Skip to main content

Clinical Aspect: Gastric Cancer

  • Chapter
  • First Online:
Lymph Node Metastasis in Gastrointestinal Cancer

Abstract

Recent advances in the development of molecular diagnostic tools have improved the detection of lymph node micrometastasis (LNM) in patients with gastric cancer. Isolated or micrometastatic tumor cells are also heterogeneously distributed in lymph nodes. Since the incidence of LNM in patients with early gastric cancer (pT1) ranges between 10% and 31.8%, even patients with early gastric cancer are at a high risk of developing LNM. Moreover, the incidence of LNM is slightly higher in patients with advanced gastric cancer than in those with early gastric cancer. A close relationship has been reported between LNM and lymphatic invasion in primary tumors. The clinical impact of LNM currently remains controversial in patients with gastric cancer. Therefore, it is clinically difficult to reach concrete conclusions regarding the prognostic significance of LNM. However, the rate of positivity for Ki-67 in LNM was previously reported to be between 92.0% and 94.2%. Consequently, tumor cells within LNM exhibit high proliferative activity. In clinical management, therapeutic strategies for LNM need to be planned in order to avoid lymph node recurrence. It is considered important to preserve the balance between quality of life and curability when selecting minimally invasive surgery, such as sentinel node navigation _surgery and endoscopic submucosal dissection, for patients with early gastric cancer. This chapter will focus on the clinical aspect of LNM in patients with gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kwon SJ, Kim GS. Prognostic significance of lymph node metastasis in advanced carcinoma of the stomach. Br J Surg. 1996;83:1600–3.

    Article  CAS  Google Scholar 

  2. Nitti D, Marchet A, Olivieri M, Ambrosi A, Mencarelli R, Belluco C, Lise M. Ratio between metastatic and examined lymph nodes is an independent prognostic factor after D2 resection for gastric cancer: analysis of a large European monoinstitutional experience. Ann Surg Oncol. 2003;10:1077–85.

    Article  Google Scholar 

  3. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14:113–23. https://doi.org/10.1007/s10120-011-0042-4.

    Article  Google Scholar 

  4. Maehara Y, Oshiro T, Endo K, Baba H, Oda S, Ichiyoshi Y, Kohnoe S, Sugimachi K. Clinical significance of occult micrometastasis lymph nodes from patients with early gastric cancer who died of recurrence. Surgery. 1996;119:397–402.

    Article  CAS  Google Scholar 

  5. Siewert JR, Kestlmeier R, Busch R, Bottcher K, Roder JD, Muller J, Fellbaum C, Hofler H. Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases. Br J Surg. 1996;83:1144–7.

    Article  CAS  Google Scholar 

  6. Ishida K, Katsuyama T, Sugiyama A, Kawasaki S. Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas. Cancer. 1997;79:1069–76.

    Article  CAS  Google Scholar 

  7. Sim SH, Kim YJ, Oh DY, Lee SH, Kim DW, Kang WJ, Im SA, Kim TY, Kim WH, Heo DS, Bang YJ. The role of PET/CT in detection of gastric cancer recurrence. BMC Cancer. 2009;9:73. https://doi.org/10.1186/1471-2407-9-73.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Yamaguchi N, Isomoto H, Fukuda E, Ikeda K, Nishiyama H, Akiyama M, Ozawa E, Ohnita K, Hayashi T, Nakao K, Kohno S, Shikuwa S. Clinical outcomes of endoscopic submucosal dissection for early gastric cancer by indication criteria. Digestion. 2009;80:173–81. https://doi.org/10.1159/000215388.

    Article  PubMed  Google Scholar 

  9. Sobin LH, Wittenkind CH. International union against cancer. TNM classification of malignant tumors. 6th ed. New York: John Wiley-Liss; 2002.

    Google Scholar 

  10. Yanagita S, Natsugoe S, Uenosono Y, Arima H, Kozono T, Ehi K, Arigami T, Higashi H, Aikou T. Morphological distribution of metastatic foci in sentinel lymph nodes with gastric cancer. Ann Surg Oncol. 2008;15:770–6.

    Article  Google Scholar 

  11. Isozaki H, Okajima K, Fujii K. Histological evaluation of lymph node metastasis on serial sectioning in gastric cancer with radical lymphadenectomy. Hepatogastroenterology. 1997;44:1133–6.

    CAS  PubMed  Google Scholar 

  12. Cai J, Ikeguchi M, Maeta M, Kaibara N. Micrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer. Surgery. 2000;127:32–9.

    Article  CAS  Google Scholar 

  13. Harrison LE, Choe JK, Goldstein M, Meridian A, Kim SH, Clarke K. Prognostic significance of immunohistochemical micrometastases in node negative gastric cancer patients. J Surg Oncol. 2000;73:153–7.

    Article  CAS  Google Scholar 

  14. Fukagawa T, Sasako M, Mann GB, Sano T, Katai H, Maruyama K, Nakanishi Y, Shimoda T. Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma. Cancer. 2001;92:753–60.

    Article  CAS  Google Scholar 

  15. Morgagni P, Saragoni L, Folli S, Gaudio M, Scarpi E, Bazzocchi F, Marra GA, Vio A. Lymph node micrometastases in patients with early gastric cancer: experience with 139 patients. Ann Surg Oncol. 2001;8:170–4.

    Article  CAS  Google Scholar 

  16. Nakajo A, Natsugoe S, Ishigami S, Matsumoto M, Nakashima S, Hokita S, Baba M, Takao S, Aikou T. Detection and prediction of micrometastasis in the lymph nodes of patients with pN0 gastric cancer. Ann Surg Oncol. 2001;8:158–62.

    Article  CAS  Google Scholar 

  17. Choi HJ, Kim YK, Kim YH, Kim SS, Hong SH. Occurrence and prognostic implications of micrometastases in lymph nodes from patients with submucosal gastric carcinoma. Ann Surg Oncol. 2002;9:13–9.

    Article  Google Scholar 

  18. Yasuda K, Adachi Y, Shiraishi N, Inomata M, Takeuchi H, Kitano S. Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer. Ann Surg Oncol. 2002;9:771–4.

    Article  Google Scholar 

  19. Morgagni P, Saragoni L, Scarpi E, Zattini PS, Zaccaroni A, Morgagni D, Bazzocchi F. Lymph node micrometastases in early gastric cancer and their impact on prognosis. World J Surg. 2003;27:558–61.

    Article  Google Scholar 

  20. Miyake K, Seshimo A, Kameoka S. Assessment of lymph node micrometastasis in early gastric cancer in relation to sentinel nodes. Gastric Cancer. 2006;9:197–202.

    Article  Google Scholar 

  21. Yonemura Y, Endo Y, Hayashi I, Kawamura T, Yun HY, Bandou E. Proliferative activity of micrometastases in the lymph nodes of patients with gastric cancer. Br J Surg. 2007;94:731–6.

    Article  CAS  Google Scholar 

  22. Ishii K, Kinami S, Funaki K, Fujita H, Ninomiya I, Fushida S, Fujimura T, Nishimura G, Kayahara M. Detection of sentinel and non-sentinel lymph node micrometastases by complete serial sectioning and immunohistochemical analysis for gastric cancer. J Exp Clin Cancer Res. 2008;27:7. https://doi.org/10.1186/1756-9966-27-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kim JH, Park JM, Jung CW, Park SS, Kim SJ, Mok YJ, Kim CS, Chae YS, Bae JW. The significances of lymph node micrometastasis and its correlation with E-cadherin expression in pT1-T3N0 gastric adenocarcinoma. J Surg Oncol. 2008;97:125–30.

    Article  Google Scholar 

  24. Kim JJ, Song KY, Hur H, Hur JI, Park SM, Park CH. Lymph node micrometastasis in node negative early gastric cancer. Eur J Surg Oncol. 2009;35:409–14. https://doi.org/10.1016/j.ejso.2008.05.004.

    Article  CAS  PubMed  Google Scholar 

  25. Cao L, Hu X, Zhang Y, Huang G. Adverse prognosis of clustered-cell versus single-cell micrometastases in pN0 early gastric cancer. J Surg Oncol. 2011;103:53–6. https://doi.org/10.1002/jso.21755.

    Article  PubMed  Google Scholar 

  26. Ru Y, Zhang L, Chen Q, Gao SG, Wang GP, Qu ZF, Shan TY, Qian N, Feng XS. Detection and clinical significance of lymph node micrometastasis in gastric cardia adenocarcinoma. J Int Med Res. 2012;40:293–9.

    Article  CAS  Google Scholar 

  27. Wang J, Yu JC, Kang WM, Wang WZ, Liu YQ, Gu P. The predictive effect of cadherin-17 on lymph node micrometastasis in pN0 gastric cancer. Ann Surg Oncol. 2012;19:1529–34. https://doi.org/10.1245/s10434-011-2115-3.

    Article  PubMed  Google Scholar 

  28. Jeuck TL, Wittekind C. Gastric carcinoma: stage migration by immunohistochemically detected lymph node micrometastases. Gastric Cancer. 2015;18:100–8. https://doi.org/10.1007/s10120-014-0352-4.

    Article  CAS  PubMed  Google Scholar 

  29. Okada Y, Fujiwara Y, Yamamoto H, Sugita Y, Yasuda T, Doki Y, Tamura S, Yano M, Shiozaki H, Matsuura N, Monden M. Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assay. Cancer. 2001;92:2056–64.

    Article  CAS  Google Scholar 

  30. Matsumoto M, Natsugoe S, Ishigami S, Nakashima S, Nakajo A, Miyazono F, Hokita S, Takao S, Eizuru Y, Aikou T. Lymph node micrometastasis and lymphatic mapping determined by reverse transcriptase-polymerase chain reaction in pN0 gastric carcinoma. Surgery. 2002;131:630–5.

    Article  Google Scholar 

  31. Arigami T, Natsugoe S, Uenosono Y, Arima H, Mataki Y, Ehi K, Yanagida S, Ishigami S, Hokita S, Aikou T. Lymphatic invasion using D2-40 monoclonal antibody and its relationship to lymph node micrometastasis in pN0 gastric cancer. Br J Cancer. 2005;93:688–93.

    Article  CAS  Google Scholar 

  32. Sonoda H, Yamamoto K, Kushima R, Yamamoto H, Naitoh H, Okabe H, Tani T. Detection of lymph node micrometastasis in pN0 early gastric cancer: efficacy of duplex RT-PCR with MUC2 and TFF1 in mucosal cancer. Oncol Rep. 2006;16:411–6.

    CAS  PubMed  Google Scholar 

  33. Wu ZY, Li JH, Zhan WH, He YL, Wan J. Effect of lymph node micrometastases on prognosis of gastric carcinoma. World J Gastroenterol. 2007;13:4122–5.

    Article  CAS  Google Scholar 

  34. Jagric T, Potrc S, Ivanecz A, Horvat M, Plankl M, Mars T. Evaluation of focused sentinel lymph node RT-qPCR screening for micrometastases with the use of the Maruyama computer program. Eur Surg. 2013;45:270–6.

    Article  CAS  Google Scholar 

  35. Yanagita S, Uenosono Y, Arigami T, Daisuke M, Okubo K, Kijima T, Arima H, Hirata M, Haraguchi N, Hagihara T, Nishizono Y, Ishigami S, Natsugoe S. The clinical usefulness of the intraoperative detection of sentinel lymph node metastases by a rapid RT-PCR system in patients with gastric cancer. Cancer. 2016;122:386–92. https://doi.org/10.1002/cncr.29740.

    Article  CAS  PubMed  Google Scholar 

  36. An JY, Baik YH, Choi MG, Noh JH, Sohn TS, Kim S. Predictive factors for lymph node metastasis in early gastric cancer with submucosal invasion: analysis of a single institutional experience. Ann Surg. 2007;246:749–53.

    Article  Google Scholar 

  37. Tajima Y, Murakami M, Yamazaki K, Masuda Y, Aoki S, Kato M, Sato A, Goto S, Otsuka K, Kato T. Risk factors for lymph node metastasis from gastric cancers with submucosal invasion. Ann Surg Oncol. 2010;17:1597–604. https://doi.org/10.1245/s10434-010-0930-6.

    Article  PubMed  Google Scholar 

  38. Kalof AN, Cooper K. D2-40 immunohistochemistry – so far! Adv Anat Pathol. 2009;16:62–4. https://doi.org/10.1097/PAP.0b013e3181915e94.

    Article  CAS  PubMed  Google Scholar 

  39. Li Y, Du P, Zhou Y, Cheng Q, Chen D, Wang D, Sun T, Zhou J, Patel R. Lymph node micrometastases is a poor prognostic factor for patients in pN0 gastric cancer: a meta-analysis of observational studies. J Surg Res. 2014;191:413–22. https://doi.org/10.1016/j.jss.2014.05.088.

    Article  PubMed  Google Scholar 

  40. Jo MJ, Park JY, Song JS, Kook MC, Ryu KW, Cho SJ, Lee JH, Nam BH, Hong EK, Choi IJ, Kim YW. Biopathologic features and clinical significance of micrometastasis in the lymph node of early gastric cancer. World J Gastroenterol. 2015;21:667–74. https://doi.org/10.3748/wjg.v21.i2.667.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Yanagita S, Natsugoe S, Uenosono Y, Kozono T, Ehi K, Arigami T, Arima H, Ishigami S, Aikou T. Sentinel node micrometastases have high proliferative potential in gastric cancer. J Surg Res. 2008;145:238–43.

    Article  CAS  Google Scholar 

  42. Arigami T, Natsugoe S, Uenosono Y, Yanagita S, Arima H, Hirata M, Ishigami S, Aikou T. CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer. Int J Oncol. 2009;35:19–24.

    Article  CAS  Google Scholar 

  43. Arigami T, Natsugoe S, Uenosono Y, Yanagita S, Ehi K, Arima H, Mataki Y, Nakajo A, Ishigami S, Aikou T. Vascular endothelial growth factor-C and -D expression correlates with lymph node micrometastasis in pN0 early gastric cancer. J Surg Oncol. 2009;99:148–53. https://doi.org/10.1002/jso.21228.

    Article  CAS  PubMed  Google Scholar 

  44. Yonemura Y, Endo Y, Fujita H, Fushida S, Ninomiya I, Bandou E, Taniguchi K, Miwa K, Ohoyama S, Sugiyama K, Sasaki T. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. Clin Cancer Res. 1999;5:1823–9.

    CAS  PubMed  Google Scholar 

  45. Onogawa S, Kitadai Y, Tanaka S, Kuwai T, Kimura S, Chayama K. Expression of VEGF-C and VEGF-D at the invasive edge correlates with lymph node metastasis and prognosis of patients with colorectal carcinoma. Cancer Sci. 2004;95:32–9.

    Article  CAS  Google Scholar 

  46. Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Swartz M, Fukumura D, Jain RK, Alitalo K. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276:1423–5.

    Article  CAS  Google Scholar 

  47. Achen MG, Jeltsch M, Kukk E, Mäkinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci U S A. 1998;95:548–53.

    Article  CAS  Google Scholar 

  48. Aikou T, Higashi H, Natsugoe S, Hokita S, Baba M, Tako S. Can sentinel node navigation surgery reduce the extent of lymph node dissection in gastric cancer? Ann Surg Oncol. 2001;8:90S–3S.

    CAS  PubMed  Google Scholar 

  49. Kitagawa Y, Kitano S, Kubota T, Kumai K, Otani Y, Saikawa Y, Yoshida M, Kitajima M. Minimally invasive surgery for gastric cancer – toward a confluence of two major streams: a review. Gastric Cancer. 2005;8:103–10.

    Article  Google Scholar 

  50. Arigami T, Natsugoe S, Uenosono Y, Mataki Y, Ehi K, Higashi H, Arima H, Yanagida S, Ishigami S, Hokita S, Aikou T. Evaluation of sentinel node concept in gastric cancer based on lymph node micrometastasis determined by reverse transcription-polymerase chain reaction. Ann Surg. 2006;243:341–7.

    Article  Google Scholar 

  51. Bok GH, Kim YJ, Jin SY, Chun CG, Lee TH, Kim HG, Jeon SR, Cho JY. Endoscopic submucosal dissection with sentinel node navigation surgery for early gastric cancer. Endoscopy. 2012;44:953–6. https://doi.org/10.1055/s-0032-1310162.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takaaki Arigami .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Arigami, T., Uenosono, Y., Yanagita, S., Ishigami, S., Natsugoe, S. (2019). Clinical Aspect: Gastric Cancer. In: Natsugoe, S. (eds) Lymph Node Metastasis in Gastrointestinal Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-10-4699-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-4699-5_10

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-4698-8

  • Online ISBN: 978-981-10-4699-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics