Oncology Flashcards

0
Q

What are the mechanisms of oncogene activation?

A

Chromosomal translocation, gene amplification, point mutations, viral insertions.

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1
Q

What are oncogenes?

A

Mutations that produce oncogenes with dominant gain of function. Retroviral sequences that are responsible for transforming properties are called viral oncogenes. They have cellular homologues called cellular oncogenes. Proto oncogene is used to describe cellular oncogenes that do not have transforming potential to form tumours in their native state but can be altered to lead to malignancy.

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2
Q

What are tumour suppressor genes?

A

Tumour formation can result from a loss of inhibitory functions associated with another class of cellular genes called the tumour suppressor genes.

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3
Q

What are the seven alterations that the vast array of cancer genotypes are a manifestation of?

A

These characteristics are acquired during the process of carcinogenesis and can be considered as: a self sufficiency in growth, an insensitivity to anti growth signals, an ability to evade programmed cell death, limitless replicative potential, an ability to sustain angiogenesis, an ability to invade and metastasise, an ability to evade host immunity.

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4
Q

What is the grade of a tumour?

A

The grade of a tumour refers to a pathological description of the tumour and is based upon several criteria. (e.g mitotic rate, tissue architecture and pleomorphism.) This should not be confused with stage, which refers to the clinical extent of the disease.

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5
Q

What is staging of a tumour?

A

Involves a consideration of primary tumour size, presence or absence of local lymph node involvement and presence or absence of distant metastases. To stage solitary tumours we use the TNM system. T= primary tumour, N=regional lymph node, M=metastases.

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6
Q

Describe Evaluating the primary tumour (T) in the TNM staging process

A

Physical examination - size of the tumour, mobility with respect to underlying tissues and degree of fixation, presence/absence and degree of erythema, presence/absence of ulceration, relationship with associated anatomical structures. Diagnostic imaging - required for deep tumours, tumours involving vital structures, bone, tumours adjacent to bone. Endoscopy or bronchoscopy in cases of suspected tumours of the GI tract, respiratory tract or urogenital system, Biopsy. The primary tumour is allocated a numerical or alphabetical suffix denoting size and extent of the tumour.

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7
Q

Describe lymph node evaluation in the TNM system

A

Physical examination - size of the lymph node, mobility with respect to underlying tissues and degree of fixation, texture and consistency, presence/absence of ulceration, relationship with associated anatomical structures. Diagnostic imaging - required for deep lymph nodes that cannot be physically examined. Aspirate or biopsy. The lymph node is allocated a numerical value depending on the presence or absence of neoplastic disease.

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8
Q

Describe how metastatic disease (M) is evaluated in the TNM staging system

A

Physical examination/history - this may give essential clues to the possibility of metastasis including weight loss, coughing or lameness. Diagnostic imaging - will depend on the tumour type and its natural biological behaviour. Particular attention should be paid to lungs, liver and bones. Biopsy - may be required too confirm metastatic disease versus nodular hyperplasia. The patient is allocated an M value depending on the presence / absence of disease at distant sites.

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9
Q

Describe staging for disseminated or multicentric disease

A

Diseases such as lymphoproliferative disorders often present as a disseminated form and thus the TNM classification is not appropriate. For diseases such as lymphoma the disease may be staged according to the various organ systems involved and assigned a numerical figure.

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10
Q

What is post surgical biopsy essential for?

A

to ensure surgical margins were adequate, the histological type and the grade of the tumour, that no follow up therapy is required, to inform prognosis.

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11
Q

What does biopsy have the potential to inform?

A

The detection of neoplastic disease in either primary or secondary sites, the tumour type, the grade of the tumour, the adequacy of surgical excision.

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12
Q

When deciding on an appropriate technique what must the clinician consider?

A

The amount of tissue that should be recovered in the biopsy, the position within the tumour that tissue is to be recovered from, the type of tissue to be biopsied, the anatomic location of the tumour.

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13
Q

What is cytology?

A

The examination of individual cells or small groups of cells which have been recovered from tumour masses or from neoplastic effusions.It is used to identify the presence of neoplastic diseases. The cells in cytological preparations often bear no relationship to their original arrangement within the tumour or to its architecture. Specimens can b e recovered with little disruption of the tumour and the surrounding tissues.

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14
Q

What is needle biopsy?

A

Used to remove small cores of tumour tissue from solid lesions. Used when it is important to recover sufficient tissue to establish tumour type. eg recovery of tissue from tumours of internal organs without surgical procedures, recovery of tissues from bone lesions.

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15
Q

What is a skin punch biopsy?

A

Excellent for skin and superficial soft tissue tumours. Recover substantially more tissue than needle aspirates. Recovered tissue retains much of its architecture and is suitable for routine processing techniques.

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16
Q

What is an incisional biopsy?

A

Surgical removal of a solid piece of tissue from a tumour for histopathological examination. It is used where a substantial amount of tumour tissue is required to enable histopathological typing and grading. Incisional biopsy provides an opportunity for exposure of the biopsy site allowing accurate selection of the site for tumour sampling and reducing the risks of post biopsy complications. Normally requires general anaesthesia.

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17
Q

What is Excisional biopsy?

A

the complete surgical extirpation of a tumour following which tissue samples are removed for histopathological examination, which should ideally be performed on all excised specimens.

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18
Q

Describe a bone marrow biopsy

A

Often indicated in the diagnosis of conditions affecting the lymphoid and myeloid systems. The biopsy may take the form of an aspirate or a core biopsy. Indications for bone marrow biopsy: non regenerative anaemia of undetermined cause, investigation for secondary immune mediated haemolytic anaemia, staging and or diagnosis of haematopoietic tumours. One can use the humerus, femur or the iliac crest. A bone marrow needle is used.

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19
Q

What is a bone marrow core sample?

A

A bone marrow biopsy is carried out, but after the aspirate has been retrieved the needle is advanced to obtain a core sample. The needle is rocked forward and backward after advancement to saver the bone in the needle from its base. When the needle is removed, a smaller wire obturator is used to retrograde the biopsy material out of the top of the needle.

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20
Q

What are paraneoplastic syndromes?

A

They are diverse clinical syndromes resulting rom systemic effects of neoplasia. The effects occur at sites distant from the tumour and can affect many end -target organs. Syndromes include hormonal, metabolic, haematologic, neuromuscular, dermatologic, musculoskeletal, renal, gastrointestinal and cardiovascular disorders. PNS may occur as a result of immune-mediated mechanisms, peptide protein or hormone secretion, cytokine secretion, production of enzymes or other biochemical mechanisms that interfere with normal metabolic pathways.

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21
Q

Name some metabolic paraneoplastic syndromes?

A

Fever, anorexia, cachexia. Associated with lymphomas, leukemias sarcomas, hepatic, renal, gut tumours.

22
Q

Name some endocrine Paraneoplastic syndomes

A

Hyperthyroidism, Hyperadrenocorticism, Hypercalcaemia, acromegaly, hypoglycaemia, Feminisation syndrome, hypertension, hypergastrinemia, hyperaldosteronism, inappropriate secretion of ADH, diabetes insipidus.

23
Q

Name some haematologic paraneoplastic syndromes

A

Anaemia, erythrocytosis, thrombocytopenia, thrombocytosis, leucocytosis, bleeding diathesis, aplastic anaemia.

24
Q

Name some dermatologic paraneoplastic syndromes?

A

Alopecia - feline pancreatic adenocarcinoma, biliary carcinoma, exfoliative dermatitis - feline thymoma, nodular dermatofibrosis -german shepherd dog renal cystadenocarcinoma.

25
Q

Describe some renal paraneoplastic syndromes and what they may be associated with?

A

Renal protein loss - lymphomas, leukaemias, melanoma. Glomerulonephritis, nephrotic syndrome - myeloma, lymphoma, leukemia, renal carcinoma.

26
Q

Describe some neuromuscular paraneoplastic syndromes

A

Myasthenia gravis - thymoma, osteosarcoma. Peripheral neuropathy - insulinoma.

27
Q

Describe hypercalcaemia as a paraneoplastic syndrome?

A

A coonsequence of deregulation of homeostatic mechanisms between PTH, calcitonin and active vitamin D (calcitriol). Frequent causes are malignancy and hypoadrenocorticism in dogs, malignancy, renal failure or idiopathic in cats. Total calcium decreases with serum albumin.

28
Q

What is humoral hypercalcaemia of malignancy?

A

In non skeletal tumours as a result of tumour derived parathyroid hormone related protein and cytokines such as transforming growth factors, interleukins and epidermal growth factor, tumour necrosis factor, e.g thyroid carcinoma, malignant melanoma, squamous cell carcinoma. increased plasma PTH concentration in a hypercalcaemic patient in the absence of renal failure gives a strong index of suspicion for neoplasia.

29
Q

What are the main clinical features of hypercalcaemia?

A

In the dog polyuria and polydipsia. in the cat lethargy and anorexia. Clinical signs may be vague and non specific or profound with multi system effects. A major clinical concern is hypercalcaemic nephropathy and renal failure.

30
Q

Are we going to improve the quality of life by removing the mass?

A

A typical example is osteosarcoma. While amputation does not influence survival, removal of the painful mass dramatically improves quality of life.

31
Q

Is it in the animals interest to remove the mass?

A

E.g lingual carcinoma. The tumour is fairly invasive but surgery would involve reconstructing the tongue.

32
Q

Are we going to prolong the animal’s life with quality?

A

We an improve the quality of life without radical treatment but with palliative therapies including surgery and or radiotherapy.

33
Q

What investigations are needed to deliver the information needed?

A

Appropriate clinical staging and investigation of any concurrent disease needs to be performed prior to treatment consideration.

34
Q

What is surgery trying to achieve?

A

Diagnosis: as part of a biopsy procedure. For curative intent, where clear surgical margins can be achieved, as part of a combined strategy to treat a tumour e.g cytoreduction to microscopic disease followed by radiotherapy, for palliation e.g amputation alone in osteosarcoma, for prevention.

35
Q

What is prophylactic surgery?

A

A prophylactic oncological surgery can be defined as one that results in a reduction of either the anticipated incidence rate of a particular tumour type or the rate of recurrence of a neoplastic disease after therapy. e.g mammary tumours in the bitch, testicular tumours in the dog, premalignant lesions of squamous cell carcinoma in the cat

36
Q

What is cytoreductive surgery?

A

In some circumstances, definitive Excisional curative surgery is not possible. Certain tumour types or grades are associated with significant rates of local recurrence even after radical surgery and resection of such tumours should always be regarded as incomplete. Cytoreductive surgery reduces the numbers of tumour cells present. It is combined with other treatment modalities such as local or systemic chemotherapy or radiotherapy to try and achieve long term remission. Cytoreductive surgery improves the efficiency of these adjunctive therapies by reducing the numbers of malignant cells to be treated. eg mast cell tumour resection to microscopic disease followed by adjunctive radiotherapy.

37
Q

What is palliative surgery?

A

A surgery performed to improve the quality of life. Examples include limb amputation for osteosarcoma causing lameness, removal of large ulcerated painful mammary carcinomas.

38
Q

What is definitive surgical excision?

A

This refers to the use of surgery as the sole treatment, without adjunctive radiotherapy or chemotherapy, to achieve a cure. The incision, the surgical exposure and the surgical margin are the most important aspects of a definitive surgery.

39
Q

What is radiotherapy?

A

Radiotherapy is the use of ionizing radiation for the treatment of neoplasia. it is an effective local treatment for many solid tumours in dogs and cats. Radiotherapy is a local treatment with no systemic effects. Cancer cells outside of the radiation field will not be affected by the radiation. Side effects are limited to the region within the radiation field. Radiation causes damage to the genetic material of cells within the tissue that is irradiated which leads to cellular death. The biological effect is expressed when the damaged cells attempt to divide.

40
Q

Describe some tumours commonly treated with radiotherapy?

A

Nasosinal tumours, brain tumours, oral tumours, soft tissue sarcoma, cutaenous mast cell tumours, anal sac adenocarcinoma, histiocytic sarcoma, thyroid carcinoma, thymoma, lymphoma, feline injection site sarcoma, primary and metastatic bone tumours.

41
Q

What are the classes of the cytotoxic drugs?

A

The alkylating agents, antimetabolites, anti tumour antibiotics, mitotic spindle inhibitors, glucocorticoids, miscellaneous agents.

42
Q

Describe the cancer cell cycle dynamics.

A

The cancer cell undergoes a cycle of activity (the cell cycle) which allows the genetic material to be doubled and the cell to divide. The cells in a tumour will be either dividing (from G1 to M) or non dividing (Go). Once a cell has acquired the necessary genotypic and phenotypic characteristics of a cancer cell in general there is an exponential growth of a tumour with very few cells in Go.

43
Q

What are the consequences of these growth characteristics of tumours?

A

Initial rapid growth curve which then flattens as the growth rate slows. The actual growth rate of a tumour is described in terms of Mass doubling time or the time taken for a tumour to double in size. MDT is a function of the number of cells which are actively dividing (Growth fraction), the cell cycle time, the number of cells being lost by cell death. Tumours with a high growth fraction have a short MDT. Chemotherapetic agents are more likely to be successful where tumours have a high GF and low MDT. Cells in Go are relatively resistant to the action of cytotoxic drugs.

44
Q

What are the effects of Cytoreductive surgery?

A

A tumour is excised when the tumour is in the plateau phase of growth. There is microscopic disease in the tissue bed. The cells left behind move into a phase of cell division and adopt a higher GF and shorter MDT than the removed mass. This is known as recruitment. This is when the cells are most sensitive to the effects of chemotherapy drugs.

45
Q

What is the tumour cell kill hypothesis?

A

cytotoxic drugs kill tumour cells according to first order kinetics. I.e a given dose of cytotoxic agent kills a fixed percentage of the total mass of cells in a tumour rather than a fixed number of cells.

46
Q

How do we dose patients?

A

Dosing drugs on the basis of weight there is a tendency to overdose large animals and under dose small ones. For this reason it has become common to dose chemotherapeutic agents according to the calculated body surface area of the patient rather than the body weight. Maximum tolerable dose of a variety of toxic drugs has been shown to correlate much better with BSA than weight.

47
Q

Describe the timing and intervals between doses of drugs.

A

The dose of drugs to be administered is limited by the toxicity to the normal tissues. The most common form of toxicity being myelosuppression and gastrointestinal toxicity. These tissues have enormous capacity for repair compared to the tumour and therefore a drug schedule is developed which allows the drug to be administered at intervals rather than continuous treatment. The intervals are timed so the normal tissue has time to repair without expansion of the residual tumour population.

48
Q

What are the alkylating agents?

A

They cause cross linking and breaking of DNA molecules, interfering with DNA replication and RNA transcription. Examples are cyclophosphamide, isosfamide and chlorambucil.

49
Q

What are the mitotic spindle inhibitors?

A

they bind to cytoplasmic microtubular proteins and arrest mitosis in metaphase.

50
Q

What are the antimetabolites?

A

Mimic normal substrates needed for nucleic acid synthesis. They inhibit cellular enzymes or lead to the production of non functional molecules.

51
Q

What are the antitumour antibiotics?

A

Bind to DNA and inhibit DNA and RNA synthesis. An example is doxorubicin. Mitozantrone is another, newer anthracycline antibiotic derivative.

52
Q

How do glucocorticoids work as cytotoxic drugs?

A

They are cytolic for lymphoid tissues and are therefore useful in the treatment of some lymphoid malignancies. Their mechanism of anti tumour action is unclear.

53
Q

What are the dangers of cytotoxic drugs?

A

Drugs may be metabolized and excreted in their active form in saliva, urine and faeces. Dogs and cats on current corticosteroid therapy may produce more urine.