Gastrointestinal cancers

ALSO KNOWN AS: Abdominal and intestinal neoplasms

RELATED CONDITIONS: Gallbladder cancer, bile duct cancer, pancreatic cancer, liver cancer, Helicobacter pylori infection, pernicious anemia, acid reflux disease, gastric polyps, familial adenomatous polyposis, ulcerative colitis, Crohn's disease

DEFINITION: Gastrointestinal cancers are tumors in the various organs of the gastrointestinal tract—the esophagus, stomach, colon, small intestine, rectum, and anus—formed when normal cells enlarge and divide abnormally.

Risk factors: Major risk factors for developing gastrointestinal cancers include age, gender, race, tobacco use, exposure to carcinogens, family history, and diet. Cancer of the small intestine usually appears after a person reaches the age of sixty; esophageal cancer, over fifty-five; stomach cancer and colorectal cancer, over fifty; and anal cancer, over thirty-five.

Approximately four times as many men as women develop esophageal cancer, and twice as many men as women get stomach cancer. More women are likely to have anal cancer of the inner part of the anus, while more men have outer involvement. Black Americans are more likely to have stomach cancer than European Americans. Tobacco use puts people at greater risk for anal, esophageal, and stomach cancer.

Exposure to rubber, leather, or certain dyes increases the risk of esophageal cancer, while industrial dust and fumes increase the risk of stomach cancer. Exposure to nitrosamine is a factor in cancer of the small intestine. A family history of polyps increases the risk of stomach cancer. A history of some types of polyps, ulcerative colitis, cancer of the breast, ovary, or uterus, or any cancer among first-degree relatives are risk factors for colon cancer.

Diet is a greater risk factor for stomach cancer in Japan, Korea, parts of Eastern Europe, and Latin America, possibly because the typical diets in those areas are high in dried, smoked, salted, and pickled foods. Diets high in fat and low in fruits, vegetables, and other high-fiber foods are risk factors for colorectal cancer.

Although cancer of the small intestine is unusual, certain inherited disorders may be risk factors. A history of genital warts, fistulas, fissures, genital herpes, gonorrhea, radiation dermatitis, receptive anal sex, symptomatic human immunodeficiency virus (HIV) disease, hemorrhoids, or anal degenerative skin changes increases the risk of anal cancer.

Etiology and the disease process: Although the causes of many gastrointestinal cancers are unknown, causative agents or factors have been found for some. Alcohol and tobacco abuse are common causes of esophageal cancer in North America. In other parts of the world, exposure to environmental carcinogens and diets deficient in riboflavin, magnesium, nicotinic acid, and zinc are causative factors. Chewing betel nuts and smoking bidi are significant factors in India. Carcinogens, notably nitrites found in smoked foods or used as preservatives, are suspect. Risk factors for colorectal cancer include a diet high in saturated fat and low in fiber and calcium, a lack of exercise, and schistosomiasis caused by the parasite Schistosoma japonicum. Cancer of the small intestine is rare, and its causes are unknown. A primary risk factor for anal cancer is chronic irritation.

Incidence: Incidence rates vary by the affected digestive tract organ. Esophageal cancer occurs much more often in China, Mongolia, central Asia, Sri Lanka, southern and southeastern Africa, the United Kingdom, the Netherlands, and Brazil than in North America. In the United States, four times as many men as women are stricken. Colorectal cancer is most common in North America, Europe, Russia, Japan, Australia, and New Zealand and least common in Africa and south-central Asia; environmental, dietary, and medical testing factors in Westernized countries may account for the higher incidence. Stomach cancer is most common throughout Asia, Eastern Europe, and some parts of South America. Cancer of the small intestine is approximately 1.4 times as common in men as in women.

Symptoms: Symptoms vary depending on the part of the affected gastrointestinal tract. Esophageal cancer is marked by difficulty in swallowing; a feeling of fullness, pressure, or burning as food passes down the tract; indigestion; heartburn; vomiting; choking on food; weight loss; coughing and hoarseness; and pain behind the breastbone or in the throat. Early stomach cancer may present no symptoms. Later, they are often vague and include indigestion or heartburn, abdominal pain or discomfort, nausea and vomiting, diarrhea or constipation, bloating after meals, loss of appetite, weakness, fatigue, and vomiting blood or bloody stools. Colorectal cancer symptoms result from local obstruction or, in more advanced stages, from extension to adjacent organs. In the early stages, symptoms are usually vague and vary according to the location of the tumor. In later stages, symptoms include pallor, cachexia, ascites, enlarged liver, and dilation of lymphatic vessels. About 10 percent of people with cancer of the small intestine experience no symptoms. Still, most patients have abdominal pain or distension because of obstruction, as well as weight loss, nausea and vomiting, fever, change in bowel habits, and general malaise. Anal cancer may exhibit no symptoms in the early stages. Later, there may be bleeding, pressure, pain, itching, and a palpable mass.

Screening, diagnosis, and staging: A colonoscopy is used in people over fifty to look for signs of polyps that might lead to colon cancer. People should monitor digestive symptoms, particularly if symptoms change or if the individual develops gastrointestinal reflux disease (acid reflux, or GERD), and immediately discuss such symptoms with their doctor. After symptoms have appeared, diagnosis usually begins with the physician performing a physical examination and taking a family medical history. Endoscopy, biopsy, and imaging tests such as a barium swallow, computed tomography (CT), and magnetic resonance imaging (MRI) facilitate further study.

When symptoms of esophageal cancer appear, physicians take a thorough family medical history and complete a physical examination. An X-ray study (barium swallow) or an esophagoscopy can find changes in the shape of the esophagus—a tissue biopsy through the endoscope and brush cells from the esophageal wall for examination by a pathologist. If cancer is present, additional tests may include a CT scan, MRI, laryngoscopy, or bronchoscopy. These tests will assess the staging or classification of the extent of the cancer. For esophageal cancer, stages include:

• Stage 0: Cancer is only in the epithelial cells lining the esophagus; it has not spread to nearby tissues, lymph nodes, or other organs.
• Stage IA: Cancer has grown into the layers below the epithelium but no deeper. It is well or moderately differentiated and has not spread to nearby lymph nodes or distant sites.
• Stage IB: Same as stage IA, but the cancer is poorly differentiated; or cancer has grown into the muscularis propria layer, but remains well or moderately differentiated. Cancer has not spread to nearby lymph nodes or other, more distant sites.
• Stage IIA: Cancer has grown into the muscularis propria layer and is poorly differentiated but has not yet spread to nearby lymph nodes or distant sites.
• Stage IIB: Cancer has grown through the esophagus wall to the adventitia (outer layer) but has not yet spread to nearby lymph nodes or distant sites; or cancer has not yet reached the adventitia but has spread to one or two nearby lymph nodes.
• Stage IIIA: Cancer has grown into layers below the epithelium, possibly including the muscularis propria, and has not yet reached the adventitia but has spread to three to six nearby lymph nodes; or cancer has reached the adventitia and spread to one or two nearby lymph nodes; or cancer has grown through the esophagus and spread to nearby tissues or organs, but it has not reached any lymph nodes and can still be removed.
• Stage IIIB: Cancer has reached the adventitia and has spread to three to six nearby lymph nodes.
• Stage IIIC: Cancer has spread to nearby tissues or organs and has reached one to six nearby lymph nodes but can still be removed; or cancer has grown into crucial structures, such as the spine, the aorta, or the trachea, and cannot be surgically removed but has not yet reached distant lymph nodes; or cancer has spread to seven or more nearby lymph nodes but no distant sites or lymph nodes.
• Stage IVA: Cancer has spread to the pleural, pericardium, diaphragm, and less than six nearby lymph nodes; or cancer has spread to the trachea, aorta, spine, or crucial structure and less than six nearby lymph nodes; or cancer has spread through layers of the esophagus and seven or more nearby lymph nodes.
• Stage IVB: Cancer has spread to distant lymph nodes or the liver and lungs. This cancer can be anywhere in the esophagus and any grade.

If the esophageal cancer is squamous-cell carcinoma rather than adenocarcinoma, the location of the tumor is also considered during staging.

When symptoms of stomach cancer appear, the doctor will take a medical history, do a physical examination, and order additional testsa fecal occult blood test, an upper gastrointestinal series (barium swallow), and an endoscopy. If cancer is identified, staging is as follows:

• Stage 0: Cancer is only in the top layer of cells in the stomach lining.
• Stage IA: Cancer has grown into the second or third layers of the stomach wall but has not spread to nearby lymph nodes.
• Stage IB: Cancer has grown into the connective tissue layer (lamina propria) and possibly the thin muscle layer (muscularis mucosa) below it or further into the submucosa, and has spread to one or two nearby lymph nodes; or cancer has grown into the main muscle layer (muscularis propria) but has not yet spread to nearby lymph nodes.
• Stage IIA: Cancer has grown into the lamina propria, muscularis mucosa, or submucosa and has spread to three to six nearby lymph nodes; or cancer has grown into the muscularis propria and has spread to one or two nearby lymph nodes; or cancer has grown through the muscularis propria into the subserosa, but it has not yet reached the outside of the stomach (serosa) and has not spread to any nearby lymph nodes or other sites.
• Stage IIB: Cancer has grown into the lamina propria, muscularis mucosa, or submucosa and has spread to seven or more nearby lymph nodes; or cancer has grown into the muscularis propria and has spread to three to six nearby lymph nodes; or cancer has grown through the muscularis propria into the subserosa and has spread to one or two nearby lymph nodes, but it has not yet reached the serosa.
• Stage IIIA: Cancer is in the muscularis propria and has spread to seven or more nearby lymph nodes; or cancer has spread into the subserosa and to three to six nearby lymph nodes, but it has not yet reached the serosa; or cancer has reached the serosa and one or two nearby lymph nodes but has not spread to other tissues or organs.
• Stage IIIB: Cancer is in the subserosa and has spread to seven or more nearby lymph nodes, but not to any more distant sites; or cancer has spread into the serosa and to three to six nearby lymph nodes, but it has not spread to other tissues or organs; or cancer has grown through the serosa into nearby tissues or organs, and possibly one or two nearby lymph nodes, but it has not yet reached distant sites.
• Stage IIIC: Cancer has grown into the serosa and has spread to seven or more nearby lymph nodes, but it has not yet reached other tissues or organs; or cancer has grown through the serosa into nearby tissues or organs and has spread to three or more nearby lymph nodes, but it has not yet reached distant sites.
• Stage IV: Cancer has spread to distant lymph nodes and other tissues and organs in the body.

Although only tumor biopsy can verify colorectal cancer, several other tests that can aid in detection include digital examination, or sigmoidoscopy, colonoscopy, CT scan, and barium X-rays. The staging is as follows:

• Stage 0: Cancer has not grown beyond the inner layer of the colon or rectum.
• Stage I: Cancer has grown through the muscularis mucosa into the submucosa, and possibly the muscularis propria, but has not yet reached nearby lymph nodes or other, more distant sites.
• Stage IIA: Cancer has spread into the outermost layers of the colon or rectum but has not yet spread to nearby lymph nodes.
• Stage IIB: Cancer has grown through the colon or rectum wall but has not yet spread to nearby lymph nodes.
• Stage IIC: Cancer has grown through the colon or rectum wall and has reached other tissues or organs, but it has not yet spread to nearby lymph nodes.
• Stage IIIA: Cancer has reached the submucosa, and possibly the muscularis propria, and has spread to one to three nearby lymph nodes or the fat near those lymph nodes; or cancer has reached the submucosa and has spread to four to six nearby lymph nodes.
• Stage IIIB: Cancer has reached the outer layers of the colon or rectum or the inner membrane surrounding the abdominal cavity (visceral peritoneum) and has spread to one to three nearby lymph nodes, or into the fat near those lymph nodes, but not to any nearby organs; or cancer has grown into the muscularis propria or the outer layers of the colon or rectum and has spread to four to six nearby lymph nodes; or cancer has grown into the submucosa, and possibly into the muscularis propria, and has spread to seven or more nearby lymph nodes.
• Stage IIIC: Cancer has reached the visceral peritoneum and has spread to four to six nearby lymph nodes but not to any nearby organs; or cancer has grown into the outer layers of the colon or rectum or through the visceral peritoneum and has spread to seven or more nearby lymph nodes but not to any nearby organs; or cancer has grown through the colon or rectum wall into nearby tissues or organs and has spread to at least one nearby lymph node.
• Stage IVA: Cancer may or may not have grown through the colon or rectum wall or spread to any nearby lymph nodes, but it has spread to one distant organ or set of lymph nodes.
• Stage IVB: Cancer may or may not have grown through the colon or rectum wall or spread to any nearby lymph nodes, but it has spread to more than one distant organ or set of lymph nodes, or to distant parts of the peritoneum.

Treatment for cancer of the small intestine is usually determined by cell type: adenocarcinomatous, lymphomatous, sarcomatous, or carcinoid. The following staging is for small intestine adenocarcinoma, which accounts for 30 to 40 percent of small intestine cancers:

• Stage 0: Cancer is only in the top cell layer of the small intestine mucosa.
• Stage I: Cancer has grown into the lamina propria, the submucosa, or the muscularis propria but has not yet spread to nearby lymph nodes.
• Stage IIA: Cancer has grown through most of the small intestine wall and into the subserosa but has not yet spread to nearby lymph nodes.
• Stage IIB: Cancer has grown through the small intestine wall and into the serosa or nearby tissues or organs, but it has not yet spread to nearby lymph nodes.
• Stage IIIA: Cancer has spread to one to three nearby lymph nodes.
• Stage IIIB: Cancer has spread to four or more nearby lymph nodes.
• Stage IV: Cancer has spread to distant sites, including other organs.

The following stages are used for anal cancer:

• Stage 0: Cancer is only in the top layer of anal tissue.
• Stage I: Cancer has spread beyond the top layer of anal tissue, and the tumor is less than 2 centimeters (0.8 inch) across.
• Stage II: Cancer is larger than 2 centimeters across but has not spread into any nearby organs or lymph nodes.
• Stage IIIA: Cancer has spread to lymph nodes around the rectum but not into any nearby organs; or cancer has grown into nearby organs, such as the vagina or bladder, but not to any nearby lymph nodes.
• Stage IIIB: Cancer has spread to nearby organs, such as the vagina or bladder, as well as lymph nodes around the rectum, but not to more distant sites; or cancer has spread to lymph nodes in the groin or pelvis, regardless of nearby organ or rectal lymph node involvement, but has not yet reached any more distant sites.
• Stage IV: Cancer has spread to distant tissues or organs.

Treatment and therapy: Treatment of gastrointestinal cancers varies depending on the tumor’s location, size, extent, and cell type, as well as the patient’s age and general health. Usual treatments include surgery to remove the tumor and nearby lymph nodes, radiation therapy to shrink the tumor before surgery or to destroy any cancerous cells remaining after surgery, and chemotherapy, alone or combined with radiation therapy. The ideal treatment for stomach cancer is radical surgery, involving a total or subtotal gastrectomy and the removal of a portion of tissue around the stomach.

Another treatment option is immunotherapy, designed to help the body’s immune system attack and destroy the malignant cells. After colorectal cancer surgery, if the healthy sections of the colon cannot be reconnected, a colostomy may be performed to allow the evacuation of body waste through an abdominal opening (stoma). The small intestine is very sensitive to radiation, but this therapy limits its usefulness. The size of the tumor may determine the method of treatment for anal cancer. Superficial in situ tumors (less than one inch) may require only local excision or radiotherapy alone. Tumors one to two inches are best treated by chemotherapy and radiation. Larger tumors may require chemotherapy, radiation, and surgery.

Prognosis, prevention, and outcomes: Five-year survival rates for gastrointestinal cancers are as follows. Figures are from the American Cancer Society unless otherwise noted.

• Esophageal cancer: localized (stage I, some stage II), 39 percent; regional (nearby lymph node or tissue involvement), 21 percent; distant (distant lymph node or organ involvement), 4 percent.
• Stomach cancer: stage IA, 71 percent; stage IB, 57 percent; stage IIA, 46 percent; stage IIB, 33 percent; stage IIIA, 20 percent; stage IIIB, 14 percent; stage IIIC, 9 percent; stage IV, 4 percent.
• Colon cancer: stage I , 74 percent; stage IIA, 67 percent; stage IIB, 59 percent; stage IIC, 37 percent; stage IIIA, 73 percent; stage IIIB, 46 percent; stage IIIC, 28 percent; stage IV, 6 percent.
• Rectum cancer: stage I , 74 percent; stage IIA, 65 percent; stage IIB, 52 percent; stage IIC, 32 percent; stage IIIA, 74 percent; stage IIIB, 45 percent; stage IIIC, 33 percent; stage IV, 6 percent.
• Small intestine adenocarcinoma: stage I, 55 percent; stage IIA, 49 percent; stage IIB, 35 percent; stage IIIA, 31 percent; stage IIIB, 18 percent; stage IV, 5 percent. Gastrointestinal stromal tumors (GISTs), which include small intestine sarcomas: 35–87 percent if localized and 10–20 percent if locally advanced or metastatic (Ko et al.); small intestine lymphoma: 25 percent for diffuse lymphoma and 50 percent or higher for nodular lymphoma (Ko et al.); small intestine carcinoma: localized, 57 percent; regional, 67 percent; distant, 40 percent (Singhal).
• Anal cancer: stage I, squamous: 71 percent, non-squamous: 59 percent; stage II, squamous: 64 percent, non-squamous: 53 percent; stage IIIA, squamous: 48 percent, non-squamous: 38 percent; stage IIIB, squamous: 43 percent, non-squamous: 24 percent; stage IV, squamous: 21 percent, non-squamous: 7 percent.

Cancer prevention involves reducing risk, which is determined in part by lifestyle, environment, and heredity. To help prevent gastrointestinal cancers, people can stop or avoid smoking, reduce the amount of fat in their diets while increasing fruit and vegetable consumption, control acid reflux and request testing if it persists, and undergo colon cancer screening after fifty.

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