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Long-Term Followup of 103 Patients with Bladder Exstrophy
0022-534 7/88/1391-0719$02.00/0
THE
Vol. 139, April
JOURNAL OF UROLOGY
Copyright © 1988 by The Williams & Wilkins Co.
Printed in U.S.A.
LONG-TERM FOLLOWUP OF 103 PATIENTS WITH BLADDER EXSTROPHY HRAIR-GEORGE J. MESROBIAN,* PANAYOTIS P. KELALIS
AND
STEPHEN A. KRAMERt
From the Department of Urology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
We reviewed 103 patients with exstrophy of the bladder. Followup was more than 15 years in 51 patients. Initial management consisted of primary bladder closure in 32 patients and urinary diversion in 71. Urinary continence, renal function, urinary tract infections and development of malignant lesions were evaluated. Factors leading to success or failure were analyzed. Although the highest continence rate (83 per cent) was achieved in 40 patients with ureterosigmoidostomy, renal functional deterioration was highest in this group, with 70 per cent of the evaluable renal units being abnormal. Furthermore, 10 per cent of this group died of renal failure and 23 per cent lost 1 kidney each. In 26 patients with an ileal conduit 69 per cent of the renal units evaluated were abnormal. Only 1 patient died of renal failure but 27 per cent lost 1 kidney each. Of 32 patients with primary bladder closure 31 had preservation of renal function. Twelve of 18 patients (67 per cent) in whom vesical neck reconstruction had been completed had total urinary continence and 3 (17 per cent) had partial continence. The incidence of significant urinary tract infections was highest in the ureterosigmoidostomy group (63 per cent) and next to the highest in the ileal conduit group (48 per cent). Malignant lesions developed in 8 patients (8 per cent). (J. Urol., 139: 719-722, 1988) Exstrophy of the bladder presents a tremendous challenge to the patient, family, pediatrician and urologist. Numerous methods of treatment have been reported. 1-s The 2 most common forms of initial management are functional bladder closure9 - 11 and ureterosigmoidostomy. 12• 13 Urinary continence, renal function, urinary infection and development of malignant lesions are affected not only by the disease but also by the method of surgical treatment and the potential complications of that treatment. An assessment of the cosmetic appearance and genital function in boys with bladder exstrophy has been reported previously. 14 We review· our experience with and long-term followup of 103 patients with bladder exstrophy. This large series has allowed us to study the natural history of the disease, compare the evolution and results of various treatment modalities for bladder exstrophy, and analyze carefully factors leading to success or failure of surgical intervention. MATERIALS AND METHODS
From 1918 through December 1983, 122 patients with exstrophy of the bladder were seen at our clinic. Of the 77 male and 45 female patients 14 and 5, respectively, were not operated upon at our institution and they were excluded from this review. Patient age at presentation ranged from 1 day to 52 years (11 were less than 9 days, 26 were 1 to 10 months, 52 were 1 to 16 years, 6 were 24 to 30 years and 8 were 31 to 52 years old). Followup from the time of initial presentation and operation ranged from 1 to 61 years (average 13 years), and it was more than 10 years in 53 patients and more than 15 years in 51. Followup consisted of detailed interviews, questionnaires or telephone calls, physical examinations, and radiological and laboratory investigations. A total of 103 patients underwent 351 operations for reasons related to exstrophy. Nineteen patients had undergone initial Accepted for publication July 20, 1987. * Current address: Section of Pediatric Urology, Department of Surgery (Urology) and Pediatrics, University of North Carolina, 428 Burnett-Womack Bldg. 229H, Chapel Hill, North Carolina 27514. tRequests for reprints: Mayo Clinic, 200 First St. S. W., Rochester, Minnesota 55905
treatment elsewhere and they were referred at various intervals after attempted primary closure of the bladder. Initial management consisted of primary bladder closure in 32 patients: 26 underwent primary closure at our clinic, 5 had undergone successful primary closure elsewhere, and 1 had failure of initial closure and underwent successful re-closure of the bladder after referral (table 1). Closed bladder exstrophy was maintained in 24 patients (75 per cent), whereas 8 had subsequent urinary diversion. The factors that led to secondary urinary diversion are outlined in table 2. Of the patients 71 underwent primary urinary diversion (table 3), including 14 (20 per cent) who required secondary diversion (table 4). The final urological anatomy of all 103 patients is outlined in table 5. RESULTS
Urinary continence. Urinary continence was defined as the ability to remain dry for 3 or more hours. Occasional episodes of daytime or nighttime incontinence (for example, 1 episode a week) were not considered to represent failure at achieving continence. Patients with minor stress incontinence (protection necessary only with considerable physical activity, such as exercise) were considered continent. Of the 32 patients who underwent primary bladder closure 8 (25 per cent) required diversion, 6 (18.75 per cent) are awaiting a further operation, 12 (37.5 per cent) are continent, 3 (9.375 per cent) are partially continent and 3 are incontinent. A closed exstrophic bladder was maintained in 24 patients and vesical neck reconstruction had been completed in 18. Of the latter 18 patients 12 (10 male and 2 female patients, 67 per cent) had complete urinary continence (greater than 3 hours), 3 (2 male and 1 female patients) had partial continence (1 to 3 hours) and 3 were incontinent. Each of the 3 incontinent patients is a candidate for augmentation cystoplasty. 15 The number of operations in these patients undergoing vesical neck reconstruction ranged from O to 2. Five patients were contine:qt after bladder closure alone and they did not require bladder neck reconstruction. Two patients required more than 1 operation. One patient required 2 bladder neck reconstructions.
719
720
MESROBIAN, KELALIS AND KRAMER
TABLE
1. Initial form of management in 103 patients with exstrophy
Initial Treatment :l?rimary closure (neonatal closure) Urinary diversion Totals
Boys
Girls
Totals
22 (10)
10 (5)
32 (15)
41
30
71
63
40
103
Factors that led to urinary diversion after primary closure
TABLE 2.
Female Pts. Massive reflux with hydronephrosis Wound dehiscence Vesical neck contracture Staged colon conduit (Arap) Totals
TABLE
4
2 0 0
0 1
2 1 1
5
3
8
3. Forms of initial urinary diversion Female Pts.
Male Pts.
20 5
29 7
Total No. (%)
49 (69) 12 (17)
2
1
3
1 2 0 1
2 0 1 0
3 2
(4)
31
40
(4) (3) (L5) 1 (L5) 71 (100.0)
4. Factors that led to re-diversion after primary diversion Cause of Failure
Male Pts.
Female Pts.
Totals
BilaL obstruction Urinary incontinence Colonic polyp Bilat. obstruction Urinary incontinence Bilat. obstruction
3 0 0 0 1 1
5
8
1 2 0
2
0
1
5
9
14
Initial Form U reterosigmoidostomy
Cutaneous ureterostomy Heitz Boyer-Hovelacque Totals
TABLE
Totals
3
Ureterosigmoidostomy Ilea! conduit Boyce-Vest Heitz Boyer-Hovelacque U reterostomy Sigmoid conduit Vesico-ileo-sigmoidostomy Totals
TABLE
Male Pts.
1
5. Final urological anatomy of 103 patients with exstrophy Female Pts.
Closed bladder U reterosigmoidostomy Ilea! conduit Cutaneous ureterostomy Boyce-Vest Sigmoid conduit Internal sigmoid conduit Vesico-ileo-sigmoidostomy Bilat. nephrostomy Heitz Boyer-Hovelacque Totals
4
14 14 3 2 0 1
0 1 40
Male Pts. 20 26 12 2
0 0 1 0
63
Totals 24 40
26 5 3 1 1 1 1 1 103
Of 40 patients with ureterosigmoidostomy 33 (83 per cent) were continent of urine and stool. Five male and 2 female pa,sn,rn,~ were incontinent and required protective padding. The ages of these 7 patients were 15 to 52 years (average age 37 Of the 3 patients who underwent a Boyce-Vest reconstruction was continent, 1 was incontinent and 1 was lost to followup. The patient who underwent a Heitz Boyer-Hovelacque procedure was incontinent of urine and stool. Both patients with internal diversion (sigmoidosigmoidostomy and vesico-ileo-sigmoidostomy) were continent. Renal function. Renal function was assessed by measure-
ments of serum creatinine (normal values 0.8 to 1.2 mg./dL), blood urea nitrogen (BUN, normal values 8 to 24 mgJdL) and electrolytes, and by review of the most recent excretory urograms (IVPs) or radioisotopic renal scans. The patients were divided into 4 groups according to the type of operation. Group 1 consisted of 24 patients in whom a closed exstrophic bladder was maintained. The interval from primary bladder closure to patient evaluation was 6 months to 17 years (average 8 years). All 24 patients had normal serum creatinine values, while 18 (75 per cent) had normal IVPs and 6 (25 per cent) had hydronephrosis. Vesicoureteral reflux was common and it occurred in 11 patients (46 per cent). This subgroup of patients requires long-term followup to detect deterioration of the upper tracts with time. Group 2 consisted of 40 patients who underwent ureterosigmoidostomy. The interval from ureterosigmoidostomy to patient evaluation was 4 to 53 years (average 28 years). Serum creatinine values, available in 19 patients, were between 0.8 and 13.5 mgJdL (average 1.84 mg./dl.). Serum BUN, available in 16 patients, was 16 to 486 mgJdL (average 80 mg./dl.). Eight patients had significant renal failure (BUN greater than 60 mg./dL or serum creatinine greater than 3 mgJdL). Eighteen patients (45 per cent) had significant hyperchloremic metabolic acidosis and 29 (73 per cent) had abnormal IVPs (hydronephrosis in 36 renal units and renal atrophy in 14 renal units). Nine patients (23 per cent) lost 1 renal unit each. Eight patients had renal calculi (20 per cent). Four patients (10 per cent) died ofrenal failure 4, 5, 12 and 27 years after ureterosigmoidostomy. Group 3 consisted of 26 patients with an ileal conduit. The interval from construction of the ileal conduit to evaluation was 1 to 30 years (average 13 years). Serum creatinine values, available in 16 patients, were 0.7 to 3.0 mg./dl. (average 1.2 mg./dL). The remaining 9 patients had serum BUN values of 20 to 63 mgJdL (average 43 mg./dL). Only 1 patient in this group had significant renal insufficiency (creatinine concentration greater than 3.0 mgJdl.). Eighteen patients (69 per cent) had abnormal IVPs: hydronephrosis was present in 27 renal units and renal atrophy was present in 9 units. Renal calculi were detected in 7 units. All renal units evaluated had vesicoureteral reflux. Seven patients (27 per cent) lost l renal unit each and only 1 patient had significant chronic renal failure, which caused death when he was 15 years old. One patient died of an undetermined cause when he was 21 years old. In Group 4, a heterogeneous group of 13 patients with various forms of internal and external urinary diversion, followup since reconstruction was 1 to 32 years (average 17 years). Serum creatinine values, available in 11 patients, were 0.4 to 3.1 mg./ dL (average 1.3 mgJdL). Serum BUN in 3 patients was 30 to 45 mg./dl. (average 37 mg./dl.). Two patients had hyperchloremic metabolic acidosis. Five patients (38 per cent) had abnormal IVPs: hydronephrosis was present in all 10 renal units and renal atrophy occurred in 5 units. Reflux was present in only 1 renal unit in the patient with the sigmoid conduit. None of the patients required nephrectomy. Urinary tract infections. The incidence of significant urinary tract infections resulting in clinical pyelonephritis (fever) or renal scarring was reviewed for each group. Over-all, 46 of 103 patients (45 per cent) had significant infections. The incidence of infections by subgroup was 26 per cent in group 1, 63 per cent in group 2, 48 per cent in group 3 and 21 per cent in group 4. Malignant lesions. Eight patients had malignant lesions, 4 of which were adenocarcinoma of the bladder. Of the patients with adenocarcinoma 3 had failed neonatal bladder closure and they did not receive further treatment. One patient had not been treated before he was 31 years old, when a fungating mass was found arising in the exstrophic bladder. These 4 patients were 31 to 52 years old (average age 42 years). Of these patients 2 died of metastatic disease. In 1 patient carcinoma in situ of the bladder remnant was diagnosed when he was 28 years old.
LONG-TERM FOLLOWUP OF 103 PATIENTS WITH BLADDER EXSTROPHY
Ureterosigmoidostomy had been done when he was 3 years old without concomitant cystectomy and he died of metastatic disease 2 years after diagnosis. Colonic polyps developed in 3 of 40 patients with ureterosigmoidostomy. Two patients had a benign colonic polyp 11 and 21 years after ureterosigmoidostomy, and 1 had a malignant colonic polyp 26 years after ureterosigmoidostomy. None of these patients died. Associated arwmalies. Of the patients 10 per cent had associated anomalies: 2 had spina bifida and 9 had 1 associated anomaly each, including ventricular septal defect, rectal septum, hypertelorism, imperforate anus, omphalocele, rudimentary uterus, absent vagina, diphallia and microcorpora. Mortality. A total of 14 patients (13 per cent) had died at the time of this review: 7 of renal failure, 4 of malignant disease and 3 of undetermined causes. DISCUSSION
More than any other urological abnormality, bladder exstrophy requires long-term followup for accurate assessment of the natural history of the disease, and the successes and failures of surgical intervention. Factors, such as urinary continence, renal function, urinary tract infections and the development of malignant disease, must be evaluated years after initial treatment. Because of the great variability of bladder exstrophy and of the age of the patient at reconstruction, there remains no single acceptable method of initial treatment. The most common method of treatment in our series was ureterosigmoidostomy (40 patients). Although the highest continence rate was achieved in this group, 33 of 40 (83 per cent), deterioration of renal function was highest in these patients, with 70 per cent of the evaluable renal units being abnormal. Furthermore, 10 per cent of these patients died of renal failure and 23 per cent lost 1 renal unit each. Despite recent improvements in surgical technique 12 the results of our long-term followup (average 28 years) tend to discourage the use of ureterosigmoidostomy as the primary method of choice in children with bladder exstrophy. Furthermore, the 8 per cent incidence of colonic neoplasia in our group is worrisome and parallels the risk of malignancy documented in other series with long-term followup. 16-18 Ileal conduit urinary diversion was the second most frequent method of treatment (26 patients). Of these patients 69 per cent had either hydronephrosis or renal atrophy on an IVP and 27 per cent lost 1 renal unit each. The significant long-term risks of reflux, pyelonephritis, renal scarring, calculi and hypertension, and the necessity for an external appliance make the use of _this form of urinary diversion unacceptable for young children with bladder exstrophy. 19 We have not performed an ileal conduit procedure for the treatment of bladder exstrophy since 1974. Among our 32 patients who underwent primary bladder closure closed bladder exstrophy was maintained in 24. The techniques of primary bladder closure with or without bilateral iliac osteotomy have been well described. 20 • 21 Of 18 patients in whom vesical neck reconstruction was completed 12 (67 per cent) were dry, 3 (17 per cent) had partial (1 to 3 hours) continence and none required intermittent self-catheterization. Although bilateral iliac osteotomy was not used uniformly in our series, our results did not indicate that this procedure was associated with increased urinary continence. Fourteen patients had bilateral iliac osteotomy: 4 were continent, 3 had partial continence and 7 were incontinent. Of the 7 incontinent patients 6 had undergone permanent urinary diversion. Eight patients underwent urinary diversion after failure of primary bladder closure (table 2) and 3 of these patients are candidates for urinary undiversion by use of augmentation cystoplasty. Our treatment of choice for children with bladder exstrophy is neonatal closure in the first 24 to 48 hours. Primary bladder closure should be done in virtually all patients irrespective of
721
bladder size. Our experience and that of others9 is that even bladder capacities of 5 ml. often enlarge rapidly after closure and subsequent distension with urine. We do not use bilateral ileac osteotomy routinely, and we have reserved this technique for difficult closures and for children seen after 7 to 10 days of life. All children are immobilized with modified Bryant's traction and liberal use of sedation with belladonna and opium rectal suppositories. With this technique we have not encountered any instances of wound dehiscence or bladder prolapse without iliac osteotomy in 10 consecutive neonatal bladder closures. Between primary bladder closure and a patient age of 3 years children are monitored carefully with serum electrolyte determinations, urine culture studies, ultrasound examinations and dimercaptosuccinic acid renal scans. When the patient is 3 years old we proceed with reconstruction of the bladder neck and bilateral ureteral reimplantation. Our experience has been that bladder size remains the single most important factor related to urinary continence. 22 In boys with small bladders preliminary urethroplasty has not produced sufficient outlet resistance to increase bladder capacity. We currently use bladder augmentation at the time of vesical neck reconstruction in children with small bladder capacities. We have used this technique in 6 recent patients and have had extremely gratifying results in short-term followup. 23 Five children are completely dry and 1 has partial continence. Each of these 6 children is being managed successfully with intermittent catheterization. Urodynamic studies involving closed bladder exstrophy24• 25 have provided objective methods to assess hyperreflexia and bladder compliance in children who remain incontinent postoperatively. These children should be treated initially with drugs and if they are unsuccessful they should be considered candidates for enterocystoplasty. The occurrence of adenocarcinoma of the bladder in 4 of our patients parallels previous reports that have demonstrated an appreciable risk of malignancy in the exstrophic bladder left open. 26 Bladder exstrophy ideally should be closed when the patient is a neonate but if permanent internal or external urinary diversion becomes necessary the exstrophic bladder should be removed. CONCLUSIONS
We reviewed our experience and long-term followup of a large series of patients with bladder exstrophy. Whereas others have dealt primarily with the successes of primary bladder closure, large reviews rarely have discussed the fate of the failed bladder exstrophy and the management of those complications. The options of internal and external diversion have been associated with significant deterioration in renal function when followup has been long-term. Clearly, primary bladder closure, ideally in the neonate, is the preferred treatment for children with bladder exstrophy. Our experience with primary bladder closure has been excellent, with 84 per cent of the patients having complete or partial urinary continence. Renal function was preserved in 31 of 32 patients. Bladder augmentation at the time of vesical neck reconstruction for children with marginal bladder capacities has provided extremely gratifying short-term results. Enterocystoplasty can avoid the long-term sequelae of urinary diversion, preserve renal function and improve the quality of life in children born with bladder exstrophy. REFERENCES
1. Arap, S., Martins Giron, A. and Menezes de Goes, G.: Initial results
of the complete reconstruction of bladder exstrophy. Urol. Clin. N. Amer., 7: 477, 1980. 2. Hendren, W. H.: Exstrophy of the bladder. Birth Defects, 13: 207, 1977. 3. Boyce, W. H. and Kroovand, R. L.: The Boyce-Vest operation for exstrophy of the bladder: 35 years later. Urol. Clin. N. Amer., 13: 307, 1986.
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MESROBIAN, KELALIS AND KRAMER
4. Cendron, J.: Bladder exstrophy from an external to an internal diversion. Birth Defects, 13: 197, 1977. 5. Gregoir, W. and Schulman, C. C.: Exstrophy of the bladder: treatment by trigonosigmoidostomy-long-term results. Brit. J. Urol., 50: 90, 1978. 6. Tacciuoli, M., Laurenti, C. and Racheli, T.: Sixteen years' experience with the Heitz Boyer-Hovelacque procedure for exstrophy of the bladder. Brit. J. Urol., 49: 385, 1977. 7. Battke, H. and Stadie, G.: Cystosigmoidostomy: indications and results. Int. Urol. Nephrol., 9: 303, 1977. 8. Lima, S. V. C., Noroes, J. A. A., Carvalheira, F. and de Mendon~a, P. P.: Bladder exstrophy: primary reconstruction with human dura mater. Brit. J. Urol., 53: 119, 1981. 9. Jeffs, R. D.: Functional closure of bladder exstrophy. Birth Defects, 13: 171, 1977. 10. Mollard, P., Sarkissian, J. and Loras, 0.: Reconstruction vesicale pour exstrophie. J. d'Urol., 87: 199, 1981. 11. Ansell, J. S.: Surgical treatment of exstrophy of the bladder with emphasis on neonatal primary closure: personal experience with 28 consecutive cases treated at the University of Washington Hospitals from 1962 to 1977: techniques and results. J. Urol., 121: 650, 1979. 12. Segura, J. W. and Kelalis, P. P.: Long-term results of ureterosigmoidostomy in children with bladder exstrophy. J. Urol., 114: 138, 1975. 13. Spence, H. M. and Hoffman, W. W.: Exstrophy of the urinary bladder treated by ureterosigmoidostomy: long-term follow-up in a series of 37 cases. Birth Defects, 13: 185, 1977. ' 14. Mesrobian, H.-G. J., Kelalis, P. P. and Kramer, S. A.: Long-term followup of cosmetic appearance and genital function in boys with exstrophy: review of 53 patients. J. Urol., 136: 256, 1986. 15. Gearhart, J.P., Albertsen, P. C., Marshall, F. F. and Jeffs, R. D.: Pediatric applications of augmentation cystoplasty: the Johns Hopkins experience. J. Urol., 136: 430, 1986. 16. Warren, R. B., Warner, T. F. C. S. and Hafez, G. R.: Late devel-
17. 18. 19.
20.
21. 22. 23.
24. 25. 26.
opment of colonic adenocarcinoma 49 years after ureterosigmoidostomy for exstrophy of the bladder. J. Urol., 124: 550, 1980. Spence, H. M., Hoffman, W. W. and Fosmire, G. P.: Tumour of the colon as a late complication of ureterosigmoidostomy for exstrophy of the bladder. Brit. J. Urol., 51: 466, 1979. Gittes, R. F.: Carcinogenesis in ureterosigmoidostomy. Urol. Clin. N. Amer., 13: 201, 1986. Shapiro, S. R., Lebowitz, R. and Colodny, A. H.: Fate of 90 children with ileal conduit urinary diversion a decade later: analysis of complications, pyelography, renal function and bacteriology. J. Urol., 114: 289, 1975. Jeffs, R. D. and Lepor, H.: Management of the exstrophy-epispadias complex and urachal anomalies. In: Campbell's Urology, 5th ed. Edited by P. C. Walsh, R. F. Gittes, A. D. Perlmutter and T. A. Stamey. Philadelphia: W. B. Saunders Co., vol. 2, sect. XIII, chapt. 43, p. 1893, 1986. Duckett, J. W.: Use ofparaexstrophy skin pedicle grafts for correction of exstrophy and epispadias repair. Birth Defects, 13: 175, 1977. Kramer, S. A. and Kelalis, P. P.: Assessment of urinary continence in epispadias: review of 94 patients. J. Urol., 128: 290, 1982. Kramer, S. A. and Kelalis, P. P.: Augmentation cystoplasty in patients with epispadias-exstrophy. Read at annual meeting of North Central Section, American Urological Association, Ranchos Mirage, California, November 9-15, 1986. Toguri, A. G., Churchill, B. M., Schillinger, J. F. and Jeffs, R. D.: Gas cystometry in cases of continent bladder exstrophy. J. Urol., 119: 536, 1978. Toguri, A. G., Churchill, B. M., Schillinger, J. F. and Jeffs, R. D.: Continence in cases of bladder exstrophy. J. Urol., 119: 538, 1978. Nielsen, K. and Nielsen, K. K.: Adenocarcinoma in exstrophy of the bladder-the last case in Scandinavia? A case report and review of literature. J. Urol., 130: 1180, 1983.
THE
Vol. 139, April
JOURNAL OF UROLOGY
Copyright © 1988 by The Williams & Wilkins Co.
Printed in U.S.A.
LONG-TERM FOLLOWUP OF 103 PATIENTS WITH BLADDER EXSTROPHY HRAIR-GEORGE J. MESROBIAN,* PANAYOTIS P. KELALIS
AND
STEPHEN A. KRAMERt
From the Department of Urology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
We reviewed 103 patients with exstrophy of the bladder. Followup was more than 15 years in 51 patients. Initial management consisted of primary bladder closure in 32 patients and urinary diversion in 71. Urinary continence, renal function, urinary tract infections and development of malignant lesions were evaluated. Factors leading to success or failure were analyzed. Although the highest continence rate (83 per cent) was achieved in 40 patients with ureterosigmoidostomy, renal functional deterioration was highest in this group, with 70 per cent of the evaluable renal units being abnormal. Furthermore, 10 per cent of this group died of renal failure and 23 per cent lost 1 kidney each. In 26 patients with an ileal conduit 69 per cent of the renal units evaluated were abnormal. Only 1 patient died of renal failure but 27 per cent lost 1 kidney each. Of 32 patients with primary bladder closure 31 had preservation of renal function. Twelve of 18 patients (67 per cent) in whom vesical neck reconstruction had been completed had total urinary continence and 3 (17 per cent) had partial continence. The incidence of significant urinary tract infections was highest in the ureterosigmoidostomy group (63 per cent) and next to the highest in the ileal conduit group (48 per cent). Malignant lesions developed in 8 patients (8 per cent). (J. Urol., 139: 719-722, 1988) Exstrophy of the bladder presents a tremendous challenge to the patient, family, pediatrician and urologist. Numerous methods of treatment have been reported. 1-s The 2 most common forms of initial management are functional bladder closure9 - 11 and ureterosigmoidostomy. 12• 13 Urinary continence, renal function, urinary infection and development of malignant lesions are affected not only by the disease but also by the method of surgical treatment and the potential complications of that treatment. An assessment of the cosmetic appearance and genital function in boys with bladder exstrophy has been reported previously. 14 We review· our experience with and long-term followup of 103 patients with bladder exstrophy. This large series has allowed us to study the natural history of the disease, compare the evolution and results of various treatment modalities for bladder exstrophy, and analyze carefully factors leading to success or failure of surgical intervention. MATERIALS AND METHODS
From 1918 through December 1983, 122 patients with exstrophy of the bladder were seen at our clinic. Of the 77 male and 45 female patients 14 and 5, respectively, were not operated upon at our institution and they were excluded from this review. Patient age at presentation ranged from 1 day to 52 years (11 were less than 9 days, 26 were 1 to 10 months, 52 were 1 to 16 years, 6 were 24 to 30 years and 8 were 31 to 52 years old). Followup from the time of initial presentation and operation ranged from 1 to 61 years (average 13 years), and it was more than 10 years in 53 patients and more than 15 years in 51. Followup consisted of detailed interviews, questionnaires or telephone calls, physical examinations, and radiological and laboratory investigations. A total of 103 patients underwent 351 operations for reasons related to exstrophy. Nineteen patients had undergone initial Accepted for publication July 20, 1987. * Current address: Section of Pediatric Urology, Department of Surgery (Urology) and Pediatrics, University of North Carolina, 428 Burnett-Womack Bldg. 229H, Chapel Hill, North Carolina 27514. tRequests for reprints: Mayo Clinic, 200 First St. S. W., Rochester, Minnesota 55905
treatment elsewhere and they were referred at various intervals after attempted primary closure of the bladder. Initial management consisted of primary bladder closure in 32 patients: 26 underwent primary closure at our clinic, 5 had undergone successful primary closure elsewhere, and 1 had failure of initial closure and underwent successful re-closure of the bladder after referral (table 1). Closed bladder exstrophy was maintained in 24 patients (75 per cent), whereas 8 had subsequent urinary diversion. The factors that led to secondary urinary diversion are outlined in table 2. Of the patients 71 underwent primary urinary diversion (table 3), including 14 (20 per cent) who required secondary diversion (table 4). The final urological anatomy of all 103 patients is outlined in table 5. RESULTS
Urinary continence. Urinary continence was defined as the ability to remain dry for 3 or more hours. Occasional episodes of daytime or nighttime incontinence (for example, 1 episode a week) were not considered to represent failure at achieving continence. Patients with minor stress incontinence (protection necessary only with considerable physical activity, such as exercise) were considered continent. Of the 32 patients who underwent primary bladder closure 8 (25 per cent) required diversion, 6 (18.75 per cent) are awaiting a further operation, 12 (37.5 per cent) are continent, 3 (9.375 per cent) are partially continent and 3 are incontinent. A closed exstrophic bladder was maintained in 24 patients and vesical neck reconstruction had been completed in 18. Of the latter 18 patients 12 (10 male and 2 female patients, 67 per cent) had complete urinary continence (greater than 3 hours), 3 (2 male and 1 female patients) had partial continence (1 to 3 hours) and 3 were incontinent. Each of the 3 incontinent patients is a candidate for augmentation cystoplasty. 15 The number of operations in these patients undergoing vesical neck reconstruction ranged from O to 2. Five patients were contine:qt after bladder closure alone and they did not require bladder neck reconstruction. Two patients required more than 1 operation. One patient required 2 bladder neck reconstructions.
719
720
MESROBIAN, KELALIS AND KRAMER
TABLE
1. Initial form of management in 103 patients with exstrophy
Initial Treatment :l?rimary closure (neonatal closure) Urinary diversion Totals
Boys
Girls
Totals
22 (10)
10 (5)
32 (15)
41
30
71
63
40
103
Factors that led to urinary diversion after primary closure
TABLE 2.
Female Pts. Massive reflux with hydronephrosis Wound dehiscence Vesical neck contracture Staged colon conduit (Arap) Totals
TABLE
4
2 0 0
0 1
2 1 1
5
3
8
3. Forms of initial urinary diversion Female Pts.
Male Pts.
20 5
29 7
Total No. (%)
49 (69) 12 (17)
2
1
3
1 2 0 1
2 0 1 0
3 2
(4)
31
40
(4) (3) (L5) 1 (L5) 71 (100.0)
4. Factors that led to re-diversion after primary diversion Cause of Failure
Male Pts.
Female Pts.
Totals
BilaL obstruction Urinary incontinence Colonic polyp Bilat. obstruction Urinary incontinence Bilat. obstruction
3 0 0 0 1 1
5
8
1 2 0
2
0
1
5
9
14
Initial Form U reterosigmoidostomy
Cutaneous ureterostomy Heitz Boyer-Hovelacque Totals
TABLE
Totals
3
Ureterosigmoidostomy Ilea! conduit Boyce-Vest Heitz Boyer-Hovelacque U reterostomy Sigmoid conduit Vesico-ileo-sigmoidostomy Totals
TABLE
Male Pts.
1
5. Final urological anatomy of 103 patients with exstrophy Female Pts.
Closed bladder U reterosigmoidostomy Ilea! conduit Cutaneous ureterostomy Boyce-Vest Sigmoid conduit Internal sigmoid conduit Vesico-ileo-sigmoidostomy Bilat. nephrostomy Heitz Boyer-Hovelacque Totals
4
14 14 3 2 0 1
0 1 40
Male Pts. 20 26 12 2
0 0 1 0
63
Totals 24 40
26 5 3 1 1 1 1 1 103
Of 40 patients with ureterosigmoidostomy 33 (83 per cent) were continent of urine and stool. Five male and 2 female pa,sn,rn,~ were incontinent and required protective padding. The ages of these 7 patients were 15 to 52 years (average age 37 Of the 3 patients who underwent a Boyce-Vest reconstruction was continent, 1 was incontinent and 1 was lost to followup. The patient who underwent a Heitz Boyer-Hovelacque procedure was incontinent of urine and stool. Both patients with internal diversion (sigmoidosigmoidostomy and vesico-ileo-sigmoidostomy) were continent. Renal function. Renal function was assessed by measure-
ments of serum creatinine (normal values 0.8 to 1.2 mg./dL), blood urea nitrogen (BUN, normal values 8 to 24 mgJdL) and electrolytes, and by review of the most recent excretory urograms (IVPs) or radioisotopic renal scans. The patients were divided into 4 groups according to the type of operation. Group 1 consisted of 24 patients in whom a closed exstrophic bladder was maintained. The interval from primary bladder closure to patient evaluation was 6 months to 17 years (average 8 years). All 24 patients had normal serum creatinine values, while 18 (75 per cent) had normal IVPs and 6 (25 per cent) had hydronephrosis. Vesicoureteral reflux was common and it occurred in 11 patients (46 per cent). This subgroup of patients requires long-term followup to detect deterioration of the upper tracts with time. Group 2 consisted of 40 patients who underwent ureterosigmoidostomy. The interval from ureterosigmoidostomy to patient evaluation was 4 to 53 years (average 28 years). Serum creatinine values, available in 19 patients, were between 0.8 and 13.5 mgJdL (average 1.84 mg./dl.). Serum BUN, available in 16 patients, was 16 to 486 mgJdL (average 80 mg./dl.). Eight patients had significant renal failure (BUN greater than 60 mg./dL or serum creatinine greater than 3 mgJdL). Eighteen patients (45 per cent) had significant hyperchloremic metabolic acidosis and 29 (73 per cent) had abnormal IVPs (hydronephrosis in 36 renal units and renal atrophy in 14 renal units). Nine patients (23 per cent) lost 1 renal unit each. Eight patients had renal calculi (20 per cent). Four patients (10 per cent) died ofrenal failure 4, 5, 12 and 27 years after ureterosigmoidostomy. Group 3 consisted of 26 patients with an ileal conduit. The interval from construction of the ileal conduit to evaluation was 1 to 30 years (average 13 years). Serum creatinine values, available in 16 patients, were 0.7 to 3.0 mg./dl. (average 1.2 mg./dL). The remaining 9 patients had serum BUN values of 20 to 63 mgJdL (average 43 mg./dL). Only 1 patient in this group had significant renal insufficiency (creatinine concentration greater than 3.0 mgJdl.). Eighteen patients (69 per cent) had abnormal IVPs: hydronephrosis was present in 27 renal units and renal atrophy was present in 9 units. Renal calculi were detected in 7 units. All renal units evaluated had vesicoureteral reflux. Seven patients (27 per cent) lost l renal unit each and only 1 patient had significant chronic renal failure, which caused death when he was 15 years old. One patient died of an undetermined cause when he was 21 years old. In Group 4, a heterogeneous group of 13 patients with various forms of internal and external urinary diversion, followup since reconstruction was 1 to 32 years (average 17 years). Serum creatinine values, available in 11 patients, were 0.4 to 3.1 mg./ dL (average 1.3 mgJdL). Serum BUN in 3 patients was 30 to 45 mg./dl. (average 37 mg./dl.). Two patients had hyperchloremic metabolic acidosis. Five patients (38 per cent) had abnormal IVPs: hydronephrosis was present in all 10 renal units and renal atrophy occurred in 5 units. Reflux was present in only 1 renal unit in the patient with the sigmoid conduit. None of the patients required nephrectomy. Urinary tract infections. The incidence of significant urinary tract infections resulting in clinical pyelonephritis (fever) or renal scarring was reviewed for each group. Over-all, 46 of 103 patients (45 per cent) had significant infections. The incidence of infections by subgroup was 26 per cent in group 1, 63 per cent in group 2, 48 per cent in group 3 and 21 per cent in group 4. Malignant lesions. Eight patients had malignant lesions, 4 of which were adenocarcinoma of the bladder. Of the patients with adenocarcinoma 3 had failed neonatal bladder closure and they did not receive further treatment. One patient had not been treated before he was 31 years old, when a fungating mass was found arising in the exstrophic bladder. These 4 patients were 31 to 52 years old (average age 42 years). Of these patients 2 died of metastatic disease. In 1 patient carcinoma in situ of the bladder remnant was diagnosed when he was 28 years old.
LONG-TERM FOLLOWUP OF 103 PATIENTS WITH BLADDER EXSTROPHY
Ureterosigmoidostomy had been done when he was 3 years old without concomitant cystectomy and he died of metastatic disease 2 years after diagnosis. Colonic polyps developed in 3 of 40 patients with ureterosigmoidostomy. Two patients had a benign colonic polyp 11 and 21 years after ureterosigmoidostomy, and 1 had a malignant colonic polyp 26 years after ureterosigmoidostomy. None of these patients died. Associated arwmalies. Of the patients 10 per cent had associated anomalies: 2 had spina bifida and 9 had 1 associated anomaly each, including ventricular septal defect, rectal septum, hypertelorism, imperforate anus, omphalocele, rudimentary uterus, absent vagina, diphallia and microcorpora. Mortality. A total of 14 patients (13 per cent) had died at the time of this review: 7 of renal failure, 4 of malignant disease and 3 of undetermined causes. DISCUSSION
More than any other urological abnormality, bladder exstrophy requires long-term followup for accurate assessment of the natural history of the disease, and the successes and failures of surgical intervention. Factors, such as urinary continence, renal function, urinary tract infections and the development of malignant disease, must be evaluated years after initial treatment. Because of the great variability of bladder exstrophy and of the age of the patient at reconstruction, there remains no single acceptable method of initial treatment. The most common method of treatment in our series was ureterosigmoidostomy (40 patients). Although the highest continence rate was achieved in this group, 33 of 40 (83 per cent), deterioration of renal function was highest in these patients, with 70 per cent of the evaluable renal units being abnormal. Furthermore, 10 per cent of these patients died of renal failure and 23 per cent lost 1 renal unit each. Despite recent improvements in surgical technique 12 the results of our long-term followup (average 28 years) tend to discourage the use of ureterosigmoidostomy as the primary method of choice in children with bladder exstrophy. Furthermore, the 8 per cent incidence of colonic neoplasia in our group is worrisome and parallels the risk of malignancy documented in other series with long-term followup. 16-18 Ileal conduit urinary diversion was the second most frequent method of treatment (26 patients). Of these patients 69 per cent had either hydronephrosis or renal atrophy on an IVP and 27 per cent lost 1 renal unit each. The significant long-term risks of reflux, pyelonephritis, renal scarring, calculi and hypertension, and the necessity for an external appliance make the use of _this form of urinary diversion unacceptable for young children with bladder exstrophy. 19 We have not performed an ileal conduit procedure for the treatment of bladder exstrophy since 1974. Among our 32 patients who underwent primary bladder closure closed bladder exstrophy was maintained in 24. The techniques of primary bladder closure with or without bilateral iliac osteotomy have been well described. 20 • 21 Of 18 patients in whom vesical neck reconstruction was completed 12 (67 per cent) were dry, 3 (17 per cent) had partial (1 to 3 hours) continence and none required intermittent self-catheterization. Although bilateral iliac osteotomy was not used uniformly in our series, our results did not indicate that this procedure was associated with increased urinary continence. Fourteen patients had bilateral iliac osteotomy: 4 were continent, 3 had partial continence and 7 were incontinent. Of the 7 incontinent patients 6 had undergone permanent urinary diversion. Eight patients underwent urinary diversion after failure of primary bladder closure (table 2) and 3 of these patients are candidates for urinary undiversion by use of augmentation cystoplasty. Our treatment of choice for children with bladder exstrophy is neonatal closure in the first 24 to 48 hours. Primary bladder closure should be done in virtually all patients irrespective of
721
bladder size. Our experience and that of others9 is that even bladder capacities of 5 ml. often enlarge rapidly after closure and subsequent distension with urine. We do not use bilateral ileac osteotomy routinely, and we have reserved this technique for difficult closures and for children seen after 7 to 10 days of life. All children are immobilized with modified Bryant's traction and liberal use of sedation with belladonna and opium rectal suppositories. With this technique we have not encountered any instances of wound dehiscence or bladder prolapse without iliac osteotomy in 10 consecutive neonatal bladder closures. Between primary bladder closure and a patient age of 3 years children are monitored carefully with serum electrolyte determinations, urine culture studies, ultrasound examinations and dimercaptosuccinic acid renal scans. When the patient is 3 years old we proceed with reconstruction of the bladder neck and bilateral ureteral reimplantation. Our experience has been that bladder size remains the single most important factor related to urinary continence. 22 In boys with small bladders preliminary urethroplasty has not produced sufficient outlet resistance to increase bladder capacity. We currently use bladder augmentation at the time of vesical neck reconstruction in children with small bladder capacities. We have used this technique in 6 recent patients and have had extremely gratifying results in short-term followup. 23 Five children are completely dry and 1 has partial continence. Each of these 6 children is being managed successfully with intermittent catheterization. Urodynamic studies involving closed bladder exstrophy24• 25 have provided objective methods to assess hyperreflexia and bladder compliance in children who remain incontinent postoperatively. These children should be treated initially with drugs and if they are unsuccessful they should be considered candidates for enterocystoplasty. The occurrence of adenocarcinoma of the bladder in 4 of our patients parallels previous reports that have demonstrated an appreciable risk of malignancy in the exstrophic bladder left open. 26 Bladder exstrophy ideally should be closed when the patient is a neonate but if permanent internal or external urinary diversion becomes necessary the exstrophic bladder should be removed. CONCLUSIONS
We reviewed our experience and long-term followup of a large series of patients with bladder exstrophy. Whereas others have dealt primarily with the successes of primary bladder closure, large reviews rarely have discussed the fate of the failed bladder exstrophy and the management of those complications. The options of internal and external diversion have been associated with significant deterioration in renal function when followup has been long-term. Clearly, primary bladder closure, ideally in the neonate, is the preferred treatment for children with bladder exstrophy. Our experience with primary bladder closure has been excellent, with 84 per cent of the patients having complete or partial urinary continence. Renal function was preserved in 31 of 32 patients. Bladder augmentation at the time of vesical neck reconstruction for children with marginal bladder capacities has provided extremely gratifying short-term results. Enterocystoplasty can avoid the long-term sequelae of urinary diversion, preserve renal function and improve the quality of life in children born with bladder exstrophy. REFERENCES
1. Arap, S., Martins Giron, A. and Menezes de Goes, G.: Initial results
of the complete reconstruction of bladder exstrophy. Urol. Clin. N. Amer., 7: 477, 1980. 2. Hendren, W. H.: Exstrophy of the bladder. Birth Defects, 13: 207, 1977. 3. Boyce, W. H. and Kroovand, R. L.: The Boyce-Vest operation for exstrophy of the bladder: 35 years later. Urol. Clin. N. Amer., 13: 307, 1986.
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4. Cendron, J.: Bladder exstrophy from an external to an internal diversion. Birth Defects, 13: 197, 1977. 5. Gregoir, W. and Schulman, C. C.: Exstrophy of the bladder: treatment by trigonosigmoidostomy-long-term results. Brit. J. Urol., 50: 90, 1978. 6. Tacciuoli, M., Laurenti, C. and Racheli, T.: Sixteen years' experience with the Heitz Boyer-Hovelacque procedure for exstrophy of the bladder. Brit. J. Urol., 49: 385, 1977. 7. Battke, H. and Stadie, G.: Cystosigmoidostomy: indications and results. Int. Urol. Nephrol., 9: 303, 1977. 8. Lima, S. V. C., Noroes, J. A. A., Carvalheira, F. and de Mendon~a, P. P.: Bladder exstrophy: primary reconstruction with human dura mater. Brit. J. Urol., 53: 119, 1981. 9. Jeffs, R. D.: Functional closure of bladder exstrophy. Birth Defects, 13: 171, 1977. 10. Mollard, P., Sarkissian, J. and Loras, 0.: Reconstruction vesicale pour exstrophie. J. d'Urol., 87: 199, 1981. 11. Ansell, J. S.: Surgical treatment of exstrophy of the bladder with emphasis on neonatal primary closure: personal experience with 28 consecutive cases treated at the University of Washington Hospitals from 1962 to 1977: techniques and results. J. Urol., 121: 650, 1979. 12. Segura, J. W. and Kelalis, P. P.: Long-term results of ureterosigmoidostomy in children with bladder exstrophy. J. Urol., 114: 138, 1975. 13. Spence, H. M. and Hoffman, W. W.: Exstrophy of the urinary bladder treated by ureterosigmoidostomy: long-term follow-up in a series of 37 cases. Birth Defects, 13: 185, 1977. ' 14. Mesrobian, H.-G. J., Kelalis, P. P. and Kramer, S. A.: Long-term followup of cosmetic appearance and genital function in boys with exstrophy: review of 53 patients. J. Urol., 136: 256, 1986. 15. Gearhart, J.P., Albertsen, P. C., Marshall, F. F. and Jeffs, R. D.: Pediatric applications of augmentation cystoplasty: the Johns Hopkins experience. J. Urol., 136: 430, 1986. 16. Warren, R. B., Warner, T. F. C. S. and Hafez, G. R.: Late devel-
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