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368prospective and the number of patients was small. Second, in our small cohort, there were no cases of poorly differentiated esophageal cancer, and the analysis might have been affected by this biased population.In conclusion, the results of this study suggest that micrometastasis to lymph nodes may be a prognostic factor, even in advanced esophageal cancer. The degree of differentiation was not related to micrometastasis or survival. Further studies are needed with more patients and addition of patients with poorly differentiated SCC to examine the underlying mechanisms.AcknowledgmentsI would like to thank Dr. Takao Ando for prior examination of the relationships among microme-tastasis, pathological differentiation grade and outcomes in patients with esophageal SCC and was a major contributor in writing this manuscript.The authors received no financial support for the study.Author contributionsTAsakura performed data analysis and wrote the first draft of the manuscript.HT corrected and approved the manuscript.TM, AA contributed to material on pathology.TAndo provided advice on micrometastasis and contributed to writing the manuscript.NT, MT, YK made significant changes in revi-sion of the manuscript.All authors read and approved the final manu-script.Conflicts of interest statementThe authors declare that there are no conflicts of interest. 1) Natsugoe S, Mueller J, Stein HJ, et al: Micrometastasis and tumor cell microinvolvement of lymph nodes from esophageal squamous cell carcinoma. Cancer, 1998; 83: 858-866. 2) Glickman JN, Torres C, Wong HH, et al: The prog-nostic significance of lymph node micrometastasis in patients with esophageal carcinoma. Cancer, 1999; 85: 769-778. 3) Komukai S, Nishimaki T, Watanabe H, et al: Significance of immunohistochemically demonstrated micrometas-tases to lymph nodes in esophageal cancer with histo-logically negative nodes. Surgery, 2000; 127: 40-47. 4) Matsumoto M, Natsugoe S, Nakashima S, et al: Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma. Cancer Lett, 2000; 153: 189-197. 5) Nakamura T, Ide H, Eguchi R, et al: Clinical implica-tions of lymph node micrometastasis inpatients with histologically node-negative (pN0) esophageal carci-noma. J Surg Oncol, 2002; 79: 224-229. 6) Izbichi JR, Hosch SB, Pichlmeier U, et al: Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer. N Engl J Med, 1997; 337: 1188-1194. 7) Hou X, Gu YK, Liu XW, et al: The impact of tumor cell differentiation on survival of patients with resectable esophageal squamous cell carcinomas. Ann Surg Oncol, 2015; 22: 1008-1014. 8) Chen SB, Liu DT, Huang SJ, et al: Prognostic value of occult lymph node metastasis in patients with completely resected esophageal squamous cell carci-noma. Sci Rep, 2020; 10: 22007. 9) Ando T, Tsurumaru M, Kajiyama M, et al: Clinical importance of detecting micrometastasis of esophageal cancer in lymph nodes by staining with anti-cytoker-atin antibody. Juntendo Med J, 2009; 55, 128-135.10) Hashiguchi T, Nasu M, Hashimoto T, et al: Docetaxel, cisplatin and 5-fluorouracil adjuvant chemotherapy following three-field lymph node dissection for stage II/III N1, 2 esophageal cancer. Mol Clin Oncol, 2014; 2: 719-724.11) Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours. 8th ed. NJ: Wiley-Blackwell; 2016.12) Kelly RJ, Ajani JA, Kuzdzal J, et al: Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med, 2021; 384: 1191-1203.FundingReferences