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Published in: Annals of Surgical Oncology 12/2013

01-11-2013 | Gastrointestinal Oncology

The Prognostic Impact of Occult Lymph Node Metastasis in Node-negative Gastric Cancer: A Systematic Review and Meta-analysis

Authors: Jin-yu Huang, MD, Ying-ying Xu, MD, PhD, Min Li, MD, Zhe Sun, MD, PhD, Zhi Zhu, MD, PhD, Yong-xi Song, MD, Zhi-feng Miao, MD, Jian-hua Wu, MD, Hui-mian Xu, MD, PhD

Published in: Annals of Surgical Oncology | Issue 12/2013

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Abstract

Purpose

To conduct a meta-analysis to clarify whether occult lymph node metastasis (OLNM), which is identified by molecular detection techniques but is not detected by routine histological examination within regional lymph nodes, represents a prognostic factor for patients with node-negative gastric cancer.

Methods

PubMed, Embase, and the Cochrane Library were searched from their inception to November 2012. The published studies that investigated the association between OLNM and the prognosis of patients with node-negative gastric cancer were included. We extracted hazard ratios (HRs) and associated standard errors from the identified studies and performed random-effects model meta-analyses on overall survival and disease-specific survival. Subgroup analyses were also conducted.

Results

A total of 14 eligible studies that included 1,478 patients were identified. Meta-analyses revealed that OLNM was associated with poor overall survival [HR 2.72; 95 % confidence interval (CI) 1.61–4.60], and disease-specific survival (HR 2.91; 95 % CI 1.25–6.79). Subgroup analyses suggested that OLNM was associated with poor survival in early gastric cancer (HR 3.57; 95 % CI 1.23–10.33). However, subgroup analyses of studies that exclusively enrolled patients with D2 lymph node dissection demonstrated that OLNM did not have an influence on the prognosis (HR 1.97; 95 % CI 0.82–4.70).

Conclusions

OLNM correlates with poor prognosis for patients with node-negative gastric cancer, and D2 lymph node dissection could eliminate this correlation. For OLNM-positive patients with node-negative gastric cancer, D2 lymph node dissection is necessary.
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.PubMedCrossRef Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.PubMedCrossRef
2.
go back to reference Kwon SJ, Kim GS. Prognostic significance of lymph node metastasis in advanced carcinoma of the stomach. Br J Surg. 1996;83:1600–3.PubMedCrossRef Kwon SJ, Kim GS. Prognostic significance of lymph node metastasis in advanced carcinoma of the stomach. Br J Surg. 1996;83:1600–3.PubMedCrossRef
3.
go back to reference Nitti D, Marchet A, Olivieri M, et al. 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.PubMedCrossRef Nitti D, Marchet A, Olivieri M, et al. 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.PubMedCrossRef
4.
go back to reference Maehara Y, Oshiro T, Endo K, et al. Clinical significance of occult micrometastasis lymph nodes from patients with early gastric cancer who died of recurrence. Surgery. 1996;119:397–402.PubMedCrossRef Maehara Y, Oshiro T, Endo K, et al. Clinical significance of occult micrometastasis lymph nodes from patients with early gastric cancer who died of recurrence. Surgery. 1996;119:397–402.PubMedCrossRef
5.
go back to reference Siewert JR, Kestlmeier R, Busch R, et al. 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.PubMedCrossRef Siewert JR, Kestlmeier R, Busch R, et al. 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.PubMedCrossRef
6.
go back to reference Ishida K, Katsuyama T, Sugiyama A, Kawasaki S. Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas. Cancer. 1997;79:1069–76.PubMedCrossRef Ishida K, Katsuyama T, Sugiyama A, Kawasaki S. Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas. Cancer. 1997;79:1069–76.PubMedCrossRef
7.
go back to reference Baba H, Maehara Y, Takeuchi H, et al. Effect of lymph node dissection on the prognosis in patients with node-negative early gastric cancer. Surgery. 1995;117:165–9.PubMedCrossRef Baba H, Maehara Y, Takeuchi H, et al. Effect of lymph node dissection on the prognosis in patients with node-negative early gastric cancer. Surgery. 1995;117:165–9.PubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference Fukagawa T, Sasako M, Shimoda T, et al. The prognostic impact of isolated tumor cells in lymph nodes of T2n0 gastric cancer: comparison of American and Japanese gastric cancer patients. Ann Surg Oncol. 2009;16:609–13.PubMedCrossRef Fukagawa T, Sasako M, Shimoda T, et al. The prognostic impact of isolated tumor cells in lymph nodes of T2n0 gastric cancer: comparison of American and Japanese gastric cancer patients. Ann Surg Oncol. 2009;16:609–13.PubMedCrossRef
11.
go back to reference Horstmann O, Fuzesi L, Markus PM, Werner C, Becker H. Significance of isolated tumor cells in lymph nodes among gastric cancer patients. J Cancer Res Clin Oncol. 2004;130:733–40.PubMedCrossRef Horstmann O, Fuzesi L, Markus PM, Werner C, Becker H. Significance of isolated tumor cells in lymph nodes among gastric cancer patients. J Cancer Res Clin Oncol. 2004;130:733–40.PubMedCrossRef
12.
go back to reference Rahbari NN, Aigner M, Thorlund K, et al. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 2010;138:1714–26.PubMedCrossRef Rahbari NN, Aigner M, Thorlund K, et al. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 2010;138:1714–26.PubMedCrossRef
13.
go back to reference Rahbari NN, Bork U, Motschall E, et al. Molecular detection of tumor cells in regional lymph nodes is associated with disease recurrence and poor survival in node-negative colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30:60–70.PubMedCrossRef Rahbari NN, Bork U, Motschall E, et al. Molecular detection of tumor cells in regional lymph nodes is associated with disease recurrence and poor survival in node-negative colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30:60–70.PubMedCrossRef
14.
go back to reference Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.PubMedCrossRef Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.PubMedCrossRef
15.
go back to reference McGuill MJ, Byrne P, Ravi N, Reynolds J. The prognostic impact of occult lymph node metastasis in cancer of the esophagus or esophago-gastric junction: systematic review and meta-analysis. Dis Esophagus. 2008;21:236–40.PubMedCrossRef McGuill MJ, Byrne P, Ravi N, Reynolds J. The prognostic impact of occult lymph node metastasis in cancer of the esophagus or esophago-gastric junction: systematic review and meta-analysis. Dis Esophagus. 2008;21:236–40.PubMedCrossRef
16.
go back to reference Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326:219.PubMedCrossRef Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326:219.PubMedCrossRef
17.
go back to reference Cai J, Ikeguchi M, Maeta M, Kaibara N, Sakatani T. Clinicopathological value of immunohistochemical detection of occult involvement in Pt3n0 gastric cancer. Gastric Cancer. 1999;2:95–100.PubMedCrossRef Cai J, Ikeguchi M, Maeta M, Kaibara N, Sakatani T. Clinicopathological value of immunohistochemical detection of occult involvement in Pt3n0 gastric cancer. Gastric Cancer. 1999;2:95–100.PubMedCrossRef
18.
go back to reference Kikuchi Y, Tsuchiya A, Ando Y, Yoshida T, Takenosita S. Immunohistochemical detection of lymph node microinvolvement in node-negative gastric cancer. Gastric Cancer. 1999;2:173–8.PubMedCrossRef Kikuchi Y, Tsuchiya A, Ando Y, Yoshida T, Takenosita S. Immunohistochemical detection of lymph node microinvolvement in node-negative gastric cancer. Gastric Cancer. 1999;2:173–8.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference Nakajo A, Natsugoe S, Ishigami S, et al. Detection and prediction of micrometastasis in the lymph nodes of patients with Pn0 gastric cancer. Ann Surg Oncol. 2001;8:158–62.PubMedCrossRef Nakajo A, Natsugoe S, Ishigami S, et al. Detection and prediction of micrometastasis in the lymph nodes of patients with Pn0 gastric cancer. Ann Surg Oncol. 2001;8:158–62.PubMedCrossRef
21.
go back to reference Morgagni P, Saragoni L, Folli S, et al. Lymph node micrometastases in patients with early gastric cancer: experience with 139 patients. Ann Surg Oncol. 2001;8:170–4.PubMedCrossRef Morgagni P, Saragoni L, Folli S, et al. Lymph node micrometastases in patients with early gastric cancer: experience with 139 patients. Ann Surg Oncol. 2001;8:170–4.PubMedCrossRef
22.
go back to reference Fukagawa T, Sasako M, Mann GB, et al. Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma. Cancer. 2001;92:753–60.PubMedCrossRef Fukagawa T, Sasako M, Mann GB, et al. Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma. Cancer. 2001;92:753–60.PubMedCrossRef
23.
go back to reference Cai J, Ikeguchi M, Tsujitani S, Maeta M, Liu J, Kaibara N. Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer. Gastric Cancer. 2001;4:66–74.PubMedCrossRef Cai J, Ikeguchi M, Tsujitani S, Maeta M, Liu J, Kaibara N. Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer. Gastric Cancer. 2001;4:66–74.PubMedCrossRef
24.
go back to reference Kim JH, Park JM, Jung CW, et al. 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.PubMedCrossRef Kim JH, Park JM, Jung CW, et al. 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.PubMedCrossRef
25.
go back to reference Ru Y, Zhang L, Chen Q, et al. Detection and clinical significance of lymph node micrometastasis in gastric cardia adenocarcinoma. J Int Med Res. 2012;40:293–9.PubMedCrossRef Ru Y, Zhang L, Chen Q, et al. Detection and clinical significance of lymph node micrometastasis in gastric cardia adenocarcinoma. J Int Med Res. 2012;40:293–9.PubMedCrossRef
26.
go back to reference Yanagita S, Natsugoe S, Uenosono Y, et al. Sentinel node micrometastases have high proliferative potential in gastric cancer. J Surg Res. 2008;145:238–43.PubMedCrossRef Yanagita S, Natsugoe S, Uenosono Y, et al. Sentinel node micrometastases have high proliferative potential in gastric cancer. J Surg Res. 2008;145:238–43.PubMedCrossRef
27.
go back to reference Youn HG, An JY, Choi MG, Noh JH, Sohn TS, Kim S. Recurrence after curative resection of early gastric cancer. Ann Surg Oncol. 2010;17:448–54.PubMedCrossRef Youn HG, An JY, Choi MG, Noh JH, Sohn TS, Kim S. Recurrence after curative resection of early gastric cancer. Ann Surg Oncol. 2010;17:448–54.PubMedCrossRef
28.
go back to reference Seto Y, Nagawa H, Muto T. Impact of lymph node metastasis on survival with early gastric cancer. World J Surg. 1997;21:186–9.PubMedCrossRef Seto Y, Nagawa H, Muto T. Impact of lymph node metastasis on survival with early gastric cancer. World J Surg. 1997;21:186–9.PubMedCrossRef
29.
go back to reference 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.PubMed 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.PubMed
30.
go back to reference Kitagawa Y, Fujii H, Mukai M, Kubota T, Otani Y, Kitajima M. Radio-guided sentinel node detection for gastric cancer. Br J Surg. 2002;89:604–8.PubMedCrossRef Kitagawa Y, Fujii H, Mukai M, Kubota T, Otani Y, Kitajima M. Radio-guided sentinel node detection for gastric cancer. Br J Surg. 2002;89:604–8.PubMedCrossRef
31.
go back to reference Matsumoto M, Natsugoe S, Ishigami S, Uenosono Y, Takao S, Aikou T. Rapid immunohistochemical detection of lymph node micrometastasis during operation for upper gastrointestinal carcinoma. Br J Surg. 2003;90:563–6.PubMedCrossRef Matsumoto M, Natsugoe S, Ishigami S, Uenosono Y, Takao S, Aikou T. Rapid immunohistochemical detection of lymph node micrometastasis during operation for upper gastrointestinal carcinoma. Br J Surg. 2003;90:563–6.PubMedCrossRef
32.
go back to reference Ichikura T, Ogawa T, Chochi K, Kawabata T, Sugasawa H, Mochizuki H. Minimum Number of lymph nodes that should be examined for the International Union against Cancer/American Joint Committee on Cancer TNM classification of gastric carcinoma. World J Surg. 2003;27:330–3.PubMedCrossRef Ichikura T, Ogawa T, Chochi K, Kawabata T, Sugasawa H, Mochizuki H. Minimum Number of lymph nodes that should be examined for the International Union against Cancer/American Joint Committee on Cancer TNM classification of gastric carcinoma. World J Surg. 2003;27:330–3.PubMedCrossRef
33.
go back to reference Shen JY, Kim S, Cheong JH, et al. The impact of total retrieved lymph nodes on staging and survival of patients with Pt3 gastric cancer. Cancer. 2007;110:745–51.PubMedCrossRef Shen JY, Kim S, Cheong JH, et al. The impact of total retrieved lymph nodes on staging and survival of patients with Pt3 gastric cancer. Cancer. 2007;110:745–51.PubMedCrossRef
34.
go back to reference Sobin LH, Wittekind CH. International Union Against Cancer. TNM classification of malignant tumors. 6th ed. New York: John Wiley-Liss; 2002. Sobin LH, Wittekind CH. International Union Against Cancer. TNM classification of malignant tumors. 6th ed. New York: John Wiley-Liss; 2002.
35.
go back to reference Arigami T, Uenosono Y, Yanagita S, et al. Clinical significance of lymph node micrometastasis in gastric cancer. Ann Surg Oncol. 2013;20:515–21.PubMedCrossRef Arigami T, Uenosono Y, Yanagita S, et al. Clinical significance of lymph node micrometastasis in gastric cancer. Ann Surg Oncol. 2013;20:515–21.PubMedCrossRef
Metadata
Title
The Prognostic Impact of Occult Lymph Node Metastasis in Node-negative Gastric Cancer: A Systematic Review and Meta-analysis
Authors
Jin-yu Huang, MD
Ying-ying Xu, MD, PhD
Min Li, MD
Zhe Sun, MD, PhD
Zhi Zhu, MD, PhD
Yong-xi Song, MD
Zhi-feng Miao, MD
Jian-hua Wu, MD
Hui-mian Xu, MD, PhD
Publication date
01-11-2013
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 12/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3021-7

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