Lung Cancer

Question 1

Define Lambert-Eaton myasthenic syndrome (LEMNs)

Answer 1

Define:

• Rare autoimmune disorder of the NMJ – antibodies against voltage-gated Ca²⁺ channels –> impairs influx of Ca²⁺ into presynaptic terminal –> thus inhibiting vesicular release of acetylcholine

Question 2

What causes LEMS and what conditions is it associated with?

Answer 2

• LEMS can occur as a para-neoplastic disorder in association with cancer i.e. CA-LEMS
  
  • N.B. LEMS can also occur as part of a generalised autoimmune state i.e. NCA-LEMS
• CA-LEMS is often associated with SCC (small cell carcinoma) of the lung
• > 40% of LEMS pts have underlying cancer (normally SCC lung)
• SCC cells have high [voltage-gated Ca2+ channels] –> presumed that this triggers antibodies against the channels

Question 3

What are the common features of LEMS?

Answer 3

• Proximal muscle weakness (starts in legs)
• Dry mouth ‘metallic taste’
• Impotence (65% of men)
• Dysphagia
• Hyporeflexia or areflexia
• Dysarthria (common but often occurs late in disease)
• Ptosis (late symptom - whereas early in myasthenia gravis)
• Diplopia (late symptom)

Question 4

What are the 4 risk factors for LEMS?

Answer 4

1. Hx of Cancer (especially small cell lung)
2. Smoking
3. Co-existing autoimmune condition
4. FHx of autoimmune

Question 5

What is the main test for LEMS?

Answer 5

Nerve conduction studies

• Initially muscle action potential amplitude is low
• After 10 seconds of exercise –> the same muscle shows significant increase in amplitude
• I.e. muscle weakness is improved on exercise

Question 6

How do you treat LEMS?

Answer 6

1. Treat underlying cancer
2. Amifampridine +/- Pyridostigmeine:
   
   • Amifampridine:
     
     • Use: treat myasthenic syndromes and LEMS
     • MoA: K+ channel antagonist which ↑ AP duration at nerve terminals –> thus Ca2+ channels can be open for longer –> ↑ vesicular ACh release
   • Pyridostigmeine:
     
     • Use: myasthenia gravis (may improve dry mouth/taste symptoms in LEMS)
     • MoA: inhibits acetylcholinesterase in the synaptic cleft –> ↑ ACh in synapse
     • Don’t use in intestinal or urinary obstruction
3. IV immunoglobulin therapy

Question 7

What calculator can be used for the probability of a nodule on CT being cancer?

Answer 7

Brock calculator

• “estimates the probability that the lung nodule you describe in the calculator will be diagnosed with cancer within an 2-4yr follow up period”

Question 8

Lung Cancer - Biostatistics:

1. Is Lung cancer the 1st, 2nd or 3rd most diagnosed cancer in the UK?
2. What is the >5yr survival of pts with lung cancer?

Answer 8

1. Lung cancer is 2nd most diagnosed cancer in the UK (after breast)
2. <10% of lung cancer pts survive for >5yrs

Question 9

What are the risk factors for Lung cancer?

Answer 9

1. Smoking (accounts for 95% of cases)
2. Ionising radiation
3. Asbestos
4. Fibrosing alveolitis (I.e. IPF)
5. Industrial chemicals; arsenic, chromium, nickel

Question 10

What are the types/classifications of lung cancer?

Answer 10

Primary:

• Small cell (~20%)
• Non-small cell (~80%):
  
  • Squamous (~35%)
  • Adenocarcinoma {~30%)
  • Large cell (~10%)
  • Other (5%)

Secondary metastasis:

• Breast, kidney, bladder, testis

Question 11

Name a lung cancer common to the pleura - and a common cause.

Answer 11

Mesothelioma - can be caused by asbestos exposure

• Image shows multieple pleural plaques suggestive of exposure to asbestos (not mesothelioma)

Question 12

What are the features of the following types of Non-small cell lung cancer?

(where in the lungs is it located, what features are the commonly associated with)

1. Squamous
2. Adenocarcinoma
3. Large cell

Answer 12

1. Squamous​​
   
   • Typically central
   • Associated with parathyroid hormone-related protein (PTHrP) secretion → hypercalcaemia
   • Clubbing (strongly associated)
   • Hypertrophic pulmonary osteoarthropathy (HPOA) - clubbing + periostitis of small hand joints and distal expansion of long bones
   • Ectopic TSH –> hyperthyroidism
2. Adenocarcinoma
   
   • Typically peripheral​​
   • HPOA
   • Most common type of lung cancer in non-smokers
3. Large cell
   
   • ​​Typically peripheral
   • Poor prognosis
   • May secrete β-hCG (producing false positive pregnancy test)

Question 13

What are some common signs/symtpoms of lung cancer?

Answer 13

• Cough / haemoptysis
• Chest pain
• SoB
• Weight loss
• Lymphadenopathy
• CXR - focal opacity, may be present with pleural effusion (may need CT to see carcinoma)
• Stridor (usually inspiratory, high-pitch)
• Hoarse voice - if tumour compresses recurrent laryngeal nerve e.g. Pancoast tumour

Question 14

What are some features of small cell lung cancer, including features caused by hormone secretion?

Answer 14

Small Cell:

• Usually central
• Ectopic ADH secretion –> SIADH –> Hyponatremia
• Ectropic ACTH secretion –> Cushing’s syndrome (hypertension, hyperglycaemia, hypokalemia, alkalosis and muscle weakness)
• Lambert-Eaton syndrome (LEMS)
• Anti-Hu antibodies - antigens released by tumour cause an immune response consisting of anti-hu antivodies which target nervous system causing anti-hu encephalitis e.g. vertigo, nystagmus

Question 15

What are 3 complications of lung cancer?

Answer 15

1. Pancoast Syndrome:
   
   • Pain / weakness ipsilateral arm - tumour can impose on brachial plexus
   • Hoarse voice + bovine cough - tumour compressing recurrent laryngeal nerve
   • Horner’s syndrome - miosis (constricted pupil), ptosis, sunken eye (enopthalmos), unilateral anhidrosis
   • Carcinoma at apex –> can protrude into supraclavicular fossa causing loss of recess
2. Superior vena caval obstruction:
   
   • Prevents venous return from head, upper mediastinum + arms
   • Facial + hand swelling (worse in mornings)
   • Headaches
3. Metastases:
   
   • Cutaneous mets e.g. large skin mass on hard palate
   • Liver mets - jaundice
   • Adrenal mets - diabetes secondary to hypercortisolism
   • Brain mets - can precipitate a haemorrhagic stroke

Question 16

What investigations might you do in Lung Cancer?

Answer 16

• CXR / CT scan
• Fibre-optic bronchoscopy - can inspect large airways
• Percutaneous needle biopsy - useful to determine cell type
• Nodal biopsy
• Mediastinoscopy - to visualise mediastinal contents and facilitate lymph node / mass biopsy
• LFTs:
  
  • Deranged in liver mets
• U+Es:
  
  • Determine renal function for medication or scans with contrast
• TFTs:
  
  • Non small cell squamous carcinoma can cause hyperthyroidism

Question 17

How is Lung Cancer treated?

Answer 17

1. Determine cell type (small vs non-small):
   
   • Small cell = rapidly dividing –> main treatment is chemotherapy
   • Non-small cell = grows slower:
     
     • If operable –> surgery
     • If inoperable –> radiacl radiotherapy or palliative
2. Getfitinib or Erlotinib:
   
   • Use: when positive for EGF-R (epidermal growth factor receptor) mutations
   • MoA: EGF-R inhibitor
   • Epidermal growth factor receptor (EGFR) mutations are found in many cancers, particularly NSCLC – tumour tissue sample can confirm EGFR +ve or –ve for mutations

Question 18

How is a pleural effusion investigated?

Answer 18

Thoracentesis‘pleural tap’

• Often involves ultrasound to determine degree of effussion + depth to insert needle
• Cannula or hollow needle inserted between ribs into pleural space under local anaesthesia for diagnostic or therapeutic purposes
• Can be used to diagnose the following:
  
  • Malignancy
  • Empyema
  • Pleuritic TB
  • Pleuritic lupus
  • Oesophageal rupture
  • Hemothorax
  • Chylothorax - type of pleural effusion resulting from accumulation of chyle in pleural space due to obstruction of thoracic duct (chyle = lymph formed in lacteals of the digestive system during absorption of dietary fatty acids – suspended in chylomicrons)

Question 19

Gross analysis of pleural effusion fluid can give some indication as to the diagnosis (non-definitive or highly accurate) - what do the following indicate:

1. Bloody
2. White (milky)
3. Black
4. Yellow-green
5. Dark green
6. Pus

Answer 19

1. Bloody = malignancy, asbestosis, pulmonary infarction
2. White (milky) = chylothorax, cholesterol effusion
3. Black = aspergillus
4. Yellow-green = rheumatoid pleurisy
5. Dark green = bilothorax
6. Pus = empyema

Question 20

Describe transudate vs exudate effusions

Answer 20

Transudate:

• Caused by imbalance of hydrostatic and oncotic pressures that results in movement of fluid out of circulation and into the pleural space
  
  • Oncotic pressure = osmotic pressure exerted by proteins, ↑ protein = ↑ oncotic pressure e.g. albumin in blood exerts oncotic pressure that tends to pull H20 into blood vessels
• Any movement of fluid from peritoneal or retroperitoneal spaces into pleural space = transudate

Excudate:

• Tends to be caused by inflammation which causes:
  
  1. Endothelial seperation
  2. Vessel dilation
• The above combo –> allows leakage of proteins, cholesterol and fluid into pleural space

Question 21

What criteria can be used to identify an exudate fluid?

Answer 21

Light’s Criteria

BTS reccomend that:

• Pleural fluid protein > 30 g/L = exudate
• Pleural fluid protein g/L = transudate
• If protein level is between 25-35 then apply Light’s Criteria

If ANY of Light’s criteria are met then fluid is exudate:

1. Pleural fluid protein : serum protein ratio > 0.5
2. Pleural fluid LDH : serum LDH > 0.6
3. Pleural fluid LDH > 2/3 the upper limit of normal serum LDH

N.B. normal serum LDH range = 100-250 U/L

Question 22

Name some causes of Transudate and Exudate effusions.

Answer 22

Transudate: - anything that ↓ blood [protein] or ↓ blood osmolality

1. Congestive heart failure (most common)
2. Liver Cirrhosis - causes hypoalbuminaemia
3. Nephrotic syndrome (↑ glomerular permeability –> causes loss of protein from plasma to urine e.g. hypoalbuminaemia –> ↓ oncotic pressure –> fluid moves out of intravascular space e.g. pitting oedema, pleural effusion, ascities and periorbital oedema)

Exudate:

1. Infection: Pneumonia (most common), TB
2. Connective tissue disease: rheumatoid arthritis, systemic lupus erythematosus (SLE)
3. Neoplasia: lung cancer, mesothelioma, metastases
4. Pancreatitis

Question 23

What other features of pleural fluid (besides protein and LDH) can be analysed?

Answer 23

• Glucose analysis:
  
  • Low glucose:
    
    • Common: pneumonia, malignant effusion
    • Rare: RA, TB
• pH:
  
  • ↓ pH seen in: –> empyema, malignancy, rheumatoid pleurisy, TB pleurisy, oesophageal rupture
  • pH < 7.2 + pneumona –> chest drain
• Amylase:
  
  • If pleural fluid amylase > upper limit of normal serum amylase or pleural fluid amylase : serum amylase ratio > 1.0 then;
    
    • Acute pancreatitis
    • Chronic pancreatic pleural effusion
• Cytology:
  
  • Useful in suspected malignancy

Question 24

If a patient has an adenocarcinoma which tests positive for EGF-R mutations - does this improve or worsen their prognosis?

Answer 24

Improve

• They can be treated with gefitinib or erlotinib –> ~ doubles survival

Question 25

What management options are there for recurrent pleural effusions?

Answer 25

1. Recurrent aspiration 2. Pleurodesis 3. Indwelling pleural catheter

Question 26

What red flags are there for Lung Cancer?

Answer 26

1. Weight loss 2. Haemoptysis 3. Lethargy 4. Clubbing 5. Dysphagia 6. Hoarse voice 7. Facial swelling - due to super vena caval obstruction 8. Limb pain - hypertrophic osteoarthropathy (HPOA) 9. Recurrent chest infections 10. Chest pain 11. Persistent SoB