Lungs

Lungs are the major organs of the body’s respiratory (breathing) system. At birth, they are a pinkish-white color, but over the years they darken to gray or black because of the particles inhaled.

They are in the rib cage, one on either side, and are enveloped in a membrane known as the pleura, or the serous coat (named for the watery fluid called serous that moistens it). The parietal (outer layer) pleura is located on the side of the nearest the rib, the visceral (inner layer) pleura is the layer nearest to the lung.

Lung parenchyma, the main tissue of the lung, consists of clusters of spongy air sacs called lobules. Each lobule is made up of tiny air sacs called alveoli that exchange oxygen for carbon dioxide. Each lung has around 130,000 lobules, and each lobule has about 2200 alveoli in its approximately 3.5 mm diameter.

The lungs are separated from each other by the mediastinum (middle chest) which consists of, among other things, the heart and the windpipe (trachea.) The midline region directly beneath the middle chest is called the hilum or hilus and is made up of blood vessels, nerves, and lymphatic tissues. The bronchial tubes also enter and exit the system here.

Both lungs are divided into upper lobes (the top is called the apex), which extend to the just above the first rib, and the lower lobes (the bottom is called the base), which extend down to the diaphragm. The diaphragm is an important muscle that separates the chest from the abdomen. It contracts and descends with each intake of air (inhalation or inspiration) and relaxes and elevates again when the air is expelled from the lungs (exhalation or expiration).

The larger and heavier right lung also has a middle lobe, a triangular section located in the upper portion. It is possible to remove one lobe without damaging the rest, which will continue to function as normal.

Each lung is connected to the heart and the windpipe by a system known as the root. Each root is made up of a bronchus, a pulmonary vein (the only veins that carry red oxygenated blood), a pulmonary artery (carries blood without oxygen to the lungs), lymphatic vessels (carriers of the clear, watery lymph fluid), nerves (messengers between the brain and various body parts), and bronchial arteries and veins (supply blood and nutrition to the lungs).

Each bronchus is a large airway that connects the trachea to the lungs. The single trachea divides into the two bronchial tubes (also called bronchi). Each bronchus enters a lung and then “branches” out, dividing and subdividing into pairs of smaller and finer tubes, creating what is known as the tracheobronchial tree.

The Tracheobronchial Tree

The primary function of the tracheobronchial tree is processing the air that is breathed into the lungs. The tree’s lining is made up of column-shaped surface cells (columnar epithelium) and glands that produce mucus and a clear plasma known as serous fluid.

Thin hairs known as cilia are attached to the columnar epithelium and assigned the duty of cleansing harmful organisms and foreign bodies from the airways. Healthy lungs self-clean with the assistance of watery mucus that is moved by the cilia. Smoking or other toxic exposures cause defective cilia and other abnormalities in the tissue lining.

Trachiobronchial branches are classified as either segmental bronchi or bronchioles. Segmental bronchi have coverings made of connective tissue and are larger than 1 mm in diameter. Bronchioles do not have the tissue coverings and are less than 1mm in diameter.

Lung Cancer

Lung cancer, like every other cancer, is the result of malfunctioning cells in the body. In a healthy system, cells divide to produce new cells on an as-needed basis. When a cell deviates from this pattern, the two cells created by the division are also abnormal.

The abnormal cells multiply quickly, upsetting the body’s proper balance of healthy cells by squeezing out others while creating an excess of themselves. This excess forms a mass known as a tumor, which will be either malignant (cancerous) or benign (non-cancerous).

Malignant tumors spread out aggressively and invade the nearby organs and tissues. When they enter into the bloodstream or the lymphatic system (a network associated with the immune system) through the lymph nodes (filters for the lymph fluid), the cancerous cells are transported to other areas of the body and begin the tumor-producing process at those sites.

The secondary sites are known as metastases. Lung cancer tends to metastasize early on and often spreads to the brain, liver, adrenal glands, or bones. The reverse is also true, and cancer of the lung is often a secondary cancer that has, metastasized from another site.

Both primary (initial) and secondary lung cancer can appear first in any part of the lung, but it is believed that over 90% of them have started in the bronchi and the bronchioles. For this reason, lung cancer is also referred to as bronchogenic carcinoma.

Types of Lung Cancers

Lung cancers are broadly classified into two groups: small cell lung cancers (SCLC) and non-small cell lung cancers (NSC LC). These classifications are based on the microscopic appearance of the cells and the different ways that they grow and spread.

Small cell lung cancers (SCLC)

Approximately 20% of all lung cancers fall into this category. Small cell lung cancers are also referred to as oat cell cancers because of their appearance. The cells are only ½ to ¾ the size of NSCLC cells. A statistic worth noting is that only 1% of these cancers occur in non-smokers.

SCLC are usually centrally located and are the most aggressive of the lung cancers. This form spreads quickly and moves fast to metastasize. In many cases, evidence that the cancer has metastasized to other areas is present at the initial diagnosis.

Non-small cell lung cancers (NSCLC)

Non-small cell lung cancers are the most common primary lung cancers and are divided into three main types: adenocarcinomas, squamous cell carcinomas, and large cell carcinomas (carcinoma = cancer).

Around 50% of all NSCLC cases in the United States are adenocarcinomas. They appear in cells that form gland-like tumors on the outer edges of the lung.

Squamous cell carcinomas (cancers) are also known as epidermoid carcinomas. Squamous cells are flat cells that make up a part of the epithelium lining. They tend to appear in the central chest area and are usually slow-growing.

Large cell cancers are the least common and behave in a manner similar to adenocarcinoma.

If the lung cancer is secondary, there will most likely be multiple tumors scattered around the outside edges of the lung.

Symptoms

Approximately one-quarter of lung cancer patients report having no symptoms at the time of diagnosis. These cases are usually discovered as a result of tests performed for other medical reasons, such as pneumonia or heart disease.

The commonly reported symptoms are directly related to the behavior of the lung cancer. For instance, if the lung cancer has metastasized to the bones, there may be anything from tenderness to excruciating pain at the site.

Signs that cancer has spread to the brain include:

• Seizures
• Headaches
• Blurry vision
• Weakness
• Loss of sensation in some body parts

In the lung itself, the cancerous invasion may cause:

• Wheezing
• Chest pain
• Shortness of breath
• Hemoptysis (coughing up blood)

Other symptoms include:

• Pneumonia
• Appetite/weight loss
• Difficulty swallowing
• Chills
• Weakness
• Pale skin
• Jaundice (yellow skin and eyes)
• Atrophy (muscle shrinkage)
• Muscle contractions
• Facial swelling or paralysis
• Speech difficulties
• Rust-colored or bloody sputum (phlegm, spit)

Horner’s Syndrome and Paraneoplastic Syndromes

There are other symptoms associated with lung cancer that fall under the categories of Horner’s syndrome and paraneoplastic syndromes.

Horner’s syndrome consists of a smaller pupil in one eye, weakness in that same eyelid, and an absence (or reduced amount) of perspiration (sweat) on that side of the face. These symptoms are caused by cancer-induced damage to a nerve that passes from the upper chest into the neck.

Paraneoplastic is Latin for “tumor-related.” Paraneoplastic syndromes are problems in other distant organs and tissues that are caused by tumor-produced substances that have traveled through the bloodstream. While the tumors are the direct cause of the disruptions, the cancer itself has not metastasized to those sites.

The paraneoplastic symptoms most often associated with SCLC are:

Blood clots—mostly in the leg veins, but they can also interrupt flow to the limbs or other internal organs.

• Cerebellar degeneration—an unexplained loss of balance.
• SIADH (syndrome of inappropriate anti-diuretic hormone)—very low levels of salt in the blood, which causes restlessness, nausea, confusion, and weakness or cramps in the muscles.

The paraneoplastic symptoms most often associated with NSCLC are:

• Blood clots
• Gynecomastia—excessive breast growth in males.
• Hypercalcemia—too much calcium in the blood, which causes (among other things) urination problems, constipation, confusion, dizziness, and other problems with the nervous system.
• Hypertrophic osteoarthropathy—excess growth of certain bones.

Diagnosis

Patients suspected of having lung cancer will be given a complete examination and a health-related interview to check for symptoms and risk factors. The doctor may also take a sputum (mucus spit up from the lungs) sample to test for cancerous cells or infectious organisms.

Imaging tests performed to find signs of cancer are:

• Positron emission tomography (PET)—PET uses a special camera that detects radioactivity. The patient takes glucose (a form of sugar) that contains a radioactive atom. Cancer cells absorb large amounts of the sugar and become detectable to the camera.
• Chest x-ray—x-rays are a form of electromagnetic radiation that can pass through a body. By using x-ray sensitive photographic film, pictures of inside the body can be taken.
• Computed tomography (CT or “CAT” scan)—a computer-assisted x-ray procedure which takes multiple pictures by rotating around you. You will most likely receive an intravenous injection of a dye that helps better outline the structures in your body. Certain body parts are better highlighted with a contrast solution that is taken orally.
• Magnetic Resonance Imaging (MRI)—a magnetic field is used to excite hydrogen ions within the body and/or specific body parts. A computer translates the pattern of radio waves given off by the tissues into a detailed image of the body part.
• Bone scans—a minute dose of a radioactive substance (usually technetium diphosphonate) is injected into a vein and after the bones have absorbed it, special equipment is used to take pictures of the bones.

There are other tests that sample tissues and cells to confirm that a lung mass seen on an imaging test is lung cancer and not a benign condition. These tests also help determine what type of lung cancer the mass is and its stage (the extent to which it has spread). One or more of the following tests will be performed:

• Needle biopsy—this is done with CT-guidance in order to guide the placement of the needle. Fine Needle Aspiration (FNA) uses a slim, hollow needle attached to a syringe to remove some suspicious cells for study. Large needle (core biopsy) uses a larger needle to obtain the needed tissue sample.
• Bronchoscopy—a pulmonologist (respiratory disease specialist) uses a fiberoptic, flexible, lighted tube to visually examine the windpipe and lung branches. This may involve using a small, brush-like device to gather cells from the tissues (brushing). A biopsy may also be performed.
• Sputum cytology—a sputum (phlegm, spit) sample is taken every morning for three days in a row and examined under a microscope.
• Blood counts—a complete blood count (CBC) determines if your blood has the correct amount of various cell types.
• Blood chemistry—this test shows abnormalities in certain organs.
• Bone marrow biopsy—the back of the hip bone is numbed with local anesthesia and a needle is inserted to remove a bone sample of the bone marrow.
• Thoracentesis—if there is a pleural effusion (build up of fluid around the lungs), the skin is numbed and a needle is placed between the ribs to drain the fluid and test it for cancerous cells.
• Thoracoscopy—a video camera and a thin, lighted tube are used to view the space between the lungs and the chest wall in order to look for cancer deposits and/or remove sample tissues.
• Mediastinoscopy—the patient is put to sleep and a hollow, lighted tube is inserted through a small cut in the neck to the area behind the breastbone (sternum). Special instruments are able to operate through the tube and take tissue samples from the lymph nodes along the windpipe and the major bronchial tube areas.
• Mediastinotomy—the patient is put to sleep and the chest cavity is opened by making an incision near the ribs or the breastbone in order to reach lymph nodes that cannot be reached by mediasinoscopy.

Staging

Once the diagnosis is confirmed, the cancer is assigned a stage. The stages are determined by the size of the tumor (T), whether or not it has moved into the lymph nodes (N), and whether or not it has metastasized (spread to other sites; M). Staging is important for determining the treatment plan. In general, the lower the stage, the more favorable the prognosis (most likely outcome).

Non-small Cell Lung Cancer Staging

Non-small cell lung cancers are usually staged according to the TNM system, a classification developed and revised by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC; International Union Against Cancer). The system looks like this:

• T = tumor size
• N = node involvement
• M = metastasis status

The primary tumor (T) is further classified as follows:

TX: The tumor cannot be evaluated, or it is proven by the presence of cancer cells in the sputum or bronchial washings, bronchial washings, but cannot be seen during imaging or bronchoscopy. This is also called an occult tumor.

T0: No evidence of a primary tumor.

Tis: Known as carcinoma in situ, the cancer is found only in the layer of cells lining the air passages.

T1: The tumor is 3 centimeters (cm) in diameter or less, has not spread to the membranes that surround the lung (visceral pleura), and is not in the main stem bronchus.

T2: One or more of the following features are present:

• The tumor is larger than 3 cm and involves a main bronchus, but is not closer than 2 cm to the carina (the point where the windpipe branches into the left and right main bronchi).

· It has spread to the membranes surrounding the lung.

• The lung has not collapsed or developed pneumonia, but the cancer partially clogs the airway.

T3: One or more of the following features are present:

• The tumor of any size has directly invaded the chest wall, diaphragm (breathing muscle that separates the chest from the abdomen), the mediastinal pleura (the membranes surrounding the space between the two lungs), or the parietal pericardium (membranes of the sac surrounding the heart).
• The cancer has invaded a main bronchial tube and is closer than 2 cm to the point where the windpipe branches into the both bronchi, but does not affect this area.
• The tumor has moved enough into the airways to cause the collapse of a lung or pneumonia in the entire lung.

T4: One or more of the following features are present:

• A tumor that that has invaded the heart, great vessels (aorta, superior or inferior vena cava, pulmonary artery, or pulmonary vein), trachea (windpipe), esophagus (tube connecting the throat to the stomach), backbone, or the carina (the point where the windpipe branches into the bronchial tubes).

· Two or more separate tumor nodules are present in the same lobe.

• There is a fluid containing cancer cells in the space surrounding the lung (malignant pleural effusion).

The Node Involvement (N) is further classified as follows:

NX: The regional lymph nodes cannot be assessed.

N0: No spread to lymph nodes.

N1: The cancer has spread to lymph nodes within the lung and/or located around the area where the bronchus enters the lung (hilar lymph nodes), but only affects lymph nodes on the same side as the cancerous lung.

N2: The lymph nodes around the point where the windpipe branches into the bronchial tubes or the mediastinum (behind the chest bone and in front of the heart) has been invaded by the cancerous cells. The affected lymph nodes are on the same side of the cancerous lung.

N3: The cancer has spread to lymph nodes near the collarbone on either side, to hilar or mediastinal lymph nodes on the side opposite the cancerous lung.

The Metastasis Status (M) is classified as follows:

MX: Distant metastasis cannot be assessed.

M0: No spread to distant organs. Sites considered distant areas include other lobes of the lungs, lymph nodes beyond the ones in the N stages, and other organs or tissues such as the liver, bones, brain, etc.

M1: The cancer has spread to distant organs.

These classifications are combined (stage grouping) and then an overall stage is assigned. Those stages are as follows:

Stage 0: Carcinoma in situ

Stage Ia: T1, N0, M0

Stage Ib: T2, N0, M0

Stage IIa: N1, M0

Stage IIb: T2, N1, M0 or T3, N0, M0

Stage IIIa: T1-2, N2, M0 or T3, N1-2, M0

Stage IV: T (any), N (any), M1

Small Cell Lung Cancer Staging

The TNM system is rarely used for staging patients with small cell lung carcinoma because most have suspected or definite metastatic disease at the time of diagnosis. Minor differences in the extent of tumor involvement is not likely to affect the prognosis of these cases.

Patients diagnosed with small cell lung cancer are rarely staged using the TNM system because most of those cases have definitely (or most likely) metastasized at the time of the initial diagnosis. Minor differences in the extent of tumor involvement is not likely to affect the prognosis of these cases. Instead, small cell lung cancers are staged using (not universally accepted) a two-tiered system created by the Veterans Administration Lung Cancer Group. That system includes the following classifications:

• Limited stage (LS) SCLC refers to cancer that is confined to its area of origin in the chest.
• Extensive stage (ES) SCLC refers to cancer that has spread beyond the chest to other body parts.

Treatment

Treatment plans for lung cancer include one or more of the following:

Surgery—there are three different surgical procedures associated with lung cancer treatment: segmentectomy (also known as wedge resection) is the removal of wedge like pieces of the area, lobectomy is the removal of an entire lobe, and pneumonectomy is the removal of a whole lung.

Chemotherapy—anti-cancer drugs are administered orally (through the mouth), intravenously (through the vein), subcutaneously (shot into the skin, not muscle), or intrathecally (through the spine).

Radiation—high energy x-rays are beamed into the diseased area to kill the dividing cells (external radiation) or radioactive material is placed inside the body near the site of the tumor (internal radiation).

Brain prophylactic radiation—radiation therapy to the brain may be given to treat micrometastasis (early spread) that is not yet detectable with CT or MRI scans.

Photodynamic Therapy (PDT)—this procedure uses a light-sensitive drug (sometimes referred to as a photosensitizing agent) combined with laser or other light sources to kill cancer cells.

Treatment for Non-small Cell Lung Cancers (NSCLC)

Stage 0 treatment is curable by surgery alone because it is limited the lining layer and has not invaded any other tissue. Unless the cancer is in a location that is difficult to remove completely without removing an entire lung, it is treated with segmentectomy.

Stage I and II treatments will probably be only surgery; which surgery will depend on various factors. Segmentectomy is usually done only for the smallest stage I cancers and for patients whose health condition make removing the entire lobe dangerous. Radiation therapy may be recommended as follow-up treatment.

Stage IIIa treatment depends on what lymph nodes have been affected and where the cancer is located. If cancer is found in the lymph nodes of the middle chest, and the lymph nodes are enlarged and abnormal, the patient is not considered a primary candidate for surgery, but will have a treatment plan consisting of chemotherapy and radiation therapy.

If there are normal-appearing mediastinal nodes, surgery for resection is likely. Sometimes chemotherapy or radiation treatment is used and if there is a response, surgery is used to remove any remaining tumor.

Stage IIIb treatment is does not include surgery. A combination of chemotherapy and radiation therapy will be considered for patients who have no cancerous cells in the fluid surrounding the lungs. If cancer cells are found in the fluid, chemotherapy with comfort care is usually suggested. Even with aggressive therapy these patients tend to survive about as long as their stage IV counterparts.

Stage IV has no cure. Comfort care (treatment of pain and other discomforts), with or without chemotherapy are the only choices at this point. Pain can be managed with medication, and while chemotherapy cannot cure this level of cancer, it can relieve some of the symptoms of the disease, and may extend the patient’s life. Clinical trials and experimental drugs are also options at this point and should be discussed with the doctor.

Treatments for Small Cell Lung Cancers (SCLC)

Limited stage (LS) SCLC is most often treated a combination of two or more chemotherapy drugs. These will be etoposide combined with either cisplatin or carboplatin, usually taken for approximately six months. Sometimes radiation therapy is used as well.

Brain radiation is often used as a preventive measure as this cancer metastasizes to the brain in 50% of the cases.

This is considered to be an aggressive treatment and very physically demanding. Patients who are unable to walk at least 50% of the time and do not have good function of the kidney, liver, heart and lung are usually not able to tolerate it.

Extensive care (ES) NSCLC treatment consists of chemotherapy treatments to treat symptoms and prolong life. The same drugs are used as in the limited stage cancer, but sometimes a second type of chemotherapy is prescribed. These medications include cyclophosphamide, doxorubicin, vincristine, ifosfamide, toptecan, paclitaxel, methotrexate, vinorelbine, gemcitabine, irinotecan, and docetaxel in various combinations.

Sometimes radiation therapy is given to control the growth within the lung or the spread to other areas like the bones or brain.

Prognosis

(The following information is from the National Cancer Institute’s Physician Data Query System, July 2002)

Non-small cell lung cancer (Five year survival with treatment)

• Occult Stage 75-85% positive cytology but no evidence of primary tumor or lymph node involvement
• Stage 0 (too few cases to evaluate)
• Stage I 54%
• Stage II 35%
• Stage IIIA 10-15% lymph nodes involved on same side (ipsilateral) as primary
• Stage IIIB < 5% contra lateral lymph nodes involved
• Stage IV < 2%

Small cell lung cancer (Two year disease-free survival with treatment)

Limited stage 25-30% (roughly equal to Stage I and II)Extensive stage 0-2% (roughly equal to Stage III and IV)

Prevention

The number one cause of lung cancer is –surprise-surprise- cigarette smoking. Tobacco smoke contains over 4,000 chemical compounds and smoking causes around 90% of the lung cancers.

Stay away from second-hand smoke as much as possible too. An estimated 3,000 lung cancer deaths a year are attributed to passive smoking (inhaling the smoke of other people’s cigarettes). If you are smoking, quit. If you haven’t started, don’t. That’s the best form of protection available. Most other factors that cause cancer are beyond a person’s control, including family health history, personal health history, and air pollution.

Final Thought

Anyone with a lung cancer diagnosis should try to get the most out of life everyday, no matter what the prognosis is.

Yeah, I know what you’re thinking; you’re thinking that people who have never been in your shoes don’t know how it is. And you’re right, they don’t. But I do. I’m a survivor of Acute Lymphoctytic Leukemia, so I do know what it’s like to lie awake at night and wonder what will happen to your child if you don't wake up in the morning, I do what it's like to have a low point when all you want to do is say a few unsavory curse words and give up, I do know how chemotherapy and its side effects feel.

I also know that I value each day more than I did before, that each moment that I'm still breathing I am happy, and that material goods are highly overrated. And if I might take the liberty of ending this piece with a bit of advice for any cancer-fighters out there...

Spend time with the ones you love, and the ones that love you—even if they aren’t the same group. And keep on believing in miracles.