Gastric Cancer

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Gastric cancer

Definition

Gastric cancer (also known as stomach cancer) is a disease in which the cells forming the inner lining of the stomach become abnormal and start to divide uncontrollably, forming a mass or a tumor.

Description

The stomach is a J-shaped organ that lies in the abdomen, on the left side. The esophagus (or the food pipe) carries the food from the mouth to the stomach. The stomach produces many digestive juices and acids that mix with the food and aid in the process of digestion. The stomach is divided into five sections. The first three are together referred to as the proximal stomach, and produce acids and digestive juices, such as pepsin. The fourth section of the stomach is where the food is mixed with the gastric juices. The fifth section of the stomach acts as a valve and controls the emptying of the stomach contents into the small intestine. The fourth and the fifth sections together are referred to as the distal stomach. Cancer can develop in any of the five sections of the stomach. The symptoms and the outcomes of the disease may vary depending on the location of the cancer.

In many cases, the cause of the gastric cancer is unknown. Several environmental factors have been linked to gastric cancer. Consuming large amounts of smoked, salted, or pickled foods has been linked to increased gastric cancer risk. Nitrates and nitrites, chemicals found in some foods such as cured meats may be linked to gastric cancer as well.

Infection by the Helicobacter pylori (H. pylori) bacterium has been found more often in people with gastric cancer. H. pylori can cause irritation of the stomach lining (chronic atrophic gastritis), which may lead to pre-cancerous changes of the stomach cells.

People who have had previous stomach surgery for ulcers or other conditions may have a higher likelihood of developing gastric cancers, although this is not certain. Another risk factor is developing polyps, benign growths in the lining of the stomach. Although polyps are not cancerous, some may have the potential to turn cancerous.

While no particular gene for gastric cancer has yet been identified, people with blood relatives who have been diagnosed with gastric cancer are more likely to develop the disease. In addition, people who have inherited disorders such as familial adenomatous polyps (FAP) and Lynch syndrome have an increased risk for gastric cancer. For unknown reasons, gastric cancers occur more frequently in people with the blood group A.

Genetic profile

Although environmental or health factors may explain frequent occurrences of gastric cancer in families, it is known that inherited risk factors also exist. Some studies show close relatives having an increased risk of gastric cancer two to three times that of the general population. Interestingly, an earlier age at the time of gastric cancer diagnosis may be more strongly linked to familial gastric cancer. Two Italian studies estimated that about 8% of gastric cancer is due to inherited factors. Some of these hereditary factors are known genetic conditions while in other instances, the factors are unknown.

Familial cancer syndromes are hereditary conditions in which specific types of cancer, and perhaps other features, are consistently occurring in affected individuals. Familial adenomatosis (FAP) and hereditary nonpolyposis colon cancer (HNPCC) are familial cancer syndromes that increase the risk of colon cancer.

FAP is due to changes in the APC gene. Individuals with FAP typically have more than 100 polyps, mushroom-like growths, in the digestive system as well as other effects. Polyps are noncancerous growths that have the potential to become cancerous if not removed. At least one study estimated that the risk of gastric cancer was seven times greater for individuals with FAP than the general population.

The number of polyps present is an important distinction between FAP and HNPCC. Polyps do not form at such a high rate in HNPCC but individuals with this condition are still at increased risk of colon, gastric, and other cancers. At least five genes are known to cause HNPCC, but alterations in the hMSH2 or hMLH1 genes have been found in the majority of HNPCC families.

Other inherited conditions such as Peutz-Jeghers, Cowden and Li-Fraumeni syndromes and other syndromes have been associated with gastric cancer. All of these syndromes have distinct features beyond gastric cancer that aid in identifying the specific syndrome. The inheritance pattern for most of these syndromes is dominant, meaning only one copy of the gene needs to be inherited for the syndrome to be present.

In 1999, the First Workshop of the International Gastric Cancer Linkage Consortium developed criteria for defining hereditary gastric cancer not due to known genetic conditions, such as those listed above. In areas with low rates of gastric cancer, hereditary gastric cancer was defined according to the Consortium as: (1) families with two or more cases of gastric cancer in first or second degree relatives (siblings, parents, children, grandparents, nieces/nephews or aunts/uncles) with at least one case diagnosed before age 50 or (2) three or more cases at any age. In countries with higher rates of gastric cancer, such as Japan, the suggested criteria are: (1) at least three affected first degree relatives (sibling, children or parents) and one should be the first degree relative of the other two; (2) at least two generations (without a break) should be affected; and (3) at least one cancer should have occurred before age 50.

Inherited changes in the E-Cadherin/CDH1 gene first were reported in three families of native New Zealander (Maori) descent with gastric cancer and later were found in families of other ancestry. The E-Cadherin/CDH1 gene, which plays a role in cell to cell connection, is located on the chromosome 16 at 16q22. The percentage of hereditary gastric cancer that is due to E-Cadherin/CDH1 gene alterations is uncertain. In summary, most gastric cancer is due to environmental or other non-genetic causes. A small portion of cancer of the stomach, about 8%, is due to inherited factors one of which is E-Cadherin/CDH1 gene alterations.

Demographics

The American Cancer Society estimated, based on previous data from the National Cancer Institute and the United States Census, that 21,700 Americans were diagnosed with gastric cancer during 2001. In some areas, nearly twice as many men are affected by gastric cancer than women. Most cases of gastric cancer are diagnosed between the ages of 50 and 70 but in families with a hereditary risk of gastric cancer, younger cases are more frequently seen. Gastric cancer is one of the leading causes of cancer deaths in many areas of the world, most notably Japan, but the number of new gastric cancer cases is decreasing in some areas, especially in developed countries. In the United States, the use of refrigerated foods and increased consumption of fresh fruits and vegetables, instead of preserved foods, may be a reason for the decline in gastric cancer.

Signs and symptoms

Gastric cancer can be difficult to detect at early stages since symptoms are uncommon and frequently unspecific. The following can be symptoms of gastric cancer:

poor appetite or weight loss
fullness even after a small meal
abdominal pain
heart burn, belching, indigestion or nausea
vomiting, with or without blood
swelling or problems with the abdomen
anemia or blood on stool (feces) examination

Diagnosis

In addition to a physical examination and fecal occult blood testing (checking for blood in the stool), special procedures are done to evaluate the digestive system including the esophagus, stomach, and upper intestine. Procedures used to diagnose gastric cancer include: barium upper gastrointestinal (GI) x rays, upper endoscopy, and endoscopic ultrasound. Genetic testing can also beused to determine an individuals predisposition to gastric cancer.

Upper GI x rays

The first step in evaluation for gastric cancer may be x ray studies of the esophagus, stomach, and upper intestine. This type of study requires drinking a solution with barium to coat the stomach and other structures for easier viewing. Air is sometimes pumped into the stomach to help identify early tumors.

Upper endoscopy

Endoscopy allows a diagnosis in about 95% of cases. In upper endoscopy, a small tube, an endoscope, is

placed down the throat so that the esophagus, stomach and upper small intestine can be viewed. If a suspicious area is seen, a small sample of tissue, a biopsy, is taken. The tissue from these samples can be examined for evidence of cancer.

Endoscopic ultrasound

Endoscopic ultrasound allows several layers to be seen and so it is useful in determining where cancer may have spread. With this test, an endoscope is placed into the stomach and sound waves are emitted. A machine analyzes the sound waves to see differences in the tissues in order to identify tumors.

Genetic testing

If a certain genetic syndrome such as FAP or HNPCC is suspected, genetic testing may be available either through a clinical laboratory or through a research study. Testing for E-cadherin/CDH1 gene alterations is mainly available through research studies. Once an E-cadherin/CDH1 gene change is identified through research, the results can be confirmed through a certified laboratory.

When a gene change is identified, genetic testing may be available for other family members. For most genetic tests, it is helpful to test the affected individual first, since they are most likely to have a gene change. Genetic testing is usually recommended for consenting adults, however, for syndromes in which gastric cancer is a common feature, testing of children may be reasonable for possible prevention of health problems.

The detection rate and usefulness of genetic testing depends on the genetic syndrome. If genetic testing is under consideration, a detailed discussion with a knowledgeable physician, genetic counselor, or other practitioner is helpful in understanding the advantages and disadvantages of the genetic test. It is also important to realize that testing positive for the E-cadherin/CDH1 gene does not necessarily mean the individual will be affected with cancer. However, they may have an increased risk compared to an individual without the gene.

Treatment and management

Regular mass screening for gastric cancer has not been found useful in areas, such as the United States,

where gastric cancer is less common. When gastric cancer is diagnosed in the United States, it is usually discovered at later, less curable stages. However, individuals with an increased risk of gastric cancer, including those with a known genetic syndrome or with a family history of the disease, may consider regular screening before the development of cancer. If a known hereditary cancer syndrome is suspected, screening should follow the generally accepted guidelines for these conditions.

In 1999, the First Workshop of the International Gastric Cancer Linkage Consortium recommended that regular detailed upper endocopy and biopsy be done in families with hereditary gastric cancer, including screening every six to 12 months for individuals with known E-cadherin gene alterations, if no other treatment has been done. Some individuals with a known hereditary gastric cancer risk have surgery to remove the stomach prior to development of any gastric cancer, but the effectiveness of this prevention strategy is uncertain. Several other less drastic prevention measures have been considered including changes in diet, use of vitamins, and antibiotic treatment of H. pylori. The American Cancer Society recommends limiting use of alcohol and tobacco.

Treatment of gastric cancer, in nearly all cases, involves some surgery. The amount of the stomach or surrounding organs that is removed depends on the size and location of the cancer. Sometimes, surgery is performed to try to remove all of the cancer in hopes of a cure while other times, surgery is done to relieve symptoms. Possible side effects of stomach surgery include leaking, bleeding, changes in diet, vitamin deficiencies, and other complications.

Chemotherapy involves administering anti-cancer drugs either intravenously (through a vein in the arm) or orally (in the form of pills). This can either be used as the primary mode of treatment or after surgery to destroy any cancerous cells that may have migrated to distant sites. Side effects (usually temporary) of chemotherapy may include low blood counts, hair loss, vomiting, and other symptoms.

Radiation therapy is often used after surgery to destroy the cancer cells that may not have been completely removed during surgery. Generally, to treat gastric cancer, external beam radiation therapy is used. In this procedure, high-energy rays from a machine that is outside of the body are concentrated on the area of the tumor. In the advanced stages of gastric cancer, radiation therapy is used to ease the symptoms such as pain and bleeding.

Prognosis

"Staging" is a method of describing cancer development. There are five stages in gastric cancer with stage 0 being the earliest cancer that has not spread while stage IV includes cancer that has spread to other organs. Expected survival rate can be roughly estimated based on the stage of cancer at the time of diagnosis.

The prognosis for patients with early stage cancer depends on the location of the cancer. When cancer is in the proximal part of the stomach, only 10-15% of people survive five years or more, even if they have been diagnosed with early stage cancer. For cancer that is in the distal part of the stomach, if it is detected at an early stage, the outlook is somewhat better. About 50% of the people survive for at least five years or more after initial diagnosis. However, only 20% of the patients are diagnosed at an early stage. Chance of survival depends on many factors and it is difficult to predict survival for a particular individual.

Resources

BOOKS

Flanders, Tamar, et al. "Cancers of the Digestive System." In Inherited Susceptibility: Clinical, Predictive and Ethical Perspectives, edited by William D. Foulkes and Shirley V. Hodgson. Cambridge University Press, 1998. pp. 158-165.

Lawrence, Walter, Jr. "Gastric Cancer." In Clinical Oncology Textbook, edited by Raymond E. Lenhard, Jr., et al. American Cancer Society, 2000, pp. 345-360.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta, Georgia 30329. (800) 227-2345. <http://www.cancer.org>.

National Cancer Institute. Office of Communications, 31 Center Dr. MSC 2580, Bldg. 1 Room 10A16, Bethesda MD 20892-2580. (800) 422-6237. <http://www.nci.nih.gov>.