Significance of Lymph Node Metastasis in the Treatment of Gastric Cancer and Current Challenges in Determining the Extent of Metastasis

Abstract

The stomach exhibits abundant lymphatic flow, and metastasis to lymph nodes is common. In the case of gastric cancer, there is a regularity to the spread of lymph node metastasis, and it does not easily metastasize outside the regional nodes. Furthermore, when its extent is limited, nodal metastasis of gastric cancer can be cured by appropriate lymph node dissection. Therefore, identifying and determining the extent of lymph node metastasis is important for ensuring accurate diagnosis and appropriate surgical treatment in patients with gastric cancer. However, precise detection of lymph node metastasis remains difficult. Most nodal metastases in gastric cancer are microscopic metastases, which often occur in small-sized lymph nodes, and are thus difficult to diagnose both preoperatively and intraoperatively. Preoperative nodal diagnoses are mainly made using computed tomography, although the specificity of this method is low because it is mainly based on the size of the lymph node. Furthermore, peripheral nodal metastases cannot be palpated intraoperatively, nodal harvesting of resected specimens remains difficult, and the number of lymph nodes detected vary greatly depending on the skill of the technician. Based on these findings, gastrectomy with prophylactic lymph node dissection is considered the standard surgical procedure for gastric cancer. In contrast, several groups have examined the value of sentinel node biopsy for accurately evaluating nodal metastasis in patients with early gastric cancer, reporting high sensitivity and accuracy. Sentinel node biopsy is also important for individualizing and optimizing the extent of uniform prophylactic lymph node dissection and determining whether patients are indicated for function-preserving curative gastrectomy, which is superior in preventing post-gastrectomy symptoms and maintaining dietary habits. Notably, advancements in surgical treatment for early gastric cancer are expected to result in individualized surgical strategies with sentinel node biopsy. Chemotherapy for advanced gastric cancer has also progressed, and conversion gastrectomy can now be performed after downstaging, even in cases previously regarded as inoperable. In this review, we discuss the importance of determining lymph node metastasis in the treatment of gastric cancer, the associated difficulties, and the need to investigate strategies that can improve the diagnosis of lymph node metastasis.

Keywords: MDCT; gastric cancer; lymph node metastasis; sentinel node; staging.

Figure 1

Regional lymph nodes and station numbers in gastric cancer. This classification and the station numbers are based on the Japanese Classification of Gastric Carcinoma. The details of the nodal station numbers have been described in Table 2 . (A) Perigastric nodes and nodes along the left gastric artery. These nodes nearly correspond to group 1 nodes. (B) Nodes around the celiac artery, along the proper hepatic artery and suprapancreatic nodes. These nodes nearly correspond to the group 2 nodes. (C) The subcategory of No. 6 nodes. (D) Nodes in deeper layers. Para-aortic lymph nodes and No. 19 nodes. These nodes nearly correspond to group 3 nodes.

Figure 2

Schematic diagram of the lymphatic system of the stomach. The lymphatic flow of the stomach spreads from the perigastric nodes, via the suprapancreatic nodes and nodes around the celiac artery, to the para-aortic nodes, following which it enters the systemic circulation. (A) Lymphatic flow from the gastric wall is directed to the root of each artery via nearby perigastric nodes (red arrows). (B) The lymphatic flow into the root of each artery flows via suprapancreatic nodes (orange arrows) and out to the paraaortic nodes from the left and right of the celiac artery (red arrows). There are also routes from #8a to #8p (the posterior side of the common hepatic artery), and routes from #6 to the root of the superior mesenteric artery via #14v (green arrows). Routes from #6 to the suprapancreatic nodes via the lymphatics under the pancreatic capsule are also available (indigo arrows). (C) Lymphatic flow around the celiac artery and the superior mesenteric artery lead to the paraaortic nodes, which are the terminal lymph nodes of gastric cancer (red arrows). A route from the left dorsal side of the cardia to #16a2 lateral nodes via #19, along the left subphrenic artery also exists (green arrows).

Figure 3

Schematic diagram of the development and molecular mechanisms of nodal metastasis in gastric cancer. Lymph node metastasis can be divided into multiple stages: lymphangiogenesis, induction of cell migration, invasion of cancer stem cells into the lymphatic system, arrival of cancer stem cells in sentinel lymph nodes, and establishment of micrometastasis in the marginal sinus. The vascular endothelial growth factor (VEGF) family is involved in lymphangiogenesis, and Wnt-5a is involved in the induction of cell migration. T, tumor; M, mucosal layer; SM, submucosal layer; MP, proper muscle layer; SS, subserosal layer; LN, lymph node; VEGF, vascular endothelial growth factor.