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Item Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?(MDPI, 2021-07-04) Baiocchi, Leonardo; Lenci, Ilaria; Milana, Martina; Kennedy, Lindsey; Sato, Keisaku; Zhang, Wenjun; Ekser, Burcin; Ceci, Ludovica; Meadows, Vik; Glaser, Shannon; Alpini, Gianfranco; Francis, Heather; Medicine, School of MedicineCholangiocarcinoma is a lethal disease with scarce response to current systemic therapy. The rare occurrence and large heterogeneity of this cancer, together with poor knowledge of its molecular mechanisms, are elements contributing to the difficulties in finding an appropriate cure. Cholangiocytes (and their cellular precursors) are considered the liver component giving rise to cholangiocarcinoma. These cells respond to several hormones, neuropeptides and molecular stimuli employing the cAMP/PKA system for the translation of messages in the intracellular space. For instance, in physiological conditions, stimulation of the secretin receptor determines an increase of intracellular levels of cAMP, thus activating a series of molecular events, finally determining in bicarbonate-enriched choleresis. However, activation of the same receptor during cholangiocytes' injury promotes cellular growth again, using cAMP as the second messenger. Since several scientific pieces of evidence link cAMP signaling system to cholangiocytes' proliferation, the possible changes of this pathway during cancer growth also seem relevant. In this review, we summarize the current findings regarding the cAMP pathway and its role in biliary normal and neoplastic cell proliferation. Perspectives for targeting the cAMP machinery in cholangiocarcinoma therapy are also discussed.Item Functional Role of the Secretin/Secretin Receptor Signaling During Cholestatic Liver Injury(AASLD, 2020-12) Wu, Nan; Baiocchi, Leonardo; Zhou, Tianhao; Kennedy, Lindsey; Ceci, Ludovica; Meng, Fanyin; Sato, Keisaku; Wu, Chaodong; Ekser, Burcin; Kyritsi, Konstantina; Kundu, Debjyoti; Chen, Lixian; Meadows, Vik; Franchitto, Antonio; Alvaro, Domenico; Onori, Paolo; Gaudio, Eugenio; Lenci, Ilaria; Francis, Heather; Glaser, Shannon; Alpini, Gianfranco; Medicine, School of MedicineLiver diseases are a major health concern and affect a large proportion of people worldwide. There are over 100 types of liver disorders, including cirrhosis, cholangiocarcinoma (CCA), hepatocellular carcinoma, and hepatitis. Despite the relevant number of people who are affected by liver diseases, and the increased awareness with regard to these disorders, the number of deaths corresponding to liver injury is expected to increase in the foreseeable future. One of the possible reasons for this is that a complete comprehension of the mechanisms of hepatic damage involving specific liver anatomical districts is lacking, and, as a consequence, current treatments available are suboptimal. A major burden in the clinical setting are chronic cholestatic liver diseases (e.g., primary biliary cholangitis [PBC], primary sclerosing cholangitis [PSC], biliary atresia), which target the biliary epithelium and are characterized by cholestasis.(1, 2) Because the secretin (Sct)/secretin receptor (SR) axis (expressed only by cholangiocytes in the liver)(3, 4) is the major regulator of ductal bile secretion,(5, 6) it is intuitive that this axis plays a key role in the maintenance of biliary homeostasis during the progression of cholangiopathies. For instance, PBC is characterized by reduced bicarbonate secretion, a phenomenon possibly impeding the formation of an HCO3 canalicular film (“bicarbonate umbrella”) on bile ducts, which has protective properties against highly concentrated bile acids (BAs).(1, 7, 8) In this review, we examined the molecular mechanisms by which the Sct/SR axis regulates biliary function and the homeostasis of the biliary epithelium in normal and pathophysiological conditions.Item Secretin-Enhanced MRCP: How and Why—AJR Expert Panel Narrative Review(American Roentgen Ray Society, 2021-05) Swensson, Jordan; Zaheer, Atif; Conwell, Darwin; Sandrasegaran, Kumar; Manfredi, Riccardo; Tirkes, Temel; Radiology and Imaging Sciences, School of MedicineSecretin-enhanced MRCP (S-MRCP) has advantages over standard MRCP for imaging of the pancreaticobiliary tree. Through the use of secretin to induce fluid production from the pancreas and leveraging of fluid-sensitive MRCP sequences, S-MRCP facilitates visualization of ductal anatomy, and the findings provide insight into pancreatic function, allowing radiologists to provide additional insight into a range of pancreatic conditions. This narrative review provides detailed information on the practical implementation of S-MRCP, including patient preparation, logistics of secretin administration, and dynamic secretin-enhanced MRCP acquisition. Also discussed are radiologists' interpretation and reporting of S-MRCP examinations, including assessments of dynamic compliance of the main pancreatic duct and of duodenal fluid volume. Established indications for S-MRCP include pancreas divisum, anomalous pancreaticobiliary junction, Santorinicele, Wirsungocele, chronic pancreatitis, main pancreatic duct stenosis, and assessment of complex postoperative anatomy. Equivocal or controversial indications are also described along with an approach to such indications. These indications include acute and recurrent acute pancreatitis, pancreatic exocrine function, sphincter of Oddi dysfunction, and pancreatic neoplasms.