Prognostic Impact of Intra-Ampullary Papillary-Tubular Neoplasm versus Flat Dysplasia as Precursor Lesions of Ampullary Adenocarcinoma

Abstract

<b><i>Background:</i></b> The aim of this study is to compare the prognostic impact of 2 precursor lesions of ampullary adenocarcinoma, intra-ampullary papillary-tubular neoplasm (IAPN) and flat dysplasia (FD). <b><i>Methods:</i></b> From December 1994 to December 2012, a total of 359 patients underwent curative surgery for ampullary adenocarcinoma. <b><i>Results:</i></b> The precursor lesions were IAPNs in 134 (37.3%) patients and FD in the other 225 (62.7%) patients. The FD group had more aggressive tumor biology with advanced T stage (<i>p</i> = 0.002), nodal involvement (<i>p</i> &#x3c; 0.001), poor differentiation (<i>p</i> &#x3c; 0.001), perineural and lymphovascular invasion (<i>p</i> &#x3c; 0.001), and pancreatobiliary or mixed subtype (<i>p</i> &#x3c; 0.001). Five-year overall survival rates were 71.1% in the IAPN group and 51.4% in the FD group (<i>p</i> = 0.002), respectively. Five-year disease-free survival rates were 69.7% in the IAPN group and 49.6% in the FD group (<i>p</i> &#x3c; 0.001), respectively. The recurrence rate was also higher in the FD group (49.8 vs. 30.6%; <i>p</i> &#x3c; 0.001). On multivariate analysis, higher levels of tumor markers including CEA and CA19-9, lymph node metastasis, poorly differentiated histology, and perineural invasion were negative predictive factors for survival. Higher levels of CEA and CA19-9, lymphovascular invasion, and FD were independent prognostic factors for recurrence. <b><i>Conclusion:</i></b> FD was significantly associated with worse prognosis and a greater tendency toward advanced disease. Further studies are needed to clarify the impacts of these precursor lesions.