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They concluded that advances in systemic treatment in the United States did not substantially change the relative mortality effect of screening mammography. A working paper by Shih, Smith, Dong, Xu, and Shen used a microsimulation developed for women at average risk for breast cancer to evaluate the association between treatment advances and the cost-effectiveness of screening mammography. They found that for the most cost-effective screening strategy i. This study tentatively concluded that treatment advances reduced the cost-effectiveness of screening mammography.

Discussions on the interaction between cancer treatment and prevention are especially important for developing countries because the limited resources in these countries often force public health officials to choose among many competing priorities. In the extreme case, when a country has no capacity to treat cancer, it begs the question whether investment in primary prevention would be far more efficient than investing in secondary prevention.

Fourthly, while the economic literature on vaccines has traditionally been less relevant to cancer prevention, the role of vaccination as a primary prevention of cancer has become increasingly important. The International Agency for Research on Cancer classified infectious agents as carcinogenic to humans in CEA of HPV vaccines, especially for low- and middle-income countries, has been an active area of research in economic evaluation Ekwunife et al.

Estimates from the United States showed that HPV infection was associated not only with the vast majority of cervical cancer cases, but also with a large percentage of vulva, vaginal, penile, anal, and oropharyngeal cancers Saraiya et al. The viewpoint was that technologies today are capable of identifying the earliest genetic changes in cells that can promote cancer development, which then allows targeted chemoprevention and vaccination for the population with the specific genetic disposition.

The economics aspect of precision prevention is largely unexplored and will be an exciting area for future research on the economics of cancer prevention and control. The following book chapters cover the topic of economics of prevention. Although the materials presented in these two book chapters are not specific to cancer prevention, they provide an excellent introduction to the basic concepts and theories relevant to the economics of cancer prevention and control. Folland, S. The health economics of bads. Folland, A. Stano Eds. New York, NY: Routledge. Find this resource:.

Kenkel, D. Newhouse Eds. Amsterdam, The Netherlands: Elsevier. To gain knowledge of various sources of biases commonly encountered in the estimation of the effect of screening on cancer mortality, please read:. Duffy, S. Lawrence, G. Correcting for lead time and length bias in estimating the effect of screen detection on cancer survival.

American Journal of Epidemiology , 1 , 98— This book is an excellent reference for empirical studies aiming to estimate potential cost savings from prevention interventions:. Manning, W. The costs of poor health habits. Lange, F. The role of education in complex health decisions: Evidence from cancer screening. Journal of Health Economics , 30 1 , 43— Baker, L. The effect of area HMO market share on cancer screening. Health Services Research , 39 6 Pt. Belkar, R. Why worry about awareness in choice problems?

Econometric analysis of screening for cervical cancer. Health Economics , 15 1 , 33— Best, A. The evolution of cancer control research: An international perspective from Canada and the United States. Birnbaum, J. The effect of treatment advances on the mortality results of breast cancer screening trials: A microsimulation model. Annals of Internal Medicine , 4 , — Bitler, M. Effects of state cervical cancer insurance mandates on pap test rates.

Health Services Research , 52 1 , — Chapman, S. Fresh row over prostate screening. BMJ , , Chen, H. Cervical cancer screening in the United States, — Characteristics of women who are never screened. Chowdhury, P. Town, M. Surveillance for certain health behaviors, chronic diseases, and conditions, access to health care, and use of preventive health services among states and selected local areas: Behavioral risk factor surveillance system, United States, Clark, C.

Diffusion of digital breast tomosynthesis among women in primary care: Associations with insurance type. Cancer Medicine , 6 5 , — Colditz, G. Transdisciplinary training in cancer prevention: Reflections on two decades of training. Journal of Cancer Education , 26 3 , — Cutler, D. Are we finally winning the war on cancer? Journal of Economic Perspectives , 22 4 , 3— McMahon, P.

Benefits and harms of computed tomography lung cancer screening strategies: A comparative modeling study for the U. Preventive Services Task Force. Annals of Internal Medicine , 5 , — Global burden of cancers attributable to infections in A review and synthetic analysis. Lancet Oncology , 13 6 , — Ehrenreich, B.

The uproar over new breast cancer screening guidelines. Ehrlich, I. Market insurance, self-insurance, and self-protection. Journal of Political Economy , 80 , — Ekwunife, O. Challenges in cost-effectiveness analysis modelling of HPV vaccines in low- and middle-income countries: A systematic review and practice recommendations. PharmacoEconomics , 35 1 , 65— Giuliano, A. Society of Surgical Oncology: Position statement on prophylactic mastectomy.

Annals of Surgical Oncology , 14 9 , — Goodwin, J. Overuse of screening colonoscopy in the Medicare population. Archives of Internal Medicine , 15 , — Grossman, M. On the concept of health capital and the demand for health. Journal of Political Economy , 80 2 , — Consumer incentives for health services in chronic illness. Mushkin Ed. Gyrd-Hansen, D. Analysing public preferences for cancer screening programmes.

Health Economics , 10 7 , — Habbema, J. Journal of the National Cancer Institute Monographs , 36 , — Hamman, M. Colorectal cancer screening and state health insurance mandates. Health Economics , 25 2 , — Henderson, L. Performance of digital screening mammography among older women in the United States. Cancer , 9 , — Hey, J. Prevention and cure? Or: is an ounce of prevention worth a pound of cure? Journal of Health Economics , 2 2 , — Hiatt, R. Principles and applications of cancer prevention and control interventions. Fraumeni Eds.

Howard, D. Preventive Medicine , 55 5 , — Huo, J. Use of CT and chest radiography for lung cancer screening before and after publication of screening guidelines: Intended and unintended uptake. Husereau, D. Force, I. Value Health , 16 2 , — Jacobsen, G. Journal of Health Economics , 30 1 , 55— Jaffee, E. Yung, A. Lancet Oncology , 18 11 , e—e Jemal, A. JAMA , 19 , — The demand for preventive medical care. Applied Economics , 26 , — Knudsen, A. Kuntz, K. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: Modeling study for the US Preventive Services Task Force.

JAMA , 23 , — Mandelblatt, J. Cronin, K. Collaborative modeling of the benefits and harms associated with different U. Milligan, M.


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Assessing willingness to pay for cancer prevention. Moyer, V. Screening for lung cancer: U. Preventive Services Task Force recommendation statement. Sicks, J. Reduced lung-cancer mortality with low-dose computed tomographic screening. New England Journal of Medicine , 5 , — Nelson, H. Harms of breast cancer screening: Systematic review to update the U. Preventive Services Task Force recommendation. Oeffinger, K. American Cancer, S. Breast cancer screening for women at average risk: guideline update from the American Cancer Society.

JAMA , 15 , — Phillips, K. Spetz, J. Are gatekeeper requirements associated with cancer screening utilization? Health Services Research , 39 1 , — Pierre-Yves, G. Rational epidemics and thier public control. International Economic Review , 37 3 , — Qin, X. Mammography rates after the revision to the United States Preventive Services Task Force breast cancer screening recommendation. Rafia, R. Wyld, L. Modeling the cost-effectiveness of alternative upper age limits for breast cancer screening in England and Wales.

Value Health , 19 4 , — Raymakers, A. Cost-effectiveness analyses of lung cancer screening strategies using low-dose computed tomography: A systematic review. Applied Health Economics and Health Policy , 14 4 , — Ronckers, E. Systematic review of economic evaluations of smoking cessation: Standardizing the cost-effectiveness.

Medical Decision Making , 25 4 , — Rosenfield, P. The potential of transdisciplinary research for sustaining and extending linkages between the health and social sciences. Rueth, N. Preoperative risk assessment among women undergoing bilateral prophylactic mastectomy for cancer risk reduction. Annals of Surgical Oncology , 18 9 , — Sabik, L. The ACA and cancer screening and diagnosis. Cancer Journal , 23 3 , — The impact of near-universal insurance coverage on breast and cervical cancer screening: Evidence from Massachusetts.

Health Economics , 25 4 , — Sambamoorthi, U. Racial, ethnic, socioeconomic, and access disparities in the use of preventive services among women. Preventive Medicine , 37 5 , — Saraiya, M. Workgroup, H. Journal of the National Cancer Institute , 6 , djv Saslow, D. Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement. Schlichte, M. Current cervical carcinoma screening guidelines. Journal of Clinical Medicine , 4 5 , — Shih, Y. Schnipper, L. Delivering high-quality and affordable care throughout the cancer care continuum.

Journal of Clinical Oncology , 31 32 , — Health Affairs Millwood , 25 4 , — Use of relative risk ratios to present uncertainty in microsimulation models with multiple comparators: An application to breast cancer screening strategies. Value in Health , 20 5 , A Assessing the cost-effectiveness of updated breast cancer screening guidelines for average-risk women. Value in Health. Do advances in breast cancer treatment render screening mammography not cost-effective for average-risk women?

Simon, K. The impact of health insurance on preventive care and health behaviors: Evidence from the first two years of the ACA Medicaid expansions. Journal of Policy Analysis and Management , 36 2 , — Skally, M. Cost effectiveness of fecal DNA screening for colorectal cancer: A systematic review and quality appraisal of the literature. Applied Health Economics and Health Policy , 11 3 , — Spratt, J. The primary and secondary prevention of cancer.

Journal of Surgical Oncology , 18 3 , — Sullivan, R. Aapro, M. Delivering affordable cancer care in high-income countries. Lancet Oncology , 12 10 , — Sun, E. The contributions of improved therapy and early detection to cancer survival gains, — Sweet, A. Applied Health Economics and Health Policy , 9 1 , 51— Tan, A. Refining physician quality indicators for screening mammography in older women: Distinguishing appropriate use from overuse.

Journal of the American Geriatrics Society , 61 3 , — Van Houtven, G. Cancer premiums and latency effects: A risk tradeoff approach for valuing reductions in fatal cancer risks. Journal of Risk and Uncertainty , 36 , — Vineis, P. The science of precision prevention of cancer. Lancet Oncology , 18 8 , — Viscusi, W. The value of a statistical life: A critical review of market estimates throughout the world.

Journal of Risk and Uncertainty , 27 1 , 5— Assessing whether there is a cancer premium for the value of a statistical life. Health Economics , 23 4 , — Anttila, A. European guidelines for quality assurance in cervical cancer screening: Summary of the supplements on HPV screening and vaccination. Papillomavirus Research , 1 , 22— Welch, H. Breast-cancer tumor size, overdiagnosis, and mammography screening effectiveness.

New England Journal of Medicine , 15 , — Smoking has also been shown to be a contributory factor in cancers of upper respiratory tract, esophagus, larynx, bladder, pancreas, and probably liver, stomach, breast, and kidney as well. Thirty-five percent of all cancers are due to dietary causes. The human papillomavirus , which is sexually transmitted, has been shown to cause cancer of the cervix. Having too many sex partners and becoming sexually active early has been shown to increase one's chances of contracting this disease. In addition, it has also been shown that women who don't have children or have children late in life have an increased risk for both ovarian and breast cancer.

The most common cancer-causing pathogens and the cancers associated with them are shown in table form. Certain cancers like breast, colon, ovarian, and uterine cancer recur generation after generation in some families. Similarly, a higher likelihood of getting bladder cancer is associated with dye, rubber and gas workers; skin and lung cancer with smelters, gold miners and arsenic workers; leukemia with glue and varnish workers; liver cancer with PVC manufacturers; and lung, bone and bone marrow cancer with radiologists and uranium miners.

Several studies have shown that there is a well-established link between asbestos and cancer. However, the main danger from pollution occurs when dangerous chemicals from the industries escape into the surrounding environment. Cancer is a progressive disease, and goes through several stages. Each stage may produce a number of symptoms. This causes pain and some pressure which may be the earliest warning signs of cancer.

Many other diseases, besides cancer, could produce the same symptoms. However, it is important to have these symptoms checked, as soon as possible, especially if they linger. Many cancers such as breast cancer may not have any early symptoms. Therefore, it is important to undergo routine screening tests such as breast self-exams and mammograms. The doctor will observe, feel and palpate apply pressure by touch different parts of the body in order to identify any variations from the normal size, feel, and texture of the organ or tissue.

By focusing a light into the mouth, he will look for abnormalities in color, moisture, surface texture, or presence of any thickening or sore in the lips, tongue, gums, the hard palate on the roof of the mouth, and the throat.

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As part of the physical examination, the doctor will also palpate the lymph nodes in the neck, under the arms and in the groin. The testicles are palpated to identify any lumps, thickening or differences in the size, weight and firmness. The blood sample is obtained by a lab technician or a doctor by inserting a needle into a vein and is relatively painless. Blood tests can be either specific or non-specific. Often, in certain cancers, the cancer cells release particular proteins called tumor markers and blood tests can be used to detect the presence of these tumor markers.

However, with a few exceptions, tumor markers are not used for routine screening of cancers, because several non-cancerous conditions also produce positive results. Imaging tests such as computed tomography scans CT scans , magnetic resonance imaging MRI , ultrasound and fiberoptic scope examinations help the doctors determine the location of the tumor even if it is deep within the body.

Conventional x rays are often used for initial evaluation, because they are relatively cheap, painless and easily accessible. Besides confirming a cancer, the biopsy also provides information about the type of cancer, the stage it has reached, the aggressiveness of the cancer and the extent of its spread. Screening examinations conducted regularly by healthcare professionals can result in the detection of cancers of the breast, colon, rectum, cervix, prostate, testis, tongue, mouth, and skin at early stages, when treatment is more likely to be successful.

A recent revolution in molecular biology and cancer genetics has contributed a great deal to the development of several tests designed to assess one's risk of getting cancers. These new techniques include genetic testing, where molecular probes are used to identify mutations in certain genes that have been linked to particular cancers. At present, however, there are a lot of limitations to genetic testing and its utility appears ambiguous, emphasizing the need to develop better strategies for early detection.

Treatment and prevention of cancers continue to be the focus of a great deal of research. In , research into new cancer therapies included cancertargeting gene therapy , virus therapy, and a drug that stimulated apoptosis, or self-destruction of cancer cells, but not healthy cells. However, all of these new therapies take years of clinical testing and research. The aim of cancer treatment is to remove all or as much of the tumor as possible and to prevent the recurrence or spread of the primary tumor. While devising a treatment plan for cancer, the likelihood of curing the cancer has to be weighed against the side effects of the treatment.

If the cancer is very aggressive and a cure is not possible, then the treatment should be aimed at relieving the symptoms and controlling the cancer for as long as possible. The decision on which type of treatment is the most appropriate depends on the type and location of cancer, the extent to which it has already spread, the patient's age, sex, general health status and personal treatment preferences.

The major types of treatment are: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, and bone-marrow transplantation. In internal radiation also known as brachytherapy , a radioactive substance in the form of pellets or liquid is placed at the cancerous site by means of a pill, injection or insertion in a sealed container. Chemotherapeutic drugs can be taken either orally by mouth or intravenously, and may be given alone or in conjunction with surgery, radiation or both.

When chemotherapy is used before surgery or radiation, it is known as primary chemotherapy or "neoadjuvant chemotherapy. It can therefore be used effectively to reduce the size of the tumor for surgery or target it for radiation. However, the toxic effects of neoadjuvant chemotherapy are severe. In addition, it may make the body less tolerant to the side effects of other treatments that follow such as radiation therapy.

The technique identified nine dugs, one of which had never before been identified for use in cancer treatment. As a result the growth of the tumor slows down and survival may be extended for several months or years. Sometimes, the amount of drugs or radiation needed to destroy cancer cells also destroys bone marrow. Bone-marrow transplantation, while not a therapy in itself, is often used to "rescue" patients, by allowing those with cancer to undergo aggressive therapy.

The radiation oncologist specializes in using radiation to treat cancer, while the surgical oncologist performs the operations needed to diagnose or treat cancer. Gynecologist-oncologists and pediatric-oncologists, as their titles suggest, are physicians involved with treating women's and children's cancers respectively. Many other specialists also may be involved in the care of a cancer patient.

For example, radiologists specialize in the use of x rays, ultrasounds, CT scans, MRI imaging and other techniques that are used to diagnose cancer. Hematologists specialize in disorders of the blood and are consulted in case of blood cancers and bone marrow cancers. The samples that are removed for biopsy are sent to a laboratory, where a pathologist examines them to determine the type of cancer and extent of the disease. Only some of the specialists who are involved with cancer care have been mentioned above.

There are many other specialties, and virtually any type of medical or surgical specialist may become involved with care of the cancer patient should it become necessary. There are a multitude of alternative treatments available to help the person with cancer. They can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation therapy. Alternative treatment of cancer is a complicated arena and a trained health practitioner should be consulted.

Although the effectiveness of complementary therapies such as acupuncture in alleviating cancer pain has not been clinically proven, many cancer patients find it safe and beneficial. Bodywork therapies such as massage and reflexology ease muscle tension and may alleviate side effects such as nausea and vomiting. Homeopathy and herbal remedies used in Chinese traditional herbal medicine also have been shown to alleviate some of the side effects of radiation and chemotherapy and are being recommended by many doctors.

Certain foods including many vegetables, fruits, and grains are believed to offer protection against various cancers. However, isolation of the individual constituent of vegetables and fruits that are anti-cancer agents has proven difficult. In laboratory studies, vitamins such as A, C and E, as well as compounds such as isothiocyanates and dithiolthiones found in broccoli, cauliflower, and cabbage, and beta-carotene found in carrots have been shown to protect against cancer.

Studies have shown that eating a diet rich in fiber as found in fruits and vegetables reduces the risk of colon cancer. Exercise and a low fat diet help control weight and reduce the risk of endometrial, breast, and colon cancer. Certain drugs, which are currently being used for treatment, could also be suitable for prevention.

For example, the drug tamoxifen Nolvadex , which has been very effective against breast cancer, is currently being tested by the National Cancer Institute for its ability to prevent cancer. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression or prevent head and neck cancers. Certain studies have suggested that cancer incidence is lower in areas where soil and foods are rich in the mineral selenium.

More trials are needed to explain these intriguing connections. In the United States , men have a one in two lifetime risk of developing cancer, and for women the risk is one in three. Overall, African Americans are more likely to develop cancer than whites. Most cancers are curable if detected and treated at their early stages. A cancer patient's prognosis is affected by many factors, particularly the type of cancer the patient has, the stage of the cancer, the extent to which it has metastasized and the aggressiveness of the cancer.

In addition, the patient's age, general health status and the effectiveness of the treatment being pursued also are important factors. The number refers to the proportion of people with cancer who are expected to be alive, five years after initial diagnosis, compared with a similar population that is free of cancer. It is important to note that while statistics can give some information about the average survival experience of cancer patients in a given population, it cannot be used to indicate individual prognosis, because no two patients are exactly alike.

According to nutritionists and epidemiologists from leading universities in the United States , a person can reduce the chances of getting cancer by following some simple guidelines:. Benign — Mild, nonmalignant. Recovery is favorable with treatment. Biopsy — The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Bone marrow — Spongy material that fills the inner cavities of the bones. The progenitors of all the blood cells are produced in this bone marrow. Carcinogen — Any substance capable of causing cancer by mutating the cell's DNA. Chemotherapy — Treatment with certain anticancer drugs. Epithelium — The layer of cells covering the body's surface and lining the internal organs and various glands. Hormone therapy — Treatment of cancer by inhibiting the production of hormones such as testosterone and estrogen.

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Immunotherapy — Treatment of cancer by stimulating the body's immune defense system. Malignant — A general term for cells and the tumors they form that can invade and destroy other tissues and organs. Metastasis — The spread of cancer from one part of the body to another. Radiation therapy — Treatment using high-energy radiation from x-ray machines, cobalt, radium, or other sources. Sore — An open wound, bruise or lesion on the skin. Tumor — An abnormal growth resulting from a cell that lost its normal growth control restraints and started multiplying uncontrollably.

X rays — High-energy radiation used in high doses, either to diagnose or treat disease. In addition, following the advice of physicians in refraining from certain activities or drugs that are proven as risk factors for certain cancers can help lower one's risk. For instance, while physicians have long known a small increased risk for breast cancer was linked to use of HRT, a landmark study released in proved the risk was greater than thought.

The Women's Health Initiative found that even relatively short-term use of estrogen plus progestin is associated with increased risk of breast cancer, diagnosis at a more advanced stage of the disease, and a higher number of abnormal mammograms. Simone, Joseph V. Cecil, et al. Philadelphia: W. Saunders Company, American Cancer Society. Atlanta, GA Cancer Research Institute National Headquarters. Cancer is a group of diseases characterized by uncontrolled growth of tissue cells in the body and the invasion by these cells into nearby tissue and migration to distant sites.

Cancer results from alterations mutations in genes that make up DNA, the master molecule of the cell. Genes make proteins, which are the ultimate workhorses of the cells, responsible for the many processes that permit humans to breathe, think, and move, among other functions. Some of these proteins control the orderly growth, division, and reproduction of normal tissue cells. Gene mutations can produce faulty proteins, which in turn produce abnormal cells that no longer divide and reproduce in an orderly manner. These abnormal cells divide uncontrollably and eventually form a new growth known as a tumor or neoplasm.

A healthy immune system can usually recognize neoplastic cells and destroy them before they divide. However, mutant cells may escape immune detection and become tumors or cancers. Many cancers have been shown to result from exposure to environmental toxins carcinogens and related alterations in DNA. Faulty DNA can also be inherited, predisposing an individual to develop cancer, although fewer than 10 percent of cancers are purely hereditary.

Hereditary links have been shown in cancers of the breast, colon, ovaries, and uterus. Inherited physiological traits can also contribute to cancer, such as inheriting fair skin increasing the risk of skin cancer , but only if accompanied by prolonged exposure to intensive sunlight. Tumors can be benign or malignant. A benign tumor is not cancer. It is slow growing, does not invade surrounding tissue, and once removed, does not usually recur. A malignant tumor is cancerous.

It invades surrounding tissue and spreads to nearby or distant organs metastasis. If the cancer cells have spread to surrounding tissue, even after the malignant tumor is removed, it will typically recur. The most common cancers affecting adults are cancer of the skin, lung, colon, breast, and prostate. Cancer of the kidneys, ovaries, uterus, pancreas, bladder, rectum, and the leukemias and lymphomas are among the 12 major cancers affecting Americans of all ages. Although children and adolescents do develop solid tumors, the most common high-risk cancers among children are:.

Childhood cancer is rare, occurring in about 14 in , children in the United States each year. However, in the entire U. Genetic predisposition, environmental causes, and individual developmental problems are responsible for most childhood cancer. The presence of other disorders, such as Down syndrome , has also been shown to be associated with cancer in children. The major risk factors that apply to adult cancer are tobacco, alcohol, sexual and reproductive behavior, and occupation, none of which increases risk in children.

Other well-known risk factors, such as family history, infectious agents, diet, environmental toxins, and pollution, can apply equally to children. Approximately 80 to 90 percent of lung cancer cases occur in smokers. Smoking is also the leading cause of bladder cancer and has been shown to contribute to cancers of the upper respiratory tract, esophagus, larynx, kidney, pancreas, stomach, and possibly breast as well.

Second-hand smoke passive smoking has been shown to increase cancer risk in children and adults who live with smokers. Cancer deaths worldwide can be traced to viruses, bacteria, or parasites. Epstein-Barr virus EBV , for example, is associated with lymphoma, the hepatitis viruses are associated with liver cancer, HIV is associated with Kaposi's sarcoma, and the bacteria Helicobacter pylori is associated with stomach cancer.

Certain cancers such as breast, colon, ovarian, and uterine cancer recur generation after generation in some families. Eye cancer retinoblastoma , a type of colon cancer, and early-onset breast cancer have been shown to be linked to the inheritance of specific genes. Radiation is believed to cause 1 to 2 percent of all cancer deaths. Ultraviolet radiation from the sun accounts for a majority of melanoma deaths. Other sources of radiation are x-rays, radon gas, and ionizing radiation from nuclear material. Studies have established links between environmental toxins, such as asbestos, and cancer.

However, the main danger from pollutants occurs when toxic industrial chemicals are released into the surrounding environment. As of an estimated 1 percent of cancer deaths are believed to be due to air, land, and water pollution. Cancer is a progressive disease that goes through several stages, each producing a number of symptoms.

Early symptoms can be produced by the growth of a solid tumor in an organ or gland. A growing tumor may press on nearby nerves, organs, and blood vessels, causing pain and pressure that may be the first warning signs of cancer. Other symptoms can include sores that do not heal, growths on the skin or below the skin, unusual bleeding, difficulty digesting food or swallowing, and changes in bowel or bladder function. Fever can be present as well as fatigue and weakness.

Despite the fact that there are hundreds of different types of cancer, each producing different symptoms, the American Cancer Society has established the following seven symptoms as possible warning signals of cancer:. Parents should report any such symptoms to the pediatrician along with unexplained fever or frequent infections. Vision problems, weight loss, lack of appetite, depression, swollen glands, paleness, or general weakness are other reasons for parents to consult the pediatrician. Generally, the earlier cancer is diagnosed and treated, the better the chance of a cure, although not all cancers have early symptoms.

Diagnosis begins with a complete medical history, including family history of cancer, and a thorough physical examination. The doctor observes and palpates applies pressure by touch different parts of the body in order to identify any variations from normal size, feel, and texture of an organ or tissue. The doctor looks inside the mouth for abnormalities in color, moisture, surface texture, or the presence of any thickening or sores in the lips, tongue, gums, the roof of the mouth, or the throat.

The doctor observes the front of the neck for swelling and may gently manipulate the neck and palpate the front and side surfaces of the thyroid gland at the base of the neck, looking for nodules or tenderness. The doctor also palpates the lymph nodes in the neck, under the arms, and in the groin, looking for enlargement.

The skin is examined for sores that are slow to heal, especially those that bleed, ooze, or crust; irritated patches that may itch or hurt; and any change in the size of a wart or a mole.

Breast cancer

In adolescent females, a pelvic exam may be conducted to detect cancers of the ovaries, uterus, cervix, and vagina. The doctor first looks for abnormal discharges or the presence of sores. Then the internal pelvic organs such as the uterus and ovaries are palpated touched while applying gentle pressure to detect abnormal masses.

Breast examination evaluates unevenness, discoloration, or scaling; both breasts are palpated to feel for masses or lumps. In adolescent males, inspection of the rectum and prostate may be included in the physical examination. The doctor inserts a gloved finger into the rectum and rotates it slowly to feel for growths, tumors, or other abnormalities. The testes are examined visually, looking for unevenness, swelling, or other abnormalities. The testicles are palpated to identify lumps, thickening or differences in size, weight, or firmness. If an abnormality is detected on physical examination, or symptoms suggestive of cancer are noted, diagnostic tests will be performed.

Laboratory studies of sputum, blood, urine, and stool can detect abnormalities that may confirm cancer. Sputum cytology involves the microscopic examination of phlegm that is coughed up from the lungs. Tumor markers , specific proteins released by certain types of cancer cells, can be detected by performing a test on venous blood. If leukemia or lymphoma is suspected, a complete blood count CBC with peripheral smear differential is done to evaluate the number, appearance, and maturity of red blood cells RBCs and white blood cells WBCs and to measure hemoglobin, hematocrit, and platelet count.

A bone marrow biopsy may be done to determine what type of cells is present in the bone marrow. Blood chemistries will be done to help determine if liver or kidney problems are present. Blood chemistries are also useful in monitoring the effectiveness of treatment for all types of cancer and in following the course of the disease and detecting recurrences. Diagnostic imaging techniques such as computed tomography CT scans , magnetic resonance imaging MRI , ultrasound, and fiberoptic scope examinations such as colonoscopy or sigmoidoscopy can help determine the location, size, and characteristics of a tumor even if it is deep within the body.

In order to increase the information obtained from a conventional x ray, air or contrast media such as barium or iodine may be used to enhance the images. The most definitive diagnostic test for cancer is a biopsy, which is the surgical removal of a piece of suspect tissue for staining and microscope examination cytochemistry.

By examining certain cell characteristics, abnormalities can be identified and the presence of specific types of cells can be diagnostic for certain cancers. The biopsy provides information about the type of cancer, its stage, the aggressiveness of the cancer in invading nearby tissue or organs, and the extent of metastases at diagnosis. The pathologist who evaluates cancer cells in biopsied tissue designates the cancer as being stage I, II, III, or IV, in terms of the degree of metastasis.

Newer molecular and cellular diagnostic testing, such as polymerase chain reaction PCR , allows the molecular genetic analysis of tumors. Cytogenetic analysis of tumor chromosomes, for example, can identify structural abnormalities that may explain the unique origins of cancer in an individual child. Spectral karyotyping SKY , an advanced method of screening chromosomes for numeric and structural abnormalities, is used to evaluate pediatric tumors.

Gene sequences can also be evaluated in a method comparative genomic hybridization that compares samples from a tumor and normal tissue after both have been exposed to the same radioactive material. This method can determine gains and losses in DNA in the region of the tumor, detecting alterations that have caused the cancer.

The developing science of proteomics studies specific proteins in cells and may someday be able to provide detailed assessment of cancer cells. The aim of cancer treatment is to remove or destroy all or as much of the primary tumor as possible and to prevent its recurrence or metastases. If the cancer is highly aggressive and cure is not likely, treatment will be aimed at relieving symptoms and controlling the cancer for as long as possible.

Cancer treatment is always tailored to the individual. The treatment choice depends on the type and location of cancer, the extent to which it has already spread, and the age, sex, and general health status of the individual. The major types of treatment are: surgery, radiation, chemotherapy , immunotherapy, hormone therapy, and bone-marrow transplantation. Advances in molecular biology and cancer genetics have contributed greatly to the development of therapies that provide cell-targeted treatment. Genetic testing uses molecular probes to identify gene mutations that have been linked to specific cancers.

In the early s ongoing research is focused on new treatment and prevention methods, including molecular-targeted therapies, virus therapy, immunotherapy, and drug therapy that stimulates the self-destruction of cancer cells apoptosis. Targeted molecular therapy, although as of still the subject of concentrated research, was being used effectively in pediatric study subjects where it has been shown to reduce the toxicity seen with conventional chemotherapy.

Unlike chemotherapy, which treats all cells uniformly, targeted molecular therapy can focus on selected cells without affecting normal cells and tissues. This refinement frees children from some of the long-term toxic effects and complications that can negatively affect quality of life and survival even if the cancer is cured.

Surgical removal of a solid tumor is most effective with small tumors confined to one area of the body. Surgery removes the tumor tumor resection and usually part of the surrounding tissue to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system , adjoining lymph nodes are sometimes removed as well.

Surgery may also be preventive or prophylactic, removing an abnormal looking area of tissue that is likely to become malignant over time. During surgery biopsies may also be performed on tissue that may be affected by metastases. Surgery is not a typical treatment for leukemia or lymphoma, which arise in the circulatory system and lymphatic systems that extend throughout the body.

Children with osteosarcoma bone cancer and other solid tumors are candidates for surgery, however. Surgery may be performed in conjunction with radiation cytoreductive surgery or chemotherapy. The surgeon removes as much of the cancer as possible and the remaining area is treated with radiotherapy or chemotherapy or both. In advanced metastatic cancer when cure is unlikely, palliative surgery aims at reducing symptoms.

Debulking surgery, for example, removes part of a tumor that is pressing on other organs and causing pain. In tumors that are dependent on hormones, one option is to remove organs that secrete the hormones. Radiation kills tumor cells and is used alone when a tumor is in a poor location for surgery.

External radiation is aimed at the tumor from outside the body. In internal radiation brachytherapy , radioactive liquid or pellets are delivered to the cancerous site via a pill, injection, or insertion in a sealed container. Chemotherapy is the administration of drugs that kill cancer cells cytotoxic drugs. It destroys hard-to-detect cancer cells that have spread metastasized through the circulation or lymph system.

Chemotherapeutic drugs are given orally or intravenously, either alone or in conjunction with surgery, radiation, or both. When chemotherapy is used before surgery or radiation, it is known as primary chemotherapy or neoadjuvant chemotherapy. Because the cancer cells have not yet been exposed to anti-cancer drugs, they are especially vulnerable, allowing neoadjuvant therapy to effectively reduce tumor size. However, the toxic effects of neoadjuvant chemotherapy may be severe, because normal cells are also destroyed.

Chemotherapy may also make the body less tolerant of the side effects of other treatments such as radiation therapy. Adjuvant therapy is the more common type of chemotherapy, used to enhance the effectiveness of other treatments. Immunotherapy uses the body's own immune system, specifically a type of disease-fighting white cell called T-cells, to destroy cancer cells. Tumor-specific proteins that are part of unique genetic mutations in pediatric cancer, for example, are believed to be ideal targets for anti-tumor immune processes.

Various immunological agents are as of still in clinical trials and are not as of that year widely available, though initial results are promising. Monoclonal antibodies are used to. Other substances are also being used experimentally. They include substances such as interferons, interleukins, growth factors, monoclonal antibodies, and vaccines. Unlike traditional vaccines, cancer vaccines do not prevent cancer but are designed to treat existing disease.

They work by boosting the immune system and training immunized cells to destroy cancer cells. Hormone therapy is standard treatment for cancers that are hormone-dependent and grow faster in the presence of specific hormones, such as cancer of the prostate, breast, and uterus. Hormone therapy blocks the production or action of these hormones, slowing growth of the tumor and extending survival for months or years.

Bone marrow is the tissue within bone cavities that produces blood cells. Sometimes drugs or radiation needed to destroy cancer cells also destroys bone marrow and only replacement with healthy cells counteracts this adverse effect. A bone marrow transplant involves removing marrow from a donor and transplanting blood-forming cells to a recipient. While not a therapy in itself, bone marrow transplantation may allow a cancer patient to undergo aggressive therapy.

Many specialists work together to treat cancer patients. The oncologist is a physician who specializes in cancer care and usually coordinates the treatment plan, directing chemotherapy, hormone therapy, and any treatment that does not involve radiation or surgery. The radiation oncologist uses radiation to treat cancer, while the surgical oncologist performs surgery to diagnose or treat cancer.

Gynecologist-oncologists and pediatric-oncologists, as their titles suggest, are physicians who treat women's and children's cancers. Hematologists specialize in disorders of the blood and bone marrow and are consulted in the evaluation of leukemia, lymphoma, and bone cancer. A range of alternative treatments are available to help treat cancer that can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation.

Alternative treatment of cancer is a complicated arena and a trained complementary health practitioner should be consulted. Although the effectiveness of complementary therapies such as acupuncture in alleviating cancer pain have not as of been clinically proven, many cancer patients find it safe and beneficial. Most cancers show good cure rates if detected and treated at early stages. The prognosis involves the type of cancer, its degree of invasiveness, and the extent of metastases at diagnosis.

In addition, age, general health status, and response to treatment are important factors. Cancer deaths in children have shown consistent declines, decreasing between and from 50 in 1 million diagnosed to 25 in 1 million. However, cancer is the leading cause of death among children and adolescents, responsible for 2, deaths each year in the United States.

Prevention of cancer means being aware of causes and risks, which involve a combination of genetic and environmental factors. Except for family history, specific genetic causes or an inherited predisposition are generally unknown in individuals until revealed in the diagnostic process. Known environmental causes can be avoided, however. A list of guidelines offered by nutritionists and epidemiologists from leading U.

Certain drugs being used as of for treatment could also be suitable for prevention, at least prevention of recurrences. For example, the drug tamoxifen has been very effective against breast cancer and is in being used to prevent recurrence in breast cancer survivors. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression of or to prevent head and neck cancers.

Certain studies suggest that cancer incidence is lower in areas where soil and foods are rich in the mineral selenium. Certain foods, including many vegetables, fruits, and grains, are believed to offer protection against various cancers. In laboratory studies, vitamins such as A, C, and E, as well as beta-carotene found in carrots and isothiocyanate and dithiolthione compounds found in cruciferous vegetables, such as broccoli, cauliflower, and cabbage, have been shown to provide protection against certain types of cancer.

Studies have shown that eating a diet rich in fiber as found in fruits, vegetables, and whole grains can reduce the risk of colon cancer. Benign — In medical usage, benign is the opposite of malignant. It describes an abnormal growth that is stable, treatable, and generally not life-threatening. Biopsy — The surgical removal and microscopic examination of living tissue for diagnostic purposes or to follow the course of a disease. Most commonly the term refers to the collection and analysis of tissue from a suspected tumor to establish malignancy.

Bone marrow — The spongy tissue inside the large bones in the body that is responsible for making the red blood cells, most white blood cells, and platelets. Carcinogenic — A substance that can cause cancer to develop. Chemotherapy — Any treatment of an illness with chemical agents. The term is usually used to describe the treatment of cancer with drugs that inhibit cancer growth or destroy cancer cells. Epithelium — The layer of cells that covers body surfaces, lines body cavities, and forms glands. Hormone therapy — Treating cancers by changing the hormone balance of the body, instead of by using cell-killing drugs.

Immunotherapy — A mode of cancer treatment in which the immune system is stimulated to fight the cancer. Malignant — Cells that have been altered such that they have lost normal control mechanisms and are capable of local invasion and spread to other areas of the body.

Often used to describe a cancer. Metastasis — A secondary tumor resulting from the spread of cancerous cells from the primary tumor to other parts of the body. Radiation therapy — A cancer treatment that uses high-energy rays or particles to kill or weaken cancer cells. Radiation may be delivered externally or internally via surgically implanted pellets. Also called radiotherapy. Sore — A wound, lesion, or ulcer on the skin. Tumor — A growth of tissue resulting from the uncontrolled proliferation of cells.

Encyclopedia of Cancer

A diagnosis of childhood cancer raises many uncertainties and concerns for parents, including how to acquire the most effective therapy. Advances in molecular and cellular technologies have improved both the diagnosis and treatment of pediatric cancer and also carry with them the possibility of someday curing and preventing cancer in children.

While cancer was at one time nearly always fatal in children, as of more than 75 percent of children diagnosed with cancer enjoyed disease-free survival. Targeted molecular therapy and immunotherapies are the ongoing focus of concentrated research, and studies using these cell-selective technologies in treating children have shown encouraging results, both in earlier responses and reduced toxicity and complications longer term.

Parents can be assured of access to the current knowledge base in molecular biology and advanced treatment technologies that promise better outcomes. Janes-Hodder, Honna, et al. Woznick, Leigh A. National Children's Cancer Society. Louis, MO To many people, the word cancer is synonymous with death; however, that is not the reality. In industrialized countries cancer mortality rates have slowly and progressively declined between and In overall cure rates reached approximately 50 percent.

Nevertheless, cancer remains the second leading cause of death in industrialized countries and a rapidly increasing cause of death in developing countries. The scope of the problem in the United States is large. Some 1. Of these, 59 percent were expected to live for at least five years in some, the cancer may be continuously present for more than five years with or without evidence of cancer.

People of all ages, from birth to advanced age, can manifest cancer, making it the second-leading cause of death in the United States. In children cancer is unusual, but it has consistently been the leading cause of death from disease. As mortality rates from cardiovascular disease decline, the proportion of cancer deaths increases.

It is anticipated that the mortality rate from cancer will surpass that from heart disease by the year Developing countries represented 80 percent of the world's approximately 6 billion people in the year In these countries, cancer has grown from a minor public health issue in the early s to a rapidly expanding problem by the beginning of the twenty-first century. The emergence of a middle class, with attendant changes in lifestyle, increased longevity and exposure to potential carcinogens, and expectations of improved medical delivery systems have fueled the growing impact of cancer in the third world.

The financial resources and socio-medical infrastructure needed to diagnose and treat, much less screen and prevent these cancers, are lacking in the developing world. A controversial issue in the United States is whether there has been progress in the "War on Cancer" declared by Congress in Since then a large flow of tax dollars has been directed to basic and clinical research with the goal of eliminating cancer.

Mortality rates from all forms of cancer have declined slightly from through , but with large variations among different types of cancer. Optimistic explanations include significant improvements in treatment and prevention. More pessimistic analyses suggest that some of the more common cancers can be diagnosed earlier so that benchmark five-year mortality rates have diminished, but that the actual course of the disease is unaffected because treatments are not really more effective.

Cancer is a disease whereby the genes regulating individual cell behavior and interactions with other cells malfunction. It is therefore a "genetic" disease, although not necessarily "inherited. Rather, the majority of cancers seem to result from complicated interactions between the environment and "normal" cells. The routine operations of cell growth, division, cell-to-cell communication, and programmed cell death apoptosis are complex and must be tightly controlled to preserve the integrity of the organism. Chromosomes, which contain DNA molecules organized into genes, control these regulatory processes.

Similar mechanisms are present in all animals and plants, are highly conserved through evolution, and so must provide significant survival benefit. The phenomenon of cancer is infrequent in wild animals and has only come to prominence in human beings since These statistics suggest that interactions of environmental agents with the genes result in fixed alterations that eventually manifest themselves as cancer.

Public health measures have increased longevity so that the progressive, possibly inherent deterioration of regulatory functions accompanying aging allows less effective repair of chronic genetic damage. Although no single cause has been or is likely to explain all of cancer, research has demonstrated that environmental factors predominate in the development of most cancer. Proven causes of DNA damage leading to malignant change include viruses, radiation, and chemicals. Viruses such as Epstein-Barr, HIV , and papilloma can contribute to cancer development carcinogenesis.

Both therapeutic and normal environmental exposure to radiation increase the risk of cancer. Multiple chemicals have been linked to cancer, of which the best examples are the constituents of tobacco. How these and other unknown environmental factors, particularly dietary and airborne, interact with human genes to cause irreversible, malignant transformation is the subject of intensive research. Malignant cells can multiply and divide in the tissue of origin and can travel through the circulatory system and create secondary deposits metastases in vital organs.

These capabilities underlie the phenomena of invasive lumps tumors and the potential for the dissemination of cancer. Most cancer cells, whether at the primary or secondary site, divide at about the same rate as their cells of origin. Malignant cells, however, do not typically undergo normal programmed cell death apoptosis and consequently accumulate. Most often, the cause of death in cancer is a poorly understood wasting process cachexia.

Prevention of cancer, or the reduction of risk for a person who has never experienced the disease, is a desirable goal. For those cancers resulting from known environmental exposures, such an approach has been most successful. Avoidance of tobacco products is no doubt the best proven means of preventing cancer. In industrialized countries, regulatory agencies monitor chemical and radiation exposure.

Dietary habits are felt to influence the risk of developing certain cancers, but there is very little evidence that dietary manipulations lead to significant risk reduction. Screening is the attempt to diagnose an established cancer as early as possible, usually before the onset of symptoms, in order to optimize the outcome. A screening technique is designed to simply, safely, and cheaply identify those patients who may have a certain type of cancer. If screening-test result is positive, further testing is always necessary to rule the diagnosis in or out. There is considerable controversy in this field.

It cannot be assumed that early detection is always in the patient's best interest, and the overall financial costs in screening a population must be weighed against the actual benefits. Screening may be counterproductive under the following conditions:.


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In spite of these limitations, there have been successes. Good evidence exists that not only early detection but also improved survival can be achieved in breast, cervical, and colorectal cancers. With minimal danger and cost, appropriate populations screened for these diseases benefit from reduced mortality.

Prostate cancer, however, is more problematic. Measurement of prostate-specific antigen PSA , a substance made by both normal prostate as well as malignant prostate cells, can identify a patient with prostate cancer before any other manifestations. But because of the relatively elderly population often with unrelated potentially serious conditions at risk, it has been difficult to prove that treatment confers a quantitative or qualitative benefit.

Continued efforts will be made to create screening techniques that truly allow more effective treatment for cancers detected earlier. Once a malignancy is suspected, tests usually imaging techniques, such as X rays, ultrasounds, nuclear medicine scans, CAT scans, and MRIs are performed for confirmation.

Encyclopedia of Cancer Prevention and Management Volume VII Researches in Cancer Therapy

Ultimately a biopsy, or removal of a piece of tissue for microscopic examination, is necessary for determination of the presence and type of cancer. Staging tests reveal whether the disease has spread beyond its site of origin. Because of the inability of current techniques to detect microscopic deposits of cancer, a cancer may frequently appear to be localized but nevertheless exist elsewhere in the body below the threshold of clinical detection. The diagnostic and staging process should permit the optimal clarification of the goals of treatment.

Curative treatment intends permanent elimination of cancer, whereas palliative treatment intends to relieve symptoms and possibly prolong life. In every cancer situation there are known probabilities of cure. For example, a specific patient with "localized" breast cancer may have a 50 — 60 percent chance of cure based on predictive factors present at the time of diagnosis.


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  6. Follow-up "negative" tests, however, do not yield the certainty that there is no cancer, whereas the documented presence of recurrent cancer has clear significance. Cancer, indeed, is the most curable of all chronic diseases, but only the uneventful passage of time allows a patient to become more confident of his or her status. Surgery is the oldest and overall most effective cancer treatment, particularly when tumors appear to be localized and cure is the goal. It is a preferred modality for breast, prostate, skin, lung, colon, testicular, uterine, brain, stomach, pancreas, and thyroid tumors.

    The aims of cancer surgery include elimination of as much cancer as possible, preservation of organ function, and minimal risk and suffering for the patient. Occasionally surgery is intentionally palliative, particularly when other treatment modalities are added in an effort to improve symptoms. Radiation therapy has been a mainstay of cancer treatment since the s, when doctors first began to understand its potential benefits and short and long-term risks. Therapeutic ionizing radiation is generated by a linear accelerator and delivered externally to a well-defined area.

    It thus shares with surgery an advantage for localized tumors. The inherent differences in radiation sensitivity between malignant tissues and the surrounding normal tissues permits the exploitation of radiation for therapeutic benefit. When the cancerous tissue is less sensitive to radiation than the normal tissues, radiation can cause more harm than good. Radiation has been a useful primary treatment modality in tumors of the head and neck, lung, cervix, brain, pancreas, and prostate. For tumors that have metastasized to tissues such as bone and brain, radiation has been very useful for palliative purposes.

    The ideal treatment would be a substance that travels throughout the body, neutralizes every cancer cell, but causes no harm to any normal cell. Research has not yet yielded such a completely specific and non-toxic substance. The s saw the advent of anticancer drugs that came to be known as "chemotherapy. In general these drugs cause irreversible cell damage and death. They tend to be more destructive to rapidly dividing cells and so take their heaviest toll on relatively few malignancies as well as predictability on normal tissues mucous membranes, hair follicles, and bone marrow.

    For some very sensitive disseminated cancers such as testicular, lymphomas, and leukemias, chemotherapy can be curative. For many others, such as advanced breast, ovarian, lung, colon cancers, chemotherapy may offer palliative benefits. Since the s chemotherapy has played an important role in the multimodality treatment of localized breast, colon, lung, and bladder tumors. Except for curable and highly chemosensitive malignancies, chemotherapy kills at most Even using high-dose chemotherapy, it appears that by the year chemotherapy may have reached a plateau of effectiveness.

    Insights into the basic genetic, molecular, and regulatory abnormalities of malignant cells have opened up entirely new systemic approaches. Antiangiogenesis agents interfere with the malignant cell's need for accessing new blood vessels. Chemicals designed to inhibit the inappropriate production of growth factors by malignant cells have been synthesized and show promise.

    Monoclonal antibodies aimed at proteins concentrated on the malignant cell's surface have achieved tumor shrinkage. By the year the thrust in basic cancer research had focused on manipulation of the fundamental processes that allow malignancies to grow and spread. The Internet has allowed patients, families, and medical providers rapid access to information previously obtainable only through libraries or physicians.

    Such information, however, may be unfiltered, unsubstantiated, and misleading. Even when the information is correct, consumers may be unable to process it properly because of fears concerning their condition. All observers agree, however, that this form of communication will rapidly affect cancer research and treatment.

    The multitude of available products and techniques is enormous: herbal extracts, vitamins, magnetic therapies, acupuncture, synthetic chemicals, modified diets, and enemas. The vast majority of these have never been evaluated in a rigorously controlled scientific way that would allow more definitive and precise evaluation of their benefits and risks. Nevertheless, evidence has shown that as many as 50 percent of all cancer patients, irrespective of treatability by conventional methods, try at least one form of complementary medicine.

    Some proponents feel that these treatments should serve as adjuncts to conventional ones, while others feel that all conventional treatments are toxic and should be replaced by alternative ones. To investigate the potential of these approaches, the National Institutes of Health established the Institute of Alternative Medicine in Because approximately 50 percent of cancer patients will die from their cancer, management of their dying takes on great importance.

    In the s and s multiple studies demonstrated that such basic concerns as pain and symptom control, respect for the right of the individual to forego life-prolonging measures, and spiritual distress have been mismanaged or ignored by many health care providers. In spite of the emergence of the modern hospice movement and improvements in techniques of symptom alleviation, most cancer patients die in hospitals or in nursing homes while receiving inadequate palliative care.

    The American Society of Clinical Oncology ASCO in mandated that part of fellowship training for oncologists include the basics of palliative care in order to rectify these problems. Ambinder, Edward P. Burns, Edith A. Chu, Edward, and Vincent T. DeVita Jr. Rosenberg eds. Groopman, Jerome.

    Hong, Waun Ki, Margaret R. Spitz, and Scott M. Ishibe, Naoko, and Andrew Freedman.