INVESTIGATIVE
UROLOGY
ANATOMIC, FUNCTIONAL, AND PATHOLOGIC CHANGES FROM INTERNAL URETERAL STENT PLACEMENT* DANIEL J. CULKIN, M.D. ROGER ZITMAN, M.D. W. STEWART BUNDRICK, M.D. YOGENDRA GOEL, M.D.
V HUGH PRICE, D.V.M. SHIRLEY LEDBETTER, R.T. JOHN A. MATA, M.D. DENNIS D. VENABLE, M.D.
From the Department of Urology, Overton Brooks Veterans Affairs Medical Center, and Louisiana State University Medical Center, Shreveport, Louisiana
ABSTRACT-The anatomic, hydrodynamic, functional, and pathologic changes associated with unilateral internal ureteral stenting were evaluated in 20 female canines. Selective glomerular filtration rates (GFR) were measured with technetium 99m diethylenetriamine pentaacetic acid (DTPA) renal scans (N = 14) prior to and several weeks afier unilateral internal stent placement. Cystometry and cystography were done at weekly intervals to determine if reflux occurred and to measure the intravesical pressure to produce this reflux (N = 16). Ureteral lumenal capacities of mid 6-cm ureteral segments of stented and unstented ureters were compared. The mid-ureteral lumenal volumes were three times greater in the stented ureters (p< 0.002). There were no significant differences in the selective GFR before and after stenting. Low-pressure vesicoureteral reflux occurred at a mean intravesical pressure of 13.7 cm of water and was present in 84.6 percent (llN3) of the canines whose stents did not migrate or obstruct from encrustation. There were no significant alterations in serum chemistries or blood counts. Fluoroscopic imaging also showed ineffective ureteral peristalsis. This study confirms that internal ureteral stents cause vesicoureteral reflux and significant lumenal dilation without altering renal function.
The retrograde or antegrade endoscopic placement of internal ureteral stents has been a very useful addition to the urologist’s available methods.1-5 Placement of these catheters can obviate the need for supravesical diversions (i.e., in the form of percutaneous nephrostomy tubes, surgically placed nephrostomy tubes, or ureterointestinal diversions) .e*7 The low morbidity associated with the placement of an internal ureteral catheter has been facilitated by the development of better endoscopes, light
sources, an assortment of ureteral catheter shapes and sixes, and guide/glide wires. However, the short-term and long-term side effects of this procedure have not been well documented. The purpose of this study is to evaluate the hydrodynamics, anatomic and functional changes associated with internal ureteral stent placement in the canine model. Material and Methods Twenty female mongrels, weighing 20-30 kg, underwent exploratory laparotomy. A 4.8F, 16cm, Double-J catheter (Surgitek, Racine, WI) was placed retrograde over a guidewire,
Supported by Research Advisory Croup and Merit Review Funding from the Department of Veterans Affairs.
UROLOGY
/
OCTOBER
1992
I
VOLUME
40, NUMBER
4
385
Two 6-cm mid-ureteral segments filled with physiologic saline at 20 cm water pressure. Segment taken from stented ureter (white arrow) i.s larger. FIGURE 2.
FIGURE 1. Excised urinary tract of canine showing
ureteral thickening of stented ureter (white arrow). through a cystotomy. The distal J portion was secured in position by placing a 3-O Prolene stitch through a hole in the distal J portion of the ureteral catheter and securing it to the bladder wall with a transmural stitch. The bladder was closed with 3-O Vicryl sutures in a simple running fashion. The dog’s abdomen was closed in layers using a polyglycolic suture. Renal function was assessed by a technetium 99m diethylenetriamine pentaacetic acid (DTPA) selective glomerular filtration rate (GFR) measurements prior to the exploratory laparotomy and after six to sixteen weeks of internal ureteral stenting. Metabolic, anatomic, and functional changes of the upper urinary tracts were assessed at weekly intervals with complete blood counts, serum electrolytes, blood urea nitrogen, creatinines, urinalyses, cystometry with fluoroscopically monitored cystography, and excretory urography. After completion of the experimental run, necropsy was performed, concentrating attention to the abdomen and retroperitoneum. The
386
entire urinary tract was excised en bloc, and gross inspection of the bladder lumen, renal units, and ureters were performed immediately (Fig. 1). At the time of necropsy, mid 6-cm lengths of ureter were excised from both the stented and unstented ureters. One end of each of the ureteral segments was ligated and the other cannulated with a small angiocath and filled with saline at a pressure of 20 cm water (Fig. 2). The volumes contained within each of the ureteral segments were measured. These measurements were classified as ureteral capacities with the difference in stented versus unstented sides approximating the degree of ureter-al dilation resulting from internal stenting. Histologic sections of the renal cortex, renal pelvis, and proximal, mid, and distal ureter were examined microscopically with hematoxylin-eosin stains. Results Renal function Of these 20 animals, 14 had undergone selective GFR determination by DTPA scan both before and several weeks after stent placement (Fig. 3). Of note, the prestenting GFR showed no significant difference between the left and the right kidney (P>O.34): the right kidney had a mean GFR of 71.9 mL/min with a standard deviation (SD) of 16.05 and a left GFR of 67.42 mL/min with a standard deviation of 12.71. The GFR just prior to sacrificing the animals demonstrated no significant difference between
UROLOGY
I OCTOBER1992
I VOLUME40,NUMBER4
FIGURE
3.
Renal scan e9”Tc
DTPA) showing selective right and left glomerular filtration rates.
right and left GFR: the mean GFR on the right was 66.5 mL/min with a SD of 18.15, and the left (stented renal unit) had a GFR of 59.6 mL/ min with SD of 22.97. Once again, the difference between the pre- and post-stenting of the right-side GFRs were not statistically different (P>O.34) (Table I). Also, the difference in the GFR of the left kidney before and after stenting was only 7.8 mL/min and was not statistically significant (P ~0.16). These animals were stented for an average of ten weeks and ranged from six weeks to sixteen weeks. In one of the animals there was a significant reduction in the GFR after the animal had been stented for approximately eight weeks. On autopsy there was demonstration of partial obstruction of the ureter due to proximal migration of the Double-J ureteral stent. Necropsy
At the time of autopsy, the detailed evaluation of the abdomen and retroperitoneum was carried out (N = 18). Autopsies were per-
TABLE
I.
Summary
Renal Unit Mean GFR (mL/ min) pre-Rx Mean GFR (mL/ min) post-Rx Ureteral capacity (mL) Mean VUR press* cm/Hz0
of stenting wsults
Right
GFR Left
P Value
71.9
67.4
NS
66.5 0.16
59.6 0.50
NS P 186% increase in stented ureteral capacity) and size as seen on low-power view of slides (hematoxylin and eosin) . Stent-induced ureterectasis, calicectasis, and interference with peristalsis also were demonstrated with excretory urography and cystoureterographic monitoring with fluoroscopy. Vesicoureteral reflux was produced in 11 of 18 animals (61.1%). However, if those animals with stent migration or with ureteral obstruction from the stabilizing sutures were excluded, low-pressure vesicoureteral reflux was present in 11 of 13 (84.6%) of the stented ureters. The calicectasis and the alteration of peristalsis that is induced by stenting would seem to indicate an obstructive phenomenon, whether it be functional or mechanical. However, the DTPA scans done prior to stent placement and repeated after the ureters had been stented for a mean of ten weeks showed no significant difference in the GFR as measured by the DTPA scans. Therefore, there appears to be no significant deleterious effects on the filtering capability of the kidney due to short term (i.e., < 4 months) internal ureteral stenting. Of significance here is that vesicoureteral reflux can be consistently produced. The changes produced by internal ureteral stent placement mimic many of the characteristics of the lower urinary tract which could make the upper urinary tract accessible to oncolytic agents through a transurethral route. That is, it can provide a reservoir to ensure a
389
prolonged contact time by delivering the agent at a predetermined infusion pressure. Also, these same anatomic changes can serve as a neoadjunct to other ureteral manipulations such as basket extraction of calculi and/or ureteroscopy. In conclusion, reproducible upper urinary tract changes occur with internal ureteral stenting. Although lumenal dilation of the ureter, interference with peristalsis, secondary inflamreflux matory changes, and vesicoureteral occur, there appears to be no alteration in GFR. Presently we are using this model to investigate the toxicities of various topical oncolytic agents delivered to the upper urinary tract through a transurethral route and the reversibility of these changes after withdrawal of the stent. Louisiana State University Medical Center Department of Urology RO. Box 33932 Shreveport, Louisiana 71130-3932 (DR. CULKIN)
390
References 1. Zimskind PD, Fetter TR, and Wilkerson JL: Clinical use of long-term indwelling silicone rubber ureteral splints inserted cystoscopically, J Urol 97: 840 (1967). 2. Finney BP: Experience with new Double-J ureteral catheter stent, J Urol 129: 678 (1978). 3. Gibbons Rp, Correa RJ Jr, and Cummings KB: Experience with indwelling ureteral stent catheters, J Urol 115: 22 (1967). 4. Goldin AR: Percutaneous ureteral splinting, Urology 10: 165 (1977). 5. Miller RD, Reinke DB, Clayman RV, and Lange PH: Percutaneous approach to the ureter, Urol Clin North Am 9: 31 (1982). 6. Hepperlen TW, Mardis HK, and Kammandel H: The pigtail ureteral stent in the cancer patient, J Urol 121: 17 (1979). 7. Andriole GL, Bettman MA, Garnick MB, and Richie JD: Indwelling Double-J ureteral stems for temporary and permanent urinary drainage: experience with 87 patients, J Urol 131: 239 (1984). 8. Krawiec DR, d al: Use of 99m Tc diethylenetriamine pentaacetic acid for assessment of renal function in dogs with suspected renal disease, JAMA 192: 1077 (1977). 9. Ulm AH, and Krauss L: Total unilateral Teflon ureteral substitute in the dog, J Uro183: 557 (1966). 10. Blum J, Skemp C, and Reiser M: Silicone rubber ureteral prosthesis, J Urol 90: 276 (1963). 11. Block NL, Stover E, and Politano VA: A prosthetic ureter in the dog, presented at 72nd Annual Meeting of American Urological Association, Chicago, Illinois, April 24-28, 1977.
UROLOGY
I
OCTOBER 1992
/
VOLUME 40, NUMBER 4
UROLOGY
ANATOMIC, FUNCTIONAL, AND PATHOLOGIC CHANGES FROM INTERNAL URETERAL STENT PLACEMENT* DANIEL J. CULKIN, M.D. ROGER ZITMAN, M.D. W. STEWART BUNDRICK, M.D. YOGENDRA GOEL, M.D.
V HUGH PRICE, D.V.M. SHIRLEY LEDBETTER, R.T. JOHN A. MATA, M.D. DENNIS D. VENABLE, M.D.
From the Department of Urology, Overton Brooks Veterans Affairs Medical Center, and Louisiana State University Medical Center, Shreveport, Louisiana
ABSTRACT-The anatomic, hydrodynamic, functional, and pathologic changes associated with unilateral internal ureteral stenting were evaluated in 20 female canines. Selective glomerular filtration rates (GFR) were measured with technetium 99m diethylenetriamine pentaacetic acid (DTPA) renal scans (N = 14) prior to and several weeks afier unilateral internal stent placement. Cystometry and cystography were done at weekly intervals to determine if reflux occurred and to measure the intravesical pressure to produce this reflux (N = 16). Ureteral lumenal capacities of mid 6-cm ureteral segments of stented and unstented ureters were compared. The mid-ureteral lumenal volumes were three times greater in the stented ureters (p< 0.002). There were no significant differences in the selective GFR before and after stenting. Low-pressure vesicoureteral reflux occurred at a mean intravesical pressure of 13.7 cm of water and was present in 84.6 percent (llN3) of the canines whose stents did not migrate or obstruct from encrustation. There were no significant alterations in serum chemistries or blood counts. Fluoroscopic imaging also showed ineffective ureteral peristalsis. This study confirms that internal ureteral stents cause vesicoureteral reflux and significant lumenal dilation without altering renal function.
The retrograde or antegrade endoscopic placement of internal ureteral stents has been a very useful addition to the urologist’s available methods.1-5 Placement of these catheters can obviate the need for supravesical diversions (i.e., in the form of percutaneous nephrostomy tubes, surgically placed nephrostomy tubes, or ureterointestinal diversions) .e*7 The low morbidity associated with the placement of an internal ureteral catheter has been facilitated by the development of better endoscopes, light
sources, an assortment of ureteral catheter shapes and sixes, and guide/glide wires. However, the short-term and long-term side effects of this procedure have not been well documented. The purpose of this study is to evaluate the hydrodynamics, anatomic and functional changes associated with internal ureteral stent placement in the canine model. Material and Methods Twenty female mongrels, weighing 20-30 kg, underwent exploratory laparotomy. A 4.8F, 16cm, Double-J catheter (Surgitek, Racine, WI) was placed retrograde over a guidewire,
Supported by Research Advisory Croup and Merit Review Funding from the Department of Veterans Affairs.
UROLOGY
/
OCTOBER
1992
I
VOLUME
40, NUMBER
4
385
Two 6-cm mid-ureteral segments filled with physiologic saline at 20 cm water pressure. Segment taken from stented ureter (white arrow) i.s larger. FIGURE 2.
FIGURE 1. Excised urinary tract of canine showing
ureteral thickening of stented ureter (white arrow). through a cystotomy. The distal J portion was secured in position by placing a 3-O Prolene stitch through a hole in the distal J portion of the ureteral catheter and securing it to the bladder wall with a transmural stitch. The bladder was closed with 3-O Vicryl sutures in a simple running fashion. The dog’s abdomen was closed in layers using a polyglycolic suture. Renal function was assessed by a technetium 99m diethylenetriamine pentaacetic acid (DTPA) selective glomerular filtration rate (GFR) measurements prior to the exploratory laparotomy and after six to sixteen weeks of internal ureteral stenting. Metabolic, anatomic, and functional changes of the upper urinary tracts were assessed at weekly intervals with complete blood counts, serum electrolytes, blood urea nitrogen, creatinines, urinalyses, cystometry with fluoroscopically monitored cystography, and excretory urography. After completion of the experimental run, necropsy was performed, concentrating attention to the abdomen and retroperitoneum. The
386
entire urinary tract was excised en bloc, and gross inspection of the bladder lumen, renal units, and ureters were performed immediately (Fig. 1). At the time of necropsy, mid 6-cm lengths of ureter were excised from both the stented and unstented ureters. One end of each of the ureteral segments was ligated and the other cannulated with a small angiocath and filled with saline at a pressure of 20 cm water (Fig. 2). The volumes contained within each of the ureteral segments were measured. These measurements were classified as ureteral capacities with the difference in stented versus unstented sides approximating the degree of ureter-al dilation resulting from internal stenting. Histologic sections of the renal cortex, renal pelvis, and proximal, mid, and distal ureter were examined microscopically with hematoxylin-eosin stains. Results Renal function Of these 20 animals, 14 had undergone selective GFR determination by DTPA scan both before and several weeks after stent placement (Fig. 3). Of note, the prestenting GFR showed no significant difference between the left and the right kidney (P>O.34): the right kidney had a mean GFR of 71.9 mL/min with a standard deviation (SD) of 16.05 and a left GFR of 67.42 mL/min with a standard deviation of 12.71. The GFR just prior to sacrificing the animals demonstrated no significant difference between
UROLOGY
I OCTOBER1992
I VOLUME40,NUMBER4
FIGURE
3.
Renal scan e9”Tc
DTPA) showing selective right and left glomerular filtration rates.
right and left GFR: the mean GFR on the right was 66.5 mL/min with a SD of 18.15, and the left (stented renal unit) had a GFR of 59.6 mL/ min with SD of 22.97. Once again, the difference between the pre- and post-stenting of the right-side GFRs were not statistically different (P>O.34) (Table I). Also, the difference in the GFR of the left kidney before and after stenting was only 7.8 mL/min and was not statistically significant (P ~0.16). These animals were stented for an average of ten weeks and ranged from six weeks to sixteen weeks. In one of the animals there was a significant reduction in the GFR after the animal had been stented for approximately eight weeks. On autopsy there was demonstration of partial obstruction of the ureter due to proximal migration of the Double-J ureteral stent. Necropsy
At the time of autopsy, the detailed evaluation of the abdomen and retroperitoneum was carried out (N = 18). Autopsies were per-
TABLE
I.
Summary
Renal Unit Mean GFR (mL/ min) pre-Rx Mean GFR (mL/ min) post-Rx Ureteral capacity (mL) Mean VUR press* cm/Hz0
of stenting wsults
Right
GFR Left
P Value
71.9
67.4
NS
66.5 0.16
59.6 0.50
NS P 186% increase in stented ureteral capacity) and size as seen on low-power view of slides (hematoxylin and eosin) . Stent-induced ureterectasis, calicectasis, and interference with peristalsis also were demonstrated with excretory urography and cystoureterographic monitoring with fluoroscopy. Vesicoureteral reflux was produced in 11 of 18 animals (61.1%). However, if those animals with stent migration or with ureteral obstruction from the stabilizing sutures were excluded, low-pressure vesicoureteral reflux was present in 11 of 13 (84.6%) of the stented ureters. The calicectasis and the alteration of peristalsis that is induced by stenting would seem to indicate an obstructive phenomenon, whether it be functional or mechanical. However, the DTPA scans done prior to stent placement and repeated after the ureters had been stented for a mean of ten weeks showed no significant difference in the GFR as measured by the DTPA scans. Therefore, there appears to be no significant deleterious effects on the filtering capability of the kidney due to short term (i.e., < 4 months) internal ureteral stenting. Of significance here is that vesicoureteral reflux can be consistently produced. The changes produced by internal ureteral stent placement mimic many of the characteristics of the lower urinary tract which could make the upper urinary tract accessible to oncolytic agents through a transurethral route. That is, it can provide a reservoir to ensure a
389
prolonged contact time by delivering the agent at a predetermined infusion pressure. Also, these same anatomic changes can serve as a neoadjunct to other ureteral manipulations such as basket extraction of calculi and/or ureteroscopy. In conclusion, reproducible upper urinary tract changes occur with internal ureteral stenting. Although lumenal dilation of the ureter, interference with peristalsis, secondary inflamreflux matory changes, and vesicoureteral occur, there appears to be no alteration in GFR. Presently we are using this model to investigate the toxicities of various topical oncolytic agents delivered to the upper urinary tract through a transurethral route and the reversibility of these changes after withdrawal of the stent. Louisiana State University Medical Center Department of Urology RO. Box 33932 Shreveport, Louisiana 71130-3932 (DR. CULKIN)
390
References 1. Zimskind PD, Fetter TR, and Wilkerson JL: Clinical use of long-term indwelling silicone rubber ureteral splints inserted cystoscopically, J Urol 97: 840 (1967). 2. Finney BP: Experience with new Double-J ureteral catheter stent, J Urol 129: 678 (1978). 3. Gibbons Rp, Correa RJ Jr, and Cummings KB: Experience with indwelling ureteral stent catheters, J Urol 115: 22 (1967). 4. Goldin AR: Percutaneous ureteral splinting, Urology 10: 165 (1977). 5. Miller RD, Reinke DB, Clayman RV, and Lange PH: Percutaneous approach to the ureter, Urol Clin North Am 9: 31 (1982). 6. Hepperlen TW, Mardis HK, and Kammandel H: The pigtail ureteral stent in the cancer patient, J Urol 121: 17 (1979). 7. Andriole GL, Bettman MA, Garnick MB, and Richie JD: Indwelling Double-J ureteral stems for temporary and permanent urinary drainage: experience with 87 patients, J Urol 131: 239 (1984). 8. Krawiec DR, d al: Use of 99m Tc diethylenetriamine pentaacetic acid for assessment of renal function in dogs with suspected renal disease, JAMA 192: 1077 (1977). 9. Ulm AH, and Krauss L: Total unilateral Teflon ureteral substitute in the dog, J Uro183: 557 (1966). 10. Blum J, Skemp C, and Reiser M: Silicone rubber ureteral prosthesis, J Urol 90: 276 (1963). 11. Block NL, Stover E, and Politano VA: A prosthetic ureter in the dog, presented at 72nd Annual Meeting of American Urological Association, Chicago, Illinois, April 24-28, 1977.
UROLOGY
I
OCTOBER 1992
/
VOLUME 40, NUMBER 4
