Gastric Carcinoma

Epidemiology

Although the incidence of gastric carcinoma is decreasing in Western countries, it remains the fourth most frequent cancer diagnosed and the second most lethal cancer worldwide, behind only lung cancer. The number of new cases of gastric carcinoma per year worldwide was recently estimated as over 683,000 in males and 349,000 in females. It is the third most common cancer in males and the fifth most common cancer in females worldwide. Some 60% of cases occur in developing countries. The areas with the highest incidence rates are Eastern Asia, South America, and Eastern Europe. Regions in which gastric carcinoma is least frequent are North America, Western Europe, and parts of Africa. There is approximately a 20-fold difference in the incidence rates between Japan and some White populations in the United States. In the United States, approximately 27,600 new cases of gastric carcinoma were expected to be diagnosed during 2020, with 11,010 estimated deaths from the disease during the same period.

Of the several classification systems that have been proposed to describe gastric carcinoma, the Lauren classification is the most widely used. The Lauren classification describes tumors based on the microscopic configuration and growth pattern into intestinal and diffuse types. Diffuse cancers are noncohesive and diffusely infiltrate the stomach. These often exhibit deep infiltration of the gastric wall and show little or no gland formation. These tumors are often associated with marked desmoplasia and inflammation, with relative sparing of the overlying mucosa. The intestinal type, conversely, shows recognizable gland formation similar in microscopic appearance to the colonic mucosa. The glandular formation ranges from well to poorly differentiated tumors and grows in expanding rather than infiltrative patterns. Intestinal cancers are believed to be related to environmental factors and are thought to arise from precancerous lesions such as gastric atrophy, and intestinal metaplasia. These are also associated with Helicobacter pylori infection and are considered an “epidemic” form of cancer. The intestinal type is gradually declining in the United States but still remains a common cause of gastric carcinoma worldwide. The diffuse cancers, conversely, are less related to environmental factors and occur more often in young patients. The relative incidence of diffuse cancers is believed to have increased mainly owing to the decrease in the incidence of intestinal type cancers.

There are regional differences in the pathology and anatomic location of gastric carcinoma. A predominance of the Lauren intestinal type of adenocarcinoma occurs in high-risk areas, whereas the Lauren diffuse type is relatively more common in low-risk areas. Proximal gastric carcinomas and cancers of the gastroesophageal junction are more common in the West, and distal gastric carcinoma is more common in high-risk regions. At the MD Anderson Cancer Center, 41% of all UGI cancers involve the gastroesophageal junction. A steady decline in the incidence and mortality rates of gastric carcinoma has been observed worldwide over the past several decades. This is mainly attributed to a decrease in the intestinal variety of gastric carcinoma, with the incidence of diffuse cancer being relatively stable.

Etiology and Risk Factors

Because gastric carcinoma is more common in Asia than in Western countries, ethnic origin was thought to be an important contributory factor for the observed difference. Although first-generation Asian immigrants to Western countries carry the same high susceptibility for gastric carcinoma as their counterparts in their native country, subsequent generations acquire risk levels approaching that of the population of their adopted countries. This epidemiologic pattern underlines the importance of environmental factors in the pathogenesis of gastric carcinoma. Diets poor in fruits and vegetables and rich in smoked or poorly preserved food, salt, nitrates, and nitrites, infection with H. pylori , and smoking have all been implicated as significant risk factors in the development of gastric carcinoma in several studies. Chronic atrophic gastritis, previous gastric surgery, gastric polyps, and obesity, as well as low socioeconomic status, are also associated with an increased risk of gastric carcinoma.

Gastric carcinoma is also seen as a part of the hereditary nonpolyposis colon cancer syndrome and other gastrointestinal (GI) polyposis syndromes such as Peutz–Jeghers syndrome and familial adenomatous polyposis. Mutations in the gene encoding E-cadherin are a well-recognized cause of hereditary diffuse gastric cancer.

Clinical Presentation

The symptoms of patients with gastric carcinoma are nonspecific. As a result, diagnosis is often delayed, and patients will have advanced disease at the time of diagnosis. Frequent symptoms associated with gastric carcinoma include dysphagia, early satiety, nausea, vomiting, and other symptoms attributable to gastric outlet obstruction or anemia. However, the most common symptoms at the time of diagnosis are upper abdominal pain and weight loss.