Pancreatic cystic lesions without overt cytologic atypia: proposed diagnostic categories for endoscopic ultrasound-guided fine-needle aspiration cytology with utilization of fluid carcinoembryonic antigen level.

OBJECTIVES: It was the aim of this study to examine pancreatic cyst cases that lack markedly atypical or malignant epithelium on endoscopic ultrasound-guided fine-needle aspirations. STUDY DESIGN: We conducted a retrospective case review study, including 24 cases that were either acellular or lacked cytologic atypia and were subsequently resected. The cases were retrospectively divided into 3 categories: (1) non-diagnostic, (2) cyst contents only, and (3) cyst contents with bland-appearing epithelium. The cyst contents were subdivided into mucinous and non-mucinous types. The cytologic diagnoses were correlated with cyst fluid carcinoembryonic antigen (CEA) levels and subsequent histologic diagnoses. RESULTS: Category 1 comprised 4 cases: 2 cases (CEA >800 ng/ml) with mucin-producing neoplasms and 2 cases (CEA not determined) with microcystic serous cystadenomas. Category 2 included 4 cases with non-mucinous and 4 with mucinous contents. In the first subgroup, 2 cases (CEA >800 ng/ml) showed mucinous cystic neoplasms and 2 cases (CEA negligible or not determined) pseudocysts. In the second subgroup, there were 3 cases with neoplastic mucinous cysts (1 CEA >800 ng/ml, 2 not determined) and 1 case with a lymphoepithelial cyst with mucinous metaplasia (CEA >800 ng/ml). Almost all cases (10/11) in category 3 had neoplastic mucinous cysts regardless of the CEA levels. CONCLUSIONS: The proposed 3 cytologic categories of pancreatic cystic lesion combined with cyst fluid CEA levels provide useful clinical information.

Activation of peroxisome proliferator-activated receptor-gamma inhibits differentiation of preosteoblasts.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is critical for phenotype determination at early differentiation stages of mesenchymal cells. Activation of this nuclear receptor inhibits gene expression in part by antagonizing the activities of several transcription factors. In this study we examined inhibitory mechanisms of osteoblast differentiation markers by activating PPAR-gamma. Our data indicate that the PPAR-gamma natural ligand 15d-PGJ2 dose-dependently inhibits expression of alkaline phosphatase and mineral deposition by primary stromal cells and by cell lines such as ST2 and MC3T3-E1. We next show that PPAR-gamma nuclear translocation coincides with duration and doses of ligand addition, indicating that 15d-PGJ2-activated PPAR-gamma rapidly translocates to the nuclear component where it exerts its biological effects. Further examination of downstream osteogenic signaling pathways induced by beta-glycerophosphate and ascorbic acid reveals that induction of osteoblast differentiation by these agents involves activation of the transcription factors Cbfa1 and NF-kappaB. The former is critical for osteoblast differentiation. To test whether inhibition of alkaline phosphatase expression and mineral deposition by activated PPAR-gamma reflects attenuation of transcriptional activity, we performed DNA protein-binding assays for NF-kappaB and Cbfa1. Our findings indicate that 15d-PGJ2-induced PPAR-gamma abrogates beta-glycerophosphate-activated Cbfa1 and NF-kappaB. These findings were consistent in primary and stromal cell lines, ST2 and MC3T3-E1. Thus activation of PPAR-gamma by 15d-PGJ2 inhibits DNA-binding activity of the transcription factors Cbfa1 and NF-kappaB, leading to diminished expression of osteoblast/stromal differentiation markers.