Gastric Cancer pp 119-145 | Cite as

Endoscopic Diagnosis

  • Takashi Nagahama
  • Noriya Uedo
  • Kenshi Yao


The strategy of early detection and early treatment of gastric cancer to reduce the mortality rate has been widely implemented in Japan. To detect early-stage gastric cancer, considerable education regarding endoscopic methods for systematic screening is carried out. If suspicious lesions for gastric cancer are detected by conventional white-light imaging, a detailed differential diagnosis of cancerous and non-cancerous lesions by image-enhancement endoscopy with/without magnification, followed by biopsy, is performed as a usual subsequent approach. In the case of lesions diagnosed as cancer by histology, a endoscopist performs a detailed examination before treatment to define the (1) histological type, (2) tumor size, (3) presence and absence of ulceration or scar, and (4) depth of invasion to determine the treatment indication, i.e., endoscopic or surgical. Regarding the tumor size, the boundary of the lesion should be precisely identified in order to determine the excision line. Recently, the ABC method using a combination of serum Helicobacter pylori antibody and pepsinogen tests, which involves an overview of risk stratification of gastric cancer, is recommended as a part of gastric cancer screening.


Endoscopy Diagnosis Stomach cancer Early gastric cancer Chromoendoscopy Narrow-band imaging 


  1. 1.
  2. 2.
    Murakami T. Pathomorphological diagnosis. Definition and gross classification of early gastric cancer. Gann Monogr Cancer Res. 1971;11:53–5.Google Scholar
  3. 3.
    Yamazaki H, Oshima A, Murakami R, Endoh S, Ubukata T. A long-term follow-up study of patients with gastric cancer detected by mass screening. Cancer. 1989;63:613–7.CrossRefGoogle Scholar
  4. 4.
    Everett AM, Axon ATR. Early gastric cancer in Europe. Gut. 1997;41:142–50.CrossRefGoogle Scholar
  5. 5.
    Hamashima C, Shibuya D, Yamazaki H, et al. The Japanese guidelines for gastric cancer screening. Jpn J Clin Oncol. 2008;38:259–67.CrossRefGoogle Scholar
  6. 6.
    Hamashima C, Ogoshi K, Narisawa R, Kishi T, Kato T, Fujita K, Sano M, Tsukioka S. Impact of endoscopic screening on mortality reduction from gastric cancer. World J Gastroenterol. 2015;21(8):2460–6.CrossRefGoogle Scholar
  7. 7.
    Matsumoto S, Yoshida Y. Efficacy of endoscopic screening in an isolated island: a case-control study. Indian J Gastroenterol. 2014;33(1):46–9.CrossRefGoogle Scholar
  8. 8.
    Jun JK, Choi KS, et al. Effectiveness of the Korean National Cancer Screening Program in reducing gastric cancer mortality. Gastroenterology. 2017;152(6):1319–28.CrossRefGoogle Scholar
  9. 9.
    Hamashima C, et al. The Japanese guidelines for gastric cancer screening version 2014. Accessed May 2018.
  10. 10.
    The Japanese Society of Gastrointestinal Cancer Screening. The 2012 report [Japanese] [online]. 2012.
  11. 11.
    Suzuki H, Gotoda T, Sasako M, Saito D. Detection of early gastric cancer: misunderstanding the role of mass screening. Gastric Cancer. 2006;9:315–9.CrossRefGoogle Scholar
  12. 12.
    Ono H, Kondo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut. 2001;48:225–9.CrossRefGoogle Scholar
  13. 13.
    Uedo N, Takeuchi Y, Ishihara R. Endoscopic management of early gastric cancer: endoscopic mucosal resection or endoscopic submucosal dissection: data from a Japanese high-volume center and literature review. Ann Gastroenterol. 2012;25:281–90.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20:1–19.CrossRefGoogle Scholar
  15. 15.
    Ono H, Yao K, Fujishiro M, et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Dig Endosc. 2016;28:3–15.CrossRefGoogle Scholar
  16. 16.
    Hosokawa O, Hattori M, Douden K, et al. Difference in accuracy between gastroscopy and colonoscopy for detection of cancer. Hepato-Gastroenterology. 2007;54:442–4.PubMedGoogle Scholar
  17. 17.
    Menon S, Trudgill N. How commonly is upper gastrointestinal cancer missed at endoscopy? A meta-analysis. Endosc Int Open. 2014;2:E46–50.CrossRefGoogle Scholar
  18. 18.
    Yao K. The endoscopic diagnosis of early gastric cancer. Ann Gastroenterol. 2013;26:11–22.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Uedo N, Yao K. Endoluminal diagnosis of early gastric cancer and its precursors: bridging the gap between endoscopy and pathology. Adv Exp Med Biol. 2016;908:293–316.CrossRefGoogle Scholar
  20. 20.
    Yao K, Nagahama T, Matsui T, et al. Detection and characterization of early gastric cancer for curative endoscopic submucosal dissection. Dig Endosc. 2013;25:44–54.CrossRefGoogle Scholar
  21. 21.
    Fujii T, Iishi H, Tatsuta M, et al. Effectiveness of premedication with pronase for improving visibility during gastroendoscopy: a randomized controlled trial. Gastrointest Endosc. 1998;47:382–7.CrossRefGoogle Scholar
  22. 22.
    Lee GJ, Park SJ, Kim SJ, et al. Effectiveness of premedication with pronase for visualization of the mucosa during endoscopy: a randomized, controlled trial. Clin Endosc. 2012;45:161–4.CrossRefGoogle Scholar
  23. 23.
    Chang CC, Chen SH, Lin CP, et al. Premedication with pronase or N-acetylcysteine improves visibility during gastroendoscopy: an endoscopist-blinded, prospective, randomized study. World J Gastroenterol. 2007;13:444–7.CrossRefGoogle Scholar
  24. 24.
    Hiki N, Kurosaka H, Tatsutomi Y, et al. Peppermint oil reduces gastric spasm during upper endoscopy: a randomized, double-blind, double-dummy controlled trial. Gastrointest Endosc. 2003;57:475–82.CrossRefGoogle Scholar
  25. 25.
    Hiki N, Kaminishi M, Yasuda K, et al. Antiperistaltic effect and safety of L-menthol sprayed on the gastric mucosa for upper GI endoscopy: a phase III, multicenter, randomized, double-blind, placebo-controlled study. Gastrointest Endosc. 2011;73:932–41.CrossRefGoogle Scholar
  26. 26.
    Manuals for Gastroscopic Screening, version 2015 issued from Japanese Society of Gastrointestinal Cancer Screening. Accessed May 2018.
  27. 27.
    Yao K, Uedo N, Muto M, et al. Development of an E-learning system for the endoscopic diagnosis of early gastric cancer: an international multicenter randomized controlled trial. EBioMedicine. 2016;9:140–7.CrossRefGoogle Scholar
  28. 28.
    Yao K, Uedo N, Muto M, Ishikawa H. Development of an e-learning system for teaching endoscopists how to diagnose early gastric cancer: basic principles for improving early detection. Gastric Cancer. 2017;20(Suppl 1):28–38.CrossRefGoogle Scholar
  29. 29.
    Ida K, Hashimoto Y, Takeda S, et al. Endoscopic diagnosis of gastric cancer with dye scattering. Am J Gastroenterol. 1975;63:316–20.PubMedGoogle Scholar
  30. 30.
    Yao K, Anagnostopoulos GK, Ragunath K. Magnifying endoscopy for diagnosing and delineating early gastric cancer. Endoscopy. 2009;41:462–7.CrossRefGoogle Scholar
  31. 31.
    Yao K. Which micro-anatomies are visualized by magnifying endoscopy with NBI and how is this achieved? In: Yao K, editor. Zoom gastroscopy. Tokyo: Nihon Medical Center; 2009. p. 75–106.Google Scholar
  32. 32.
    Doyama H, Yoshida N, Tsuyama S, et al. The “white globe appearance” (WGA): a novel marker for a correct diagnosis of early gastric cancer by magnifying endoscopy with narrow-band imaging (M-NBI). Endosc Int Open. 2015;2:120–4.Google Scholar
  33. 33.
    Yoshida N, Doyama H, Nakanishi H, et al. White globe appearance is a novel specific endoscopic marker for gastric cancer: a prospective study. Dig Endosc. 2016;28:59–66.CrossRefGoogle Scholar
  34. 34.
    Ezoe Y, Muto M, Uedo N, et al. Magnifying narrowband imaging is more accurate than conventional white-light imaging in diagnosis of gastric mucosal cancer. Gastroenterology. 2011;141:2017–25.CrossRefGoogle Scholar
  35. 35.
    Yao K, Doyama H, Gotoda T, et al. Diagnostic performance and limitations of magnifying narrow-band imaging in screening endoscopy of early gastric cancer: a prospective multicenter feasibility study. Gastric Cancer. 2014;17:669–79.CrossRefGoogle Scholar
  36. 36.
    Muto M, Yao K, Kaise M, et al. Magnifying endoscopy simple diagnostic algorithm for early gastric cancer (MESDA-G). Dig Endos. 2016;28:379–93.CrossRefGoogle Scholar
  37. 37.
    Fujiwara S, Yao K, Nagahama T, et al. Can we accurately diagnose minute gastric cancers (≤5mm)? Chromoendoscopy vs. magnifying endoscopy with narrow band imaging. Gastric Cancer. 2015;18:590–6.CrossRefGoogle Scholar
  38. 38.
    Maki S, Yao K, Nagahama T, et al. Magnifying endoscopy with narrow-band imaging is useful in the differential diagnosis between low-grade adenoma and early cancer of superficial elevated gastric lesions. Gastric Cancer. 2013;16:140–6.CrossRefGoogle Scholar
  39. 39.
    Miwa K, Doyama H, Ito R, et al. Can magnifying endoscopy with narrow band imaging be useful for low grade adenomas in preoperative biopsy specimens? Gastric Cancer. 2012;15:170–8.CrossRefGoogle Scholar
  40. 40.
    Kimura-Tsuchiya R, Dohi O, Fujita Y. Magnifying endoscopy with blue laser imaging improves the microstructure visualization in early gastric cancer: comparison of magnifying endoscopy with narrow-band imaging. Gastroenterol Res Pract. 2017;2017:8303046.CrossRefGoogle Scholar
  41. 41.
    Sasazuki S, Inoue M, Iwasaki M, et al. Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Japanese men and women: a nested case-control study. Cancer Epidemiol Biomarkers Prev. 2006;15:1341–7.CrossRefGoogle Scholar
  42. 42.
    Watabe H, Mitsushima T, Yamaji Y, et al. Predicting the development of gastric cancer from combining helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study. Gut. 2005;54:764–8.CrossRefGoogle Scholar
  43. 43.
    Terasawa T, Nishida H, Kato K, et al. Prediction of gastric cancer development by serum pepsinogen test and helicobacter pylori seropositivity in eastern Asians: a systematic review and meta-analysis. PLoS One. 2014;9:e109783.CrossRefGoogle Scholar
  44. 44.
    Boda T, Ito M, Yoshihara M, et al. Advanced method for evaluation of gastric cancer risk by serum markers: determination of true low-risk subjects for gastric neoplasm. Helicobacter. 2014;19:1–8.CrossRefGoogle Scholar
  45. 45.
    Kishikawa H, Kimura K, Ito A, et al. Predictors of gastric neoplasia in cases negative for helicobacter pylori antibody and with normal pepsinogen. Anticancer Res. 2015;35:6765–71.PubMedGoogle Scholar
  46. 46.
    Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy. 1969;1:87–97.CrossRefGoogle Scholar
  47. 47.
    Nomura S, Ida K, Terao S, Adachi K, Kato T, Watanabe H, Shimbo T. Research group for establishment of endoscopic diagnosis of chronic gastritis. Endoscopic diagnosis of gastric mucosal atrophy: multicenter prospective study. Dig Endosc. 2014;26:709–19.CrossRefGoogle Scholar
  48. 48.
    Masuyama H, Yoshitake N, Sasai T, et al. Relationship between the degree of endoscopic atrophy of the gastric mucosa and carcinogenic risk. Digestion. 2015;91:30–6.CrossRefGoogle Scholar
  49. 49.
    Fukuta N, Ida K, Kato T, Uedo N, et al. Endoscopic diagnosis of gastric intestinal metaplasia: a prospective multicenter study. Dig Endosc. 2013;25:526–34.CrossRefGoogle Scholar
  50. 50.
    Sugimoto M, Ban H, Ichikawa H, et al. Efficacy of the Kyoto classification of gastritis in identifying patients at high risk for gastric cancer. Intern Med. 2017;56:579–86.CrossRefGoogle Scholar
  51. 51.
    Kamada T, Tanaka A, Yamanaka Y, et al. Nodular gastritis with helicobacter pylori infection is strongly associated with diffuse-type gastric cancer in young patients. Dig Endosc. 2007;19:180–4.CrossRefGoogle Scholar
  52. 52.
    Watanabe M, Kato J, Inoue I, et al. Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis. Int J Cancer. 2012;131:2632–42.CrossRefGoogle Scholar
  53. 53.
    Sekikawa A, Fukui H, Sada R, et al. Gastric atrophy and xanthelasma are markers for predicting the development of early gastric cancer. J Gastroenterol. 2016;51:35–42.2.CrossRefGoogle Scholar
  54. 54.
    Nagahama T, Yao K, Maki S, et al. Usefulness of magnifying endoscopy with narrow-band imaging for determining the horizontal extent of early gastric cancer when there is an unclear margin by chromoendoscopy (with video). Gastrointest Endosc. 2011;74:1259–67.CrossRefGoogle Scholar
  55. 55.
    Kiyotoki S, Nishikawa J, Satake M, et al. Usefulness of magnifying endoscopy with narrow-band imaging for determining gastric tumor margin. J Gastroenterol Hepatol. 2010;25:1636–41.CrossRefGoogle Scholar
  56. 56.
    Asada-Hirayama I, Kodashima S, Sakaguchi Y, et al. Magnifying endoscopy with narrow-band imaging is more accurate for determination of horizontal extent of early gastric cancers than chromoendoscopy. Endosc Int Open. 2016;4:E690–8.CrossRefGoogle Scholar
  57. 57.
    Okabe H, Ohida M, Okada N, et al. A new disk method for the endoscopic determination of gastric ulcer area. Gastrointest Endosc. 1986;32:20–4.CrossRefGoogle Scholar
  58. 58.
    Kanesaka T, Nagahama T, Uedo N, et al. Clinical predictors of histologic type of gastric cancer. Gastrointest Endosc. 2018;87:1014–22.CrossRefGoogle Scholar
  59. 59.
    Yao K, Yao T, Matsui T, Iwashita A, Oishi T. Hemoglobin content in intramucosal gastric carcinoma as a marker of histologic differentiation: a clinical application of quantitative electronic endoscopy. Gastrointest Endosc. 2000;52:241–5.CrossRefGoogle Scholar
  60. 60.
    Baba Y, Shimizu H, Takemoto N, et al. Histological classification of gastric cancer related to radiological and endoscopic manifestations (in Japanese, with English Abstract).Stomach Intest (Tokyo). 1991;26:1109–24.Google Scholar
  61. 61.
    Nakayoshi T, Tajiri H, Matsuda K, et al. Magnifying endoscopy combined with narrow band imaging system for early gastric cancer: correlation of vascular pattern with histopathology (including video). Endoscopy. 2004;36:1080–4.CrossRefGoogle Scholar
  62. 62.
    Yokoyama A, Inoue H, Minami H, et al. Novel narrow-band imaging magnifying endoscopic classification for early gastric cancer. Dig Liver Dis. 2010;42:704–8.CrossRefGoogle Scholar
  63. 63.
    Kanesaka T, Sekikawa A, Tsumura T, et al. Absent microsurface pattern is characteristic of early gastric cancer of undifferentiated type: magnifying endoscopy with narrow-band imaging. Gastrointest Endosc. 2014;80:1194–8.CrossRefGoogle Scholar
  64. 64.
    Sano T, Okuyama Y, Kobori O, et al. Early gastric cancer. Endoscopic diagnosis of depth of invasion. Dig Dis Sci. 1990;35:1340–4.CrossRefGoogle Scholar
  65. 65.
    Choi J, Kim SG, Im JP, et al. Endoscopic prediction of tumor invasion depth in early gastric cancer. Gastrointest Endosc. 2011;73:917–27.CrossRefGoogle Scholar
  66. 66.
    Abe S, Oda I, Shimazu T, et al. Depth-predicting score for differentiated early gastric cancer. Gastric Cancer. 2011;14:35–40.CrossRefGoogle Scholar
  67. 67.
    Tsujii Y, Kato M, Inoue T, et al. Integrated diagnostic strategy for the invasion depth of early gastric cancer by conventional endoscopy and EUS. Gastrointest Endosc. 2015;82:452–9.CrossRefGoogle Scholar
  68. 68.
    Nagahama T, Yao K, Imamura K, et al. Diagnostic performance of conventional endoscopy in the identification of submucosal invasion by early gastric cancer: the “non-extension sign” as a simple diagnostic marker. Gastric Cancer. 2017;20:304–13.CrossRefGoogle Scholar
  69. 69.
    Matsumoto Y, Yanai H, Tokiyama H, et al. Endoscopic ultrasonography for diagnosis of submucosal invasion in early gastric cancer. J Gastroenterol. 2000;35:326–31.CrossRefGoogle Scholar
  70. 70.
    Mouri R, Yoshida S, Tanaka S, et al. Usefulness of endoscopic ultrasonography in determining the depth of invasion and indication for endoscopic treatment of early gastric cancer. J Clin Gastroenterol. 2009;43:318–22.CrossRefGoogle Scholar
  71. 71.
    Yanai H, Tada M, Karita M, et al. Diagnostic utility of 20-megahertz linear endoscopic ultrasonography in early gastric cancer. Gastrointest Endosc. 1996;44:29–33.CrossRefGoogle Scholar
  72. 72.
    Yanai H, Noguchi T, Mizumachi S, et al. A blind comparison of the effectiveness of endoscopic ultrasonography and endoscopy in staging early gastric cancer. Gut. 1999;44:361–5.CrossRefGoogle Scholar
  73. 73.
    Choi J, Kim SG, Im JP, et al. Comparison of endoscopic ultrasonography and conventional endoscopy for prediction of depth of tumor invasion in early gastric cancer. Endoscopy. 2010;42:705–13.CrossRefGoogle Scholar
  74. 74.
    Hirasawa D, Maeda Y. Submucosal fibrosis detected by endoscopic ultrasonography may predict incomplete endoscopic submucosal dissection. Dig Endosc. 2015;27:24.CrossRefGoogle Scholar
  75. 75.
    Lee Y-C, Chiang T-H, Chou C-K, Yu-Kang T, Liao W-C, Wu M-S, Graham DY. Association between helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology. 2016;150:1113–24.CrossRefGoogle Scholar
  76. 76.
    Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–9.CrossRefGoogle Scholar
  77. 77.
    Nagahama T, Yao K, Uedo N, et al. Delineation of the extent of early gastric cancer by magnifying narrow-band imaging and chromoendoscopy: a multicenter randomized controlled trial. Endoscopy. 2018;50:566–76.Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Takashi Nagahama
    • 1
  • Noriya Uedo
    • 2
  • Kenshi Yao
    • 1
  1. 1.Department of EndoscopyFukuoka University Chikushi HospitalFukuokaJapan
  2. 2.Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan

Personalised recommendations