Use of indwelling, double-pigtail stents for treatment of malignant ureteral obstruction in dogs: 12 cases (2006–2009)

Allyson C. Berent The Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Chick Weisse The Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Matthew W. Beal Department of Clinical Studies, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

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Dorothy C. Brown The Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Kimberly Todd The Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Demetrius Bagley Department of Urology, Thomas Jefferson University Hospital, Philadelphia, PA 19107.

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Abstract

Objective—To determine the outcome of minimally invasive ureteral stent placement for dogs with malignant ureteral obstructions.

Design—Retrospective case series.

Animals—12 dogs (15 ureters) with ureteral obstruction secondary to a trigonal urothelial carcinoma.

Procedures—In all patients, indwelling, double-pigtail ureteral stents were placed by means of percutaneous antegrade needle and guide wire access under ultrasound and fluoroscopic guidance.

Results—Stents were successfully placed in all patients. In 11 of 12 patients, percutaneous antegrade access was accomplished. One patient required access via laparotomy because percutaneous access could not be achieved. The median survival time from the date of diagnosis was 285 days (range, 10 to 1,571 days), with a median survival time of 57 days (range, 7 to 337 days) from the date of stent placement. Three complications occurred in 1 patient. Seven patients required concurrent urethral stent placement for relief of urethral obstruction. All animals were discharged from the hospital (median hospitalization time after stent placement, 18 hours [range, 4 hours to 7 days]) with an indwelling, double-pigtail ureteral stent (3 bilateral and 9 unilateral) in place. All stents evaluated 0.25 to 11 months after placement were considered patent.

Conclusions and Clinical Relevance—Findings suggested that ureteral stent placement was safe, effective, and well tolerated in patients with malignant ureteral obstructions. Stents could be reliably placed in a minimally invasive manner and remain patent long-term. Ureteral stent placement should be considered as early as possible in patients with neoplasia, prior to the development of permanent renal damage.

Abstract

Objective—To determine the outcome of minimally invasive ureteral stent placement for dogs with malignant ureteral obstructions.

Design—Retrospective case series.

Animals—12 dogs (15 ureters) with ureteral obstruction secondary to a trigonal urothelial carcinoma.

Procedures—In all patients, indwelling, double-pigtail ureteral stents were placed by means of percutaneous antegrade needle and guide wire access under ultrasound and fluoroscopic guidance.

Results—Stents were successfully placed in all patients. In 11 of 12 patients, percutaneous antegrade access was accomplished. One patient required access via laparotomy because percutaneous access could not be achieved. The median survival time from the date of diagnosis was 285 days (range, 10 to 1,571 days), with a median survival time of 57 days (range, 7 to 337 days) from the date of stent placement. Three complications occurred in 1 patient. Seven patients required concurrent urethral stent placement for relief of urethral obstruction. All animals were discharged from the hospital (median hospitalization time after stent placement, 18 hours [range, 4 hours to 7 days]) with an indwelling, double-pigtail ureteral stent (3 bilateral and 9 unilateral) in place. All stents evaluated 0.25 to 11 months after placement were considered patent.

Conclusions and Clinical Relevance—Findings suggested that ureteral stent placement was safe, effective, and well tolerated in patients with malignant ureteral obstructions. Stents could be reliably placed in a minimally invasive manner and remain patent long-term. Ureteral stent placement should be considered as early as possible in patients with neoplasia, prior to the development of permanent renal damage.

Indwelling ureteral stents have been routinely placed in human patients with a variety of disorders to maintain urine flow from the renal pelvis into the urinary bladder.1–11 Ureteral stents were first placed with an open surgical approach in the 19th century,1 and it was not until 1967 that the first endoscopic ureteral stent placement was reported.2 Subsequently, the endoscopic technique has become routine and is considered the standard of care in human patients with many conditions.3–9 A double-J stent was first described in 1978,3 and the design was ultimately modified to the current double pigtail to minimize stent migration. To our knowledge, ureteral stent placement has never been described in a small animal veterinary patient beyond abstract form.a

A double-pigtail ureteral stent is typically a multifenestrated catheter with a pigtail loop on each end. The proximal loop is curled inside the renal pelvis, the shaft of the catheter sits inside the ureteral lumen, and the distal pigtail terminates inside the urinary bladder. This type of stent bypasses the ureteral obstruction, transporting urine from the renal pelvis directly into the urinary bladder through and around the stent.

Ureteral stents are commonly used in human patients with ureteral obstructions secondary to ureterolithiasis,3,4,9,12 ureteral or trigonal obstructive neoplasia,1,5,9,10 or ureteral stenosis.12 Ureteral stents have been placed clinically at the authors' facilities in > 150 dogs and cats, both surgically and minimally invasively13 with various conditions including ureterolithiasis, ureteral stricture, ureteral trauma, and trigonal urothelial tumors.

Ureteral stent placement for management of malignant ureteral obstruction has been a mainstay of palliative treatment for humans with nonresectable tumors to preserve renal function.1,6,7,10 Ureteral stents have also been placed preoperatively for patient stabilization prior to surgical intervention. Various techniques have been described for stent placement. Reported success rate exceeds 90% when an antegrade approach (via percutaneous renal access)14 combined with an interventional radiologic technique is used, compared with an approximately 25% success rate when retrograde endoscopic-guided ureteral access is attempted15 because of the tumor covering the UVJ. Another common but less ideal alternative to ureteral stent placement in human patients with UVJ tumors is the placement of a PN tube for urinary diversion.7,14–17

Urothelial neoplasia in dogs is often complicated by local tumor invasion and obstruction of the urethra, ureters, or both. Although distant metastases have been reported18–20 in 17% to 50% of patients at the time of diagnosis, clinical signs on initial examination are most often (84% to 88% of patients) associated with the local disease,18–20 and the cause of death can be attributed to local tumor effects in > 60% of cases.19 Historically, once ureteral obstruction and subsequent renal compromise are identified, few management options existed. Nephrostomy tube placement or hemodialysis can provide temporary relief, but radical surgeries have been the only viable alternative for long-term management. The purpose of the study reported here was to describe a minimally invasive, potentially long-term treatment option to provide decompression of the renal collection system with the use of indwelling double-pigtail ureteral stents in dogs with obstructive trigonal malignant carcinoma. We hypothesized that the ureteral stent placement procedure would be a safe and effective technique for the management of malignant ureteral obstructions in dogs and would be associated with low morbidity and mortality rates.

Materials and Methods

Criteria for case selection—Medical records of dogs examined at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania or the Michigan State University Veterinary Teaching Hospital between January 2006 and January 2009 were reviewed to identify dogs in which a diagnosis of ureteral obstruction secondary to a carcinoma affecting the bladder, trigone, urethra, prostate, or any combination thereof had been made on the basis of cytologic or histologic examination.

Patients were included in the study if percutaneous placement of a double-pigtail ureteral stent for relief of malignant UVJ obstruction secondary to a carcinoma of the urinary tract had been attempted. For purposes of the present study, ureteral obstruction was defined as ultrasonographic evidence of dilatation of the ureter to the level of the UVJ. During the study period, patients were considered candidates for stent placement only if the renal pelvis was ≥ 5 mm in diameter, as this was the smallest size for which antegrade percutaneous access could safely be obtained. Patients were excluded from the study if ureteral stent placement was performed surgically and percutaneous placement was not attempted prior to surgery or if a stent had been placed in a retrograde fashion with cystoscopic guidance prior to a UVJ obstruction. Only patients diagnosed with a trigonal urothelial carcinoma (including TCC, prostatic adenocarcinoma, and undifferentiated urothelial carcinoma) were included in this study.

Medical records review—For patients included in the study, information regarding signalment; body weight; history of previous chemotherapy, radiation treatment, or surgical treatment; date of diagnosis of neoplasia; initial clinical signs; physical examination findings; and body condition score (1 to 9) were obtained from the medical record, along with results of clinicopathologic testing (ie, CBC, serum biochemical profile, coagulation profile, and urinalysis) performed prior to stent placement and results of bacteriologic culture and susceptibility testing of a urine sample.

Diagnostic imaging—In all patients, diagnostic imaging prior to stent placement included thoracic radiography (3 views) and abdominal ultrasonography. Renal pelvis diameter was measured in a transverse plane on an ultrasound image. Ureteropyelography and cystourethrography were also performed in each patient during the stent placement procedure.

Ureteral stent placement—Owner consent was obtained prior to stent placement. Owners were required to consent to surgery or euthanasia if the percutaneous attempt failed because the puncture in the renal parenchyma and pelvis would have led to a uroperitoneum or retroperitoneum if the ureteral obstruction was not relieved.

Ureteral stents were typically inserted in an antegrade direction (Figure 1) because of the lack of visibility of the UVJ during cystoscopic examination. However, in some female patients, transurethral cystoscopy was performed with the patient in dorsal recumbency to assess whether retrograde insertion was possible. Cystoscopy was typically not performed in male patients.

Figure 1—
Figure 1—

Fluoroscopic images obtained during antegrade ureteral stent placement in a 8-year-old sexually intact male Beagle with TCC. The dog was positioned in lateral recumbency, with cranial to the right and dorsal to the top of the image. A—A renal access needle (white arrowhead) has been advanced under ultrasound guidance into the renal pelvis (asterisk), and antegrade ureteropyelography has been performed. Notice the tortuous ureter (white arrows). B—A guide wire (black arrowheads) has been inserted through the renal access needle and advanced from the renal pelvis down the ureter to the level of the obstruction at the UVJ. A marker catheter in the descending colon can also be seen. C—The guide wire and an angiographic catheter have been advanced through the ureteral obstruction into the bladder and out the urethra (black arrows), allowing for though-and-through access. D—An introducer sheath and dilator set (white arrows) has been advanced in a retrograde manner from the urethra into the bladder and through the tumor to the level of the mid ureter. The marker catheter (asterisks) was used to measure ureteral length. E—The dilator was removed, and a second guide wire was inserted through the introducer sheath. A double-pigtail ureteral stent was advanced over this second guide wire and advanced in a retrograde manner until it curled inside the renal pelvis (short white arrow). The second guide wire was then removed, allowing the other end of the ureteral stent to curl inside the urinary bladder (long white arrow). The original guide wire can still be seen (black arrows).

Citation: Journal of the American Veterinary Medical Association 238, 8; 10.2460/javma.238.8.1017

The technique for ureteral stent placement varied slightly among patients. In general, however, the patient was placed in lateral recumbency with the affected kidney facing up. Hair was clipped on the dorsal paracostal and flank areas and the perineum (female) or prepuce (male), and these areas were aseptically prepared and draped. A marker catheterb was inserted in the rectum and advanced into the descending colon to allow for ureteral length measurement and to aid in choosing the appropriate stent length. A 3-mm skin incision was made over the kidney. With ultrasonographicc and fluoroscopicd guidance, an 18-gauge renal access needlee was used for antegrade ureteropyelography. A urine sample was obtained and submitted for bacteriologic culture and susceptibility testing. A volume of iodinated contrast materialf diluted 50:50 with sterile saline (0.9% NaCl) solution approximately equal to the volume of urine removed was injected. With fluoroscopic guidance, a 0.035-inch, stiffened, angle-tipped hydrophilic guide wireg was advanced through the needle and guided caudally through the lumen of the ureter to the level of the ureteral obstruction at the UVJ. The guide wire was then manipulated gently and advanced into the urinary bladder. If necessary, a combination guide wire and 4F angled angiographic catheterh were used to achieve access across the tumor. Once urinary bladder access was achieved, the wire (and catheter if used) was directed toward the bladder trigone and down the urethra caudally until through-and-through wire access was obtained as the wire exited the urethra. This wire was designated the safety wire. A 7F 45-cm introducer sheathi and dilator set were advanced retrograde over the safety wire through the urethral lumen and across the tumor and UVJ to the level of the mid ureter. This dilated the ureteral obstruction. The dilator was removed over the guide wire, leaving the sheath in place. A second 0.035-inch, unstiffened, angled hydrophilic guide wirej was inserted through the sheath in a retrograde manner, with the soft-angled tip advanced cranially in the ureteral lumen until it curled in the dilated renal pelvis. The second wire allowed the stent to be placed without losing the first through-and-through wire access (the safety wire) in the event that stent placement was not ideal and needed manipulation. A double-pigtail ureteral stentk–n of appropriate length was then advanced over the second guide wire through the sheath in a retrograde manner to bypass the ureteral obstruction. A pusher catheter was advanced over the same wire to advance the ureteral stent into position. Once the proximal end of the stent was advanced into the renal pelvis, the 7F sheath and guide wire were withdrawn into the urethra to allow the stent's proximal pigtail to curl in the renal pelvis and to push the distal end of the stent into the bladder with the pusher catheter. Once the stent was in place, the through-and-through safety wire was carefully removed through the urethra, leaving the double pigtail stent in place.

Procedure time and any associated complications were recorded. Data regarding additional procedures, such as urethral stento placement for concurrent malignant urethral obstruction, were also recorded. When urethral stent placement was necessary, the procedure was performed as reported20 after ureteral stent placement.

Postoperatively, patients were administered buprenorphine (10 μg/kg [4.5 μg/lb], IV, q 6 h for 1 to 3 doses) following recovery from the procedure. The urethra was infused with a 1:1 mixture of bupivacaine (1 mg/kg [0.45 mg/lb]) and saline solution for local transurethral analgesia. Fluids were administered (3 to 5 mL/kg/h [1.4 to 2.3 mL/lb/h], IV) after stent placement in all patients until discharge. At the time of discharge, owners were instructed to administer tramadol (2 to 4 mg/kg [0.9 to 1.8 mg/lb], PO, q 6 to 12 h for 1 to 2 days) as needed to relieve signs of pain and amoxicillin-clavulanic acid (13 to 18 mg/kg [5.9 to 8.2 mg/lb], PO, q 12 h) for 7 to 14 days, unless patients were concurrently being treated with another antimicrobial because of previously diagnosed urinary tract infection.

Follow-up—Information on complications, management, adjunctive treatment (eg, chemotherapy and radiation therapy), and results of follow-up serum biochemical analyses and microbiological testing were recorded. A CBC, measurement of BUN and serum creatinine concentrations, urinalysis with bacteriologic culture and susceptibility testing, and focal urinary tract ultrasonography were performed approximately 1 to 2 weeks after the procedure in all patients and then every 1 to 3 months thereafter, when permitted. Routine bacterial culture and susceptibility testing of a urine sample were recommended for all patients 2 weeks after the procedure and then every 2 to 3 months. If an infection was documented, treatment for 6 to 8 weeks was recommended with appropriate documentation of clearance. Long-term outcome variables that were evaluated included duration of survival, results of serum biochemical analyses, evidence of recurrent ureteral obstruction, serial imaging results, and reason for death or euthanasia.

Statistical analysis—Cox multivariable survival analysis was used to identify factors associated with survival time following ureteral stent placement and with survival time from the date of tumor diagnosis. Factors investigated included the presence of metastatic disease at the time of stent placement; other treatments (chemotherapy, surgery, radiation, or laser ablation) prior to stent placement; treatments following stent placement; body condition score at the time of stent placement (≥ 4 vs < 4 on a scale from 1 to 9); high BUN concentration, high serum creatinine concentration, or both prior to stent placement; concurrent placement of a urethral stent; presence of unilateral or bilateral ureteral obstruction; age; body weight; sex; breed; and time from diagnosis to stent placement. Continuous variables were centered prior to analysis. Centering, or subtracting the mean from each case, was used because the continuous variables did not have a meaningful value for 0 (eg, weight = 0 or age = 0) which could influence the graphic interpretation of the estimates. Factors for which the P value in the univariate analysis was < 0.20 were tested for significance in the multivariable model. Factors for which the P value was < 0.05 in the multivariable model were retained. The Wilcoxon rank sum test was used to compare the number of days from diagnosis to stent placement in patients that did and did not receive chemotherapy prior to stent placement. Kaplan-Meier estimates of survival functions were calculated for time from stent placement to death, time from diagnosis to death, and time from diagnosis to death stratified by treatment with chemotherapy prior to stent placement. All analyses were performed with a statistical software package.p

Results

Ten patients treated at the University of Pennsylvania and 2 patients treated at Michigan State University met the criteria for inclusion in the study. There was 1 sexually intact male, 5 castrated male, and 6 spayed female dogs. There were 4 mixed-breed dogs, 3 Beagles, 2 Shetland Sheepdogs, 2 Shih Tzus, and 1 German Shorthaired Pointer. Age ranged from 8 to 15.5 years (median, 10.5 years), and body weight ranged from 5.5 to 31.2 kg (12.1 to 68.6 lb; median, 19.1 kg [42.0 lb]). All patients had clinical signs of dysuria, including pollakiuria (n = 12), stranguria (12), hematuria (11), oliguria (3), and urinary incontinence (2). Six patients also had partial or complete urethral obstruction substantial enough to necessitate placement of a urethral stent. One additional patient had already had a urethral stent placed 1 month prior to ureteral stent placement. Eight patients had a decreased appetite with intermittent vomiting and nausea. Two patients with dark diarrheic feces were suspected to have melena, and 2 patients had severe tenesmus.

Median body condition score at the time of initial evaluation was 2.5 on a scale from 1 to 9, with 7 patients having poor body condition (score, 1.5 to 3.0), 2 patients being slightly overweight (score, 5 to 5.5), and 3 patients being of appropriate weight (score, 4 to 4.5). Physical examination findings related to the urogenital system included a palpable urethral mass during rectal examination (n = 9), a palpable caudal abdominal mass (4), and a large mass palpable in the perineal area between the rectum and urethra (1; site of previous surgical access to the urethra for an ultrasound-guided, endoscopic tumor laser ablation procedureq performed at a referring facility).

Results of a CBC, serum biochemical profile, urinalysis, urine bacteriologic culture and susceptibility testing, and coagulation profile performed prior to ureteral stent placement were available for all 12 patients. Seven of the 12 had evidence of azotemia prior to stent placement (BUN concentration, 64 to 139 mg/dL [median, 85 mg/dL; reference interval, 5 to 30 mg/dL]; creatinine concentration, 2.5 to 5.5 mg/dL [median, 3.8 mg/dL; reference interval, 0.7 to 1.8 mg/dL]) with a low urine specific gravity (range, 1.010 to 1.018; reference interval, > 1.035). Two of 12 patients had evidence of hyperkalemia (range, 3.9 to 7.1 mmol/L; median, 4.6 mmol/L; reference interval, 3.9 to 4.9 mmol/L), and 6 had evidence of hyperphosphatemia (range, 6.2 to 11.1 mmol/L; median, 6.5 mmol/L; reference interval, 2.8 to 6.1 mmol/L). Results of bacterial culture of a urine sample were positive for 4 patients, and appropriate antimicrobials were administered for a minimum of 48 hours prior to stent placement (range, 2 to 14 days). In all 4 patients, results of bacterial culture of a follow-up urine sample collected prior to or during stent placement were negative.

Diagnosis—In 7 patients, the diagnosis of ureteral obstruction secondary to a urinary tract carcinoma was made on the basis of histologic examination of cystoscopic-guided or fluoroscopic-guided biopsy specimens. In the remaining 5 patients, the diagnosis was made on the basis of cytologic examination of a voided urine sample or cytologic examination of samples obtained by means of traumatic catheterization or ultrasound-guided fine-needle aspiration. Overall, 9 of the 12 patients had a TCC, 2 had a prostatic carcinoma, and 1 had an undifferentiated carcinoma.

Previous treatment—Eight of the 12 patients received 1 or more treatments for the urinary tract carcinoma prior to ureteral stent placement. Some patients received > 1 treatment modality. Seven patients received chemotherapy of various types and durations. This included 1 patient that also underwent radiation therapy prior to receiving chemotherapy; 1 patient that underwent prostatectomy 1.5 years prior to documentation of ureteral obstruction, cystotomy for debulking of the tumor 2 months prior to documentation of ureteral obstruction, and chemotherapy; and 1 patient that was undergoing chemotherapy for hemangiosarcoma before the diagnosis of TCC was made. Two patients were treated with ultrasound-guided endoscopic laser ablationq prior to the diagnosis of ureteral obstruction. One patient had already undergone self-expanding metallic stent placement for malignant urethral obstruction 1 month prior to examination for ureteral obstruction.

Imaging—Three-view thoracic radiographs obtained within 3 weeks prior to ureteral stent placement were available for review in all 12 patients, with no evidence of pulmonary metastatic disease. All patients underwent abdominal ultrasonography prior to stent placement; 10 had bilateral hydroureter and 2 had unilateral hydroureter, whereas 6 had bilateral hydronephrosis and 6 had unilateral hydronephrosis. The renal pelvis diameter ranged from 5 to 40 mm (median, 18 mm) on the side where the stent was placed. Six of 12 patients had evidence of moderate sublumbar lymphadenopathy. Three of 12 patients had distant lymphadenopathy (inguinal and hypogastric). One patient had evidence of multiple masses throughout the mesentery ranging from 1 mm to > 4 cm in diameter. This was the patient with splenic hemangiosarcoma with a history of splenectomy 7 months earlier. All patients had evidence of neoplasia at the bladder trigone, and all patients had evidence of UVJ invasion by tumor on the side with hydroureter or hydronephrosis. Seven of 12 patients had evidence of urethral and bladder involvement.

Metastasis—Metastatic urothelial carcinoma lesions were identified in 4 of 12 patients (with 1 patient having 2 different sites of metastasis) on the basis of cytologic or histologic examination of biopsy specimens (sublumbar lymph nodes, 1; inguinal lymph nodes, 2; perineal region, 1; and maxillary gingival mass, 1) and were suspected in an additional 3 patients with enlarged sublumbar lymph nodes at the time of stent placement.

Ureteral stent placement—Four patients (3 females and 1 male) had cystoscopy performed at the time of stent placement. The ureteral orifice could not be seen in any of the 4 patients, which therefore did not permit retrograde stent placement. In all 12 patients, antegrade ureteropyelography was performed during stent placement. All ureters were enlarged, dilated, and tortuous. In 11 of the 12 patients, percutaneous antegrade access was accomplished. One patient required access via a laparotomy because the guide wire became coiled in the left renal pelvis and could not be advanced down the ureter and through the UVJ percutaneously. During surgery, a right ureteral stent was placed and a left ureteronephrectomy was performed because of the lack of any renal parenchyma and severe hydronephrosis (> 3.5 cm renal pelvis dilation).

Stent sizes ranged from 4.7 to 6F in diameter and from 8 to 32 cm in length. Procedure time for antegrade placement was recorded for 11 of the 12 patients and ranged from 25 to 185 minutes (median, 65 minutes). In the 2 patients in which bilateral ureteral stents were placed during a single anesthetic episode, procedure times were 65 and 75 minutes. For the patient in which a laparotomy was performed, procedure time was 65 minutes. Six patients underwent urethral stent placement following ureteral stent placement because of malignant urethral obstruction; 1 patient had had a urethral stent placed 1 month prior to ureteral stenting.

Only 3 of the 6 patients with bilateral hydronephrosis had bilateral stent placement. One patient underwent stent placement in the second ureter when azotemia did not resolve satisfactorily following the first stent placement. Median hospitalization time for all 12 patients was 18 hours (range, 4 to 168 hours).

One patient had 3 procedure-related complications. During ureteropyelography prior to stent placement, substantial contrast extravasation, suggestive of renal pelvis disruption, was seen at the cranial pole of the renal pelvis. After the ureteral stent was placed, a 6F locking-loop nephrostomy tuber was inserted over the safety guide wire to allow for urinary diversion and healing of the renal pelvis.s Within 12 hours, there was no evidence of abdominal or retroperitoneal effusion and the nephrostomy tube was capped. Forty-eight hours after stent placement, the distal end of the ureteral stent was documented to have migrated in a retrograde direction up the ureter, and by 72 hours, the distal end of the ureteral stent was inside the bulk of the tumor, resulting in reobstruction of the ureter (Figure 2). The nephrostomy tube was reopened, and the ureteral stent was percutaneously exchanged for a longer one. The nephrostomy tube was left in place when the patient was discharged, with a plan for removal in 7 days. However, 3 days after discharge, the patient inadvertently removed the nephrostomy tube while running. No adverse effect associated with premature removal of the nephrostomy tube was observed.

Figure 2—
Figure 2—

Lateral radiographic view of the abdomen of a 10-year-old castrated male Shetland Sheepdog. A—There is a double-pigtail ureteral stent (white arrows) and a urethral stent (black arrowheads) placed because of TCC obstructing the UVJ and the urethra. B—Notice that the distal end of the ureteral stent (white arrows) has migrated into the ureter, with no portion of the stent remaining in the urinary bladder (UB).

Citation: Journal of the American Veterinary Medical Association 238, 8; 10.2460/javma.238.8.1017

Postprocedure chemotherapy—Five of the 12 patients received chemotherapy following ureteral stent placement. Nine patients were being treated with NSAIDs at the time of hospital discharge (piroxicam, n = 4; meloxicam, 3; firocoxib, 1; and carprofen, 1) and 8 were maintained on NSAIDs long term (> 30 days).

Follow-up—In all patients that had azotemia prior to ureteral stent placement, there was an improvement in BUN and serum creatinine concentrations following stent placement prior to discharge. Results of bacterial culture of urine samples were available for review in 7 patients. Samples from 6 of the 7 patients evaluated after stent placement failed to yield any growth. In 1 patient, results of bacterial culture of urine collected 6 weeks after stent placement were positive. After antimicrobial treatment, subsequent urine samples were negative.

Follow-up ultrasonography was performed in 10 patients, and all 10 had evidence of improved hydronephrosis and hydroureter, although mild persistent renal pelvis dilation was noted in 3 patients despite resolution of ureteral dilation and improvement in BUN and serum creatinine concentrations. In 2 of these 3 patients, antegrade pyelography was performed to confirm stent patency and allow collection of a urine sample from the renal pelvis for bacterial culture. In both patients, bladder filling was evident and bacterial culture failed to yield any growth.

Survival time—Median survival time from the date of diagnosis was 285 days (range, 10 to 1,571 days; Figure 3), and median survival time from the date of ureteral stent placement was 57 days (range, 7 to 337 days). In univariate analyses, sex (P = 0.16) and age (P = 0.13) were associated with survival time from the date of stent placement; however, neither variable was significant in the multivariate analysis. Similarly, in univariate analyses, administration of chemotherapy prior to stent placement (P = 0.01) and time from diagnosis to stent placement (P = 0.04) were associated with survival time from the date of diagnosis; however, neither variable was significant in the multivariate analysis. Patients that received chemotherapy prior to stent placement had a significantly (P = 0.007) longer median time from diagnosis to stent placement (180 days; range, 25 to 1,520 days) than did patients that did not receive chemotherapy prior to stent placement (median, 3 days; range, 0 to 7 days).

Figure 3—
Figure 3—

Kaplan-Meier survival curves for time from diagnosis of malignant ureteral obstruction to death (A) and for time from ureteral stent placement to death (B) for 12 dogs that underwent ureteral stent placement because of UVJ obstruction and for time from diagnosis to death (C) for dogs in which chemotherapy was (median survival time, 331 days; n = 7) or was not (5) administered prior to stent placement.

Citation: Journal of the American Veterinary Medical Association 238, 8; 10.2460/javma.238.8.1017

Outcome—Two animals were lost to follow-up. In the remaining 10 patients, the ureteral stents were determined to be patent on the basis of results of diagnostic imaging (n = 10) at the time of last follow-up examination or on postmortem examination (4) between 0.25 and 11 months after stent placement. Causes of death included chemotherapeutic-induced toxicoses (n = 3), metastasis of the urinary tract tumor (3), septic peritonitis secondary to a gastric foreign body (1), and metastasis of a concurrent hemangiosarcoma (1). The cause of death was not known in the remaining 2 patients. None of the patients died because of known ureteral stent complications or urinary tract obstruction. No patient had evidence of stent intolerance (eg, signs of pain, dysuria, pollakiuria, hematuria, or signs of renal pain), oliguria, or anuria prior to death.

Discussion

Results of the present study suggested that ureteral stent placement was safe, effective, and well tolerated in patients with malignant ureteral obstructions. Stents could be placed percutaneously in 11 of the 12 patients and remained patent long term. Median survival time from the date of stent placement was 57 days (range, 7 to 337 days) and from the date of diagnosis was 285 days (range, 10 to 1,571 days).

In patients with ureteral obstructions, early intervention preserves functional renal tissue. Thus, obstruction relief should be recommended as soon as possible, before irreversible renal damage occurs. Studies21–26 have shown that following complete ureteral obstruction, decompression of the renal pelvis is essential to preserving renal function in the ipsilateral kidney. Following complete experimental ureteral obstruction in dogs, ureteral pressures increase immediately, resulting in a decrease in the GFR.21 The longer the ureter remains obstructed, the greater the likelihood and extent of irreversible damage.24 In studies involving clinically normal dogs, it was concluded that after 7 days of obstruction the GFR was permanently diminished by 35%,25 after 14 days the GFR was permanently diminished by 54%,26 and after 40 days there was nearly 100% irreversible decrease of the GFR.24–26 The recovery that was documented took weeks to months.24–26 These values were obtained in clinically normal dogs with acute, complete ureteral obstruction without preexisting azotemia or chronic obstructive disease. In patients with malignant obstructions, it is expected that initial partial obstruction would result in some degree of nephron hypertrophy. At the time of stent placement, most of the patients in the present report had nearly complete ureteral obstruction. A worse outcome might be anticipated for dogs with chronic or bilateral obstructions, compared with that for clinically normal research dogs, as compensatory hypertrophy could be exhausted. These patients may not have months of life remaining to allow for slow recovery of residual renal function. Taken together, these data encourage aggressive and timely intervention, particularly when ureteral obstruction is bilateral.

Controversy exists in human medicine regarding whether PN tubes or indwelling ureteral stents should be placed for palliative treatment of patients with non-resectable malignant ureteral obstructions.6,7,9,14,16,17 For intrinsic ureteral obstruction at the UVJ, indwelling ureteral stents have been recommended.6,7,9 For extrinsic ureteral compression resulting from retroperitoneal neoplasia, PN tubes have been recommended because of recurrent stent compression and obstruction.14–17 Many new stents with various designs and materials have been developed for placement in human patients with malignant ureteral obstruction and are currently being investigated for use in veterinary patients. In small animals, long-term management of a PN tube would be difficult and complicated for many owners. The risks of urinary tract infection and accidental dislodgment combined with the extensive maintenance that is required makes this option less than ideal for long-term use in veterinary patients, although temporary use can be successful.r In the present report, a PN tube was placed in 1 patient but the dog accidentally dislodged the tube at home prematurely.

In the present study, a total of 15 stents were placed in 12 patients. The 4 patients that had no systemic signs of illness (eg, lethargy, inappetence, and weight loss) on initial examination survived a median of 240 days, whereas those that had signs of systemic illness on initial examination survived a median of 52 days. Although median survival time did not differ significantly between the 2 groups, we currently recommend treatment as early as possible.

The authors have performed cystoscopic-guided retrograde ureteral stenting in > 75 dogs for various conditions other than malignant obstructions (eg, ureterolithiasis, ureteral strictures, and ureteral trauma). This technique is less invasive than antegrade ureteral stent placement, and most patients can be discharged the day of the procedure. Once hydroureter is present, the UVJ is likely completely obscured by the tumor, and the chance of cannulating the UVJ with a guide wire during cystoscopy is low. Preemptive or prophylactic placement of a ureteral stent prior to complete tumor obstruction can be performed, with benefits including avoidance of renal puncture, prevention of associated renal damage, absence of pain from hydroureter and hydronephrosis, and a lower risk of pyelonephritis attributable to stagnation of urine. Risks associated with retrograde ureteral stent placement include ureteral perforation, iatrogenic pyelonephritis, and stent migration. We recommend that this option be discussed with owners when tumor progression is imminent and documented and should be carefully considered as the risks and benefits are currently unclear. In our practice, patients with TCC are routinely and carefully evaluated via cystoscopy and ultrasonography for the development of ureteral obstruction in an attempt to prevent development of acute renal failure and to allow kidney decompression before severe nephron loss occurs.

In the present study, 1 patient had the stent placed surgically when through-and-through guide wire access was not achieved percutaneously. Extreme dilatation of the pelvis facilitates percutaneous access to the renal pelvis but complicates ureteral access because the normal funnel shape of the renal pelvis is lost. We have subsequently found that aspiration of renal pelvic fluid can facilitate ureteral access in these patients by restoring a more normal anatomic renal pelvic shape.

Complications associated with stent placement were rare in the present study and included urine extravasation from the kidney, retrograde stent migration, and premature nephrostomy tube dislodgement (all 3 complications occurred in a single patient). Although not observed in any of the patients in the present study, ureteral laceration, injury to the renal vasculature, and excessive bleeding during renal puncture are potential complications of percutaneous antegrade ureteral stent placement, and owners should be made aware of these risks. Reported27 complication rates for similar procedures in humans range from 2% to 10%, but most complications are minor and not life-threatening.

Nine patients in the present study were treated with NSAIDs following ureteral stent placement because of their previously reported antitumor effects.28 Adjunctive chemotherapy or radiation therapy was recommended or discussed for all patients, but only 5 received chemotherapy following ureteral stent placement.

For all patients in the present study that had azotemia prior to ureteral stent placement, BUN and serum creatinine concentrations improved following stent placement. All 10 patients that underwent follow-up ultrasonography had improvements in degree of hydronephrosis and hydroureter. Mild renal pelvis dilation persisted in 3 patients, but all 3 had resolution of hydroureter after placement of the stent.

Ureteral stents seemed to be generally well tolerated in the patients in the present study. In humans, ureteral stents are reported to be uncomfortable in some circumstances as demonstrated by signs of dysuria in 40% to 80% of patients.1,4–7,27,29–31 This did not seem to be the case for the patients in the present study. How long indwelling ureteral stents remain patent in human patients reportedly varies,7,15,16 with recommended exchange times ranging from every 3 months to every 20 months. In our clinical experience, ureteral stents placed for treatment of benign diseases in animals have remained patent for > 48 months in cats and > 36 months in dogs. Results of the present study suggest that stent exchange may be unnecessary in the lifetime of an animal with neoplasia, but this has not yet been evaluated in a large number of dogs. If patients live longer than expected (eg, > 1 year), as has been reported to be possible in dogs,19,28,32–35 stent exchange may become necessary, and this can be done endoscopically or fluoroscopically. To our knowledge, none of the ureteral stents became obstructed as a result of tumor ingrowth in the present report; however, this was difficult to confirm because of the lack of routine postmortem or imaging examinations at the time of death in the 10 patients for which follow-up information was available.

In the present study, patients with the longest survival times did not have azotemia at the time of initial examination, did not require urethral stent placement, did not have evidence of metastatic disease, and had a body condition score ≥ 4 on a scale from 1 to 9. None of these variables were significantly associated with survival time in the multivariate analysis; however, the small sample size likely prevented us from identifying factors associated with survival time. In addition, owners willing to pursue chemotherapy at the time of diagnosis may also have been more likely to elect aggressive treatments and, potentially, to wait longer before electing euthanasia. One patient in the present study lived 1,571 days from the time of tumor diagnosis, but this patient also underwent the most aggressive oncological management of all the patients in the study (ie, radiation therapy, intra-arterial chemotherapy, laser ablation therapy, IV chemotherapy, and bilateral ureteral and urethral stent placement).

Median survival time has been reported to be approximately 181 days in patients with TCC treated with piroxicam alone28 and approximately 150 to 300 days in patients treated with piroxicam and mitoxantrone,32 adriamycin,33 carboplatin,33,34 or some combination of these drugs.32,35 Survival times from the time of diagnosis were similar for patients in the present study (median, 285 days), some of which did not receive chemotherapy before or after ureteral stent placement. Theoretically, prevention of urinary outflow obstruction through ureteral and urethral stent placement in combination with specific tumor treatment (eg, chemotherapy, radiation therapy, or surgery) should result in the longest possible survival times. In addition, earlier ureteral stent placement should theoretically preserve renal function for a longer time and reduce associated signs of systemic illness, which are considered a poor prognostic indicator.

Interestingly, all 7 patients in the present study that were initially azotemic required a urethral stent in addition to ureteral stents. It is possible, therefore, that some component of the azotemia was a result of urethral obstruction. In addition, 1 patient developed a ureteral obstruction 1 month after placement of a urethral stent. This patient had bilateral (renal pelvis diameter, < 3 mm) pyelectasia prior to urethral stent placement and, 3 weeks later, had severe bilateral hydronephrosis (renal pelvis diameters, 8.8 and 15 mm). There was some concern that placement of the urethral stent resulted in compression of the tumor against the UVJ, worsening the partial ureteral obstruction. Alternatively, the ureteral obstruction could be explained by tumor progression alone.

None of the patients in the present study for which long-term follow-up (> 30 days) information was available reportedly died of urinary obstruction. The 3 patients with the shortest survival times in the present study died secondary to chemotherapeutic-induced toxicoses immediately after stent placement, and we speculate that because postobstructive diuresis can develop following ureteral stent placement, possibly causing some degree of dehydration, immediate administration of chemotherapeutic drugs or NSAIDs could exacerbate drug-associated toxic effects. Therefore, we currently delay administration of chemotherapeutic drugs and NSAIDs until 7 to 10 days after stent placement.

Limitations of the present study include its retrospective nature, the small number of patients, and the lack of standardization in treatment and follow-up protocols. Patient follow-up was variable, and scheduled recheck ultrasonography to document stent patency at the time of death was inconsistently performed because of variations in owner compliance, although imaging was performed in the patients at some time during the long-term follow-up period (> 30 days). Future prospective studies should be considered to better assess survival times.

It is important to emphasize that the lack of standardization of treatment plans and the failure to use chemotherapy or radiation therapy in all patients in the present study likely affected survival times in this population of patients with malignant ureteral obstructions. With improved education of owners and referring veterinarians, earlier stent insertion can be performed, which will hopefully slow the progression of the renal failure and improve survival times and quality of life of affected patients.

ABBREVIATIONS

GFR

Glomerular filtration rate

PN

Percutaneous nephrostomy

TCC

Transitional cell carcinoma

UVJ

Ureterovesicular junction

a.

Berent A, Weisse C, Bagley D, et al. Ureteral stenting for benign and malignant disease in dogs and cats (abstr). Vet Surg 2007;36:E3.

b.

Marker catheter (5F, 45 cm), Infiniti Medical, Malibu, Calif.

c.

SonoSite Titan Ultrasound, SonoSite Inc, Bothell, Wash.

d.

ISO-C Fluoroscopy Unit, Siemens Medical Solutions, Malvern, Pa.

e.

Percutaneous renal access trocar needle (18 g × 15 cm), Cook Inc, Bloomington, Ind.

f.

Omnipaque, Amersham Health, Princeton, NJ.

g.

0.035-inch stiffened hydrophilic Weasel Wire, Infiniti Medical, Malibu, Calif.

h.

4F 65-cm angiographic Berenstein Catheter, Infiniti Medical, Malibu, Calif.

i.

7F Flexor Check-Flo Introducer Sheath, Ansel Modification, Cook Inc, Bloomington, Ind.

j.

0.035-inch unstiffened Weasel Wire, Infiniti Medical, Malibu, Calif.

k.

Double-pigtailed ureteral stents, Cook Inc, Bloomington, Ind.

l.

Double-pigtailed ureteral stents, Bard Urological, Covington, Ga.

m.

Double-pigtailed ureteral stents, variable length, Infiniti Medical, Malibu, Calif.

n.

Silhouette ureteral stent, Applied Medical, Santa Rosa, Calif.

o.

Vet Stent Urethra, Infiniti Medical, Malibu, Calif,

p.

STATA, version 10, StataCorp, College Station, Tex.

q.

Cerf DJ, Lingquist EC. Ultrasound guided endoscoic laser ablation (UGELAB) of canine distal urinary carcinomas, in Proceedings. Am Coll Vet Intern Med Annu Forum 2008.

r.

6F locking loop nephrostomy tube, Infiniti Medical, Malibu, Calif.

s.

Berent A, Weisse C, Solomon J, et al. The use of locking-loop pigtail nephrostomy catheters in dogs and cats. Vet Surg 2009;38:E26.

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