The genetic damage or mutations must be – Genetic damage must be non-lethal Three classes of regulatory genes
Until recently, nutritional management of cancer patients has not been considered important. This despite the fact that patients not eating is one of the biggest problems facing cancer patients. Therefore, It is now recognized that proper nutritional management is important in treating cancer cachexia (which is a clinical condition due to severe malnutrition) In addition, proper nutrition can control the malignancies of cancer and certain nutrients can help limit the side effects associated with chemotherapy and radiation therapy.
Cancer severely alters the metabolism of proteins, carbohydrates, and lipids in the patient. This results in inefficient uses of nutrients. This occurs early in all cancers and decreases quality and quantity of life. The metabolic and clinical alterations in cancer have been described in four phases…
So to prevent and reverse clinical conditions like cachexia, we need to give the best nutrients available to our patients. Specific nutritional requirements of animals with cancer is unknown but we do know in general what nutrients are needed for healthy animals. What is different in cancer patients is the change in metabolism that occurs as mentioned earlier.
So, Cancer affects carb metabolism. Bottom line on carb metabolism; Tumors preferentially metabolize glucose for energy by anaerobic glycolysis forming lactate. This forces the body to waste energy converting lactate to glucose.
Tumors preferentially use protein for energy at the expense of the host. When protein degradation and loss exceed synthesis you see decreased immune function, decreased GI function, and surgery healing.
However, research has shown that increases in the consumption of certain AA can be beneficial to cancer patients. I’ve just listed a few above, but as more research is done, the benefits of different AA will be discovered So the bottom line is that a diet with moderate amounts of highly bioavailable protein may be of value to the cancer patient.
So, tumor cells readily utilize protein and carbs but tend to have problems utilizing lipids as a energy source. Therefore, they are usually the last to be depleted in the patient. Some research indicates that the type of the fats consumed is more important than the amount of fat, specifically n-3 fatty acids.
Okay, vitamins and minerals. There has been some research on that certain vitamins and minerals (as listed above) can have some positive effects for cancer patients. Although, it seems like as one research study say Vit X does this, another study comes out saying that it does nothing so in my personal opinion that in moderation, supplementation of vitamins and minerals wouldn’t hurt, and may improve the QOL of the patient.
Can’t forget adequate amount of fiber to maintain normal bowel health. Garlic is also commonly mentioned in helping prevent and treat cancer in humans and animals (by inhibiting carcinogens),but no concrete studies on the efficacy. Similarly, there is absolutely no proof that shark cartilage works so we shouldn’t recommend giving that to patients since its expensive and maybe we can save a few sharks in the process.
Okay food aversion . A common phenomenon in human patients, it is the act of the patient associating eating, sight or smell of food (or all three) with unpleasant side effects such as nausea and pain). There has been a lot of anecdotal evidence it occurs in animals and it should be assumed that they do experience food aversion. Food aversion can be avoided by created a feeding plan.
So we have all this wonder nutrition information so now we need to develop a feeding plan. The three main things we want to ask ourselves is what the best food to feed, how to feed the food, and is the patient getting better on this feeding plan we chose? Also, don’t forget none of this matters unless the clients are educated about the importance of nutrition in the management of the cancer.
The ideal diet would have minimal simple carbs, highly bioavailable proteins with the aforementioned AA, and higher fate levels with n-3 fatty acids. It also helps that the food taste great and has a pleasant aroma. There are several commercial veterinary therapeutic foods that provide the key nutrients in appropriate levels. In addition, these requirements can be achieved by homemade diets (sources available in books, online).
Euthanasia should be discussed constantly with the client; before and during cancer treatment is occurring. The client should be educated on all their options available besides euthanasia. Although, sometimes doing everything medically possible is not the best choice for the patient and owner. Therefore, once the client makes the decision for euthanasia, we as doctors should support their decisions in their final kind act toward their pet.
Prince NandaNikunj 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
James EWING & BJ Kennedy- Father of Oncology TERMINOLOGY 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
Characteristic Benign MalignantShape Round, wart like or Irregular pedunculatedMetastasis Not present PresentMitotic figures Less MoreBlood 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: Papilloma –Epithelial surface Polyp -Mucosal surface Adenoma – Glandular surface Malignant: name of the tissue (suffix -carcinoma)
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 damageGrowth promoting proto-oncogenes Genes that regulate apoptosis Growth inhibiting cancer suppressor genes 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.
Trans coelomic lymphatics Localised tumour Haematogenous Invasion of extra cellular Matrix Detached tumour penetrate basement membraneIntegrins helps to bind to ECM Invasion is assisted by secretion Further Migration also occurs of Proteases 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
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 Molecular Dx Biochemical Assays
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
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
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 agent As adjunct Systemic therapy cancers Given to hematologic patients with malignancies no overt metastatic evidence of carcinomas residual cancer Metastatic sarcomas 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 Chemotherapy + Surgery Certain drugs are Shrink large tumors radiosensitizers prior to surgery This increases the Help eradicate efficacy of the radiation microscopic cancer cells which remain after Help slow down surgery metastatic growth 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 + Hyperthermia + Chemo. Radiation Some drugs work more In humans, combining efficiently above normal these two therapies to body temperatures treat cancer was found to double the number of complete responses Hyperthermia may offer a protective effect for In dogs, this normal tissues against combination improved drug toxicities the rate of complete response in primary Some studies have tumors resulting in shown that combining prolonged survival time these therapies actually However, many dogs increases toxicity later succumb to metastatic disease
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
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 dogsand cats.•Glioma is the most common primary brain tumor inbrachycephalic 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 presentwith 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.
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.
Exophthalmos and strabismus are the two mostcommon presenting signs associated with orbitaltumors
Nodular granulomatous episcleritis Meibomian adenomas Diffuse iris melanoma extending from the 1 o’clock to 6 o’clock position.
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.
Lateral cervical radiograph of a dog with a This bronchoscopic image from a dog demonstratesspaceoccupying soft tissue mass within the laryngeal a large mass that extends from the wall of thelumen (arrow). Biopsy of this mass revealed a trachea and nearly occludes the entire trachealrhabdomyosarcoma. lumen.
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.
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
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