- Email: [email protected]
Augmentation cystoplasty in renal transplantation: a good and safe option—experience with 25 cases
ADULT UROLOGY
AUGMENTATION CYSTOPLASTY IN RENAL TRANSPLANTATION: A GOOD AND SAFE OPTION—EXPERIENCE WITH 25 CASES WILLIAM CARLOS NAHAS, EDUARDO MAZZUCCHI, MARCO ANTONIO ARAP, IOANNIS MICHEL ANTONOPOULOS, ELIAS DAVID NETO, LUIZ ESTEVAM IANHEZ, SAMI ARAP
AND
ABSTRACT Objectives. To assess the surgical and long-term results of renal transplantation in 25 patients with bladder dysfunction and augmentation cystoplasty. Methods. We retrospectively reviewed the evolution and surgical outcome of 25 renal transplants in 24 recipients with augmentation cystoplasty. The mean patient age at transplantation was 27.6 years. The etiology of bladder dysfunction was neurogenic bladder with detrusor hyperreflexia (11 patients), tuberculosis (5 patients), vesicoureteral reflux (4 patients), posterior urethral valves (3 patients), and interstitial cystitis (1 patient). Seventeen transplants were from living donors. Augmentation cystoplasty was performed before transplantation in 21 patients. The bowel segments used in the augmentation cystoplasty included ileum in 16, ileocecal segments in 2, and sigmoid in 5 patients. The donor ureter was anastomosed to the native bladder in 16 patients, to the bowel segment in 6, and to the native ureter in 3. Results. Twenty kidneys (80%) were functioning at a mean follow-up of 53.2 months (range 6 to 118). The mean serum creatinine was 1.56 mg/dL (range 0.7 to 2.6). Three patients died of unrelated causes and 1 of adenocarcinoma that originated at the vesicointestinal anastomosis. The actuarial graft survival at 1, 2, and 5 years was 96%, 92%, and 78%, respectively. Complications included symptomatic urinary infection, ureteral stenosis, and lymphocele. Conclusions. Augmentation cystoplasty is a safe and effective method to restore function in noncompliant bladders. Renal transplantation can be performed safely after augmentation cystoplasty. UROLOGY 60: 770–774, 2002. © 2002, Elsevier Science Inc.
T
he need for a normal lower urinary tract has been recognized since the beginning of renal transplantation programs.1 If the pressure inside the reservoir is high or cannot be adequately emptied out, the kidney will be affected and renal function impaired.2 Patients with end-stage renal disease with small volume, noncompliant bladders mostly do not respond to clinical measures, and the management of the lower urinary tract dysfunction requires augmentation to decrease intravesical pressure, preserving continence in social volumes. A better knowledge of bladder physiolFrom the Division of Urology, Hospital of Clinics, University of Sa˜o Paulo School of Medicine, Sa˜o Paulo, Brazil Reprint requests: William Carlos Nahas, M.D., Division of Urology, Hospital Clinics, University of Sa˜o Paulo School of Medicine, R. Adma Jafet, No. 50, Sa˜o Paulo, SP 01308-050, Brazil Submitted: February 4, 2002, accepted (with revisions): June 3, 2002
770
© 2002, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
ogy, advances in reconstructive surgery using intestinal segments, and the introduction of clean intermittent catheterization (CIC) have improved the success rate of lower urinary dysfunction correction, even in renal transplant patients.3 McGuire and Morissey4 have reinforced the idea that patients with low voiding pressures do not experience renal function impairment despite vesicoureteral reflux (VUR). However, the risk of infection in patients with CIC is increased, making an antireflux procedure useful in controlling urinary tract infection (UTI). We report our retrospective experience with renal transplantation in patients with enterocystoplasty. MATERIAL AND METHODS Between 1987 and April 2001, 1178 renal transplants were performed at the Clı´nicas Hospital, University of Sa˜o Paulo School of Medicine. Twenty-five renal transplants were per0090-4295/02/$22.00 PII S0090-4295(02)01947-7
formed in 24 patients (15 males and 9 females) with augmentation cystoplasty required because of lower urinary tract dysfunction. The mean patient age at transplantation was 27.6 years (range 12 to 53). The etiology of bladder dysfunction was neurogenic bladder with detrusor hyperreflexia (11 patients), tuberculosis (5 patients), VUR (4 patients), posterior urethral valves (3 patients), and interstitial cystitis (1 patient), according to the pathologic findings. The initial evaluation was made with abdominal ultrasonography, voiding cystourethrography, and urodynamic studies. All patients presenting with VUR and posterior urethral valves had a noncompliant, high-pressure bladder, as determined by the urodynamic studies. Patients with tuberculosis and a contracted (less than 50-mL capacity), noncompliant bladder could not undergo the urodynamic evaluation. Three patients had previously undergone ureterocystoplasty with a poor outcome and were candidates for a new enlargement.5 Bladder augmentation was performed before transplantation in 21 patients. Five patients had their bladder enlarged before the development of end-stage renal disease, four with a nondetubularized bowel segment (two ileocecal, one sigmoidal, and one ileal segment) and one with a detubularized ileal all were long before the benefits of bowel detubularization were known. The mean interval from cystoplasty to transplantation, excluding these 5 patients, was 5 months (range 2 to 13). All patients underwent weekly bladder washing with saline solution during one of the dialysis procedures, segment. Three patients underwent cystoplasty after transplantation, all with detubularized ileal segments. The first had a neurogenic bladder secondary to a sacral teratoma operated on during childhood. Her bladder condition was not well understood before transplantation, and she developed a ureteral stenosis soon after transplantation. The ureter was reimplanted without an antireflux technique because of local conditions. She underwent cystoplasty 4 months later. Another patient had interstitial cystitis diagnosed long after transplantation and developed a very-low-capacity, poorly compliant bladder. She underwent bladder augmentation 30 months after transplantation. The last patient had a complex urogenital anomaly (cake kidney, bilateral ureterocele, and vaginal atresia) associated with neurogenic bladder and underwent transplantation elsewhere. She had her bladder enlarged and her ureter reimplanted with an antireflux technique 46 months after transplantation because of ureterohydronephrosis, reflux, and poor bladder compliance. Ileocystoplasty was performed in a total of 16 patients, sigmoid cystoplasty in 5, and ileocecocystoplasty in 2; 1 patient with a bladder previously enlarged with a nondetubularized sigmoid segment had a detubularized ileal segment included in the reservoir. The bladder incision was U-shaped to obtain a bigger anastomotic area. Patients with small urine volumes after bladder enlargement had their reservoir washed at least once a week to remove mucus secretions. Seventeen transplants were from living and eight from cadaveric donors. All kidneys were located extraperitoneally, and the ureter was reimplanted in the bladder in 15 patients using the Gregoir technique6 and in 1 without an antireflux technique. The Leadbetter technique7 was used for reimplantation in the sigmoid in 4 patients. The ureter was implanted in the ileum in 2 patients, with a direct anastomosis in the patient with an ileocecocystoplasty and by the Le Duc technique8 in the other. In 3 other patients, the ureter was anastomosed to the native ureter. A double J catheter was left for 6 to 8 weeks in 6 patients, in whom the ureteral anastomosis was difficult because of surgical reasons, to decrease the risk of urologic complications; 2 had a ureteroureteral anastomosis and 3 had the ureter reimplanted into the sigmoid and 1 into the bladder. A Foley catheter was maintained for a minimum of 10 days in all patients. UROLOGY 60 (5), 2002
FIGURE 1. Bladder pressures and capacities in relation to augmentation. Pressure (P ⫽ 0.0046) and capacity (P ⫽ 0.0003) varied significantly in the phases before and after augmentation.
The first 15 patients of the series were re-evaluated with a urodynamic study after bladder enlargement, 3 and 12 months after transplantation (Fig. 1). In the remaining patients, the urodynamic status was evaluated only a few months after bladder enlargement. Patients voiding spontaneously received antibiotics only when they presented with symptomatic UTIs. Patients treated with CIC received continuous oral antibiotic prophylaxis in a rotational way with trimethoprim-sulfamethoxazole, nitrofurantoin, or norfloxacin daily. Oral bicarbonate was administered according to the gasometric evaluation. These patients had normal renal function and received bicarbonate replacement on the basis of the gasometric findings. None of them developed chronic renal acidosis. Immunosuppression was based on a triple drug regimen: cyclosporine (Neoral after 1998), azathioprine or mycophenolate mofetil, and prednisone. Patients undergoing repeated transplantation received anti-CD3 in a sequential immunosuppressive regimen. The details of the immunosuppression therapy have been previously described.9 The graft and patient survival rates using Kaplan-Meier analysis were determined from transplantation to the last follow-up visit.
RESULTS The bladder capacity and compliance in all augmented patients markedly improved, mainly after renal transplantation (Fig. 1). The mean follow-up was 53.2 months (range 6 to 118). Thirteen patients were followed up for more than 4 years and six for more than 2 but less than 4 years. The mean 771
FIGURE 2. Kaplan-Meier curve (patient and graft survival).
serum creatinine was 1.56 mg/dL (range 0.7 to 2.6); it was less than 2.0 mg/dL in 19 patients. All patients remained continent except for one with a neurogenic bladder who had minimal sporadic losses. Ten patients (40%) were using a CIC regimen, and the other 14 voided with the Valsalva maneuver, without residual urine according to a sonographic evaluation. UTI occurred at least once in 14 patients (56%), 8 voiding with CIC and 6 with the Valsalva maneuver. Three patients had seven, 1 patient had four, and 10 had one or two UTIs. Eight patients (32%) were hospitalized 14 times for intravenous antibiotic treatment, and transient creatinine elevation occurred in 8 of such episodes, with a mean serum creatinine of 1.6 mg/ dL. The creatinine values of all patients returned to previous levels after antibiotic treatment, except for 1 patient using CIC because of a neurogenic bladder, who had reflux to the transplanted kidney. This patient lost the graft 39 months later from chronic interstitial nephritis secondary to VUR and repeated UTIs. She received a second cadaveric kidney graft that was functioning well after 97 months. All patients underwent urethrocystography 3 months after transplantation. With the exception of the patients transplanted without an antireflux technique (3 patients), no one presented with VUR. Six patients had the ureter reimplanted into a bowel segment; two of those with implantation at the sigmoid developed ureteral stenosis at the implantation site. One had the ureter reimplanted and the other was treated percutaneously with the Acucise catheter. One patient presenting with a lymphocele was treated through external drainage. All patients had a good outcome. Four patients died with functioning grafts. Three of them died of causes not related to the cysto772
plasty. One died of sepsis due to pneumonia 30 days after transplantation, another of a cavernous sinus thrombosis secondary to acute sinusitis 18 months after transplantation, and the third had sudden death at home 19 months after transplantation. One patient with tuberculosis augmented with an ileocecal segment died of carcinomatosis due to an adenocarcinoma that originated at the vesicointestinal anastomosis 25 years after enlargement and 6.5 years after transplantation. This patient voided with the Valsalva maneuver and had not presented with UTI or residual urine. The actuarial patient survival rate was 96%, 86%, and 86% and the graft survival rate was 96%, 86%, and 78% at 12, 36, and 60 months, respectively (Fig. 2). COMMENT Transplanted patients with lower urinary problems may have increased morbidity and mortality if the problems are not recognized before transplantation. The bladder capacity and compliance are the most important factors to be evaluated, and a consistent method of complete bladder emptying is needed, either by spontaneous voiding or CIC. Pretransplant evaluation of the lower urinary tract is sometimes difficult. A trial of bladder cycling is helpful in restoring bladder capacity and in assessing the need for augmentation in patients with previous urinary diversions or defunctionalized bladders. Bladder augmentation is a well-known procedure for low-capacity and poor compliance bladders.10 The advantages in using the ureter as a source of enlargement are many11; however, when the ureter is not available, is nondilated, or has been previously manipulated, the use of intestinal UROLOGY 60 (5), 2002
segments is the best alternative.5 Marshall et al.12 first described augmentation cystoplasty combined with renal transplantation in 1982. Since then, other reports have been published showing good outcomes in these patients.13,14 However, Alfrey et al.15 had poor outcomes with bladder augmentation and renal transplantation. They believe a nonfree-draining intestinal urinary reservoir can impose a high risk of a poor outcome because of recurrent UTIs and immunosuppression. The most important aspect for the success in all of the procedures is detubularization, which interrupts the peristaltic activity, abolishes massive contractions, and enhances capacity.10 The detrusor should be widely incised to avoid coordinated autonomic contractions. A U-shaped incision is performed longitudinally, creating a large surface for the bowel anastomosis and avoiding the formation of an “hourglass”-shaped augmented bladder. Detubularized ileum remains the most commonly used segment because of its abundance and reduced complication rates. We preferred sigmoid segments in patients with tuberculosis, because they have minimal capacity, making ureteral reimplantation into the bladder impossible. The “tenia coli” provides significant advantages over the ileum in the sense that it is an excellent site for ureteral reimplantation with an antireflux procedure. We reimplanted one ureter into the ileum using the Le Duc technique without major difficulties or complications. The bladder portion of the augmented reservoir should be used for the ureteral reimplantation. None of the patients whose ureter was implanted into the bladder presented with urologic complications compared with 2 patients who presented with ureteral stenosis in ureters implanted into the bowel segment. When the reservoir cannot be adequately dissected, a ureteroureteral anastomosis with the native ureter is a good option and was used in 3 patients. Every cystoplasty was performed before transplantation, except for 3 patients whose bladder dysfunction was not recognized and who developed impairment of graft function long after the surgery. The adequate timing for cystoplasty is at least 8 to 12 weeks before transplantation and the introduction of immunosuppression, ensuring a functioning reservoir with adequate capacity, compliance, and bladder drainage. Motivation and training with CIC before transplantation are very important issues and must be routine for patients with a neurogenic bladder. None of the patients with bladder enlargement needed bladder cycles while waiting for transplantation, even the ones who waited for a cadaveric donor. Nine patients with a neurogenic bladder and one with posterior urethral valves used CIC. The reUROLOGY 60 (5), 2002
maining patients voided using the Valsalva maneuver with adequate bladder emptying, as evaluated by ultrasonography or urinary catheterization. CIC is safe even in patients who undergo kidney transplantation.13 The most important problem associated with bladder enlargement is UTIs, mainly in the group of patients using CIC. The antireflux procedure is important in this group of patients because of the higher risk of UTI. An antireflux procedure could prevent pyelonephritis, because it prevents contaminated urine from refluxing into the upper urinary tract. One patient in the CIC group whose ureter was reimplanted without an antireflux procedure presented with seven episodes of pyelonephritis and lost her graft after 39 months from interstitial chronic nephritis. Her enlarged bladder was re-evaluated and showed good compliance and capacity voiding by CIC. She underwent a second cadaveric donor transplant after 11 months and was well after a follow-up of 97 months. After the first series of patients, the urodynamic evaluation was reduced to only one study, performed 2 to 3 months after bladder enlargement. A better knowledge of the enterocystoplasty behavior allowed this kind of surveillance, reducing urinary manipulation and the risk of UTI. The risk of a malignant neoplasia is well known16 and could be raised by immunosuppression. Analysis of the Cincinnati Transplant Tumor Registry revealed that the frequency of cancer common to the general population (eg, carcinoma of the prostate, breast, and colon) is not increased among transplant patients. However, cancers uncommon to the general population (eg, lymphomas, Kaposi’s sarcoma, and hepatobiliary tumors) occur more often in transplant recipients.17,18 One of our patients died of carcinomatosis due to an adenocarcinoma that originated at the vesicointestinal anastomotic site.19 CONCLUSIONS Augmentation cystoplasty is a safe and efficient treatment for lower urinary dysfunction, and renal transplantation can be performed in these patients with no increased risk for graft outcome. Patients must be followed up closely with special attention to UTIs. Excellent graft and patient survival rates and controlled episodes of infection make bladder enlargement a good option for patients with serious bladder diseases. REFERENCES 1. Hamburger J, Vaisse J, Crosnier J, et al: Renal homotransplantation in man after radiation of the recipient. Am J Med 132: 854 –871, 1962. 773
2. Hinman F Jr: Selection of intestinal segments for bladder substitution: physical and physiological characteristics. J Urol 139: 519 –523, 1988. 3. Barnett MG, Bruskewitz R, Glass N, et al: Ileocecocystoplasty bladder augmentation and renal transplantation. J Urol 138: 855–858, 1987. 4. McGuire E, and Morrissey SG: The development of neurogenic vesical dysfunction after experimental spinal cord injury or sacral rhizotomy in non-human primates. J Urol 128: 1390 –1393, 1982. 5. Nahas WC, Mazzucchi E, Antonopoulos IO, et al: End stage renal disease and bladder dysfunction–algorithm for renal transplantation. J Urol 163(suppl 4): 330, 2000. 6. Gregoir W. Le traitement chirurgical du reflux ve´ sicoure´ te´ ral conge´ nital. Acta Chir Belg 63: 431– 439, 1964. 7. Leadbetter WF: Consideration of problems incident to performance of uretero-enterostomy: report of a technique. J Urol 65: 818 –830, 1951. 8. Le Duc A, Camey M, and Teillac P: Antireflux ureteroileal implantation via a mucosal sulcus. Ann Urol 21: 33–34, 1987. 9. Neto DE, Americo da Fonseca J, and Jota de Paula FJ: The impact of azathioprine on chronic viral hepatitis in renal transplantation: a long term, single center, prospective study on azathioprine withdrawal. Transplantation 68: 976 –980, 1999. 10. Studer UE, deKernion JB, and Zimmern PE: A model for a bladder replacement plasty by an ileal reservoir: an experimental study in dogs. Urol Res 13: 243, 1985.
774
11. Gonzales R, Buson H, Reid C, et al: Seromuscular colocystoplasty lined with urothelium: experience with 16 patients. Urology 45: 124 –129, 1994. 12. Marshall FF, Smolev JK, Spees ER, et al: The urological evaluation and management of patients with congenital lower urinary tract anomalies prior to renal transplantation. J Urol 127: 1078 –1081, 1982. 13. Zaragoza MR, Ritchey ML, Bloom DA, et al: Enterocystoplasty in renal transplantation candidates: urodynamic evaluation and outcome. J Urol 150: 1463–1466, 1993. 14. Nahas WC, Mazzucchi E, Antonopoulos IO, et al: Kidney transplantation in patients with bladder augmentation: surgical outcome and urodynamic follow-up. Transplant Proc 29: 157–158, 1997. 15. Alfrey EJ, Conley SB, Tanney DC, et al: Use of an augmented urinary bladder can be catastrophic in renal transplantation. Transplant Proc 29: 154 –155, 1997. 16. Filmer RB, and Spencer JR: Malignancies in bladder augmentation and intestinal conduits. J Urol 143: 671–678, 1990. 17. Penn I: Why do immunosuppressed patients develop cancer? Crit Rev Oncog 1: 27–52, 1989. 18. Penn I: The changing pattern of posttransplant malignancies. Transplant Proc 23: 1101–1103, 1991. 19. Nahas WC, Izuka FH, Mazzucchi E, et al: Adenocarcinoma of an augmented bladder 25 years after ileocecocystoplasty and 6 years after renal transplantation. J Urol 162: 490 – 491, 1999.
UROLOGY 60 (5), 2002
AUGMENTATION CYSTOPLASTY IN RENAL TRANSPLANTATION: A GOOD AND SAFE OPTION—EXPERIENCE WITH 25 CASES WILLIAM CARLOS NAHAS, EDUARDO MAZZUCCHI, MARCO ANTONIO ARAP, IOANNIS MICHEL ANTONOPOULOS, ELIAS DAVID NETO, LUIZ ESTEVAM IANHEZ, SAMI ARAP
AND
ABSTRACT Objectives. To assess the surgical and long-term results of renal transplantation in 25 patients with bladder dysfunction and augmentation cystoplasty. Methods. We retrospectively reviewed the evolution and surgical outcome of 25 renal transplants in 24 recipients with augmentation cystoplasty. The mean patient age at transplantation was 27.6 years. The etiology of bladder dysfunction was neurogenic bladder with detrusor hyperreflexia (11 patients), tuberculosis (5 patients), vesicoureteral reflux (4 patients), posterior urethral valves (3 patients), and interstitial cystitis (1 patient). Seventeen transplants were from living donors. Augmentation cystoplasty was performed before transplantation in 21 patients. The bowel segments used in the augmentation cystoplasty included ileum in 16, ileocecal segments in 2, and sigmoid in 5 patients. The donor ureter was anastomosed to the native bladder in 16 patients, to the bowel segment in 6, and to the native ureter in 3. Results. Twenty kidneys (80%) were functioning at a mean follow-up of 53.2 months (range 6 to 118). The mean serum creatinine was 1.56 mg/dL (range 0.7 to 2.6). Three patients died of unrelated causes and 1 of adenocarcinoma that originated at the vesicointestinal anastomosis. The actuarial graft survival at 1, 2, and 5 years was 96%, 92%, and 78%, respectively. Complications included symptomatic urinary infection, ureteral stenosis, and lymphocele. Conclusions. Augmentation cystoplasty is a safe and effective method to restore function in noncompliant bladders. Renal transplantation can be performed safely after augmentation cystoplasty. UROLOGY 60: 770–774, 2002. © 2002, Elsevier Science Inc.
T
he need for a normal lower urinary tract has been recognized since the beginning of renal transplantation programs.1 If the pressure inside the reservoir is high or cannot be adequately emptied out, the kidney will be affected and renal function impaired.2 Patients with end-stage renal disease with small volume, noncompliant bladders mostly do not respond to clinical measures, and the management of the lower urinary tract dysfunction requires augmentation to decrease intravesical pressure, preserving continence in social volumes. A better knowledge of bladder physiolFrom the Division of Urology, Hospital of Clinics, University of Sa˜o Paulo School of Medicine, Sa˜o Paulo, Brazil Reprint requests: William Carlos Nahas, M.D., Division of Urology, Hospital Clinics, University of Sa˜o Paulo School of Medicine, R. Adma Jafet, No. 50, Sa˜o Paulo, SP 01308-050, Brazil Submitted: February 4, 2002, accepted (with revisions): June 3, 2002
770
© 2002, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
ogy, advances in reconstructive surgery using intestinal segments, and the introduction of clean intermittent catheterization (CIC) have improved the success rate of lower urinary dysfunction correction, even in renal transplant patients.3 McGuire and Morissey4 have reinforced the idea that patients with low voiding pressures do not experience renal function impairment despite vesicoureteral reflux (VUR). However, the risk of infection in patients with CIC is increased, making an antireflux procedure useful in controlling urinary tract infection (UTI). We report our retrospective experience with renal transplantation in patients with enterocystoplasty. MATERIAL AND METHODS Between 1987 and April 2001, 1178 renal transplants were performed at the Clı´nicas Hospital, University of Sa˜o Paulo School of Medicine. Twenty-five renal transplants were per0090-4295/02/$22.00 PII S0090-4295(02)01947-7
formed in 24 patients (15 males and 9 females) with augmentation cystoplasty required because of lower urinary tract dysfunction. The mean patient age at transplantation was 27.6 years (range 12 to 53). The etiology of bladder dysfunction was neurogenic bladder with detrusor hyperreflexia (11 patients), tuberculosis (5 patients), VUR (4 patients), posterior urethral valves (3 patients), and interstitial cystitis (1 patient), according to the pathologic findings. The initial evaluation was made with abdominal ultrasonography, voiding cystourethrography, and urodynamic studies. All patients presenting with VUR and posterior urethral valves had a noncompliant, high-pressure bladder, as determined by the urodynamic studies. Patients with tuberculosis and a contracted (less than 50-mL capacity), noncompliant bladder could not undergo the urodynamic evaluation. Three patients had previously undergone ureterocystoplasty with a poor outcome and were candidates for a new enlargement.5 Bladder augmentation was performed before transplantation in 21 patients. Five patients had their bladder enlarged before the development of end-stage renal disease, four with a nondetubularized bowel segment (two ileocecal, one sigmoidal, and one ileal segment) and one with a detubularized ileal all were long before the benefits of bowel detubularization were known. The mean interval from cystoplasty to transplantation, excluding these 5 patients, was 5 months (range 2 to 13). All patients underwent weekly bladder washing with saline solution during one of the dialysis procedures, segment. Three patients underwent cystoplasty after transplantation, all with detubularized ileal segments. The first had a neurogenic bladder secondary to a sacral teratoma operated on during childhood. Her bladder condition was not well understood before transplantation, and she developed a ureteral stenosis soon after transplantation. The ureter was reimplanted without an antireflux technique because of local conditions. She underwent cystoplasty 4 months later. Another patient had interstitial cystitis diagnosed long after transplantation and developed a very-low-capacity, poorly compliant bladder. She underwent bladder augmentation 30 months after transplantation. The last patient had a complex urogenital anomaly (cake kidney, bilateral ureterocele, and vaginal atresia) associated with neurogenic bladder and underwent transplantation elsewhere. She had her bladder enlarged and her ureter reimplanted with an antireflux technique 46 months after transplantation because of ureterohydronephrosis, reflux, and poor bladder compliance. Ileocystoplasty was performed in a total of 16 patients, sigmoid cystoplasty in 5, and ileocecocystoplasty in 2; 1 patient with a bladder previously enlarged with a nondetubularized sigmoid segment had a detubularized ileal segment included in the reservoir. The bladder incision was U-shaped to obtain a bigger anastomotic area. Patients with small urine volumes after bladder enlargement had their reservoir washed at least once a week to remove mucus secretions. Seventeen transplants were from living and eight from cadaveric donors. All kidneys were located extraperitoneally, and the ureter was reimplanted in the bladder in 15 patients using the Gregoir technique6 and in 1 without an antireflux technique. The Leadbetter technique7 was used for reimplantation in the sigmoid in 4 patients. The ureter was implanted in the ileum in 2 patients, with a direct anastomosis in the patient with an ileocecocystoplasty and by the Le Duc technique8 in the other. In 3 other patients, the ureter was anastomosed to the native ureter. A double J catheter was left for 6 to 8 weeks in 6 patients, in whom the ureteral anastomosis was difficult because of surgical reasons, to decrease the risk of urologic complications; 2 had a ureteroureteral anastomosis and 3 had the ureter reimplanted into the sigmoid and 1 into the bladder. A Foley catheter was maintained for a minimum of 10 days in all patients. UROLOGY 60 (5), 2002
FIGURE 1. Bladder pressures and capacities in relation to augmentation. Pressure (P ⫽ 0.0046) and capacity (P ⫽ 0.0003) varied significantly in the phases before and after augmentation.
The first 15 patients of the series were re-evaluated with a urodynamic study after bladder enlargement, 3 and 12 months after transplantation (Fig. 1). In the remaining patients, the urodynamic status was evaluated only a few months after bladder enlargement. Patients voiding spontaneously received antibiotics only when they presented with symptomatic UTIs. Patients treated with CIC received continuous oral antibiotic prophylaxis in a rotational way with trimethoprim-sulfamethoxazole, nitrofurantoin, or norfloxacin daily. Oral bicarbonate was administered according to the gasometric evaluation. These patients had normal renal function and received bicarbonate replacement on the basis of the gasometric findings. None of them developed chronic renal acidosis. Immunosuppression was based on a triple drug regimen: cyclosporine (Neoral after 1998), azathioprine or mycophenolate mofetil, and prednisone. Patients undergoing repeated transplantation received anti-CD3 in a sequential immunosuppressive regimen. The details of the immunosuppression therapy have been previously described.9 The graft and patient survival rates using Kaplan-Meier analysis were determined from transplantation to the last follow-up visit.
RESULTS The bladder capacity and compliance in all augmented patients markedly improved, mainly after renal transplantation (Fig. 1). The mean follow-up was 53.2 months (range 6 to 118). Thirteen patients were followed up for more than 4 years and six for more than 2 but less than 4 years. The mean 771
FIGURE 2. Kaplan-Meier curve (patient and graft survival).
serum creatinine was 1.56 mg/dL (range 0.7 to 2.6); it was less than 2.0 mg/dL in 19 patients. All patients remained continent except for one with a neurogenic bladder who had minimal sporadic losses. Ten patients (40%) were using a CIC regimen, and the other 14 voided with the Valsalva maneuver, without residual urine according to a sonographic evaluation. UTI occurred at least once in 14 patients (56%), 8 voiding with CIC and 6 with the Valsalva maneuver. Three patients had seven, 1 patient had four, and 10 had one or two UTIs. Eight patients (32%) were hospitalized 14 times for intravenous antibiotic treatment, and transient creatinine elevation occurred in 8 of such episodes, with a mean serum creatinine of 1.6 mg/ dL. The creatinine values of all patients returned to previous levels after antibiotic treatment, except for 1 patient using CIC because of a neurogenic bladder, who had reflux to the transplanted kidney. This patient lost the graft 39 months later from chronic interstitial nephritis secondary to VUR and repeated UTIs. She received a second cadaveric kidney graft that was functioning well after 97 months. All patients underwent urethrocystography 3 months after transplantation. With the exception of the patients transplanted without an antireflux technique (3 patients), no one presented with VUR. Six patients had the ureter reimplanted into a bowel segment; two of those with implantation at the sigmoid developed ureteral stenosis at the implantation site. One had the ureter reimplanted and the other was treated percutaneously with the Acucise catheter. One patient presenting with a lymphocele was treated through external drainage. All patients had a good outcome. Four patients died with functioning grafts. Three of them died of causes not related to the cysto772
plasty. One died of sepsis due to pneumonia 30 days after transplantation, another of a cavernous sinus thrombosis secondary to acute sinusitis 18 months after transplantation, and the third had sudden death at home 19 months after transplantation. One patient with tuberculosis augmented with an ileocecal segment died of carcinomatosis due to an adenocarcinoma that originated at the vesicointestinal anastomosis 25 years after enlargement and 6.5 years after transplantation. This patient voided with the Valsalva maneuver and had not presented with UTI or residual urine. The actuarial patient survival rate was 96%, 86%, and 86% and the graft survival rate was 96%, 86%, and 78% at 12, 36, and 60 months, respectively (Fig. 2). COMMENT Transplanted patients with lower urinary problems may have increased morbidity and mortality if the problems are not recognized before transplantation. The bladder capacity and compliance are the most important factors to be evaluated, and a consistent method of complete bladder emptying is needed, either by spontaneous voiding or CIC. Pretransplant evaluation of the lower urinary tract is sometimes difficult. A trial of bladder cycling is helpful in restoring bladder capacity and in assessing the need for augmentation in patients with previous urinary diversions or defunctionalized bladders. Bladder augmentation is a well-known procedure for low-capacity and poor compliance bladders.10 The advantages in using the ureter as a source of enlargement are many11; however, when the ureter is not available, is nondilated, or has been previously manipulated, the use of intestinal UROLOGY 60 (5), 2002
segments is the best alternative.5 Marshall et al.12 first described augmentation cystoplasty combined with renal transplantation in 1982. Since then, other reports have been published showing good outcomes in these patients.13,14 However, Alfrey et al.15 had poor outcomes with bladder augmentation and renal transplantation. They believe a nonfree-draining intestinal urinary reservoir can impose a high risk of a poor outcome because of recurrent UTIs and immunosuppression. The most important aspect for the success in all of the procedures is detubularization, which interrupts the peristaltic activity, abolishes massive contractions, and enhances capacity.10 The detrusor should be widely incised to avoid coordinated autonomic contractions. A U-shaped incision is performed longitudinally, creating a large surface for the bowel anastomosis and avoiding the formation of an “hourglass”-shaped augmented bladder. Detubularized ileum remains the most commonly used segment because of its abundance and reduced complication rates. We preferred sigmoid segments in patients with tuberculosis, because they have minimal capacity, making ureteral reimplantation into the bladder impossible. The “tenia coli” provides significant advantages over the ileum in the sense that it is an excellent site for ureteral reimplantation with an antireflux procedure. We reimplanted one ureter into the ileum using the Le Duc technique without major difficulties or complications. The bladder portion of the augmented reservoir should be used for the ureteral reimplantation. None of the patients whose ureter was implanted into the bladder presented with urologic complications compared with 2 patients who presented with ureteral stenosis in ureters implanted into the bowel segment. When the reservoir cannot be adequately dissected, a ureteroureteral anastomosis with the native ureter is a good option and was used in 3 patients. Every cystoplasty was performed before transplantation, except for 3 patients whose bladder dysfunction was not recognized and who developed impairment of graft function long after the surgery. The adequate timing for cystoplasty is at least 8 to 12 weeks before transplantation and the introduction of immunosuppression, ensuring a functioning reservoir with adequate capacity, compliance, and bladder drainage. Motivation and training with CIC before transplantation are very important issues and must be routine for patients with a neurogenic bladder. None of the patients with bladder enlargement needed bladder cycles while waiting for transplantation, even the ones who waited for a cadaveric donor. Nine patients with a neurogenic bladder and one with posterior urethral valves used CIC. The reUROLOGY 60 (5), 2002
maining patients voided using the Valsalva maneuver with adequate bladder emptying, as evaluated by ultrasonography or urinary catheterization. CIC is safe even in patients who undergo kidney transplantation.13 The most important problem associated with bladder enlargement is UTIs, mainly in the group of patients using CIC. The antireflux procedure is important in this group of patients because of the higher risk of UTI. An antireflux procedure could prevent pyelonephritis, because it prevents contaminated urine from refluxing into the upper urinary tract. One patient in the CIC group whose ureter was reimplanted without an antireflux procedure presented with seven episodes of pyelonephritis and lost her graft after 39 months from interstitial chronic nephritis. Her enlarged bladder was re-evaluated and showed good compliance and capacity voiding by CIC. She underwent a second cadaveric donor transplant after 11 months and was well after a follow-up of 97 months. After the first series of patients, the urodynamic evaluation was reduced to only one study, performed 2 to 3 months after bladder enlargement. A better knowledge of the enterocystoplasty behavior allowed this kind of surveillance, reducing urinary manipulation and the risk of UTI. The risk of a malignant neoplasia is well known16 and could be raised by immunosuppression. Analysis of the Cincinnati Transplant Tumor Registry revealed that the frequency of cancer common to the general population (eg, carcinoma of the prostate, breast, and colon) is not increased among transplant patients. However, cancers uncommon to the general population (eg, lymphomas, Kaposi’s sarcoma, and hepatobiliary tumors) occur more often in transplant recipients.17,18 One of our patients died of carcinomatosis due to an adenocarcinoma that originated at the vesicointestinal anastomotic site.19 CONCLUSIONS Augmentation cystoplasty is a safe and efficient treatment for lower urinary dysfunction, and renal transplantation can be performed in these patients with no increased risk for graft outcome. Patients must be followed up closely with special attention to UTIs. Excellent graft and patient survival rates and controlled episodes of infection make bladder enlargement a good option for patients with serious bladder diseases. REFERENCES 1. Hamburger J, Vaisse J, Crosnier J, et al: Renal homotransplantation in man after radiation of the recipient. Am J Med 132: 854 –871, 1962. 773
2. Hinman F Jr: Selection of intestinal segments for bladder substitution: physical and physiological characteristics. J Urol 139: 519 –523, 1988. 3. Barnett MG, Bruskewitz R, Glass N, et al: Ileocecocystoplasty bladder augmentation and renal transplantation. J Urol 138: 855–858, 1987. 4. McGuire E, and Morrissey SG: The development of neurogenic vesical dysfunction after experimental spinal cord injury or sacral rhizotomy in non-human primates. J Urol 128: 1390 –1393, 1982. 5. Nahas WC, Mazzucchi E, Antonopoulos IO, et al: End stage renal disease and bladder dysfunction–algorithm for renal transplantation. J Urol 163(suppl 4): 330, 2000. 6. Gregoir W. Le traitement chirurgical du reflux ve´ sicoure´ te´ ral conge´ nital. Acta Chir Belg 63: 431– 439, 1964. 7. Leadbetter WF: Consideration of problems incident to performance of uretero-enterostomy: report of a technique. J Urol 65: 818 –830, 1951. 8. Le Duc A, Camey M, and Teillac P: Antireflux ureteroileal implantation via a mucosal sulcus. Ann Urol 21: 33–34, 1987. 9. Neto DE, Americo da Fonseca J, and Jota de Paula FJ: The impact of azathioprine on chronic viral hepatitis in renal transplantation: a long term, single center, prospective study on azathioprine withdrawal. Transplantation 68: 976 –980, 1999. 10. Studer UE, deKernion JB, and Zimmern PE: A model for a bladder replacement plasty by an ileal reservoir: an experimental study in dogs. Urol Res 13: 243, 1985.
774
11. Gonzales R, Buson H, Reid C, et al: Seromuscular colocystoplasty lined with urothelium: experience with 16 patients. Urology 45: 124 –129, 1994. 12. Marshall FF, Smolev JK, Spees ER, et al: The urological evaluation and management of patients with congenital lower urinary tract anomalies prior to renal transplantation. J Urol 127: 1078 –1081, 1982. 13. Zaragoza MR, Ritchey ML, Bloom DA, et al: Enterocystoplasty in renal transplantation candidates: urodynamic evaluation and outcome. J Urol 150: 1463–1466, 1993. 14. Nahas WC, Mazzucchi E, Antonopoulos IO, et al: Kidney transplantation in patients with bladder augmentation: surgical outcome and urodynamic follow-up. Transplant Proc 29: 157–158, 1997. 15. Alfrey EJ, Conley SB, Tanney DC, et al: Use of an augmented urinary bladder can be catastrophic in renal transplantation. Transplant Proc 29: 154 –155, 1997. 16. Filmer RB, and Spencer JR: Malignancies in bladder augmentation and intestinal conduits. J Urol 143: 671–678, 1990. 17. Penn I: Why do immunosuppressed patients develop cancer? Crit Rev Oncog 1: 27–52, 1989. 18. Penn I: The changing pattern of posttransplant malignancies. Transplant Proc 23: 1101–1103, 1991. 19. Nahas WC, Izuka FH, Mazzucchi E, et al: Adenocarcinoma of an augmented bladder 25 years after ileocecocystoplasty and 6 years after renal transplantation. J Urol 162: 490 – 491, 1999.
UROLOGY 60 (5), 2002