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Diagnosis

Endoscopy

EGD is currently the procedure of choice for the diagnosis of gastric cancer (Fig. 54-5A). When a nonhealing gastric ulcer is found, at least 6 to 8 biopsy specimens from the edge and base of the ulcer are recommended.311 The American Gastroenterological Association (AGA) has recommended that an upper endoscopy be performed in patients who are older than 55 years with new-onset dyspepsia and in patients younger than 55 years who have “alarm” symptoms (weight loss, recurrent vomiting, dysphagia, evidence of bleeding, anemia).312 Dyspeptic patients in whom an empirical trial of PPIs and eradication of Hp do not relieve symptoms should undergo prompt endoscopic evaluation as well. The basis for these recommendations is the low incidence of gastric cancer in individuals younger than 55 years. The yield of upper endoscopy for the detection of gastric cancer in patients with occult bleeding and a normal colonoscopy will vary based on the patient’s baseline risk of gastric cancer.

In Japan and other areas of high gastric cancer prevalence, chromoendoscopy, magnification endoscopy, and narrow band imaging are used alone or in combination as aids in the detection of early gastric cancer (see Fig. 54-5B). Distinct irregular mucosal surface and vascular patterns have been found to correlate with the presence of dysplasia and carcinoma.313 There are also ongoing investigations into the utility of newer techniques such as autofluorescence and confocal microendoscopy for the diagnosis of early gastric neoplasia.314,315 In the past, barium studies have been reported to have 60% to 70% sensitivity and 90% specificity for the detection of advanced gastric cancer.316 Nevertheless, upper GI series has been largely replaced by upper endoscopy as the initial test of choice for the diagnosis of gastric cancer.

A classification system has been developed for early gastric cancer based on endoscopic appearance,317 the purpose of which is to assess early lesions for risk of submucosal invasion as well as risk of lymph node spread (Fig. 54-6). The 3 types include superficial polypoid (type 0-I), superficial flat/ depressed (types 0-IIa-c), and superficial excavated (type 0-III) lesions. The most commonly observed subtype is 0-IIc, the non-polypoid depressed lesion.317 This classification system is used most often in Japan, where endoscopic mucosal resection and submucosal dissection are frequently performed for early gastric neoplasia.

CT Gastrography

While CT colonography has gained significant attention for its potential role as a screening modality for colon polyps and colon cancer, CT gastrography has also been studied for the diagnosis of early gastric cancer. In a study from South Korea of 39 patients with early gastric cancer, CT gastrography had a sensitivity of 73% to 76% and good interobserver reliability (κ = 0.84).318 Only small studies have been performed thus far using this imaging modality, and CT gastrography cannot yet be recommended for screening outside of the research setting.

Serum Markers

To date, no reliable serum marker has been identified with high sensitivity and specificity for the diagnosis of gastric cancer. Low serum PGI levels, low ratios of PGI to PGII, and hypergastrinemia have been reported in patients with atrophic gastritis and intestinal metaplasia, but the results for the detection of gastric cancer have been mixed.319,320 In a study of 17,000 Japanese males, a positive PG test (defined as PGI < 50 μg/L, and PGI/II < 3.0) in combination with upper GI series identified gastric cancer in only 0.28% of subjects; however, 88% of these cancers were early cancers.321 Additionally, 89% of the cancers identified by the PG test alone were early gastric cancers. The major limitation of this test is the low specificity for the diagnosis of gastric cancer.322

Serum CEA and carbohydrate antigen (CA) 19-9 have both been extensively studied for the diagnosis of gastric cancer. The sensitivities of these markers is especially low for early gastric cancer,323and elevated levels are levels are also seen in other epithelial malignancies. These tumor markers are frequently elevated in recurrent gastric cancer, especially in patients who had elevated levels prior to surgical resection.324 More recent studies have identified, among others, TGF-β1, CA 72-4, tumor M2-pyruvate kinase, and hepatocyte growth factor as potential markers for the diagnosis of gastric cancer.325-328 However, larger studies are required to determine their clinical utility.