GH-3082 Seminar Booklet - Garden State Veterinary Specialists

GARDEN STATE
VETERINARY SPECIALISTS
Is Proud to Sponsor
A Full Day
Free Seminar
on
Small Animal
Oncology & Neurology
CE credit sanctioned by the New Jersey Veterinary Medical Association
Sunday, May 18, 2003
One Pine Street
Tinton Falls, New Jersey
Tel: 732-922-0011
Fax: 732-922-0991
w w w. g s vs. o rg
9:00-10:50Clinical Overview of
Small Animal Oncology
Philip J. Bergman DVM, MS, PhD
Diplomate ACVIM (Oncology)
Head, Donaldson-Atwood Cancer Clinic & Flaherty Comparative Oncology Laboratory
Adjunct Associate Faculty Member, Memorial Sloan-Kettering Cancer Center
The Animal Medical Center, 510 East 62nd St., New York, NY 10021
What’s New in Veterinary Oncology??
I will concentrate the following discussion around what
is new in veterinary oncology at the Donaldson-Atwood
Cancer Clinic (DACC) and Flaherty Comparative Oncology
Lab (FCOL) within the Animal Medical Center (AMC).
Within the FCOL & DACC, we are working on a number of
very exciting projects. Some of the most exciting projects involve collaborating with medical oncologists and
researchers at Memorial Sloan-Kettering Cancer Center
(MSKCC) which is the leading human cancer center in
the world.
Canine Malignant Melanoma (CMM)
Active immunotherapy in the form of DNA vaccines represents one potential therapeutic strategy for cancer.
Collaborators at MSKCC have shown that vaccination of
mice with DNA is ineffective when mouse DNA is used,
but effective tumor immunity and breaking of tolerance
can be induced by using DNA from another species (i.e.
xenogeneic).1,2
In our studies, we have chosen to target melanoma antigens of the tyrosinase family which are essential in
black pigment synthesis. Within the last thirty months,
we have completed three xenogeneic tyrosinase-family
DNA vaccine studies on dogs with advanced malignant
melanoma and are currently accruing patients on a
fourth trial. In the first phase I canine malignant
melanoma trial, 9 dogs (WHO stage II-IV; melanoma > 2
cm + LN + distant metastases) received four biweekly IM
injections of DNA encoding human tyrosinase (huTyr).
Importantly, one stage IV dog experienced a durable
complete response, one stage IV dog continues to be
alive at ~ 625 days and no local nor systemic toxicity
was seen. The median survival time was 389 days,
which appears to be significantly increased when com-
pared with stage-matched historical controls.3 In addition, we have recently looked at dogs receiving DNA vaccines from the first two vaccine studies with stage II/III
disease (melanoma > 2 cm + LN metastasis, but no evidence of distant metastasis) after good loco-regional
tumor control was effected by surgery and/or radiation
therapy. The median survival time for these dogs is currently greater than 600 days.
These studies have shown that: 1) dogs with malignant
melanoma benefit from an immunotherapy approach,
especially those with good local tumor control, 2) dogs
are likely the most faithful model of human malignant
melanoma, and 3) veterinary and human cancer centers
can collaborate effectively to benefit all patients afflicted with cancer.
Figure I. Median survival times for CMM treated with surgery.4
Figure II. Kaplan-Meier Survival Curve for 9 dogs with
advanced malignant melanoma (WHO stage II, III and
IV) treated with 4 biweekly xenogeneic human tyrosinase
vaccinations.3 KM Median survival time is 389 days.
Time as shown on X-axis is in days, and three dogs are
censored at 496, 501 and 588 days.
If you have a patient with malignant melanoma that
lives within a 50 mile radius of the AMC, the presently
ongoing studies pay for the vast majority of costs except
for a $20 co-pay per visit once on the trial. Please have
the client set up an appointment with the oncology
service by calling 212-838-8100, or you can call the
referral coordinator for the AMC at 212-329-8890. If
you have a patient that lives outside the aforementioned
50-mile radius, the vaccine would continue to be free,
however all other associated costs with the five visits
every 2 weeks (4 vaccinations and one 2 week recheck)
would come to ~ $2000-$2500 and not be covered by
the study. Other sites that may be doing melanoma vaccine studies include, but may not be limited to, the
University of Wisconsin-Madison and Colorado State
University.
Canine Mast Cell Tumors
Canine cutaneous mast cell tumors (MCT’s) are the most
common skin tumor in dogs.5 They usually present as
raised, often erythemic and/or ulcerated masses, the
biologic behavior of which generally correlates to a
three-tier Patnaik grading system, where grade I tumors
are well differentiated and grade III tumors are poorly
differentiated.6 Unfortunately, the grade II category has
become a grouping for tumors which do not clearly fit
into the other grades, and hence the ability to prognosticate this large group of tumors is reduced. As recently
shown in the Seguin et al MCT paper, many grade II
MCT’s can have a good prognosis with aggressive local
tumor control, however, some do poorly and recur and/or
metastasize.7 In addition, metastatic Grade I MCT and
Grade III MCT that do well with local tumor control only
cases are seen, strongly suggesting that MCT grading is
not the complete solution for prognostication. Because
of this problem, refining the current MCT grading system
is strongly encouraged by oncologists and pathologists
alike.
The development of immunohistochemical molecular proliferation markers may complement subjective morphologic grading schemes for canine cutaneous MCT’s.
Various laboratories have previously investigated the
prognostic significance of various markers in single fashion.8-10 We are presently performing all of these markers
as an “MCT panel” on surgically-resected formalin-fixed
paraffin-embedded canine MCT’s. While it is presently
unknown whether this panel approach will allow for
prognostication, we have recently had many cases where
histologic grading suggested a middle grade II MCT that
concurrently had no evidence of metastasis at the time
of resection but on MCT panel had extremely high special stain values. Unfortunately, many of these dogs
have gone on to develop metastasis, suggesting preliminarily that this panel may have importance in prognostication. We hope with this information in the future that
we will be able to expand the current problematic grading system to create a robust histological grading
scheme that can more accurately predict clinical behavior.
If you believe you have a canine MCT patient that you
would like to have this panel performed on, please call
the Flaherty Comparative Oncology Laboratory at 212329-8675. We generally require ~ 8 unstained positively-charged specimen slides and the cost is $200, which
includes histopathologist review of the results. Slides
with return contact information including your hospital’s
fax number can be sent to: Flaherty Comparative
Oncology Laboratory, The Animal Medical Center, 510
East 62nd St., New York, NY 10021.
FUNDED Canine Mast Cell Tumor Study
In addition to this MCT panel, the AMC is one of the
sites for a multi-center industrial-sponsored trial evaluating the efficacy of a novel, investigational protein
kinase inhibitor for the treatment of dogs with recurrent
MCT’s.
Enrollment Criteria:
• Recurrent cutaneous mast cell tumor of Grade II or
Grade III
• Prior “curative” surgery required
• Measurable disease required (at least one lesion >
20 mm)
• Metastasis beyond skin limited to one region of
lymph nodes
• Limited prior systemic chemotherapy
• Prior radiation therapy accepted
• Age at least 1 year and may not be used for breeding purposes, nor pregnant
• Washout from prior chemotherapeutics, steroids or
other investigational agents required
Trial support/funding includes:
• diagnostic tests (to confirm eligibility and for follow-up)
• treatment agent & follow-up examinations
Trial Conditions:
• This is a randomized, placebo-controlled clinical
trial
• Those dogs randomized to placebo will have a
chance to crossover to active agent at either 3
weeks or 6 weeks if the disease advances
• There will be an initial 6 week phase where the
patient must be seen weekly and then two visits
every 3 weeks
• Follow-up treatment with the investigational drug
will continue for at least 6 months at 6 week intervals for those patients who benefit from treatment
If you believe you have a patient that may qualify
for this study, please contact:
• Ruby Rivera (AMC referral coordinator) @ 212-3298890, OR
• Have the client set up a new patient oncology
appointment by calling 212-838-8100
The magical “3 cm rule”
Current recommendations for canine cutaneous MCT excision are to include a 3 cm lateral and one fascial plane
deep margin. The purpose of our study was to determine if these guidelines are appropriate. Prior to incision, a surgical pen was used to mark the tissue 1, 2,
and 3 cm from the tumor edge at 0, 90, 180, and 270
degrees. Each tumor was excised with a 3 cm margin laterally and a deep margin of at least one fascial plane.
Eight, 1 cm long, full thickness tissue sections were
evaluated at 0, 45, 90, 135, 180, 225, 270, and 315
degrees along the 3 cm margin. Four, 1 cm long, full
thickness sections taken at 0, 90, 180, and 270 degrees
from the 1 and 2 cm margins were also examined. The
Patnaik grading system was used. Statistical analysis was
performed and a P value of <0.05 was considered significant. Seventeen client-owned dogs with 19 cutaneous
MCTs were included in this study. Two masses were
located on the neck (11%), 5 on the limbs (26%), and
12 on the trunk (63%). There were 3 Grade I and 16
Grade II MCTs. No neoplastic mast cells were detected
at the 2 or 3 cm margins in any patient. Two Grade II
tumors were incompletely resected at the deep margin.
A tumor on the limb was significantly associated with an
incomplete deep margin (P<0.01). There were significant associations between the 2 and 3 cm margin and
complete resection (P<0.02). These data strongly suggest that for most canine cutaneous MCTs, a 2 cm lateral
margin with one fascial plane deep to the tumor is adequate for complete excision. These data also suggest
that MCTs located on the limb may require a deep margin in excess of one fascial plane.
Other AMC projects:
Sterile Hemorrhagic Cystitis. The development of sterile hemorrhagic cystitis (SHC) in dogs after the administration of cyclophosphamide is occasionally seen and is
a serious side effect.11 We wished to perform a study to
better understand cyclophosphamide-associated SHC in
the dog based on the significant caseload at the AMC.
The study purpose was twofold: first, determine incidence and ascertain any predisposing factors of
cyclophosphamide-associated SHC in dog lymphoma
chemotherapy protocols; second, determine whether IV
furosemide administered concurrently with IV cyclophosphamide decreases incidence of SHC. 216 dogs treated
with one of two protocols were analyzed retrospectively.
One protocol used furosemide concurrently with
cyclophosphamide while the other protocol didn’t.
Twelve cases of SHC (12/133; 9%) were seen when
furosemide was not used, whereas 1 case (1/83; 1.2%)
was seen with concurrent use of furosemide (p=0.02).
Results suggest incidence of SHC can be significantly
reduced with concurrent use of furosemide. Interestingly,
dogs with immune mediated diseases were more likely to
develop cyclophosphamide-associated SHC (p=0.001).
The number of cyclophosphamide doses was negatively
correlated with SHC (p=0.06). In this study, the inci-
dence of SHC with intravenous cyclophosphamide without concurrent furosemide is similar to incidence of SHC
with oral cyclophosphamide in previous studies. This
study should be published in the May 15th, 2003 edition
of JAVMA.
thoracic cavity (p=0.005). 3/14 animals experienced
mild side effects with intracavitary treatment (GI with
mitoxantrone and GI and neutropenia with carboplatin).
No pain on administration of intracavitary treatment was
noted.
Intracavitary Chemotherapy. Carcinomatosis, serosal
metastasis, and malignant effusions carry a poor prognosis. Treatments to date have included IV chemotherapy,
chemical pleurodesis, and intracavitary (IC) cisplatin
chemotherapy.12 Unfortunately, administration of IC cisplatin still causes significant emesis and nephrotoxicity
necessitating the concurrent use of anti-emetics and
aggressive saline diuresis. The purpose of this study was
to assess the safety and efficacy of IC carboplatin
(300mg/m2) and mitoxantrone (5 to 5.5 mg/m2) in an
alternating fashion every 4 weeks. Age, species, gender,
tumor class, carcinomatosis, serosal metastasis, malignant effusion and disease at time of treatment, type of
treatment, resolution of clinical signs post treatment,
cavity affected, and survival were analyzed for significance. Side effects were noted. 8 dogs and 6 cats were
treated. 5/14 had intravenous and intracavitary treatment. 9/14 had intracavitary treatment only. The range
of the number of intracavitary treatments was 1-10
(mean=3.5, median =3). Overall median survival time
was 229 days. Median survival times for dogs and cats
respectively were 300 days and 12 days. Cats were statistically less likely to survive (p=0.0016) as were animals with clinical signs at the time of intracavitary
treatment (p=0.016) and animals with disease in the
Veterinary Cancer Society
One of the very best ways to keep up with what is new
in veterinary oncology is to become a member of the
Veterinary Cancer Society (VCS)! As the current president of the VCS, I am proud to say that we are an
extremely diverse group of individuals ranging from technicians (we have a great Technician VCS group) and veterinary students to oncologists that have interests in
medical, surgical, radiation and other aspects of veterinary oncology. Upon becoming a member you will
receive a quarterly newsletter as well as receive reduced
rates for the annual VCS meeting, the premiere veterinary oncology meeting in the world. The upcoming
annual VCS meeting will be in Madison, Wisconsin from
September 26-29, 2003. In addition, every other year
we have a mid-year VCS meeting that focuses on a single subject. The next mid-year VCS meeting will be held
in Napa April 1-4, 2004 and focus on rationally-targeted
therapies. It will be a great combination of science,
location and maybe a just a lil’ California wine. If you
are interested in becoming a VCS member, please go to
www.vetcancersociety.org, or call Barb McGehee @ (619)
474-8929//Fax (619) 474-8947.
References
1.
2.
Bowne,W.B. et al. Coupling and uncoupling of tumor immunity and autoimmunity. J. Exp. Med. 190, 1717-1722 (1999).
Wolchok,J.D. & Livingston,P.O. Vaccines for melanoma: translating basic immunology into new therapies. Lancet Oncol JID - 100957246
2, 205-211 (2001).
3. Bergman,P.J. et al. Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human
tyrosinase: a phase I trial. Clin. Cancer Res. 9, 1284-1290 (2003).
4. MacEwen,E.G., Patnaik,A.K., Harvey,H.J., Hayes,A.A. & Matus,R. Canine Oral Melanoma: Comparison of Surgery Versus Surgery Plus
Corynebacterium parvum. Cancer Investigation 4(5), 397-402 (1986).
5. Macy,D.W. Canine and feline mast cell tumors: biologic behavior, diagnosis, and therapy. Semin Vet Med Surg (Small Anim) 1, 72-83 (1986).
6. Patnaik,A.K., Ehler,W.J. & MacEwen, E.G. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet
Pathol 21, 469-474 (1984).
7. Seguin,B. et al. Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996-1999). J. Am. Vet.
Med. Assoc. 218, 1120-1123 (2001).
8. Kravis,L.D., Vail,D.M., Kisseberth,W.C., Ogilvie,G.K. & Volk,L.M. Frequency of argyrophilic nucleolar organizer regions in fine- needle
aspirates and biopsy specimens from mast cell tumors in dogs. J. Am. Vet. Med. Assoc. 209, 1418-1420 (1996).
9. Reguera,M.J., Rabanal,R.M., Puigdemont,A. & Ferrer,L. Canine mast cell tumors express stem cell factor receptor. Am. J. Dermatopathol.
22, 49-54 (2000).
10. Simoes,J.P.C., Schoning,P. & Butine,M. Prognosis of canine mast cell tumors: A comparison of three methods. Vet. Pathol. 31, 637-647 (1994).
11. Laing,E.J.,Miller,C.W. & Cochrane,S.M. Treatment of cyclophosphamide-induced hemorrhagic cystitis in five dogs. J Am Vet Med Assoc
193(2), 233-236 (1988).
12. Moore,A.S., Kirk,C. & Cardona, A. Intracavitary Cisplatin Chemotherapy Experience with Six Dogs. J. Vet. Intern. Med. 5, 227-231 (1991).
TOP 10 Recent Advances in Veterinary Oncology
Philip J. Bergman DVM, MS, PhD
Diplomate ACVIM (Oncology)
Head, Donaldson-Atwood Cancer Clinic & Flaherty Comparative Oncology Laboratory
Adjunct Associate Faculty Member, Memorial Sloan-Kettering Cancer Center
The Animal Medical Center, 510 East 62nd St., New York, NY 10021
This discussion will review what I feel to be the top 10
clinically relevant advances in veterinary oncology over
the last ~ 10 years. Topic #10 will be a “stinker topic”
and will briefly summarize advances that have really NOT
been advances :). I will post the abstracts from these
publications and then summarize them in the lecture. It
is important to point out that major advances in surgical
oncology have occurred over the last 30 years (e.g.
hemipelvectomy, limb-sparing, nasal planectomy,
scapulectomy, etc.) but they will not be discussed here.
1. Six month chemo for lymphoma.1
The purpose of this study was to compare a maintenance-free chemotherapy protocol based on CHOP (H
from hydroxydaunorubicin = doxorubicin, O from Oncovin
= vincristine) to a similar protocol with a maintenance
phase for the treatment of canine lymphoma. Fifty-three
dogs with multicentric lymphoma were treated with a 6month modified version of the University of Wisconsin
(UW)-Madison chemotherapy protocol (UW-25). Diseasefree interval (DFI) and survival were compared to a historical control group of 55 dogs treated with a similar
protocol with a prolonged maintenance phase. Remission
rate for the study dogs was 94.2% (complete remission =
92.3%, partial remission = 1.9%). DFI and survival
between the 2 groups did not differ significantly, with
median DFI and survival of the study dogs equal to 282
and 397 days compared to 220 and 303 days for the
control dogs (P = .2835 and .3365, respectively).
Univariate analysis identified substage b (P = .0087),
German Shepherd breed (P = .0199), and body weight >
18 kg (P = .0016) as significant for worse survival.
Longer survival was associated with thrombocytopenia (P
= .0436). Multivariate analysis revealed that substage (P
= .0388) and weight (P = .0125) retained significance
for DFI, whereas substage (P = .0093), thrombocytopenia (P = .0150), and weight (P = 0 .0050) retained significance for survival. Overall, the protocol was well tolerated by the dogs, with 41.5% (22/53) requiring a
treatment delay or dose modification, but only 9.4%
(5/53) needing hospitalization. The 6-month chemother-
apy protocol based on CHOP with no maintenance phase
provides similar DFI and survival times when compared
to a similar protocol with a prolonged maintenance
phase.
2. FNA of non-palpable LN’s.2
OBJECTIVE: To determine sensitivity and specificity of
physical examination, fine-needle aspiration, and needle
core biopsy of the regional lymph nodes for evidence of
metastasis in dogs and cats with solid tumors. DESIGN:
Case series. ANIMALS: 37 dogs and 7 cats. PROCEDURE:
Regional lymph nodes were evaluated by means of physical examination (palpation), fine-needle aspiration, and
needle core biopsy. Results were compared with results
of histologic examination of the entire lymph node, the
current standard. RESULTS: Tumors included 18 sarcomas,
16 carcinomas, 7 mast cell tumors, and 3 other tumors.
Carcinomas were more likely to have metastasized to the
regional lymph node (7/16 animals) than were sarcomas
(2/18). Sensitivity and specificity of physical examination were 60 and 72%, respectively. Sensitivity and
specificity of cytologic examination of fine-needle aspirates were 100 and 96%, respectively. Sensitivity and
specificity of histologic examination of needle core biopsy specimens were 64 and 96%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that
fine-needle aspiration may be a sensitive and specific
method of evaluating the regional lymph nodes in dogs
and cats with solid tumors, because results correlated
well with results of histologic examination of the entire
lymph node. Physical examination alone was not a reliable method and should not be used to decide whether
to aspirate or biopsy the regional lymph nodes.
3. Surgical Debulking before definitive
therapy.
A. OBJECTIVE: To compare, for dogs with intracranial
meningiomas, survival times for dogs treated with surgical resection followed by radiation therapy with survival
times for dogs treated with surgery alone. DESIGN:
Retrospective study. ANIMALS: 31 dogs with intracranial
meningiomas. PROCEDURE: Medical records of dogs with
histologic confirmation of an intracranial meningioma
were reviewed. For each dog, signalment, clinical signs,
tumor location, treatment protocol, and survival time
were obtained from the medical record and through follow-up telephone interviews. RESULTS: Dogs that underwent tumor resection alone and survived > 1 week after
surgery had a median survival time of 7 months (range,
0.5 to 22 months). Dogs that underwent tumor resection
followed by radiation therapy had a median survival time
of 16.5 months (range, 3 to 58 months). CONCLUSIONS
AND CLINICAL RELEVANCE: Results suggest that in dogs
with intracranial meningiomas, use of radiation therapy
as a supplement to tumor resection can significantly
extend life expectancy.3
B. Naturally-occurring urinary tract transitional cell carcinoma (TCC) comprises approximately 1.5 to 2% of cancer in dogs and is the most common urinary tract neoplasm. Numerous treatment modalities have been used
for TCC including surgery, radiation, chemotherapeutic
agents, and non-steroidal anti-inflammatory drugs.
Although surgical resection has been attempted in many
cases, survival times have been low (usually less than 6
months), and cure is rarely possible due to the location,
invasive nature, and metastatic behavior of this tumor.
It is possible, however, that removing part of the tumor
(i.e. surgical debulking) could have a beneficial effect.
The purpose of this retrospective study was to compare
the survival times of dogs with TCC who had surgical
debulkment to the survival times of those not having
surgical debulkment. A retrospective review of Purdue
University Veterinary Teaching Hospital (PUVTH) records
of all dogs with a diagnosis of transitional cell carcinoma (TCC) between 1985 and 1998 was conducted. Cases
included in this study had histopathological confirmation of TCC, complete information on surgery type performed, information on subsequent treatment (if any),
and known survival information. Dogs who had a diagnosis made by cystoscopy, catheter biopsy, or cystotomy
with biopsy were categorized in the “nonsurgery” group.
Dogs in which the bulk of macroscopic tumor was
removed via cystotomy for the purpose of palliation as
well as diagnosis were categorized in the “debulking surgery” group. Survival of dogs in the debulking surgery
group was significantly longer (P = 0.002; n = 350 days)
than survival of dogs in the nonsurgery group (n = 207
days), and surgical debulking prolonged survival regard-
less of tumor location. Tumor location was also associated with survival, which was significantly shorter for dogs
with tumor in the urethra and trigone compared to dogs
with no tumor in those locations, regardless of treatment. The results of this study strongly suggest a beneficial role of debulking surgery in prolonging survival
times of dogs with TCC.4
4. Efficacy of RT for incompletely
resected MCT & STS.
A. OBJECTIVE: To evaluate efficacy of radiation for treatment of incompletely resected soft-tissue sarcomas in
dogs. DESIGN: Prospective serial study. ANIMALS: 48
dogs with soft-tissue sarcomas. PROCEDURE: Tumors were
resected to < 3 cm3 prior to radiation. Tumors were
treated on alternate days (three 3-Gy fractions/wk) until
21 fractions had been administered. Cobalt 60 radiation
was used for all treatments. RESULTS: Five-year survival
rate was 76%, and survival rate was not different among
tumor types or locations. Four (8%) dogs developed
metastases. Eight (17%) dogs had tumor recurrence after
radiation. Development of metastases and local recurrence were significantly associated with reduced survival
rate. Median survival time in dogs that developed metastases was 250 days. Median disease-free interval for all
dogs was 1,082 days. Median time to recurrence was 700
days. Dogs that developed recurrence after a prolonged
period responded well to a second surgery. Acute radiation toxicosis was minimal; osteosarcoma developed at
the radiation site in 1 dog. CONCLUSIONS AND CLINICAL
RELEVANCE: An excellent long-term survival rate may be
achieved by treating soft-tissue sarcomas in dogs with
resection followed by radiation. Amputation is not necessary for long-term control of soft-tissue sarcomas in
limbs. Development of metastases and recurrence of
local tumors after radiation treatment are associated
with decreased survival rate. Acute and delayed radiation
toxicosis was minimal with the protocol used in this
study.5
B. The records of 56 dogs treated with megavoltage radiation for mast cell neoplasia were reviewed to determine
the efficacy of this treatment modality. Total radiation
dose ranged from 45 to 57 Gray (Gy), dose per fraction
ranged from 3.0 to 4.0 Gy, and radiation treatment time
ranged from 14-28 days. Median disease free interval
(95% CI) was 32.7 (19-70) months. Median disease free
interval for dogs older than 7.5 years was 15 (lower
limit 7) months as compared to 62 (lower limit 20) for
dogs younger than 7.5 years of age (p = 0.006). Median
disease free interval for dogs with measurable disease
was 12 (lower limit 5) months as compared to 54 (3270) months for dogs with microscopic disease (p =
0.006). Radiation treatment time was also significantly
related to disease free interval. Median disease free
interval for dogs treated longer than 22 days was 12 (719) months as compared to greater than 50 (lower limit
20) months for dogs treated in 22 or fewer days (p <
0.001). This appeared to be due to more recurrences in
dogs treated with 3-per-week fractionation and suggests
that tumor proliferation in the interfraction interval may
be important. Sex, tumor location, histologic grade, WHO
clinical stage, number of radiation fractions, total radiation dose, and dose-per-fraction, as well as the following
“yes/no” variables: steroids given, surgery prior to radiation, lymph nodes irradiated, and development of another mast cell tumor did not appear to influence median
disease free interval or survival. Data presented herein
support megavoltage radiation as an effective treatment
for canine mast cell neoplasia, and suggest that disease
free interval in dogs treated with daily fractions may be
longer than that achieved with alternating day
fractions.6
5. LSA Rescue Protocols.
A. The purpose of this retrospective study was to evaluate the efficacy and toxicity of the MOPP chemotherapy
protocol (mechlorethamine, vincristine, procarbazine,
and prednisone) as a rescue regimen in dogs with lymphoma. One hundred seventeen dogs that had resistance
to previously administered chemotherapy were evaluated.
Before treatment with MOPP, all dogs received a median
of 6 chemotherapy drugs for a median duration of 213
days. Thirty-one percent (36 of 117) had a complete
response (CR) to MOPP for a median of 63 days, and
34% (40 of 117) had a partial response (PR) for a median of 47 days. Sixteen percent (19 of 117) had stable
disease (SD) for a median of 33 days. Predictors for
response to MOPP were not identified. Gastrointestinal
(GI) toxicity occurred in 28% (33 of 117) of the dogs,
and 13% (15 dogs) required hospitalization. Five dogs
developed septicemia, and 2 died as a result. MOPP was
an effective treatment for dogs with resistant lymphoma
and was well tolerated by the majority of affected dogs.7
B. Forty-three dogs with lymphoma that had relapsed or
had failed to achieve complete remission to previous
chemotherapy were treated with lomustine (1-(2-
chloroethyl)-3-chyclohexyl-1-nitrosourea [CCNU]) at a
dosage of 90-100 mg/m2 body surface area PO every 3
weeks. Durable complete or partial responses occurred in
11 dogs for a median of 86 days. The acutely dose-limiting toxicosis was neutropenia 7 days after administration, resulting in a recommended dosage of 90 mg/m2.
Cumulative thrombocytopenia occurred in dogs receiving
continued CCNU treatment, and a dose interval of 3
weeks may be too short for continued administration of
this drug. Toxicoses evident as fever or central nervous
system signs or renal damage were uncommon or rare.
CCNU is effective in the treatment of relapsed lymphoma.8
6. Chemotherapy for canine MCT.
A. Prednisone alone. Twenty-five dogs with naturally
occurring mast cell tumors were treated with daily oral
prednisone (1 mg/kg) for 28 days. Five dogs (20%) had
reduction in tumor volume and were considered responders. Four of these underwent partial remission and one
underwent complete remission. Survival times for the
five responders were 3, 5, 6, 7.5, and greater than 28
months, respectively. We therefore conclude that prednisone is effective in some canine mast cell tumors.
Further studies are indicated to determine the most
effective dose of prednisone, the appropriate duration of
treatment, and the efficacy in more benign mast cell
tumors, and in combination with other forms of therapy.9
B. Prednisone & Vinblastine. Forty-one dogs with mast
cell tumors (MCTs) were treated with oral prednisone and
injectable vinblastine (VBL), both in the adjuvant setting (23 dogs) and in dogs with gross disease (18 dogs).
Adverse effects were noted in 20% (8/41) of the
patients, usually after the 1st dose of VBL. Adverse
effects were considered mild in 6, and severe, necessitating treatment discontinuation, in 2 (5%). Overall
response rate in the evaluable dogs with gross disease
was 47% (7/15), consisting of 5 complete responses and
2 partial responses. Median response duration was 154
days (24 to >645 days). As adjuvant therapy to incomplete surgical resection, prednisone and VBL conferred a
57% 1- and 2-year disease-free rate. Median survival
time (MST) for the entire patient population was not
reached with a median follow-up of 573 days; however,
the MST for dogs with grade III MCT was 331 days, with
45% of dogs alive at 1 and 2 years. This is an apparent
improvement over historical survival data employing surgery alone. Upon univariate analysis, significant prognostic factors (P < .05) for survival included presence of
a locally recurrent tumor, presence of gross disease,
argyrophilic nucleolar organizer region frequency, lymph
node status, histologic grade, previous chemotherapy,
and ulceration of the tumor. Similar criteria were significant when analyzed for time to treatment failure.
Response to therapy was also predictive of survival in
the gross disease group. Upon multivariate analysis, histologic grade (P = .012) and presence of a locally recurrent tumor (P < .001) were significant factors for survival.10
platelet count may occur 14-21 days after treatment.
The median platelet count at the nadir was 43,500
cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and
additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable
responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen
of 50-60 mg/m3 every 6 weeks.11
C. CCNU alone. 1-(2-Chloroethyl)3-cyclohexyl-1nitrosourea (CCNU) is an alkylating agent in the
nitrosourea subclass. A prospective evaluation of CCNU
was done to determine the maximally tolerated dosage
of CCNU in tumor-bearing cats. Response data were
obtained when available. Twenty-five cats were treated
with CCNU at a dosage of 50-60 mg/m3 body surface
area. Complete hematologic data were available for 13
cats. Neutropenia was the acute dose-limiting toxicity.
The median neutrophil count at the nadir was 1,000
cells/microL (mean, 2,433 cells/microL; range, 0-9,694
cells/microL). The time of neutrophil nadir was variable,
occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after
the nadir. Based on these findings, a 6-week dosing
interval and weekly hematologic monitoring after the 1st
treatment with CCNU are recommended. The nadir of the
7. Diagnostic Imaging Advances.
To be reviewed at the lecture with special emphasis on
importance to feline vaccine-associated sarcoma.
8. Immunohistochemistry for Diagnosis &
Prognostication.
To be reviewed at the lecture with special emphasis on
importance to lymphoma, mast cell tumor and other
malignancies.
9. Putting the cart before the horse.
To be reviewed at the lecture with special emphasis on
MAb 23112, Acemannan13, Bladder TCC tests, Gemzar
and others.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Garrett,L.D., Thamm,D.H., Chun,R., Dudley,R. & Vail,D.M. Evaluation of a 6-month chemotherapy protocol with no maintenance therapy
for dogs with lymphoma. J Vet. Intern. Med. 16, 704-709 (2002).
Langenbach,A., McManus,P.M., Hendrick,M.J., Shofer,F.S. & Sorenmo,K.U. Sensitivity and specificity of methods of assessing the regional lymph nodes for evidence of metastasis in dogs and cats with solid tumors. J Am Vet. Med. Assoc 218, 1424-1428 (2001).
Axlund,T.W., McGlasson,M.L. & Smith,A.N. Surgery alone or in combination with radiation therapy for treatment of intracranial meningiomas in dogs: 31 cases (1989-2002). J Am Vet. Med. Assoc 221, 1597-1600 (2002).
Josel,J.R. et al. The role of surgical debulkment in dogs with transitional cell carcinoma of the urinary bladder: A retrospective study of
122 dogs. Proc. Vet. Canc. Soc. 5 (2002).
McKnight,J.A., Mauldin,G.N., McEntee,M.C., Meleo,K.A. & Patnaik,A.K. Radiation treatment for incompletely resected soft-tissue sarcomas in dogs. J Am Vet. Med. Assoc 217, 205-210 (2000).
LaDue,T., Price,G.S., Dodge,R., Page,R.L. & Thrall,D.E. Radiation therapy for incompletely resected canine mast cell tumors. Vet. Radiol.
Ultrasound 39, 57-62 (1998).
Rassnick,K.M. et al. MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000).
J. Vet. Intern. Med. 16, 576-580 (2002).
Moore,A.S. et al. Lomustine (CCNU) for the treatment of resistant lymphoma in dogs. J. Vet. Intern. Med. 13, 395-398 (1999).
McCaw,D.L. et al. Response of canine mast cell tumors to treatment with oral prednisone. J Vet. Intern. Med. 8, 406-408 (1994).
Thamm,D.H., Mauldin,E.A. & Vail,D.M. Prednisone and vinblastine chemotherapy for canine mast cell tumor—41 cases (1992-1997). J
Vet. Intern. Med. 13, 491-497 (1999).
Rassnick,K.M. et al. Treatment of canine mast cell tumors with CCNU (lomustine). J. Vet. Intern. Med. 13, 601-605 (1999).
Jeglum,K.A. Chemoimmunotherapy of canine lymphoma with adjuvant canine monoclonal antibody 231. Vet. Clin. North Am Small Anim
Pract. 26, 73-85 (1996).
King,G.K. et al. The effect of Acemannan Immunostimulant in combination with surgery and radiation therapy on spontaneous canine
and feline fibrosarcomas. J. Am. Anim. Hosp. Assoc. 31, 439-447 (1995).
11:00-12:00
What is New in the Treatment of Canine Mast Cell
Tumors and Feline Vaccine-Induced Fibrosarcoma
Gerald Post, DVM, Diplomate ACVIM (Oncology), Garden State Veterinary Specialists, Staff Oncologist
Canine Mast Cell Tumors
MCTs
Biology
• Diagnosis
• Staging
• Therapy
Biology
• Metachromatic granules
• Histamine
• Heparin
• Cytokines
• Proteolytic enzymes
Biology
• The most common skin tumor of dogs
- 20-25% of cutaneous and subcutaneous tumors
• Can also occur in the intestines, liver, spleen,
bone marrow
Biology
• Clinical signs
• Firm to solid nodular mass
• May mimic ANY other type of skin mass
• ie lipoma
• GI signs-vomiting, diarrhea, gastric ulceration
• Local ulceration and edema
• Delayed wound healing
Genetics
C-kit mutation
• Juxtamembrane domain
- Duplications
- Deletions
• More aggressive lesion
• Higher grade
Diagnosis
Cytology
• Aspirates are excellent at telling you: YES or NO
• Can be used for grading ONLY with
AgNOR of cytologic preparation
Diagnosis
Biopsy
• Needed for grading
• Pre-treatment with steroids and diphenhydramine
Staging
• Lymph node aspirate/biopsy
• Chest radiographs
• Low percentage
• Abdominal ultrasound
• Value of splenic aspirates debatable
• Choose your cases carefully
- Aspirate a lesion
• Bone marrow - >10/ 1000 nucleated cells -value?
• Buffy coat-value?
Staging in the future
• C-kit mutation
• AgNOR
• DNA ploidy-?
• Others
Treatment
Surgical removal
• Solitary
• Less than 3-4 cm
• 2 separate lesions?
Treatment
Grade II tumors
Seguin, et al; JAVMA 2001
• 5% recurred locally-62 days
• 11% developed another tumor at a different location-240 days
• 5% developed metastasis-158 days
• 84% free of mast cell tumors -540 days
Treatment
Surgery and Radiation therapy
•
•
•
•
Solitary
Large
Residual disease
Draining node only?
Treatment
Chaffin and Thrall; Vet Radiol Ultrasound 2002
• 16 dogs with grade II
• Stage 2-local lymph node positive
• Surgery and full course RT to primary tumor and
regional lymph node
• Median disease free survival 1240 days
Treatment
Radiation alone
Al-Sarraf et al
• Grade II tumors
• Surgically resected
• 86% 5 year disease free interval
LaDue, et al
• Daily fractionation better than MWF scheme
Treatment
Radiation and chemotherapy
•
•
•
•
Large non-resectable
High grade?
Palliative vs Curative intent
Draining node positive?
Treatment
Thamm et al; JVIM 1999
•
•
•
•
•
Vinblastine and prednisone
As adjuvant therapy for incompletely resected disease
57% 1 and 2 year disease free
Grade III mast cell tumors
45% of dogs alive at 1 and 2 years
Treatment
Lomustine Rassnick et al; JVIM 1999
• 42% response rate-77-440 days
Feline Fibrosarcomas
Biology
• Vaccine Associated
• Multi-nucleated giant cells a prominent feature
• Fluid filled cavitations frequently observed
• Secondary to rapid tumor growth and central necrosis
Biology
• Kidney et al; AJVR 2001
• FeLV and FIV
• Expression unlikely involved with vaccine associated
sarcomas
• Papillomaviruses
• Not detected
• Polyomavirus
• Not detected
Biology
• p53 tumor suppressor gene
• Mutations seen in many types of malignancies
• 42-62% of tumor cell nuclei stain in feline vaccine
associated sarcomas
• Nambiar et al; Vet Pathol 2001
Diagnosis
• Biopsy-incisional
• Area that can be removed
Diagnosis
• Chest radiographs
• 12-25% metastatic rate
• CBC
• Chemistry
• Urinalysis
Diagnosis
• Contrast enhanced CT
• Detect disease extension up to 5cm from primary
tumor
• see tendril of tumor extending along facial planes
• Good aid prior to surgical removal
• use Conray 400
• use 3-5 mm sections
• use radio-opaque marker on pre-existing biopsy or
surgery site
Treatment
Surgery
• Hershey et al; JAVMA 2000
• Tumor free recurrence
- Radical first surgery-325 days
- Marginal first surgery-79 days
- Limb location -325 days
- Surgery alone many times NOT curative
- Other site-66 days
Treatment
Surgery and post-operative RT
•
•
•
•
•
•
Cohen et al; JAVMA 2001
Median disease free interval 405 days
1 and 2 year survival times 86% and 44%
More than 1 surgery prior to RT-poorer prognosis
Longer interval between surgery and RT-poorer prognosis
Larger tumors-poorer prognosis
Treatment
• Pre-operative RT and Surgery
• Kobayashi et al; Vet Radiol Ultrasound 2002
• Disease free survival
• 986 days with complete surgical excision
• 292 days with incomplete surgical excision
Treatment
NCSU study
•
•
•
•
•
•
Carboplatin—2 hours prior to RT (2 cycles)
4-5 cycles total
better control with chemo
40% of cats with failure had metastasis
median time to failure= 204 days
pre-operative RT may prevent “huge field” RT
Treatment
Chemotherapy
• Williams et al; AJVR 2001
- Establishment of cell lines
- Sensitive to doxorubicin and mitoxantrone
• Banerji et al; AJVR 2002
- Cell lines sensitive to vincristine and paclitaxel
Treatment
Chemotherapy for non-resectable Doxorubicin and cyclophosphamide
• Barber et al; JAAHA 2000
• Median response 125 days
• Responders had 242 day median survival time
Prevention
• Use non-adjuvanted vaccine
• Merial
• only one to have no reaction immediately post-vaccination
• Record site of vaccination
• Use SQ injection site at:
• distant Left rear limb—leukemia
• distant Right rear limb-rabies
Prevention
• Remove and biopsy all reactions > 3 months
1:30-3:00
Diseases of the Vestibular System
Noemie Bernier DVM, Diplomate ACVIM (Neurology)
Garden State Veterinary Specialists, Staff Neurologist
Overview:
Functions:
• Sensation of head motion and rotation
• Maintenance of equilibrium and body orientation in
space
• Coordination of head and eye movements to maximize visual acuity during movement of the head.
Functional anatomy and physiology:
• The inner ear
• The vestibulocochlear nerve
• Vestibular nuclei
Clinical signs:
- Central pathways: Medial Longitudinal Fasciculus
Nuclei of Cr. Nerves III, IV, VI; Vestibulospinal tracts
facilitatory to ipsilateral motor neurons of extensor
limb muscles, inhibitory to ipsilateral motor neurons
of flexor limb muscles, inhibitory to contralateral
motor neurons of extensor limb muscles. Caudal cerebellar peduncle‡ cerebellum (ipsilateral flocculus,
nodulus and fastigial nucleus)
• Cerebellum
• Unilateral
-
Head tilt, head turn, body turn
Ataxia- leaning, falling, circling, rolling
Pathological nystamus
Vestibular strabismus
• Bilateral
- Crouched, wide-based stance.
- Staggering/ falling to either side
- Jerky side to side head movement, wide head
excursions from side to side.
- No pathological or physiological nystagmus.
Neurolocalization:
Clinical signs
Other brainstemsigns such as:
Mental dullness
UMN paresis
GP ataxia
Other cranial nerves
Cerebellar signs
Persistent rolling
Nystagmus
Peripheral
No
No
No
No
Facial paralysis,
Horner’s syndrome
No
No
Always opposite the head
tilt - rotary or horizontal.
Central
Possible
Possible
Possible
Possible
Cr. Nerves V-XII
Possible
Possible
Any direction, possibly vertical,
may change direction with head mvt
Differential diagnosis - common vestibular
diseases.
Peripheral
• Feline idiopathic vestibular disease
- Severe, peracute
- All ages but usually young to middle aged
- Outdoor
- Late summer, early falls
- Tx: Supportive care
• Canine idiopathic geriatric vestibular disease
- Usually older than 8 years of age
- May have multiple episodes.
- Tx: supportive
• Otitis media-interna
- Otitis externa may not be present
- May have facial paralysis or Horner’s syndrome
- DX: otoscopic exam, +/- imaging (bulla series, CT,
MRI)+/- culture and sensitivity+/- BAER.
- May extend to cranial cavity with no to minimal
central signs.
- Tx: antibiotherapy, surgery.
• Idiopathic vestibular disease with facial paralysis
- No evidence of OM-OI.
- No evidence of hypothyroidism
• Hypothyroidism
• Intoxication
- Ex: aminoglycoside antibiotics.
• Neoplasia
- Temporal bone: sarcoma, squamous cell carcinoma.
- Peripheral nerve: neurofibroma, lymphoma.
Central
• Neoplasia
- Primary brain tumor- meningioma, neurofibroma,
medulloblastoma, choroids plexus, lymphoma, glioma.
- Secondary: hemangiosarcoma, pulmonary carcinoma, other.
• Metronidazole toxicity
- Tx: supportive and immediately stop drug administration.
- Often vertical nystagmus.
• Infectious non-infectious meningoencephalomyelitides
- GME often affects the cerebellomedullary area in
dogs.
- FIP occurs commonly in the caudal fossa of cats.
- Non-infectious or immune-mediated: usually GME in
this location.
- Infectious: Fungal (Cryptococcus), protozoal (toxoplasma, neospora), rickettsial (rickettsia,
ehrlichia,...), viral (distemper, FeLV rel. lymphoma,
FIP,...), bacterial (intracranial extension of otitis
media-interna)
• Thiamine deficiency
- Anorexic cats
- Raw fish diets, rich in thiaminase.
- Tx: 50 mg thiamine IM BID.
Diagnostics:
Peripheral:
• Idiopathic syndromes: observation.
• OM-OI: otoscopic exam +/- myringotomy +/- imaging
(bulla series, CT, MRI)+/-BAER.
• Hypothyroidism: Thyroid panel.
• Neoplasia: CBC, chem..,radiographs of the chest-3
views, radiographs of the skull, CT, MRI.
• Trauma: observation, CT of the head.
Central:
• CBC, chem.., chest rads x 3, MRI of the brain, CSF tap,
titers for infectious meningoencephalomyelitides.
Diseases of the Vestibular System
Functions
The vestibular system:
• Detects and responds to rotational and linear acceleration (including gravity).
• With visual and proprioceptive input, maintains the
position of the eyes, head, trunk and limbs in reference to the position and movement of the head.
• Allows maintenance of equilibrium and body orientation in space.
Anatomy and physiology
The inner ear: receptors (macula and crista
ampullaris)
Bony labyrinth
Fluid-filled (perilymph- derived from CSF) ossified
structure, contained within the petrose portion of the
temporal bone.
3 communicating portions:
- Large vestibule
- Three semi-circular canals
- Cochlea
Membranous labyrinth
Fluid-filled (endolymph- derived from blood) lumen
surrounded by an epithelial wall with predetermined
sites modified to form a receptor organ.
4 communicating compartments:
• Saccule and utricule located within the bony
vestibule
- Receptor organ: Macula
- Macula: Oval plaque formed by thickened connective
tissue covered by neuroepithelium (hair cell and
supporting cells).
- Otolithic membrane: Gelatinous material covering
the hair cells.
- Statoconia (otoliths): Calcareous crystalline bodies
on the surface of the otolithic membrane.
- The hair cells contain projections of their luminal
cell membrane called stereocilia and kinocilia.
Movements of the otoliths away from the sterocilia/kinocilia is the
initiating factor in stimulating an impulse in the dendritic zone of
the vestibular neurons that are in synaptic relationship with the
base of the hair cells. The macula in the saccule being oriented in
a vertical direction (sagittal plane), while that of the utriculus
being in a horizontal direction (dorsal plane), gravitational forces
continually affect the position of the otoliths in relationship to the
hair cells. These are responsible for the sensation of the static position of the head and linear acceleration and deceleration.
• Three semi-circular ducts
- two vertical (anterior and posterior)
- one horizontal (lateral)
- All at right angle (90 degrees) of each other
- Receptor organ: Crista ampullaris
- Ampulla: Dilation at one end of each semicircular
duct
- Crista: Transverse ridge of connective tissue lined by
neuroepithelium on the internal surface (hair cells
and supporting cells) and on the surface of the
crest covered by the cupula.
- The hair cell: On their luminal surface, they project
into the cupula, 40-80 modified microvilli (stereocilia) and a single modified kinocilium
- Cupula: Gelatinous structure composed of a proteinpolysaccharide
- The dendritic zone of the neurons of the vestibular
portion of the vestibulocochlear nerve is in synaptic
relationship to the hair cells.
• Cochlear duct
Movement of fluid in the semicircular duct causes deflection of
the cupula which bends the stereocilia and is the source of stimulus by way of the hair cell to the dendritic zone of the vestibular neuron.
The 3 semicircular ducts being at right angle with each other and
each semicircular duct containing an ampulla at one end, movement of the head in any plane or angular rotation will stimulate
a crista ampullaris and the vestibular neuron. Each semicircular
duct on one side may be paired to a semicircular duct on the
opposite side by their common position in a parallel plane. The
vestibular neurons are tonically active, and their activity is excited or inhibited by deflection of the cupula in different directions.
While movement in the direction of one of these three planes
stimulates the vestibular neuron of the crista in one duct, they
are inhibited in the opposite duct of the synergic pair. These
receptors are not affected by constant velocity of movement but
respond to acceleration or deceleration, especially when there is
rotation of the head.
The vestibulocochlear nerve
Vestibular neuron: a bipolar neuron
• The dendritic zone is in synaptic relationship with
the hair cells
• The axons course through the internal acoustic
meatus with those of the cochlear division
• The cell bodies are within the vestibular ganglion
along the course of the axons within the petrosal
bone.
• The facial nerve also leaves the petrous temporal
via the internal acoustic meatus.
• After the ganglion, the axons pass to the lateral
surface of the rostral medulla, at the cerebellomedullary angle (level of trapezoid body & attachment of the caudal cerebellar peduncle to the cerebellum)
• They penetrate the medulla between the caudal
cerebellar peduncle and the spinal tract of the
trigeminal nerve.
• They terminate in telodendria in one of two sites:
• Vestibular nuclei
• Cerebellum via caudal cerebellar peduncle to the
• Reticular formation: sends afferents to the vomiting center, which is the pathway underlying motion
sickness.
• Pathway of conscious projection:
- ill-defined
- Projections through the midbrain to the contralateral
medial geniculate nucleus of the thalamus. After a
synapse within the MGN, the neurons project to the
internal capsule to the gyri of the temporal lobe, primarily the rostral suprasylvian gyrus.
Cerebellum:
Caudal cerebellar peduncle: Terminates to the flocculus of the hemisphere and the nodulus of the caudal
vermis (flocculonodular lobe) and the fastigial nucleus.
fastigial nucleus and flocculonodular lobe.
There are numerous projections from the vestibular
nuclei:
Clinical signs
Spinal cord:
Unilateral disease
The vestibulospinal tract: Descends in the ipsilateral
ventral funiculus through the entire spinal cord, terminating in all segments on interneurons in the ventral
grey column.
Facilatory to:
- ipsilateral alpha & gamma motor neurons to extensor
muscles
Inhibitory to:
- ipsilateral alpha motor neurons to flexor muscles
- contralateral alpha & gamma motor neurons to extensor muscles
The medial longitudinal fasciculus (MLF): Descends
in the dorsal portion of the ventral funiculus through
the cervical and cranial thoracic segments.
These spinal cord pathways coordinate the position
and activity of the limbs and trunk with movements
of the head.
Brain Stem:
• MLF & reticular formation: Ascends the brainstem
to the nuclei of cranial nerves III, IV and VI (oculomotor, trochlear and abducens). Provides coordinated conjugate eyeball movements associated with
changes in position of the head.
Assymetric ataxia with preservation of strength.
Abnormal posture and ataxia:
Head tilt towards side of the lesion, wide-based stance,
trunk tipping, falling, rolling towards the side of the
lesion. Trunk incurvation towards the side of the lesion.
Circling towards the side of the lesion- usually tight circles. Hypertonia/hyperreflexia opposite the side of the
lesion.
Nystagmus:
Pathological/abnormal:
•
•
•
•
Jerking: direction= fast phase.
Resting or spontaneous: head in normal position.
Positional: head flexed laterally or fully extended.
Horizontal, rotatory, vertical.
Postrotatory nystagmus:
• The jerk nystagmus is on the opposite side of the
rotation.
• When the patient is rotated in a direction opposite
to the side of a peripheral receptor lesion, postrotatory nystagmus is depressed.
Caloric nystagmus:
• The jerk nystgamus is on the opposite side of the
stimulation.
• If the peripheral receptor is not functional, we will
be unable to stimulate nystagmus with irrigation of
the ear.
• Unreliable test.
Postural reactions:
• Normal except for righting response- exaggerated
toward the side of the lesion.
Vestibular strabismus:
• Ventral to ventrolateral deviation of the ipsilateral
eyeball.
• Occasional dorsal deviation of the contralateral eyeball.
• Not static.
Bilateral disease
• Symmetric ataxia-loss of balance of either side,
with strength preserved.
• Characteristic jerky side to side head movement.
Wide excursions of the head to either side (Stevie
Wonder Syndrome).
• No pathological nystagmus.
• No normal nystagmus.
Neurolocalization
Appropriately localizing a vestibular lesion to the central
or peripheral system is crucial to obtain a definitive
diagnosis and offer an accurate prognosis. As a general
rule, the prognosis for central vestibular diseases is
guarded to poor as opposed to peripheral vestibular diseases. There are exceptions to this rule. A squamous cell
carcinoma causing peripheral vestibular disease has a
terrible prognosis. Metronidazole (Flagyl) intoxication
producing central vestibular signs has a good prognosis
if administration of the drug is stopped promptly. In
most instances, diseases of the central vestibular system
require extensive and expensive diagnostic measures. The
brainstem and cerebellum are hidden and well protected
within the skull. The petrous temporal bone is a very
hard and thick bone causing artifacts when performing a
CT scan, sometimes impeding on our ability to obtain a
diagnosis. MRI is the best diagnostic tool to image the
brain and diagnose central vestibular disorders.
Peripheral vestibular diseases, with the exception of otitis media-interna, rarely require advanced imaging techniques. In a matter of fact, supportive care and monitoring are often the only steps taken to manage peripheral
vestibular disorders (especially for canine and feline
idiopathic vestibular syndromes).
Central:
The lesion is localized to the central pathways mostly by
the presence of signs that accompany the brain stem
involvement of other functional systems. These additional systems are: 1) the ascending reticular activating system (ARAS), 2) the upper motor neuron (UMN) system,
3) the general proprioception (GP) system, 4) additional
cranial nerves or cranial nuclei. The reticular activating
system is part of the reticular formation, which consists
of a network of neurons in the central portion or core of
the brain stem from the medulla, though the pons and
midbrain, into the diencephalons. The ARAS functions to
arouse the cerebral cortex, to awaken the brain to consciousness, to prepare the cortex to receive ascending
impulses from any sensory modality. It is responsible for
maintaining wakefulness and mental awareness. An
altered mental status (mental dullness, obtundation, stupor, or coma) would indicate a lesion affecting the
ARAS.
The UMN system is responsible for initiation of voluntary movement, maintenance of tone for support of the
body against gravity, and the regulation of posture to
provide a stable background upon which to initiate the
voluntary activity. These pathways traverse the brainstem. An UMN lesion will cause spastic paresis, increased
extensor tone and increased reflexes. The GP system
detects the state of position and movement in muscles,
tendons, and joints. These pathways also course through
the brainstem. Proprioceptive ataxia (circumduction,
crossing over, knucling, longer stride, hypermetria) and
postural reaction deficits will be observed with a GP
lesion. The vestibular system is localized within the
cerebellomedullary angle, rostral medulla and cerebellum.
Other cranial nerves and nuclei are located within this
area. The trigeminal nerve in located within the pons.
Trigeminal nerve or nuclei lesions may cause masticatory
muscle atrophy and decreased facial sensation ipsilateral
to the lesion. The facial nerve is closely associated with
the vestibulocochlear nerve within the petrous temporal
bone, internal acoustic meatus, cranial cavity and rostral
medulla. Damage to the facial nerve and nuclei will
cause facial paralysis ipsilateral to the lesion. The abducent nerve and nuclei are also located within the rostral
medulla. An abducent lesion may cause medial strabismus and ocular retraction deficits. Glossopharyngeal
and vagal nerves and nuclei lesions may cause dysphagia and laryngeal paresis. They are located within the
caudal medulla. The hypoglossal nerve and nuclei are
also located within the caudal medulla. Deficits will
reveal themselves by ipsilateral tongue paralysis (atrophy and deviation). The olfactory (olfactory lobes), optic
(forebrain), oculomotor and trochlear (midbrain) nerves,
central pathways and nuceli are located too far away
from the vestibular system for a single lesion to interfere with their functions.
Cerebellar signs such as dysmetria, dysdiadochokinesia,
intention tremors, ocular dysmetria may be observed.
Central nervous system nystagmus may be horizontal,
rotary, vertical or dissociated (present in one eye only).
The direction may be towards or opposite the side of the
lesion. The direction may also change with different
head posture or movement. Vestibular ataxia may not be
present. Rarely downbeat, convergence or see-saw nystagmus may be seen. Ocular bobbing (fast drift downwards, slow drifts upwards) and opsoclonus (rapid, random, conjugate jerks of eyes) may also be seen with
central lesions.
to the normal side. The nystagmus may be horizontal or
rotary, but never vertical. In severe cases, the nystagmus
is resting or spontaneous and gradually settles to a positional nystagmus with recovery. Vestibular ataxia, with
varying degree of severity, usually accompanies the nystagmus.
Peracute to acute
If a patient is severely affected by unilateral peripheral
vestibular disease, he or she may be extremely incapacitated and the examiner may not recognize that the signs
present are strictly attributable to the peripheral
vestibular system. A severe head tilt, head and body
turn, falling, leaning, circling and rolling to the side of
the lesion may be observed. The patient may struggle
and roll, enabling our ability to perform an adequate
postural reaction evaluation. Hospitalization over the
period of most severe disorientation (24-72 hours) may
provide the veterinarian the opportunity to reevaluate
the patient to confirm his or her neurolocalization. For
the first 72 hours, a resting nystagmus occurs in a direction opposite the head tilt (horizontal or rotary). At the
onset, a head or eyelid oscillation may occur simultaneously with the nystagmus. The spontaneous nystagmus
usually abates after 3-5 days and a pathological nystagmus may be elicited on altering the position of the head
(always opposite the head tilt, horizontal or rotary).
Typically with acquired, acute peripheral vestibular disease, a head tilt, vestibular ataxia and pathological nystagmus are present together at onset. The ataxia and
nystagmus may abate with compensation after several
days. A clinical progression differing from this pattern
may indicate a central lesion. For example, a worsening
head tilt without obvious vestibular ataxia or nystagmus.
This represents a softer sign of central disease but warrants further evaluation.
Chronic
Peripheral:
Paradoxical
With peripheral vestibular disease, the clinical signs are
strictly limited to vestibular disturbances, with the
exception of a Horner’s syndrome and/or facial paralysis.
The pathways for sympathetic innervation to the eyes
course through the middle ears in the dog and cat. The
facial nerve is closely associated with the vestibulocochlear nerve within the petrous temporal bone.
As mentioned previously, with unilateral peripheral
vestibular system lesions, the head and body tilt are
always toward the side of the lesion. With rare exceptions, the same occurs with lesions of the central components of the vestibular system. These exceptions are,
therefore, referred to as paradoxical signs.
The nystagmus is always a jerk nystagmus with the slow
phase toward the side of the lesion and the fast phase
Experimental ablation of the caudal cerebellar peduncle
on one side will produce a head tilt to the opposite side
and a pathological nystagmus toward the lesion.
With chronic peripheral vestibular disease, the clinical
signs are compensated by functional vestibular components of the brain stem and cerebellum. A head tilt is
usually the most salient sign. Vestibular ataxia is often
mild or absent. If the animal is suddenly stressed, a mild
degree of disturbance of balance may be apparent.
There is usually no pathological nystagmus.
Similarly, ablation of one flocculus and the nodulus will
cause a paradoxical syndrome with the head and body
tilted away from the side of the floccular lesion.
Diagnostic plan
With natural lesions, there is usually interference with
the GP system afferent to the cerebellum, causing a mild
GP ataxia (hypermetria) and postural deficit, always on
the same side as the lesion. This observation is the most
reliable to localize the side of the lesion.
Brain Auditory Evoked Response test (BAER)
Differential diagnosis
Central:
Degenerative
- Thiamine deficiency
Anomaly
- Arachnoid cyst, other.
Metabolic
Neoplastic
- Primary (meningioma, nerve sheath tumor, lymphoma,
glioma, choroids plexus) vs secondary
Inflammatory
- Meningoencephalitis
- Infectious: viral, protozoal, bacterial, fungal, parasitic, rickettsial.
- Immune-mediated or non-infectious: GME, ...
Infarction
Trauma
Toxic
- Metronidazole intoxication
- Lead
- Hexachlorophene
Peripheral:
Degenerative
Anomaly
- Congenital peripheral vestibular disorders
Metabolic
- Hypothyroidism
Neoplastic
- Nerve (nerve sheath tumor, lymphoma, other)
- Temporal bone (osteosarcoma, squamous cell carcinoma, other)
Inflammatory
- Otitis interna/labyrinthitis
- Neuritis infectious or not
Idiopathic
- Feline idiopathic vestibular disease
- Canine geriatric vestibular disease
Trauma
Toxic
- Aminoglycoside antibiotics
- Blue tail lizzard
Central
Brain stem responses to far field auditory stimuli can be
recorded percutaneously from the brains of dogs and
cats. The various wave forms have been related to specific components of the peripheral and central portions
of the auditory system. A lesion at one level blocks the
responses at that level and succeeding levels. It is a
simple and non-invasive test that may help to differentiate peripheral from central disease in cases where the
neurological exam is inconclusive. It is important to
note that BAER’s may be normal if the brainstem lesion
is discrete and of insufficient severity to disrupt the
extensive networks of the auditory pathway.
Imaging: Magnetic Resonance Imaging (MRI) vs
Computed Tomography(CT) scan
Advanced imaging is often necessary to determine the
nature of a central vestibular lesion. MRI is preferable to
CT scan to evaluate central vestibular disease. MRI
allows the acquisition of images in several planes: axial,
dorsal and longitudinal. It offers better anatomical
details and it is more sensitive to brain tissue changes.
There is also no bone artifact which may be problematic
with CT scan due to the presence of the petrous temporal bones.
Cerebrospinal fluid analysis
CSF analysis is useful to determine the etiology of confirmed central vestibular structural lesions. It may reveal
neoplastic cells (rare), microorganisms, inclusion bodies
or determine the nature of an inflammatory process. For
example, it may confirm the diagnosis of eosinophilic
meningoencephalitis. It may suggest a parasitic, protozoal or viral cause or support an immune-mediated
process. In most instances, CSF analysis has little value
(unless neoplastic or microorganisms or inclusion bodies
are detected) as a diagnostic tool by itself due to the
low specificity. In conjunction with advanced imaging
techniques, it is a very valuable test.
CSF culture and sensitivity may also be performed in
cases of suspected intracranial sepsis. Aerobic and
anaerobic cultures and sensitivities should be performed
in cases intracranial invasion of otitis media-interna.
Serum and CSF infectious meningoencephalitides’ titers
Thyroid panel
Meningoencephalitis may be caused by infectious agents
such as viral (Distemper, FIP, FeLV,...), protozoal
(Toxoplasma, Neospora,...), fungal (mainly Cryptococcus,
in this area of the country), rickettsial (Rickettsia rickettsi, ehrlichia canis,...), parasitic migrations
(Heartworm,...). It may also be caused by immune-mediated process (GME, small dog encephalitis, eosinophilic
menigoencephalomyelitis, other). Titers for infectious
meningoencephalitides may be performed on serum and
CSF. This is helpful to confirm or rule-out a diagnosis of
infectious meningoencephalitides.
Hypothyroidism has been associated with signs of
peripheral vestibular disease and/or facial paralysis. A
panel is recommended to rule out thyroid sick syndrome.
Peripheral
Otoscopic exam
Inflammation of the middle ear is present in more than
50% of dogs with chronic otitis externa. Spread of infection from the middle ear to the inner ear may occur and
cause peripheral vestibular signs. Although otitis mediainterna is most commonly associated with otitis externa,
it is not dependent on it. The nasopharynx is also a
source of infection by way of the auditory tube. A thorough examination of the external acoustic meatus and
tympanum should be performed. Damaged tympanum and
exudates in the middle ear may be detected.
Otitis media-interna may be confirmed by further imaging. Bulla series, CT Scan and MRI may be performed.
Rarely, spread of infection from the middle-inner ear to
the brain may occur by erosion through the medial
aspect of the petrous temporal bone, by migration of
bacteria along existing vascular and neuronal pathways,
or via hematogeneous spread, and can result in meningitis, encephalitis or abscess formation. Clinical signs of
intracranial invasion may be absent or subtle. MRI is
useful to determine the presence of extradural and subdural abscesses and large parenchymal abscesses requiring surgical drainage.
Samples for culture and sensitivity may be collected via
a myringotomy. In cases of intracranial sepsis, CSF aerobic and anaerobic culture and sensitivity should be performed.
Advanced imaging
CT and MRI may be helpful to better define or diagnose
certain peripheral vestibular disorders. Head injuries may
fracture the petrosal bone and cause vestibular signs and
facial paralysis. CT is very useful to diagnose skull fracture and recent hemorrhage. Various neoplasms may
involve the temporal bone and produce peripheral
vestibular system disturbance, often with facial paralysis. Fibrosarcoma, osteosarcoma, chondrosarcoma and
squamous cell carcinoma have been reported. These are
usually evident on radiographs but adequate surgical
treatment or radiotherapy will require advanced imaging
with a CT scan. A nerve sheath tumor of the vestibulocochlear nerve or lymphoma invading the nerve may be
better diagnosed by MRI.
Clinical Cases
Peanut:
Diagnosis: Granulomatous meningoencephalomyeltis (GME)
Signalment: 2 year old, male neutered, Miniature
Pinscher.
Presenting complaint: Circling to the left, severe right
head tilt, difficulty walking.
Neurological exam: Dull. Severe right head tilt with
head and body incurved to the left. Unwilling to walk.
Tendency to circle to the left. Assymetric R>>>L proprioceptive ataxia and UMN tetraparesis. Absent menace OS.
Dilated pupil OS. Poor PLRs OS. Absent menace OD.
Absent palpebral reflex OD. Rare pathological rotary nystagmus with fast phase to the right.
Neuroanatomic diagnosis: Multifocal including obvious
right central vestibular signs.
Differential diagnosis: Non-infectious meningoencephalomyelitides such as GME, infectious meningoencephalitides such as protozoal, rickettsial, fungal, viral
and larval migration, neoplasia such as lymphoma or
metastatic disease, vascular.
Diagnostic plan: CBC, Chemistry panel: NSF. MRI of the
brain: multifocal, hyperintense on T2WI and Flair,
hypointense on T1WI and non-contrast enhancing
lesions within the brain, mainly affecting the white matter and the right cerebellomedullary junction. CSF analysis: mononuclear pleocytosis .Titers for toxoplasmosis
and neosporosis: negative. Tick serology: negative.
Granulomatous meningoencephalitis is a non-infectious
inflammatory disease of the CNS. Three forms have been
described: focal, disseminated and ocular (optic neuritis).
GME is seen in dogs of all ages, sex and breeds. It usually
affects middle aged dogs (2-6 years of age). Poodles and
terriers may be predisposed. It appears to be more common in females. The underlying cause remains unknown
but it is likely an immune-mediated disease. The onset of
clinical signs is usually abrupt. It is a progressive disorder
(slowly to fulgurant). Clinical signs are variable depending
on the location of the lesion or lesions. Deficits referable
to the caudal brainstem and cervical spinal cord are most
common and include facial paralysis, vestibular signs and
cervical pain. The lesions predominate in the white matter, particularly of the cerebellomedullary region.
Histopathologically, the hallmark of GME is a unique pattern of inflammatory cell (mainly lymphocytes, plasma
cells and large mononuclear cells) accumulation and/or
proliferation around blood vessels- called vascular cuffs.
The diagnosis is obtained by advanced imaging (preferably MRI) and CSF analysis. Infectious encephalitides
should be ruled out by performing serum and/or CSF
titers. The differential diagnosis includes: other non-infectious encephalitides such as small dog encephalitis
(Maltese, Yorkie and Pug encephalitides), CNS lymphoma
and infectious meningoencephalomyelitides.
Treatment: Slow tapering course of steroids: prednisone
1-2 mg/kg po bid for 2-4 weeks, then 1-2 mg/kg po sid
for 2-4 weeks, then 1-2 mg/kg po eod for 2-4 weeks.
Cytosine arabinoside: 50 mg/m2 S.Q bid for 2 days,
every 3 weeks. A CBC is initially performed 10-14 days
following the first course of treatment. A CBC may be
repeated every 2-3 months afterwards if no evidence of
bone marrow suppression is documented.
Bangles:
Signalment: 7 years old, spayed female, Golden Retriever.
Presenting complaint: Worsening left head tilt over the
last 3 weeks.
Neurological exam: Quiet and alert. Severe left head tilt
(>45 degrees). Wide-based stance. No obvious leaning,
falling, circling or rolling. No other cranial nerve
involvement. Subtle upper motor neuron left hemiparesis
and proprioceptive ataxia. Mild postural reaction deficits
on the left side.
Neuroanatomic diagnosis: Left central vestibular disease.
Differential diagnosis: Neoplasia, granuloma infectious
or not, abscess, encephalitis infectious or not.
Diagnostic plan: CBC, chemistry panel: NSF. Chest radiographs 3 views: NSF. MRI of the brain: large, extraaxial,
hyperintense on T2WI, isointense on T1WI, strongly and
homogeneously contrast enhancing mass, ventrolaterally
located on the left side of the floor of the cranial vault,
causing compression of the brain stem and cerebellum.
The mass forms a plaque on the below and on the left
side of the brainstem. A dural tail sign is present. CSF:
neutrophilic pleocytosis.
Diagnosis: Most likely meningioma.
Meningiomas are the most common primary brain tumor
in dogs. These tumors are believed to be derived from the
arachnoid cap cells and arachnoid granulations, particularly where arachnoid cells project into the dural venous
sinuses. Hence meningiomas are regularly attached to the
dura. Canine meningiomas are more common in the brain
than the spinal cord. Within the cranium they occur over
the convexities, in the midline attached to the falx cerebri, below the brainstem, attached to the tentorium cerebelli, or at an intraventricular location associated with a
choroid plexus. Their attachment to the dura or leptomeninges may be broad(sessile), narrow(pedunculated),
or total (en plaque). Where they impinge on the brain,
the most salient effect is compression rather than infiltration. Invasion along Virchow-Robin spaces is common.
Clinical signs they incite depend on their location, speed
of growth, and secondary effects. Many are associated
with a progressive course. Meningiomas tend to invade the
brain in dogs. Areas of focal necrosis and pools of neutrophils are present in many cases. Metastasis of intracranial meningioma to the lungs is rare but has been reported in at least three dogs.
Treatment: The treatment options are: 1) control of secondary effects with corticosteroids; 2) palliation with
chemotherapy- hydroxyurea is recommended at 50 mg/kg
3 times weekly (Monday, Wednesday, Friday); 3) radiatiotherapy- usually 15 treatments- 5 treatments/week, at 34 Grays/fraction. The use of a linear accelerator, CT planning and 3 dimensional treatment planning systems are
ideal to maximize the dose to the tumor site while minimizing the dose to surrounding normal tissue, especially
when vital structures such as the brain are involved; 4)
Surgery is helpful to reduce tumor size to microscopic
disease, decompress the brain and reduce intracranial
pressure. Surgery will also allow obtaining a biopsy sample for definitive diagnosis. Stereotactic biopsies (where
available) may be performed to obtain a sample for
histopathology without extensive surgery. Surgery is
indicated when the mass is accessible, when reduction
to microscopic disease is feasible and when rapid
decompression or control of increased intracranial pressure is required. Bangles’ mass is extensive and located
in proximity to vital structures. Accessibility and complete removal of macroscopic disease, with minimal morbidity are unlikely to be achieved with current techniques. The use of an ultrasonic aspirator (where available) is strongly recommended for removal of such neoplasm.
Hershey:
ears +/- inner ears. Due to the chronic nature of the disease and the need to manage the disease surgically, further imaging was recommended. An MRI was performed.
The MRI revealed inflamed and thickened external ear
canals, a fluid filled and inflamed right bulla, an
inflamed nasopharynx and meningitis. CSF
analysis:Neutrophilic pleocytosis. CSF aerobic/anaerobic
culture and sensitivity: no growth.
Signalment: 8 years old, spayed female, Labrador
Retriever.
Presenting complaint: Falling/leaning, eyes rolling.
History: Life-long history of otitis externa and pruritis,
treated with various topical ointments and solutions and
systemic antibiotics. Hershey was presumptively diagnosed with allergy (atopy vs food); she is presently on
fish and potato diet. Recently diagnosed with hypothyroidsm; treated with soloxine. Peracute onset of vestibular signs today.
Neurological exam: Right head tilt, broad based stance,
leaning, falling to the right, resting rotary nystagmus
with fast phase to the left, vestibular strabismus in the
right eye.
Neuroanatomic diagnosis: Right peripheral vestibular.
Differential diagnosis: otitis media-interna, geriatric
idiopathic vestibular syndrome, hypothyroidism, neoplasia.
Diagnostic plan: Otoscopic exam: Dark brown discharge
filling both external ear canals, impairing visualization
of the tympanum. Narrowed and inflamed ear canals.
Cytology of aural discharge: AS: 3+ yeast; AD: numerous
cocci and neutrophils, 1+ yeast. Referral thyroid panel:
hypothyroidism. Referral CBC and chemistry panel: NSF.
Ear flushes and otoscopic exam under anesthesia to evaluate the tympanum and possibly collect samples for culture and sensitivity vs imaging to evaluate the middle
Diagnosis: Otitis media-interna with intracranial sepsis.
Treatment: TECA and bulla osteotomy on the right side.
Culture and sensitivity of the bulla. Systemic antibiotherapy- broad spectrum bactericidal antibiotic with
good penetration of the blood-brain barrier, pending culture and sensitivity results. Supportive care with fluids
and meclizine to treat nausea from vertigo. Continue
treatment for hypothyroidism. Continue treatment of otitis externa for the left ear. Allergy work-up.
GSVSOur Specialists
By sharing each specialist’s particular expertise and using the most modern, state-of-the-art
therapeutic and diagnostic tools, our team at GSVS is committed to offering the highest
quality, progressive and personalized veterinary care for our patients and clients.
Thomas D. Scavelli, DVM
Diplomate American College of Veterinary Surgeons
Roxane Lea Collins, DVM, MS
Diplomate American College of Veterinary Surgeons
Lisa Corti, DVM
Diplomate American College of Veterinary Surgeons
Gerald Steven Post, DVM
Diplomate American College of Veterinary Internal Medicine (Oncology)
David L. Denman, PhD
Petra Anna Lackner, DVM
Diplomate American College of Veterinary Ophthalmologists
JoAnn DeMarco, DVM
Diplomate American College of Veterinary Internal Medicine
Shannon Flood, DVM
Diplomate American College of Veterinary Internal Medicine
Katharine Palmer, DVM
Diplomate American College of Veterinary Internal Medicine
Diplomate American College of Veterinary Emergency Critical Care
Noemie M. Bernier, DVM
Diplomate American College of Veterinary Internal Medicine (Neurology)
Richard Joseph, DVM
Diplomate American College of Veterinary Internal Medicine (Neurology)
Kathleen Kalaher, DVM
Diplomate American College of Veterinary Dermatology
Marc S. Kraus, DVM
Diplomate American College of Veterinary Internal Medicine (Cardiology)
OUR FACILITY
arden State Veterinary Specialists was founded in 1994 by Dr. Thomas D.
G
Scavelli. GSVS is a multi-disciplinary REFERRAL ONLY HOSPITAL located in Tinton
Falls, New Jersey. Our goal is to provide progressive state-of-the-art veterinary care in the
fields of surgery, internal medicine, cardiology, neurology/neurosurgery, ophthalmology,
dermatology, oncology, nuclear medicine and critical care. Our 24 hour referral hospital and
emergency/critical care unit consist of a team of experienced, dedicated
specialists utilizing state-of-the-art diagnostic technologies and
cutting edge medical procedures in a caring, nurturing,
comprehensive environment. We are committed to making the
referral experience one of personal service.