title: Substaging Nodal Status in Ampullary Carcinomas has Significant Prognostic Value: Proposed Revised Staging Based on an Analysis of 313 Well-Characterized Cases.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Serdar
authors.initials: S
authors.lastname: Balci
authors.affiliation: Department of Pathology, New York University, New York, NY, USA.
authors.forename: Olca
authors.initials: O
authors.lastname: Basturk
authors.affiliation: Department of Pathology, İstanbul Medipol University, İstanbul, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Saka
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Pelin
authors.initials: P
authors.lastname: Bagci
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Postlewait
authors.affiliation: Department of Pathology, Tokai University Hachiouji Hospital, Tokyo, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Tajiri
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kee-Taek
authors.initials: KT
authors.lastname: Jang
authors.affiliation: Department of Pathology, Showa University Fujigaoka Hospital, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohike
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kim
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Krasinskas
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyejeong
authors.initials: H
authors.lastname: Choi
authors.affiliation: Division of General and Gastrointstinal Surgery, Emory University, Atlanta, GA, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Sarmiento
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Kooby
authors.affiliation: Department of Oncology, Emory University, Atlanta, GA, USA.
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
authors.affiliation: Department of Epidemiology, Emory University, Atlanta, GA, USA.
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Knight
authors.affiliation: Department of Epidemiology, Emory University, Atlanta, GA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Gizem
authors.initials: G
authors.lastname: Akkas
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Reid
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA. volkan.adsay@emory.edu.
authors.forename: Volkan
authors.initials: V
authors.lastname: Adsay
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology* / Q000601:surgery; D003138:Common Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000592:standards*; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D015996:Survival Rate