The respiratory system - Tobacco smoking and lung cancer Flashcards
Name 6 harmful substances in tobacco and their effect
Tar - carcinogenesis
Polycyclic aromatic hydrocarbons - carcinogenesis
Nicotine - Ganglionic stimulation and depression; tumour promotion
Benzo(a)pyrene - Carcinogenesis
Carbon monoxide - Impaired oxygen transport and utilization
Formaldehyde - Toxicity to cilia; mucosal irritation
Nitrogen oxides -Toxicity to cilia; mucosal irritation
Nitrosamine - Carcinogenesis
Describe the 3 patterns of emphysema
Centrilobular (also known as centriacinar)
- Central/proximal apolar until invollved
- Distal alveoli spared
- More severe in the upper lobes
Panacinar (pan lobular)
- Whole of the alveolar unit involved
- More commonly in the lower lobes
- Associated with alpha 1 antitrypsin deficiency
Paraseptal (distal acinar)
- Proximal alveolar unti normal
- Emphysematous change more evident near the pleura, along septa and markings of lobules
Describe the cellular transformation of the respiratory tract in smokers. What is this transformation known as?
Columnar epithelium becomes squamous epithelium
This is known as metaplasia
Describe the advantages and disadvantages of tracheobronchial squamous metaplasia in smokers
Advantages
- Squamous epithelium is more resistant to thermal and chemical damage
Disadvantages
- Reduced function
- Increase propensity for malignant transformation
Describe the role of the pathologist in the lung cancer pathway
Diagnosis
- Bronchial washings and brushings
- Endobronchial ultrasound guided transbronchial (finde) needle aspirations (EBUS TBNA)
- Lung biopsy
- Bronchial biopsy
Staging and reporting of lung excision
- Type of tumour
- Size
- Margins
- Pleural involvement
- Vascular invasion involvement of adjacent structures
- Lymph node involvement
Aiding personalised oncological treatment with molecular markers/analysis
Give the two main categories of lung cancer
Non-small cell lung cancer
Small-cell lung cancer
Give the 3 types of non-small cell lung cancer
- Adenocarcinoma
- Squamous cell carcinoma
- (Undifferentiated) Large cell
Risk factors of lung cancer
- Cigarette smoking
- Occupational exposure (asbestos, motor vehicle emissions, pollutants, radon gas)
- Genetics/family history of cancer
- Low level radiation
- Smoking and low intake of beta carotene
- Lung disease history
Describe the features of adenocarcinoma
- Localisation: lung peripheries
- Cancer of mucus-secreting cells
- Most common form of lung cancer
- Most common lung cancer in non-smokers
- Risk factors: smoking and asbestos
- Commonly invades the mel lymph nodes and the pleura and spreads to the broad and bones
- Non-invasive subtype: brochioalveolar carcinoma
- Does not usually cavitate
- Most likely cause of pleural effusions
Describe the features of squamous cell carcinoma
- Localisation: central airways
- Second most common form of lung cancer
- Smoking is the most common cause
- Metastases tend to occur late, histopathology classically shows keratin
- Occasionally cavities (10% at presentation)
- Can cause neoplastic syndrome: associated with ectopic produced of parathyroid hormone-related peptide (PTHrP) leading to hypercalcaemia and hypertrophic osetoarthopathy
Describe the features of undifferentiated (large cell)
- Undifferentiated neoplasms accounting for 5% of lung cancers
- Grow quickly and tend to metastasise early so usually diagnosed in later stages
good prognostic factors of NSCLC
- Early-stage disease at diagnosis
- Good performance status
- No significant weight loss
- Female gender
Describe the features of small cell lung cancer
- Considered separately due to its fast-doubling time, aggressive nature, and early metastasis
- It is a cancer of the APUD cells, a neuroendocrine cell found in the lungs
- Occurs also exclusively in smokers
- Associated with paraneoplastic syndromes: SIADH, ectopic ACTH production (Cushing’s syndrome), Lambert-Eaton myasthenia syndrome, ectopic PTHrP (hypercalcaemia), hypertrophic osteoarthropathy
- Metastasises to:
Brain, adrenal, lung and skeleton - Has an extremely poor prognosis, by the time of diagnosis curative therapy is rarely possible
Where does SCLC commonly metastasises to?
“BALS”
- Brain
- Adrenal
- Lung
- Skeleton
Symptoms of lung cancer
- Cough
- Chest pain
- Fever
- SOB
- Malaise
- Nausea
- Haemoptysis
- Hoarseness (due to involvement of the recurrent laryngeal nerve)
- Loss of appetite/weight loss
Signs of lung cancer
- Lymphadenopathy
- Stridor
- Wheeze
- Clubbing
- Pain under ribcage: swollen liver
- Hypertrophic pulmonary osteoarthropathy
- Signs of pleural effusion (exudative): stony dull percussion, reduced vocal fremitus, reduced breath sounds
- SVC obstruction: facial swelling, engorgement of vessels in the neck and face, SOB, and headache
- Pan-coast tumour (tumour of pulmonary apex): Horner’s syndrome (mitosis, ptosis and enophthalmos) pain in shoulder that radiates into the arm and hand, atrophy of muscles of the upper limb, oedema of the upper limb
- Metastasis
1. Bone: Bone pain, raised ALP
2. Brain: Focal and non-focal neurology
3. Liver: abnormal LFTs
4. Adrenal glands: though a common site of metastasis, normally asymptomatic
Describe the paraneoplastic syndromes (commonly associated with SCLC)
Ectopic production of parathyroid hormone-related protein (PTHrP)
- Hypercalcaemia: renal calculi, bone pain, abdominal pain, polyuria and signs of altered mental state
Syndrome of inappropriate anti-diuretic hormone (SIADH)
- Hyponatraemia, Cerebral oedema (extreme cases)
Ectopic adrenocorticotrophic hormone (ACTH) secretion
- Cushing’s syndrome: hyperpigmentation, weight gain, purple striae, depression, impaired blood glucose, hypertension
Lamber-Eaton syndrome
- Caused by antibodies to voltage-gated calcium channels
- Characterised by proximal and ocular muscle weakness (e.g., ptosis and double vision)
- Limb weakness initially improving with movement although the weakness will return when exertion is sustained
- Reports of autonomic symptoms such as dry mouths, impotence, and difficulty urinating
Hypertrophic osteoarthropathy
- Characterised by clubbing, periostitis, painful arthropathy (symmetrical and affecting the distal joints
What are the indications for a two-week wait referral to specialists in patients
- Suggestive CXR findings
- Unexplained haemoptysis and are aged over 40
What are the indications to consider an urgent CXR 9within 2 weeks) in those aged over 40
Unexplained haemoptysis
OR
- Chest and/or shoulder pain
- SOB
- Weight loss/loss appetite
- Abnormal chest signs
- Hoarseness
- Finger clubbing
- Cervical and/or supraclavicular lymphadenopathy
- Cough
- Features suggestive of metastasis from a lunger cancer (e.g., in brain, bone, liver or skin)
Describe the investigations for lung cancer
Bloods - FBC, U&Es, LFTs, bone profile
Imaging
-CXR
- Contrast enhanced CT chest: to localise lesion before bronchoscopy/EBUS-TBNA
- PET-CT
- CT/MRI of brain
Special
- Bronchoscopy
- Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA)
- Lung function tests
Histology and cytology
- Tissue biopsy
- Cytology
What system is used to stage lung cancer?
TNM staging
What do the following letters in TNM staging represent?
a) T
b) N
c) M
a) Size and extent of the the tumour
b) Extent of spread to lymph nodes
c) Presence of metastasis
SCLC may be staged in a simpler two stage system. What is this called?
VASLG staging
SCLC may be staged in a simpler two stage system named VALSG staging.
Describe the categories
Limited disease: tumour not spread beyond hemithorax, regional nodes that may be treated with single radiotherapy field
Extensive disease: tumour spread beyond hemithorax or extensively through the hemithorax, distant metastasis, malignant effusions, or contralateral hilar/supraclavicular involvement
Describe the management of lung cancer
- Smoking cessation
- Surgical - surgical resection/thoracotomy
- For early disease (stage I, II, IIIA) - Radiotherapy
- For locally advanced disease
- Can be used as a combination with chemotherapy - Chemotherapy
- Can be used as neoadjuvant therapy and palliative - Biologic agents
- Can be very effective in NSCLC, especially if they have an EGFR mutation
- Especially in non-smokers, asians, females, bronchioles-alveolar cell carcinoma
Systemic anti-cancer therapy (SACT)
- Specific therapies used in non-squamous NSCLC
Palliative care
- Where anticancer therapy is not appropriate
Describe the management of NSCLC
Curative ( Stage I, II and stage IIIA)
- Surgical resection +/- adjuvant chemotherapy
- If surgery is not possible: polychemotherapy + radiation therapy
Curative (Pancoast tumours up to stage IIIB)
- Neoadjuvant radiation therapy + polychemotherapy
- Surgery therapy
Palliative (Stage IIIB and IV)
- Polychemotherapy +/- targeted therapy
- Alternative: symptom-orientated palliative supply
- Radiation therapy may be considered for management of metastases and complications
Systemic anti-cancer therapy (SACT) used in non-squamous NSCLC
Describe the management of SCLC
Early disease
- Polychemotherapy (cisplatin-based) and/or radiotherapy
- Usually unresectable, consider surgery in patients with very small, resectable lesions
Extensive stage disease
- Polychemotherapy alone
+/- prophylactic cranial irradiation in patients who respond to the initial chemotherapy treatment
Contraindications to surgery in lung cancer
- Malignant pleural effusion
- Superior vena cava obstruction
- Horner’s syndrome
- Vocal cord paralysis
- Phrenic nerve paralysis
Surgical complications of lung cancer
- Displacement of the heart towards the operated side
- Bronchial pump insufficiency leading to respirator failure
- Chylothorax (damage to the thoracic duct)
- Ateclectasis (Partial collapse or incomplete inflation of the lung)
- Pneumonia
smoking is a choice. However what other factors is it strongly influenced by?
Psychological factors - beliefs, coping response, risk factors e.g., stress
Micro-social - background, school and area, culture, and identity
Macro-social factors - advertising, wider society
What social groups do those who smoke commonly belong to?
- Homeless
- Severe mental illness
- Substance misuse
- Criminal justice system
Describe the legislistaions involved in tobacco control
Describe the legislations involved in tobacco control
- Tobacco tax
- Tobacco advertising an promotion act (TAPA) 2022 - Ban of all tobacco advertising in UK
- Legal age of smoking change from 16 to 18 in 2007
- Against law to smoke in public (2007): Smoke-free public spaces
- Illegal to smoke in car with children (2015): smoke free private vehicles
- Vending machine ban: Cannot sell tobacco in vending machine (2011)
- EU tobacco products directive (2016)
- Plain packaging - mush show graphic images of smoke related disease (2016)
What tobacco harm reduction is offered to addicted smokers (when conventional methods to stop smoking have not worked)?
E-cigarettes
Name two drugs that can be taken aid in smoking cessation
Varenicline (champix)
Bupropion (Zyban or Wellbutrin)
