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Cancer, new growth of tissue resulting from a continuous growth of abnormal cells that have the ability to enter and destroy other tissues. Cancer, which may arise from any type of cell and in any type of body tissue, is not a single disease but a large number of diseases classified according to the tissue and type of cell of origin. Several hundred such classes exist, constituting three major subtypes: Sarcomas – from connective and supportive tissue, such as bone, cartilage, nerve, blood vessel, muscle, and fat. Carcinomas, – include the most frequently occurring forms of human cancer, arise from soft tissues, such as the skin and the lining of the body cavities and organs, and the glandular tissue of the breast and prostate. Carcinomas, with a structure resembling skin, are termed squamous cell carcinomas. Those that resemble glandular tissue are called adenocarcinomas.Leukemia s and lymphomas – cancers that involve blood-forming tissue and are typed by the enlargement of the lymph nodes, the invasion of the spleen and bone marrow, and the overproduction of immature white blood cells. A cancerous growth, or neoplasm, is clonal – that is, all it s cells are descendants of a single cell. These cells have escaped the control of the normal forces regulating cellular growth by using an enzyme called telomerase, which allows the malignant cells to reproduce endlessly and at a rapid pace. Resembling embryonic cells, they are unable to differentiate or mature into an adult, functioning state. As these cells multiply, they may form a mass called a tumor, which enlarges and continues to grow without regard to the function of the tissue of its origin.Almost all cancers form tumors, but not all tumors are cancerous, or malignant; the greatest number are benign. Benign tumors are characterized by localized growth and are usually separated from neighboring tissue. Benign tumors generally grow slowly, and in structure closely resembling the tissue of origin. In some instances they may endanger the patient by obstructing, compressing, or displacing neighboring structures, as in the colon. A few benign tumors, such as polyps of the colon, may be precancerous.The most significant attribute of malignant tumors is their ability to spread beyond the site of origin. Cancer may invade neighboring tissues by direct extension or infiltration, or it may disseminate to distant sites, forming secondary growths known as metastases. The routes and sites of metastases vary with different primary cancers:(1) When a cancer extends through the surface of the organ of origin into a cavity, cells may break away from the surface and implant on the surface of adjacent organs.(2) Tumor cells may migrate into the lymphatic channels and be carried to the draining lymph nodes, or they may penetrate the blood vessels. Once in the bloodstream, the tumor cells are carried to the point at which the vessels become too small for the large tumor cells to pass. Cells from tumors of the gastrointestinal tract will be stopped in the liver. Later they may go on to the lungs. Cells from all other tumors will go to the lungs before being carried to other organs. The lungs and liver are therefore common sites of metastases.(3) Many cancers tend to shed cells into the bloodstream early in their growth. Most such cells die in the bloodstream, but some lodge against the surface and penetrate into the wall of other tissues. A few may find themselves in a favorable tissue in which they are able to survive and grow into a tumor, a metastasis. Others may divide only a few times, forming a small nest of cells that then remain dormant as a micrometastasis. They may remain dormant for many years, only to begin to grow again as recurrent cancer for reasons unknown. Cancer cells, even when widely spread, may retain the physical and biological characteristics of their tissue of origin. Thus, a pathologist can often determine the site of origin of metastatic tumors by microscopic examination of the cancerous tissue. Identification of tumors of the endocrine glands is simple because they may produce excessive amounts of the hormone that is produced by the tissue of origin. Such tumors may also respond to the administration of the hormones that normally control that tissue.In general, the less a cancer resembles it s tissue of origin, the more malignant and rapidly invasive it tends to be, but the rate of growth of a cancer depends not only on cellular type and the degree the cloning of it s parent tissue, but also on various host factors. Because of the abnormalities of in tumor cells, they are more susceptible to mutation. With time a tumor tends to become less different and to grow more rapidly. It may also develop an increased resistance to chemotherapy or radiation treatment (irradiation).A number of factors produce cancer in exposed individuals. Among these factors are heredity, viruses, ionizing radiation, chemicals, and changes in the immune system. For a long time these factors seemed to work in different ways, but now researchers are studying how they might interact in a multifactorial, sequential process resulting in malignancy. Basically, cancer is a genetic process. Gene abnormalities can be inherited or they can be induced in a body cell by a virus or by damage from an outside source. Researchers say that is probable a series of sequential mutations eventually leads to a single cell that is malignant and proliferates as a clone. Originally it was thought that a malignant clone was completely abnormal, and that the only way to cure cancer was to rid the body of all the abnormal cells. Considerable evidence now indicates that the problem may be a loss of the ability of the cell to change into its final, functioning state, perhaps because of the inability to produce a necessary normalcy factor.Researchers estimate that no more than 20 percent of cancers are based on inheritance. Several types of cancer, however, do run in families. Breast cancer is an example. Cancer of the colon is more common in families that tend toward polyps in the colon. A type of retinoblastoma has been demonstrated to occur only when a specific gene is deleted. A genetic abnormality that weakens the body’s defenses against carcinogens has been linked to prostate cancer. In some hereditary disorders, the chromosomes exhibit a high frequency of breakage; such diseases carry a high risk of cancer.Viruses are the cause of many cancers in animals. In humans the Epstein-Barr virus is associated with Burkitt’s lymphoma and lymphoepitheliomas, the hepatitis virus with hepatocarcinoma, and a papilloma virus with carcinoma of the cervix. These viruses associated with human tumors are DNA viruses. The HTLV virus that produces a T-cell leukemia is an RNA virus, or retrovirus, as are most of the viruses associated with animal tumors. In the presence of an enzyme called reverse transcriptase, they induce the infected cell to make DNA copies of the virus’s genes, which can be incorporated into the cell genome (the full complement of DNA). Such viruses may contain a gene, called a viral oncogene, capable of transforming normal cells into malignant cells. Research indicates that each viral oncogene has a counterpart in the normal human cell called a proto-oncogene, or cellular oncogene. Oncogene gene products (proteins for which they code), have been identified as growth factors or proteins necessary for the action of growth factors. They are therefore importantly related to cell proliferation.Ionizing radiation is a potent cause of cancer. Radiation changes DNA, including chromosome breaks and transpositions, in which the broken-off ends of two chromosomes are exchanged. It acts as an initiator of carcinogenesis, inducing a change that progresses to cancer after a period of years. This delay provides opportunity for exposure to other factors.The process by which chemical agents cause cancer has been extensively studied. Some chemicals act as initiators. Only a single exposure is required, but cancer does not follow until after a long latent period and after exposure to another agent that acts as a promoter. Initiators produce irreversible changes in DNA. Promoters do not change DNA, but they do increase synthesis of DNA and stimulate proper growth (expression) of genes. They have no effect if given before the initiator, only if given after the initiator and given repeatedly over a period of time. For example, tobacco smoke contains many chemical initiators and promoters. The promoter action of cigarettes is very important, and if smoking is stopped, the risk of lung cancer falls rapidly. Alcohol is another important promoter; chronic abuse greatly increases the risk of cancers known to be induced by other agents, such as lung cancer in smokers. Carcinogenetic chemicals also produce chromosome breaks and translocations.The immune system appears to be able to recognize malignant cells and stimulate the production of cells able to destroy them. An important factor in the development of cancer may be a disease or other damaging event leading to a state of immune deficiency. Such states are a consequence of AIDS, inherited immune deficiency diseases, and the administration of immunosuppressive drugs.Research estimates that about 80 percent of cancers may be caused by environmental factors. The best established cause is tobacco smoke, actively or passively inhaled, which is responsible for about 30 percent of all deaths from cancer in the United States. Dietary factors may account for about 40 percent, but the cause / effect relationship is not as clear, and the responsible items of a diet have not been clearly defined. Obesity is a risk factor for a number of cancers, especially cancers of the breast, colon, uterus, and prostate. Dietary fat and low dietary fiber are associated with incidences of colon cancer. Dietary fat and obesity, like alcohol, appear to act as promoters. The common component that unites these cells may be the oncogene. Oncogenic viruses may insert their genes at many places in the animal genome. A viral oncogene that is inserted in connection with a cellular oncogene influences the oncogene and induces cancer. Radiation and carcinogenetic chemicals produce DNA damage, mutations, and chromosome changes, and oncogenes are often located on the chromosome near the fragile site or breakpoint.A malignancy appears to be the result of a series of mishaps beginning with an abnormal gene or a somatic mutation (a mutation of a normal body tissue cell), probably more than one, followed by a promoting activity that stimulates one or more oncogenes, leading to the release of growth factors. The prior event leads to the loss of production of metabolites necessary for the normal growth of the cell. The stimulation of growth factors then causes the clone of undifferentiated cells to proliferate, and a defect in the immune system permits the abnormal cells to escape destruction by the body s normal defense mechanisms.It is estimated that more than 1 million new cases of cancer occur in the United States each year. It is the second leading cause of death in the nation, accounting for about 500,000 deaths annually, and is the leading cause of death from disease in children between the ages of 1 and 14. The incidence of cancer varies enormously among different geographic areas. The age-adjusted death rate from all cancers in males is 310.9 per 100,000 in Luxembourg (the highest) as compared to 37.5 in El Salvador (the lowest). The figures for the United States are 216.6 per 100,000 men and 136.5 per 100,000 women. For particular cancers, the difference between countries may be as high as 40 – fold. Evidence from studies of populations that have migrated from one geographic area to another suggests that these variations are due to differences in life-style rather than ethnic origin. This is consistent with other evidence that most cancers are predominately related to environmental causes rather than heredity, although the two interact.The cancers that cause the most deaths in the United States are lung cancer (first in each sex), colorectal cancer (second in both sexes combined), breast and uterine cancers in women, and prostate cancer in men. Together they account for more than 55 percent of all deaths from cancer. The most frequently occurring cancers are cancers of the skin, with over 500,000 cases per year, which, except for malignant melanoma, are not counted in statistics.Since 1949, cancer mortality in the United States has been higher among men than among women. The sex ratios of different cancers vary considerably. Cancer mortality is higher among black people than among white people for reasons that are not fully understood but are under intensive study.The earlier a cancer is diagnosed and treated, the greater the chance of cure. The regular screening of apparently healthy people is very rewarding because it permits diagnosis before development of symptoms, when the cancer is most curable. The cancers for which excellent or reasonably good screening is available are among the major killers: breast, colon and rectum, cervix, and prostate.Early diagnosis of cancers, not susceptible to screening, depends upon recognition of early signs of disease by the patient. The following is a list of the classic seven danger signals of cancer: Change in bowel or bladder habitsA sore that does not healUnusual bleeding or dischargeThickening or lump in breast or elsewhereIndigestion or difficulty in swallowingObvious change in a wart or moleNagging cough or hoarseness

Diagnostic study for cancer begins with a thorough history and physical examination, including inspection of all accessible sites, especially the skin, neck, breasts, abdomen, testicles, and lymph-node-bearing areas. It specifically includes examination of bodily orifices, particularly rectal examination for cancers of the rectum or prostate and pelvic examination for cancers of the cervix or body of the uterus.Tests for genetic predispositions to certain cancers began to appear in 1995. However, there is still considerable debate over whether these tests will help doctors detect cancers earlier, or whether they will simply alarm currently healthy individuals with knowledge of their possible medical future.Biopsy remains the only definitive method for the diagnosis of a cancer. In a biopsy, a section of tissue is removed from the tumor itself or from a metastasis. Modern technology has greatly reduced the need for open surgical biopsy. Guided by palpation or a computerized axial tomography (CAT or CT) scan, a tumor in almost any part of the body can be biopsied through a thin, flexible needle. This permits diagnosis before surgery, so the doctor and patient can better plan for treatment and surgery.Once a diagnosis of cancer has been made, the extent (stage), of the disease must be evaluated because prognosis and appropriate treatment vary with the stage of the disease. For each type of tumor, the stage (I, II, III, or IV) is defined in terms of findings with progressively more severe prognostic implications: small local tumor, more extensive local tumor, regional lymph node involvement, and distant metastases. The clinical stage, defined by information obtained prior to surgical exploration, is used to decide appropriate initial treatment. The surgical stage, which may be different from the clinical, incorporates the findings of the surgical exploration, and is used as a basis for later treatment and for prognosis. It is also used to analyze the effects of different treatments.The traditional means of treating cancer have been surgery, radiation, and chemotherapy. Currently, studies are under way of the usefulness of immunotherapy and biologic response modifiers.The basic (principle) approach to curing cancer is to remove all of the malignant cells by surgical operation. In the past this meant the removal of all of the involved (damaged) tissue(s) and as much potentially involved tissue as possible, including adjacent tissues and lymph nodes. For some tumors, notably cancer of the breast, this radical degree of surgery is not always necessary. Refinements in surgical techniques, improved knowledge of physiology, advances in anesthesiology, availability of blood products, and potent antibiotics have permitted less extensive surgery with more rapid recovery. Many cancers, though, are at too advanced a stage at the time of diagnosis to permit cure by surgery. If local extension involves neighboring tissues that cannot be sacrificed or if distant metastases are already present, traditional surgery will not cure the cancer. Even when it is clear that surgical cure is not possible, however, surgery may help to relieve symptoms, as of obstruction, or to reduce the size of the tumor in an effort to improve the response to subsequent radiation or chemotherapy. A new surgical procedure called cryoblation, affording more hope, uses ultrasound technology to locate the tumor, inserting a needle and injecting liquid nitrogen (-200 degrees) to eblate the tumor. This surgery, useful when a tumor is located where it cannot be removed because surgery would damage vital adjacent tissue or because a tumor has begun to infiltrate adjacent structures that cannot be sacrificed.Ionizing radiation, which may be either electromagnetic or particulate, is destructive to tissue. Electromagnetic radiation includes gamma rays, which are emitted by radioactive decay, and X rays, which are produced when a beam of electrons strikes a heavy-metal target. Particulate radiation includes beams of electrons, protons, neutrons, alpha particles (helium nuclei), and negative pi mesons (pions).Tumors vary greatly in their sensitivity to radiation. A sensitive tumor is one that is more sensitive than the surrounding normal tissues. When such a tumor is readily accessible – a superficial tumor, for example, or one in an organ like the uterus, into which a radiation source can be introduced – it may be curable by radiation therapy. Because of its relatively sparing effect on normal tissues, radiation is useful when a tumor is located where it cannot be removed because surgery would damage vital adjacent tissue or because a tumor has begun to infiltrate adjacent structures that cannot be sacrificed. Radiation therapy is also extremely useful for metastatic tumors.` Radiation can also be useful in conjunction with surgery. Preoperative radiation may rapidly sterilize the tumor cells and prevent them from seeding (spreading) at surgery. It may also shrink the tumor and make surgery easier, or shrink an inoperable tumor so that it becomes operable. For other tumors, postoperative radiation is commonly used.Chemotherapy is the use of drugs in the treatment of cancer. Since a drug is distributed throughout the body by the bloodstream, chemotherapy is useful for tumors that have spread beyond the area accessible by surgery or radiotherapy. A number of different types of anticancer drugs are used, but nearly all work by interfering with DNA synthesis or function. Rapidly dividing cells are therefore more sensitive to chemotherapy. Cancers have a larger number of dividing cells than do normal tissues. Replenishing cells are dormant and resistant to drug effect. The most rapidly proliferating normal tissues are the bone marrow and the lining cells of the gastrointestinal tract. These are the most sensitive normal areas of chemotherapeutic effect and constitute the sites of toxicity that will limit the tolerable dose of most drugs.To be effectively treated, a tumor must have a sensitivity greater than that of the most sensitive normal tissue. Some tumors may be many times more sensitive, but many are only slightly more sensitive. Fortunately, the normal bone marrow cells can divide faster than malignant cells and thus recover more rapidly. This permits a repeat cycle of the drug before the tumor has regrown very much. Repeated cycles can steadily deplete a tumor before resistance occurs. Some tumors are so sensitive to chemotherapy that a chemotherapeutic cure is possible in a high percentage: uterine cancer; acute leukemia, especially in children; Hodgkin’s disease and diffuse large-cell lymphoma; testicular carcinoma; ovarian carcinoma; small-cell carcinoma of the lung; and several of the cancers of children are examples. These cancers have often already spread at the time of diagnosis and cannot be treated by other means. Still other advanced cancers respond well to chemotherapy and can be controlled for a long time, so chemotherapy is commonly used for palliation.Two major problems limiting the usefulness of chemotherapy are toxicity and resistance. Techniques that avoid or control toxicity and reduce the risk of resistance have steadily improved. It is important to begin treatment as early as possible, to use the optimal dose of the drug, and to repeat cycles as quickly as possible, while giving the patient a chance to recover somewhat from toxicity.The use of multiple drugs is effective. Combination chemotherapy employs several drugs (often three to six at a time), each of which is effective as a single agent. The drugs used have different mechanisms of action, making cross-resistance less likely, and different types of toxicity, so that each may be given at optimal dose without causing fatal additive toxicity.Chemotherapy may be used with surgery or radiation as combined modality therapy. It is often used as an adjuvant, or helper, when surgery is the primary therapy. As such it is usually given after surgery. This type of therapy has greatly increased the cure rate of breast cancer. The major purpose of chemotherapy as an adjuvant is to kill off micrometastasis that may have been established before surgery. Recently, chemotherapy has been used before surgery as a neoadjuvant. This therapy has the same effect as adjuvant chemotherapy but may also shrink a tumor, making it more easily operable.Many cancers arising from tissues that are hormone-dependent, such as the breast, the prostate, the endometrium, and the thyroid, are responsive to hormone manipulation. This may consist of removing the source of the stimulating hormone or the administration of various hormones and antihormones.Several promising new approaches to the treatment of cancer are being taken. In one, biological agents known as biological response modifiers are used to modify the response of the body to cancer. Another approach involves biological agents that stimulate certain cells, which can then attack the malignant cells. The best example is the use of interleukin-2 to stimulate the patient’s lymphokine-activated killer lymphocytes (LAK cells). Research has been very active concerning tumor-specific antigens against which antibodies could be raised. These antitumor antibodies would be used to treat cancer either directly or by coupling to a chemotherapeutic agent. The antibody could identify the malignant cell and stick to it, thus delivering the drug directly to affected cells (tissue). Seeking information about their condition and participating in support groups have been shown to increase the survival time of people with breast cancer.Even if cured, a cancer patient may be left with serious handicaps. Every effort must be made to achieve the maximum possible quality of life through rehabilitative techniques, including reconstructive surgery. For the patient who is not cured, palliative therapy may achieve comfort and good function for months or years. Pain is a severe problem and can be relieved today much more than in the past.It is estimated that more than 5 million living Americans have had cancer. Three million of these have survived more than five years, and nearly all of the survivors can be regarded as cured.The death rate from cancer has fallen for all age groups below the age of 55, probably because they have developed more healthful habits, environmental controls that have been established reduce prolonged exposure to carcinogens and because of earlier diagnosis. This drop is expected to extend to older age groups as these younger people age.The most important preventive measure in controlling cancer is stopping tobacco use, which is the cause of 30 percent of all deaths from cancer. A large reduction might follow better dietary habits: optimal calorie intake to avoid obesity, reduction of calories from fat to 20 percent of the diet, reduced red-meat intake, and increased intake of dietary fiber (whole grain, fruits, and vegetables) and protective foods (foods that contain vitamins A and C, as well as cruciferous vegetables as cabbage, cauliflower, broccoli etc.). Moderate the eating of salt-cured, smoked, and nitrite-cured foods and in alcohol consumption. Avoiding exposure to sunlight and the routine use of sunscreens is also important in preventing cancer of the skin.The environment can be improved by the elimination of carcinogenic chemicals from the workplace, home, exposure to asbestos dust, and by the reduction of radon accumulation at home.Effective screening is available for cancer of the colon, cervix, breast, rectum, and prostate. According to resources, people without symptoms should have a cancer-related checkup every three years from age 20 to 40 and every year after 40. Women past 20 should do breast self-examinations every month and have a breast examination and pelvic examination yearly. A mammogram should be done between age 35 and 39, every one or two years from 40 to 49, and yearly thereafter, although some researchers suggest that mammograms may not benefit women under 50. Women who are sexually active or have reached the age of 18 are advised to have a yearly Pap test for three negative tests and less frequently thereafter. A digital rectal exam should be done every year after age 40 and a stool blood test every year after 50. A flexible proctoscopy should be done annually for two negative examinations and then every 3 to 5 years thereafter. Finally, young men are advised to do monthly self-examinations of the testes.Adoption of these measures could virtually eliminate lung cancer, reduce the incidence of breast and colon cancer, and thus cause a higher rate of cure of cancers of the colon, breast, rectum, cervix, and prostate. Such measures, together with full use of present technology for diagnosis and treatment, may permit the achievement of the goal, announced in 1985, of a 50-percent reduction in cancer deaths in the United States by the year 2000, by the American Medical Association. Bibliography:1995 American Medical Association JournalNCI Cancer Centers Program (http://www.nci.nih.gov/cancercenters/)PDQ Clinical Trials Search Form – Patients ( Johns Hopkins Oncology Center (http://ww2.med.jhu.edu/cancerctr/)National Cancer Institute (http://www.nci.nih.gov/)Colon Cancer Information Center (Medicine Online) (http://www.meds.com/colon/colon.html)Encyclopedia Britannica (copyright 1996)Compton s Concise reference (America Online – keyword: reference)

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