Prognostic Analysis And Clinical Predictors Of Lymph Node Metastasis In Nonfunctional Pancreatic Neuroendocrine Tumors(NF-pNETs)

Objective:To explore the clinical and pathological factors associated with the prognosis of non-funcational pancreatic neuroendocrine tumors(NF-pNETs)and lymph node metastasis.We evaluated the feasibility of predicting lymph node metastasis by use of pre-operative variables(LNM).Methods:We conducted a mono-institutional retrospective cohort study to analyze 122 patients with NF-pNETs who underwent resection between January 2002 and December 2015.We evaluated prognostic risk factors using the Kaplan-Meier method and the Cox regression model.Predictors of lymph node metastasis were evaluated using the logistic regression analysis and the predictive power of these models were evaluated using receiver operating characteristic(ROC)curve analysis.Results:Five-year disease-free survival(DFS)and overall survival(OS)of resected NF-pNETs was 70.2%and 76%,respectively.High tumor grading(G2 vs.G1:HR=8.107,P=0.003;G3 vs.G1:HR=115.470,P=0.000),LNM(HR=7.274,P=0.023)and angioinvasion(HR=2.805,P=0.027)were independently associated with decreased DFS.Prognostic scoring system of postoperative recurrence was reliable,with a C-index of 0.717.Female patients(HR=0.16,p=0.013),high tumor grade(G2 vs.G1:HR=3.92,p=0.151;G3 vs.G1:HR=86.319,p=0.000),lymph node metastasis(HR=5.140,p=0.014),CA199>35U/mL(HR=4.890,p=0.017)were independent prognostic factors of overall survival in resected NF-pNETs.Totally,30(24.6%)of these 122 patients had LNM.Multivariate analysis revealed tumor grade was an independent factor associated with LNM(G2 vs.G1:OR=3.340,P=0.044;G3 vs.G1:OR=4.679,P=0.031).When tumor grade was excluded,female patients(OR=0.311,p=0.016),radiological tumor size>2.5 cm(OR=5.874,P=0.003)and presence of symptoms(OR=4.764,P=0.004)were significantly associated with LNM,the area under the curve(AUC)of this model was 0.835.The risk of LNM was remarkably lower in tumors<2.5 cm than that in tumors>2.5 cm(37.7%vs.7.5%,p<0.001),indicating the reliability of this parameter in predicting LNM(AUC=0.730)Incidentally discovered NF-pNETs<2.5 cm were associated with low risk of LNM and excellent survivalConclusions:Tumor grade and LNM are significantly associated with prognosis of nonfunctional pancreatic neuroendocrine tumors,the DFS assessment model can accurately evaluate the risk of recurrence after resection.Radiological tumor size is a reliable predictor of LNM in NF-pNETs and the models are effective in predicting LNM.Our results demonstrate that lymphadenectomy in small(<2.5 cm)NF-pNETs is not routinely necessary.