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Megan G. Palmisano Rhinebeck Equine LLP, Rhinebeck, NY

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Laura H. Javsicas Rhinebeck Equine LLP, Rhinebeck, NY

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Jim N. Nutt Rhinebeck Equine LLP, Rhinebeck, NY

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History

A 20-year-old 582-kg warmblood mare was referred because of a 3-month history of pollakiuria and suspected sabulous cystitis, which is an accumulation of calcium carbonate sludge in the bladder leading to inflammation. Three weeks prior, the referring veterinarian performed a urinary workup, during which transrectal palpation revealed an enlarged bladder. A urinary catheter was passed, the bladder was drained, and a large amount of debris was noticed. Urinalysis and systemic bloodwork revealed no clinically remarkable abnormalities. No change in pollakiuria followed, and 1 week later, a urolith (approx 1 × 1 × 2 cm) covered with a blood clot was discovered after the mare urinated a normal stream.

On referral examination, the mare’s vital signs were within reference limits, there was no evidence of urine scald secondary to urinary incontinence, and the remaining findings on physical examination were unremarkable. Abdominal ultrasonography was performed and revealed no abnormalities. On transrectal palpation, the urinary bladder extended cranial to the pelvic inlet. Transrectal ultrasonography of the urinary bladder was performed (Figure 1).

Figure 1
Figure 1

Transrectal ultrasonographic image of the urinary bladder of a 20-year-old 582-kg warmblood mare with a 3-month history of pollakiuria. Cranial is to the left. The scale on the right is in centimeters.

Citation: Journal of the American Veterinary Medical Association 260, 3; 10.2460/javma.20.12.0657

Diagnostic Imaging Findings and Interpretation

On transrectal ultrasonography, a large, lobulated, homogeneously echogenic mass (approx 7 × 6 × 6 cm) was visualized in the cranioventral aspect of the bladder lumen and contiguous with the bladder wall (Figure 2). Color flow Doppler ultrasonography (not shown) confirmed mild vasculature infiltrate within the mass, with an area of distal acoustic shadowing along the ventral margin of the mass, consistent with a cystolith. The mare’s perineum was aseptically prepared, the mare was sedated with detomidine (5 mg, IV) and butorphanol (3 mg, IV), and a urinary catheter was passed aseptically through the urethra. A moderate amount of serosanguinous urine was voided, then a sample was obtained for bacterial culture. Cystoscopy was performed with a sterilized 1.5-m endoscope and confirmed the presence of a large, lobulated, irregularly shaped mass that originated from the mucosal wall, was covered in sludge consistent with calcium carbonate, ranged in color, and had areas of necrosis (Figure 3). Presumed calcium carbonate stones were along the ventral border of the mass. Based on findings from cystoscopy and transrectal ultrasonography, the mass appeared continuous with the bladder wall, and neoplasia was the top differential diagnosis.

Figure 2
Figure 2
Figure 2

Same image as in Figure 1 (A) plus an additional transrectal ultrasonographic image (B) showing a large (approx 6.02 × 6.89 cm between the calipers as imaged), lobulated mass (red arrows) of which the dorsal border (red outline) extends into the urinary bladder lumen (white arrow).

Citation: Journal of the American Veterinary Medical Association 260, 3; 10.2460/javma.20.12.0657

Figure 3
Figure 3

Cystoscopic image obtained of the mass in the urinary bladder of the mare described in Figure 1 on initial evaluation.

Citation: Journal of the American Veterinary Medical Association 260, 3; 10.2460/javma.20.12.0657

Treatment and Outcome

Biopsy samples of the mass were obtained with endoscopic biopsy forceps threaded through the biopsy channel of the endoscope (multiple friable samples) and a sterile uterine biopsy instrument (a larger sample). The mare was treated with flunixin meglumine (0.9 mg/kg, IV) and ceftiofur sodium (2.2 mg/kg, IM), then discharged with owner instructions to provide access to clean water and a salt block or electrolyte water to encourage water intake. Results of histopathologic examination of the biopsy samples were consistent with transitional cell carcinoma arising from the urinary bladder. On the basis of success in the use of piroxicam (a cyclooxygenase-2–specific NSAID) in treating canids with transitional cell carcinoma1 and in treating humans2 and equids35 with squamous cell or transitional cell carcinoma, the mare was started on piroxicam (100 mg, PO, q 24 h).

One week later, the mare was returned for surgical debulking of the urinary mass and chemotherapy. With the mare in standing sedation (owner declined general anesthesia), approximately 50% to 60% of the tumor was able to be debulked, and 2 small uroliths (approx 1 and 2 cm in diameter) were removed. The remaining portion of the mass in the mare was injected with 10 mL of cisplatin (1 mL/cm3). The mare recovered uneventfully from sedation, and treatment was initiated with ceftiofur sodium (2.2 mg/kg, IV, q 12 h for 48 hours), gentamicin (6.6 mg/kg, IV, q 24 h for 48 hours), and flunixin meglumine (1.1 mg/kg, IV, q 12 h for 48 hours). To decrease possible adverse effects associated with simultaneous administration of 2 NSAIDs, piroxicam treatment was halted while flunixin was administered. Postoperatively, hematuria was observed; however, the mare had stable PCV and plasma concentration of total solids. Cystoscopy the following morning revealed that the small remaining portion of the mass had minimal bleeding and that there was moderate urethral irritation. The mare was maintained on antimicrobials until discharge the following morning with prescriptions for ceftiofur sodium (2.2 mg/kg, IM, q 24 h) and flunixin meglumine paste (0.9 mg/kg, PO, q 12 h) for 3 days, after which treatment with piroxicam (100 mg, PO, q 24 h) was to resume. Additionally, phenazopyridine (2 mg/kg, PO, q 12 h for 5 days) was prescribed to relieve irritation of the urinary mucosa.

One month after surgery, the mass was approximately 5 × 5 × 6 × cm on transrectal ultrasonography (Supplementary Figure S1). On cystoscopy, the mass was smaller than it was on initial evaluation but had a few small nodules that could have indicated metastasis. It was possible that the nodules were previously present but not visualized due to the size of the mass. Cisplatin (1 mL/cm3) was injected into the mass, and repeated injections every 3 to 4 weeks were recommended. However, the mare was not returned until 3 months after surgery, and although the mare’s clinical signs had improved; transrectal ultrasonography revealed that the mass encompassed 80% to 90% of the bladder lumen. The mare was euthanized 1 month later due to progressive clinical signs.

Comments

Common differential diagnoses for horses with pollakiuria include urolithiasis leading to secondary cystitis, neurogenic bladder dysfunction leading to sabulous cystitis or infection, or trauma, with congenital defects less likely in older horses. Tumors associated with the urinary bladder are rare, offer a poor prognosis for long-term survival, and are often metastatic.6 For the mare of the present report, transrectal ultrasonography was integral in our ruling out more common causes of pollakiuria, such as a cystolith and sabulous cystitis, and prioritizing neoplasia, such as transitional cell carcinoma. Transrectal ultrasonography, cystoscopy, and histopathology were necessary for a definitive diagnosis; although diagnosis of urinary bladder neoplasia was based on results of histopathology, findings on ultrasonography and cystoscopy indicated the need and location for biopsy. Without ultrasonography and cystoscopy, the lesion in this mare could have remained undiagnosed.

In equids, the most commonly reported neoplasms associated with the bladder include squamous cell carcinoma and transitional cell carcinoma.7 Squamous cell carcinomas are overrepresented and carry a worse prognosis.7 As was the case for the mare of the present report, treatment of urinary tumors is rarely successful, as it is difficult to take complete margins and often the masses are infiltrative and rapidly growing. Often, management is palliative, not curative.7,8

Management involves combination treatment of surgical debulking or removal, chemotherapy, and the use of anti-inflammatory drugs, such as piroxicam. Anecdotally, piroxicam has been used in the management of equine transitional cell carcinoma and has improved long-term prognosis.3 Piroxicam is a cyclooxygenase-2–specific NSAID acting as an angiogenesis antagonist and causing apoptosis of neoplastic cells.4,5 Intratumoral chemotherapy agents, such as cisplatin and 5-fluorouracil, have been used with success to decrease both size and inflammation associated with varying neoplastic masses in horses.4,5,9 Although median survival time can be improved by treatment, it varies greatly based on whether metastasis has occurred and the amount of tumor removed. A case report of urinary bladder squamous cell carcinoma in a horse showed that surgical resection under general anesthesia and then subsequent debulking under general anesthesia resulted in no further recurrence of the mass in the bladder; however, euthanasia was elected secondary to metastasis < 1 year afterward.5 A gelding with transitional cell carcinoma underwent standing perineal urethrostomy for debulking of a mass and showed no clinical signs of disease recurrence at 30 months after surgery.9 Intratumoral administration of cisplatin in conjunction with treatment with piroxicam has been reported in each published case5,7,8 with varying success dependent on the severity of the neoplasia and evidence of metastasis on presentation.

Supplementary Materials

Supplementary materials are posted online at the journal website: avmajournals.avma.org

Acknowledgments

The authors thank Tony Moore, BVSc, MVSc, DACVIM (Oncology), for aiding in the design of a chemotherapy protocol for this mare.

References

  • 1.

    Boria PA, Glickman NW, Schmidt BR, et al. Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder. Vet Comp Oncol. 2005;3(2): 7380. doi: 10.1111/j.1476-5810.2005.00070.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Mohammed SI, Craig BA, Mutsaers AJ, et al. Effects of cyclooxygenase inhibitor, piroxicam, in combination with chemotherapy on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer. Mol Cancer Ther. 2003;2(2): 183188.

    • Search Google Scholar
    • Export Citation
  • 3.

    Elce YA, Orsini JA, Blikslager AT. Expression of cyclooxygenase-1 and -2 in naturally occurring squamous cell carcinomas in horses. Am J Vet Res. 2007;68(1): 7680. doi: 10.2460/ajvr.68.1.76

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Lisowski ZM, Mair TS, Fews D. Transitional cell carcinoma of the urinary bladder in a 12-year-old Belgian Warmblood gelding. Equine Vet Educ. 2013;27(7): e20e24. doi: 10.1111/eve.12021

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Zantingh AJ, Gaughan EM, Bain FT. Case report: squamous cell carcinoma of the urinary bladder in a horse. Compend Contin Educ Vet. 2012;34(10): E1E5.

    • Search Google Scholar
    • Export Citation
  • 6.

    Divers T, Brault SA, Burton AJ. Diseases of the renal system; urinary tract neoplasia. In: Smith BP, Van Metre DC, Pusterla N, eds. Large Animal Internal Medicine. 6th ed. Elsevier; 2020: 971973.

    • Search Google Scholar
    • Export Citation
  • 7.

    Knottenbelt DC, Patterson-Kane JC, Snalune KL. Tumors of the urinary tract. In: Clinical Equine Oncology. Elsevier; 2014: 652662.

  • 8.

    Patterson-Kane JC, Tramontin RR, Giles RC Jr, Harrison LR. Transitional cell carcinoma of the urinary bladder in a Thoroughbred, with intra-abdominal dissemination. Vet Pathol. 2000;37(6): 692695. doi: 10.1354/vp.37-6-692

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Theon AP, Galuppo LD, Snyder JR, Wilson WD. Intratumoral administration of cisplatin for treatment of sarcoids in 378 horses. In: AAEP Proceedings. American Association of Equine Practitioners; 2006: 337339.

    • Search Google Scholar
    • Export Citation

Supplementary Materials

  • Figure 1

    Transrectal ultrasonographic image of the urinary bladder of a 20-year-old 582-kg warmblood mare with a 3-month history of pollakiuria. Cranial is to the left. The scale on the right is in centimeters.

  • Figure 2

    Same image as in Figure 1 (A) plus an additional transrectal ultrasonographic image (B) showing a large (approx 6.02 × 6.89 cm between the calipers as imaged), lobulated mass (red arrows) of which the dorsal border (red outline) extends into the urinary bladder lumen (white arrow).

  • Figure 3

    Cystoscopic image obtained of the mass in the urinary bladder of the mare described in Figure 1 on initial evaluation.

  • 1.

    Boria PA, Glickman NW, Schmidt BR, et al. Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder. Vet Comp Oncol. 2005;3(2): 7380. doi: 10.1111/j.1476-5810.2005.00070.x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Mohammed SI, Craig BA, Mutsaers AJ, et al. Effects of cyclooxygenase inhibitor, piroxicam, in combination with chemotherapy on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer. Mol Cancer Ther. 2003;2(2): 183188.

    • Search Google Scholar
    • Export Citation
  • 3.

    Elce YA, Orsini JA, Blikslager AT. Expression of cyclooxygenase-1 and -2 in naturally occurring squamous cell carcinomas in horses. Am J Vet Res. 2007;68(1): 7680. doi: 10.2460/ajvr.68.1.76

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Lisowski ZM, Mair TS, Fews D. Transitional cell carcinoma of the urinary bladder in a 12-year-old Belgian Warmblood gelding. Equine Vet Educ. 2013;27(7): e20e24. doi: 10.1111/eve.12021

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Zantingh AJ, Gaughan EM, Bain FT. Case report: squamous cell carcinoma of the urinary bladder in a horse. Compend Contin Educ Vet. 2012;34(10): E1E5.

    • Search Google Scholar
    • Export Citation
  • 6.

    Divers T, Brault SA, Burton AJ. Diseases of the renal system; urinary tract neoplasia. In: Smith BP, Van Metre DC, Pusterla N, eds. Large Animal Internal Medicine. 6th ed. Elsevier; 2020: 971973.

    • Search Google Scholar
    • Export Citation
  • 7.

    Knottenbelt DC, Patterson-Kane JC, Snalune KL. Tumors of the urinary tract. In: Clinical Equine Oncology. Elsevier; 2014: 652662.

  • 8.

    Patterson-Kane JC, Tramontin RR, Giles RC Jr, Harrison LR. Transitional cell carcinoma of the urinary bladder in a Thoroughbred, with intra-abdominal dissemination. Vet Pathol. 2000;37(6): 692695. doi: 10.1354/vp.37-6-692

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Theon AP, Galuppo LD, Snyder JR, Wilson WD. Intratumoral administration of cisplatin for treatment of sarcoids in 378 horses. In: AAEP Proceedings. American Association of Equine Practitioners; 2006: 337339.

    • Search Google Scholar
    • Export Citation

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