Prognostic role of examined and positive lymph nodes after distal pancreatectomy for non-functioning neuroendocrine neoplasms

Background The most appropriate nodal staging system for non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) remains unclear. Despite some evidence are available for pancreaticoduodenectomy (PD), the adequate nodal staging is still unknown for distal pancreatectomy (DP). Aim of the present study was to evaluate the prognostic impact of the number of positive lymph nodes after DP for NF-PanNENs and to define the minimal number of lymph nodes to be harvested for an appropriate nodal staging. Methods Data were retrospectively collected from patients who underwent DP with curative intent (R0-R1) for sporadic well-differentiated NF-PanNETs in four Europeans high-volume centers. NF-PanNETs with nodal involvement (N+) were sub-classified into N1 (1 to 3 positive lymph nodes) and N2 (4 or more positive lymph nodes). Univariate and multivariate analyses of disease-free survival (DFS) were performed. Results Out of 271 patients in the study, 62 (23%) had nodal involvement (N+). A higher probability of N+ was associated to the following factors: grading, resection margins status, perineural and microvascular invasion and the number of examined lymph nodes. 3-years DFS rate for N0, N1 and N2 patients was 92%, 72% and 50%, respectively (P< 0.001). At multivariate analysis independent predictors of DFS were grading, T stage, presence of necrosis and nodal status. For patients with ≥ 12 examinedresected lymph nodes, the N status remained a significant predictor of disease recurrence (P< 0.001), while it failed to predict recurrence in patients with <12 lymph nodes examinedresected (P= 0.116). Conclusions A minimal number of 12 nodes should be harvested in case of distal pancreatectomy for NF-PanNET for an appropriate nodal staging. The number of positive lymph-nodes is an independent predictor of DFS survival after DP for NF-PanNET and the N0/N1/N2 nodal classification seems to be more relevant than the current N0/N+ staging.