Brush cytology is helpful for differentiating between benign and malignant biliary strictures, especially in suspected cholangiocarcinoma. Dysplastic cells may occur in the absence of malignancy and their presence should therefore be interpreted cautiously.

TGF-␤ strongly promotes local tumor progression in advanced epithelial tumors, though the underlying mechanisms are poorly understood. In the present study, we demonstrate the potential of TGF-␤ to increase the invasiveness of the pancreatic cancer cell lines PANC-1 and IMIM-PC1. TGF-␤-induced tumor cell invasion occurred in a time-dependent manner, started after 12 hr and continued to increase even 48 hr after a single application of the growth factor. Blocking of secreted TGF-␤1 by application of neutralizing antibodies 24 hr after TGF-␤ treatment completely prevented the sustained effects of TGF-␤ on tumor cell invasion. Together with our previous observation that TGF-␤1 up-regulates its own expression in both cell lines, our data suggest that TGF-␤1 acts in an autocrine manner to maintain tumor cell invasion. As measured by Northern blot hybridization and zymography, TGF-␤ treatment of PANC-1 and IMIM-PC1 cells resulted in strong up-regulation of expression and activity of both matrix metalloproteinase-2 (MMP-2) and the urokinase plasminogen activator (uPA) system. Treatment with MMP inhibitors or inhibitors of the uPA system caused significant reduction of TGF-␤-induced invasiveness in both cell lines. In contrast, expression and activity of MMP-2 and uPA as well as tumor cell invasiveness remained unaffected in cell lines with defects of the TGF-␤ type II receptor (MiaPaca2) or the Smad4 gene (IMIM-PC2 and CAPAN-1). In these cell lines, TGF-␤ also failed to auto-induce its own expression. In conclusion, our results suggest that TGF-␤1 is a strong promotor of pancreatic cancer progression. TGF-␤ thereby acts in an autocrine manner to induce tumor cell invasion, which is mediated by MMP-2 and the uPA system.

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Although techniques for high-resolution imaging of the pancreas are constantly being improved, the evaluation of pancreatic function remains crucial for the workup of pancreatic diseases. More than 20 direct and indirect tests are available for the assessment of pancreatic function. Measurement of fecal elastase-1 is recommended as the most suitable test for the initial assessment of pancreatic function. Among other techniques, the pancreolauryl test, and alternatively the BT-PABA (N-benzoyl-L-tyrosyl-p-aminobenzoic acid) or the (13)C-mixed-triglyceride test, yield the best sensitivity and specificity. Nevertheless, all indirect tests are of limited value in patients with mild to moderate impairment of pancreatic function. In these patients, the secretin-caerulein test remains the gold standard.