Everyone there is so positive and professional, and, although we came there for a sad reason, we are so grateful to have met all of you.
West Orange, NJ
Stallion is a 12 ½ year old male castrated Chihuahua mix who presented for possible seizures and weakness. Approximately 6 months earlier he started to lose his balance and stumble, stare into space and became polyuric and polydypsic (PU/PD). On neurologic exam neck pain, left facial nerve paresis and occasional knuckling on the right thoracic limb were noted. Neuroanatomic localization was multifocal CNS disease. Blood work revealed mildly increased in Alkaline Phosphatase of 352 and ALT of 137. Further bloodwork including a serum cortisol, Accuplex (Lyme/Hearworm/Anaplasma/Ehrlichia ), thyroid panel and Rocky Mountain Spotted Fever titers were submitted. A low TSH was noted on the thyroid panel (TSH 1.46 ng/ml, normal 0-0.6). Serum cortisol, RMSF titer and the Accuplex were all normal. Treatment with thyroxine was initiated. Possible seizure like episodes continued at home and magnetic resonance imaging (MRI) of the brain was elected.
Standard MRI sequences of the brain were performed including sagittal T2-weighted series, transverse T2-weighted, FLAIR, T1-weighted and T2*-GRE series and T1-weight series in transverse, dorsal and sagittal planes following intravenous contrast administration of gadolinium.
The MRI demonstrated a large sellar/suprasellar mass which was hyperintense to adjacent white matter of the brain in T2-W images (Figure 1), isointense in T1-W images and strongly contrast enhancing. The mass was causing marked dorsal and lateral displacement of the overlying hypothalamus and thalamus.
Differential diagnoses for a suprasellar mass include a pituitary tumor, meningioma, craniopharyngioma, germ cell tumor, and hypothalamic glial tumor. Pituitary tumors are by far the most common suprasellar neoplasia and include both adenomas and adenocarcinomas. These originate from the pars intermedius or pars distalis of the pituitary. In general pituitary masses greater than 1 cm in diameter are considered pituitary macroadenomas/adenocarcinomas. Pituitary tumors may be functional or nonfunctional .
The most common clinical signs associated with pituitary macrotumors include those signs indicative of Cushing’s disease. When neurologic signs develop they are consistent with intra-cranial disease with lethargy, anorexia, stupor and tetraparesis most common. Ataxia circling and behavioral changes are also frequently noted (Sarfaty 1988). Blindness is uncommon in contrast to what is seen in people and seizures are actually also uncommon. Disorders of water metabolism and thermoregulation may occur secondary to invasion of the hypothalamus.
Treatment options for pituitary macrotumors include medical treatment for pituitary dependent hyperadrenocorticism (Cushing’s disease) if present with either Mitotane or Trilostane. Neither has been shown to be superior to the other. An anticonvulsant such as phenobarbital to control seizures may be necessary and prednisone can help control peri-tumoral edema and inflammation.
Surgical treatment via a transphenoidal hypophysectomy has been described and is technically difficult but can lead to successful clinical outcome with 2 year survival rates reaching 80% (Meij 1988). Possible complications include tumor recurrence because of incomplete removal, mild post-operative hyponatremia or permanent diabetes insipidus post-operatively. There is also certainly an upper limit as to size of tumor which can be removed and hypophysectomy has most often been performed in dogs with microadenomas rather than macroadenomas.
Radiation therapy is becoming more common in veterinary medicine as availability at Universities and referral practices increases. Median survival time for dogs with pituitary tumors treated with radiation therapy can reach 22-43 month in patients with no neurologic signs at time of presentation. In patients presenting with neurologic signs median survival is lower but can still reach 11.7-22 months (Bley 2005, Dow 1990, Theon 1998), demonstrating the benefit of early intervention in cases of pituitary dependent hyperadrenocorticism. Advanced diagnostic imaging such as CT or MRI in cases of pituitary dependent hyperadrenocorticism can identify those patients with macrotumors who would benefit most from radiation therapy. The diagnostic imaging studies also then are used for radiation therapy treatment planning with fusion of CT and MRI images allowing for precise localization for the delivery of radiation (Figure 2). The recent availability of Cyberknife (stereotatic radiation therapy) also provides exciting and promising new treatment options with many advances over tradition radiation therapy including a much shorter treatment course and improved sparing of normal tissue adjacent to a tumor.
Stallion received a full coarse of traditional radiation therapy (51 Gy) divided over 17 treatments. Repeat MRI 10 months later when neurologic signs recurred showed a marked reduction in tumor size however significant peri-tumoral edema had developed (Figure 3). A second course of radiation therapy was elected utilizing Cyberknife and consisted of a single dose of 15 Gy.
Although the oral cavity may not be the most common location we think of when discussing cancer in companion animals, oral cancer represents a significant risk in both our canine and feline patients. Oral cancer accounts for 6-7% of all canine cancers and 3% of all feline cancers. Oropharyngeal cancers are 2.6 times more likely to be found in dogs than in cats.
Breeds that are reported to have a higher risk for developing oral tumors include: cocker spaniels, German shepherds, German shorthaired pointers, Weimaraners, golden retrievers, Gorden setters, miniature poodles, Chow chows and boxers. In dogs the most common malignant oral tumors include malignant melanoma, squamous cell carcinoma (SCC) and fibrosarcoma. Other tumors reported less commonly in the oral cavity of dogs include osteosarcoma, chondrosarcoma, multilobular osteochondrosarcoma, hemangiosarcoma, mast cell tumor, lymphoma and transmissible venereal tumor. We will discuss the three most common canine oral tumors in greater detail.
Malignant melanoma of the oral cavity represents 30-40% of all malignant, canine oral tumors. It is typically a very aggressive tumor. Not only does this tumor invade local oral tissues (often including bone), it also has a high propensity to metastasize to both the local lymph nodes and the lungs. As a result of its high metastatic potential, any patient diagnosed with a malignant melanoma should have sampling performed of the local lymph nodes as well as three-view thoracic radiographs and a minimum database (CBC/Serum Chemistry/UA). Despite its aggressive behavior, there are therapies that can slow disease progression and keep patients more comfortable.
Figure 1. Patient with amelanotic melanoma
Because of its aggressive behavior, both local and systemic treatment is recommended. Local treatment options consist of surgery and radiation therapy. Obtaining excellent local control with surgery and/or radiation therapy is vital. In many cases a CT scan may be helpful to determine the full extent of the tumor and help plan either surgical excision or radiation therapy. If the tumor can be completely excised, surgery is the preferred treatment method, but if the tumor is not excisable or the surgical margins are incomplete, radiation therapy is an excellent option to help control local disease. Radiation therapy is typically handled well by these patients and melanomas are very sensitive to radiation therapy, often resulting in good outcomes.
If we only work to control the local disease, we can expect to see metastatic disease within months of the initial diagnosis. Historically, melanoma has not responded well to chemotherapy. The addition of immunotherapy and specifically the Merial Melanoma Vaccine (Oncept) has been beneficial in treating this disease. Prior to the addition of the vaccine, the average survival time for patients with oral melanoma with surgery alone was less than 1 year. With the addition of the vaccine (with excellent local disease control) we are seeing patients live 1-3 years after diagnosis! The vaccine is typically handled well. Potential side effects include pain/inflammation at the injection site and very rare anaphylactic reactions.
Squamous cell carcinoma represents 17-25% of all malignant oral tumors in dogs, making it the second most common tumor found in the canine oral cavity. These tumors are locally aggressive, often invading bone. The metastatic rate is site dependent, with rostral SCCs having a low metastatic potential and tumors of the caudal tongue and tonsil having a high metastatic rate. As with any oral tumor, staging should include local lymph node palpation/aspiration, three-view thoracic radiographs, and a minimum database (CBC/Serum Chemistry/UA). Due to the high risk of bone involvement, a CT scan is recommended to determine the full extent of the tumor and help plan therapy. The treatment of choice for these tumors is surgery and/or radiation therapy. For tumors located in the rostral oral cavity complete surgical excision is more likely and with excellent local control the median survival time is 26-36 months. For caudally located tumors or tonsillar tumors, surgery and/or radiation therapy are still recommended, but given the higher propensity to metastasize, survival times are typically shorter and systemic therapy is often recommended. Piroxicam has been shown to benefit dogs with oral SCC and the benefit is even greater when combined with injectable carboplatin.
Fibrosarcoma is the third most common tumor found in the canine oral cavity representing 8-25% of oral tumors. The metastatic rate of these tumors is low; but they tend to be very aggressive locally, often invading bone. Despite the low metastatic potential staging with local lymph node palpation/aspiration, three view thoracic radiographs and a minimum database is recommended. The most common treatments employed for this tumor type include surgery and radiation therapy. Fibrosarcomas have a poor to fair response to radiation therapy, but when combined with surgical excision can result in good outcomes. With excellent local control the median survival time is 18-26 months.
Although oral tumors are more commonly found in dogs, they can be found in our feline patients as well.
Squamous cell carcinomas are the most common malignant oral tumor found in cats (70-80% of feline oral tumors are SCCs). These tumors are most commonly seen in middle aged to older cats. The metastatic rate is low, but they are very locally invasive causing pain and discomfort. Bone involvement is common. Treatment for these patients is aimed at slowing disease progression and decreasing pain and discomfort. Surgical response is poor with a median survival time of 45 days. Surgery combined with radiation therapy results in a slightly longer median survival of 90 days. In one study non-steroidal anti-inflammatory drugs were shown to benefit patients and slow disease progression. The oral tyrosine kinase inhibitor, Palladia may also be beneficial in slowing disease progression. Often a combination of radiation therapy, palladia, metacam and pain medications is beneficial at decreasing the pain that these cats experience as well as slowing disease progression. With this combination of treatments we may see survival times of 3-6 months. Any NSAID used in cats must be done cautiously with careful monitoring of renal values. The administration of analgesics is extremely important to maintain comfort in these patients. Buprenorphine is a common choice and is easy to administer even in cats with oral discomfort.
Fibrosarcomas are the second most common oral tumor found in the cat, comprising 13-17% of feline oral tumors. As with SCC this tumor has a low metastatic potential but is very locally aggressive, often involving bone. Again, the combination of surgery and radiation therapy offers the best outcome. A CT scan prior to initiating therapy is recommended due to the high potential for bone involvement. With excellent local control survival times of a year or more can be seen.
Oral tumors in both cats and dogs tend to be locally aggressive with a low to high potential for metastasis. However, there are many potential treatment options that can lead to a better quality of life for our patients. Tumor control and slowing disease progression is important. However, it is vital to remember that many of these tumors are painful and judicious use of analgesics is just as important as trying to control disease.
The Veterinary Cancer Center – November 2014
Bergman PJ, McKnight J, Novosad A, et al: Long-Term Survival of dogs with advancer malignant melanoma after DNA vaccination with xenogenic human tyrosinase: a phade I trial, Clin Cancer Res 9:1284; 2003.
Oral tumors are often devastating for our patients. For an animal having any tumor is not easy…but when that tumor is in the mouth it also can also cause major problems such as pain, difficulty eating or swallowing food, bleeding, infection, and an overall decrease in quality of life. Oral tumors are best treated with surgical excision, as this can fix the local problem quickly. However, many times oral tumors can not be treated with surgery or surgery can not completely remove the tumor. In these cases, radiation therapy is often very useful in controlling tumors and improving quality of life. Here are the top five oral tumors in pets where radiation can really make a difference:
Radiation therapy can be very effective in the treatment of melanomas in dogs. The good news concerning melanoma and radiation is that hypofractionated radiation seems to be very effective. This involves using a small number of treatments (3 to 6) with a larger dose for each treatment (5 to 10 Gy). This means less visits, fewer anesthetic episodes, minimal side effects and less cost to the owners. Two main published studies have shown that dogs with gross tumor have overall response rates in 85-95% of cases with a complete response in 50 -75% of dogs. Side effects of this type of radiation are minimal (Bateman, JVIM 1994 and Blackwood, JAVMA 1996)
Soft tissue sarcomas
The second most common oral tumor in dogs is oral fibrosarcoma. Also dogs can develop other soft tissue sarcomas in the mouth that can be very difficult to handle. Aggressive surgery is usually the treatment of choice. However, for cases where surgery is not possible, or the mass is incompletely removed, radiation can be beneficial. In one study treatment of sarcomas after an incomplete excision resulted in a survival time of 540 days (Forrest, JVIM 2000). For tumors that were not able to be surgically excised, in another study, oral sarcomas were controlled for 11 months with definitive radiation and 6 months with palliative radiation. Another interesting facet about this study is that dogs treated with palliative radiation lived almost as long (10months) as dogs treated with definitive radiation (11months) (Poirier, In Vivo 2006)
Figure 2 Treatment of canine oral sarcomas with radiation can result in tumor control for 6 to 11 months. These images show pre and post treatment images for a dog in a complete remission one year after palliative radiation for a fibrosarcoma.
These tumors are uncommon in dogs. Typically, they are locally invasive, but they can be cured with an aggressive, complete surgical removal. However, in cases where surgery is not an option, radiation can also be very effective. In one study dogs treated with radiation had an overall survival of over 3 years, with many dogs living even longer. (McEntee, Vet Radiol Ultrasound 2004)
Figure 3 Acanthomatous epulides can be controlled long term with radiation alone.
Although it is relatively rare, some dogs will develop a localized lymphoma, involving just the oral mucosa. While we typically think of chemotherapy first for lymphoma, this tumor seems to respond best to treatment with radiation to the oral cavity. In the best study looking at this to date 1/3 of dogs responded to radiation with a median survival of over 2 years (Berlato, Vet Comp Oncol 2012)
Oral Tumors in Cats
Unfortunately oral tumors in cats are most commonly squamous cell carcinomas. A number of studies using various accelerated radiation protocols have shown responses and prolonged survival. Unfortunately, these responses re usually short lived and survival for cats with oral squamous cell carcinomas is typically 2-6 months on average (Poirier, Vet Radiol Ultrasound 2013 and Fidel, Vet Radiol Ultraosund 2007).
However, palliative radiation may help control pain and improve quality of life in some cats (Sabhlok, Vet Radiol Ultrasound 2014)
Radiation can also be used to treat other tumor such as sarcomas or melanomas in cats. However, given how uncommon these tumors are there are limited studies describing treatment (Farrelly, Vet Radiol Ultrasound 2004)
Blackwood L, Dobson JM. Radiotherapy of oral malignant melanomas in dogs. J Am Vet Med Assoc. 1996 Jul 1;209(1):98-102.
Bateman KE, Catton PA, Pennock PW, Kruth SA.
J Vet Intern Med. 1994 Jul-Aug;8(4):267-72.
Forrest LJ, Chun R, Adams WM, Cooley AJ, Vail DM. Postoperative radiotherapy for canine soft tissue sarcoma. J Vet Intern Med. 2000 Nov-Dec;14(6):578-82.
Poirier VJ, Bley CR, Roos M, Kaser-Hotz B. Efficacy of radiation therapy for the treatment of macroscopic canine oral soft tissue sarcoma. In Vivo. 2006 May-Jun;20(3):415-9.
McEntee MC, Page RL, Théon A, Erb HN, Thrall DE. Malignant tumor formation in dogs previously irradiated for acanthomatous epulis.
Vet Radiol Ultrasound. 2004 Jul-Aug;45(4):357-61
Berlato D, Schrempp D, Van Den Steen N, Murphy S. Radiotherapy in the management of localized mucocutaneous oral lymphoma in dogs: 14 cases. Vet Comp Oncol. 2012 Mar;10(1):16-23.
Sabhlok A, Ayl R. Palliative radiation therapy outcomes for cats with oral squamous cell carcinoma (1999-2005). Vet Radiol Ultrasound. 2014 Sep-Oct;55(5):565-70.
Poirier VJ, Kaser-Hotz B, Vail DM, Straw RC. Efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral squamous cell carcinoma. Vet Radiol Ultrasound. 2013 Jan-Feb;54(1):81-8.
Fidel JL, Sellon RK, Houston RK, Wheeler BA. A nine-day accelerated radiation protocol for feline squamous cell carcinoma. Vet Radiol Ultrasound. 2007
Farrelly J, Denman DL, Hohenhaus AE, Patnaik AK, Bergman PJ. Hypofractionated radiation therapy of oral melanoma in five cats.
Vet Radiol Ultrasound. 2004
- Signalment: 8-year-old male castrated beagle (22 kg)
- Presenting complaint: Progressively worsening stranguria with near complete urinary obstruction
- Pertinent history: Recent history (four months previously) of suspected urinary tract infection that did not improve with antibiotics; Follow-up ultrasonography and prostatic fine-needle aspirate diagnosed urothelial carcinoma
- Medications: Piroxicam (5mg PO SID), Misoprostal (50ug PO BID)
- Physical examination findings: Quiet, alert, and responsive; Heart rate 140 bpm; body condition score 5/9; Multiple soft moveable subcutaneous masses; Moderate bilateral hindlimb muscle atrophy; Very large caudal abdominal structure consistent with distended urinary bladder; Large, firm, lobulated, irregular prostate palpated on rectal examination, lumbar lymph nodes not palpable on rectal examination; Drops of urine dripping from prepuce
- Complete blood count: Mild stress leukogram
- Serum chemistry profile: ALT 79, AST 39, ALP 420
- Abdominal radiography: Enlarged, mineralized prostate; Hepatomegaly
- Thoracic radiography: Unremarkable
- Abdominal ultrasonography: Soft-tissue mass located at urinary bladder trigone and extending into/from proximal urethra; Intra-pelvic urethra not visualized; Lumbar lymph nodes within normal limits; No evidence of hydroureter or hydronephrosis; slightly enlarged hyperechoic liver; Remaining structures unremarkable
- Urinalysis / Urine Culture: Pending
This patient was determined to have a complete or near complete urethral obstruction due to the progressive urothelial carcinoma. An 8Fr urethral catheter was placed in the emergency room and 400 ml of hematuria was removed from the urinary bladder. The elevated heart rate came down following bladder drainage. Discussion with the owner included surgery (cystostomy tube), radiation therapy (palliative or full course) with periodic urinary catheterization (BID-TID) until urethral patency, or urethral stenting. Tumor extension into the trigone, as well as prostatic involvement, made complete surgical resection an unlikely option. Medical management (chemotherapy) was discussed but acute response permitting urination was unlikely. The owner chose urethral stenting as a rapid, effective, minimally-invasive, out-patient procedure shown to provide immediate relief of stranguria by immediate restoration of a patent urethra.
The patient was placed under general anesthesia and positioned in lateral recumbency and the urinary catheter was removed. A 4Fr angiographic marker catheter was placed within a 14Fr red rubber catheter that was advanced per rectum into the descending colon (Figure 1). This marker catheter would be used to calculate radiographic magnification. The prepuce was clipped, scrubbed and draped. All wire, catheter, and stent manipulations were performed under fluoroscopic guidance. A 0.035” angled hydrophilic guidewire was placed transurethrally and advanced into the urinary bladder. An 8Fr introducer sheath was advanced over the guidewire and secured to the prepuce with a single nylon suture. A 4Fr berenstein catheter was advanced over the wire, through the introducer sheath, and into the urinary bladder. The guidewire was removed, a sample of urine is collected for culture, and a 1:1 combination of iodinated contrast and sterile saline was injected until the urinary bladder was full. A urethrogram was then performed with the same contrast mixture through the introducer sheath in order to distend the urethra and define the extent and location of the urethral obstruction (Figure 2). Maximal urethral diameter was then determined and an appropriately-sized laser-cut, nitinol, self-expanding metallic stent (SEMS) was chosen. The berenstein catheter was removed over the guidewire and the stent delivery system was advanced over the guidewire across the urethral obstruction (Figure 3). The stent was deployed across the urethral obstruction and a repeat urethrogram was performed through the introducer sheath to confirm urethral patency (Figure 4). A final radiograph was obtained, the guide wire and introducer sheath were removed and the patient was recovered.
This patient was discharged from the hospital the same day with immediate resolution of the urethral obstruction. Discharge medications included a 2-week tapering dose of enrofloxacin pending the urine culture results. Initially he would drip urine on occasion between normal strong urinations, but this resolved after the first week. A recheck examination was scheduled two weeks later with an oncologist to discuss further treatment options.
Malignant urethral obstructions can cause life-threatening biochemical changes in veterinary patients. Urothelial/Transitional cell carcinomas are the most common lower urinary tract tumors encountered in dogs, often involving the trigone, urethra, and/or prostate. Greater than 80% of these patients experience significant dysuria and approximately 10% of these patients progress to develop complete urinary tract obstruction. 1,2 While chemotherapy has been demonstrated to result in improved survival times, substantial tumor responses are uncommon, complete cures are rare, and tumor progression is typical. Once signs of urinary obstruction occur, few good options exist. Cystostomy tube placement, transurethral resection, and surgical diversion have been described but are either invasive or associated with significant morbidity including need for manual urine drainage, tube dislodgement, urinary tract infection, incontinence, and/or surgical complications).3-6 More recently, transurethral placement of self-expanding metallic stents (SEMS) under fluoroscopic guidance has been described which results in rapid and effective restoration of urethral patency and urine flow. 7 These procedures are performed on an out-patient basis and avoid the need for manual drainage and other surgical-associated complications. A recent study reported good results following urethral stent placement in 42 dogs; a major incontinence rate of 25% (3/4 dogs had minor or no incontinence) and median survival time of approximately 250 days if the patients received chemotherapy following stent placement.8 The cause of death in these patients is rarely due to repeat urinary obstruction; the most common cause of death is secondary to tumor metastases and signs of systemic illness. These stenting techniques have also been effective in cats as well as for malignancy or benign urethral strictures.
A video of the procedure can be viewed at http://www.amcny.org/node/342#Urethral_Stenting. The stenting procedure is fairly short and the patients are typically discharged from the hospital the same day. Medical management with antibiotics (short-term), NSAIDs, and chemotherapy continue post-stenting. For more case studies and to see how interventional radiology and interventional endoscopy can benefit patients, visit http://www.amcny.org/interventional-radiology-endoscopy/IR-IE-procedures.
Figure 1: Lateral caudal abdominal static fluoroscopic image demonstrating marker catheter in descending colon (black block arrows) and guidewire (white arrows) placed retrograde into the urethra and urinary bladder.
Figure 2: Lateral caudal abdominal fluoroscopic image obtained during retrograde contrast urethrocystogram demonstrating normal penile urethra but narrowed prostatic urethra (white arrows) with contrast extravasation into prostatic tumor. There is also a filling defect in the bladder dorsal bladder trigone (white arrows).
Figure 3: Lateral caudal abdominal static fluoroscopic image demonstrating stent delivery system placed over the guidewire and the compressed radio-opaque stent (white arrows) placed across the malignant obstruction prior to stent deployment.
Figure 4: Lateral caudal abdominal fluoroscopic image obtained during a repeat retrograde contrast urethrocystogram demonstrating the deployed stent (white arrows) and a patent urethra.
Staff writer Amy Worden for the Philadelphia Inquirer discusses her personal experience with squamous cell carcinoma in her pet cat, Katya and the clinical trials offered to pet owners facing the same struggle today.