A simple method is to inject tumor cells into a lymph node and examine the presence of tumor cells in each organ [1].

Inoculation of luciferase-expressing tumor cells into the subiliac lymph node.

Metastasis to the proper axillary lymph node was confirmed (left). Tumor cells were also found in distant organs (right).

Figure. Tumor cells inoculated into the subiliac lymph nodes metastasize to the proper axillary lymph nodes via the lymphatic vessels. The organs were removed 14 days after inoculation, and luciferase activity was measured. Metastases were also found in other lymph nodes, liver and lung [1].

We have proposed the theory of lymph node-mediated hematogenous metastasis, in which tumor cells metastasize to distant organs in the bloodstream via sentinel lymph nodes [2-4].

The method developed based on this theory is the lymphatic drug delivery system [5-8].

Prophylactic treatment of lymph node metastasis may be important at the stage of confirmation of the primary tumor site.

References
[1] L. Li, S. Mori, M. Sakamoto, S. Takahashi, T. Kodama, Mouse model of lymph node metastasis via afferent lymphatic vessels for development of imaging modalities, PloS one, 8 (2013) e55797.
[2] T. Kodama, S. Mori, M. Nose, Tumor cell invasion from the marginal sinus into extranodal veins during early-stage lymph node metastasis can be a starting point for hematogenous metastasis, Journal of Cancer Metastasis and Treatment, 4 (2018) 56.
[3] L. Shao, K. Takeda, S. Kato, S. Mori, T. Kodama, Communication between lymphatic and venous systems in mice, Journal of immunological methods, 424 (2015) 100-105.
[4] K. Takeda, S. Mori, T. Kodama, Study of fluid dynamics reveals direct communications between lymphatic vessels and venous blood vessels at lymph nodes of mice, Journal of immunological methods, 445 (2017) 1-9.
[5] H. Fujii, S. Horie, A. Sukhbaatar, R. Mishra, M. Sakamoto, S. Mori, T. Kodama, Treatment of false-negative metastatic lymph nodes by a lymphatic drug delivery system with 5-fluorouracil, Cancer Med, 8 (2019) 2241-2251.
[6] R. Fukumura, A. Sukhbaatar, R. Mishura, M. Sakamoto, S. Mori, T. Kodama, Study of the physicochemical properties of drugs suitable for administration using a lymphatic drug delivery system, Cancer Sci, (2021).
[7] T. Kodama, D. Matsuki, A. Tada, K. Takeda, S. Mori, New concept for the prevention and treatment of metastatic lymph nodes using chemotherapy administered via the lymphatic network, Scientific reports, 6 (2016) 32506.
[8] A. Tada, S. Horie, S. Mori, T. Kodama, Therapeutic effect of cisplatin given with a lymphatic drug delivery system on false-negative metastatic lymph nodes, Cancer Sci, 108 (2017) 2115-2121.