Jun Sanada

Nuclear cyclin D1 overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis.

Abstract: Cyclin D1 overexpression is remarkably frequent in several human carcinomas and is believed to be a critical event in oncogenesis. We examined cyclin D1 expression, p53 expression, and the Ki-67 labeling index by immunostaining in human gallbladder mucosa in conditions varying from normal to malignant tissue. We also examined K-ras codon 12 mutations in these tissues with a two-step polymerase chain reaction. Nuclear cyclin D1 overexpression was observed in 48% of carcinomas occurring independently of adenoma, but not in adenomas, carcinomas arising in adenomas, or nonneoplastic lesions. Cytoplasmic cyclin D1 overexpression was observed in about 15% of abnormal specimens, irrespective of the type of epithelial abnormality. Carcinomas showing nuclear cyclin D1 overexpression had significantly higher Ki-67 labeling indexes than those with no overexpression. Moderately to poorly differentiated adenocarcinomas showed a higher incidence of nuclear cyclin D1 overexpression than papillary to well differentiated carcinomas. Specimens with cyclin D1 overexpression showed a high incidence of lymph permeation, venous permeation, and lymph node metastasis. We conclude that nuclear cyclin D1 overexpression is a critical event importantly associated with cell proliferation and invasive growth in gallbladder carcinogenesis, and that cyclin D1 immunostaining may become a useful marker for evaluating gallbladder carcinomas.

Assessment of Occult Pancreatobiliary Reflux by Biliary Amylase Levels in Patients with Pancreaticobiliary Disease

Assessment of Occult Pancreatobiliary Reflux by Biliary Amylase Levels in Patients with Pancreaticobiliary Disease Takao Itoi, Kazuto Nakamura, Atsushi Sofuni, Fumihide Itokawa, Kazuhiro Kakimi, Jun Sanada, Fuminori Moriyasu Objectives: Pancreatobiliary maljunction (PBM) is a high risk factor for biliary tract cancer. Carcinogenesis by PBMhas yet to be completely clarified; however, it has been suggested that the mixing of pancreatic juice and bile could activate pancreatic enzymes. Recently, however, several investigators reported existence of pancreatobiliary reflux in patients with a normal pancreaticobiliary junction. The aim of this study was to prospectively examine pancreatobiliary reflux in patients with a normal pancreaticobiliary junction by measuring the amylase level in bile obtained during ERCP. Methods: Eligible patients included 86 consecutive cases of pancreaticobiliary disease with prospective implementation of bile collection during an ERCP procedure. Patients with PBM were excluded. Nineteen cases of eligible patients had simultaneous collection of gallbladder bile. Bile was further collected by cholecystectomy in eight cases. Results: Twenty-two cases (26%) revealed a common bile duct higher than serum amylase (high bile amylase level HBA group) and sixty-six cases exhibited a common bile duct amylase level lower than serum (LBA group). The mean values of common bile duct amylase level in the HBA and LBA groups were 5,502 IU/L and 29 IU/L, respectively. The rate of HBA was significantly higher in patients who were elderly, had a dilated common bile duct, and with choledocholithiasis (p<0.05). Three cases (16%) showed a common bile duct amylase level greater than twice the gallbladder amylase level. Eleven cases (58%) exhibited a gallbladder amylase level higher than the common bile duct amylase level. The values of gallbladder amylase level obtained during ERCP and cholecystectomy were consistent. Conclusions: In conclusion, the data in our study suggested that non-PBMpatients with pancreaticobiliary disease that shows a normal pancreaticobiliary junction might have occult pancreatobiliary reflux under physiological conditions, thereby possibly leading to biliary diseases. *T1442 Importance of Real Time Interpretation (INTERP) of ERCP Films Over Conventional Static Images: Medicolegal Implications Miriam Thomas, Joseph E. Geenen, Marc F. Catalano ERCP is a complex procedure requiring technical skill, careful attention to endoscopic and radiographic (INTERP) that frequently requires evaluation of both real time & hard film copies. Although ERCP X-Rays are reviewed & formally reported by radiologist (RAD), gastroenterologist (GE) perform the studies & interpret fluoroscopic images. Differences in INTERP could lead to medicolegal liability. METHOD: ERCP records of 154 consecutive pts were prospectively evaluated.GE INTERP of ERCP films using real time&hard copies were documented & compared with available text documentation by RAD. Components of each exam were assessed for differences in final INTERP between GE andRAD. Biliary &pancreatic cases were reviewed for documentation of duct diameter, duct INTERP, strictures, stones, cytology, dilatation & stone removal. RESULT: Bile duct (BD) INTERP byGE&RADwere ABN&NL in 64%, 36% compared to 56%, 44% respectively. PD INTERP by GE was documented to be ABN in 63%, NL in 38% compared to 53% & 46% respectively by RAD. There was significant disagreement between GE & RAD regarding ductal INTERP (P<0.05). For the presence of BD stones, PD stones, BD stricture, PD stricture there was an agreement of 52%, 73%, 79% & 84% respectively. In therapeutic cases agreement between RAD & GE of BD cytology, duct dilation, stone removal, PD cytology, PDdilatation, PD stone removal was present in 73%, 50%, 32%, 53%, 44%, & 42% respectively. When compared to GE documentation RAD failed to document the CBD & PD diameter, 27% of BD cytology cases, 50% of biliary dilatation, 68% of BD stone removal, 47% of PD cytology, 55% of PD dilatation & 58%of PD stone removal. Under INTERP of findings frequently occurred in RAD dictated report when compared to GE. CONCLUSION: Many important aspects of the ERCP findings are under documented when interpreting findings using hard copies only. This could be due to lack of adequate film documentation of the procedure. The extent of documentation carries clinical & medicolegal importance. Careful reviews of both real time images & hard film copies are essential to ensure accurate final INTERP.