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Thursday, February 14, 2019

Coronary artery disease

From Wikipedia, the free encyclopedia

Coronary artery disease
SynonymsAtherosclerotic heart disease, atherosclerotic vascular disease, coronary heart disease
Blausen 0257 CoronaryArtery Plaque.png
Illustration depicting atherosclerosis in a coronary artery.
SpecialtyCardiology, cardiac surgery
SymptomsChest pain, shortness of breath
ComplicationsHeart failure, abnormal heart rhythms
CausesAtherosclerosis of the arteries of the heart
Risk factorsHigh blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol
Diagnostic methodElectrocardiogram, cardiac stress test, coronary computed tomographic angiography, coronary angiogram
PreventionHealthy diet, regular exercise, maintaining a healthy weight, not smoking
TreatmentPercutaneous coronary intervention (PCI), coronary artery bypass surgery (CABG)
MedicationAspirin, beta blockers, nitroglycerin, statins
Frequency110 million (2015)
Deaths8.9 million (2015)

Coronary artery disease (CAD), also known as ischemic heart disease (IHD), involves the reduction of blood flow to the heart muscle due to build up of plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, myocardial infarction, and sudden cardiac death. A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Occasionally it may feel like heartburn. Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and improve with rest. Shortness of breath may also occur and sometimes no symptoms are present. In many cases, the first sign is a heart attack. Other complications include heart failure or an abnormal heartbeat.

Risk factors include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, and excessive alcohol. A number of tests may help with diagnoses including: electrocardiogram, cardiac stress testing, coronary computed tomographic angiography, and coronary angiogram, among others.

Ways to reduce CAD risk include eating a healthy diet, regularly exercising, maintaining a healthy weight, and not smoking. Medications for diabetes, high cholesterol, or high blood pressure are sometimes used. There is limited evidence for screening people who are at low risk and do not have symptoms. Treatment involves the same measures as prevention. Additional medications such as antiplatelets (including aspirin), beta blockers, or nitroglycerin may be recommended. Procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) may be used in severe disease. In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improves life expectancy or decreases heart attack risk.

In 2015, CAD affected 110 million people and resulted in 8.9 million deaths. It makes up 15.6% of all deaths, making it the most common cause of death globally. The risk of death from CAD for a given age decreased between 1980 and 2010, especially in developed countries. The number of cases of CAD for a given age also decreased between 1990 and 2010. In the United States in 2010, about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45; rates were higher among men than women of a given age.

Signs and symptoms

Chest pain that occurs regularly with activity, after eating, or at other predictable times is termed stable angina and is associated with narrowings of the arteries of the heart

Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction. In adults who go to the emergency department with an unclear cause of pain, about 30% have pain due to coronary artery disease.

Risk factors

Coronary artery disease has a number of well determined risk factors. These include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, family history, and excessive alcohol. About half of cases are linked to genetics. Smoking and obesity are associated with about 36% and 20% of cases, respectively. Smoking just one cigarette per day about doubles the risk of CAD. Lack of exercise has been linked to 7–12% of cases. Exposure to the herbicide Agent Orange may increase risk. Rheumatologic diseases such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and psoriatic arthritis are independent risk factors as well.

Job stress appears to play a minor role accounting for about 3% of cases. In one study, women who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis. In contrast, women who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression. Having a type A behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience, is linked to an increased risk of coronary disease.

Blood fats

Dietary cholesterol does not appear to have a significant effect on blood cholesterol and thus recommendations about its consumption may not be needed. Saturated fat is still a concern.

Genetics

The heritability of coronary artery disease has been estimated between 40% and 60%. Genome-wide association studies have identified around 60 genetic susceptibility loci for coronary artery disease.

Other

  • Endometriosis in women under the age of 40.
  • Depression and hostility appear to be risks.
  • The number of categories of adverse childhood experiences (psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill, suicidal, or incarcerated) showed a graded correlation with the presence of adult diseases including coronary artery (ischemic heart) disease.
  • Hemostatic factors: High levels of fibrinogen and coagulation factor VII are associated with an increased risk of CAD.
  • Low hemoglobin.
  • In the Asian population, the b fibrinogen gene G-455A polymorphism was associated with the risk of CAD.

Pathophysiology

Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing. Masson's trichrome.
 
Illustration depicting coronary artery disease

Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the heart's muscle cells. The heart's muscle cells may die from lack of oxygen and this is called a myocardial infarction (commonly referred to as a heart attack). It leads to damage, death, and eventual scarring of the heart muscle without regrowth of heart muscle cells. Chronic high-grade narrowing of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into a dangerous heart rhythm known as ventricular fibrillation, which often leads to death.

Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a coronary artery (the arteries that supply blood to the heart muscle) develops atherosclerosis. With atherosclerosis, the artery's lining becomes hardened, stiffened, and accumulates deposits of calcium, fatty lipids, and abnormal inflammatory cells – to form a plaque. Calcium phosphate (hydroxyapatite) deposits in the muscular layer of the blood vessels appear to play a significant role in stiffening the arteries and inducing the early phase of coronary arteriosclerosis. This can be seen in a so-called metastatic mechanism of calciphylaxis as it occurs in chronic kidney disease and hemodialysis (Rainer Liedtke 2008). Although these people suffer from a kidney dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing a partial obstruction to blood flow. People with coronary artery disease might have just one or two plaques, or might have dozens distributed throughout their coronary arteries. A more severe form is chronic total occlusion (CTO) when a coronary artery is completely obstructed for more than 3 months.

Cardiac syndrome X is chest pain (angina pectoris) and chest discomfort in people who do not show signs of blockages in the larger coronary arteries of their hearts when an angiogram (coronary angiogram) is being performed. The exact cause of cardiac syndrome X is unknown. Explanations include microvascular dysfunction or epicardial atherosclerosis. For reasons that are not well understood, women are more likely than men to have it; however, hormones and other risk factors unique to women may play a role.

Diagnosis

Coronary angiogram of a man
 
Coronary angiogram of a woman
 
For symptomatic people, stress echocardiography can be used to make a diagnosis for obstructive coronary artery disease. The use of echocardiography, stress cardiac imaging, and/or advanced non-invasive imaging is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease.

The diagnosis of "Cardiac Syndrome X" – the rare coronary artery disease that is more common in women, as mentioned, is a diagnosis of exclusion. Therefore, usually the same tests are used as in any person with the suspected of having coronary artery disease:
The diagnosis of coronary disease underlying particular symptoms depends largely on the nature of the symptoms. The first investigation is an electrocardiogram (ECG/EKG), both for "stable" angina and acute coronary syndrome. An X-ray of the chest and blood tests may be performed.

Stable angina

In "stable" angina, chest pain with typical features occurring at predictable levels of exertion, various forms of cardiac stress tests may be used to induce both symptoms and detect changes by way of electrocardiography (using an ECG), echocardiography (using ultrasound of the heart) or scintigraphy (using uptake of radionuclide by the heart muscle). If part of the heart seems to receive an insufficient blood supply, coronary angiography may be used to identify stenosis of the coronary arteries and suitability for angioplasty or bypass surgery.

Stable coronary artery disease (SCAD) is also often called stable ischemic heart disease (SIHD). A 2015 monograph explains that "Regardless of the nomenclature, stable angina is the chief manifestation of SIHD or SCAD." There are U.S. and European clinical practice guidelines for SIHD/SCAD.

Acute coronary syndrome

Diagnosis of acute coronary syndrome generally takes place in the emergency department, where ECGs may be performed sequentially to identify "evolving changes" (indicating ongoing damage to the heart muscle). Diagnosis is clear-cut if ECGs show elevation of the "ST segment", which in the context of severe typical chest pain is strongly indicative of an acute myocardial infarction (MI); this is termed a STEMI (ST-elevation MI) and is treated as an emergency with either urgent coronary angiography and percutaneous coronary intervention (angioplasty with or without stent insertion) or with thrombolysis ("clot buster" medication), whichever is available. In the absence of ST-segment elevation, heart damage is detected by cardiac markers (blood tests that identify heart muscle damage). If there is evidence of damage (infarction), the chest pain is attributed to a "non-ST elevation MI" (NSTEMI). If there is no evidence of damage, the term "unstable angina" is used. This process usually necessitates hospital admission and close observation on a coronary care unit for possible complications (such as cardiac arrhythmias – irregularities in the heart rate). Depending on the risk assessment, stress testing or angiography may be used to identify and treat coronary artery disease in patients who have had an NSTEMI or unstable angina.

Risk assessment

There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on different variables above. A notable example is Framingham Score, used in the Framingham Heart Study. It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking and systolic blood pressure.

Prevention

Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. Prevention involves adequate physical exercise, decreasing obesity, treating high blood pressure, eating a healthy diet, decreasing cholesterol levels, and stopping smoking. Medications and exercise are roughly equally effective. High levels of physical activity reduce the risk of coronary artery disease by about 25%.

Most guidelines recommend combining these preventive strategies. A 2015 Cochrane Review found some evidence that counseling and education in an effort to bring about behavioral change might help in high risk groups. However, there was insufficient evidence to show an effect on mortality or actual cardiovascular events.

In diabetes mellitus, there is little evidence that very tight blood sugar control improves cardiac risk although improved sugar control appears to decrease other problems such as kidney failure and blindness. The World Health Organization (WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary artery disease while high intake increases the risk.

Diet

A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death. Vegetarians have a lower risk of heart disease, possibly due to their greater consumption of fruits and vegetables. Evidence also suggests that the Mediterranean diet and a high fiber diet lower the risk.

The consumption of trans fat (commonly found in hydrogenated products such as margarine) has been shown to cause a precursor to atherosclerosis and increase the risk of coronary artery disease.

Evidence does not support a beneficial role for omega-3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death). There is tentative evidence that intake of menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), may reduce the risk of CAD mortality.

Secondary prevention

Secondary prevention is preventing further sequelae of already established disease. Effective lifestyle changes include:
Aerobic exercise, like walking, jogging, or swimming, can reduce the risk of mortality from coronary artery disease. Aerobic exercise can help decrease blood pressure and the amount of blood cholesterol (LDL) over time. It also increases HDL cholesterol which is considered "good cholesterol".

Although exercise is beneficial, it is unclear whether doctors should spend time counseling patients to exercise. The U.S. Preventive Services Task Force found "insufficient evidence" to recommend that doctors counsel patients on exercise but "it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity and mortality", only the effectiveness of counseling itself. The American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise.

Treatment

There are a number of treatment options for coronary artery disease:

Medications

It is recommended that blood pressure typically be reduced to less than 140/90 mm Hg. The diastolic blood pressure however should not be lower than 60 mm Hg. Beta blockers are recommended first line for this use.

Aspirin

In those with no previous history of heart disease, aspirin decreases the risk of a myocardial infarction but does not change the overall risk of death. It is thus only recommended in adults who are at increased risk for coronary artery disease where increased risk is defined as "men older than 90 years of age, postmenopausal women, and younger persons with risk factors for coronary artery disease (for example, hypertension, diabetes, or smoking) are at increased risk for heart disease and may wish to consider aspirin therapy". More specifically, high-risk persons are "those with a 5-year risk ≥ 3%".

Anti-platelet therapy

Clopidogrel plus aspirin (dual anti-platelet therapy ) reduces cardiovascular events more than aspirin alone in those with a STEMI. In others at high risk but not having an acute event the evidence is weak. Specifically, its use does not change the risk of death in this group. In those who have had a stent more than 12 months of clopidogrel plus aspirin does not affect the risk of death.

Surgery

Revascularization for acute coronary syndrome has a mortality benefit. Percutaneous revascularization for stable ischaemic heart disease does not appear to have benefits over medical therapy alone. In those with disease in more than one artery coronary artery bypass grafts appear better than percutaneous coronary interventions. Newer "anaortic" or no-touch off-pump coronary artery revascularization techniques have shown reduced postoperative stroke rates comparable to percutaneous coronary intervention. Hybrid coronary revascularization has also been shown to be a safe and feasible procedure that may offer some advantages over conventional CABG though it is more expensive.

Epidemiology

Deaths due to ischaemic heart disease per million persons in 2012
  160–288
  289–379
  380–460
  461–576
  577–691
  692–894
  895–1,068
  1,069–1,443
  1,444–2,368
  2,369–7,233

Disability-adjusted life year for ischaemic heart disease per 100,000 inhabitants in 2004.
  no data
  less than 350
  350–700
  700–1,050
  1,050–1,400
  1,400–1,750
  1,750–2,100
  2,100–2,450
  2,450–2,800
  2,800–3,150
  3,150–3,500
  3,500–4,000
  greater than 4,000

As of 2010, CAD was the leading cause of death globally resulting in over 7 million deaths. This increased from 5.2 million deaths from CAD worldwide in 1990. It may affect individuals at any age but becomes dramatically more common at progressively older ages, with approximately a tripling with each decade of life. Males are affected more often than females.

It is estimated that 60% of the world's cardiovascular disease burden will occur in the South Asian subcontinent despite only accounting for 20% of the world's population. This may be secondary to a combination of genetic predisposition and environmental factors. Organizations such as the Indian Heart Association are working with the World Heart Federation to raise awareness about this issue.

Coronary artery disease is the leading cause of death for both men and women and accounts for approximately 600,000 deaths in the United States every year. According to present trends in the United States, half of healthy 40-year-old men will develop CAD in the future, and one in three healthy 40-year-old women. It is the most common reason for death of men and women over 20 years of age in the United States.

Society and culture

Names

Other terms sometimes used for this condition are "hardening of the arteries" and "narrowing of the arteries". In Latin it is known as morbus ischaemicus cordis (MIC).

Support groups

The Infarct Combat Project (ICP) is an international nonprofit organization founded in 1998 which tries to decrease ischemic heart diseases through education and research.

Industry influence on research

In 2016 research into the archives of the Sugar Association, the trade association for the sugar industry in the US, had sponsored an influential literature review published in 1965 in the New England Journal of Medicine that downplayed early findings about the role of a diet heavy in sugar in the development of CAD and emphasized the role of fat; that review influenced decades of research funding and guidance on healthy eating.

Research

Research efforts are focused on new angiogenic treatment modalities and various (adult) stem-cell therapies. A region on chromosome 17 was confined to families with multiple cases of myocardial infarction. Other genome-wide studies have identified a firm risk variant on chromosome 9. However, these and other loci are found in intergenic segments and need further research in understanding how the phenotype is affected.

A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.

Since the 1990s the search for new treatment options for coronary artery disease patients, particularly for so called "no-option" coronary patients, focused on usage of angiogenesis and (adult) stem cell therapies. Numerous clinical trials were performed, either applying protein (angiogenic growth factor) therapies, such as FGF-1 or VEGF, or cell therapies using different kinds of adult stem cell populations. Research is still going on – with first promising results particularly for FGF-1 and utilization of endothelial progenitor cells.

Myeloperoxidase has been proposed as a biomarker.

Dietary changes can decrease coronary artery disease. For example, data supports benefit from a plant-based diet and aggressive lipid lowering to improve heart disease.

War on Cancer

From Wikipedia, the free encyclopedia

The War on Cancer refers to the effort to find a cure for cancer by increased research to improve the understanding of cancer biology and the development of more effective cancer treatments, such as targeted drug therapies. The aim of such efforts is to eradicate cancer as a major cause of death. The signing of the National Cancer Act of 1971 by United States president Richard Nixon is generally viewed as the beginning of this effort, though it was not described as a "war" in the legislation itself.
 
Despite significant progress in the treatment of certain forms of cancer (such as childhood leukemia), cancer in general remains a major cause of death 40+ years after this war on cancer began, leading to a perceived lack of progress and to new legislation aimed at augmenting the original National Cancer Act of 1971. New research directions, in part based on the results of the Human Genome Project, hold promise for a better understanding of the genetic factors underlying cancer, and the development of new diagnostics, therapies, preventive measures, and early detection ability. However, targeting cancer proteins can be difficult, as a protein can be undruggable.

History

National Cancer Act of 1971

The war on cancer began with the National Cancer Act of 1971, a United States federal law. The act was intended "to amend the Public Health Service Act so as to strengthen the National Cancer Institute in order to more effectively carry out the national effort against cancer". It was signed into law by President Nixon on December 23, 1971.

Health activist and philanthropist Mary Lasker was instrumental in persuading the United States Congress to pass the National Cancer Act. She and her husband Albert Lasker were strong supporters of medical research. They established the Lasker Foundation which awarded people for their research. In the year of 1943, Mary Lasker began changing the American Cancer Society to get more funding for research. Five years later she contributed to getting federal funding for the National Cancer Institute and the National Heart Institute. In 1946 the funding was around $2.8 million and had grown to over $1.4 billion by 1972. In addition to all of these accomplishments, Mary became the president of the Lasker Foundation due to the death of her husband in 1952. Lasker's devotion to medical research and experience in the field eventually contributed to the passing of the National Cancer Act.

The improved funding for cancer research has been quite beneficial over the last 40 years. In 1971, the number of survivors in the U.S. was 3 million and as of 2007 has increased to more than 12 million.

NCI Director's Challenge

In 2003, Andrew von Eschenbach, the director of the National Cancer Institute (who served as FDA Commissioner from 2006-2009 and is now a Director at biotechnology company BioTime) issued a challenge "to eliminate the suffering and death from cancer, and to do so by 2015". This was supported by the American Association for Cancer Research in 2005 though some scientists felt this goal was impossible to reach and undermined von Eschenbach's credibility.

John E. Niederhuber, who succeeded Andrew von Eschenbach as NCI director, noted that cancer is a global health crisis, with 12.9 million new cases diagnosed in 2009 worldwide and that by 2030, this number could rise to 27 million including 17 million deaths "unless we take more pressing action."

Harold Varmus, former director of the NIH and current director of the NCI, held a town hall meeting in 2010 in which he outlined his priorities for improving the cancer research program, including the following:
  1. reforming the clinical trials system,
  2. improving utilization of the NIH clinical center (Mark O. Hatfield Clinical Research Center),
  3. readjusting the drug approval and regulation processes,
  4. improving cancer treatment and prevention, and
  5. formulating new, more specific and science-based questions.

Renewed focus on cancer

Recent years have seen an increased perception of a lack of progress in the war on cancer, and renewed motivation to confront the disease. On July 15, 2008, the United States Senate Committee on Health, Education, Labor, and Pensions convened a panel discussion titled, Cancer: Challenges and Opportunities in the 21st Century. It included interviews with noted cancer survivors such as Arlen Specter, Elizabeth Edwards and Lance Armstrong, who came out of retirement in 2008, returning to competitive cycling "to raise awareness of the global cancer burden."

Livestrong Foundation

The Livestrong Foundation created the Livestrong Global Cancer Campaign to address the burden of cancer worldwide and encourage nations to make commitments to battle the disease and provide better access to care. In April 2009, the foundation announced that the Hashemite Kingdom of Jordan pledged $300 million to fund three important cancer control initiatives – building a cutting-edge cancer treatment and research facility, developing a national cancer control plan and creating an Office of Advocacy and Survivorship. The Livestrong Foundation encourages similar commitments from other nations to combat the disease. 

Livestrong Day is an annual event established by the LAF to serve as "a global day of action to raise awareness about the fight against cancer." Individuals from around the world are encouraged to host cancer-oriented events in their local communities and then register their events with the Livestrong website.

21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act

The US Senate on 26 March 2009 issued a new bill (S. 717), the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act intended to "overhaul the 1971 National Cancer Act." The bill aims to improve patient access to prevention and early detection by:
  1. providing funding for research in early detection,
  2. supplying grants for screening and referrals for treatment, and
  3. increasing access to clinical trials and information.

Obama-Biden Plan to Combat Cancer

During their 2008 U.S. presidential campaign then Senators Barack Obama and Joe Biden published a plan to combat cancer that entailed doubling "federal funding for cancer research within 5 years, focusing on NIH and NCI" as well as working "with Congress to increase funding for the Food and Drug Administration." Their plan would provide additional funding for:
  • research on rare cancers and those without effective treatment options,
  • the study of health disparities and evaluation of possible interventions,
  • and efforts to better understand genetic factors that can impact cancer onset and outcomes.
President Obama's 2009 economic stimulus package includes $10 billion for the NIH, which funds much of the cancer research in the U.S., and he has pledged to increase federal funding for cancer research by a third for the next two years as part of a drive to find "a cure for cancer in our time." In a message published in the July 2009 issue of Harper's Bazaar, President Obama described his mother's battle with ovarian cancer and, noting the additional funding his administration has slated for cancer research, stated: "Now is the time to commit ourselves to waging a war against cancer as aggressive as the war cancer wages against us." On 30 September 2009, Obama announced that $1 billion of a $5 billion medical research spending plan would be earmarked for research into the genetic causes of cancer and targeted cancer treatments.

Cancer-related federal spending of money from the 2009 Recovery Act can be tracked online.

World Cancer Campaign

The International Union Against Cancer (UICC) has organized a World Cancer campaign in 2009 with the theme, "I love my healthy active childhood," to promote healthy habits in children and thereby reduce their lifestyle-based cancer risk as adults. The World Health Organization is also promoting this campaign and joins with the UICC in annually promoting World Cancer Day on 4 February.

Progress

Though there has been significant progress in the understanding of cancer biology, risk factors, treatments, and prognosis of some types of cancer (such as childhood leukemia) since the inception of the National Cancer Act of 1971, progress in reducing the overall cancer mortality rate has been disappointing. Many types of cancer remain largely incurable (such as pancreatic cancer) and the overall death rate from cancer has not decreased appreciably since the 1970s. The death rate for cancer in the U.S., adjusted for population size and age, dropped only 5 percent from 1950 to 2005. Cancer was expected to surpass cardiovascular disease as the leading cause of death in the world by 2010, according to the World Health Organization's World Cancer Report 2008. As of 2012, WHO reported 8.2 million annual deaths from cancer Heart disease (including both Ischaemic and hypertensive) accounted for 8.5 million annual deaths. Stroke accounted for 6.7 million annual deaths. 

There is evidence for progress in reducing cancer mortality. Age-specific analysis of cancer mortality rates has had progress in reducing cancer mortality in the United States since 1955. An August 2009 study found that age-specific cancer mortality rates have been steadily declining since the early 1950s for individuals born since 1925, with the youngest age groups experiencing the steepest decline in mortality rate at 25.9 percent per decade, and the oldest age groups experiencing a 6.8 percent per decade decline. Dr. Eric Kort, the lead author of this study, claims that public reports often focus on cancer incidence rates and under appreciate the progress that has been achieved in reduced cancer mortality rates.

The effectiveness and expansion of available therapies has seen significant improvements since the 1970s. For example, lumpectomy replaced more invasive mastectomy surgery for the treatment of breast cancer. Treatment of childhood leukemia and chronic myeloid leukemia (CML) have undergone major advances since the war on cancer began. The drug Gleevec now cures most CML patients, compared to previous therapy with interferon, which extended life for approximately 1 year in only 20-30 percent of patients.

Dr. Steven Rosenberg, chief of surgery at the NCI has said that as of the year 2000, 50% of all diagnosed cases of cancer are curable through a combination of surgery, radiation, and chemotherapy. Cancer surveillance experts have reported a 15.8 percent decrease in the age-standardized death rate from all cancers combined between 1991 and 2006 along with an approximately 1 percent annual decrease in the rate of new diagnoses between 1999 and 2006. A large portion of this decreased mortality for men was attributable to smoking cessation efforts in the United States.

A 2010 report from the American Cancer Society found that death rates for all cancers combined decreased 1.3% per year from 2001 to 2006 in males and 0.5% per year from 1998 to 2006 in females, largely due to decreases in the 3 major cancer sites in men (lung, prostate, and colorectum) and 2 major cancer sites in women (breast and colorectum). Cancer death rates between 1990 and 2006 for all races combined decreased by 21.0% among men and by 12.3% among women. This reduction in the overall cancer death rates translates to the avoidance of approximately 767,000 deaths from cancer over the 16-year period. Despite these reductions, the report noted, cancer still accounts for more deaths than heart disease in persons younger than 85 years.

An improvement in the number of cancer survivors living in the U.S. was indicated in a 2011 report by the CDC and the NCI, which noted that the number of cancer survivors in 2007 (11.7 million) increased by 19% from 2001 (9.8 million survivors). The number of cancer survivors in 1971 was 3 million. Breast, prostate, and colorectal cancers were the most common types of cancer among survivors, accounting for 51% of diagnoses. As of January 1, 2007, an estimated 64.8% of cancer survivors had lived ≥5 years after their diagnosis of cancer, and 59.5% of survivors were aged ≥65 years. A continued decline in cancer rates in the U.S. among both women and men, across most major racial groups, and in the most common cancer sites (lung, colon and rectum), was indicated in a 2013 report by the National Cancer Institute. However, the same report indicated an increase from 2000 to 2009 in cancers of the liver, pancreas and uterus.

Challenges

A multitude of factors have been cited as impeding progress in finding a cure for cancer and key areas have been identified and suggested as important to accelerate progress in cancer research. Since there are many different forms of cancer with distinct causes, each form requires different treatment approaches. However, this research could still lead to therapies and cures for many forms of cancer. Some of the factors that have posed challenges for the development of preventive measures and anti-cancer drugs and therapies include the following:
  • Inherent biological complexity of the disease:
  • Roadblocks to translational medicine
  • Challenges of early detection and diagnosis
  • The drug approval process
  • Availability of and access to patients with suitable tumor tissue for research
  • Challenges in implementing preventive measures, such as the development and use of preventive drugs and therapies
  • Choropleth mapping of the changes over time, of the national incidence rate, by cancer type, relative to the population at risk, is a technical challenge.
“The public is so jaded by cancer research media attention at the moment... And let’s face it, rather embarrassingly, most claimed ‘breakthroughs’ are not proving to significantly advance cancer therapies... It is a real conundrum for researchers today, because ‘early publicity’ is needed for funding, capital raising and professional kudos, but not too helpful for the public who then think that an immediate cure might be just around the corner.” Professor Brendon Coventry, 9 July 2013

Modern cancer research

Genome-based cancer research projects

The rise of a new class of molecular technologies developed during the Human Genome Project opens up new ways to study cancer and holds the promise for the discovery of new aspects of cancer biology that could eventually lead to novel, more effective diagnostics and therapies for cancer patients. These new technologies are capable of screening many biomolecules and genetic variations such as SNPs and copy number variations in a single experiment and are employed within functional genomics and personalized medicine studies.

Speaking on the occasion of the announcement of $1 billion in new funding for genome-based cancer research, Dr. Francis Collins, director of the NIH claimed, "We are about to see a quantum leap in our understanding of cancer." Harold Varmus, after his appointment to be the director of the NCI, said we are in a "golden era for cancer research," poised to profit from advances in our understanding of the cancer genome.

High-throughput DNA sequencing has been used to study the whole genome sequence of two different cancer tissues: a small-cell lung cancer metastasis and a malignant melanoma cell line. The sequence information provides a comprehensive catalog of approximately 90% of the somatic mutations in the cancerous tissue, providing a more detailed molecular and genetic understanding of cancer biology than was previously possible, and offering hope for the development of new therapeutic strategies gleaned from these insights.

The Cancer Genome Atlas

The Cancer Genome Atlas (TCGA), a collaborative effort between the National Cancer Institute and the National Human Genome Research Institute, is an example of a basic research project that is employing some of these new molecular approaches. One TCGA publication notes the following:
Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas...Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
In a cancer research funding announcement made by president Obama in September 2009, TCGA project is slated to receive $175 million in funding to collect comprehensive gene sequence data on 20,000 tissue samples from people with more than 20 different types of cancer, in order to help researchers understand the genetic changes underlying cancer. New, targeted therapeutic approaches are expected to arise from the insights resulting from such studies.

Cancer Genome Project

The Cancer Genome Project at the Wellcome Trust Sanger Institute aims to identify sequence variants/mutations critical in the development of human cancers. The Cancer Genome Project combines knowledge of the human genome sequence with high throughput mutation detection techniques.

Cancer research supportive infrastructure

Advances in information technology supporting cancer research, such as the NCI's caBIG project, promise to improve data sharing among cancer researchers and accelerate "the discovery of new approaches for the detection, diagnosis, treatment, and prevention of cancer, ultimately improving patient outcomes."

Modern cancer treatment

Cancer clinical trials

Researchers are considering ways to improve the efficiency, cost-effectiveness, and overall success rate of cancer clinical trials.

Increased participation in rigorously designed clinical trials would increase the pace of research. Currently, about 3% of people with cancer participate in clinical trials; more than half of them are patients for whom no other options are left, patients who are participating in "exploratory" trials designed to burnish the researchers' résumés or promote a drug rather than to produce meaningful information, or in trials that will not enroll enough patients to produce a statistically significant result.

Targeted tumor treatment

A major challenge in cancer treatment is to find better ways to specifically target tumors with drugs and chemotherapeutic agents in order to provide a more effective, localized dose and to minimize exposure of healthy tissue in other parts of the body to the potentially adverse effects of the treatments. The accessibility of different tissues and organs to anti-tumor drugs contributes to this challenge. For example, the blood–brain barrier blocks many drugs that may otherwise be effective against brain tumors. In November 2009, a new, experimental therapeutic approach for treating glioblastoma was published in which the anti-tumor drug Avastin was delivered to turmor site within the brain through the use of microcatheters, along with mannitol to temporarily open the blood–brain barrier permitting delivery of the chemotherapy into the brain.

Public education and support

An important aspect to the war on cancer is improving public access to educational and supportive resources, to provide individuals with the latest information about cancer prevention and treatment, as well as access to support communities. Resources have been created by governmental and other organizations to provide support for cancer patients, their families and caregivers, to help them share information and find advice to guide decision making.

Child abandonment

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