Anal cancer

Definition

Anal cancer is an uncommon cancer occurring in the tissues that make up the opening through which stool passes out of the body.

Description

The anus is the opening at the end of the large intestine (rectum) through which solid waste passes out of the body. The anus is a junction between two types of tissues: mucosa, which lines the intestines, and skin. Cancer located at the junction between the rectum and anus is called "anal canal cancer" (also known as transitional-cell, squamous, epidermoid, or basal cell cancer). Cancer located near the external skin is called "anal margin cancer." Anal canal cancer is more common in women, and anal margin cancer is more common in men.

Approximately 3, 400 cases of anal cancer were diagnosed in the United States in 2000. Anal cancer accounts for 1.5% of the cancers of the digestive system. The average age at diagnosis is 62 years. Most anal cancers are squamous cell carcinomas.

Demographics

Women are much more likely than men to develop anal cancer. Anal cancer is more prevalent in Caucasians than other races.

Causes and symptoms

The previously-held belief that anal cancer is caused by the chronic irritation associated with cracks (fissures), hemorrhoids, and abnormal passageways (fistulae), is falling out of favor. It is now believed that most cases of anal cancer are caused by human papilloma virus (HPV), a sexually-transmitted virus that can cause genital warts. Cancer is caused when the normal mechanisms that control cell growth become disturbed, causing the cells to grow continually without stopping. This may be the result of damage to the DNA in the cell or viral infection.

Symptoms of anal cancer may include:

• bleeding from the anus
• pain around the anus
• the sensation of anal pressure or a mass
• anal itching
• anal discharge
• straining to pass stool (rectal tenesmus)

Diagnosis

To diagnose anal cancer, the physician will first examine the skin of the anus and then will perform a digital rectal examination by inserting a greased, gloved finger into the rectum to feel for lumps. He or she will look for blood on the glove. If a lump is felt, a small sample of the lump will be removed (biopsy ) through a small endoscope (flexible viewing instrument) to examine the tissue under a microscope. The biopsy may be performed using local anesthesia in the physician's office.

Although the diagnosis of anal cancer can be made by the examination alone, the cancer may be further evaluated by conducting other procedures. Endoscopic examinations of the anus (anoscopy ) or rectum (proctoscopy) may be performed to see the tumor. Endorectal ultrasound , in which a wand-like ultrasound probe is inserted into the anus, enables the physician to determine how deep the tumor lies and whether or not nearby organs have been affected. Other possible diagnostic procedures include x ray and/or computed tomography (CT scan) to detect tumor spread (metastasis ). It is common, however, for the cancer to be misdiagnosed at first as a benign lesion, such as a tissue lesion or hemorrhoid; due to this, treatment regimens may be delayed.

Treatment team

The treatment team for anal cancer may include a colorectal surgeon, gastroenterologist, oncologist, radiation oncologist, nurse oncologist, psychiatrist, psychological counselor, and social worker.

Clinical staging, treatments, and prognosis

Clinical staging

The American Joint Committee on Cancer and the Union Internationale Contra le Cancer developed a staging system for anal cancer. Anal cancer is categorized into five stages (0, I, II, III, and IV) which may be further subdivided (A and B) based on the depth or spread of cancerous tissue. This staging system does not apply to anal melanomas or sarcomas . Seventy-five percent of anal cancer patients have stage I or stage II disease. The stages of anal cancer are:

• Stage 0. Cancer has not spread below the limiting membrane of the first layer of anal tissue.
• Stage I. Cancer is 2 cm (approximately 0.75 in) or less in greatest dimension and has not spread anywhere else.
• Stage II. Cancer is between 2 and 5 cm in diameter and has spread beyond the topmost layer of tissue. There is no evidence of regional lymph node metastasis or distant metastasis.
• Stage IIIA. Cancer has spread to adjacent organs (e.g. vagina, bladder) or to the perirectal lymph nodes. Tumor may be of any size.
• Stage IIIB. Cancer has spread to nearby lymph nodes in the abdomen or groin or has spread to both adjacent organs and perirectal lymph nodes. Tumor may be of any size.
• Stage IV. Cancer has spread to distant abdominal lymph nodes or to distant organs in the body.

Treatments

The specific treatment depends on the stage of cancer, type of cancer, and the age and overall health of the patient. Anal cancer is most frequently treated with a combination of radiation therapy and chemotherapy .

Radiation therapy uses high-energy radiation from x rays and gamma rays to kill the cancer cells. Radiation given from a machine that is outside the body is called external radiation therapy. Radiation given internally is called internal radiation therapy or brachytherapy. Sometimes applicators containing radioactive compounds are placed directly into the cancerous lesion (interstitial radiation). The skin in the treated area may become red and dry and may take as long as a year to return to normal. Fatigue , upset stomach, diarrhea , and nausea are also common complaints of patients having radiation therapy. Women may develop vaginal narrowing (stenosis) caused by radiation therapy in the pelvic area, which makes intercourse painful. Radiation may injure the anal sphincter and may cause anal ulcers and anal stenosis.

Chemotherapy uses anticancer drugs to kill the cancer cells. The drugs are given by mouth (orally) or intravenously. They enter the bloodstream and can travel to all parts of the body to kill cancer cells. Generally, a combination of drugs is given because it is more effective than a single drug in treating cancer. The side effects of chemotherapy are significant and include stomach upset, vomiting, appetite loss (anorexia ), hair loss (alopecia ), mouth sores, and fatigue. Women may experience vaginal sores, menstrual cycle changes, and premature menopause. There is also an increased chance of infections.

Surgery may occasionally be employed in the treatment of advanced or recurrent anal cancer. Associated lymph nodes may be surgically removed (lymphadenectomy) if they contain metastatic disease. Most frequently, the cancerous tissue is removed by a procedure called a local resection. In this procedure, the muscle (sphincter muscle) that opens and closes the anus to allow the passage of stool is usually preserved. Alternatively, an abdominoperineal resection is rarely performed surgery in which the anus and lower portion of the rectum are removed. This procedure involves cutting into the abdomen and the perineum, which lies between the anus and vagina in women or between the anus and scrotum in men. An opening is created so that stool can pass out of the body (colostomy ) and into a special bag (colostomy bag) affixed to the skin. Because of the success of radiation therapy and chemotherapy, abdominoperineal resection is infrequently performed. It is reserved for certain patients with recurrent cancer and cancer that is not responding to more conservative treatments.

Prognosis

Anal cancer is a curable disease. Tumors that are located in the anal canal, are less than 2 cm in diameter, and are well-differentiated have a favorable prognosis. Anal cancer patients treated with radiation therapy and chemotherapy (without surgery) have a five-year survival rate of approximately 80%. In the United States, approximately 500 people die from anal cancer each year.

Anal cancer can spread locally and invade other pelvic organs such as the vagina, prostate gland, and bladder. Anal cancer that spreads through the bloodstream (hematogenous spread) most often strikes the liver and lungs.

Alternative and complementary therapies

Although alternative and complementary therapies are used by many cancer patients, very few controlled studies on the effectiveness of such therapies exist. Mind-body techniques such as prayer, biofeedback, visualization, meditation, and yoga have not demonstrated any effect in reducing cancer but can reduce stress and have been shown to lessen some of the side effects of cancer treatments.

Clinical studies of hydrazine sulfate found that it had no effect on cancer and actually worsened the health and well-being of the study subjects. Laetrile, or amygdalin, is often suggested as a cure for cancer and leukemia. No human or animal studies conducted in the last few decades have shown any benefit other than relief of some pain. Laetrile can, however, cause cyanide poisoning.

Shark cartilage is another popular treatment, but has not shown anticancer activity in a clinical setting. Although the results are mixed, clinical studies suggest that the hormone melatonin may increase the survival time and quality of life for cancer patients.

Vitamin E, broccoli, and ellagic acid (found in raspberries, strawberries, cranberries, etc.) may help to prevent colorectal cancer. Selenium, in safe doses, may delay the progression of cancer. Laboratory and animal studies suggest that curcumin, the active ingredient of turmeric, has anticancer activity. According to laboratory and animal studies, maitake mushrooms may boost the immune system. Some laboratory studies suggest that mistletoe has anticancer properties; however, clinical studies have not been conducted.

Coping with cancer treatment

The patient should consult their treatment team regarding any side effects or complications of treatment. Many of the side effects of chemotherapy can be relieved by medications. Vaginal stenosis can be prevented and treated by vaginal dilators, gentle douching, and sexual intercourse. A water-soluble lubricant may be used to make sexual intercourse more comfortable. Patients should consult a psychotherapist and/or join a support group to deal with the emotional consequences of cancer and its treatment.

Clinical trials

As of 2001, there is one active clinical trial that is specifically studying anal cancer. The trial (protocol RTOG-9811) is sponsored by the National Cancer Institute and is open to patients with stage II or III anal cancer. This study aims to compare the effectiveness of radiation therapy with either of two different pairs of chemotherapeutic agents (fluorouracil and mitomycin versus fluorouracil and cisplatin ). There are other trials underway that include all types of gastrointestinal cancers , which may include anal cancer. Patients should consult with their treatment team to determine if they are candidates for any ongoing studies. The National Cancer Institute also provides information on clinical trials , and can be reached at (800) 4-CANCER or at <http://www.nci.nih.gov>.

Prevention

There is moderately strong evidence linking anal cancer with human immunodeficiency virus (AIDS) infection, cigarette smoking, or long-term use of corticosteroids . Other factors that are strongly associated with the development of anal cancer include:

• Anogenital warts. Warts in and around the genitals and anus are found in 20% of women and heterosexual men and in 50% of homosexual men with anal cancer.
• Sexual activity. Having more than 10 sexual partners or being the recipient of anal intercourse increases the risk of developing anal cancer.
• Infections. Infection by sexually-transmitted microbes, such as human papilloma virus HPV, herpesvirus, Neisseria gonorrhoeae, or Chlamydia trachomatis, places one at a higher risk of developing anal cancer.
• Gynecologic cancer. Women with a history of vaginal, vulvar, or cervical cancer are at risk of developing anal cancer. This risk is not due to therapeutic radiation exposure for gynecologic cancer.
• Chronic immunosuppression. The long-term use of drugs by organ transplant recipients to suppress the immune system increases the chance of developing a squamous carcinoma , such as anal cancer.

Because anal cancer is believed to be caused by HPV, like cervical cancer, it may be a preventable disease. Practicing safe-sex methods should help to prevent anal cancer. Persons who are at a high risk of developing anal cancer may benefit from routine screening by a physician.

Special concerns

The effect of pelvic radiation therapy on fertility can be a concern for both men and women. The need for a colostomy raises many issues, including those related to body image and self esteem.

See Also Fertility issues

Resources

BOOKS

American Cancer Society's Guide to Complementary and Alternative Cancer Methods. Bruss, Katherine, Christina Salter, and Esmeralda Galan, eds. Atlanta: American Cancer Society, 2000.

Minsky, Bruce, John Hoffman, and David Kelsen. "Cancer of the Anal Region." In Cancer: Principles & Practice of Oncology. DeVita, Vincent, Samuel Hellman, and Steven Rosenberg, eds. Philadelphia: Lippincott Williams & Wilkins, 2001.

PERIODICALS

Ryan, David, Carolyn Compton, and Robert Mayer. "Carcinoma of the Anal Canal." New England Journal of Medicine 342 (March 2000): 792-800.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta, GA 30329. (800) ACS-2345. <http://www.cancer.org>.

Cancer Research Institute, National Headquarters. 681 Fifth Ave., New York, NY 10022. (800) 992-2623. <http://www.cancerresearch.org>.

National Institutes of Health. National Cancer Institute. 9000Rockville Pike, Bethesda, MD 20982. (800) 4-CANCER. <http://cancernet.nci.nih.gov>.

OTHER

"Anal Cancer." Cancernet. Dec. 2000. 13 Apr. 2001. 9 July 2001 <http://cancernet.nci.nih.gov>.

Belinda Rowland, Ph.D.

KEY TERMS

Anal sphincter

—The muscle located between the rectum and anus that opens and closes to allow the passage of stool.

Colostomy

—An opening created in the skin that allows stool to pass out of the body. A colostomy is necessary when the anus and rectum are removed.

Human papilloma virus (HPV)

—A sexually-transmitted virus that causes genital and anal warts. It is associated with anal cancer and certain gynecologic cancers.

Stenosis

—Narrowing of a passageway, such as radiation-induced narrowing of the vagina (vaginal stenosis) or anus (anal stenosis).

QUESTIONS TO ASK THE DOCTOR

• What type of cancer do I have?
• What stage of cancer do I have?
• What is the 5 year survival rate for persons with this type and stage of cancer?
• Has the cancer spread?
• What are my treatment options?
• What are the risks and side effects of these treatments?
• What medications can I take to relieve treatment side effects?
• Are there any clinical studies underway that would be appropriate for me?
• Is surgery necessary?
• Will my anal sphincter be affected by surgery?
• Are there any alternatives to abdominoperineal resection?
• What effective alternative or complementary treatments are available for this type of cancer?
• How debilitating is the treatment? Will I be able to continue working?
• Are there any local support groups for anal cancer patients?
• What is the chance that the cancer will recur?
• Is there anything I can do to prevent recurrence?
• How often will I have follow-up examinations?

Anal Cancer

Definition

Anal cancer is an uncommon form of cancer affecting the anus. The anus is the inch-and-a-half-long end portion of the large intestine, which opens to allow solid wastes to exit the body. Other parts of the large intestine include the colon and the rectum.

Description

Different cancers can develop in different parts of the anus, part of which is inside the body and part of which is outside. Sometimes abnormal changes of the anus are harmless in their early stages but may later develop into cancer. Some anal warts, for example, contain precancerous areas and can develop into cancer. Types of anal cancer include:

• Squamous Cell Carcinomas. Approximately half of anal cancers are squamous cell carcinomas, which arise from the cells lining the anal margin and the anal canal. The anal margin is the part of the anus that is half inside and half outside the body, and the anal canal is the part of the anus that is inside the body. The earliest form of squamous cell carcinoma is known as carcinoma in situ, or Bowen's disease.
• Cloacogenic Carcinomas. Approximately one-fourth to one-third of anal tumors are cloacogenic carcinomas. These tumors develop in the transitional zone, or cloaca, which is a ring of tissue between the anal canal and the rectum.
• Adenocarcinomas. About 15% of anal cancers are adenocarcinomas, which affect glands in the anal area. One type of adenocarcinoma that can occur in the anal area is called Paget's disease, which can also affect the vulva, breasts, and other areas of the body.
• Skin cancers. A small percentage of anal cancers are either basal cell carcinomas, or malignant melanomas, two types of skin cancer. Malignant melanomas, which develop from skin cells that produce the brown pigment called melanin, are far more common on areas of the body exposed to the sun.

Approximately 3,500 Americans will be diagnosed with anal cancer in 2001, and an estimated 500 individuals will die of the disease during this same interval, according to the American Cancer Society. Anal cancers are fairly rare: they make up only 1% to 2% of cancers affecting the digestive system. The disease affects women somewhat more often than men, although the number of cases among men, particularly homosexual men, seems to be increasing.

Causes and symptoms

The exact cause of most anal cancers is unknown, although certain individuals appear to have a higher risk of developing the disease. Smokers are at higher risk, as are individuals with certain types of the human papillomavirus (HPV), and those with long-term problems in the anal area, such as abnormal openings known as fistulas. Since it increases the risk of HPV infection, the practice of anal sex appears to increase the risk of anal cancer—male homosexuals who practice anal sex are about 33 times more likely to have anal cancers than heterosexual men. Those with weakened immune systems, such individuals with HIV, or transplant patients taking immunosuppressant drugs, are also at higher risk. Most individuals with anal cancer are over the age of 50.

Symptoms of anal cancer resemble those found in other harmless conditions. They include pain, itching and bleeding, straining during a bowel movement, change in bowel habits, change in the diameter of the stool, discharge from the anus, and swollen lymph nodes in the anal or groin area.

KEY TERMS

Biopsy— A procedure in which a small piece of body tissue is removed and examined under a microscope for cancer.

Chemotherapy— A cancer treatment in which drugs delivered into the blood stream kill cancer cells or make them more vulnerable to radiation therapy.

Human papillomavirus (HPV)— A virus with many subtypes, some of which cause cell changes that increase the risk of certain cancers.

Human immunodeficiency virus (HIV)— The virus that causes acquired immune deficiency syndrome (AIDS).

Lymph nodes— Bean-shaped structures found throughout the body that produce and store infection-fighting cells.

Radiation therapy— A cancer treatment that uses high-energy rays to kill or weaken cancer cells. Radiation may be delivered externally or internally via surgically implanted pellets.

Diagnosis

Anal cancer is sometimes diagnosed during routine physicals, or during minor procedures such as hemorrhoid removal. It may also be diagnosed during a digital rectal examination (DRE), when a physician inserts a gloved, lubricated finger into the anus to feel for unusual growths. Individuals over the age of 50 who have no symptoms should have a digital rectal examination (DRE) every five to 10 years, according to American Cancer Society (ACS) guidelines for early detection of colorectal cancer.

Other diagnostic procedures for anal cancer include: Anoscopy. A procedure that involves use of a special device to examine the anus. Proctoscopy. A procedure that involves use of a lighted scope to see the anal canal. Transrectal ultrasound. A procedure in which sound waves are used to create an image of the anus and nearby tissues.

A biopsy is performed on any suspicious growths; that is, a tiny piece of the growth is examined under a microscope for cancer cells. The physician may also perform a procedure called a fine needle aspiration biopsy, in which a needle is used to withdraw fluid from lymph nodes located near the growth, to make sure the cancer has not spread to these nodes.

Anal cancer severity is categorized by the following stages:

• Stage 0 anal cancer is found only in the top layer of anal tissue.
• Stage I anal cancer has spread beyond the top layer of anal tissue, but is less than 1 inch in diameter.
• Stage II anal cancer has spread beyond the top layer of anal tissue and is larger than 1 inch in diameter, but has not spread to nearby organs or lymph nodes.
• Stage IIIA anal cancer has spread to the lymph nodes around the rectum or to nearby organs such as the vagina or bladder.
• Stage IIIB anal cancer has spread to lymph nodes in the mid-abdomen or groin, or to nearby organs and the lymph nodes around the rectum.
• Stage IV anal cancer has spread to distant lymph nodes within the abdomen or to distantorgans.

Treatment

Anal cancer is treated using three methods, used either in concert or individually: surgery, radiation therapy, and chemotherapy.

Two types of surgery may be performed. A local resection, performed if the cancer has not spread, removes the tumor and an area of tissue around the tumor. An abdominoperineal resection is a more complex procedure in which the anus and the lower rectum are removed, and an opening called a colostomy is created for body wastes to exit. This procedure is fairly uncommon today because radiation and chemotherapy are just as effective.

Chemotherapy fights cancer using drugs, which may be delivered via pill or needle. Some chemotherapy types kill cancer cells directly, while others act indirectly by making cancer cells more vulnerable to radiation. The main drugs used to treat anal cancer are 5-fluorouracil (5-FU) and mitomycin or 5-FU and cisplatin. Side effects of chemotherapy, which damages normal cells in addition to cancer cells, may include nausea and vomiting, hair loss, loss of appetite, diarrhea, mouth sores, fatigue, shortness of breath, and a weakened immune system.

Alternative treatment

Research suggests acupuncture can help manage chemotherapy-related nausea and vomiting and control pain associated with surgery.

Prognosis

Anal cancer is often curable. The chance of recovery depends on the cancer stage and the patient's general health.

Prevention

Reducing the risks of the sexually transmitted diseases HPV and HIV also reduces the risk of anal cancer. In addition, quitting smoking lowers the risk of anal cancer.

Resources

PERIODICALS

Murakami, M, K. J. Gurski, and M. A. Steller "Human Papillomavirus Vaccines For Cervical Cancer." Journal of Immunotherapy 22, no. 3 (1999): 212-8.

ORGANIZATIONS

American Cancer Society 1599 Clifton Road, NE, Atlanta, GA 30329. (404) 320-3333 or (800) ACS-2345. Fax: (404) 329-7530. 〈http://www.cancer.org〉.

American College of Gastroenterology. 4900 B South 31st St., Arlington, VA 22206-1656. (703) 820-7400. 〈http://www.acg.gi.org〉.

American Gastroenterological Association. 7910 Woodmont Ave., Seventh Floor, Bethesda, MD 20814. (301) 654-2055. 〈http://www.gastro.org〉.

American Society of Colon and Rectal Surgeons. 85 W. Algonquin Road, Suite 550, Arlington Heights, Illinois 60005. (847) 290-9184.

National Cancer Institute (National Institutes of Health). 9000 Rockville Pike, Bethesda, MD 20892. (800) 422-6237. 〈http://www.nci.nih.gov〉.

National Coalition for Cancer Survivorship. 1010 Wayne Avenue, 5th Floor, Suite 300, Silver Spring, MD 20910. (888) 650-9127.

NCI Office of Cancer Complementary and Alternative Medicine. 〈http://occam.nci.nih.gov〉.

NIH National Center for Complementary and Alternative Medicine. Post Office Box 8218, Silver Spring, MD 20907-8218. (888) 644-6226. 〈http://nccam.nih.gov〉.

United Ostomy Association. (800) 826-0826. 〈http://www.uoa.org〉.