Abstract Acute Pancreatitis Research Articles

Precision Medicine in Pancreatitis: The Future of Acute Pancreatitis Care.

Acute pancreatitis (AP) continues to present a substantial burden to patients and healthcare personnel. Despite its occasionally severe progression and high mortality rate, there is no specific therapy that could be routinely applied in patients with AP. Here, we review treatment possibilities in AP, describe how the treatment approaches have changed in pancreatic cancer as an analogy, and point out potential causes for the failure of clinical trials on AP. We highlight that instead of attempting to discover generalized treatment options that could be used in any AP patient, it is time for a paradigm shift in the treatment of AP, which would help to focus more on individual patients or specific patient subpopulations when designing clinical trials and therapeutic approaches (similarly as in pancreatic cancer). Since the recruitment of specific patient subpopulations with AP could take excessive time if clinical centers work separately, the development of precision medicine in AP would require to establish an expert committee, eg, Pancreatitis Precision Medicine Interest Group, which could organize and coordinate the activities of the joined centers. With the joined forces of expert clinicians and leading centers, a new era could start in the treatment of AP, in which personalized treatment options could be discovered and introduced to efficiently reduce the burden of the disease on patients and healthcare workers.

Inhibition of Notch activity suppresses hyperglycemia-augmented polarization of macrophages to the M1 phenotype and alleviates acute pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory disorder characterized by acinar cell death and inflammation. Multiple factors cause hyperglycemia after AP. Macrophage polarization is involved in tissue injury and repair, and is regulated by Notch signaling during certain inflammatory diseases. The present study explores the relationship among hyperglycemia, macrophage polarization, and Notch signaling during AP and the related mechanisms. A cerulein-induced AP model was established in FVB/N mice, and AP with hyperglycemia was initiated by injection of 50% concentration glucose. Tissue damage, Notch activity, and macrophage polarization were assessed in pancreatic tissues. The role of Notch signaling in macrophage polarization during AP was also assessed in vitro by co-culturing primary macrophages and pancreatic acinar cells, and establishing a lipopolysaccharide (LPS)-induced inflammatory model in RAW264.7 cells. Pancreatic acinar cells were damaged and proinflammatory factor levels were increased in pancreatic tissues during AP. The hyperglycemic conditions aggravated pancreatic injury, increased macrophage infiltration, promoted macrophage polarization towards an M1 phenotype, and led to excessive up-regulation of Notch activity. Inhibition of Notch signaling by DAPT or Notch1 knockdown decreased the proportion of M1 macrophages and reduced the production of proinflammatory factors, thus mitigating pancreatic injury. These findings suggest that hyperglycemia induces excessive Notch signaling after AP and further aggravates AP by promoting pancreatic macrophage polarization towards the M1 phenotype. The Notch signaling pathway is a potential target for the prevention and treatment of AP.

The anti-inflammatory mechanism of SAHA in acute pancreatitis through HDAC5/SLIT2/Akt/β-catenin axis.

Acute pancreatitis (AP) is widely recognized to be an inflammation-related disease, in which HDAC was upregulated. The anti-inflammatory role of suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor, has been documented. In this context, this research was implemented to figure out whether SAHA manipulated inflammation in AP. Subsequent to induction of AP mouse model, HDAC5 expression was detected. The binding of HDAC5 and SLIT2 was detected by Co-Immunoprecipitation and Chromatin immunoprecipitation assays. SAHA treatment and gain- and loss-of-function approaches were used in AP mice and lipopolysaccharide (LPS)-induced pancreatic acinar cells. In mice, biochemical methods were implemented to measure activities of pancreatic lipase, trypsin, myeloperoxidase (MPO) and pancreatic edema, TUNEL staining to determine pancreatic cell apoptosis, and flow cytometry to assess the total number of leukocytes and neutrophils in pancreas. In pancreatic acinar cells, CCK-8 was performed to evaluate cell viability. HDAC5 exhibited overexpression in AP mice. Mechanical analysis showed that HDAC5 facilitated SLIT2 deacetylation to downregulate SLIT2, thus activating Akt/β-catenin pathway in pancreatic acinar cells. SAHA treatment, HDAC5 silencing or SLIT2 overexpression diminished inflammation in AP in vivo and in vitro. SAHA treatment, HDAC5 silencing or SLIT2 overexpression reduced activities of pancreatic lipase, trypsin, MPO, pancreatic edema and cell apoptosis in AP mice as well as elevated viability of LPS-induced pancreatic acinar cells. SAHA might exert anti-inflammatory effects in AP mice via HDAC5/SLIT2/Akt/β-catenin axis.

Acute Postoperative Pancreatitis after Craniotomy for Excision of Insular Glioma: A Classic Case of Whodunit

Abstract Acute pancreatitis (AP) has been reported following abdominal surgeries. There are rare reports of AP developing following operations remote to the pancreas. We report a case of postoperative AP following craniotomy for tumor excision. A 15-year-old girl presented with a history of one episode of seizure, headache, and recent left-sided hemiparesis. She was found to have a right frontal glial lesion with extensive white matter tract edema. Craniotomy and excision was done. On the first postoperative day, she developed acute abdominal pain, with guarding and tenderness on examination. Radiological and biochemical evidence for AP was found. AP is a rare, but life-threatening complication. A number of drugs commonly used in neurosurgical practice can cause AP, which include steroids, antiepileptics, and propofol which are extensively used during surgery and for sedation in the intensive care area.

Traditional Chinese Medicine Formulas Alleviate Acute Pancreatitis: Pharmacological Activities and Mechanisms.

Acute pancreatitis (AP) is a common clinical gastrointestinal disorder with a high mortality rate for severe AP and lacks effective clinical treatment, which leads to considerable comorbidity and financial burden. Traditional Chinese medicine (TCM) has had the unique advantage of treating AP for a long time in China. Clinically, TCM formulas such as Da-cheng-qi decoction, Chai-qin-cheng-qi decoction, Qing-yi decoction, Da-chai-hu decoction, and Da-huang-fu-zi decoction are widely administrated to AP patients. All of these TCM formulas can improve gastrointestinal function, regulate the inflammatory response, and enhance immunity, thus preventing complications, reducing the mortality rate and financial burden. This review will summarize the pharmacological activities and mechanisms of TCM formulas in alleviating AP.

Interventional endoscopic treatment in acute pancreatitis

Acute pancreatitis (AP) represents a frequent gastrointestinal diseases. Approximately 80% of patients have amild course of the disease and conservative treatment is sufficient; however, 20% of patients develop asevere AP with local and systemic complications. This article focuses on the currently recommended endoscopic management of severe AP. Classification of AP by the revised Atlanta classification and the occurrence of local or systemic complications. Summary of current evidence with respect to endoscopic management. Inspection of the current literature from specialist journals and current guidelines. The AP is classified as mild, moderate or severe based on systemic (hypotension, renal failure, lung failure) and/or local complications, such as acute peripancreatic fluid collections (APFC), peripancreatic pseudocysts (PPC), acute necrotic collections (ANC) and walled-off necrosis (WON). In recent years the staged endoscopic treatment of infected ANC, WON and PPC has become established. The initial step is the endoscopic ultrasound-guided puncture and drainage with plastic or lumen-apposing metal stents. For solid components or insufficient drainage, atransgastric endoscopic necrosectomy is recommended. The treatment of severe AP requires an interdisciplinary management in specialized centers and regular re-evaluation of the therapeutic efficacy. Interventional endoscopy has become established as the standard for treatment of severe AP.

Ghee Butter from Bovine Colostrum Reduces Inflammation in the Mouse Model of Acute Pancreatitis with Potential Involvement of Free Fatty Acid Receptors.

Acute pancreatitis (AP) is an inflammatory disease that causes severe tissue damage. Ghee butter from bovine colostrum (GBBC) is a clarified butter produced by heating milk fat to 40 °C and separating the precipitating protein. As colostrum mainly contains fatty acids (FAs), immunoglobulins, maternal immune cells, and cytokines, we hypothesized that it may exert anti-inflammatory effects. We investigated the effects of GBBC on experimental AP in mice. Two intraperitoneal (ip) injections of L-arginine (8%) were given 1 h apart to generate the AP murine model. After 12 h from the first L-arginine injection, mice were divided into the following experimental groups: AP mice treated with GBBC (oral gavage (po) every 12 h) and non-treated AP mice (po vehicle every 12 h). Control animals received vehicle only. At 72 h, mice were euthanized. Histopathological examination along with myeloperoxidase (MPO) and amylase/lipase activity assays were performed. In a separate set of experiments, FFAR1 and FFAR4 antagonists were used to verify the involvement of respective receptors. Administration of GBBC decreased MPO activity in the pancreas and lungs along with the microscopical severity of AP in mice. Moreover, treatment with GBBC normalized pancreatic enzyme activity. FFAR1 and FFAR4 antagonists tended to reverse the anti-inflammatory effect of GBBC in mouse AP. Our results suggest that GBBC displays anti-inflammatory effects in the mouse model of AP, with the putative involvement of FFARs. This is the first study to show the anti-inflammatory potential of a nutritional supplement derived from GBBC.

Blood glucose-related indicators are associated with in-hospital mortality in critically ill patients with acute pancreatitis

Acute pancreatitis (AP) results in potentially harmful blood glucose fluctuations, affecting patient prognosis. This study aimed to explore the relationship between blood glucose-related indicators and in-hospital mortality in critically ill patients with AP. We extracted data on AP patients from the Multiparameter Intelligent Monitoring in Intensive Care III database. Initial glucose (Glucose_initial), maximum glucose (Glucose_max), minimum glucose (Glucose_min), mean glucose (Glucose_mean), and glucose variability (glucose standard deviation [Glucose_SD] and glucose coefficient of variation [Glucose_CV]) were selected as blood glucose-related indicators. Logistic regression models and the Lowess smoothing curves were used to display the association between significant blood glucose-related indicators and in-hospital mortality. Survivors and non-survivors showed significant differences in Glucose_max, Glucose_mean, Glucose_SD, and Glucose_CV (P < 0.05). Glucose_max, Glucose_mean, Glucose_SD, and Glucose_CV were risk factors for in-hospital mortality in AP patients (OR > 1; P < 0.05). According to the Lowess smoothing curve, the overall trends of blood glucose-related indicators showed a non-linear correlation with in-hospital mortality. Glucose_max, Glucose_mean, Glucose_SD, and Glucose_CV were associated with in-hospital mortality in critically ill patients with AP.

Guidelines for the diagnosis and treatment of acute pancreatitis in China (2021)

Abstract Acute pancreatitis (AP) is a common acute abdominal condition of the digestive system. In recent years, treatment concepts, methods, and strategies for the diagnosis of AP have advanced, and this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients. On the basis of previous guidelines and expert consensus, this guideline adopts an evidence-based, problem-based expression; synthesizes important clinical research data at home and abroad in the most recent 5 years; and forms 29 recommendations through multidisciplinary expert discussion, including diagnosis, treatment, and follow-up. It is expected to provide evidence support for the treatment of AP in the clinical setting in China.

Prognostic value of peripheral blood CD14+HLA-DR+ monocytes in patients with acute pancreatitis

ABSTRACT Acute pancreatitis (AP) is characterized by a potent pro-inflammatory response and concomitant anti-inflammatory response leading to a state of immunosuppression. Decreased HLA (Human Leukocyte Antigen)-DR expression on monocytes is a reliable cellular marker of immune suppression. The main objective of this study was to investigate the clinical value of the percentage of peripheral blood CD14+ HLA-DR+ monocytes (mHLA-DR) for diagnosis and assessment of severity, development of organ failures (OF), local complications (LC), and infected necrosis (IN), and outcome in patients with AP. Flow cytometry was used to measure the percentage of peripheral blood mHLA-DR at different time points in 82 patients with AP enrolled during the period of 2012–2018 admitted to University Hospital Stara Zagora, Bulgaria. The percentages of peripheral blood mHLA-DR in AP patients were significantly associated with severity, development of LC, OF, IN (measured at admission, on the 48th hour and on the 5th day) and with outcome (measured on the 5th day) of AP. The value of peripheral blood mHLA-DR may be used as a biological marker in the diagnosis and assessment of severity, development of OF, LC, IN and to predict outcome in AP.

A Rare Case: Gall Stone Induced Acute Pancreatitis with Normal Amylase and Lipase Levels

Acute pancreatitis (AP) is most commonly diagnosed by increased values of serum amylase and lipase. Acute pancreatitis where value of serum amylase and lipase is normal is very rare. This is a case of gall stone induced AP where levels of serum amylase and lipase are normal but the clinical suspicion and imaging are strongly confirming pancreatitis.

Role of adipokines in the assessment of severity and predicting the clinical course of acute pancreatitis.

Acute pancreatitis (AP) is one of the most common diseases requiring hospitalization with increasing incidence. This pathology has variable severity and is associated with significant morbidity and mortality. Early diagnosis, including prognosis of clinical course of the disease is key in the initial clinical management. However, currently available prognostic markers have variable efficacy and the limited utility. Adipokines that are released from the peripancreatic adipose tissue during AP may represent the easy to use and practical AP prognostic markers. This review discusses the current state of knowledge concerning the clinical value of the adipokines in AP, such as adiponectin, ghrelin, interleukin 6, interleukin 8, interleukin 18, leptin, neutrophil gelatinase associated lipocalin, obestatin, resistin, visfatin. Among described adipokines, interleukin 6, neutrophil gelatinase associated lipocalin and resistin seem to be the most valuable as the diagnostic and prognostic markers in AP.

Multiple extra-splanchnic venous thromboses - an unusual vascular complication of acute pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas with variable clinical presentations. Splanchnic venous thrombosis is a well-known vascular complication of AP and commonly present as thrombosis of the splanchnic venous system: splenic vein (SplV), portal vein (PV) and superior mesenteric vein (SMV), either separately or in combinations. Involvement of extra-splanchnic vessels is rare and associated with morbidity and mortality. Vascular complications are late phenomena and usually associated with local complications of AP, namely acute fluid collections, necrotizing pancreatitis and walled-off pancreatic necrosis. Pathogenesis of venous thrombosis is multifactorial in which pancreatic inflammation and systemic inflammatory response play a key role. At present, there are no consensus guidelines on treatment and use of anticoagulation for venous thrombosis in the setting of AP. Limited literature suggests the use of anticoagulation in presence of PV with or without SMV thrombosis and extrasplanchnic vessel involvement. Literature on extra-splanchnic vessels involvement in acute pancreatitis is sparse. Here we present two cases with multiple extra-splanchnic vessels involvement and their management.

Early Risk Stratification in Acute Pancreatitis: The Role of Biochemical and Hematological Parameters

Abstract Acute pancreatitis (AP) represents an inflammatory condition,-with a wide spectrum of local and systemic complications. Early stratification of severity of pancreatitis is an important step in guiding the management of the disease and improving outcomes. Throughout the years many researchers have looked at various risk stratification parameters which could be used from the admission of patients, however current available scores are cumbersome. Our aim was to evaluate the role of biochemical and hematological parameters in the early stratification of severity of AP, regarding the length of hospitalization. We conducted an observational study which included 100 patients with AP admitted to the Gastroenterology Department over a period 18 months. AP diagnosis was set according to 2013 ACG criteria. Demographic, clinical and imaging data related to the pancreatitis flare were collected from their charts. Length of hospital stay was used as surrogate marker for severity of AP. We evaluated different biochemical and hematological parameters which influenced the length of hospitalization. Several hematological parameters and ratio did not correlate with length of hospital stay in our study cohort, however there was a significant relation of hyperglycemia and alkaline phosphatase levels with hospitalization duration. Early risk stratification in AP remains difficult with routine blood work done at admission. Glycemic control and serum level of alkaline phosphatase seems to be correlated with length of hospital stay.

Idiopathic acute pancreatitis: a single-center investigation of clinical and biochemical features

Acute pancreatitis (AP) is termed as idiopathic (IAP) when the underlying conditions of pancreatic inflammation remain unknown. The aim of this study was to identify different clinical features in patients with IAP and AP of known aetiology. All patients hospitalized in our Gastroenterology Unit with an initial diagnosis of AP were recruited. AP was classified as of known aetiology or idiopathic according to clinical examination, serum biochemistry testing, and radiological imaging investigations, and clinical data in both patient groups were compared. A total of 127 patients (80 males, mean age: 57years) were eligible for the analysis, 92 of which (73%) with AP of known aetiology and 35 (27%) with IAP. The major causes of AP were biliary obstruction (65%) or alcohol abuse (25%). Previous cholecystectomy was more frequent in patients with AP of known aetiology than in patients with IAP (14% versus 0%); patients with IAP showed lower gamma-glutamyl transpeptidase levels, lower daily alcohol intake, and higher frequency of gastroenteritis than patients with AP of known aetiology (34.3% versus 15.2%). Previous intake of nonsteroidal anti-inflammatory drugs was more frequent in patients with IAP than in patients with AP of known aetiology (23% versus 0%). No further differences in clinical features were found between the two patient groups. IAP accounts for almost 20% of cases of AP. An association of AP with gastroenteritis or the use of NSAIDs should be considered if time-related with disease onset, especially in patients with no recurrent attacks.

Analysis of risk factors associated with acute pancreatitis after endoscopic papillectomy

Acute pancreatitis (AP) is a common adverse event (AE) of endoscopic papillectomy (EP). Prophylactic plastic pancreatic stent (PPS) placement appears to prevent AP. We evaluated factors associated with post-EP AP by a retrospective analysis of patients with tumors of the duodenal papilla who underwent EP from January 2008 to November 2016 at 2 tertiary care centers. Clinical, laboratory, endoscopic ultrasound parameters, and PPS placement were evaluated. Seventy-two patients underwent EP (37 men), with mean age of 60.3 (31–88) years. Mean main pancreatic duct (MPD) diameter was 0.44 (0.18–1.8) cm. Mean tumor size was 1.8 (0.5–9.6) cm. Tumors were staged as uT1N0, uT2N0, and uT1N1 in 87.5%, 11.1%, and 1.4%. Thirty-eight AEs occurred in 33 (45.8%) patients, with no mortality. Total bilirubin, tumor size, MPD diameter, and PPS placement had odds ratios (ORs) of 0.82, 0.14, 0.00, and 6.43 for AP. Multivariate analysis (PPS placement × MPD diameter) showed ORs of 4.62 (95%CI, 1.03–21.32; p = 0.049) and 0.000 (95%CI, 0.00–0.74; p = 0.042) for AP. In conclusion, patients with jaundice, large tumors, and dilated MPD seem less likely to have post-EP AP. PPS placement was associated with a higher risk of AP, which may question its use.

Heparanase in Acute Pancreatitis.

Acute pancreatitis (AP) is one of the most common diseases in gastroenterology, affecting 2% of all hospitalized patients. Nevertheless, neither the etiology nor the pathophysiology of the disease is fully characterized, and no specific or effective treatment has been developed. Heparanase (Hpa) is an endoglycosidase that cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans (HSPGs) into shorter oligosaccharides, activity that is highly implicated in cell invasion associated with cancer metastasis and inflammation. Given that AP is a typical inflammatory disease, we investigated whether Hpa plays a role in AP. Our results provide keen evidence that Hpa expression and activity are significantly increased following cerulein-induced AP in wild type mice. In parallel to the classic manifestations of AP, namely elevation of amylase and lipase levels, pancreas edema and inflammation as well as induction of cytokines and signaling molecules, have been detected in this experimental model of the disease. Noteworthy, these features were far more profound in transgenic mice overexpressing heparanase (Hpa-Tg), suggesting that these mice can be utilized as a model system to reveal the molecular mechanism by which Hpa functions in AP. Further support for the involvement of Hpa in the pathogenesis of AP emerged from our observation that treatment of experimental AP with PG545 or SST0001(= Ronepastat), two potent Hpa inhibitors, markedly attenuated the biochemical, histological and immunological manifestations of the disease. Hpa, therefore, emerges as a potential new target in AP, and Hpa inhibitors are hoped to prove beneficial in AP along with their promising efficacy as anti-cancer compounds.

Effects of Fluid Resuscitation on Organ Failure and Mortality in Patients with Acute Pancreatitis and Systemic Inflammatory Response Syndrome: A Retrospective Cohort Study

Acute pancreatitis (AP), or inflammation of the pancreas, is a common gastrointestinal condition sometimes associated with systemic inflammatory response syndrome...

VALUE OF COMBINATION OF HAP SCORE AND BISAP SCORE IN PREDICTING SEVERITY IN PATIENTS OF ACUTE PANCREATITIS

Acute pancreatitis (AP) is an acute inflammation of the pancreas, usually occurs suddenly with a variety of clinical symptoms, complications of multiple organ failure and high mortality rates. Objectives: To determine the value of combination of HAP score and BISAP score in predicting the severity of acute pancreatitis of the Atlanta 2012 Classification. Patients and Methods: 75 patients of acute pancreatitis hospitalized at Hue Central Hospital between March 2017 and July 2018; HAP and BISHAP score is calculated within the first 24 hours. The severity of AP was classified by the revised Atlanta criteria 2012. Results: When combining the HAP and BISAP scores in predicting the severity of acute pancreatitis, the area under the ROC curve was 0,923 with sensitivity value was 66.7%, specificity value was 97.1%; positive predictive value was 66.7%, negative predictive value was 97.1%. Conclusion: The combination of HAP and BISAP scores increased the sensitivity, predictive value, and prognostic value in predicting the severity of acute pancreatitis of the revised Atlanta 2012 classification in compare to each single scores. Key words: HAPscore, BiSAP score, acute pancreatitis, predicting severity

Carbon Monoxide Impairs CD11b+Ly-6Chi Monocyte Migration from the Blood to Inflamed Pancreas via Inhibition of the CCL2/CCR2 Axis.

Acute pancreatitis (AP) is a sterile inflammation, in which inflammatory monocytes (CD11b+Ly-6Chi) are recruited into the inflamed tissue at the onset of disease. Monocyte infiltration and activation at the site of inflammation are critical to the pathogenesis of AP. Our previous studies have shown a protective role for CO in AP, which is partially mediated by inhibition of macrophage activation via TLR4 signaling. In the current study, to gain a better understanding of CO's therapeutic effect, we further investigated whether CO could affect inflammatory monocyte trafficking during AP. In a mouse model of AP, we found that treatment with CO-releasing molecule-2 (CORM-2) impaired recruitment of inflammatory monocytes, but not that of neutrophils, from peripheral blood to inflamed pancreas. During the early stage of AP, a single dose of CORM-2 decreased pancreatic CCL2 and soluble ICAM-1 expression. In addition, using in vivo and in vitro experiments, we found that CORM-2 had the ability to inhibit CD11b+Ly-6Chi monocyte migration via blockade of CCR2 endocytosis. Notably, we showed that CORM-2 inhibited CCR2 endocytosis of inflammatory monocytes (CD14hiCD16-) from AP patients. Taken together, our results highlighted CO's effect on inflammatory monocyte trafficking, shedding additional light on its therapeutic potential in AP.