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URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION: A LONG-TERM PROSPECTIVE CONTROLLED TRIAL IN A PORCINE MODEL
00225347/98/1605-1826$03.00/0
Vol. 160,1826-1829,November 1998 Printed in U S A
"HE JOURNAL OF UROLOGY Copyright 0 1998 by AMERICAN UROLOCICAL k s s o c I ~ n O N INC. ,
URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION: A LONG-TERM PROSPECTIYE CONTROLLED TRIAL IN A PORCINE MODEL MICHAEL D. STIFELMAN, EDWARD F. IKEGUCHI
AND
TERRY W. HENSLE
From the Department of Urology, Columbia-Presbyterian Medical Center, Babies and Children's Hospital of New York, New York.New York
ABSTRACT
Purpose: We recently described a technique that iatrogenically produces segmental megaureter while preserving renal function. In our initial report in 5 of 8 pigs that underwent this procedure bladder augmentation with the expanded ureter was successful. Throughout the expansion and reconstructive process renal function was preserved and all 5 animals that underwent augmentation had increased bladder capacity at sacrifice 1month postoperatively. In the present study we evaluated the long-term durability and performance of the ureteral segment used for augmentation. Materials and Methods: We performed a prospective, controlled, double armed study in 8 pigs, including 4 control animals that underwent subtotal cystectomy only (group 1)and 4 animals that underwent subtotal cystectomy followed by bladder augmentation using the expanded ureteral segment (group 2). End point measurements included cystography, and measurement of bladder capacity, serum creatinine and random bladder residual urine volumes. All cystograms were performed using passive filling conditions a t a standard filling pressure of 32 cm. water. Results: Bladder capacity throughout the study revealed consistently higher volumes in group 2 than in group 1.In 3 of the 4 group 1subjects vesicoureteral reflw developed compared to no reflux in group 2. Creatinine levels were elevated a t sacrifice in 50%of the animals in group 1 compared to none in group 2. Random bladder residual urine was less than 150 cc in 3 of the 4 group 2 subjects. Conclusions: Serial cystograms in pigs after ureteral augmentation suggest that the tissue does not contract with time. Animals that underwent ureteral augmentation had significantly greater bladder capacity than controls. Random bladder residual urine volume remained low throughout the study period. Ureteral tissue expansion for bladder augmentation appears to be feasible and durable in this animal model. In addition, it may be protective against the deleterious effects associated with small capacity bladders. KEYWORDS: swine, ureter, bladder, cystectomy
Ureteral augmentation has been shown to be an effective method of bladder reconstruction.14 Since the native transitional epithelium of a dilated ureter is used, ureteral augmentation is the most physiological procedure for improving bladder capacity. This form of augmentation is only applicable in the rare situation when a patient in need of bladder augmentation also has an enlarged ureter. In addition, ureterocystoplasty usually involves ipsilateral nephrectomy and, therefore, assumes the presence of a nonfmctioning or poorly functioning renal unit. Thus, ureterocystoplasty is not suitable in the majority of patients requiring bladder augmentation. We recently described a technique in which a tissue expander was placed into the distal ureter of a pig in an antegrade fashion.4 With a nephrostomy tube maintaining constant kidney drainage the distal ureter was dilated by the gradual inflation of the tissue expander. An initial feasibility trial determined that the ideal time for tissue expansion to an optimum volume of 200 to 250 cc was 3 to 4 weeks. We used these parameters in a repeat trial to determine the long-term efficacy of the procedure in study compared to control animals. As controls we chose a group of pigs that underwent subtotal cystectomy to mimic most closely the condition of patients with a diseased bladder (small capacity Accepted for publication June 26, 1998.
and poor compliance).We compared animals that underwent subtotal cystectomy only versus subtotal cystectomy and bladder augmentation using ureteral segments after tissue expansion. We posed certain questions, including what the durability of the dilated ureteral segment is after augmentation, whether it contracts with time, whether renal function and the integrity of the upper tracts may be preserved, and whether the animals empty the bladder effectively after augmentation. MATERIALS AND METHODS
We designed a prospective double armed study using 8 pigs, including 4 controls that underwent subtotal cystectomy only (group 1)and 4 animals that underwent subtotal cystectomy followed by ureterocystoplasty (group 2). Segmental ureteral dilation was performed by placing a ureteral tissue expander into the ureter and dilating a 5 cm. segment of distal ureter to a capacity of 200 to 250 cc during a 4-week period. This segment was then used to perform bladder augmentation. End points measured in both study arms included cystography, and determination of bladder capacity, serum creatinine at sacrifice and random bladder residual urine volume. In group 1, 4 conditioned pigs weighing 55 to 60 kg. were anesthetized, intubated and placed supine. Intraoperatively
1826
1827
URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION
a first generation cephalosporin was given and continued for 48 hours. Through a lower midline incision the bladder was exposed, and the ureters and superior vesical arteries were identified. The superior vesical arteries were ligated with care taken not to injure the ureter. Subtotal cystectomy was performed by sparing only the bladder neck and trigone. The bladder, fascia and skin were closed using absorbable sutures, nonabsorbable sutures and clips, respectively. An indwelling urethral catheter remained in place for 10 days postoperatively. In group 2 animals underwent ureteral tissue expansion followed by cystoplasty or ureteral augmentation, For phase 1of ureteral tissue expansion 4 conditioned pigs weighing 55 to 60 kg. were anesthetized, intubated and placed in the left flank position. Intraoperatively a first generation cephalosporin was given and continued for 48 hours. A 12th rib flank incision was made to access the retroperitoneum. With the kidney and ureter exposed a 1 cm. incision was made in the renal pelvis to allow passage of the ureteral tissue expander. The tissue exI pander was constructed using a latex balloon reservoir on the distal portion of a 7F 100 cm. ureteral stent. The tissue expander was made to span 5 cm. and the stent was constructed with 2 available infusion ports, including 1each communicating with the tissue expander reservoir and the distal tip of the stent, respectively. The tissue expander was passed antegrade down the ureter, such that the latex balloon was positioned in the distal third of the ureter as close as possible to the ureterovesical junction. Balloon position was confirmed by x-ray and ureterography with the injection of contrast medium into the distal port of the ureteral catheter. In addition to the ureteral tissue expander, a nephrostomy tube was placed to provide kidney drainage during ureteral expansion. The infusion ports of the ureteral tissue expander and nephrostomy tube exited through a middle or lower pole calix and were brought out through the skin. The renal pelvis, flank incision and skin were closed with a running absorbable suture, nonabsorbable suture and clips, respectively. Careful attention was given to securing the nephrostomy tube and infusion port of the ureteral expander. During a 4-week period the tissue expander was inflated to 200 to 250 cc with sterile water in an exponential fashion. After 48 hours of intravenous antibiotics the animal was placed on oral suppression antibiotics (trimethoprimsulfamethoxazole)daily. For phase 2 the 4 study animals underwent bladder augmentation with expanded ureter following subtotal cystectomy. One week preoperatively contrast material was injected into the tissue expander in all subjects to ensure proper placement in the distal ureter, nephrostography was performed to
document good kidney drainage by the nephrostomy tube, urine for culture was obtained from the nephrostomy tube and serum chemistry studies were done. Broad-spectrum antibiotics were started the night before surgery and continued for 48 hours. The animals were placed supine, and the bladder, ureter and dilated ureteral segment were accessed through a lower midline incision. Subtotal cystectomy was then performed, as in group 1. The dilated segment of ureter was isolated, excised at the proximal and distal aspect, and used to augment the remaining bladder. Continuity of the remaining ureter was obtained by primary ipsilateral ureteroureterostomy. Ureteroureterostomy was accomplished without difficulty and without the need for a psoas hitch. An indwelling Foley catheter and internal-external ureteral stent traversing the ureteroureterostomy remained in place for 10 days postoperatively, while the animals were maintained on suppression antibiotics. As a study end point cystography was performed in all animals 1, 2 and 4 months after cystectomy and augmentation, and at sacrifice 6 to 8 months postoperatively. All cystograms were done using passive filling conditions at a standard filling pressure of 32 cm. water and half diluted contrast material. Plain x-rays were done before, during and at 32 cm. water pressure specific volume. Radiographic images from each group were compared in regard to bladder size and shape, and reflux. Vesicoureteral reflux was documented as bilateral, unilateral or none. Bladder capacity was determined by the volume required to obtain a filling pressure of 32 cm. water. Data points representing bladder capacity with time at 1, 2 , 4 , 6 and 8 months were charted for each group and a trend line was fitted. In each subject 3 or 4 random bladder residual urine volumes were determined at cystography. Residual volumes in each animal were averaged and the groups were compared. Blood chemistry studies were done a t the time of sacrifice. RESULTS
A significant difference was noted between the 2 groups when bladder capacity was plotted with time (fig. 2) and trend lines were fitted (fig. 1).Group 1 animals had smaller bladder capacity 1month postoperatively than those in group 2. This trend persisted and increased with time (fig. 1).In group 1pressure specific capacity was approximately 400 cc at 8 months compared with approximately 1,200 cc in group 2 (fig. 1). Vesicoureteral reflux was evaluated just before sacrifice
I
0 0
1
2
3
4
5
6
7
rwmonthr)
FIG. 1. Trend lines of pressure specific bladder capacity with time
a
9
URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION
1828
-+-subgtllcyrt=tamy cystactanyand Uletml Augment
+-5ubtotsl
1400
1200
1000
l m E
'
J
6W 0
0
0
40(
20(
I
0
1
2
3
4
5
6
7
8
9
Time (monU~s)
FIG. 2.
F'ressure specific capacity with time per animal
by passive filling cystograms at 32 cm. water (table 1).Of the 4 group 1animals 3 (75%)had reflux, while 0 of the 4 group 2 subjects had evidence of reflux (table 1). Serum creatinine measurements on the day of sacrifice revealed elevations in 2 group 1animals (50%)but none in group 2 (table 2). Random residual urine volume determined at cystography and averaged in each animal did not appear significantly different in the 2 groups (table 3). Residual urine volume was slightly lower in group 1 than in group 2, although the subjects in group 1 also had lower bladder capacity. No animal in group 1 had clinically significant post-void residual urine and only 1 in group 2 had random residual urine volume greater than 150 cc. DISCUSSION
It is evident that the optimal tissue for bladder augmentation is the native transitional epithelium of the ureter when this tissue is available. This finding is supported by the success described in studies of ureterocystoplasty.13 Unfortunately the majority of patients in need of bladder augmentation are not candidates for ureterocystoplasty due to the absence of a megaureter. To accommodate patients without excess ureter who require bladder augmentation a method of ureteral tissue expansion was developed to create redundant ureteral tissue while preserving renal function. Initial studies addressing the feasibility of this procedure in a porcine model established procedural parameters, such as the optimum time of tissue expansion and ideal total volume of dilation.4 After completing a pilot study to determine the feasibility of ureteral tissue expansion we evaluated this technique for the long term in a diseased bladder model using 2 groups of pigs serving as a study and a control group. When selecting a control group, we chose animals undergoing subtotal cystecTABLE1. Presence of ureteral r e f l u at sacrifice in group 1 Subiect No.
R~flnx ~~
1 2 3 4 There was no reflux in group 2.
Unilat. Bilat. Unilat. None
TABLE2. Serum creatinine at sacrifice Creatinine (rngldl.1 Subject No.
Group 1
Group 2
3.0 1 2.8 2 3 2.0 4 2.0 Serum creatinine reference interval 1.0 to 2.6 mg./dl.
2.0 2.0
2.0 1.7
TABLE3. Average random bladder residual urine volume Urine (cc) Subject No.
1 2 3 4
Group 1
Group 2
102 67 80 60
133 333 90 135
tomy to mimic more closely conditions found in the setting of a low capacity, poorly compliant diseased bladder. This control group was then compared to a group of animals undergoing subtotal cystectomy followed by ureterocystoplasty using urothelium obtained from ureteral tissue expansion. The 2 groups were followed longitudinally with serial cystograms. While doing so, we addressed whether the ureteral segments contracted with time after bladder augmentation. In addition, we made basic observations about the emptying efficacy of the augmented bladders by performing random bladder catheterization and comparing residual urine volumes to overall bladder capacity, as determined by cystometry. When bladder capacity was measured in each group, capacity in group 2 was consistently greater than in controls (fig. 2). This finding persisted throughout the 8-month study period. Also, vesicoureteral reflux was common in the control group and nonexistent in any study animal (table 1).It is clear from these data and associated cystograms comparing the 2 groups that the ureteral segments did not contract during the 8 months after bladder augmentation. Bladder augmentation using expanded ureteral segments improved bladder capacity and prevented the ultimate detrimental changes seen on the cystograms of the control group from occurring.
URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION
In addressing the final question of our study we found that random bladder residual urine volumes were comparable in the study and control groups. Ideally a true post-void residual urine volume would have been obtained, although this was impossible due to the difficulty of inducing voluntary voiding in the porcine model. Nevertheless, when catheterization was performed in each study animal at random times after bladder augmentation, the volumes obtained suggested some functional ability to empty the bladder. CONCLUSIONS
Serial cystograms in pigs after ureterocystoplasty suggest that ureteral tissue after expansion and augmentation does not contract with time. Animals that underwent ureteral augmentation had a bladder capacity significantly greater than controls. Random bladder residual urine volume remained low throughout the study period. Ureteral tissue
1829
expansion appears to be feasible and durable in the long term in the porcine model presented. Studies are currently under way to perform more complex urodynamic analysis, compliance and tensometry analysis as well as histological evaluation of inflammatory changes and collagen deposition. REFERENCES
1. Churchill, B. M., Aliabadi, H., Landau, E. H., McLorie, G. A., Stickler, R. E., McKenna, P. H. and Khoury, A. E.: Ureteral bladder augmentation. J. Urol., 150 716, 1993. 2. Bellinger, M.F.: Ureterocystoplasty:a unique method for vesical augmentation in children. J. Urol., 149 811, 1993. 3. Hitchcock, R. J., Duffy, P. G. and Malone, P. S.: Ureterocystoplasty: the bladder augmentation of choice. Brit. J. Urol., 73 575, 1994. 4. Ikeguchi, E. F., Stifelman, M. D. and Hensle, T. W.: Ureteral tissue expansion for bladder augmentation. J. Urol., 159 1665,1998.
Vol. 160,1826-1829,November 1998 Printed in U S A
"HE JOURNAL OF UROLOGY Copyright 0 1998 by AMERICAN UROLOCICAL k s s o c I ~ n O N INC. ,
URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION: A LONG-TERM PROSPECTIYE CONTROLLED TRIAL IN A PORCINE MODEL MICHAEL D. STIFELMAN, EDWARD F. IKEGUCHI
AND
TERRY W. HENSLE
From the Department of Urology, Columbia-Presbyterian Medical Center, Babies and Children's Hospital of New York, New York.New York
ABSTRACT
Purpose: We recently described a technique that iatrogenically produces segmental megaureter while preserving renal function. In our initial report in 5 of 8 pigs that underwent this procedure bladder augmentation with the expanded ureter was successful. Throughout the expansion and reconstructive process renal function was preserved and all 5 animals that underwent augmentation had increased bladder capacity at sacrifice 1month postoperatively. In the present study we evaluated the long-term durability and performance of the ureteral segment used for augmentation. Materials and Methods: We performed a prospective, controlled, double armed study in 8 pigs, including 4 control animals that underwent subtotal cystectomy only (group 1)and 4 animals that underwent subtotal cystectomy followed by bladder augmentation using the expanded ureteral segment (group 2). End point measurements included cystography, and measurement of bladder capacity, serum creatinine and random bladder residual urine volumes. All cystograms were performed using passive filling conditions a t a standard filling pressure of 32 cm. water. Results: Bladder capacity throughout the study revealed consistently higher volumes in group 2 than in group 1.In 3 of the 4 group 1subjects vesicoureteral reflw developed compared to no reflux in group 2. Creatinine levels were elevated a t sacrifice in 50%of the animals in group 1 compared to none in group 2. Random bladder residual urine was less than 150 cc in 3 of the 4 group 2 subjects. Conclusions: Serial cystograms in pigs after ureteral augmentation suggest that the tissue does not contract with time. Animals that underwent ureteral augmentation had significantly greater bladder capacity than controls. Random bladder residual urine volume remained low throughout the study period. Ureteral tissue expansion for bladder augmentation appears to be feasible and durable in this animal model. In addition, it may be protective against the deleterious effects associated with small capacity bladders. KEYWORDS: swine, ureter, bladder, cystectomy
Ureteral augmentation has been shown to be an effective method of bladder reconstruction.14 Since the native transitional epithelium of a dilated ureter is used, ureteral augmentation is the most physiological procedure for improving bladder capacity. This form of augmentation is only applicable in the rare situation when a patient in need of bladder augmentation also has an enlarged ureter. In addition, ureterocystoplasty usually involves ipsilateral nephrectomy and, therefore, assumes the presence of a nonfmctioning or poorly functioning renal unit. Thus, ureterocystoplasty is not suitable in the majority of patients requiring bladder augmentation. We recently described a technique in which a tissue expander was placed into the distal ureter of a pig in an antegrade fashion.4 With a nephrostomy tube maintaining constant kidney drainage the distal ureter was dilated by the gradual inflation of the tissue expander. An initial feasibility trial determined that the ideal time for tissue expansion to an optimum volume of 200 to 250 cc was 3 to 4 weeks. We used these parameters in a repeat trial to determine the long-term efficacy of the procedure in study compared to control animals. As controls we chose a group of pigs that underwent subtotal cystectomy to mimic most closely the condition of patients with a diseased bladder (small capacity Accepted for publication June 26, 1998.
and poor compliance).We compared animals that underwent subtotal cystectomy only versus subtotal cystectomy and bladder augmentation using ureteral segments after tissue expansion. We posed certain questions, including what the durability of the dilated ureteral segment is after augmentation, whether it contracts with time, whether renal function and the integrity of the upper tracts may be preserved, and whether the animals empty the bladder effectively after augmentation. MATERIALS AND METHODS
We designed a prospective double armed study using 8 pigs, including 4 controls that underwent subtotal cystectomy only (group 1)and 4 animals that underwent subtotal cystectomy followed by ureterocystoplasty (group 2). Segmental ureteral dilation was performed by placing a ureteral tissue expander into the ureter and dilating a 5 cm. segment of distal ureter to a capacity of 200 to 250 cc during a 4-week period. This segment was then used to perform bladder augmentation. End points measured in both study arms included cystography, and determination of bladder capacity, serum creatinine at sacrifice and random bladder residual urine volume. In group 1, 4 conditioned pigs weighing 55 to 60 kg. were anesthetized, intubated and placed supine. Intraoperatively
1826
1827
URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION
a first generation cephalosporin was given and continued for 48 hours. Through a lower midline incision the bladder was exposed, and the ureters and superior vesical arteries were identified. The superior vesical arteries were ligated with care taken not to injure the ureter. Subtotal cystectomy was performed by sparing only the bladder neck and trigone. The bladder, fascia and skin were closed using absorbable sutures, nonabsorbable sutures and clips, respectively. An indwelling urethral catheter remained in place for 10 days postoperatively. In group 2 animals underwent ureteral tissue expansion followed by cystoplasty or ureteral augmentation, For phase 1of ureteral tissue expansion 4 conditioned pigs weighing 55 to 60 kg. were anesthetized, intubated and placed in the left flank position. Intraoperatively a first generation cephalosporin was given and continued for 48 hours. A 12th rib flank incision was made to access the retroperitoneum. With the kidney and ureter exposed a 1 cm. incision was made in the renal pelvis to allow passage of the ureteral tissue expander. The tissue exI pander was constructed using a latex balloon reservoir on the distal portion of a 7F 100 cm. ureteral stent. The tissue expander was made to span 5 cm. and the stent was constructed with 2 available infusion ports, including 1each communicating with the tissue expander reservoir and the distal tip of the stent, respectively. The tissue expander was passed antegrade down the ureter, such that the latex balloon was positioned in the distal third of the ureter as close as possible to the ureterovesical junction. Balloon position was confirmed by x-ray and ureterography with the injection of contrast medium into the distal port of the ureteral catheter. In addition to the ureteral tissue expander, a nephrostomy tube was placed to provide kidney drainage during ureteral expansion. The infusion ports of the ureteral tissue expander and nephrostomy tube exited through a middle or lower pole calix and were brought out through the skin. The renal pelvis, flank incision and skin were closed with a running absorbable suture, nonabsorbable suture and clips, respectively. Careful attention was given to securing the nephrostomy tube and infusion port of the ureteral expander. During a 4-week period the tissue expander was inflated to 200 to 250 cc with sterile water in an exponential fashion. After 48 hours of intravenous antibiotics the animal was placed on oral suppression antibiotics (trimethoprimsulfamethoxazole)daily. For phase 2 the 4 study animals underwent bladder augmentation with expanded ureter following subtotal cystectomy. One week preoperatively contrast material was injected into the tissue expander in all subjects to ensure proper placement in the distal ureter, nephrostography was performed to
document good kidney drainage by the nephrostomy tube, urine for culture was obtained from the nephrostomy tube and serum chemistry studies were done. Broad-spectrum antibiotics were started the night before surgery and continued for 48 hours. The animals were placed supine, and the bladder, ureter and dilated ureteral segment were accessed through a lower midline incision. Subtotal cystectomy was then performed, as in group 1. The dilated segment of ureter was isolated, excised at the proximal and distal aspect, and used to augment the remaining bladder. Continuity of the remaining ureter was obtained by primary ipsilateral ureteroureterostomy. Ureteroureterostomy was accomplished without difficulty and without the need for a psoas hitch. An indwelling Foley catheter and internal-external ureteral stent traversing the ureteroureterostomy remained in place for 10 days postoperatively, while the animals were maintained on suppression antibiotics. As a study end point cystography was performed in all animals 1, 2 and 4 months after cystectomy and augmentation, and at sacrifice 6 to 8 months postoperatively. All cystograms were done using passive filling conditions at a standard filling pressure of 32 cm. water and half diluted contrast material. Plain x-rays were done before, during and at 32 cm. water pressure specific volume. Radiographic images from each group were compared in regard to bladder size and shape, and reflux. Vesicoureteral reflux was documented as bilateral, unilateral or none. Bladder capacity was determined by the volume required to obtain a filling pressure of 32 cm. water. Data points representing bladder capacity with time at 1, 2 , 4 , 6 and 8 months were charted for each group and a trend line was fitted. In each subject 3 or 4 random bladder residual urine volumes were determined at cystography. Residual volumes in each animal were averaged and the groups were compared. Blood chemistry studies were done a t the time of sacrifice. RESULTS
A significant difference was noted between the 2 groups when bladder capacity was plotted with time (fig. 2) and trend lines were fitted (fig. 1).Group 1 animals had smaller bladder capacity 1month postoperatively than those in group 2. This trend persisted and increased with time (fig. 1).In group 1pressure specific capacity was approximately 400 cc at 8 months compared with approximately 1,200 cc in group 2 (fig. 1). Vesicoureteral reflux was evaluated just before sacrifice
I
0 0
1
2
3
4
5
6
7
rwmonthr)
FIG. 1. Trend lines of pressure specific bladder capacity with time
a
9
URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION
1828
-+-subgtllcyrt=tamy cystactanyand Uletml Augment
+-5ubtotsl
1400
1200
1000
l m E
'
J
6W 0
0
0
40(
20(
I
0
1
2
3
4
5
6
7
8
9
Time (monU~s)
FIG. 2.
F'ressure specific capacity with time per animal
by passive filling cystograms at 32 cm. water (table 1).Of the 4 group 1animals 3 (75%)had reflux, while 0 of the 4 group 2 subjects had evidence of reflux (table 1). Serum creatinine measurements on the day of sacrifice revealed elevations in 2 group 1animals (50%)but none in group 2 (table 2). Random residual urine volume determined at cystography and averaged in each animal did not appear significantly different in the 2 groups (table 3). Residual urine volume was slightly lower in group 1 than in group 2, although the subjects in group 1 also had lower bladder capacity. No animal in group 1 had clinically significant post-void residual urine and only 1 in group 2 had random residual urine volume greater than 150 cc. DISCUSSION
It is evident that the optimal tissue for bladder augmentation is the native transitional epithelium of the ureter when this tissue is available. This finding is supported by the success described in studies of ureterocystoplasty.13 Unfortunately the majority of patients in need of bladder augmentation are not candidates for ureterocystoplasty due to the absence of a megaureter. To accommodate patients without excess ureter who require bladder augmentation a method of ureteral tissue expansion was developed to create redundant ureteral tissue while preserving renal function. Initial studies addressing the feasibility of this procedure in a porcine model established procedural parameters, such as the optimum time of tissue expansion and ideal total volume of dilation.4 After completing a pilot study to determine the feasibility of ureteral tissue expansion we evaluated this technique for the long term in a diseased bladder model using 2 groups of pigs serving as a study and a control group. When selecting a control group, we chose animals undergoing subtotal cystecTABLE1. Presence of ureteral r e f l u at sacrifice in group 1 Subiect No.
R~flnx ~~
1 2 3 4 There was no reflux in group 2.
Unilat. Bilat. Unilat. None
TABLE2. Serum creatinine at sacrifice Creatinine (rngldl.1 Subject No.
Group 1
Group 2
3.0 1 2.8 2 3 2.0 4 2.0 Serum creatinine reference interval 1.0 to 2.6 mg./dl.
2.0 2.0
2.0 1.7
TABLE3. Average random bladder residual urine volume Urine (cc) Subject No.
1 2 3 4
Group 1
Group 2
102 67 80 60
133 333 90 135
tomy to mimic more closely conditions found in the setting of a low capacity, poorly compliant diseased bladder. This control group was then compared to a group of animals undergoing subtotal cystectomy followed by ureterocystoplasty using urothelium obtained from ureteral tissue expansion. The 2 groups were followed longitudinally with serial cystograms. While doing so, we addressed whether the ureteral segments contracted with time after bladder augmentation. In addition, we made basic observations about the emptying efficacy of the augmented bladders by performing random bladder catheterization and comparing residual urine volumes to overall bladder capacity, as determined by cystometry. When bladder capacity was measured in each group, capacity in group 2 was consistently greater than in controls (fig. 2). This finding persisted throughout the 8-month study period. Also, vesicoureteral reflux was common in the control group and nonexistent in any study animal (table 1).It is clear from these data and associated cystograms comparing the 2 groups that the ureteral segments did not contract during the 8 months after bladder augmentation. Bladder augmentation using expanded ureteral segments improved bladder capacity and prevented the ultimate detrimental changes seen on the cystograms of the control group from occurring.
URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION
In addressing the final question of our study we found that random bladder residual urine volumes were comparable in the study and control groups. Ideally a true post-void residual urine volume would have been obtained, although this was impossible due to the difficulty of inducing voluntary voiding in the porcine model. Nevertheless, when catheterization was performed in each study animal at random times after bladder augmentation, the volumes obtained suggested some functional ability to empty the bladder. CONCLUSIONS
Serial cystograms in pigs after ureterocystoplasty suggest that ureteral tissue after expansion and augmentation does not contract with time. Animals that underwent ureteral augmentation had a bladder capacity significantly greater than controls. Random bladder residual urine volume remained low throughout the study period. Ureteral tissue
1829
expansion appears to be feasible and durable in the long term in the porcine model presented. Studies are currently under way to perform more complex urodynamic analysis, compliance and tensometry analysis as well as histological evaluation of inflammatory changes and collagen deposition. REFERENCES
1. Churchill, B. M., Aliabadi, H., Landau, E. H., McLorie, G. A., Stickler, R. E., McKenna, P. H. and Khoury, A. E.: Ureteral bladder augmentation. J. Urol., 150 716, 1993. 2. Bellinger, M.F.: Ureterocystoplasty:a unique method for vesical augmentation in children. J. Urol., 149 811, 1993. 3. Hitchcock, R. J., Duffy, P. G. and Malone, P. S.: Ureterocystoplasty: the bladder augmentation of choice. Brit. J. Urol., 73 575, 1994. 4. Ikeguchi, E. F., Stifelman, M. D. and Hensle, T. W.: Ureteral tissue expansion for bladder augmentation. J. Urol., 159 1665,1998.