BACKGROUND Biliary papillomatosis (BP) is a rare disease that is characterized by multiple numerous papillary adenomas in the biliary tree. The clinical features and outcome, however, are not well known. The authors retrospectively analyzed their clinicopathologic features and long‐term follow‐up results. METHODS Between March 1995 and January 2003, 58 patients were diagnosed with BP by cholangioscopic and histologic findings at a tertiary referral center, Asan Medical Center (University of Ulsan College of Medicine, Seoul, Korea). The authors retrospectively reviewed the medical records to obtain demographic, radiologic, cholangioscopic, and pathologic data. RESULTS The common clinical manifestations at the presentation of patients were repeated episodes of abdominal pain, jaundice, and acute cholangitis. Acute cholangitis was more common in patients with mucin‐hypersecreting BP (MBP), whereas patients with nonmucin‐producing BP (NMBP) were more asymptomatic (P < 0.05). Papillary adenocarcinoma and mucinous carcinoma were detected in 48 patients (83%) with papillary adenomas. Overall survival rates of NMBP and MBP were 89% and 69% at 1 year, 57% and 37% at 3 years, and 52% and 19% at 5 years, respectively. The mean survival period of NMBP and MBP was 52.27 ± 6.72 months and 30.84 ± 8.36 months, respectively. CONCLUSIONS BP should be regarded as a premalignant disease with high malignant potential. The pathogenesis of progression from benign to malignant disease may follow the adenomacarcinoma sequence. Although clinical presentations were somewhat different for patients with NMBP and MBP, the long‐term survival rate was similar. Cancer 2004;100:783–93. © 2004 American Cancer Society.

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In our previous study, we showed that Helicobacter pylori gamma-glutamyltranspeptidase (GGT) is associated with H. pylori-induced apoptosis through a mitochondrial pathway. To better understand the role of GGT in apoptosis, we examined the effect of GGT on cell cycle regulation in AGS cells. To determine the effect of recombinant GGT (rGGT) on cell cycle distribution and apoptosis, rGGT-treated and untreated AGS cells were analyzed in parallel by flow cytometry using propidium iodide (PI). We found that rGGT inhibited the growth of AGS cells in a time-dependent manner, and that the pre-exposure of cells to a caspase-3 inhibitor (z-DEVD-fmk) effectively blocked GGT-induced apoptosis. Cell cycle analysis showed G1 phase arrest and apoptosis in AGS cells following rGGT treatment. The rGGT-mediated G1 phase arrest was found to be associated with down-regulation of cyclin E, cyclin A, Cdk 4, and Cdk 6, and the up-regulation of the cyclin-dependent kinase (Cdk) inhibitors p27 and p21. Our results suggest that H. pylori GGT induces cell cycle arrest at the G1-S phase transition.