DISEASES OF THE LUNGS

Lung Anatomy

The lungs are the body's major organs of breathing (respiration). The lungs are located on each side of the chest within the rib cage. They are separated by the heart and other contents of the mediastinum—the tissues and organs of the middle chest (e.g., large blood vessels, windpipe). The lungs are shaped like an upside-down butterfly. The top of each lung (called the apex) extends into the lowest part of the neck, just above the level of the first rib. The bottom, or base, of each lung extends down to the diaphragm, which is the major breathing-associated muscle that separates the chest from the abdominal cavity.

Each lung is divided into upper and lower lobes. The right lung is larger and heavier than the left lung, which is somewhat smaller in size because of the position of the heart. The upper lobe of the right lung contains another triangular subdivision known as the middle lobe. At birth, the lungs are pinkish-white in color; however, with age, the lungs darken to gray or mottled black because of deposits of carbon and other particles that are inhaled over time.

The relationships of the pleural reflections and the lobes of the lung to the ribs

Correlated applied anatomy of the bronchial tree and lungs with a system of nomenclature.

The lungs are the body's major organs of breathing (respiration). The lungs are located on each side of the chest within the rib cage. They are separated by the heart and other contents of the mediastinum—the tissues and organs of the middle chest (e.g., large blood vessels, windpipe). The lungs are shaped like an upside-down butterfly. The top of each lung (called the apex) extends into the lowest part of the neck, just above the level of the first rib. The bottom, or base, of each lung extends down to the diaphragm, which is the major breathing-associated muscle that separates the chest from the abdominal cavity.

Each lung is divided into upper and lower lobes. The right lung is larger and heavier than the left lung, which is somewhat smaller in size because of the position of the heart. The upper lobe of the right lung contains another triangular subdivision known as the middle lobe. At birth, the lungs are pinkish-white in color; however, with age, the lungs darken to gray or mottled black because of deposits of carbon and other particles that are inhaled over time.

The root connects the lungs to the heart and the trachea (windpipe). Each root is made up of a main stem bronchus (large air passage connecting the windpipe to the right or left lungs), pulmonary artery (major artery that delivers oxygen-poor blood back to the right or left lungs), pulmonary vein (major vein receiving oxygen-rich blood from the lobes of the right or left lungs), the bronchial arteries and veins, as well as nerves and lymphatic vessels.

A clear, thin, shiny covering (known as the serous coat, or pleura) covers the lungs. The inner, visceral layer of the pleura is attached to the lungs and the outer, parietal layer is attached to the chest wall. Both layers are held in place by a film of pleural fluid in a manner similar to two microscope slides that are wet and stuck together. Beneath the pleura is a layer of elastic fibers that span the lung surface and extend down into its subdivisions.

The trachea splits into right and left main stem bronchi. The main stem bronchi are the major air passages from the trachea to the lungs and are similar to the trachea in tissue composition. The main stem bronchi enter each lung and progressively branch off into paired subdivisions throughout the entire organ (called the tracheobronchial tree).

The tracheobronchial tree serves to conduct, humidify, and heat air that is breathed in, or inspired. At its endpoints, the tracheobronchial tree connects with the blood vessels. The lining of the tracheobronchial tree is composed of columnar epithelium (column-shaped surface cells) and glands that produce mucus and serous (clear plasma) fluid. The cilia (hair-like projections on columnar epithelium) move in a constant, beating motion to cleanse the airways of foreign bodies and infectious organisms. In normal lungs, the cilia are covered by a watery "mucous blanket"—a gel-like liquid that is moved by the cilia and aids the lungs' self-cleaning.

Lungs that have been damaged by smoking or other toxic exposures often have defective or missing cilia and show other abnormalities in the tissue lining. Coughing triggers a high-speed flow of air, which mobilizes the mucous blanket. The sputum produced by such mobilization contains mucus, nasal secretions, and saliva.

The essential tissue of the lung—lung parenchyma—is made up of clusters of spongy air sacs called lobules. There are about 130,000 primary lobules in each lung. Each lobule is approximately 3.5 millimeters in diameter and contains about 2,200 alveoli (air sacs and ducts). Tracheobronchial branches that are larger than 1 millimeter in diameter and have connective tissue coverings are called segmental bronchi.

The smallest subdivisions, which are less than 1 millimeter in diameter and do not have connective tissue coverings, are called bronchioles. The final branches of the bronchioles are called terminal bronchioles. The

bronchioles end in irregular, swollen projections known as alveolar ducts (terminal branches composed of special gas-exchanging tissue) and alveolar sacs (blind passage of an alveolar duct). The fluid that lines the alveolar regions contains a detergent-like substance known as surfactant, which reduces surface tension within the alveoli and keeps them from collapsing during breathing.

Blood Vessels

Oxygen-poor blood is brought back to the lungs by means of the pulmonary artery. The pulmonary artery divides into branches that parallel the bronchial tubes and it ends in a network of pulmonary capillaries (tiny blood vessels) within the walls of the small air passages and alveoli of the lungs.

The pulmonary veins carry oxygen-rich blood away from the lungs. They begin in the pulmonary capillaries, unite to form larger branches (e.g., the left and right superior and inferior pulmonary veins), and eventually lead into the left atrium of the heart. The heart then pumps the oxygenated blood out to the body parts via the aorta (the great artery arising from the left ventricle of the heart).

The bronchial arteries are blood vessels that branch off from the aorta to supply blood and nutrition for the lung itself and the bronchial tubes. The bronchial vein begins at the root of the lung and receives blood from vessels near the bronchial arteries.

Nerves

The lungs receive their nerve supply from the anterior (front) and posterior (back) nerve networks, called pulmonary plexuses. These plexuses are offshoots of larger nerves, such as the sympathetic nerves of the trunk and the pneumogastric (tenth cranial, or vagus) nerve. The nerves of the lung contain small, knot-like masses known as ganglia.

Lymphatic System

Lymphatic vessels are structures that drain lymph. Lymph is the clear, yellowish fluid containing lymphocytes (white blood cells that fight disease) from the tissues of the body. The lungs have two sets of lymphatic vessels—a surface, or superficial set, and a deep set. The superficial lymphatic vessels are located beneath the pleura (thin, serous covering of the lungs), whereas the deep set follow the blood vessels and extend along the bronchi. Both sets of lymphatic vessels end at the root of the lungs, within the bronchial glands.

Two or three efferent (outward-leading) vessels travel up the trachea (windpipe) to the base of the neck, where they cross the trachea and esophagus (tube that passes from the mouth to the stomach). These vessels end at either the thoracic duct (passage that empties a large amount of lymph and lymph-related compounds into the blood) on the left side or the lymphatic duct on the right.

Lung segments

Clinically,

the syndrome is characterized by tenderness and swelling of the ankles, feet, forearms, and hands. It is because of periostitis of the fibula, tibia, radius, metacarpals, and metatarsals.

Hypercalcemia occurs in up to 10 percent of patients with lung cancer and is most often because of metastatic disease. However, 15 percent of cases are because of secretion of ectopic parathyroid hormone–related peptide, most often with squamous cell carcinoma. A diagnosis of ectopic parathyroid hormone secretion can be made by measuring elevated serum levels of parathyroid hormone; however, the clinician must also rule out concurrent metastatic bone disease by a bone scan.

Symptoms of hypercalcemia

lethargy, depressed level of consciousness, nausea, vomiting dehydration.

Most patients have resectable tumors, and following complete resection the calcium level will normalize. Endocrinopathies are caused by the release of hormones or hormone analogues into the systemic circulation. Most occur with SCLCs.

Metastatic Symptoms

Nonspecific Symptoms

Lung cancer often produces a variety of nonspecific symptoms such as anorexia, weight loss, fatigue, and malaise. The cause of these symptoms is often unclear, but should raise concern about possible metastatic disease.

Diagnosis, Evaluation, and Staging

In a patient with either a histologically confirmed lung cancer or a pulmonary lesion suspected to be a lung cancer, assessment encompasses three areas:

1) Assessment of the primary tumor. Assessment includes questions regarding the presence or absence of pulmonary, nonpulmonary, thoracic, and paraneoplastic symptoms. Patients often have already undergone a chest radiograph or CT scan before their initial visit with the surgeon; the location of the tumorcan then help direct the history. A routine chest CT should include intravenous contrast for delineation of mediastinal lymph nodes relative to normal mediastinal structures. Chest CT allows assessment of the primary tumor and its relationship to surrounding and contiguous structures and may demonstrate invasion of contiguous structures.

Thoracotomy should not be denied because of presumptive evidence of invasion of the chest wall, vertebral body, or mediastinal structures; proof of invasion may require thoracoscopy or even thoracotomy. Magnetic resonance imaging (MRI), because of its excellent imaging of vascular structures, maybe of value primarily to define a tumor’s relationship to a major vessel.

Tissue diagnosis of the primary tumor can be obtained through bronchoscopy or needle biopsy. Bronchoscopy is particularly useful for centrally located tumors with a higher probability of being visualized and biopsied and may discover additional unsuspected endobronchial lesions.

Diagnostic tissue from bronchoscopy can be obtained by one of four methods:

1. brushings and washings for cytology, 2. direct forceps biopsy of a visualized lesion,3. FNA with a Wang needle of an externally compressing lesion without visualized endobronchial

tumor, and 4. transbronchial biopsy with the use of forceps guided to the lesion by fluoroscopy.

Transthoracic needle aspiration is ideally suited for peripheral lesions not easily accessible by bronchoscopy. Using image guidance (fluoroscopy or CT), either an FNA or core-needle biopsy is performed. The primary complication is pneumothorax (in up to 50 percent of patients) usually is minor and requires no treatment. Three biopsy results are possible: malignant, a specific benign process, or indeterminate. The overall false-negative rate is 20–30 percent, therefore unless a specific benign diagnosis (such as granulomatous inflammation or hamartoma) is made, malignancy is not ruled out and further efforts at diagnosis are warranted.

A thoracotomy occasionally is necessary to diagnose and stage a primary tumor. Although this occurs in fewer than 5 percent of patients, two circumstances may require such an approach:

a deep-seated lesion that yielded an indeterminate needle biopsy result or that could not be biopsied for technical reasons, or

inability to determine invasion of a mediastinal structure by any method short of palpation. In the circumstance of a deep-seated lesion without a diagnosis, FNA, a Tru-Cut biopsy, or preferably an excisional biopsy, can be performed with frozen-section analysis. If the biopsy result is indeterminate, a lobectomy may instead be necessary. When a pneumonectomy is required, a tissue diagnosis of cancer must be made before excision.

2) Assessment of metastatic disease. Distant metastases are found in about 40 percent of patients with newly diagnosed lung cancer. As with the primary tumor, assessment for the presence of metastatic disease should begin with the history and physical examination, focusing on the presence or absenceof new bone pain, neurologic symptoms, and new skin lesions. Additionally, constitutional symptoms (e.g., anorexia, malaise, and unintentional weight loss of greater than 5 percent of body weight) suggest either a large tumor burden or the presence of metastases.

Physical examination should focus on the patient’s overall appearance, noting any evidence of weight loss with muscle wasting. The appearance of cervical and supraclavicular lymph nodes and that of the oropharynx should also be examined for tobacco-associated tumors. Routine laboratory studies include serum glutamic oxaloacetic transaminase and alkaline phosphatase and serum calcium (to detect bone metastases or the ectopic parathyroid syndrome). Elevation of either hepatic enzymes or serum calcium levels typically occurs with extensive metastases.

Mediastinal lymph nodes.

Chest CT is the most effective noninvasive method available to assess the mediastinal and hilar nodes for enlargement.

Positron emission tomography (PET) scanning for metastatic disease is now routine and allows whole body imaging permiting simultaneous evaluation of the primary lung lesion, mediastinal lymph nodes, and distant organs.

Cervical mediastinoscopy is commonly employed to evaluate mediastinal lymph nodes. It has several advantages over other techniques of mediastinal lymph node staging. It can provide a tissue diagnosis, allows sampling of all paratracheal and subcarinal lymph nodes, and permits visual determination of the presence of extracapsular extension of nodal metastasis. An absolute indication for mediastinoscopy is mediastinal lymph node enlargement greater than 1.0 cm by CT scan. When the size of mediastinal lymph nodes is normal, mediastinoscopy is generally recommended for centrally located tumors, for T2 and T3 primary tumors, and occasionally for T1 adenocarcinomas.

Pleural effusion. The presence of pleural effusion on a CT scan (or chest radiograph) is not synonymous with a malignant effusion. Malignant pleural effusion can only be diagnosed by finding malignant cells in a sample of pleural fluid examined microscopically. Pleural effusion is often secondary to the atelectasis or consolidation seen with central tumors. However, pleural effusion associated with a peripherally based tumor, particularly one that abuts the visceral or parietal pleural surface, does have a higher probability of being malignant. Regardless, no pleural effusion should be assumed to be malignant.

Distant metastases. Until recently, detection of distant metastases outside the thorax was performed with a combination of chest CT scan and multiorgan scanning (e.g., brain CT or MRI, abdominal CT, and bone scan).

Chest CT scans always include the upper abdomen and allowvisualization of the liver and adrenal glands. Routine preoperative multiorgan scanning is not recommended for patients with a negative clinical evaluation and clinical stage I disease. However, it is recommended for patients with regionally advanced (clinical stage II, IIIA, and IIIB) disease. Any patient, regardless of clinical stage who has a positive clinical evaluation should also undergo radiographic evaluation for metastatic disease.

PET scanning has supplanted multiorgan scanning in the search for distant metastases to the liver, adrenal glands, and bones. Currently, chest CT and PET are routine in the evaluation of patients with lung cancer. Brain MRI should be performed when the suspicion or risk of brain metastases is increased. Several reports show that PET scanning appears to detect an additional 10–15 percent of distant metastases not detected by routine chest or abdominal CT and bone scans.

Assessment of functional status. For patients with a potentially resectable primary tumor, their functional status and ability to tolerate either lobectomy or pneumonectomy needs to be carefully assessed. The surgeon should first estimate the likelihood of pneumonectomy, lobectomy, or possibly sleeve resection, given the CT scan results. A patient’s history is the most important tool for gauging risk.

Pulmonary function studies are routinely performed when any resection

greater than a wedge resection will be performed. The two most valuable

measurements are FEV-1 and DLco. General guidelines for the use of FEV-1

in assessing the patient’s ability to tolerate pulmonary resection are as follows:

greater than 2.0 L can tolerate pneumonectomy, and greater than 1.2 L can tolerate lobectomy.

PULMONARY INFECTIONS

LUNG ABSCESS

A lung abscess is a localized area of pulmonary parenchymal necrosis caused by an infectious organism; tissue destruction results in a solitary or dominant cavity measuring at least 2 cm in diameter. Based on this lung abscesses are classified as primary or secondary.Aprimary lung abscess occurs, for example, in immunocompromised patients (as a result of malignancy, chemotherapy, or an organ transplant, etc.), in patients as a result of highly virulent organisms inciting a necrotizing pulmonary infection, or in patients who

have a predisposition to aspirate oropharyngeal or gastrointestinal secretions. A secondary lung abscess occurs in patients with an underlying condition such as a partial bronchial obstruction, a lung infarct, or adjacent suppurative infections (subphrenic or hepatic abscesses).

The distinctive characteristic of lung abscess, the air-fluid level, can only be observed on a chest x-ray film taken with the patient upright or in the lateral decubitus position. The extent of the air-fluid level within a

lung abscess is often the same in posteroanterior or lateral views. In the presence of associated pleural thickening, atelectasis, or pneumothorax, the air-fluid level may be obscured.

Microbiology. In community-acquired pneumonia, the causative bacteria are predominantly gram-positive; in hospital-acquired pneumonia, 60–70 percent of the organisms are gram-negative. Gram-negative bacteria associated with nosocomial pneumonia include

Klebsiella pneumoniae, Haemophilus influenzae,

Proteus species, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, and Eikenella corrodens.

Normal oropharyngeal secretions contain many more Streptococcus species and more anaerobes (about 108 organisms/mL) than aerobes (about 107 organisms/mL Overall, at least 50 percent of these infections are caused by purely anaerobic bacteria, 25 percent are caused by mixed aerobes and anaerobes, and 25 percent or fewer are caused by aerobes only.

Clinical features and diagnosis.

productive cough, fever, chills, leukocytosis (>15,000 cells/mm3), weight loss, fatigue, malaise, pleuritic chest pain, and dyspnea. Lung abscesses may also present in a more indolent fashion, with weeks to months of cough, malaise, weight loss, low-grade fever, night sweats, leukocytosis, and anemia.

After aspiration pneumonia, 1–2 weeks typically elapse before cavitation occurs; 40–75 percent of such patients produce a putrid, foul-smelling sputum. Severe complications such as massive hemoptysis, endobronchial spread to other portions of the lungs, rupture into the pleural space and development of pyopneumothorax, or septic shock and respiratory failure are rare in the modern antibiotic era. The mortality rate is about 5–10 percent, except in the presence of immunosuppression, in which rates range from 9–28 percent.

Investigation

Chest radiograph shows a density or mass with a relatively thin-walled cavity and air-fluid level, indicating a communication with the tracheobronchial tree. CT scan is useful to clarify the diagnosis when the radiograph is equivocal, to help rule out endobronchial obstruction, and to look for an associated mass or other pathologic anomalies.Acavitating lung carcinoma is frequently mistaken for a lung abscess. Bronchoscopy is essential to rule out endobronchial obstruction, which is usually because of tumor or foreign body, and to obtain uncontaminated cultures by bronchoalveolar lavage. Cultures can also be obtained by percutaneous, transthoracic FNA under ultrasound or CT guidance.

Management.

Systemic antibiotics are the mainstay of therapy. For community-acquired infections secondary to aspiration, likely pathogens are oropharyngeal streptococci and anaerobes. Penicillin G, ampicillin, or amoxicillin are the main therapeutic agents. failure of medical therapy; an abscess under tension; an abscess increasing in size during appropriate treatment; contralateral lung contamination; an abscess larger than 4–6 cm in diameter; necrotizing infection with multiple abscesses, hemoptysis, abscess rupture, or pyopneumothorax; and inability to exclude a cavitating carcinoma. External drainage may be accomplished with tube thoracostomy, percutaneous drainage, or surgical cavernostomy. Surgical resection is required in fewer than 10 percent of lung abscess patients.

Mycobacterial Infections

Microbiology. Mycobacterium tuberculosis is the highly virulent bacillus of this species that produces invasive infection among humans, principally pulmonary tuberculosis. Because of improper application of antimycobacterial drugs and multifactorial interactions, MDRTB organisms have emerged that are defined by their resistance to two or more first-line antimycobacterial drugs. Approximately 10 percent of newtuberculosis cases, and as many as 40 percent of recurrent cases, are attributed to MDRTB organisms. The more important NTM organisms include M. kansasii, M. avium, and M. intracellulare complex (MAC), and M. fortuitum. The highest incidence of M. kansasii infection is in midwestern U.S. cities among middle-aged males from good socioeconomic surroundings. MAC organisms are important infections in older adult and immunocompromised patient groups. M. fortuitum infections are common complications of underlying severe debilitating disease. None of these organisms are as contagious as M. tuberculosis.

Pathogenesis and pathology. The main route of transmission is via airborne inhalation of viable mycobacteria. Three stages of primary infection have been described. In the first stage, alveolar macrophages ingest the bacilli. In the second stage, from days –21, the bacteria continue to multiply in macrophages. The patient is often asymptomatic. The third stage is characterized by the onset of cell-mediated immunity (CD4 + helper T cells) and delayed-type hypersensitivity. Activated macrophages acquire an increased capacity for bacterial killing. Macrophage death increases, resulting in the formation of a granuloma, the characteristic lesion found on pathologic examination.

Clinical presentation and diagnosis. About 80–90 percent of tuberculosis patients present with clinical disease in the lungs. In 85–90 percent of these patients, involution and healing occur, leading to a dormant phase that may last a lifetime. The only evidence of tuberculosis infection may be a positive skin reaction to tuberculin challenge or a Ghon complex observed on chest radiograph. Within the first 2 years of primary infection, reactivation may occur in up to 10–15 percent of infected patients. In 80 percent, reactivation occurs in the lungs; other reactivation sites include the lymph nodes, pleura, and the musculoskeletal system. After primary infection, pulmonary tuberculosis is frequently asymptomatic.

Systemic symptoms

low-grade fever, malaise, and weight loss are subtle and may go unnoticed. productive cough may develop, usually after tubercle cavitation. Hemoptysis often develops from complications of disease such asbronchiectasis or erosion into vascular malformations associated with cavitation.

LUNG CANCER

The problem of cancer in Malaysia is a growing one. It is now the fourth leading cause of death among medically certified deaths. Cancer of the lung is the most common killer among malignancies. It is estimated that the annual incidence of cancer is 30 000. The majority of patients are found at a late stage of the disease.

Causes

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 over time; 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 can also cause lung cancer, although the risk is not as high as with cigarette smoking. 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. For more, please read the Smoking and Quitting Smoking article.

Passive smoking Passive smoking, or the inhalation of tobacco smoke from other smokers sharing living or working quarters, is also an established risk factor for the development of lung cancer. Research has shown that non-smokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with other non-smokers. An estimated 3,000 lung cancer deaths occur each year in the U.S. that are attributable to passive smoking.

Asbestos fibers Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace is a common source of exposure to asbestos fibers, as asbestos was widely used in the past for both thermal and acoustic insulation materials. Today, asbestos use is limited or banned in many countries including the Unites States. Both lung cancer and mesothelioma (a type of cancer of the pleura or 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 exposed workers. Asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than non-smokers, and those asbestos workers who smoke have a risk that is 50 to 90 times greater than non-smokers.

Radon gas Radon gas is a natural, chemically inert gas that is a natural decay product of uranium. It decays to form products that emit 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 15,000 to 22,000 lung cancer-related deaths annually in the U.S. 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 can be detected with simple test kits.

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 non-smoking relatives of those who have had lung cancer than in the general population. Recent research has localized a region on the long (q) arm of the human chromosome number 6 that is likely to contain a gene that confers an increased susceptibility to the development of lung cancer in smokers.

Mesothelioma The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with a slightly increased risk (four to six times the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded.

Prior history of lung cancer Survivors of lung cancer have a greater risk than the general population of developing a second 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) the risk for development of second 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% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk similar to that of passive smoking for the development of lung cancer.

Types of Lung Cancer

There are several different types of lung cancer. Common types of lung cancer classification (e.g., based on histopathologic [diseased tissue] factors) include the following:

Small cell carcinoma (also called oat cell carcinoma; lung cancer composed of anaplastic [unspecialized, undifferentiated] small cells)

Squamous cell carcinoma (cancer of the layered, squamous epithelium [surface cells] of the lungs or bronchi)

Adenocarcinoma (cancer of the glandular tissue, or cancer in which the tumor cells form recognizable glandular patterns)

Large cell carcinoma (lung cancer composed of large-sized cells that are anaplastic in nature and often arise in the bronchi)

Broncho-alveolar carcinoma

Mixed and undifferentiated pulmonary carcinomas

Because of treatment concerns, most experts separate lung cancers into two groups: small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Small cell lung carcinoma often is widespread by the time of diagnosis; therefore, treatment usually is limited to chemotherapy and/or radiation therapy. By contrast, non-small cell carcinoma may not have spread at the time of diagnosis, so that surgical resection (cutting away) of the tumor may be possible.

Non-Small Cell Lung Carcinoma (NSCLC)

Non-small cell lung carcinoma (NSCLC) includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Large cell carcinoma and adenocarcinoma usually are found on the periphery (outer edges) of the lungs and may occur as solitary nodules, masses, or scar cancer. Squamous cell carcinoma and small cell carcinoma often are centrally located and may appear to be pneumonia (inflammation of the lungs), atelectasis (collapsed lung), or pit-like masses. Squamous cell cancers frequently are slow growing and can take several years to progress from a confined tumor into

invasive cancer. Adenocarcinoma tends to have a worse prognosis than squamous cell cancer in all stages. The prognosis of large cell cancer, an uncommon NSCLC, is similar to that of adenocarcinoma.

Small Cell Lung Carcinoma (SCLC)

Small cell lung carcinoma (SCLC) accounts for approximately 20% of all primary lung cancers, or about 30,000–35,000 cases per year. The histologic distinction between non-small cell lung cancer and small cell lung cancer is extremely important. There are substantial differences between the two groups in both treatment and prognosis. In general, small cell lung cancer tends to be more aggressive and spreads sooner to distant sites. Some studies suggest that 60–70% of patients with small cell lung cancer have evidence of distant spread at the time of initial diagnosis. Yet, small cell lung cancer also is inclined to be more responsive to chemotherapy and chest radiotherapy (radiation).

In smokers, lung cancer usually is associated with three principal histologic types–small cell carcinoma, squamous cell carcinoma, and adenocarcinoma.

SMALL CELL LUNG CARCINOMA NON SMALL CELL LUNG CARCINOMA

Signs and Symptoms of Lung Cancer

In many cases, people decide to visit the doctor only after they have been bothered by certain symptoms over a period of time. Common symptoms of lung cancer include the following:

Cough

Shortness of breath

Wheezing

Chest pain

Hemoptysis (bloody, coughed-up sputum)

Loss of appetite

Weight loss

Pneumonia (inflammation of the lungs)

Other symptoms that are associated with lung cancer include the following:

Weakness

Chills

Swallowing difficulties

Speech difficulties or changes (e.g., hoarseness)

Finger/nail abnormalities (e.g., "clubbing," or overgrowth of the fingertip tissue)

Skin paleness or bluish discoloration

Muscle contractions or atrophy (shrinkage)

Joint pain or swelling

Facial swelling or paralysis

Eyelid drooping

Bone pain/tenderness

Breast development in me

Staging

Lung cancer staging helps the physician to determine how a patient is expected do over the long term (called a prognosis). It distinguishes patients who have limited disease from patients with distant metastasis. Staging provides an estimate of disease-free survival, overall survival, and risk for cancer recurrence or relapse. Staging also helps the physician to develop an appropriate treatment for each patient. The influence of staging is particularly important when radiation or surgical therapy are added to chemotherapy in treating patients with limited stage disease. Lung cancer staging usually is described in terms of the TNM system

Tumors

The primary tumor (T) is classified according to the following categories:

TX: Tumor cannot be evaluated or tumor is proven by the presence of cancer cells in the sputum or bronchial washings, but it cannot be seen during imaging or bronchoscopy ("occult" tumor)

T0: No evidence of primary tumor

Tis: Carcinoma in situ

T1: Tumor 3 centimeters (< 3 cm) or less in greatest dimension, surrounded by lung or pleura, and not located in the main stem bronchus

T2: Tumor more than 3 centimeters (> 3 cm) in greatest dimension, or tumor involving the main stem

bronchus, 2 cm or more from the carina, or tumor invading the visceral pleura, or tumor with incomplete lung expansion or obstructive lung infection that does not involve the entire lung

T3: Tumor of any size that directly invades the chest wall, diaphragm, pleura, or pericardium, or tumor that involves the main stem bronchus less than 2 centimeters (< 2 cm) from the carina (ridge between the right and left main stem bronchi), or tumor that is associated with complete lung collapse or obstructive lung infection involving the entire lung.

T4: Tumor of any size that invades the heart, great vessels (aorta, superior or inferior vena cava, pulmonary artery, or pulmonary vein), trachea, esophagus, vertebral body, or carina, or separate tumor nodules in the same lung lobe, or tumor associated with a malignant pleural effusion.

Nodes

The regional lymph nodes (N) are clinically divided into the following categories:

NX: Regional lymph nodes cannot be assessed

N0: Regional lymph nodes contain no metastases

N1: Metastasis to same-side peribronchial (around the bronchi) and/or hilar (pit in the lungs where vessels enter and exit) lymph nodes and nodes within the lungs that are involved by direct spread of the primary tumor

N2: Metastasis to same-side mediastinal and/or subcarinal (under the carina, or tracheal ridge) lymph nodes.

N3: Metastasis to opposite-side mediastinal or hilar nodes or to same- or opposite-side scalene (neck/upper rib) or supracalvicular (above collarbone) lymph nodes.

Metastasis

The state of metastasis (M) is defined as follows:

MX: Distant metastases cannot be assessedM0: No distant metastases are found

M1: Distant metastases are present (this also includes separate tumor nodules in a different lobe of lung on either side).

Staging

The TNM system—which includes the overall features of the tumor, lymph nodes, and metastatic status—places lung cancer growth at a particular stage. Apart from hidden, yet to be identified tumors (occult: TxN0M0) and confined carcinomas in situ (stage 0; tis), there are four basic stages within the tnm classification system:

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 IIIb: T(any), N3, M0 or T4, N(any), M0

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

The TNM staging system is not often used for patients with small cell lung carcinoma (SCLC), because most have suspected or definite metastatic disease at the time of diagnosis. Survival in these patients usually is unaffected by minor differences in the extent of tumor involvement. Instead, most experts use a simple, two-stage system created by the Veterans Administration Lung Cancer Study Group. This system defines SCLC as being of "limited" or "extensive" stage.

Diagnosis of Lung Cancer

Physical Examination & Lung Cancer Diagnosis

Patients who are suspected of having lung cancer should undergo a thorough physical examination. In addition, the physician may ask the patient to provide a sample of sputum (matter from the throat and lungs, which is spit out through the mouth). The sputum sample is sent for laboratory testing to see if it contains bacteria, other infectious organisms, or cancer cells; cancer cells may be present in the sputum in certain types of lung cancer.

If sputum analysis does not provide a definite diagnosis, additional tests are performed. Diagnostic tests include the following:

Chest radiograph (x-ray) is used to detect enlarged lymph nodes in the chest or a localized mass in the lungs.

Computed tomography (CT or "CAT" scan) is a computer-assisted technique that produces cross-sectional images of the body.

Right upper lobe (RUL) mass due to lung cancer.

CT-Large left lung and a hilar mass, with invasion of the left pulmonary artery.

Magnetic resonance imaging (MRI scan) is a diagnostic method in which hydrogen ions within the body (and/or specific body parts) are excited by exposure to a magnetic field. The resulting signals are processed by a computer to create an image of the chest to define the location and extent of lung involvement.

Bronchoscopy is a visual examination of the windpipe and lung branches performed by a pulmonologist (respiratory disease specialist) using a flexible scope. Bronchoscopy may involve brushings (using a small, brush-like device to gather cells from the tissue lining the respiratory system), washings of the respiratory tissues for cell analysis, and biopsy (removal and examination of small amounts of tissue). If the bronchoscopy is still unrevealing, or "negative," a needle biopsy may be performed.

Needle biopsy, with CT-guidance, may be performed on suspicious areas in the lungs or pleura. Fine needle aspiration (FNA) uses a slim, hollow needle that is attached to a syringe. The needle is inserted into the suspicious mass and it is pushed back and forth to free some cells, which are aspirated (drawn up) into the syringe and are smeared on a glass slide for analysis. Large needle, or core biopsy, uses a large-bore needle to obtain a tissue sample for analysis.

Bone scan may also be performed to rule out suspicions of metastasis to the bones. Metastasis is the process wherein cancerous cells break away from the original tumor, travel, and grow within other body parts.

A newer imaging test, called CT/PET fusion imaging, combines the technology of CT scan with the technology of PET (positive emission tomography) scan. PET scans involve injecting a sugar-based radiopharmaceutical, which travels through the body and collects in organs and tissues. The PET scan is used to detect cancer cells in the body and the CT scan provides detailed images that can determine the location and size of the cancer.

Lung cancer, small cell. Coronal positron emission tomogram shows abnormal areas of increased metabolic activity in the left hilar

Once a lung cancer diagnosis is made, the oncology team determines if the patient is a candidate for surgery by reviewing the imaging studies (e.g., x-ray, CT scan, bone scan) to rule out distant metastasis.

If there is no evidence of metastasis, the patient may then undergo mediastinoscopy, a surgical inspection of the mediastinum (tissues and organs of the middle chest, such as the the heart, large vessels, and windpipe). In this procedure, a small flexible device with a camera, called an endoscope, is inserted into the chest via an incision at the top of the sternum (breastbone), and the chest cavity is then examined.

The mediastinal lymph nodes usually are removed during this procedure. If the mediastinal lymph nodes are "negative" (do not contain any cancer cells), the patient may be a candidate for surgery. However, if mediastinal lymph nodes are "positive" (contain cancer cells) or are abnormally large on imaging studies (suggesting tumor involvement), the patient is not considered to be a surgical candidate.

Additional blood tests may be performed to look for lung cancer "markers"—that is, elements in the blood that are associated with the presence of lung cancer. For example, lung cancer may be indicated by abnormalities in the following.

PTH (parathyroid hormone)—Blood levels of PTH or PTH-related protein may help to distinguish lung cancer from cancer of the pleura or other diseases.

CEA (carcinogenic antigen)—a cancer-specific immune system protein that is present in many adenocarcinomas, including lung adenocarcinoma. Increased preoperative levels of CEA usually suggest a poor prognosis. A CEA level greater than 50 may indicate advanced stage lung cancer and should discourage treatment by resection.

CYFRA21-1 (cytokeratin fragment 19)—a protein marker of lung cancer.

Lung Cancer Treatments - Surgical Resection

Surgical Resection to Treat Lung Cancer

Surgical resection (cutting away) of the tumor generally is indicated for cancer that has not spread beyond the lung. Surgery for lung cancer may be conducted using a variety of techniques. Thoracotomy, which is performed throught the chest wall, and median sternotomy, which is performed by cutting through the breastbone, are standard methods used for lung cancer surgery.

Wedge Resection

A wedge resection can be performed if the tumor / mass is confined to one area of the lung. This procedure removes only the affected tissue.

Lobectomy

The lungs are composed of sections called lobes. A lobectomy removes an entire lobe. By removing the entire lobe, the lobectomy hopefully removes all traces of cancer cells. Surrounding lymph nodes may be removed at the same time in a procedure called a lymphadenectomy.

Pneumonectomy

A pneumonectomy removes an entire lung. Removal may be needed if cancer appears to have spread through one entire side of the lungs, but the exact location is hard to pinpoint. People often worry that their breathing will be compromised after lung removal, but the remaining lung is usually more than sufficient.

Alternative approaches include anterior limited thoractomy (ALT), which is performed on the frontal chest using a small incision; anterioraxillary thoracotomy(AAT), which is performed on the frontal chest near the underarm; and posterolateral thoracotomy (PLT), which is performed on the back/side region of the trunk.

Recently, surgeons have developed other less invasive procedures for the removal of cancerous lung tissue. For example, video-assisted thoracoscopy (VAT), also known as video-assisted thoracic surgery (VATS), involves using a video camera to help visualize and operate on the lung within the chest cavity. The surgical incisions made during VAT are much smaller than those required for thoracotomy or sternotomy.

However, some physicians caution that VAT does not allow complete lung examination to identify and remove metastases that are not detected by preoperative chest x-ray. VAT is perhaps most appropriate for Stage 1 and Stage 2 cancers that require lobectomy (surgical removal of a lung lobule) with lymphadenectomy (removal of one or more lymph nodes) and for peripheral (outer edge) lung tumors that can be removed by wedge resection. In such cases, follow-up is required to establish a long-term prognosis.

Chemotherapy

Standard chemotherapy for lung cancer typically consists of combinations of two or more of these drugs. Such combination therapy has been shown to improve the overall response to treatment. Well-known drug pairings in combination therapy include the following:

Paclitaxel plus carboplatin

Cisplatin plus vinorelbine tartrate

Cisplatin plus VP-16

Carboplatin plus VP-16

Concurrent radiotherapy is very often used with the combinations of cisplatin plus VP-16 or carboplatin plus VP-16. In addition, researchers are now studying the effects of radiotherapy with the combination of paclitaxel plus carboplatin.

Prognosis

Stage 1a —more than 60 months (> 5 years)Stage 1b —about 36 months (3 years)Stage 2a —about 24 months (2 years)Stage 2b —about 20 months (< 2 years)Stage 3a —about 15 months (< 1.5 years)Stage 3b —about 12 months (1 year)Stage 4 —about 8 months (< 1 year)

LUNG ABSCESS

Lung abscess is a necrotizing lung infection characterized by a pus-filled cavitary lesion. It is almost always caused by aspiration of oral secretions by patients who have impaired consciousness. Symptoms are persistent cough, fever, sweats, and weight loss. Diagnosis is based primarily on chest x-ray. Treatment usually is with clindamycin or combination β-lactam/β-lactamase inhibitors.

EtiologyMost lung abscesses develop after aspiration of oral secretions by patients with gingivitis or poor oral hygiene. Typically, patients have altered consciousness as a result of alcohol intoxication, illicit drugs, anesthesia, sedatives, or opioids. Older patients and those unable to handle their oral secretions, often because of neurologic disease, are also at risk.

A less common cause of lung abscess is necrotizing pneumonia that may develop from hematogenous seeding of the lungs due to suppurative thromboembolism (eg, septic embolism from IV drug use) or right-sided endocarditis. In contrast to aspiration, these conditions typically cause multiple rather than isolated lung abscesses.

The most common pathogens of lung abscesses due to aspiration are anaerobic bacteria, but about half of all cases involve both anaerobic and aerobic organisms. The most common aerobic pathogens are streptococci and staphylococci—sometimes methicillin-resistantStaphylococcus aureus (MRSA). An unusual but very important acute and often lethal form of lung necrosis is caused by S. aureus with genes for Panton-Valentine leukocidin. Very serious and fulminant cases may be caused by MRSA (USA 300 strain), which has become a rare but very important cause of necrotizing pneumonia in young previously healthy adults and children. Occasionally, cases are due to gram-negative bacteria, especially Klebsiella. Immunocompromised patients with lung abscess may have infection with Nocardia, Mycobacteria sp, or fungi. Some people, especially those from developing countries, are at risk of abscess due to Mycobacterium tuberculosis, and rare cases are due to amebic infection (eg, with Entamoeba histolytica), paragonimiasis, or Burkholderia pseudomallei.

Introduction of these pathogens into the lungs first causes inflammation, which leads to tissue necrosis and then abscess formation. The abscess usually ruptures into a bronchus, and its contents are expectorated, leaving an air- and fluid-filled cavity. In about one third of cases, direct or indirect extension (via bronchopleural fistula) into the pleural cavity results in empyema.

Cavitary pulmonary lesions are not always caused by infection. Noninfectious causes include the following:

Bullae with air-fluid level

Bronchiectasis

Lung cancer

Lung infarction

Nodular silicosis nodule with central necrosis

Pulmonary embolism

Pulmonary sequestration

Sarcoidosis

Wegener's granulomatosis

Symptoms and SignsSymptoms of abscess due to anaerobic bacteria or mixed anaerobic and aerobic bacteria are usually chronic (eg, over weeks or months) and include productive cough, fever, sweats, and weight loss. Severe prostration may occur. Sputum may be purulent or blood-streaked and classically smells or tastes foul. Symptoms of abscess due to aerobic bacteria develop more acutely and resemble bacterial pneumonia. Abscesses due to organisms other than anaerobes (eg, Mycobacteria , Nocardia) lack putrid respiratory secretions and may be more likely to occur in nondependent lung regions.

Signs of lung abscess, when present, are nonspecific and resemble those of pneumonia: decreased breath sounds indicating consolidation or effusion, temperature ≥ 38° C, crackles over the affected area, egophony, and dullness to percussion in the presence of effusion. Patients typically have signs of periodontal disease and a history of a predisposing cause of aspiration, such as dysphagia or a condition causing impaired consciousness.

Diagnosis Chest x-ray

CT as needed

Sputum cultures (unless anaerobic infection is very likely), including for fungi and mycobacteria

Bronchoscopy as needed to exclude cancer

Lung abscess is suspected based on history in a patient who is aspiration-prone due to altered consciousness or dysphagia and is confirmed by chest x-ray. In an anaerobic infection due to aspiration, chest x-ray classically shows consolidation with a single cavity containing an air-fluid level in portions of the lung that would be dependent when the patient is recumbent (eg, the posterior segment upper lobes or the superior or lateral basal segments of the lower lobes). This pattern helps distinguish anaerobic abscess from other causes of cavitary pulmonary disease, because diffuse or embolic pulmonary disease often causes multiple cavitations, and TB typically involves the apices.

CT is not routinely needed but may be useful when the x-ray suggests a cavitating lesion or when an underlying pulmonary mass obstructing the drainage of a lung segment is suspected.

Bronchial carcinoma can lead to obstruction that causes pneumonia and abscess formation. This should be suspected in smokers, recent smokers, and patients with unexplained cavitary lesions and no fever. Bronchoscopy is sometimes done to exclude cancer or the presence of a foreign body or to detect unusual pathogens, such as fungi.

Cultures: Anaerobic bacteria are rarely identifiable on culture because uncontaminated specimens are difficult to obtain and because most laboratories do not culture anaerobes well or often. If sputum is putrid, then anaerobic infection is assumed to be the cause. However, if empyema is present, pleural fluid provides a good source for anaerobic culture.

When clinical findings make anaerobic infection less likely, aerobic, fungal, or mycobacterial infection should be suspected, and attempts should be made to identify a pathogen. Cultures of sputum, bronchoscopic aspirates, or both are helpful. MRSA is generally found in both the sputum and blood cultures.

Treatment IV antibiotics or, for less seriously affected patients, oral antibiotics

Percutaneous drainage or surgery if empyema present or no response to antibiotics