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Flashcards in Lung cancer Deck (22):
1

How common is lung cancer?

Lung cancer is the second most common cancer diagnosed in the UK after breast cancer.

Lung cancer is the second most common cancer in men after prostate cancer,

Lung cancer is the third most common cancer in women after breast and bowel cancer.

Around 40,800 people were diagnosed with lung cancer in the UK in 2008, that’s 112 people every day

Overall, less than 10% of lung cancer patients survive the disease for at least five years after diagnosis.

2

What are the causes of lung cancer?

1. Smoking (90%)
2. Ionising radiation
3. Asbestos
4. Fibrosing alveolitis
5. Other industrial chemicals: arsenic, chloromethyl ethers, chromium, nickel, polyaromatic hydrocarbons, vinyl chloride


Stopping smoking before middle age avoids most of the risk of smoking-related lung cancer. Living with someone who smokes, increases risk of lung cancer in non-smokers by about a quarter. Exposure to passive smoke in the home causes around 11,000 deaths every year in the UK from lung cancer, stroke and ischaemic heart disease.

3

What are the different type of primary lung cancers and how common are they?

1. Small cell cancer (24%)

2. Non-small cell cancer (76%)
a. Adenocarcinoma (13%)
b. Squamous (48%)
c. Large cell (10%)
d. Other (5%)

4

How do lung cancers present?

o cough
o haemoptysis
o chest pain
o breathlessness
o stridor
o hoarse voice
o weight loss
o facial swelling
• Chest radiograph
• Metastases
• Non-metastatic manifestations
• (post mortem)

5

What are the signs of a lung cancer on examination?

o weight loss
o finger clubbing
o lymphadenopathy
o chest asymmetry
o focal chest signs: consolidation/ fluid
o hepatomegaly
o neuropathy
o Pancoasts tumour

6

How can lung cancers be detected on a chest x-ray?

Areas of consolidation (usually dense and semi-well defined)

Large pleural effusions can be caused by the cancer

7

How can lung metastases present?

Pancoasts tumour:
- Supraclavicular fossa is filled in – apex of lung tumour is growing up into the supraclavicular fossa.
- The tumour may affect the brachial plexus and result in pain of the inner aspect of the arm.
- The patient may also have Horner’s syndrome, because the sympathetic nerve that supplies the eye, arises at T1 and reaches the lower part of the brachial plexus before continuing.


Superior vena cava obstruction
The tumour grows in the mediastinum and squashes the SVC. This compromises venous return from the head, upper mediastinum and arms. The patient will complain of swelling in the face and arms, which resolves during the day but occurs the following morning again.
Eventually the face and hands swelling will be consistent and the patient will complain of headaches.

Brain metastasis
Patient may present with ‘stroke’ like symptoms due to space occupying lesions

Cutaneous metastasis:
Right shoulder, hard palate

8

How is lung cancer diagnosed?

History

Examination

Chest radiograph / CT Scan

Bloods (FBC, LFTs, Calcium)

Tests to determine cell type:
o Fibreoptic bronchoscopy ~ 60%
o Percutaneous needle biopsy
o Node biopsy
o Mediastinoscopy / mediastinotomy
o Thoracotomy
o Thoracoscopy [Visceral and parietal pleural deposits (mesothelioma tumour – found in pleural space)]

9

When is lung cancer deemed inoperable?

•Distant metastasis
•Mediastinal spread e.g. tumour invading atrium or invading chest wall
•Recurrent laryngeal nerve palsy
•Phrenic nerve palsy
•Poor pulmonary function
•Frequent angina / heart failure
•Psychological failure

10

What is the treatment for small cell lung cancer?

Small cell tumours are nearly always dissemination at presentation. They may respond well to chemotherapy but invariably relapse.

Palliation: radiotherapy is used fro bronchial obstruction, SVC obstruction, haemoptysis, bone pain and cerebral metastasis. SVC stent, radiotherapy and dexamethasone for SVC obstruction

11

What is the treatment for non-small cell lung cancer?

Excision is the treatment of choice for peripheral tumours, with no metastatic spread.: stage I/II.
2. Curative radiotherapy is an alternative is respiratory reserve is poor.
3. Chemotherapy +/- radiotherapy is used for more advance disease
4. Palliation: Symptomatic relief (painkillers, drain effusion), radiotherapy + chemotherapy

12

How is EGFR related to lung cancer?

Epidermal growth factor receptor (EGFR) is a protein found in abnormally high levels on the surface of many types of cancer cells, particularly non-small cell lung cancer (NSCLC) cells. A patient‘s EGFR mutation status (positive or negative) can be confirmed using a sample of tumour tissue. EGFR mutation positive cells predict response to specific chemotherapy – gefitinib. Gefitinib only used if mutation present.

13

What is the pathophysiology of cancer?

Cancer is a loss of normal growth control. If a cell is damaged beyond repair, the normal process is cell apoptosis. In cancer, the damaged cells don’t undergo apoptosis but instead begin to replicate and undergo mutations. This leads to uncontrolled growth. Initially it is in situ, contained to the area the original ‘damaged cell’ arose. Over time, the cancer cells begive to invade surrounding tissues and blood vessel. The cells are transported by the circulatory system to distant sites, to re-invade and grow at new locations.

Benign tumours are cells that may have grown quickly but are localised and cannot spread by invasion or metastasis. Malignant cells develop properties to invade neighbouring tissues, enter blood vessels and metastasis to different sites.

When the cells become mutated they stop functioning correctly and severe dysplasia occurs (carcinoma in situ). As this gains a blood supply and begins to erode local tissue, the cancer can invade and metastasis to distant sites.

14

How do cancer cells appear microscopically?

Large number or irregularly shaped dividing cells

Large, variably shaped nuclei

Small cytoplasmic volume relative to nuclei

Variation in cell size and shape

Loss of normal specialised cell features

Disorganised arrangement of ells

Poorly defined tumour boundary.

15

What local complications can lung cancer cause?

Local complications:
As the cancer increases in size, it can block the bronchioles of the lungs and obstruct/prevent gas exchange occurring. This can case wheezing and shortness of breath.

Partial obstruction can cause pathogens to travel into the lung on inhalation but block the removal of pathogens on exhalation and this can result in infections.

Tumours can grow to compress other structures i.e. nerves.
• For example, Pancoast tumours (at the lung apices) can impinge on the phrenic nerve and consequently affect the movements of the diaphragm and consequently the control of breathing.
• Impinged laryngeal nerve can result in a hoarse voice
• Impinged sympathetic nerves can result in Horner’s syndrome (miosis, partial ptosis and anhidrosis)

Compressed superior vena cava – insufficient drainage, oedema (blood backup into upper limbs and face)

Rib erosion

Pericarditis

* Non-small cell cancers tend to develop in the apices of the lung and small cell cancers tend to develop in the middle zone of the lung.

16

What complications can the spread of cancer cause?

Spread to the brain – can result in CNS problem e.g. dizziness, seizures

Spread to the bone – bone pain, bone weakness, fractures

Spread to the liver – Jaundice (liver dysfunction)

Spread to the adrenal gland – Change the level of hormones secreted

Spread to the hilar lymph nodes

17

What are the complications of the immune response to the cancer?

The immune response causes inflammation and an ongoing fever. In small cell cancers, the immune system produces antibodies that act against the cancer, but also against neurones in muscles. The antibodies damage the muscles ability to send signals and therefore results in muscle weakness and dysfunction.

18

What are the endocrine complications of lung cancer?

Non-small cell produces Parathyroid- related proteins.
• Calcium is removed from the bones and is found in high concentrations in the blood. This results in weakening of the bones which often results in breaks.

Small cell produces Anti-diuretic hormone
• Decreased urine volume
• Increased blood pressure.
• More sodium excreted.

Small cell cancers produced Adreno-corticotropic hormones
• Increased corticosteroids
• Immune suppression

19

How is calcium normally controlled?

The parathyroid gland is important in controlling the amount of calcium within a carefully prescribed range (8.5-10mg/dl). A reduction in calcium stimulates the parathyroid gland to produce parathyroid hormone (PTH). PTH is distributed in the blood to 3 main areas around the body.
1. Kidneys: stimulates the nephron tubules to increase reabsorption of calcium
2. Bones: stimulates the osteoblasts to release RANKL which activate osteoclast precursors to stimulate the production of osteoclasts. Osteoclast cause the destruction of bone tissue which releases stored calcium in the bone into the blood stream
3. Gut: Increase absorption of calcium.

20

How can cancer cause hypercalcaemia?

Breast cancer cells, squamous cell lung cancer (non-small cell), cholangiocarcinoma and multiple myeloma all have genetic mutations that cause a production of aberrant proteins called Parathyroid- related-Protein (PTrP). This PTrP is similar enough to PTH that it can bind to PTH receptors in the kidney, bone and gut. PTrP is secreted due to the cancer and not in response to the calcium levels and therefore cause hypercalcaemia. This occurs in 10% of cancer patients and is often recognised late and mis-managed.

21

What are the signs and symptoms of hypercalcaemia?

Nervous system:
• Normal: Calcium stimulates vesicles in the pre-synaptic neurone to bind with the membrane and release its neurotransmitter into the synaptic cleft.
• Hypercalcaemia: anxiety, depression, cognitive changes, lethargy, coma

Muscles:
• Normal: Calcium is involved in binding troponin and myosin for cross-links during contraction and relaxations
• Hypercalcaemia: cramping of the smooth muscle in the gut --> nausea and vomiting, anorexia

Cardiac:
• Normal: Calcium maintains the prolonged action potential in cardiomyocytes.
• Hypercalcaemia: sinus arrhythmias, ventricular arrhythmias (calcium >14)

22

What is the treatment for hypercalcaemia?

The main treatment is to treat the underlying cause e.g. treat the tumour causing the production of PTrP.

Pharmacological treatments for hypercalcemia include:
1. Fluid and Lasix, which cause calciuresis (excretion of calcium in the urine, especially in excessive amounts)
2. Bisphosphonates +/- calcitonin can be used if calcium is persistently elevated.