NEOPLASIA & ENDOCRINE Flashcards
what are the most prevalent cancers in females?
1.breast- 2. lung- 3. colon
what are the most prevalent cancers in males?
- prostate- 2. lung- 3. colon
what is the use of imaging in cancer?
screening, detection (either investigating or incidental- person may have clinical signs), monitoring (imaging shows if the selected therapy is effective)
what is detection based on?
identified abnormalities of soft tissue or bone, functional imaging, molecular imaging
what is diagnosis ultimately based on?
biopsy/pathological examination
what is neoplasia?
a spectrum of diseases based on biopsy/pathological examination- cause defect in control of cell growth leading to excessive, unregulated growth leading to tissue mass- new, uncontrolled growth of cells that are not under physiological control- create neoplasm
what is neoplasm?
an abnormal mass of tissue that results when cells divide more than they should or do not die when they should (apoptosis)
what is normal cell growth controlled by?
by humoral (endocrine) factors & direct cell to cell interactions
what is a tumour and a cancer?
tumour is a lump which may not be neoplastic- cancer implies malignancy
what can cells undergo?
can undergo atrophy (smaller), hyperplasia (increase in cells- too much can lead to dysplasia), metaplasia (cells change- may lead to dysplasia)- hypertrophy (cells increase in size- can lead to hyperplasia)
what do cancers result in?
proliferation, invasion & metastasis- can be mutations (change in genetic code) or epigenetic changes (influence gene expression & cell behaviour, transmitted to daughter cells but not changes in genetic code)- may occur in cancer stem cells
what are cargionogens?
radiation, chemicals, oncogenic viruses, chronic inflammation, physical substances
how is radiation carcinogenic?
dependent on dose & additive- radiation damaged cells are more susceptible to other carcinogens- radiation damages DNA and also affect gene involved in DNA repair
how are chemicals carcinogenic?
2 steps: initiation (carcinogen leads to DNA damage but not neoplastic change)- promotion (2nd carcinogen leads to damage to iniated cells & neoplastic changes)- doesnt cause neoplastic change in uninitiated cells
what are examples of carinogens?
oncogenic virus (virus that has potential to cause cancer, by damaging the DNA by inserting their viral DNA to the host DNA)- chronic inflammation- physical substances
what has to occur to have a neoplastic transformation?
believed to almost always be multifactorial, with a series of cellular events adding to each other
where do cancers come from?
90% of cancers are environmental (non-heritable), 10% are genetic (inherited from your parents)
how does carcinogenisis occur?
environmental agents damage DNA & inhertied mutations- cells can either repair or be damaged, which cause mutations & can either undergo oncogenesis, impaired apoptosis (cells that should die dont, inactivation of tumor suppressor genes- alters gene production causing malignant tumour
what are the causes of breast cancer?
more than 90% of women with BRCA mutation develop breast cancer BUT 90-95% of breast cancer in women do not have the mutation- cancer is due to spontaneous after birth- only way a mutation can be passed on is if cancer is in a oocyte or sperm cell
where must the mutation occur to pass to the next generation?
must occur in germ cell e.g. sperm or oocyte
what are characteristics of cancer cells?
proliferate despite lack of growth initiating signals, avoid apoptosis due to presence of telomerase (excessive shortening which prevents it to repair), lose differentiated features & don’t contribute to organ function, ability to metastasise (malignant= spreads to different sites in the body)
is the tumour cell population heterogenous?
yes- overtime, many cancers become more adapted to the environment & difficult to treat
how do tumour cells change?
changes to metabolic pathway to help tumours cope to hypoxic environment & increase angiogenesis
what are hypoxic cells?
cells are deprived of oxygen- has an adverse effect on radiotherapy- cause selection of cells with apoptotic insensitvity & increased angiogenic potential- adaptation that helps them to survive
how are cancer classified?
by their tissue of origin or anatomic location
what are the 3 cell lineages established during development?
ectoderm (rise to external surface), endoderm (internal body surface), mesoderm (rise to tissue in between)
where do malignant carcinomas & sarcomas arise from?
carcinomas (ectoderm or endoderm e.g. lung, colon, breast)- sarcomas (mesoderm e.g. bone, muscle, cartilage, blood)- most common form of cancer & travel via lymphatic system- tumours that arisen from the ectoderm
what population are sarcomas & carcinomas popular in?
carcinomas (adults)- sarcomas (active in growing infants & children because mesenchymal tissue are active)
what are carcinomas derived form?
epithelial cells (squamous cell carcinoma) & glandular epithelium (breast, prostate, lung, stomach)- most common form of cancer
what are sarcomas derived from?
haemotopoietic tissue (leukaemia & lympoma), connective tissue (cartilage, fat, muscle, bone)- usually spread by blood- more common in growing infants & children because mesenchymal tissues are very active
what are examples of benign tumours?
have suffix “oma” e.g. adipose tissue (lipoma), skin (papilloma)
what are preinvasive (or carnicoma in situ) carcinoma?
not invaded any surrounding tissue
what are invasive carcinomas?
invaded surrounding tissue
what are metastatic tumours?
spread to distant organs & other tissue via lymphatics or blood stream
what may indicate a preclinical phase?
e.g. polyps in colon- may precede the development of cancer by years or may not progress to cancer
what can growth indicate with benign or malignant tumours?
benign (encapsulated- grow in to surrounding tissue)- malignant (invade adjacent tissues & rarely have a capsule)
how can differentiation determine benign or malignant?
Benign tumours are generally well-differentiated malignant tumours generally poorly differentiated
how can rate of growth determine benign or malignant?
Most benign tumours grow slowly. Malignant tumours grow quickly in parallel with degree of anaplasia. Malignant tumours often have many mitoses.
how can invasion determine benign or malignant?
benign tumours do not invade adjacent tissue & do not metastasize
what are the processes of metastasis?
direct seeding of body cavities & surfaces, lymphatic spread (most common pathway- usually into lymph nodes initially), hematogenous spread (typical pathway for sarcomas but also carcinomas- vascular spread may occur to liver, lungs & bones)-
what is a primary & secondary tumour?
primary is the original tumour e.g. tumour started in pancreas- secondary is the primary tumour that spreads to the bone is secondary
what are the systematic effect of tumours?
mass effect (obstruct blood vessels, bowel, impinge on nerves, cause destruction of normal tissue)- systemic effects (cachexia- caused by cytokines produced by tumour and/or host response or paraneoplastic synodrome, which is caused by abnormal immune response to tumour e.g. fever, skin or nervous dysfunction)
what is the TNM system?
t= primary tumour site (the higher the score, the larger it is), N= describes regional lymph node involvement (indicates if it spread- higher the N score, more involvement of lymoh nodes), M= describes the presence or otherwise of distant metastatic spread (higher the score, more spread)
what is TNM staging?
determines treatment plan- considers site of origin of cancer, histological/biological characteristics, anatomical extent of cancer
what are common methods of TNM?
CT, PET-CT & MRI
what is the mainstay of diagnosis of cancer?
histological exam- tissue is obtained by direct surgical biopsy or resection
what is therapy selection based on?
aggressiveness of cancer, potential of spread, therapy hazards, established success rate of therapy
what are methods to remove stem cells to eradicate neoplasm?
surgery or radiation therapy (cell death will not occur until cell attempts to divide)
what is radiation therapy based on?
cell cycle 4 cycles
what are the 4 cycles of radiation therapy?
G1 (gap 1- dormant cells remain in G1 indefinitely- cell cycle begins when cells pass through restriction point late in G1)- S (synthesis- dna duplication), G2, MITOSIS
what cells of the cell cycle are most sensitive to radiation?
mitotic cells
what happens if G1 has an appreciable length?
there is a resistant period that declines towards the S phase
when does resistant increase in cell cycle?
S phase, when DNA duplicates
is G2 phase as sensitive as mitosis stage in cell cycle?
yes
can temporal response to radiation vary between tumour types?
sarcomas show little cell loss, carcinomas show high ates of cell loss
what is chemotherapy used for?
when cancer is disseminated, surgery or radiation impractical, demostrated efficacy, or an adjunct to surgery
what is immunotherapy?
acts as a vaccine that immune system can destroy
what causes physical and psychological injury to patients during chemo?
drugs interfere with cell cycle is all cells- rapidly proliferating cells are worst affected
what is the aim of chemo?
remove a large proportion of cells in order to allow natural immunity to handle tumour - larges tumours less affected than smaller tumours because there are fewer dividing cells- chemotherapeutic agents induce tolerance due to selection of drug resistant cells
what is RECIST?
response evaluation criteria in solid tumours) defining when cancer patient improve, stay the same, or worsen
how is treatment response monitored?
by measuring the dimensions of primary tumour & dimensions of a # of lymph nodes & abnormalities- uses function & molecular imaging
what are hormones?
chemicals that are produced by secretory cells, secreted into blood, carried to all parts of body by blood- act by combining with receptors either intracellular (lipid soluble) or on cell surface (protein)- hormones are not effecting every cell in the body- only target cells contain receptors to recognise the hormone
what are exocrine secretions?
secretions on to body surface + pancreas (digestive enzymes)
what are secretory tissues?
endocrine glands & neurohumeral organs
what are endocrine glands?
secretory cells that are chemically stimulated & intermingled with capillaries- release directly in to the blood
what are neurohumoral organs?
neurons that terminate at capillaries & are neuronally stimulated
what does the combination of hormone & receptor result in?
production of second messenger (additional chemicals)
what does the hypothalamus stimulate?
pituitary gland
what are the 2 parts of pituitary gland?
posterior (neurohypophysis) + anterior (adenohypophysis)
what does the hypothalamus produce?
TRH, GnRH, GHRH
what does TRH stimulate?
pituitary to produce TSH, which stimulate thyroid to produce T3 & T4
what does GnRH stimulate?
pituitary to produce FSH & LH, whcih stimulates the repro tissue to produce testosterone & estrogen
what does GHRH stimulate?
stimulates pituitary to produce GH which stimulates growth in tissu e
what is the hormone system controlled by?
negative feedback
what can a tumour in the pituitary result in?
uncontrolled TSH production leading to hyperthyroidism
what could a tumour surrouding the tumour lead to?
pressure atrophy of gland leading to decreased TSH production leadin to hypothyroidism
how do we investigate endocrine diseases?
laboratory testing, non invasive imaging e.g. MRI, CT, ultrasound (only after laboratiry testing), venous sampling (pituitary, kidney, adrenal, pancreas, parathyroid- draining a specific gland within the body)
what are the 3 major types of endorine disease?
hormone excess (neoplasia, autoimmune disorders, excess hormone administration), hormone deficiency (surgery, iatrogenic, infection, inflammation, autoimmune), hormone resistance (defects in membrane receptors or acquired
what are symptoms of endocrine disease?
results in multisystem signs & symptoms e.g. myopathy (effecting the muscle due to adrenal dysfunction, thyroid dysfunction, parathyroid dysfunction)- not completely understood
what are 2 parts of the adrenal gland?
adrenal medulla (produces adrenaline, noradrenalie & dopamine- catecholamines) & adrenal cortex (cortisol, aldosterone for blood volume, DHEA sex hormone)
what is elevated and low blood cortisol?
hyperadrenocorticism (cushing syndrome)- low blood cortisol is hypoadrenocorticism
what controls cortisol production?
hypothalamus produced CRH to pituitary, which produced ACTH, which travels to adrenal and produces cortisol, cortisol then goes back to hypothalamus & pituitary
why would we have high levels of cortisol in blood?
hypothalamic problem (CRH is high, ACTH is high, cortisol is high)- pituitary problem (CRH is low, ACTH is high, cortisol is high), adrenal problem (CRH is low, ACTH is low, cortisol is high)
why would we have low levels of cortisol in blood?
hypothalamic issue (CRH is low, ACTH is low, cortisol is low), pituitary problem (CRH is high, ACTH is low, cortisol is low), adrenal issue (CRH is high, ACTH is high, cortsol is low)
once cushings syndrome is confirmed, what is further imaging dictated by?
by ACTH testing
what happens if ACTH is suppressed, normal or high?
ACTH suppressed (likely primary adrenocortical lesion & CT scan of adrenal is required)- normal or high (either pituitary disease or ectopic source of ACTH)
what does anterior pituitary produce?
FSH & LH, GH, prolactin, ACTH, TSH
what does posterior pitutary produce?
oxytocin & ADH
what are benign endocrine tumours?
adenomas- often non function, incidental finding- some potential to become malignant (adenocarcinomas)- need to differenitate from cysts
