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.


FAIR USE NOTICE

This article contains copyrighted material, the use of which has not always been specifically authorized by the copyright owner. I am making such material available in my efforts to provide background knowledge on areas related to canine cancer. I believe this constitutes a 'fair use' of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material in this article is distributed without profit for educational purposes.



 

 

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