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  1. Hatta W, Tong D, Lee YY, Ichihara S, Uedo N, Gotoda T
    Dig Endosc, 2017 Apr;29 Suppl 2:18-25.
    PMID: 28425657 DOI: 10.1111/den.12808
    Esophagogastric junction (EGJ) adenocarcinoma has been on the increase in Western countries. However, in Asian countries, data on the incidence of EGJ adenocarcinoma are evidently lacking. In the present review, we focus on the current clinical situation of EGJ adenocarcinoma in three Asian countries: Japan, Hong Kong, and Malaysia. The incidence of EGJ adenocarcinoma has been reported to be gradually increasing in Malaysia and Japan, whereas it has stabilized in Hong Kong. However, the number of cases in these countries is comparatively low compared with Western countries. A reason for the reported difference in the incidence and time trend of EGJ adenocarcinoma among the three countries may be explained by two distinct etiologies: one arising from chronic gastritis similar to distal gastric cancer, and the other related to gastroesophageal reflux disease similar to esophageal adenocarcinoma including Barrett's adenocarcinoma. This review also shows that there are several concerns in clinical practice for EGJ adenocarcinoma. In Hong Kong and Malaysia, many EGJ adenocarcinomas have been detected at a stage not amenable to endoscopic resection. In Japan, histological curability criteria for endoscopic resection cases have not been established. We suggest that an international collaborative study using the same definition of EGJ adenocarcinoma may be helpful not only for clarifying the characteristics of these cancers but also for improving the clinical outcome of these patients.
  2. Soh YSA, Lee YY, Gotoda T, Sharma P, Ho KY, Asian Barrett's Consortium
    Dig Endosc, 2019 Nov;31(6):609-618.
    PMID: 30892742 DOI: 10.1111/den.13402
    Barrett's esophagus (BE), a premalignant condition of the lower esophagus, is increasingly prevalent in Asia. However, endoscopic and histopathological criteria vary widely between studies across Asia, making it challenging to assess comparability between geographical regions. Furthermore, guidelines from various societies worldwide provide differing viewpoints and definitions, leading to diagnostic challenges that affect prognostication of the condition. In this review, the authors discuss the controversies surrounding the diagnosis of BE, particularly in Asia. Differences between guidelines worldwide are summarized with further discussion regarding various classifications of BE used, different definitions of gastroesophageal junction used across geographical regions and the clinical implications of intestinal metaplasia in the setting of BE. Although many guidelines recommend the Seattle protocol as the preferred approach regarding dysplasia surveillance in BE, some limitations exist, leading to poor adherence. Newer technologies, such as acetic acid-enhanced magnification endoscopy, narrow band imaging, Raman spectroscopy, molecular approaches and the use of artificial intelligence appear promising in addressing these problems, but further studies are required before implementation into routine clinical practice. The Asian Barrett's Consortium also outlines its ongoing plans to tackle the challenge of standardizing the diagnosis of BE in Asia.
  3. Kusano C, Singh R, Lee YY, Soh YSA, Sharma P, Ho KY, et al.
    Dig Endosc, 2022 Nov;34(7):1320-1328.
    PMID: 35475586 DOI: 10.1111/den.14342
    Endoscopic diagnosis of gastroesophageal junction and Barrett's esophagus is essential for surveillance and early detection of esophageal adenocarcinoma and esophagogastric junction cancer. Despite its small size, the gastroesophageal junction has many inherent problems, including marked differences in diagnostic methods for Barrett's esophagus in international guidelines. To define Barrett's esophagus, gastroesophageal junction location should be clarified. Although gastric folds and palisade vessels are landmarks for identifying this junction, they are sometimes difficult to observe due to air entry or reflux esophagitis. The possibility of diagnosing a malignancy associated with Barrett's esophagus <1 cm, identified using palisade vessels, should be re-examined. Nontargeted biopsies of Barrett's esophagus are commonly used to detect intestinal metaplasia, dysplasia, and cancer as described in the Seattle protocol. Barrett's esophagus with intestinal metaplasia has a high risk of becoming cancerous. Furthermore, the frequency of cancer in patients with Barrett's esophagus without intestinal metaplasia is high, and the guidelines differ on whether to include the presence of intestinal metaplasia in the diagnosis of Barrett's esophagus. Use of advanced imaging technologies, including narrow-band imaging with magnifying endoscopy and linked color imaging, is reportedly valid for diagnosing Barrett's esophagus. Furthermore, artificial intelligence has facilitated the diagnosis of Barrett's esophagus through its deep learning and image recognition capabilities. However, it is necessary to first use the endoscopic definition of the gastroesophageal junction, which is common in all countries, and then elucidate the characteristics of Barrett's esophagus in each region, for example, length differences in the risk of carcinogenesis with and without intestinal metaplasia.
  4. Tan PO, Soh AYS, Kusano C, Lee YY, Gotoda T
    Digestion, 2022;103(1):37-44.
    PMID: 34781299 DOI: 10.1159/000519922
    BACKGROUND: Epidemiology data of gastroesophageal junction (GEJ) cancers in Asia are extremely scarce. It is hardly registered by any cancer registry in the region, and only a few reports are available. Based on existing literature works, the overall trend indicates similar or gradually increasing GEJ cancers in Asia but comparably less than the West. The increasing trend in Asia is likely a result of rising risk factors, especially of gastroesophageal reflux disease and obesity.

    SUMMARY: However, epidemiology data may be misleading due to several contentious diagnostic issues. The diagnostic conundrums are due to inherent complexity of the GEJ as a functional and pathological unit. Challenging diagnostic issues in Asia include the following: nonstandardized landmark of the GEJ, misclassification of Barrett esophagus, targeted versus nontargeted tissue sampling, histopathology disagreement and challenges in screening or surveillance of dysplastic BE and early GEJ cancer. The recent Asian-Pacific survey led by the Asian Barrett Consortium (ABC) has provided useful insights into these contentious issues. A key learning point from these diagnostic limitations is that the awareness of the disease and adherence to existing recommendations or guidelines are poor in the region. Key Messages: Standardization in diagnostic methodology is vital for accurate epidemiology data, and this can only come from better awareness and adherence through educational and international efforts. Last, surveillance strategy may need a paradigm shift from a purely diagnostic approach to a combined targeted surveillance and treatment approach using novel endoscopic techniques.

  5. Gotoda T, Uedo N, Yoshinaga S, Tanuma T, Morita Y, Doyama H, et al.
    Dig Endosc, 2016 Apr;28 Suppl 1:2-15.
    PMID: 26836611 DOI: 10.1111/den.12623
    Endoscopic diagnosis of gastrointestinal tumors consists of the following processes: (i) detection; (ii) differential diagnosis; and (iii) quantitative diagnosis (size and depth) of a lesion. Although detection is the first step to make a diagnosis of the tumor, the lesion can be overlooked if an endoscopist has no knowledge of what an early-stage 'superficial lesion' looks like. In recent years, image-enhanced endoscopy has become common, but white-light endoscopy (WLI) is still the first step for detection and characterization of lesions in general clinical practice. Settings and practice of routine esophagogastroduodenoscopy (EGD) such as use of antispasmodics, number of endoscopic images taken, and observational procedure are customarily decided in each facility in each country and are not well standardized. Therefore, in the present article, we attempted to outline currently available evidence and actual Japanese practice on gastric cancer screening using WLI, and provide tips for detecting EGC during routine EGD which could become the basis of future research.
  6. Uedo N, Gotoda T, Yoshinaga S, Tanuma T, Morita Y, Doyama H, et al.
    Dig Endosc, 2016 Apr;28 Suppl 1:16-24.
    PMID: 26856704 DOI: 10.1111/den.12629
    The mortality rate of gastric cancer (GC) is close to the incidence rate worldwide. However, in Korea and Japan, the mortality rate of GC is less than half of the incidence rate. We hypothesized that good-quality routine esophagogastroduodenoscopy (EGD) contributes to a high detection rate for early GC (EGC) and improves mortality in these countries.
  7. Uedo N, Yoshio T, Yoshinaga S, Takeuchi M, Hatta W, Yano T, et al.
    Dig Endosc, 2017 Apr;29 Suppl 2:26-36.
    PMID: 28425653 DOI: 10.1111/den.12849
    BACKGROUND AND AIM: Western studies have suggested two distinct etiologies of esophagogastric junction (EGJ) cancer: Helicobacter pylori-associated atrophic gastritis and non-atrophic gastric mucosa resembling esophageal adenocarcinoma. The present study investigated whether endoscopic gastric mucosal atrophy can distinguish between these two types of EGJ adenocarcinoma.

    METHODS: Data were collected from patients with Siewert type II, T1 EGJ adenocarcinoma who underwent endoscopic or surgical resection at eight Japanese institutions in 2010-2015. Clinicopathological characteristics of EGJ cancers with and without endoscopic gastric mucosal atrophy were compared. EGJ was defined as the lower end of the palisade vein and/or the top of the gastric folds.

    RESULTS: Of the 229 patients identified, 161 had endoscopic gastric mucosal atrophy and 68 did not. The latter group was younger (64 vs 70 years, P = 0.000); had a higher proportion of patients negative for H. pylori (90% vs 47%, P 
  8. Sung JJ, Chiu PW, Chan FKL, Lau JY, Goh KL, Ho LH, et al.
    Gut, 2018 10;67(10):1757-1768.
    PMID: 29691276 DOI: 10.1136/gutjnl-2018-316276
    Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.
  9. Chiu PWY, Uedo N, Singh R, Gotoda T, Ng EKW, Yao K, et al.
    Gut, 2019 02;68(2):186-197.
    PMID: 30420400 DOI: 10.1136/gutjnl-2018-317111
    BACKGROUND: This is a consensus developed by a group of expert endoscopists aiming to standardise the preparation, process and endoscopic procedural steps for diagnosis of early upper gastrointestinal (GI) cancers.

    METHOD: The Delphi method was used to develop consensus statements through identification of clinical questions on diagnostic endoscopy. Three consensus meetings were conducted to consolidate the statements and voting. We conducted a systematic literature search on evidence for each statement. The statements were presented in the second consensus meeting and revised according to comments. The final voting was conducted at the third consensus meeting on the level of evidence and agreement.

    RESULTS: Risk stratification should be conducted before endoscopy and high risk endoscopic findings should raise an index of suspicion. The presence of premalignant mucosal changes should be documented and use of sedation is recommended to enhance detection of superficial upper GI neoplasms. The use of antispasmodics and mucolytics enhanced visualisation of the upper GI tract, and systematic endoscopic mapping should be conducted to improve detection. Sufficient examination time and structured training on diagnosis improves detection. Image enhanced endoscopy in addition to white light imaging improves detection of superficial upper GI cancer. Magnifying endoscopy with narrow-band imaging is recommended for characterisation of upper GI superficial neoplasms. Endoscopic characterisation can avoid unnecessary biopsy.

    CONCLUSION: This consensus provides guidance for the performance of endoscopic diagnosis and characterisation for early gastric and oesophageal neoplasia based on the evidence. This will enhance the quality of endoscopic diagnosis and improve detection of early upper GI cancers.

  10. Kew GS, Soh AYS, Lee YY, Gotoda T, Li YQ, Zhang Y, et al.
    World J Gastrointest Oncol, 2021 Apr 15;13(4):279-294.
    PMID: 33889279 DOI: 10.4251/wjgo.v13.i4.279
    BACKGROUND: Major societies provide differing guidance on management of Barrett's esophagus (BE), making standardization challenging.

    AIM: To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists.

    METHODS: Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE.

    RESULTS: Five hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (n = 310, 54.5%) and China (n = 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0% vs 10.0%, P < 0.001) while outside Japan, squamo-columnar junction was preferred (59.5% vs 27.4%, P < 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (P < 0.001). Most Asian endoscopists (70.8%) would survey long-segment BE without dysplasia every two years. Adherence to Seattle protocol was poor with only 6.3% always performing it. 73.2% of Japanese never did it, compared to 19.3% outside Japan (P < 0.001). The most preferred (74.0%) treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis. For BE with low-grade dysplasia, 6-monthly surveillance was preferred in 61.9% within Japan vs 47.9% outside Japan (P < 0.001).

    CONCLUSION: Diagnosis and management of BE varied within Asia, with stark contrast between Japan and outside Japan. Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.

  11. Liou JM, Malfertheiner P, Lee YC, Sheu BS, Sugano K, Cheng HC, et al.
    Gut, 2020 12;69(12):2093-2112.
    PMID: 33004546 DOI: 10.1136/gutjnl-2020-322368
    OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC).

    METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed.

    RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori.

    CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

  12. Sugano K, Spechler SJ, El-Omar EM, McColl KEL, Takubo K, Gotoda T, et al.
    Gut, 2022 Aug;71(8):1488-1514.
    PMID: 35725291 DOI: 10.1136/gutjnl-2022-327281
    OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ.

    DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised.

    RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO).

    CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

  13. Kitagawa Y, Matsuda S, Gotoda T, Kato K, Wijnhoven B, Lordick F, et al.
    Gastric Cancer, 2024 May;27(3):401-425.
    PMID: 38386238 DOI: 10.1007/s10120-023-01457-3
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