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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 œperianal

cells have become cancerous. Occasionally. such as melanoma. but do not show evidence of invasion into the surrounding tissue. women with history of cervical cancer are at increased risk of developing anal cancer. The incidence of anal cancer increases with age: patients with anal cancer have an average (median) age of 62 years. or break way to other parts of the body. it most commonly spreads through direct invasion into the surrounding tissue or through the lymphatic system. Over time. but have not begun to invade normal tissue yet. Anal dysplasia is made up of cells of the anus that have abnormal changes. Several factors have been associated with anal cancer. The vast majority (~85%) of cases are in Caucasians. They may respond more poorly to treatment than other forms of anal cancers. The most severe form of anal dysplasia is called carcinoma in situ. What causes anal cancer and am I at risk? Each year. and lymphoma may develop in the anus.000 cases of anal cancer in the United States. HPV can be transmitted from person to person through sexual contact.skin cancers. In general. anal receptive intercourse. These other types of cancer will be discussed separately. so individuals with a history of multiple sexual partners. although it can occur. 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. When anal cancer does spread. Probably due to the association between HPV and anal cancer. anal dysplasia changes to the point where cells become invasive and gain the ability to metastasize. Spread of anal cancer through the blood is less common. while the incidence of cancers of the anal verge is roughly equal in both men and women. In the case of carcinoma in situ. or a pre-cancer. other types of cancer.because they usually behave more like skin cancers than like anal cancers. the incidence of anal cancers has been increasing over the past 30-40 years. Anal cancers frequently begin as anal dysplasia. Cancers of the anal canal are more common in women. Anal dysplasia is sometimes referred to as anal intraepithelial neoplasia (AIN). there are approximately 4. and genital warts are at an increased risk for infection. Kaposis sarcoma. Most importantly. Perianal skin cancers represent about 25% of all anal cancers. and will not be addressed further in this review. Another sexually transmitted .

anal fissures. 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. or hemorrhoids. 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. This relationship between HIV and HPV is not related to the immune status or the sexual practices of the patient infected with HIV. Alternatively. 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. This is likely related to the fact that patients with HIV are at an increased risk for infection with HPV as well. The rate of anal cancer is higher in patients who are immunosuppressed after organ transplants. and individuals infected with HIV are at increased risk for infection with HPV. perianal abscesses. it does not appear that these benign conditions are a cause of anal cancer. anal cancer is not considered an . Patients who smoke are three times more likely to develop anal cancer as those that don't smoke. Although there appears to be an increased rate of anal cancer in patients who have benign anal conditions such as anal fistulae. The incidence of anal cancer is increased in patients with HIV. Anal cancer has been associated with smoking. has been linked to anal cancers. an undiagnosed anal cancer may actually be causing these conditions. a severe disease that results in loss of the ability of the body to fight off certain types of infections. How are anal cancer and HIV/AIDS related? HIV is the virus responsible for Acquired Immune Deficiency Syndrome (AIDS). the human immunodeficiency virus (HIV). 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. and then is subsequently diagnosed when the benign condition is being treated. although this relationship is not clear. Currently.virus.

resulting in loss of control of bowel movements. these symptoms are vague and non-specific. A number of studies examining the role of HPV vaccines and anal cancer are currently under development. anal cancers can disrupt the function of the anal muscles.. has been developed.AIDS-defining illness. but. it can be quite severe. and a higher rate of cure with treatment. What are the signs of anal cancer? The most common initial symptom of anal cancer is rectal bleeding. patients who have been newly diagnosed with anal cancer are tested for HIV if they have other risk factors for infection with HIV. which can cause the development of additional areas of anal dysplasia. however. these symptoms may be associated with the presence of warts in the anal region. Occasionally. In certain patients. frequently. the patient remains infected with HPV. The rate of recurrence of anal dysplasia after surgical or laser removal is very high. The vaccine has not been studied in boys and men. Recently. In patients who are known have anal dysplasia. . and the risk of developing anal cancer is quite low. patients have the sensation of having a mass in the anus and may experience itching or anal discharge. Rarely. By far. Avoiding smoking and unsafe sexual practices can reduce the risk of anal cancer. Removal of areas of anal dysplasia is usually unsuccessful. careful surveillance can result in early detection of anal cancer. a vaccine directed against HPV. This is likely due to the fact that even if areas of dysplasia are removed. This vaccination is currently recommended only for girls and young women for prevention of cervical cancer. seen in about 30% of patients with new anal cancers. to date. however. however. Vaccination against HPV would certainly be expected to reduce the incidence of anal cancer in both men and women. the most important factor in developing anal cancer is infection with HPV. which occurs in about half of patients with new anal cancers. Gardasil. How can I prevent anal cancer? Anal cancer is an uncommon cancer. Avoidance of risk factors for anal cancer. In general. Pain is somewhat less common. will reduce the risk of development of anal cancer even further. However. no studies have been published confirming this. in advanced cases. but data on this topic will likely be available in the future.

The "T stage" represents the extent of the primary tumor itself. a delay of up to 6 months occurs between the time when symptoms start and when a diagnosis is made. additional test should be ordered to determine the extent of the disease. 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. Because a number of benign tumors and lesions can resemble anal cancer on physical examination. To perform a biopsy. 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. in one-half to two-thirds of patients with anal cancer. and this bleeding can last for a few days after the procedure. anal cancer can only be diagnosed with a biopsy. The "M stage" represents whether or not there is spread of the cancer to distant parts of the body. a biopsy should always be performed before initiating treatment for anal cancer. 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. the physician uses a needle or a small pair of scissors or clamps to remove a piece of the tumor. A CT (CAT) scan or MRI of the abdomen and pelvis should be performed to look for abnormally enlarged lymph nodes. It is common for there to be some mild bleeding after a biopsy is taken. Anal cancer is most commonly staged using the TNM staging system which is determined by the American Joint Committee on Cancer. How is anal cancer diagnosed? When anal cancer is suspected. These are scored as follows: T Stage  Tis: Carcinoma in situ  T0: No evidence of primary tumor . Ultimately. the physician should perform a thorough history and physical examination. How is anal cancer staged? Once a diagnosis of anal cancer is made. 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. thin instrument that is inserted into the anus to allow the physician to see the inside of the anus and rectum).As a result. The "N stage" represents the degree of involvement of the lymph nodes. which can result from spread of the cancer. In some cases.

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

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

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

and the patient can avoid the potential side effects of chemoradiotherapy. the patient may have radiation with or without chemotherapy given at a separate time. 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. If this is the case. combined modality treatment is recommended for most patients with anal cancer. and require a colostomy to handle bowel movements. patients have already lost their sphincter function. unless a certain patient is unable to tolerate chemotherapy and radiation together. This bag can then be emptied by the patient as needed. extensive anal cancers that have destroyed the anal sphincter. Because patients in this . Patients with carcinoma in situ or small. For this reason. the results of surgical excision can be quite good. Because the combination of chemotherapy and radiation therapy result in similar rates of local control and survival when compared to surgery. When performed. including the anal muscles. using chemotherapy and radiation together has been shown to reduce the risk of cancer recurring (coming back) in the anus. with placement of a permanent colostomy. which consists of a wide excision of the anus. surgical resection usually is an abdominal perineal resection (APR).significantly improved when 5FU and mitomycin with chemotherapy are used. are often treated with surgery (an APR). however. its role has greatly diminished since then. In these early cases. In these cases. There are several situations in which surgery should be considered for anal cancer. avoiding the need for permanent colostomy. such that the patient cannot control bowel movements. Alternatively. Using chemotherapy and radiation together has not been shown to change the rate of survival of patients when compared to radiation alone. as compared to radiation alone. Surgery Although surgery was the primary treatment for anal cancer 20 years ago. well-differentiated anal cancers that have not invaded into the anal sphincter can sometimes undergo a surgical excision without removing the anal muscles. chemoradiation has been favored over surgery because it offers patients a good chance at preserving anal sphincter function.

In general. Therefore. the medical oncologist. 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. the chance of longterm cure of anal cancer depends on the extent of the disease at the time it was first diagnosed. it is not unusual to have a residual mass immediately after treatment. which will usually be followed by radiation. The treatment of anal cancer should be a cooperative effort among the patient. This article was intended to help answer some of the common questions patients face when they have anal cancer. surgery is often performed if cancer recurs in the anus following previous treatment with radiation therapy if additional chemotherapy and radiation cannot be given. with or without chemotherapy. they usually do so within the first 2 years after treatment. and the surgeon. . although recurrences after 2 years can occur. It is important that all patients with anal cancer know about their disease so that they can make an informed decision about their treatment. After I am treated for anal cancer. If anal cancers do recur. Overall.situation usually have very large tumors. If you have any additional questions. after the operation. the radiation oncology. Anal cancers can take some time to respond to treatment and often continue to shrink months after chemotherapy and radiation have ended. or who do not want radiation therapy Finally. please contact your doctor. the further out from treatment a patient is without evidence of a recurrence. The most important aspect of follow-up after completion of treatment is a thorough physical examination including a digital rectal exam. patients are usually followed every 3-6 months for several years with or without CT scans. Surgery can also be performed in patients who cannot otherwise tolerate radiation therapy. how will I be followed? After treatment for anal cancer. the better the chances that the cancer will never come back. they may require surgical removal of the tumor. The presence of a residual mass does not mean that the treatment did not work.

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