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Lung Cancer

From Mediwikis
Chest X ray of patient with Lung Cancer

Lung Cancer is a very serious diagnosis, often patients do very poorly and response to treatment is variable. Survival is very poor, 50% of lung cancer patients die within 6 months of diagnosis.[1]

Risk Factors

Risk factors for the development of lung cancer include:

  • Smoking
  • Asbestos Exposure
  • Industrial Pollution
  • Ionising Radiation

But it should be noted that 15-20% of patients with lung cancer have never smoked.

Presenting Clinical Features

As lung cancer patients often already suffer from chronic lung conditions such as COPD/asbestosis because of exposure to risk factors (smoking, asbestos etc), it can be difficult to detect the presenting clinical feature. Patients present in two main groups; often, a change to current background symptoms, sometimes mistaken for an infection, leads a patient to present, or they present as many other cancer patients do, with general lethargy and unexplained weight loss.

Presenting symptoms include:

  • Cough - sometimes nocturnal (More than half of patients present with a cough, especially after the recent patient information campaign[2])
  • Haemoptysis
  • Chest pain
  • SOB - caused by pleural effusions, phrenic nerve palsy, lobar/total lung collapse due to obstruction by the tumour
  • Dysphagia - due to compression of the oesophagus by a large tumour mass
  • Hoarse voice - indicating invasion of the recurrent laryngeal nerve - this has a poor prognosis
  • Anorexia
  • Fever
  • Lethargy

Presenting signs include:

  • Finger clubbing (particularly with squamous cell carcinoma)
  • Tar staining
  • Lymphadenopathy
  • Signs of pulmonary collapse/consolidation
  • Superior vena cava obstruction (a medical emergency)

Patients may also present with features of metastasis:

  • Neuro - Headaches, seizures, focal neurological signs (e.g. weakness)
  • Liver - Jaundice, liver capsule pain (aching in RUQ)
  • Mskel - Pathological fracture/pain due to boney met

Paraneoplastic manifestations can occur:

  • Humoral paraneoplastic features, mostly seen in Small Cell Lung Cancer, i.e. SIADH (Syndrome of Inappropriate release of Anti Diuretic Hormone), this leads to a low sodium state (hyponatraemia)
  • Antibody-mediated paraneoplastic features, i.e. Eaton-Lambert Syndrome

It is important to note that whilst humoral paraneoplastic syndromes can be cured with tumour removal, antibody-mediated paraneoplastic syndromes may not be cured due to lingering antibodies and are thus considered as an autoimmune disease.

Investigations

Initially:

  • Full History and Examination
  • Chest X-ray
  • Lung Function Tests
  • Bloods - including full blood count and a biochemical profile (including U&Es, LFTs etc

Followed by:

  • Sputum cytology
  • Bronchoscopy
  • Transthoracic needle biopsy, guided by CT

It may be useful to include a test for LDH (lactate dehydrogenase), which is an enzyme secreted during necrosis, this suggests that the cancer is growing faster than it's blood supply and some areas are dying off. It is an indicator of poor prognosis.

Patients suspected of having small cell lung cancer, should have imaging of their upper abdomen.

Patients suspected of having non-small cell lung cancer being considered for radical treatment (i.e. surgical resection of the whole tumour) may require:

  • Pulmonary function tesets (to determine suitability for surgical treatment)
  • Contrast CT of thorax and upper abdomen
  • MRI/ V/Q / PET scans
  • Ultrasound scan

Histological Types of Lung Cancer

Non Small Cell Lung Cancer (NSCLC)

Squamous Cell Carcinoma

Around half of all cases of lung cancer, meaning it is the most common form.

  • Usually found in the proximal bronchi
  • Many are found to have a mutation in p53
  • Local spread is common, but metastasis is usually late, but frequent.
  • Usually present as obstructive masses on the bronchus which lead to infection.
  • Resemble abscesses on X-ray, in that the lesions cavitate but on CT a tumour can usually be identified.
  • It is important to check calcium levels as hypercalcaemia can be a direct result of squamous cell carcinoma due to bone destruction or PTH analogues.

Large Cell Carcinoma

A rarer form of lung cancer, representing about a 10% of cases.

  • Usually found in more distal areas of the lung with well circumscribed borders
  • These develop quickly and are associated with a worse prognosis due to early metastasis.
  • Somewhere between small call and squamous in terms of features

Adenocarcinoma

Around 15% of cases.

  • Can be found in old scar tissue/fibrotic areas
  • Slow growing, metastasise late
  • Seen more in non-smokers and in women
  • classically spreads along airways and often found in the peripheral lung (may involve plerua)

Small Cell Lung Cancer (SCLC)

Around 12% of newly diagnosed cases.

  • Rapidly growing tumours often involving proximal large bronchi
  • Pathogenesis almost invariably involves the loss of p53 and myc family oncogenes are often involved
  • These tumours can secrete hormones including ACTH, ADH and Calcitonin
  • Invade the bloodstream very early, there is early metastasis and thus a poor prognosis.
  • Tumours are often inoperable at presentation as the disease is so extensive

Sites of Metastasis

Distant blood borne metastases are frequently seen in lung cancer patients, typical sites are:

  • Skeleton
  • Bone Marrow
  • Brain
  • Liver
  • Adrenals

Prognostic Factors associated with Lung Cancer

High

  • Moderate to poor performance status
  • Any site of metastasis
  • Elevated LDH

Medium

  • Bone metastasis
  • Liver metastasis
  • Male
  • > 5% weight loss

Low

  • Brain metastasis
  • >65 years old
  • Non squamous type

Complications of Lung Cancer

Hypercalcaemia

Hypercalcaemia can be due to parathyroid hormone related peptide, and is usually associated with non small call lung cancer, head and neck cancers or renal cancer. This phenomenon is rare in breast cancer, where hypercalcaemia is usually due to bone metastasis.

Presentation:

  • Rapid-onset, difficult-to-control nausea
  • Polyuria
  • Polydypsia
  • Cardiac arrythmias

Polyuria and polydypsia combine to cause life threatening dehydration.

Diagnosis is achieved via corrected serum calcium, taking account of albumin. Treatment begins with 1L of normal saline, as this prevents left ventricular hypovolaemia, the primary cause of death. IV bisphosphonate is also required.

Ectopic ACTH (Cushings)

This presents with truncal obesity, fatigue, weakness and hirsutism, alongside various other non-specific symptoms. IT is caused by inappropriate overproduction of adenocorticotrophic hormone precursors, and is a frequent result of small cell lung cancer.

Pancoast Syndrome

Pancoast Syndrome can be a noteworthy presentation of an underlying lung cancer. It can present with pain, weakness in the hand and tingling on the inner aspect of the arm.

Pancoast syndrome is due to an apical tumour pressing on the sympathetic chain and classically presents with a Horners' syndrome in one of the eyes, specifically:

  • Ptosis - drooping of the upper eyelid
  • Anhydrosis - lack of sweating
  • Enopthalmos - the eye appears sunken
  • Miosis - Decreased pupil size (due to unopposed parasympathetic activity)

It should be noted that anhydrosis is only a feature if the causative lesion is between the hypothalamus and the carotid arch. If the lesion is distal to the carotid arch, there is skin sparing.

A Horners' Syndrome is not only caused by apical lung tumours, it can also be caused by:

  • An embryological remnant (i.e. branchial cyst)
  • An aortic arch defect (i.e. aortic arch dissection caused by Marfan's Syndrome)
  • A carotid body tumour
  • Migraine

Environmental Pollutants in Lung Cancer

Environmental pollutants are a major cause after smoking, these include asbestos, combustion products and second hand smoke.

Examples of populational interventions:

·      The Smog of 52 – clean air act

·      The domestic burning of coal – Health and safety act

·      Motor Vehicle and workplace dust – health and safety act

·      Cigarette smoking – smoking ban 2007

As a doctor you’ll treat people affected by pollution and those affected by workplace toxicity.

Toxicity factors of the pollutants:

Aerosolisability: particles that can form aerosol are more likely to be inhaled.

Inhalability: ability to pass through the respiratory airways. Particles <10μm will do so

Respirability: ability to pass from alveoli to the blood. Particles <2.5μm will do so

Particle size and aspect ratio

Solubility and durability

Surface reactivity

Defence

Physical defence: barriers, filtration and mucociliary transport

Chemical defence: Cytokines, chemokines, IgA and IgG immune responses and Clara cell metabolism of xenobiotics

Cellular defence: neutrophils and macrophages

Remember that SCAB (silica coal asbestos and beryillium) materials are industrial/occupational toxicants. The most common others are the SCAM toxicants (Smoking, Cocaine, Air pollutants such as diesel exhaust particles and Medicines) which are mostly ‘avoidable’.

Environmental causes of cancer cause other conditions such as fibrosis, asthma, COPD, and Dust in the lungs or 'Pneumoconiosis'

References

  1. http://www.bbc.co.uk/news/health-26871259 
  2. http://www.nhs.uk/be-clear-on-cancer/lung-cancer/home