eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract

Rectal Cancer

Author: Elizabeth Cirincione, MD, Director of Colon and Rectal Surgery, Department of Surgery, Nassau University Medical Center
Coauthor(s): Burt Cagir, MD, FACS, Assistant Professor of Surgery, State University of New York, Upstate Medical Center; Consulting Staff, Director of Surgical Research, Robert Packer Hospital; Associate Program Director, Department of Surgery, Guthrie Clinic
Contributor Information and Disclosures

Updated: Feb 16, 2007

Introduction

Background

Approximately 135,000 new cases of colorectal cancer occur in the United States each year, resulting in approximately 55,000 deaths per year. Two thirds of these cases occur in the colon and one third in the rectum. The incidence and epidemiology, etiology, pathogenesis, and screening recommendations are common to both colon cancer and rectal cancer. These areas are addressed together.

Adenocarcinomas (98%) comprise most rectal cancers and are the focus of this discussion. Other rare rectal cancers, including carcinoid (0.1%), lymphoma (1.3%), and sarcoma (0.3%), are not discussed. Squamous cell carcinomas may develop in the transition area from rectum to anal verge and are considered anal carcinomas. Very rare cases of squamous cell carcinoma of the rectum have been reported.

Pathophysiology

Carcinomas are found in as many as 4% of neoplastic polyps. Cells must accumulate 4-5 molecular defects, including activation of oncogenes and inactivation of tumor suppressor genes, to undergo malignant transformation. In normal mucosa, the surface epithelium regenerates approximately every 6 days. Crypt cells migrate from the base of the crypt to the surface, where they undergo differentiation, maturation, and, ultimately, lose the ability to replicate.

In adenomas, several genetic mutations alter this process, starting with inactivation of the adenomatous polyposis coli (APC) gene, allowing unchecked cellular replication at the crypt surface. With the increase in cell division, further mutations occur, resulting in activation of the K-ras oncogene in the early stages and p53 mutations in later stages. These cumulative losses in tumor suppressor gene function prevent apoptosis and give the cell eternal life.

Frequency

United States

The lifetime risk of developing a colorectal malignancy is approximately 5.9% in the general population.

Race

• Western nations tend to have a higher incidence than Asian and African countries; however, within the United States, little difference in incidence exists among whites, African Americans, and Asian Americans.
• Among religious denominations, colorectal cancer occurs more frequently in the Jewish population.

Sex

The incidence of colorectal malignancy is slightly higher in males than in females.

Age

Incidence peaks in the seventh decade; however, cases have been reported in young children.

Clinical

History

• 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.
• Bleeding
  • This is the most common symptom of rectal cancer and occurs in 60% of patients.
  • Bleeding often is attributed to other causes (eg, hemorrhoids), especially if the patient has a history of other problems.
  • Profuse bleeding and anemia are rare.
  • Bleeding may be accompanied by the passage of mucus, which warrants further investigation.
• Change in bowel habits
  • Present in 43% of patients, this symptom has several different presentations. Often, it occurs in the form of diarrhea, particularly if the tumor has a large villous component.
  • These patients may have hypokalemia on laboratory studies.
  • The capacity of the rectal reservoir may mask the presence of a small lesion.
  • Some patients experience a change in caliber of the stool.
  • Large tumors can cause obstructive symptoms.
  • Tumors located low in the rectum can cause a feeling of incomplete evacuation and tenesmus.
• Occult bleeding: This is detected on screening fecal occult blood test (FOBT) in 26% of cases.
• Abdominal pain
  • Partial large-bowel obstruction may cause colicky abdominal pain and bloating and is present in 20% of cases.
  • Back pain is usually a late sign caused by a tumor invading or compressing nerve trunks.
  • Urinary symptoms may occur if the tumor is invading or compressing the bladder or prostate.
• Malaise: This nonspecific entity is the presenting symptom in 9% of cases.
• Bowel obstruction: Complete obstruction of the large bowel is rare and is the presenting symptom in 9% of cases.
• Pelvic pain: This late symptom usually indicates nerve trunk involvement and is present in 5% of cases.
• Other presentations include emergencies such as peritonitis from perforation (3%) or jaundice, which may occur with liver metastases ( <1%).

Physical

• Physical examination is performed with specific attention to possible metastatic lesions, including enlarged lymph nodes or hepatomegaly. The remainder of the colon is also examined.
• Digital rectal examination
  • The easy accessibility of the rectum provides an opportunity to readily detect abnormal lesions via digital rectal examination (DRE). The average finger can reach approximately 8 cm above the dentate line.
  • 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) 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.

Causes

• The etiology of colorectal cancer is unknown, but colorectal cancer appears to be multifactorial in origin and includes environmental factors and a genetic component. Diet may have an etiologic role, especially diet with high fat content.
• Approximately 75% of colorectal cancers are sporadic and develop in people with no specific risk factors. The remaining 25% of cases occur in people with significant risk factors. Most (15-20%) colorectal cancers develop in people with either a positive family history or a personal history of colorectal cancer or polyps. The remaining cases occur in people with certain genetic predispositions, such as hereditary nonpolyposis colorectal cancer (HNPCC, 4-7%) or familial adenomatous polyposis (FAP, 1%) or in people with inflammatory bowel disease (IBD, 1%).
• Environmental factors
  • Diet
    • A high-fat, low-fiber diet is implicated in the development of colorectal cancer. Specifically, people who ingest a diet high in unsaturated animal fats and highly saturated vegetable oils (eg, corn, safflower) have a higher incidence of colorectal cancer. The mechanism by which these substances are related to the development of colorectal cancer is unknown.
    • Saturated fats from dairy products do not have the same effect, nor do oils containing oleic acid (eg, olive, coconut, fish oils). Omega-3 monounsaturated fatty acids and omega-6 monounsaturated fatty acids also appear to be less carcinogenic than unsaturated or polyunsaturated fats. In fact, recent epidemiologic data suggest that high fish consumption may provide a protective effect against development of colorectal cancer.
    • Long-term diets high in red meat or processed meats appear to increase the risk of distal colon and rectal cancers.
    • The ingestion of a high-fiber diet may be protective against colorectal cancer. Fiber causes the formation of a soft, bulky stool that dilutes out carcinogens; it also decreases colonic transit time, allowing less time for harmful substances to contact the mucosa. The decreased incidence of colorectal cancer in African individuals is attributed to their high-fiber, low–animal-fat diet. This favorable statistic is reversed when African people adopt a western diet.
    • Increased dietary intake of calcium appears to have a protective effect on colorectal mucosa by binding with bile acids and fatty acids. The resulting calcium salts may have antiproliferative effects, decreasing crypt cell production in the mucosa.
    • Other dietary components, such as selenium, carotenoids, and vitamins A, C, and E, may have protective effects by scavenging free-oxygen radicals in the colon.
  • Alcohol: Daily alcohol drinkers experience a 2-fold increased risk of developing colorectal carcinoma. Specifically, beer consumption in excess of 15 liters per month increases the risk of rectal cancer in men.
  • Tobacco: Smoking, and in particular, smoking starting at a young age, increases the risk of colorectal cancer. Possible mechanisms for tumor development include the production of toxic polycyclic aromatic amines and the induction of angiogenic mechanisms by tobacco smoke.
  • Bile acids: After cholecystectomy, bile acids circulate continuously, increasing exposure to the degrading action of intestinal bacteria. While this process is known to occur in the formation of certain carcinogens, a direct connection between cholecystectomy and the development of colorectal cancer has not been established.
• Hereditary factors
  • Family history: The relative risk of developing colorectal cancer is increased in the first-degree relatives of affected patients. The relative risk of developing this malignancy if one first-degree family member is affected with colorectal cancer is 1.72; with two first-degree family members affected, the relative risk increases to 2.75. If the first-degree family member is younger than 45 years at the time of diagnosis, the risk increases to 5.37.
  • Personal history of colorectal cancer or polyps: Of patients with colorectal cancer, 30% have synchronous lesions, usually adenomatous polyps. Approximately 40-50% of patients have polyps on follow-up colonoscopy. Of patients who have adenomatous polyps on colonoscopy, 29% have additional polyps on repeat colonoscopy 1 year later. Malignancy develops in 2-5% of patients. The risk of cancer in people who have had polyps removed is 2.7-7.7 times that of the general population.
• Genetic disorders
  • Familial adenomatous polyposis
    • FAP is an autosomal dominant inherited syndrome that results in the development of more than 100 adenomatous polyps and a variety of extraintestinal manifestations.
    • The defect is in the APC gene, which is located on chromosome 5 at locus q21.
    • The disease process causes the formation of hundreds of intestinal polyps, osteomas of the bone, desmoid tumors, and, occasionally, brain tumors.
    • Individually, the polyps do not have a risk of malignant transformation greater than polyps in the general population. The increased number of polyps, however, predisposes patients to a greater risk of cancer. If left untreated, colorectal cancer develops in nearly 100% of these patients by age 40 years.
    • While the hereditary link is documented, approximately 20% of FAP cases are caused by spontaneous mutation.
  • Hereditary nonpolyposis colorectal cancer
    • HNPCC is an autosomal dominant inherited syndrome that occurs because of defective mismatch repair genes located on chromosomes 2, 3, and 7.
    • Patients have the same number of polyps as the general population, but their polyps are more likely to become malignant. These patients also have a higher incidence of endometrial, gastric, thyroid, and brain cancers.
    • The revised Amsterdam criteria are used to select at-risk patients (all criteria must apply): 3 or more relatives who are diagnosed with an HNPCC-associated cancer (colorectal, endometrium, small bowel, ureter, or renal pelvis); 1 affected person is a first-degree relative of the other 2; 1 or more cases of cancer are diagnosed before age 50 years; at least 2 generations are affected; FAP has been excluded, and tumors have undergone pathology review.
• Inflammatory bowel disease
  • Ulcerative colitis
    • The incidence of malignancy increases with duration. After 10 years, the incidence of colorectal cancer in ulcerative colitis (UC) is approximately 1% per year.
    • Evaluate patients for dysplastic changes with annual colonoscopy. Dysplasia is a precursor of cancer and, when present, the risk of cancer is 30%.
  • Crohn disease
    • The incidence of colorectal cancer in patients with Crohn disease is 4-20 times greater than that of the general population. Cancer occurs in patients with disease of at least 10 years' duration. The average age at diagnosis (ie, 46-55 y) is younger than that of the general population.
    • Cancers often develop in areas of strictures and in defunctionalized segments of intestine. In patients with perianal Crohn disease, malignancy often presents in fistulous tracts.
    • Patients with Crohn colitis undergo the same surveillance regimen as those with UC.

• Search for CME/CE on This Topic »

• Rigid Sigmoidoscopy (Clinical Procedures)
• Radiation Cystitis (Urology)
• Villous Adenoma (Gastroenterology)
• Gardner Syndrome (General Surgery)

• Colonoscopy Introduction
• Abdominal Pain in Adults Overview
• Esophagus, Stomach, and Intestine Center
• Colon Cancer Overview
• Sigmoidoscopy Introduction
• Rectal Bleeding Overview
• Rectal Cancer Overview
• Cancer and Tumors Center

• Biomarkers May Predict Rectal Cancer Response to Cetuximab
• Lymph Node Ratio Predicts Survival in Stage III Rectal Cancer
• Rectal Cancer Survival Improved With Response to Radiation Therapy

• UFT (tegafur-uracil) in Rectal Cancer
• Controversies of Total Mesorectal Excision for Rectal Cancer in Elderly Patients: Commentary from F1000
• National Comprehensive Cancer Network (NCCN) Colon Cancer and Rectal Cancer Guidelines, Version 1.2009