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Gastric cancer and micrometastases: fourth updating

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

March 2003.     Review Article.

To previous article about micrometastases
To the first updating
To the second updating
To the third updating

Regional lymph node metastasis is well established as the most important prognostic factor in patients with gastric cancer. Despite curative resection of their primary tumor, some patients with histologically node-negative gastric cancer will die as a result of local or distant tumor recurrence. Therefore, additional markers would be helpful for predicting patients at risk for recurrence.
Some studies examined the frequency of lymph node micrometastasis in histologically node-negative gastric cancer limited to the mucosa or submucosa. However, T1 tumors have a good prognosis, and the prognostic significance of lymph node micrometastasis from gastric cancer remains unclear.
To clarify the prognostic importance of lymph node micrometastasis in patients with gastric cancer, histologically node-negative gastric cancers invading the muscularis propria or deeper (T2 and T3) were selected by Yasuda.
The author's results indicate that lymph node micrometastasis is an independent prognostic indicator for patients with histologically node-negative gastric cancer invading the muscularis propria or deeper (T2 or T3).
Micrometastasis of four or more lymph nodes or micrometastasis of level 2 nodes was significantly associated with a poor outcome.

Lymph node metastasis is linked to tumor progression.Lymph node micrometastasis in gastric cancer is also associated with deep invasion through the gastric wall, large tumor size, and positive lymphatic or venous invasion.
In this study, although no relationship was found between the presence of lymph node micrometastasis and clinico-pathologic characteristics, a weak association was found between lymph node micrometastasis and depth of wall invasion.

In this series, the most common pattern of recurrence was peritoneal and lung metastasis. Similar to these results, previous studies reported that lymph node micrometastasis was strongly associated with subsequent development of hematogenous and peritoneal metastases, but not locoregional lymph node recurrence ( 1 ).

While the presence of lymph node metastases in early gastric cancer (EGC) is the most significant prognostic factor, the relevance of lymph node micrometastases remains uncertain. Morgagni et al. studied 5400 lymph nodes dissected from 300 patients treated surgically for EGC between 1976 and 1999, all of whom were histologically pN0. Micrometastases were defined as single or small clusters of neoplastic cells identifiable only by immunohistochemical methods. Lymph node micrometastases were observed in 30 of the 300 patients (10%). No significant correlation was observed between micrometastases and other clinicopathological characteristics. Analysis of overall survival showed no significant difference between positive or negative micrometastasis groups. The results of their study show that the presence of lymph node micrometastases in EGC does not influence patient prognosis ( 2 ).

The intraoperative diagnosis of lymph node micrometastasis (LNM) may help guide the area of appropriate lymph node dissection. Matsumoto et al aimed to evaluate the rapid immunohistochemical detection of LNMs using frozen sections during operation for gastro-oesophageal cancer.
Rapid immunostaining with anticytokeratin (AE1/AE3) antibody was compared with conventional immunostaining. A total of 210 lymph nodes obtained from 47 patients with oesophageal squamous cell carcinoma and from 32 with gastric adenocarcinoma were examined during operation. Lymph nodes were frozen, sectioned, and examined by histological and immunohistochemical methods.
It took 30 min to complete the rapid immunostaining procedure; the expression of cytokeratin by rapid immunostaining was similar to that by conventional immunostaining. The incidence of lymph node metastasis detected by histological and immunohistochemical examination was 17 and 23 per cent respectively. LNM was solely detected in 12 lymph nodes by immunostaining: three micrometastases and nine with tumour cell microinvolvement.
Intraoperative rapid immunostaining is a simple and useful technique for detecting LNMs. Further study should investigate the role of rapid immunostaining during cancer surgery to select appropriate areas for lymphadenectomy ( 7 ).


1) Kazuhiro Yasuda, Yosuke Adachi, Norio Shiraishi, Masafumi Inomata, Hiroaki Takeuchi, and Seigo Kitano. Prognostic Effect of Lymph Node Micrometastasis in Patients With Histologically Node-Negative Gastric Cancer. Annals of Surgical Oncology, 9(8):771-774. Pub Med

2) Paolo Morgagni et al. Lymph Node Micrometastases in Early Gastric Cancer and Their Impact on Prognosis. World J. Surg. 27, 558-561, 2003. Pub Med

3) Cai J, Ikeguchi M, Maeta M, et al. Micrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer. Surgery 2000;127:32-39. Pub Med

4) Cai J, Ikeguchi M, Tsujitani S, et al. Micrometastasis in lymph nodes of mucosal gastric cancer. Gastric Cancer 2000;3:91-96. Pub Med

5) Folli S, Morgagni P, Roviello F, et al. Risk factors for lymph node metastases and their prognostic significance in Early Gastric Cancer for the Italian Research Group for Gastric Cancer (IRGGC). Jpn. J. Clin.Oncol. 2001;31:495-499. Pub Med

6) Saragoni L, Gaudio M, Morgagni P, et al. Identification of occult micrometastases in patients with early gastric cancer using anti cytokeratin monoclonal antibodies. Oncol. Rep. 2000;7:535-539. Pub Med

7) M. Matsumoto, S. Natsugoe, S. Ishigami, Y. Uenosono, S. Takao and T. Aikou. Rapid immunohistochemical detection of lymph node micrometastasis during operation for upper gastrointestinal carcinoma. British Journal of Surgery 2003;90 563 -566. Pub Med

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