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    Substaging nodal status in ampullary carcinomas has significant prognostic value: Proposed revised staging based on an analysis of 313 well-characterized cases
    (Society of Surgical Oncology, 2015) Balcı, Serdar; Baştürk, Olca; Saka, Burcu; Bağcı, Pelin; Postlewait, Lauren Mc Lendon; Tajiri, Takuma; Jang, Kee-taek; Ohike, Nobuyuki; Kim, Grace Eun Hye; Krasinskas, Alyssa; Choi, Hyejeong; Sarmiento, Juan Martinez; Kooby, David; El-Rayes, Bassel; Knight, Jessica; Goodman, Michael; Akkaş, Gizem; Reid, Michelle Dian; Maithel, Shishir Kumar; Adsay, Nazmi Volkan
    Background: Current nodal staging (N-staging) of ampullary carcinoma in the TNM staging system distinguishes between node-negative (N0) and node-positive (N1) disease but does not consider the metastatic lymph node (LN) number. Methods: Overall, 313 patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma were categorized as N0, N1 (1–2 metastatic LNs), or N2 (?3 metastatic LNs), as proposed by Kang et al. Clinicopathological features and overall survival (OS) of the three groups were compared. Results: The median number of LNs examined was 11, and LN metastasis was present in 142 cases (45 %). When LN-positive cases were re-classified according to the proposed staging system, 82 were N1 (26 %) and 60 were N2 (19 %). There was a significant correlation between proposed N-stage and lymphovascular invasion, perineural invasion, increased tumor size (each p < 0.001), and surgical margin positivity (p = 0.001). The median OS in LN-negative cases was significantly longer than that in LN-positive cases (107.5 vs. 32 months; p < 0.001). Patients with N1 and N2 disease had median survivals of 40 and 24.5 months, respectively (p < 0.0001). In addition, 1-, 3-, and 5-year survivals were 88, 76, 62 %, respectively, for N0; 90, 55, 31.5 %, respectively, for N1; and 68, 34, 30 %, respectively for N2 (p < 0.001). Even with multivariate modeling, the association between higher proposed N stage and shorter survival persisted (hazard ratio 1.6 for N1 and 1.9 for N2; p = 0.018). Conclusions: Classification of nodal status in ampullary carcinomas based on the number of metastatic LNs has a significant prognostic value. A revised N-staging classification system should be incorporated into the TNM staging of ampullary cancers.