Rectum Cancer

On chromosome 5 is the APC gene associated with familial adenomatous polyp sis (FAP) syndrome. There are multiple mutations that occur at this site, yet they all cause a defect in tumor suppression that results in early and frequent development of colon cancer. This is transmitted to 50% of offspring and each of those affected will develop colon or rectal cancer, usually at an early age. Another syndrome, hereditary non-polyp sis colon cancer (HNPCC), is related to mutations in any of four genes responsible for DNA mismatch repair. In patients with colon or rectal cancer, the p53 gene is mutated 70% of the time. When the p53 gene is mutated and ineffective, cells with damaged DNA escape repair or destruction, allowing the damaged cell to multiply. Continued replication of the damaged DNA may lead to tumor development. Though these syndromes (FAP and HNPCC) have a very high incidence of colon or rectal cancer, family history without the syndromes is also a substantial risk factor. When considering first-degree relatives, history of one with colon or rectal cancer raises the baseline risk from 2% to 6%; the presence of a second raises the risk to 17%.

The development of polyps of the colon or rectum commonly precedes the development of rectal cancer. Polyps are growths of the rectal lining. They can be unrelated to cancer, pre-cancerous, or malignant. Polyps, when identified, are removed for diagnosis. If the polyp, or polyps, are benign, the patient should undergo careful surveillance for the development of more polyps or the development of colon or rectal cancer.

Symptoms of rectal cancer most often result from the local presence of the tumor and its capacity to invade surrounding pelvic structure:

• bright red blood present with stool

• abdominal distention (stretching from internal pressure), bloating, inability to have a bowel movement

• narrowing of the stool, so-called ribbon stools

• pelvic pain

• unexplained weight loss

• persistent chronic fatigue

• rarely, urinary infection or passage of air in urine in males (late symptom)

• rarely, passage of feces through vagina in females(late symptom)

If the tumor is large and obstructing the rectum, the patient will not be evacuating stool normally and will get bloated and have abdominal discomfort. The tumor itself may bleed and, since it is near the anus, the patient may see bright red blood on the surface of the stool. Blood alone (without stool) may also be passed. Thus, hemorrhoids are often incorrectly blamed for bleeding, delaying the diagnosis. If anemia develops, which is rare, the patient will experience chronic fatigue. If the tumor invades the bladder in the male or the vagina in the female, stool will get where it does not belong and cause infection or discharge. (This condition is also rare.) Patients with widespread disease lose weight secondary to the chronic illness.

Diagnosis

Screening evaluation of the colon and rectum are accomplished together. Screening involves physical exam, simple laboratory tests, and the visualization of the lining of the rectum and colon. X rays (indirect visualization) and endoscopy (direct visualization) are used to visualize the organs' lining.

The physical examination involves the performance of a digital rectal exam (DRE). At the time of this exam, the physician checks the stool on the examining glove with a chemical to see if any occult (invisible), blood is present. At home, after having a bowel movement, the patient is asked to swipe a sample of stool obtained with a small stick on a card. After three such specimens are on the card, the card is then easily chemically tested for occult blood. These exams are accomplished as an easy part of a routine yearly physical exam.

Proteins are sometimes produced by cancers and these may be elevated in the patients blood. When this occurs the protein produced is known as a tumor marker. There is a tumor marker for cancer of the colon and rectum; it is known as carcinoembryonic antigen, (CEA). Unfortunately, this may be made by other adenocarcinomas as well, or it may not be produced by a particular colon or rectal cancer. Therefore, screening by chemical analysis for CEA has not been helpful. CEA has been helpful in patients treated for colon or rectal cancer if their tumor makes the protein. It is used in a follow-up role, not a screening role.

Direct visualization of the lining of the rectum is accomplished using a scope or endoscope. The physician introduces the instrument into the rectum and is able to see the epithelium of the rectum directly. A simple rigid tubular scope may be used to see the rectal epithelium; however, screening of the colon is done at the same time. The lower colon may be visualized using a fiberoptic flexible scope in a procedure known as flexible sigmoidoscopy. When the entire colon is visualized, the procedure is known as total colonoscopy. Each type of endoscopy requires pre-procedure preparation (evacuation) of the rectum and colon.

The American Cancer Society has recommended the following screening protocol for colon and rectal cancers those over age 50:

• yearly fecal occult blood test
• flexible sigmoidoscopy at age 50
• flexible sigmoidoscopy repeated every 5 years
• double contrast barium enema every five years
• colonoscopy every 10 years

If there are predisposing factors such as positive family history, history of polyps, or a familial syndrome, screening evaluations should start sooner.

Evaluation of patients with symptoms

When patients visit their physician because they are experiencing symptoms that could possibly be related to colon or rectal cancer, the entire colon and rectum must be visualized. Even if a rectal lesion is identified, the entire colon must be screened to rule out a syndromous polyp or cancer of the colon. The combination of a flexible sigmoidoscopy and double contrast barium enema may be performed, but the much preferred evaluation of the entire colon and rectum is that of complete colonoscopy. Colonoscopy allows direct visualization, photography, as well as the opportunity to obtain a biopsy, (a sample of tissue), of any abnormality visualized. If, for technical reasons the entire colon is not visualized endoscopically, a double contrast barium enema should complement the colonoscopy. A patient who is identified to have a problem in one area of the colon or rectum is at greater risk to have a similar problem in area of the colon or rectum. Therefore the entire colon and rectum need to be visualized during the evaluation.

The diagnosis of rectal cancer is actually made by the performance of a biopsy of any abnormal lesion in the rectum. Many rectal cancers are within reach of the examiner's finger. Identifying how close to the anus the cancer has developed is very important in planning the treatment. Another characteristic ascertained by exam is whether the tumor is mobile or fixed to surrounding structure. Again, this will have implications related to primary treatment. As a general rule, it is easier to identify and adequately obtain tissue for evaluation in the rectum as opposed to the colon. This is because the lesion is closer to the anus.

If the patient has advanced disease, areas where the tumor has spread, such as the liver, may require biopsy. Such biopsies are usually obtained using a special needle under local anesthesia.

Once a diagnosis of rectal cancer has been established by biopsy, in addition to the physical exam, an endorectal ultrasound will be performed to assess the extent of the disease. For rectal cancer, endorectal ultrasound is the most preferred method for staging both depth of tumor penetration and local lymph node status. Endorectal ultrasound:

• differentiates areas of invasion within large rectal adenomas that seem benign
• determines the depth of tumor penetration into the rectal wall
• determines the extent of regional lymph node invasion
• can be combined with other tests (chest x rays and computed tomography scans, or CT scans) to determine the extent of cancer spread to distant organs, such as the lungs or liver

The resulting rectal cancer staging allows physicians to determine the need for-and order of-radiation, surgery, and chemotherapy. In 2003, it was reported that magnetic resonance imaging (MRI) also may be useful in staging rectal cancer. MRI may help physicians determine if a tumor can be resected and risk of cancer recurrence.

Treatment

Once the diagnosis has been confirmed by biopsy and the endorectal ultrasound has been performed, the clinical stage of the cancer is assigned. The treating physicians use staging to plan the specific treatment protocol for the patient. In addition, the stage of the cancer at the time of presentation gives a statistical likelihood of the treatment outcome (prognosis).

Clinical staging

Rectal cancer first invades locally and then progresses to spread to regional lymph nodes or to other organs. Stage is derived using the characteristics of the primary tumor, its depth of penetration through the rectum, local invasion into pelvic structure, and the presence or absence of regional or distant metastases. A CT scan of the pelvis is helpful in staging because tumor invasion into the sacrum or pelvic sidewalls may mean surgical therapy is not initially possible. On this basis, clinical staging is used to begin treatment. The pathologic stage is defined when the results of analyzing the surgical specimen are available. (typically stage I and II).

Rectal cancer is assigned stages I through IV, based on the following general criteria:

• Stage I: the tumor is confined to the epithelium or has not penetrated through the first layer of muscle in the rectal wall.
• Stage II: the tumor has penetrated through to the outer wall of the rectum or has gone through it, possibly invading other local tissue or organs.
• Stage III: Any depth or size of tumor associated with regional lymph node involvement.
• Stage IV: any of previous criteria associated with distant metastasis.

Surgery

The first, or primary, treatment modality utilized in the treatment of rectal cancer is surgery. Stage I, II, and even suspected stage III disease are treated by surgical removal of the involved section of the rectum along with the complete vascular and lymphatic supply. Most Stage II and Stage III rectal cancers (based on endorectal ultrasound, CT scan, and chest x ray) are treated with radiation and possibly chemotherapy prior to surgery.

When determining primary treatment for rectal cancer, the surgeon's ability to reconnect the ends of the rectum. The pelvis is a confining space that makes the performance of the hook-up more difficult to do safely when the tumor is in the lower rectum. The upper rectum does not usually present a substantial problem to the surgeon restoring bowel continuity after the cancer has been removed. Mid-rectal tumors, (especially in males where the pelvis is usually smaller than a woman's), may present technical difficulties in hooking the proximal bowel to the remaining rectum. Technical advances in stapling instrumentation have largely overcome these difficulties. If the anastomosis (hook-up) leaks postoperatively, infection can occur. In the past, this was a major cause of complications in resection of rectal cancers. Today, utilizing the stapling instrumentation, a hook-up at the time of original surgery is much safer. If the surgeon feels that the hook-up is compromised or may leak, a colostomy may be performed. A colostomy is performed by bringing the colon through the abdominal wall and sewing it to the skin. In these cases the stool is diverted away from the hook-up, allowing it to heal and preventing the infectious complications associated with leak. Later, when the hook-up has completely healed, the colostomy can be taken down and bowel continuity restored.

Stapling devices have allowed the surgeon to get closer to the anus and still allow the technical performance of a hook-up, but there are limits. It is generally felt that there should be at least three centimeters of normal rectum below the tumor or the risk of recurrence locally will be excessive. In addition, if there is no residual native rectum, the patient will not have normal sensation or control and will have problems with uncontrollable soilage, (incontinence). For these reasons, patients presenting with low rectal tumors may undergo total removal of the rectum and anus. This procedure is known as an abdominal-perineal resection. A permanent colostomy is performed in the lower left abdomen.

Radiation

As mentioned, for many late stage II or stage III tumors, radiation therapy can shrink the tumor prior to surgery. The other roles for radiation therapy are as an aid to surgical therapy in locally advanced disease that has been removed, and in the treatment of certain distant metastases. Especially when utilized in combination with chemotherapy, radiation used postoperatively has been shown to reduce the risk of local recurrence in the pelvis by 46% and death rates by 29%. Such combined therapy is recommended in patients with locally advanced primary tumors that have been removed surgically. Radiation has been helpful in treating effects of distant metastases, particularly in the brain. In very few cases, radiation alone may be the curative treatment for rectal cancer.

Chemotherapy

Adjuvant chemotherapy, (treating the patient who has no evidence of residual disease but who is at high risk for recurrence), is considered in patients whose tumors deeply penetrate or locally invade (late stage II and stage III). If the tumor was not locally advanced, this form of chemotherapeutic adjuvant therapy may be recommended without radiation. This therapy is identical to that of colon cancer and leads to similar results. Standard therapy is treatment with 5-fluorouracil, (5-FU) combined with leucovorin for a period of six to 12 months. 5-FU is an antimetabolite and leucovorin improves the response rate. Another agent, levamisole, (which seems to stimulate the immune system), may be substituted for leucovorin. These protocols reduce rate of recurrence by about 15% and reduce mortality by about 10%. The regimens have some toxicity but usually are tolerated fairly well.

Similar chemotherapy is administered for stage IV disease or if a cancer progresses and metastasis develops. Results show response rates of about 20%. A response is a temporary regression of the cancer in response to the chemotherapy. Unfortunately, these patients eventually succumb to the disease. Clinical trials have now shown that the results can be improved with the addition of another agent to this regimen. Irinotecan does not seem to increase toxicity but has improved response rates to 39%, added two to three months to disease free survival, and prolonged overall survival by a little more than two months.

Alternative treatment

Most alternative therapies have not been studied in clinical trials. Large doses of vitamins, fiber, and green tea are among therapies tried. A 2003 report on a large Harvard University study showed that people who took multivitamins for at least 15 years had a 34% reduction in risk of rectal cancer. Before initiating any alternative therapies, the patient should consult his or her physician to be sure that these therapies do not complicate or interfere with the recommended therapy.

Prognosis

Prognosis is the long-term outlook or survival after therapy. Overall, about 50% of patients treated for colon and rectal cancer survive the disease. As expected, the survival rates are dependent upon the stage of the cancer at the time of diagnosis, making early detection crucial.

About 15% of patients present with stage I disease, or are diagnosed with Stage I disease when they initially visit a doctor, and 85-90% survive. Stage II represents 20-30% of cases and 65-75% survive; 30-40% comprise the stage III presentation, of which 55% survive. The remaining 20-25% present with stage IV disease and are rarely cured.

Prevention

There is not an absolute method for preventing colon or rectal cancer. An individual can lessen risk or identify the precursors of colon and rectal cancer. The patient with a familial history can enter screening and surveillance programs earlier than the general population. High-fiber diets and vitamins, avoiding obesity, and staying active lessen the risk. In fact, a 2003 report said that vigorous exercise (to the point of sweating or feeling out of breath) lowered risk of rectal cancer by nearly 40% compared to those who exercised less. Avoiding cigarettes and alcohol may be helpful. By controlling these environmental factors, an individual can lessen risk and to this degree prevent the disease.

By undergoing appropriate screening when uncontrollable genetic risk factors have been identified, an individual may be rewarded by the identification of benign polyps that can be treated as opposed to having these growths degenerate into a malignancy.