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Aims: Periampullary adenocarcinomas comprise pancreatic ductal (PDAC), distal bile duct (DBDAC), ampullary (AMPAC) and duodenal (DUOAC) adenocarcinoma. The epithelia of these anatomical structures share a common embryologic origin from the foregut. While there seem to be significant differences regarding tumor biology, the classification, grading, staging and treatment of these entities remains a matter of substantial debate. Due to the anatomical complexity of the periampullary region, there is still considerable debate on how carcinomas and their precursor lesions arising in this region should be classified. Our study aimed at a detailed analysis of clinical, pathological and immunohistochemical parameters for assessment of tumor biology and identification of prognostic factors after resection of periampullary carcinomas.
Material and Methods
198 patients who had resection of periampullary adenocarcinoma from 2001 to 2011 were identified. All tissue samples were processed by a standardized protocol for pathological workup of pancreatoduodenectomy specimen. Archived Hematoxylin-Eosin stained slides were reevaluated by three experienced pathologists for accuracy of diagnosis. For the growthpattern, three typical subtypes were defined: intestinal, pancreatobiliary, mixed intestinal-pancreatobiliary and Poorly-differentiated carcinomas. Additionally for immunohistochemical subtyping of the growth pattern CK7, CK20 and CDX2 staining were performed for each slide. Furthermore we established a modified tumorgrading system.
Results
127 patients had PDAC, 39 had AMPAC, 23 had DBDAC and nine had a DUOAC. The distribution of subtypes was significantly different among the carcinoma groups. Tumor location, histological subtype and grading were highly significant predictors of survival (p<0.001). In accordance, a high CK7 expression and a low CDX2 expression, which characterize PB differentiation, were significant predictors of poor survival. Only histological subtype, grading and lymph node ratio were found to represent independent predictors of survival in multivariate analysis.
Conclusions:
Our results demonstrate that there should be a change in the pathological management of making diagnoses in periampullary carcinomas. By multivariate analysis, traditional parameters as tumorlocation, TNM classification lost their prominence as a source of prognosticating survival of periampullary carcinoma. Therefore, we recommend comprising the histological subtype and our adjusted histological grading for a better valuation of survival.