JC18 (Medicine) - Pleural Effusion and Lung Cancer Flashcards
Define Pleural effusion
4 types of Pleural Effusion
Pleural effusion: accumulation of serous fluid within pleural space
□ Empyema: accumulation of frank pus
□ Haemothorax: accumulation of blood
□ Chylothorax: accumulation of lymph
□ Hydropneumothorax: accumulation of fluid + air
Describe 4 factors that determine amount of fluid in pleural cavity (push and pull forces)
□ Hydrostatic pressure at arterial end
□ Oncotic pressure at venous end
□ Capillary permeability
□ Lymphatic drainage
Compare Transudative and exudative effusion causes
Symptoms of Pleural effusion
Dyspnoea: most common symptom, due to
□ Altered chest wall and diaphragm mechanics
□ Compression of lungs
□ Underlying lung or heart disease
Pleuritic chest pain: may not always be present, usually indicates exudative pathologies
□ Usually ↓intensity with ↑effusion size when inflamed pleural surfaces are no longer in contact
Signs of Pleural Effusion
Inspection: tachypnoea
Palpation:
□ ↓chest expansion
□ ± contralateral deviation of mediastinum
Percussion: stony dullness
Auscultation:
□ Increase transmission above effusion = bronchial breathing, ↑vocal resonance
□ Decrease transmission below effusion = ↓breath sounds, ↓vocal resonance
first-line investigations for pleural effusion
CXR
Ultrasound
CT ± PET/CT (if malignancy suspected or initial tap non-diagnostic)
Diagnostic thorcacentesis
Pleural Biopsy
Typical Xray appearance of pleural effusion
CXR: meniscus or blunted costophrenic angle seen
□ Requires ~200mL of fluid to be visible
□ May be loculated due to presence of pleural scarring or adhesions
Typical Ultrasound findings of pleural effusion
Ultrasound: more accurate than CXR
□ Transudate: clear hypoechoic space
□ Exudate: moving floating densities or septations
Indication for Diagnostic theracocentesis
Pleural fluid appearance for different causes of pleural effusion (4)
Indication: ALL effusions except bilateral effusion strongly suggestive of transudative process
Appearance:
Straw-coloured → serous (transudative)
Blood → traumatic haemothorax, malignancy, PE
Pus → empyema
Milky → chylothorax
Criteria for distinguishing transudative vs exudative pleural effusion
Light’s criteria: exudative if ≥1 positive
→ Pleural fluid:serum protein ratio > 0.5
→ Pleural fluid:serum LDH ratio > 0.6
→ Pleural fluid LDH > 2/3 of URL for serum
Pleural fluid biochemistry should be sent together with blood sample
List all metrics in diagnostic thoracentesis to find cause of effusion
- Appearance
- Glucose and pH compared to blood
- Cell count and WBC differentials (neutrophil vs lymphocyte predominant)
- Cytology for malignancy (2 taps minimum)
- Microbiology: Gram stain and culture, TB workup
Conditions that change glucose and pH level of pleural fluid
Glucose and pH: ↓Glc (lower than blood) and ↓pH (<7.30) in
Empyema (not in uncomplicated parapneumonic effusion)
Connective tissue disease, eg. RA, SLE
Malignant effusion
TB pleurisy → also a/w ↑adenosine deaminase (ADA) >40
Ruptured oesophagus
Indication for pleural biopsy
2 forms of pleural biopsy
Indication: exudative effusion with non-diagnostic thoracentesis (esp for TB and cancer)
1) Percutaneous:
- Blind if diffusely involved (eg. TB)
- CT- or USG-guided can be done but is inferior to thoracoscopic biopsy
2) Medical thoracoscopy (pleuroscopy) (allow therapeutic pleurodesis in the same procedure)
List management options for pleural effusion
- Treat underlying cause
- Therapeutic thoracentesis (therapeutic tap)
- Thoracostomy (chest tube) drainage
- In-dwelling pleural catheter (IDC) insertion
- Pleurodesis: chemical or surgical to obliterate pleural space
Risk factors of lung cancer
1) Environmental:
→ Smoking: responsible for ~90% CA lung, 40× death rate in smokers
→ Passive smoking
→ Toxin exposure: asbestos, cooking fumes
→ Radiation: thoracic RT, radon exposure
→ TB: ‘scar tumours’
2) Genetics: 1.5× risk with positive family Hx (e.g. EGFR mutation)
3) Previous lung conditions, eg. idiopathic pulmonary fibrosis (IPF)
Histological types of lung cancer
Prevalence of subtypes of lung cancer
□ Squamous cell carcinoma (SCC, 20-30%)
□ Adenocarcinoma (AD, 45-55%)
□ Large cell carcinoma (LCLC, 5-10%)
□ Small cell carcinoma (SCLC, 5-10%)
High-risk genetic changes asso. with lung cancer
EGFR mutation (55% in local AD) ALK translocation (5% in local AD) KRAS mutation (5-10% in local AD)
Most common presenting symptoms of Lung Cancer
cough (45-74%),
weight loss (46-68%),
SOB (37-58%),
chest pain (27-49%),
haemoptysis (27-29%),
bone pain (20-21%),
hoarseness (8-18%).
Primary lung cancer Tumor mass effects
Bronchial mucosa ulceration:
- Cough (80%): usually dry, ± sputum if secondary infection
- Haemoptysis (70%): common esp in central bronchial tumours
Partial Bronchial obstruction:
- Monophonic, unilateral wheeze not cleared with coughing
- Recurrent pneumonia due to poor drainage
- Stridor
Complete Bronchial obstruction:
- Lung Collapse
Primary lung cancer - List 10 structures affected in intrathoracic spread
- Lymphangitis carcinomatosis
- Pleural effusion
- Pericardial effusion and cardiac tamponade
- Chest wall and ribs (pain)
- Phrenic nerve damage and diaphragm paralysis
- SVC obstruction (emergency)
- Left RLN damage (hoarseness, bovine cough)
- Brachial plexus (Pancoast syndrome)
- Inferior cervical sympathetic chain - Horner’s syndrome
- Esophagus (dysphagia)
S/S of SVC obstruction
- Dyspnoea and stridor
- Facial plethora, headache and conjunctiva oedema
- Early morning headache
- Dilated veins on chest wall and neck
- Pemberton’s sign: exaggeration of symptoms when lift both arms (narrow thoracic inlet → ↑obstruction)
S/S of pancoast syndrome
pain in inner aspect of arm ± small hand muscle wasting
classically a/w NSCLC, only <5% SCLC
S/S of Horner syndrome
SPAM = sunken eyeball, partial ptosis, anhidrosis, miosis
(ipsilateral partial ptosis, miosis, enophthalmos, anhidrosis)
Anatomical location of lung cancer most likely to cause:
- SVCO
- Horner syndrome
- Pancoast syndrome
- Hoarseness
Rt suprahilar → SVCO
Lt upper lobe (near aortic arch) → hoarseness
Apex → Pancoast and/or Horner syndrome
Common metastatic spread of lung cancer
most commonly liver, adrenals, bone, brain
Others: spinal cord, supraclavicular and cervical lymphadenopathy
Systemic non-metastatic effects of lung cancer **
- Haematological
- Connective tissue
- Endocrine
- Neuromuscular
Haematological: anaemia of chronic disease, leukocytosis, thrombocytosis
Connective tissues:
→ Clubbing
→ Hypertrophic pulmonary osteoarthropathy (HPOA)
Ectopic hormones (12%):
→ SIADH (usu SCLC) → hypoNa → confusion, weakness
→ ACTH (usu SCLC) → Cushing’s syndrome (ectopic ACTH)
→ PTHrP (usu SCC) → hyperCa → polyuria, thirst, confusion
Neuromuscular:
→ Eaton-Lambert myasthenia syndrome (3% SCLC) - weakness
→ Paraneoplastic encephalitis, eg. limbic encephalitis, encephalomyelitis, cerebellar degeneration
→ Peripheral neuropathy - paraesthesia
→ Dermatomyositis and polymyositis - skin rash, weakness
S/S of PTHrP release from lung cancer
hypercalcemia:
- ‘Stones’: nephrocalcinosis, renal stones
- ‘Bones’: bone pain, osteoporosis
- ‘Groans’: lethargy, fatigue
- ‘Moans’: constipation, abdominal pain, nausea, vomiting
- ‘Thrones’: polyuria, dehydration, polydipsia
- ‘Psychiatric overtones’: confusion, depression, anxiety, hallucinations
2 causes of hypercalcemia due to lung cancer
- Bony metastasis and bony destruction: a/w ↑PO43-
- PTHrP production: a/w ↓PO43-
First line investigations for Lung Cancer
- General evaluation: blood tests, cardiac and lung function assessment
- Radiological: CXR for screening, CT or PET for confirmation, TNM, guide biopsy
- Tissue biopsy: confirmation, genetic information
8 possible radiological features of lung cancer
Function of Contrast CT thorax + upper abdomen for lung cancer
- Diagnostic
- Guide biopsy
- Staging (limitations of nodal, chest wall and mediastinal invasion)
- Treatment: Radiotherapy planning, assess treatment response
Function of PET/CT and MRI in Lung Cancer
PET/CT Whole body: Metastatic disease
MRI thorax: Pancoast tumor, assess chest wall/brachial plexus invasion\
Contrast MRI/ CT brain: Brain metastasis
Methods of tissue sampling for dx of lung cancer (cytology)
For Cytology:
- Sputum
- Bronchial washing
- Pleural thoracocentesis
- FNAC
For Biopsy:
- Conventional bronchoscopy
- Endobronchial ultrasound transbronchial needle aspiration (EBUS- TBNA)
- Transthoracic needle aspiration/ Biopsy (TTNA/ TTNB)
- Mediatinoscopy
- Video-assisted thoracic surgery (VATS)
- Medical pleuroscopy
Method of biopsy for lung cancer mass
For Biopsy:
- Conventional bronchoscopy
- Endobronchial ultrasound transbronchial needle aspiration (EBUS- TBNA)
- Transthoracic needle aspiration/ Biopsy (TTNA/ TTNB)
- Mediatinoscopy
- Video-assisted thoracic surgery (VATS)
- Medical pleuroscopy
Indication for convention bronchoscopy
Modalities for lung cancer located centrally and peripherally?
only for directly visualized lesions in bronchi
Modalities:
Directly visualized lesions → saline washing, brushing or endobronchial forcep biopsy
Lesions close to airways → transbronchial Bx or needle aspiration
Peripheral lesions → bronchoalveolar lavage
Indication for EBUS- TBNA
→ Diagnosis and staging by sampling central tumours and paratracheal/subcarinal/hilar LNs
→ Alternative dx for mediastinal lymphadenopathy (eg. TB, sarcoidosis, lymphoma)
Indication for TTNA/ TTNB
Transthoracic needle aspiration/biopsy (TTNA/TTNB):
□ Indication: sample peripheral nodules (2nd line after other modalities)
□ Use: CT-guided
List 3 minimally invasive modalities of tissue collection for Lung cancer
□ Sputum cytology for pt unfit for invasive biopsy
□ Endoscopic ultrasound-guided FNA (EUS-FNA) for subcarinal and paratracheal nodes
□ Electromagnetic navigation bronchoscopy for peripheral lesions (new technique for image-guidance)
Management outline for SCLC
SCLC
□ All patients → chemo + RT
Management outline for NSCLC
- *Surgery: as definitive treatment (1st line)**
- *± adjuvant chemotherapy** for pathologic stage II-III or high-risk stage IB
- *± adjuvant RT** for +ve surgical margin or mediastinal LN involvement
Definitive RT: as alternative if medically unfit or refuse surgery
Criteria for surgery:
□ Appropriate stage: stage I, stage II, T3N1, selected T4N0-1
□ NO mediastinal involvement (N2 precludes resection)
□ Adequate cardiac and lung function
Outline 2 pre-operative fitness tests for NSCLC surgery
Cardiac function: echocardiogram or cardiac catheterization
Lung function:
Spirometry: FEV1 and DLCO for predicted postop values (ppoPEV1, ppoDLCO)
Cardiopulmonary exercise test (CPET): VO2 max and threshold
Surgical options for NSCLC resection (4)
1.Lobectomy: gold-standard for Ca lung ***
→ Approach: open, VATS, robotic
2.Sublobar resection, eg. segmentectomy, wedge resection
→ Indication: intolerant to full lobectomy + primary tumour ≤3cm
3.Sleeve lobectomy: alternative to pneumonectomy
→ Indication: for tumour close to main bronchus
4.Pneumonectomy: proximal tumours
± en bloc resection of chest wall invasion
+ mediastinal LN dissection
Treatment option for non-resectable NSCLC
- Chemotherapy regimen: usually cisplatin + etoposide or weekly carboplatin + paclitaxel
- Radiotherapy
- Targeted therapy and immunotherapy (durvalumab)
Indication for genetic testing for lung cancer
Name 3 driver mutations in NSCLC
Advanced NSCLC - cannot resect
All adenocarcinoma
All never-smokers with early lung CA
Genetic test on biopsy sample or plasma/ urine cell-free DNA: EGFR, ALK and ROS1
Treatment for EGFR +ve NSCLC
S/E
1st/2nd generation EGFR TKIs eg. gefitinib (Iressa), erlotinib (Tarceva), afatinib (Gilotrif)
S/E: acneiform rash, radiation dermatitis, mucositis, GI disturbance, corneal erosion, pulmonary and hepatic fibrosis (drug induced pneumonitis and liver cirrhosis)
Treatment for TKI-resistant NSCLC
Types: EGFR 2o mutation as exon 20 T790M (~60%), HER2 amplification (8-12%), Met activation (4-8%), conversion to SCLC (<5%)
If T790M+, then use 3rd generation TKI, i.e. osimertinib
If T790M-, then use afatinib/cetuximab or chemotherapy
Treatment of ALK translocation or ROS1 rearrangement NSCLC
1st generation ALK TKIs, eg. crizotinib
Resistant to Crizotinib: start 2nd generation ALK TKIs, eg. ceritinib, alectinib, brigatinib
Treatment of non-resectable/ end-stage NSCLC with no driver mutations
Check Tumour PD-L1 expression
- *PD-L1 high (≥50%) → pembrolizumab monotherapy**
- *PD-L1 low (<50%) or unknown → pembrolizumab + platinum-based chemotherapy**
Supportive treatment: analgesics, cough suppression, pleurodesis, end-of-life care, Palliative radiotherapy for SVCO
Treatment for Stage 1-2 SCLC with no met.
Primary surgery: lobectomy + mediastinal LN dissection
Adjuvant chemotherapy: 4 cycles of cisplastin-based chemotherap ± adjuvant chemo/RT if LN involvement
Treatment of unresectable/ advanced SCLC with met.
Unresectable:
- *Chemoirradiation**: mainstay, etoposide + cisplatin (EP) + thoracic EBRT
- *Prophylactic cranial irradiation (PCI):** prophylaxis against brain metastasis
Very late stage:
- Induction chemotherapy: atezelizumab, PD-L1 mAb
- Thoracic EBRT ± PCI
Common primaries of metastatic lung cancer
Haematological spread:
□ Common primaries: breast, kidneys, uterus, ovary, testes, thyroid
Lymphatic spread → lymphangitis carcinomatosis
□ Common primaries:
→ Cervix, Colon, Stomach, Breast, Pancreas, Thyroid, Larynx and lungs
