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Prospective Followup in Patients After Complete Primary Repair of Bladder Exstrophy
Prospective Followup in Patients After Complete Primary Repair of Bladder Exstrophy Patricio C. Gargollo, Joseph G. Borer,* David A. Diamond, W. Hardy Hendren, Ilina Rosoklija, Rosemary Grant and Alan B. Retik From the Departments of Urology and Surgery (WHH), Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts
Purpose: The new technique of complete primary repair of bladder exstrophy has offered the promise of improved bladder functional outcomes and yet longitudinal followup in patients with exstrophy who have undergone this form of closure is sparse. We present our median 5-year data on patients who have undergone complete primary repair of bladder exstrophy. Materials and Methods: The records of patients who underwent complete primary repair of bladder exstrophy were analyzed retrospectively. Patients were followed prospectively using case report forms, radiological and clinical data, and semistructured parental and patient interviews. We reviewed parameters including clinical events, scarring on renal scan, vesicoureteral reflux, surgical procedures, urodynamic studies, urinary and fecal continence status, and episodes of urinary tract infection. Results: From 1994 to 2007 complete primary repair of bladder exstrophy was performed in 32 patients. Of these patients 28 underwent closure within 72 hours of life, including 20 males and 8 females, and 4 underwent it after 72 hours at ages 7 days to 12 months. One patient underwent complete primary repair of bladder exstrophy elsewhere. Median followup was 5 years (range 1 to 13). In 32 patients a total of 193 surgical procedures were done, of which 40% were minor endoscopic cases. Six of 23 males (26%) underwent bladder neck reconstruction at a median age of 4.5 years (range 4 to 10). Two boys and 1 girl received Deflux® injection to the bladder neck at ages 3 to 5 years. To date no patient has undergone bladder augmentation. Nine patients (28%) had 1 to 4 episodes of pyelonephritis and 6 had cortical defects on renal scan. A total of 30 patients were voiding or incontinent via the urethra. One patient performed clean intermittent catheterization via the urethra and 1 performed it via appendicovesicostomy. All 4 children who were at least 6 months from bladder neck reconstruction after complete primary repair of bladder exstrophy had urinary continence periods of 2 to 3 hours or greater. Parents did not report any fecal incontinence or soiling in children older than 4 years. Relative to males the females had better urinary continence and a decreased need for bladder neck reconstruction. Conclusions: Complete primary repair of bladder exstrophy has been shown to be safe and efficacious. Prospective followup in this small number of evaluable patients reveals that continence periods of more than 2 hours are possible in patients after bladder neck reconstruction. Long-term followup in patients after complete primary repair of bladder exstrophy continues to be necessary to establish the long-term effects of this procedure. Key Words: urinary bladder, bladder exstrophy, reconstructive surgical procedures, complications, abnormalities
atients with BE present with complex management issues beginning in the newborn period. Some controversy exists as to the ideal surgical technique for initial repair. Some groups favor MSRE, in which the bladder plate and posterior urethra are closed as the initial step with the subsequent steps of epispadias repair and finally BNR.1,2 Groups at several centers have advocated CPRE.3,4 CPRE involves closure of the bladder plate and epispadias repair. In some cases ureteral reimplantation is also performed at CPRE. Further controversy exists regarding the use, timing and specific type of iliac osteotomy in the newborn period.1,5 Despite these controversies the goals of reconstruction remain to provide an adequate reservoir for urinary emptying, create functional and cosmetically acceptable external genitalia, and preserve renal function.
P
Study received institutional review board approval. * Correspondence: Department of Urology, Children’s Hospital Boston, 300 Longwood Ave., Boston, Massachusetts 02115 (telephone: 617-355-7796; FAX: 617-730-0474; e-mail: joseph.borer@ childrens.harvard.edu).
0022-5347/08/1804-1665/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
Although initial results in patients after CPRE have been published,6 longitudinal outcomes such as further surgery, and renal and bladder function with continence status have not been thoroughly discussed or universally included in the CPRE literature. We provide a detailed analysis of our cohort of patients with CPRE.
MATERIALS AND METHODS From 1994 to 2007 all patients with BE were treated with complete primary repair. CPRE was performed with the incorporation of modifications to a technique that has previously been described.7,8 Our technique of CPRE has been previously described.6 It does not involve routine osteotomies in the newborn. A comprehensive BE database was generated using SPSS® Data Entry Builder™. The records of patients who underwent CPRE were initially analyzed retrospectively and then patients were followed prospectively through standardized case report forms. Data were obtained from hospi-
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Vol. 180, 1665-1670, October 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.05.076
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FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY
tal, departmental and computer records. The parameters examined included clinical events, surgical procedures and complications, and data from urodynamic studies. The radiographic studies examined included renal ultrasound, plain abdominal x-ray, magnetic resonance imaging of the pelvis and 99mtechnetium labeled DMSA renal scans. All reflux grades were recorded using the international system for VUR grading.9 Radionuclide cystogram reflux grades 1, 2 and 3 were converted to voiding cystourethrogram grades 1 to 3 and 4 or 5, respectively, by 1 of us (JB or PG). Semistructured parental and patient interviews were performed at each clinic visit to assess urinary and fecal continence status. Figure 1 shows our protocol for followup evaluation. BC and PPBC For voiding cystourethrogram, radionuclide cystogram and UDS actual BC was recorded as the volume of fluid instilled or infused at the onset of voiding. Predicted BC for age was calculated using a previously published formulas for age specific predicted values.10 For age younger than 2 years BC in ml ⫽ [(2 ⫻ (age in years) ⫹ 2] ⫻ 30 and for age 2 years or older BC in ml ⫽ ([(age in years)/2] ⫹ 6) ⫻ 30. BC was converted to PPBC to eliminate the confounding variable of age during comparison. PPBC was calculated using the formula, PPBC ⫽ (actual recorded capacity/predicted capacity) ⫻ 100. UDS UDS was performed in all patients as previously described.11 Bladder compliance was calculated as the change in volume from outset of the CMG filling phase to capacity (⌬V) divided by the change in detrusor pressure (⌬P) from
the outset of filling to pressure at capacity (end filling pressure), such that bladder compliance in ml/cm H2O ⫽ ⌬V/⌬P. Detrusor overactivity was defined as any detrusor contraction occurring during the CMG filling phase. Synergic vs dyssynergic interaction between the detrusor and external urethral sphincter muscle was assessed during the CMG voiding phase in patients who were simultaneously evaluated with needle EMG. The characterization of motor unit potentials and sacral reflex evaluation were included in the EMG evaluation. EMG was only performed early in our experience since all 13 initial patients were found to have synergic voiding.6 Statistical analysis was performed using SPSS® 15.0. To compare differences in proportions experiencing a specific outcome across categories Fisher’s exact test was used. A linear regression model was used to establish whether there was a correlation between patient age and PPBC. Means between groups were compared by the 2-sample t test.
RESULTS From 1994 to 2007 we treated 23 male and 9 female patients who underwent CPRE for BE. All except 1 patient underwent CPRE at our institution. Three of 32 patients (9%) were siblings of a twin pregnancy and 16 of 32 (50%) were diagnosed prenatally with ultrasound. This prenatal diagnosis was subsequently confirmed by magnetic resonance imaging in 4 patients. One patient was black, 2 were Hispanic and 29 were white. Median followup was 5 years (range 3 months to 13 years). A total of 28 patients underwent CPRE within 72 hours after birth without osteotomies.
Pre- and Postoperative Evaluation Protocol for CPRE Patients Study ID: __ __ __ - __ Date of Complete Primary Repair: ____/____/________ STUDY
Pre- 3 3 6 1 2 3 4 5 6 7 8 9 op wks mos mos yr yrs yrs yrs yrs yrs yrs yrs yrs
10 yrs
RUS Plain abd x-ray MRI of Pelvis
**
VCUG
Combined UDS, RNC
*
DMSA renal scan CMC, electrolytes,Creatinine Surgical Procedure†
FIG. 1. Preoperative and postoperative followup protocol in patients with CPRE
*
FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY
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TABLE 1. Endoscopic and surgical procedures beyond CPRE Procedure
No. Pts
Mean ⫾ SD Mos Age (range)
Examination with anesthesia without cystourethroscopy Cystourethroscopy Cystourethroscopy and UDS catheter Cystourethroscopy with calibration ⫹/or dilation of ureteral stricture or stenosis Direct vision internal urethrotomy Inguinal hernia repair Hypospadias repair Bilat Cohen ureteroneocystostomy Bilat cephalotrigonal ureteroneocystostomy Meatotomy/meatoplasty Buried penis repair Endoscopic injection of implant material into urethra ⫹/or bladder neck submucosal tissue Proximal ventral urethrocutaneous fistula excision Free skin graft to penis Minor cosmetic scrotal plastic operation of penis Orchiopexy Monsplasty Young-Dees-Leadbetter bladder neck reconstruction Urethral diverticulum excision Suprapubic cystotomy with bladder stone removal Umbilicoplasty Abdominal scar revision Glanuloplasty Repeat bladder exstrophy closure with bilat posterior iliac osteotomy Appendicovesicostomy Urethroplasty using bladder mucosa Urethroplasty using acellular matrix Urethral dehiscence repair Chordee repair Female epispadias repair Female genitoplasty repair of dehiscence Vaginoplasty Perineal anoplasty Distal dorsal urethrocutaneous fistula excision Major plastic reconstruction of penis with local skin flaps only
6 31 30 10 2 19 12 10 8 6 4 3 2 2 2 4 2 6 2 3 8 2 2 1 1 1 1 1 1 1 1 1 1 1 1
22.5 ⫾ 19.5 (1–53) 38.6 ⫾ 20.2 (3–154) 46.1 ⫾ 38.7 (0–126) 30 ⫾ 21.7 (1.0–73) 108 ⫾ 65.7 (61–154) 9.5 ⫾ 20.5 (0–75) 17.6 ⫾ 5.6 (10.0–24.9) 35.9 ⫾ 32.9 (0–100) 35 ⫾ 31.2 (0–67) 40 ⫾ 17.0 (19–62.0) 23 ⫾ 17.1 (8–49) 45 ⫾ 14.0 (30–64) 24.4 ⫾ 13.4 (14.9–33.9) 29.0 ⫾ 29.0 (8.5–49.4) 18.7 ⫾ 17.0 (6.7–30.7) 24.5 ⫾ 34.7 (0–49) 47.6 ⫾ 24.2 (30.5–64.7) 66.2 ⫾ 19.8 (48–120) 87 ⫾ 91.2 (22–152) 79 ⫾ 6.1 (72–83) 34.1 ⫾ 38 (0–100) 110 ⫾ 60.1 (67–152) 58.7 ⫾ 6.0 (54.4–63.0)
Total
193
Four patients who received CPRE between ages 7 days and 12 months underwent posterior iliac osteotomies at CPRE.
BNR was 108 ml. All patients underwent UDS with CMG before BNR.
Surgical Procedures Following CPRE 32 patients underwent a total of 193 surgical procedures (table 1). Of these procedures 40% were minor endoscopic procedures. Of the patients 44% underwent fewer than 5 procedures after CPRE and 82% underwent 10 or fewer after CPRE (table 2). Most surgeries were clustered at younger ages (table 1). Two boys and 1 girl received Deflux injection to the bladder neck at ages 3 to 5 years. To date no patient has undergone bladder augmentation. One underwent appendicovesicostomy at BNR. Following CPRE 17 patients underwent bilateral ureteral reimplantation, which was done in 9 by the Cohen technique and in 8 using a cephalotrigonal technique, including in 6 at BNR. Six of the remaining 15 patients had unilateral VUR, 6 had bilateral VUR and 3 had no reflux.
Renal Function and Hydronephrosis Nine of 32 patients (28%) had 1 to 4 episodes of pyelonephritis and 6 (19%) had cortical defects on renal scan, which was bilateral and unilateral in 3 each. Seven patients had mild to moderate hydronephrosis on the last renal ultrasound, which was bilateral and unilateral in 4 and 3, respectively.
BNR Our indications for BNR were persistent incontinence after attempted toilet training, evidence of inadequate bladder outlet resistance on UDS, and a child and family who were willing to take part in the postoperative voiding and catheterization regimen, if necessary. In general BC before BNR was 100 ml or greater. One patient in our series had a BC of 60 ml before BNR. Six males (26%) underwent BNR via a modified Young-Dees-Leadbetter technique at a median age of 5 years (range 4 to 10). Median BC in these patients at
UDS and Bladder Function Of the patients 27 underwent a total of 88 UDS (median 3, range 0 to 8). A total of 13 patients underwent sphincter EMG at UDS, which revealed normal motor unit potentials, normal sacral reflexes and normal synergy with voiding. Detrusor overactivity was noted in 2 of 27 cases (7%). All except 1 male patient had a BC of less than 70% of the predicted value for age. Figure 2 shows a linear regression analysis of PPBC vs age, which showed a significant positive correlation between these variables (p ⫽ 0.003). Continence A total of 31 patients voided or were incontinent via the urethra. One patient performed CIC via the urethra and 1 performed CIC via an appendicovesicostomy. Dry interval data were available as reported by a caretaker or witnessed by a medical professional on all 21 patients, including 14 boys and 7 girls 4 years or older. A dry interval was estimated as less than 1 hour in 7 patients, 1 to 2 hours in 6, 2
FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY TABLE 2. Procedures beyond CPRE
No. Procedures
No. Pts (%)
0–5 6–10 11–15 16–20 Greater than 20
14 (44) 12 (38) 2 (6) 3 (9) 1 (3)
Total
32 (100)
to 3 hours in 4 and more than 3 hours in 4. Relative to males the females had a decreased need for BNR (p ⫽ 0.05). The mean ⫾ SD continent intervals in males and females were not statistically significantly different (2.1 ⫾ 1.2 and 1.8 ⫾ 1.1, respectively, p ⫽ 0.55). When comparing dry intervals after CPRE, only 4 of 21 children (19%) older than 4 years had 3-hour or greater urinary continence periods. After CPRE and BNR 1 of 4 evaluable patients with more than 6 months of followup after BNR had more than 3-hour continent intervals and 3 had dry periods of 2 to 3 hours. Parents did not report any fecal incontinence or soiling in children older than 4 years. DISCUSSION Published series of outcomes after CPRE have been limited to short-term followup studies.6,12 We present our prospective experience with a cohort of patients with BE followed at 1 center for a median of 5 years. When evaluating outcomes in patients with BE, several factors must be evaluated. The goals of reconstruction are to create a bladder that can store urine and provide adequate continence, generate functional and cosmetically acceptable genitalia, and preserve renal function. Therefore, outcomes in these physiological parameters must be examined and the means to accomplish these end points must be addressed. Knowing the number and types of surgery that patients with BE undergo is important information when establishing clinical care plans and counseling parents as to what should be expected in the future of their child. Ebert et al reported that the mean number of operations performed in their patients after MSRE was 2.95 (range 1 to 8) with only 13.6% requiring more than 4 surgeries.13 However, because this information was obtained from self-reports by patients, it is unclear whether they reported all of the procedures that they had undergone. It is also not stated whether these were major or minor surgeries requiring general anesthesia. Stjernqvist and Kockum reported that children in their MSRE series underwent a median of 12 procedures.14 In a group of 80 patients treated with staged repair others reported that 48% required further surgery after BNR. In a questionnaire study of 122 patients with BE and CE Lee et al noted that of younger patients 0 to 4 and 5 to 13 years old males received more interventions than females (mean 3 and 5 respectively).15 Of older patients 16 to 20 and older than 20 years females underwent more surgical interventions than males (mean 7 vs 3.5).15 They attributed the higher rate in older females to procedures such as genitoplasty and monsplasty as well as to vaginal dilation. Our 32 patients with CPRE underwent a total of 193 surgical procedures (mean 4 ⫾ 5.8, range 1 to 31). It must be emphasized that 40% of these surgeries were minor endoscopic procedures. Of our patients 82% underwent 10 or
fewer procedures after CPRE. When examining the distribution of procedures by age, it was noted that most surgeries in our group were clustered before age 4 years (table 1). Therefore, clearly there is wide variability in the number of surgeries that should be expected in patients with BE. Based on our and other published series it is reasonable to assume that children with BE will undergo at least 3 to 6 procedures after the end of the staged repair cycle or CPRE. Recurrent urinary tract infections, pyelonephritis, hydronephrosis and upper tract function/cortical scarring have not been uniformly studied in all BE patient series. Early series using urinary diversion have shown significantly poor outcomes regarding renal function. In a series of 103 patients with BE Mesrobian et al reported a high incidence of renal deterioration with 70% and 69% of renal units abnormal in their ureterosigmoidostomy and ileal conduit groups, respectively.16 Furthermore, 10% of patients in the ureterosigmoidostomy group died of renal failure and 23% lost 1 kidney each. Most recent series have not specifically evaluated their patients with renal scintigraphy and, thus, renal damage in these groups is difficult to assess. We previously reported a high rate of pyelonephritis and an equally concerning rate of cortical defects on DMSA (each 22%) in our early experience after CPRE.6 Our current series shows a slightly decreased rate of cortical defects on DMSA and a higher rate of pyelonephritis (19% and 28%, respectively). Whether this was due to abnormal lower tract dynamics or other variables is still not clear and it warrants further evaluation. Adequate analysis of CPRE patient outcomes regarding renal function will likely require further prospective evaluation with a protocol such as ours that includes serial nuclear renal scan, ultrasound, voiding cystourethrogram, UDS and serum evaluation of renal function (fig. 1). We have previously reported that bladder growth appeared to be equivalent when comparing PPBC in patients after CPRE or MSRE with time.11 In the current study we noted that all patients except 1 male had a PPBC for age that was less than 70%. Linear regression analysis of PPBC vs age revealed a statistically significant positive correlation
Percent Predicted Bladdder Capacity by Age
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R square =0.3
80
60
40
20
0
4
8
12
Age at Study (years) FIG. 2. Linear regression analysis of PPBC vs age in years showed significant positive correlation between these variables.
FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY with bladders increasing in capacity with time (fig. 2). This suggests that bladder growth after CPRE may be inadequate but it increases as patients become older. Bladder growth may also be a function of establishing adequate outlet resistance. Published urinary continence rates after BE repair are variable at 12% to 83%.17–21 There are various factors confounding these results, including patient age at bladder closure, the type of closure performed, the number and type of procedures required to establish continence, the need for concomitant bladder augmentation and the need for CIC. The situation is further confused in that there is no standard definition for continence and studies classify continence in a nonuniform way. Traditionally in the exstrophy literature continence has been defined as maintaining 3-hour or greater dry periods during the day with no stress incontinence. However, this is not the definition of continence established by the International Children’s Continence Society.22 One also wonders whether the requirement for CIC, previous bladder augmentation and multiple surgeries to achieve this continence should be treated as success or failure. Because of the lack of standard definitions, this remains a highly subjective measure of outcome. Bladder augmentation is a common adjunctive procedure performed in patients with BE to achieve continence and augmentation rates published in the literature are 0% to 82%.18,20,23 However, this is certainly not a normal physiological situation. Data on continence after CPRE are not as readily available as those after MSRE. Furthermore, the need for BNR after CPRE is not clear. In our initial series we found that 5 of 8 patients (63%) 4 years or older had grossly inadequate bladder outlet resistance and would likely need BNR.6 Grady et al reported that 72% of females and 86% of males who underwent CPRE as newborns eventually required BNR.4 In our current series BNR was performed in 6 males and it will likely be needed in 5 more patients, including 3 males and 2 females, so that at least 11 of 21 (52%) patients 4 years or older will likely require formal BNR to achieve sufficient bladder outlet resistance. Dry intervals have improved after CPRE and BNR with all 4 evaluable patients experiencing 2 to 3-hour or greater dry periods more than 6 months after BNR. In comparison dry intervals after CPRE only are 3 hours or greater in 4 of 21 patients (19%). This further suggests that CPRE alone does not provide sufficient outlet resistance to achieve urinary continence and BNR is required in most patients. In our patient population females had a decreased need for BNR. However, given our small cohort size, it is not clear whether this will continue to be the case at longer followup. Several studies of patients with BE have shown that gender may have a role in eventual continence with females showing a higher rate than males.17,24 We did not find that females had longer dry intervals than males in our cohort. As we have experienced, outcomes differ significantly and studies are confounded by patient recall and clinician bias. Most continence assessments are performed by surgeons, which is clearly not an ideal way to perform a valid study. We have designed a parent and patient based questionnaire to assess continence status, although this suffers from its lack of validation. For these reasons proper prospective trials must be designed using standardized and validated urinary continence questionnaires, which are becoming more readily available for use in the pediatric population.25
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CONCLUSIONS Mitchell, one of the pioneers of the CPRE technique, has stated, “We . . . believe that the need to catheterize, divert, or augment a patient with exstrophy should be considered a failure of the initial treatment and voiding with continence should be the anticipated norm. . . . Most exstrophy patients should anticipate normal voiding with few operations and have little regard for their condition at birth.”26 Although this quote represents the ideal situation, it often cannot be the anticipated norm, given that all of these patients have major abdominal, lower urinary tract and genital abnormalities requiring complex reconstruction. As more data become available, it is clear that most patients with BE will require multiple operations to achieve normal voiding and provide cosmetically acceptable and functional genitalia. The psychosexual status of mature patients with exstrophy remains an important unknown factor. Long-term followup in patients after CPRE continues to be necessary to establish the long-term and lifelong effects of this procedure.
Abbreviations and Acronyms BC BE BNR CIC CMG CPRE
⫽ ⫽ ⫽ ⫽ ⫽ ⫽
DMSA EMG MSRE PPBC UDS VUR
⫽ ⫽ ⫽ ⫽ ⫽ ⫽
bladder capacity bladder exstrophy bladder neck reconstruction clean intermittent catheterization cystometrogram complete primary repair of bladder exstrophy dimercapto-succinic acid electromyography modern staged repair of exstrophy percent predicted bladder capacity urodynamic studies vesicoureteral reflux
REFERENCES 1.
2.
3. 4.
5.
6.
7. 8.
Baker LA and Gearhart JP: The staged approach to bladder exstrophy closure and the role of osteotomies. World J Urol 1998; 16: 205. Mathews R and Gearhart JP: Modern staged reconstruction of bladder exstrophy—still the gold standard. Urology 2005; 65: 2. Pippi-Salle JL and Chan PT: One stage bladder exstrophy and epispadias repair in newborn male. Can J Urol 1999; 6: 757. Grady R, Joyner BD, Roedel M, Feng W, Casale P and Mitchell M: The complete primary repair of exstrophy (CPRE) technique for repair of bladder exstrophy and epispadias: longterm followup. Presented at meeting of American Academy of Pediatrics, New Orleans, Louisiana, November 1–5, 2003. Halachmi S, Farhat W, Konen O, Khan A, Hodapp J, Bagli DJ et al: Pelvic floor magnetic resonance imaging after neonatal single stage reconstruction in male patients with classic bladder exstrophy. J Urol 2003; 170: 1505. Borer JG, Gargollo PC, Hendren WH, Diamond DA, Peters CA, Atala A et al: Early outcome following complete primary repair of bladder exstrophy in the newborn. J Urol 2005; 174: 1674. Hendren WH: Penile lengthening after previous repair of epispadias. J Urol 1979; 121: 527. Grady RW and Mitchell ME: Complete primary repair of exstrophy. J Urol 1999; 162: 1415.
1670 9.
10.
11.
12.
13.
14. 15.
16.
17.
18. 19.
20.
21.
22.
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Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM and Tamminen-Mobius TE: International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 1985; 15: 105. Kaefer M, Zurakowski D, Bauer SB, Retik AB, Peters CA, Atala A et al: Estimating normal bladder capacity in children. J Urol 1997; 158: 2261. Borer JG, Gargollo PC, Kinnamon DD, Bauer SB, Khoshbin S, Hendren WH et al: Bladder growth and development after complete primary repair of bladder exstrophy in the newborn with comparison to staged approach. J Urol 2005; 174: 1553. Hammouda HM and Kotb H: Complete primary repair of bladder exstrophy: initial experience with 33 cases. J Urol 2004; 172: 1441. Ebert A, Scheuering S, Schott G and Roesch WH: Psychosocial and psychosexual development in childhood and adolescence within the exstrophy-epispadias complex. J Urol 2005; 174: 1094. Stjernqvist K and Kockum CC: Bladder exstrophy: psychological impact during childhood. J Urol 1999; 162: 2125. Lee C, Reutter HM, Grasser MF, Fisch M and Noeker M: Gender-associated differences in the psychosocial and developmental outcome in patients affected with the bladder exstrophy-epispadias complex. BJU Int 2006; 97: 349. Mesrobian HG, Kelalis PP and Kramer SA: Long-term followup of 103 patients with bladder exstrophy. J Urol 1988; 139: 719. Capolicchio G, McLorie GA, Farhat W, Merguerian PA, Bagli DJ and Khoury AE: A population based analysis of continence outcomes and bladder exstrophy. J Urol 2001; 165: 2418. Hollowell JG and Ransley PG: Surgical management of incontinence in bladder exstrophy. Br J Urol 1991; 68: 543. Lottmann HB, Melin Y, Cendron M, Lombrail P, BezeBeyrie P and Cendron J: Bladder exstrophy: evaluation of factors leading to continence with spontaneous voiding after staged reconstruction. J Urol 1997; 158: 1041. Surer I, Baker LA, Jeffs RD and Gearhart JP: Combined bladder neck reconstruction and epispadias repair for exstrophy-epispadias complex. J Urol 2001; 165: 2425. Shaw MB, Rink RC, Kaefer M, Cain MP and Casale AJ: Continence and classic bladder exstrophy treated with staged repair. J Urol 2004; 172: 1450. Neveus T, von Gontard A, Hoebeke P, Hjalmas K, Bauer S, Bower W et al: The standardization of terminology of lower
23.
24.
25.
26.
urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol 2006; 176: 314. McMahon DR, Cain MP, Husmann DA and Kramer SA: Vesical neck reconstruction in patients with the exstrophyepispadias complex. J Urol 1996; 155: 1411. Mouriquand PD, Bubanj T, Feyaerts A, Jandric M, Timsit M, Mollard P et al: Long-term results of bladder neck reconstruction for incontinence in children with classical bladder exstrophy or incontinent epispadias. BJU Int 2003; 92: 997. Nelson CP, Park J, Bloom DA, Wan J and Kieran K: Incontinence Symptom Index: development and initial validation of a urinary incontinence instrument for the pediatric population. Presented at meeting of American Academy of Pediatrics Section on Urology, Atlanta, Georgia, October 7–9, 2006. Mitchell ME: Bladder exstrophy repair: complete primary repair of exstrophy. Urology 2005; 65: 5.
EDITORIAL COMMENT CPRE adds considerably to the care of boys and girls with BE. When CPRE was first described (reference 8 in article), many hoped that this approach would provide continence with a single operation. This series shows that even in skilled hands multiple surgeries are required to provide continence and cosmetically acceptable genitalia while preserving renal function. MSRE and CPRE depend on successful initial bladder closure to provide enough bladder outlet resistance to ensure bladder cycling in the newborn period. Continence occurs only if an adequate bladder volume develops. In this series despite excellent CPRE BNR was required or will likely be required in most patients. Whether additional outlet resistance in the form of the injection of bulking agents to the bladder neck following successful CPRE can fine tune the bladder outlet and result in volitional voiding with little residual urine without BNR remains unclear. Douglas A. Canning Division of Urology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania
Purpose: The new technique of complete primary repair of bladder exstrophy has offered the promise of improved bladder functional outcomes and yet longitudinal followup in patients with exstrophy who have undergone this form of closure is sparse. We present our median 5-year data on patients who have undergone complete primary repair of bladder exstrophy. Materials and Methods: The records of patients who underwent complete primary repair of bladder exstrophy were analyzed retrospectively. Patients were followed prospectively using case report forms, radiological and clinical data, and semistructured parental and patient interviews. We reviewed parameters including clinical events, scarring on renal scan, vesicoureteral reflux, surgical procedures, urodynamic studies, urinary and fecal continence status, and episodes of urinary tract infection. Results: From 1994 to 2007 complete primary repair of bladder exstrophy was performed in 32 patients. Of these patients 28 underwent closure within 72 hours of life, including 20 males and 8 females, and 4 underwent it after 72 hours at ages 7 days to 12 months. One patient underwent complete primary repair of bladder exstrophy elsewhere. Median followup was 5 years (range 1 to 13). In 32 patients a total of 193 surgical procedures were done, of which 40% were minor endoscopic cases. Six of 23 males (26%) underwent bladder neck reconstruction at a median age of 4.5 years (range 4 to 10). Two boys and 1 girl received Deflux® injection to the bladder neck at ages 3 to 5 years. To date no patient has undergone bladder augmentation. Nine patients (28%) had 1 to 4 episodes of pyelonephritis and 6 had cortical defects on renal scan. A total of 30 patients were voiding or incontinent via the urethra. One patient performed clean intermittent catheterization via the urethra and 1 performed it via appendicovesicostomy. All 4 children who were at least 6 months from bladder neck reconstruction after complete primary repair of bladder exstrophy had urinary continence periods of 2 to 3 hours or greater. Parents did not report any fecal incontinence or soiling in children older than 4 years. Relative to males the females had better urinary continence and a decreased need for bladder neck reconstruction. Conclusions: Complete primary repair of bladder exstrophy has been shown to be safe and efficacious. Prospective followup in this small number of evaluable patients reveals that continence periods of more than 2 hours are possible in patients after bladder neck reconstruction. Long-term followup in patients after complete primary repair of bladder exstrophy continues to be necessary to establish the long-term effects of this procedure. Key Words: urinary bladder, bladder exstrophy, reconstructive surgical procedures, complications, abnormalities
atients with BE present with complex management issues beginning in the newborn period. Some controversy exists as to the ideal surgical technique for initial repair. Some groups favor MSRE, in which the bladder plate and posterior urethra are closed as the initial step with the subsequent steps of epispadias repair and finally BNR.1,2 Groups at several centers have advocated CPRE.3,4 CPRE involves closure of the bladder plate and epispadias repair. In some cases ureteral reimplantation is also performed at CPRE. Further controversy exists regarding the use, timing and specific type of iliac osteotomy in the newborn period.1,5 Despite these controversies the goals of reconstruction remain to provide an adequate reservoir for urinary emptying, create functional and cosmetically acceptable external genitalia, and preserve renal function.
P
Study received institutional review board approval. * Correspondence: Department of Urology, Children’s Hospital Boston, 300 Longwood Ave., Boston, Massachusetts 02115 (telephone: 617-355-7796; FAX: 617-730-0474; e-mail: joseph.borer@ childrens.harvard.edu).
0022-5347/08/1804-1665/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
Although initial results in patients after CPRE have been published,6 longitudinal outcomes such as further surgery, and renal and bladder function with continence status have not been thoroughly discussed or universally included in the CPRE literature. We provide a detailed analysis of our cohort of patients with CPRE.
MATERIALS AND METHODS From 1994 to 2007 all patients with BE were treated with complete primary repair. CPRE was performed with the incorporation of modifications to a technique that has previously been described.7,8 Our technique of CPRE has been previously described.6 It does not involve routine osteotomies in the newborn. A comprehensive BE database was generated using SPSS® Data Entry Builder™. The records of patients who underwent CPRE were initially analyzed retrospectively and then patients were followed prospectively through standardized case report forms. Data were obtained from hospi-
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Vol. 180, 1665-1670, October 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.05.076
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FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY
tal, departmental and computer records. The parameters examined included clinical events, surgical procedures and complications, and data from urodynamic studies. The radiographic studies examined included renal ultrasound, plain abdominal x-ray, magnetic resonance imaging of the pelvis and 99mtechnetium labeled DMSA renal scans. All reflux grades were recorded using the international system for VUR grading.9 Radionuclide cystogram reflux grades 1, 2 and 3 were converted to voiding cystourethrogram grades 1 to 3 and 4 or 5, respectively, by 1 of us (JB or PG). Semistructured parental and patient interviews were performed at each clinic visit to assess urinary and fecal continence status. Figure 1 shows our protocol for followup evaluation. BC and PPBC For voiding cystourethrogram, radionuclide cystogram and UDS actual BC was recorded as the volume of fluid instilled or infused at the onset of voiding. Predicted BC for age was calculated using a previously published formulas for age specific predicted values.10 For age younger than 2 years BC in ml ⫽ [(2 ⫻ (age in years) ⫹ 2] ⫻ 30 and for age 2 years or older BC in ml ⫽ ([(age in years)/2] ⫹ 6) ⫻ 30. BC was converted to PPBC to eliminate the confounding variable of age during comparison. PPBC was calculated using the formula, PPBC ⫽ (actual recorded capacity/predicted capacity) ⫻ 100. UDS UDS was performed in all patients as previously described.11 Bladder compliance was calculated as the change in volume from outset of the CMG filling phase to capacity (⌬V) divided by the change in detrusor pressure (⌬P) from
the outset of filling to pressure at capacity (end filling pressure), such that bladder compliance in ml/cm H2O ⫽ ⌬V/⌬P. Detrusor overactivity was defined as any detrusor contraction occurring during the CMG filling phase. Synergic vs dyssynergic interaction between the detrusor and external urethral sphincter muscle was assessed during the CMG voiding phase in patients who were simultaneously evaluated with needle EMG. The characterization of motor unit potentials and sacral reflex evaluation were included in the EMG evaluation. EMG was only performed early in our experience since all 13 initial patients were found to have synergic voiding.6 Statistical analysis was performed using SPSS® 15.0. To compare differences in proportions experiencing a specific outcome across categories Fisher’s exact test was used. A linear regression model was used to establish whether there was a correlation between patient age and PPBC. Means between groups were compared by the 2-sample t test.
RESULTS From 1994 to 2007 we treated 23 male and 9 female patients who underwent CPRE for BE. All except 1 patient underwent CPRE at our institution. Three of 32 patients (9%) were siblings of a twin pregnancy and 16 of 32 (50%) were diagnosed prenatally with ultrasound. This prenatal diagnosis was subsequently confirmed by magnetic resonance imaging in 4 patients. One patient was black, 2 were Hispanic and 29 were white. Median followup was 5 years (range 3 months to 13 years). A total of 28 patients underwent CPRE within 72 hours after birth without osteotomies.
Pre- and Postoperative Evaluation Protocol for CPRE Patients Study ID: __ __ __ - __ Date of Complete Primary Repair: ____/____/________ STUDY
Pre- 3 3 6 1 2 3 4 5 6 7 8 9 op wks mos mos yr yrs yrs yrs yrs yrs yrs yrs yrs
10 yrs
RUS Plain abd x-ray MRI of Pelvis
**
VCUG
Combined UDS, RNC
*
DMSA renal scan CMC, electrolytes,Creatinine Surgical Procedure†
FIG. 1. Preoperative and postoperative followup protocol in patients with CPRE
*
FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY
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TABLE 1. Endoscopic and surgical procedures beyond CPRE Procedure
No. Pts
Mean ⫾ SD Mos Age (range)
Examination with anesthesia without cystourethroscopy Cystourethroscopy Cystourethroscopy and UDS catheter Cystourethroscopy with calibration ⫹/or dilation of ureteral stricture or stenosis Direct vision internal urethrotomy Inguinal hernia repair Hypospadias repair Bilat Cohen ureteroneocystostomy Bilat cephalotrigonal ureteroneocystostomy Meatotomy/meatoplasty Buried penis repair Endoscopic injection of implant material into urethra ⫹/or bladder neck submucosal tissue Proximal ventral urethrocutaneous fistula excision Free skin graft to penis Minor cosmetic scrotal plastic operation of penis Orchiopexy Monsplasty Young-Dees-Leadbetter bladder neck reconstruction Urethral diverticulum excision Suprapubic cystotomy with bladder stone removal Umbilicoplasty Abdominal scar revision Glanuloplasty Repeat bladder exstrophy closure with bilat posterior iliac osteotomy Appendicovesicostomy Urethroplasty using bladder mucosa Urethroplasty using acellular matrix Urethral dehiscence repair Chordee repair Female epispadias repair Female genitoplasty repair of dehiscence Vaginoplasty Perineal anoplasty Distal dorsal urethrocutaneous fistula excision Major plastic reconstruction of penis with local skin flaps only
6 31 30 10 2 19 12 10 8 6 4 3 2 2 2 4 2 6 2 3 8 2 2 1 1 1 1 1 1 1 1 1 1 1 1
22.5 ⫾ 19.5 (1–53) 38.6 ⫾ 20.2 (3–154) 46.1 ⫾ 38.7 (0–126) 30 ⫾ 21.7 (1.0–73) 108 ⫾ 65.7 (61–154) 9.5 ⫾ 20.5 (0–75) 17.6 ⫾ 5.6 (10.0–24.9) 35.9 ⫾ 32.9 (0–100) 35 ⫾ 31.2 (0–67) 40 ⫾ 17.0 (19–62.0) 23 ⫾ 17.1 (8–49) 45 ⫾ 14.0 (30–64) 24.4 ⫾ 13.4 (14.9–33.9) 29.0 ⫾ 29.0 (8.5–49.4) 18.7 ⫾ 17.0 (6.7–30.7) 24.5 ⫾ 34.7 (0–49) 47.6 ⫾ 24.2 (30.5–64.7) 66.2 ⫾ 19.8 (48–120) 87 ⫾ 91.2 (22–152) 79 ⫾ 6.1 (72–83) 34.1 ⫾ 38 (0–100) 110 ⫾ 60.1 (67–152) 58.7 ⫾ 6.0 (54.4–63.0)
Total
193
Four patients who received CPRE between ages 7 days and 12 months underwent posterior iliac osteotomies at CPRE.
BNR was 108 ml. All patients underwent UDS with CMG before BNR.
Surgical Procedures Following CPRE 32 patients underwent a total of 193 surgical procedures (table 1). Of these procedures 40% were minor endoscopic procedures. Of the patients 44% underwent fewer than 5 procedures after CPRE and 82% underwent 10 or fewer after CPRE (table 2). Most surgeries were clustered at younger ages (table 1). Two boys and 1 girl received Deflux injection to the bladder neck at ages 3 to 5 years. To date no patient has undergone bladder augmentation. One underwent appendicovesicostomy at BNR. Following CPRE 17 patients underwent bilateral ureteral reimplantation, which was done in 9 by the Cohen technique and in 8 using a cephalotrigonal technique, including in 6 at BNR. Six of the remaining 15 patients had unilateral VUR, 6 had bilateral VUR and 3 had no reflux.
Renal Function and Hydronephrosis Nine of 32 patients (28%) had 1 to 4 episodes of pyelonephritis and 6 (19%) had cortical defects on renal scan, which was bilateral and unilateral in 3 each. Seven patients had mild to moderate hydronephrosis on the last renal ultrasound, which was bilateral and unilateral in 4 and 3, respectively.
BNR Our indications for BNR were persistent incontinence after attempted toilet training, evidence of inadequate bladder outlet resistance on UDS, and a child and family who were willing to take part in the postoperative voiding and catheterization regimen, if necessary. In general BC before BNR was 100 ml or greater. One patient in our series had a BC of 60 ml before BNR. Six males (26%) underwent BNR via a modified Young-Dees-Leadbetter technique at a median age of 5 years (range 4 to 10). Median BC in these patients at
UDS and Bladder Function Of the patients 27 underwent a total of 88 UDS (median 3, range 0 to 8). A total of 13 patients underwent sphincter EMG at UDS, which revealed normal motor unit potentials, normal sacral reflexes and normal synergy with voiding. Detrusor overactivity was noted in 2 of 27 cases (7%). All except 1 male patient had a BC of less than 70% of the predicted value for age. Figure 2 shows a linear regression analysis of PPBC vs age, which showed a significant positive correlation between these variables (p ⫽ 0.003). Continence A total of 31 patients voided or were incontinent via the urethra. One patient performed CIC via the urethra and 1 performed CIC via an appendicovesicostomy. Dry interval data were available as reported by a caretaker or witnessed by a medical professional on all 21 patients, including 14 boys and 7 girls 4 years or older. A dry interval was estimated as less than 1 hour in 7 patients, 1 to 2 hours in 6, 2
FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY TABLE 2. Procedures beyond CPRE
No. Procedures
No. Pts (%)
0–5 6–10 11–15 16–20 Greater than 20
14 (44) 12 (38) 2 (6) 3 (9) 1 (3)
Total
32 (100)
to 3 hours in 4 and more than 3 hours in 4. Relative to males the females had a decreased need for BNR (p ⫽ 0.05). The mean ⫾ SD continent intervals in males and females were not statistically significantly different (2.1 ⫾ 1.2 and 1.8 ⫾ 1.1, respectively, p ⫽ 0.55). When comparing dry intervals after CPRE, only 4 of 21 children (19%) older than 4 years had 3-hour or greater urinary continence periods. After CPRE and BNR 1 of 4 evaluable patients with more than 6 months of followup after BNR had more than 3-hour continent intervals and 3 had dry periods of 2 to 3 hours. Parents did not report any fecal incontinence or soiling in children older than 4 years. DISCUSSION Published series of outcomes after CPRE have been limited to short-term followup studies.6,12 We present our prospective experience with a cohort of patients with BE followed at 1 center for a median of 5 years. When evaluating outcomes in patients with BE, several factors must be evaluated. The goals of reconstruction are to create a bladder that can store urine and provide adequate continence, generate functional and cosmetically acceptable genitalia, and preserve renal function. Therefore, outcomes in these physiological parameters must be examined and the means to accomplish these end points must be addressed. Knowing the number and types of surgery that patients with BE undergo is important information when establishing clinical care plans and counseling parents as to what should be expected in the future of their child. Ebert et al reported that the mean number of operations performed in their patients after MSRE was 2.95 (range 1 to 8) with only 13.6% requiring more than 4 surgeries.13 However, because this information was obtained from self-reports by patients, it is unclear whether they reported all of the procedures that they had undergone. It is also not stated whether these were major or minor surgeries requiring general anesthesia. Stjernqvist and Kockum reported that children in their MSRE series underwent a median of 12 procedures.14 In a group of 80 patients treated with staged repair others reported that 48% required further surgery after BNR. In a questionnaire study of 122 patients with BE and CE Lee et al noted that of younger patients 0 to 4 and 5 to 13 years old males received more interventions than females (mean 3 and 5 respectively).15 Of older patients 16 to 20 and older than 20 years females underwent more surgical interventions than males (mean 7 vs 3.5).15 They attributed the higher rate in older females to procedures such as genitoplasty and monsplasty as well as to vaginal dilation. Our 32 patients with CPRE underwent a total of 193 surgical procedures (mean 4 ⫾ 5.8, range 1 to 31). It must be emphasized that 40% of these surgeries were minor endoscopic procedures. Of our patients 82% underwent 10 or
fewer procedures after CPRE. When examining the distribution of procedures by age, it was noted that most surgeries in our group were clustered before age 4 years (table 1). Therefore, clearly there is wide variability in the number of surgeries that should be expected in patients with BE. Based on our and other published series it is reasonable to assume that children with BE will undergo at least 3 to 6 procedures after the end of the staged repair cycle or CPRE. Recurrent urinary tract infections, pyelonephritis, hydronephrosis and upper tract function/cortical scarring have not been uniformly studied in all BE patient series. Early series using urinary diversion have shown significantly poor outcomes regarding renal function. In a series of 103 patients with BE Mesrobian et al reported a high incidence of renal deterioration with 70% and 69% of renal units abnormal in their ureterosigmoidostomy and ileal conduit groups, respectively.16 Furthermore, 10% of patients in the ureterosigmoidostomy group died of renal failure and 23% lost 1 kidney each. Most recent series have not specifically evaluated their patients with renal scintigraphy and, thus, renal damage in these groups is difficult to assess. We previously reported a high rate of pyelonephritis and an equally concerning rate of cortical defects on DMSA (each 22%) in our early experience after CPRE.6 Our current series shows a slightly decreased rate of cortical defects on DMSA and a higher rate of pyelonephritis (19% and 28%, respectively). Whether this was due to abnormal lower tract dynamics or other variables is still not clear and it warrants further evaluation. Adequate analysis of CPRE patient outcomes regarding renal function will likely require further prospective evaluation with a protocol such as ours that includes serial nuclear renal scan, ultrasound, voiding cystourethrogram, UDS and serum evaluation of renal function (fig. 1). We have previously reported that bladder growth appeared to be equivalent when comparing PPBC in patients after CPRE or MSRE with time.11 In the current study we noted that all patients except 1 male had a PPBC for age that was less than 70%. Linear regression analysis of PPBC vs age revealed a statistically significant positive correlation
Percent Predicted Bladdder Capacity by Age
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R square =0.3
80
60
40
20
0
4
8
12
Age at Study (years) FIG. 2. Linear regression analysis of PPBC vs age in years showed significant positive correlation between these variables.
FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY with bladders increasing in capacity with time (fig. 2). This suggests that bladder growth after CPRE may be inadequate but it increases as patients become older. Bladder growth may also be a function of establishing adequate outlet resistance. Published urinary continence rates after BE repair are variable at 12% to 83%.17–21 There are various factors confounding these results, including patient age at bladder closure, the type of closure performed, the number and type of procedures required to establish continence, the need for concomitant bladder augmentation and the need for CIC. The situation is further confused in that there is no standard definition for continence and studies classify continence in a nonuniform way. Traditionally in the exstrophy literature continence has been defined as maintaining 3-hour or greater dry periods during the day with no stress incontinence. However, this is not the definition of continence established by the International Children’s Continence Society.22 One also wonders whether the requirement for CIC, previous bladder augmentation and multiple surgeries to achieve this continence should be treated as success or failure. Because of the lack of standard definitions, this remains a highly subjective measure of outcome. Bladder augmentation is a common adjunctive procedure performed in patients with BE to achieve continence and augmentation rates published in the literature are 0% to 82%.18,20,23 However, this is certainly not a normal physiological situation. Data on continence after CPRE are not as readily available as those after MSRE. Furthermore, the need for BNR after CPRE is not clear. In our initial series we found that 5 of 8 patients (63%) 4 years or older had grossly inadequate bladder outlet resistance and would likely need BNR.6 Grady et al reported that 72% of females and 86% of males who underwent CPRE as newborns eventually required BNR.4 In our current series BNR was performed in 6 males and it will likely be needed in 5 more patients, including 3 males and 2 females, so that at least 11 of 21 (52%) patients 4 years or older will likely require formal BNR to achieve sufficient bladder outlet resistance. Dry intervals have improved after CPRE and BNR with all 4 evaluable patients experiencing 2 to 3-hour or greater dry periods more than 6 months after BNR. In comparison dry intervals after CPRE only are 3 hours or greater in 4 of 21 patients (19%). This further suggests that CPRE alone does not provide sufficient outlet resistance to achieve urinary continence and BNR is required in most patients. In our patient population females had a decreased need for BNR. However, given our small cohort size, it is not clear whether this will continue to be the case at longer followup. Several studies of patients with BE have shown that gender may have a role in eventual continence with females showing a higher rate than males.17,24 We did not find that females had longer dry intervals than males in our cohort. As we have experienced, outcomes differ significantly and studies are confounded by patient recall and clinician bias. Most continence assessments are performed by surgeons, which is clearly not an ideal way to perform a valid study. We have designed a parent and patient based questionnaire to assess continence status, although this suffers from its lack of validation. For these reasons proper prospective trials must be designed using standardized and validated urinary continence questionnaires, which are becoming more readily available for use in the pediatric population.25
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CONCLUSIONS Mitchell, one of the pioneers of the CPRE technique, has stated, “We . . . believe that the need to catheterize, divert, or augment a patient with exstrophy should be considered a failure of the initial treatment and voiding with continence should be the anticipated norm. . . . Most exstrophy patients should anticipate normal voiding with few operations and have little regard for their condition at birth.”26 Although this quote represents the ideal situation, it often cannot be the anticipated norm, given that all of these patients have major abdominal, lower urinary tract and genital abnormalities requiring complex reconstruction. As more data become available, it is clear that most patients with BE will require multiple operations to achieve normal voiding and provide cosmetically acceptable and functional genitalia. The psychosexual status of mature patients with exstrophy remains an important unknown factor. Long-term followup in patients after CPRE continues to be necessary to establish the long-term and lifelong effects of this procedure.
Abbreviations and Acronyms BC BE BNR CIC CMG CPRE
⫽ ⫽ ⫽ ⫽ ⫽ ⫽
DMSA EMG MSRE PPBC UDS VUR
⫽ ⫽ ⫽ ⫽ ⫽ ⫽
bladder capacity bladder exstrophy bladder neck reconstruction clean intermittent catheterization cystometrogram complete primary repair of bladder exstrophy dimercapto-succinic acid electromyography modern staged repair of exstrophy percent predicted bladder capacity urodynamic studies vesicoureteral reflux
REFERENCES 1.
2.
3. 4.
5.
6.
7. 8.
Baker LA and Gearhart JP: The staged approach to bladder exstrophy closure and the role of osteotomies. World J Urol 1998; 16: 205. Mathews R and Gearhart JP: Modern staged reconstruction of bladder exstrophy—still the gold standard. Urology 2005; 65: 2. Pippi-Salle JL and Chan PT: One stage bladder exstrophy and epispadias repair in newborn male. Can J Urol 1999; 6: 757. Grady R, Joyner BD, Roedel M, Feng W, Casale P and Mitchell M: The complete primary repair of exstrophy (CPRE) technique for repair of bladder exstrophy and epispadias: longterm followup. Presented at meeting of American Academy of Pediatrics, New Orleans, Louisiana, November 1–5, 2003. Halachmi S, Farhat W, Konen O, Khan A, Hodapp J, Bagli DJ et al: Pelvic floor magnetic resonance imaging after neonatal single stage reconstruction in male patients with classic bladder exstrophy. J Urol 2003; 170: 1505. Borer JG, Gargollo PC, Hendren WH, Diamond DA, Peters CA, Atala A et al: Early outcome following complete primary repair of bladder exstrophy in the newborn. J Urol 2005; 174: 1674. Hendren WH: Penile lengthening after previous repair of epispadias. J Urol 1979; 121: 527. Grady RW and Mitchell ME: Complete primary repair of exstrophy. J Urol 1999; 162: 1415.
1670 9.
10.
11.
12.
13.
14. 15.
16.
17.
18. 19.
20.
21.
22.
FOLLOWUP AFTER COMPLETE PRIMARY REPAIR OF BLADDER EXSTROPHY
Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM and Tamminen-Mobius TE: International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 1985; 15: 105. Kaefer M, Zurakowski D, Bauer SB, Retik AB, Peters CA, Atala A et al: Estimating normal bladder capacity in children. J Urol 1997; 158: 2261. Borer JG, Gargollo PC, Kinnamon DD, Bauer SB, Khoshbin S, Hendren WH et al: Bladder growth and development after complete primary repair of bladder exstrophy in the newborn with comparison to staged approach. J Urol 2005; 174: 1553. Hammouda HM and Kotb H: Complete primary repair of bladder exstrophy: initial experience with 33 cases. J Urol 2004; 172: 1441. Ebert A, Scheuering S, Schott G and Roesch WH: Psychosocial and psychosexual development in childhood and adolescence within the exstrophy-epispadias complex. J Urol 2005; 174: 1094. Stjernqvist K and Kockum CC: Bladder exstrophy: psychological impact during childhood. J Urol 1999; 162: 2125. Lee C, Reutter HM, Grasser MF, Fisch M and Noeker M: Gender-associated differences in the psychosocial and developmental outcome in patients affected with the bladder exstrophy-epispadias complex. BJU Int 2006; 97: 349. Mesrobian HG, Kelalis PP and Kramer SA: Long-term followup of 103 patients with bladder exstrophy. J Urol 1988; 139: 719. Capolicchio G, McLorie GA, Farhat W, Merguerian PA, Bagli DJ and Khoury AE: A population based analysis of continence outcomes and bladder exstrophy. J Urol 2001; 165: 2418. Hollowell JG and Ransley PG: Surgical management of incontinence in bladder exstrophy. Br J Urol 1991; 68: 543. Lottmann HB, Melin Y, Cendron M, Lombrail P, BezeBeyrie P and Cendron J: Bladder exstrophy: evaluation of factors leading to continence with spontaneous voiding after staged reconstruction. J Urol 1997; 158: 1041. Surer I, Baker LA, Jeffs RD and Gearhart JP: Combined bladder neck reconstruction and epispadias repair for exstrophy-epispadias complex. J Urol 2001; 165: 2425. Shaw MB, Rink RC, Kaefer M, Cain MP and Casale AJ: Continence and classic bladder exstrophy treated with staged repair. J Urol 2004; 172: 1450. Neveus T, von Gontard A, Hoebeke P, Hjalmas K, Bauer S, Bower W et al: The standardization of terminology of lower
23.
24.
25.
26.
urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol 2006; 176: 314. McMahon DR, Cain MP, Husmann DA and Kramer SA: Vesical neck reconstruction in patients with the exstrophyepispadias complex. J Urol 1996; 155: 1411. Mouriquand PD, Bubanj T, Feyaerts A, Jandric M, Timsit M, Mollard P et al: Long-term results of bladder neck reconstruction for incontinence in children with classical bladder exstrophy or incontinent epispadias. BJU Int 2003; 92: 997. Nelson CP, Park J, Bloom DA, Wan J and Kieran K: Incontinence Symptom Index: development and initial validation of a urinary incontinence instrument for the pediatric population. Presented at meeting of American Academy of Pediatrics Section on Urology, Atlanta, Georgia, October 7–9, 2006. Mitchell ME: Bladder exstrophy repair: complete primary repair of exstrophy. Urology 2005; 65: 5.
EDITORIAL COMMENT CPRE adds considerably to the care of boys and girls with BE. When CPRE was first described (reference 8 in article), many hoped that this approach would provide continence with a single operation. This series shows that even in skilled hands multiple surgeries are required to provide continence and cosmetically acceptable genitalia while preserving renal function. MSRE and CPRE depend on successful initial bladder closure to provide enough bladder outlet resistance to ensure bladder cycling in the newborn period. Continence occurs only if an adequate bladder volume develops. In this series despite excellent CPRE BNR was required or will likely be required in most patients. Whether additional outlet resistance in the form of the injection of bulking agents to the bladder neck following successful CPRE can fine tune the bladder outlet and result in volitional voiding with little residual urine without BNR remains unclear. Douglas A. Canning Division of Urology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania