Outline the distribution and composition of the normal flora of the upper respiratory tract
[*] Common (normally non-pathogenic)
- Viridans streptococci
- Neisseria spp
- Candida spp
[*] Less common (transient colonisers – tend to come and go, tend to pathogenic leading to invasion of the lower respiratory tract, sinuses and ear causing inflection)
- Streptococcus pneumonia
- Streptococcus pyogenes
- Haemophillus influenzae
[*] Other (usually found in patients on long term antibiotics or in hospital for a long time, can be pathogenic)
- E. coli
Outline the natural defences of the respiratory tract against infection
[*] Cough and Sneezing Reflex
[*] Muco-ciliary clearance mechanisms
- Ciliated columnar epithelium
- Nasal hairs
[*] Respiratory mucosal immune system:
- Lymphoid follicles of the pharynx and tonsils in the submucosa
- Alveolar macrophages
- Secretary IgA and IgG
List the main infectious diseases of the upper respiratory tract and state the organisms commonly causing these infections
[*] Worldwide, lower respiratory tract infections in the elderly. Pneumonias due to Influenza and Streptococcus pneumoniae are x3 more common in the elderly (>75 years) compared to young adults.
[*] Upper Respiratory Tract Infections
- Rhinitis (common cold)
- Otitis media (inflammation of middle/inner ear)
[*] URT infections are most commonly caused by Viruses:
- Respiratory Syncytial Virus (RSV)
[*] May also be caused by Bacterial Super-Infection (secondary infection often develops after viral infection)
Common with sinusitis and otitis media
Can lead to
- Brain abscess
What is the difference between Acute Bronchitis and Chronic Bronchitis?
[*] Acute bronchitis is caused predominantly by viruses and rarely by bacteria. It may lead to pneumonia due to further spread of the organisms into the lung parenchyma
[*] Chronic bronchitis is not primarily infective. Exacerbations have been associated with many organisms, but the role of infection remains controversial (non-infective cause).
What is the difference between Pneumonia and Pneumonitis? What is the pathology behind Pneumonia?
[*] Pneumonia is a general term denoting inflammation of the gas exchanging region of the lung usually due to infection; pneumonia is therefore an infection of the lung parenchyma with consolidation.
[*] Inflammation due to other causes such as physical or chemical damage, is often called ‘pneumonitis’ (non-infective inflammatory disease).
[*] The common feature of pneumonias is a cellular exudate in the alveolar spaces.
- An exudate occurs when there is an inflammatory process causing increased capillary permeability hence there will be a higher protein content in an exudate (but not in a transudate)
- This results in fluid filled air spaces and consolidation (heavy and stiff lungs)
- Gas exchange is impaired as fluid replaces air, resulting in local and systemic manifestations.
What is the difference between Lobar pneumonia and Bronchopneumonia?
- Localised to a particular lobe/s of the lungs – “lobar pneumonia”. Most often due to Streptococcus pneumoniae. Confluent consolidation involving a complete lung lobe. Usually seen in community-acquired pneumonia.
- A typical acute inflammatory response => exudation of fibrin-rich fluid with neutrophil and macrophage infiltration.
- Resolution: immune system plays a part as antibodies lead to opsonisation, phagocytosis of bacteria
- May be diffuse or more patchy “bronchopneumonia”. Infection starts in the airways and spreads to adjacent alveoli and lung tissue. Can infect multiple places in the lobes, normally gets into both lungs. Streptococcus pneumonia, Haemophilus influenza, Staphylococcus aureus, anaerobes, coliforms. More often seen in the context of pre-existing disease. Clinical context
Complication of viral infection (influenza).
Aspiration of gastric contents
Pathology: the consolidation is patchy and not confined by lobar architecture
Patchy infiltrates on X ray
Describe Aspiration pneumonia
[*] Aspiration Pneumonia: aspiration of food, drink, saliva or vomitus can lead to pneumonia.
- This is more likely in individuals whose level of consciousness is altered, due to anaesthesia, alcohol or drug abuse or having swallowing related problems due to neuromuscular problems or oesophageal disease.
- Aspiration of exogenous material (e.g. people who are drowning) or endogenous secretions (most commonly bowel flora) into the respiratory tract.
- Common in patients with neurological dysphagia (strokes), epilepsy, alcoholics, drowning
- Causative organisms include oral flora and anaerobes – organisms primarily from throat and GI tract.
- Mixed infection – Viridans streptococci and anaerobes
What is interstitial pneumonia and chronic pneumonia?
[*] Interstitial Pneumonia: inflammation of the intersticium of the lung (alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues)
[*] Chronic Pneumonia: inflammation of the lungs that persists for an extended period of time.
How may pneumonias be classified?
[*] Pneumonias may be classified by the infecting organism (bacterial, atypical, viral, fungal or protozoan) but different organisms do not lead to different, well-recognised clinical syndromes.
[*] Hence a more useful classification depends on source of infection and other aetiological factors. This classification offers a logical approach to treatment because different organisms and factors are involved in each case.
Describe community-acquired pneumonia
[*] The commonest causative organism of community acquired pneumonia is Streptococcus Pneumoniae (~30%). It is less commonly caused by Haemophilus influenzae (13%), Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pyogenes.
- May also be caused by ‘Atypical bacteria’ (10% such as Mycoplasma pneumoniae (the commonest of the atypical organisms), Chlamydia pneumonia and Legionella pneumophila
- Atypical bacterial have different structures / characteristics to typical bacteria
- Mycoplasma has no cell wall therefore antibiotics such as amoxicillin have no effect.
- Viruses (10%) such as influenza, parainfluenza, respiratory syncytial virus (RSV), adenovirus
- Mixed infections (10%)
Describe Nosocomial pneumonia
[*] Nosocomial/Hospital Acquired pneumonia: defined as an infection of the lower respiratory tract in hospitalised patients, which was not incubating at the time of admission.
- Often occurs 2-3 days after admission. Here the infection is more often associated with impaired defences.
- A different range of organisms is usual. Important causative organisms include Gram negative enteric bacteria (10%), pseudomonas and Staphylococcus aureus including MRSA.
What could also lead to pneumonia?
M tuberculosis and Atypical Mycobacteria can also lead to pneumonia
Describe Viral Pneumonia and Influenza
- Direct damage to cells lining the airways / alveoli by the virus and immune cells.
- Fluid filled air spaces interferes with gas exchange
- Most of the time but severe pneumonia can lead to severe viral pneumonia necrosis/haemorrhage into the lung parenchyma – picture similar to adult respiratory distress syndrome. There is diffuse bilateral necrosis which leads to respiratory failure as there is no normal lung tissue to compensate (due to diffuse damage)
- Patchy or diffuse ground glass opacity on chest X-ray
Influenza is the most important viral infection in terms of highest mortality – caused by a RNA virus
- ‘Flu’ seen predominantly in the winter months
- Genetic makeup of the virus changes constantly through mutations => can also acquire large genetic elements => have lead to epidemics and pandemics (immunity from a previous strain is not protective against next seasonal strain)
- The current circulating strain of the virus is H3N1
- Severe infection/infection in pregnancy and in the immunocompromised offer antiviral drugs (oseltamivir and zanamivir)
List the aetiological clues for the common respiratory tract pathogens
[*] Streptococcus pneumoniae: elderly, co-morbidities, acute onset (become unwell within a couple of days), high fever, pleuritic chest pain
[*] H. influenza: COPD (damaged lungs)
[*] Legionella: recent travel, younger patient, smokers, illness, multi-system involvement
[*] Mycoplasma: young, prior antibiotics, extra-pulmonary involvement (haemolysis, skin and joint)
[*] Staphyloccus aureus: post-viral pneumonia, intra-venous drug user, secondary infection
[*] Chlamydia: contact with birds – parrots, budgerigars, cockatoos, pigeons, turkeys
[*] Coxiella: animal contact (sheep, cattle goats)
[*] Klebsiella: thrombocytopenia, leucopenia
[*] S. milleri: dental infections, abdominal source, aspiration
Understand the spectrum of clinical features of acute community acquired and acute hospital acquired pneumonias
[*] The presentation of pneumonia can be variable but there is almost always malaise, fever and cough productive of sputum.
- The sputum may be purulent, or rusty coloured (due to blood) or frankly blood stained.
- There is commonly pleuritic chest pain
- Patients often feel breathless (dyspnoea)
- Pneumonias may be of very rapid onset, particularly if pneumococcal or staphylococcal, with a fatal outcome in a short period of time.
[*] Symptoms of pneumonia
- Fever, chills, sweats, rigors
- Sputum: clear/purulent/’rust-coloured’/haemoptysis
- Pleuritic chestp ain
- Anorexia and vomiting
[*] Atypical pneumonias e.g. Mycoplasma pneumonia may have a more prolonged prodromal period with symptoms lasting for several weeks
[*] Factors such as the age of the patient, whether it was community acquired or hospital-acquired, the presence of chronic lung disease, immunosuppression, ownership of a pet, may give clues to the underlying cause/organism of the pneumonia
[*] The chest x-ray will usually reveal shadowing in at least one section of the lung field
What are the Specific Chest Signs?
Bronchial breath sounds
Dullness to percussion
Reduced vocal resonance (if consolidation is present)
Describe hospital acquired pneumonia
- Pneumonia occurring 48 hours after hospital admission
- Makes up ~15% of all hospital acquired infections
- Common in ITU and ventilated and post surgical patients
- Organisms: Enteric Gram negative bacteria (E coli), Pseudomonas, Anaerobes, S aureus / MRSA, mixed infections
- Usually require treatment with broad spectrum antibiotics
How would you assess the severity of pneumonia?
[*] Assessing the severity of pneumonia: the severity can be assessed using the CURB 65 score, where the presence of 2 or more of the following features is an indication for hospital treatment, and patients with high scores may require ICU treatment.
- C: New mental confusion (AMT <8)
- U: Urea > 7 mmol/L
- R: Respiratory rate > 30 per minute
- B: Blood pressure (systolic BP <90mmHg or diastolic BP <60 mmHg)
- Age > 65
Describe the non-microbiological investigations of pneumonia
- CXR (very reliable, rarely radiological signs can lag behind clinical characteristics 24-48 hours)
- O2 saturation and blood gases
- FBC, WBC, platelets
- WCC (>20 or <4) indicates severe disease
- Urea Liver Function Test and CRP - C reactive protein useful in assessing response to treatment
Explain about microbiological examinations in pneumonia
[*] Microbiology: it may be possible to identify the infecting organism by gram stain and culture of the sputum.
[*] In severely ill patients blood culture is important.
- Macroscopic (mucoid, purulent, blood stained)
- Microscopy (gram staining, acid fast and special stains)
- Culture (bacteria and viruses)
- PCR (respiratory viruses)
- Antigen detection (legionella)
- Antibody detection (serology)
What kind of samples would you collect to investigate pneumonia?
- Nose and throat swabs or naso-pharyngeal aspirates
- Endotracheal aspirates
- Broncho Alveolar Lavage fluid (BAL)
- Open Lung Biopsy
- Blood culture (Preferably before antibiotics)
- Urine (Detect the antigens of legionella/pneumococcus)
- Serum (Antibody detection – acute and convalescent sera)
Why may you need to do additional tests in Atypical Pneumonia?
- Sputum gram stain and culture (atypical bacteria very difficult to culture in the lab – culture is normally negative as organisms don’t grow in standard medium)
- Mycoplasma pneumoniae, Chlamydia pneumoniae, psittaci and trachmatis, Legionella pneumophila
- Look for antigens in urine (Legionella and pneumococcal) and antibody in blood (serology)
- Treatment: Levofloxacin, Erythromycin, Clarythromycin, Doxycycline
- Legionella pneumonia is a notifiable disease
- Treatment is difficult e..g. as mycoplasma doesn’t have a cell wall, it doesn’t respond to co-amoxiclav (amoxicillin combined with clavulanic acid)
List the common opportunistic pathogens causing pneumonias in immunosuppressed hosts
[*] Pathogens infecting immunosuppressed hosts may be:
[*] Virulent infection with common organism
[*] Infection with opportunistic pathogen
- Viruses: Cytomegalovirus (CMV), HSV, VZV
- Bacteria: Mycobacterium avium intracellulare
- Fungi: Aspergillus, candida, pneumocystis jiroveci
- Protozoa: Cryptosporidia, toxoplasma
- High index of suspicion
- Teamwork (physician, microbiologist, pathologist)
- Broncho-alveolar lavage
- Lung Biopsy (with lots of special stains)
[*] Example: Pneumocystis Pneumonia (PCP) can lead to acute alveolitis (CXR would show highly diffuse shadowing)
High dose cotrimoxazole is the drug of choice for treatment
What is the prognosis of pneumonia?
- Pneumococcal pneumonia in a previously well individual has a mortality of about 5%
- Prognosis is poorer in older patients.
- Prognosis is also poorer if there is a high CURB 65 score, a very high or very low white cell count, absence of fever, extensive x-ray shadowing, significant hypoxia or rise in blood urea
- Pneumonias due to some other organisms can have a much higher mortality in some groups
Describe the treatment of acute bacterial pneumonia
- Target the most common bacterial pathogens
- Amoxicillin: mild to moderate
- Co-amoxiclav: severe
- Outcome: Resolution or organisation (fibrous scarring), when organism is virulent or immune system insufficient
- Complications: lung abscess, bronchiectasis (permanent damage to bronchial tree, enlarged air spaces are fluid and secretion filled), empyema (pus in the pleural cavity as infection extends beyond the lungs into the lung parenchyma)
What are General Measures to take in Managemen of Pneumonia?
[*] General Measures: patients with pneumonia need encouragement to maintain a good oral fluid intake/IV fluids to avoid dehydration.
- Anti-pyretic drugs (e.g. paracetamol) are used to reduce fever and malaise, together with stronger analgesics for pleural pain
- More severe illness may require intravenous fluids and oxygen if there is cyanosis with a good respiratory drive
[*] The infection is treated with antibiotics which will vary with the type of pneumonia.
[*] In community-acquired pneumonia, the target organism is Pneumococcus which is usually sensitive to penicillin or related antibiotics.
[*] As hospital-acquired pneumonia is more likely to be due to gram negative organisms, it is necessary to use antibiotics which would cover these organisms e.g. intravenous Co-Amoxiclav (Amoxicillin).
Describe the use of antibiotics in Pneumonia
- Refer to local guidelines
- Penicillin class antibiotics (amoxicillin) are the first choice – but need to take into account travel history and where they have acquired pneumonia as some countries have high rates of penicillin resistance
- Penicllin + clavulanic acid for severe infection (co-amoxiclav) – hospital-acquired pneumonia
- Legionella pneumonia – treat with levofloxacin
- Other atypical organisms treat with Tetracyclines or Macrolides
- Poor response/atypical presentations – discuss with microbiology
Describe the outcomes of Pneumonia
- Organisation (fibrous scarring)
- Pleural effusion
- Lung abscess formation
- Bronchiectasis (the airways of the lungs become abnormally widened, leading to a build of excess mucus)
- Empyema (pus in pleural cavity)
Describe the prevention of Pneumonia
- Flu vaccine – given annually to high risk patients
- Pneumococcal vaccine – two vaccines (23 polyvalent polysaccharide vaccine dose and 13 valent conjugate vaccine – given to patients with co-morbities that increase risk of invasive pneumococcal disease)
Chemoprophylaxis (antibiotic prophylaxis)
- - Oral pencillin / erythromycin to patients with higher risk of lower respiratory tract infections e.g. asplenia (absence of normal spleen function), dysfunctional spleen, immunodeficiency
When would you need to inform ITU?
- Respiratory failure
- Rising pCO2
- Worsening metabolic acidosis
- Hypotension despite fluid resuscitation
- ? Patient suitability to ITU
- Age and Quality of Life (QoL) + co morbidities determine decision
Describe the problem of LRTIs in Cystic Fibrosis
[*] Cystic Fibrosis: lower respiratory tract infections are major problem – CF sufferers have recurrent LRTIS
- 1 in 2500 live Caucasian births
- Viscid bronchial secretions
- Early infections – H influenza and S aureus
- Later Pseudomans auruginosa and Burkholderia cepecia – lungs are so damaged and so filled with secretion so get infected with environmental organisms, very difficult to treat, may be multi-drug resistant
Describe Whooping Cough
- Bacterial form of pneumonia
- Disease of the respiratory tract caused by Bordetella pertussis
- Starts with cold like symptoms develops into bouts of severe coughing followed by characteristic whoop or vomiting.
- Cough can last 2-3 months
- Spreads easily from person to person by droplets
- Most dangerous < 1 year
- Older children and adults can have a prolonged cough
- Worldwide regular epidemic every 4 years due to waning immunity (seen in elderly people)
- Significant increase in incidence in late 2011/2012 (4971 cases with 9 deaths < 3 months so far in 2012)
- Specimens for diagnosis – per nasal swabs, nasopharyngeal swabs or aspiratres
- Culture / PCR
- Treat with erythromycin
- Prevention – childhood vaccination, vaccination of pregnant mothers (28-30 weeks)
Describe the incidence of lung cancer in different groups
[*] Lung cancer is the commonest male cancer and now exceeds breast cancer as a cause of death in women in many areas of the UK
[*] The male mortality rate is around 100 per 100,000 and is falling gradually as a result of a reduction in cigarette smoking around 20 years ago. For women, the rate was around 40 per 100,000 in 1990 and is steadily rising.
[*] Around 40,000 people die from lung cancer each year in the UK
[*] There are wide variations in incidence between different areas of the UK and between different social groups; the rate is nearly 2x higher in the lowest socio-economic group compared to the highest
[*] Commonest cause of death from cancer in the UK – a quarter of all cancer deaths.
Give an account of the aetiological factors involved in lung cancer
[*] Lung cancer is overwhelming related to smoking with the risk being proportional to the duration of the habit and the number of cigarettes smoked. Around 90% of lung cancers in men and 80% in women are caused by smoking.
- 20% of lung cancer cases in nonsmokers
- One third of all cancer deaths
[*] Other aetiological factors include asbestos exposure and radon from mining or indoor exposure
[*] Other occupational carcinogens – chromium, nickel, arsenic
[*] Genetic and dietary factors also influence individual susceptibility
[*] Around 5000 cases a year in never smokers
Describe the typical pattern of symptoms reported by patients with lung cancer
[*] Signs and symptoms of lung cancer are relatively non-specific, with overlap with those of many respiratory diseases.
[*] Many patients first come to medical attention when they have advanced disease.
[*] Primary tumour: cough, dyspnoea, wheezing, haemoptysis, chest pain, post-obstructive pneumonia, weight loss, lethargy/malaise
[*] Regional metastases: superior vena cava obstruction, hoarseness (left recurrent laryngeal nerve palsy), dyspnoea (phrenic nerve palsy), dysphagia
[*] Distant metastases: bone pain / fractures, CNS symptoms (headache, double vision, confusion etc)
Describe the common clinical signs associated with disease and understand the structural abnormalities underlying them
[*] Paraneoplastic Syndrome is the presence of a symptom or disease due to the presence of cancer in the body but not due to the local presence of cancer cells.
They are mediated by humoral factors (cytokines and hormones) secreted by tumour cells or the immune response against tumour cells.
- Cushing’s syndrome
- Inappropriate Antidiuretic Hormone Secretion (SIADH)
- Peripheral neuropathy
- Eaton-Lambert syndrome
- - Finger clubbing
- Disseminated intravascular coagulation (DIC)
- Nephrotic syndrome
- Anorexia or cachexia
Understand the imaging techniques used in the diagnosis and staging of the disease
[*] Imaging investigations of various types are central to both the diagnosis and the assessment of the disease – this is known as staging. This is one of the most important determinants of treatment and prognosis.
[*] First Clinical Suspicion: plain chest x-ray
[*] Diagnosis and Staging:
- Serum Biochemistry (Sodium, Liver Function Tests, Calcium)
- Imaging: Cross-sectional imaging: CT and PET-CT scans. Isotope bone scan etc.
- Tissue: Bronchoscopy (+/- endobronchial ultrasound); CT guided needle biopsy of lung; Lymph Node Biopsy (neck); biopsy of metastasis (e.g. liver); Mediastinoscopy, Pleural Biopsy/Cytology
[*] Diagnosis and staging:
- CT scan
- PET scan
- Isotope bone scan
[*] There are two staging systems for Lung Cancer: Number and TMN
Look over Session 7 Imaging Lecture
Describe the number staging system
- Stage 1: small cancer, localised to one area of the lung
- Stage 2 and 3: larger cancer, may have grown into surrounding tissues (lymph nodes)
- Stage 4: cancer has metastasised
Describe the TNM Staging System
[*] TNM Staging System
T: Size and Position of tumour
- T1: Cancer contained within lung (<3cm diameter)
- T2: Cancer has grown (3-7cm diameter) into main bronchus <2cm from the carina, into the visceral pleura, made part of the lung collapse
- T3: Cancer has grown (>7cm diameter). It is invading the chest wall, mediastinal pleura, diaphragm, pericardium => complete lung collapse, more than 1 cancer nodule in the same lobe of the lung
- T4: Cancer invading mediastinum, heart, major blood vessel, trachea, carina, oesophagus, spine, recurrent laryngeal nerve, Cancer nodules in more than one lobe of the same lung
N: Lymph node involvement
- N0: No cancer in lymph nodes
- N1: Cancer in lymph nodes nearest the affected lung
- N2: Cancer in lymph nodes in mediastinum on the same side
- N3: Cancer in lymph nodes on the opposite side of the mediastinum / supraclavicular lymph nodes
- M0: no evidence of distal cancer spread
- M1a: lung nodules, pleural effusion
- M1b: lung cancer cells in distant parts of the body such as pleura, opposite lung, liver or bones etc.
Describe the common methods used to obtain material for histological diagnosis
[*] Tissues for diagnostic purposes is usually obtained either by bronchoscopy, needle biopsy of the lung or pleural tap or biopsy.
[*] Making a histological diagnosis is important not only to confirm that the patient has lung cancer but also to decide the cell type, which is important both in terms of the prognosis and treatment.
Describe the pathology of lung cancer
[*] Pathology of Lung Cancer: carcinoma is an invasive malignant epithelial tumour.
[*] Lung tumours are divided into two groups, depending on the presence or absence of cells:
[*] Non-Small Cell Lung Cancer
- Squamous cell carcinoma (~40%)
- Adenocarcinoma (~35%)
- Large cell carcinoma (~5%)
[*] Small Cell Lung Cancer (~12%)
[*] There are rare tumours (e.g. carcinoid) ~5%
Describe Squamous Cell Carcinoma
- Often central tumours (when bronchial epithelium undergoes metaplasia into squamous cell)
- Angulate cells
- Eosinophilic (pink) cytoplasm (due to production of keratin)
- Intercellular bridges – “prickles”
- Keratin pearls
- Immunohistochemistry (monoclonal antibodies recognize particular proteins “markers”: CK5/6 and P63+, TTF-1-)
- Often peripheral tumours
- Columnar/cuboidal cells
- Form glands (acini)
- Papillary structures
- May line alveoli
- Some produce mucin
- Immunohistochemistry: Most TTF-1+, CK5/6-, p63-
Describe Small Cell Carcinoma
- “oat cell carcinoma”
- Very cellular tumour
- Small nuclei = approximately size of lymphocyte
- Little cytoplasm
- Nuclear moulding
- Often necrosis, lots of mitoses
- Immunnohistochemistry: CD56+, Sytaptophysin+, Chromogranin+
Describe the spread of lung cancer
Locally within the lung
- Necrosis +/- cavitation
- Ulceration (=> haemoptysis)
- Infection – abscess formation
- Bronchial bstruction – lung collapse, consolidation
Locally within the thorax
- Diret spread or metastasis – pleural/pericardial effusions
- Mediastinal structures – superior vena caval obstruction, dysphagia
- Recurrent laryngeal nerve: vocal cord palsy and hoarseness
- Phrenic nerve: diaphragm palsy (paralysis)
- - Other lung, liver, adrenals, bone brain
Describe the behaviour of different histological types and their relationship to prognosis and treatment
[*] Non-Small Cell: more than 2/3rds have inoperable disease at presentation
[*] Small Cell: ¾ have metastatic disease at presentation
[*] Lung cancer survival: overall survival poor: 10-15% live to 5 years. Survival (i.e. prognosis depends on)
- Cell type (small cell worse than non-small cell)
- Stage of disease
- Performance status (general level of fitness)
- Biochemical markers e.g. hyponatraemia
- Co-mordbidites (e.g. cardiac or chronic respiratory disease)
[*] Overall median survival a little over 6 months
[*] Survival worse in UK than in most other western countries.
[*] Survival at 1 year is greater if presentation of disease is earlier (i.e. not present as an emergency case to the specialists but GP-related or due to two week wait)
Discuss the treatment of lung cancer
[*] Treatments include surgery, chemotherapy, radiotherapy and palliative therapy. Often these are used in combination and are very much tailored to the individual patient. Management is best provided by an expert Multi-Disciplinary Team (MDT) covering all the relevant sub-specialties.
- Surgery: mostly non-small cell (<20% operable)
Radical: Curative intent (includes stereotactic RT which targets small areas)
Palliative: Symptom control (for pain relief in cancer that has metastasised to bone)
- Combination chemotherapy (2 or more different agents)
Small cell – potentially curative (minority)
Non-small cell – modest survival increase, symptom control
- Combination therapy
- Combination of chemo and radiotherapy - potentially curative
- Biological targeted therapies: e.g. EGFR and VEGF
- Palliative care
[*] The overall ‘cure’ rate in this type of cancer is worse than for many others, with the 5-year survival rate for all patients being no more than 10% in the UK.
[*] Surgery is the treatment most likely to result in long-term survival but smaller numbers of patients will also live beyond 5 years with chemotherapy and radiotherapy.
[*] Even without the prospect of long-term survival many patients can be offered significant increases in short to medium term life expectancy and significant relief from their symptoms.
Describe the management on Non-Small Cell Lung Cancer
[*] Management of Non-Small Lung Cancer: usually involves multiple modality therapy
- Palliative radiotherapy for local symptoms e.g. cough, haemoptysis, airway obstruction, chest wall pain, bony metastases)
- Chemotherapy: 50-60% response rates. Modest improvement in survival; now targeted at specific cell types.
- Combination therapy: important in locally advanced disease
- Targeted agents: Epidermal Growth Factor Receptor Antagonists (e.g. Erlotinib,Gefitinib), ALK inhibitors (e.g. crizotinib) and Immunotherapy (PD-1, PD-L1 antagonists e.g. Nivolumab) – very promising area of treatment.
Describe the management of Small Cell Carcinoma
[*] Management of Small Cell Cancer:
- A systemic disease in >80% of cases
- Rarely operable
- ~3 months median survival untreated
- Combination therapy: responds well (80-95%), adding ~1 year of survival from chemotherapy combined with radiotherapy in early stage disease
- 10-15% survive 2 years; less than 8% survive 5 years
- Palliative chemotherapy for symptoms
- Death from cerebral metastases common
What kind of supportive care should be part of lung cancer management?
- A disease with multiple symptoms and often poor survival – need for prompt treatment of symptoms
- Clinical nurse specialists have a central role
- Need for early involvement of palliative care services
- Specific palliation usually best done by appropriate specialist e.g. respiratory physician, medical or clinical oncologist.
- Communication between, and co-ordination of the various treatment agencies is vital.
What public health problems are there in Lung Cancer?
[*] Lung Cancer: what are the problems?
- Late Diagnosis (patients present with advanced disease)
- Overall poor prognosis but optimal treatment clearly improves outcomes
- Very symptomatic
- Professional nihilism
- Variable standards of care
- Lack of public pressure
[*] Grounds for optimism
- Incidence falling
- Potential for screening and early diagnosis initiatives
- Better organisation of care (rapid access clinics, multi-disciplinary teams, etc)
- Better diagnostics and staging e.g. EBUS (endobronchial ultrasound scan; PET scans)
- Treatment advances:
More effective radiotherapy
A range of new ‘biological’ targeted agents (molecular subtyping)
Better surgical techniques and higher resection rates
- Raised profile (charities, research, government, etc)
- Survival improving (10% increase in 1 year survival)