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Gastric Cancer

, Volume 11, Issue 3, pp 134–148 | Cite as

Predicting lymph node status in early gastric cancer

  • Robert Michael Kwee
  • Thomas Christian Kwee
Review Article

Abstract

Accurate prediction of lymph node (LN) status is of crucial importance for appropriate treatment planning in patients with early gastric cancer (EGC). However, there is no definitive consensus yet on which patient and/or tumor characteristics are associated with LN metastasis. A systematic search for studies investigating the relationship between patient and/or tumor characteristics and LN metastasis in EGC was performed in PubMed/MEDLINE. Patient and/or tumor characteristics associated with LN metastasis were identified by meta-analyzing results of individual studies. Forty-five studies were included. Variables significantly associated with LN metastasis in gastric cancer limited to the mucosa were: age younger than 57 years, tumor location in the middle part of the stomach, larger tumor size, macroscopically depressed tumor type, tumor ulcerations, undifferentiated tumors, diffuse tumor type according to the Lauren classification, lymphatic tumor invasion, tumors with a proliferating cell nuclear antigen (PCNA) labeling index of more than 25%, and matrix metalloproteinase-9-positive tumors. Variables significantly associated with LN metastasis in gastric cancer limited to the submucosa were: female sex, tumor location in the lower part of the stomach, larger tumor size, undifferentiated tumors, increasing depth of submucosal invasion, lymphatic tumor invasion, vascular tumor invasion, increased submucosal vascularity, tumors with a PCNA labeling index of more than 25%, tumors with a gastric mucin phenotype, and vascular endothelial growth factor-C-positive tumors. We identified several variables associated with LN metastasis in EGC. These variables should be included in future research, in order to assess which of these variables remain as significant predictors of LN metastasis.

Key words

Early gastric cancer Lymph node metastasis Prediction Systematic review Meta-analysis 

References

  1. 1.
    Rubin E, Palazzo JP. The gastrointestinal tract. In: Rubin E, Gorstein F, Rubin F, Schwarting R, Strayer D, editors. Rubin’s pathology. Clinicopathologic foundations of medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 660–739.Google Scholar
  2. 2.
    Siewert JR. Gastric cancer: the dispute between East and West. Gastric Cancer 2005;8:59–61.PubMedCrossRefGoogle Scholar
  3. 3.
    Soetikno R, Kaltenbach T, Yeh R, Gotoda T. Endoscopic mucosal resection for early cancers of the upper gastrointestinal tract. J Clin Oncol 2005;23:4490–4498.PubMedCrossRefGoogle Scholar
  4. 4.
    Brennan MF. Current status of surgery for gastric cancer: a review. Gastric Cancer 2005;8:64–70.PubMedCrossRefGoogle Scholar
  5. 5.
    Nakajima T. Gastric cancer treatment guidelines in Japan. Gastric Cancer 2002;5:1–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Gotoda T, Yanagisawa A, Sasako M, Ono H, Nakanishi Y, Shimoda T, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer 2000;3:219–225.PubMedCrossRefGoogle Scholar
  7. 7.
    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;94:731–736.PubMedCrossRefGoogle Scholar
  8. 8.
    Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma — 2nd English edition. Gastric Cancer 1998;1:10–24.PubMedCrossRefGoogle Scholar
  9. 9.
    Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Imunol Scand 1965;64:31–49.Google Scholar
  10. 10.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22:719–748.PubMedGoogle Scholar
  11. 11.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.PubMedCrossRefGoogle Scholar
  12. 12.
    Okabayashi T, Kobayashi M, Sugimoto T, Okamoto K, Hokimoto N, Araki K. Clinicopathological investigation of early gastric carcinoma; is less invasive surgery right for early gastric carcinoma? Hepatogastroenterology 2007;54:609–612.PubMedGoogle Scholar
  13. 13.
    Lo SS, Wu CW, Chen JH, Li AF, Hsieh MC, Shen KH, et al. Surgical results of early gastric cancer and proposing a treatment strategy. Ann Surg Oncol 2007;14:340–347.PubMedCrossRefGoogle Scholar
  14. 14.
    Nakamoto J, Torisu R, Aoki R, Kimura Y, Yasuda M, Shiota K, et al. Clinicopathological evaluation of biological behavior of submucosal invasive gastric carcinomas: relationship among lymph node metastasis, mucin phenotype and proliferative activity. J Med Invest 2007;54:99–108.PubMedCrossRefGoogle Scholar
  15. 15.
    Ishikawa S, Togashi A, Inoue M, Honda S, Nozawa F, Toyama E, et al. Indications for EMR/ESD in cases of early gastric cancer: relationship between histological type, depth of wall invasion, and lymph node metastasis. Gastric Cancer 2007;10:35–38.PubMedCrossRefGoogle Scholar
  16. 16.
    Kunisaki C, Akiyama H, Nomura M, Matsuda G, Otsuka Y, Ono HA, et al. Lymph node status in patients with submucosal gastric cancer. Ann Surg Oncol 2006;13:1364–1371.PubMedCrossRefGoogle Scholar
  17. 17.
    Onogawa S, Kitadai Y, Amioka T, Kodama M, Cho S, Kuroda T, et al. Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in early gastric carcinoma: correlation with clinicopathological parameters. Cancer Lett 2005;226:85–90.PubMedCrossRefGoogle Scholar
  18. 18.
    Son HJ, Song SY, Kim S, Noh JH, Sohn TS, Kim DS, et al. Characteristics of submucosal gastric carcinoma with lymph node metastatic disease. Histopathology 2005;46:158–165.PubMedCrossRefGoogle Scholar
  19. 19.
    Park DJ, Lee HK, Lee HJ, Lee HS, Kim WH, Yang HK, et al. Lymph node metastasis in early gastric cancer with submucosal invasion: feasibility of minimally invasive surgery. World J Gastroenterol 2004;10:3549–3552.PubMedGoogle Scholar
  20. 20.
    Song SY, Park S, Kim S, Son HJ, Rhee JC. Characteristics of intramucosal gastric carcinoma with lymph node metastatic disease. Histopathology 2004;44:437–444.PubMedCrossRefGoogle Scholar
  21. 21.
    Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H, Noguchi Y. Indications of limited surgery for gastric cancer with submucosal invasion-analysis of 715 cases with special reference to site of the tumor and level 2 lymph nodes. Hepatogastroenterology 2003;50:1727–1730.PubMedGoogle Scholar
  22. 22.
    Higashi H, Natsugoe S, Ishigami S, Uenosono Y, Matsumoto M, Nakajo A, et al. Distribution of lymph node metastasis including micrometastasis in gastric cancer with submucosal invasion. World J Surg 2003;27:455–459.PubMedCrossRefGoogle Scholar
  23. 23.
    Matsuzaki H, Kikuchi S, Kakita A. Evaluation of the morphology of submucosal tumor invasion and its volume in early gastric cancer. In Vivo 2003;17:41–44.PubMedGoogle Scholar
  24. 24.
    Shimoyama S, Yasuda H, Mafune K, Kaminishi M. Indications of a minimized scope of lymphadenectomy for submucosal gastric cancer. Ann Surg Oncol 2002;9:625–631.PubMedCrossRefGoogle Scholar
  25. 25.
    Kabashima A, Yao T, Sugimachi K, Tsuneyoshi M. Relationship between biologic behavior and phenotypic expression in intramucosal gastric carcinomas. Hum Pathol 2002;33:80–86.PubMedCrossRefGoogle Scholar
  26. 26.
    Takeno S, Noguchi T, Kikuchi R, Sato T, Uchida Y, Yokoyama S. Analysis of early (pT1) gastric cancer with submucosal invasion: surgical management and possibility to schedule less invasive surgery. Ann Surg Oncol 2001;8:605–610.PubMedCrossRefGoogle Scholar
  27. 27.
    Shimada S, Yagi Y, Shiomori K, Honmyo U, Hayashi N, Matsuo A, et al. Characterization of early gastric cancer and proposal of the optimal therapeutic strategy. Surgery 2001;129:714–719.PubMedCrossRefGoogle Scholar
  28. 28.
    Yamada H, Nihei Z, Yamashita T, Shirota Y, Ichikawa W, Sugihara K. Is lymphadenectomy needed for all submucosal gastric cancers? Eur J Surg 2001;167:199–203.PubMedCrossRefGoogle Scholar
  29. 29.
    Seto Y, Shimoyama S, Kitayama J, Mafune K, Kaminishi M, Aikou T, et al. Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer. Gastric Cancer 2001;4:34–38.PubMedCrossRefGoogle Scholar
  30. 30.
    Shimoyama S, Seto Y, Yasuda H, Kaminishi M. Wider indications for the local resection of gastric cancer by adjacent lymphadenectomy. J Surg Oncol 2000;75:157–164.PubMedCrossRefGoogle Scholar
  31. 31.
    Kabashima A, Maehara Y, Kakeji Y, Baba H, Koga T, Sugimachi K. Clinicopathological features and overexpression of matrix metalloproteinases in intramucosal gastric carcinoma with lymph node metastasis. Clin Cancer Res 2000;6:3581–3584.PubMedGoogle Scholar
  32. 32.
    Jiang BJ, Sun RX, Lin H, Gao YF. Study on the risk factors of lymphatic metastasis and the indications of less in vasive operations in early gastric cancer. World J Gastroenterol 2000;6:553–556.PubMedGoogle Scholar
  33. 33.
    Takano Y, Teranishi Y, Terashima S, Motoki R, Kawaguchi T. Lymph node metastasis-related carbohydrate epitopes of gastric cancer with submucosal invasion. Surg Today 2000;30:1073–1082.PubMedCrossRefGoogle Scholar
  34. 34.
    Yasuda K, Shiraishi N, Suematsu T, Yamaguchi K, Adachi Y, Kitano S. Rate of detection of lymph node metastasis is correlated with the depth of submucosal invasion in early stage gastric carcinoma. Cancer 1999;85:2119–2123.PubMedCrossRefGoogle Scholar
  35. 35.
    Ishigami S, Natsugoe S, Hokita S, Tokushige M, Saihara T, Watanabe T, et al. Carcinomatous lymphatic invasion in early gastric cancer invading into the submucosa. Ann Surg Oncol 1999;6286-6289.Google Scholar
  36. 36.
    Tsujitani S, Oka S, Saito H, Kondo A, Ikeguchi M, Maeta M, et al. Less invasive surgery for early gastric cancer based on the low probability of lymph node metastasis. Surgery 1999;125:148–154.PubMedGoogle Scholar
  37. 37.
    Ishigami S, Hokita S, Natsugoe S, Tokushige M, Saihara T, Iwashige H, et al. Carcinomatous infiltration into the submucosa as a predictor of lymph node involvement in early gastric cancer. World J Surg 1998;22:1056–1059.PubMedCrossRefGoogle Scholar
  38. 38.
    Namieno T, Koito K, Higashi T, Shimamura T, Yamashita K, Kondo Y. Tumor recurrence following resection for early gastric carcinoma and its implications for a policy of limited resection. World J Surg 1998;22:869–873.PubMedCrossRefGoogle Scholar
  39. 39.
    Kurihara N, Kubota T, Otani Y, Ohgami M, Kumai K, Sugiura H, et al. Lymph node metastasis of early gastric cancer with submucosal invasion. Br J Surg 1998;85:835–839.PubMedCrossRefGoogle Scholar
  40. 40.
    Morita M, Baba H, Fukuda T, Taketomi A, Kohnoe S, Seo Y, et al. Submucosal gastric cancer with lymph node metastasis. J Surg Oncol 1998;68:5–10.PubMedCrossRefGoogle Scholar
  41. 41.
    Takeshita K, Saeki I, Tani M, Honda T, Saito N, Endo M. Rational lymphadenectomy for early gastric cancer with submucosal invasion: a clinicopathological study. Surg Today 1998;28:580–586.PubMedCrossRefGoogle Scholar
  42. 42.
    Kanai T, Konno H, Maruyama K, Baba M, Tanaka T, Maruo Y, et al. p53 overexpression and proliferative activity do not correlate with lymph node metastasis in early gastric cancer. Eur Surg Res 1997;29:35–41.PubMedCrossRefGoogle Scholar
  43. 43.
    Namieno T, Koito K, Higashi T, Sato N, Uchino J. General pattern of lymph node metastasis in early gastric carcinoma. World J Surg 1996;20:996–1000.PubMedCrossRefGoogle Scholar
  44. 44.
    Yamao T, Shirao K, Ono H, Kondo H, Saito D, Yamaguchi H, et al. Risk factors for lymph node metastasis from intramucosal gastric carcinoma. Cancer 1996;77:602–606.PubMedCrossRefGoogle Scholar
  45. 45.
    Maeda K, Chung YS, Onoda N, Ogawa M, Kato Y, Nitta A, et al. Association of tumor cell proliferation with lymph node metastasis in early gastric cancer. Oncology 1996;53:1–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Ichikura T, Uefuji K, Tomimatsu S, Okusa Y, Yahara T, Tamakuma S. Surgical strategy for patients with gastric carcinoma with submucosal invasion. A multivariate analysis. Cancer 1995;76:935–940.PubMedCrossRefGoogle Scholar
  47. 47.
    Maekawa S, Takeo S, Ikejiri K, Anai H, Saku M. Clinicopathological features of lymph node metastasis in early gastric cancer. Int Surg 1995;80:200–203.PubMedGoogle Scholar
  48. 48.
    Tsuchiya A, Kikuchi Y, Ando Y, Yoshida T, Abe R. Lymph node metastases in gastric cancer invading the submucosal layer. Eur J Surg Oncol 1995;21:248–250.PubMedCrossRefGoogle Scholar
  49. 49.
    Oya M, Yao T, Nagai E, Tsuneyoshi M. Metastasizing intramucosal gastric carcinomas. Well differentiated type and proliferative activity using proliferative cell nuclear antigen and Ki-67. Cancer 1995;75:926–935.PubMedCrossRefGoogle Scholar
  50. 50.
    Takeda J, Toyonaga A, Koufuji K, Kodama I, Aoyagi K, Ohta J, et al. Resected early gastric cancer-clinicopathological studies on 610 cases. Kurume Med J 1995;42:87–94.PubMedGoogle Scholar
  51. 51.
    Jatzko G, Lisborg PH, Klimpfinger M. Extended lymphadenectomy against early gastric cancer. Jpn J Clin Oncol 1992;22:26–29.PubMedGoogle Scholar
  52. 52.
    Yonemura Y, Ninomiya I, Ohoyama S, Fushida S, Kimura H, Tsugawa K, et al. Correlation of c-erbB-2 protein expression and lymph node status in early gastric cancer. Oncology 1992;49:363–367.PubMedGoogle Scholar
  53. 53.
    Tsujitani S, Kakeji Y, Watanabe A, Kohnoe S, Maehara Y, Sugimachi K. Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer. Cancer 1990;66:2012–2016.PubMedCrossRefGoogle Scholar
  54. 54.
    Iriyama K, Asakawa T, Koike H, Nishiwaki H, Suzuki H. Is extensive lymphadenectomy necessary for surgical treatment of intramucosal carcinoma of the stomach? Arch Surg 1989;124:309–311.PubMedGoogle Scholar
  55. 55.
    Korenaga D, Okamura T, Saito A, Baba H, Sugimachi K. DNA ploidy is closely linked to tumor invasion, lymph node metastasis, and prognosis in clinical gastric cancer. Cancer 1988;62:309–313.PubMedCrossRefGoogle Scholar
  56. 56.
    Kelly S, Harris KM, Berry E, Hutton J, Roderick P, Cullingworth J, et al. A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma. Gut 2001;49:534–539.PubMedCrossRefGoogle Scholar
  57. 57.
    Yang DM, Kim HC, Jin W, Ryu CW, Kang JH, Park CH, et al. 64 multidetector-row computed tomography for preoperative evaluation of gastric cancer: histological correlation. J Comput Assist Tomogr 2007;31:98–103.PubMedCrossRefGoogle Scholar
  58. 58.
    Monig SP, Zirbes TK, Schroder W, Baldus SE, Lindemann DG, Dienes HP, et al. Staging of gastric cancer: correlation of lymph node size and metastatic infiltration. AJR Am J Roentgenol 1999;173:365–367.PubMedGoogle Scholar
  59. 59.
    Nakamura K, Morisaki T, Noshiro H, Torata N, Kinukawa N, Tanaka M. Morphometric analysis of regional lymph nodes with and without metastasis from early gastric carcinoma. Cancer 2000;88:2438–2442.PubMedCrossRefGoogle Scholar
  60. 60.
    Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology 2004;231:305–332.PubMedCrossRefGoogle Scholar
  61. 61.
    Mukai K, Ishida Y, Okajima K, Isozaki H, Morimoto T, Nishiyama S. Usefulness of preoperative FDG-PET for detection of gastric cancer. Gastric Cancer 2006;9:192–196.PubMedCrossRefGoogle Scholar
  62. 62.
    Yun M, Lim JS, Noh SH, Hyung WJ, Cheong JH, Bong JK, et al. Lymph node staging of gastric cancer using (18) F-FDG PET: a comparison study with CT. J Nucl Med 2005;46:1582–1588.PubMedGoogle Scholar
  63. 63.
    Tian J, Chen L, Wei B, Shao M, Ding Y, Yin D, et al. The value of vesicant 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in gastric malignancies. Nucl Med Commun 2004;25:825–831.PubMedCrossRefGoogle Scholar
  64. 64.
    Tatsumi Y, Tanigawa N, Nishimura H, Nomura E, Mabuchi H, Matsuki M, et al. Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10. Gastric Cancer 2006;9:120–128.PubMedCrossRefGoogle Scholar
  65. 65.
    Shinya S, Sasaki T, Nakagawa Y, Guiquing Z, Yamamoto F, Yamashita Y. The usefulness of diffusion-weighted imaging (DWI) for the detection of gastric cancer. Hepatogastroenterology 2007;54:1378–1381.PubMedGoogle Scholar
  66. 66.
    Hiratsuka M, Miyashiro I, Ishikawa O, Furukawa H, Motomura K, Ohigashi H, et al. Application of sentinel node biopsy to gastric cancer surgery. Surgery 2001;129:335–340.PubMedCrossRefGoogle Scholar
  67. 67.
    Tonouchi H, Mohri Y, Tanaka K, Konishi N, Ohmori Y, Kobayashi M, et al. Lymphatic mapping and sentinel node biopsy during laparoscopic gastrectomy for early cancer. Dig Surg 2003;20:421–427.PubMedCrossRefGoogle Scholar
  68. 68.
    Song X, Wang L, Chen W, Pan T, Zhu H, Xu J, et al. Lymphatic mapping and sentinel node biopsy in gastric cancer. Am J Surg 2004;187:270–273.PubMedCrossRefGoogle Scholar
  69. 69.
    Mura G, Vagliasindi A, Framarini M, Mazza P, Solfrini G, Verdecchia GM. The sentinel node biopsy in early gastric cancer: a preliminary study. Langenbecks Arch Surg 2006;391:113–117.PubMedCrossRefGoogle Scholar
  70. 70.
    Kitagawa Y, Fujii H, Kumai K, Kubota T, Otani Y, Saikawa Y, et al. Recent advances in sentinel node navigation for gastric cancer: a paradigm shift of surgical management. J Surg Oncol 2005;90:147–151.PubMedCrossRefGoogle Scholar
  71. 71.
    Parsons SL, Watson SA, Brown PD, Collins HM, Steele RJ. Matrix metalloproteinases. Br J Surg 1997;84:160–166.PubMedCrossRefGoogle Scholar
  72. 72.
    Kampschoer GH, Maruyama K, van de Velde CJ, Sasako M, Kinoshita T, Okabayashi K. Computer analysis in making preoperative decisions: a rational approach to lymph node dissection in gastric cancer patients. Br J Surg 1989;76:905–908.PubMedCrossRefGoogle Scholar
  73. 73.
    Hohenberger P, Gretschel S. Gastric cancer. Lancet 2003;362:305–315.PubMedCrossRefGoogle Scholar
  74. 74.
    Matsubara Y, Yanai H, Ishiguro K, Ryozawa S, Okazaki Y, Matsui N, et al. Clinical interpretation of the histological typing of gastric cancer using endoscopic forceps biopsy. Hepatogastroenterology 2004;51:285–288.PubMedGoogle Scholar
  75. 75.
    Kwee RM, Kwee TC. The accuracy of endoscopic ultrasonography in differentiating mucosal from deeper gastric cancer. Am J Gastroenterol 2008;103:1801–1809.PubMedCrossRefGoogle Scholar
  76. 76.
    Gotoda T. Endoscopic resection of early gastric cancer. Gastric Cancer 2007;10:1–11.PubMedCrossRefGoogle Scholar
  77. 77.
    Everett SM, Axon AT. Early gastric cancer in Europe. Gut 1997;41:142–150.PubMedCrossRefGoogle Scholar
  78. 78.
    Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H, Noguchi Y. Is D2 lymph node dissection necessary for early gastric cancer? Ann Surg Oncol 2002;9:401–405.PubMedCrossRefGoogle Scholar

Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2008

Authors and Affiliations

  • Robert Michael Kwee
    • 1
  • Thomas Christian Kwee
    • 2
  1. 1.Department of RadiologyUniversity Medical Center MaastrichtMaastrichtThe Netherlands
  2. 2.Department of RadiologyUniversity Medical Center UtrechtUtrechtThe Netherlands

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