Transitional cell carcinoma is the most common malignant neoplasia of the lower urinary tract in dogs, representing approximately 1.5% to 2% of all tumors in this species.1 In dogs, TCC is rarely amenable to surgery because it typically affects the trigonal area of the urinary bladder, the proximal aspect of the urethra, or both. Metastasis has been reported as present in 8 of 34 (24%) to 17 of 44 (39%) dogs at the time of diagnosis.2,3 Dogs with TCC are commonly treated with a combination of systemic chemotherapy and NSAIDs. Results of a 2003 investigation4 revealed that dogs that had TCC treated with mitoxantrone and piroxicam had a median survival time of 350 days. Ureteral or urethral obstruction (or both) frequently develops in dogs with this disease; the authors of 1 report5 indicated that the most common cause of death in dogs with TCC was urethral obstruction resulting from progression of the local disease (found for 52/85 [61%] dogs), followed by metastatic disease (12/85 [14%]).
Results of a previous study6 showed that placement of a urethral stent provided palliation for dogs with neoplastic urethral obstruction. In that study,6 resolution of urethral obstruction was achieved in 41 of 42 (98%) dogs. However, the incidence of incontinence is high with this technique (reported for 27/42 [64%]6 and 7 of 18 [39%]7 dogs in 2 retrospective studies).
Balloon dilation has been described as an effective method for relieving urethral obstruction caused by prostatic enlargement, traumatic injury, and infectious diseases in people. In 1 study, 43 of 51 (84%) human patients who had urethral obstruction caused by nonneoplastic diseases (eg, infectious diseases and trauma) had successful short-term outcomes following urethral balloon dilation.8 There are few reports of urethral balloon dilation in the literature for dogs.9–12 In these cases, urethral obstructions were caused by catheter-induced urethral trauma, urethritis, or stenosis following prostatectomy.9–12 All these patients had clinical improvement without reobstruction after balloon dilation. To the best of our knowledge, no study of the effectiveness of balloon dilation as a treatment for tumor-associated urethral obstruction in dogs has been published. The objective of the study reported here was to describe the outcomes of dogs that underwent balloon dilation for palliative treatment of urethral obstruction caused by urothelial carcinoma. Because TCC and prostatic carcinoma were not always distinguishable, the term urothelial carcinoma was used to include both diseases.
Materials and Methods
Case selection
Electronic medical records of Hokkaido University Veterinary Teaching Hospital were searched to identify all dogs with urothelial carcinoma (affecting the urinary bladder, urethra, or prostate) that underwent balloon dilation of the urethra between April 1, 2010, and December 31, 2015. Keywords used to search the records database included dog, balloon dilation, and urethral obstruction. Dogs were included in the study if they had histologic diagnosis of urothelial carcinoma of the urinary bladder, urethra, or prostate and had adequate follow-up information available to determine the effect or duration of response for the balloon dilation. Dogs with insufficient follow-up information, including those for which adequate information regarding quality of urination was not discernable from the record, were excluded.
Medical records review
Records were reviewed by 1 investigator (SK). Age, sex, breed, relevant medical history (including clinical signs and medical or radiologic treatments), BUN and serum creatinine concentrations, primary site of the tumor (bladder, urethra, or prostate), diagnostic imaging findings, severity of the obstruction, details of the balloon dilation technique used (including method of anesthesia or sedation, dilation pressure, and duration of dilation), whether resolution or improvement of clinical signs was observed after treatment, duration that signs were alleviated (if applicable), complications related to the procedure, whether the procedure was repeated if signs recurred, and cause of death (if known) were recorded for each dog.
The primary site of the tumor was not always discernable; therefore, the site of the largest tumor mass was defined as the primary site by 1 investigator (SK) reviewing the medical record. Obstruction was considered mild if the dog was able to urinate voluntarily but required a subjectively long time to empty its bladder with no evidence of an overdistended bladder, hydroureter, or hydronephrosis; moderate if the dog was able to urinate but not in sufficient volume (ie, there was evidence of an overdistended bladder, hydroureter, or hydronephrosis [alone or in combination]); or severe if the dog was unable to urinate voluntarily owing to near-complete obstruction of the urethra. In dogs with prostatic tumors, the type of obstruction was further categorized as extraluminal if the mucosal surface lining the prostatic portion of the urethra was smooth or as intraluminal if it was irregular on review of fluoroscopic images obtained during retrograde urethrography. These classifications were determined by the author (SK) reviewing the medical record and diagnostic images, including ultrasonographic and fluoroscopic images.
The clinical effect of the treatment was classified as follows: no effect (no difference in the severity of the obstruction after treatment, compared with that prior to treatment), partial resolution (severity of the obstruction was improved after treatment, but the dog was still considered unable to urinate normally), or complete resolution (no signs of urethral obstruction after the treatment).
Diagnostic imaging
All dogs underwent diagnostic imaging as part of tumor staging. Thoracic radiography (3 views) and abdominal ultrasonography were performed by standard methods. Fluoroscopic evaluations were performed to assess urethral patency during retrograde urethrography as described for the balloon dilation procedures.
Balloon dilation procedure
All balloon dilation procedures were performed with a urethral balloon dilation cathetera under fluoroscopic guidance.b Dogs were deeply sedated with a combination of medetomidine hydrochloridec (0.03 mg/kg [0.014 mg/lb]), midazolamd (0.15 mg/kg [0.07 mg/lb]), and butorphanol tartratee (0.02 mg/kg [0.009 mg/lb]), IV, or had anesthesia induced with propofolf (6 mg/kg [2.7 mg/lb], IV) and maintained with isofluraneg in oxygen for the procedure. Briefly, the location and length of the urethral obstruction were identified by retrograde urethrography with iodide-containing contrast mediumh and fluoroscopic imaging (Figure 1). A 0.035-inch guidewirei was passed through the obstruction site, and the balloon dilation catheter was advanced over the wire. The size of balloon (6- or 10-mm diameter and 6-cm length) appropriate for dilation was chosen on the basis of estimated size of the unaffected urethra adjacent to the obstruction site. If the length of the obstructed portion of the urethra exceeded the desired length of the balloon dilation, the procedure was performed twice (once for the proximal half and once for the distal half of the obstruction site).
Intraprocedural fluoroscopic images depicting balloon dilation for management of urethral obstruction in a male dog with TCC of the urethra. A—Image obtained during retrograde contrast-enhanced urethrography before balloon dilation. The obstruction was detected from the prostatic region to the pelvic portion of the urethra. B—Image depicting the balloon dilation catheter, which was introduced over a guidewire through the affected portion of the urethral lumen and inflated with contrast medium by use of an inflation device. C—Image obtained during retrograde contrast-enhanced urethrography after the procedure. Notice dilation of the affected portion of the urethra and filling with contrast medium. In all panels, arrowheads indicate the affected portion of the urethra.
Citation: Journal of the American Veterinary Medical Association 255, 3; 10.2460/javma.255.3.330
Intraprocedural fluoroscopic images depicting balloon dilation for management of urethral obstruction in a male dog with TCC of the urethra. A—Image obtained during retrograde contrast-enhanced urethrography before balloon dilation. The obstruction was detected from the prostatic region to the pelvic portion of the urethra. B—Image depicting the balloon dilation catheter, which was introduced over a guidewire through the affected portion of the urethral lumen and inflated with contrast medium by use of an inflation device. C—Image obtained during retrograde contrast-enhanced urethrography after the procedure. Notice dilation of the affected portion of the urethra and filling with contrast medium. In all panels, arrowheads indicate the affected portion of the urethra.
Citation: Journal of the American Veterinary Medical Association 255, 3; 10.2460/javma.255.3.330
Intraprocedural fluoroscopic images depicting balloon dilation for management of urethral obstruction in a male dog with TCC of the urethra. A—Image obtained during retrograde contrast-enhanced urethrography before balloon dilation. The obstruction was detected from the prostatic region to the pelvic portion of the urethra. B—Image depicting the balloon dilation catheter, which was introduced over a guidewire through the affected portion of the urethral lumen and inflated with contrast medium by use of an inflation device. C—Image obtained during retrograde contrast-enhanced urethrography after the procedure. Notice dilation of the affected portion of the urethra and filling with contrast medium. In all panels, arrowheads indicate the affected portion of the urethra.
Citation: Journal of the American Veterinary Medical Association 255, 3; 10.2460/javma.255.3.330
After the balloon was placed in the targeted portion of the urethra, the balloon was dilated with contrast medium diluted 1:1 (vol/vol) in sterile saline (0.9% NaCl) solution (Figure 1). An inflation devicej was used to apply sufficient pressure to accomplish dilation. The obstructed portion of the urethra was dilated with a pressure of 7,600 or 11,400 mm Hg (measured as atmospheres [where 1 atm = 760 mm Hg] and converted for reporting purposes) for 5 minutes; then the balloon was temporarily deflated, and the same dilation pressure was applied for another 5 minutes. After the second dilation, the balloon catheter and the guidewire were removed, and retrograde urethrography was repeated to assess the result. When dilation was deemed insufficient, the same procedure was repeated until the desired degree of dilation was achieved (according to the clinician's judgment) or the treatment was judged ineffective. Analgesic and anti-inflammatory medications were administered at the clinician's discretion.
Dogs with continued dysuria after balloon procedures were managed by urethral catheterization until resolution of clinical signs. Dogs were discharged from the hospital after voluntary urination was observed to confirm relief of urethral obstruction. When the balloon dilation was determined to have no effect, clinicians offered an alternative treatment such as placement of a urethral stent, low-profile cystostomy tube, or urethral catheter.
Data analysis
Descriptive data were reported. Numeric results were summarized as median and range.
Results
During the 5-year study period, urethral balloon dilation procedures were performed in 13 dogs. One dog was excluded because of inadequate follow-up. The remaining 12 dogs included 7 males (6 castrated) and 5 females (3 spayed). There were 2 Miniature Dachshunds, 2 Miniature Schnauzers, and 1 each of 6 other breeds (Cavalier King Charles Spaniel, Collie, Papillon, Dalmatian, Maltese, and Labrador Retriever). Two were mixed-breed dogs. The median body weight was 7.6 kg (16.7 lb; range, 3.5 to 28.7 kg [7.7 to 63.1 lb]), and median age was 9 years (range, 6 to 11 years). The primary site of the tumor was the urinary bladder in 5 dogs, the urethra in 3 dogs, and the prostate in 4 dogs (Supplementary Table S1, available at avmajournals.avma.org/doi/suppl/10.2460/javma.255.3.330). Diagnosis of malignant urothelial tumor was made by histologic evaluation of a biopsy sample for 8 dogs and by cytologic examination of the urine sediment for the remaining 4 dogs.
Initial clinical signs included straining and difficulty urinating (n = 10), pollakiuria (8), hematuria (6), anorexia (4), urinary incontinence (3), tenesmus (1), and hematochezia (1). All dogs had tumor staging performed; pulmonary metastasis was suspected in 3 dogs, and metastasis to the lumbar lymph nodes was suspected in 1 dog. Three dogs had bilateral hydroureter with hydronephrosis, and 1 dog had unilateral hydroureter with hydronephrosis and contralateral hydroureter. Hematologic data were available for 12 dogs, and azotemia was identified in 3 (median BUN concentration, 64.2 mg/dL [range, 53.0 to 137.2 mg/dL; reference range, 17.6 to 32.8 mg/dL]; median creatinine concentration, 1.0 mg/dL [range, 0.7 to 9.1 mg/dL; reference range, 0.8 to 1.8 mg/dL]). The median duration between the onset of urinary signs (straining to urinate; n = 10) and the initial balloon dilation procedure was 29 days (range, 1 to 365).
Previous treatments included piroxicamk (0.2 to 0.3 mg/kg [0.09 to 0.14 mg/lb], PO, q 24 h; n = 3), firocoxibl (4.3 mg/kg [2.0 mg/lb], PO, q 24 h; 1), or a combination of mitoxantronem (3.0 to 4.5 mg/m2, IV, q 3 wk) and piroxicam (0.2 to 0.3 mg/kg; 2). One of the dogs that received mitoxantrone and piroxicam was also treated with carboplatinn (200 to 300 mg/m2, IV, q 3 wk) and piroxicam (0.3 mg/kg) after initial treatment failure. One dog with a prostatic tumor received curative-intent radiation therapy (total dose of 54 Gy, administered in 20 fractions) followed by chemotherapy with mitoxantrone and piroxicam at the described dosages.
The urethral obstruction was classified as mild in 2 dogs, moderate in 5 dogs, and severe in 5 dogs. The urethral lumen obstruction of dogs with prostatic tumors (n = 4) was categorized as extraluminal in 1 and intraluminal in 2; the fluoroscopic data could not be retrieved for the remaining dog. Eleven of 12 dogs had only the balloon dilation procedure performed to relieve obstruction. The remaining dog (which had prostatic carcinoma with extension to the trigonal region of the urinary bladder) had concurrent bilateral ureteral obstruction and underwent unilateral (left-sided) ureteral stent placement at the time of the balloon dilation procedure. The site of obstruction in the 7 male dogs included the prostatic region of the urethra (n = 5), the bladder neck and proximal aspect of the urethra (1), and the area from the prostatic to pelvic region of the urethra (1). The site of obstruction in the 5 female dogs included the entire length of the urethra (n = 2) and the bladder neck and proximal aspect of the urethra (3). The dilation procedure was performed in dogs under deep sedation (n = 7) or under general anesthesia (5). The reason for general anesthesia was signs of pain caused by urethral manipulation in 1 dog and necessity to place ureteral stents in 1 dog; no reason was recorded for the other 3 dogs. Analgesics, anti-inflammatory drugs, or both were administered on the day of the dilation procedure for 8 dogs; the drugs included meloxicamo (0.2 mg/kg, SC; n = 5), buprenorphine hydrochloridep (0.02 mg/kg, SC; 2), and dexamethasoneq (0.1 mg/kg [0.05 mg/lb], IV; 1). The median duration of hospitalization was 1 day (range, 0 to 3 days).
Clinical improvement of urethral obstruction after the balloon dilation procedure was reported for 9 of 12 dogs (4/7 males and 5/5 females); obstruction sites in the 4 male dogs included the prostatic region of the urethra (n = 2), the bladder neck and proximal aspect of the urethra (1), and the area from the prostatic to pelvic region of the urethra (1). Obstruction prior to treatment for these 9 dogs was rated as mild in 1, moderate in 4, and severe in 4. All 9 dogs showed clinical improvement ≤ 7 days after the procedure. The median duration of response in these dogs was 84 days (range, 5 to 296 days).
The degree of obstruction relief was classified as partial resolution for 1 dog and complete resolution for 8 dogs. One of the 8 dogs continued to have difficulty with urination after the balloon dilation procedure and was temporarily managed by placement of a urethral catheter. Four days after treatment, clinical improvement was confirmed for this dog. One female dog that had moderate obstruction before and complete resolution after the procedure died suddenly 5 days after the procedure from an unknown cause; clinical and laboratory findings on the day of the death were consistent with disseminated intravascular coagulation and hemothorax, but the underlying etiopathogenesis could not be determined. One male dog with moderate obstruction and 1 female with severe obstruction were lost to follow-up without signs of reobstruction 14 and 84 days after the dilation procedure, respectively. One male dog that had mild obstruction died of metastatic disease 109 days after balloon dilation without developing urethral reobstruction.
Reobstruction of the urethra was known to develop in 5 of the 9 dogs that responded to the initial treatment (2 males with moderate and 3 females with severe obstruction) a median of 84 days (range, 48 to 296 days) after the initial procedure. At this time, 2 female dogs had alternative procedures performed (surgery for removal of a urinary bladder mass in one and placement of a low-profile cystotomy tube in both). The remaining 3 dogs (2 males and 1 female) underwent a second balloon dilation procedure and had clinical improvement (complete resolution for 2 dogs and partial resolution for 1 dog) that lasted for 41, 57, and 70 days, respectively, until reobstruction was again detected. Buprenorphine was administered as previously described on the day of the dilation procedure for 1 dog. One of these 3 dogs had a urethral catheter placed for 7 days because of transient dysuria after the procedure. At the time of the second reobstruction (70 days after the second dilation procedure), 1 male dog with a tumor in the prostatic portion of the urethra had a urethral stent placed as a rescue procedure. The other 2 dogs (a male and a female) underwent a third balloon dilation procedure; this treatment resulted in complete resolution in the male dog, which died of progressive metastatic disease 22 days after the third procedure, and had no effect in the female, which had low-profile cystostomy tube placement performed as a rescue procedure the day after the third balloon dilation procedure. This dog was lost to follow-up 62 days after the cystostomy tube placement.
For 3 of 12 dogs, the initial (and only) balloon dilation procedure had no clinical effect; all 3 of these dogs were male, and the primary tumor site was the prostate in 2 and the urinary bladder neck in 1. The prostatic tumors in the 2 dogs (extraluminal in one dog and unclassified in the other) were firm in consistency, and the prostatic region of the urethra immediately reobstructed when the balloon was deflated. These dogs had moderate and severe obstruction at the time of the procedure and were subsequently treated with urethral stent and urethral catheter placement, respectively; the dog that had stent placement developed renal failure because of ureteral obstruction and died 12 days after stent placement, and the dog that had urethral catheterization was subsequently lost to follow-up at our facility. In the dog with the tumor at the neck of the bladder, the obstruction was mild, and the urethra appeared dilated on urethrography after the procedure; however, the dog continued to strain when urinating after the procedure. This dog had a large cystic prostate with some kinking of the urethra observed on ultrasonographic examination, but it was lost to follow-up 20 days after the procedure, and the cause for lack of clinical improvement could not be determined.
Complications observed following the first urethral balloon dilation included hematuria (n = 4) and urinary incontinence (1). These complications were noted in different patients. Dysuria was observed for 1 dog after the second procedure. These clinical signs spontaneously resolved within a few days after the procedure. The dog that developed signs consistent with disseminated intravascular coagulation and hemothorax had been returned to the hospital with a sudden onset of epistaxis 4 days after the balloon dilation procedure and died the following day. Whether the condition resulted from the dilation procedure could not be determined.
Discussion
Results of the present study revealed that clinical improvement was achieved by the urethral balloon dilation in 9 of 12 dogs with tumor-induced urethral obstruction. In dogs with extensive or multiple obstruction sites, the obstruction was successfully treated by performing the procedure twice (once for each lesion, or once for the proximal half and once for the distal half of extensive obstruction sites). The ability to treat an extensive portion of the urethra with the balloon dilation technique is especially advantageous, compared with urethral stent placement; such cases would have required multiple stents to achieve resolution of the obstruction,6 which can be cost-prohibitive and can cause permanent urinary incontinence in some patients.
We considered the duration of effect obtained by the balloon dilation in the present study sufficient for palliative treatment. Nine of 12 dogs had partial (n = 1) or complete (8) resolution of urinary obstruction after 1 dilation procedure, and these dogs were able to urinate without other interventions for a median of 84 days. In previous studies6,7 on treatment with urethral stents in dogs that had urethral obstruction secondary to urothelial carcinoma, the median survival time after stent placement was 78 days. In addition, 28 of 39 (72%) dogs in 1 study6 were eventually euthanized because of perceived decreases in quality of life attributed to causes other than urethral reobstruction, including anorexia, vomiting, and lethargy. These results indicate that median survival time after relieving urethral obstruction is relatively short when the condition is caused by a malignant tumor. Thus, it is important to maintain the patency of the urethra even in the short term to help maintain a dog's quality of life.
Although the technique used in this study successfully alleviated urethral obstruction in many dogs, the optimal dilation pressure and dilation time were not determined. In previous reports9,11,12 of urethral balloon dilation in dogs, dilation performed for a few seconds to 5 minutes resulted in expansion of the lumen in the affected region to approximate the inner diameter of the normal (unaffected) urethra. Recommended pressure for the urethral dilation in human patients varies, depending on the type of catheter used; however, the authors of 1 study8 reported that dilation for 5 minutes had better results than did dilation for 3 minutes. In the present study, all balloon dilations were performed with the manufacturer-recommended pressure for use with human patients (equivalent to 7,600 mm Hg) for 5 minutes except that in 1 case a higher pressure (equivalent to 11,400 mm Hg) was applied for 5 minutes. Future prospective studies are needed to optimize the conditions of urethral dilation in dogs.
Urethral balloon dilation may have limited effects in dogs with extraluminal obstruction, and other treatments such as stent placement might provide better results for such cases. In a previous study,6 urethral obstruction secondary to urothelial carcinoma, including TCC and prostatic adenocarcinoma, was resolved in 42 of 42 dogs by urethral stent placement regardless of the site of obstruction. In the present study, although the numbers were small, the balloon dilation procedure was classified as having no effect in 3 of the 5 dogs with prostatic diseases. In 2 of these 3 dogs (both had prostatic carcinoma), the dilated portion of the urethra immediately closed after releasing the balloon pressure. One dog with extraluminal obstruction in this region did not have clinical improvement, but 2 dogs with intraluminal obstruction did, suggesting that the technique may not be effective for extraluminal obstruction. The remaining dog classified as having no clinical effect from the dilation procedure had mild obstruction with a primary tumor affecting the urinary bladder but also had a large cystic prostate. On abdominal ultrasonography, a kink in the urethra between the bladder neck and prostate was observed before and after the dilation procedure. This suggested that the urethra might have been unable to maintain its straight shape even after the balloon dilation.
Urethral catheter placement during the first few days after balloon dilation or anti-inflammatory treatment (with NSAIDs or corticosteroids) may help to prevent temporary urethral obstruction after the procedure, although the study was not designed to evaluate this. Continued straining on urination or signs of dysuria were uncommon but were presumably related to thickening of the urethral mucosa associated with inflammation or possible clot formation due to hematuria after the dilation procedure. All complications (including hematuria, dysuria, and urinary incontinence) resolved within a few days after the procedure in the present study.
Although reobstruction developed at least once in 5 of 9 dogs that had partial or complete resolution of urethral obstruction after the first balloon dilation treatment in our study and this is likely to be a common feature for dogs receiving such treatment for neoplastic urethral obstruction, in our view, this does not restrict its utility as a palliative treatment option because a second dilation procedure yielded similar results to the first procedure for 3 of 3 dogs that had the procedure repeated when clinical signs recurred (likely because of tumor progression). The median duration of response after the second treatment was 57 days (range, 41 to 70 days). For 1 of 2 dogs that had the procedure repeated after a second reobstruction (ie, a third procedure), urethral patency was maintained without other treatments until death from progressive metastatic disease.
Limitations of the present study included its retrospective nature, small sample size, unstandardized treatments before and after urethral balloon dilation, and the lack of a control group for comparison, which prevented a meaningful assessment of treatment efficacy for palliation of clinical signs. Accordingly, prospective studies are required to identify optimal techniques for balloon dilation in dogs with neoplastic obstruction of the urethra, including dilation pressure, dilation time, and balloon size, and to identify patients that are likely to benefit most from the treatment by evaluating results in dogs undergoing similar adjuvant treatments.
ABBREVIATIONS
| TCC | Transitional cell carcinoma |
Footnotes
X-Force U-30, Bard Medical, Covington, Ga.
SXT-9000A, Toshiba Medical Systems Inc, Tochigi, Japan.
Dorbene, Kyoritsu Pharma Inc, Tokyo, Japan.
Dormicum, Astellas Pharma Inc, Tokyo, Japan.
Vetorphale, Meiji Seika Pharma Inc, Tokyo, Japan.
Mylan, Mylan Pharma Inc, Osaka, Japan.
Isoflu, Dainippon Sumitomo Pharma Inc, Osaka, Japan.
Omnipaque 300, Daiich-Sankyo Pharmaceutical Co Ltd, Tokyo, Japan.
Hydra Jagwire Guidewire, Boston Scientific Japan Inc, Tokyo, Japan.
Bard Eagle Inflation Device, Bard Medical, Covington, Ga.
Baxo, Taisho Toyama Pharmaceutical Co Ltd, Tokyo, Japan.
Previcox, Nippon Zenyaku Kogyo Co Ltd, Fukushima, Japan.
Novantrone, Aska Pharmaceutical Co Ltd, Tokyo, Japan.
Carboplatin, Nichi-Iko Pharmaceutical Co Ltd, Toyama, Japan.
Metacam, Boehringer Ingelheim Vetmedica Japan Co Ltd, Tokyo, Japan.
Lepetan, Otsuka Pharmaceutical Co Ltd, Tokyo, Japan.
Dexamethasone, Dainippon Sumitomo Pharma Inc, Osaka, Japan.
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