Who should we consider high risk and offer screening EGD?
With available evidence to date, screening for gastric cancer in a general U.S. population is not recommended. However, it is important to acknowledge the aforementioned varying incidence of gastric cancer in the United States among ethnicity, immigrant status, and country of origin. Immigrants from high-incidence regions maintain a higher risk of gastric cancer and related mortality even after migration to lower-incidence regions. The latter comprehensive study estimated that as many as 12.7 million people (29.4% of total U.S. immigrant population) have emigrated from higher-incidence regions including East Asian and some Central American countries.9 Indeed, an opportunistic nationwide gastric cancer screening program has been implemented in South Korea (beginning at age 40, biannually)23 and Japan (beginning at age 50, biannually).24 Two decision-analytic simulation studies have provided insight into the uncertainty about the cost effectiveness for potential targeted gastric cancer screening in higher-risk populations in the United States. One study demonstrated that esophagogastroduodenoscopy (EGD) screening for otherwise asymptomatic Asian American people (as well as Hispanics and non-Hispanic Blacks) at the time of screening colonoscopy at 50 years of age with continued endoscopic surveillance every 3 years was cost effective, only if gastric intestinal metaplasia (GIM) or more advanced lesions were diagnosed at the index screening EGD.25 Previous studies analyzing the cost effectiveness for gastric cancer screening in the United States had the limitation of not stratifying according to race or ethnicity, or accounting for patients diagnosed with GIM. Subsequently, the same research group extended this model analysis and has published additional findings that this strategy is cost effective for each of the most prevalent Asian American ethnicities (Chinese, Filipino, Southeast Asian, Vietnamese, Korean, and Japanese Americans) in the United States irrespective of sex.26 Although the authors raised a limitation that additional risk factors such as family history, tobacco use, or persistent H. pylori infection were not considered in the model because data regarding differentiated noncardia gastric cancer risk among Asian American ethnicities based on these risk factors are not available.
Figure 1. A 77-year-old woman who was found to have a 0-IIc+IIc lesion in the gastric antrum. Biopsy confirmed the presence of intramucosal adenocarcinoma. The lesion was resected en bloc by ESD. Row 1, from left: Initial inspection of the lesion under HDWL; NBI magnification (near focus function); Perimeter marking of the lesion. Row 2, from left: Submucosal dissection; En-bloc resection; Resected specimen.
These two model analytic studies added valuable insights to the body of evidence that subsequent EGDs after the one-time bundled EGD is cost effective for higher-risk asymptomatic people in the United States, if the index screening EGD with gastric mucosal biopsies demonstrates at least GIM. Further population-based research to elucidate risk stratification among higher-risk people will provide a schema that could standardize management and resource allocation as well as increase the cost effectiveness of a gastric cancer screening program in the United States. The degree of risk of developing gastric cancer in autoimmune gastritis varies among the reported studies.27-29 Although the benefit of endoscopic screening in patients with autoimmune gastritis has not been established, a single endoscopic evaluation should be recommended soon after the diagnosis of autoimmune gastritis in order to identify prevalent neoplastic lesions.30
Practical consideration when we perform EGD for early gastric cancer screening
Identification of higher-risk patients should alert an endoscopist to observe mucosa with greater care with a lower threshold to biopsy any suspicious lesions. Preprocedural risk stratification for each individual before performing diagnostic EGD will improve early gastric cancer detection. While we perform EGD, detecting precursor lesions (atrophic gastritis and GIM) is as important as diagnosing an early gastric cancer. Screening and management of patients with precursor lesions (i.e., atrophic gastritis and GIM) is beyond the scope of this article, and this was published in a previous issue of the New Gastroenterologist. It is important to first grossly survey the entire gastric mucosa using high-definition while light (HDWL) endoscopy and screen for any focal irregular (raised or depressed) mucosal lesions. These lesions are often erythematous and should be examined carefully. Use of mucolytic and/or deforming agents (e.g., N-acetylcysteine or simethicone) is recommended for the improvement of visual clarity of gastric mucosa.31 Simethicone is widely used in the United States for colonoscopy and should also be available at the time of EGD for better gastric mucosal visibility. If irregular mucosal lesions are noted, this area should also be examined under narrowband imaging (NBI) in addition to HDWL. According to a simplified classification consisting of mucosal and vascular irregularity, NBI provides better mucosal surface morphology for diagnosis of early gastric cancer compared with HDWL, and a thorough examination of the surface characteristics is a prerequisite.32 This classification was further validated in a randomized control trial, and NBI increased sensitivity for the diagnosis of neoplasia compared with HDWL (92 % vs. 74 %).33 The majority of institutions in the United States have a newer-generation NBI (Olympus America, EVIS EXERA III video system, GIF-HQ190), which provides brighter endoscopic images to better characterize gastric neoplastic lesions. Once we recognize an area suspicious for neoplasia, we should describe the macroscopic features according to a classification system.
The Paris classification, one of the most widely recognized classification systems among U.S. gastroenterologists, is recommended for gastric neoplastic lesions.34Gastric neoplastic lesions with a “superficial” endoscopic appearance are classified as subtypes of “type 0.” The term “type 0” was chosen to distinguish the classification of “superficial” lesions from the Borrmann classification for “advanced” gastric tumors, which includes types 1 to 4. In the classification, a neoplastic lesion is called “superficial” when its endoscopic appearance suggests that the depth of penetration in the digestive wall is not more than into the submucosa (i.e., there is no infiltration of the muscularis propria). The distinctive characters of polypoid and nonpolypoid lesions are summarized in Table 1. Endoscopic submucosal dissection (ESD) has steadily gained acceptance for the treatment of early gastric cancer in the United States. The American Gastroenterological Association recommended in the 2019 institutional updated clinical practice guideline that ESD should be considered the first-line therapy for visible, endoscopically resectable, superficial gastric neoplasia.35 This recommendation is further supported by the published data on efficacy and safety of ESD for early gastric neoplasia in a large multicenter cohort in the United States.36 For all suspicious lesions, irrespective of pathological neoplastic confirmation, referral to an experienced center for further evaluation and endoscopic management should be considered. Lastly, all patients with early gastric cancer should be evaluated for H. pylori infection and treated if the test is positive. Eradication of H. pylori is associated with a lower rate of metachronous gastric cancer,37 and treatment of H. pylori as secondary prevention is also recommended.
