CANCER
Cancer is new growth of tissue
resulting from a continuous proliferation of abnormal cells that have the
ability to invade and destroy other tissues. Cancer, which may arise from any
type of cell and in any body tissue, is not a single disease but a large number
of diseases classified according to the tissue and type of cell of origin.
Several hundred such classes exist, constituting three major subtypes:
Sarcomas arise from connective and
supportive tissue, such as bone, cartilage, nerve, blood vessels, muscle and
fat. Carcinomas, which include the most frequently occurring forms of human
cancer, arise from epithelial tissue, such as the skin and the lining of the
body cavities and organs and the glandular tissue of the breast and prostate.
Carcinomas with a structure resembling skin are termed squamous-cell
carcinomas. Those that resemble glandular tissue are called adenocarcinomas.
Leukaemias and lymphomas include the cancers that
involve blood-forming tissue and are typified by the enlargement of the lymph
nodes, the invasion of the spleen and bone marrow and the overproduction of
immature white cells.
Prognosis and the Long-Term Picture
Many people are now successfully
treated for cancer. The modern approach to cancer treatment also includes an
emphasis on the patient's quality of life—both physical and mental. It is
estimated that more than five million living Americans have had cancer: three
million have survived more than five years and 
nearly all the survivors can be
regarded as cured. There are many forms of cancer where the chances of survival
are many times better than they were just a few years ago. The field of
children's cancers is perhaps the most encouraging. For instance, nine out of
ten children recover from Hodgkin's disease, but 30 years ago only about half
survived. Other forms of cancer such as non-Hodgkin's disease and some leukaemias can be successfully treated as can certain forms
of non-invasive bladder cancer, which if detected early can be contained over a
period of several years.
The death rate from cancer has
fallen progressively in people under 50 probably because healthier habits and
environment have reduced prolonged exposure to carcinogens. Earlier diagnosis,
which is absolutely vital in all cases and improved treatments are also
involved. This drop is expected to extend to older age groups as these younger
people age.
Decreases in the number of smokers
in some countries are starting to have an impact on the cancer figures.
Scottish women have the highest rate of death from lung cancer in the world.
The overall risk of death from cancer has increased over the past 30 years.
This is because cancer is mainly a disease of older age and as we become more
successful at preventing early deaths from other illnesses such as heart
attacks more people are living long enough to reach an age where their cancer
risk is higher.
How Cancer Occurs
Cancer is a multi-stage process
where a series of irreversible genetic errors occur in a cell in the body
during a patient's lifetime. The early stages are critical for setting the
process off. Later changes lead to spread and increased growth rate and are
triggered by a range of external factors known as promotors.
These errors may happen because the person has been exposed to cancer-causing
agents (carcinogens). For instance cigarette smoke contains many chemical
initiators and promotors.
In some people, however, there are
also inherited gene defects which can give a potential cancerous cell a head
start. Genes are made of DNA and are found in the center of the cell in
structures known as chromosomes. Humans have 23 pairs of chromosomes and over
50,000 genes. If a chromosome is likened to a book each gene is a paragraph; a
fault in a gene may be likened to a misprint.
Every time a cell divides a copy is
made of the DNA. Sometimes an error occurs and a new cell ends up 
with an altered gene—a mutation. If
the mutation occurs in a gene which normally controls cell growth, that cell
may acquire the potential to become a cancer cell.
A cancerous growth or neoplasm is
therefore clonal—that is, all its cells are
descendants of a single cell. These cells have escaped the control of the
normal forces regulating cellular growth. Resembling embryonic cells they are
unable to differentiate or mature into an adult functioning state. As these
cells multiply, they may form a mass called a tumor, which enlarges and
continues to grow without regard to the function of the tissue of origin.
The body has ways of fighting back
against mutations and a number of faults has to
accumulate before a tumor develops. This can take a long time, which is why
cancer is mainly a disease of older people; for instance 95% of bowel cancers
occur in those over 50.
Tumors
Almost all cancers form tumors, but
not all tumors are cancerous or malignant; the greatest number are benign.
Benign tumors are characterized by entirely localized growth and are usually
separated from neighboring tissue by a surrounding capsule. Benign tumors
generally grow slowly and in structure closely resemble the tissue of origin.
In some instances they may endanger the patient by obstructing, compressing or
displacing neighboring structures as in the brain. A few benign tumors such as
polyps of the colon may be precancerous.
Invasion and Spreading
The most significant attribute of
malignant tumors is their ability to spread beyond the site of origin. Cancer
may invade neighboring tissues by direct extension or infiltration or it may disseminate
to distant sites forming secondary growths known as metastases. The routes and
sites of metastases vary with different primary cancers:
(1) When a cancer extends through
the surface of the organ of origin into a cavity, cells may break away from the
surface and become implanted on the surface of adjacent organs.
(2) Tumor cells may migrate into the
lymphatic channels and be carried to the draining lymph nodes or they may
penetrate the blood vessels. Once in the bloodstream the tumor cells are carried
to the point at which the vessels become too small for the large tumor cells to
pass. Cells from tumors of the gastrointestinal tract will be stopped in the
liver. Later they may go on to the lungs. Cells from all other tumors will go
to the lungs before being carried to other organs. The lungs and liver are
therefore common sites of metastases.
(3) Many cancers tend to shed cells
into the bloodstream early in their course. Most of these cells die in the
bloodstream, but some lodge against the surface and penetrate the wall into the
tissue. A few may find themselves in a favorable tissue in which they are able
to survive and grow into a tumor; this is known as a metastasis. Others may
divide only a few times, forming a small nest of cells that then remain dormant
as a micrometastasis. They may remain dormant for
many years, only to begin to grow again as recurrent 
cancer, for reasons unknown.
Cancer cells even when widely
disseminated may retain the physical and biological characteristics of their tissue
of origin. Thus a pathologist can often determine the site of origin of metastatic tumors by microscopic examination of the
cancerous tissue. Identification of tumors of the endocrine glands is
simplified because they may produce excessive amounts of the hormone that is
produced by the parent tissue. Such tumors may also respond to administration
of the hormones that normally control that tissue.
In general, the less closely a
cancer resembles its tissue of origin, the more malignant and rapidly invasive
it tends to be; however, the rate of growth of a cancer depends not only on
cellular type and the degree of dedifferentiation from the tissue of origin,
but also on various host factors. A characteristic of malignancy is tumor-cell
heterogeneity. Because of the abnormalities of proliferation in tumor cells,
they are more susceptible to mutation. With time, a tumor tends to become less
differentiated and to grow more rapidly. It may also develop increased
resistance to chemotherapy or irradiation.
Occurrence
Cancer is the second leading cause
of death in adults in the Western world and is one of the leading causes of
death from disease in children between the ages of 1 and 14. However despite
this it is still rare in young people.
For particular cancers, the
difference between countries may be as high as 40-fold. Evidence from studies
of populations that have migrated from one geographical area to another
suggests that these variations are due to differences in lifestyle rather than
ethnic origin. This is consistent with other evidence that most cancers are
predominately related to environmental causes rather than heredity, although
the two may interact.
The cancers that cause
the most deaths in
Causes, Prevention, and Early Detection
About 80% of cancers are potentially
preventable. The biggest known cause is smoking, which accounts for 30% of
deaths from the disease. Although all the causes of cancer are yet to be
ascertained, accumulating evidence about the effects of smoking, diet,
radiation, hereditary factors, hormones, chemicals and certain types of
infection shows that these factors may be involved.
It is already known that there are
several things people can do to cut the risk of cancer. Everyone should:
Avoid getting sunburnt;
Take up offers
of cancer screening tests;
Eat a healthy
diet;
Only drink
moderate amounts of alcohol;
Observe safety
rules in jobs where exposure to chemicals, radiation, and other hazards
increases risk; and most importantly,
Not smoke.
Smoking
Smoking is one of the biggest causes
of premature death in the Western world. Not only does it cause 
over one third of cancers, but it
also causes heart disease and major forms of lung disease, such as chronic
bronchitis and emphysema. Smoking has already killed 60 million people
worldwide since 1950 and is likely to kill half a billion of those alive today
unless current habits are changed. Out of 1,000 young adults (if they all
smoke) on average 1 will be murdered; 6 will be killed on the roads and 250
will be killed by smoking in middle age alone.
Smoking causes 90% of lung cancers.
It can also cause cancer in a number of other parts of the body, including the
mouth, pharynx, larynx, oesophagus, pancreas, renal
pelvis, bladder and cervix.
There can be no doubt that giving up
smoking brings down the risk. If a person manages to give up
smoking before developing cancer (or some other serious disease), most of the
risk of dying from smoking-related diseases may be avoided. After ten
years the risk will be more than halfway towards that of someone who has never
smoked.
Diet
Diet is probably linked to about
30-35% of cancers. Many researchers believe that it plays a part in many of the
most common cancers, such as those of the breast and bowel. However as yet
there is no concrete proof of which elements can cause cancer and which help to
protect against it.
At the moment evidence suggests a
protective role for fruit, vegetables, fiber and certain vitamins. Other
factors such as a high-fat or excessive meat diet are thought to increase risk.
For instance many researchers think that an increased intake of fresh fruit and
vegetables decreases the risk of stomach cancer. People who eat moderate
amounts of fruit such as one piece of fruit per day have a substantially lower
risk of developing this cancer.
Reducing calories from fat to 20% of
the diet, cutting down on red meat, increasing dietary fiber (such as wholemeal bread, fruits and vegetables) and eating
protective foods (foods that contain vitamins C and A, as well as vegetables such
as cabbage, cauliflower, broccoli and Brussels sprouts) all provide benefits.
Foods (mainly vegetables) containing beta-carotene, an antioxidant which is
converted to vitamin A in the body, are thought to provide some protection
against the cell changes that may lead to cancer. Moderation in eating
salt-cured, smoked and nitrite-cured foods and in the consumption of alcohol is
also advised.
Apart from eating a healthy diet,
keeping weight down is also an important measure in cutting cancer risk. Obesity
increases the risk of breast, bowel, uterus and prostate cancers. Some recent
studies have shown that moderate exercise may also play a part in preventing
cancer as well as maintaining general good health.
Over-consumption of alcohol is
responsible for 3% of cancer deaths. Cancers of the mouth, throat and oesophagus are linked to this, with those most at risk
being people who drink excessively and smoke cigarettes.
Infections 
There is growing evidence that some
infections are linked to certain cancers. In particular, infections have been
found to be involved in cancers of the stomach, liver, cervix and in Kaposi's
sarcoma—a rare cancer which is common in AIDS patients.
The bacterium Helicobacter pylori
may help to cause many cases of stomach cancer. Studies have shown that people
infected with the bacterium are four times more likely to develop this cancer.
Cervical cancer is linked to two
sexually transmitted types of human papilloma
virus—HPV-16 and HPV-18. HPV infection is quite common and most women who are
infected do not develop cervical cancer. However, it does seem that HPV
infection is an extremely important step in the development of the
disease—often occurring several years before the appearance of cancer. Research
is now under way to find a vaccine against these types of HPV.
People who are carriers of some
types of viruses are at greatly increased risk of cancer. Childhood infection
may be particularly important. When viruses like hepatitis B (which contributes
to liver cancer) are contracted at birth or during early childhood, the patient
becomes a carrier. In countries like
Hormones, Radiation, and Occupational Factors
Certain cancers particularly of the
breast and prostate have a hormonal link and some medical researchers
think that hormones may act as tumor promoters in these cancers. Research is
continuing into how the growth of cancer cells may be accelerated by hormones
and slowed down by hormone-b
locking drugs.
As well as being a successful
treatment for cancer, radiation can cause cancer. The risk from radiation is
related directly to the dose received, and therefore for most people the amount
received in a lifetime is relatively small. People who live in areas with high
levels of radon, a radioactive gas, are more at risk of developing lung cancer.
Ultraviolet (UV) radiation types A
and B from sunlight are responsible for most skin cancers. UV is at its
strongest during the summer months and people need to protect themselves by not
exposing the skin for long periods and by wearing a hat with a wide brim which
shades the face; by avoiding exposure to the midday sun; and by applying a
high-factor sunscreen of at least SPF15 on exposed skin at regular intervals,
especially before and after swimming. These precautions apply equally to summer
in European climates as to summer in hotter ones. Particular attention to this
problem in Australia has resulted in health campaigns encouraging people to take
precautions against sun exposure.
Skin cancer rates in
Certain occupations carry an
increased risk of cancer because workers are exposed to hazardous substances
such as chemicals, asbestos or radiation. It is therefore very important for
work safety procedures to be put in place, to provide as much protection for
workers as possible and for workers to follow the guidelines.
Hereditary Factors
It is estimated that 5-10% of
cancers are inherited and extensive research is being done to find the faulty
genes responsible. Some of these genes have already been found; for instance,
the genes BRCA1 and BRCA2 are linked to some hereditary breast cancers.
Mutations in BRCA1 are also responsible for about 80% of inherited ovarian
cancers.
Detection and Diagnosis
The earlier a cancer is diagnosed
and treated the greater the chance is of a cure. Screening is useful for
detecting some cancers, but people still need to be aware of symptoms as
cancers may occur between screenings and everyone should take notice of the
early warning signs of cancers for which there is no screening available. The
following list of symptoms warrants attention:
Change in
bowel or bladder habits.
A sore throat that does not heal.
Unusual bleeding or discharge.
Thickening or
lump in the breast or elsewhere.
Indigestion or difficulty in swallowing.
Obvious change in a wart or mole.
Nagging cough or hoarseness.
Any of these symptoms, indeed any
unexplained lump, pain, weight loss, or lethargy, should be referred to a
doctor. Although one or more symptoms may be indicative of something other than
cancer, a check-up to confirm their cause is the best course of action.
A physical examination for cancer
includes inspection and palpation of all accessible sites, especially the skin,
neck, breasts, abdomen, testicles, and lymph-node areas. It may include
examination of bodily orifices, particularly rectal examination for cancers of
the rectum or prostate, and pelvic examination for
cancers of the cervix or uterus.
Screening and Self-examination
The earlier a cancer is diagnosed
the greater the chance of cure. A monthly check for changes in the way your
body looks and feels can help early detection of breast, skin and testicular
cancer. Some cancers 
can be detected at an early or
pre-cancerous stage through screening.
Cervical screening can detect
cervical cancer. More importantly, it can prevent this cancer because it
detects pre-cancerous cells. Doctors are now considering ways of improving the
screening program—including the possibility of adding a test for HPV-16 to the
smear test.
Bowel cancer also has a
pre-cancerous stage which can be detected by screening. One method under
consideration uses a thin flexible tube (a sigmoidoscope)
to detect polyps in the bowel which, if left, may turn cancerous. Studies suggest
that removing these benign growths will nearly halve a person's risk of cancer
for about ten years. Some doctors recommend that screening should begin at a
younger age, but recent studies indicate that mammography may not benefit
pre-menopausal women because their breast tissue is more dense making
mammograms consequently much harder to read.
Biopsy
The biopsy remains the only
definitive method for the diagnosis of a cancer. In a biopsy a section of
tissue is removed from the tumor itself or from a metastasis. Modern technology
has greatly reduced the need for open surgical biopsy. Guided by palpation or a
computerized axial tomography (CAT or CT) scan a tumor in almost any part of
the body can be biopsied through a thin flexible
needle. This permits diagnosis before surgery so that the doctor and patient
can better plan for treatment and surgery, if it is necessary.
Staging
Once a tissue diagnosis of cancer
has been made the extent or stage of the disease must be evaluated because
prognosis and appropriate treatment vary with the stage of the disease. For
each type of tumor the stage (I, II, III, or IV) is defined in terms of
findings with progressively more severe prognostic implications: small local
tumor, more extensive local tumor, regional lymph node involvement and distant
metastases. The clinical stage, defined by information obtained prior to
surgical exploration, is used to decide appropriate initial treatment. The
surgical stage, which may be different from the clinical, incorporates the findings
of the surgical exploration, and is used as a basis for later treatment and for
prognosis. It is also used to analyze the effects of different treatments.
Treatment
The traditional means of treating
cancer have been surgery, radiation and chemotherapy. However, revolutionary
treatments are now under development and researchers are using laboratory
discoveries to design drugs that will exploit specific biological processes in
cancer.
Surgery
The principal approach to curing
cancer is to remove all the malignant cells by a surgical operation. In the
past this meant the removal of all of the involved tissue and as much
potentially involved tissue as possible including adjacent tissues and lymph
nodes. For some tumors notably cancer of the breast this radical degree of
surgery (mastectomy) is not always necessary. Refinements in surgical
techniques improved knowledge of physiology, advances in anesthesia, ready
availability of blood products and potent antibiotics have permitted less
extensive surgery with more rapid recovery and less resulting disability. Many
cancers though are at too advanced a stage at the time of diagnosis to be
eradicated by surgery. If local extension involves neighboring tissues that cannot
be sacrificed or if distant metastases are already present surgery will not
cure the cancer. Even when it is clear that surgical cure is not possible,
however, surgery may help to relieve symptoms, such as obstruction, or to
reduce the size of the tumor in an effort to improve the patient's response to
subsequent radiotherapy or chemotherapy.
Radiation Therapy 
Ionizing radiation, which may be
either electromagnetic or particulate, is destructive to tissue.
Electromagnetic radiation includes gamma rays, which are emitted by radioactive
decay and X-rays, which are produced when a beam of electrons strikes a
heavy-metal target. Particulate radiation includes beams of electrons, protons,
neutrons, alpha particles (helium nuclei) and negative pi mesons (pions).
Tumors vary greatly in their
sensitivity to radiation. A “sensitive” tumor is one that is more sensitive
than surrounding normal tissues. When such a tumor is readily accessible—a
superficial tumor or one in an organ like the uterus into which a radiation
source can be introduced—it may be curable by radiation therapy. Because of its
relatively sparing effect on normal tissues, radiation is useful when a tumor
cannot be removed because surgery would damage vital adjacent tissue or because
it has begun to infiltrate adjacent structures that cannot be sacrificed.
Radiation therapy is also extremely useful for palliation (temporary relief)
especially of metastatic tumors.
Radiation can also be a valuable
adjunct to surgery. Pre-operative radiation may rapidly sterilize the tumor
cells and prevent them from seeding at surgery. It may also shrink the tumor
and make surgery easier or shrink an inoperable tumor so that it becomes
operable. In other tumors post-operative radiation is used.
Chemotherapy
Chemotherapy is the use of drugs in
the treatment of cancer. Since a drug is distributed throughout the body by the
bloodstream, chemotherapy is prescribed for tumors that have spread beyond the
area accessible by surgery or radiotherapy. A number of different types of
anticancer drugs are used, but nearly all work by interfering with DNA
synthesis or function. Rapidly dividing cells are therefore more sensitive to
chemotherapy. Cancers have a larger proportion of dividing cells than do normal
tissues, in which stem, or replenishing, cells are dormant. This means they are
more resistant to drug effect than the cancer cells, which proliferate rapidly.
The most rapidly proliferating normal cells are in the bone marrow and the
cells lining the gastrointestinal tract. These are the most sensitive normal
areas likely to be affected by chemotherapy and therefore constitute the sites
of toxicity that will limit the tolerable dose of most drugs.
Therefore, to be effectively treated
a tumor must have a sensitivity greater than that of the most sensitive normal
tissue. Some tumors may be many times more sensitive, but many are only
slightly more sensitive. Fortunately, the normal bone marrow cells can divide
faster than malignant cells and thus recover more rapidly. This permits a
repeat cycle of the drug before the tumor has regrown
to any great extent. Repeated cycles can steadily deplete a tumor before
resistance occurs. Some tumors are so sensitive to chemotherapy that a
chemotherapeutic cure is possible in a high percentage: uterine cancer; acute
leukemia, especially in children; Hodgkin's disease and diffuse large-cell
lymphoma; testicular carcinoma; and several childhood cancers are examples.
These cancers have often already spread at the time of diagnosis and cannot be
treated by other means. However, other advanced cancers respond well to
chemotherapy and can be controlled for a long time, so chemotherapy is commonly
used for palliation.
Two major problems limiting the
usefulness of chemotherapy are toxicity and resistance. Techniques that avoid
or control toxicity and reduce the risk of resistance have steadily improved.
It is important to begin treatment as early as possible, to use the optimal
dose of the drug, and to repeat cycles as quickly as possible, while giving the
patient a chance to recover somewhat from toxicity.
The use of multiple drugs is
effective. Combination chemotherapy employs several drugs (often
High doses of chemotherapy can be
given if a bone marrow transplant or bone marrow or stem cell rescue is part of
the treatment regime. This is most often used in leukemia treatment, but there
are trials under way in other cancers.
Chemotherapy may be used with
surgery or radiation as combined modality therapy. It is often used as an
adjuvant, or helper, when surgery is the primary therapy. As such it is usually
given after surgery. This type of therapy has greatly increased the cure rate
of breast cancer. The major purpose of chemotherapy as an adjuvant is to kill
off micrometastases that may have been established
before surgery. Recently, chemotherapy has been used before surgery as a neoadjuvant. This therapy has the same effect as adjuvant
chemotherapy but may also shrink a tumor making it more easily operable.
Hormone Therapy
Many cancers arising from tissues
that are hormone-dependent such as the breast, prostate, endometrium (uterine
lining) and thyroid are responsive to hormone manipulation. This may consist of
removing the source of the stimulating hormone or the administration of various
hormones and antihormones.
Other Approaches
Several promising new approaches to
the treatment of cancer are being taken. In one, biological agents known as
biological response modifiers are used to modify the response of the body
(particularly the immune system) to cancer. Another approach involves
biological agents that stimulate certain cells, which can then attack the
malignant cells. The best example is the use of interleukin-2 to stimulate the
patient's lymphokine-activated killer lymphocytes
(LAK cells). Research is also concerned with tumor-specific antigens against
which antibodies could be raised. These anti-tumor antibodies would be used to
treat cancer either directly or by coupling to a chemotherapeutic agent. The
antibody could identify the malignant cell and stick to it, thus delivering the
drug directly to the target.
Other New Approaches
Another growing area of research is
gene therapy. This employs various methods to introduce genetic material into
the cancer to make it more recognizable to the immune system. It can also make
the cancer cells more sensitive to drug treatments, or it can place new genes
into T-cells to make them more active. Work is under way to develop vaccines by
removing cells from the patient and modifying them in the laboratory so that
they secrete a protein that stimulates the immune system. The cells are
irradiated to stop them dividing, and are then injected into the patient.
Even if cured, a cancer patient may be
left with serious disabilities. Every effort must be made to achieve the
maximum possible quality of life through rehabilitative techniques, including
reconstructive surgery. For the patient who is not cured, palliative therapy
may achieve comfort and good function for months or years. Pain can be a severe
problem, as can depression, but both can be relieved today much more than in
the past.
