Lung Cancer Flashcards
1
Q
Define Lambert-Eaton myasthenic syndrome (LEMNs)
A
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
2
Q
What causes LEMS and what conditions is it associated with?
A
- 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
3
Q
What are the common features of LEMS?
A
- 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)
4
Q
What are the 4 risk factors for LEMS?
A
- Hx of Cancer (especially small cell lung)
- Smoking
- Co-existing autoimmune condition
- FHx of autoimmune
5
Q
What is the main test for LEMS?
A
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
6
Q
How do you treat LEMS?
A
- Treat underlying cancer
-
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
- Amifampridine:
- IV immunoglobulin therapy
7
Q
What calculator can be used for the probability of a nodule on CT being cancer?
A
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”
8
Q
Lung Cancer - Biostatistics:
- Is Lung cancer the 1st, 2nd or 3rd most diagnosed cancer in the UK?
- What is the >5yr survival of pts with lung cancer?
A
- Lung cancer is 2nd most diagnosed cancer in the UK (after breast)
- <10% of lung cancer pts survive for >5yrs
9
Q
What are the risk factors for Lung cancer?
A
- Smoking (accounts for 95% of cases)
- Ionising radiation
- Asbestos
- Fibrosing alveolitis (I.e. IPF)
- Industrial chemicals; arsenic, chromium, nickel
10
Q
What are the types/classifications of lung cancer?
A
Primary:
- Small cell (~20%)
-
Non-small cell (~80%):
- Squamous (~35%)
- Adenocarcinoma {~30%)
- Large cell (~10%)
- Other (5%)
Secondary metastasis:
- Breast, kidney, bladder, testis
11
Q
Name a lung cancer common to the pleura - and a common cause.
A
Mesothelioma - can be caused by asbestos exposure
- Image shows multieple pleural plaques suggestive of exposure to asbestos (not mesothelioma)
12
Q
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)
- Squamous
- Adenocarcinoma
- Large cell
A
-
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
-
Adenocarcinoma
- Typically peripheral
- HPOA
- Most common type of lung cancer in non-smokers
-
Large cell
- Typically peripheral
- Poor prognosis
- May secrete β-hCG (producing false positive pregnancy test)
13
Q
What are some common signs/symtpoms of lung cancer?
A
- 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
14
Q
What are some features of small cell lung cancer, including features caused by hormone secretion?
A
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
15
Q
What are 3 complications of lung cancer?
A
-
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
-
Superior vena caval obstruction:
- Prevents venous return from head, upper mediastinum + arms
- Facial + hand swelling (worse in mornings)
- Headaches
-
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
16
Q
What investigations might you do in Lung Cancer?
A
- 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
17
Q
How is Lung Cancer treated?
A
-
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
-
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
18
Q
How is a pleural effusion investigated?
A
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)
19
Q
Gross analysis of pleural effusion fluid can give some indication as to the diagnosis (non-definitive or highly accurate) - what do the following indicate:
- Bloody
- White (milky)
- Black
- Yellow-green
- Dark green
- Pus
A
- Bloody = malignancy, asbestosis, pulmonary infarction
- White (milky) = chylothorax, cholesterol effusion
- Black = aspergillus
- Yellow-green = rheumatoid pleurisy
- Dark green = bilothorax
- Pus = empyema
20
Q
Describe transudate vs exudate effusions
A
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:
- Endothelial seperation
- Vessel dilation
- The above combo –> allows leakage of proteins, cholesterol and fluid into pleural space
21
Q
What criteria can be used to identify an exudate fluid?
A
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:
- Pleural fluid protein : serum protein ratio > 0.5
- Pleural fluid LDH : serum LDH > 0.6
- Pleural fluid LDH > 2/3 the upper limit of normal serum LDH
N.B. normal serum LDH range = 100-250 U/L
22
Q
Name some causes of Transudate and Exudate effusions.
A
Transudate: - anything that ↓ blood [protein] or ↓ blood osmolality
- Congestive heart failure (most common)
- Liver Cirrhosis - causes hypoalbuminaemia
- 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:
- Infection: Pneumonia (most common), TB
- Connective tissue disease: rheumatoid arthritis, systemic lupus erythematosus (SLE)
- Neoplasia: lung cancer, mesothelioma, metastases
- Pancreatitis
23
Q
What other features of pleural fluid (besides protein and LDH) can be analysed?
A
-
Glucose analysis:
- Low glucose:
- Common: pneumonia, malignant effusion
- Rare: RA, TB
- Low glucose:
-
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
- If pleural fluid amylase > upper limit of normal serum amylase or pleural fluid amylase : serum amylase ratio > 1.0 then;
-
Cytology:
- Useful in suspected malignancy
24
Q
If a patient has an adenocarcinoma which tests positive for EGF-R mutations - does this improve or worsen their prognosis?
A
Improve
- They can be treated with gefitinib or erlotinib –> ~ doubles survival
25
Q
What management options are there for recurrent pleural effusions?
A
- Recurrent aspiration
- Pleurodesis
- Indwelling pleural catheter
26
Q
What red flags are there for Lung Cancer?
A
- Weight loss
- Haemoptysis
- Lethargy
- Clubbing
- Dysphagia
- Hoarse voice
- Facial swelling - due to super vena caval obstruction
- Limb pain - hypertrophic osteoarthropathy (HPOA)
- Recurrent chest infections
- Chest pain
- Persistent SoB
