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Background & Aims Pancreatic intraepithelial neoplasia (PanIN) are pancreatic cancer precursor lesions of unclear origin and significance. PanIN aberrantly express sonic hedgehog (Shh), an initiator of pancreatic cancer, and gastrointestinal mucins. A majority of PanIN are thought to arise from ducts. We identified a novel ductal compartment that is gathered in gland-like outpouches (pancreatic duct glands [PDG]) of major ducts and characterized its role in injury and metaplasia. Methods The ductal system was analyzed in normal pancreata and chronic pancreatitis in humans and mice. Anatomy was assessed by serial hematoxylin and eosin sections and scanning electron microscopy of corrosion casts. Expression of mucins and developmental genes and proliferation were assessed by immunohistochemistry or real-time quantitative polymerase chain reaction. Effects of Shh on ductal cells were investigated by exposure to Shh in vitro and transgenic misexpression in vivo. Results Three-dimensional analysis revealed blind-ending outpouches of ducts in murine and human pancreata. These PDG are morphologically and molecularly distinct from normal ducts; even in normal pancreata they display PanIN and metaplastic features, such as expression of Shh and gastric mucins. They express other developmental genes, such as Pdx-1 and Hes-1. In injury, Shh is up-regulated along with gastric mucins. Expansion of the PDG compartment results in a mucinous metaplasia. Shh promotes this transformation in vitro and in vivo. Conclusions PDG are distinct gland-like mucinous compartments with a distinct molecular signature. In response to injury, PDG undergo an Shh-mediated mucinous gastrointestinal metaplasia with PanIN-like features. PDG may provide a link between Shh, mucinous metaplasia, and neoplasia.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas arising in branch ducts are thought to be less aggressive than their main-duct counterparts, and guidelines for their conservative management were recently proposed. This study describes the combined experience of 2 tertiary centers with branch-duct IPMNs aiming to validate these recommendations.A review of 145 patients with resected, pathologically confirmed, branch-duct IPMNs between 1990 and 2005 was conducted.Sixty-six patients (45.5\%) had adenoma, 47 (32\%) borderline tumors, 16 (11\%) carcinoma in situ, and 16 (11\%) invasive carcinoma. Median age was similar between benign and malignant subgroups (66 vs 67.5 years, respectively). Jaundice was more frequent in patients with cancer (12.5\% vs 1.8\%, respectively, P = .022) and abdominal pain in patients with benign tumors (45\% vs 25\%, respectively, P = .025). Forty percent of tumors were discovered incidentally. Findings associated with malignancy were the presence of a thick wall (P < .001), nodules (P < .001), and tumor diameter >or=30 mm (P < .001). All neoplasms with cancer were larger than 30 mm in size or had nodules or caused symptoms. After a mean follow-up of 45 months, the 5-year disease-specific survival for branch-duct IPMNs with noninvasive neoplasms was 100\% and, for invasive cancer, was 63\%.This large cohort of resected branch-duct IPMNs shows that cancer is present in 22\% of cases and validates the recent guidelines that indicate absence of malignancy in tumors

G A A b st ra ct s reported abdominal complaints as opposed to 7.6% of those without PC(s) (p = 0.589). None of the individuals with PC(s) had pancreatic disease in their medical history. Conclusion: In individuals undergoing preventive medical examination with MRI, the prevalence of PCs was 2.2%. Of these PCs, 5.3% were ≥30 mm, 8% were multilocular and in 10% of cases may represent side-branch IPMN. Cyst presence correlated with increasing age, no difference of prevalence by sex was found. Abdominal complaints did not correlate with PC presence.