Iatrogenic Tumor Seeding After Ureteral Stenting in a Dog with Urothelial Carcinoma
A 5 yr old castrated male miniature dachshund presented with clinical signs attributable to carcinoma involving the bladder neck and prostate. On day 84 following diagnosis, the dog developed bilateral ureteral obstruction and ureteral stenting was attempted. The stents were inserted in a normograde fashion via percutaneous puncture of the dilated renal pelvises. Two wk later, the dog developed nodules at both sites of renocentesis. En block resection of the masses was performed, and histologic examination confirmed that the masses were urothelial carcinoma, likely caused by iatrogenic tumor seeding. Ureteral stenting is a useful technique to relieve malignant ureteral obstruction; however, risk of iatrogenic tumor seeding must be considered.
Introduction
Prostatic carcinoma is an aggressive malignant neoplasia in dogs with a high rate of metastasis to the regional lymph nodes early in the course of disease.1–4 Later onset of distant metastasis to other organs, such as the lungs and bones, is also common. Due to the highly aggressive nature of prostatic carcinoma, definitive treatment such as total cystourethrectomy has rarely been performed, and the aims of the treatment are often palliative, focusing on slowing further tumor progression and either preventing or treating upper and lower urinary tract obstruction. The ureteral stenting technique has been described to relieve ureteral obstruction, and to date, no major complications associated with the technique appear to have been reported. The purpose of this report was to document a case of uroepithelial carcinoma in which ureteral stenting resulted in the iatrogenic implantation of the tumor to the abdominal wall.
Case Report
A 5 yr old castrated male miniature dachshund was referred to Hokkaido University Veterinary Teaching Hospital for evaluation of hematuria and dysuria. The owner reported that the dog recently started straining to urinate with reddish discoloration of the urine. The dog had been unable to express a sufficient amount of urine at one time, making only a small stream of urine repeatedly over multiple attempts. At the time of initial presentation, complete physical examination, complete blood count, serum biochemical profile, and urinalysis were performed. A moderately enlarged prostate was palpated on rectal examination, with an irregular shape and firm consistency. Abdominal ultrasonography confirmed the presence of a prostatic mass with intralesional calcification, suggesting the mass was a malignant neoplasia. A small portion of the prostatic tumor extended proximally into the bladder neck. The sublumbar lymph nodes were mildly enlarged and irregularly shaped. Urinalysis revealed marked contamination of red blood cells. The cytology of the urine sediment and prostatic massage lavage fluid was consistent with malignant epithelial neoplasia. Three-view thoracic radiographs were unremarkable.
At that point, a tentative diagnosis of either prostatic carcinoma or transitional cell carcinoma of the prostatic urethra partially obstructing the lower urinary tract was made. Treatment options, including local radiation therapy, total prostatectomy, total cystectomy with urethrectomy, medical treatment with mitoxantrone and piroxicam, urethral stenting, and balloon dilation of the urethra were discussed with the owner. They elected balloon dilation followed by systemic mitoxantrone and piroxicam.
On day 21 following diagnosis, the dog was anesthetized with propofol and isoflurane for the ballooning procedure. A retrograde urethrogram was performed to define the location and length of the stenosed portion. A dilational balloon catheter (measuring 6 mm in diameter)a was introduced into the prostatic portion of the urethra in a retrograde fashion. The balloon portion of the catheter was positioned to cover the entire length of the prostatic urethra using fluoroscopic guidance. The balloon was dilated to an intracavital pressure of 10 atm, and the pressure was maintained for 5 min before deflation. The process was repeated twice. A retrograde urethrogram was also repeated to ensure resolution of the obstruction. Recovery from anesthesia was uneventful, and the dog was able to urinate without straining immediately after the procedure. Systemic chemotherapy was initiated on the same day, consisting of three doses of IV mitoxantrone (5 mg/m2, 6 mg/m2, and 6 mg/m2, respectively) at 3 wk intervals, and piroxicam (0.3 mg/kg per os q 24 h) with no significant adverse event. The urethral dilation procedure was repeated on day 121 when signs of urethral obstruction recurred.
On day 84, the dog acutely developed severe lethargy and complete anorexia. A serum biochemical profile revealed increased blood urea nitrogen (46.6 mg/dL; reference range, 9.2–29.2 mg/dL) and creatinine (2.3 mg/dL; reference range, 0.4–1.4 mg/dL). Abdominal ultrasonography revealed that the trigonal portion of the mass had obstructed the ureters, resulting in bilateral hydroureter and hydronephrosis. An excretory ureterogram was performed that demonstrated an anuric right kidney and near-complete obstruction of the left ureteral inlet by the tumor (Figures 1A, B). To relieve the obstruction, bilateral ureteral stenting was attempted on day 96. The dog was anesthetized with propofol and maintained with isoflurane. The left renal pelvis was punctured with an 18 gauge catheter needle percutaneously. A 0.8 mm guide wire was passed through the outer sheath of the catheter into the renal pelvis and was advanced through the dilated ureter into the urinary bladder in a normograde fashion. Due to partial obstruction of the proximal urethra by the tumor, the guide wire could not be passed into the urethra. The 18 gauge catheter was removed, and an in-dwelling double pigtail ureteral stent (3.5 mm diameter, 16 cm in length)b was passed over the wire percutaneously in a normograde fashion. The stent was positioned so that each end was placed within the left renal pelvis and the bladder lumen, respectively, under fluoroscopic guidance. The guide wire was then removed by pulling the proximal end of the wire from the cutaneous puncture site. The placement of the right ureteral stent was attempted by the same technique; however, due to complete obstruction of the ureteral inlet at the trigone, it was impossible to pass the guide wire through the obstruction site. The wire was removed through the cutaneous puncture site. A postoperative series of excretory ureterograms showed that the left ureteral obstruction was improved, with faster filtration of the contrast media by the left kidney into the urine (Figures 2A, B).
Citation: Journal of the American Animal Hospital Association 49, 4; 10.5326/JAAHA-MS-5865
Citation: Journal of the American Animal Hospital Association 49, 4; 10.5326/JAAHA-MS-5865
The azotemia resolved, and the dog became active again. The owner reported that the previously seen lethargy and anorexia had completely resolved following the stenting procedure; however, reinitiation of the systemic chemotherapy was declined.
Approximately 2 wk after the stenting, the referring veterinarian palpated small subcutaneous nodules at both sites where the renal pelvic puncture procedure was performed. At that time, the nodules were attributed to the inflammation and possible granuloma formation at the sites of abdominal puncture; however, the nodules did not regress over time and started increasing in size 23 days after they were noticed. On day 182, the dog was again referred to Hokkaido University Veterinary Teaching Hospital for evaluation of the nodules. The dog’s general condition was good, and hematologic and serum biochemical examinations, 3-view thoracic radiographs, and abdominal ultrasonography showed no signs of tumor progression other than the previously documented sublumbar lymph node enlargement. Fine-needle aspiration cytology of the nodules within the abdominal wall was performed, and the findings were consistent with anaplastic epithelial neoplasia, indicating dissemination of the prostatic carcinoma by an iatrogenic implantation at the time of ureteral stenting. Considering the dog’s otherwise unaffected quality of life and lack of marked tumor progression elsewhere, removal of the nodules were elected after discussion with the owner. Both nodules were removed en block by resecting the abdominal wall in areas (measuring 4 cm in diameter) that were potentially punctured by the needle at the time of the previous procedure (Figure 3). The defects were closed with simple interrupted sutures.
Citation: Journal of the American Animal Hospital Association 49, 4; 10.5326/JAAHA-MS-5865
Histopathology of the masses was consistent with malignant epithelial neoplasia, most likely iatrogenically seeded prostatic carcinoma. Neither local recurrence of the tumor in the renocentesis sites nor peritoneal spread was observed after the last surgery during the follow-up period. However, the prostatic carcinoma continued to progress at the primary site and the urinary bladder, causing almost complete filling of the bladder and reobstruction of the urethra on day 198, which was managed by permanent placement of a urinary catheter.
According to the referring veterinarian, the dog’s general condition gradually declined, presumably due to further progression of the tumor within the bladder and/or unidentified distant sites. No evidence of intra-abdominal seeding was seen by abdominal ultrasonography by the referring veterinarian. The dog died at home 247 days after the diagnosis (49 days after the excision of the abdominal wall masses). Necropsy was not performed.
Discussion
Urinary tract carcinomas (i.e., transitional cell carcinomas, prostatic carcinomas) are poor candidates for definitive, radical surgery, and many patients eventually either succumb to death or are euthanized because of urethral or ureteral obstruction by the tumor. The authors of this report used a combination of urethral ballooning and ureteral stenting techniques to address the lower and upper urinary tract obstructions, respectively. Use of ballooning techniques in dogs with urinary tract neoplasia have not been documented in the literature, although there is one recent report of benign urethral stenosis in a dog treated by balloon dilation.5 Both techniques were fairly effective in the current case, successfully achieving immediate relief of the obstruction. Those procedures are minimally invasive and may be viable treatment options for either benign or malignant urinary tract obstructions.
The current case, however, poses a potentially critical complication of the ureteral stenting procedure. The dog likely developed iatrogenic tumor seeding to the punctured abdominal wall. The tumor cells probably were seeded into the abdominal wall musculature via the guide wire at the time of its removal. This is because the wire was in direct contact with the tumor tissue during the procedure, in contact with the outflowing urine containing cancer cells, or both. The reason for lack of peritoneal dissemination is unclear. Because urine spillage must have occurred in the peritoneal space as well, one might expect peritoneal carcinomatosis in this case. Abdominal wall musculature, rich in vascular supply, might have been a more ideal environment for survival and growth of the implanted tumor cells than the peritoneal space. Another possibility, though unlikely, is hematogenous metastasis of the tumor into the sites of needle puncture for stent placement, as previous trauma or surgery creating a local microenvironment enriched with growth factors is a known predisposing factor for skeletal muscle metastasis in humans.6
Although a situation like the present case may leave no alternative option to performing the procedure knowing the risk of tumor implantation, the likelihood of tumor seeding must be minimized. One possible alternative technique that could have been used was to pass the guide wire normograde from the renal pelvis into the urethra then placing a stent retrograde so that contact of tumor-contaminated guide wire with either intraperitoneal tissue and abdominal wall or spillage of tumor-containing urine into the peritoneal cavity can be minimized. Recently, a ureteral stenting technique for malignant upper urinary tract obstruction was described in 12 dogs.7 Normograde passing of the guide wire from renal pelvis to the urethral opening was used in all dogs, and no iatrogenic tumor seeding was reported. Guiding the wire into the urethra was attempted in the current case, but was impossible due to narrowing of the urethral lumen at the prostatic urethra. Whether the cause of tumor implantation in this case was related to removal of the contaminated guide wire from either the renocentesis sites or because of the highly aggressive nature of the primary tumor remains unknown; however, the risk of iatrogenic tumor seeding should be considered when performing a ureteral stenting procedure in dogs with malignant upper urinary tract obstruction.
Conclusion
This case report highlights the potential benefits of minimally invasive percutaneous ureteral stenting techniques in physically resolving malignant ureteral obstruction; however, it also points out the potentially serious complication of iatrogenic tumor implantation/dissemination associated with a normograde ureteral stenting technique.
A lateral projection (A) and a ventrodorsal projection (B) of excretory ureterography before ureteral stenting. Note the severe hydronephrosis and hydroureter of the left kidney and lack of contrast filtration from the right kidney, indicating cease of urine production due to complete obstruction of the right ureter.
A lateral projection (A) and a ventrodorsal projection (B) of excretory contrast ureterocystogram after left-sided ureteral stenting. Improvement of the hydronephrosis and hydroureter was apparent, and flow of the contrast media into the urinary bladder via the stent was seen.
Photograph showing the abdominal wall mass during en block resection. The mass was present within the muscular layer of the abdominal wall. Histopathology confirmed that the mass was a malignant epithelial neoplasia. No intraperitoneal dissemination was apparent at the time of surgery.
Contributor Notes
