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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: updating.

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



February 2002.     Review Article.     To the previous article about lymph node staging

There are several purposes for a staging system: (1) to give some indication of prognosis for cancer patients, (2) to aid the clinician in planning treatment, and (3) to compare the interinstitutional and international treatment results. To accomplish these purposes, the staging system must be feasible, reproducible, and accurate for prognostic stratification without stage migration.

Kentaro Inoue et al. compared the prognostic determinant of the 1997 UICC/AJCC classification with the classification based on the lymph node ratio (0%, <<25%, <<50%, and >50%) in patients who underwent an R0 resection. From the analysis by multiple stepwise regression analysis with the Cox proportional hazards model, the ratio-based classification was selected as the most significant prognostic determinant when both N classifications were included in the analysis. Thus, the lymph node classification according to lymph node ratio was considered a better prognostic determinant than the 1997 UICC/AJCC staging system.
They also found that the 1997 UICC/AJCC N staging system had different survival between the two groups (36 or fewer examined lymph nodes vs. more than 36 examined lymph nodes). These findings are suggestive of the effect of lymph node dissection on prognosis, but the role of the lymph node dissection in the survival of gastric cancer is still highly speculative.

The authors affirm that the 1997 UICC/AJCC N staging system had different survival according to the number of examined lymph nodes as the result of the stage migration of the number-based N classification. The number of involved lymph nodes is influenced by the number of examined nodes.

They conclude that an extended lymph node dissection with careful examination for metastases allows more accurate number-based N staging, and this should be performed whenever feasible. However, at institutions where the extended lymph node dissection is not a standard procedure, the procedure is more complicated, and the number-based staging is of no value in such a situation. The ratio-based N classification minimized this potential source of clinicians' error or bias, and we could single out this classification as the most important prognostic factor by multivariate analysis. Their findings strongly suggest that the ratio-based N classification is more appropriate as an international staging system.

Previous researchers have shown no definitive superiority of the ratio-based N classification regarding the prognostic significance, compared with the number-based N classification. These investigators analyzed data by univariate analysis alone. In most malignant tumors, there are several interactions of risk for death among the different factors. Therefore, to investigate the prognostic factors, univariate analysis alone is not sufficient; multivariate techniques are mandatory ( 1 ).

Woo Jin Hyung et al affirm that there have been many studies on the prognosis of gastric cancer based on fifth UICC TNM classification, but rarely have the previous studies analyzed the fifth UICC system in terms of the prognostic factors or the prognostic impact of LN metastasis when specific depth of invasion is involved, especially in the T3 classification which is responsible for more than 40% of gastric cancers. Therefore, the precise determination of the prognostic factors for T3 gastric cancer has substantial clinical importance.

The metastatic LN ratio was an independent risk factor for recurrence and poor prognosis. Their data suggested that the metastatic LN ratio was a significant prognostic factor for T3 gastric cancer. Furthermore, the application of the metastatic LN ratio could provide information not only about the extent of LN metastasis but also about the extent of lymphadenectomy in T3 gastric cancer. The application of the metastatic LN ratio has proved to be a good alternative in helping to avoid stage migration and it is applicable in cases when fewer than 15 LNs were retrieved or when D1 LN dissection or noncurative resection was performed.

A preliminary analysis revealed the cutoff values for T3N1M0 to be 10% and for T3N2M0 to be 25%. The mean metastatic LN ratio was 9.0% for T3N1M0 cancer and 26.9% for T3N2M0 cancer. For the T3N1M0 stage, the patients who showed less than 10% of the metastatic LN ratio were grouped as N1-low with the others grouped as N1-high. For the T3N2M0 stage group, those who had less than 25% of the metastatic LN ratio were grouped as N2-low, the remainder as N2-high.
The metastatic LN ratio decreased in proportion to the extent of lymphadenectomy and it increased in relation to the increasing scale of the fourth N classification.
The rates of recurrence were significantly different according to the metastatic LN ratio in N1 and N2 classification of the fifth UICC classification (p < 0.05). The 5-year survival rates after gastrectomy decreased significantly by increasing the metastatic LN ratio in both T3N1M0 cancers (p = 0.0026) and T3N2M0 cancers (p = 0.0057) ( 2 ).

H. K. Lee et al. riaffirm that one major concern about the 1997 node staging system is that the number of metastatic nodes is likely to be influenced by the number of lymph nodes resected and examined. The higher probability of detecting lymph node metastases with increasing nodal yields has been confirmed by an exponential model. Simply examining a small number of lymph nodes can lead to an underestimation of stage, resulting in stage migration. This is known as the Will Rogers phenomenon and can cause a substantial difference in stage-specific survival rates and confound comparison of treatment results. The number of lymph nodes examined is affected not only by the extent of lymphadenectomy, but also by techniques and intensity for the retrieval of lymph nodes, and personal variation

They concluded that the number of lymph nodes examined did not significantly affect node staging of gastric cancer as long as at least 15 nodes were examined. For stage IIIB, more than 15 lymph nodes may be required for optimal staging ( 3 ).

References

1) Kentaro Inoue, Yasushi Nakane, Hitoshi Iiyama, Mutsuya Sato, Tatsuya Kanbara, Koji Nakai, Syunichiro Okumura, Keigo Yamamichi, and Koshiro Hioki. The Superiority of Ratio-Based Lymph Node Staging in Gastric Carcinoma. Annals of Surgical Oncology 9:27-34 (2002)

2) Woo Jin Hyung, Sung Hoon Noh, Chang Hak Yoo, Ji Hun Huh, Dong Woo Shin, Ki Hyeok Lah, Jun Ho Lee, Seung Ho Choi, and Jin Sik Min. Prognostic Significance of Metastatic Lymph Node Ratio in T3 Gastric Cancer. World Journal of Surgery, Volume 26 - Number 3, 2002, 323-329.

3) H. K. Lee, H.-K. Yang, W. H. Kim, K. U. Lee, K. J. Choe and J.-P. Kim. Influence of the number of lymph nodes examined on staging of gastric cancer. British Journal of Surgery, Volume 88 Issue 10 Page 1408 - October 2001

4) Klein Kranenbarg E, Hermans J, van Krieken JHJM, van de Velde CJH. Evaluation of the 5th edition of the TNM classification for gastric cancer: improved prognostic value. Br J Cancer 2001; 84:64-71.

5) Hundahl SA, PhillipsJL, MenckHR. 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.

6) Hermanek P, Alterdorf-Hofmann A, Mannsmann U, Dworak O, Wittekind CH, Hohenberger W. Improvements in staging of gastric carcinoma from using the new edition of TNM classification. Eur J Surg Oncol 1998; 24: 536-41.

7) 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. 8) 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.

9) Kim JP, Jung S-E. Patients with gastric cancer and their prognosis in accordance with number of lymph node metastases. Scand J Gastroenterol 1987; 22 (Suppl 133): 33-5.

10) Shiu MH, Perrotti M, Brennen MF. Adenocarcinoma of the stomach: a multivariate analysis of clinical, pathologic and treatment factors. Hepatogastroenterology 1989; 36: 7-12.

11) Ichikura T, Tomimatsu S, Okusa Y, Uefuji K, Tamakuma S. Comparison of the prognostic significance between the number of metastatic lymph nodes and nodal stage based on their location in patients with gastric cancer. J Clin Oncol 1993; 11: 1894-900.

12) De Manzoni G, Verlato G, Gugliemi A, Laterza E, Genna M, Cordiano C. Prognostic significance of lymph node dissection in gastric cancer. Br J Surg 1996; 83: 1604-97.

13) Wu CW, Hsieh MC, Lo SS, Tsay SH, Lui WY, P'eng FK. Relation of number of positive lymph nodes to the prognosis of patients with primary gastric adenocarcinoma. Gut 1996; 38: 525-7.

14) Kim J.P. (1999) Surgical results in gastric cancer. Semin. Surg. Oncol. (1999) 17:132-138.

15) Roder J.D., B÷ttcher K., Busch R., et al. (1998) Classification of regional lymph node metastasis from gastric cancer. Cancer 82:621-631.



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