7. Premalignant Conditions of the Stomach and Gastric Cancer

Possible premalignant gastric conditions include pernicious anemia, atrophic gastritis, polyps and previous gastric surgery. People with a family history that is positive for gastric cancer also have an increased risk of developing this disease. Benign gastric ulcer is not a premalignant condition, but can appear so because of the long natural history of some ulcerating cancers. At present, regular endoscopy is not necessary for most patients with conditions predisposing to gastric ulcer. A high index of suspicion for cancer, however, must be maintained. If endoscopy and biopsy have been performed and distinct dysplastic changes are found in the epithelium, regular follow-up endoscopy and biopsy are advised.

7.1.1 PERNICIOUS ANEMIA

Patients with pernicious anemia have long been considered at risk for gastric cancer, but the risk is likely to be low and does not justify intensive endoscopic screening. Pernicious anemia is invariably associated with fundal gland atrophy, usually with intestinal metaplasia and sometimes with polyps. When cancer develops, it tends to occur in the body or fundus of the stomach.

7.1.2 ATROPHIC GASTRITIS

There are two main types of atrophic gastritis: fundal gland (type A), and pyloric (antral) gland (type B). These occur in older people. Antral gastritis increasingly involves the fundal gland area with advanced age. Both types A and B are associated with intestinal metaplasia and a predisposition to gastric cancer. Type A gastritis is less common and its distribution in the stomach resembles that of pernicious anemia. Type B gastritis is predominant in those areas of the body where gastric cancer is common and appears to be a risk factor mainly for the intestinal type of gastric cancer. Helicobacter pylori, which is the cause of type B gastritis, has been implicated as a risk factor for gastric cancer.

7.1.3 GASTRIC POLYPS

There are two main types of gastric polyps: hyperplastic and adenomatous. Hyperplastic polyps are small, often multiple, and do not become malignant. Adenomatous polyps are uncommon and are usually larger than 2 cm in diameter. They are premalignant, and a substantial minority show areas of cancer at the time of detection. Endoscopic or surgical excision is recommended.

7.1.4 PREVIOUS GASTRIC SURGERY

Patients who have had a partial gastrectomy for peptic ulcer disease may have an increased probability of developing gastric cancer some 15 to 20 years after the operation. Endoscopic surveillance of these patients does not appear to be justified in North America, since the risk is low.

Individuals with a parent or sibling with gastric cancer are three times as likely to develop gastric cancer as the general population. People born in a country where gastric cancer is common (e.g., Japan or Eastern Europe) are also at increased risk, even if they have lived in North America for many years. Although regular screening is not warranted in either case, minor symptoms should be promptly and thoroughly investigated.

Barrett's epithelium (columnar cell lining of the lower esophagus) is a proven precursor of esophageal adenocarcinoma, and there is increasing suspicion that lesser degrees of Barrett's epithelium may predispose to the much more common adenocarcinoma of the gastric cardia.

Adenocarcinoma is the most common gastric cancer, but lymphoma and leiomyosarcoma also occur. The frequency of gastric cancer has decreased considerably over the past 50 years in North America, but it still ranks as the second most common GI malignancy (after colon cancer). Most patients are over 60 years of age. Men are affected about twice as often as women. The cancer usually involves the antrum, body or cardia with about equal frequency. The three main macroscopic types are polypoid, ulcerative and infiltrative. The two main microscopic types are intestinal and diffuse. The intestinal type is often associated with atrophic gastritis and intestinal metaplasia; the diffuse type is often manifest as a linitis plastica.

Most patients have advanced incurable disease by the time they have significant complaints, but some patients with early gastric cancer may have mild epigastric discomfort or ulcer-like symptoms. Physical examination is usually normal but may reveal a mass or a succussion splash in a minority of patients. There may be evidence of metastases, such as a supraclavicular node, hepatomegaly, ascites, a shelf on a rectal examination, an ovarian mass or an umbilical node. Iron deficiency anemia is found in about 50% of patients and occult blood is present in the stool in about 75% of cases. Occasionally, the neurological signs of subacute combined degeneration of the spinal cord from associated pernicious anemia will be found. Measurement of gastric acid secretion or carcinoembryonic antigen (CEA) is not helpful. Barium radiograph is usually the first diagnostic procedure. Experienced radiologists can show some abnormality in up to 90% of patients, particularly if double contrast techniques are used. While there are distinguishing clinical and radiological features, every patient with a presumed benign gastric ulcer should have biopsies obtained to exclude a malignant ulcer. Endoscopy and biopsy, with or without brush cytology, are required to establish the diagnosis.

The diffuse type of gastric cancer often manifests itself as a linitis plastica. It is harder to diagnose than the intestinal type, particularly in the earlier stages. Thus, although diagnostic techniques have improved, some gastric cancers are still missed on the initial investigation. Although routine endoscopic screening is not feasible in North America, minor symptoms should be thoroughly investigated in people with predisposing conditions. It is also important to ensure that only benign gastric ulcers are treated medically; if a gastric ulcer fails to heal after three months of intensive medical therapy, surgery is generally recommended.

Early surgery offers the only hope for cure, but is not performed if there is evidence of metastatic disease, unless the patient suffers from gastric outlet obstruction. Cancers of the distal and mid-stomach are treated by subtotal gastrectomy. In order to remove the regional lymph nodes, the lesser and greater omenta are resected and, if necessary, the spleen is removed. Cancers of the proximal stomach are usually treated by esophagogastrectomy. With the increased proportion of diffusely infiltrating cancer, total gastrectomy with biliary diversion is being performed more often. Palliative resection, bypass, surgery or laser photoablation is justified in those patients with gastric outlet obstruction. Palliative esophagogastrectomy or total gastrectomy is not recommended. The prognosis after surgical treatment is related to the depth of the tumorís penetration. Overall, about 10-15% of patients survive five years. Occasionally, patients have a long course without treatment or with only palliative surgery.

Therapy includes chemotherapy with 5-fluorouracil, doxorubicin and mitomycin (FAM). This approach achieves a response rate of up to 40% but gives a disappointing median survival of less than one year. Occasionally, good responses are obtained, and a trial is recommended for patients in good condition and with advanced disease. Adjuvant chemotherapy or radiotherapy remains of unproven value, but palliative radiotherapy is useful to control bleeding, to alleviate pain from bone metastases and to relieve dysphagia. Esophageal dilation and endoscopically placed plastic tubes can also help dysphagia caused by persistent spread of a cardia tumor.

General supportive care is important, including dietary advice, replacement of iron and vitamin B₁₂, judicious use of analgesics, antiemetics, and antacid support. Emotional support is particularly important and increasingly includes guidance in interpreting the common, overoptimistic "breakthroughs" reported in the press.