eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract

Rectal Cancer

Author: 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
Coauthor(s): Douglas R Trostle, MD, MBA, FACS,, Chairman of Surgery, The Guthrie Clinic and Robert Packer Hospital; Clinical Professor of Surgery, The Medical College of Pennsylvania
Contributor Information and Disclosures

Updated: Sep 25, 2009

Introduction

Background

Colon and rectal cancer incidence was negligible before 1900. The incidence of colorectal cancer has been rising dramatically following economic development and industrialization. Currently, colorectal cancer is the third leading cause of cancer deaths in both males and females in the United States.^1,2  

Adenocarcinomas comprise the vast majority (98%) of colon and rectal cancers. Other rare rectal cancers, including carcinoid (0.4%), lymphoma (1.3%), and sarcoma (0.3%), are not discussed in this article. 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

The incidence and epidemiology, etiology, pathogenesis, and screening recommendations are common to both colon cancer and rectal cancer. These areas are addressed together.

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.

The significant portions of colorectal carcinomas are adenocarcinomas. The adenoma-carcinoma sequence is well described in the medical literature.^1,4  Colonic adenomas precede adenocarcinomas. Approximately 10% of adenomas will eventually develop into adenocarcinomas. This process may take up to 10 years.¹

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.

Frequency

United States

Colon and rectal cancer is the third most common cancer in both females and males. The American Cancer Society estimates that 106,100 new cases of colon cancer and 40,870 new cases of rectal cancer will occur in 2009; 75,590 cases of colorectal cancers are expected in men and 71,380, in women.²  Approximately 54,090 deaths from colon cancer and 17,290 deaths from rectal cancer are expected to occur in 2009.
Both colon and rectal cancer incidences as well as mortality rates have been decreasing for the last two decades, from 66.3 per 100,000 population in 1985 to 46.4 in 2005.² The rate of decrease accelerated from 1998-2005 (to 2.8% per year in men and 2.2% per year in women), in part because of increased screening, allowing the detection and removal of colorectal polyps before they progress to cancer. The lifetime risk of developing a colorectal malignancy is approximately 6% in the general U.S. population. This decrease is due to a declining incidence and improvements in both early detection and treatment

International

Although the incidence of colon and rectal cancer varies considerably by country, an estimated 944,717 cases were identified worldwide in 2000. High incidences of colon and rectal cancer cases are identified in the US, Canada, Japan, parts of Europe, New Zealand, Israel, and Australia. Low colorectal cancer rates are identified in Algeria and India. The majority of colorectal cancers still occur in industrialized countries. Recent rises in colorectal cancer incidence have been observed in many parts of the Japan, China (Shanghai) and in several Eastern European countries.¹

Mortality/Morbidity

The American Cancer Society estimates that colorectal cancer will account for 9% of all cancer deaths (49,920) in 2009. In the US, mortality rates have been decreasing in both sexes for the past 2 decades. (The 1- and 5-year rate for patients with colon and rectal cancer is 83% and 64%, respectively.) When colorectal cancers are detected early and localized, the 5-year survival rate is 90%.²

Race

The incidence of colorectal cancer tends to be higher in Western nations than in Asian and African countries; however, within the United States, minor differences in incidence exist among whites, African Americans, and Asian Americans. Five-year survival rates are lower among blacks (55%)than whites (66%). Among religious denominations, colorectal cancer occurs more frequently in the Jewish population.²

Sex

The incidence of colorectal malignancy is slightly higher in males than in females. The overall age-standardized incidence of colorectal cancer was 65/100,000 for males and 47/100,000 for females between 1995 and 1999. The male-female ratio is 1.37%. Mortality rates for colorectal cancer were also higher in males (25.4 per 100,000) than in females (18 per 100,000) in 1999. Left colon carcinomas were more likely to be observed in males and right colon carcinomas were more likely to be observed in females.²    

Age

The incidence of colorectal cancer starts to increase after age 35 and rises rapidly after age 50, peaking in the seventh decade. More than 90% of colon cancers occur after age 50. However, cases have been reported in young children and adolescents.¹    

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 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. Bleeding may be accompanied by the passage of mucus, which warrants further investigation.

Change in bowel habits is present in 43% of patients; change is not evident in some cases because the capacity of a rectal reservoir can mask the presence of small lesions. When change does occur it is often in the form of diarrhea, particularly if the tumor has a large villous component. These patients may have hypokalemia, as shown in laboratory studies. Some patients experience a change in the 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 is detected via a fecal occult blood test (FOBT) in 26% of all cases. 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.

Malaise is a nonspecific symptom and present in 9% of rectal cancer cases. Bowel obstruction due to a high-grade rectal lesion is rare, occurring in 9% of all cases. Pelvic pain is a late symptom, usually indicating nerve trunk involvement, and is present in 5% of all cases. Other manifestations 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 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.

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 commonly, a family history or personal history of colorectal cancer or polyps, which are present in 15-20% of all cases. Other significant risk factors are certain genetic predispositions, such as hereditary nonpolyposis colorectal cancer (HNPCC; 4-7% of all cases) and familial adenomatous polyposis (FAP, 1%); and inflammatory bowel disease (IBD; 1% of all cases).

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 carcinogenic 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.^4,7  
 
The ingestion of a high-fiber diet may be protective against colorectal cancer. Fiber causes the formation of a soft, bulky stool that dilutes carcinogens; it also decreases colonic transit time, allowing less time for harmful substances to contact the mucosa. The decreased incidence of colorectal cancer in Africans is attributed to their high-fiber, low–animal-fat diet. This favorable statistic is reversed when African people adopt a western diet. Meta-analysis of case-controlled studies found that reduction in colorectal cancer risk occurs with increasing intake of dietary fiber.⁴  

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. A double-blind placebo-controlled study showed a statistically significant reduction in the incidence of metachronous colorectal adenomas.⁸ 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
Alcohol intake of more than 30 g daily has been associated with increased risk of developing colorectal carcinoma, with risk of rectal cancer greater than that of colon cancer. Risk appears greater with beer than with wine.⁹ Specifically, Kabat et al found that daily beer consumption of 32 ounces or more increases the risk of rectal cancer in men (odds ratio 3.5).¹⁰

Tobacco
Smoking, particularly when started at a young age, increases the risk of colorectal cancer.¹¹ Possible mechanisms for tumor development include the production of toxic polycyclic aromatic amines and the induction of angiogenic mechanisms due to tobacco smoke.

Cholecystectomy 

Following cholecystectomy, bile acids flow freely, increasing exposure to the degrading action of intestinal bacteria. This constant exposure increases the proportion of carcinogenic bile acid byproducts.  A meta-analysis by Giovannucci et al revealed an increased risk of proximal colon carcinoma following cholecystectomy. Although a large number of studies suggest the increased risk of proximal colon cancer in patients following cholecystectomy, the data are not compelling enough to warrant enhanced screening in this patient population.¹  

Hereditary factors

The relative risk of developing colorectal cancer is increased in the first-degree relatives of affected patients. For offspring, the relative risk is 2.42 (95% CI: 2.20-2.65); when more than one family member is affected, the relative risk increases to 4.25 (95% CI; 3.01-6.08). If the first-degree family member is younger than 45 years at the time of diagnosis, the risk increase is even higher.¹²
 
Regarding the 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 a follow-up colonoscopy. Of all patients who have adenomatous polyps discovered via a colonoscopy, 29% of them have additional polyps discovered on a repeat colonoscopy one 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.¹³


Genetic disorders

Familial adenomatous polyposis (FAP)
FAP is an autosomal dominant inherited syndrome that results in the development of more than 100 adenomatous polyps and a variety of extra-intestinal 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 bone, desmoid tumors, and, occasionally, brain tumors. Individually, these polyps are no more likely to undergo malignant transformation than are 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. Whenever the hereditary link is documented, approximately 20% of FAP cases are found to be 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):

• three or more relatives who are diagnosed with an HNPCC-associated cancer (colorectal, endometrium, small bowel, ureter, or renal pelvis)
• one affected person is a first-degree relative of the other two
• one or more cases of cancer are diagnosed before age 50
• at least two generations are affected
• FAP has been excluded
• tumors have undergone a pathology review.

Inflammatory bowel disease

The malignant pathway in these patients does not involve any adenoma-carcinoma sequence. Cancer risk increases with duration of disease. After 10 years, the incidence of colorectal cancer in ulcerative colitis (UC) is approximately 1% per year. Patients should be evaluated for dysplastic changes via an annual colonoscopy. Dysplasia is a precursor of cancer and when present, the risk of cancer is 30%.

The incidence of colorectal cancer in patients with Crohn's 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 cancer diagnosis, 46-55 years, is younger than that of the general population. Cancers often develop in areas of strictures and in de-functionalized segments of intestine. In patients with perianal Crohn's disease, malignancy is often present in fistulous tracts. Patients with Crohn's colitis should undergo the same surveillance regimen as those with UC.

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