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Sunday, November 12, 2023

Cancer treatment

From Wikipedia, the free encyclopedia
 
Cancer treatment
A patient prepared for radiation therapy
SpecialtyOncology
ICD-10-PCS110000053

Cancer treatments are a wide range of treatments available for the many different types of cancer, with each cancer type needing its own specific treatment. Treatments can include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy including small-molecule drugs or monoclonal antibodies, and PARP inhibitors such as olaparib . Other therapies include hyperthermia, immunotherapy, photodynamic therapy, and stem-cell therapy. Most commonly cancer treatment involves a series of separate therapies such as chemotherapy before surgery. Angiogenesis inhibitors are sometimes used to enhance the effects of immunotherapies.

The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient. Biomarker testing can help to determine the type of cancer, and indicate the best therapy. A number of experimental cancer treatments are continuously under development. In 2023 it was estimated that one in five people will be diagnosed with cancer at some point in their lifetime.

The primary goal of cancer treatment is to either cure the cancer by its complete removal, or to considerably prolong the life of the individual. Palliative care is involved when the prognosis is poor and the cancer termed as terminal. There are many types of cancer, and many of these can be successfully treated if detected early enough.

Types of treatments

The treatment of cancer has undergone evolutionary changes as understanding of the underlying biological processes has increased. Tumor removal surgeries have been documented in ancient Egypt, hormone therapy and radiation therapy were developed in the late 19th century. Chemotherapy, immunotherapy and newer targeted therapies are products of the 20th century. As new information about the biology of cancer emerges, treatments will be developed and modified to increase effectiveness, precision, survivability, and quality of life.

Surgery

Malignant tumours can be cured if entirely removed by surgery. But if the cancer has already spread (metastasized) to other sites, complete surgical excision is usually impossible. In the Halstedian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body. This has given rise to the popularity of local-only treatments such as surgery for small cancers. Even small localized tumors are increasingly recognized as possessing metastatic potential.

Examples of surgical procedures for cancer include mastectomy, and lumpectomy for breast cancer, prostatectomy for prostate cancer, and lung cancer surgery for non-small cell lung cancer. The goal of the surgery can be either the removal of only the tumor, the entire organ, or part of the organ. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.

In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes. Staging is a major determinant of prognosis and of the need for adjuvant therapy. Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatment.

Surgery may be performed before or after other forms of treatment. Treatment before surgery is often described as neoadjuvant. In breast cancer, the survival rate of patients who receive neoadjuvant chemotherapy are no different from those who are treated following surgery. Giving chemotherapy earlier allows oncologists to evaluate the effectiveness of the therapy, and may make removal of the tumor easier. However, the survival advantages of neoadjuvant treatment in lung cancer are less clear.

Radiation therapy

Radiation therapy (radiotherapy) is the use of ionizing radiation to kill cancer cells and shrink tumors by damaging their DNA causing cellular death. Radiation therapy can either damage DNA directly or create charged particles (free radicals) within the cells that can in turn damage the DNA. Radiation therapy can be administered externally via external beam radiotherapy or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.

Radiation therapy may be used to treat almost every type of solid tumor, and may also be used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radio sensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.

Radiation therapy can lead to dry mouth from exposure of salivary glands to radiation, resulting in decreased saliva secretion. Post therapy, the salivary glands will resume functioning but rarely in the same fashion. Dry mouth caused by radiation can be a permanent problem. Radiation might not be a choice of treatment if the tumor was diagnosed in late stages or is in a vulnerable location, as radiation might be more likely to cause damage to organs at effective doses. Moreover, radiation therapy for patients under 14 can cause particularly significant long-term side effects, such as hearing loss and blindness, that influence the lifestyle of the young patients. Children who had received cranial radiotherapy are deemed at a high risk for academic failure and cognitive delay.

Chemotherapy

Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. Chemotherapy can be given in a variety of ways such as injections into the muscles, skin, artery, or vein, or it could even be taken by mouth in the form of a pill. In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific to cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.

Since chemotherapy affects the whole body, it can have a wide range of side effects. Patients often find that they start losing their hair since the drugs that are combatting the cancer cells also attack the cells in the hair roots. This powerful treatment can also lead to fatigue, loss of appetite, and vomiting depending on the person.

The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body's ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous stem cell transplantation.

Targeted therapies

Targeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule drugs are targeted therapy drugs that are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib (Gleevec/Glivec) and gefitinib (Iressa).

Monoclonal antibody therapy is another strategy in which the therapeutic agent is an antibody which specifically binds to a protein on the surface of the cancer cells. Examples include the anti-HER2/neu antibody trastuzumab (Herceptin) used in breast cancer, and the anti-CD20 antibody rituximab, used in a variety of B-cell malignancies.

Targeted therapy can also involve small peptides as "homing devices" which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclides which are attached to these peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell. Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.

Photodynamic therapy (PDT) is a ternary treatment for cancer involving a photosensitizer, tissue oxygen, and light (often using lasers). PDT can be used as treatment for basal cell carcinoma (BCC) or lung cancer; PDT can also be useful in removing traces of malignant tissue after surgical removal of large tumors. In February 2019, medical scientists announced that iridium attached to albumin, creating a photosensitized molecule, can penetrate cancer cells and, after being irradiated with light, destroy the cancer cells.

High-energy therapeutic ultrasound could increase higher-density anti-cancer drug load and nanomedicines to target tumor sites by 20x fold higher than traditional target cancer therapy.

Targeted therapies under pre-clinical development as potential cancer treatments include morpholino splice switching oligonucleotides, which induce ERG exon skipping in prostate cancer models, multitargeted kinase inhibitors that inhibit the PI3K with other pathways including MEK and PIM, and inhibitors of NF-κB in models of chemotherapy resistance.

Immunotherapy

A renal cell carcinoma (lower left) in a kidney

Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor. Contemporary methods for generating an immune response against tumors include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. Cancer vaccines to generate specific immune responses are the subject of intensive research for a number of tumors, notably malignant melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells. It gained FDA approval in 2010.

Allogeneic hematopoietic stem cell transplantation (usually from the bone marrow) from a genetically non-identical donor can be considered a form of immunotherapy, since the donor's immune cells will often attack the tumor in a phenomenon known as graft-versus-tumor effect. For this reason, allogeneic HSCT leads to a higher cure rate than autologous transplantation for several cancer types, although the side effects are also more severe.

The cell based immunotherapy in which the patients own natural killer cells (NKs) and cytotoxic T cells are used has been in practice in Japan since 1990. NK cells and TCs primarily kill the cancer cells when they are developed. This treatment is given together with the other modes of treatment such as surgery, radiotherapy or chemotherapy and termed autologous immune enhancement therapy (AIET).

Immune checkpoint therapy focuses on two immune checkpoint proteins, cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Under normal conditions, the immune system utilizes checkpoint proteins as negative feedback mechanisms to return to homeostasis once pathogens have been cleared from the body. In a tumor microenvironment, cancer cells can commandeer this physiological regulatory system to "put a brake" on the anti-cancer immune response and evade immune surveillance. 2018 Nobel Prize in medicine is awarded to Dr. James Allison of University of Texas MD Anderson Cancer Center in U.S. and Dr. Tasuku Honjo Kyoto University in Japan for their contributions in advance of PD-1 and CTLA-4 immune checkpoint therapy.

Hormonal therapy

The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers. Blocking estrogen or testosterone is often an important additional treatment. In certain cancers, administration of hormone agonists, such as progestogens may be therapeutically beneficial. Although the side effects from hormone therapy vary depending on the type, patients can experience symptoms such as hot flashes, nausea, and fatigue.

Angiogenesis inhibitors

Angiogenesis inhibitors prevent the extensive growth of blood vessels (angiogenesis) that tumors need to survive and grow. Continued growth allows the invasion of cells into neighbouring tissues, and metastasis into distal tissues. There are many approved angiogenesis inhibitors including bevacizumab, axitinib, and cabozantinib.

Flavonoids have been shown to downregulate the angiogenic stimulation of VEGF and Hypoxia-inducible factor (HIF) but none have reached clinical trials.

Exercise prescription

Exercise prescription is becoming a mainstream adjunct treatment for cancer, based on studies which show that exercise (compared to no exercise) is associated with reduced recurrence rates, improved mortality outcomes, reduction of side effects from traditional cancer treatments. Although it is uncertain whether improved outcomes with exercise are correlated or causative, the benefit-risk ratio of including exercise as part of cancer treatment is large, as exercise has further benefits (e.g. cardiovascular, mental health) without major risks, although there is a small risk of overuse injury if added too aggressively. Exercise physiologists and exercise medicine specialists can assist oncologists and primary care practitioners with exercise prescription in cancer patients.

Walking is usually an excellent exercise option as an adjunct cancer treatment

Synthetic lethality

Synthetic lethality arises when a combination of deficiencies in the expression of two or more genes leads to cell death, whereas a deficiency in only one of these genes does not. The deficiencies can arise through mutations, epigenetic alterations or inhibitors of one or both of the genes.

Cancer cells are frequently deficient in a DNA repair gene. (Also see DNA repair deficiency in cancer.) This DNA repair defect either may be due to mutation or, often, epigenetic silencing (see epigenetic silencing of DNA repair). If this DNA repair defect is in one of seven DNA repair pathways (see DNA repair pathways), and a compensating DNA repair pathway is inhibited, then the tumor cells may be killed by synthetic lethality. Non-tumorous cells, with the initial pathway intact, can survive.

Ovarian cancer

Mutations in DNA repair genes BRCA1 or BRCA2 (active in homologous recombinational repair) are synthetically lethal with inhibition of DNA repair gene PARP1 (active in the base excision repair and in the microhomology-mediated end joining pathways of DNA repair).

Ovarian cancers have a mutational defect in BRCA1 in about 18% of patients (13% germline mutations and 5% somatic mutations) (see BRCA1). Olaparib, a PARP inhibitor, was approved in 2014 by the US FDA for use in BRCA-associated ovarian cancer that had previously been treated with chemotherapy. The FDA, in 2016, also approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation.

Colon cancer

In colon cancer, epigenetic defects in the WRN gene appear to be synthetically lethal with inactivation of TOP1. In particular, irinotecan inactivation of TOP1 was synthetically lethal with deficient expression of the DNA repair WRN gene in patients with colon cancer. In a 2006 study, 45 patients had colonic tumors with hypermethylated WRN gene promoters (silenced WRN expression), and 43 patients had tumors with unmethylated WRN gene promoters, so that WRN protein expression was high. Irinotecan was more strongly beneficial for patients with hypermethylated WRN promoters (39.4 months survival) than for those with unmethylated WRN promoters (20.7 months survival). The WRN gene promoter is hypermethylated in about 38% of colorectal cancers.

There are five different stages of colon cancer, and these five stages all have treatment:

  • Stage 0, is where the patient is required to undergo surgery to remove the polyp (American Cancer Society).
  • Stage 1, depending on the location of the cancer in the colon and lymph nodes, the patient undergoes surgery just like Stage 0.
  • Stage 2 patients undergoes removing nearby lymph nodes, but depending on what the doctor says, the patent might have to undergo chemotherapy after surgery (if the cancer is at higher risk of coming back).
  • Stage 3, is where the cancer has spread all throughout the lymph nodes but not yet to other organs or body parts. When getting to this stage, Surgery is conducted on the colon and lymph nodes, then the doctor orders Chemotherapy (FOLFOX or CapeOx) to treat the colon cancer in the location needed (American Cancer Society). The last a patient can get is Stage 4.
  • Stage 4 patients only undergo surgery if it is for the prevention of the cancer, along with pain relief. If the pain continues with these two options, the doctor might recommended radiation therapy. The main treatment strategy is chemotherapy due to how aggressive the cancer becomes in this stage, not only to the colon but to the lymph nodes.

Symptom control and palliative care

Although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments. In general, doctors have the therapeutic skills to reduce pain including, chemotherapy-induced nausea and vomiting, diarrhea, hemorrhage and other common problems in cancer patients. The multidisciplinary specialty of palliative care has increased specifically in response to the symptom control needs for these groups of patients.

Pain medication, such as morphine, oxycodone, and antiemetics are drugs to suppress nausea and vomiting. These are very commonly used in patients with cancer-related symptoms. Improved antiemetics such as ondansetron and analogues, as well as aprepitant have made aggressive treatments much more feasible in cancer patients.

Cancer pain can be associated with continuing tissue damage due to the disease process, or the treatment (i.e. surgery, radiation, chemotherapy). There is always a role for environmental factors and affective disturbances in the genesis of pain behaviors, However these are not usually the predominant etiologic factors in patients with cancer pain. Some patients with severe pain associated with cancer are nearing the end of their lives, but in all cases, palliative therapies should be used to control the pain. Issues such as the social stigma of using opioids and health care consumption can be concerns and may need to be addressed for the person to feel comfortable taking the medications required to control his or her symptoms. The typical strategy for cancer pain management is to get the patient as comfortable as possible using the least amount of medications possible, even if that means using opioids, surgery, and physical measures.

Historically, doctors were reluctant to prescribe narcotics to terminal cancer patients due to addiction and respiratory function suppression. The palliative care movement, a more recent offshoot of the hospice movement, has engendered more widespread support for preemptive pain treatment for cancer patients. The World Health Organization also noted uncontrolled cancer pain as a worldwide problem and established a "ladder" as a guideline for how practitioners should treat pain in patients who have cancer

Cancer-related fatigue is a very common symptom of cancer, and there are a number of approaches put forward for helping with this.

Mental struggles/pain

Cancer patients undergo many obstacles and one of these includes mental strain. It is very common for cancer patients to become stressed, overwhelmed, uncertain, and even depressed. The use of chemo is a very harsh treatment causing the cells of the body to die. Physical effects like this do not only inflict pain but also cause patients to become mentally exhausted and want to give up. For a lot of reasons including these, hospitals offer many types of therapy and mental healing. Some of these include yoga, meditation, communication therapy, and spiritual ideas. All of these are meant to calm and relax the mind, or to give hope for the patients that may feel drained.

Insomnia

A common disorder experienced by people that have survived cancer treatments is insomnia. Almost 60% of cancer survivors experience insomnia, and if it is not treated properly it can have long term effects on physiological and physical health. Insomnia is defined as dissatisfaction with sleep duration or quality and difficulties initiating or maintaining sleep. Insomnia can heavily reduce one's quality of life. Cognitive behavioral therapy has been seen to reduce insomnia and depression for cancer survivors.

Muscle strength

Decreased muscle strength is a common side effect to many different cancer treatments. Because of this, exercise is very important especially in the first year after treatment. It has been shown that yoga, water exercise, and pilates can improve the emotional well-being and quality of life of breast cancer survivors.

Hospice care

Hospice care provides palliative care at home, or in a dedicated hospice institution, for a person with an advanced illness termed as terminal. Untreated cancer will prove terminal, and sometimes a choice is made to forgo treatment and its unpleasant side effects, and opt instead for hospice care. Hospice care aims to provide support for the person's medical, emotional, social, practical, psychological, and spiritual needs.

Advance care planning (ACP) can help a person to decide for themself their future care wishes as they approach end of life. ACP helps adults at any stage of health to decide, and record in writing, their wishes for medical treatment preferences, and future wants, preferably as previously discussed with relatives or carers.

Research

Clinical trials, also called research studies, test new treatments in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy.

A clinical trial is one of the final stages of a long and careful cancer research process. The search for new treatments begins in the laboratory, where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.

Patients who take part may be helped personally by the treatment they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. At the same time, new treatments also may have unknown risks, but if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit. There is no guarantee that a new treatment being tested or a standard treatment will produce good results. In children with cancer, a survey of trials found that those enrolled in trials were on average not more likely to do better or worse than those on standard treatment; this confirms that success or failure of an experimental treatment cannot be predicted.

Exosome research

Exosomes are lipid-covered microvesicles shed by solid tumors into bodily fluids, such as blood and urine. Current research is being done attempting to use exosomes as a detection and monitoring method for a variety of cancers. The hope is to be able to detect cancer with a high sensitivity and specificity via detection of specific exosomes in the blood or urine. The same process can also be used to more accurately monitor a patient's treatment progress. Enzyme linked lectin specific assay or ELLSA Archived 13 July 2011 at the Wayback Machine has been proven to directly detect melanoma derived exosomes from fluid samples. Previously, exosomes had been measured by total protein content in purified samples and by indirect immunomodulatory effects. ELLSA directly measures exosome particles in complex solutions, and has already been found capable of detecting exosomes from other sources, including ovarian cancer and tuberculosis-infected macrophages.

Exosomes, secreted by tumors, are also believed to be responsible for triggering programmed cell death (apoptosis) of immune cells; interrupting T-cell signaling required to mount an immune response; inhibiting the production of anti-cancer cytokines, and has implications in the spread of metastasis and allowing for angiogenesis. Studies are currently being done with "Lectin affinity plasmapheresis" (LAP), LAP is a blood filtration method which selectively targets the tumor based exosomes and removes them from the bloodstream. It is believed that decreasing the tumor-secreted exosomes in a patient's bloodstream will slow down progression of the cancer while at the same time increasing the patients own immune response.

Complementary and alternative

Complementary and alternative medicine (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not part of conventional medicine and have not been shown to be effective. "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine. CAM use is common among people with cancer; a 2000 study found that 69% of cancer patients had used at least one CAM therapy as part of their cancer treatment. Most complementary and alternative medicines for cancer have not been rigorously studied or tested. Some alternative treatments which have been investigated and shown to be ineffective continue to be marketed and promoted.

Special circumstances

In pregnancy

The incidence of pregnancy-associated cancer has risen due to the increasing age of pregnant mothers. Cancers may also be detected incidentally during maternal screening.

Cancer treatment needs to be selected to do least harm to both the woman and her embryo/fetus. In some cases a therapeutic abortion may be recommended.

Radiation therapy is out of the question, and chemotherapy always poses the risk of miscarriage and congenital malformations. Little is known about the effects of medications on the child.

Even if a drug has been tested as not crossing the placenta to reach the child, some cancer forms can harm the placenta and make the drug pass over it anyway. Some forms of skin cancer may even metastasize to the child's body.

Diagnosis is also made more difficult, since computed tomography is infeasible because of its high radiation dose. Still, magnetic resonance imaging works normally. However, contrast media cannot be used, since they cross the placenta.

As a consequence of the difficulties to properly diagnose and treat cancer during pregnancy, the alternative methods are either to perform a Cesarean section when the child is viable in order to begin a more aggressive cancer treatment, or, if the cancer is malignant enough that the mother is unlikely to be able to wait that long, to perform an abortion in order to treat the cancer.

In utero

Fetal tumors are sometimes diagnosed while still in utero. Teratoma is the most common type of fetal tumor, and usually is benign. In some cases these are surgically treated while the fetus is still in the uterus.

Racial and social disparities

Cancer is a significant issue that is affecting the world. Specifically in the U.S, it is expected for there to be 1,735,350 new cases of cancer, and 609,640 deaths by the end of 2018. Adequate treatment can prevent many cancer deaths but there are racial and social disparities in treatments which has a significant factor in high death rates. Minorities are more likely to receive inadequate treatment while white patients are more likely to receive efficient treatments in a timely manner. Having satisfactory treatment in timely manner can increase the patients likelihood of survival. It has been shown that chances of survival are significantly greater for white patients than for African American patients.

The annual average mortality of patients with colorectal cancer between 1992 and 2000 was 27 and 18.5 per 100,000 white patients and 35.4 and 25.3 per 100,000 black patients. In a journal that analyzed multiple studies testing racial disparities when treating colorectal cancer found contradicting findings. The Veterans administration and an adjuvant trial found that there were no evidence to support racial differences in treating colorectal cancer. However, two studies suggested that African American patients received less satisfactory and poor quality treatment compared to white patients. One of these studies specifically was provided by the Center for Intramural Research. They found that black patients were 41% less likely to receive colorectal treatment and were more likely to be hospitalized in a teaching hospital with less certified physicians compared to white patients. Furthermore, black patients were more likely to be diagnosed with oncologic sequelae, which is a severity of the illness in result of poorly treated cancer. Lastly, for every 1,000 patients in the hospital, there were 137.4 black patient deaths and 95.6 white patient deaths.

In a breast cancer journal article analyzed the disparities of breast cancer treatments in the Appalachian Mountains. African American women were found to be 3 times more likely to die compared to Asians and two times more likely to die compared to white women. According to this study, African American women are at a survival disadvantage compared to other races. Black women are also more likely to receive less successful treatment than white women by not receiving surgery or therapy. Furthermore, The National Cancer Institute panel, identified breast cancer treatments, given to black women, as inappropriate and not adequate compared to the treatment given to white women.

From these studies, researchers have noted that there are definite disparities in the treatment of cancer, specifically who have access to the best treatment and can receive it in a timely manner. This eventually leads to disparities between who is dying from cancer and who is more likely to survive.

The cause of these disparities is generally that African Americans have less medical care coverage, insurance and access cancer centers than other races. For an example, black patients with breast cancer and colorectal cancer were shown to be more likely to have medicaid or no insurance compared to other races. The location of the health care facility also plays a role in why African Americans receive less treatment in comparison to other races. However, some studies say that African Americans don't trust doctors and don't always seek the help they need and this explains why there are less African Americans receiving treatment. Others suggest that African Americans seek even more treatment than whites and that it is simply a lack of the resources available to them. In this case, analyzing these studies will identify the treatment disparities and look to prevent them by discovering potential causes of these disparities.

Code refactoring

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Code_refactoring

In computer programming and software design, code refactoring is the process of restructuring existing computer code—changing the factoring—without changing its external behavior. Refactoring is intended to improve the design, structure, and/or implementation of the software (its non-functional attributes), while preserving its functionality. Potential advantages of refactoring may include improved code readability and reduced complexity; these can improve the source code's maintainability and create a simpler, cleaner, or more expressive internal architecture or object model to improve extensibility. Another potential goal for refactoring is improved performance; software engineers face an ongoing challenge to write programs that perform faster or use less memory.

Typically, refactoring applies a series of standardized basic micro-refactorings, each of which is (usually) a tiny change in a computer program's source code that either preserves the behavior of the software, or at least does not modify its conformance to functional requirements. Many development environments provide automated support for performing the mechanical aspects of these basic refactorings. If done well, code refactoring may help software developers discover and fix hidden or dormant bugs or vulnerabilities in the system by simplifying the underlying logic and eliminating unnecessary levels of complexity. If done poorly, it may fail the requirement that external functionality not be changed, and may thus introduce new bugs.

By continuously improving the design of code, we make it easier and easier to work with. This is in sharp contrast to what typically happens: little refactoring and a great deal of attention paid to expediently add new features. If you get into the hygienic habit of refactoring continuously, you'll find that it is easier to extend and maintain code.

— Joshua Kerievsky, Refactoring to Patterns

Motivation

Refactoring is usually motivated by noticing a code smell. For example, the method at hand may be very long, or it may be a near duplicate of another nearby method. Once recognized, such problems can be addressed by refactoring the source code, or transforming it into a new form that behaves the same as before but that no longer "smells".

For a long routine, one or more smaller subroutines can be extracted; or for duplicate routines, the duplication can be removed and replaced with one shared function. Failure to perform refactoring can result in accumulating technical debt; on the other hand, refactoring is one of the primary means of repaying technical debt.

Benefits

There are two general categories of benefits to the activity of refactoring.

  1. Maintainability. It is easier to fix bugs because the source code is easy to read and the intent of its author is easy to grasp. This might be achieved by reducing large monolithic routines into a set of individually concise, well-named, single-purpose methods. It might be achieved by moving a method to a more appropriate class, or by removing misleading comments.
  2. Extensibility. It is easier to extend the capabilities of the application if it uses recognizable design patterns, and it provides some flexibility where none before may have existed.

Performance engineering can remove inefficiencies in programs, known as software bloat, arising from traditional software-development strategies that aim to minimize an application's development time rather than the time it takes to run. Performance engineering can also tailor software to the hardware on which it runs, for example, to take advantage of parallel processors and vector units.

Challenges

Refactoring requires extracting software system structure, data models, and intra-application dependencies to get back knowledge of an existing software system. The turnover of teams implies missing or inaccurate knowledge of the current state of a system and about design decisions made by departing developers. Further code refactoring activities may require additional effort to regain this knowledge. Refactoring activities generate architectural modifications that deteriorate the structural architecture of a software system. Such deterioration affects architectural properties such as maintainability and comprehensibility which can lead to a complete re-development of software systems. 

Code refactoring activities are secured with software intelligence when using tools and techniques providing data about algorithms and sequences of code execution. Providing a comprehensible format for the inner-state of software system structure, data models, and intra-components dependencies is a critical element to form a high-level understanding and then refined views of what needs to be modified, and how.

Testing

Automatic unit tests should be set up before refactoring to ensure routines still behave as expected. Unit tests can bring stability to even large refactors when performed with a single atomic commit. A common strategy to allow safe and atomic refactors spanning multiple projects is to store all projects in a single repository, known as monorepo.

With unit testing in place, refactoring is then an iterative cycle of making a small program transformation, testing it to ensure correctness, and making another small transformation. If at any point a test fails, the last small change is undone and repeated in a different way. Through many small steps the program moves from where it was to where you want it to be. For this very iterative process to be practical, the tests must run very quickly, or the programmer would have to spend a large fraction of their time waiting for the tests to finish. Proponents of extreme programming and other agile software development describe this activity as an integral part of the software development cycle.

Techniques

Here are some examples of micro-refactorings; some of these may only apply to certain languages or language types. A longer list can be found in Martin Fowler's refactoring book and website. Many development environments provide automated support for these micro-refactorings. For instance, a programmer could click on the name of a variable and then select the "Encapsulate field" refactoring from a context menu. The IDE would then prompt for additional details, typically with sensible defaults and a preview of the code changes. After confirmation by the programmer it would carry out the required changes throughout the code.

  • Techniques that allow for more understanding
    • Program Dependence Graph - explicit representation of data and control dependencies 
    • System Dependence Graph - representation of procedure calls between PDG 
    • Software intelligence - reverse engineers the initial state to understand existing intra-application dependencies
  • Techniques that allow for more abstraction
    • Encapsulate field – force code to access the field with getter and setter methods
    • Generalize type – create more general types to allow for more code sharing
    • Replace type-checking code with state/strategy
    • Replace conditional with polymorphism
  • Techniques for breaking code apart into more logical pieces
    • Componentization breaks code down into reusable semantic units that present clear, well-defined, simple-to-use interfaces.
    • Extract class moves part of the code from an existing class into a new class.
    • Extract method, to turn part of a larger method into a new method. By breaking down code in smaller pieces, it is more easily understandable. This is also applicable to functions.
  • Techniques for improving names and location of code
    • Move method or move field – move to a more appropriate class or source file
    • Rename method or rename field – changing the name into a new one that better reveals its purpose
    • Pull up – in object-oriented programming (OOP), move to a superclass
    • Push down – in OOP, move to a subclass
  • Automatic clone detection

Hardware refactoring

While the term refactoring originally referred exclusively to refactoring of software code, in recent years code written in hardware description languages has also been refactored. The term hardware refactoring is used as a shorthand term for refactoring of code in hardware description languages. Since hardware description languages are not considered to be programming languages by most hardware engineers, hardware refactoring is to be considered a separate field from traditional code refactoring.

Automated refactoring of analog hardware descriptions (in VHDL-AMS) has been proposed by Zeng and Huss. In their approach, refactoring preserves the simulated behavior of a hardware design. The non-functional measurement that improves is that refactored code can be processed by standard synthesis tools, while the original code cannot. Refactoring of digital hardware description languages, albeit manual refactoring, has also been investigated by Synopsys fellow Mike Keating. His target is to make complex systems easier to understand, which increases the designers' productivity.

History

The first known use of the term "refactoring" in the published literature was in a September, 1990 article by William Opdyke and Ralph Johnson. Griswold's Ph.D. thesis, Opdyke's Ph.D. thesis, published in 1992, also used this term. Although refactoring code has been done informally for decades, William Griswold's 1991 Ph.D. dissertation is one of the first major academic works on refactoring functional and procedural programs, followed by William Opdyke's 1992 dissertation on the refactoring of object-oriented programs, although all the theory and machinery have long been available as program transformation systems. All of these resources provide a catalog of common methods for refactoring; a refactoring method has a description of how to apply the method and indicators for when you should (or should not) apply the method.

Martin Fowler's book Refactoring: Improving the Design of Existing Code is the canonical reference.

The terms "factoring" and "factoring out" have been used in this way in the Forth community since at least the early 1980s. Chapter Six of Leo Brodie's book Thinking Forth (1984) is dedicated to the subject.

In extreme programming, the Extract Method refactoring technique has essentially the same meaning as factoring in Forth; to break down a "word" (or function) into smaller, more easily maintained functions.

Refactorings can also be reconstructed posthoc to produce concise descriptions of complex software changes recorded in software repositories like CVS or SVN.

Automated code refactoring

Many software editors and IDEs have automated refactoring support. Here is a list of a few of these editors, or so-called refactoring browsers.

Software rot

From Wikipedia, the free encyclopedia

Software rot (bit rot, code rot, software erosion, software decay, or software entropy) is either a slow deterioration of software quality over time or its diminishing responsiveness that will eventually lead to software becoming faulty, unusable, or in need of upgrade. This is not a physical phenomenon; the software does not actually decay, but rather suffers from a lack of being responsive and updated with respect to the changing environment in which it resides.

The Jargon File, a compendium of hacker lore, defines "bit rot" as a jocular explanation for the degradation of a software program over time even if "nothing has changed"; the idea behind this is almost as if the bits that make up the program were subject to radioactive decay.

Causes

Several factors are responsible for software rot, including changes to the environment in which the software operates, degradation of compatibility between parts of the software itself, and the appearance of bugs in unused or rarely used code.

Environment change

When changes occur in the program's environment, particularly changes which the designer of the program did not anticipate, the software may no longer operate as originally intended. For example, many early computer game designers used the CPU clock speed as a timer in their games. However, newer CPU clocks were faster, so the gameplay speed increased accordingly, making the games less usable over time.

Onceability

There are changes in the environment not related to the program's designer, but its users. Initially, a user could bring the system into working order, and have it working flawlessly for a certain amount of time. But, when the system stops working correctly, or the users want to access the configuration controls, they cannot repeat that initial step because of the different context and the unavailable information (password lost, missing instructions, or simply a hard-to-manage user interface that was first configured by trial and error). Information Architect Jonas Söderström has named this concept Onceability, and defines it as "the quality in a technical system that prevents a user from restoring the system, once it has failed".

Unused code

Infrequently used portions of code, such as document filters or interfaces designed to be used by other programs, may contain bugs that go unnoticed. With changes in user requirements and other external factors, this code may be executed later, thereby exposing the bugs and making the software appear less functional.

Rarely updated code

Normal maintenance of software and systems may also cause software rot. In particular, when a program contains multiple parts which function at arm's length from one another, failing to consider how changes to one part that affect the others may introduce bugs.

In some cases, this may take the form of libraries that the software uses being changed in a way which adversely affects the software. If the old version of a library that previously worked with the software can no longer be used due to conflicts with other software or security flaws that were found in the old version, there may no longer be a viable version of a needed library for the program to use.

Online connectivity

Modern commercial software often connects to an online server for license verification and accessing information. If the online service powering the software is shut down, it may stop working.

Since the late 2010s most websites use secure HTTPS connections. However this requires encryption keys called root certificates which have expiration dates. After the certificates expire the device loses connectivity to most websites unless the keys are continuously updated.

Another issue is that in March 2021 old encyption standards TLS 1.0 and TLS 1.1 were deprecated. This means that operating systems, browsers and other online software that do not support at least TLS 1.2 cannot connect to most websites, even to download patches or update the browser, if these are available. This is occasionally called the "TLS apocalypse".

Products that cannot connect to most websites include PowerMacs, old Unix boxes and Microsoft Windows versions older than Server 2008/Windows 7. The Internet Explorer 8 browser in Server 2008/Windows 7 does support TLS 1.2 but it is disabled by default.

Classification

Software rot is usually classified as being either dormant rot or active rot.

Dormant rot

Software that is not currently being used gradually becomes unusable as the remainder of the application changes. Changes in user requirements and the software environment also contribute to the deterioration.

Active rot

Software that is being continuously modified may lose its integrity over time if proper mitigating processes are not consistently applied. However, much software requires continuous changes to meet new requirements and correct bugs, and re-engineering software each time a change is made is rarely practical. This creates what is essentially an evolution process for the program, causing it to depart from the original engineered design. As a consequence of this and a changing environment, assumptions made by the original designers may be invalidated, thereby introducing bugs.

In practice, adding new features may be prioritized over updating documentation; without documentation, however, it is possible for specific knowledge pertaining to parts of the program to be lost. To some extent, this can be mitigated by following best current practices for coding conventions.

Active software rot slows once an application is near the end of its commercial life and further development ceases. Users often learn to work around any remaining software bugs, and the behaviour of the software becomes consistent as nothing is changing.

Examples

AI program example

Many seminal programs from the early days of AI research have suffered from irreparable software rot. For example, the original SHRDLU program (an early natural language understanding program) cannot be run on any modern day computer or computer simulator, as it was developed during the days when LISP and PLANNER were still in development stage, and thus uses non-standard macros and software libraries which do not exist anymore.

Online forum example

Suppose an administrator creates a forum using open source forum software, and then heavily modifies it by adding new features and options. This process requires extensive modifications to existing code and deviation from the original functionality of that software.

From here, there are several ways software rot can affect the system:

  • The administrator can accidentally make changes which conflict with each other or the original software, causing the forum to behave unexpectedly or break down altogether. This leaves them in a very bad position: as they have deviated so greatly from the original code, technical support and assistance in reviving the forum will be difficult to obtain.
  • A security hole may be discovered in the original forum source code, requiring a security patch. However, because the administrator has modified the code so extensively, the patch may not be directly applicable to their code, requiring the administrator to effectively rewrite the update.
  • The administrator who made the modifications could vacate their position, leaving the new administrator with a convoluted and heavily modified forum that lacks full documentation. Without fully understanding the modifications, it is difficult for the new administrator to make changes without introducing conflicts and bugs. Furthermore, documentation of the original system may no longer be available, or worse yet, misleading due to subtle differences in functional requirements.

Refactoring

Refactoring is a means of addressing the problem of software rot. It is described as the process of rewriting existing code to improve its structure without affecting its external behaviour. This includes removing dead code and rewriting sections that have been modified extensively and no longer work efficiently. Care must be taken not to change the software's external behaviour, as this could introduce incompatibilities and thereby itself contribute to software rot.

 

Rheumatism

From Wikipedia, the free encyclopedia
 
Rheumatism
Other namesRheumatic disease
SpecialtyRheumatology
ComplicationsAmplified musculoskeletal pain syndrome

Rheumatism or rheumatic disorders are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. Rheumatism does not designate any specific disorder, but covers at least 200 different conditions, including arthritis and "non-articular rheumatism", also known as "regional pain syndrome" or "soft tissue rheumatism". There is a close overlap between the term soft tissue disorder and rheumatism. Sometimes the term "soft tissue rheumatic disorders" is used to describe these conditions.

The term "Rheumatic Diseases" is used in MeSH to refer to connective tissue disorders. The branch of medicine devoted to the diagnosis and therapy of rheumatism is called rheumatology.

Types

Many rheumatic disorders of chronic, intermittent pain (including joint pain, neck pain or back pain) have historically been caused by infectious diseases. Their etiology was unknown until the 20th century and not treatable. Postinfectious arthritis, also known as reactive arthritis, and rheumatic fever are other examples.

In the United States, major rheumatic disorders are divided into 10 major categories based on the nomenclature and classification proposed by the American College of Rheumatology (ACR) in 1983.

Diagnosis

Blood and urine tests will measure levels of creatinine and uric acid to determine kidney function, an elevation of the ESR and CRP is possible. After a purine-restricted diet, another urine test will help determine whether the body is producing too much uric acid or the body isn't excreting enough uric acid. Rheumatoid factor may be present, especially in the group that is likely to develop rheumatoid arthritis. A fine needle is used to draw fluid from a joint to determine if there is any build up of fluid. The presence of uric acid crystals in the fluid would indicate gout. In many cases there may be no specific test, and it is often a case of eliminating other conditions before getting a correct diagnosis.

Management

Initial therapy of the major rheumatological diseases is with analgesics, such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). Steroids, especially glucocorticoids, and stronger analgesics are often required for more severe cases.

Etymology

The term rheumatism stems from the Late Latin rheumatismus, ultimately from Greek ῥευματίζομαι "to suffer from a flux", with rheum meaning bodily fluids, i.e., any discharge of blood or bodily fluid.

Before the 17th century, the joint pain which was thought to be caused by viscous humours seeping into the joints was always referred to as gout, a word adopted in Middle English from Old French gote "a drop; the gout, rheumatism".

The English term rheumatism in the current sense has been in use since the late 17th century, as it was believed that chronic joint pain was caused by excessive flow of rheum which means bodily fluids into a joint.

Authorship of the Bible

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