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Published in: Annals of Surgical Oncology 5/2010

01-05-2010 | Gastrointestinal Oncology

New Metastatic Lymph Node Ratio System Reduces Stage Migration in Patients Undergoing D1 Lymphadenectomy for Gastric Adenocarcinoma

Authors: Ugwuji N. Maduekwe, MD, MMSc, Gregory Y. Lauwers, MD, Carlos Fernandez-del-Castillo, MD, David L. Berger, MD, Charles M. Ferguson, MD, David W. Rattner, MD, Sam S. Yoon, MD

Published in: Annals of Surgical Oncology | Issue 5/2010

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Abstract

Background

The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for gastric cancer incorporates the absolute number of metastatic lymph nodes (N status) and is optimally used when ≥15 nodes are examined. The ratio of metastatic to examined nodes (N ratio) is an effective prognostic tool, but has not been examined in Western patients undergoing primarily D1 lymphadenectomy.

Methods

Two hundred and fifty seven patients with gastric adenocarcinoma who underwent gastric resection between 1995 and 2005 at our institution were examined. Novel N ratio intervals were determined using the best cutoff approach (Nr0: N ratio = 0 and ≥15 nodes examined; Nr1: 0 ≤ N ratio ≤ 0.3; Nr2: 0.3 < N ratio ≤ 0.7; and Nr3: N ratio > 0.7). Overall survival was examined according to N status and N ratio.

Results

83% of patients underwent D1 lymphadenectomy with a median of 14 lymph nodes examined. Overall survival stratified by N status was significantly different in patients with <15 nodes examined compared with those with ≥15 nodes examined. When we stratified by N ratio intervals, there was no significant difference in overall survival in patients with <15 versus ≥ 15 nodes examined. On multivariate analysis, N ratio but not N status was retained as an independent prognostic factor.

Conclusions

The use of N status for staging patients undergoing primarily D1 lymphadenectomy results in significant stage migration due to varying numbers of nodes examined. Use of N ratio reduces stage migration and may be a more reliable method of staging these patients.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed
2.
go back to reference Lee J, Demissie K, Lu SE, Rhoads GG. Cancer incidence among Korean-American immigrants in the United States and native Koreans in South Korea. Cancer Control. 2007;14:78–85.PubMed Lee J, Demissie K, Lu SE, Rhoads GG. Cancer incidence among Korean-American immigrants in the United States and native Koreans in South Korea. Cancer Control. 2007;14:78–85.PubMed
4.
go back to reference Smith DD, Schwarz RR, Schwarz RE. Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database. J Clin Oncol. 2005;23:7114–24.CrossRefPubMed Smith DD, Schwarz RR, Schwarz RE. Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database. J Clin Oncol. 2005;23:7114–24.CrossRefPubMed
5.
go back to reference Greene FL, Page DL, Fleming ID et al. AJCC cancer staging manual. 6th ed. New York: Springer; 2002. Greene FL, Page DL, Fleming ID et al. AJCC cancer staging manual. 6th ed. New York: Springer; 2002.
6.
go back to reference Lee HK, Yang HK, Kim WH, Lee KU, Choe KJ, Kim JP. Influence of the number of lymph nodes examined on staging of gastric cancer. Br J Surg. 2001;88:1408–12.CrossRefPubMed Lee HK, Yang HK, Kim WH, Lee KU, Choe KJ, Kim JP. Influence of the number of lymph nodes examined on staging of gastric cancer. Br J Surg. 2001;88:1408–12.CrossRefPubMed
7.
go back to reference Bunt AM, Hermans J, Smit VT, van de Velde CJ, Fleuren GJ, Bruijn JA. Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries. J Clin Oncol. 1995;13:19–25.PubMed Bunt AM, Hermans J, Smit VT, van de Velde CJ, Fleuren GJ, Bruijn JA. Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries. J Clin Oncol. 1995;13:19–25.PubMed
8.
go back to reference Okusa T, Nakane Y, Boku T, et al. Quantitative analysis of nodal involvement with respect to survival rate after curative gastrectomy for carcinoma. Surg Gynecol Obstet. 1990;170:488–94.PubMed Okusa T, Nakane Y, Boku T, et al. Quantitative analysis of nodal involvement with respect to survival rate after curative gastrectomy for carcinoma. Surg Gynecol Obstet. 1990;170:488–94.PubMed
9.
go back to reference Celen O, Yildirim E, Berberoglu U. Prognostic impact of positive lymph node ratio in gastric carcinoma. J Surg Oncol. 2007;96:95–101.CrossRefPubMed Celen O, Yildirim E, Berberoglu U. Prognostic impact of positive lymph node ratio in gastric carcinoma. J Surg Oncol. 2007;96:95–101.CrossRefPubMed
10.
go back to reference Inoue K, Nakane Y, Iiyama H, et al. The superiority of ratio-based lymph node staging in gastric carcinoma. Ann Surg Oncol. 2002;9:27–34.CrossRefPubMed Inoue K, Nakane Y, Iiyama H, et al. The superiority of ratio-based lymph node staging in gastric carcinoma. Ann Surg Oncol. 2002;9:27–34.CrossRefPubMed
11.
go back to reference Marchet A, Mocellin S, Ambrosi A, et al. The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients. Ann Surg. 2007;245:543–552.CrossRefPubMed Marchet A, Mocellin S, Ambrosi A, et al. The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients. Ann Surg. 2007;245:543–552.CrossRefPubMed
12.
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;10:1077–1085.CrossRefPubMed 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;10:1077–1085.CrossRefPubMed
13.
go back to reference Rodriguez Santiago JM, Munoz E, Marti M, Quintana S, Veloso E, Marco C. Metastatic lymph node ratio as a prognostic factor in gastric cancer. Eur J Surg Oncol. 2005;31:59–66.CrossRefPubMed Rodriguez Santiago JM, Munoz E, Marti M, Quintana S, Veloso E, Marco C. Metastatic lymph node ratio as a prognostic factor in gastric cancer. Eur J Surg Oncol. 2005;31:59–66.CrossRefPubMed
14.
go back to reference Saito H, Fukumoto Y, Osaki T, et al. Prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in patients with advanced gastric cancer. J Surg Oncol. 2008;97:132–5.CrossRefPubMed Saito H, Fukumoto Y, Osaki T, et al. Prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in patients with advanced gastric cancer. J Surg Oncol. 2008;97:132–5.CrossRefPubMed
15.
go back to reference Xu DZ, Geng QR, Long ZJ, et al. Positive lymph node ratio is an independent prognostic factor in gastric cancer after d2 resection regardless of the examined number of lymph nodes. Ann Surg Oncol. 2009;16:319–26.CrossRefPubMed Xu DZ, Geng QR, Long ZJ, et al. Positive lymph node ratio is an independent prognostic factor in gastric cancer after d2 resection regardless of the examined number of lymph nodes. Ann Surg Oncol. 2009;16:319–26.CrossRefPubMed
16.
go back to reference Marchet A, Mocellin S, Ambrosi A, et al. The prognostic value of N-ratio in patients with gastric cancer: validation in a large, multicenter series. Eur J Surg Oncol. 2008;34:159–65.PubMed Marchet A, Mocellin S, Ambrosi A, et al. The prognostic value of N-ratio in patients with gastric cancer: validation in a large, multicenter series. Eur J Surg Oncol. 2008;34:159–65.PubMed
17.
go back to reference Persiani R, Rausei S, Antonacci V, et al. Metastatic lymph node ratio: a new staging system for gastric cancer. World J Surg. 2009. Persiani R, Rausei S, Antonacci V, et al. Metastatic lymph node ratio: a new staging system for gastric cancer. World J Surg. 2009.
18.
go back to reference Bando E, Yonemura Y, Taniguchi K, Fushida S, Fujimura T, Miwa K. Outcome of ratio of lymph node metastasis in gastric carcinoma. Ann Surg Oncol. 2002;9:775–784.CrossRefPubMed Bando E, Yonemura Y, Taniguchi K, Fushida S, Fujimura T, Miwa K. Outcome of ratio of lymph node metastasis in gastric carcinoma. Ann Surg Oncol. 2002;9:775–784.CrossRefPubMed
19.
go back to reference Yu J, Yang D, Wei F, et al. The staging system of metastatic lymph node ratio in gastric cancer. Hepatogastroenterology. 2008;55:2287–90.PubMed Yu J, Yang D, Wei F, et al. The staging system of metastatic lymph node ratio in gastric cancer. Hepatogastroenterology. 2008;55:2287–90.PubMed
20.
go back to reference Siewert JR, Bottcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg. 1998;228:449-61.CrossRefPubMed Siewert JR, Bottcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg. 1998;228:449-61.CrossRefPubMed
21.
go back to reference Siewert JR, Feith M, Werner M, Stein HJ. Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg. 2000;232:353–61.CrossRef Siewert JR, Feith M, Werner M, Stein HJ. Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg. 2000;232:353–61.CrossRef
22.
go back to reference Japanese Research Society for Gastric Cancer: the general rules for the gastric cancer study in surgery. Jpn J Surg. 1973;3:61. Japanese Research Society for Gastric Cancer: the general rules for the gastric cancer study in surgery. Jpn J Surg. 1973;3:61.
23.
go back to reference Yoon SS, Yang HK. Lymphadenectomy for gastric adenocarcinoma: should west meet east? Oncologist. 2009;14:871–82.CrossRefPubMed Yoon SS, Yang HK. Lymphadenectomy for gastric adenocarcinoma: should west meet east? Oncologist. 2009;14:871–82.CrossRefPubMed
24.
go back to reference Therneau TM, Grambsch PM, Fleming TR. Martingale-based residuals for survival models. Biometrika. 1990;77:147–60.CrossRef Therneau TM, Grambsch PM, Fleming TR. Martingale-based residuals for survival models. Biometrika. 1990;77:147–60.CrossRef
25.
go back to reference Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;457–81. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;457–81.
26.
go back to reference Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977;35:1–39.PubMed Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977;35:1–39.PubMed
27.
go back to reference Cox D. Regression models and life-tables. J R Stat Soc. 1972;34:187–220. Cox D. Regression models and life-tables. J R Stat Soc. 1972;34:187–220.
28.
go back to reference D’Angelica M, Gonen M, Brennan MF, Turnbull AD, Bains M, Karpeh MS. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004;240:808–16.CrossRefPubMed D’Angelica M, Gonen M, Brennan MF, Turnbull AD, Bains M, Karpeh MS. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004;240:808–16.CrossRefPubMed
29.
go back to reference Sun Z, Zhu GL, Lu C, et al. The impact of N-ratio in minimizing stage migration phenomenon in gastric cancer patients with insufficient number or level of lymph node retrieved: results from a Chinese mono-institutional study in 2159 patients. Ann Oncol. 2009;20:897–905.CrossRefPubMed Sun Z, Zhu GL, Lu C, et al. The impact of N-ratio in minimizing stage migration phenomenon in gastric cancer patients with insufficient number or level of lymph node retrieved: results from a Chinese mono-institutional study in 2159 patients. Ann Oncol. 2009;20:897–905.CrossRefPubMed
30.
go back to reference Bonenkamp JJ, Hermans J, Sasako M, et al. Extended lymph-node dissection for gastric cancer. N Engl J Med. 1999;340:908–14.CrossRefPubMed Bonenkamp JJ, Hermans J, Sasako M, et al. Extended lymph-node dissection for gastric cancer. N Engl J Med. 1999;340:908–14.CrossRefPubMed
31.
go back to reference Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br J Cancer. 1999;79:1522–30.CrossRefPubMed Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br J Cancer. 1999;79:1522–30.CrossRefPubMed
32.
go back to reference Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.CrossRefPubMed Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.CrossRefPubMed
33.
go back to reference Hundahl SA, Macdonald JS, Benedetti J, Fitzsimmons T. Surgical treatment variation in a prospective, randomized trial of chemoradiotherapy in gastric cancer: the effect of undertreatment. Ann Surg Oncol. 2002;9:278–86.CrossRefPubMed Hundahl SA, Macdonald JS, Benedetti J, Fitzsimmons T. Surgical treatment variation in a prospective, randomized trial of chemoradiotherapy in gastric cancer: the effect of undertreatment. Ann Surg Oncol. 2002;9:278–86.CrossRefPubMed
34.
go back to reference Peeters KC, Hundahl SA, Kranenbarg EK, Hartgrink H, van de Velde CJ. Low Maruyama index surgery for gastric cancer: blinded reanalysis of the Dutch D1-D2 trial. World J Surg. 2005;29:1576–84.CrossRefPubMed Peeters KC, Hundahl SA, Kranenbarg EK, Hartgrink H, van de Velde CJ. Low Maruyama index surgery for gastric cancer: blinded reanalysis of the Dutch D1-D2 trial. World J Surg. 2005;29:1576–84.CrossRefPubMed
35.
go back to reference Lee JH, Ryu KW, Lee JH, et al. Learning curve for total gastrectomy with D2 lymph node dissection: cumulative sum analysis for qualified surgery. Ann Surg Oncol. 2006;13:1175–81.CrossRefPubMed Lee JH, Ryu KW, Lee JH, et al. Learning curve for total gastrectomy with D2 lymph node dissection: cumulative sum analysis for qualified surgery. Ann Surg Oncol. 2006;13:1175–81.CrossRefPubMed
36.
go back to reference Cuschieri A, Fayers P, Fielding J, et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet. 1996;347:995–9.CrossRefPubMed Cuschieri A, Fayers P, Fielding J, et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet. 1996;347:995–9.CrossRefPubMed
37.
go back to reference Bonenkamp JJ, Songun I, Hermans J, et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet. 1995;345:745–8.CrossRefPubMed Bonenkamp JJ, Songun I, Hermans J, et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet. 1995;345:745–8.CrossRefPubMed
38.
go back to reference Kitamura K, Nishida S, Ichikawa D, et al. No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer. Br J Surg. 1999;86:119–22.CrossRefPubMed Kitamura K, Nishida S, Ichikawa D, et al. No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer. Br J Surg. 1999;86:119–22.CrossRefPubMed
39.
go back to reference Kodera Y, Yamamura Y, Shimizu Y, et al. Lack of benefit of combined pancreaticosplenectomy in D2 resection for proximal-third gastric carcinoma. World J Surg. 1997;21:622–7.CrossRefPubMed Kodera Y, Yamamura Y, Shimizu Y, et al. Lack of benefit of combined pancreaticosplenectomy in D2 resection for proximal-third gastric carcinoma. World J Surg. 1997;21:622–7.CrossRefPubMed
40.
go back to reference Sano T, Yamamoto S, Sasako M. Randomized controlled trial to evaluate splenectomy in total gastrectomy for proximal gastric carcinoma: Japan clinical oncology group study JCOG 0110-MF. Jpn J Clin Oncol. 2002;32:363–4.CrossRefPubMed Sano T, Yamamoto S, Sasako M. Randomized controlled trial to evaluate splenectomy in total gastrectomy for proximal gastric carcinoma: Japan clinical oncology group study JCOG 0110-MF. Jpn J Clin Oncol. 2002;32:363–4.CrossRefPubMed
41.
go back to reference Degiuli M, Sasako M, Ponti A, Soldati T, Danese F, Calvo F. Morbidity and mortality after D2 gastrectomy for gastric cancer: results of the Italian Gastric Cancer Study Group prospective multicenter surgical study. J Clin Oncol. 1998;16:1490–3.PubMed Degiuli M, Sasako M, Ponti A, Soldati T, Danese F, Calvo F. Morbidity and mortality after D2 gastrectomy for gastric cancer: results of the Italian Gastric Cancer Study Group prospective multicenter surgical study. J Clin Oncol. 1998;16:1490–3.PubMed
42.
go back to reference Wu CW, Hsiung CA, Lo SS et al. Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol. 2006;7:309–15.CrossRefPubMed Wu CW, Hsiung CA, Lo SS et al. Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol. 2006;7:309–15.CrossRefPubMed
43.
go back to reference Debruyne PR, Waldman SA, Schulz S. Pathological staging and therapy of oesophageal and gastric cancer. Expert Opin Pharmacother. 2003;4:1083–96.CrossRefPubMed Debruyne PR, Waldman SA, Schulz S. Pathological staging and therapy of oesophageal and gastric cancer. Expert Opin Pharmacother. 2003;4:1083–96.CrossRefPubMed
Metadata
Title
New Metastatic Lymph Node Ratio System Reduces Stage Migration in Patients Undergoing D1 Lymphadenectomy for Gastric Adenocarcinoma
Authors
Ugwuji N. Maduekwe, MD, MMSc
Gregory Y. Lauwers, MD
Carlos Fernandez-del-Castillo, MD
David L. Berger, MD
Charles M. Ferguson, MD
David W. Rattner, MD
Sam S. Yoon, MD
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-0914-6

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