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World Journal of Gastroenterology Feb 2008Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to... (Review)
Review
Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis (SAP). An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as effective as multifactorial scoring systems (MFSS) at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen (BUN), creatinine, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis (PN), infected PN (IPN) and mortality.
Topics: Acute Disease; Humans; Necrosis; Pancreas; Pancreatitis; Predictive Value of Tests; Prognosis; Severity of Illness Index
PubMed: 18205255
DOI: 10.3748/wjg.14.675 -
United European Gastroenterology Journal Oct 2020The human microbiota exerts multiple physiological functions such as the regulation of metabolic and inflammatory processes. High-throughput sequencing techniques such... (Review)
Review
The human microbiota exerts multiple physiological functions such as the regulation of metabolic and inflammatory processes. High-throughput sequencing techniques such as next-generation sequencing have become widely available in preclinical and clinical settings and have exponentially increased our knowledge about the microbiome and its interaction with host cells and organisms. There is now emerging evidence that microorganisms also contribute to inflammatory and neoplastic diseases of the pancreas. This review summarizes current clinical and translational microbiome studies in acute and chronic pancreatitis as well as pancreatic cancer and provides evidence that the microbiome has a high potential for biomarker discovery. Furthermore, the intestinal and pancreas-specific microbiome may also become an integrative part of diagnostic and therapeutic approaches of pancreatic diseases in the near future.
Topics: Biomarkers; DNA, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Intestinal Mucosa; Metagenome; Metagenomics; Microbiota; Pancreas; Pancreatic Neoplasms; Pancreatitis; RNA, Ribosomal, 16S
PubMed: 32703080
DOI: 10.1177/2050640620944720 -
World Journal of Gastroenterology Dec 2014Acute pancreatitis is a nonbacterial disease of the pancreas. The severe form of this ailment is characterized by high mortality. Whether acute pancreatitis develops as... (Review)
Review
Acute pancreatitis is a nonbacterial disease of the pancreas. The severe form of this ailment is characterized by high mortality. Whether acute pancreatitis develops as the severe type or resolves depends on the intensity of the inflammatory process which is counteracted by the recruitment of innate defense mechanisms. It has been shown that the hormones ghrelin, leptin and melatonin are able to modulate the immune function of the organism and to protect the pancreas against inflammatory damage. Experimental studies have demonstrated that the application of these substances prior to the induction of acute pancreatitis significantly attenuated the intensity of the inflammation and reduced pancreatic tissue damage. The pancreatic protective mechanisms of the above hormones have been related to the mobilization of non-specific immune defense, to the inhibition of nuclear factor kappa B and modulation of cytokine production, to the stimulation of heat shock proteins and changes of apoptotic processes in the acinar cells, as well as to the activation of antioxidant system of the pancreatic tissue. The protective effect of ghrelin seems to be indirect and perhaps dependent on the release of growth hormone and insulin-like growth factor 1. Leptin and ghrelin, but not melatonin, employ sensory nerves in their beneficial action on acute pancreatitis. It is very likely that ghrelin, leptin and melatonin could be implicated in the natural protection of the pancreatic gland against inflammatory damage because the blood levels of these substances increase in the initial phase of pancreatic inflammation. The above hormones could be a part of the innate resistance system which might remove noxious factors and could suppress or attenuate the inflammatory process in the pancreas.
Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Ghrelin; Humans; Inflammation Mediators; Leptin; Melatonin; Pancreas; Pancreatitis; Signal Transduction
PubMed: 25493003
DOI: 10.3748/wjg.v20.i45.16902 -
Revista Espanola de Enfermedades... Aug 2009Gastrointestinal symptoms in patients with SLE are common, specifically abdominal pain. However, the rate of pancreatic diseases is much lower and does not reach 5%... (Review)
Review
Gastrointestinal symptoms in patients with SLE are common, specifically abdominal pain. However, the rate of pancreatic diseases is much lower and does not reach 5% according to published series in Europe and the USA. This association between SLE and pancreatic disease is basically at the expense of episodes of acute pancreatitis. An association with chronic pancreatitis is much more uncommon, and only four articles have been published showing this relationship. Three cases of SLE-associated pancreatitis are described, and disease onset, etiological factors, and clinical progression are analyzed. A review of the literature and a brief discussion about pathophysiological mechanisms and the role of corticosteroids are also included.
Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Cholangiopancreatography, Magnetic Resonance; Disease Progression; Endosonography; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Pancreas; Pancreatitis; Pancreatitis, Chronic; Time Factors; Tomography, X-Ray Computed
PubMed: 19785498
DOI: 10.4321/s1130-01082009000800009 -
World Journal of Gastroenterology Nov 2014Despite enthusiastic efforts directed at elucidating critical underlying mechanisms towards the identification of novel therapeutic targets for severe acute pancreatitis... (Review)
Review
Despite enthusiastic efforts directed at elucidating critical underlying mechanisms towards the identification of novel therapeutic targets for severe acute pancreatitis (SAP), the disease remains without a specific therapy to be executed within the first hours to days after onset of symptoms. Although earlier management for SAP should aim to either treat organ failure or reduce infectious complications, the current standard of care for the general management of AP in the first hours to days after onset of symptoms include intravenous fluid replacement, nutritional changes, and the use of analgesics with a close monitoring of vital signs. Furthermore, repeated evaluation of severity is very important, as the condition is particularly unstable in the early stages. In cases where biliary pancreatitis is accompanied by acute cholangitis or in cases where biliary stasis is suspected, an early endoscopic retrograde cholangiopancreatography is recommended. However, practice guidelines regarding the treatment of pancreatitis are suboptimal. In chronic pancreatitis, conservative management strategies include lifestyle modifications and dietary changes followed by analgesics and pancreatic enzyme supplementation. Recently, attention has been focused on phytoceuticals or antioxidants as agents that could surpass the limitations associated with currently available therapies. Because oxidative stress has been shown to play an important role in the pathogenesis of pancreatitis, antioxidants alone or combined with conventional therapy may improve oxidative-stress-induced organ damage. Interest in phytoceuticals stems from their potential use as simple, accurate tools for pancreatitis prognostication that could replace older and more tedious methods. Therefore, the use of antioxidative nutrition or phytoceuticals may represent a new direction for clinical research in pancreatitis. In this review article, recent advances in the understanding of the pathogenesis of pancreatitis are discussed and the paradigm shift underway to develop phytoceuticals and antioxidants to treat it is introduced. Despite the promise of studies evaluating the effects of antioxidants/phytoceuticals in pancreatitis, translation to the clinic has thus far been disappointing. However, it is expected that continued research will provide solid evidence to justify the use of antioxidative phytoceuticals in the treatment of pancreatitis.
Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Antioxidants; Disease Models, Animal; Humans; Oxidative Stress; Pancreas; Pancreatitis; Pancreatitis, Chronic; Phytotherapy; Plant Extracts; Plants, Medicinal; Severity of Illness Index
PubMed: 25469025
DOI: 10.3748/wjg.v20.i44.16570 -
Biochimica Et Biophysica Acta Jun 2016In a recent study we explored Group-1-p21-activated kinases (GP.1-PAKs) in rat pancreatic acini. Only PAK2 was present; it was activated by...
In a recent study we explored Group-1-p21-activated kinases (GP.1-PAKs) in rat pancreatic acini. Only PAK2 was present; it was activated by gastrointestinal-hormones/neurotransmitters and growth factors in a PKC-, Src- and small-GTPase-mediated manner. PAK2 was required for enzyme-secretion and ERK/1-2-activation. In the present study we examined PAK2's role in CCK and TPA-activation of important distal signaling cascades mediating their physiological/pathophysiological effects and analyzed its role in pathophysiological processes important in early pancreatitis. In rat pancreatic acini, PAK2-inhibition by the specific, GP.1.PAK-inhibitor, IPA-3-suppressed cholecystokinin (CCK)/TPA-stimulated activation of focal-adhesion kinases and mitogen-activated protein-kinases. PAK2-inhibition reversed the dual stimulatory/inhibitory effect of CCK/TPA on the PI3K/Akt/GSK-3β pathway. However, its inhibition did not affect PKC activation. PAK2-inhibition protected acini from CCK-induced ROS-generation; caspase/trypsin-activation, important in early pancreatitis; as well as from cell-necrosis. Furthermore, PAK2-inhibition reduced proteolytic-activation of PAK-2p34, which is involved in programmed-cell-death. To ensure that the study did not only rely in the specificity of IPA-3 as a PAK inhibitor, we used two other approaches for PAK inhibition, FRAX597 a ATP-competitive-GP.1-PAKs-inhibitor and infection with a PAK2-dominant negative(DN)-Advirus. Those two approaches confirmed the results obtained with IPA-3. This study demonstrates that PAK2 is important in mediating CCK's effect on the activation of signaling-pathways known to mediate its physiological/pathophysiological responses including several cellular processes linked to the onset of pancreatitis. Our results suggest that PAK2 could be a new, important therapeutic target to consider for the treatment of diseases involving deregulation of pancreatic acinar cells.
Topics: Acinar Cells; Animals; Cell Death; Enzyme Activation; Male; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley; Signal Transduction; p21-Activated Kinases
PubMed: 26912410
DOI: 10.1016/j.bbadis.2016.02.008 -
JOP : Journal of the Pancreas May 2011Groove pancreatitis is a rare condition characterized by fibrotic inflammation affecting the groove anatomical area between the head of the pancreas, the duodenum and... (Review)
Review
CONTEXT
Groove pancreatitis is a rare condition characterized by fibrotic inflammation affecting the groove anatomical area between the head of the pancreas, the duodenum and the common bile duct.
OBJECTIVES
We report a miniseries of five cases treated surgically in our centre over a period of four years. A review of the literature is also discussed.
METHODS
Patients undergoing pancreaticoduodenectomy over a four-year period were retrospectively reviewed. Patients with a confirmed histological diagnosis of groove pancreatitis were assessed under the headings; patient demographics, presenting symptoms, radiological and histological findings.
RESULTS
One-hundred and 60 pancreaticoduodenectomies were performed. Thirty-nine cases demonstrated benign disease and within this, five cases (3.1% of total series; 12.8% of benign cases) were groove pancreatitis. All patients presented with abdominal pain and weight loss, and the majority consumed excess alcohol and were smokers. Radiological findings (CT/MRCP/EUS) revealed duodenal wall thickening in all cases, abnormalities at the head of pancreas and bile duct dilation in four, and cystic changes in the duodenal wall and pancreatic duct dilation in three cases. Groove fibrosis, Brunner's gland hyperplasia and cystic changes in duodenal wall were present in all cases on histological review. All patients reported significant improvement in quality of life at 12 months after surgery.
CONCLUSION
Groove pancreatitis can present in a similar fashion to head of pancreas cancer and chronic pancreatitis. For this reason it is paramount for clinicians to be aware of groove pancreatitis, as this can lead to the correct diagnosis and management of this unique disease.
Topics: Adult; Aged; Common Bile Duct; Duodenum; Female; Humans; Male; Middle Aged; Pancreas; Pancreatitis; Retrospective Studies
PubMed: 21546697
DOI: No ID Found -
Journal of Veterinary Internal Medicine May 2022Lipase measurements and ultrasonographic (US) evidence of pancreatitis correlate poorly.
BACKGROUND
Lipase measurements and ultrasonographic (US) evidence of pancreatitis correlate poorly.
OBJECTIVES
Identify explanations for discrepant lipase and pancreatic US results.
ANIMALS
Two hundred and thirty-four dogs with gastrointestinal signs.
METHODS
A retrospective study was conducted, in which lipase activity and US were performed within 30 hours. Medical history, clinical examination results, lipase activity, and US results were recorded.
RESULTS
Lipase and US results were weakly correlated (r = .25, P < .001). At both evaluated time cut-offs, median lipase activities were significantly higher with shorter durations of clinical signs before presentation (≤2 days, 334 U/L; >2 days, 118 U/L; P = .03; ≤7 days, 334 U/L; >7 days, 99 U/L; P = .004), but US was not significantly more frequently positive. For both cut-offs (>216/≤216 U/L, >355/≤355 U/L; reference range, 24-108 U/L), median disease duration was significantly shorter (3 vs 4 days) with higher lipases. Previous pancreatitis episodes were significantly associated with an US diagnosis of pancreatitis (P = .04), but median lipase activities were not significantly higher (386 U/L vs 153 U/L; P = .06) in these dogs. Pancreatic US was significantly more often positive when the request contained "suspicion of pancreatitis" (P < .001) or "increased lipase" (P = .01). Only changes in pancreatic morphology, echogenicity, and peripancreatic mesentery were significantly associated with a positive US diagnosis, and also had significantly higher lipase activities.
CONCLUSIONS AND CLINICAL IMPORTANCE
Duration of clinical signs before presentation differently affects laboratory and US evidence of pancreatitis. Previous pancreatitis episodes and information given to radiologists influence US results. These findings can be helpful for future studies on pancreatitis in dogs.
Topics: Animals; Dog Diseases; Dogs; Lipase; Pancreas; Pancreatitis; Retrospective Studies
PubMed: 35438226
DOI: 10.1111/jvim.16426 -
Biochimica Et Biophysica Acta.... Jan 2021Protein kinase D (PKD) family, which includes PKD/PKD1, PKD2, and PKD3, has been increasingly implicated in the regulation of multiple cellular functions and human...
BACKGROUND
Protein kinase D (PKD) family, which includes PKD/PKD1, PKD2, and PKD3, has been increasingly implicated in the regulation of multiple cellular functions and human diseases. We recently reported that pharmacologic inhibition of PKD ameliorated the pathologic responses and severity of pancreatitis. However, to further investigate the importance of PKD family members in pancreatitis, it is necessary to explore the effects of pancreas-specific genetic inhibition of PKD isoform on pathology of pancreatitis.
METHODS
We generated a mouse model (referred as PKD3Δpanc mice) with pancreas-specific deletion of PKD3, the predominant PKD isoform in mouse pancreatic acinar cells, by crossing Pkd3flox/flox mice with Pdx1-Cre transgenic mice which express Cre recombinase under the control of the mouse Pdx1 promoter. Pancreas-specific deletion of the PKD3 gene and PKD3 protein was confirmed by PCR and Western blot analysis. Experimental pancreatitis was induced in PKD3Δpanc and Pkd3flox/flox (control mice) littermates by intraperitoneal injections of cerulein or L-arginine.
RESULTS
Compared to the control mice, PKD3Δpanc mice displayed significant attenuation in inflammation, necrosis, and severity of pancreatitis in both experimental models. PKD3Δpanc mice had markedly decreased NF-κB and trypsinogen activation, pancreatic mRNA expression of multiple inflammatory molecules, and the receptor-interacting protein kinase 1 (RIP1) activation in pancreatitis. PKD3Δpanc mice also had less pancreatic ATP depletion, increased pro-survival Bcl-2 family protein expression, and autophagy promotion.
CONCLUSION
With PKD3Δpanc mouse model, we further demonstrated that PKD plays a critical role in pathobiological process of pancreatitis and PKD constitutes a novel therapeutic target to treat this disorder.
Topics: Animals; Disease Models, Animal; Gene Deletion; Inflammation; Mice; Mice, Knockout; Necrosis; Organ Specificity; Pancreas; Pancreatitis; Protein Kinase C; Severity of Illness Index
PubMed: 33039594
DOI: 10.1016/j.bbadis.2020.165987 -
Current Opinion in Gastroenterology Sep 2010This review focuses on studies from the past year that highlight molecular and cellular mechanisms of pancreatic injury arising from acute and chronic pancreatitis. (Review)
Review
PURPOSE OF REVIEW
This review focuses on studies from the past year that highlight molecular and cellular mechanisms of pancreatic injury arising from acute and chronic pancreatitis.
RECENT FINDINGS
Factors that induce or ameliorate injury as well as cellular pathways involved have been examined. Causative or sensitizing factors include refluxed bile acids, hypercalcemia, ethanol, hypertriglyceridemia, and acidosis. In addition, the diabetes drug exendin-4 has been associated with pancreatitis, whereas other drugs may reduce pancreatic injury. The intracellular events that influence disease severity are better understood. Cathepsin-L promotes injury through an antiapoptotic effect, rather than by trypsinogen activation. In addition, specific trypsinogen mutations lead to trypsinogen misfolding, endoplasmic reticulum stress, and injury. Endogenous trypsin inhibitors and upregulation of proteins including Bcl-2, fibroblast growth factor 21, and activated protein C can reduce injury. Immune cells, however, have been shown to increase injury via an antiapoptotic effect.
SUMMARY
The current findings are critical to understanding how causative factors initiate downstream cellular events resulting in pancreatic injury. Such knowledge will aid in the development of targeted treatments for pancreatitis. This review will first discuss factors influencing pancreatic injury, and then conclude with studies detailing the cellular mechanisms involved.
Topics: Animals; Apoptosis; Endoplasmic Reticulum; Humans; Pancreas; Pancreatitis, Acute Necrotizing; Pancreatitis, Chronic; Trypsin; Trypsinogen
PubMed: 20651589
DOI: 10.1097/MOG.0b013e32833d119e