The introduction of mass screening using esophagogastroduodenoscopy (EGD) offers a chance to perform procedure for early detection of cancers in otherwise healthy cohorts. We endoscopists perform many procedures during daily practice and it is therefore very important to know the risk factors and precursors for effective early detection. Helicobactor pylori infection and related diseases such as severe atrophic gastritis or intestinal metaplasia are well known factors associated with gastric cancer.1 In addition, alcohol consumption and tobacco abuse are the well known, strongest cause of squamous cell carcinoma at the upper aerodigestive tract including laryngopharynx and esophagus.2 The flushing reaction after drinking small amount of alcohol that indicates severe acetaldehydemia due to inactive aldehyde dehydrogenase is the simple questionnaire and can serve to identify populations at high risk of esophageal squamous cell carcinoma.3 Keeping these findings based on high-quality evidence in mind during our busy working hours may trigger us to consider modifying the imaging modality to image- enhanced endoscopy or chromoendoscopy.

In Western countries, esophageal adenocarcinoma (EAC) is the most common malignancy that can be identified with EGD. Advanced EAC has a poor prognosis, and gastroesophageal reflux disease, obesity, smoking, white race, and male sex are reported as common clinical background risk factors.4 Barrett's esophagus (BE) is one of the most important findings associated with risk for EAC and can be identified only with EGD.4 And the length or severity of BE is determined as the important associated factors to the development of carcinogenesis at gastroesophageal junction. In Western countries, the definition of BE is that columnar epithelium spreading upward 1 cm or longer and presence of intestinal metaplasia, but this remains controversial since there are various classifications of BE proposed by professional societies in several countries. From the results of a multi-center prospective study in the United States to assess the risk of EAC in patients with BE <1 cm of histological intestinal metaplasia, referred to as an irregular Z line, they found a negligible risk compared with patients with BE greater than or equal to 1 cm with 5 years follow-up of endoscopic evaluation (progression to high grade dysplasia or EAC: 0% in irregular Z line and 4.4% in BE >1 cm, P = 0.005).5

The incidence of patients with EAC is reportedly increasing in Japan as evidenced by the annual registered number of EAC cases between 2007 and 2014 in the hospital registration data of Akita prefecture in the northern region of Japan.6 Therefore, it is a pressing issue to elucidate the cohort at a high risk of EAC in the Japanese population to encourage early detection and treatment. Fukuda et al.,7 the research team from Akita University, assessed the risk of EAC based on the length of BE, and concluded that there was a negligible risk of developing EAC in cohorts with ultrashort segment BE (USSBE), similar to the risk of gastric cancer in those without atrophic gastritis. The difference of the definition of irregular Z line and USSBE is the presence of the intestinal metaplasia, USSBE was diagnosed as columnar-lined epithelium <1 cm regardless of the presence of intestinal metaplasia in the study. With authors' great effort to review numerous stored still images, they found that the proportion of the presence of BE in the Japanese cohorts who received annual checkup EGD in clinics. They retrospectively diagnosed BE in 45% of the sample population and approximately 80% of cases were USSBE, even with the inferior inter-observer agreement compared with short-segment or long-segment BE. The authors then evaluated the risk of EAC in patients with BE and the risk of gastric cancer in patients with atrophic gastritis. With more than 50 months and three annual checkup EGD for 9121 individuals, gastric cancer, esophageal squamous cell carcinoma, and EAC were detected 89, 20, and two cases, respectively. They confirmed the increase of the development of gastric cancer according to the degree of the atrophic gastritis. Similar to other studies, the incidence of gastric cancer was approximately 100 times greater in individuals with open-type atrophic gastritis (0.53%/year, P < 0.01) compared with those without evidence of atrophic gastritis (0.0059%/year). On the other hand, the total incidence of EAC was lower and the risk stratification of EAC was difficult to establish. Most importantly, authors established the annual and cumulative incidence of EAC and gastric cancer according to annual surveillance by EGD in a same cohort with a relatively long-term follow-up. They also compared the risk of EAC and gastric cancer based on the endoscopic findings of BE and gastric atrophy that to be easily accepted by readers.

The limitation of the study described in the article was the retrospective evaluation of the degree of BE and the lack of information about the H. pylori infection or the behavioral habits, including alcohol consumption and tobacco abuse. As the authors pointed out, the presence or absence of USSBE is very difficult to judge through captured still images without the knowledge of the protocol including the control of examinees' breath. Furthermore, there was a lack of histological findings from the columnar epithelium. The landmark large nationwide population-based cohort study in Denmark to clarify the risk of high grade dysplasia or EAC in patients with BE revealed that the incidence rate of EAC was five times higher in patients with low grade dysplasia than in those without dysplasia.8 The authors concluded that annual surveillance endoscopy is of doubtful value for patients with non-dysplastic BE. From the updated American Society for Gastrointestinal Endoscopy guidelines on BE screening and surveillance, the role of surveillance endoscopy in patients with non-dysplastic BE remains controversial, and randomized control trial is warranted at the point of impact to determine the cost-effectiveness of reducing mortality related to EAC.9

The study by Fukuda et al. encouraged us to determine future research questions. In their study, authors assessed the captured still images of white light imaging without standardized protocol for detection of EAC. However, it is important to clarify the most suitable modalities or methods to capture the precursor of EAC, such as narrow band imaging for the pharyngeal region or Lugol's chromoendoscopy for thoracic esophagus. Therefore, we should determine the standard protocol for the capturing still images or endoscopic diagnosis of EAC including the timing of patients' deep inspiration breath hold or appropriate image enhanced endoscopy. Since the study included only data from one prefecture in Japan, further studies with several prefectures or urban versus rural areas would be interesting to include in the future. Furthermore, because of the low incidence of EAC in Japan, an analysis using nationwide registered data of Japan is warranted to identify the risk factors and findings associated with the development of EAC. In Japan, residents have many opportunities to receive EGD using new high-definition endoscopic system, with easy access to inexpensive examination only with minor symptom covered by the universal insurance, health checks provided by employer, and national screening program. Accessibility for endoscopic examination is a strong point of Japan’s health care system compared with other countries. The Japan Gastroenterological Endoscopy Society launched the Japan Endoscopy Database (JED) project to build a nationwide database of captured still images with tagged clinical information. This large-scale data collection is aimed at providing evidence for large clinical research based on members' clinical question.10 JED database is a good potential source for furthering the proposed research herein, which requires big data for analysis.

The gastroesophageal junction must be a next hot spot of the surveillance using EGD in the future. Therefore, Japanese endoscopists continuously make an effort to find the next critical advancement for the detection of EAC since it is one of the most endoscopy-friendly countries in the world.

Author T.Y. is an Associate Editor of Digestive Endoscopy and has received honoraria for lectures from Olympus. He has also received research grants from Olympus, Fujifilm and Hoya Pentax out of this work.