Diagnosis and Management of Chronic Pancreatitis

Singh, Vikesh K.; Yadav, Dhiraj; Garg, Pramod Kumar

doi:10.1001/jama.2019.19411

Cited by 327 publications

(263 citation statements)

References 132 publications

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“…In the late stages of the disease, islets are digested with the leaking pancreatic enzymes, leading to insulin-dependent diabetes [ 105 ]. During the early stages of chronic pancreatitis, when acute pancreatitis is transitioning into the chronic phase, the body can maintain normal glucose homeostasis, as the remaining pancreatic islets compensate for those destroyed [ 106 ]. Although this cannot be diagnosed via currently available diagnostic methods, detection of the β-cell function using MRI can potentially detect progression from acute to chronic pancreatitis.…”

Section: Detection Of Zinc With Magnetic Resonance Imagingmentioning

confidence: 99%

“…Although this cannot be diagnosed via currently available diagnostic methods, detection of the β-cell function using MRI can potentially detect progression from acute to chronic pancreatitis. Early diagnosis of progression toward chronic pancreatitis could have a considerable impact on public health, as not only is it the most important risk factor for pancreatic cancer, but it annually costs our healthcare system more than $2 billion [ 106 , 107 ].…”

Section: Detection Of Zinc With Magnetic Resonance Imagingmentioning

confidence: 99%

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Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

2020

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Paramagnetic metal ion complexes, mostly based on gadolinium (Gd3+), have been used for over 30 years as magnetic resonance imaging (MRI) contrast agents. Gd3+-based contrast agents have a strong influence on T1 relaxation times and are consequently the most commonly used agents in both the clinical and research environments. Zinc is an essential element involved with over 3000 different cellular proteins, and disturbances in tissue levels of zinc have been linked to a wide range of pathologies, including Alzheimer’s disease, prostate cancer, and diabetes mellitus. MR contrast agents that respond to the presence of Zn2+ in vivo offer the possibility of imaging changes in Zn2+ levels in real-time with the superior spatial resolution offered by MRI. Such responsive agents, often referred to as smart agents, are typically composed of a paramagnetic metal ion with a ligand encapsulating it and one or more chelating units that selectively bind with the analyte of interest. Translation of these agents into clinical radiology is the next goal. In this review, we discuss Gd3+-based MR contrast agents that respond to a change in local Zn2+ concentration.

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Section: Detection Of Zinc With Magnetic Resonance Imagingmentioning

confidence: 99%

Section: Detection Of Zinc With Magnetic Resonance Imagingmentioning

confidence: 99%

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

2020

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“…Chronic pancreatitis also increases the risk of pancreatic cancer, but the association weakens with long-term follow-up [58]. For a comprehensive review of the current diagnosis and management of chronic pancreatitis, see [59]. Diabetes is also a known risk factor for PDAC but can also be an initial symptom of the disease [9,60].…”

Section: Urgent Need For Early Diagnosis: Identification Of Salivary mentioning

confidence: 99%

Defining Parallels between the Salivary Glands and Pancreas to Better Understand Pancreatic Carcinogenesis

Tiffon

2020

Biomedicines

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Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis, largely due to its late presentation. Methods for early detection, the development of reliable screening tools, and the identification of sensitive and specific biomarkers have remained essential research priorities to improve early patient management and outcomes. The pancreas and salivary glands share histological and functional similarities, and the salivary glands have demonstrated a role in oral and systemic health. This review focuses on the similarities and differences between the pancreas and salivary glands and how these can inform our understanding of PDAC genesis and early diagnosis. In particular, chemical exposure, which alters salivary gland gene transcription and morphogenesis, may not only directly impact salivary gland regulation but alter pancreatic function via the systemic secretion of growth hormones. Diabetes and obesity are associated with an increased risk of pancreatic cancer, and a link between chemical exposure and the development of diabetes, obesity, and consequently PDAC genesis is proposed. Possible mechanisms include altering salivary or pancreatic morphology and organ function, disrupting endocrine signaling, or altering pro-inflammatory homeostasis. Finally, saliva contains putative specific biomarkers that show promise as non-invasive diagnostic tools for PDAC.

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“…Chronic pancreatitis (CP) is a progressive fibroinflammatory syndrome of the pancreatic tissue caused by genetic and environmental factors (Singh, Yadav, & Garg, 2019). Most pancreatitis risk genes encode digestive proteases, trypsin inhibitors, or other proteins highly expressed in the pancreas (Mayerle et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

TRPV6 variants confer susceptibility to chronic pancreatitis in the Chinese population

et al. 2020

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Chronic pancreatitis (CP) is a progressive fibroinflammatory syndrome of the pancreatic tissue caused by genetic and environmental factors. Previously reported susceptibility genes in CP explain less than half of the apparent heritability. To uncover novel pathogenic mechanisms, we initially performed low‐coverage whole‐genome sequencing on 464 Chinese CP patients and 504 controls. The transient receptor potential cation channel, Subfamily V, Member 6 (TRPV6) gene was found to be significantly associated with CP after a burden test of aggregated rare nonsynonymous variants with a combined annotation dependent depletion score > 20 (p = .020). In the replication stage, we analyzed the entire coding sequence and exon/intron boundaries of the TPRV6 gene by Sanger sequencing in another 205 patients with CP and 105 controls. Integration of the findings from the two stages resulted in the identification of 25 TRPV6 variants: 1 rare nonsense variant, 20 rare missense variants, and 4 common missense variants. Loss‐of‐function variants, as determined by intracellular Ca2+ concentration in transfected HEK293T cells, were significantly overrepresented in patients as compared to controls (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022). This study provides evidence suggesting that TRPV6 is a novel susceptibility gene for CP.

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Diagnosis and Management of Chronic Pancreatitis

Cited by 327 publications

References 132 publications

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

Defining Parallels between the Salivary Glands and Pancreas to Better Understand Pancreatic Carcinogenesis

TRPV6 variants confer susceptibility to chronic pancreatitis in the Chinese population

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