflux may be to some extent inversely proportional to the length of the intravesical ureter. Other factors which may influence reflux were noted by Gruber. In the rabbit, where there is a high incidence of reflux, the trigone and Bell's muscle was very poorly developed, but in the male cat in which there is also frequent reflux experimentally Bell's muscle was wen· developed. In pigs the trigone and Bell's muscle are said to be well developed. The same is true in man. Thus it might be inferred that the presence of reflux is also partially dependent on the lack of the development of the trigone. However in the cat and dog in which the incidence of reflux is relatively high, Bell's muscle is said to be a prominent feature. Perhaps it is logical therefore to place most importance on the length and condition of the intravesical ureter as the factor which prevents reflux. Summarizing the data on this subject available to me it would appear reasonable to assume that for reflux to occur it is necessary to have sustained tonus of bladder musculature as it resists distention, and that the anatomical features of the uretero-vesical junction (principally the length and condition of the intravesical ureter) govern the frequency or incidence of vesico-ureteral regurgitation. The oblique course of the intramural ureter probably provides an additional measure of protection. There is universal agreement that no sphincter exists at the uretero-vesical junction. In contrast to the normal it is well known that vesico-ureteral reflux is not uncommon when there is distortion of the uretero-vesical valve (intravesical ureter). Sampson17 was well aware of this fact 40 years ago. Distortion may be caused by an inflammatory process, malignancy, or mechanical influence from changes in the bladder, trigone, or bladder neck and thus allow the valve to become incompetent, Bumpus 18 reviewed 1036 cystograms in patients with various types of urinary tract pathology and found reflux into one or both ureters occurred in 8.59 per cent. Since there is both experimental1 9 and clinical evidence that an incompetent valve permits direct ascending infection and if continued over a long period of time produces a hydrometer it behooves us to attempt to remedy this abnormality when found in clinical practice. An opportunity of this type recently presented itself in a soldier at the Ashford General Hospital. Several factors will be evident as the possible cause of vesico-ureteral reflux in this patient and since at least two factors were removed it will be difficult to say which was the most important. The case report of the soldier follows. CASE REPORT
A soldier entered the Ashford General Hospital September 29, 1943. On February 16, 1943, near Algiers, a command car in which he was riding overturned. The patient sustained a fracture of the pelvis, an incomplete dislocation 17 Sampson, J. A.: Ascending renal infection; with special reference to the reflux of urine from the bladder into the ureters as an etiological factor in its causation and maintenance. Johns Hopkins Hosp. Bull., Dec., 1903. 18 Bumpus, R. C.: Urinary reflux. J. Urol., 12: 341, 1924. 19 Gruber, C. M.: The function of the uretero-vesical valve and the experimental production of hydroureters without obstruction. J. Urol., 23: 161, 1930.
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GEORGE C. PRATHER
of the left sacro iliac joint, an intraperitoneal rupture of the bladder, an incomplete rupture of the posterior urethra and a Colles fractt1re of the right forearm. Suprapubic cystotomy with splinting of the posterior urethra by catheter was performed immediately at a British general hospital. The suprapubic tube remained in place 45 days. After removal of the suprapubic tube, the suprapubic wound soon healed and the urethral catheter was removed. Shortly afterward the patient passed a small calculus per urethram. This was followed by a spontaneous opening of the suprapubic incision and drainage of urine but the wound healed without the aid of urethral drainage. Again the patient passed small stones and had a temporary recurrence of leakage of urine from the suprapubic wound. Cystoscopy revealed a bladder calculus. The pelvic fracture had been first treated with traction, later with a body cast. On August 5, 1943, the patient was transferred to an evacuation hospital where cystoscopy disclosed marked cystitis, a large bladder calculus and a bladder capacity of 125-150 cc. Urinalysis showed 4+ albumin, no sugar, with the
Fm. 3. An x-ray of the pelvis at an overseas general hospital demonstrates the bladder stone and fracture of pelvis (6 months after injury).
sediment containing many pus cells. An intravenous urogram is reported to have shown normal kidneys and a contracted irregular bladder containing a calculus 2. 7 cm. by 2.2 cm. On August 12, 1943, at a general hospital, litholapaxy under intravenous anesthesia was unsuccessful. An x-ray of the pelvis as of about that date is shown in figure 3. The patient was then transferred to the Zone of the Interior and when admitted to Ashford General Hospital complained of diurnal and nocturnal urinary frequency, difficulty with urination, and dysuria. It was necessary for him to lie down or set well forward and strain severely to void. Physical examination was normal except for a slightly tender lower abdominal nidline scar and hypalgesia over a rectangular area on the lateral aspect of the left thigh at the level of the buttocks. Blood cell counts were normal. Blood serology was negative. The urine showed 2 albumin, no sugar, and many pus cells in the centrifuged sediment. Urine culture revealed an overgrowth of B. proteus vulgaris. Blood urea nitrogen was 11.5 mg.
+
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On October 1, 1943, a urethrogram was done with 25 cc. of Lipiodol to disclose any changes in the posterior urethra, secondary to fracture of the pelvis. This demonstrated an irregular stricture in the posterior urethra and a small bladder with reflux up both ureters, each of ,vhich showed moderate dilation (fig. 4). The following day a plain x-ray of the urinary tract and intravenous urography revealed a small amount of Lipiodol in the lower calyce3 of both kidneys, moderate bilateral pyelectasis and some delay in the excretion of the dye (figs. 5 and 6). The patient was instructed to lie with his head and trunk lmver than his hips for 20 minutes, twice each day, in an attempt to drain the iodized oil from the calyces. A plain x-ray film of the urinary tract 6 days later (October 7, 1943) indicated that all Lipiodol had disapp2ared from the kidneys (fig. 7). On October 8, 1943, suprapubic cystolithotomy was performed under spinal
Fm. 4. Urethrogram shows an irregularity of the prostatic urethra, with refl.ux up both -0f the dilated ureters. The bladder calculus is visible in 1 side of the bladder.
anesthesia. In order to avoid distending the bladder with fluid when vesicoureteral reflux was known to exist a Foley catheter with balloon was passed to the bladder and distended to 45 cc in order to facilitate the cystotomy. The bladder was found to be of the hour glass type with a transverse fibrous .septum on the posterior bladder wall which apparently confined the calculus to the distal or trigonal segment of the bladder (fig. 8). It was thought that this septum was probably secondary to the surgical closure of the old intraperitoneal rupture and that by distortion of the ureteric regions it might be responsible for reflux up the ureters. After removal of the bladder calculus the transverse band was bisected with scissors allmving the bladder to become one compartment. The bladder was closed around a Ko. 32 F. Malecot catheter and the prevesical .space drained with rubber tissue. Convalescence was uneventful. The suprapubic catheter was removed 10 days after operation and the patient placed on urethral drainage for a period of 11 days. During this period the patient received 2 gm. of sulfadiazine each day. Following removal of the urethral catheter the patient voided easily and comfortably in large amounts, There was no rise in temperature.
Fm. 5. A plain x-ray film of the urinary tract the day after the urethrogram discloses lipiodol in the lower calyces of both kidneys, more in the right than in the left. Some material remains in tissue adjacent to the prostatic urethra.
Fm. 6. Intravenous urogram demonstrates moderate pyelectasis in both kidneys. cretion of the dye was delayed. 444
Ex-
Fm. 7. A plain x-ray of the urinary tract after 6 days of postural drainage shows no remaining lipidodol in either kidney. The bladder calculus has increased in size in 2 months (compare with figure 3).
Fm. 8. Diagrammatic sketch of findings at operation which disclosed a transverse fibrous band partially dividing the bladder into 2 compartments. 445
446
GEORGE C. PRATHER
FIG. 9. Urethrogram with Lipiodol 33 days after operation. No reflux is evident. prostatic urethra is smoother and the bladder shadow much less deformed.
The
FIG.10 Frn.11 FIG. 10. Intravenous urogram about 5 weeks after operation shows imporved condition of kidneys. FIG. 11. Intravenous urogram about 3-months after operation. Kidneys appear normal and bladder shadow satisfactory. The lower right ureter is visible.
VESICO-URETERAL REFLUX
447
On November 12, 1943, for further data of the urethra and bladder and for a decision as to the prognosis, a urethrogram was done using the same quantity and substance as previously employed. The stricture of the posterior urethra was still evident, but no vesico-ureteral reflux occurred (fig. 9). Intravenous urograms on November 18, 1943 (fig. 10), about 5 weeks after operation showed remarkable improvement in the pyelectasis. Urine culture at this time revealed a growth of a urea splitting staphylococcus organism even though the urinary pH was found to be 5.8. Calcium mandelate and acidification was used for 8 days at the end of which time the urinary sediment contained 8-10 leukocytes per high dry field. The patient then enjoyed a 30 day convalescent furlough and returned to hospital on Janyary 6, 1944. The urine did not show a positive albumin test but culture revealed a growth of B. proteus vulgaris and Staphylococcus aureus. Sulfathiazole improved the urinary picture and further intravenous urography (fig. 11) demonstrated essentially normal pyelograms. On January 17, 1944 the urine contained only scattered leukocytes and urine culture was reported as showing only 1 colony of Staphylococcus aureus. The patient was discharged to a limited type of military duty. In the case report just described there would appear to be 3 possible factors producing the vesico-ureteral reflux. Mechanical distortion of the ureterovesical junction by the transverse band in the bladder does not appear improbable. An inflammatory change due to cystitis is a possibility. Inflammatory changes secondary to the irritation of the confined calculus also merits consideration. The mechanical factor and the stone were removed prior to the second urethrogram, and it is difficult to state which of these most important. It will be realized that correction of one factor at a time did not appear feasible. The excellent result in this patient with recovery from pyelectasis should stimulate further interest in the mechanisms of vesico-ureteral reflux and the possibility of correcting the condition in certain instances.