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Original Investigation |

Pattern and Clinical Predictors of Lymph Node Involvement in Nonfunctioning Pancreatic Neuroendocrine Tumors (NF-PanNETs)

Stefano Partelli, MD1; Sebastien Gaujoux, MD, PhD2,3; Letizia Boninsegna, MD, PhD1,3; Rim Cherif, MD2; Stefano Crippa, MD1; Anne Couvelard, MD3,4; Aldo Scarpa, MD2; Philippe Ruszniewski, MD3,5; Alain Sauvanet, MD2,3; Massimo Falconi, MD1
[+] Author Affiliations
1Departments of Surgery and Pathology, University of Verona, Verona, Italy
2Department of Hepato-Biliary-Pancreatic Surgery, Pole des maladies de l’appareil digestif, Hopital Beaujon, Assistance Publique–Hopitaux de Paris, Clichy, France
3University Paris 7 Denis Diderot, Paris, France
4Department of Pathology, Hopital Bichat, Assistance Publique–Hopitaux de Paris, Paris, France
5Department of Gastroenterology-Pancreatology, Pole des maladies de l’appareil digestif, Hopital Beaujon, Assistance Publique–Hopitaux de Paris, Clichy, France
JAMA Surg. 2013;148(10):932-939. doi:10.1001/jamasurg.2013.3376.
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Importance  Nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs) are often indolent neoplasms without lymph node (LN) metastasis at diagnosis. Therefore, in patients with low risk of LN metastasis, the extent of surgery and lymphadenectomy could be limited and follow-up adjusted to the very low risk of relapse.

Objective  To construct a predicting model to assess the risk of pN+ prior to surgical resection for NF-PanNETs using preoperative retrievable variables.

Design  Retrospective review using multiple logistic regression analysis to construct predictive model of pN+ based on preoperatively available data.

Setting  The combined prospective databases of the Surgical Departments of the University of Verona, Verona, Italy, and Beaujon Hospital, Clichy, France, were queried for clinical and pathological data.

Participants  All patients with resected (R0 or R1), pathologically confirmed NF-PanNETs between January 1, 1993 and December 31, 2009.

Main Outcome and Measure  Risk of lymph node metastases in patients with pancreatic neuroendocrine tumors.

Results  Among 181 patients, nodal metastases were reported in 55 patients (30%) and were associated with decreased 5-year disease-free survival (70% vs 97%, P < .001). Multivariable analysis showed that independent factors associated with nodal metastasis were radiological nodal status (rN) (odds ratio [OR], 5.58; P < .001) and tumor grade (NET-G2 vs NET-G1: OR, 4.87; P < .001) (first model). When the tumor grade was excluded, rN (OR, 4.73; P = .001) and radiological tumor size larger than 4 cm (OR, 2.67; P = .03) were independent predictors of nodal metastasis (second model). The area under the receiver operating characteristic curve for the first and second models were 80% and 74%, respectively.

Conclusions and Relevance  Patients with NF-PanNET-G1 have a very low risk of pN+ in the absence of radiological signs of node involvement. When preoperative grading assessment is not achieved, the radiological size of the lesion is a powerful alternative predictor of pN+. The risk of pathological nodal involvement in patients with NF-PanNETs can be accurately estimated by a clinical predictive model.

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Figure 1.
Disease-Free Survival

Disease-free survival curve (Kaplan-Meier) for the 181 patients with nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs) who underwent resection with curative intent.

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Figure 2.
Disease-Free Survival Comparison of Patients With N0 With Patients With N1

Disease-free survival curves (Kaplan-Meier) comparing 126 patients with N0 with 55 patients with N1 (P < .001, log-rank comparison).

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Figure 3.
Receiver Operator Characteristic Curves for the Predictive Model

Receiver operator characteristic (ROC) curve for the first predictive model (A) and second predictive model (B).

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