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Carcinosin lung 30C [ Cancer lung and respiratory tract]

Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and the second most common in women (after breast cancer),[1] is responsible for 1.3 million deaths worldwide annually.[2] The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.[3]

The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma. This distinction is important, because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with surgery, while small cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation.[4] The most common cause of lung cancer is long-term exposure to tobacco smoke.[5] The occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases [6], is often attributed to a combination of genetic factors,[7][8] radon gas,[9] asbestos,[10] and air pollution,[11][12][13] including secondhand smoke.[14][15]

Lung cancer may be seen on chest x-ray and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed via bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. With treatment, the five-year survival rate is 14%.[3]

Staging

See also: lung cancer staging with EUS

Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the prognosis and potential treatment of lung cancer. Non-small cell lung carcinoma is staged from IA ("one A"; best prognosis) to IV ("four"; worst prognosis).[26] Small cell lung carcinoma is classified as limited stage if it is confined to one half of the chest and within the scope of a single radiotherapy field; otherwise, it is extensive stage.[22]

 

Signs and symptoms

Symptoms that suggest lung cancer include:[27]

If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. This can lead to accumulation of secretions behind the blockage, predisposing the patient to pneumonia. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.

Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease.[28] In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors,[29] may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome) as well as muscle weakness in the hands due to invasion of the brachial plexus.

Many of the symptoms of lung cancer (bone pain, fever, and weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness.[4] In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the bone, such as the spine (causing back pain and occasionally spinal cord compression); the liver; and the brain. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest x-rays.[3]

 

Causes

The main causes of lung cancer (and cancer in general) include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.[4]

 

Smoking

The incidence of lung cancer is highly correlated with smoking. Source: NIH.

Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.[30] Across the developed world, almost 90% of lung cancer deaths are caused by smoking.[31] In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).[32] Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women.[33] Cigarette smoke contains over 60 known carcinogens,[34] including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.[35]

The length of time a person smokes (as well as rate of smoking) increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed.[36] In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,[37] and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.[38]

Passive smoking-the inhalation of smoke from another's smoking-is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker as well. Studies from the U.S.,[39] Europe,[40] the UK,[41] and Australia[42] have consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests that it is more dangerous than direct smoke inhalation.[43]

 

 Radon gas

Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer, after smoking.[9] Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/).[44] Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk, with prolonged radon exposure above the EPA's action level of 4 pCi/L.[45][46]

 

Asbestos

Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer.[10] In the UK, asbestos accounts for 2-3% of male lung cancer deaths.[47] Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).

 

 Viruses

Viruses are known to cause lung cancer in animals,[48][49] and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus,[50] JC virus,[51] simian virus 40 (SV40), BK virus, and cytomegalovirus.[52] These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.

Genetics

Main article: Carcinogenesis

Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.[53] Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.[54] Mutations in the K-ras proto-oncogene are responsible for 10-30% of lung adenocarcinomas.[55][56] The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.[55] Mutations and amplification of EGFR are common in non-small cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently.[55] Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small cell lung carcinoma. The p53 tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases.[57] Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.[55]

Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for interleukin-1,[58] cytochrome P450,[59] apoptosis promoters such as caspase-8,[60] and DNA repair molecules such as XRCC1.[61] People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens.

Diagnosis

Chest x-ray showing a cancerous tumor in the left lung.

Performing a chest x-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. If there are no x-ray findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. Bronchoscopy or CT-guided biopsy is often used to identify the tumor type.[3]

CT scan showing a cancerous tumor in the left lung.

The differential diagnosis for patients who present with abnormalities on chest x-ray includes lung cancer as well as nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers.[4] Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest x-ray or CT scan taken for an unrelated reason.

 

Prevention

See also: Smoking ban and List of smoking bans

Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventative tool in this process.[62] Most importantly, are prevention programs that target the youth. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies.[63] Between the settlement money and tobacco taxes, each state's public health department funds their prevention programs, although none of the states are living up to the Center for Disease Control's recommended amount by spending 15 percent of tobacco taxes and settlement revenues on these prevention efforts.[63]

Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, and France in 2008. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005.[64] In many countries, pressure groups are campaigning for similar bans. In 2007, Chandigarh became the first city in India to become smoke-free. India introduced a total ban on smoking at public places on Oct 2 2008.

Arguments cited against such bans are criminalisation of smoking, increased risk of smuggling, and the risk that such a ban cannot be enforced.[65]

A 2008 study performed in over 75,000 middle-aged and elderly people demonstrated that the long-term use of supplemental multivitamins-such as vitamin C, vitamin E, and folate-did not reduce the risk of lung cancer. To the contrary, the study indicates that the long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer.[66]

The World Health Organization has called for governments to institute a total ban on tobacco advertising in order to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where already instituted.[67]

 

Screening

Main article: Lung cancer screening

Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest x-ray or computed tomography (CT) of the chest. So far, screening programs for lung cancer have not demonstrated any clear benefit. Randomized controlled trials are underway in this area to see if decreased long-term mortality can be directly observed from CT screening

 
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