small animal oncology
DESCRIPTION
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Prince Nanda
Nikunj Gupta
Cancer is the major cause of death in pets greater than 10 years old
45% of all dogs older than 10 years of age die of cancer
23% of all dogs die of cancer
Neoplasms: defined as growth of new cells that proliferates without control, serves no useful function and has an orderly arrangement.
Tumour: neoplastic masses that causes swelling on the body surface.
Cancer: it is specifically referred to the malignant tumours
Oncology: defined as field of medicine which deals with cancerous tumors, monitoring its development, diagnosis and the course of the treatment and follow-up
James EWING & BJ Kennedy-Father of Oncology
TERMINOLOGY
Characteristic Benign Malignant
Shape Round, wart like or pedunculated
Irregular
Metastasis Not present Present
Mitotic figures Less More
Blood supply Less Marked
Mesenchymal tumours: tumours derived from connective tissue (cartilage, bone, muscle, fibrous tissue)
Benign : Name of the tissue (suffix oma) e.g. fibroma
Malignant: name of the tissue (suffix -sarcoma) e.g. fibrosarcoma
Epithelial tumours: tumours derived from embryonic cell layers viz. mesoderm, endoderm and ectoderm
Benign:
Malignant: name of the tissue (suffix -carcinoma)
Papilloma –Epithelial surfacePolyp -Mucosal surfaceAdenoma – Glandular surface
Undifferentiated tumours: these tumours give no clue about their cell of origin
Mixed tumours: contains multiple cell types derived from single or multiple germ layers. E.g.
• Teratomas – contain more than one germ layer
• Mixed mammary tumour – contains epithelial elements + mesenchymal elements (Fat, bone, cartilage)
Anaplasia of cells (poor cellular and nuclear disintegration)
Cells are hyperchromatic because of increased DNA content
Increased nuclear : Cytoplasmic ratio (Becomes 1:1 instead of 1:4 / 1:6)
Numerous mitotic figures (are the chromosomal aggregations in the mitotic cells)
Basophillic cytoplasm: because of large number of ribosomes
Cancers result because of transformations of normal proto oncogenes to its mutant form – ONCOGENES
Target of genetic damage
Growth promoting proto-oncogenes
Growth inhibiting cancer suppressor genes
Genes that regulate apoptosis
GENETIC DAMAGE MUST BE NON-LETHAL
Self sufficiency in growth signals – coz of production of oncoproteins which don’t depend on external signals
Evasion of apoptosis
Limitless replicative potential coz of increase production of enzyme Telomerase – this enzyme restores the length of DNA and makes the cell immortal and continuously dividing.
Sustained angiogenesis
Ability to invade and metastize.
Localised tumour
HaematogenouslymphaticsTrans coelomic
Invasion of extra cellular Matrix
Detached tumour penetrate basement membrane
Integrins helps to bind to ECM Invasion is assisted by secretion of ProteasesFurther Migration also occurs
in same manner
CELL MEDIATED RESPONSE
Three type of cells are involved
NK cells: first line of defense against tumour cells
Cytotoxic T-lymphocytes (CD8 + T-cells) by recognising MHC class-I antigens expressed on tumour cells
Activated macrophages
HUMORAL RESPONSE By ADCC (antibody dependent cellular toxicity) - by NK-
CELLS
By activation of complement.
1.)By altered MHC expression
2.)By antigen masking – when complexed with gyycocalyx molecules
3.)Tolerance
4.)Immunosuppression – tumours produce TGF – alpha which inhibit proliferation of lymphocytes and macrophages
Heriditary factors:
DOGS : Heriditary multifocal Renal cystadenocarcinoma & nodular dermatofibrosis in German Shepherd.
Brain Tumors :Boston Terrier & Bull Dog.
Chemicals: Toxins from bracken fern causes urinary bladder
Radiation : UV-Rays:
Squamous Cell Carcinoma. In ear in white cats.
Squamous Cell Carcinoma in eyes in Herford Cattle
INFECTIOUS AGENTS:
Mostly oncogenic RNA Retroviruses.
Papovaviruses.
Marek’s diease (Herpes virus)
HORMONES:
Increase testosterone level causes Prostate Cancer in dogs.
CACHEXIA: Loss of body weight, loss of body muscle & fat.Due to annorexia, nutritional demand of cancer tissue.
Hypertrophy osteopathy in dogs & cats.
Thrombocytopenia is seen in one-third of all dogs suffering with cancer.
Anemia & DIC are seen in dogs with hemengiosarcoma.
Parneoplastic Syndrome: Related to hypercalcemia & hyperglycemia.
Histological and cytological method
Biochemical Assays
Molecular Dx
Samples can be taken by Biopsy
Fine needle aspiration
Cytological smears
Exfoliative cytology
Tumour associated enzymes, hormones and other tumour markers in the blood are estimated
Two tumour markers in the blood are –
Carcino-embryonic antigen (CEA)
Alpha-foeto proteins
PCR
FISH technique (Flourescent Insitu Hybridisation)
DNA micro array analysis
Gene chip technology
Southern blot analysis
Flow cytometry
Immunocytochemistry
DNA probe analysis
Radiographs
CAT scan
MRI
Ultrasonography
What about extent?
What about its stage?
Number of LN involvement
Whether it is metastatic or not?
Lets see….
T = primary tumor size or extent
Tis: preinvasive tumor (in situ)
T0: no evidence of tumor
T1: tumor <5 cm in diameter but confined to primary site
T2: tumor >5 cm in diameter or ruptured tumor
T3: infiltrative tumor
a: no bone invasion
b: bone invasion
N = nodes
N0: no evidence of lymph node enlargement
N1: moveable ipsilateral nodes enlarged
N2: moveable contralateral/bilateral nodes enlarged
N3: fixed nodes
M = metastasis
M0: no metastasis
M1: metastasis detected
Surgery
Radiation therapy
Chemotherapy
Hyperthermia
Photodynamic therapy
Others
Gene therapy
Anti-angiogenic drugs
Immunotherapy
Alternative therapies
Mammary tumors (except inflammatory mammary cancer)
Prostate tumors
Oropharyngeal tumors
Skin cancers
GI tumors
Lung tumors
Bone tumors
Risks increase with age of patient
Most mortalities resulting from surgery are associated with:
pulmonary emboli
Pneumonia
cardiovascular collapse
primary disease
Other complications include:
Abscesses
wound infections
blood loss
incomplete wound healing
Brain tumors
Curative: small pituitary tumors
Longer survival time: intracranial tumors and spinal lymphomas
Tumors of the nasal cavity
Thyroid tumors
Soft tissue sarcomas
Mast cell tumors
Survival of cancer cells at the center of larger tumors
Local effects to skin, lining of GI tract, and hair
Long term effects:
Necrosis
Non-healing ulcerations
Organ dysfunction
blindness
Used prior to surgery to shrink tumor size
Used following surgery to destroy remaining cancer cells that were left behind
Limitations:
Radiation must be postponed until surgical incision has completely healed
Cancer cells in the area of scar tissue are often more resistant to radiation
As sole agentSystemic
cancers hematologic
malignancies
metastatic carcinomas
Metastatic sarcomas
As adjunct therapyGiven to
patients with no overt evidence of residual cancer following surgery or radiation
Toxicities are particularly against cells of the bone marrow, GI lining, and hair follicles and can result in:
Immunosuppression
Anemia
Nausea and vomitting
Delayed wound healing
Hair loss
Chemotherapy + Radiation
Certain drugs are radiosensitizers
This increases the efficacy of the radiation
Help slow down metastatic growth
Chemotherapy + Surgery
Shrink large tumors prior to surgery
Help eradicate microscopic cancer cells which remain after surgery
Help slow down metastatic growth
Most effective in the treatment of localized tumors in combination with radiation or chemotherapy
Used to treat small (<1.0 cm in diameter) benign and malignant superficial tumors
Equally damaging to both cancer and normal cells
Frequency of skin burns and infarcts can be as high as 45%
Hyperthermia + Radiation
In humans, combining these two therapies to treat cancer was found to double the number of complete responses
In dogs, this combination improved the rate of complete response in primary tumors resulting in prolonged survival time
However, many dogs later succumb to metastatic disease
Hyperthermia + Chemo.
Some drugs work more efficiently above normal body temperatures
Hyperthermia may offer a protective effect for normal tissues against drug toxicities
Some studies have shown that combining these therapies actually increases toxicity
Has been used limitedly in veterinary medicine
Used in dogs with localized, superficial, and minimally invasive tumors such as those affecting skin and linings of urinary bladder and oral cavity
Inability of light to penetrate deeply into tumor tissue
Tissue retention time of photosensitizers
Patient must remain in subdued light for 4-6 weeks
Not all tumors absorb photosensitizers at same rate and at same concentration
Gene therapy
Anti-angiogenic drugs
Immunotherapy
Alternative therapies
Acupuncture
Massage
Herbal and botanical medicine
Suicide gene therapy
Genetic immunotherapy
Tumor suppressor gene therapy
Drug resistance gene therapy
Inhibit tumor growth by cutting off tumor’s blood supply
Many of these drugs are in the early stages of clinical development in the treatment of both human and canine cancer
Biologic Reponse Modifiers:
Nonspecific immunomodulators
Lymphokines/monokines
Adoptive cellular therapy
Antibody therapy
Growth factors
Indications:
Lymphoma
Melanoma
Mastocytoma
Oteosarcoma
Soft tissue sarcomas, including fibrosarcoma and hemangiosarcoma
Acupuncture
Palliative treatment
Pain
Post-op & chemo-induced nausea and vomiting
Massage
May be contraindicated
Herbal and Botanical Medicine
Herbs are used in conjunction with chemotherapy or radiation to help strengthen the individual and mitigate side effects
Often ignored aspect of cancer treatment
Important in treating cancer cachexia
May control growth of certain tumors
Decrease side effects of cancer treatments
Animals with cancer have alterations in metabolism which results in clinical alterations
This occurs early in all cancers and decreases quality and quantity of life
Broken in four phases
Specific nutritional requirements of animals with cancer is unknown
Nutrients in order of importance
water
calories and protein
minerals and vitamins
Carbohydrate metabolism
Tumors preferentially metabolize glucose for energy by anaerobic glycolysis forming lactate
buildup of lactate results in net energy loss by the body and net gain by the tumor (uses ATP to convert lactate to glucose)
Protein metabolism
Good source of energy for tumor
Can result in clinically significant deficiency in AA
decreased immune function
surgery healing
decreased GI function
Benefits of certain AA
Arginine- decrease tumor growth and metastatic rate in some rodents
Glycine-shown to decrease cisplatin induced nephrotoxicity
others as well…
Lipid metabolism
Some tumors cells have problems utilizing lipids as fuel source
fats are usually last to be depleted
type of lipid verses amount of lipid
polyunsaturated n-3 fatty acids
Vitamins- some evidence indicate might be helpful in cancer patients
Retinoids, beta carotene, Vitamin C, D, and E
Minerals- May be helpful
Zinc, Cu, Se, etc…
Fiber- insoluble and soluble
Garlic- may help cancer patients
Green/Black tea- Black tea may have soothing properties associated with radiation-induced oral mucositis.
Shark cartilage-NO
Food aversion- a common outcome of side effects of cancer and cancer treatments in humans
Difficult to prove it occurs in animals
What food to feed?
How to feed the food?
Monitor and reassess feeding plan constantly (Is the patient getting better)?
Ideal diet would have
minimal simple carbohydrates, fiber
highly bioavailable protein with certain AA
higher fat levels with polyunsaturated n-3 fatty acids
adequate levels of antioxidants
a great smell and taste great!
Achieve with homemade diets or various commercial diets
Should be discussed constantly with client
Educate client on options
Final humane treatment
•Meningioma is the most common primary brain tumor in dogs and cats.•Glioma is the most common primary brain tumor in brachycephalic breeds.•Seizure is the most common clinical sign of brain tumors in dogs•Lymphoma is the most common spinal cord tumor in cats, whereas meningioma is most common in dogs.• Dogs with peripheral nerve sheath tumors commonly present with chronic lameness and severe muscle atrophy.
Melanoma, squamous cell carcinoma (SCC), andfibrosarcoma are the most common malignant oral tumors in dogs;
Approximately 5% of oral tumors in dogs are benigndental tumors (epulides), which do not metastasize and warrant an excellent prognosis.
The presence of loose teeth in a patient with otherwise good dentition warrants a search for oral neoplasia.
Maxillary fibrosarcoma (FSA) Epulides
Dogs with intranasal tumors are often presented for unilateral or bilateral nasal discharge that may be hemorrhagic and is often initially antibiotic responsive.
Radiation therapy is the primary treatment for canine intranasal tumors, with a median survival time of approximately 1 year.
Facial deformity which may be due malignancy
Exophthalmos and strabismus are the two mostcommon presenting signs associated with orbitaltumors
Diffuse iris melanoma extending from the 1 o’clock to 6 o’clock position.
Nodular granulomatous episcleritis Meibomian adenomas
Chondrosarcoma with severe local infiltration of the calvarium and frontal sinus
• Laryngeal tumors encompass a wide variety of histologic types but nearly identical clinical signs ofvoice changes, dyspnea, and cough.
Primary tracheal tumors most frequently lead to development of chronic cough, stridor, and wheezing.
Advanced diagnostics, including laryngoscopy, bronchoscopy, and CT or MRI, are often necessary to definitively diagnose laryngeal and tracheal tumors.
This bronchoscopic image from a dog demonstrates a large mass that extends from the wall of the trachea and nearly occludes the entire tracheal lumen.
Lateral cervical radiograph of a dog with a spaceoccupying soft tissue mass within the laryngeal lumen (arrow). Biopsy of this mass revealed a rhabdomyosarcoma.
Identification of a solitary, well-circumscribed lung parenchymal mass with plain radiography in a middle- aged to older dog or cat should raise suspicion for a primary lung tumor
Surgical excision is the treatment of choice for primary lung tumors. Those amenable to complete resection are associated with longer patient post-surgical survival time
Thymoma and lymphoma are the most common tumors of the cranial mediastinum.
Metastases in Lung
Primary cardiac tumors are uncommon in dogs and cats.
HSA (Haemagiosarcoma) is the most common cardiac tumor of dogs
An intraluminal leiomyoma protruding from the vulva
Ovarian carcinoma
Squamous cell carcinomas
Cutaneous plasma cell tumors
Melanoma Mast Cell Tumour
cecum is the most common site forGastrointestinalstromal tumors (GISTs
Surgical resection is the treatment of choice
Osteosarcoma
Most common tumours in female dogs
Can be prevented upto a higher extent by OH
Found with greatest frequency in poodles, boston terriers, fox terriers, daschunds.
Most commonly occur in middle aged in old dogs
Most common site is caudal mammary gland
Normally seen intact and aged bithes (which is due to hormonal imbalance)
Gross swelling which can be bleeding.
Cytology can also be done but not usually preferred.
Radiographs are taken to rule out malignancy
Surgery
Chemotherapy
Radiotherapy
Immunotherapy
Hormonal Therapy
5-FU (150 mg/m2 IV and cyclophosphamide (100 mg/m2 IV) once weekly for 4 weeks to that of dogs.
Successful in human beings but still unexplored in canines
Dogs less than 6 years of age are more commonly affected
Usually present in prepuce or vagina but can also be found on nose or on skin.
Endemic in free roaming dogs
The glans penis and prepuce are often concurrently affected.
Masses may have a cauliflower-like appearance or be friable and bleed easily.
These tumours have low metastatic rate.
First neoplasm to be successfully transmitted from one animal to another done by M A Novinsky
Tumour transmitted at coitus by transfer of intact tumour cells
It is tumour of young dogs (1-6 years of age)
More common in females
Present in vaginal mucosa protude from vulva and in males protude from prepucial cavity
H/O: Stray roaming
Continuous dribbling of urine and frequent licking of penis by dog
Oozing of blood may be there from prepucial cavity
Cauliflower like friable masses are found on vaginal or prepucial examination.
Cytopathologic sample of a canine TVT. Note the discrete round cells, somewhat eccentric nuclei, moderate amount of cytoplasm, and characteristic
multiple discrete clear cytoplasmic vacuoles.
Chemotherapy (treatment of choice)
Surgical resection
Radiation Therapy
Most effective approach remains monotherapy with the tubulin binding agent vincristine.
Vincristine is relatively safe, inexpensive, and provides a complete and durable response in over 90% to 95% of treated dogs, typically following two to six weekly treatments.
Vincristine is generally administered at a dosage of 0.5 to 0.75 mg/m2 IV once weekly for three to six treatments.
The anthracycline doxorubicin, at 25 to 30 mg/m2 IV every 21 days for two to three cycles (used in Vincristine resistance cases)
Before vincristine therapy After vincristine therapy
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