Week 3 - Lecture 3a - Clinical Models Pt.1 Flashcards
Lung cancer pathophysiology
leading cause of cancer deaths world wide
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
- tumour enlarges
- penetrates epithelial layer
- moves into lung tissue, pleural cavity, chest wall (Seeding)
- metastatic spread : lymph channels, blood vessels
lung cancer metastases are tropic to bone, liver, brain
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
adenocarcinoma (lung cancer)
develop in peripheral bronchiolar and alveolar lung tissue
leads to pleural fibrosis and adhesions
further subdivisions
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)
small cell carcinoma
highly malignant
grows and develops metastases rapidly
tumour cells cause hemorhharge and necrosis
strongly linked to smoking
large cell carcinoma
tumour cells are large
high levels of anaplasia
metastasise readily
diagnosis is based on exclusion of others
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
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
Lung cancer diagnostic criteria
history taking, physical examination, imaging
- bronchoscopy
- chest x ray
- MRI/CT/ultrasound
- carcinoembryonic antigen (CEA) may be present
prognosis for lung cancer is dependant on
CEA level
ability to surgically remove the tumour
lymph node involvement
presence of metastasis
Lung cancer treatment
based on tumour type
- 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
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%
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
colorectal cancer
tumours are most often of epithelial origin
- adenoma (benign)
- adenocarcinoma (malignant)
three groups of colorectal cancer
- non - neoplastic polyps (not generally considered a cancer precursor)
- neoplastic polyps (adenomatous polyps, adenomas, increased carcinoma development, considered a cancer precursor)
- cancers (most often adenocarcinoma)
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
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
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
diagnostic criteria : colorectal cancer
history taking, P/E
rectal cancer : Digital examination
colon cancers : colonoscopy (direct visualisation )
recommended >50 yrs
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%
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%)
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
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
Brain cancer patho
meninges meningioma
-emerge middle/late adulthood
slow growing
erode the cranium
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
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
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
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
