Rehabilitation Systems

Cancer is a class of diseases in which a group of cells display uncontrolled growth, invasion, and sometimes metastasis. These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, and do not invade or metastasize. Most cancers form a tumor, but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Cancer affects people at all ages with the risk for most types increasing with age. Cancer caused about 13% of all human deaths in 2007 (7.6 million). Cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may randomly occur through errors in DNA replication, or are inherited, and thus present in all cells from birth. The heritability of cancers is usually affected by complex interactions between carcinogens and the host's genome. Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are then inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system. Definitive diagnosis requires the histologic examination of a biopsy specimen, although the initial indication of malignancy can be symptomatic or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.
Pathophysiology Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat. Cancer is fundamentally a disease of regulation of tissue growth. In order for a normal cell to transform into a cancer cell, genes which regulate cell growth and differentiation must be
altered.

Genetic changes can occur at many levels, from gain or loss of entire chromosomes to a mutation affecting a single DNA nucleotide. There are two broad categories of genes which are affected by these changes. Oncogenes may be normal genes which are expressed at inappropriately high levels, or altered genes which have novel properties. In either case, expression of these genes promotes the malignant phenotype of cancer cells. Tumor suppressor genes are genes which inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes. Typically, changes in many genes are required to transform a normal cell into a cancer cell. There is a diverse classification scheme for the various genomic changes which may contribute to the generation of cancer cells. Most of these changes are mutation, or changes in the nucleotide sequence of genomic DNA. Aneuploidy, the presence of an abnormal number of chromosomes, is one genomic change which is not a mutation, and may involve either gain or loss of one or more chromosomes through errors in mitosis. Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase. Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, and such an event may also result in the expression of viral oncogenes in the affected cell and its descendants.

Common Cancers Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and women, is responsible for 1.3 million deaths worldwide annually. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss. The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma. This distinction is important, because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with surgery, while small cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation. The most common cause of lung cancer is long-term exposure to tobacco smoke.

The occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases, is often attributed to a combination of genetic factors, radon gas, asbestos, and air pollution, including second hand smoke. Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed via bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. Depending on the stage and treatment, the five-year survival rate is 14%.
Breast cancer refers to cancers that originate from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. There are different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup. Survival varies greatly depending on those factors; with best treatment, 10-year disease-free survival varies from 98% to 10%. Treatment includes surgery, drugs, (hormonal therapy and chemotherapy), and radiation. Worldwide, breast cancer comprises 10.4% of all cancer incidences, making it the second most common type of non-skin cancer (after lung cancer) and the fifth most common cause of cancer death. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). Breast cancer is about 100 times more common in women than in men, but survival rates are equal in both sexes. Some breast cancers require the hormones estrogen and progesterone to grow, and have receptors for those hormones. After surgery those cancers are treated with drugs that interfere with those hormones, usually tamoxifen, and with drugs that shut off the production of estrogen in the ovaries or elsewhere; this may damage the ovaries and end fertility. Low-risk, hormone-sensitive breast cancers may be treated with hormone therapy and radiation alone. Breast cancers without hormone receptors, or which have spread to the lymph nodes in the armpits, or which express certain genetic characteristics, are higher-risk, and are treated more aggressively. One standard regimen, popular in the U.S., is cyclophosphamide plus doxorubicin (Adriamycin), known as CA; these drugs damage DNA in the cancer, but also in fast-growing normal cells where they cause serious side effects. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer cells. An equivalent treatment, popular in Europe, is cyclophosphamide, methotrexate, and fluorouracil (CMF). Monoclonal antibodies, such as trastuzumab, are used for cancer cells that have the HER2 mutation. Radiation is usually added to the surgical bed to control cancer cells that were missed by the surgery, which usually extends survival, although radiation exposure to the heart may cause damage and heart failure in the following years. Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. The cancer cells may metastasize (spread) from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, problems during sexual intercourse, or erectile dysfunction.

Other symptoms can potentially develop during later stages of the disease. Rates of detection of prostate cancers vary widely across the world, with South and East Asia detecting less frequently than in Europe, and especially the United States. Prostate cancer tends to develop in men over the age of fifty and although it is one of the most prevalent types of cancer in men, many never have symptoms, undergo no therapy, and eventually die of other causes. This is because cancer of the prostate is, in most cases, slow-growing, symptom free and men with the condition often die of causes unrelated to the prostate cancer, such as heart/circulatory disease, pneumonia, other unconnected cancers, or old age. Many factors, including genetics and diet, have been implicated in the development of prostate cancer. The presence of prostate cancer may be indicated by symptoms, physical examinations, prostate specific antigen (PSA), or biopsy. There is controversy about the accuracy of the PSA test and the value of screening. Suspected prostate cancer is typically confirmed by taking a biopsy of the prostate and examining it under a microscope. Further tests, such as CT scans and bone scans, may be performed to determine whether prostate cancer has spread. Treatment options for prostate cancer with intent to cure are primarily surgery, radiation therapy, and proton therapy. Other treatments, such as hormonal therapy, chemotherapy, cryosurgery, and high intensity focused ultrasound (HIFU) also exist, depending on the clinical scenario and desired outcome. The age and underlying health of the man, the extent of metastasis, appearance under the microscope, and response of the cancer to initial treatment are important in determining the outcome of the disease. The decision whether or not to treat localized prostate cancer (a tumor that is contained within the prostate) with curative intent is a patient trade-off between the expected beneficial and harmful effects in terms of patient survival and quality of life. Colorectal cancer, also called colon cancer or large bowel cancer, includes cancerous growths in the colon, rectum and appendix. With 655,000 deaths worldwide per year, it is the fourth most common form of cancer in the United States and the third leading cause of cancer-related death in the Western world. Colorectal cancers arise from adenomatous polyps in the colon. These mushroom-shaped growths are usually benign, but some may develop into cancer over time. The majority of the time, the diagnosis of localized colon cancer is through colonoscopy. Invasive cancers that are confined within the wall of the colon (TNM stages I and II) are curable with surgery. If untreated, they spread to regional lymph nodes (stage III), where up to 73% are curable by surgery and chemotherapy. Cancer that metastasizes to distant sites (stage IV) is not curable, although chemotherapy can extend survival. Radiation is used with rectal cancer Melanoma is a malignant tumor of melanocytes which are found predominantly in skin but also in the bowel and the eye (see uveal melanoma). It is one of the less common types of skin cancer but causes the majority (75%) of skin cancer related deaths.

Melanocytes are normally present in skin, being responsible for the production of the dark pigment melanin. Despite many years of intensive laboratory and clinical research, the greatest chance of cure is in the early surgical resection of thin tumors. Around 60,000 new cases of melanoma invasive melanoma are diagnosed in the US each year, more frequently in males and in Caucasians. It is more common in Caucasian populations living in sunny climates than in other groups, or in those who use tanning salons. According to a WHO report about 48,000 melanoma related deaths occur worldwide per year. The treatment includes surgical removal of the tumor, adjuvant treatment, chemo- and immunotherapy, or radiation therapy.

Leukemia is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader group of diseases called hematological neoplasms.

Lymphoma is a cancer that begins in the lymphocytes of the immune system and presents as a solid tumor of lymphoid cells. They often originate like balls in lymph nodes, presenting as an enlargement of the node (a tumor). Lymphomas are closely related to lymphoid leukemias, which also originate in lymphocytes but typically involve only circulating blood and the bone marrow (where blood cells are generated in a process termed hematopoiesis) and do not usually form static tumors. There are many types of lymphomas, and in turn, lymphomas are a part of the broad group of diseases called hematological neoplasms.. Thomas Hodgkin published the first description of lymphoma in 1832, specifically of the form named after him, Hodgkin‘s lymphoma. Since then, many other forms of lymphoma have been described, grouped under several proposed classifications. The 1982 Working formulation classification became very popular. It introduced the category non-Hodgkin lymphoma (NHL), divided into 16 different diseases. However, since these different lymphomas have little in common with each other, the NHL label is of limited usefulness for doctors or patients and is slowly being abandoned. The latest classification by the WHO (2001) lists 43 different forms of lymphoma divided in four broad groups. Some forms of lymphoma are categorized as indolent (e.g. small lymphocytic lymphoma), compatible with a long life even without treatment, whereas other forms are aggressive (e.g. Burkitt‘s lymphoma), causing rapid deterioration and death. However, most of the aggressive lymphomas respond well to treatment and are curable. The prognosis therefore depends on the correct classification of the disease, established by a pathologist after examination of a biopsy. Although older classifications referred to histiocytic lymphomas, these are recognized in newer classifications as of B, T or NK cell lineage. True histiocytic malignancies are rare and are classified as sarcomas.

Diagnosis The most important diagnostic tool remains the medical history: the character of the complaints and any specific symptoms (fatigue, weight loss, unexplained anima, fever of unknown origin, paraneoplastic phenomena and other signs). Often a physical examination will reveal the location of a malignancy. Diagnostic methods include:  Biopsy, either incisional or excisional;  Endoscopy, either upper or lower gastrointestinal, bronchoscopy, or nasendoscopy;  X-rays, CT scanning, MRI scanning, ultrasound and other radiological techniques;  Scintigraphy, Single Photon Emission Computed Tomography, Position emission tomography and other methods of nuclear medicine;  Blood tests, including Tumor markers, which can increase the suspicion of certain types of tumors or even be pathognomonic of a particular disease. Apart from in diagnosis, these modalities (especially imaging by CT scanning) are often used to determine operability, i.e. whether it is surgically possible to remove a tumor in its entirety. Generally, a "tissue diagnosis" (from a biopsy) is considered essential for the proper identification of cancer. When this is not possible, "empirical therapy" (without an exact diagnosis) may be given, based on the available evidence (e.g. history, x-rays and scans.) Occasionally, a metastatic lump or pathological lymph node is found (typically in the neck) for which a primary tumor cannot be found. This situation is referred to as "carcinoma of unknown primary", and again, treatment is empirical based on past experience of the most likely origin.
Therapy It depends completely on the nature of the tumor identified what kind of therapeutical intervention will be necessary. Certain disorders will require immediate admission and chemotherapy (such as ALL or AML), while others will be followed up with regular physical examination and blood tests. A detailed discussion of treatment options according to the type of cancer is at the National Cancer Institute website with sections on adult cancers, pediatric cancers, and supportive care. There is also a section on complementary and alternative methods of treatment.

Often, surgery is attempted to remove a tumor entirely. This is only feasible when there is some degree of certainty that the tumor can in fact be removed. When it is certain that parts will remain, curative surgery is often impossible, e.g. when there are metastases elsewhere, or when the tumor has invaded a structure that cannot be operated upon without risking the patient's life. Occasionally surgery can improve survival even if not all tumour tissue has been removed; the procedure is referred to as "debulking" (i.e. reducing the overall amount of tumour tissue). Surgery is also used for the palliative treatment of some of cancers, e.g. to relieve biliary obstruction, or to relieve the problems associated with some cerebral tumors. The risks of surgery must be weighed up against the benefits. Chemotherapy and radiotherapy are used as a first-line radical therapy in a number of malignancies. They are also used for adjuvant therapy, i.e. when the macroscopic tumor has already been completely removed surgically but there is a reasonable statistical risk that it will recur. Chemotherapy and radiotherapy are commonly used for palliation, where disease is clearly incurable: in this situation the aim is to improve the quality of and prolong life. Hormone manipulation is well established, particularly in the treatment of breast and prostate cancer. There is currently a rapid expansion in the use of monoclonal antibody treatments, notably for lymphoma (Rituximab), and breast cancer (Trastuzumab).

Vaccines and Other Immunotherapies are the Subject of Intensive Research A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters. Immunotherapy is a medical term defined as "Treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as Activation Immunotherapies. Immunotherapies designed to reduce, suppress or more appropriately direct an existing immune response, as in cases of autoimmunity or allergy, are classified as Suppression Immunotherapies.

Palliative care Approximately 50% of all cancer cases in the Western world can be cured with radical treatment. For pediatric patients, that number is much higher. A large number of cancer patients will die from the disease, and a significant proportion of patients with incurable cancer will die of other causes. There may be ongoing issues with symptom control associated with progressive cancer, and also with the treatment of the disease. These problems may include pain, nausea, anorexia, fatigue, immobility, and depression. Not all issues are strictly physical: personal dignity may be affected. Moral and spiritual issues are also important. While many of these problems fall within the remit of the oncologist, palliative care has matured into a separate, closely allied specialty to address the problems associated with advanced disease. Palliative care is an essential part of the multidisciplinary cancer care team. Palliative care services may be less hospital-based than oncology, with nurses and doctors who are able to visit the patient at home.

Ethical issues There are a number of recurring ethical questions and dilemmas in oncological practice. These include:  What information to give the patient regarding disease extent/progression/prognosis.  Entry into clinical trials, especially in the face of terminal illness..  Withdrawal of active treatment.  "Do Not Resuscitate‖ orders and other end of life issues. These issues are closely related to the patients' personality, religion, culture, personal, and family life. The answers are rarely black and white. It requires a degree of sensitivity and very good communication on the part of the oncology team to address these problems properly.