Jejunal response to secretin is independent of the pancreatic response in secretin-enhanced magnetic resonance cholangiopancreatography

Hafezi-Nejad, Nima; Singh, Vikesh K.; Faghih, Mahya; Kamel, Ihab R.; Zaheer, Atif

doi:10.1016/j.ejrad.2018.12.024

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…[25] Several studies demonstrated that SCT signaling affects physiological pathways in different organs, including the pancreas, kidney, and intestine, concerning the possible adverse effects of chronic SCT 5-27 administration. [26,27] Our experiments demonstrate that (1) the increased activity of the SCT/SR axis and the corresponding increase in biliary proliferation/senescence, liver inflammation, and fibrosis (observed in Mdr2 −/− mice) are reversed by chronic administration of and (2) no significant toxic effects are observed in peripheral organs when SCT 5-27 is chronically administered to WT or Mdr2 −/− mice. The development of a small molecule targeting SR or a long-acting version of SCT 5-27 (analogous to newer GLP-1 receptor agonists currently in clinical trials) [28] could be delivered by weekly subcutaneous injections during fibrosis development as well as in severe onion-skin fibrosis, a stage that is presented as early as 4 weeks in Mdr2 −/− mice and progressively increases with aging.…”

Section: Discussionmentioning

confidence: 79%

“…We chose a 12-wk treatment time for SCT 5–27 since several experimental pharmacological trials considered this period adequate to evaluate therapeutic changes in PSC patients 25. Several studies demonstrated that SCT signaling affects physiological pathways in different organs, including the pancreas, kidney, and intestine, concerning the possible adverse effects of chronic SCT 5–27 administration 26,27. Our experiments demonstrate that (1) the increased activity of the SCT/SR axis and the corresponding increase in biliary proliferation/senescence, liver inflammation, and fibrosis (observed in Mdr2 −/− mice) are reversed by chronic administration of SCT 5–27; and (2) no significant toxic effects are observed in peripheral organs when SCT 5–27 is chronically administered to WT or Mdr2 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged administration of a secretin receptor antagonist inhibits biliary senescence and liver fibrosis in Mdr2−/− mice

Zhou

Carpino

et al. 2023

Hepatology

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Background and Aims: Secretin (SCT) and secretin receptor (SR, only expressed on cholangiocytes within the liver) play key roles in modulating liver phenotypes. Forkhead box A2 (FoxA2) is required for normal bile duct homeostasis by preventing the excess of cholangiocyte proliferation. Short-term administration of the SR antagonist (SCT 5–27) decreased ductular reaction and liver fibrosis in bile duct ligated and Mdr2−/− [primary sclerosing cholangitis (PSC), model] mice. We aimed to evaluate the effectiveness and risks of long-term SCT 5–27 treatment in Mdr2−/− mice. Approach and Results: In vivo studies were performed in male wild-type and Mdr2−/− mice treated with saline or SCT 5–27 for 3 months and human samples from late-stage PSC patients and healthy controls. Compared with controls, biliary SCT/SR expression and SCT serum levels increased in Mdr2−/− mice and late-stage PSC patients. There was a significant increase in ductular reaction, biliary senescence, liver inflammation, angiogenesis, fibrosis, biliary expression of TGF-β1/VEGF-A axis, and biliary phosphorylation of protein kinase A and ERK1/2 in Mdr2−/− mice. The biliary expression of miR-125b and FoxA2 decreased in Mdr2−/− compared with wild-type mice, which was reversed by long-term SCT 5–27 treatment. In vitro, SCT 5–27 treatment of a human biliary PSC cell line decreased proliferation and senescence and SR/TGF-β1/VEGF-A axis but increased the expression of miR-125b and FoxA2. Downregulation of FoxA2 prevented SCT 5–27–induced reduction in biliary damage, whereas overexpression of FoxA2 reduced proliferation and senescence in the human PSC cell line. Conclusions: Modulating the SCT/SR axis may be critical for managing PSC.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Prolonged administration of a secretin receptor antagonist inhibits biliary senescence and liver fibrosis in Mdr2−/− mice

Zhou

Carpino

et al. 2023

Hepatology

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“…Secretin simulation may induce increased fluid from cells in the jejunum itself as well as the pancreas. Hafezi-Nejad et al [65] demonstrated that fluid signal in the descending duodenum, however, was significantly lower in patients with CP than those without CP.…”

Section: Equivocal Indications For Use Of Secretinmentioning

confidence: 98%

Secretin-Enhanced MRCP: How and Why—AJR Expert Panel Narrative Review

Swensson

Zaheer

Conwell

et al. 2021

American Journal of Roentgenology

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Secretin-enhanced MRCP (S-MRCP) provides multiple advantages compared with standard MRCP for imaging the pancreaticobiliary tree. By using secretin to induce fluid production from the pancreas, and leveraging fluid-sensitive MRCP sequences, S-MRCP increases visualization of ductal anatomy and provides insight into pancreatic function, allowing radiologists to offer additional insight for a range of pancreatic-related 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. Considerations are given for radiologists' interpretation and reporting of S-MRCP examinations, including assessment of dynamic compliance of the main pancreatic duct and of duodenal fluid volume. Established indications for S-MRCP are reviewed, including 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 presented, along with the authors' approach to such indications; these include acute or recurrent acute pancreatitis, pancreatic exocrine function, sphincter of Oddi dysfunction, and pancreatic neoplasms.

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“…This can either be graded based on presence and extension of fluid from proximal to distal duodenum and proximal jejunum or by more objective quantification by calculating the volume of secreted fluid [32]. Care must be taken not to confuse with Secretin-induced jejunal secretion of fluid [33].…”

Section: Role Of Mri/mrcpmentioning

confidence: 99%

Cross-sectional imaging-based severity scoring of chronic pancreatitis: why it is necessary and how it can be done

et al. 2019

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Chronic pancreatitis (CP) remains a diagnostic challenge as clinical symptoms are non-specific, histopathological appearances are varied and pathogenesis remains incompletely understood. Multiple classifications and grading systems have been proposed for CP, but none leverage the full capabilities of cross-sectional imaging modalities and are not widely accepted or validated. CT and MRI/MRCP are useful in identifying a wide spectrum of histopathological changes in CP and can also assess exocrine reserve of pancreas. Advanced MRI techniques such as T1 mapping and extracellular volume fraction can potentially identify early CP. Cross-sectional imaging-based severity scoring can quantify CP disease burden and may have positive implications for clinicians and researchers. In this review, we discuss the need for cross-sectional imaging-based severity scoring for CP, role of CT, and MRI/MRCP in assessment of CP and how these modalities can be used to obtain severity scoring for CP. We summarize relevant information from recently published CT and MRI/MRCP reporting standards for CP, and from international guidelines for cross-sectional imaging and severity scoring for CP.

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Jejunal response to secretin is independent of the pancreatic response in secretin-enhanced magnetic resonance cholangiopancreatography

Cited by 4 publications

References 25 publications

Prolonged administration of a secretin receptor antagonist inhibits biliary senescence and liver fibrosis in Mdr2−/− mice

Prolonged administration of a secretin receptor antagonist inhibits biliary senescence and liver fibrosis in Mdr2−/− mice

Secretin-Enhanced MRCP: How and Why—AJR Expert Panel Narrative Review

Cross-sectional imaging-based severity scoring of chronic pancreatitis: why it is necessary and how it can be done

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