Carcinoma of the Stomach and Duodenum

Dietary Factors

Diets rich in salted, smoked, or poorly preserved foods are associated with an increased risk of gastric cancer, ^, whereas diets rich in fruits and vegetables are associated with a decreased risk. ^, Foods containing nitrates or nitrites have also been implicated in the development of gastric carcinoma, as these compounds are converted by bacteria to potentially carcinogenic nitrosamines. Conversely, vitamin C (ascorbic acid) appears to have a protective effect by reducing nitrites to nitric oxide and preventing nitrosamine formation. This observation could explain why diets rich in fruits and vegetables are associated with a lower cancer risk.

Helicobacter Pylori Gastritis

H. pylori gastritis is now thought to be the leading cause of gastric cancer worldwide. People with this infection are more likely to develop atrophic gastritis, a known precursor for gastric cancer (see later, “Atrophic Gastritis”). ^, While people with chronic H. pylori gastritis have a two to six times greater risk of developing gastric cancer, ^, only a tiny percentage of all infected individuals develop these tumors, so other environmental or genetic factors likely contribute to cancer pathogenesis.

Atrophic Gastritis

Atrophic gastritis has been classified into two types (A and B). Type A gastritis predominantly involves the gastric fundus and body and is thought to result from immunologic injury by antiparietal cell antibodies in patients with pernicious anemia. Affected individuals have a two to three times greater risk of developing gastric cancer than the general population. ^, Some investigators therefore advocate radiologic or endoscopic surveillance of patients with known pernicious anemia, but others believe that the cancer risk is not high enough to warrant routine surveillance.

In contrast, the more common type B gastritis predominantly involves the antrum and usually results from chronic H. pylori infection (see Chapter 18 ). About 10% of patients with type B gastritis develop gastric carcinoma within 10 to 20 years. It has been postulated that chronic atrophic gastritis leads to gastric atrophy, intestinal metaplasia, dysplasia, and, eventually, the intestinal type of adenocarcinoma. ^, Thus, chronic H. pylori –associated atrophic gastritis is thought to be a major risk factor for the development of gastric cancer.

Gastric Polyps

Although uncommon, adenomatous polyps in the stomach are premalignant lesions that can undergo malignant degeneration via an adenoma-carcinoma sequence similar to that in the colon. Nearly 50% of gastric adenomas larger than 2 cm are found to harbor carcinomatous foci. All adenomatous polyps should therefore be resected because of the risk of malignant transformation. Nevertheless, adenocarcinoma is about 30 times more common than adenomatous polyps in the stomach, so most gastric cancers are thought to originate de novo and not from preexisting polyps.

Partial Gastrectomy

Patients who undergo partial gastrectomy are at increased risk for developing gastric carcinoma. A gastric stump cancer is defined as a primary carcinoma of the gastric remnant occurring a minimum of 5 years after partial gastrectomy (usually a Billroth II) for gastric ulcers or other benign disease. ^, It has been postulated that recurrent bile reflux into the gastric remnant causes chronic gastritis, intestinal metaplasia, and, eventually, gastric carcinoma. The mortality from gastric cancer 15 years or more after partial gastrectomy is three to seven times greater than that of the general population. Some investigators therefore advocate regular endoscopic surveillance of the gastric remnant. Nevertheless, the need for surveillance in this clinical setting remains controversial.

Ménétrier’s Disease

Anecdotal cases of gastric carcinoma have been described in patients with Ménétrier’s disease, a rare form of hypertrophic gastropathy (see Chapter 18 ). It is unclear, however, whether this association is coincidental or whether Ménétrier’s disease is truly a premalignant condition.

Gross Features

The Borrmann classification of gastric carcinoma includes four morphologic types—type I (polypoid), type II (fungating), type III (ulcerated), and type IV (infiltrating). Most gastric carcinomas are polypoid or ulcerated lesions. Polypoid carcinomas are lobulated or fungating lesions that protrude into the lumen, whereas ulcerated carcinomas contain irregular areas of ulceration caused by tumor necrosis. Diffusely infiltrating cancers spread via the gastric wall with less intraluminal growth, whereas scirrhous cancers produce a linitis plastica appearance. Finally, superficial spreading lesions are confined to the mucosa or submucosa without invading the deep muscle layers of the gastric wall.

Rarely, gastric carcinomas occur as multiple primary lesions separated by normal intervening mucosa. In various studies, two or more synchronous tumors have been found in 2% to 8% of all patients with gastric cancer.

Histologic Features

More than 95% of malignant neoplasms in the stomach are adenocarcinomas. These tumors are classified into two types: (1) an intestinal type characterized by well-formed glandular structures that grow in a fungating manner; and (2) a diffuse type characterized by poorly cohesive cells that infiltrate and thicken the gastric wall without producing a discrete mass. Intestinal-type lesions are more likely to involve the distal stomach and are often associated with atrophic gastritis, whereas diffuse-type lesions are more likely to involve the entire stomach and have a worse prognosis.

Gastric carcinomas have been further classified by the World Health Organization into four histologic types—papillary, tubular, mucinous, and signet ring cell. Most tumors that are capable of forming glandular structures secrete mucinous substances and, occasionally, excessive mucin accumulates extracellularly in colloid or mucinous adenocarcinomas. Other adenocarcinomas are composed of distinctive signet ring cells containing large amounts of intracytoplasmic mucin and compressed, eccentric nuclei. As they infiltrate the gastric wall, these signet ring cells often incite a marked desmoplastic response in the submucosa and muscularis propria, producing the classic pathologic features of a scirrhous carcinoma. These scirrhous tumors have been found to account for 5% to 15% of all gastric cancers. ^,

Most adenocarcinomas of the stomach are diagnosed at an advanced stage. By definition, advanced gastric cancers have already invaded the muscularis propria. These tumors are usually associated with metastases to regional lymph nodes or other local or distant structures. In contrast, early gastric cancer (EGC) is defined histologically as cancer in which malignant invasion is limited to the mucosa or submucosa, regardless of the presence or absence of local lymph node metastases. ^, Unlike advanced gastric carcinomas, EGCs are curable lesions associated with 5-year survival rates greater than 90%.

Distribution

At one time, most gastric carcinomas were located in the antrum. During the past 70 years, however, there has been a gradual shift in the distribution of gastric cancer from the antrum proximally to the body and fundus. This changing distribution has been attributed primarily to a rising incidence of carcinoma of the cardia, which has increased at a rate exceeding that of any other cancer. ^, As a result, gastric cancers now have a relatively even distribution in the stomach, with about 30% in the antrum, 30% in the body, and 40% in the fundus or cardiac region. ^,