The Biopsy
Clinical Oncology Service,
Veterinary Hospital of the University of PA
A biopsy is the surgical removal of a piece of
tissue from your animal, and is recommended by your
veterinarian in order to establish a tissue
diagnosis. The diagnosis is determined by the
examination of this tissue under a microscope by a
pathologist. Microscopic evaluation of the tissue(s)
allows the pathologist to determine whether the
tissue is inflammatory, infectious, or cancerous. If
the tissue is cancerous, the biopsy provides
important information regarding the type and nature
of the cancer. In some cases, a biopsy specimen can
be useful to evaluate whether a tumor has been
completely removed ("clean" margins) or whether some
tumor cells have been left behind ("dirty" margins).
The biopsy specimen may be a representative piece
of an abnormal tissue (incisional biopsy) or may be
a large piece of tissue including the entire
diseased area (excisional biopsy). It is the
judgment of the clinician whether the biopsy
specimen should be excisional or incisional.
Once the tissue is removed it is immersed in a
10% formalin solution for fixation. Fixation is a
method of preserving the material and prevents
decomposition. Once the tissue is received by a
pathology laboratory, representative samples are
processed, the microscopic slides prepared, and the
slides evaluated by the pathologist. The pathologist
will then provide a final report to the referring
clinician.
In most cases a report will be available in three
working days. However, in some instances this may
take longer. These include:
Bone biopsies which need to be softened
prior to processing.
Special staining techniques that may be
required to identify cells, cell products,
bacteria, fungi, etc.
Difficult or unusual cases for which the
pathologist will seek a consultation with other
pathologists.
Canine Cancer: Surgery Options and Limb Sparing
The following articles give a great overview of the many options involved in
canine cancer surgeries.
Surgery and
Cancer Treatment
Clinical Oncology
Service, Veterinary Hospital of the University of PA
There are
many ways to treat cancer including surgery, radiation
therapy, chemotherapy, and immunotherapy. Among these,
surgery is the oldest and most commonly used form of
therapy. Specifically, surgery means the cutting away of
tissues. Your veterinarian may recommend surgery for several
reasons. These include complete removal of a tumor, partial
removal of a tumor, or exploration of a particular area to
obtain a sample of tumor tissue and evaluate the extent of
normal tissue involvement. In all cases, any tissue removed
by surgery is submitted for biopsy (i.e., given to a
pathologist to obtain a specific diagnosis).
Complete cancer removal
Surgery is the standard, and often the only, form of
treatment for most benign and some malignant cancers. In
these instances the goal of surgery is to remove all of the
tumor cells present in a given location, thereby curing the
patient or at the least relieving symptoms for an extended
period of time. The expected success rate depends on many
factors, including size and location of the tumor, specific
tumor type, and type and extent of the surgical procedure.
Partial removal of the cancer: debulking
Some cancers are too large or are in locations where
they cannot be removed completely by surgery alone. In these
cases surgery is used to remove as much of the cancer as
possible, while minimizing damage to surrounding normal
tissues and vital structures. Because cancer cells have been
left behind, some additional form of cancer treatment is
used following debulking surgery, such as radiation or
chemotherapy.
Exploratory surgery
When cancers are located within the body cavities (i.e.,
the chest and abdomen), it may be impossible to determine
prior to surgery whether complete tumor removal can be
accomplished. In these cases, surgery is used to explore, or
get a better look at, the tumor and make a decision
intraoperatively as to the best surgical approach. This may
be a complete removal, debulking, or simply a small biopsy
for diagnostic purposes. Before exploratory surgery is
considered, the pet owner, oncologist, and surgeon should
discuss the various treatment options available depending on
what is found during surgery.
Anesthesia
The majority of pets having surgery undergo general
anesthesia. VHUP uses the most modern and safe anesthetic
drugs available, and patients are continuously monitored
with state of the art technology. Anesthetic protocols are
individually tailored to each pet's medical status, which
takes into account such factors as age, liver, kidney, and
heart function, and any underlying medical problems. Most
pets are at minimal risk for problems associated with
general anesthesia.
Recovery from surgery
All pets experience mild pain and discomfort after surgery.
Pain medication is available and is used routinely. Most
surgical wounds require little or no care beyond observation
and simple hygiene. Each specific surgery and tumor type has
it's own set of potential complications. Not all of these
potential complications are predictable; however, unforseen
complications are rare. If risk factors are present,
supportive measures before, during, and after surgery are
employed. Prior to surgery, your veterinarian will discuss
with you any recognized risk factors and known potential
complications relevant to your pet. For those pets that will
require nutritional support after surgery, a variety of
feeding tubes may be placed at the time of surgery.
Follow-up care
Depending on many factors, such as cancer type, completeness
of surgical removal, and the likelihood of cancer spread,
additional treatments may be recommended for your pet, and
you will be referred to the appropriate cancer specialists
to discuss these options. If surgery is the only treatment
indicated at this time, your doctor will recommend an
appropriate reexamination schedule and follow-up testing to
monitor your pet for recurrence of cancer. The type of tests
and frequency of reexamination vary with each case, and will
be discussed on an individual basis.
Limb Sparing in Dogs
Clinical Oncology Service, Veterinary Hospital of the University of Pennsylvania
"Limb sparing" (also known as "limb salvage") is a surgical procedure that
provides an alternative to amputation in selected dogs being treated for
bone tumors. Most dogs function very well with an amputation—dogs are
not burdened by the psychological aspects of missing a limb in the same way,
as are humans. However, there are some dogs that have concurrent orthopedic
problems, such as severe arthritis, that might not do as well on three legs.
The idea of preserving a limb in dogs is not new, but it is only recently
that advances in medical technology have made this procedure possible. The
goal in limb sparing is to remove the diseased bone and surrounding tissues
while still preserving the function of the remaining limb. The piece of
diseased bone that is removed is replaced by a combination of healthy bone
from a donor and bone graft from other parts of the patient's body. While
much of the leg's function is preserved, there is decreased range of motion
in the treated limb, which results in limited activity for the dog.
There are several restrictions, as to which tumors and what size and
location can be treated with limb sparing, so a thorough evaluation of each
patient is required. This evaluation consists of complete blood cell count,
blood chemistries, and urinalysis; radiographs (X-rays) of the primary tumor
site and the lungs; tumor
biopsy; and often other tests such as CT, MRI or bone scan to thoroughly
evaluate the extent of the tumor.
Limb sparing is performed in
conjunction with
chemotherapy (and in some instances,
radiation therapy as well). The biopsy results help determine which type
of additional therapy is required. Chemotherapy helps control the growth of
any tumor cells that have spread beyond the primary tumor site to areas
elsewhere in the body such as the lungs and other bones.
Surgery and
chemotherapy are well tolerated by most dogs. The surgery requires a five to
seven day hospitalization. After the surgery your dog may be in a padded
bandage or splint which will need to be checked periodically. Chemotherapy
is done on an outpatient basis, but does require multiple visits to the
hospital for treatment and monitoring. Periodic radiographs of the limb are
taken to evaluate the rate of healing at the surgery site. Chest radiographs
are taken to monitor for spread of the tumor.
At this time, the only
good results are in dogs with tumors of the distal radius (the "wrist"
joint). More than three-quarters of these patients return to near normal
function. Dogs with tumors of the proximal humerus ("shoulder" joint) only
did well about 10% of the time. Dogs with tumors in the tibia did not do
well if arthrodesis ("joint fusion") of either the tarsus ("ankle") or the
stifle ("knee") joints was required. Generally, at this time, limb sparing
is recommended only for tumors of the distal radius.
While limb
sparing can prolong a good
quality of life for a dog with bone cancer, it is important to realize
that a complete cure is unlikely. It is our expectation that dogs with
osteosarcoma treated by limb sparing and chemotherapy may be free of tumor
for about one year. Dogs receiving only
palliative therapy to control symptoms such as pain (which can include
pain medication, radiation therapy, or amputation alone) have an average
survival of about four to five months. It is important that you understand
all your treatment options -- the risks, benefits, common complications,
costs, and time commitments. Please discuss any questions and concerns with
your veterinarian.
Limb Sparing and Osteosarcoma—SOTAL
Stephen J. Withrow, DVM, Professor of Surgery and Chief of
Clinical Oncology Service
WSAVA World Congress, Vancouver 2001
Dr. Withrow is Professor of Surgery
and Chief of the Clinical Oncology Service at the
Colorado State University College of Veterinary
Medicine and Biomedical Sciences. He is a Diplomate
of the American College of Veterinary Surgeons and
the American College of Veterinary Internal Medicine
(oncology). Dr. Withrow graduated from the
University of Minnesota in 1972 and completed an
internship and surgical residency at the Animal
Medical Center in New York City.
Dr. Withrow has been at Colorado
State University in Fort Collins, Colorado since
1978. He has received numerous teaching, service,
and research awards, and is the author of over 200
scientific articles and one textbook. His research
interests include multimodality treatment of cancer
in animals as a model for humans with cancer.
Dr. Withrow is the only veterinarian
admitted as a member of the Musculoskeletal Tumor
Society. He is also the past president of the
Veterinary Cancer Society and is a member of
numerous professional organizations.
Canine osteosarcoma (OSA) is
a common malignancy of dogs with over 10,000 new
dogs affected each year. It is by far the most
common primary bone cancer. It generally occurs in
large breed (> 20 kg), middle-aged dogs with a
slight predilection for males over females.
Seventy-five percent affect the limbs with 60% in
the front leg and 40% in the back leg. Metaphyseal
sites are most common with only rare involvement of
the bones of the elbow. Histologic varieties occur
(osteoblastic, chondroblastic, fibroblastic, and
telangiectatic) but no proof exists that these
variants have a different biologic behavior or
response to therapy. Radiographic features are
generally of a mixed pattern (lytic and blastic
change). Many tumors can be “diagnosed” on
signalment, history, and radiographs but a needle
core biopsy (Jamshidi) is generally recommended. If
limb sparing is contemplated, the biopsy technique
and position should be carefully planned.
The pretreatment evaluation
should generally include a CBC, urinalysis,
biochemical profile (paying particular emphasis to
the serum alkaline phosphatase, which has negative
prognostic implications), thoracic radiographs, and
bone survey or nuclear bone scan. As many as 10-15%
of patients will have multiple lesions demonstrable
at presentation and these patients carry a very poor
prognosis. Metastasis is generally hematogenous to
lung or other bones while lymph node metastasis is
rare. Once a diagnosis is confirmed, numerous
options exist for therapy. Two major areas of
concern must be addressed: leg and life.
Leg
Without treatment, most dogs
will be euthanized within one to two months for
intractable pain. Minimal local treatment would
include nonsteroidal anti-inflammatories and/or
palliative radiation. Amputation is an easy,
inexpensive, and effective method of permanent local
disease control. Virtually any size dog can undergo
an amputation with good quality of life
postoperatively.
Limb sparing is designed to
produce a pain-free and functional extremity without
jeopardizing survival. In a series of almost 400
limb sparings performed at CSU, the following
conclusions can be drawn:
-
Front
leg sites (radius, ulna, and occasionally diaphyseal
sites in any bone) are better salvage candidates
than most metaphyseal sites.
-
Preoperative
treatment that produces significant local tumor
death will facilitate the surgical resection and
decrease local recurrences. The “best” preoperative
treatment appears to be cisplatin to act as a
radiation sensitizer and a moderate dose of
radiation (30 Gy in 10 fractions). The optimal
dose, route of delivery, and timing of cisplatin
relative to the radiation is still unclear. This
adds significantly to the cost of treatment and is
not in common usage.
-
The
tumor is excised and replaced with a cortical
allograft. Plate fixation usually results in fusion
of the radiocarpal or adjacent joint. Occasionally,
osteoarticular or composite (bone and prosthesis)
grafts are utilized. Partial ulnectomy does not
require an allograft or internal fixation.
-
Complications
include infection (~30%), local recurrence (10–20%),
and mechanical instability (< 5%). Most of these
complications can be controlled or corrected (except
local recurrence) with re-operation or antibiotics
(oral and/or local antibiotic beads). The “overall”
success rate with limb sparing is approximately 80%
for a pain free and functional leg.
-
Graft
instability and infection have been decreased by the
use of antibiotic impregnated cement in the marrow
space of the allograft.
-
A
new biodegradable form of local chemotherapy using a
polymer sponge and cisplatin has allowed immediate
limb salvage and a less than 20% local recurrence
rate.
-
Limb
salvage is difficult, costly, and not as predictable
as amputation but offers an alternative to
amputation for selected patients.
-
A
palliative form of limb salvage is course fractions
of radiation (800 rads) given two or three times to
the local or metastatic site. Pain relief is often
good but long-term control (> 6 months) is rare.
Feldene (nonsteroidal anti-inflammatory agent) may
allow transient pain relief.
-
Newer
techniques under investigation include intraoperative irradiation of the exposed bone (70
Gy) and reimplantation as well as full course
fractionated radiation with cisplatin
chemosensitization.
Life
With local disease control
alone (amputation or limb sparing), the
one-year survival is less than 10% and most patients
die of pulmonary metastasis. The most intensely
studied chemotherapies for OSA are doxorubicin,
cisplatin, and carboplatin. Most chemotherapy
regimens (doxorubicin alone or doxorubicin and one
of the platinum drugs) result in an approximate 50%
one-year survival, 30% two-year survival, and 15%
long-term systemic control rate. The optimal
adjuvant chemotherapy protocol is unclear at this
time.
Metastasis, especially to
lung, is not hopeless; pulmonary metastasectomy in
carefully selected patients can result in long-term
remission or cure.
These treatments are expensive
and for a M2 dog (~ 30 kg), the cost of
each drug treatment with cisplatin is approximately
$400, carboplatin is approximately $1,000, and
doxorubicin is approximately $200. Limb salvage
alone is approximately $4,000–$5,000 U.S.
Canine OSA offers a readily
available and biologically predictable model for
study to benefit both dogs and man. Studies on
normal dogs as well as dogs with osteosarcoma have
led to many innovations and advances in the use of
allografts and the treatment of malignant bone
tumors in humans.
Selected References
1. Straw RC, Withrow SJ,
Richter SL, et al. Amputation and cisplatin for
treatment of canine osteosarcoma. J Vet Int Med 5
(No 4), 1991.
2. Carberry CA, Harvey HJ.
Owner satisfaction with limb amputation in dogs and
cats. J Am Anim Hosp Assoc 1987;23:227-232.
3. Mauldin GN, Matus RE,
Withrow SJ, Patnaik AK. Canine osteosarcoma:
Treatment by amputation versus amputation and
adjuvant chemotherapy using doxorubicin and
cisplatin. J Vet Int Med 1988;2:177-180.
4. Powers BE, LaRue SM,
Withrow SJ, et al. Jamshidi needle biopsy for
diagnosis of bone lesions in small animals. J Am Vet
Med Assoc 1988;193:205-210.
5. Withrow SJ, Powers BE,
Straw RC, et al. Comparative aspects of osteosarcoma.
Clin Orthop Rel Res 1991;270:159-168.
6. Straw RC, Powers BE,
Withrow SJ, et al. The effect of intramedullary
polymethylmethacrylate on healing of intercalary
cortical allografts in a canine model. J Orthop Res
1992;10:434-439.
7. Withrow SJ, Thrall DE,
Straw RC, et al. Intra-arterial cisplatin with or
without radiation in limb sparing for canine
osteosarcoma. Cancer 1993;71:2484-2490.
8. O'Brien MG, Straw RC,
Withrow SJ, et al. Resection of pulmonary metastases
in canine osteosarcoma: 36 cases (1983-1992). Vet
Surg 1993;22:105-109.
9. Straw RC, Withrow SJ,
Douple EB, et al. Effects of Cis-diamminedichloroplatinum
II released from D,L-polylactic acid implanted
adjacent to cortical allografts in dog. J Orthop Res
1994;12:871-877.
10. Bergman PJ, MacEwen EG,
Kurzman ID, et al. Amputation and carboplatin for
treatment of dogs with osteosarcoma: 48 cases (1991
to 1993). J Vet Int Med 1996;10:76-81.
11. Withrow SJ, Straw RC,
Brekke JH, et al. Slow release adjuvant cisplatin
for treatment of metastatic canine osteosarcoma. Eur
J Exp Musculoskel Res 1995;4:105-110.
12. Straw RC, Withrow SJ.
Limb-sparing surgery versus amputation for dogs with
bone tumors. Vet Clin North Am: Small Anim Pract
1996;26:135-143.
13. Withrow SJ. Surgery for
skeletal sarcomas. Clin Tech Small Anim Pract
1998;13:53-58.
14. Ehrhart N, Dernell WS,
Hoffmann WE, et al. Prognostic importance of
alkaline phosphatase activity in serum from dogs
with appendicular osteosarcoma: 75 cases
(1990-1996). J Am Vet Med Assoc 1998;213:1002-1006.
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