This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nitti, D. Articles by Lise, M. Search for Related Content PubMed PubMed Citation Articles by Nitti, D. Articles by Lise, M. Related Collections Prognostic factors

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

From the Department of Oncological and Surgical Science, University of Padova, Italy.

Correspondence: Address correspondence and reprint requests to: Donato Nitti, MD, Istituto di Clinica Chirurgica Generale II, Università di Padova, Via Giustiniani, 2, 35128 - Padova, Italy; Fax: 39-049-651891; E-mail: donato.nitti{at}unipd.it

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Background: In view of the lack of consensus on the level and number of lymph nodes to be examined for accurate staging of patients with gastric cancer, our aim was to evaluate the prognostic significance of lymph node status in a large European monoinstitutional experience.

Methods: A review was made of our prospective database from 1980 to 2000, when 314 of 445 patients operated for gastric adenocarcinoma underwent radical resection (R0) with D2 lymphadenectomy. Survival was determined by the Kaplan-Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression.

Results: In 277 evaluable patients, 5-year survival was 57% (median follow-up, 48 months; range, 2–251). A total of 7668 lymph nodes were examined (median, 27; range, 11–62). The 5-year survivals according to the metastatic/examined lymph nodes ratio (N ratio) were 14%, 50%, 61%, and 82% in the group of patients with N ratio >25%, 11%–25%, 1%–10%, and 0%, respectively (P < .0001). At multivariate analysis, the N ratio was the best single independent prognostic factor (P = .000).

Conclusions: After R0 resection for gastric cancer, the N ratio is a potent prognostic factor. It should therefore be considered in the clinical decision making process.

Key Words: Gastric cancer • Lymphadenectomy • Prognostic factor • Staging • Lymph nodes ratio

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Surgery is the most widely used treatment for resectable gastric carcinoma. However, although the resectability rate has increased in Western countries, now ranging from 70% to 80%, the prognosis after surgical resection is poor, and the 5-year survival of patients with lymph node metastases does not exceed 30%.^1–4

Accurate disease staging is of fundamental importance in clinical practice, mainly when adjuvant treatment is to be tested. The promising results reported after treatment for gastric cancer with modalities, such as radio-chemotherapy⁵ or neoadjuvant chemotherapy,^6,7 have yet to be confirmed in future trials in which the bias from inadequate surgery and unsatisfactory staging must be reduced.

Lymph node involvement (N) with deep penetration of the primary carcinoma into the gastric wall (T) is still considered the most important prognostic factor for patients with resectable gastric cancer.

In the eighties, the Japanese Research Society for Gastric Carcinoma (JRSGC) proposed a classification based upon the anatomical location of positive nodes.⁸ This classification was subsequently reviewed by the Japanese Gastric Cancer Association.⁹ In 1997, the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) in the 5th edition of the tumor, node, metastasis (TNM) system, proposed a new classification for N categories based on the number of metastatic lymph nodes.¹⁰ Moreover, the new UICC/AJCC classification stated that the "histological examination of a regional lymphadenectomy specimen will ordinarily include 15 or more lymph nodes."

At present, there is no consensus on the anatomical extent and number of lymph nodes to be examined for accurate staging of patients with gastric cancer. When limited lymph node dissection (D1) is performed, no information is obtained on lymph nodes other than the perigastric nodes. On the other hand, if only the number of metastatic lymph nodes is used as a criterion, extended lymphadenectomy (D2) could result in stage migration.^11–16

Recently, a new factor for survival has been proposed for patients with gastric cancer who undergo radical resection (R0). This factor, taking into account the ratio between metastatic and examined lymph nodes, appears to obviate the risks of overstaging or understaging incurred in the N classification used in the TNM system.^14–19

To identify the prognostic factors with the greatest influence on the survival of gastric cancer patients who undergo radical resection, the number of examined lymph nodes, the anatomical location and the number of metastatic lymph nodes, and the ratio between metastatic and examined lymph nodes were considered in a series of 277 patients observed at a single European Institution (Clinica Chirurgica II, Padova University, Italy).

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Between February 1980 and December 1999, among 445 patients with histologically confirmed carcinoma of the stomach operated on at Clinica Chirurgica II of Padova University, 131 (29%) underwent palliative surgery (R1-R2) for unresectable locoregional tumor, distant metastases, and microscopic residual disease in the resection margins or in the gastric bed. Of 314 patients who underwent radical resection (R0), 37 were excluded from the analysis: 23 (7%) were not evaluable because they had tumors in the gastric stump or an inadequate pathological evaluation, and 14 (4%) died in the postoperative period. Therefore, the present analysis is based on data from 277 patients who underwent radical resection (R0).

In the 277 patients considered, the tumor location was as follows: lower third in 165 cases (59.6%), middle third in 54 cases (19.5%), upper third in 36 cases (13.0%), and cardias in 22 cases (7.9%). Gastric resection was performed in 198 patients (71.5%), total gastrectomy in 68 patients (24.5%), and extended total gastrectomy in 11 cases (4.0%). Fifty patients (18%) underwent splenectomy (Table 1).

Lymphadenectomy, depending on the number of lymph nodes removed and examined, was classified as follows: LNR 1, 11 to 25; and LNR 2, >25.

The N ratio parameter was determined by the best cut-off approach, in terms of the log-rank test. We also examined the functional form of the covariate under study by Martingale residual analysis.²⁰ Both analyses suggest the presence of the indicated cut-off values: N ratio 0, 0%; N ratio 1, 1%–10%; N ratio 2, 11%–25%; N ratio 3, >25%.

All patients had follow-up controls at regular intervals until they died; the final date of follow-up was December 31, 2001. The median follow-up was 48 months (range, 2–251 months).

The statistical analysis was made using the Statistical Product and Service Solutions, SPSS 11.0 for Windows, 2001 (SPSS Inc, Chicago, IL). Survival was determined using the Kaplan-Meier method, and the log-rank test was used to assess statistical differences between groups.²¹ Factors considered were (1) age (< or >70 years), (2) sex (male or female), (3) tumor site (antrum, corpus, fundus, or cardias), (4) type of surgical resection (subtotal gastric resection, total gastrectomy, or extended total gastrectomy), splenectomy (yes or no), (5) T stage (T1a, mucosa; T1b, submucosa; T2a, muscularis; T2b, subserosa; T3, serosa; or T4, extension to other structures), (6) venous and lymphatic vessels involvement (yes or no), (7) grading (G1, G2, G3, or G4),²² (8) Lauren type (intestinal or diffuse), (9) Ming type (expansive or infiltrative), (10) number of lymph nodes examined (11–25 or >25), (11) anatomical location of lymph nodes metastases (n0, n1, or n2), (12) number of lymph nodes metastases (N0, N1, N2, or N3), and (13) metastatic/examined lymph nodes ratio (N ratio 0, N ratio 1, N ratio 2, or N ratio 3).

Multivariate analysis was performed using the Cox proportional hazards model selected in forward stepwise regression.²³ Values of P < .05 were considered significant. The number of lymph nodes examined, the anatomical location, the number of metastatic lymph nodes, and the N ratio were analyzed as a continuous variable.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
From 277 patients, a total of 7668 lymph nodes (median, 27; mean, 27.6; range, 11–62) were removed and examined. In 245 patients (88.4%), lymphadenectomy including 15 lymph nodes or more was performed, whereas in 32 patients (21.6%) <15 nodes were assessed. Lymphadenectomy included 11–25 nodes in 116 patients (41.8%) and more than 25 nodes in 161 patients (58.2%). A total of 1280 lymph nodes were metastatic (median, 5; mean, 8.25; range, 1–47). The anatomical location of metastatic lymph nodes was classified as n0 in 117 patients (42%), n1 in 68 patients (25%), and n2 in 92 patients (33%). Based on the number of metastatic lymph nodes, 117 patients (42%) were classified as N0, 92 (33%) as N1, 41 (15%) as N2, and 27 (10%) as N3. The metastatic/examined lymph node ratio was 0 in 117 cases (42%), 1 in 46 (16%), 2 in 41 (14%), and 3 in 73 cases (27%).

On considering the distribution of N ratio categories (1 to 3) among the lymph node staging categories (N1, N2, and N3), in the group of N1 tumors, all of the 3 N ratio categories were present (50% N ratio 1; 37% N ratio 2 and 13% N ratio 3). In the group of N2 tumors, N ratio 2 and N ratio 3 categories were present (17% and 83%, respectively), whereas the group of N3 tumors consisted of only the N ratio 3 category (Table 2).

For the 277 patients, the 5-year survival rate was 57%; it was 82% for the 117 patients without lymph node metastases, and 37% for the 160 patients with lymph node metastases (Fig. 1). Table 1 reports findings at univariate analysis for prognostic factors. The factors retained at univariate analysis were as follows: (1) age (patients younger than 70 years had a better 5-year survival rate than the older patients; 60% vs. 48%; P = .048); (2) tumor site (patients with tumors of the cardias or the upper third of the stomach had a worse prognosis than those with tumors of the middle third or the lower third of the stomach; 37% and 31% vs. 52% and 66%; P < .001); (3) type of resection (survival was better in patients who underwent gastric resection than in those who underwent total gastrectomy or extended total gastrectomy; 63% vs. 40% vs. 36%; P = .002); (4) for patients who underwent splenectomy, the 5-year survival was 37% vs. 61% in those who did not undergo splenectomy (P < .0001); (5) T stage (the 5-year survival was 88% for T1a, 78% for T1b, 74% for T2a, 31% for T2b, 41% for T3, and 16% for T4 patients; P < .001); (6) patients without lymphatic and venous involvement had a better survival than those with involvement (65% and 62% vs. 36% and 34%; P < .001); (7) grading (patients with well-differentiated tumors had a better survival than those with moderately, poorly, or undifferentiated tumors; 68%, 49%, 49%, and 30%, respectively; P < .001); (8) anatomical location of lymph nodes metastasis (the 5-year survival for n0, n1, and n2 patients was 82%, 48%, and 32%, respectively; P < .001); (9) number of metastatic nodes (the 5-year survival was 82% for N0, 51% for N1, 27% for N2, and 5% for N3; P < .001); and (10) N ratio (the 5-year survival was 82% for ratio 0, 61% for ratio 1, 50% for ratio 2 and 14% for ratio 3; P < .0001) (Fig. 2).

View larger version (18K): [in this window] [in a new window]   FIG. 1. Kaplan-Meier survival curves according to lymph nodes status.

View larger version (24K): [in this window] [in a new window]   FIG. 2. Kaplan-Meier survival curves according to different lymph node staging systems.

View larger version (10K): [in this window] [in a new window]   FIG. 3. Kaplan-Meier survival curves for different N ratios among N1 and N2 (TNM) cases.

When multivariate analysis was performed considering only the anatomical location of metastatic nodes as a factor related to nodal status, the retained factors were as follows: age (relative risk [RR] = 1.67), T (RR of T1b, T2a, T2b, T3, and T4 were 1.57, 1.19, 3.20, 2.15, and 13.43, respectively), and anatomical location of nodal metastasis (RR of n1 = 1.45; RR of n2 = 2.19) (Table 3).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

Metastases to the lymph nodes are considered the main prognostic factor for patients with gastric carcinoma who undergo radical resection. Subgroups of patients with different prognoses were classified according to the JRSGC and the UICC/AJCC staging systems. The nodal staging in the JRSGC classification is considered to reflect the anatomical pathway of lymphatic spread, but Western surgeons believe it is too complicated for clinical use.^15,16 With the UICC/AJCC TNM system, regional lymph nodes metastases are classified simply according to the number of metastatic lymph nodes present. In different series in literature, the two classifications have been compared, and the UICC/AJCC system is currently considered a better prognostic determinant than the Japanese system.^{14,15,24–28} Moreover, one major concern regarding the TNM staging system is that the number of metastatic nodes is influenced by the number of lymph nodes resected and examined. Thus, this classification, which is easily reproducible, may be influenced by the operator’s attitude toward the dissection of lymph nodes and, if only the number of metastatic lymph nodes is used to classify the patient after an extended lymphadenectomy (D2), in 5%–15% of cases stage migration occurs, whatever the prognostic superiority of extended surgery.^13,15

Extended lymphadenectomy (D2) is used less in the West than in Japan. Doubts concerning its therapeutic effect are supported by the results obtained in two recent trials conducted in Europe, comparing D1 with D2 lymphadenectomy.^29,30 After D2 lymphadenectomy, both studies report a significant increase in the mortality and morbidity rates and longer mean hospital stays, without evident benefit in terms of overall and disease-free survival. Although numerous institutions in Europe and USA dedicated to gastric surgery do not agree with these results,^31,32 D1 lymph node dissection is widely performed in Western counties. In an overview on gastric cancer treatment in the USA, D2 dissection ranged from only 4% to 7% of cases.^3,33,34

Because the number of regional gastric lymph nodes differs from individual to individual,³⁵ if lymphadenectomy is limited to the perigastric lymph nodes, fewer than 15 lymph nodes may be removed, and patients may therefore not be classified according to the tumor, node, metastasis system.

The lymph node metastatic/examined ratio has been proposed in the attempt to identify a new prognostic factor independent of the number of lymph node removed and examined, while avoiding the stage migration phenomenon related to the TNM staging system. Our results are in line with an accumulating body of evidence from both Western and Japanese series, indicating that the N ratio is a powerful prognostic parameter after radical resection for gastric cancer. In their analysis of the results of the German Gastric Cancer Study on 1654 patients, Siewert el al.¹⁹ identified an N ratio of 20%, and showed that this record, in association with residual tumor status (R classification), is the major independent prognostic factor. Yu et al.,³⁶ in 886 patients who underwent R0 gastric resection with D2 lymphadenectomy, demonstrated that the N ratio cut-off was 0 (N0), 1%–25% (N1), and >25% (N2), with significant differences between the prognoses of these three classes of patients. In a study by Kodera et al.,¹⁸ 656 patients who underwent radical surgery for advanced gastric cancer (tumor spread beyond the muscolaris propria = T>2a) with a lymphadenectomy of D2 or more were evaluated with univariate analysis to identify the prognostic significance of the number of lymph nodes excised, the number of metastatic lymph nodes, and the N ratio. The study selected four cut-offs for the N ratio: 0%, 1%–19%, 20%–60%, and >60%. The N ratio, which was correlated significantly with N status (UICC classification) but not with the number of lymph nodes resected, can be utilized even when a D1 dissection is performed. Hyung et al.¹⁷ performed a retrospective analysis on 833 gastric cancer patients with T3 tumors (T3N1 and T3N2, UICC classification). The cut-offs retained for the N ratio varied in relation to N status: 10% for N1 patients and 25% for N2 patients. However, the N ratio was considered an independent risk factor for recurrence and survival in both N1 and N2 patients. Moreover, the authors stressed that the N ratio can be utilized as a prognostic factor irrespective of the extent of lymphadenectomy and the depth of tumor invasion. Inoue et al.¹⁶ analyzed findings in 474 patients who underwent an R0 resection and a D2 lymphadenectomy for gastric cancer with lymph nodes metastases. The N ratio cut-offs were found to be 25%, 50%, and >50%. For multivariate analysis, the N ratio was selected as the most significant prognostic factor when the analysis considered both the N ratio and the N (UICC) classification. The N classification, retained at multivariate analysis only when the N ratio was excluded, was influenced by the number of lymph nodes examined. Thus, the prognostic value of the N (UICC) classification may depend on stage migration. In a study by Bando et al.,¹⁵ 650 gastric cancer patients who underwent curative D2 gastrectomy were analyzed with regard to location and number of lymph nodes involved and N ratio. The N ratio cut-off was classified as follows: 0 (no involvement), 1% to 10%, 11% to 25%, and >25%. A statistically significant difference was found between the survivals of patients with different N ratios. At multivariate analysis, all the three modalities for classifying lymph node involvement (n level, N stage, and N ratio) had a prognostic value if considered separately, but the N ratio was retained as the only independent prognostic factor when the three methods were used in the same analysis.

To our knowledge, the present study is the first report from a Western country to confirm that the N ratio is of greater prognostic value than the TNM/UICC and JRSGC staging systems. On comparing N level and N stage, multivariate analysis retained only N stage as a prognostic factor, thus confirming that the TNM/UICC classification is more effective than the JRSGC classification. However, when each classification was included in the same analysis, the stepwise methods showed that the N ratio is the most important prognostic indicator and is the only independent lymph node classification to be retained.

Moreover, the evaluation of the N ratio may obviate possible confounding factors related to the number of lymph nodes excised and the number of gastric lymph nodes, which varies in each individual.^15,35

D2 dissection is defined by the site of lymph nodes removed. Within this type of dissection the number of lymph nodes assessed depends on the attitude of the surgeon and on the accuracy of the pathological evaluation undertaken. The ratio between metastatic and examined lymph nodes may obviate the possible confounding effect of these variables, thus providing more reliable information on the adequacy of lymph node dissection when a D2 dissection is performed.

In conclusion, the N ratio can be considered a simple and reproducible modality for assessing the prognosis of patients who undergo radical resection for gastric cancer.

	ACKNOWLEDGMENTS

 
ACKNOWLEDGMENTS

The acknowledgments are available online at www.annalssurgicaloncology.org.

This work was supported in part by a grant (Progetti di Ricerca di Rilevante Interesse Nazionale 2002) from the M.I.U.R. (Ministero dell’Istruzione, dell’Università e della Ricerca). The authors thank Sara Pearcey for correcting the English language in the paper, and Patzizia Pegoraro for her secretarial assistance.

	FOOTNOTES

 
Presented at the 56th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, California, March 5–9, 2003.

A review was made of a European monoinstitutional prospective database from 1980 to 2000, when 314 patients underwent radical resection with D2 lymphadenectomy for gastric adenocarcinoma. At multivariate analysis, the metastatic/examined lymph nodes ratio was the single best independent prognostic factor.

Received for publication March 6, 2003. Accepted for publication July 6, 2003.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 

1. Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base Report on poor survival of US gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer Staging, proximal disease, and the "different disease" hypothesis. Cancer 2000; 88: 921–32.[CrossRef][Medline]
2. Berrino F, Sant M, Verdecchia A, et al. Survival of cancer patients in Europe: the Eurocare study. IARC Sci. Publ. No. 132. Lyon: International Agency for Research on Cancer, 1995.
3. Wanebo HJ, Kennedy BJ, Chmiel J, Steele G, Winchester D, Osteen R. Cancer of the stomach: a patient care evaluation study by the American College of Surgeons. Ann Surg 1993; 218: 583–92.[Medline]
4. Siewert JR, Bottcher K, Roder JC, Busch R, Hermanek P, Meyer HJ. Prognostic relevance of lymph node dissection in gastric carcinoma: German Gastric Carcinoma Study Group. Br J Surg 1993; 80: 1015–8.[Medline]
5. 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.[Abstract/Free Full Text]
6. Morant R. Neoadjuvant and adjuvant chemotherapy of locally advanced stomach cancer. Onkologie 2001; 24: 116–21.[Medline]
7. Lowe AM, Feig BW, Janjan N, et al. A pilot study of preoperative chemoradiotherapy for resectable gastric cancer. Ann Surg Oncol 2001; 8: 519–24.[Abstract/Free Full Text]
8. Japanese Research Society for Gastric Cancer. The general rules for the gastric cancer study in surgery and pathology: part I. Jpn J Surg 1981; 11: 127–39.[CrossRef][Medline]
9. Japanese Gastric Cancer Association. Japanese Classification of Gastric Carcinoma. 2nd English ed. Gastric Cancer 1998; 1: 10–4.[Medline]
10. Sobin LH, Wittekind CH. International Union Against Cancer (UICC). TNM Classification of Malignant Tumors. 5th ed. New York: John Wiley 38 Sons, 1997.
11. Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenon: stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 1985; 312: 1604–8.[Abstract]
12. Bonder BE. Will Rogers and gastric carcinoma (letter). Arch Surg 1988; 123: 1023–4.[Medline]
13. de Manzoni G, Verlato G, Roviello F, et al. The new TNM classification of lymph node metastasis minimises stage migration problems in gastric cancer patients. Br J Cancer 2002; 87: 171–4.[CrossRef][Medline]
14. Bunt AMG, Hermans J, Smit VTHBM, van de Velde CJH, Fleuren GJ, Brujin JA. Surgical/pathologic-stage migration confronts comparisons of gastric cancer survival rate between Japan and Western countries. J Clin Oncol 1995; 13: 19–25.[Abstract/Free Full Text]
15. 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: 775–84.[Abstract/Free Full Text]
16. 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.[Abstract/Free Full Text]
17. Hyung WJ, Noh SH, Yoo CH, et al. Prognostic significance of metastatic lymph node ratio in T3 gastric cancer. World J Surg 2002; 26: 323–9.[CrossRef][Medline]
18. Kodera Y, Yamamura Y, Shimizu Y, et al. Lymph node status assessment for gastric carcinoma: is the number of metastatic lymph nodes really practical as a parameter for N categories in the TNM classification? J Surg Oncol 1998; 69: 15–20.[CrossRef][Medline]
19. Siewert JR, Bittcher K, Stein HJ, Roder J, and the German Gastric Carcinoma Study Group. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg 1998; 228: 449–61.[CrossRef][Medline]
20. Therneau TM, Grambsh PM, Flemming TR. Martingale based residuals for survival models. Biometrika 1990; 77: 147–60.[Abstract/Free Full Text]
21. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–81.[CrossRef]
22. Compton C, LH Sobin for the Cancer Committee, College of American Pathologists, and the Task Force for Protocols on the Examination of Specimens from Patients With Gastric Cancer. Protocol for the examination of specimens removed from patients with gastric carcinoma: a basis for checklists. Arch Pathol Lab Med 1998; 122: 9–14.[Medline]
23. Cox DR. Regression models and life-tables. J R Stat Soc B 1972; 34: 187–220.
24. Karpeh MS, Leon L, Klimstra D, Brennan MF. Lymph node staging in gastric cancer: is location more important than number? An analysis of 1,038 patients. Ann Surg 2000; 232: 362–71.[CrossRef][Medline]
25. Kato M, Saji S, Kawaguchi Y, et al. A comparison of the prognostic significance between the number of metastatic lymph nodes and nodal stage in gastric carcinoma. Hepatogastroenterology 1999; 46: 3281–6.[Medline]
26. Ichikura T, Furuya Y, Tomimatsu S, et al. Relationship between nodal stage and the number of dissected perigastric nodes in gastric cancer. Surg Today 1998; 28: 879–83.[CrossRef][Medline]
27. Hermanek P. The superiority of the new International Union Against Cancer and American Joint Committee on Cancer TNM staging of gastric carcinoma. Cancer 2000; 88: 1763–5.[CrossRef][Medline]
28. Katai H, Yoshinura K, Maruyama K, Sasako M, Sano T. Evaluation of the new International Union Against Cancer TNM staging for gastric carcinoma. Cancer 2000; 88: 1796–1800.[CrossRef][Medline]
29. Bonekamp JJ, Hermans J, Sasako M, van de Velde CJH. Extended lymph-node dissection for gastric cancer. N Engl J Med 1999; 340: 908–14.[Abstract/Free Full Text]
30. Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resections for gastric cancer. Long term results of the MRC randomised surgical trial. Br J Cancer 1999; 79: 1522–30.[CrossRef][Medline]
31. Brennan MF. Lymph node dissection for gastric cancer. N Engl J Med 1999; 340: 956–8.[Free Full Text]
32. Sasako M. Risk factors for surgical treatment in the Dutch Gastric Cancer Trial O l. Br J Surg 1997; 84: 1567–71.[CrossRef][Medline]
33. Hundal SA, Macdonald JS, Benedetti J, Fitzsimmons T, for the Southwest Oncology Group and the Gastric Intergroup. Surgical treatment variation in a prospective, randomized trial of chemoradiotherapy in gastric cancer: the effect of undertreatment. Ann Surg Oncol 2002; 9: 278–86.[Abstract/Free Full Text]
34. Wanebo HJ, Kennedy BJ, Winchester DP, Fregmen A, Stewart AK. Gastric carcinoma: does lymph node dissection alter the survival? J Am Coll Surg 1996; 183: 616–24.[Medline]
35. Wagner PK, Ramaswamyi A, Schmitz-Moormann P, Rothmund M. Lymph node counts in the upper abdomen: anatomical basis for lymphadenectomy in gastric cancer. Br J Surg 1991; 78: 825–7.[Medline]
36. Yu W, Choi GS, Wang I, Suh IS. Comparison of five systems for staging lymph node metastasis in gastric cancer. Br J Surg 1997; 84: 1305–9.[CrossRef][Medline]

This article has been cited by other articles:

				X. Wang, J.-J. Wang, and F. Wan A Common Misuse of Stepwise Regression in Studies of Ratio of Metastatic Lymph Nodes for Gastric Cancer Ann. Surg. Oncol., June 1, 2008; 15(6): 1805 - 1806. [Full Text] [PDF]

				C. R. Rossi, S. Mocellin, S. Pasquali, P. Pilati, and D. Nitti N-Ratio: a Novel Independent Prognostic Factor for Patients with Stage-III Cutaneous Melanoma Ann. Surg. Oncol., January 1, 2008; 15(1): 310 - 315. [Abstract] [Full Text] [PDF]

				H.-Y. Lee, H.-J. Choi, K.-J. Park, J.-S. Shin, H.-C. Kwon, M.-S. Roh, and C. Kim Prognostic Significance of Metastatic Lymph Node Ratio in Node-Positive Colon Carcinoma Ann. Surg. Oncol., May 1, 2007; 14(5): 1712 - 1717. [Abstract] [Full Text] [PDF]

				A. Marchet, S. Mocellin, C. Belluco, A. Ambrosi, F. DeMarchi, E. Mammano, M. Digito, A. Leon, A. D'Arrigo, M. Lise, et al. Gene Expression Profile of Primary Gastric Cancer: Towards the Prediction of Lymph Node Status Ann. Surg. Oncol., March 1, 2007; 14(3): 1058 - 1064. [Abstract] [Full Text] [PDF]

				J.-H. Cheong, W. J. Hyung, J. G. Shen, C. Song, J. Kim, S. H. Choi, and S. H. Noh The N Ratio Predicts Recurrence and Poor Prognosis in Patients With Node-Positive Early Gastric Cancer Ann. Surg. Oncol., March 1, 2006; 13(3): 377 - 385. [Abstract] [Full Text] [PDF]

				D. D. Smith, R. R. Schwarz, and R. E. Schwarz 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., October 1, 2005; 23(28): 7114 - 7124. [Abstract] [Full Text] [PDF]

				O. Bouche, M. Ychou, P. Burtin, L. Bedenne, M. Ducreux, G. Lebreton, J. Baulieux, B. Nordlinger, C. Martin, J. F. Seitz, et al. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801) Ann. Onc., September 1, 2005; 16(9): 1488 - 1497. [Abstract] [Full Text] [PDF]

				M. D. McKee and M. C. Posner The Staging of Gastric Cancer: Nothing Novel but Perhaps Better Ann. Surg. Oncol., November 1, 2003; 10(9): 1005 - 1006. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nitti, D. Articles by Lise, M. Search for Related Content PubMed PubMed Citation Articles by Nitti, D. Articles by Lise, M. Related Collections Prognostic factors