Abstract
Background: The clinical significance of pancreatic intraepithelial neoplasia (PanIN)-III, known as carcinoma in situ of pancreatic ductal adenocarcinoma (PDAC), remains unclear yet. Recent research showed inflammation enhanced early cellular invasion of PanIN-III by facilitating epithelial to mesenchymal transition (EMT), even before frank malignancy in experimental model. Therefore we decided to investigate whether PanIN-III accompanying chronic pancreatitis (CP) might have an important prognostic impact in patient who underwent curative resection for PDAC. Methods: Medical records of 125 PDAC patients with R0 resection were reviewed. Presence and grade of PanIN and CP in resected specimen were determined based on College of American Pathologists protocol. Overall survival (OS) and disease free survival (DFS) were analyzed according to PanIN-III and CP. Results: CP was observed in 27.2% (34/125) of resected specimen and PanIN-III in 25.6% (32/125). In the group with CP, PanIN-III was associated with poor prognosis in univariate analysis (4.3 months vs. 15.5 months, P=0.021 for DFS and 16.3 months vs. 30.9 months, P=0.004 for OS), whereas PanIN-III was not a prognostic factor in the group without CP. When we divided into two groups [PanIN-III accompanying CP (n=12) vs. the others (n=113)], it showed that median DFS and OS were significantly shorter in PanIN-III and CP group than those of the others (4.3 months and 16.3 months vs. 11.3 months and 21.3 months, p= 0.034 and p=0.019, respectively). In multivariate analysis, PanIN-III accompanying CP remained a statistically significant poor prognostic factor (HR: 2.97; 95% CI: 1.36 to 6.30; P=0.006 for DFS, HR: 2.31; 95% CI: 1.13 to 4.73; P=0.022 for OS using Cox proportional hazard ratio). Conclusions: PanIN-III accompanying CP might influence on poor long-term outcomes in patients who underwent R0 resection for PDAC. Therefore, it would support that chronic inflammation could enhance the dissemination of carcinoma in situ.
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