Anal Cancer

What is the anus?

The anus is an organ that lies at the end of the digestive tract
below the rectum. It consists of two sections: the anal canal and the
anus (or anal verge). The anal canal is a 3-4 cm long structure that
lies between the anal sphincter (one of the muscles controlling bowel
movements) just below the rectum and the anal verge which
represents the transition point between the digestive tract and the skin
on the outside of the body. Muscles within the anal canal and anus
control the passage of stool from the rectum to outside the body.

What is anal cancer?

Normally, cells in the body will grow and divide to replace old or
damaged cells in the body. This growth is highly regulated, and once
enough cells are produced to replace the old ones, normal cells stop
dividing. Tumors occur when there is an error in this regulation and
cells continue to grow in an uncontrolled way. Tumors can either be
benign or malignant. Although benign tumors may grow in an
uncontrolled fashion sometimes, they do not spread beyond the part of
the body where they started (metastasize) and do not invade into
surrounding tissues. Malignant tumors, however, will grow in such a
way that they invade and damage other tissues around them. They
also may spread to other parts of the body, usually through the blood
stream or through the lymphatic system where the lymph nodes are
located. Over time, the cells within a malignant tumor become more
abnormal and appear less like normal cells. This change in the
appearance of cancer cells is called the tumor grade, and cancer cells
are described as being well-differentiated, moderately-differentiated,
poorly-differentiated, or undifferentiated. Well-differentiated cells are
quite normal appearing and resemble the normal cells from which they
originated. Undifferentiated cells are cells that have become so
abnormal that often we cannot tell what types of cells they started
from.
Anal cancer is a malignant tumor of either the anal canal or anal
verge. In the United States, 80% of anal cancers are squamous cell
cancers,, resembling the cells found in the anal canal., This is not true
in other parts of the world, however. In Japan, 80% of anal cancers
are adenocarcinomas, resembling the glandular cells seen in the
rectum. Cancers of the anal verge may be referred to as perianal

skin cancers,because they usually behave more like skin cancers than
like anal cancers. They may respond more poorly to treatment than
other forms of anal cancers. Perianal skin cancers represent about
25% of all anal cancers. Occasionally, other types of cancer, such as
melanoma, Kaposis sarcoma, and lymphoma may develop in the anus.
These other types of cancer will be discussed separately, and will not
be addressed further in this review.
Anal cancers frequently begin as anal dysplasia. Anal dysplasia is
made up of cells of the anus that have abnormal changes, but do not
show evidence of invasion into the surrounding tissue. The most
severe form of anal dysplasia is called carcinoma in situ. In the case of
carcinoma in situ, cells have become cancerous, but have not begun to
invade normal tissue yet. Over time, anal dysplasia changes to the
point where cells become invasive and gain the ability to metastasize,
or break way to other parts of the body. Anal dysplasia is sometimes
referred to as anal intraepithelial neoplasia (AIN), or a pre-cancer.
When anal cancer does spread, it most commonly spreads through
direct invasion into the surrounding tissue or through the lymphatic
system. Spread of anal cancer through the blood is less common,
although it can occur.

What causes anal cancer and am I at risk?

Each year, there are approximately 4,000 cases of anal cancer in
the United States. In general, the incidence of anal cancers has been
increasing over the past 30-40 years. The vast majority (~85%) of
cases are in Caucasians. The incidence of anal cancer increases with
age: patients with anal cancer have an average (median) age of 62
years. Cancers of the anal canal are more common in women, while
the incidence of cancers of the anal verge is roughly equal in both men
and women.
Several factors have been associated with anal cancer. Most
importantly, infection with the human papilloma virus (HPV) has been
shown to be related to anal cancers and has been associated with
several other cancers including cervical cancer and cancers of the head
and neck. HPV can be transmitted from person to person through
sexual contact, so individuals with a history of multiple sexual
partners, anal receptive intercourse, and genital warts are at an
increased risk for infection. Probably due to the association between
HPV and anal cancer, women with history of cervical cancer are at
increased risk of developing anal cancer. Another sexually transmitted

virus, the human immunodeficiency virus (HIV), has been linked to

anal cancers, and individuals infected with HIV are at increased risk for
infection with HPV. The relationship between HIV and anal cancer will
be discussed in more detail in the next section (entitled "How are anal
cancer and HIV/AIDS related?")
Several other factors have been linked to anal cancer. Anal
cancer has been associated with smoking. Patients who smoke are
three times more likely to develop anal cancer as those that don't
smoke. The risk of anal cancer increases with the number of cigarettes
smoked per day and the number of years that a person has been
smoking.
There may be an association between anal cancer and
suppression of the immune system. The rate of anal cancer is higher in
patients who are immunosuppressed after organ transplants, although
this relationship is not clear.
Although there appears to be an increased rate of anal cancer in
patients who have benign anal conditions such as anal fistulae, anal
fissures, perianal abscesses, or hemorrhoids, it does not appear that
these benign conditions are a cause of anal cancer. Alternatively, an
undiagnosed anal cancer may actually be causing these conditions,
and then is subsequently diagnosed when the benign condition is being
treated.

How are anal cancer and HIV/AIDS related?

HIV is the virus responsible for Acquired Immune Deficiency
Syndrome (AIDS), a severe disease that results in loss of the ability of
the body to fight off certain types of infections. The incidence of anal
cancer is increased in patients with HIV. This is likely related to the
fact that patients with HIV are at an increased risk for infection with
HPV as well. This relationship between HIV and HPV is not related to
the immune status or the sexual practices of the patient infected with
HIV. The rate of infection of HPV is increased in patients with HIV even
if they do not engage in anal receptive intercourse and do not have
evidence of suppression of their immune system. A patient is
considered to have progressed from being HIV positive to having AIDS
if they develop certain infections or diseases that are uncommon
except in AIDS patients. Currently, anal cancer is not considered an

AIDS-defining illness. However, frequently, patients who have been

newly diagnosed with anal cancer are tested for HIV if they have other
risk factors for infection with HIV.

How can I prevent anal cancer?

Anal cancer is an uncommon cancer, and the risk of developing
anal cancer is quite low. Avoidance of risk factors for anal cancer,
however, will reduce the risk of development of anal cancer even
further. By far, the most important factor in developing anal cancer is
infection with HPV. Recently, Gardasil, a vaccine directed against HPV,
has been developed. This vaccination is currently recommended only
for girls and young women for prevention of cervical cancer.
Vaccination against HPV would certainly be expected to reduce the
incidence of anal cancer in both men and women, but, to date, no
studies have been published confirming this. The vaccine has not been
studied in boys and men, but data on this topic will likely be available
in the future. A number of studies examining the role of HPV vaccines
and anal cancer are currently under development.
Avoiding smoking and unsafe sexual practices can reduce the risk
of anal cancer. In patients who are known have anal dysplasia, careful
surveillance can result in early detection of anal cancer, and a higher
rate of cure with treatment., Removal of areas of anal dysplasia is
usually unsuccessful, however. The rate of recurrence of anal dysplasia
after surgical or laser removal is very high. This is likely due to the fact
that even if areas of dysplasia are removed, the patient remains
infected with HPV, which can cause the development of additional
areas of anal dysplasia.

What are the signs of anal cancer?

The most common initial symptom of anal cancer is rectal
bleeding, which occurs in about half of patients with new anal cancers.
Pain is somewhat less common, seen in about 30% of patients with
new anal cancers; however, it can be quite severe. Occasionally,
patients have the sensation of having a mass in the anus and may
experience itching or anal discharge. In certain patients, these
symptoms may be associated with the presence of warts in the anal
region. Rarely, in advanced cases, anal cancers can disrupt the
function of the anal muscles, resulting in loss of control of bowel
movements. In general, these symptoms are vague and non-specific.

As a result, in one-half to two-thirds of patients with anal cancer, a

delay of up to 6 months occurs between the time when symptoms
start and when a diagnosis is made.

How is anal cancer diagnosed?

When anal cancer is suspected, the physician should perform a
thorough history and physical examination. The physical exam should
consist of a digital rectal examination (DRE) as well as visualization of
the anal canal using an anoscope or bronchoscope (a long, thin
instrument that is inserted into the anus to allow the physician to see
the inside of the anus and rectum). Ultimately, anal cancer can only be
diagnosed with a biopsy. To perform a biopsy, the physician uses a
needle or a small pair of scissors or clamps to remove a piece of the
tumor. It is common for there to be some mild bleeding after a biopsy
is taken, and this bleeding can last for a few days after the procedure.
The tissue is then sent to a pathologist who looks at the tissue
underneath a microscope to determine whether the tumor is cancerous
or not. Because a number of benign tumors and lesions can resemble
anal cancer on physical examination, a biopsy should always be
performed before initiating treatment for anal cancer.

How is anal cancer staged?

Once a diagnosis of anal cancer is made, additional test should
be ordered to determine the extent of the disease. A CT (CAT) scan or
MRI of the abdomen and pelvis should be performed to look for
abnormally enlarged lymph nodes, which can result from spread of the
cancer, and to examine the liver for metastatic disease. A chest x-ray
is often performed to look for spread of the cancer to the lungs. In
some cases, an ultrasound of the tumor using a probe that is inserted
into the anus can be used to determine the amount of invasion of the
tumor into the surrounding tissues.
Anal cancer is most commonly staged using the TNM staging
system which is determined by the American Joint Committee on
Cancer. The "T stage" represents the extent of the primary tumor
itself. The "N stage" represents the degree of involvement of the
lymph nodes. The "M stage" represents whether or not there is spread
of the cancer to distant parts of the body. These are scored as follows:
T Stage

Tis: Carcinoma in situ

T0: No evidence of primary tumor

T1: Tumor 2 cm or less in greatest dimension

T2: Tumor is greater than2 cm but less than 5 cm in
greatest dimension

T3: Tumor is greater than5 cm in greatest dimension

T4: Tumor of any size that invades adjacent organs including
the vagina, urethra, or bladder. Tumors that invade the anal
sphincter only do not qualify as T4 tumors

N Stage

N0: No evidence of spread to the lymph node

N1: Spread of cancer to the lymph nodes directly adjacent to

the rectum (perirectal lymph nodes)

N2: Spread of the cancer to lymph nodes of the inguinal or

internal iliac lymph node chains on one side only.

N3: Spread of the cancer to lymph nodes of the inguinal or

internal iliac lymph node chains on both sides OR cancer
involvement of both the perirectal lymph nodes and the
inguinal lymph nodes

M Stage

M0: No evidence of distant spread of the cancer

M1: Evidence of distant spread of the cancer to other
organs, or to lymph node chains other than the ones lists
under "N stage"

The stage of the cancer is reported by stating the stage of the T, the
N, and the M. For example, a patient with a 4 cm tumor that had
spread to perirectal lymph nodes, but did not invade into adjacent
organs or spread to any other lymph nodes would be classified as
T2N1M0. The staging can be further condensed into a stage group,
which takes the various combinations of TNM and places them into
groups designated stage 0-IV. While there is a system for stage
grouping of anal cancers, these tumors are more commonly referred to
by their direct TNM stage.
Although this system of cancer staging is quite complicated, it is
designed to help physicians describe the extent of the cancer, and
therefore, helps to direct what type of treatment is given.

How is anal cancer treated?

Radiation Therapy
Radiation therapy has become the mainstay of treatment of anal
cancer. The radiation comes in the form of high energy x-rays that are
delivered to the patient only in the areas at highest risk for cancer.
These x-rays are similar to those used for diagnostic x-rays, but they
are of a much high energy. The high energy of x-rays in radiation
therapy results in damage to the DNA of cells. Cancer cells divide
faster than healthy cells, and so their DNA is more likely to be
damaged than that of normal cells. Additionally, cancer cells are
generally less able to repair damaged DNA than normal cells are, so
cancer cells are killed more easily by radiation than normal cells are.
Radiation therapy exploits this difference to treat cancers by killing
cancer cells, while killing fewer cells in normal, healthy tissue.
Typically, radiation for anal cancer is given daily, Monday through
Friday, for 5 to 6 weeks. The radiation treatments themselves are
short, lasting only a few minutes. Like diagnostic x-rays, radiation
treatments cannot be felt and do not hurt. Radiation is delivered like a
beam of light, only affecting areas where it is aimed. In treatment of
anal cancer, the radiation is usually aimed at the entire pelvis for the
first 2-3 weeks so that any cells in the lymph nodes surrounding the
anus are treated with radiation. After this, the radiation is aimed more
specifically at the anus in the lower part of the pelvis. Most commonly,
radiation treatment for anal cancer can result in irritation to the skin.
This reaction can be quite severe with redness, dryness, and
breakdown of the skin. Often, patients will require a break during
radiation treatment to allow the skin to heal prior to resuming
treatment. Other side effects of radiation can include fatigue, diarrhea,
and lowering of blood counts.

Chemotherapy
Chemotherapy refers to medications that are usually given
intravenously or in pill form. Chemotherapy travels throughout the
bloodstream and throughout the body to kill cancer cells. This is one of
the big advantages of chemotherapy. If cancer cells have broken off
from the tumor and are somewhere else inside the body,
chemotherapy has the chance killing them, while radiation does not. In
the setting of anal cancer, chemotherapy is most commonly given at
the same time as radiation. This will be discussed further below under
the section entitled "Combined Modality (Chemoradiotherapy)."
A number of different chemotherapeutic agents exist, each with
their own side effects. The most common chemotherapies used in anal
cancer are 5 flourouracil (5FU) and mitomycin C. Sometimes,
mitomycin C may be replaced with cisplatin in order to reduce
toxicities from chemotherapy. Exactly which chemotherapeutic agents
are given for anal cancer varies according to the physician giving
them. It is important to discuss the risk of each of these medications
with your medical oncologist. Based on your own health status and the
risks of side effects that you are willing to accept, the choice of
chemotherapy can vary.
Chemotherapy is used in different situations to treat anal cancer.
If the cancer is localized to the anus and pelvic lymph nodes, it may be
used in combination with radiation therapy to achieve the best chance
of killing all of the cancer cells (see Combined Modality
(Chemoradiotherapy).If the cancer has spread to distant parts of the
body, chemotherapy drugs such as cisplatin, carboplatin, and 5FU may
be used without radiation to reduce the number of tumor cells and
prevent or minimize symptoms all over the body. This is the case
because chemotherapy is able to travel throughout the bloodstream,
while radiation is not. In this setting, radiation may be used separately
to relieve certain symptoms, such as pain, from cancer in other parts
of the body. Unfortunately, if cancer is present in organs distant from
the anus, chemotherapy is generally not very successful at controlling
it.
Combined Modality (Chemoradiotherapy)
Chemotherapy has been shown to be radiosensitizing when given
at the same time as radiation therapy. This means that the effect of
the radiation is increased when given together with chemotherapy.
Several large trials have shown that local control of the tumor is

significantly improved when 5FU and mitomycin with chemotherapy

are used, as compared to radiation alone. Using chemotherapy and
radiation together has not been shown to change the rate of survival of
patients when compared to radiation alone; however, using
chemotherapy and radiation together has been shown to reduce the
risk of cancer recurring (coming back) in the anus. For this reason,
combined modality treatment is recommended for most patients with
anal cancer, unless a certain patient is unable to tolerate
chemotherapy and radiation together. If this is the case, the patient
may have radiation with or without chemotherapy given at a separate
time.
Surgery
Although surgery was the primary treatment for anal cancer 20
years ago, its role has greatly diminished since then. When performed,
surgical resection usually is an abdominal perineal resection (APR),
which consists of a wide excision of the anus, including the anal
muscles, with placement of a permanent colostomy. A colostomy is
performed by connecting the bowel to a hole in the abdominal wall
(called a stoma). The stool that passes through the stoma is collected
in a bag that is attached to the outside of the abdominal wall with
adhesive. This bag can then be emptied by the patient as needed.
Because the combination of chemotherapy and radiation therapy result
in similar rates of local control and survival when compared to surgery,
chemoradiation has been favored over surgery because it offers
patients a good chance at preserving anal sphincter function, avoiding
the need for permanent colostomy.

There are several situations in which surgery should be

considered for anal cancer. Patients with carcinoma in situ or small,
well-differentiated anal cancers that have not invaded into the anal
sphincter can sometimes undergo a surgical excision without removing
the anal muscles. In these early cases, the results of surgical excision
can be quite good, and the patient can avoid the potential side effects
of chemoradiotherapy. Alternatively, extensive anal cancers that have
destroyed the anal sphincter, such that the patient cannot control
bowel movements, are often treated with surgery (an APR). In these
cases, patients have already lost their sphincter function, and require a
colostomy to handle bowel movements. Because patients in this

situation usually have very large tumors, they may require surgical
removal of the tumor, which will usually be followed by radiation, with
or without chemotherapy, after the operation. Surgery can also be
performed in patients who cannot otherwise tolerate radiation therapy,
or who do not want radiation therapy Finally, surgery is often
performed if cancer recurs in the anus following previous treatment
with radiation therapy if additional chemotherapy and radiation cannot
be given.

After I am treated for anal cancer, how will I be

followed?
After treatment for anal cancer, patients are usually followed
every 3-6 months for several years with or without CT scans. The most
important aspect of follow-up after completion of treatment is a
thorough physical examination including a digital rectal exam. Anal
cancers can take some time to respond to treatment and often
continue to shrink months after chemotherapy and radiation have
ended. Therefore, it is not unusual to have a residual mass
immediately after treatment. The presence of a residual mass does not
mean that the treatment did not work. Overall, the chance of longterm cure of anal cancer depends on the extent of the disease at the
time it was first diagnosed. Patients with smaller disease without
lymph node involvement or distant metastases have a better chance at
long-term tumor control than those with larger disease or with lymph
node involvement or distant metastases. If anal cancers do recur, they
usually do so within the first 2 years after treatment, although
recurrences after 2 years can occur. In general, the further out from
treatment a patient is without evidence of a recurrence, the better the
chances that the cancer will never come back.
The treatment of anal cancer should be a cooperative effort
among the patient, the radiation oncology, the medical oncologist, and
the surgeon. It is important that all patients with anal cancer know
about their disease so that they can make an informed decision about
their treatment. This article was intended to help answer some of the
common questions patients face when they have anal cancer. If you
have any additional questions, please contact your doctor.

TUGAS L.BAHASA INGGRIS

Disusun Oleh :
YULIANTO WICAKSON ( 06.092 )

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