BACKGROUND & AIMS Excessive consumption of ethanol is one of the most common causes of acute and chronic pancreatitis. Alterations to the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) also cause pancreatitis. However, little is known about the role of CFTR in the pathogenesis of alcohol-induced pancreatitis. METHODS We measured CFTR activity based on chloride concentrations in sweat from patients with cystic fibrosis, patients admitted to the emergency department because of excessive alcohol consumption, and healthy volunteers. We measured CFTR levels and localization in pancreatic tissues and in patients with acute or chronic pancreatitis induced by alcohol. We studied the effects of ethanol, fatty acids, and fatty acid ethyl esters on secretion of pancreatic fluid and HCO3− , levels and function of CFTR, and exchange of Cl− for HCO3− in pancreatic cell lines as well as in tissues from guinea pigs and CFTR knockout mice after administration of alcohol. RESULTS Chloride concentrations increased in sweat samples from patients who acutely abused alcohol but not in samples from healthy volunteers, indicating that alcohol affects CFTR function. Pancreatic tissues from patients with acute or chronic pancreatitis had lower levels of CFTR than tissues from healthy volunteers. Alcohol and fatty acids inhibited secretion of fluid and HCO3− , as well as CFTR activity, in pancreatic ductal epithelial cells. These effects were mediated by sustained increases in concentrations of intracellular calcium and adenosine 3’,5’-cyclic monophosphate, depletion of adenosine triphosphate, and depolarization of mitochondrial membranes. In pancreatic cell lines and pancreatic tissues of mice and guinea pigs, administration of ethanol reduced expression of CFTR messenger RNA, reduced the stability of CFTR at the cell surface, and disrupted folding of CFTR at the endoplasmic reticulum. CFTR knockout mice given ethanol or fatty acids developed more severe pancreatitis than mice not given ethanol or fatty acids. CONCLUSIONS Based on studies of human, mouse, and guinea pig pancreata, alcohol disrupts expression and localization of the CFTR. This appears to contribute to development of pancreatitis. Strategies to increase CFTR levels or function might be used to treat alcohol-associated pancreatitis.
Purpose To determine the linearity, bias, and precision of hepatic proton density fat fraction (PDFF) measurements by using magnetic resonance (MR) imaging across different field strengths, imager manufacturers, and reconstruction methods. Materials and Methods This meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search identified studies that evaluated the linearity and/or bias of hepatic PDFF measurements by using MR imaging (hereafter, MR imaging-PDFF) against PDFF measurements by using colocalized MR spectroscopy (hereafter, MR spectroscopy-PDFF) or the precision of MR imaging-PDFF. The quality of each study was evaluated by using the Quality Assessment of Studies of Diagnostic Accuracy 2 tool. De-identified original data sets from the selected studies were pooled. Linearity was evaluated by using linear regression between MR imaging-PDFF and MR spectroscopy-PDFF measurements. Bias, defined as the mean difference between MR imaging-PDFF and MR spectroscopy-PDFF measurements, was evaluated by using Bland-Altman analysis. Precision, defined as the agreement between repeated MR imaging-PDFF measurements, was evaluated by using a linear mixed-effects model, with field strength, imager manufacturer, reconstruction method, and region of interest as random effects. Results Twenty-three studies (1679 participants) were selected for linearity and bias analyses and 11 studies (425 participants) were selected for precision analyses. MR imaging-PDFF was linear with MR spectroscopy-PDFF (R = 0.96). Regression slope (0.97; P < .001) and mean Bland-Altman bias (-0.13%; 95% limits of agreement: -3.95%, 3.40%) indicated minimal underestimation by using MR imaging-PDFF. MR imaging-PDFF was precise at the region-of-interest level, with repeatability and reproducibility coefficients of 2.99% and 4.12%, respectively. Field strength, imager manufacturer, and reconstruction method each had minimal effects on reproducibility. Conclusion MR imaging-PDFF has excellent linearity, bias, and precision across different field strengths, imager manufacturers, and reconstruction methods. RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on October 2, 2017.
Objective To analyse the prevalence, incidence and clinical relevance of pancreatic cysts detected as incidental finding in a population-based longitudinal study. Design A total of 1077 participants (521 men, mean age 55.8±12.8 years) of 2333 participants from the population-based Study of Health in Pomerania (SHIP) underwent magnetic resonance cholangiopancreaticography (MRCP) at baseline (2008)(2009)(2010)(2011)(2012). MRCP was analysed for pancreatic cysts with a diameter ≥2 mm. 676/1077 subjects received a 5-year follow-up (2014-2016). The prevalence and incidence of pancreatic cysts (weighted for study participation) were assessed in association to age, gender and suspected epidemiological risk factors. Mortality follow-up was performed in 2015 for all SHIP participants (mean follow-up period 5.9 years, range 3.2-7.5 years). results At baseline pancreatic cysts had a weighted prevalence of 49.1%, with an average number of 3.9 (95% CI 3.2 to 4.5) cysts per subject in the subgroup harbouring cysts. Cyst size ranged from 2 to 29 mm. Prevalence (p<0.001), number (p=0.001) and maximum size (p<0.001) increased significantly with age. The 5-year follow-up revealed a weighted incidence of 12.9% newly detected pancreatic cysts. 57.1% of the subjects initially harbouring pancreatic cysts showed an increase in number and/or maximum cyst size. Of all subjects undergoing MRCP, no participant died of pancreatic diseases within mortality follow-up. conclusion The prevalence of pancreatic cysts in the general population is unexpectedly high, and their number and size increase with age. Overall, no pancreatic cancer was observed in this collective during a 5-year follow-up. Nevertheless, prospective follow-up imaging showed minimal progress in more than 50%. Only about 6% of cysts and 2.5% of the study group initially presented with cysts of more than 1 cm and thus might be clinically meaningful. IntrODuctIOnCystic lesions of the pancreas are closed cavities containing liquid or semisolid material, which can either be neoplastic or non-neoplastic. Among the neoplastic cysts accounting for 10%-15% of all pancreatic cystic lesions, 1 the serous type is seen as benign, whereas the mucinous form tends to have malignant potential.2 Reports indicate that common cystic tumours with a mucinous epithelial lining can harbour carcinoma in situ or invasive cancer in up to 60% of resected specimen depending on the size of the lesion, clinical symptoms caused by the PancreasORIgINAl ARTICle
Purpose:To investigate the effect of the multipeak spectral modeling of fat on R2* values as measures of liver iron and on the quantification of liver fat fraction, with biopsy as the reference standard. Materials and Methods:Institutional review board approval and informed consent were obtained. Patients with liver disease (n = 95; 50 men, 45 women; mean age, 57.2 years 6 14.1 [standard deviation]) underwent a nontargeted liver biopsy, and 97 biopsy samples were reviewed for steatosis and iron grades. MR imaging at 1.5 T was performed 24-72 hours after biopsy by using a three-echo three-dimensional gradient-echo sequence for water and fat separation. Data were reconstructed off-line, correcting for T1 and T2* effects. Fat fraction and R2* maps (1/T2*) were reconstructed and differences in R2* and steatosis grades with and without multipeak modeling of fat were tested by using the Kruskal-Wallis test. Spearman rank correlation coefficient was used to assess fat fractions and steatosis grades. Linear regression analysis was performed to compare the fat fraction for both models. Results:Mean steatosis grade at biopsy ranged from 0% to 95%. Biopsy specimens in 26 of 97 patients (27%) showed liver iron (15 mild, six moderate, and five severe). In all 71 samples without iron, a strong increase in the apparent R2* was observed with increasing steatosis grade when single-peak modeling of fat was used (P = .001). When multipeak modeling was used, there were no differences in the apparent R2* as a function of steatosis grading (P = .645), and R2* values agreed closely with those reported in the literature. Good correlation between fat fraction and steatosis grade was observed (r S = 0.85) both without and with spectral modeling. Conclusion:In the presence of fat, multipeak spectral modeling of fat improves the agreement between R2* and liver iron. Single-peak modeling of fat leads to underestimation of liver fat.q RSNA, 2012Supplemental material: http://radiology.rsna.org/lookup /suppl
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