Screening for gastric cancer in Asia: current evidence and practice
Gastric cancer is the second most common cause of death from cancer in Asia. Although surgery is the standard treatment for this disease, early detection and treatment is the only way to reduce mortality. This Review summarises the epidemiology of gastric cancer, and the evidence for, and current practices of, screening in Asia. Few Asian countries have implemented a national screening programme for gastric cancer; most have adopted opportunistic screening of high-risk individuals only. Although screening by endoscopy seems to be the most accurate method for detection of gastric cancer, the availability of endoscopic instruments and expertise for mass screening remains questionable—even in developed countries such as Japan. Therefore, barium studies or serum-pepsinogen testing are sometimes used as the initial screening tool in some countries, and patients with abnormal results are screened by endoscopy. Despite the strong link between infection with Helicobacter pylori and gastric cancer, more data are needed to define the role of its eradication in the prevention of gastric cancer in Asia. At present, there is a paucity of quality data from Asia to lend support for screening for gastric cancer. 
The Japanese Guidelines for Gastric Cancer Screening
Gastric cancer is the leading cause of death from cancer in Japan. In 2004, there were 50 562 deaths from gastric cancer; they accounted for 15.8% of the total number of cancer deaths. Since 1983, under the Health Service Law for the Aged, gastric cancer screening has been conducted nationwide for all residents aged 40 years and over.
On the basis of the standardized method developed for the Japanese Guidelines for Cancer Screening, the efficacies of various methods for gastric cancer screening were evaluated and the guideline was developed.
Four methods for gastric cancer screening were evaluated: photofluorography, endoscopy, serum pepsinogen testing and Helicobacter pylori antibody testing. On the basis of the analytic framework involving key questions, 1715 articles, published from January 1985 to February 2005, were selected using MEDLINE, the Japanese Medical Research Database and other methods. After the systematic literature review, 10 articles were identified as direct evidence and 49 articles as indirect evidence. The studies that evaluated mortality reduction from gastric cancer included five case–control and two cohort studies for radiographic screening. On the basis of the balance of benefits and harms, the recommendations for population-based and opportunistic screening were formulated. Gastric cancer screening using photofluorography was recommended for both screening programs. The other methods were not recommended for population-based screening due to insufficient evidence.
The guideline for gastric cancer screening guideline was developed based on the previously established method. Gastric cancer screening using photofluorography is recommended for population-based and opportunistic screening in Japan. 
The time to eradicate gastric cancer is now
Worldwide gastric cancer remains one of the most common cancers, killing upwards of one million people each year. While the molecular pathogenesis remains unclear, infection with the bacterium Helicobacter pylori is considered a “necessary but not sufficient” cause, not surprisingly as gastric cancer has long been known to be associated with atrophic gastritis. Eradication of H pylori is expected to virtually eliminate gastric cancer and H pylori associated peptic ulcer within approximately 40 years and thus reduce overall mortality. In the USA, the incidence of gastric cancer in the general population is low, reflecting the change in the pattern of gastritis from atrophic to non-atrophic and in the low and decreasing prevalence of H pylori infection in the middle and upper classes. However, the plan for eradication of this important pathogen must be considered within the context of the prevalence and outcome within specific populations. 
The Expression of Human Epididymis Protein 4a (HE4) in the Normal Gastric Epithelia and Its Role in the Development of Intestinal Metaplasia and Gastric Cancer
Background: Biomarkers that allow early diagnosis of gastric carcinoma (GC) patients are limited. Human epididymal protein 4 (HE4) is a novel biomarker for epithelial ovarian and lung cancer. This study was designed to evaluate the role of HE4 in the development of intestinal metaplasia (IM) and gastric carcinoma.
Methods: A total of 41 patients with a diagnosis of GC and 48 patients with a diagnosis of IM were enrolled. Gastric cancer samples were taken from patients who underwent gastric resection due to GC. For IM, biopsies obtained from patients who underwent endoscopic examination for non-tumoral reasons were used. Intestinal metaplasia adjacent to GC was also examined separately. For HE4 expression, immunohistochemistry was used and the results were compared to demographic, clinic, pathologic and prognostic parameters.
Results: The patients were 38–90 years-old (mean: 65.6). Tumor localization were antrum in 37.8%, corpus in 27%, lesser curvature in 21.6%, greater curvature in 5.4%, and cardia in 8.1% of patients. Tumor sizes ranged between1-13 cm (mean 5.54). There were 37.8% well to moderately, and 62.2% poorly differentiated carcinoma. Pathological T evaluations were as follows: pT1=13.5%; pT2=8.1%; pT3=59.4%; pT4=18.9% patients. The expression of HE4 was seen in 50% of tumors. Among the tumor samples that harbor intestinal metaplasia, HE4 expression in metaplastic cells was seen in 61.1% of the cases. Diffuse type carcinoma had more HE4 expression than intestinal type cancers and there was an inverse correlation between depth of tumor invasion and the presence of HE4 (p=0.037).
Conclusions: Human epididymal protein 4 was expressed in normal oxyntic glands and metaplastic cells as well as GC cells but not in the surface foveolar epithelium. It was expressed mostly in diffuse type carcinoma. HE4 may be involved in personalized treatment in gastric cancer. 
The Morphological Features of “Cavitary” Type Angiogenesis in Diffuse and Intestinal Types of Gastric Cancer and Its Relationship with Tumor-Infiltrating Immune Cells
Background: Previously we have described the “cavitary” type of angiogenesis by gastric cancer (GC) consisting of the formation of “cavitary structures” (CS) in tumor stroma, which are then lined by endothelial cells and merged into the blood vessels of the organ. The morphological features of the “cavitary” type of angiogenesis in intestinal and diffuse types of GC and the relations of CS with the tumor-infiltrating immune cells, was the purpose of this study.
Materials and Methods: The samples of tumor and adjacent gastric mucosa (GM) in 73 patients with GC who had undergone radical surgery were being studied. The sections were stained with hematoxylin and eosin and immunohistochemically using antibodies to CD34, CD4, CD8, CD20 Ð¸ CD68.
Results: The differences of “cavitary” type of angiogenesis in the intestinal and diffuse types of GC are only associated with CS type-1 that are formed as a result of the abruption of epithelial cells from the underlying stroma. In the intestinal type of GC the basis for the formation of CS type-1 are the tumor glands. The wall of such CS is most likely the basement membrane bordering the connective tissue. In the diffuse type of GC the CS type-1 are presented as the structures limited from outside by the tumor cells. In their lumen the fragments of tumor tissue having the same structure as the surrounding one are being detected. The performed analysis showed that the number of CS type-1 was associated with the density of CD68, whereas the presence of CS type-2 – with the presence of lymphoid follicles (LF) and B-cell infiltrations at the boundary of tumor and GM. The density of CD68 in GM was higher in cases with multiple CS type-1 (72.6±47.0 vs. 41.6±15.4 cells per unit area, P= .03). In turn, CS type-2 were more often met in the presence of multiple LF (72,3% vs. 33,3%, P= ,04) and B-cell infiltrations (90% vs. 26,3%, P= ,001).
Conclusion: The obtained data testify about the relation of CD20 lymphocytes and CD68 macrophages with the “cavitary” type of angiogenesis. 
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 Celik, B., Bulut, T. and Yalcin, A. (2018) “The Expression of Human Epididymis Protein 4a (HE4) in the Normal Gastric Epithelia and Its Role in the Development of Intestinal Metaplasia and Gastric Cancer”, Journal of Advances in Medicine and Medical Research, 27(2), pp. 1-10. doi: 10.9734/JAMMR/2018/41815.
 Senchukova, M., Ryabov, A., Karmakova, T., Tomchuk, O. and Stadnikov, A. (2015) “The Morphological Features of ‘Cavitary’ Type Angiogenesis in Diffuse and Intestinal Types of Gastric Cancer and Its Relationship with Tumor-Infiltrating Immune Cells”, Journal of Advances in Medicine and Medical Research, 7(4), pp. 272-284. doi: 10.9734/BJMMR/2015/15695.