Lung Cancer

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Cancer of the lung like all cancers, results from an abnormality in the body's basic unit of life, the cell. Normally, the body maintains a system of checks and balances on cell growth so that cells divide to produce new cells only when new cells are needed. Disruption of this system of checks and balances on cell growth results in an uncontrolled division and proliferation of cells that eventually forms a mass known as a tumor.

Tumors can be benign or malignant ; when we speak of "cancer," we are referring to those tumors that are malignant. Benign tumors usually can be removed and do not spread to other parts of the body. Malignant tumors, on the other hand, often grow aggressively locally where they start, but tumor cells also can enter into the bloodstream or lymphatic system and then spread to other sites in the body.

This process of spread is termed metastasis; the areas of tumor growth at these distant sites are called metastases. Since lung cancer tends to spread ormetastasize very early after it forms, it is a very life-threatening cancer and one of the most difficult cancers to treat. While lung cancer can spread to any organ in the body, certain locations -- particularly the adrenal glands, liver, brain, and bones -- are the most common sites for lung cancer metastasis.

The lung also is a very common site for metastasis from malignant tumors in other parts of the body. Tumor metastases are made up of the same types of cells as the original (primary) tumor. For example, if prostate cancer spreads via the bloodstream to the lungs, it is metastatic prostate cancer in the lung and is not lung cancer.

The principal function of the lungs is to exchange gases between the air we breathe and the blood. Through the lung, carbon dioxide is removed from the bloodstream and oxygen enters the bloodstream. The right lung has three lobes, while the left lung is divided into two lobes and a small structure called the lingula that is the equivalent of the middle lobe on the right. The major airways entering the lungs are the bronchi, which arise from the trachea, which is outside the lungs. The bronchi branch into progressively smaller airways called bronchioles that end in tiny sacs known as alveoli where gasexchange occurs. The lungs and chest wall are covered with a thin layer of tissue called the pleura.

Lung cancers can arise in any part of the lung, but 90%-95% of cancers of the lung are thought to arise from the epithelial cells, the cells lining the larger and smaller airways (bronchi and bronchioles); for this reason, lung cancers are sometimes called bronchogenic cancers or bronchogenic carcinomas. (Carcinoma is another term for cancer.) Cancers also can arise from the pleura (called mesotheliomas) or rarely from supporting tissues within the lungs, for example, the blood vessels.

How common is lung cancer?
Lung cancer is the most common cause of death due to cancer in both men and women throughout the world. Statistics from the American Cancer Society estimated that in 2015 about 221,000 new cases of lung cancer in the U.S. occurred and over 157,000 deaths were due to the disease. According to the U.S. National Cancer Institute, approximately one out of every 14 men and women in the U.S. will be diagnosed with cancer of the lung at some point in their lifetime.

Lung cancer is predominantly a disease of the elderly; almost 70% of people diagnosed with lung cancer are over 65 years of age, while less than 3% of lung cancers occur in people under 45 years of age.

Lung cancer was not common prior to the 1930s but increased dramatically over the following decades as tobacco smoking increased. In many developing countries, the incidence of lung cancer is beginning to fall following public education about the dangers of cigarette smoking and the introduction of effective smoking-cessation programs. Nevertheless, lung cancer remains among the most common types of cancers in both men and women worldwide. In the U.S., lung cancer has surpassed breast cancer as the most common cause of cancer-related deaths in women.

What causes lung cancer?

Smoking
The incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use. The risk of lung cancer increases with the number of cigarettes smoked and the time over which smoking has occurred; doctors refer to this risk in terms of pack-years of smoking history (the number of packs of cigarettes smoked per day multiplied by the number of years smoked). For example, a person who has smoked two packs of cigarettes per day for 10 years has a 20 pack-year smoking history.
While the risk of lung cancer is increased with even a 10-pack-year smoking history, those with 30-pack-year histories or more are considered to have the greatest risk for the development of lung cancer . Among those who smoke two or more packs of cigarettes per day, one in seven will die of lung cancer.



Pipe and cigar smoking also can cause lung cancer, although the risk is not as high as with cigarette smoking. Thus, while someone who smokes one pack of cigarettes per day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker.

Tobacco smoke contains over 4,000 chemical compounds, many of which have been shown to be cancer-causing or carcinogenic. The two primary carcinogens in tobacco smoke are chemicals known as nitrosamines and polycyclic aromatic hydrocarbons. The risk of developing lung cancer decreases each year following smoking cessation as normal cells grow and replace damaged cells in the lung. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking.

Passive smoking

Passive smoking or the inhalation of tobacco smoke by nonsmokers who share living or working quarters with smokers, also is an established risk factor for the development of lung cancer. Research has shown that nonsmokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with nonsmokers who do not reside with a smoker.
The risk appears to increase with the degree of exposure (number of years exposed and number of cigarettes smoked by the household partner). It is estimated that over 7,000 lung cancer deaths occur each year in the U.S. that are attributable to passive smoking.

What causes lung cancer? (Part 2)

Asbestos fibers
Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace was a common source of exposure to asbestos fibers, as asbestos was widely used in the past as both thermal and acoustic insulation. Today, asbestos use is limited or banned in many countries, including the U.S. Both lung cancer and mesothelioma (cancer of the pleura of the lung as well as of the lining of the abdominal cavity called the peritoneum) are associated with exposure to asbestos.

Cigarette smoking drastically increases the chance of developing an asbestos-related lung cancer in workers exposed to asbestos; asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers, but asbestos workers who smoke have a risk that is fifty- to ninety-fold greater than nonsmokers.

Radon gas
Radon gas is a natural radioactive gas that is a natural decay product of uranium that emits a type of ionizing radiation. Radon gas is a known cause of lung cancer, with an estimated 12% of lung-cancer deaths attributable to radon gas, or about 21,000 lung-cancer-related deaths annually in the U.S., making radon the second leading cause of lung cancer in the U.S. after smoking. As with asbestos exposure, concomitant smoking greatly increases the risk of lung cancer with radon exposure. Radon gas can travel up through soil and enter homes through gaps in the foundation, pipes, drains, or other openings.

The U.S. Environmental Protection Agency estimates that one out of every 15 homes in the U.S. contains dangerous levels of radon gas. Radon gas is invisible and odorless , but it can be detected with simple test kits.

What causes lung cancer? (Part 3)

Familial predisposition
While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Numerous studies have shown that lung cancer is more likely to occur in both smoking and nonsmoking relatives of those who have had lung cancer than in the general population. One study in never-smokers showed that a genetic change at a single region on chromosome 13 was associated with an increase in risk for developing non-small cell lung cancer.

A large genetic study of lung cancer that involved over 10,000 people from 18 countries and led by the International Agency for Research on Cancer (IARC), identified a small region in the genome (DNA) that contains genes that appear to confer an increased susceptibility to lung cancer in smokers. The specific genes, located on the q arm of chromosome 15, code for proteins that interact with nicotine and other tobacco toxins (nicotinic acetylcholine receptor genes).

Lung diseases

The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with an increased risk (four- to six-fold the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded. Pulmonary fibrosis (scarring of the lung) appears to increase the risk about seven-fold, and this risk does not appear to be related to smoking.

Prior history of lung cancer
Survivors of lung cancer have a greater risk of developing a second lung cancer than the general population has of developing a first lung cancer. Survivors of non-small cell lung cancers (NSCLCs, see below) have an additive risk of 1%-2% per year for developing a second lung cancer. In survivors of small cell lung cancers (SCLCs, see below), the risk for development of second lung cancers approaches 6% per year.

Air pollution
Air pollution from vehicles, industry, and power plants can raise the likelihood of developing lung cancer in exposed individuals. Up to 1%-2% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk for the development of lung cancer similar to that of passive smoking.

What are the types of lung cancer? Lung cancers, also known as bronchogenic carcinomas, are broadly classified into two types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). This classification is based upon the microscopic appearance of the tumor cells themselves, specifically the size of the cells. These two types of cancers grow and spread in different ways and may have different treatment options, so a distinction between these two types is important.

SCLC comprise about 20% of lung cancers and are the most aggressive and rapidly growing of all lung cancers. SCLC are strongly related to cigarette smoking, with only 1% of these tumors occurring in nonsmokers. SCLC metastasize rapidly to many sites within the body and are most often discovered after they have spread extensively. Referring to a specific cell appearance often seen when examining samples of SCLC under the microscope, these cancers are sometimes called oat cell carcinomas.

NSCLC are the most common lung cancers, accounting for about 80% of all lung cancers. NSCLC can be divided into three main types that are named based upon the type of cells found in the tumor:
• Adenocarcinomas are the most commonly seen type of NSCLC in the U.S. and comprise up to 50% of NSCLC. While adenocarcinomas are associated with smoking, like other lung cancers, this type is observed as well in nonsmokers who develop lung cancer. Most adenocarcinomas arise in the outer, or peripheral, areas of the lungs.

• Bronchioloalveolar carcinoma is a subtype of adenocarcinoma that frequently develops at multiple sites in the lungs and spreads along the preexisting alveolar walls.

• Squamous cell carcinomas were formerly more common than adenocarcinomas; at present, they account for about 30% of NSCLC. Also known as epidermoid carcinomas, squamous cell cancers arise most frequently in the central chest area in the bronchi.

• Large cell carcinomas , sometimes referred to as undifferentiated carcinomas, are the least common type of NSCLC.

• Mixtures of different types of NSCLC also are seen.

Other types of cancers can arise in the lung; these types are much less common than NSCLC and SCLC and together comprise only 5%-10% of lung cancers:
• Bronchial carcinoids account for up to 5% of lung cancers. These tumors are generally small (3 cm-4 cm or less) when diagnosed and occur most commonly in people under 40 years of age. Unrelated to cigarette smoking, carcinoid tumors can metastasize, and a small proportion of these tumors secrete hormone-like substances that may cause specific symptoms related to the hormone being produced. Carcinoids generally grow and spread more slowly than bronchogenic cancers, and many are detected early enough to be amenable to surgical resection.

• Cancers of supporting lung tissue such as smooth muscle, blood vessels, or cells involved in the immune response can rarely occur in the lung. As discussed previously, metastatic cancers from other primary tumors in the body are often found in the lung. Tumors from anywhere in the body may spread to the lungs either through the bloodstream, through the lymphatic system, or directly from nearby organs.

Metastatic tumors are most often multiple, scattered throughout the lung, and concentrated in the peripheral rather than central areas of the lung.

What are lung cancer symptoms and signs?

Symptoms of lung cancer are varied depending upon where and how widespread the tumor is. Warning signs of lung cancer are not always present or easy to identify. Lung cancer may not cause pain or other symptoms in some cases. A person with lung cancer may have the following kinds of symptoms:
• No symptoms: In up to 25% of people who get lung cancer, the cancer is first discovered on a routinechest X-ray or CT scan as a solitary small mass sometimes called a coin lesion, since on a two-dimensional X-ray or CT scan, the round tumor looks like a coin. These patients with small, single masses often report no symptoms at the time the cancer is discovered.

• Symptoms related to the cancer: The growth of the cancer and invasion of lung tissues and surrounding tissue may interfere with breathing, leading to symptoms such as cough, shortness of breath, wheezing, chest pain, and coughing up blood (hemoptysis). If the cancer has invaded nerves, for example, it may cause shoulder pain that travels down the outside of the arm (called Pancoast syndrome) orparalysis of the vocal cords leading to hoarseness. Invasion of the esophagusmay lead to difficulty swallowing (dysphagia). If a large airway is obstructed, collapse of a portion of the lung may occur and cause infections (abscesses,pneumonia) in the obstructed area.

• Symptoms related to metastasis: Lung cancer that has spread to the bones may produce excruciating pain at the sites of bone involvement. Cancer that has spread to the brain may cause a number of neurologic symptoms that may includeblurred vision, headaches, seizures, or symptoms of stroke such as weakness or loss of sensation in parts of the body.

• Paraneoplastic symptoms: Lung cancers frequently are accompanied by symptoms that result from production of hormone-like substances by the tumor cells. These paraneoplastic syndromes occur most commonly with SCLC but may be seen with any tumor type. A common paraneoplastic syndrome associated with SCLC is the production of a hormone called adrenocorticotrophic hormone (ACTH) by the cancer cells, leading to oversecretion of the hormone cortisol by the adrenal glands (Cushing's syndrome). The most frequent paraneoplastic syndrome seen with NSCLC is the production of a substance similar to parathyroid hormone, resulting in elevated levels of calcium in the bloodstream.

• Nonspecific symptoms: Nonspecific symptoms seen with many cancers, including lung cancers, include weight loss, weakness, and fatigue. Psychological symptoms such as depression and mood changes also are common.

When should one consult a doctor?

One should consult a health-care professional if he or she develops the symptoms associated with lung cancer, in particular, if they have
• a new persistent cough or worsening of an existing chronic cough,
• blood in the sputum,
• persistent bronchitis or repeated respiratory infections,

Managing Treatment Side Effects

The body’s reaction to chemotherapy, radiation, or targeted treatments depends on a number of factors such as length of treatment, dosage prescribed, and a person’s health history. Most side effects are short term, but some can last throughout your treatment and even for some time afterward. Although side effects can be uncomfortable or painful, doctors now have many ways to reduce and even prevent side effects from treatment. The following are possible side effects you may experience and resources to help you manage:
Blood clots
People with cancer are at risk for developing blood clots for various reasons, but steps can be taken to prevent and treat blood clots.

Bone issues
Cancer that starts in or spreads to the bones can lead to bone pain and an increase in risk for complications, including weakening of the bone, fractures, and high calcium levels in the blood. Cancer treatments may also affect your bones.

Chemobrain
Problems with memory and concentration, along with a general feeling of not functioning as well mentally as usual, are informally referred to by patients as chemobrain.

Dental issues
Side effects from cancer treatment may include tooth decay and other mouth issues, including dry mouth and mouth sores. It’s important to address any dental concerns you have, especially before beginning treatment, but also during and after with both your treating physician and dentist.

Diarrhea
Defined as two or more loose bowel movements per day, diarrhea may be caused by some types of chemotherapy and radiation to certain areas of the body. There are many things you can do to help control diarrhea.

Fatigue
Fatigue is the most commonly reported side effect of cancer and its treatment. Make sure to report fatigue to your health care team so that everything can be done to manage it.

Hair loss
Hair loss from chemotherapy treatment occurs because hair follicles are weakened by chemotherapy, which causes your hair to fall out much more quickly than it would normally.

Lymphedema
People with cancer who have undergone lymph node removal and/or radiation as part of their treatment are at risk for developing lymphedema, a painful swelling that happens when your body’s lymphatic fluid is unable to circulate properly and builds up in your soft tissues instead.

Mouth sores
“Oral mucositis” refers to mouth sores caused by irritation of the mucosa—the soft tissues that cover the tongue and inside of the mouth, and can be a serious side effect of chemotherapy treatment.

Nausea and vomiting
While many people who are treated for cancer experience nausea and vomiting, medicines exist that can help control these side effects.

Neuropathy
Some people who receive chemotherapy experience numbness or tingling in their hands and feet, what doctors call peripheral neuropathy.

Pain
If you are experiencing pain as a result of your cancer or its treatment, you should know that managing this pain is an important part of your overall care and should be brought to the attention of your physician. They may find it helpful to provide a referral to a pain management specialist.

Rash
A type of targeted treatment that blocks epidermal growth factor receptors (EGFRs) often causes rashes and other bothersome skin conditions.

Weight loss or gain
Cancer treatments can usually lead to weight loss, but people with cancer can also experience weight gain from chemotherapy treatment, steroid medications, and hormone therapy.





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