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- W1556674986 abstract "The aims of this study were to assess the occurrence of gallbladder abnormalities and dysfunction, to evaluate clinically useful biomarkers for premalignancy and malignancy in gallbladder epithelium and to assess presence of pancreatic duct changes and early pancreatic abnormalities in patients with primary sclerosing cholangitis (PSC). In paper I and III we investigated presence of gallbladder abnormalities in 286 patients with PSC. Gallbladder abnormalities were found in 41% of the patients, gallstones in 25% and cholecystitis in 25%. Six % (18/286) of the patients had a gallbladder mass lesion with a mean size of 21(±9) mm (SD) of whom 56% (10/18) constituted adenocarcinoma. All available gallbladder specimens (n=53) were rereviewed and immunohistochemical staining was compared on all available paraffin blocks of gallbladdercarcinoma/dysplasia (n=13) and benign tissue (n =6). A significant association was found between presence of moderate-severe lymphoplasmacytic chronic inflammation and fibrosis and dysplasia/adenocarcinoma. Immunoreactivity for the cell-cycle-regulating proteins p53, Ki67, Cyclin D1 and pCEA were detected in significantly more cases of dysplasia and carcinoma of the gallbladder compared to non-cancerous epithelium, and the thioredoxin family proteins TrxR1-v,2,3,5 was significantly overexpressed in the dysplastic and tumors tissue whereas Grx1 was downregulated. In paper II we studied gallbladder volumes in patients with PSC (n=20) and healthy controls (n=10) with magnetic resonance imaging (MRI). Median fasting and postprandial gallbladder volumes PSC were significantly larger than in healthy controls. There was no difference in ejection fraction or gallbladder emptying volume between PSC patients and controls. Contrast enhancement of the gallbladder wall in PSC patients was higher than in controls. No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls. Paper IV evaluated the presence of pancreatic parenchymal and duct changes using MRI and magnetic resonance cholangio pancreatography (MRCP) in 103 patients with PSC. Pancreatic duct changes were found in 24%. The pancreatic duct changes were associated with extrahepatic biliary involvement and long duration of PSC but neither associated with early radiological signs of chronic pancreatitis such as pancreas-spleen signal intensity ratio (SIR), arterial and early venous phase ratio (A/PV) nor to pancreas size, previous episodes of acute pancreatitis. Severe pancreatic duct changes were significantly associated to abdominal pain. Conclusions: Gallbladder and pancreatic abnormalities are common in PSC and gallbladder mass lesions regardless of their size are frequently malignant in PSC. Our data support an inflammation-fibrosis-dysplasia-carcinoma sequence of the gallbladder epithelium. The overexpression of TrxR1-v2,3,5 and downregulation of Grx1 in dysplastic gallbladder epithelium may be of help for the early diagnosis of biliary malignancy in PSC but needs to be further evaluated. Pancreatic duct changes seem to be part of the spectrum of PSC and should not be defined as chronic pancreatitis. Severe pancreatic duct changes may contribute to abdominal pain in PSC, however, gallbladder size or emptying does not seem to be involved in the development of abdominal pain in PSC. LIST OF PUBLICATIONS I. Said K, Glaumann H, Bergquist A. Gallbladder disease in patients with primary sclerosing cholangitis. J Hepatol. 2008 Apr; 48(4):598-605. II. Said K, Edsborg N, Albiin N, Bergquist A. Gallbladder emptying in patients with primary sclerosing cholangitis. World J Gastroenterol. 2009 Jul 28;15(28):3498-503. III. Said K, Glaumann H, Bjornstedt H, Bergquist A. Thioredoxin family proteins and proliferation markers in dysplastic and malignant gallbladders in patients with primary sclerosing cholangitis. Submitted for publication. IV. Said K, Albiin N, Lindberg B, B Brismar T, Karrar A, Permert J, Bergquist A. Pancreatic duct changes are not associated with early signs of chronic pancreatitis at magnetic resonance imaging (MRI) in patients with primary sclerosing cholangitis. Scand J Gastroenterol. 2010 Apr 12. [Epub ahead of print]" @default.
- W1556674986 created "2016-06-24" @default.
- W1556674986 creator A5077811550 @default.
- W1556674986 date "2010-05-21" @default.
- W1556674986 modified "2023-09-27" @default.
- W1556674986 title "Gallbladder and pancreatic disease in patients with primary sclerosing cholangitis" @default.
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