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Peritumoral Lymphatic Vessels Associated with Resistance to Neoadjuvant Chemotherapy and Unfavorable Survival in Esophageal Cancer

  • Health Services Research and Global Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Peri- or intra-tumor lymphangiogenesis is induced in several types of cancer. However, the significance of peritumoral lymphatic vessels (LVs) in esophageal cancer (EC) remains to be clarified.

Methods

This study included 162 eligible EC patients with or without neoadjuvant chemotherapy (NAC). The numbers of non-tumoral and peritumoral LVs were counted in resected specimens based on podoplanin immunostaining. The association between peritumoral LV number and clinicopathologic parameters, including tumor heterogeneity as measured by positron emission tomography, NAC response, and patient survival were analyzed.

Results

In non-NAC patients, the number of peritumoral LVs was highest in the lamina propria mucosa (LPM), followed by non-tumoral LVs in the LPM, peritumoral LVs in the submucosa (SM), and non-tumoral LVs in the SM. The patients with a low number of peritumoral LVs in the LPM versus those with a high number constituted a larger fraction of the NAC patients (67.8% vs. 50.0%; P = 0.022) and had a poorer pathologic response to NAC (grades 0–1a: 68.8% vs. 47.2%; P = 0.035), as well as greater tumor heterogeneity and worse survival (5-year overall survival: 50.6% vs. 72.8%; P = 0.0097). The number of peritumoral LVs in the LPM was identified as an independent prognostic factor with the highest hazard ratio (HR) of overall survival (HR 2.06; P = 0.0049) in the multivariate analysis.

Conclusion

For EC patients, peritumoral LVs in the LPM layer are associated with tumor heterogeneity, response to NAC, and unfavorable survival.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Takeo Hara MD, PhD, Tomoki Makino MD, PhD, Makoto Yamasaki MD, PhD, Koji Tanaka MD, PhD, Kotaro Yamashita MD, PhD, Yuya Nogi MD, Takuro Saito MD, PhD, Tsuyoshi Takahashi MD, PhD, Yukinori Kurokawa MD, PhD, Kiyokazu Nakajima MD, PhD, Hidetoshi Eguchi MD, PhD & Yuichiro Doki MD, PhD

  2. Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Mitsuaki Tatsumi MD, PhD

  3. Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Eiichi Morii MD, PhD

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Correspondence to Tomoki Makino MD, PhD.

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Supplemental Figure 1

Kaplan–Meier analysis of overall survival in NAC patients (A), and non-NAC patients (B) according to number of peritumoral lymphatic vessels (LVs) in the lamina propria mucosa. (TIFF 92 kb)

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Hara, T., Makino, T., Yamasaki, M. et al. Peritumoral Lymphatic Vessels Associated with Resistance to Neoadjuvant Chemotherapy and Unfavorable Survival in Esophageal Cancer. Ann Surg Oncol 27, 3762–3769 (2020). https://doi.org/10.1245/s10434-020-08474-x

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