Spread and metastasis of esophageal cancer

The spread and metastasis of esophageal cancer are as follows:

1. Diffusion within the esophageal wall

Cancer cells most often spread within the esophageal wall along the submucosal lymphatic vessels and invade the esophageal muscularis.

(ii) Direct infiltration

Since the esophagus has no serosal layer, direct infiltration can occur. Upper esophageal cancer can invade the larynx, trachea, and soft tissue of the neck; middle esophageal cancer can invade the trachea, bronchi, hilum, lung tissue, aorta, and azygos vein; lower esophageal cancer can invade the cardia, pericardium, and abdominal organs.

(III) Lymphatic metastasis

Lymphatic metastasis of esophageal cancer is relatively common, often involving the left supraclavicular lymph nodes, paraesophageal and regional lymph nodes. The site of metastasis is related to the direction of lymphatic drainage.

(IV) Hematogenous metastasis

Most of them are advanced cases, metastasizing to tissues such as the liver, lungs, bones, kidneys and adrenal glands. A large number of experiments have found that tumors cannot grow in organs that lack vascularization, and tumor growth and metastasis depend on vascularization. Tumor cells can secrete a large amount of vascular endothelial growth factor (VEGF). VEGF plays a key role in the formation of tumor stroma and neovascularization, and is related to tumor infiltration and metastasis. VEGF is a highly specific mitogen for vascular endothelial cells with dual functions: increasing microvascular permeability, promoting plasma fibrin extravasation, and providing a fibrous network for the migration of multiple cells during the angiogenesis process. VEGF directly stimulates endothelial cell proliferation by binding to two special tyrosine kinase receptors on endothelial cells, thereby promoting angiogenesis. Experiments have confirmed that tumors are in a dormant state before angiogenesis activity is manifested, and their cell replication rate is the same as that of tumor cells in a growing state. The production and death of tumor cells in a dormant state are balanced, so tumor cells do not show excessive growth. Micrometastases in a dormant state also have similar conditions, and metastatic symptoms do not appear. However, when blood vessels are formed vigorously in the tumor, stimulating factors that promote tumor growth play a large role, and the number of new capillaries in the tumor increases, promoting tumor growth. Due to the increase in blood vessels in the tumor, the chance of tumor cells metastasizing to distant sites is increased, and the micrometastases that were originally in a dormant state also grow rapidly and show obvious clinical symptoms. The positive expression of VEGF in esophageal cancer tissue is significantly higher than that in negative tissue, and the expression of VEGF protein at the front edge of tumor infiltration is significantly higher than that in other parts, and the microvascular density is also higher, indicating that VEGF protein expression is consistent with the site of angiogenesis. Therefore, the abundant blood vessels not only increase the probability of tumor cells entering the circulation, but also can invade the adjacent lymphatic vessels accompanying the capillaries, or enter the lymphatic vessels through the lymphatic vein connection, thereby promoting lymphatic metastasis. In cases with strong positive VEGF expression, almost all of them have lymph node metastasis. In all cases of esophageal cancer, the depth of invasion is positively correlated with the intensity of VEGF expression, indicating that VEGF expression is closely related to TNM staging, that is, cases with poor TNM staging have higher VEGF expression than those with good TNM staging. Therefore, VEGF protein expression in esophageal cancer is closely related to tumor metastasis behavior. It may be used as one of the indicators for determining tumor metastasis.