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Neutrophil/lymphocyte ratio as a predictor of lymph node metastasis in extramammary Paget disease: A retrospective study

Ebata, Aoi Taki, Tomoki Mori, Shoichiro Murakami, Yoshie Urata, Toru Okumura, Mao Akanabe, Honami Imai, Satoko Yokota, Kenji Akiyama, Masashi 名古屋大学

2021.10

概要

To the Editor:
We evaluated the potential of neutrophil-to-lymphocyte ratio (NLR) as a biomarker for lymph node metastasis (LNM) risk in extramammary Paget’s disease (EMPD).

Our retrospective study involved 137 EMPD patients who underwent sentinel lymph node biopsy (SLNB) at our hospital from March 2003 to March 2020. The period between diagnosis and blood test, and that between blood test and SLNB averaged 9.7 (range of 0-68) days and 34.0 (range of 0-103) days, respectively. This study was approved by our institutional review board. The χ² test, Mann–Whitney U test, logistic regression analysis and Kruskal–Wallis test were used to analyze the correlations between NLR and clinical features/laboratory findings, and between SLNB positivity and clinical features/laboratory findings. Receiver–operator curves were constructed using the DeLong model to define the optimal NLR cutoff value. All analyses were performed using EZR version 1.50 for Mac OS X.

The NLR cutoff value was defined as 3.0. The high-NLR group had 30 patients whose NLRs exceeded 3 (NLR>3), and 23% of the patients showed sentinel LNM (SLNM). The low-NLR group had 107 patients whose NLRs were no more than 3 (NLR≦3), and 8% of the patients had SLNM (Table 1). Then, we classified the patients into two groups by SLNB results. 16 of the 137 patients (11.7%) showed SLNM. The rate of SLNM was significantly higher in the high-NLR group than in the low-NLR group (χ² test, p- value=0.0245). The odds ratio of SLNM for patients with NLR>3 was 3.311 (95% CI 1.117 to 9.804, p-value=0.0380) compared to patients with NLR≦3 (Table 2). In the logistic regression analysis of five variables in 137 patients (Table 2) and six variables including CEA in 55 patients (Supplementary Table 1) for SLNB positivity, only NLR was found to be significantly associated with was found in the exact NLR value between the No significant difference and -negative groups, nor among patient groups with 0, 1, 2 or >2 metastatic LNs (Supplementary Figures 1, 2).

Since the NLR integrates information on the inflammatory environment and physiological stress, many studies have proposed that NLR is superior to other leukocyte parameters for predicting the prognoses of various diseases.1, 2 Additionally, NLR is less likely to be affected by many factors such as smoking, body weight and blood pressure.3 Many recent studies have suggested that an elevated NLR is associated with poor outcomes for various cancers, but the mechanisms are poorly understood.4 The high NLR may reflect the patients’ greater tumor burden or more prolonged chronic inflammation, which are associated with disease progression and poor prognosis.

The utility of SLNB has not been established in EMPD. Here we reported NLR might be a significant predictor for LNM in EMPD patients, providing us with a clue for determining which of them could benefit from SLNB. The conclusion should be validated by larger prospective studies. Further investigations are required to explore the impact of NLR on disease-free survival, progression-free survival, overall survival and even response to therapy.

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参考文献

1. Azab B, Shah N, Radbel J, Tan P, Bhatt V, Vonfrolio S et al. Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients. Med Oncol 2013;30:432.

2. Huang W, Huang J, Liu Q, Lin F, He Z, Zeng Z et al. Neutrophil-lymphocyte ratio is a reliable predictive marker for early-stage diabetic nephropathy. Clin Endocrinol (Oxf) 2015;82:229-33.

3. Ma J, Kuzman J, Ray A, Lawson BO, Khong B, Xuan S et al. Neutrophil-to- lymphocyte Ratio (NLR) as a predictor for recurrence in patients with stage III melanoma. Sci Rep 2018;8:4044.

4. Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 2014;106:dju124.

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