A novel scoring system associating with preoperative platelet/lymphocyte and clinicopathologic features to predict lymph node metastasis in early gastric cancer

doi:10.1016/j.jss.2016.10.011

Journal of Surgical Research

Volume 209, March 2017, Pages 153-161

https://doi.org/10.1016/j.jss.2016.10.011 Get rights and content

Abstract

Background

Precise determination of the lymph node status is critical for determining appropriate treatment for early gastric cancer (EGC). This study attempted to establish a simple, effective risk scoring system to predict lymph node metastasis (LNM) in EGC by investigating the relationship between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and EGC LNM.

Materials and methods

We retrospectively reviewed 312 operable patients with EGC. The clinical utility of PLR and NLR was tested by receiver operating characteristic curves. The scoring system was developed using independent risk factors. Finally, 89 EGC patients were collected from prospective database to validate the scoring system's accuracy.

Results

The optimal PLR and NLR cut-off values were 106 and 2.97, respectively. High NLR (P = 0.009) and PLR (P = 0.007) values were associated with LNM of EGC in univariate analyses, although only high PLR (P = 0.025) was an independent risk factor in multivariate analyses, together with age (P = 0.009), differentiation (P = 0.017), invasive depth (P < 0.001), and tumor size (P = 0.003). The scoring system's accuracy for retrospective and prospective data was 0.781 (95% confidence interval: 0.721-0.841) and 0.817 (95% confidence interval 0.714-0.920), respectively.

Conclusions

Preoperative PLR and NLR correlate with EGC LNM. Our scoring system is reliable, accurate, and effective in predicting LNM in EGC patients.

Introduction

Early gastric cancer (EGC) is defined as cancer cells invading the mucosa (T1a) or submucosa (T1b) of the gastric wall, regardless of regional lymph node metastasis (LNM).¹ In the last 50 y, although the incidence of gastric cancer (GC) has been decreasing, the portion of GC diagnosed as clinical early stage has been increasing because of the progress of endoscopic diagnostic technology and other screening programs, especially in Japan and Korea.² With improved early diagnosis of GC, the overall survival of EGC has been increasing, but it declines once LNM develops.³ Currently, compared with traditional invasive treatment ways like laparotomy and laparoscopic resection, minimally invasive approaches to cure EGC, including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR), have increased in frequency. However, these approaches are contraindicated if LNM is present; hence, gastrectomy with lymphadenectomy is required.⁴ In contrast with advanced GC, standard D2 lymphadenectomy is not necessary for EGC without LNM; D1 or D1+ lymphadenectomy could be selected to achieve curative resection.⁵ Therefore, to avoid insufficient treatment or overtreatment, it is essential to confirm whether patients with EGC have LNM before choosing the optimal treatment scheme.

To assess for the presence of LNM, some imaging studies, such as axial computed tomography (CT), magnetic resonance imaging, and positron emission tomography–computed tomography (PET-CT), are typically used. However, these tools are still unable to consistently and precisely predict LNM, especially in EGC.6, 7 In addition, some studies reported that several new methods and biomarkers were useful in identifying LNM in GC,8, 9, 10 but considering economic efficiency and feasibility, these techniques are difficult to use widely in the clinic. Therefore, we still lack an effective preoperative biomarker that can be conveniently be put into widespread use for predicting LNM in patients with EGC.

Recently, numerous investigations have demonstrated that the systemic inflammatory response is closely related to tumor progression.¹¹ Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), two novel inflammation-related biomarkers, have been confirmed to be prognostic indicators in epithelial ovarian cancer, esophageal squamous cell cancer, and colorectal neoplasms.12, 13, 14 However, as far as we are aware, no studies have reported the association between PLR, NLR, and LNM in EGC.

Therefore, this study was designed to detect the relationship between PLR and NLR and EGC LNM and to develop a novel, simple, and practical risk scoring system combining inflammation-related variables with other clinicopathologic factors to predict LNM in EGC.

Section snippets

Patients

We retrospectively collected 649 patients with EGC who underwent curative gastrectomy with standard D1 or D2 lymphadenectomy, confirmed by postoperative pathology, from January 2006 to January 2014 in the First Affiliated Hospital of Wenzhou Medical University, China. The exclusion criteria for this study were (1) fewer than 15 dissected lymph nodes (LNs; the patients were included if the final pathology shown LNM even if lacking enough dissected LNs), (2) hepatocirrhosis or hematological

Clinicopathologic characteristics

Of the 312 patients with EGC, 225 patients (72.1%) were men, 87 (27.9%) were women, and the mean age was 60.0 ± 10.8 y (range 29-81). Postoperative pathologic inspection confirmed 75 patients (24.0%) with LNM, and the number with N1, N2, and N3 stages were 47 (62.7%), 19 (25.3%), and 9 (12%), respectively, according to the Union for International Cancer Control TNM Classification of Malignant Tumors, Seventh Edition.¹⁶ Other clinicopathologic characteristics, including tumor size, tumor

Discussion

In recent years, many studies have found that LNM is significantly associated with poor prognosis in EGC patients.¹⁷ To keep relatively normal stomach functioning, promote faster postoperative recovery, and provide a better postoperative quality of life, minimally invasive treatments, including ESD and EMR, have become routine procedures for EGC. Although the indications for ESD and EMR are expanding, LNM remains a contraindication for these procedures. A second procedure, radical gastrectomy

Conclusion

This is the first study to investigate the relationship between inflammation-related factors (NLR and PLR) and LNM in patients with EGC. We found that NLR and PLR are both novel preoperative biomarkers that are closely associated with LNM of EGC, and that PLR is especially important. The new scoring system combining PLR and clinicopathologic factors in our study has been demonstrated to be an economical, reliable, and convenient tool to predict LNM in patients with EGC. This tool could assist

Acknowledgment

Authors' contribution: N.L. analyzed and interpreted the data and drafted the manuscript. L.Z. designed the study. X.-D.C. and W.-Y.P. performed statistical analysis. C.A. and C.-L.Z. interpreted the data and revised the manuscript. Y.-P.H. acquired data. X.S. contributed to the conception of the study.

Supported by the National Nature Science Foundation of China (Grant Nos. 31470891, 81001343).

References (36)

F. Balkwill et al.
Inflammation and cancer: back to Virchow?
Lancet
(2001)
J.F. Feng et al.
The combination of platelet count and neutrophil lymphocyte ratio is a predictive factor in patients with esophageal squamous cell carcinoma
Translational Oncol
(2014)
S.A. Weitzman et al.
Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis
Blood
(1990)
I.E. Ertas et al.
Can preoperative neutrophil:lymphocyte and platelet:lymphocyte ratios be used as predictive markers for lymph node metastasis in squamous cell carcinoma of the vulva?
Eur J obstetrics, Gynecol Reprod Biol
(2013)
T. Kajitani
The general rules for the gastric cancer study in surgery and pathology. Part I. Clinical classification
Jpn J Surg
(1981)
C. Hamashima et al.
The Japanese guidelines for gastric cancer screening
Jpn J Clin Oncol
(2008)
V. Pasechnikov et al.
Gastric cancer: prevention, screening and early diagnosis
World J Gastroenterol
(2014)
B.W. Eom et al.
Optimal submucosal invasion of early gastric cancer for endoscopic resection
Ann Surg Oncol
(2015)
Japanese gastric cancer treatment guidelines 2010 (ver. 3)
Gastric Cancer
(2011)
M. Nakagawa et al.
Difficulty of predicting the presence of lymph node metastases in patients with clinical early stage gastric cancer: a case control study
BMC Cancer
(2015)

R. Seevaratnam et al.

How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis

Gastric Cancer

(2012)

K.H. Huang et al.

The correlation between miRNA and lymph node metastasis in gastric cancer

Biomed Research International

(2015)

W. Li et al.

Protein predictive signatures for lymph node metastasis of gastric cancer

Int J Cancer

(2013)

Y.W. Wang et al.

Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers

Tumour Biol

(2016)

S. Raungkaewmanee et al.

Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer

J Gynecol Oncol

(2012)

M. Ishizuka et al.

Combination of platelet count and neutrophil to lymphocyte ratio is a useful predictor of postoperative survival in patients with colorectal cancer

Br J Cancer

(2013)

R. Fluss et al.

Estimation of the Youden Index and its associated cutoff point

Biometrical J Biometrische Z

(2005)

A. Biondi et al.

Seventh edition of TNM classification for gastric cancer

J Clin Oncol

(2011)

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¹: Co-first coauthors, these authors contributed equally to this work.

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GastrointestinalA novel scoring system associating with preoperative platelet/lymphocyte and clinicopathologic features to predict lymph node metastasis in early gastric cancer

Abstract

Background

Materials and methods

Results

Conclusions

Introduction

Section snippets

Patients

Clinicopathologic characteristics

Discussion

Conclusion

Acknowledgment

Lancet

Translational Oncol

Blood

Eur J obstetrics, Gynecol Reprod Biol

The general rules for the gastric cancer study in surgery and pathology. Part I. Clinical classification

Jpn J Surg

The Japanese guidelines for gastric cancer screening

Jpn J Clin Oncol

Gastric cancer: prevention, screening and early diagnosis

World J Gastroenterol

Optimal submucosal invasion of early gastric cancer for endoscopic resection

Ann Surg Oncol

Japanese gastric cancer treatment guidelines 2010 (ver. 3)

Gastric Cancer

Difficulty of predicting the presence of lymph node metastases in patients with clinical early stage gastric cancer: a case control study

BMC Cancer

How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis

Gastric Cancer

The correlation between miRNA and lymph node metastasis in gastric cancer

Biomed Research International

Protein predictive signatures for lymph node metastasis of gastric cancer

Int J Cancer

Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers

Tumour Biol

Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer

J Gynecol Oncol

Combination of platelet count and neutrophil to lymphocyte ratio is a useful predictor of postoperative survival in patients with colorectal cancer

Br J Cancer

Estimation of the Youden Index and its associated cutoff point

Biometrical J Biometrische Z

Seventh edition of TNM classification for gastric cancer

J Clin Oncol

Gastrointestinal
A novel scoring system associating with preoperative platelet/lymphocyte and clinicopathologic features to predict lymph node metastasis in early gastric cancer