Oncology Flashcards
What causes neoplastic disorders?
Interaction between genetic and environmental factors
What can be classed as an environmental carcinogenic?
Chemical - Radiation - Radionuclie - Mitogens
How can environmental mitogens cause neoplasia?
Stimulate cell proliferation and promote oncogenes
What factors can increase susceptibility to neoplastic disorders?
Genetic - Hormonal - Environmental carcinogenics
What is the definition of an oncogene?
A gene, when inappropriately activated, can cause the formation of a tumour
Give two examples of two anti-oncogenes
Rb - p53
When would mutations of genes normally become clinically significant?
Cumulative mutations of oncogenes and tumour suppressor genes
What are the six ‘Hallmarks of Cancer’ that a cell needs to be cancerous?
1) Sustaining proliferative signalling
2) Evading growth suppressors
3) Resisting cell death
4) Enabling replicative immortality
5) Inducing angiogenesis
6) Activating invasion and metastasis
Define combination chemotherapy. What are the benefits of it?
Targeting more than one property of cancer cells to try and destroy them - Less dosage of each agent so less adverse affects
Name the three ways in which cancer cells become self sufficient in terms of growth signals.
1) Secretion of endogenous growth factors - autocrine/paracrine manner
2) Mutation of GF receptors - overexpressed or active receptors even in absence of ligand
3) Mutation of intracellular signalling molecules - proto-oncogenes such as Ras and Raf activate MAPK pathways
Give an example of where a cancer cell overexpresses GF receptors
In Mast Cell tumours - on the KIT receptor (about 50% of mast cell tumours)
What do Rb and p53 decide? How else are they known?
Whether a cell enters mitosis or goes into senescence/apoptosis - Tumour suppressors
How does a) Rb and b) p53 operate?
a) Transduces growth-inhibitory signals that originate outside the cell
b) Receives information from intracellular operating systems (such as cell viability is subnormal)
What is the cellular apoptotic machinery divided into?
Upstream regulators - Downstream effectors
What are the apoptotic regulators divided into?
Extrinsic pathway (receive extracellular death-inducing signals) - Intrinsic pathway (receive intracellular signals - p53)
What do the extrinsic and intrinsic pathways culminate the activation of?
Caspase cascade
Give an example of anti-apoptosis molecules
Bcl-2
Why do cells have a proliferative limitation?
Associated with erosion of telomeres that protect the end of chromosomes during cell division
What is the function of telomerase? How is it utilised in cancer cells?
Specialised DNA polymerase which adds telomere repeat segments to the end of DNA - Up-regulated to give replicative immortality
Why is angiogenesis vital to cancer cells?
Cells in the centre of a cluster of tumour cells will undergo hypoxia-induced necrosis so require a dedicated blood supply - Can facilitate metastasis
Give an example of an angiogenic factor used by cancer cells
Vascular Endothelial Growth Factor (VEGF)
What are the steps of metastatic invasion by malignant tumours?
Local invasion - Intavasation into local lymph/blood vessels - Disseminate via lymphatic or haematogenic - Extravasate into other tissues - Metastatic lesions
What two factors influence the ability of a tumour to metastasis?
Ability to get through tissues (enzyme production) and ability to detach from primary tumour (loss of cell adhesion molecules)
What are the emerging hallmarks and characteristics found in cancer cells?
Deregulating cellular energetics - Avoiding immune destruction - Genome instability and mutation - Tumour-promoting inflammation
Why does an inflammatory response, which seems detrimental for a tumour, in fact promote it?
Release of growth factors, angiogenic cytokines and immunosuppressive mediators by inflammatory cells enhance malignant potential
When presented with an animal with a mass, what should you try to find out about it from the owner?
How long present? - Trauma? - Hot/painful? - Solid/fluid filled? - Well or ill-defined?
What is the first port of call when taking samples of a mass? Why?
Cytology - using a Fine Needle Aspiration (FNA) - Cheap, quick and easy to perform
What is the main difference of cellular content of inflammatory masses and neoplastic masses?
Inflammatory has a range of cells (neutrophils, macrophages, etc) whereas a neoplastic mass will have one cell which predominates
What information can cell morphology give?
If a tumour is malignant or benign
If cytology doesn’t give definite diagnosis, what other sample can be taken? What in particular does this tell us that cytology doesn’t?
Histopathology (biopsy of tissue) - Gives the tissue architecture, mitotic index, invasion of vasculature, degree of necrosis
What can be used in conjunction with histopathology to further investigation?
Special stains - Immunochemistry - Flow cytometry
What is tumour grade?
Given by the pathologist - Helps predict the behaviour of tumour
How is tumour grade found?
Assessment of mitotic index, cellular differentiation, invasion of tissues/vasculature/lymphatics, amount of necrosis
What are the categories of tumour grading?
Patnaik system - 1=low grade (benign) 2=intermediate 3=high grade (malignant)
Kiupel system - either good or bad
What does Staging the tumour mean?
Assess the extent of the disease in the patient performed by clinician
What does staging the tumour involve the assessment of?
Primary tumour - Drainage lymph nodes - Distant metastatic disease
What is the TNM system used for? Define each letter
Staging tumours
T = Primary tumour
N = Node
M = Distant metastasis
What are paraneoplastic syndromes?
The systemic effects of a tumour
How do paraneoplastic syndromes occur?
Result of secretion of hormone, hormone-like substance, enzyme or cytokine by tumour
What are the four baseline tests to assess the cancer patient?
Haematology/complete blood count - Biochemistry - Urinalysis - Coagulation parameters
Which test is the best to use when investigating paraneoplastic syndromes?
Biochemistry
What are the common paraneoplastic effects?
Hypercalcaemia - Hypoglycaemia - Hyperviscosity - Gastric ulceration (vomiting) - Endocrine problems - Pyrexia - Immune-mediated diseases - Hypertrophic osteopathy - Dermatologic manifestations - Cancer cachexia
When is surgery a viable option for treatment of cancer?
Carcinomas - Sarcomas - Mast cell tumours
When is Radiation treatment a viable option for treatment of cancer?
Primary - nasal tumours, localised radiosensitive
Adjunctive - following incomplete recession/prior to surgery
When is Chemotherapy (anti-cancer drug therapy) a viable option for treatment of cancer?
Treatment of systemic disease - lymphoma, leukaemias, myeloma, systemic mast cell
Highly metastatic tumour
Also used as adjunctive treatment
What is fundamental for accurate diagnosis of neoplasia?
Good communication between the pathologist and clinician
Give the characteristics macroscopically of a benign tumour
Low to moderate growth rate - Demarcated from surrounding tissue - Surrounding connective tissue capsule - Freely mobile on palpation - Homogeneous cut surface - Little haemorrhage or necrosis
Give the microscopic features of a benign tumour
Similar to tissue of origin - Well organised - Can be functional - Tumor doesn’t broach capsule - Few or mitosis
Give the macroscopic characteristics of a malignant tumour
Growth by invasion - Not encapsulated - Not mobile - Frequent internal necrosis and haemorrhage - Metastasise
Give the microscopic features of a malignant tumour
Variable cell/nuclei size and shape - Increased nucleus:cytoplasm ratio - Prominent nucleoli - Normal and abnormal mitoses - Secondary changes
What are the names of benign tumors of epithelial origin?
Surface of epithelia = papilloma - Glandular = adenoma
What are the names of malignant tumors of epithelial origin?
Surface of epithelia = carcinoma - Glandular = adenocarcinoma
What are the names of benign tumors of mesenchymal origin?
Fibrous = fibroma - Bone = osteoma - Cartilage = chondroma - Adipose = lipoma - Smooth muscle = leiomyoma - Endothelium = haemangioma - Skeletal muscle = rhabdomyoma
For malignant tumors of mesenchymal origin, what is the difference in name than benign tumours?
Add sarcoma on the end
What are the different types of tumour metastasis?
Lymphatic - Vascular - Trans-cavity - Local
What sort of metastasis are typical of carcinomas?
Lymphatic
What sort of tumour type typically has vascular metastasis?
Sarcoma
What type of tumor typically has trans-cavity metastasis?
Mesothelioma
What’s a multicentric tumour?
Malignant tumour with multiple sites with no way to determine the primary origin
If a tumour can not be diagnosed by morphology, what other tests can be performed to diagnose?
Immunohistochemistry
Give examples of cell surface markers that may assist identification of tumours? What do they identify?
Cytokeratin - epithelial marker (carcinoma)
Vimentin - mesenchymal marker (sarcoma)
CD3 - T cell marker (lymphoma)
CD79a - B cell marker (lymphoma)
What is tumour grading?
Measure of differentiation - High grade = poor differentiation - Low grade = good differentiation
What are the four methods used for tumour grading?
Light microscopy - Immunophenotyping - Detection of genetic mutations - Proliferation markers
What is looked for when tumour grading with light microscopy?
Do the tumour cells look like the parent cell
How can immunohistochemistry be used to grade tumours?
Tumours loose antigenic markers as they become less differentiated - have less stain
What does a pathologist require in order to make an accurate diagnosis?
Representative sample - Correctly submitted sample - Full clinical history
When making an incision for a pathology lab, what should be avoided? What is the exception?
Necrotic and cavitated areas - Except bone tumours where most cavitated area required
Why is it better to treat a tumour with chemotherapy as early as possible? Why is this not normally possible?
Drugs more effective in the log growth phase of tumour (earlier on) - Clinical signs generally not shown until later in development when tumour is nearing plateau of growth
What is the cell kill hypothesis?
Tumour cell kill follows first order kinetics - a given dose of drug with kill a certain percentage of population instead of a given number of cells
What are the principles that should be considered when doing combination therapy for chemotherapy?
Each drug is individually effective - Different modes of action that don’t interfere with each other - Act on different stages of cell cycle - No overlapping toxicities
Give a couple of exams of chemotherapy protocols used in cats and dogs
COP-based - Doxorubicin-containing (CHOP)
How do you figure out the doses of cytotoxic chemotherapy agents? What is the exception?
Maximum tolerated dose = mg/m2 - Small dogs and cats so measured on mg/kg
What is metronomic chemotherapy? How does it work?
Low doses of cytotoxic drug are given on continuous basis alongside a NSAID - Inhibits angiogenesis and immunomodulatory effects
What is another method of chemotherapy apart from conventional and metronomic? How does it work?
Receptor tyrosine kinase inhibitors - Inhibit aberrant signalling which inhibits angiogenesis, reduces proliferation and promotes apoptosis
What is MDR1? What does it do?
Mult-drug resistance gene acquired - Leads to increased P-glycoprotein (Pgp) which pumps cytotoxic drugs out of the cell
What are the four main cytotoxic effects caused by chemotherapy drugs?
Myelosuppression - Gastrointestinal toxicity - Poor hair/whisker loss - Drug extravasation
What is the mechanism of action of Alkylating agents?
Substitute alkyl group for H+ ion in DNA - cause cross-linkage and breaking of DNA - Interfering with DNA replication and transcription
Give some examples of Alkylating agents
Cyclophosphamide - Lomustine - Melphalan - Chlorambucil - Procarbazine - Dacarbazine
What are the toxic effects of Cyclophosphamide? What type of anti-cancer agent is it?
Haemorrhagic cystitis in dogs - Metabolite irritant to bladder lining
Alkylating agent
What is the mechanism of action for Mitotic Spindle inhibitors?
Bind to tubulin - Prevent normal microtubule assembly - Arrest of mitosis in metaphase - Cell cycle specific
Give some examples of Mitotic Spindle inhibitors
Viscristine - Vinblastine - Vinorelbine - Taxanes
What are the toxic effects of Viscristine? What type of anti-cancer drug is it?
Peripheral neuropathies - Constipation in cats - Skins sloughs if injected perivascularly
Mitotic Spindle inhibitor
What is the mechanism of action of Anti-metabolites?
Mimic normal metabolites used by nucleic acid metabolism - Interfere with DNA synthesis - Cell cycle specific
Give some examples of Anti-metabolite drugs
Cytosine arabinoside/cytarabine - Methotrexate - Hydroxycarbamide
What is the mechanism of action of Anti-tumour antibiotics?
Inhibition of topoisomerase II which untangles DNA strands - Breaking DNA strands - Cross-linking of DNA pairs - Free radical oxidative damage
Give examples of Anti-tumour antibiotics
Doxorubicin - Epirubicin - Mitoxantrone - Actinomycin-D
What are the toxic effects of Doxorubicin? What kind of anti-cancer drug is it?
Cardiotoxicity in dogs - Chronic toxicity leading to dilated cardiomyopathy - Mast cell degranulation (rare) - Nephrotoxicity in cats
What is the mechanism of action of Platinum compounds?
Work the same as alkylating agents - Cause inter and intrastrand crosslinks in DNA - Interfere with DNA synthesis and transcription
Give some examples of Platinum compounds
Cisplatin - carboplatin
What other miscellaneous agents that aren’t classed as cytotoxic drugs can be used in cancer treatment?
Corticosteroids (prednisolone) - L-asparaginase - NSAIDs - Receptor Tyrosine Kinase Inhibitors (RTKIs)
Why do margins for surgery need to be bigger than the tumour?
Assume there are invasive cells locally around the tumour
What are the two ways that ionizing radiation destroy cells?
Direct damage to the DNA - Indirect damage via creating free radicals which then damage the DNA
What are the units for Radiation Therapy?
Greys
What would a) <1 grey cause b) cause cells to not divide c) between 10 and 100 greys cause?
a) Mitosis delayed
b) <10 greys
c) Intermitotic death after 1 or 2 tries
What are the most radiation sensitive sensitive cells in the body?
Undifferentiated cells with a high mitotic rate - bone marrow, intestinal crypt cells, germinal layer of epidermis, TUMOURS
Why are tumour cells more susceptible to radiation therapy than normal cells?
Have a poor DNA repair mechanism
What is fractionation of radiation therapy?
Total dose of radiation used to treat a tumour is divided into a number of fractions
What are the four R’s of radiation therapy?
Repair - Repopulation - Reoxygenation - Redistribution
What may happen after a dosing of RT in tumour cell population? What are the consequences for RT?
Tumour cells may counteract cell death with accelerated repopulation - Need to treat again before they gain the opportunity to repopulate
Which cells of a tumour may only die when treated with RT?
Oxygenated cells - Necrotic cells aren’t susceptible
Which phase of the cell cycle are cells more sensitive to RT?
G1 and G2
What is the name of the main modern machine which does RT?
Linear accelerator (megavoltage)
What can be used for RT?
X-rays - Gamma rays - Particles
An animal has a superficial tumour, what type of RT would be best to use on this? Why?
Electron beam - Therapeutic penetration of 1.5-5.6cm - RT will attack tumour whilst not attacking underlying organs
What sort of RT are Proton beams used for?
High penetration - Used for deep tumours such as Lungs and Intestinal
What is necessary to perform before undergoing Proton beam RT?
An accurate CT scan
What can be used to keep an animal in the same position for RT?
Multi-leaf collimator, vacuum pillows and a Bitebloc
When is Radiotherapy used as a curative measure?
Brain tumours - Tumours of head and neck (oral and nasal) - Mast cell tumours - Epulis (gingival)
What are the adverse a) Acute and b) Late effects of radiation therapy?
a) Damage to skin, mucosa, GI epithelium
b) Permanent damage to bone, muscle, brain, CNS, lens, retina, etc
What is needed in order to perform a successful surgical excision of neoplasia?
Thorough understanding of anatomy and physiology
What is the role of surgery in management of cancer?
Diagnosis - Resection for cure - Palliative care - Debulking - Prevention of neoplasia
How should a biopsy sample be properly fixated?
10% neutral buffered formalin - 1 part tissue to 10 parts fixture - Tissue less than 1cm thick
What is prophylactic surgery?
Surgery where either normal (eg gonads) or abnormal (eg pre-malignant changes) tissue is excised to reduce incidence of occurrence/recurrence of neoplasia
Give an example of prophylactic surgery and what it prevents
Gonadectomy - mammary tumours, perianal adenomas and testicular tumours - recurrence of vaginal leiomyomas
What are tell-tale signs that a local lymph node is effected by metastases rather than inflammation or infection?
Firm - Irregular - Fixed to surrounding tissue
What are the three types of excision?
Local - Wide local - Radical local
What two circumstances should lymph nodes be removed?
Positive for tumour and is not fixed to surrounding tissues
Normal-appearing lymph nodes which drain the primary tumour may be sampled (biopsy)
What two circumstances should lymph nodes not be removed?
Lymph nodes in critical areas attached to surrounding tissue (should only be biopsied in situ)
If intending to remove prophylactically with no intention of sampling
When would you perform a local excision of a tumour?
Benign tumours - no infiltration
For which types of tumour would you perform a wide local excision?
Benign tumours with infiltration - Malignant tumours with limited infiltration potential (well differentiated)
What are the three methods of radical excision?
Compartmental excision - Muscle group excision - Amputation
Define cytoreductive surgery
Surgery performed to debulk the tumour to make way for other forms of cancer treatment (chemo/RT)
