Atlas of pathophysiology, 2 Edition
Part I - Central concepts
Cancer refers to a group of more than 100 different diseases characterized by DNA damage that causes abnormal cell development and growth. Malignant cells have two defining characteristics: first, they can no longer divide and differentiate normally and, second, they can invade surrounding tissues and travel to distant sites within the body. In the United States, cancer is the number one cause of death in people younger than age 85 and accounts for more than half a million deaths each year.
The healthy body is well equipped to defend itself against cancer. Only when the immune system and other defenses fail does cancer prevail. Current evidence suggests that cancer develops from a complex interaction of exposure to carcinogens and accumulated mutations in several genes. Researchers have identified approximately 100 cancer genes, oroncogenes.
Oncogenes provide growth-promoting signals, thereby causing one or more characteristics of cancer cells when overexpressed or mutated. The two types of oncogenes are:
· proto-oncogenes, which are genes that can be converted to oncogenes by transforming cells or contributing to tumor formation
· anti-oncogenes, also known as tumor suppressor genes, which are growth-suppressing genes that inhibit tumor development.
Both types of oncogenes remain dormant unless they're transformed by genetic or acquired mutation. Common causes of acquired genetic damage are viruses, radiation, environmental and dietary carcinogens, and hormones. Other factors that interact to increase a person's likelihood of developing cancer are age, genetics, nutritional status, hormonal balance, and response to stress.
Cancer is recognized as a multistage disease involving multiple, distinct changes in cell genotype and phenotype.
Many cancers are related to specific environmental factors (air pollution, tobacco and alcohol, occupation, and radiation) and lifestyle factors (sexual practices and diet) that predispose a person to develop cancer. Accumulating data suggest that some of these risk factors initiate carcinogenesis, others act as promoters, and some both initiate and promote the disease process. In addition, age and genetics can also determine a person's risk of cancer.
Environmental factors such as air pollution have been linked to the development of cancer, particularly lung cancer. Many outdoor air pollutants—such as arsenic, benzene, hydrocarbons, polyvinyl chlorides, and other industrial emissions as well as motor vehicle exhaust—have been studied for their carcinogenic properties. Indoor air pollution, such as cigarette smoke and radon gas, also poses an increased risk of cancer. In fact, indoor air pollution is considered to be more carcinogenic than outdoor air pollution.
Tobacco and alcohol
A cigarette smoker's risk of lung cancer is more than 10 times greater than that of a nonsmoker's by late middle age. Tobacco smoke contains carcinogens that are known to cause mutations. The risk of lung cancer from cigarette smoking correlates directly with the duration of smoking and the number of cigarettes smoked per day. Research also shows that a person who stops smoking decreases his risk of lung cancer.
Although the risk associated with pipe and cigar smoking is similar to that of cigarette smoking, some evidence suggests that the effects are less severe. Smoke from cigars and pipes is more alkaline. This alkalinity decreases nicotine absorption in the lungs and is also more irritating to the lungs, so that the smoker doesn't inhale as readily.
Inhalation of secondhand smoke, or passive smoking, by nonsmokers also increases the risk of lung and other cancers. Use of smokeless tobacco, in which the oral tissue directly absorbs nicotine and other carcinogens, is linked to an increase in oral cancers that seldom occur in persons who don't use the product.
Alcohol consumption is commonly associated with cirrhosis of the liver, a precursor to hepatocellular cancer. The risk of breast and colorectal cancers also increases with alcohol consumption. Heavy use of alcohol and cigarette smoking synergistically increases the incidence of cancers of the mouth, larynx, pharynx, and esophagus. It's likely that alcohol acts as a solvent for the carcinogenic substances in smoke, thus enhancing their absorption.
Certain occupations that expose workers to specific substances increase the risk of cancer. For example, persons exposed to asbestos are at risk for a specific type of lung cancer, called mesothelioma. Asbestos also may act as a promoter for other carcinogens. Workers involved in the production of dyes, rubber, paint, and beta-naphthylamine are at increased risk for bladder cancer.
Exposure to ultraviolet radiation, including sunlight (UVB) or tanning booths (UVA), causes genetic mutation in the P53 control gene. Sunlight also releases tumor necrosis factor alpha in exposed skin, possibly diminishing the immune response. Ultraviolet sunlight is a direct cause of basal and squamous cell cancers of the skin. The amount of exposure to ultraviolet radiation also correlates with the type of cancer that develops. For example, cumulative exposure to ultraviolet sunlight is associated with basal and squamous cell skin cancer, and severe episodes of burning and blistering at a young age are associated with melanoma.
Ionizing radiation (such as X-rays) is associated with acute leukemia, thyroid, breast, lung, stomach, colon, and urinary tract cancers as well as multiple myeloma. Low doses of radiation can cause DNA mutations and chromosomal abnormalities, and large doses can inhibit cell division. Ionizing radiation can also enhance the effects of genetic abnormalities. Other compounding variables include the part and percentage of the
body exposed, the person's age, hormonal balance, use of prescription drugs, and preexisting or concurrent conditions.
Sexual practices have been linked to specific types of cancer. The age of first sexual intercourse and the number of sexual partners are positively correlated with a woman's risk of cervical cancer. Furthermore, a woman who has had only one sexual partner is at higher risk if that partner has had multiple partners. The suspected underlying mechanism here involves virus transmission, most likely human papilloma virus (HPV). Of the approximately 70 types of HPV, types 6 and 11 are associated with genital warts. HPV is the most common cause of abnormal Papanicolaou (Pap) tests, and cervical dysplasia is a direct precursor to squamous cell carcinoma of the cervix, both of which have been linked to HPV (especially types 16 and 31).
Hormones—specifically, the sex steroid hormones estrogen, progesterone, and testosterone—have been implicated as promoters of breast, endometrial, ovarian, or prostate cancer.
Numerous aspects of diet are linked to an increase in cancer, including:
· high consumption of dietary fat
· high consumption of smoked foods and salted fish or meats and foods containing nitrites
· naturally occurring carcinogens, such as hydrazines and aflatoxin, in foods
· carcinogens produced by microorganisms stored in foods
· low-fiber diet.
It's also important to note that childhood obesity may increase the risk of cancer development in later life. Obesity is a prominent risk factor for breast, colon, and prostate cancers. Because cancer is a disease of abnormal cell proliferation, the increased total number of cells in the body associated with obesity undergo a greater number of cell divisions, thereby increasing their susceptibility to abnormal changes and an increased risk of cancer development.
Age is a major determinant in the development of cancer. The longer men and women live, the more likely they are to develop the disease. For example, because of the long natural history of common cancers, prostate cancer may take up to 60 years to become invasive, while colon cancer may take as long as 40 years to develop into an invasive stage. Possible explanations for the increased incidence of cancer with advancing age include:
· altered hormonal levels, which may stimulate cancer
· ineffective immunosurveillance, which fails to recognize and destroy abnormal cells
· prolonged exposure to carcinogenic agents, which is more likely to produce neoplastic transformation
· inherent physiologic changes and functional impairments, which decrease the body's ability to tolerate and survive stress.
Genes, through the proteins they encode, are the chemical messages of heredity. Located at specific locations on the 46 chromosomes within the cell's nucleus, genes transmit specific hereditary traits.
Most cancers develop from a complex interplay among multiple genes and between genes and internal or external environmental factors. Phenomenal progress has been made in the fields of cancer genetics and cytogenetics that has established specific chromosomal changes as diagnostic and prognostic factors in acute and chronic leukemias, as diagnostic factors in various solid tumors, and as indicators for the localization and characterization of genes responsible for tumor development.
Moreover, in the past 25 years, research has identified and characterized many of the genetic alterations that lead to tumor transformation at the chromosomal and molecular cell level. The Human Genome Project, started in 1988 to identify the entire sequence of human DNA, has helped to increase knowledge about genetics and cancer carcinogenesis. The Philadelphia (Ph) chromosome was the first chromosomal anomaly caused by translocation implicated in a human disease (chronic myelocytic leukemia [CML]). However, it's important to note that not all mutated genes always lead to disease.
As previously discussed, two sets of genes, oncogenes and tumor suppressor genes, participate in the transformation of a normal cell into a malignant cell; however, because multiple, successive changes in distinct cellular genes are required to complete the entire process, the human cell rarely sustains the necessary number of changes needed for tumor transformation. Gene mutations are either inherited from a parent (hereditary or germline mutation) or acquired (somatic mutation). Inheritance accounts for about 10% of all cancers. Acquired mutations are changes in DNA that develop throughout a person's lifetime. Carcinogenic agents, such as radiation or toxins, commonly are able to damage cellular genes, which are present in the cancer cell genome, thereby triggering cancer development.
Genes implicated in hereditary cancer include:
· mutation of the adenomatous polyposis coli (APC) suppressor gene, which is altered by somatic mutations in colonic epithelial cells, permitting the outgrowth of early colonic polyps
· familial adenomatous polyposis (FAP) or APC, which acts as an autosomal dominant inherited condition in which hundreds of potentially cancerous polyps develop in the colon and rectum
· familial cutaneous malignant melanoma gene, on the distal short arm of chromosome 1
· expression of the N-myc oncogene in neuroblastoma, with amplification of this oncogene associated with rapid disease progression in children
· loss of regulation of N-myc gene expression, which is also a pivotal factor in the development of retinoblastoma, the most common pediatric intraocular tumor
· germline mutation of the P53 gene, which is mapped to the short arm of chromosome 17 and is associated with Li-Fraumeni syndrome, an extremely rare familial cancer syndrome that increases susceptibility to breast cancer, soft tissue sarcomas, brain tumors, bone cancer, leukemia, and adrenocortical carcinoma
· human epidermal growth factor receptor-2 (HER-2)/neu proto-oncogene, which is involved in regulation of normal cell growth. Gene amplification or HER-2/neu overexpression, which occurs in 25% to 30% of human breast cancers and to varying degrees in other tumor types, produces activated HER-2/neu receptors and stimulates cell growth. Tumors positive for the
HER-2/neu gene are associated with poor clinical outcomes, shortened disease-free survival, more rapid cancer progression, and poor response to standard clinical interventions.
Gene mutations have also been linked to inherited tendencies toward common cancers, including colon cancer and breast cancer. The BRCA 1 gene normally helps to restrain cell growth. Researchers have found that families who carry inherited mutations of breast cancer susceptibility genes may also have an increased risk of other cancers, for example, women with an altered copy of the BRCA 1 breast cancer susceptibility gene (located on chromosome 17q21) have increased susceptibility to ovarian cancer as well. Moreover, BRCA 2, a second breast cancer susceptibility gene mapped to chromosome 13q, may account for a significant number of hereditary breast cancers not associated with BRCA 1.
The characteristic features of cancer are rapid, uncontrollable proliferation of cells and independent spread from a primary site, the site of origin, to other tissues where it establishes secondary foci (metastases). (See Histologic characteristics of cancer cells.) This spread occurs through circulation in the blood or lymphatic fluid, by unintentional transplantation from one site to another during surgery, and by local extension. Thus, cancer cells differ from normal cells in terms of cell size, shape, number, differentiation, function, and ability to travel to distant tissues and organ systems.
Histologic characteristics of cancer cells
Cancer is a destructive (malignant) growth of cells, which invades nearby tissues and may metastasize to other areas of the body. Dividing rapidly, cancer cells tend to be extremely aggressive.
Typically, each of the billions of cells in the human body has an internal clock that tells the cell when it's time to reproduce. Mitotic reproduction occurs in a sequence called the cell cycle. Normal cell division occurs in direct proportion to cells lost, thus providing a mechanism for controlling growth and differentiation. These controls are absent in cancer cells, and cell production exceeds cell loss. The loss of control over normal growth is termed autonomy. This independence is further evidenced by the ability of cancer cells to break away and travel to other sites in the body.
Normal cells reproduce at a rate controlled through the activity of specific control or regulator genes. These genes produce proteins that act as “on” and “off” switches. There is no generalized control gene; different cells respond to specific control genes. In cancer cells, the control genes fail to function normally. The actual control may be lost, or the gene may become damaged. An imbalance of growth factors may occur, or the cells may fail to respond to the suppressive action of the growth factors. Any of these mechanisms may lead to uncontrolled cellular reproduction.
Hormones, growth factors, and chemicals released by neighboring cells or by immune or inflammatory cells can influence control gene activity. These substances bind to specific receptors on the cell membranes and send out signals causing the control genes to stimulate or suppress cell reproduction.
Substances released by nearby injured or infected cells or by cells of the immune system also affect cellular reproduction. For example, interleukin, released by immune cells, stimulates cell proliferation and differentiation, and interferon, released from virus-infected and immune cells, may affect the cell's rate of reproduction.
Additionally, cells that are close to one another appear to communicate with one another through gap junctions (channels through which ions and other small molecules pass). This communication provides information to the cell about the neighboring cell types and the amount of space available. The nearby cells send out physical and chemical signals that control the rate of reproduction. Cancer cells fail to recognize the signals about available tissue space. Instead of forming only a single layer, cancer cells continue to accumulate in a disorderly array.
Normally, during development, cells become specialized—that is, they develop highly individualized characteristics that reflect their specific structure and functions. As the cells become more specialized, their reproduction and development slow down. Eventually, highly differentiated cells become unable to reproduce, and some—skin cells, for example—are programmed to die and be replaced.
Cancer cells lose the ability to differentiate; that is, they enter a state, called anaplasia, in which they no longer appear or function like the original cell. Anaplasia occurs in varying degrees. The less the cells resemble the cell of origin, the more anaplastic they are said to be. As anaplastic cells continue to reproduce, they lose the typical characteristics of the original cell. Some anaplastic cells begin functioning as another type of cell, possibly beginning to produce hormones. Anaplastic cells
of the same type in the same site exhibit many different shapes and sizes. Mitosis is abnormal, and chromosome defects are common.
The abnormal and uncontrolled proliferation of cancer cells is also associated with numerous changes within the cancer cell itself. These changes affect cell components as follows:
· cell membrane—affects the organization, structure, adhesion, and migration of the cells. Impaired intercellular communication, enhanced response to growth factors, and diminished recognition of other cells causes uncontrolled growth and greatly increases metabolic demand for nutrients.
· cytoskeleton—disrupts protein filament networks, including actin and microtubules. Normally, actin filaments exert a pull on the extracellular organic molecules that bind cells together. Microtubules control cell shape, movement, and division.
· cytoplasm—becomes fewer in number and abnormally shaped. Less cellular work occurs because of a decrease in endoplasmic reticulum and mitochondria.
· nucleus—becomes pleomorphic (enlarged and misshapen) and highly pigmented. Nucleoli are larger and more numerous than normal. The nuclear membrane is often irregular and commonly has projections, pouches, or blebs and fewer pores. Chromatin may clump along the outer areas of the nucleus. Chromosomal breaks, deletions, translocations, and abnormal karyotypes are common and seem to stem from the increased mitotic rate in cancer cells.
Tumor development and growth
Typically, a long time passes between the initiating event and the onset of the disease. During this time, cancer cells continue to develop, grow, and replicate, each time undergoing successive changes and further mutations.
For a tumor to grow, an initiating event or events must cause a mutation that will transform the normal cell into a cancer cell. After the initial event, the tumor continues to grow only if available nutrients, oxygen, and blood supply are adequate and the immune system fails to recognize or respond to the tumor.
Two important tumor characteristics affecting growth are location of the tumor and available blood supply. The location determines the originating cell type, which in turn determines the cell cycle time. For example, epithelial cells have a shorter cell cycle than connective tissue cells. Thus, tumors of epithelial cells grow more rapidly than do tumors of connective tissue cells.
Tumors need an available blood supply to provide nutrients and oxygen for continued growth and to remove wastes, but a tumor larger than 1 to 2 mm in size has typically outgrown its available blood supply. Some tumors secrete tumor angiogenesis factors, which stimulate the formation of new blood vessels, to meet the demand.
The degree of anaplasia also affects tumor growth. Remember that the more anaplastic the cells of the tumor, the less differentiated the cells and the more rapidly they divide.
Many cancer cells also produce their own growth factors. Numerous growth factor receptors are present on the cell membranes of rapidly growing cancer cells. This increase in receptors, in conjunction with the changes in the cell membranes, further enhances cancer cell proliferation.
Important characteristics of the host that affect tumor growth include age, sex, overall health status, and immune system function.
A person's age is an important factor affecting tumor growth. Relatively few cancers are found in children, and the incidence of cancer correlates directly to increasing age. This suggests that numerous or cumulative events are necessary for the initial mutation to continue, eventually forming a tumor.
Certain cancers are more prevalent in females; others, in males. For example, sex hormones influence tumor growth in breast, endometrial, cervical, and prostate cancers. Researchers believe that sex hormones sensitize the cell to the initial precipitating factor, thus promoting carcinogenesis.
Overall health status is also an important characteristic affecting tumor growth. As tumors obtain nutrients for growth from the host, they can alter normal body processes and cause cachexia. Conversely, if the person is nutritionally depleted, tumor growth may slow down. Chronic tissue trauma has also been linked with tumor growth because healing involves increased cell division. Therefore, the more rapidly cells divide, the greater the likelihood of mutations.
Between the initiating event and the emergence of a detectable tumor, some or all of the mutated cancer cells may die. The survivors, if any, reproduce until the tumor reaches a diameter of 1 to 2 mm. New blood vessels form to support continued growth and proliferation. As the cells further mutate and divide more rapidly, they become more undifferentiated, and the number of cancerous cells soon begins to exceed the number of normal cells. Eventually, the tumor mass extends and invades the surrounding tissues. When the local tissue is blood or lymph, the tumor can gain access to the circulation. When access is gained, tumor cells that detach may travel to distant sites in the body, where they can survive and form a new tumor in the secondary site. This process is called metastasis. (See How cancer metastasizes, page 10.)
Not all cells that proliferate rapidly go on to become cancerous. Throughout a person's life span, various body tissues experience periods of benign rapid growth such as during wound healing. In some cases, changes in the size, shape, and organization of cells leads to a condition called dysplasia. Exposure to chemicals, viruses, radiation, or chronic inflammation causes dysplastic changes that may be reversed by removing the initiating stimulus or treating its effects. However, if the stimulus isn't removed, precancerous or dysplastic lesions can progress and give rise to cancer.
Initially, a tumor remains localized. Recall that cancer cells communicate poorly with nearby cells. As a result, the cells continue to grow and enlarge, forming a mass or clumps of cells. The mass exerts pressure on the neighboring cells, blocking their blood supply, and subsequently causing their death.
How cancer metastasizes
Cancer cells may invade nearby tissues or metastasize (spread) to other organs. They may move to other tissues by any or all of the three routes described below.
Invasion is growth of the tumor into surrounding tissues. It's actually the first step in metastasis. Five mechanisms are linked to invasion:
· cellular multiplication—By their very nature, cancer cells multiply rapidly.
· mechanical pressure—As cancer cells grow, they exert pressure on surrounding cells and tissues, which eventually die because their blood supply has been cut off or blocked. Loss of mechanical resistance opens the way for cancer cells to spread along the lines of least resistance and occupy the space once filled by the dead cells.
· lysis of nearby cells—Vesicles on the cancer cell surface contain a rich supply of receptors for laminin, a complex glycoprotein that's a major component of the basement membrane. These receptors permit the cancer cells to attach to the basement membrane, forming a bridgelike connection. Some cancer cells produce and excrete powerful proteolytic enzymes; other cancer cells induce normal host cells to produce them. These enzymes, such as collagenases and proteases, destroy the normal cells and break through their basement membrane, enabling the cancer cells to enter.
· reduced cell adhesion—Cancer cells' adhesion decreases, likely the result of damage to the cell membrane.
· increased motility—Cancer cells secrete a chemotactic factor that stimulates motility. Thus, they can move independently into adjacent tissues, and into the circulation, and then to a secondary site. Finally, cancer cells develop fingerlike projections called pseudopodia that facilitate cell movement. These projections injure and kill neighboring cells and attach to vessel walls, enabling the cancer cells to enter.
Metastatic tumors are those in which the cancer cells have traveled from the original or primary site to a second or more distant site. Most commonly, metastasis occurs through the blood vessels and lymphatic system. Tumor cells can also be transported from one body location to another by external means, such as surgical instruments or gloves.
Invasive tumor cells break down the basement membrane and walls of blood vessels, and the tumor sheds malignant cells into the circulation. Most of the cells die, but a few escape the host defenses and the turbulent environment of the bloodstream. From here, the surviving tumor mass of cells travels downstream and commonly lodges in the first capillary bed it encounters. When lodged, the tumor cells develop a protective coat of fibrin, platelets, and clotting factors to evade detection by the immune system. Then they become attached to the epithelium, ultimately invading the vessel wall, interstitium, and the parenchyma of the target organ. To survive, the new tumor develops its own vascular network and, when established, may ultimately spread again.
The lymphatic system is the most common route for distant metastasis. Tumor cells enter the lymphatic vessels through damaged basement membranes and are transported to regional lymph nodes. In this case, the tumor becomes trapped in the first lymph node it encounters. The consequent enlargement, possibly the first evidence of metastasis, may be due to the increased tumor growth within the node or a localized immune reaction to the tumor. The lymph node may filter out or contain some of the tumor cells, limiting their further spread. The cells that escape can enter the blood from the lymphatic circulation through plentiful connections between the venous and lymphatic systems.
Typically, the first capillary bed, whether lymphatic or vascular, encountered by the circulating tumor mass determines the location of the metastasis. For example, because the lungs receive all of the systemic venous return, they're a frequent site for metastasis.
Signs and symptoms
In most patients, the earlier the cancer is found, the more effective the treatment is likely to be and the better the prognosis. Some cancers may be diagnosed by a routine physical examination, even before the person develops any signs or symptoms. Others may display some early warning signals. (See Cancer's seven warning signs.)
Unfortunately, a person may not notice or heed cancer warning signs. These patients may present with some of the more common signs and symptoms of advancing disease, such as fatigue, cachexia, pain, anemia, thrombocytopenia and leukopenia, and infection. Unfortunately, these signs and symptoms are nonspecific and can be attributed to many other disorders.
A thorough history and physical examination should precede sophisticated diagnostic tests. The choice of diagnostic tests is determined by the patient's presenting signs and symptoms and the suspected body system involved. Diagnostic tests serve several purposes, including:
· establishing tumor presence and extent of disease
· determining possible sites of metastasis
· evaluating affected and unaffected body systems
· identifying the stage and grade of tumor.
Useful tests for early detection and staging of tumors include screening tests, X-rays, radioactive isotope scanning (nuclear medicine imaging), computed tomography (CT) scanning, position emission tomography (PET) scanning, endoscopy, ultrasonography, and magnetic resonance imaging (MRI). The single most important diagnostic tool is the biopsy for direct histologic study of the tumor tissue.
Cancer's seven warning signs
The American Cancer Society has developed a simple way to remember the seven warning signs of cancer. Each letter in the word CAUTION represents a possible warning sign that should prompt an individual to see his health care provider.
· Change in bowel or bladder habits
· Asore that doesn't heal
· Unusual bleeding or discharge
· Thickening or lump in the breast or elsewhere
· Indigestion or difficulty swallowing
· Obvious change in a wart or mole
· Nagging cough or hoarseness
· Screening tests are perhaps the most important diagnostic tools in the prevention and early detection of cancer. They may provide valuable information about the possibility of cancer even before the patient develops signs and symptoms. Examples of screening tests are mammograms, Pap tests, and fecal occult blood tests.
· X-rays are most commonly ordered to identify and evaluate changes in tissue densities. The type and location of the X-ray are determined by the patient's signs and symptoms and the suspected location of the tumor or metastases.
· Radioactive isotope scanning involves the use of a specialized camera, which detects radioactive isotopes that are injected into the bloodstream or ingested. The radiologist evaluates their distribution (uptake) throughout tissues, organs, and organ systems. This type of scanning provides a view of organs and regions within an organ that can't be seen with a simple X-ray.
· CT scanning evaluates successive layers of tissue by using a narrow beam X-ray to provide a cross-sectional view of the structure. It can also reveal different characteristics of tissues within a solid organ.
· PET scans use radioisotope technology to create a picture of the body in action. Computers construct images from the emission of positive electrons (positrons) by radioactive substances administered to the patient. Unlike other diagnostic methods that simply create images of how the body looks, PET scans provide real-time imaging of the body while it functions. To study cancer spread, PET scans involve injecting the cancer patient with a small amount of radioactive glucose. Cancerous cells metabolize sugar more quickly than healthy cells, and this process can be viewed on the scanned image. The three-dimensional PET scan pictures show malignancies as having a greater concentration of sugar.
· Endoscopy provides a direct view of a body cavity or passageway to detect abnormalities. During endoscopy, the health care provider can excise small tumors, aspirate fluid, or obtain tissue samples for histologic examination.
· Ultrasonography uses high-frequency sound waves to detect changes in the density of tissues that are difficult or impossible
to observe by radiology or endoscopy. Ultrasound helps to differentiate cysts from solid tumors.
· MRI uses magnetic fields and radio frequencies to show a cross-sectional view of the body organs and structures.
· Biopsy, removing a portion of suspicious tissue, is the only definitive method to diagnose cancer. Biopsy tissue samples can be taken by curettage, fluid aspiration, fine-needle aspiration, dermal punch, endoscopy, and surgical excision. The specimen then undergoes laboratory analysis for cell type and characteristics to provide information about the grade and stage of the cancer.
Some cancer cells release substances that normally aren't present in the body or are present only in small quantities. These substances, called tumor markers or biologic markers, are produced either by the cancer cell's genetic material during development and growth or by other cells in response to the presence of cancer. Markers may be found on the cell membrane of the tumor or in the blood, cerebrospinal fluid, or urine. Tumor cell markers include hormones, enzymes, genes, antigens, and antibodies.
Unfortunately, several disadvantages of tumor markers may preclude their use alone. For example:
· By the time the tumor cell marker level is elevated, the disease may be too far advanced to treat.
· Most tumor cell markers aren't specific enough to identify one certain type of cancer.
· Some nonmalignant diseases, such as pancreatitis or ulcerative colitis, are also associated with tumor cell markers.
· Perhaps the worst drawback, the absence of a tumor cell marker doesn't mean that a person is free from cancer.
Tumors are initially classified as benign or malignant depending on their specific features. Typically, benign tumors are well differentiated; that is, their cells closely resemble those of the tissue of origin. Commonly encapsulated with well-defined borders, benign tumors grow slowly, often displacing but not infiltrating surrounding tissues and, therefore, causing only slight damage. Benign tumors don't metastasize.
Conversely, most malignant tumors are undifferentiated to varying degrees, having cells that may differ considerably from those of the tissue of origin. They're seldom encapsulated and are typically poorly delineated. They rapidly expand in all directions, causing extensive damage as they infiltrate surrounding tissues. Most malignant tumors metastasize through the blood or lymph to secondary sites.
Malignant tumors are further classified by tissue type, degree of differentiation (grading), and extent of the disease (staging). High-grade tumors are poorly differentiated and are more aggressive than low-grade tumors. Early-stage cancers carry a more favorable prognosis than later-stage cancers that have spread to nearby or distant sites.
The number of cancer treatments is constantly increasing. They may be used alone or in combination (multimodal therapy), depending on the type, stage, localization, and responsiveness of the tumor and on limitations imposed by the patient's clinical status. Cancer treatment has four goals:
· cure—eradicating the cancer and promoting long-term patient survival
· control—arresting tumor growth
· palliation—alleviating symptoms when the disease is beyond control
· prophylaxis—providing treatment when no tumor is detectable, although the patient is known to be at high risk of tumor development or recurrence.
Cancer treatment is further categorized by type according to when it's used:
· primary—to eradicate the disease
· adjuvant—in addition to primary, to eliminate microscopic disease and promote a cure or improve the patient's response
· salvage—to manage recurrent disease.
Any treatment regimen can cause complications. Indeed, many complications of cancer are related to the adverse effects of treatment.
Surgery, once the mainstay of cancer treatment, is now typically combined with other therapies. It may be performed to diagnose the disease, initiate primary treatment, or achieve palliation and is occasionally done for prophylaxis.
Radiation therapy uses high-energy radiation to treat cancer. Used alone or in conjunction with other therapies, it aims to destroy dividing cancer cells while damaging normal cells as little as possible. Two types of radiation are used to treat cancer: ionizing radiation and particle beam radiation. Radiation therapy has both local and systemic adverse effects, because it affects both normal and malignant cells.
Chemotherapy includes a wide range of antineoplastic drugs, which may induce regression of a tumor and its metastasis. It's particularly useful in controlling residual disease and as an adjunct to surgery or radiation therapy. It can induce long remissions and sometimes effect cure. As a palliative treatment, chemotherapy aims to improve the patient's quality of life by temporarily relieving pain and other symptoms.
Every dose of a chemotherapeutic agent destroys only a percentage of tumor cells. Therefore, regression of the tumor requires repeated doses of drugs. The goal is to eradicate enough of the tumor so that the immune system can destroy the remaining malignant cells. Unfortunately, chemotherapy also causes numerous adverse effects.
The most commonly used types of chemotherapeutic agents are:
· alkylating agents and nitroureas
· antitumor antibiotics
· plant (Vinca) alkaloids
· hormones and hormone antagonists.
Hormonal therapy is based on studies showing that certain hormones can inhibit the growth of certain cancers.
Biotherapy, also known as immunotherapy, is treatment with agents known as biologic response modifiers. Biologic agents are usually combined with chemotherapy or radiation therapy and are most effective in the early stages of cancer. Many types of biotherapy are still experimental; their availability may be restricted, and their adverse effects are generally unpredictable.
The U.S. Food and Drug Administration has approved several new promising drugs for treatment of cancer. For example, rituximab—a monoclonal antibody—is effective to treat relapsed or refractory B-cell non-Hodgkin's lymphoma.
The major types of biotherapy agent classifications include interferons, interleukins, hematopoietic growth factors, and monoclonal antibodies.