BACKGROUND: To assess the prognostic significance of nodal microinvolvement in patients with carcinoma of the papilla of Vater. METHODS: From 1993 to 2003 at the University Clinic Hamburg, 777 patients were operated upon pancreatic and periampullary carcinomas. The vast majority of patients were operated upon pancreatic ductal adenocarcinoma (n = 566, 73%), followed by carcinomas of the papilla of Vater (n = 112, 14%), pancreatic neuroendocrine carcinomas (n = 39, 5%), intraductal papillary mucinous neoplasms (n = 33, 4%), and distal bile duct carcinomas (n = 27, 3%). Fresh-frozen tissue sections from 169 lymph nodes (LNs) classified as tumor free by routine histopathology from 57 patients with R0 resected carcinoma of the papilla of Vater who had been spared from adjuvant chemotherapy were immunohistochemically (IHC) examined, using a sensitive IHC assay with the anti-epithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathology, 39 (63%) of the patients were staged as pT1/pT2, 21 (37%) as pT3/pT4, 30 (53%) as pN0, while 38 (67%) as G1/G2. RESULTS: Of the 169 "tumor-free" LNs, 91 LNs (53.8%) contained Ber-EP4-positive tumor cells. These 91 LNs were from 40 (70%) patients. The mean overall survival in patients without nodal microinvolvement of 35.8 months (median-not yet reached) was significantly longer than that in patients with nodal microinvolvement (mean 16.6; median 13; p = 0.019). Multivariate Cox regression analysis for overall survival revealed that grading was the most significant independent prognostic factor (p = 0.001), followed by nodal microinvolvement (p = 0.013). CONCLUSIONS: The influence of occult tumor cell dissemination in LNs of patients with histologically proven carcinoma of the papilla of Vater supports the need for further tumor staging through immunohistochemistry.
