Neutrophil-to-lymphocyte ratio (NLR) is one of the systemic inflammation markers, which has prognostic values in many types of tumor. However, hardly any research has reported the relationship between NLR and pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to evaluate the predictive value of the preoperative peripheral blood NLR on the clinical outcomes in patients of resectable PanNETs.
Ninety-five cases of PanNETs registered in the First Affiliated Hospital of Zhejiang University between March 2009 and May 2016 and underwent pancreatic surgery were included in this study. Univariate and multivariate analyses were applied to identify the prognostic factors for PanNETs. Prognostic nomogram and its calibration curve then used R (version 3.3.2) to predict lymph node (LN) metastasis.
Among these 95 patients, 52 (54.7%) patients were diagnosed as grade 1 (G1) NET (mitotic count <2/10 HPF, Ki-67 ≤2%), 32 (33.7%) as G2 NET (mitotic count 2–20/10 HPF, Ki-67 3–20%), and 11 (11.6%) as G3 NEC (mitotic count >20/10 HPF, Ki-67 >20%). Increased NLR was found to relate with advanced T stage, LN metastasis, tumor thrombus formation, and advanced grade (p < 0.05 for all). Multivariate logistic regression was performed and indicated that NLR (HR 6.74; p = 0.02) was an independent prognostic factor for LN metastasis. Furthermore, we developed a nomogram based on the combination of NLR, T stage, and grade for LN metastasis with a good discrimination ability with the AUC (area under the curve) of 0.885. This nomogram showed larger AUC than those using NLR (0.725), T stage (0.808), or grade (0.708) alone as a prognostic factor, which means this system achieved a more optional performance in predicting clinical outcomes. Finally, the Kaplan–Meier curve indicated that the recurrence-free survival (RFS) of patients with high NLR (NLR >1.40, RFS 61.1 ± 4.4 months) decreased significantly as compared with those of low NLR (NLR ≤1.40, RFS 63.8 ± 2.9 month, p < 0.05).
The preoperative NLR is a potential independent predictor for LN metastasis and RFS. Our nomogram highlighted the important role of NLR in prognosis, which might be considered as a convenient indicator for lymph node metastasis, especially during the initial diagnosis for resectable PanNETs.
Kim J, Bae JS. Tumor-associated macrophages and neutrophils in tumor microenvironment. Mediat Inflamm. 2016;2016:6058147.
Toste PA, Kadera BE, Tatishchev SF, Dawson DW, Clerkin BM, Muthusamy R, Watson R, Tomlinson JS, Hines OJ, Reber HA, Donahue TR. Nonfunctional pancreatic neuroendocrine tumors <2 cm on preoperative imaging are associated with a low incidence of nodal metastasis and an excellent overall survival. J Gastrointest Surg. 2013;17:2105–13. CrossRefPubMed
Bettini R, Boninsegna L, Mantovani W, Capelli P, Bassi C, Pederzoli P, Delle Fave GF, Panzuto F, Scarpa A, Falconi M. Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours. Ann Oncol. 2008;19:903–8. CrossRefPubMed
Lindberg JM, Walters DM, Stelow EB, Adams RB, Bauer TW. The incidence and preoperative detection of nodal metastases in resected pancreatic neuroendocrine tumors. J Clin Oncol. 2012;30:178. CrossRef
Tao L, Zhang L, Peng Y, Tao M, Li G, Xiu D, Yuan C, Ma C, Jiang B. Preoperative neutrophil-to-lymphocyte ratio and tumor-related factors to predict lymph node metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Oncotarget. 2016;7(45):74314–324
Hirasawa Y, Nakashima J, Yunaiyama D, Sugihara T, Gondo T, Nakagami Y, Horiguchi Y, Ohno Y, Namiki K, Ohori M, Tokuuye K, Tachibana M. Sarcopenia as a novel preoperative prognostic predictor for survival in patients with bladder cancer undergoing radical cystectomy. Ann Surg Oncol. 2016;23(Suppl 5):1048–54.
Caputo D, Caricato M, Coppola A, La Vaccara V, Fiore M, Coppola R. Neutrophil to lymphocyte ratio (NLR) and derived neutrophil to lymphocyte ratio (d-NLR) predict non-responders and postoperative complications in patients undergoing radical surgery after neo-adjuvant radio-chemotherapy for rectal adenocarcinoma. Cancer Invest. 2016;14:1–12.
Bosman FT, Carneiro F, Hruban RH, Theise ND, Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system: International Agency for Research on Cancer. 2010.
Wang H, Taverna D, Stram DO, Fortini BK, Cheng I, Wilkens LR, Burnett T, Makar KW, Lindor NM, Hopper JL, Gallinger S, Baron JA, Haile R, Kolonel LN, Henderson BE, Newcomb PA, Casey G, Duggan D, Ulrich CM, Le Marchand L. Genetic variation in the inflammation and innate immunity pathways and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2013;22:2094–101. CrossRefPubMed
Ten Kate M, Aalbers AG, Sluiter W, Hofland LJ, Sonneveld P, Jeekel J, Van Eijck CH. Polymorphonuclear leukocytes increase the adhesion of circulating tumor cells to microvascular endothelium. Anticancer Res. 2007;27:17–22. PubMed
Katz SC, Donkor C, Glasgow K, Pillarisetty VG, Gonen M, Espat NJ, Klimstra DS, D’Angelica MI, Allen PJ, Jarnagin W, Dematteo RP, Brennan MF, Tang LH. T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases. HPB (Oxford). 2010;12:674–83. CrossRef
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science (New York, NY). 2006;313:1960–4. CrossRef
Mehrazin R, Uzzo RG, Kutikov A, Ruth K, Tomaszewski JJ, Dulaimi E, Ginzburg S, Abbosh PH, Ito T, Corcoran AT, Chen DY, Smaldone MC, Al-Saleem T. Lymphopenia is an independent predictor of inferior outcome in papillary renal cell carcinoma. Urol Oncol. 2015;33:388.e19-25. PubMed
- Predictive value of preoperative peripheral blood neutrophil/lymphocyte ratio for lymph node metastasis in patients of resectable pancreatic neuroendocrine tumors: a nomogram-based study
- BioMed Central
Neu im Fachgebiet Chirurgie
e.Med Kampagnen-Visual, Mail Icon II