Stomach cancer (also known as gastric cancer) is one of the most common cancers worldwide with the highest incidence in areas such as Japan, South America, and Eastern Europe. The incidence is much lower in the United States with about 22,000 new cases per year. The overall incidence of stomach cancer in the United States is decreasing, but cancers of the upper stomach and stomach-esophagus junction are increasing. These tumors typically occur in people in their 60s and 70s, but can also occur in younger and older individuals.

The vast majority of stomach cancers are classified as adenocarcinomas, which are tumors arising from the inner mucosal lining of the stomach. These tumors grow from this inner lining and can spread to the deeper layers of the stomach. Eventually, tumors can penetrate the stomach wall and invade adjacent organs or spread along the peritoneum (the inner lining of the abdomen). In addition, stomach cancers can spread through lymphatic vessels to regional lymph nodes and though the bloodstream to the liver and lung. The goal of surgical resection of stomach cancers is to remove the involved stomach and regional lymph nodes before the tumor can spread to other sites.

Stomach cancers not classified as adenocarcinomas comprise only 5-10% of all stomach cancers. These cancers include:

• lymphomas
• gastrointestinal stromal tumors (GIST)
• neuroendocrine tumors (carcinoids).

The remainder of the information presented will be specific for stomach adenocarcinomas except as noted below.

Risk Factors
There are various genetic and acquired factors that can increase one’s risk for stomach cancer. The wide disparity in the incidence of stomach cancer in different countries has been attributed to differences in diet. Diets high is smoked or salted foods and high in red meat have been associated with an increase risk of stomach cancer. Countries with a high incidence of stomach cancer also have a high rate of infection with a bacterium known as Helicobacter pylori. This organism is thought to increase the risk of gastric cancer by causing chronic inflammation in the stomach. Other risk factors associated with gastric cancer include cigarette smoking, pernicious anemia (vitamin B12 deficiency), and prior stomach surgery (usually for peptic ulcer disease).

Certain genetic factors have now been identified as increasing one’s risk of stomach cancer. Members of families with cancer syndromes such as Li-Fraumeni syndrome and Lynch syndrome have higher than normal stomach cancer rates. Families with a mutation in the E-cadherin gene also have an increased risk of stomach cancer. The genetic changes that lead to sporadic stomach cancers are currently being actively investigated.

Symptoms
Stomach cancers often do not cause symptoms until they have grown to a significant size, and even then symptoms can be non-specific. The most common symptoms include:

• weight loss
• loss of appetite
• abdominal discomfort or pain
• fatigue.

Occasionally, tumor can cause obstruction of the stomach (leading to vomiting) or cause bleeding (resulting in dark stools or vomiting of blood).

Diagnosis/Workup
Clinicians at Massachusetts General Hospital have developed a standardized algorithm for the diagnosis and workup of stomach cancers.

Medical history and physical examination
The medical history is required to determine all symptoms, possible risk factors, and other medical problems. Physical examination is essential to rule out distant spread of disease

Diagnostic imaging
The initial diagnostic test to identify a stomach cancer is usually a barium x-ray of the stomach (upper GI series) or an endoscopic examination of the stomach (upper endoscopy). Upper endoscopy can accurately identify abnormalities in the lining of the stomach, where stomach adenocarcinomas originate. An even more sensitive study is an endoscopic ultrasound, which combines an endoscope with an ultrasound probe. This study can identify how deep the tumor has penetrated into the stomach wall and identify disease in regional lymph nodes.

The definitive diagnosis of stomach cancer requires a biopsy, which is performed at the time of upper endoscopy. Once the diagnosis is established, a workup is performed to determine if the cancer is localized or has spread to other sites. The most common sites of spread of stomach cancer are to regional lymph nodes, peritoneum, liver, and lung. Abdominal CT scans can sometimes identify stomach wall thickening but overall is a relatively insensitive method of identifying stomach tumors. However, chest, abdomen, and pelvic CT scans are very useful for ruling out the spread of disease beyond the stomach.

Laparoscopy
Stomach cancers can shed small deposits of tumor cells throughout the peritoneum, and this mode of spread is difficult to detect by any radiologic study. A procedure called laparoscopy is very sensitive in detecting peritoneal spread of tumor, and is often performed prior to surgical resection of stomach cancers. In this procedure, two or three tiny incisions are made in the abdominal wall, and a telescope and other small instruments are inserted into the abdomen.