Upper urinary tract transitional cell carcinoma in patients with bladder carcinoma and associated vesicoureteral reflux

Of 269 patients with bladder neoplasms treated during a 20-year period 47 had associated vesicoureteral reflux. All 47 patients were followed for 3 years or more, or until death. Upper urinary tract transitional cell cancer developed in 3, each of whom had recurrent bladder cancer. Among the 222 patients who had vesical cancer without reflux transitional cell carcinoma of the ureter developed in only 1, 11 years after transurethral resection for a bladder tumor. The incidences of upper tract transitional cell cancer in patients with and without vesicoureteral reflux were 6.4 and 0.44 per cent, respectively, which support the suggested role of reflux in disseminating or seeding of cancer cells from the bladder into the upper urinary tract. Patients with bladder cancer and associated vesicoureteral reflux have an approximately 15-fold greater risk of upper tract cancer developing compared with those without reflux. We recommend vigilant scrutiny of patients with recurrent bladder cancer and associated vesicoureteral reflux for early detection of upper urinary tract transitional cell carcinoma.     

Urinary tract infection in boys

Considerable literature exists regarding the evaluation and treatment of children with urinary tract infection yet little has been reported solely about boys. We reviewed retrospectively 83 boys who were seen after an initial urinary tract infection. Fever was the most common presenting sign (50 per cent) and the most common organisms encountered were of the gram-positive group of bacteria. Escherichia coli accounted for only 21 per cent of the infections. Of the boys 75 per cent (62 patients) had an anatomic abnormality, most commonly vesicoureteral reflux, although more than 25 per cent of our patients had obstructive lesions. Renal scarring was present in half and 58 per cent required early surgical intervention. Urinary tract infection seems to have a higher morbidity in boys and the finding of an atypical organism is to be expected. Based on our findings, we strongly recommend an excretory urogram and a voiding cystourethrogram as the minimal evaluation of boys following an initial urinary tract infection.     

Association of urinary tract infection and reflux with uninhibited bladder contractions and voluntary sphincteric obstruction.

We studied 53 neurologically normal children with recurrent urinary tract infection who were found to have bladder-sphincter incoordination characterized by voluntary sphincteric constriction during involuntary uninhibited bladder contraction. Increased intravesical pressure was documented during these events and was associated with vesicoureteral reflux in nearly 50 per cent of the children and with abnormalities of the ureteral orifice in 30 per cent of those without reflux. We hypothesize that increased intravesical pressure causes urinary infection in these children and produces a spectrum of intravesical anatomic distortion that predisposes to vesicoureteral reflux. In a prospective uncontrolled study treatment of the uninhibited bladder contractions allowed 58 per cent of the patients to maintain sterile urine without subsequent antimicrobial therapy after cure of the initial infection.     

Incidence of urinary tract complications with myelomeningocele

Children born with myelomeningocele face the morbidity of urinary tract complications after they have survived the neurologic complications of the first years of life. The incidence of urinary tract complications was evaluated in 258 children before any operation or intermittent catheter management was performed. In 119 children under one year of age the incidence of urinary tract infection of more than 10(5) colonies was 23 per cent, reflux was 22 per cent, and upper tract dilatation was 6 per cent. In children of all ages the incidence of urinary tract infection of more than 10(5) colonies was 26 per cent, reflux 34 per cent, upper tract dilatation 18 per cent, and urinary incontinence 87 per cent. In 11 children with complete denervation of the pelvic floor muscles reflux developed in 2 (18%) and upper tract dilatation in 1 (9%). In 13 children with slight or moderate denervation of the pelvic floor muscles reflux developed in 5 (38%) and upper tract dilatation in 7 (54%). The development of upper tract changes with myelomeningocele was mainly related to some innervation of the pelvic floor muscles (including periurethral striated muscle) with incoordinate detrusor/sphincter activity. These changes mainly occurred in the first two to four years of life.     

Protective factors in posterior urethral valves

Patients with posterior urethral valves may present with or contract renal insufficiency. High intravesical pressure that is transmitted to the upper urinary tract in utero is a likely contributing cause. We have identified 3 anatomical associations with posterior urethral valves that provide a pressure "pop-off" mechanism resulting in preservation of better renal function: 1) the syndrome of posterior urethral valves, unilateral vesicoureteral reflux and renal dysplasia; 2) large congenital type bladder diverticula and 3) urinary extravasation with or without urinary ascites. Followup of 71 boys with posterior urethral valves was sufficient to permit long-term analysis. Serum creatinine was used as an index of renal function and prognosis. Of the 71 boys 20 (28 per cent) had 1 of the 3 protective mechanisms. Only 1 child (5 per cent) had a serum creatinine greater than 1.0 mg. per cent. Of the remaining 51 boys without a "pop-off" mechanism 20 (39 per cent) had serum creatinine greater than 1.0 mg. per cent and 7 had already progressed to renal dialysis and/or transplantation. The difference in serum creatinine was statistically significant (p less than 0.01). Thus, the syndrome of posterior urethral valves, unilateral vesicoureteral reflux and renal dysplasia; large congenital bladder diverticula and urinary extravasation can serve as a "pop-off" mechanism to buffer high pressures in the urinary tract and to lead to the preservation of better renal function in boys with posterior urethral valves.     

Cessation of prophylactic antibiotics for managing persistent vesicoureteral reflux

PURPOSE: We reviewed our experience with patients with vesicoureteral reflux treated off prophylactic antibiotics. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with vesicoureteral reflux treated off prophylactic antibiotics, noting the intervals on and off antibiotics, urinary tract infection, signs and symptoms associated with urinary tract infection, and renal ultrasound and dimercapto-succinic acid scan findings. RESULTS: We identified 196 patients with vesicoureteral reflux treated off prophylactic antibiotics, including 122 who were infection-free while on and 124 who had no urinary tract infection while off prophylactic antibiotics. The infection rate on and off prophylactics was 0.29 and 0.24 urinary tract infections per patient per year, respectively. New scars were identified in 5 patients while on prophylactics and in 7 after antibiotics were discontinued. Comparing different subgroups off prophylactic antibiotics showed that children who presented with scarring had statistically fewer new scars than those with normal initial dimercapto-succinic acid imaging (p <0.043). Girls had significantly more urinary tract infections than boys while off prophylactics (p <0.01) despite the older age at antibiotic cessation. However, after infection occurred while off prophylactic antibiotics, new renal scars developed at about the same rate in boys and girls. Because most patients did not have a urinary tract infection while off prophylactic antibiotics, new renal scars developed in only 2.2% of all boys and 4% of all girls. CONCLUSIONS: Our findings imply that discontinuing antibiotics is reasonable and safe in patients in whom vesicoureteral reflux fails to resolve.     

Urinary tract infections in children with posterior urethral valves after kidney transplantation.

The records of 14 boys with posterior urethral valves who had renal failure and subsequently underwent renal transplantation were reviewed to determine the postoperative incidence of urinary tract infection relative to that of 29 male transplant children without valves, who served as controls. There were no significant differences between the posterior urethral valve patients and controls with regard to age, donor source, immunosuppression, followup after transplantation or mean calculated creatinine clearance. Vesicoureteral reflux was found in 1 child with posterior urethral valves and 3 of the children in the control group (p not significant). A total of 15 urinary tract infections occurred in 5 children (36%) with posterior urethral valves, for a rate of 1 per 30 patient-months of followup, and 6 urinary tract infections occurred in 2 controls (7%), for a rate of 1 per 216 patient-months of followup (p < 0.05). However, only 1 of 26 controls (4%) without vesicoureteral reflux had urinary tract infection, for a rate 1 per 1,144 patient-months (p < 0.01). Conversely, the rate of urinary tract infections in controls with vesicoureteral reflux was similar to that of children with posterior urethral valves. Of the 5 children with posterior urethral valves 4 had the initial urinary tract infection within 2 months of transplantation and 10 of 15 episodes occurred within the first 4 months. Antimicrobial prophylaxis did not appear to decrease the rate of infection in children with posterior urethral valves. A history of posterior urethral valves increases the frequency of urinary tract infection after renal transplantation but the usefulness of antimicrobial prophylaxis and the relationship to long-term graft function remain to be determined. Urinary tract infection rarely develops in other transplanted boys without vesicoureteral reflux.     

Vesicorenal reflux and upper urinary tract transitional cell carcinoma after transurethral resection of recurrent superficial bladder carcinoma

Of 288 patients with superficial transitional cell carcinoma of the bladder vesicorenal reflux developed after transurethral resection in 26 per cent. This proportion was higher (77 per cent) when we considered only those tumors located near the ureteral orifices. There was a statistically significant relationship (p less than 0.001) between the development of upper urinary tract tumors and vesicorenal reflux (20 per cent of the patients with reflux and 0.9 per cent without reflux had a tumor), which corresponds to a 22-fold greater risk in the former group. Close followup is advised, since 1 of 5 patients with reflux after transurethral resection may have upper urinary tract transitional cell carcinoma.     

Surgical management of vesicoureteral reflux in children

The authors report on ten years of experience in ureteroneocystostomies on 80 ureters in 50 children suffering from vesicoureteral reflux. Complete follow-up was obtained in all cases. Postoperative radiograms revealed cure of reflux in 85 per cent of the renal units. A slightly modified Politano-Leadbetter procedure was used in all of the cases. Postoperative urinary tract infection occurred in 13 patients. This relatively low success rate is discussed briefly.     

Enuresis as protective factor in vesicoureteral reflux

In 83 patients with non-neurologic, nonoperated vesicoureteral reflux the relation between enuresis and nephropathy was analyzed. The material showed that in spite of identical age, sex distribution, previous history of recurrent urinary tract infections, and the number of refluxing units, patients with enuresis showed a significantly lower degree of reflux nephropathy. This significant difference was even more pronounced when the age of the patients was considered. Thus patients below the age of ten showed reflux nephropathy in 25 per cent of the refluxing units in enuretic patients compared with 30.8 per cent in the nonenuretic patients. Above the age of ten 76.2 per cent of the refluxing units showed renal scarring in the nonenuretics compared with 27.8 per cent in the enuretics. The study stresses the importance of lower urinary tract malfunction in the pathogenesis of reflux. Enuresis might act as a safety valve mechanism reducing the possibility of reflux nephropathy.     

Vesicoureteral reflux diagnosed in adulthood. Incidence of urinary tract infections, hypertension, proteinuria, back pain and renal calculi

Study purpose: To determine the incidence of urinary tract infections, hypertension, back pain, and renal calculi in adult patients with vesicoureteral reflux and reflux nephropathy. Methods: A group of 115 patients (16-60 years of age, median 28 years) with vesicoureteral reflux, combined with reflux nephropathy in 101 patients, first detected between 1967 and 1984, was studied retrospectively. The group comprised 99 women and 16 men. Results: Symptoms and findings associated with the urinary tract preceded the diagnosis of vesicoureteral reflux by median 14 years (1-60 years). Intravenous pyelography preceded investigation with micturating cystography in 99 patients. Fifteen patients had no urinary tract infections, 17 patients had only lower urinary tract infections, and 83 patients had upper with or without lower urinary tract infections. Females had 12 times more lower and seven times more upper urinary tract infections than males, whereas males had impairment of renal function and proteinuria more often than females. Hypertension was present in 39 patients (34%) and five times more frequent in patients with bilateral than in those with unilateral reflux nephropathy. The median age at the first recording of hypertension was 33 years (16-60 years). Malignant hypertension was uncommon and occurred in two patients. An older group (>45 years of age at presentation) of 19 patients showed a 90% incidence of hypertension compared with 23% in 96 patients in the younger group (⩽45 years of age at presentation). Back pain of varying type and severity was present in 48 patients (42%). A total of 38 renal calculi was found in 21 (18%) patients, of whom 14 were completely asymptomatic. Conclusions: The natural history of vesicoureteral reflux first detected in adulthood has shown a strikingly high incidence of urinary tract infections, arterial hypertension, back pain, and renal calculi.     

A 22-year followup of ileal conduits in children with a neurogenic bladder

Previously, the ileal conduit had been used in children for diversion of urine from the neurogenic bladder to prevent deterioration of the upper urinary tracts and to manage urinary incontinence. Long-term results after ileal conduits in children have revealed upper tract deterioration and a high complication rate. The complications and renal deterioration rates in 139 children with ileal conduits followed up to 22 years were evaluated. Of 224 complications 114 required surgical correction. Upper urinary tract deterioration occurred in 16.5 per cent of 50 children followed for 10 or more years (mean 13.3 years). The ileal conduit has been replaced by clean intermittent catheterization, ureteral reimplantation for reflux, the artificial sphincter and undiversion in the management of neurogenic bladders in children. Long-term followup will be necessary to compare the results of these procedures to the known long-term results of the ileal conduit to determine the appropriate role of the ileal conduit in the management of children with neurogenic bladders.     

Clean intermittent catheterization in the management of the neurogenic bladder in children

Clean intermittent catheterization has been successful in the management of urinary incontinence and upper tract changes associated with a neurogenic bladder. The results of clean intermittent catheterization controlling urinary incontinence, ureteral reflux, upper tract dilatation and urinary infection in 84 children with a neurogenic bladder were evaluated for up to 3 years of followup. Of the children 41 (49 per cent) were totally incontinent and 14 (17 per cent) were slightly damp. Preexisting ureteral reflux deteriorated in 25 per cent of the patients, ceased in 35 per cent and was unchanged in 40 per cent, while pre-existing upper tract dilatation improved in 12.5 per cent and was unchanged in 87.5 per cent. On clean intermittent catheterization and antibacterial medication 90 per cent of the children had sterile urine and 7.5 per cent had 10(5) or more colonies per ml. Complications occurred on 54 occasions but were minor in nature and were corrected easily. Half of the parents, schools and children found clean intermittent catheterization very acceptable or acceptable but a quarter of the parents and patients found it unacceptable or slightly unacceptable, or were undecided. Initial management of urinary complications associated with neurogenic bladder in children has changed to the clean intermittent catheterization program, with greatly improved results compared to Credé's expression of the bladder, an indwelling urethral catheter or urinary diversion. However, the clean intermittent catheterization regimen was not effective completely, not without complications and not accepted completely by parents, schools and children.     

Can recurrent urinary tracts infections with existing vesicoureteral reflux be checked (author's transl)

Of 35 female patients with vesicoureteral reflux, 9 had a cessation of their urinary tract infections while the reflux persisted. These findings contrast with the thesis that vesicoureteral reflux is the major cause of susceptibility to urinary tract infections in these patients.     

Comparative results of urological evaluation of children with initial and recurrent urinary tract infection.

Complete urologic evaluation was done on male and female children having initial or recurrent urinary tract infection. Of 200 girls having recurrent urinary tract infection 43 per cent showed ureterovesical reflux on the cystogram. Of 39 boys with recurrent urinary tract infection 41 per cent had reflux. Thus, the incidence of reflux is comparable in male versus female patients. Of 47 girls studied after only 1 episode of urinary tract infection 36 per cent had reflux and of 20 boys studied after initial infection 45 per cent had reflux. The data indicate that initial or recurrent urinary tract infection in boys or girls is of equal significance. All other factors being equal, failure to evaluate a patient urologically after 1 or more episodes of urinary tract infection solely because of the sex of the child could mean that a potentially severe urinary tract abnormality can be undetected and untreated.     

Management of vesicoureteral reflux

The retrospective analysis of 210 patients between 1 month and 17 years old with 314 primary vesicoureteral units with reflux was reviewed. Our results show that there was a direct correlation between the grade of reflux and the per cent of abnormal ureteral orifices. Medical management of low grade reflux produced successful results in 60 per cent of the cases. Operation was highly successful in grade I, II, and III reflux as opposed to grade IV. The distal tunnel (Glenn-Anderson) and Politano-Leadbetter procedures were equally effective in curing reflux. Postoperative urinary infection occurred equally in all grades and usually was confined to the bladder.     

Pre-transplant urologic investigation and treatment of end stage renal disease

We investigated 112 patients with end stage renal disease. Clinical evaluations included cystoscopy, cystometry, voiding cystography, bilateral retrograde pyelograms, history and physical examination, and appropriate serum and urinary studies. Of the 112 patients 28 (25 per cent) had significant abnormalities of the urinary tracts. Of the 28 patients 17 had lower tract abnormalities, such as detrusor hyporeflexia, obstructing prostatic hyperplasia and urethral stricture, and 11 had upper tract disease, 9 of whom required a pre-transplant surgical procedure. Included in the group of 9 patients were those with polycystic kidneys, staghorn calculi, renin-related renal hypertension, chronic pyelonephritis and persistent vesicoureteral reflux. None of the azotemic patients had significant morbidity with the timing of the surgical procedures. We believe that eradication of such conditions in the pre-transplant period resulted in a more suitable candidate for renal transplantation. Furthermore, we believe that our finding of 25 per cent abnormalities underscores the need for early urologic evaluation of these patients to ensure their functional capabilities as a recipient.     

Ileal conduits in children at the Massachusetts General Hospital from 1955 to 1970.

The 45 ileal conduits performed on children at the Massachusetts General Hospital from 1955 to 1963 are reviewed and compared to the 45 ileal conduits performed from 1964 to 1970. Late complications involving the conduits occurred in 60 per cent of the early group and in 51 per cent of the late group. Of the renal units judged normal pyelographically preoperatively in the early group 77 per cent went on to at least some deterioration, while 62 per cent of the late group judged normal later deteriorated. Combining all renal units, 34 per cent remained unchanged, 26 per cent improved and 41 per cent showed some degree of deterioration after ileal conduit urinary diversion. The late complication and renal deterioration rates seem to increase progressively with time. There was no apparent urinary obstruction in 13 per cent of the renal units that deteriorated. Theoretical and experimental considerations indicate the reflux of infected urine as the etiology of the renal deterioration. Because of the late complications and the unacceptably high rate of renal deterioration we no longer perform ileal conduits in children. Instead every effort is made to reconstruct the urinary tract or if urinary diversion is necessary, a colon conduit with non-refluxing ureterocolonic anastomoses is performed.     

Late sequelae of the management of ureteral calculi with the ureterorenoscope

We examined 42 patients 19 to 20 months after ureteral calculi had been removed with the ureterorenoscope. All 42 patients were asymptomatic and showed no evidence of an increased rate of urinary tract infection or hypertension. An excretory urogram in 38 patients demonstrated no abnormality related to the procedure, in particular no ureteral stenosis and renal scarring. Renal sonography in the remaining 4 patients likewise was normal. Reflux cystography revealed low grade (sterile) vesicoureteral reflux in 2 patients. In view of a 92 per cent success rate in 236 renoureteral units, with serious complications in only 2 per cent, the technique can be considered safe and effective.     

Intrarenal reflux and renal damage.

The retrograde flow of dye from the calices into the collecting tubules (intrarenal reflux) seen during cystrography in children and its effect on the kidneys were evaluated. A retrospective analysis was made of 175 patients with excretory urograms revealing cortical atrophy. Of these patients 68 per cent had cystograms revealing vesicoureteral reflux. Intrarenal reflux was seen in 8 patients less than 6 years old, an incidence of 13.5 per cent in that age group. There was a high correlation, 7 of 8 or 87.5 per cent, between the areas of intrarenal reflux, and associated renal cortical atrophy and calicectasis. Intrarenal reflux provides a pathway by which bacteria and hydrostatic pressure may produce injury to the renal parenchyma. The presence of intrarenal reflux is an absolute indication for ureteroneocystostomy.