Lung cancer Flashcards
Risk factors
main smoking - many carcinogens, if smoke cells will be exposed
radon
asbestos
mutational compensation
all cells have a tendency to become immortal
p53 gene prevents this by apoptosis
smoking stops this - process is unchecked in smoker
have genetic tendency too - oncogenes too.
smoking and prevalence of lung cancer
the curves of prevalence of cancer and smoking are out of phase by 10 years but match up
there is a significant risk of cancer in passive smokers, dose dependant effect of the number of cigarettes smoked
there is a commulative risk of smoking - still risk increases if continue smoking at age 60 - always worth stopping
Symptoms
haemoptysis - cough up blood symptoms that are unexplained that last >3 wks: cough shoulder/chest pain dyspnoea hoarseness finger clubbing - angle between nail and nail bed more obtuse, nail bed more boggy weight loss lethargy declining appetite
features seen on examination with lung cancer
clubbing of fingers
nicotine staining
cachexia - loss of appetite and weight
diminished air entry into R base
survival according to stage
related to suitability for surgery
considered in stage 1, 2 and 3a
need to detect early
5% overall risk and 10% major complications
prognosis
80% die in a year
5yr survical/cure rate <6%
where does lung cancer arise
large airway
terminal airway
alveoli
causes of lung cancer
smoking - 75% attributable - 25% attributed to passive smoking; tumour initiators, promoters and complete carninogens - polycyclic aromatic hydrocarbons, phenols, Nickle and arsenic
asbestos
radiation - radon exposure and therapeutics
genetic predisposition - rare
heavy metals - chromates, arsenic nickle
molecular abnormality
risks multiplicative
Development of carcinoma
multistep accumulation of mutations cause:
metastasis
disordered growth
loss of cell adhesion
invasion of tissue by tumour
stimulation of new vessel formation around tumours
mutations in epi cells and stem cells
pathways diff for diff tumour types - molecular therapies
early stages can be reversible
reflected in histology of tumours
benign lung tumours
don’t metastasise
local complications
chondroma - airway obstruction
malignant lung tumours
potential to met variable clinical behaviour commonest epithelial - carcinoma non-epi - sarcoma and lymphoma non-small cell 80% small cell 20% `
non-small cell carcinoma
squamous - 20-40%
adenocarcinoma 20-40%
large cell carcinoma - uncommon
small cell carcinoma
advance
aggressive
small survival
poor prognosis
presentation with lung cancer
asymptomatic symptoms vague: cough haemoptysis recurrent infection weight loss/malaise
local effects
bronchial obstruction - collapse of distal lung = shortness of breath or impaired drainage of bronchus - chest infection = pneumonia/abscess
invasion local structures - airways and vessels = haemoptysis and cough, large vessel = SVC syndrome - venous congestion of head arm oedema and upper circ collapse, oesophagus = dusphagia, chest wall = pain, nerves = horners syndrome
inflame/irritation/invasion of pleura/pericardium - pleuritus or pericarditis with effusion = breathlessness, cardiac compromise, fluid needs to be drained
systemic effects of bronchogenic carcinoma
don't present with primary cancer fits - brain met lumps on skin - stained to show primary lung liver pain/deranged LFTs - liver met bone pain/fracture - bones paraneoplastic syndromes
change in classification of tumour
used to be small lung cancer/non-lung small cancer
now more sub groups
immunotype the tumour
see if squamous cell carcinoma
adenocarcinoma
adenosquamos carcinoma
molecular phenotype - have different phenotypes
molecular phenotype of cancers
look at molecular fingertype
PDL-1 - death ligand - if >50% then the patients are suitable for immunotherapy
adenocarcinoma - tumour of EGFR gene for tyrosine kinase, ALK gene, ROS -1, kRAS - can give targeted treatment if mutations in these are present (crizotinib for AlK gene mutation)
Treatment
small cell cancer - rapidly dividing - chemo
non-small cell lung cancer - slow - cut out and can use chemo/radio after surgery
non-metastatic manifestations of lung cancer - eg wrist pain from tumour or increased Ca causing swelling - chemo/immunotherapy
death from malignant change of different types of cancer
squamous - 9.6
adenocarcinoma - 17.6
undifferentiated - 9.4
small cell - 3.2
squamous cell carcinoma development
squamous epithelium
not normally in lung
cilia irritated by carcinogens - metaplasia to squamous
more resistant to smoke
cant remove debris
chronic cough
dysplasia - disordered growth and differentiation
carcinoma in situ
mutation produce enzymes and MMP so invade stroma
metastasise
molecular and genetic changes in development of squamous cell carcinoma
3pLOH microsatellite alterations Myc overexpression and telomerase dysregulation neoangiogenesis gene methylation P16ink4 K-ras mutation
location of squamous cell carcinoma
previously in central airway
now smoke breathed more deeply
in lower airways SqCC - peripheral
squamnous cell carcinoma
25-40% pul carcinoma
smoking
local spread
met late