Mode of spread in the early phase of lymphatic metastasis in pancreatic ductal adenocarcinoma - Prognostic significance of nodal microinvolvement

Background: The aim of this study was to assess the prognostic significance of nodal microinvolvement as well as the mode of spread in the early phase of lymphatic metastasis in patients with node-negative pancreatic ductal adenocarcinoma. Methods: Lymph nodes from 48 node-negative patients with R-o resected pancreatic ductal adenocarcinoma were sampled from 3 different compartments: 1) distal hepatoduodenal ligament, 2) superior-anterior compartment, and 3) posterior-inferior. Tissue sections of 148 lymph nodes classified as tumor free by routine histopathology were examined, using a sensitive immunohistochemical assay with the antiepithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathologic tumor staging and grading, 26 (54.2%) of the patients were staged as pT(1)/pT(2), 22 (45.8%) as pT(3)/pT(4), while 31 (64.6%) as G(1)/G(2) and 17 (35.4%) patients as G(3). Of the 148 "tumor free" lymph nodes, 56 contained Ber-EP4-positive tumor cells. These 56 lymph nodes were from 28 of the 48 patients. The multivariate Cox regression analysis revealed the independent prognostic impact of nodal microinvolvement on relapse-free and overall survival. Analysis by compartment, from which the lymph nodes were collected, revealed that overall survival time (P = 0.006) and time to local recurrence (P = 0.015) depend on. the presence of nodal microinvolvement in the superior-anterior compartment. Conclusions: The influence of occult tumor cell dissemination in lymph nodes of patients with histologically proven pancreatic ductal adenocarcinoma supports the need for further tumor staging through immunohistochemistry. This could be a helpful tool in proper selection of patients for adjuvant chemotherapy.