Gastric Cancer

, Volume 22, Issue 1, pp 223–230 | Cite as

Risk factors for lymph node metastasis in non-sentinel node basins in early gastric cancer: sentinel node concept

  • Masashi Takeuchi
  • Hiroya TakeuchiEmail author
  • Hirofumi Kawakubo
  • Ayako Shimada
  • Tadaki Nakahara
  • Shuhei Mayanagi
  • Masahiro Niihara
  • Kazumasa Fukuda
  • Rieko Nakamura
  • Koichi Suda
  • Norihito Wada
  • Yuko Kitagawa
Original Article



Sentinel node (SN) concept is being applied to early gastric cancer. However, when SNs are positive for metastasis, it is unclear how often LNs in other LN basins show metastasis. We aimed to investigate LN metastasis possibility in LN basins without SNs (non-SN basins). We determined risk factors for metastasis in non-SN basins and identified a prediction model for non-SN basin metastasis using classification and regression tree (CART) analysis.


We enrolled 550 patients who were diagnosed with cT1N0M0 or cT2N0M0 gastric cancer with a single lesion and underwent SN mapping. We adopted a dual-tracer method using a radioactive colloid and blue dye to detect SNs.


Of all, 45 (8.2%) patients had SN metastasis; we divided them into two groups: LN metastasis positive and LN metastasis negative in non-SN basins. Univariate analysis showed that the groups differed significantly regarding lymphatic invasion (p = 0.007), number of identified SNs (p = 0.032), and macrometastasis in SN basins (p = 0.005). The CART decision tree for predicting LN metastasis in non-SN basins had area under the curve value of 0.86. Moreover, there were significantly differences in cancer-specific survival (CSS) between the two groups (p = 0.028).


Macrometastasis in SN basins, lymphatic invasion, and number of identified SNs ≥ 5 are risk factors for LN metastasis in non-SN basins among gastric cancer patients. We identified a prediction model with CART analysis; patients with macrometastasis in SN basins and lymphatic invasion were considered to be at the highest risk for LN metastasis.


Stomach neoplasms Gastrectomy Sentinel lymph node biopsy 



The authors thank Kumiko Motooka, who is a staff member at the Department of Surgery in the Keio University School of Medicine, for her help in the preparation of this manuscript.

Compliance with ethical standards

Ethical standards

All procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

Conflict of interest

Yuko Kitagawa has received grants from Daiichi Sankyo Co., Ltd.


  1. 1.
    Isobe Y, Nashimoto A, Akazawa K, Oda I, Hayashi K, Miyashiro I, et al. Gastric cancer treatment in Japan: 2008 annual report of the JGCA nationwide registry. Gastric Cancer. 2011;14:301–16.CrossRefGoogle Scholar
  2. 2.
    Leung WK, Wu MS, Kakugawa Y, Kim JJ, Yeoh KG, Goh KL, et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 2008;9:279–87.CrossRefGoogle Scholar
  3. 3.
    Kitagawa Y, Kitano S, Kubota T, Kumai K, Otani Y, Saikawa Y, et al. Minimally invasive surgery for gastric cancer—toward a confluence of two major streams: a review. Gastric Cancer. 2005;8:103–10.CrossRefGoogle Scholar
  4. 4.
    Takeuchi H, Kitagawa Y. New sentinel node mapping technologies for early gastric cancer. Ann Surg Oncol. 2013;20:522–32.CrossRefGoogle Scholar
  5. 5.
    Wong JH, Cagle LA, Morton DL. Lymphatic drainage of skin to a sentinel lymph node in a feline model. Ann Surg. 1991;214:637–41.CrossRefGoogle Scholar
  6. 6.
    Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9.CrossRefGoogle Scholar
  7. 7.
    Haigh PI, Giuliano AE. Intraoperative lymphatic mapping and sentinel lymphadenectomy for breast cancer. Oper Tech Gen Surg. 2000;2:161–5.CrossRefGoogle Scholar
  8. 8.
    Morita D, Tsuda H, Ichikura T, Kimura M, Aida S. Analysis of sentinel node involvement in gastric cancer. Clin Gastroenterol Hepatol. 2007;5:1046–52.CrossRefGoogle Scholar
  9. 9.
    Ohdaira H, Nimura H, Mistumuro N, Takahashi N, Kashiwagi H, Yanaga K. Validity of modified gastrectomy combined with sentinel node navigation surgery for early gastric cancer. Gastric Cancer. 2007;10:117–22.CrossRefGoogle Scholar
  10. 10.
    Seto Y, Nagawa H, Muto Y, Kaizaki S, Kitayama J, Muto T. Preliminary report on local resection with lymphadenectomy for early gastric cancer. Br J Surg. 1999;86:526–8.CrossRefGoogle Scholar
  11. 11.
    Matsuda T, Kaneda K, Takamatsu M, Aishin K, Awazu M, Okamoto A, et al. Segmental gastrectomy with radical lymph node dissection for early gastric cancer. World J Gastroenterol. 2010;16:5247–51.CrossRefGoogle Scholar
  12. 12.
    Zhang D, Shimoyama S, Kaminishi M. Feasibility of pylorus-preserving gastrectomy with a wider scope of lymphadenectomy. Arch Surg. 1998;133:993–7.CrossRefGoogle Scholar
  13. 13.
    Takeuchi H, Goto O, Yahagi N, Kitagawa Y. Function-preserving gastrectomy based on the sentinel node concept in early gastric cancer. Gastric Cancer. 2017;20:53–9.CrossRefGoogle Scholar
  14. 14.
    Takeuchi H, Oyama T, Kamiya S, Nakamura R, Takahashi T, Wada N, et al. Laparoscopy-assisted proximal gastrectomy with sentinel node mapping for early gastric cancer. World J Surg. 2011;35:2463–71.CrossRefGoogle Scholar
  15. 15.
    Takeuchi H, Kitagawa Y. Sentinel lymph node biopsy in gastric cancer. Cancer J. 2015;21:21–4.CrossRefGoogle Scholar
  16. 16.
    Kodera Y, Sano T. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20:1–19.CrossRefGoogle Scholar
  17. 17.
    Sobin LH, Gospodarowicz MK, Wittekind Ch, editors. TNM: classification of malignant tumours. 7th ed. Hoboken: Wiley-Blackwell; 2009.Google Scholar
  18. 18.
    Mayanagi S, Takeuchi H, Kamiya S, Niihara M, Nakamura R, Takahashi T, et al. Suitability of sentinel node mapping as an index of metastasis in early gastric cancer following endoscopic resection. Ann Surg Oncol. 2014;21:2987–93.CrossRefGoogle Scholar
  19. 19.
    Shimada A, Takeuchi H, Kamiya S, Fukuda K, Nakamura R, Takahashi T, et al. Clinical significance of the anterosuperior lymph nodes along the common hepatic artery identified by sentinel node mapping in patients with gastric cancer. Gastric Cancer. 2016;19:1088–94.CrossRefGoogle Scholar
  20. 20.
    Kinami S, Fujimura T, Ojima E, Fushida S, Ojima T, Funaki H, et al. PTD classification: proposal for a new classification of gastric cancer location based on physiological lymphatic flow. Int J Clin Oncol. 2008;13:320–9.CrossRefGoogle Scholar
  21. 21.
    Nakahara T, Kitagawa Y, Takeuchi H, Fujii H, Suzuki T, Mukai M, et al. Preoperative lymphoscintigraphy for detection of sentinel lymph node in patients with gastric cancer—initial experience. Ann Surg Oncol. 2008;15:1447–53.CrossRefGoogle Scholar
  22. 22.
    Takeuchi H, Kitajima M, Kitagawa Y. Sentinel lymph node as a target of molecular diagnosis of lymphatic micrometastasis and local immunoresponse to malignant cells. Cancer Sci. 2008;29:441–50.CrossRefGoogle Scholar
  23. 23.
    Yanagita S, Natsugoe S, Uenosono Y, Arigami T, Arima H, Kozono T, et al. Detection of micrometastases in sentinel node navigation surgery for gastric cancer. Surg Oncol. 2008;17:203–10.CrossRefGoogle Scholar
  24. 24.
    Ishii K, Kinami S, Funaki K, Fujita H, Ninomiya I, Fushida S, et al. 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.CrossRefGoogle Scholar
  25. 25.
    Kitagawa Y, Takeuchi H, Takagi Y, Natsugoe S, Terashima M, Murakami N. Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan. J Clin Oncol. 2013;31:3704–10.CrossRefGoogle Scholar
  26. 26.
    Garzotto M, Beer TM, Hudson RG, Peters L, Hsieh YC, Barrera E, et al. Improved detection of prostate cancer using classification and regression tree analysis. J Clin Oncol. 2005;23:4322–9.CrossRefGoogle Scholar
  27. 27.
    Breiman L, Friedman J, Stone CJ, Olshen RA. Classification and regression trees. 1st ed. Belmont: CRC Press; 1984.Google Scholar
  28. 28.
    Williams G. Data mining with rattle and R: the art of excavating data for knowledge discovery. Use R! New York: Springer; 2011. pp. 205–244CrossRefGoogle Scholar
  29. 29.
    Shida A, Mitsumori N, Nimura H, Takano Y, Iwasaki T, Fujisaki M, et al. Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer. World J Gastroenterol. 2016;22:7431–9.CrossRefGoogle Scholar
  30. 30.
    Lee K, Park DJ, Choe G, Kim HH, Kim WH, Lee HS. Increased intratumoral lymphatic vessel density correlates with lymph node metastasis in early gastric carcinoma. Ann Surg Oncol. 2010;17:73–80.CrossRefGoogle Scholar
  31. 31.
    Osaka H, Yashiro M, Sawada T, Katsuragi K, Hirakawa K. Is a lymph node detected by the dye-guided method a true sentinel node in gastric cancer? Clin Cancer Res. 2004;10:6912–8.CrossRefGoogle Scholar
  32. 32.
    Arigami T, Natsugoe S, Uenosono Y, Mataki Y, Ehi K, Higashi H, et al. 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.CrossRefGoogle Scholar
  33. 33.
    Takeuchi H, Kitagawa Y. Sentinel node and mechanism of lymphatic metastasis. Ann Vasc Dis. 2012;5:249–57.CrossRefGoogle Scholar
  34. 34.
    Ono H, Yao K, Fujishiro M, Oda I, Nimura S, Yahagi N, et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Dig Endosc. 2016;28:3–15.CrossRefGoogle Scholar
  35. 35.
    Miwa K, Kinami S, Taniguchi K, Fushida S, Fujimura T, Nonomura A. Mapping sentinel nodes in patients with early-stage gastric carcinoma. Br J Surg. 2003;90:178–82.CrossRefGoogle Scholar
  36. 36.
    Park SS, Ryu JS, Min BW, Kim WB, Kim SJ, Kim CS. Impact of skip metastasis in gastric cancer. ANZ J Surg. 2005;75:645–9.CrossRefGoogle Scholar
  37. 37.
    Lee SE, Lee JH, Ryu KW, Cho SJ, Lee JY, Kim CG, et al. Sentinel node mapping and skip metastases in patients with early gastric cancer. Ann Surg Oncol. 2009;16:603–8.CrossRefGoogle Scholar
  38. 38.
    Kamiya S, Takeuchi H, Nakahara T, Niihara M, Nakamura R, Takahashi T, et al. Auxiliary diagnosis of lymph node metastasis in early gastric cancer using quantitative evaluation of sentinel node radioactivity. Gastric Cancer. 2016;19:1080–7.CrossRefGoogle Scholar

Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018

Authors and Affiliations

  • Masashi Takeuchi
    • 1
  • Hiroya Takeuchi
    • 1
    • 2
    Email author
  • Hirofumi Kawakubo
    • 1
  • Ayako Shimada
    • 1
  • Tadaki Nakahara
    • 3
  • Shuhei Mayanagi
    • 1
  • Masahiro Niihara
    • 4
  • Kazumasa Fukuda
    • 1
  • Rieko Nakamura
    • 1
  • Koichi Suda
    • 1
  • Norihito Wada
    • 1
  • Yuko Kitagawa
    • 1
  1. 1.Department of SurgeryKeio University School of MedicineTokyoJapan
  2. 2.Department of SurgeryHamamatsu University School of MedicineHamamatsuJapan
  3. 3.Department of RadiologyKeio University School of MedicineTokyoJapan
  4. 4.Division of Esophageal SurgeryShizuoka Cancer Center HospitalShizuokaJapan

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