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Blog aimed at residents in surgery
 URL :  www.surgical-oncology.net             e mail surgoncnet@gmail.com
Lymph node staging in gastric cancer.

Romeo Giuli MD, resident.
School of General and Emergency Surgery.
University of Siena.   Italy.



August 2001.     Review Article.     To the updating

Preoperative assessment of regional lymph nodes in patients with gastric carcinoma by imaging procedures has a low accuracy (51-68%), thus the N classification is used predominantly in the postsurgical classification ( 2 ).

A classification system based on the number of metastatic lymph nodes has been adopted by the fifth edition of the American Joint Committee on Cancer ( AJCC) Manual for Staging of Cancer and the international Union Against Cancer ( UICC ) TNM Classification of Malignant Tumours, both published in 1997.
The current Japanese Classification of gastric carcinoma and the previous edition of the AJCC / UICC classification are solely based on the location of positive lymph nodes ( 1 ).

In the new 1997 UICC / AJCC lymph node classification at least 15 lymph nodes have to be dissected and investigated histologically before an exact n-classification can be determined. In fact establishing a minimum number of nodes to examine addresses the so called stage migration phenomenon ( 4, 9, 10, 11 ).
Stage migration can occur easily in any category of TNM, especially in N or pN stage, for several reasons including more extended nodal dissection, retrieving more nodes from the specimen or more sectioning of each node ( 19 ).

The assignment of 3 groups of lymph nodes defined by Hayashi et al (N1, 1-6; N2, 7-15; N3,>15) has a significant prognostic impact .
Moreover the so called lymph node ratio (the quotient between dissected and involved lymph nodes) also appears to be relevant indipendent prognostic factor after an R0 resection ( 4, 5 ).However this parameter is largely dependent on the extent of lymphadenectomy and describes the extent of surgery rather than the anatomic extent of cancer ( 15 ).Yu suggests that the classification of metastases to regional lymph nodes as N0 (no nodal metastases), N1 (metastases in 1-25 % of dissected nodes) and N2 (metastases in more than 25 % of dissected nodes) would be simple, convenient, reproducible staging system with an ability to predict surgical results ( 16 ).
Obviously the old TNM classification only differentiates between three prognostic groups regarding lymph node metastases (pN0-pN2), whereas the new classification identifies four subgroups (pN0-pN3) which show a significant difference in the survival rates among the subgroups ( 3 ). Furthermore hepatoduodenal nodes are classified as regional lymph nodes ( 8 ).

The 1997 UICC / AJCC lymph node classification shows simplicity, reduction of methodic problems, less subjectivity, and thus, higher reproducibility.
The pathologists can stage the cases directly from the gastric resection specimen and is not dependent on the preparation of lymph nodes by surgeons and / or the surgeon's information on the localization of separately submitted lymph nodes.
The problematic assessment of the distance of involved lymph nodes to the edge of the primary tumour (within 3 cm or more than 3 cm, measured on the fresh or fixed specimen?) is eliminated.
The histopathologic method can be simplified because the lymph nodes need not be embedded separately for the different lymph node locations (lymph node groups) ( 2 ).
But a disadvantage is the possibility of increase in the number of unclassified patients. In the Katai's study, 13% of patients have fewer than 15 lymph nodes examined and therefore could strictly not be fully staged according to the new rules ( 3 ). Karpeh et al say that 23% of patients in their study have fewer than the required 15 nodes examined ( 9 ). And the number of pNx cases may increase in the future , because the incidence of early gastric cancer is increasing in western countries as well as in Japan ( 14 ).

The prognosis of the various stages in the 1997 classification is more homogeneous than in the former edition, except for stage IV and the new stage grouping allows better identification of patients with particularly poor prognosis after resection for cure (R0) ( 2, 8, 9, 3, 1, 15 ).
Differences between the two systems become apparently when survival is analysed for the later stages ( 9 ). Unlike the results of the German Study, Katai affirms that that the discrimination between Stage IIIB and IV is poor according to the new classification; the author suggests to reclassify pT4/ pN1 as Stage IIIB ( 3 ).

In the Adachi's studies univariate analysis confirms that survival rate is significantly influenced by anatomical level of lymph node metastasis, total number of positive nodes, number of positive level I nodes, and number of positive level II nodes. However multivariate analysis clarifies that the number of positive level II nodes are the most important prognostic indicator in patients with node positive gastric cancer who undergo a D2 or D3 gastrectomy. When there are two or more metastases in the level II nodes, prognosis is poor even after D2 or D3 gastrectomy ( 12, 13 ).
Fujii et al agree that the category of lymph node metastases based on the TNM system (fifth edition) rather than the Japanese classification proves to be a better indicator with respect to the prognosis of patients with gastric cancer who undergo systematic lymphadenectomy. However the M1 category for distant lymph node metastases may not be necessary. Moreover even when the total number of involved lymph nodes is the same, the prognosis of patients with distant lymph node metastases is worse than that of those without such metastases.
Concerning the therapeutic use of these classifications systems, the Japanese system is useful for establishing the anatomical extent of lymph node dissection during surgery, while the TNM classification lacks indicators for the extent of lymphadenectomy. Thus the classifications have separate benefits and should be used simultaneously for treatment of gastric cancer ( 14, 15 ).

The lymph node staging is important for some reasons.
First the prognosis can be estimated accurately; second it is possible to compare treatment results at different centers, that is a prerequisite for further development of surgical therapy and the negative attitude toward adjuvant postoperative chemotherapy or immunotherapy could experience a marked change if this therapy could be investigated once more on the basis of an exact lymph node staging; third counting lymph nodes is a contribution to quality management after an operation ( 4 ).

References

1) Takashi Ichikura et al. Evaluation of the New American Joint Committee on Cancer/International Union Against Cancer Classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification. Cancer 1999; 86: 553-8.

2) Paul Hermanek. The superiority of the new international union against cencer and american joint committee on cancer TNM staging of gastric carcinoma. Cancer April 15, 2000; Volume 88, number 8.

3) H Katai, K Yoshimura, K Maruyama, M Sasako, T Sano. Evaluation of the new international union against cancer TNM staging for gastric carcinoma. Cancer 2000; 88:1976-800.

4) J Rudiger Siewert. Invited commentary: are the staging systems for lymphatic spread important in gastric cancer? Surgery, 2000; 127: 129-35.

5) Siewert JR, Bottcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten years results of the German Gastric Cancer study. Ann Surg 1998; 228: 449-61.

6) Hermanek P et al. Improvements in staging of gastric carcinoma from using the New edition of TNM classification. Eur J Surg Oncol 1998; 24: 536-41.

7) Mendes de Almeida JC et al. Does the new TNM classification (1997) improve prognostic stratification in gastric cancer submitted to R0 surgery ? Eur J Surg Oncol 1999 ; 25 : 280-3.

8) Hideki Hayashi et al. Superiority of a new UICC-TNM staging system for gastric carcinoma. Surgery 2000; 127: 129-35.

9) Martin S Karpeh, Larry Leon, David Klimstra and Murray F Brennan. Lymph node staging in gastric cancer: is location more important than number? Annals of Surgery 2000, Vol 232, n 3, 362-371.

10) Bunt AM et al. Lymph node retrival in a randomized trial on Western-type Japanese-type surgery in gastric cancer. J Clin Oncol 1996; 14: 2289-2294.

11) Kodera Y et al. The number of metastatic lymph nodes : a promising prognostic determinant for gastric carcinoma in the latest edition of the TNM classification. J Am Coll surg 1998; 187: 597-603.

12) Yosuke Adachi et al. Most important lymph node information in gastric cancer : multivariate prognostic study. Annals of Surgical Oncology, 2000, 7 (7): 503-507.

13) Yosuke Adachi et al. Perigastric lymph node status as a prognostic indicator in patients with gastric cancer. British Journal of Surgery 1998, 85, 1281-1284.

14) K Fujii et al. Clinical evaluation of lymph node metastases in gastric caner defined by the fifth edition of the TNM classification in comparison with the Japanese system. British Journal Surgery 1999, 86, 685-689.

15) Jurgen D Roder, K Bottcher, R Bush, C Wittekind, P Hermanek, J Rudiger Siewert. Classification of regional lymph nodes metastases from gastric carcinoma. Cancer 1998; 82:621-31.

16) W Yu et al. Comparison of five systems for staging lymph node metastases in gastric cancer. British Journal of Surgery 1997, 84, 1305-1309.

17) Y Adachi et al. Prognostic factors of node-negative gastric carcinoma: univariate and multivariate analysis. J Am Coll Surg 1997, 184: 373-377.

18) Y Kodera et al. Metastatic gastric lymph node rate is a significant prognostic factor for resectable stage IV stomach cancer. J Am Coll Surg 1997; 185: 65-69.

19) N Noda et al. Ignoring small lymph nodes can be a major cause of staging error in gastric cancer. British Journal of Surgery 1998, 85, 831-834.

20) C H Yoo et al. Comparison of prognostic significance of nodal staging between old ( 4th edition) and new ( 5th edition) UICC TNM classification for gastric carcinoma. World J Surg 23, 492-497, 1999.

21) J D Roder. Invited Commentary. World J Surg 23, 497-498, 1999.

22) G De Manzoni et al. Classification of lymph node metastases from carcinoma of the stomach: comparison of the old (1987) and new (1997) TNM systems. World J Surg 23, 664-669,1999.



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