What is the Anus?

The anus is the lowest part of the digestive tract, directly below the rectum. It is composed of 2 parts: the anal canal and the anal orifice. Altogether, the anus is about 4 cm. (a bit less than 2 inches) long. The anus is a marvelously engineered system for Upreserving man's dignity" - it is able to distinguish between solid, liquid and gas and release each at the appropriate time. The muscles that surround the anus are called 4sphincters" meaning they open and close about a tube. The anal sphincter, when not damaged by disease, is under voluntary control so we can pass a bowel movement ( defecate.) at will. To defecate, stool must have already entered the lower portion of the rectum. It is actually then held in place by "shelves" that come out from the inner anal lining, until the sphincter opens and the stool passes through the anal canal. The uppermost portion of the anal canal is identified by placing an examining finger into the anus and detecting the upper border of the muscular anal sphincter. It is important to understand the intemal anatomy of anus, since this will determine the types of cancers that can arise there. The intemal lining of the anus changes as we proceed from the end of the rectum toward the outside skin. The uppermost part is continuous with the rectum and has the same type of lining, or Umucosa" as does the rectum. The scientific name for lining cells in most any area of the body, inside (i.e. uterus or lungs) and out (i.e. skin) is called "epithelium". In the lower part of the rectum and upper anal ca" the specific type of epithelium is called "modified columnar epithelium", since it seems to form "columns" when viewed with a microscope. Proceeding downward, there is then a Utransitional" area, also called the "dentate line" region, where the lining starts to change to something called "modified squamous epithelium". Squamous epithelium cells each look like fried eggs (sunny side up) under the microscope. This bpe of lining cell is very resistant to injury and quickly replaced if damaged. This type is found all the way to the "anal verge", that is where the anus meets the skin at the inside of the buttocks. This tissue is hairless and has no glands. Finally, there is a special area of skin surrounding the anal verge, called the Uperianal. area, which is made of the same type of epithelium found in skin (comefied squamous cell) and has hair and sweat glands, becoming continuous with the regular skin in the cleft between the buttocks (the "gluteal cleft").

The anal region is has a rich blood supply, called the "hemorrhoidal" vessels, that act as an important conduit for blood to go from the intestines to back to the heart, especially if the liver is diseased. Hemorrhoids occur when clots form in the slow moving blood in the small veins of this system. People with cirrhosis of the liver from viruses or alcoholism commonly develop hemorrhoids. The blood from the anus will eventually drain up to the liver, but from the lowest part of the anus may drain to the lungs first, spreading cancer there. In addition, a system of glands (Iymph nodes) about the size-of a pea each helps purify the blood coming from the anal area, and a cancer in the anal region can spread to these glands and enlarge them.

What is Anal Cancer?

Normally the cells which make up the anal canal divide and grow very quickly during life in the womb and childhood, up through puberty. After this, they only divide to replace cells which have died due to old age or injury. Division of cells is under very tight control by the genes within each cell. The genes, which are units of genetic material, are somehow able to sense the appropriate time for cell division and run the cell through this complicated process. If a cells genes have been damaged, say by a virus or chemical, there are built-in safeguards to prevent this cell from dividing. In all cancers, something goes awry with this system and the cell starts to divide out of control. As with all cancers, anal cancer starts in just one cell! This cell, and all of the "daughtern cells it produces, are damaged and put all their energies into making yet more defective cells. They do not function as they normally should, but only Ulive to breed". When there are about 1 billion of them, they form a "tumor" about 1 cm. (1/2") across. A Utumor" simply means a swelling, and can be caused by infection or cancer or whatever. A tumor which only can grow in it's local area, and can not spread, is then called "benign". Benign tumors can grow to enormous sizes and occasionally be lifethreatening, but they are not cancer. When a tumor has the capability to spread to distant organs, it is then called "malignant". Malignant tumors can spread to any area of the body, and they are cancer. The process of spread is called "metastasis". So, only malignant tumors can metastasize. It is this penchant for spreading which makes a cancer so dangerous.

How Common is Anal Cancer?

There are about 1,500 new cases of anal cancer each year in the U.S.A., leading to 300 deaths. This makes anal cancer less than 1% of new cancers, and quite rare compared to prostate, lung or rectal cancer. Slightly more women than men get anal cancer. In women, the cancer tends to arise closer to the recturr', that is above the "dentate line", while in men the cancer is commonly lower, near the anal verge. The average patient is 60 years old; it is extremely rare in those under 40. The number of cases of anal cancer has been gradually rising over the past 30 years, but so has the availability of affective treatment.

What Causes, or Increases the Risk for Anal Cancer?

Like any cancer, the exact reason why one person gets anal cancer and another does not remains unknown. However, several things have been noted in which seem to increase the risk that someone will get anal anal cancer. These include:

Longstanding Hemorrhoids and anal irritation. As will be seen, anal cancer is often initially confused with simple hemorrhoids. Any chronic irritation of an area causes the cells there to divide more frequently to repair local injury' and the more often cells divide, the more likely a cancerous one will arise.

Sexually Transmitted Diseases (STD's) like those than cause genital warts (papilloma virus) and that causing AIDS (HIV). viruses get inside the genes and cause changes which may lead to cancer. Obviously, only a minority of people with herpes, papilloma virus or HIV get anal cancer, but some do.

Receptive Anal Intercourse, especially when repetitive, has been associated with increased risk for anal cancer. In younger men, almost all cases involve homosexual activity. This is probably linked with both irritation of the anal canal and the transmission of the viruses noted above.

Immunosuppression, meaning lowered immune system activity, can be caused by the HIV virus, drugs, or inborn "immune-deficiency" states. Normally, the white blood cells in the immune system are able to identify diseased and defective cells, such as those which have turned cancerous, and destroy them. If immune function is compromised, this "immunosurveillance" can fail, allowing a cancer cell to divide unhindered. When people get organ transplants, they have to take anti-rejection drugs that weaken their immune systems, and are at a greater risk for a whole variety of cancers. Recent evidence suggests that chronic emotional depression also weakens the immune system are increases cancer risk!

Tobacco Smoking is related to many cancers of the "aero-digestive" tract, that is the lungs and intestinal tract. The anal canal is the final part of the intestinal tract, and is exposed to the swallowed irritants from cigarette smoke. However, the link of smoking and anal cancer is not nearly as strong as for lung cancer.

Another Genital Tract Cancer, such as vulvar or penile cancer, will predispose to development of anal cancer. This is probably due to common risk factors, like sexually transmitted viruses, for these cancers.

What are the Symptoms of Anal Cancer?

Like any cancer, very early anal cancer will have no symptoms. As the cancer grows, the following may occur:

1) Bleeding out of the anus, which is bright red blood. The color of the blood is important, since the blood from stomach ulcers shows up as black, tarry and sticky by the time it is passed through the anus. While bleeding is seen in 70% of patients with anal cancer, it much more commonly means benign conditions like hemorrhoids and anal tears (Ufissures") so alone cannot diagnose cancer.

2) Irritation when the anal area, including itching (Upruritis") and pain, are also seen in over onehalf of patients. They are likewise much more likely to be caused by non-cancerous conditions. However, the symptoms of anal cancer will gradually yet definitely worsen, while for other conditions may improve.

3) Discharge of pus or non-stool debris from the anus is suspicious for infection or cancer, so must be evaluated.

4) Changes in Bowel Habits are a warning sign for many bowel cancers. Pencilthin stools or diarrhea can be from obstruction of the ano-rectal area by tumor, and a feeling of retained stool in the rectum ("tenesmus") after a bowel movement is classic for cancer in this area.

5) Lump or Bump in the anal area may be cancer, but more commonly is just a hemorrhoid or genital wart. However, anal cancers don't shrink on their own! If something grows very quickly it is much more likely not cancer. A cancer will grow slowly (over months) but continuously. It doesn't "come up overnight".)

6) Fecal Incontinence, that is soiling of the underwear and inability to control bowel movements, may be seen in advanced anal cancer. The anal sphincter may also develop painful spasms. While some soiling is common, only 5% of patients have frank incontinence when first seen for their disease.

7) Swollen Glands in the groin may be from cancer, infection, or both.

8) Signs of Distant Spread may occasionally be the first finding. The common sites of distant spread are the lung, liver, bone and brain. However, it can go to any area of the body, usually after it has grown large in it's local area.

How Does Anal Cancer Spread?

As mentioned, anal cancer starts as a single cell and gradually grows in to a visible tumor. Initially, the tumor tends to bulge outward into the anal canal, but as it grows it can transform into a ulcerous pit. About 10% of patients have the cancer confined to the lining "mucosa" at diagnosis. Then the tumor breaks through the epithelial lining cells into the muscles surrounding the anal canal. It can grow locally to invade the prostate or vagina. At this point the cancer is at high risk for spread to local Iymph glands, called "Iymphogenous metastasis". The risk for spread to these Iymph nodes is also related to the size and degree of aggressiveness of the particular tumor. If the tumor is less than 1 inch, the chance is less than 10% for spread to Iymph nodes, but if it is over 2 inches, then the change for spread to Iymph nodes is over 40%. However, only one-half the patients with these positive Iymph nodes will have them picked up on physical examination; other tests must be used to identify them. The other route of cancer spread is through the bloodstream to distant organs, this is called "hematogenous metastasis". About 10% of patients will have signs of distant spread when they first come to their doctor. The most common site of distant spread is to liver and lung, with bone, brain, intestinal tract and skin less frequent.

How is Anal Cancer Diagnosed and Evaluated?

The only way to absolutely diagnose any cancer is to get a piece of it, called a biopsy, and submit it to a pathologist (a physician who specializes in making diagnoses from tissue samples). The pathologist will then determine whether cancer is present, and if so, what type and degree of aggressiveness (called the grade"). Low grade cancers look a like their normal tissue of origin, they tend to grow more slowly and be less likely to spread. High grade cancers, though, look very "cancerous" under the microscope. This means they hardly resemble their tissue of origin, are dividing very quickly, and are likely to spread quickly. The pathologist can look for viral infection and use special stains and the electron microscope to further categorize the cancer.

In the patient with a suspected anal or rectal cancer, the following are routinely done:

1) Complete Physical Examination includes a "digital rectal exam" where a gloved finger is placed up into the rectum. It can often detect and describe the tumor, as well as enlargement of the prostate in males. Stool retained on the examining finger is smeared on a special card and developer placed upon it to detect blood (guiac test). Rectal exam can detect enlarged Iymph nodes in the pelvis in 30% of patients. In women, a complete pelvic exam is performed. The Iymph glands of the groin are palpated for enlargement. The abdomen is checked for enlargement of the liver and spleen. The head and neck area are checked for other cancers, especially in smokers. Full exam is essential!

2) Routine Lab Tests include the standard pre-operative tests of Complete Blood Count (CBC) which detects anemia and infection. In many colon and ano-rectal cancers, a slow bleeding process has results in an iron-deficiency anemia, where the red blood cells are smaller a paler than normal. This will eventually cause paleness and fatigue in the patient. A Blood Chemistry Test (SMA) checks sodium, potassium, sugar, cholesterol, and liver and kidney function at a low cost. It also checks whether there has been very recent heart damage (CPK) and if bone is being destroyed (Alkaline Phosphatase). Urinalysis (UA) checks for blood, protein and sugar in the urine, as well as signs of urinary tract infection. If surgery is planned, blood clotting tests (bleeding time, PT, and PTT) will be requested by the surgeon. Unfortunately, there are currently no specific blood tests ("tumor markers") for anal cancer, but the standard profile above indicates the general health of the patient.

3) Routine Radiology Tests include usual Chest X-ray to look for pneumonias and signs of spread to the lungs. If anything suspicious is found, a Chest CT is more precise (and expensive). CT scan is basically a computer combined series of X-rays that allow tumors as small as 1 cm. (1/2 inch) to be seen. An Abdominal CT is commonly ordered, to look for spread to the liver, abdominal Iymph nodes and kidney area. Pelvic CT scan can often show the tumor, and demonstrate how far it invades locally, as well as the pelvic Iymph nodes. A normal Iymph node is less than 1 cm, larger ones are suspicious for cancer. Barium Enema places some contrast material up into the rectum and then a series of X-rays are taken which outline the tumor. To view the tumor directly, light anesthesia is given and a special tube is inserted up the rectum, this procedure is called "proctoscopy". The proctoscope has a special scissors to take biopsy samples of the tumor. About 2% of patients have a second cancer in the colo-rectum which may be seen as the tube is inserted further. Magnetic Resonance Imaging (MRI) is a newer test that does not use any radiation and is excellent for checking soft-tissue and extent of tumor growth. However, it is very expensive (over $1000) and not part of the standard workup (yet). Other tests like bone scan or brain CT are only for specific symptoms.

What are the Types of Anal Cancer?

Over 80% of anal cancers are "epidermoid", meaning they come from the lining squamous epithelial cells that resemble skin. For anal cancer, three varieties of this "epidermoid" cancer have historically been noted" Squamous (70%), Basaloid (25%) and Mucoepidermoid (5%) - But the specific subtype doesn't make clinical difference! That is, they all do about the same with treatment. They may produce keratin, which is what gives the skin it's thickened texture. The closer the anal cancer is to the anus, the more likely it will produce keratin, and the easier it is to treat. Of the other 20% of anal cancers, the majority are "adenocarcinomas" meaning they come from glands and resemble typical rectal cancer. Other rarer types include melanoma from the skin pigment cells, sarcoma from the muscle cells or fat cells, and Iymphoma from the immune cells. The treatment of these rare types follows their treatment for other body areas where they are more common.

How is the Extent of Anal Cancer Gauged?

Like all cancers, the extent of anal cancer is defined by it's "stage". The most common staging system is that from the American Joint Committee on Cancer, or "AJCC" for short:

Stage 0 means "Carcinoma in Situn" - microscopic cancer that doesn't invade.
Stage I means the cancer is smaller that 2 cm. and has not spread at all.
Stage II means the cancer is smaller than 5 cm. and has not spread at all.
Stage IIIA means the cancer has spread to local Iymph nodes, or invades the vagina, urethra or bladder.
Stage IIIB means the cancer has spread to local Iymph nodes and invades the vagina, urethra or bladder, or simply invades distant Iymph nodes.
Stage IV means the cancer has spread to distant organs (i.e. Iung or liver).

What is the Survival from Anal Cancer?

This depends upon many factors, including the stage, grade, patient condition and treatment selected. Overall, the conventional survival, from textbooks is:

** In general, cancers above the dentate line (closer to the rectum) to somewhat worse than those below the dentate line (closer to the outside skin).

It is important to realize that many individuals live quality lives for many years with their cancer, and no one can accurately predict survival in any particular case. Since many patients are older and have other medical problems, things other than the cancer may lead to their demise. We are M.D.'s, not M. Deities!

What is the Conventional Treatment of Anal Cancer?

Up until the mid 1980's, surgery was the the conventional treatment for anal or rectal cancers, and it is still used extensively. Surgery is performed by a "colorectal" surgeon, which is a board-certified subspecialty. The only way to know for absolute sure whether the Iymph glands around the anal canal canal are involved with cancer is to remove them surgically. The historic operation used for anal and rectal cancer is called and "Abdomino-Perineal Resection", or "APR'' for short. It involves making two incisions, one on the abdomen and one one in the area between the genitals and anus ("peritoneal"). The conventional surgery used was a major operation which basically removed all of the tissue in the anal canal region, and then diverted stool flow to a hole created in the abdomen. This hole, called a "colostomy" has a disposable bag placed over it to collect the stool. Thus, and "APR" always ruins the normal anal area, which is sewn shut. The operation removes any suspicious Iymph nodes in the area, and can remove the prostate or wall of the vagina is those areas appear involved. Extending the operation to remove Iymph nodes or tissues further away did not improve the survival rate.

Unfortunately, there are many problems with the conventional APR. Firstly, it is a very major operation with about a 2% death risk and a 10% major complication rate, even when performed by an expert surgeon. Then, there is the psychological consequence of having a colostomy, which smells foul when full of stool and needs to be tended to carefully. It can interfere with sexual relations and general self-image. Also, the surgery can damage the nerves in the area leading to impotence in men and lack of sensation in the genital area in both sexes. Normal urination may also be impaired if these nerves are damaged at surgery, leading to urinary incontinence. And, worse of all perhaps, the surgery was only 50% effective (on average) of curing the cancer, so one-half of patients still died of their disease within 5 yearsl Although APR is still done, the drawbacks lead surgeons and cancer doctors (Uoncologists'') to look for better alternatives in anal and rectal cancers.

A possible less aggressive alternative for selected patients is limited surgery to just remove the tumor, and keep normal bowel function. This is "local excision" and has been used for older individuals who cannot tolerate radical surgery. Ideally, a patient getting this local excision should have a very early cancer that does not penetrate into the muscle (stages O or 1), is of low grade, and therefore has little chance for spread to local Iymph nodes ("2%). The problem with local excision is that it is poor cancer operation, since it only removes the actual tumor does not examine the Iymph nodes or other sites of possible spread. If cancer cells remain, they will probably (but not always) grow back and cause problems, often within months. Of course, this is balanced by the fact that local excision is a much more simple operation that APR and does not require a colostomy. As will be seen, newer treatments involve combining the simplicity of local excision with other treatments (radiation and chemotherapy) to mop up cancer cells missed by local excision, with results comparable or even better than the drastic APR.

Radiation Therapy is another conventional treatment for anal cancer which has been used for over 6 decades. The technology for administering radiation has had a rapid advancement, and results are better than ever before. Radiation is given by a physician specializing in cancer called a "radiation oncologist", who's department is usually in the basement of a hospital or in a free-standing facility. Two ways of giving radiation treatments are recognized for anal cancer: Extemal Beam and Intracavitary Applicator. External Beam is the most commonly used, it is given with a large machine called a "Linear Accelerator" or ULinac" for short. It gives out a poweRul beam of photons or electrons, and the patient lies immobile on a special treatment table to get the therapy. Linac head swivels around the patient so that the treatment can be given from several different angles. Thus the treatment can cover the whole pelvis, or whatever area is appropriate. In contrast, Intracavitary, also called the "Papillon" technique is a local radiation treatment given by inserting a cone into the anus, who's radiation source is powered by a weaker Uorthovoltagen machine. With the cone, a radiation beam is aimed directly at the tumor to shrink it, so it doesn't cover the Iymph nodes or further away tissues. Thus it has much in common with the "local excision" surgery described above.

Prior to getting radiation treatments, the patient is seen in consultation by the radiation oncologist, who reviews the X-rays and scans. If the patient is to get conventional beam therapy, they are scheduled for "simulation". At simulation, a mock machine is used to establish the proper patient positioning for treatment, and some barium contrast is often placed in the rectum to demonstrate the tumor. The patient is aligned with special laser lights. Plain X-rays are taken, and watercolor marks are applied to the patient's body to mark out the area to be treated. Ultimately, pinpoint tattoos are used to permanently mark out the area treated for future reference. The process takes about 1 hour, and a CT scan may be ordered in conjunction with the simulation. The patient returns home. Information from the simulation is then fed into a "treatment planning computer" which generates a "plan" to be reviewed by the doctor and a Uradiation physicist". This plan tells how much radiation is going to the tumor, and how much to surrounding tissues. Special lead-like blocks, which fit into the head of the linac, may be molded to protect areas which don't require treatment.

The patient then retums to the department for their utreatment start". After being positioned on the treatment table, Uverification films" (X-rays) are taken to confirm proper position, and the treatment is then given. It takes only a couple of minutes each day, usually Monday through Friday, for 4 to 6 weeks. If a treatment must be missed, it is tacked on at the end, so the same total prescribed dose is given. A typical dose for rectal cancer is 50 Gray (units of radiation) given at a rate of 2 Gray per treatment.

When getting pelvic radiation, the patient does not lose their scalp hair, become UradioactiveD, or get Uradiation sicknessn. The anticipated side effects are in the area of treatment, and are divided into "acute" and "late" reactions. Acute reactions occur during the treatment time, and include rectal irritation, diarrhea and urinary frequency.

There is also some general fatigue. Late reactions are less likely to occur, and will depend upon the dose per day given, the skill of the radiation oncologist in designing a proper treatment field, and individual patient tolerances. Late reactions may occur months to years after treatment and include narrowing ("stenosis") of the anal canal, chronic urinary problems or diarrhea, or bowel blockage requiring surgery. While the odds are very small, a second cancer in the area caused by radiation would be a late effect. For the "contact radiationn or Papillon technique, a cone is inserted into the rectum, the tumor is visualized, and treatments are given 3 to 5 times per week for 4 to 6 weeks. There is usually more acute soreness, but less late reaction for this method, since it treats a much smaller area. Suppositories containing cortisone (i.e. anusol HC) or antispasmodic ("Belladonna and Opiumn) can help the patient be more comfortable through treatment. In general, radiation is well tolerated, painless treatment, and has helped many patients avoid radical surgery.

The results of radiation have shown, overall, that overall survival at 5 years is about 70%, locally recurrent cancer occurs in 30%, and 75% of patients retain their functioning anus. About 15% of patients will ultimately require surgery, usually with colostomy, from bowel problems due to the radiation or recurrent cancer. These numbers compare favorably with APR which has a 5 year survival rate of 50% and a relapse rate of 50% overall. For the Papillon technique, the results are even better, with 75% survival, over 80% functional anus, and just 25% relapse. Recall, however, that these patients are carefully selected for small cancers close to the anal verge. Thus, new interest is being paid to the role of radiation therapy in anal cancer.

Chemotherapy drugs, such as 5-Fluorouracil and Mitomycin-C, are not curative alone for anal cancer, but are used in combination with other treatments. Chemotherapy can be used up front an initial treatment to shrink the tumor, or to "salvage" the patient after relapse. In general, if a patient relapses after APR, average survival is only 8 months with salvage therapy. For any treatment, if a patient is without disease for 2 years, the chances of relapse decline quickly, and the chance for cure increases.

What is the Latest Effective Treatment for Anal Cancer?

Given the unacceptability for many patients of a colostomy, and the success seen with radiation treatments at anal preservation, researchers in the 1 980's developed "combination therapy" (using more than one method) for "sphincter sparing" (anal preservation). Among the most noted researchers were Dr. Nigro at the Wayne State University in Detroit, Dr. Cummings at Princess Margaret Hospital in Toronto, and Dr. Papillon, whose local radiation technique is named for him. Excellent results were found for anal cancers when 30 Gray of radiation given in 15 "fractions" was combined with intravenous (into the veins) chemotherapy of 5-FU and Mitomycin-C. This therapy is called "chemoradiation", and patients have increased local irritation in the rectal area, and blood counts must be monitored for anemia. However, the results were great, with complete tumor disappearance and anal saving in over 90% of patients!

Chemoradiation was so successful in this area that it led to similar treatments for cancers of the vulva and head and neck. If an area of tumor remained, it could be treated with local excision surgery, eliminating the radical APR for the vast majority of patients. Many University Hospitals are doing this combination therapy now, check and see that the oncologist is familiar with the work of Dr. Cummings, Dr. Nigro and Dr. Minsky (who has published extensively on sphincter sparing therapy for rectal cancer).

A remaining controversy is the need for combined therapy, instead of radiation therapy alone, for anal cancers. Obviously, we do not want to overtreat the patient, since this leads to more side-effects. Given the excellent results with radiation alone for many tumors, some researchers question the need for giving chemotherapy. A good reason for chemotherapy, besides for it's local value in shrinking the tumor, is that it is the only therapy which can kill cancer cells which may have broken off of the primary tumor and migrated to other organs. Surgery and radiation are strictly local therapies; they will do nothing for cancer cells which have metastasized to other body areas. However, the chance of this metastasis with small, low grade tumors is tiny.

The venerable Dr. Gunderson at the Mayo Clinic has reviewed this controversy, he is one of the most experienced physicians in the world in digestive tract cancers. He has concluded that for early anal cancers, there is no advantage to combined therapy versus just giving radiation alone. However, for larger cancers, it is appropriate to give combined therapy with 5-FU and Mitomycin-C, since they do not do as well with only radiation. If radiation is given alone, then the dose is higher and the area treated usually larger than when chemotherapy can be relied upon to mop up any cancer cells at the periphery. Thus, the decision on which therapy to use must be made wisely, and the patient should be fully informed about the risks and benefits of their therapy.

In conclusion, we have come a long way in the management of anal cancer, which once had only 50% survival with radical surgery, and invariably left the patient with a colostomy bag. With early detection of anal cancer, well over 90% can expect to be alive at 5 years, and thus probably cured, with the latest effective treatment. Also, over 90% of these patients can retain normal anal function, and avoid colostomy. If an APR is recommended, patients should definitely get a second opinion before proceeding with radical surgery, which may be appropriate for "salvage" of recurrence, but avoided as the initial treatment.