Week 3 - Lecture 3a - Clinical Models Pt.1 Flashcards Preview

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Flashcards in Week 3 - Lecture 3a - Clinical Models Pt.1 Deck (28):
1

Lung cancer pathophysiology

leading cause of cancer deaths world wide

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lung cancer patho # 2

tumour growth is initiated by mutations that can
- activate oncogenes
-subdue tumour suppressor genes
-cause deletion in chromosome 3

lung cancer is the end stage of multiple mutations and cellular transformation
1. tumour enlarges
2. penetrates epithelial layer
3. moves into lung tissue, pleural cavity, chest wall (Seeding)
4. metastatic spread : lymph channels, blood vessels

lung cancer metastases are tropic to bone, liver, brain

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lung cancer patho #3

tumours originate most frequently in the epithelial lining of the
- bronchi
-bronchioles
-alveoli
four subtypes
1. adenocarcinoma (35%) - C
2. squamous cell carcinoma (30%) - A
3. small cell carcinoma (20%) - B
4. Large cell carcinoma (15%) - D

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adenocarcinoma (lung cancer)

develop in peripheral bronchiolar and alveolar lung tissue
leads to pleural fibrosis and adhesions
further subdivisions

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squamous cell carcinoma (lung cancer patho)

cell injury of bronchiolar columnar epithelium (smoking) triggers metaplasia -- dysplasia -- carcinoma in situ -- invasive carcinoma

tumour cells can be detected in sputum (coughed up from respiratory tract)

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small cell carcinoma

highly malignant
grows and develops metastases rapidly
tumour cells cause hemorhharge and necrosis
strongly linked to smoking

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large cell carcinoma

tumour cells are large
high levels of anaplasia
metastasise readily
diagnosis is based on exclusion of others

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subtypes prevalence vary by gender

adenocarcinoma : most common in women and non smokers
small cell carcinoma : higher rate in males
squamous cell carcinoma : higher rate in males, linked to smoking

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clinical manifestations of lung cancer

common clinical manifestations relates to location
- persistent cough
-hemoptysis
-chest pain
-shortness of breath
often ignored as 'smoker's cough'

common general manifestations are present
paraneoplastic manifestations are present

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Lung cancer diagnostic criteria

history taking, physical examination, imaging
-bronchoscopy
- chest x ray
- MRI/CT/ultrasound
-carcinoembryonic antigen (CEA) may be present

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prognosis for lung cancer is dependant on

CEA level
ability to surgically remove the tumour
lymph node involvement
presence of metastasis

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Lung cancer treatment

based on tumour type
1. small cell carcinoma
-chemotherapy
-- more likely to respond
-- more likely to be widely disseminated at diagnosis
- - patients develop distant metastases
- - surgical resection and radiation : limited contribution to long term survival

non small cell carcinoma : treatment depends on the ability to resect (surgery) (adenocarcinoma, squamous cell carcinoma, and large cell)
-resectable : may be cured by surgery alone or with chemotherapy combination.

- non resectable : local control of tumour growth with radiation, cure is unlikely

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lung cancer treatment part 2

least favourable prognosis
- small cell carcinoma
- large cell carcinoma

many lung carcinoma are not detected until tumour is well advanced
early symptoms (chronic cough ) often ignored

overall 5 year survival rate 15%

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colorectal cancer patho

exact cause is often not clear
primary risk factor : age
90% of cases in adults diagnosed over >50
multiple lifestyle risk factors
protection
- selenium, ACE vitamins, veggies

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colorectal cancer

tumours are most often of epithelial origin
-adenoma (benign)
- adenocarcinoma (malignant)

three groups of colorectal cancer
1. non - neoplastic polyps (not generally considered a cancer precursor)
2. neoplastic polyps (adenomatous polyps, adenomas, increased carcinoma development, considered a cancer precursor)
3. cancers (most often adenocarcinoma)

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colorectal cancer patho cont' 3

number of major deleterious mutations required to promote tumour development : average 5-7
number of major deleterious mutations in cancerous tumours of the colon/rectum : average 9

two pathways identified to lead to carcinoma development

- series of events triggering chromosomal instability (85%)
- loss of tumour suppressor ability
--imparied DNA repair
-mutations in the APC tumour suppressor gene (adenomatous polyposis coli) lead adenomatous polyp (precursor to malignant tumour)

replication errors (15%)
- chromosomes remain intact, defects in DNA repair

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colorectal patho pt 4

in both mutations (chromosomal instability and replication errors)
- cellular transformation in mucosal epithelium begins at the base of the crypts
-cells move to the surface, die and slough off

- with APC (adenomatous polyposis coli) mutation, tumour cells resist apoptosis and accumulate on the bowel surface
- continue to proliferate to form benign adenomatous polyps (precursor)
-mutation of DCC (deleted in colon cancer) and P53 tumour suppressor gene leads to further transformation and malignant tumour

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colorectal cancer : clinical manifestations

manifestations depend on location and characteristics pf the tumour

early stages : asymptomatic
enlargement of tumour : ulceration and haemorrhage
- tumour is along ascending colon : occult blood in stool
-tumour is along descending colon or rectum : frank blood in stool
- abdominal pain
- bowel obstruction
-anaemia : the result of blood loss in the stool
- change in bowel habits

common general manifestations are present
paraneoplastic manifestations are present

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diagnostic criteria : colorectal cancer

history taking, P/E
rectal cancer : Digital examination

colon cancers : colonoscopy (direct visualisation )
recommended >50 yrs

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treatment of colorectal cancer

when localised in bowel : highly treatable and often curable

- localised tumour : surgery- results in cure in 50% of patients

locally advanced or metastatic disease : combination drug chemotherapy and radiation

prognosis depends on
- location of the tumour
- degree of penetration
- bowel obstruction or perforation
-lymph node involvement
- presence of distant metastasis (usually liver)

resectable (surgically cut) hepatic metastasis at diagnosis (50% of patient) 5 year survival rate of 25-40%

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Brain cancer patho

brain cancer affect men more frequently than women
caucasians are affected more than other races
cause is unknown
- exposure to ionising radiation during treatment increase risk

metastasis of other cancer types to the brain is much more common than primary brain tumours (10:1 ratio)

metastasis originates most commonly : lung, breast, skin, colon

tropic tumours
-preference for cerebral hemispheres (80%)
-cerebellum (15%)
-Brainstem(5%)

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pt 2 Patho brain cancer

primary tumour originate from
- glial cells : non-neurone in the CNS and PNS
- astrocytes, oliodendrocytes, microglia

Meninges : membranous covering of the brain

schwann cells : produce myelin and collagen
- schwannoma : within the brain, spinal nerve, peripheral nerves
- rarely malignant

ectopic tissues : embryonic cells migrated to brain and spinal cord
-lipoma (embryonic adipose tissue)
-slow growth - undetected for lifetime

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Brain cancer patho : primary tumour

glial cell origin: glioma
specific astrocyte origin : astrocytoma
- most common tumour originating in brain
-differentiation level varies at diagnosis
-20% well differentiated
-40% highly undifferentiated
(rest in between)
Benign or malignant
-as glioma enlarge
-- impinge on vital brain structures
--become fatal
--metastases development is rare

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Brain cancer patho

meninges meningioma
-emerge middle/late adulthood
slow growing
erode the cranium

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brain cancer clinical manifestation

depend on size and location of tumour
- neurologic deficit appear as the tumour erodes functional neurons
- sensory and motor loss
-- visual changes, numbness, weakness paralysis
-cognitive and personality changes
pressure increase in cranium : growing tumour/inflammation /fluid accumulation
- headache
-vomiting

cell irritation
- seizures

tumour compression of respiratory and cardiac centre : death

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brain cancer diagnostic criteria

history P/E

neurological examination
- testing cranial nerve
-reflexes
-sensory
-motor

direct visualisation
Brain scan
CT/MRI
-X-ray
-Cerebral angiography
PET scan

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Brain cancer diagnostic criteria classification

TNM classification is not used for brain tumours
-tumour size is less relevant than the location and histology
-the brain and spinal cord have no lymphatics
-metastatic disease spread is rare

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brain cancer treatment

treatment depends on
location
extent
nature of neoplasm

primary tumours : surgical resection
- goal to remove it completely
-preserve neuro function

radiation
chemo
- spinal canal
-directly in brain during surgery

widespread tumours : whole brain radiation
palliative care for seizures