It was clear that you not only felt for us-but with us.
Pamela and David
Upper Chichester, PA
Hope VS is now offering the CADETSM BRAF Assay for diagnosis and monitoring of canine urinary cancer. Transitional cell carcinoma is the most common type of urinary cancer in dogs. The BRAF mutation is present in 85% of all canine TCC’s, thus can serve as a non-invasive biomarker for many dogs with this cancer. Since the test is performed on free catch urine samples, it can allow the medical team to obtain a diagnosis of TCC without fine needle aspirate or biopsy.
The BRAF mutation is present in 85% of all canine TCC cases, thus test sensitivity is 85% (15% false negatives).
The mutation is not present in urine samples of dogs with other non-TCC cancers nor non-cancerous urinary diseases, thus specificity is 100% (no false positives).
The test is not affected by the presence of bacteria or blood.
The test permits detection up to 4 months before clinical signs may be evident.
Ideal scenarios to employ this test (canine patients only):
1. Chronic lower urinary tract disease
2. If a mass, polyp, or thickening is noted in the urinary tract on ultrasound
3. Monitoring before and after surgical removal of TCC
4. Screening for at-risk breeds (e.g. Scottish terriers)
Please schedule a consultation with the oncology department at HopeVS if your dog is diagnosed with or suspected to have urinary cancer.
The U.S. Food and Drug Administration recently announced that it’s given conditional approval for the first new animal drug to treat canine lymphoma. Also called lymphosarcoma, lymphoma is a type of cancer in dogs. The FDA said the active ingredient in Tanovea-CA1 is rabacfosadine, a substance that kills rapidly growing cancer cells.
Tanovea-CA1 must be prescribed by a licensed veterinarian because professional expertise is needed to correctly diagnose lymphoma in dogs, determine the best treatment, and manage potential side effects. Tanovea-CA1, which comes in a concentrated form, is diluted and given into a vein over 30 minutes. The infusion should be given by or under the supervision of a veterinarian experienced in chemotherapy.
The “CA1” in Tanovea-CA1 means the drug is conditionally approved. Only animal drugs intended for minor species, such as ferrets or fish, or for minor uses in a major species, such as to treat certain types of cancer in dogs, are eligible for conditional approval. Tanovea-CA1’s conditional approval means that when used according to the label, the drug is safe and has a “reasonable expectation of effectiveness” for treating lymphoma in dogs.
At HopeVS, our oncology service is excited to add this agent to our current list of drugs to treat lymphoma. We have been using this drug as part of clinical trials for the past several years and have treated well over 150 patients. If you have any questions regarding the drug or patients that may be eligible, please contact us.
Phone: 610 296-2099
Since our inception in 2004, Hope Veterinary Specialists has been striving to provide the highest level of care to patients, clients, and referring veterinarians. Early on, we learned that the medicine is the easiest part of what we do. Effectively communicating with clients, veterinarians, and even colleagues within our own practice is much more of a challenge. Since communication is key to providing the level of care that we want to provide, we began looking for tools that would allow us to communicate more effectively. What we found was that those tools did not exist. Given that, we took on the challenge of developing our own practice management system and within that system, our own set of communication tools.
In the past, our focus was on sending information in a timely manner. We kept referring veterinarians updated by sending them each progressive record entry as that entry was made. After a patient left the hospital, lab results were sent to the primary veterinarian when we received them. Those updates went by fax or e-mail as per the recipient’s preference. Although this system is still one of the most effective available for real time communication with referring veterinarians, it was designed around technology that existed in 2005 before the first smart phone was released. Much of what is possible today was unimaginable when the system was developed. Over time, the new tools such as two-way text messaging with clients directly from the medical record were incorporated, but the tried and true methods for communicating with primary vets remained the same.
A recent trend among referral centers is the development of ‘web portal systems.’ These systems post information from medical records on-line and allow referring vets to log on and look up data. Many practices have abandoned their previous methods of communication and have limited themselves to using a portal. Anyone who has logged onto one of these systems knows that they can be VERY frustrating to use. They typically take bulk data and post the ‘blobs’ of information on the site. The primary vet is left to search for the information that they are looking for.
The idea of a web portal as a complement to the communication system that we already have in place was a fascinating one because a web portal could overcome the one major limitation of our system by making it much easier to retrospectively look at cases. That is obviously important to primary veterinarians who are following up with a patient days or weeks after they were seen. At that time, it is not helpful to look through the ‘play by play’ updates that were previously sent. The strength of our system in providing real time updates when a patient was at Hope was a major weakness when looking back at a case after the fact since it required a vet to look through many updates to find what they were looking for.
Hope has developed a new web portal system which complements our existing communication system and which overcomes all the downsides of the common web portal systems. Our new portal is available today at http://portal.hopevs.com. The system is unlike any other portal system in use today. They key features are:
1.Primary veterinarians can log on and see the record for any patient that they have referred for a full year from the date of the last visit.
2. Each entry is posted to the site with FIFTEEN MINUTES of when it was saved in our system. The entries are provided as PDFs that can easily be downloaded and imported into any medical record keeping system. They can, of course, be printed for paper records if desired.
3. The entries are formatted in a logical order that follows the flow of the visit.
4. At the end of any given visit, a comprehensive entry which contains the record for the entire visit is posted.
5. All prescription data is posted. That includes the details of the prescription, how much was dispensed, when the dispensed medication expires, and the number of refills.
6. All lab work is posted within 15 minutes of being entered in the record. For lab work from our Idexx equipment, you see the same pages and graphs that you are used to seeing print from the equipment.
7. All the images from radiographs, ultrasounds, MRIs, and CTs are available on the site. You can view animated loops of ultrasounds and echocardiograms. You can also navigate CT scans and MRIs in multiple planes. If 3D reconstructions of a CT exist, you can view the full 3D reconstruction.
8. Cases can be referred through the portal system. Cases referred to the Emergency Department appear on our triage board within 30 seconds of being submitted.
In short, our portal new portal system overcomes all the limitations of other portals and provides veterinarians with an unmatched level of access to their patients’ records. You can access the portal at http://portal.hopevs.com. Each practice has a unique username and password. Those were sent to each practice via fax and e-mail. If you need to get your credentials for the site, call the hospital at 610-296-2099 or send an e-mail to mail@HopeVS.com
Our new portal is just the beginning. We are now working on the companion smartphone / tablet app. Our hope is to have all the information that is available on the portal available through that app within 6 months.
Hope has invested hundreds of hours in the development of this portal to ensure that we continue to meet the every changing and developing expectations of the veterinarians who refer to our hospital. We welcome any feedback and are always open to suggestions for new features.
Submitted by: Tom Garg, VMD
A 7 year old male castrated Boxer presented for evaluation of hematuria. He had a history of chronic otitis, interdigital dermatitis, a I/VI systolic murmur, and periodic episodes of gastrointestinal upset which resolve without any intervention. In 2015, pre-anesthesia CBC and chemistry prior to a sebaceous adenoma removal showed TP 7.7 (5-7.4) and Glob 3.9 (1.6-3.6). His T4 was normal. A urinalysis had a urine specific gravity (USG) of 1.020 with +1 protein, WBC 2-3, RBC 21-50, struvite 11-20, cocci <10, and squamous epithelial cells 2-3. The method of urine sampling was not listed in the medical record. During wellness lab work in November, a CBC, Superchem, T4 and UA were performed. His TP was 7.7 (5-7.4), Glob 4.1 (1.6-3.6), and ALP 149 (5-131) with +2 hemolysis. His T4 was normal. His urinalysis showed a USG of 1.023 with +2 protein, +2 bilirubin, +3 blood, WBC 2-3, and RBC >50. His Accuplex was negative x 4 and fecal O&P showed no ova or parasites and the Giardia ELISA was negative. A urine cystocentesis the following week was very muddy brown. A urine culture showed no growth of bacteria. The patient has no other urinary symptoms other than having brownish urine noticed when it snowed. He did not have any stranguria or pollakiuria. He was active and otherwise healthy at the time of presentation to Hope Veterinary Specialists.
On physical examination, interdigital dermatitis was present. There were no abnormalities noted on examination of the penis or prepuce and his rectal examination was normal. An abdominal ultrasound was normal. Two weeks of empirical enrofloxacin were prescribed in case of pyelonephritis that was not diagnosed on cystocentesis urine culture. A urinalysis was performed at the end of the two week course of therapy while still on the antibiotics. The urine specific gravity was 1.023 with +1 protein, +3 blood, WBC 2-3, RBC >50, squamous epithelial cells 0-1.
Given the history and diagnostics, idiopathic renal hematuria was the top differential but urethral disease or disease within the bladder that was unable to be seen with the ultrasound could not be ruled out. Cystoscopy was performed. The urethral and bladder were normal. Both the left and right ureterovesicular junctions were visualized. Normal urine came was seen jetting from the left. Hematuria was noted from the right. The diagnosis of idiopathic renal hematuria was confirmed.
(Click link below to view cystoscopy video)
Idiopathic renal hematuria, also called benign essential hematuria and idiopathic renal hemorrhage, is a rare condition in which a patient has gross hematuria from the kidney from unknown cause. It is a diagnosis of exclusion. The condition occurs in both dogs and cats. There are no breed, age, or sex predilections. Many patients will have hematuria as their only symptom but urinary obstruction or other lower urinary signs from blood clots or systemic signs of anemia can also occur.
If the patient’s only clinical symptom is hematuria, as was the case for this patient, no further therapy is necessary. Typically, in these patients, periodic monitoring of the PCV or hematocrit will be performed to monitor for anemia. Historically, nephrectomy was recommended if the disease was unilateral, but this therapy has fallen out of favor since about 30% of patients will eventually develop bilateral disease. For more significantly impacted patients, medical management is recommended as the first tier of therapy. Benazepril can be used to decrease intrarenal pressure. Bazelle and Foale reported on the use of benazepril at 0.22 to 0.53 mg/kg PO q 24 in 4 dogs. Resolution of macroscopic hematuria was observed in all dogs but microscopic hematuria persisted in 2 of the 4 dogs. Anecdotal reports since this 2013 suggest that the overall success rate of benazepril is not as high as was reported in this abstract. Yunnan Baiyou can also be used to decrease bleeding. Allyson Berent, one of the leading experts in this disease, sites a 10-15% success rate with Yunnan Baiyou. If significant bleeding continues despite these therapies, urethroscopy can be performed to find and cauterize the bleeding vessel.
Sclerotherapy is the most successful approach for patients with significant bleeding. In 2013, Di Cicco et al used sclerotherapy with silver nitrate to treat bilateral idiopathic renal hematuria in a dog. The symptoms resolved for 10 months prior to recurrence. Berent et al, 2013 used a povidone iodine mixture followed by a sterile silver nitrate solution administered into the renal pelvis. Complete resolution of macroscopic hematuria occurred in 4 of the 6 patients. The 2 additional patients had moderate improvement of their symptoms. In 2017, Adelman, Barges and Whittemore reported resolution of macroscopic hematuria in 2 dogs within 12 hours of povidone iodine sclerotherapy.
The patient evaluated at Hope was not having significant enough clinical signs to warrant therapy at this time. We will closely monitor him for signs of anemia or lower urinary symptoms secondary to cystic blood clot formation. We plan to recheck his PCV/TS several times a year to monitor him for anemia.
Submitted by: Laurie Prober, VMD, DACVIM
Bazelle J, Foale R. The Successful Treatment of Idiopathic Renal Haemorrhage with Benazepril in Four Dogs. British Small Animal Veterinary Congress 2011. http://www.vin.com/doc/?id=4823393
Berent AC et al. Endoscopic-guided sclerotherapy for renal-sparing treatment of idiopathic renal hematuria in dogs: 6 cases (2010-2012). J Am Vet Med Assoc. 2013;242(11):1556-63. http://avmajournals.avma.org/doi/abs/10.2460/javma.242.11.1556
Adelman LB, Bartges J, Whittemore JC. Povidone iodine sclerotherapy for treatment of idiopathic renal hematuria in two dogs. J Am Vet Med Assoc. 2017;250(2):205-210. http://avmajournals.avma.org/doi/abs/10.2460/javma.250.2.205
Di Cicco MF et al. Management of bilateral idiopathic renal hematuria in a dog with silver nitrate. Can Vet J. 2013;54(8):761-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711164/
HELPFUL HINT 1: KNOW TUMOR BIOLOGY
Mast cell tumors are the most common cutaneous tumor in dogs (1). They do not have a specific look or feel (1) – we have diagnosed mast cell tumors that have a similar appearance to that of small pimples, skin tags, large ulcerated lesions, and soft fatty masses. Increased risk is associated with the following breeds: Boxer, Boston Terrier, English Bulldogs, Pugs, Labrador Retriever, Golden Retriever, Cocker Spaniel, Schnauzer, Staffordshire Terrier, Beagle, Rhodesian Ridgeback, Weimaraner, Shar-Pei (1). These tumors occur more often in middle-older aged dogs (1).
Mast cells contain biologically active compounds within the basophilic granules that are seen in the cytoplasm on microscopic evaluation (1). Histamine is the best-known compound; however these granules also contain heparin, proteases, and growth factors (1). These compounds play a role in the localized clinical symptoms and post-operative delay in wound healing seen in some patients with these tumors; specifically, histamine induced inflammation, heparin induced decrease in clot production and prolongation of bleeding, and protease induced protein and tissue breakdown. These granules may also play a role in systemic side effects from mast cell cancer including gastric ulceration induced vomiting, melena, hematochezia, weight loss and diminished appetite.
Mast cell tumors are locally aggressive and often extend beyond what is palpable on the surface (1). Metastasis depends on tumor grade with Grade 1, 2 and 3 tumors (Patnaik Grading Scale) metastasizing less than 10%, less than 20%, and approximately 90% of the time, respectively (2). More recently, a 2-tier grading scale (Kiupel Scale) has been established, with low grade vs high grade (3). The 2-tier scale was established to provide a more objective set of grading criteria for pathologists as the previously used scales may be prone to subjectivity and result in discordant grading results among pathologists (3). Metastatic disease is most often found in regional lymph nodes, liver, spleen, and less commonly the bone marrow (1). Low grade (Grade 1 or Grade 2) tumors typically grow slowly and are relatively quiescent while high grade (Grade 3) tumors have more aggressive behavior with rapid growth and may be associated with ulceration (1-3).
Approximately 20% of dogs will develop multiple cutaneous mast cell tumors (1). Therefore, a dog with prior history of mast cell tumor presenting for a new skin or subcutaneous mass should have that mass aspirated and cytology performed. Several studies have found that dogs with multiple mast cell tumors do not have a poorer prognosis than dogs with just one mast cell tumor (4, 5), although this is somewhat controversial.
EXAMPLES OF WHY IT IS IMPORTANT TO KNOW TUMOR BIOLOGY
- Patient presents for a mass with recent rapid growth. The mass was present for months to years with minimal change but in the past 2 weeks it has doubled in size, growing from a pea to a tennis ball size. The mass is removed and histopathology indicated Grade 1, complete margins. Given the histopathology you may consider this cured with the complete margins and Grade 1 designation; however, the ‘recent rapid growth’ history is concerning and indicates more aggressive tumor behavior. For this reason, a discussion with the pathologist, second opinion pathology review, and/or additional testing on the tumor, such as mast cell tumor proliferation panel, should be considered.
- Tumor biology helps us in our diagnostic plan. The most common staging tests recommended for dogs with mast cell cancer are routine baseline bloodwork (CBC/Chemistry), abdominal ultrasound, needle aspirate of the mass, either needle aspirate and cytology (or more preferred, removal and histopathology) of the regional/draining lymph node, and histopathology with margin assessment of the tumor (1).
- Tumor biology helps us in our treatment plan. With wide roots, 2-3cm margins are generally recommended although for low grade (Grade 1 and Grade 2) tumors, less aggressive margins may be adequate (further discussion below). With incomplete excision (roots left behind), high grade tumors have higher risk for recurrence than low grade, as such adjuvant therapy such as additional surgery or radiation is often recommended (1, 3). Furthermore, high grade tumors have highest risk for metastasis as such adjuvant chemotherapy is recommended in these cases (1, 3, 6). With incomplete excision of low grade (Grade 1 and Grade 2) tumors, additional surgery or radiation is recommended to help reduce risk of recurrence (1).
HELPFUL HINT 2: REVIEW THE MICROSCOPIC DESCRIPTION ON THE HISTOPATHOLOGY REPORT
The microscopic description provides key information in helping predict the behavior of the tumor, aiding in prognostication and treatment planning. Key elements of this description include: mitotic index, presence and number of multinucleated cells, presence and number of bizarre nuclei, presence of karyomegaly, degree of granulation, margins (1-3).
High grade (Grade 3) tumors generally have some of the following characteristics: a mitotic index greater than 5-7 mitotic figures/10 high power field, 3 or more multinucleated cells, 3 or more bizarre nuclei per 10 high powder field, karyomegaly (enlarged cellular nucleus), poorly granulated cells (1-3).
Low grade (Grade 1 and Grade 2) tumors generally have some of the following characteristics: infrequent-rare mitosis (less than 2 mitotic figures/10 high power field), abundant cytoplasmic granules, rare-no multinucleated cells and/or bizarre nuclei (1-3).
In the past, 3cm margins were the standard recommendation. More recent studies are finding 1cm lateral margins and 0.4cm deep margins are sufficient at controlling the tumor in many dogs with low grade (Grade 1 and Grade 2) tumors (7, 8). Wider margins are generally recommended for dogs with high grade tumors due to higher risk for recurrence with this phenotype.
It is important to request and read the microscopic description to get a clear view of the histologic appearance of the tumor and compare this to the historic behavior of the tumor (what your physical exam shows you and what the clients described). For example – if the tumor has been present for months to years with minimal growth and microscopic descriptors are that of low-intermediate grade tumor than this corroborates. If there is discordant data between the history/exam and microscopic description then this warrants further investigation (conversation with pathologist, second opinion pathology review, and/or mast cell tumor proliferation panel).
WHEN TO RECOMMEND THE MAST CELL TUMOR PROLIFERATION PANEL
This panel tests for markers of cellular proliferation, c-kit, AgNOR, KI67, and PCNA, through immunohistochemistry (special stains) and tests for the c-kit mutation through PCR (polymerase chain reaction) (9). This panel is not automatically run on every mast cell tumor and requires additional fee. This panel may be performed on every mast cell tumor if the clinician/client chose; however, this can be cost prohibitive. There are many labs that offer this testing a la carte, so you can pick and choose which tests within this profile you would like performed.
Instances on when to recommend the panel may include:
- Incompletely excised low-intermediate grade tumor, to help further elucidate risk for recurrence (recommend performing the entire panel)
- High grade tumors or tumors with high grade biology, i.e. already metastasized, to help determine chemotherapy protocol (recommend performing the c-kit PCR alone). A recent study demonstrated that tumors with c-kit mutation respond to the small molecule inhibitor Toceranib more often than tumors without the c-kit mutation, as such, Toceranib may be considered as part of the chemotherapy plan in this subset of patients.
HELPFUL HINT 3: TREATMENT RECOMMENDED
The standard of care treatment, first and foremost is surgery (1). If bulky mast cell disease is present, antihistamine (H1 and H2) blockers are recommended including: diphenhydramine or chlorpheniramine (H1 blockers), cimetidine, famotidine, ranitidine (H2 blockers) or proton pump inhibitor omeprazole (instead of H2 blockers). In some cases, surgical pre-treatment with steroid such as prednisone for 1-2 weeks may be recommended to reduce inflammation caused by the tumor and facilitate improved surgical margins (10).
Here are some helpful hints on when to recommend adjuvant therapy or alternative therapy if surgery is not an option.
WHEN TO RECOMMEND RADIATION
There are several common scenarios in which radiation is recommended (not exhaustive list):
- Incompletely excised mast cell tumor if second surgery not feasible (any grade)
- Bulky mast cell tumor that is not amenable to surgery (palliative purposes in this setting)
WHEN TO RECOMMEND CHEMOTHERAPY
There are several common scenarios in which chemotherapy is recommended (not exhaustive list):
- High grade (Grade 3) designation
- Known metastasis to regional lymph node, liver, spleen, etc
- Incompletely excised mast cell tumor (any grade)
- Bulky mast cell tumor that is not amenable to surgery
HELPFUL HINT 4: PROGNOSIS
As with any cancer, outcomes vary depending on stage, grade, treatment chosen, and interpatient variability.
Dogs with low grade (Grade 1 or Grade 2) mast cell tumors, with no evidence of metastasis, receiving surgery with wide and clean margins OR adequate local tumor control (surgery then treat roots with radiation or scar revision surgery) then there is good chance for long term control of this tumor (1). Inform the client that approximately 20% will develop another mast cell tumor in another location so diligent monitoring is recommended.
Dogs with high grade (Grade 3) mast cell tumors, or biologically aggressive tumors (i.e. those tumors with Grade 1 or Grade 2 designation but have known lymph node metastasis), receiving surgery with complete margins, removal of metastatic lymph node, followed by chemotherapy have an average survival time of over 3 years in one study (11).
Dogs with distant metastasis (liver/spleen/bone marrow) may receive radiation and chemotherapy for palliative purposes. Prognosis is generally poor but these treatments may help slow growth and progression as well as palliate clinical symptoms of illness for an estimated 3-4 months, depending on tumor response with therapy.
Dogs with large tumors not amenable to surgery may receive palliative radiation and chemotherapy to help slow growth and metastasis for a median progression free interval of approximately 300 days (12).
Submitted by: Dr. Kate Vickery, VMD, MS, Diplomate ACVIM, CVA
1- Withrow and McEwen. Small Animal Clinical Oncology. 5th ed. Eds Withrow, Vail, Page. Mast Cell Tumors. 335-355.
2 -Patnaik, AK, et al. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Veterinary Pathology. 1984. 21(5): 469—74. https://www.ncbi.nlm.nih.gov/pubmed/6435301
3- Kiupel, M, et al. Proposal of a 2-tier histologic grading systemi for canine cutanoes mast cell tumors to more accurately predict biological behavior. Veterinary Pathology. 2011. Jan; 48(1): 147-55. https://www.ncbi.nlm.nih.gov/pubmed/21062911
4- Mullins, M, et al. Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004). JAVMA. 2006. 228(1): 91-95. https://www.ncbi.nlm.nih.gov/pubmed/16426175
5- Thamm, D, et al. Prednisone and vinblastine for canine mast cell tumor – 41 cases. JVIM 1999. 13: 491-97. https://www.ncbi.nlm.nih.gov/pubmed/10499735
6- Stefanello D, et al. Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous mast cell tumors: 386 cases (2009-2014). JAVMA 2015. 246(7): 765-69. https://www.ncbi.nlm.nih.gov/pubmed/25794126
7- Schultheiss, PC, et al. Association of histologic tumor characteristics and size of surgical margins with clinical outcome after surgical removal of cutaneous mast cell tumors in dogs. JAVAM. 2011. 238(11): 1464-69. https://www.ncbi.nlm.nih.gov/pubmed/21627510
8- Pratschke, KM, et al. Evaluation of a modified proportional margins approach for surgical resection of mast cell tumor sin dogs: 40 cases (2008-2012). JAVMA. 2013. 243(10): 1436-41. https://www.ncbi.nlm.nih.gov/pubmed/24171373
9- Bergman, P, et al. Correlation of histologic grading of canine mast cell tumors with KI67/PCNA/AgNOR/c-kit scores: 38 cases. VCO. 2004. 2: 98. http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5810.2004.0045a.x/abstract
10- Stanclift, RM, et al. Evaluation of neoadjuvant prednisone administration and surgical excision in treatment of cutaneous mast cell tumors in dogs. JAVMA. 2008. 232: 53-62. https://www.ncbi.nlm.nih.gov/pubmed/18167109
11- Thamm, D, et al. Outcome and prognostic factors following adjuvant prednisone/vinblastine chemotherapy for high-risk canine mast cell tumor: 61 cases. J Vet Med Sci. 2006. 68: 581-87. https://www.ncbi.nlm.nih.gov/pubmed/16820715
12- Carlsten, KS, et al. Multicenter Prospective Trial of Hypofractionated Radiation Treatment, Toceranib, and Prednisone for Measurable Canine Mast Cell Tumors. JVIM. 2012. 26: 135–141. https://www.ncbi.nlm.nih.gov/pubmed/22176473