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Gastroenterology May 2019Since the discovery of the first trypsinogen mutation in families with hereditary pancreatitis, pancreatic genetics has made rapid progress. The identification of... (Review)
Review
Since the discovery of the first trypsinogen mutation in families with hereditary pancreatitis, pancreatic genetics has made rapid progress. The identification of mutations in genes involved in the digestive protease-antiprotease pathway has lent additional support to the notion that pancreatitis is a disease of autodigestion. Clinical and experimental observations have provided compelling evidence that premature intrapancreatic activation of digestive proteases is critical in pancreatitis onset. However, disease course and severity are mostly governed by inflammatory cells that drive local and systemic immune responses. In this article, we review the genetics, cell biology, and immunology of pancreatitis with a focus on protease activation pathways and other early events.
Topics: Animals; Apoptosis; Enzyme Activation; Genetic Predisposition to Disease; Humans; Inflammation Mediators; Mutation; Necrosis; Pancreas; Pancreatitis; Peptide Hydrolases; Phenotype; Prognosis; Protein Folding; Risk Factors; Signal Transduction
PubMed: 30660731
DOI: 10.1053/j.gastro.2018.11.081 -
Pancreatology : Official Journal of the... 2013There have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment...
BACKGROUND
There have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these guidelines using an evidence-based approach.
METHODS
Twelve multidisciplinary review groups performed systematic literature reviews to answer 38 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The review groups presented their recommendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting.
RESULTS
The 38 recommendations covered 12 topics related to the clinical management of acute pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C) imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G) nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancreatitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recommendations, were rated as 'strong' and plenary voting revealed 'strong agreement' for 34 (89%) recommendations.
CONCLUSIONS
The 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical and surgical management of acute pancreatitis based on the currently available evidence. These recommendations should serve as a reference standard for current management and guide future clinical research on acute pancreatitis.
Topics: Acute Disease; Cholecystectomy; Disease Management; Fluid Therapy; Humans; Pancreas; Pancreatitis; Pancreatitis, Acute Necrotizing
PubMed: 24054878
DOI: 10.1016/j.pan.2013.07.063 -
Current Opinion in Gastroenterology Sep 2015This report reviews recent animal model and human studies associated with inflammatory responses in acute and chronic pancreatitis. (Review)
Review
PURPOSE OF REVIEW
This report reviews recent animal model and human studies associated with inflammatory responses in acute and chronic pancreatitis.
RECENT FINDINGS
Animal model and limited human acute and chronic pancreatitis studies unravel the dynamic nature of the inflammatory processes and the ability of the immune cells to sense danger and environmental signals. In acute pancreatitis, such molecules include pathogen-associated molecular pattern recognition receptors such as toll-like receptors, and the more recently appreciated damage-associated molecular pattern molecules or 'alarmin' high mobility group box 1 and IL-33. In chronic pancreatitis, a recent understanding of a critical role for macrophage-pancreatic stellate cell interaction offers a potential targetable pathway that can alter fibrogenesis. Microbiome research in pancreatitis is a new field gaining interest but will require further investigation.
SUMMARY
Immune cell contribution to the pathogenesis of acute and chronic pancreatitis is gaining more appreciation and further understanding in immune signaling presents potential therapeutic targets that can alter disease progression.
Topics: Acute Disease; Animals; Disease Models, Animal; Disease Progression; Fecal Microbiota Transplantation; Humans; Inflammation; Pancreas; Pancreatitis; Pathogen-Associated Molecular Pattern Molecules; Risk Assessment; Sensitivity and Specificity; Signal Transduction; Toll-Like Receptors
PubMed: 26107390
DOI: 10.1097/MOG.0000000000000195 -
Journal of Veterinary Internal Medicine Nov 2021In the last 20 years, the diagnosis of pancreatitis has become more frequent as a result of improved diagnostic modalities such as abdominal ultrasound examination,... (Review)
Review
In the last 20 years, the diagnosis of pancreatitis has become more frequent as a result of improved diagnostic modalities such as abdominal ultrasound examination, advanced imaging, and immunoassays for the measurement of pancreatic lipase. Our aim is to provide a state-of-the-art overview of the clinical diagnosis of acute pancreatitis (AP) in dogs with a particular focus on pancreatic lipase assay validation and clinical performance, in addition to advanced imaging modalities. We also discuss the potential indications for cytology and histopathology in dogs with suspected AP.
Topics: Acute Disease; Animals; Dog Diseases; Dogs; Lipase; Pancreas; Pancreatitis; Ultrasonography
PubMed: 34751442
DOI: 10.1111/jvim.16292 -
World Journal of Gastroenterology May 2023Acute pancreatitis (AP) is an inflammatory disease of the pancreas, which can progress to severe AP, with a high risk of death. It is one of the most complicated and... (Review)
Review
Acute pancreatitis (AP) is an inflammatory disease of the pancreas, which can progress to severe AP, with a high risk of death. It is one of the most complicated and clinically challenging of all disorders affecting the abdomen. The main causes of AP are gallstone migration and alcohol abuse. Other causes are uncommon, controversial and insufficiently explained. The disease is primarily characterized by inappropriate activation of trypsinogen, infiltration of inflammatory cells, and destruction of secretory cells. According to the revised Atlanta classification, severity of the disease is categorized into three levels: Mild, moderately severe and severe, depending upon organ failure and local as well as systemic complications. Various methods have been used for predicting the severity of AP and its outcome, such as clinical evaluation, imaging evaluation and testing of various biochemical markers. However, AP is a very complex disease and despite the fact that there are of several clinical, biochemical and imaging criteria for assessment of severity of AP, it is not an easy task to predict its subsequent course. Therefore, there are existing controversies regarding diagnostic and therapeutic modalities, their effectiveness and complications in the treatment of AP. The main reason being the fact, that the pathophysiologic mechanisms of AP have not been fully elucidated and need to be studied further. In this editorial article, we discuss the efficacy of the existing diagnostic and therapeutic modalities, complications and treatment failure in the management of AP.
Topics: Humans; Pancreatitis; Acute Disease; Pancreas; Diagnostic Imaging; Biomarkers; Severity of Illness Index
PubMed: 37274068
DOI: 10.3748/wjg.v29.i18.2747 -
Expert Review of Gastroenterology &... Nov 2019: Pancreas divisum is the most common congenital malformation of the pancreas with the majority asymptomatic. The etiological role, pathogenesis, clinical significance... (Review)
Review
: Pancreas divisum is the most common congenital malformation of the pancreas with the majority asymptomatic. The etiological role, pathogenesis, clinical significance and management of pancreas divisum in pancreatic disease has not been clearly defined and our understanding is yet to be fully elucidated.: This review describes the role of pancreas divisum in the development of pancreatic disease and the ambiguity related to it. In our attempt to offer clarity, a comprehensive search on PubMed, Ovid, Embase and Cochrane Library from inception to May 2019 was undertaken using key words "pancreas divisum", "idiopathic recurrent acute pancreatitis" and "chronic pancreatitis".: Current research fails to define a clear association between pancreas divisum and pancreatic disease. Though debatable, several studies do suggest a pathological role of pancreas divisum in pancreatic disease and a benefit of minor papilla therapy in the setting of acute recurrent pancreatitis. Surgical and endoscopic therapeutic modalities have not been directly compared. With the current data available, it would be imprudent to advise a definitive line of management for pancreatic disease associated with pancreas divisum and should involve a comprehensive discussion with the individual patient to define expectations before embarking on any medical and/or interventional therapy.
Topics: Digestive System Abnormalities; Humans; Pancreas; Pancreatitis; Pancreatitis, Chronic; Predictive Value of Tests; Prognosis; Recurrence; Risk Assessment; Risk Factors
PubMed: 31663403
DOI: 10.1080/17474124.2019.1685871 -
Gastroenterology May 2019Acute pancreatitis is an inflammatory disorder of the exocrine pancreas associated with tissue injury and necrosis. The disease can be mild, involving only the pancreas,... (Review)
Review
Acute pancreatitis is an inflammatory disorder of the exocrine pancreas associated with tissue injury and necrosis. The disease can be mild, involving only the pancreas, and resolve spontaneously within days or severe, with systemic inflammatory response syndrome-associated extrapancreatic organ failure and even death. Importantly, there are no therapeutic agents currently in use that can alter the course of the disease. This article emphasizes emerging findings that stressors (environmental and genetic) that cause acute pancreatitis initially cause injury to organelles of the acinar cell (endoplasmic reticulum, mitochondria, and endolysosomal-autophagy system), and that disorders in the functions of the organelles lead to inappropriate intracellular activation of trypsinogen and inflammatory pathways. We also review emerging work on the role of damage-associated molecular patterns in mediating the local and systemic inflammatory response in addition to known cytokines and chemokine pathways. In the review, we provide considerations for correction of organelle functions in acute pancreatitis to create a discussion for clinical trial treatment and design options.
Topics: Acute Disease; Alarmins; Animals; Cytokines; Humans; Inflammation Mediators; Organelles; Pancreas; Pancreatitis; Prognosis; Signal Transduction
PubMed: 30660726
DOI: 10.1053/j.gastro.2018.11.082 -
Polskie Archiwum Medycyny Wewnetrznej 2013Recently, the original Atlanta classification of 1992 was revised and updated by the Working Group using a web-based consultative process involving multiple... (Review)
Review
Recently, the original Atlanta classification of 1992 was revised and updated by the Working Group using a web-based consultative process involving multiple international pancreatic societies. The new understanding of the disease, its natural history, and objective description and classification of pancreatic and peripancreatic fluid collections make this new 2012 classification a potentially valuable means of international communication and interest. This revised classification identifies 2 phases of acute pancreatitis - early (first 1 or 2 weeks) and late (thereafter). Acute pancreatitis can be either edematous interstitial pancreatitis or necrotizing pancreatitis, the latter involving necrosis of the pancreatic parenchyma and peripancreatic tissues (most common), pancreatic parenchyma alone (least common), or just the peripancreatic tissues (~20%). Severity of the disease is categorized into 3 levels: mild, moderately severe, and severe. Mild acute pancreatitis lacks both organ failure (as classified by the modified Marshal scoring system) and local or systemic complications. Moderately severe acute pancreatitis has transient organ failure (organ failure of <2 days), local complications, and/or exacerbation of coexistent disease. Severe acute pancreatitis is defined by the presence of persistent organ failure (organ failure that persists for ≥2 days). Local complications are defined by objective criteria based primarily on contrast-enhanced computed tomography; these local complications are classified as acute peripancreatic fluid collections, pseudocyst (which are very rare in acute pancreatitis), acute (pancreatic/peripancreatic) necrotic collection, and walled-off necrosis. This classification will help the clinician to predict the outcome of patients with acute pancreatitis and will allow comparison of patients and disease treatment/management across countries and practices.
Topics: Disease Progression; Humans; Multiple Organ Failure; Pancreas; Pancreatitis; Severity of Illness Index; Tomography, X-Ray Computed
PubMed: 23396317
DOI: 10.20452/pamw.1627 -
Nature Immunology Sep 2023Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and...
Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs. Pancreas TRMs had an extracellular matrix remodeling phenotype that was important for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and death, due to impaired acinar cell survival and recovery. During pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.
Topics: Mice; Animals; Pancreas; Macrophages; Pancreatitis; Fibrosis; Pancreatic Neoplasms
PubMed: 37563309
DOI: 10.1038/s41590-023-01579-x -
Surgical Pathology Clinics Dec 2016Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is... (Review)
Review
Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed.
Topics: Alcohol-Induced Disorders; Autoimmune Diseases; Carcinoma, Pancreatic Ductal; Chronic Disease; Diagnosis, Differential; Humans; Pancreas; Pancreatic Ducts; Pancreatic Pseudocyst; Pancreatitis
PubMed: 27926364
DOI: 10.1016/j.path.2016.05.008