principles clinical oncology Flashcards
causes predispositions to female mammary cancer
oestrogens and progesterones
causes predisposition to male prostate carcinoma or perianal adenoma
testosterone
3 viruses that cause cancer
- retrovirus
- poxvirus
- helicobacter pylori
define proto-oncogenes
genes that promote cell growth and proliferation or inhibit apoptosis
2 tumour suppressor genes
- Rb
- p53
2 things that need to mutate to allow oncogenesis
- tumour suppressor genes
- proto-oncogenes
number of mutations to make oncogenesis clinically significant
10-12
Rb action
- prevents excessive cell growth by inhibiting cell cycle till its ready to divide
- stops G1 going into S phase
p53 action
stops G1 to S phase in prescence of DNA damage
- can cause apoptosis if damage not fixed
tumour mutation development
mutation inactivates suppressor gene –> call proliferation (benign) –> mutation inactivates DNA repair genes –> protooncogenes turned into oncogenes –> more mutations and more genetic instability –> metastasis
hallmarks of cancer (6)
- sustaining proliferative signal
- evading growth suppressors
- active invasion and metastasis
- enabling replicative immortality
- inducee angiogenesis
- resist cell death
sustaining proliferative signal done by
- local stimulation
- altering to always be on
- overexpression of receptors
example of a gene mutation to sustain proliferative signal
KIT gene mutation meaning receptor autophosphorylates so is always on
evading growth suppressors how
- loosing growth suppressor receptors
- making receptors unfunctional
avoiding cell death
- upregulation of survival factors
- not displaying death receptor
enabling replicative immortality
enzyme telomerase is needed to add telomeres to DNA
telomeres and DNA
some are lost during every replication so eventually replication stops as no more telomeres
induction of angiogenesis
secrete angiogenic factors
activating invasion and metastasis
- need matrix metalloproteinases to disrupt surroundings
- need change in cell adhesion molecules so that no longer stuck to neighbouring cells
2 emerging hallmarks of cancer
- deregulation of cell energetics
- avoiding immune destruction
how cancers avoid immune destruction (4)
- decrease immunogenic antigen
- kill tumour infiltrating lymphocytes
- immunosuppressive mediators
- inducing immune tolerance
inflammation and tumours
promote tumour growth as inflammation is immunosuppressive, has growth factors and angiogenic mediators
gold standard for cancer diagnosis
histopathology
patnaik system grading mast cell tumours grade 1
- low grade
- acts benign
- well behaved
patnaik system grading mast cell tumours grade 2
intermediate
patnaik system grading mast cell tumours grade 3
- high grade
- aggressive
- likely to spread
staging of tumours define
decide if local or if has spread
TNM system for staging tumour
T - primary tumour
N - associated lymph node
M - metastasis
For T of TNM staging system
- size
- mobility- ulceration
- relationship to surrounding tissues
for N of TNM staging system (5)
- size
- mobility
- relationship to surrounding tissues
- texture
- consistency
- may need to FNA for metastasis
for M of TNM staging system
- history
- physical exam
- imaging?
lymphoma stage 1
limited to single lymph node or lymphoid tissue in organ excluding bone marrow
lymphoma stage 2
more than 1 lymph node affected in local area
lymphoma stage 3
generalised involvment across the diaphragm
stage 4 lymphoma
liver and or spleen involvment
stage 5 lymphoma
maifestation in blood or bone marrow/other organ systems affected
2 substages in the staging of lymphoma
a - no systemic signs
b - systemic signs
prior to cancer tx do
- CBC
- haematology
- urinalysis
- coagulation profile
- as then you have a baseline for any changes
define hyperviscosity
thick sludgy blood
tx options cancer
- cure
- remission
- palliation
- control
important to consider in cancer treatment
ensure a good quality of life!
chemotherapy is mainly used in tumours with
high metastatic potential
cytotoxic drugs must not be
- handled by pregnant women
if in tablet or capsule form - must not be crushed or opened
when giving chemotherapy use what system
phaseal
chemotherapy patient animal poop and urine
- double bag poo and wee
- do not let animal go where children play
4 ways that tumours spread
- lymphatic
- vascular
- local
- trans-cavity
local spread is usually done by what tumour type
carcinomas
vascular spread is usually done by what tumour type
sarcomas
trans-cavity spread is usually done by what tumour type
mesotheliomas
what cell type makes a mesothelioma
lining of body cavity
define multicentric tumours
where cant determine primary tumour/tumour of origin at presentation
immunohistochemistry and tumours
can be used to identify surface markers on tumour cells so can figure out cell types
cytokeratin is a marker for what cell types
epithelial
carcinomas are made of what type of cell
epithelial
vimentin is a marker for what cell type
mesenchymal
sarcomas are made of what cell types
mesenchymal
CD3 is a marker for what cell
T cell
CD79a is a marker for what cell
B cell
2 things to think about when fixing a sample in formalin
- formalin to sample ratio no smaller than 4:1
- longest dimension 2cm max
6 reasons for chemotherapy
- primary treatment for disseminated (widespread) disease
- adjuvant therapy following surgery on highly metastatic tumour
- following incomplete resection
- neoadjuvant therapy to shrink prior to surgery
- treatment of tumours not amenable to radiation or surgery
- primary tx for venereal tumour
when giving adjuvant chemo consider
surgical wound needs time to heal before you start
cell kill hypothesis (chemo)
a given dose will kill a fixed percentage of the tumour population
theory of pulse dosing (chemo)
time between doses is so much to allow body to recover but not too long that tumour regrows
drugs used for chemo better
if used in combination
combination therapy use drugs that (chemo) 4
- are effective against tumour individually
- do not have overlapping toxicities
- different modes of action
- affect cells at different stage of cell cycle
combination therapy chemo pro
can use less of each drug
4 stages of chemo
- induction
- maintenance
- re-induction
- rescue
rescue stage in chemo is when
tumour becomes resistant to therapy so need different drugs
metronomic chemotherapy
continuous low dose cytotoxic drugs
aim of metronomic chemotherapy
to slow growth of tumour
receptor tyrosine kinase inhibitors and chemo (4)
- inhibit angiogenesis
- promote apoptosis
- reduce proliferation
- not cytotoxic
4 adverse effects chemo
- myelosuppression
- GIT toxicity
- poor hair growth
- drug extravasation
define myelosuppression
bone marrow suppression
define drug extravasation (chemo)
where drug spills onto tissues, can do a lot of damage in chemo
if drug is extravasated then (3)
- keep catheter in place
- try to withdraw as much as possible
- apply ice pack or heat. this is drug specific so contact drug company
doxorubicin side effects
- dysrhythmias during administration
- chronic toxicity leads to dilated cardiomyopathy
- mast cell degranulation causes allergy like response
cyclophosphamide side effects
haemorrhagic cystitis
vincristine side effects
- peripheral neuropathies
- constipation
lomustine side effects
- hepatotoxicity
- nephrotoxicity
platinum drugs side effects
- nephrotoxic
- vomiting
do not give cats 2 drugs for chemo
- cisplatin
- 5-FU
alkylating agents chemo action
- substitute alkyl group for H+ causing breaking of DNA strands
- not cell cycle phase specific
mitotic spindle inhibitors chemo action
- bind to tubulin stopping microtubule formation
- stop cycle in metaphase
anti-metabolites chemo action
- inhibit enzymes or cause production of non-functioning molecules
- work during S-phase
anti-tumour antibiotics chemo action
- stop DNA/RNA synthesis
- not cell cycle phase specific
platinum compounds chemo action
- interferes with DNA/RNA synthesis similar to alkylating agents
- not cell cycle phase specific
corticosteroids in chemo why
cause apoptosis of lymphoid cells
L-asparaginase in chemo why
- treatment of lymphoma and leukaemia
- cancer cells rely on other sources of L-asparagine as they cant make it like normal cells
NSAIDs chemo use why
- inhibit angiogenesis
- promote apoptosis
- anti-inflammatory
- analgesic
- used in metronomic therapy
3 different types of radiation used in radiation therapy
- x-ray photons
- gamma ray photons
- particles
effect of radiation in radiation therapy
- particle effect
- creates oxygen free radicles
effect of oxygen free radicals in tissues
damages cell membranes, proteins and nucleic acid
best tumours for radiation therapy
- well oxygenated ones so smaller tumours
- proliferative tumours
acute effects of radiation therapy occur
- in rapidly dividing tissue in radiation field
- no permanent damage
late effects of radiation therapy occur
- in slow dividing cells in irradiation field
- radiation kills of stem cells so when the slow proliferating cells die theres nothing to replace them
- permanent changes
5 common tumours for radiation therapy
- brain
- nasal
- oral
- soft tissue sarcomas
- mast cell tumours
when taking multiple biopsies consider
use fresh instruments for each one to limit contamination
a biopsy should include
junction of normal and abnormal tissue
most active and invasive parts of a tumour are
the edges
when dissecting a tumour do not
handle the tumour directly instead handle normal adjacent tissue
after tumour removal change
instruments for closure
ligation and tumours
ligate the veins and lymphatic drainage of tumour then the arteries before removal
3 types surgical margin of excision of tumours
- local excision
- wide local excision
- radical local excision
local excision of tumours is where
tumour removal through natural capsule, immediate boundaries or with minimum adjacent tissue
indications for local tissue excision of tumours
benign tumors with no tendency for local infiltaration
wide local excision of tumours is where
tumour is removed with substantial margin of surrounding tissue
2 indications for wide local excision of tumour
- benign with capacity for local infiltration
- malignant with limited potential for infiltration
radical local excision is
tumour removed with margins that extend into fascial planes that are undisturbed by tumour growth
3 techniques for radical local excision of tumours
- compartmental excision
- muscle group excision
- amputation
compartmental excision is
removal of tumour with all the blood vessles and nerves in the compartment and overlying skin
muscle group excision
tumour removed with whole muscle that it involves
amputation and local radical excision
tumour removed with entire limb
define debulking of tumour (cytoreductive surgery)
incomplete removal to improve efficacy of treatment
palliative surgery define
improves patients quality of life but not the length
