Lung cancer

Lung cancer

Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the 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 also the most common in women, is responsible for 1.3 million deaths worldwide annually.[1] The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.[2]

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.[3] The most common cause of lung cancer is long-term exposure to tobacco smoke.[4] The occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases [5], is often attributed to a combination of genetic factors,[6][7] radon gas,[8] asbestos,[9] and air pollution,[10][11][12] including secondhand smoke.[13][14]

Lung cancer may be seen on chest radiograph 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%.[2]

Classification

The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. There are two main types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80.4%) and small-cell (16.8%) lung carcinoma.[15] This classification, based on histological criteria, has important implications for clinical management and prognosis of the disease.

Non-small cell lung carcinoma (NSCLC)

The non-small cell lung carcinomas are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma, and large cell lung carcinoma.

Accounting for 25% of lung cancers,[19] squamous cell lung carcinoma usually starts near a central bronchus. A hollow cavity and associated necrosis are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.[3]

Adenocarcinoma accounts for 40% of lung cancers.[19] It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer.[20] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.[21]

Small cell lung carcinoma (SCLC)

Small cell lung carcinoma (SCLC, also called "oat cell carcinoma") is less common. It tends to arise in the larger airways (primary and secondary bronchi) and grows rapidly, becoming quite large.[22] The "oat" cell contains dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this an endocrine/paraneoplastic syndrome association.[23] While initially more sensitive to chemotherapy, it ultimately carries a worse prognosis and is often metastatic at presentation. Small cell lung cancers are divided into limited stage and extensive stage disease. This type of lung cancer is strongly associated with smoking.[24]

Others

In infants and children, the most common primary lung cancers are pleuropulmonary blastoma and carcinoid tumor.[25]

Secondary cancers

The lung is a common place for metastasis from tumors in other parts of the body. These secondary cancers are identified by the site of origin; thus, a breast cancer metastasis to the lung is still known as breast cancer. They often have a characteristic round appearance on chest radiograph.[26] In children, the majority of lung cancers are secondary.[25]

Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.[3]

Staging

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).[27] 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]

Lung cancer Signs and symptoms

Symptoms that suggest lung cancer include:[28]
dyspnea (shortness of breath)
hemoptysis (coughing up blood)
chronic coughing or change in regular coughing pattern
wheezing
chest pain or pain in the abdomen
cachexia (weight loss), fatigue, and loss of appetite
dysphonia (hoarse voice)
clubbing of the fingernails (uncommon)
dysphagia (difficulty swallowing).

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.[29] 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,[30] 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.[3] 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 brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys.[31] About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.[2]

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.[3]

Smoking

Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.[32] Across the developed world, almost 90% of lung cancer deaths are caused by smoking.[33] In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).[34] 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.[35] Cigarette smoke contains over 60 known carcinogens,[36] including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.[37]

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.[38] In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,[39] and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.[40]

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.,[41] Europe,[42] the UK,[43] and Australia[44] 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.[45]

Roughly ten-fifteen percent of lung cancer patients have never smoked.[46] That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United States each year. Because of the five-year survival rate, each year in the U.S. more never-smokers die of lung cancer than do patients of leukemia, ovarian cancer, or AIDS.[47]

Lung cancer Diagnosis

Performing a chest radiograph 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 radiographic 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.[2]

Abnormal findings in cells ("atypia") in sputum are associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may have a role in the early detection of lung cancer.[67]

The differential diagnosis for patients who present with abnormalities on chest radiograph 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.[3] Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason.

Lung cancer Prevention

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.[68] Most importantly, are prevention programs that target the young. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies.[69] 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.[69]

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, France in 2008 and Turkey in 2009. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005.[70] 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.[71]

The long-term use of supplemental multivitamins—such as vitamin C, vitamin E, and folate—does not reduce the risk of lung cancer. Indeed long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer.[72]

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.[73]

Lung cancer Treatment

Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include surgery, chemotherapy, and radiation therapy.[2][75]

Lung cancer
Norovirus Marfan syndrome Nasal Cancer Marburg Hemorrhagic Fever Malignant Hyperthermia Male Breast Cancer Lyme disease Lung cancer Legionellosis Latex Allergy Lassa Fever Jaundice / Kernicterus Hypothyroidism Kawasaki disease Genetic-Brain-Disorders Gallbladder-Diseases Fetal alcohol syndrome Diabetes Crimean-Congo Hemorrhagic Fever Dengue-and-Dengue-Hemorrhagic-Fever Chikungunya-Fever Cat Scratch Disease Cancer Larynx Cancer Among Children Borderline Personality Disorder Bladder cancer Baylisascaris Infection Benign tumor Skin Cancer African trypanosomiasis Coming Soon	Lung cancer Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the 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 also the most common in women, is responsible for 1.3 million deaths worldwide annually.[1] The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.[2] 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.[3] The most common cause of lung cancer is long-term exposure to tobacco smoke.[4] The occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases [5], is often attributed to a combination of genetic factors,[6][7] radon gas,[8] asbestos,[9] and air pollution,[10][11][12] including secondhand smoke.[13][14] Lung cancer may be seen on chest radiograph 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%.[2] Classification The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. There are two main types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80.4%) and small-cell (16.8%) lung carcinoma.[15] This classification, based on histological criteria, has important implications for clinical management and prognosis of the disease. Non-small cell lung carcinoma (NSCLC) The non-small cell lung carcinomas are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma, and large cell lung carcinoma. Accounting for 25% of lung cancers,[19] squamous cell lung carcinoma usually starts near a central bronchus. A hollow cavity and associated necrosis are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.[3] Adenocarcinoma accounts for 40% of lung cancers.[19] It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer.[20] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.[21] Small cell lung carcinoma (SCLC) Small cell lung carcinoma (SCLC, also called "oat cell carcinoma") is less common. It tends to arise in the larger airways (primary and secondary bronchi) and grows rapidly, becoming quite large.[22] The "oat" cell contains dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this an endocrine/paraneoplastic syndrome association.[23] While initially more sensitive to chemotherapy, it ultimately carries a worse prognosis and is often metastatic at presentation. Small cell lung cancers are divided into limited stage and extensive stage disease. This type of lung cancer is strongly associated with smoking.[24] Others In infants and children, the most common primary lung cancers are pleuropulmonary blastoma and carcinoid tumor.[25] Secondary cancers The lung is a common place for metastasis from tumors in other parts of the body. These secondary cancers are identified by the site of origin; thus, a breast cancer metastasis to the lung is still known as breast cancer. They often have a characteristic round appearance on chest radiograph.[26] In children, the majority of lung cancers are secondary.[25] Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.[3] Staging 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).[27] 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] Lung cancer Signs and symptoms Symptoms that suggest lung cancer include:[28] dyspnea (shortness of breath) hemoptysis (coughing up blood) chronic coughing or change in regular coughing pattern wheezing chest pain or pain in the abdomen cachexia (weight loss), fatigue, and loss of appetite dysphonia (hoarse voice) clubbing of the fingernails (uncommon) dysphagia (difficulty swallowing). 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.[29] 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,[30] 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.[3] 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 brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys.[31] About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.[2] 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.[3] Smoking Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.[32] Across the developed world, almost 90% of lung cancer deaths are caused by smoking.[33] In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).[34] 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.[35] Cigarette smoke contains over 60 known carcinogens,[36] including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.[37] 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.[38] In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,[39] and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.[40] 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.,[41] Europe,[42] the UK,[43] and Australia[44] 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.[45] Roughly ten-fifteen percent of lung cancer patients have never smoked.[46] That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United States each year. Because of the five-year survival rate, each year in the U.S. more never-smokers die of lung cancer than do patients of leukemia, ovarian cancer, or AIDS.[47] Lung cancer Diagnosis Performing a chest radiograph 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 radiographic 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.[2] Abnormal findings in cells ("atypia") in sputum are associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may have a role in the early detection of lung cancer.[67] The differential diagnosis for patients who present with abnormalities on chest radiograph 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.[3] Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason. Lung cancer Prevention 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.[68] Most importantly, are prevention programs that target the young. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies.[69] 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.[69] 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, France in 2008 and Turkey in 2009. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005.[70] 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.[71] The long-term use of supplemental multivitamins—such as vitamin C, vitamin E, and folate—does not reduce the risk of lung cancer. Indeed long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer.[72] 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.[73] Lung cancer Treatment Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include surgery, chemotherapy, and radiation therapy.[2][75]
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