ABSTRACT The rectum is part of digestive system.

Once food nutrients have been absorbed by the small intestines, the waste is moved by muscular contractions into the large intestine (bowel). Water is removed and the waste is temporarily stored in the rectum, which makes up the last 20cm or so of the bowel. From the rectum, wastes pass out of the body through the anus. The rectums lining (ephitelium) secretes mucus that help to lubricate the faeces throuh the anus. Cancer of the rectum begins as cellular changes in the topmost layer of the epithelium. Rectal cancer tends to affect people over the age of 50 years, with men more at risk than woman. Some people have an increase due to genetic factors and may develop the disease sometime after the age of 40 years.

Adenocarcinomas comprise the vast majority (98%) of colon and rectal cancers. Squamous cell carcinomas may develop in the transition area from the rectum to the anal verge and are considered anal carcinomas. Very rare cases of squamous cell carcinoma of the rectum have been reported.[1, 3] Approximately 20% of colon cancers develop in the cecum, another 20% in the rectum, and an additional 10% in the rectosigmoid junction. Approximately 25% of colon cancers develop in the sigmoid colon.[1] ETIOLOGY The etiology of colorectal cancer is unknown, but colorectal cancer appears to be multifactorial in origin and includes environmental factors and a genetic component. 1. Approximately 75% of colorectal cancers are sporadic and develop in people with no specific risk factors. 2. The remaining 25% of cases occur in people with significant risk factors--most commonly, a family history or personal history of colorectal cancer or polyps, which are present in 15-20% of all cases. familial polyposis is almost certain to lead to rectal cancer. a person who has already had rectal cancer may develop this disease a second time. 3. Hereditary nonpolyposis colorectal cancer (HNPCC; 4-7% of all cases) It is caused by changes in an HNPCC gene.

4. Familial adenomatous polyposis (FAP, 1%); and inflammatory bowel disease (IBD; 1% of all cases). It is caused by a change in a specific gene called APC. Family members of people who have HNPCC or FAP can have genetic testing to check for specific genetic changes. For those who have changes in their genes, health care providers may suggest ways to try to reduce the risk of colorectal cancer, or to improve the detection of this disease 5. Ulcerative colitis or Crohn's disease. A person who has had a condition that causes inflammation of the colon (such as ulcerative colitis or Crohn's disease) for many years 6. Diet. Studies suggest that diets high in fat (especially animal fat) and low in calcium, folate, and fiber may increase the risk of colorectal cancer. Also, some studies suggest that people who eat a diet very low in fruits and vegetables

PATHOPHYSIOLOGY The mucosa in the large intestine regenerates approximately every 6 days. Crypt cells migrate from the base of the crypt to the surface, where they undergo differentiation and maturation, and ultimately lose the ability to replicate. Three pathways to colon and rectal carcinoma have been described:

the adenomatous polyposis coli (APC) gene adenoma-carcinoma pathway the hereditary nonpolyposis colorectal cancer (HNPCC) pathway ulcerative colitis dysplasia. 1. The APC adenoma carcinoma pathway involves several genetic mutations, starting with inactivation of the APC gene, which allows unchecked cellular replication at the crypt surface.. If the APC mutation is inherited, it will result in familial adenomatous polyposis syndrome. 2. HNPCC is an autosomal dominant inherited syndrome that occurs because of defective mismatch repair genes located on chromosomes 2, 3, and 7 (it called mutation in DNA). Patients have the same number of polyps as the general population, but their polyps are more likely to become malignant.

3. Chronic inflammation such as in ulcerative colitis can result in genetic alterations which then lead into dysplasia and carcinoma formation.[1]

SYMPTOMS All patients should undergo a complete history (including a family history) and assessment of risk factors for the development of rectal cancer. Many rectal cancers produce no symptoms and are discovered during digital or proctoscopic screening examinations. 1. Bleeding is the most common symptom of rectal cancer, occurring in 60% of patients. Bleeding often is attributed to other causes (eg, hemorrhoids), especially if the patient has a history of other rectal problems. Profuse bleeding and anemia are rare. 2. Change in bowel habits is present in 43% of patients. Urgency to pass bowel motions, if the Tumors located low in the rectum can cause a feeling of incomplete evacuation and tenesmus. or a sensation that the bowel isnt empty after going to the toilet. When change does occur it is often in the form of diarrhea, particularly if the tumor has a large villous component. Large tumors can cause obstructive symptoms. 3. Abdominal pain is present in 20% of the cases. Partial large-bowel obstruction may cause colicky abdominal pain and bloating. Back pain is usually a late sign caused by a tumor invading or compressing nerve trunks. Urinary symptoms may also occur if the tumor is invading or compressing the bladder or prostate. 4. Pelvic pain is a late symptom, usually indicating nerve trunk involvement, and is present in 5% of all cases. 5. Other manifestations include emergencies such as peritonitis from perforation (3%) or jaundice, which may occur with liver metastases (< 1%). PHYSICAL EXAMINATIONS Physical examination is performed with specific attention to size and location of rectal cancer in addition to possible metastatic lesions, including enlarged lymph nodes or hepatomegaly. The remainder of the colon is also evaluated. Digital rectal examination (DRE) provides an opportunity to readily detect abnormal lesions. The average finger can reach approximately 8 cm above the dentate line. Rectal

tumors can be assessed for size, ulceration, and presence of any pararectal lymph nodes. Fixation of the tumor to surrounding structures (eg, sphincters, prostate, vagina, coccyx and sacrum) also can be assessed. DRE also permits a cursory evaluation of the patient's sphincter function. This information is necessary when determining whether a patient is a candidate for a sphincter-sparing procedure. Rigid proctoscopy is also performed to identify the exact location of the tumor in relation to the sphincter mechanism. DIAGNOSTIC TEST 1. A fecal occult blood test (FOBT) is a test used to check for hidden blood in the stool. Sometimes cancers or polyps can bleed, and FOBT is used to detect small amounts of bleeding. A sample of stool is tested for traces of blood. 2. A sigmoidoscopy is an examination of the rectum and lower colon (sigmoid colon) using a lighted instrument called a sigmoidoscope. This allows the doctor to look at the inside of the rectum and part of the colon for cancer or polyps. Because the tube is only about 2 feet long, the doctor is only able to see about half of the colon. 3. A colonoscopy is an examination of the rectum and entire colon using a lighted instrument called a colonoscope, a longer version of the sigmoidoscope. It allows the doctor to see the entire colon. If a polyp is found, the doctor may remove it. If anything else looks abnormal, a biopsy might be done. 4. A virtual colonoscopy is like a super x-ray of the colon. Air is pumped into the colon to cause it to expand, then a special CT scan is done. More studies are needed to find out if it is as good as or better than other methods of finding colon cancer early. 5. DNA stool tests. Colon polyps and cancers continuously shed mutated cells that eventually make their way into stool. Analyzing these cells for genetic mutations may detect polyps and early-stage cancers. Although not yet widely used, this test is likely to become more common in the future. 6. A double contrast barium enema (DCBE) is a series of x-rays of the colon and rectum. A chalky substance is used to partly fill and open up the colon. Air is then pumped in to cause the colon to expand. This allows good x-ray films to be taken. You will need to use laxatives the night before the exam and have an enema the morning of the exam. 7. Staging tests. Identifying the extent and spread of the disease is essential for choosing the best treatment for you. Staging tests, such as computerized tomography (CT),positron emission tomography (PET) scan and X-rays help your doctor determine how deeply the

cancer has invaded the colon wall and whether it spread to nearby lymph nodes or organs. Your doctor may perform a colonoscopy andendoscopic ultrasound of the rectum, mark the location of a lesion, and then perform an ultrasound-guided fine-needle aspiration of any suspicious lymph nodes.

STAGING
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Stage 0. The cancer is very early. It is found only in the innermost lining of the rectum. Stage I. The cancer involves more of the inner wall of the rectum. Stage II. The cancer has spread outside the rectum to nearby tissue, but not to the lymph nodes. (Lymph nodes are small, bean-shaped structures that are part of the body's immune system.)

Stage III. The cancer has spread to nearby lymph nodes, but not to other parts of the body.

Stage IV. The cancer has spread to other parts of the body. Rectal cancer tends to spread to the liver and/or lungs.

Recurrent. Recurrent cancer means the cancer has come back after treatment. The disease may recur in the colon or rectum or in another part of the body.

Tumor, Node, Metastasis (TNM) System The TNM system is a universal staging system for all solid cancers that is based on clinical and pathologic information. Each category is independent. Neither the Dukes nor the TNM system includes prognostic information such as histologic grade, vascular or perineural invasion, or tumor DNA ploidy. TNM staging of rectal cancer correlates well with 5-year survival rates of patients with rectal cancer (see the TNM stagedependent 5-year survival rate for rectal carcinomas). TNM classification for cancer of the colon and rectum (AJCC) Primary tumor (T) includes the following:

TX - Primary tumor cannot be assessed or depth of penetration not specified T0 - No evidence of primary tumor Tis - Carcinoma in situ (mucosal); intraepithelial or invasion of the lamina propria

T1 - Tumor invades submucosa T2 - Tumor invades muscularis propria T3 - Tumor invades through the muscularis propria into the subserosa or into nonperitonealized pericolic or perirectal tissue T4 - Tumor directly invades other organs or structures and/or perforates the visceral peritoneum Regional lymph nodes (N) include the following:

NX - Regional lymph nodes cannot be assessed N0 - No regional lymph node metastasis N1 - Metastasis in 1-3 pericolic or perirectal lymph nodes N2 - Metastasis in 4 or more pericolic or perirectal lymph nodes N3 - Metastasis in any lymph node along the course of a named vascular trunk Distant metastasis (M) include the following:

MX - Presence of metastasis cannot be assessed M0 - No distant metastasis M1 - Distant metastasis Table 1. Comparison of AJCC Definition of TNM Staging System to Dukes Classification. (Open Table in a new window) Rectal Cancer Stages TNM Staging Duke Staging 5-Year Survival Stage I Stage II A B Stage I A B C Stage IV T1-2 N0 M0 T3 N0 M0 T4 N0 M0 T1-2 N1 M0 T3-4 N1 M0 T1-4 N2 M0 T1-4 N0-2 M1 C A B >90% 60%-85% 60%-85% 55%-60% 35%-42% 25%-27% 5%-7%

The TNM stage dependent 5-year survival rate for rectal carcinomas is as follows[26] :

Stage I - 90% Stage II - 60-85%

Stage III - 27-60% Stage IV - 5-7%

TREATMENT Methods of Rectal Cancer Treatment Rectal cancer treatment may involve surgery, radiation therapy, or chemotherapy. Some people have a combination of treatments. Colon cancer sometimes is treated differently from rectal cancer. Treatments for colon and rectal cancer are described separately. At any stage of rectal cancer, treatments are available to control pain and other symptoms, and to relieve the side effects of therapy. This kind of treatment is called supportive care, symptom management, or palliative care. People with rectal cancer may want to talk to the doctor about taking part in a clinical trial, a research study of new rectal cancer treatment methods. The section on "The Promise of Cancer Research" has more information about clinical trials. Surgery for Rectal Cancer Surgery is the most common rectal cancer treatment. It is a type of local therapy. It treats the cancer in the colon or rectum and the area close to the tumor. A small malignant polyp may be removed from the colon or upper rectum with a colonoscope. Some small tumors in the lower rectum can be removed through the anus without a colonoscope. For a larger cancer, the surgeon makes an incision into the abdomen to remove the tumor and part of the healthy colon or rectum. Some nearby lymph nodes also may be removed. The surgeon checks the rest of the intestine and the liver to see if the cancer has spread. When a section of the colon or rectum is removed, the surgeon can usually reconnect the healthy parts. However, sometimes reconnection is not possible. In this case, the surgeon creates a new path for waste to leave the body. The surgeon makes an opening (a stoma) in the wall of the abdomen, connects the upper end of the intestine to the stoma, and closes the other end. The operation to create the stoma is called a colostomy. A flat bag fits over the stoma to collect waste, and a special adhesive holds it in place.

For most people who have a colostomy, it is temporary. It is needed only until the colon or rectum heals from surgery. After healing takes place, the surgeon reconnects the parts of the intestine and closes the stoma. Some people, especially those with a tumor in the lower rectum, need a permanent colostomy. Rectal Cancer Chemotherapy Chemotherapy uses anticancer drugs to kill cancer cells. It is called systemic therapy because it enters the bloodstream and can affect cancer cells throughout the body. The patient may have chemotherapy alone or combined with surgery, radiation therapy, or both. Chemotherapy given before surgery is called neoadjuvant therapy. Chemotherapy before surgery may shrink a large tumor. Chemotherapy treatment after surgery is called adjuvant therapy. Adjuvant therapy is used to destroy any remaining cancer cells and prevent the cancer from coming back in the colon or rectum, or elsewhere. Chemotherapy is also used to treat people with advanced disease. Anticancer drugs are usually given through a vein, but some also may be given by mouth. The patient may be treated in an outpatient part of the hospital, at the doctor's office, or at home. Rarely, a hospital stay may be needed. Radiation Therapy for Rectal Cancer Radiation therapy (also called radiotherapy) is local therapy. It uses high-energy rays to kill cancer cells. It affects cancer cells only in the treated area. Doctors use two types of radiation therapy to treat cancer. Sometimes people receive both types:

External radiation: The radiation comes from a machine. Most patients go to the hospital or clinic for their treatment, generally 5 days a week for several weeks. In some cases, external radiation is given during surgery.

Internal radiation (implant radiation): The radiation comes from radioactive material placed in thin tubes put directly into or near the tumor. The patient stays in the hospital, and the implants generally remain in place for several days. Usually they are removed before the patient goes home.

PROGNOSIS Overall 5-year survival rates for rectal cancer are as follows:

Stage I, 90% Stage II, 60% to 85% Stage III, 27% to 60% Stage IV, 5% to 7% Fifty percent of patients develop recurrence, which may be local, distant, or both. Local recurrence is more common in rectal cancer than in colon cancer.

Disease recurs in 5-30% of patients, usually in the first year after surgery. Factors that influence the development of recurrence include surgeon variability, grade and stage of the primary tumor, location of the primary tumor, and ability to obtain negative margins.

Surgical therapy may be attempted for recurrence and includes pelvic exenteration or APR in patients who had a sphincter-sparing procedure. Radiation therapy generally is used as palliative treatment in patients who have locally unresectable disease.