Persistently High Procalcitonin and C-Reactive Protein Are Good Predictors of Infection in Acute Necrotizing Pancreatitis: A Systematic Review and Meta-Analysis.

Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic therapy can save patients' lives. We systematically searched three databases on 27 October 2022. In the eligible studies, the presence of infection in necrotizing pancreatitis was confirmed via a reference test, which involved either the identification of gas within the necrotic collection through computed tomography imaging or the examination of collected samples, which yielded positive results in Gram staining or culture. Laboratory biomarkers compared between sterile necrotizing pancreatitis and INP were used as the index test, and our outcome measures included sensitivity, specificity, the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval (CI): 0.62-0.76), for procalcitonin (PCT), it was 0.69 (CI: 0.60-0.78), and for white blood cell count, it was 0.61 (CI: 0.47-0.75). After the first 72 h, the pooled AUC of CRP showed an elevated level of 0.88 (CI: 0.75-1.00), and for PCT, it was 0.86 (CI: 0.60-1.11). The predictive value of CRP and PCT for infection is poor within 72 h after hospital admission but seems good after the first 72 h. Based on these results, infection is likely in case of persistently high CRP and PCT, and antibiotic initiation may be recommended.

Immunomodulation Through Beta-D-glucan in Chemically-induced Necrotizing Pancreatitis.

BACKGROUND: Although the ability of ß-D-glucan and monophosphoryl lipid A (MPLA) to modulate immune responses has been studied in human primary cells, their effect on sterile inflammation models such as necrotizing pancreatitis has never been investigated. MATERIALS AND METHODS: 85 male New Zealand rabbits were assigned into following groups: A: control, B: pretreatment with ß-D-glucan 3 d before pancreatitis, C: pretreatment with MPLA 3 d before pancreatitis, D: pretreatment with ß-D-glucan and laminarin 3 d before pancreatitis, E: treatment with ß-D-glucan 1 d after pancreatitis, and F: MPLA 1 d after pancreatitis. Pancreatitis was induced by sodium taurocholate injection into the pancreatic duct and parenchyma. Survival was recorded for 21 d. On days 1, 3, and 7, blood was collected for amylase measurement. Peripheral blood mononuclear cells were isolated and stimulated for tumor necrosis factor alpha and interleukin 10 production. Pancreatic necrosis and tissue bacterial load were assessed. RESULTS: 21-d survival was prolonged after pretreatment or treatment with ß-D-glucan; this benefit was lost with laminarin administration. At sacrifice, pancreatic inflammatory alterations were more prominent in the control group. Bacterial load was lower after pretreatment or treatment with ß-D-glucan and MPLA. Tumor necrosis factor alpha production from stimulated peripheral blood mononuclear cells was significantly decreased, whereas interleukin 10 production remained unaltered after pretreatment or treatment with ß-D- glucan. CONCLUSIONS: ß-D-glucan reduces mortality of experimental pancreatitis in vivo. This is mediated through attenuation of cytokine production and prevention of bacterial translocation.

Predictive value of serum soluble B7-H4 in acute pancreatitis.

BACKGROUND: Studies reported that soluble B7-H4 (sB7-H4) was significantly related to the progression and prognosis of inflammatory diseases, and whether sB7-H4 is related to the severity and prognosis of acute pancreatitis (AP) timely has not been reported. MATERIALS AND METHODS: Clinical database data of 446 AP patients were retrospectively collected, and the correlation between the expression serum levels of sB7-H4 with inflammatory factors and prognostic scores was analysed in AP patients. RESULTS: Soluble B7-H4 was significantly correlated with IL-6, IL-8, TNF-α, PCT, CRP levels and WBC count (P < .01), with correlation coefficients of R = .61, .53, .46, .60, .57 and .47, respectively, and AUCs were 0.905, 0.837, 0.797, 0.858, 0.890, 0.841 and 0.855, respectively. In addition, sB7-H4 was significantly correlated with the Ranson score, APACHE II score and BISAP score (P < .001), with correlation coefficients of R = .58, .63 and .59, respectively. The AUCs of assessing local complications of AP were 0.908, 0.863, 0.785 and 0.844, respectively; assessing organ failure were 0.872, 0.790, 0.796 and 0.857, respectively; and assessing in-hospital mortality were 0.839, 0.821, 0.796 and 0.823, respectively. CONCLUSIONS: Soluble B7-H4 could be used as a marker for the diagnosis, severity assessment and poor prognosis assessment of AP patients, which may have potential clinical applications.

A simple new scoring system for predicting the mortality of severe acute pancreatitis: A retrospective clinical study.

It is critical to accurately identify patients with severe acute pancreatitis (SAP) in a timely manner. This study aimed to develop a new simplified AP scoring system based on data from Chinese population.We retrospectively analyzed a consecutive series of 585 patients diagnosed with SAP at the Changhai hospital between 2009 and 2017. The new Chinese simple scoring system (CSSS) was derived using logistic regression analysis and was validated in comparison to 4 existing systems using receiver operating characteristic curves.Six variables were selected for incorporation into CSSS, including serum creatinine, blood glucose, lactate dehydrogenase, heart rate, C-reactive protein, and extent of pancreatic necrosis. The new CSSS yields a maximum total score of 9 points. The cut-offs for predicting mortality and severity (discriminating moderately SAP from SAP) were set as 6 points and 4 points respectively. Compared with 4 existing scoring systems, the area under the receiver operating characteristic of CSSS for prediction of mortality was 0.838, similar to acute physiology and chronic health evaluation II (0.844) and higher than Ranson's score (0.702, P < .001), bedside index of severity in acute pancreatitis (0.615), and modified computed tomography severity index (MCTSI) (0.736). For predicting SAP severity, CSSS was the most accurate (0.834), followed by acute physiology and chronic health evaluation II (0.800), Ranson's score (0.702), MCTSI (0.660), and bedside index of severity in acute pancreatitis (0.570). Further, the accuracy of predicting pancreatic infection with CSSS was the highest (0.634), similar to that of MCTSI (0.641).A new prognostic scoring system for SAP was derived and validated in a Chinese sample. This scoring system is a simple and accurate method for prediction of mortality.

Superoxide Dismutase Predicts Persistent Circulation Failure and Mortality in the Early Stage of Acute Pancreatitis.

OBJECTIVES: Oxidative stress is an important event in the pathogenesis of acute pancreatitis. Superoxide dismutase is a major antioxidant enzyme in the body. The aim of this study was to investigate the changes in superoxide dismutase activity early in the onset of acute pancreatitis and its value in predicting the risk of organ failure and mortality. METHODS: Data for 2549 patients hospitalized from 2013 to 2017 were extracted from the prospective database, and we selected 854 adult patients who were admitted within 24 h of disease onset with complete data. Serum superoxide dismutase activities on the first, second, and third days of hospital admission for patients with different severities, organ failure, and mortality were compared. The areas under the curve for the prediction of organ failure, pancreatic necrosis, and mortality were estimated using receiver operating characteristic curves. RESULTS: Among the 854 adult patients, superoxide dismutase activities were significantly different among patients with mild acute pancreatitis, moderately severe acute pancreatitis, and severe acute pancreatitis (P = 0.005). Superoxide dismutase activity was significantly decreased in patients with persistent renal failure (77.8 ± 37.2), persistent circulatory failure (66.2 ± 14.9), and mortality (64.3 ± 16.0). The accuracy of superoxide dismutase with regard to predicting persistent circulatory failure and mortality was high, and the areas under the receiver operating characteristic curves were 0.83 and 0.84, respectively. CONCLUSIONS: Superoxide dismutase activity was negatively correlated with the severity and clinical outcome of AP. Superoxide dismutase activity is highly accurate at predicting persistent circulation failure and mortality in the early stage of AP.

Heme Oxygenase-1 Polymorphism Is Associated With the Development of Necrotic Acute Pancreatitis Via Vascular Cell Adhesion Molecule-1 and the E-Selectin Expression Regulation Pathway.

OBJECTIVES: Severe acute pancreatitis can lead to systemic complications. Here, we explore the mechanisms based on our previous study associated with the deregulation of heme oxygenase-1 (HO-1) and development of severe acute pancreatitis. METHODS: Acute pancreatitis patients (n = 135) and age- and sex-matched healthy controls (n = 108) were studied. The polymerase chain reaction products were analyzed with an ABI 3130 genetic analyzer and GeneMapper software. A short allele was defined ≤27 dinucleotide (GT) repeats, whereas a long allele was defined >27 GT. Levels of 12 different cytokines in blood serum were measured by enzyme-linked immunosorbent assay. All samples in this study were consistently stored in -80°C. RESULTS: Patients with the long long genotype expressed E-selectin and vascular cell adhesion molecule-1 at statistically significantly higher levels in serum compared with short short genotype or short long genotypes. Vascular cell adhesion molecule-1 and E-selectin serum levels significantly correlate with the total allele length of the HO-1 promoter region. CONCLUSION: Polymorphism of the GT repeats in the HO-1 promoter region may be a risk factor for developing acute necrotizing pancreatitis due to deregulation of the immune response.

Association of elevated serum triglyceride levels with a more severe course of acute pancreatitis: Cohort analysis of 1457 patients.

BACKGROUND: Previous publications have reported an association between hypertriglyceridemia (HTG) and severity of acute pancreatitis, but this relationship remains somewhat controversial. OBJECTIVE: To evaluate the outcome of acute pancreatitis according to serum triglyceride levels on admission. METHODS: Retrospective analysis of prospectively collected data, which included all consecutive cases of acute pancreatitis admitted to a tertiary hospital (January 2002-December 2014). Acute pancreatitis patients were classified into 3 groups based on serum triglyceride levels (mg/dl) measured within 48 h from admission: normal triglycerides-mild HTG (<200); moderate HTG (200-749); severe HTG (≥750). Primary outcomes were the difference in organ failure, pancreatic necrosis, acute peripancreatic collections and mortality among the three groups. RESULTS: A total of 1,457 cases were included: 1,335 with normal-mild HTG, 77 with moderate HTG and 45 with severe HTG. The rates of organ failure (11.2% in normal-mild HTG group, 15.6% in moderate HTG and 20.0% in severe HTG), persistent multiple organ failure (2.5% vs. 5.2% vs. 6.7%), pancreatic necrosis (9.2% vs. 14.3% vs. 26.7%) and acute collections (21.6% vs. 40.3% vs. 55.6%) increased significantly with hypertriglyceridemia severity grades. On multivariate analysis, triglycerides as a quantitative variable, evaluated in increments of 100 mg/dl, was independently associated with organ failure, pancreatic necrosis, acute collections and mortality (p < 0.05). CONCLUSIONS: Elevated serum triglyceride levels are independently associated with a more severe course of pancreatitis. It must be highlighted the elevated frequency of local complications in patients with HTG that increases proportionally and significantly with HTG severity grades.

Association of the hypertriglyceridemic waist phenotype and severity of acute pancreatitis.

BACKGROUND: The aim of this study was to evaluate the effect of a simple visceral obesity phenotype, known as the hypertriglyceridemic waist phenotype and its quantitative indicator waist circumference index on the severity of acute pancreatitis. MATERIALS AND METHODS: Diagnosis and severity analysis of acute pancreatitis were determined according to the Atlanta classification guidelines, revised in 2012. We considered the hypertriglyceridemic waist phenotype as characterized by increased waist circumference and elevated triglyceride concentrations. We investigated the association between the acute pancreatitis severity and hypertriglyceridemic waist phenotype, including waist circumference index. RESULTS: The hypertriglyceridemic waist phenotype was significantly associated with systemic inflammatory response syndrome, organ failure, and severe acute pancreatitis. The median waist circumference index and demonstration of hypertriglyceridemic waist phenotype were positively correlated with acute pancreatitis severity. In addition, multivariate logistic analysis showed that patients with the hypertriglyceridemic waist phenotype had 1.664 times the risk of organ failure and 1.891 times the risk of systemic inflammatory response syndrome, compared with the other groups. CONCLUSION: Upon admission, the hypertriglyceridemic waist phenotype was strongly associated with acute pancreatitis in patients. This phenotype, including waist circumference index, might be a simple method for evaluating individuals at high risk of severe acute pancreatitis.

The Relationship between Liver Injury and Serum Levels of C-Reactive Protein and Procalcitonin in Patients with Acute Pancreatitis.

Acute pancreatitis (AP) can cause damage to multiple organs in the whole body, and the liver is one of the most frequently affected by AP. Ninety-six AP patients, consisting 67 patients with liver injury, were enrolled. They were classified as mild AP (MAP) and severe AP (SAP), according to the Atlanta Revised Classification, with 50 healthy subjects serving as the controls. The serum levels of C-reactive protein (CRP) and procalcitonin (PCT) were measured by ELISA. Serum levels of alanine aminotransferase (ALT), alkaline phosphatase (AKP) and aspartate aminotransferase (AST) were also analysed. AP patients had high incidence of liver injury which was greater in SAP than in MAP patients, the levels of serum CRP and serum PCT were positively correlated to ALT, AKP and AST levels in AP patients with liver injury. Serum levels of CRP and PCT may be used as indicators of liver injury in the AP patients.

Role of increased immature granulocyte percentage in the early prediction of acute necrotizing pancreatitis.

BACKGROUND: Acute necrotizing pancreatitis (ANP) is the most severe form of acute pancreatitis (AP), and it has high mortality rates. Therefore, early diagnosis and treatment are of critical importance for the prognosis. The aim of this study was to investigate the effectiveness of immature granulocyte percentage (IG%) in the early prediction of ANP. METHODS: This retrospective study included 96 adult patients hospitalized with a diagnosis of AP. Demographic data of the patients were recorded. The white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), IG%, C-reactive protein (CRP), and amylase levels were determined. Furthermore, computed abdominal tomography was applied to the patients, and the length of hospital stay was recorded. Patients were divided into two groups as those with acute edematous pancreatitis and ANP, according to the tomography results. The differences between the groups were analyzed statistically. RESULTS: The WBC count, NLR, CRP, and IG% were significant markers in the prediction of ANP. However, IG% had higher values with regard to the sensitivity, specificity, AUROC, and negative and positive predictive values (100%, 95%, 0.982, 78.9%, and 100%, respectively). CONCLUSION: An increased IG% is a simple, fast, and effective marker in the early prediction of ANP. METHODS: This retrospective study was carried out on 96 adult patients who were hospitalized with a diagnosis of acute pancreatitis. Demographic data of the patients were recorded. White blood cell count, neutrophil/lymphocyte ratio, IG%, C-reactive protein and amylase levels were determined. Furthermore computed abdominal tomography was applied to the patients and the length of hospital stay was recorded. The patients were divided into two groups as acute edematous pancreatitis and acute necrotizing pancreatitis according to the tomography results. The differences between the groups were analyzed statistically. RESULTS: White blood cell count, neutrophil/lymphocyte ratio, C-reactive protein and IG% were significant markers in the prediction of acute necrotizing pancreatitis. However, IG% had higher values of sensitivity, specificity, AUROC, negative and positive predictive values ( 100%, 95%, 0.982, 78.9%, 100%,respectively). CONCLUSION: Increased IG% is a simple, fast, and effective marker in the early prediction of acute necrotizing pancreatitis.

Clinical effects of hemoadsorption with CytoSorb® in patients with severe acute pancreatitis: A case series.

Hemoadsorption using CytoSorb® has recently gained attention as a new therapy aimed at modulating the inflammatory response syndrome in critically ill patients. The aim of our study was to assess the clinical effects of CytoSorb in patients with severe acute pancreatitis. We prospectively included 12 patients admitted to the intensive care unit for severe acute pancreatitis. After inclusion, continuous venovenous hemodiafiltration in conjunction with CytoSorb was applied. Clinical data, number of organ dysfunctions, paraclinical data, and vasopressor support were collected before and after the treatment. The use of CytoSorb was associated with a decrease in C-reactive protein from 242 (30, 300) to 180 (20, 252) mg/L (p = 0.04) and procalcitonin from 2.21 (0.01, 15.02) to 1.10 (0.01, 3.79) ng/mL (p = 0.02). The median vasopressor support was 0.1 (0, 0.9) mg/h at the beginning of the treatment and it was discontinued in all cases after the treatment. In conclusion, the use of CytoSorb in patients with severe acute pancreatitis was associated with improved hemodynamics and decreased inflammatory markers.

Comparison of endoscopic and percutaneous drainage of symptomatic necrotic collections in acute necrotizing pancreatitis.

INTRODUCTION: Primary endoscopic and percutaneous drainage for pancreatic necrotic collections is increasingly used. We aim to compare the relative effectiveness of both modalities in reducing the duration and severity of illness by measuring their effects on systemic inflammatory response syndrome (SIRS). METHODS: We retrospectively reviewed all cases of endoscopic and percutaneous drainage for pancreatic necrotic collections performed in 2011-2016 at two hospitals. We assessed the post-procedure length of hospital stay, reduction in C-reactive protein levels, resolution of SIRS, the complication rates, and the number of procedures required for resolution. RESULTS: Thirty-two patients were identified and 57 cases (36 endoscopic, 21 percutaneous) were included. There was no significant difference in C-reactive protein reduction between endoscopic and percutaneous drainage (69.5% vs 68.8%, P = 0.224). Resolution of SIRS was defined as the post-procedure normalization of white cell count (endoscopic vs percutaneous: 70.4% vs 64.3%, P = 0.477), temperature (endoscopic vs percutaneous: 93.3% vs 60.0%, P = 0.064), heart rate (endoscopic vs percutaneous: 56.0% vs 11.1%, P = 0.0234), and respiratory rate (endoscopic vs percutaneous: 83.3% vs 0.0%, P = 0.00339). Post-procedure length of hospital stay was 27 days with endoscopic drainage and 46 days with percutaneous drainage (P = 0.0183). CONCLUSION: Endoscopic drainage was associated with a shorter post-procedure length of hospital stay and a greater rate of normalization of SIRS parameters than percutaneous drainage, although only the effects on heart rate and respiratory rate reached statistical significance. Further studies are needed to establish which primary drainage modality is superior for pancreatic necrotic collections.

Determinants of Severity in Acute Pancreatitis: A Nation-wide Multicenter Prospective Cohort Study.

OBJECTIVE: The aim of this study was to compare and validate the different classifications of severity in acute pancreatitis (AP) and to investigate which characteristics of the disease are associated with worse outcomes. SUMMARY OF BACKGROUND DATA: AP is a heterogeneous disease, ranging from uneventful cases to patients with considerable morbidity and high mortality rates. Severity classifications based on legitimate determinants of severity are important to correctly describe the course of disease. METHODS: A prospective multicenter cohort study involving patients with AP from 23 hospitals in Spain. The Atlanta Classification (AC), Revised Atlanta Classification (RAC), and Determinant-based Classification (DBC) were compared. Binary logistic multivariate analysis was performed to investigate independent determinants of severity. RESULTS: A total of 1655 patients were included; 70 patients (4.2%) died. RAC and DBC were equally superior to AC for describing the clinical course of AP. Although any kind of organ failure was associated with increased morbidity and mortality, persistent organ failure (POF) was the most significant determinant of severity. All local complications were associated with worse outcomes. Infected pancreatic necrosis correlated with high morbidity, but in the presence of POF, it was not associated to higher mortality when compared with sterile necrotizing pancreatitis. Exacerbation of previous comorbidity was associated with increased morbidity and mortality. CONCLUSION: The RAC and DBC both signify an advance in the description and differentiation of AP patients. Herein, we describe the complications of the disease independently associated to morbidity and mortality. Our findings are valuable not only when designing future studies on AP but also for the improvement of current classifications.

Cytokine profile in prediction of acute lung injury in patients with acute pancreatitis.

OBJECTIVES: To study the role of cytokines in prediction of acute lung injury (ALI) in acute pancreatitis. METHODS: Levels of TNFα, IL-6, IL-10, IL-8 and IL-1ß were measured in 107 patients at presentation and at 72 h in patients who developed acute lung injury. A model was devised to predict development of ALI using cytokine levels and SIRS score. RESULTS: The levels of TNF α (p < 0.0001), IL-6 (p < 0.0001), IL-8 (p < 0.0001) and IL-1ß (p < 0.0001) were significantly higher in the ALI group. IL-10 levels were significantly lower in persistent ALI (p-ALI) than in transient ALI (t-ALI) patients (p < 0.038). p-ALI group had significant rise of TNFα (p = 0.019) and IL-1ß (p = 0.001) while t-ALI group had significant rise of only IL-1ß (p = 0.044) on day 3 vs day 1. Combined values of IL-6 and IL-8 above 251 pg/ml had sensitivity of 90.9% and a specificity of 100% to predict future development of ALI. Composite marker-I (IL6 ≥ 80 pg/ml + SIRS) yielded sensitivity and specificity of 73% and 98% whereas composite marker-II (IL8 ≥ 100 pg/ml + SIRS) yielded sensitivity and specificity of 73% and 95% to predict future ALI. CONCLUSIONS: IL-6 and IL-8 can predict future development of ALI. When they are combined with SIRS, they can be used as comprehensive composite markers.

Plasma mtDNA Analysis Aids in Predicting Pancreatic Necrosis in Acute Pancreatitis Patients: A Pilot Study.

BACKGROUND: Specific plasma biomarkers in predicting pancreatic necrosis (PNec) are needed in treating acute pancreatitis (AP). AIMS: To investigate the prognostic value of plasma mitochondrial DNA fragments (mtDNA) in patient with AP for PNec. METHODS: AP patients with symptoms onset within 72 h were prospectively enrolled from June 2015 through June 2017 and were assessed for PNec using contrast-enhanced CT scan. Plasma mtDNA concentration (specific mitochondrial gene ND1) was measured using qRT-PCR. RESULTS: Of the 74 AP patients included, significant higher median level of plasma mtDNA was found in severe AP patients than in mild AP patients and healthy controls, but not in moderately severe AP patients. Patients with PNec had higher level of plasma mtDNA than those without PNec (774.2 [IQR 397.6-2205.0] vs. 169.5 [IQR 73.6-683.4] pg/ml, P < 0.05). The area under the receiver operator characteristic curve (ROC-AUC) of mtDNA for predicting PNec was higher than that of CRP (0.813 [95% CI 0.705-0.895] vs. 0.678 [95% CI 0.558-0.783]). Using a cutoff value of 302.5 pg/ml, the sensitivity and specificity for diagnosing PNec were 90.9 and 68.3%, respectively. Finally, plasma mtDNA levels decreased significantly after continuous renal replacement therapy (717.7 [IQR 307.00-1370.00] vs. 237.5 [IQR 117.20-464.80] pg/ml, P < 0.01). CONCLUSIONS: Elevated plasma mtDNA content in AP patients may be used as a more accurate early predictor of PNec in contrast to traditional CRP.

New predictor of acute necrotizing pancreatitis: Red cell distribution width.

BACKGROUND: Acute pancreatitis (AP) is inflammation of the pancreas of various severity ranging from mild abdominal pain to mortality. AP may be classified as acute interstitial edematous pancreatitis (AEP) or acute necrotizing pancreatitis (ANP), according to the revised Atlanta criteria. Most of the patients with AP are AEP (75-85% of patients), while 15-25% of patients have ANP. The mortality rate is 3% in AEP and 15% in ANP. Thus, it is important to predict the severity of AP to decrease the morbidity and mortality. OBJECTIVES: The aim of the study was to evaluate the relationship between red cell distribution width (RDW) and the severity of AP on admission to hospital. MATERIAL AND METHODS: Patients admitted to Adana Numune Research and Educational Hospital with a diagnosis of AP through the time frame of January 2014-May 2016 were included in our study. Diagnosis of AP was made according to the revised Atlanta classification. Patients' age, sex, etiology of AP, and RDW values were recorded on admission to the hospital. RESULTS: A total of 180 patients were included in the study. Eighty patients (44%) were male and 100 patients were female. Mean age was 56.25 ±18.3 years (52.66 ±14.4 in males; 59.84 ±20.2 in females). There was no statistically significant difference between patients' age. The most frequently observed etiologic factor was gallstone disease followed by alcohol intake and the use of pharmaceuticals. Drug-related AP was associated with azathioprine, furosemide, and thiazide diuretics. One hundred forty-four (80%) patients had AEP and 36 (20%) patients had ANP. RDW values showed a statistically significant difference between patients with AEP and ANP (p = 0.011). The cut-off value of RDW was 16.4 and the area under curve (AUC) value was 0.591 (p = 0.0227) with a sensitivity of 29.2% and specificity of 89.83%. CONCLUSIONS: Red cell distribution width could be used to evaluate the prognosis of acute pancreatitis.

Inhibition of 5-lipoxygenase represses neutrophils activation and activates apoptosis in pancreatic tissues during acute necrotizing pancreatitis.

Pancreatic glandular necrosis is rapid inflammation of the pancreas and contributes to severe acute pancreatitis in humans. The pathogenesis of pancreatic tissue inflammation during acute pancreatitis is still largely unknown. Recent studies suggest that 5-lipoxygenase (5-LOX) is an essential mediator in modulating cell death pathways in human diseases. In this study, we aimed to evaluate the effects of a 5-LOX inhibitor, zileuton, on tissue apoptosis and neutrophils activation in pancreatic tissues during acute necrotizing pancreatitis (ANP) in a rat model. In this present study, both mRNA and protein levels of 5-LOX are upregulated during ANP and zileuton treatment is shown to repress ANP-induced upregulation of 5-LOX levels. In addition, zileuton treatment is found to repress blood biomarkers of neutrophils activation such as soluble intercellular adhesive molecular 1 (ICAM-1), soluble E-selectin (E-selectin), soluble P-selectin (P-selectin), leukotriene B4 (LTB4), and myeloperoxidase (MPO). Also, zileuton treatment attenuates pancreatic tissue pathology, upregulates caspase-3, downregulates B-cell lymphoma 2 (Bcl-2), and activates tissue apoptosis evaluated by TUNEL staining. Our results show that 5-LOX plays an important role in activating apoptosis and repressing neutrophils activation during ANP. The current study suggests that 5-LOX can be used as a potential target for the treatment of ANP.

The immune imbalance in the second hit of pancreatitis is independent of IL-17A.

BACKGROUND: Severe acute pancreatitis (SAP) is characterised by two distinct clinical phases. Organ dysfunction and death is initially as a result of a systemic inflammatory response syndrome (SIRS). Systemic sepsis from infected pancreatic necrosis characterises the second phase, the so called 'second hit' of acute pancreatitis (AP). An immune imbalance during the second hit is postulated to contribute to the formation of the septic complications that occur in these patients. The pro-inflammatory T-helper (Th) 17 pathway has been shown to be an initiator of early SIRS in AP, however to date its role has not been established in the second hit in AP. METHODS: Thirty-six patients with mild (n = 16), moderate (n = 10) and severe (n = 10) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for analysis of routine clinical markers as well as cytokine analysis. Flow cytometry and a IL-17A ELISA was performed to determine cytokine concentrations. RESULTS: There were no significant differences between days 7, 9, 11 and 13 for either the mild/moderate or SAP groups for IL-17A (CBA assay or ELISA), IFN-γ, TNF-α, IL-2 or IL-4. For each of the study days, the mean IL-6 and IL-10 concentrations were significantly higher in the SAP group compared to the mild/moderate group. WCC, CRP and PCT were all significantly higher in severe acute pancreatitis over the study days. CONCLUSIONS: An immune imbalance exists in patients with SAP, however secreted IL-17A is not responsible for the second hit in AP.

Cav 1.2 and Cav 2.2 expression is regulated by different endogenous ghrelin levels in pancreatic acinar cells during acute pancreatitis.

Ghrelin influences pancreatic endocrine and exocrine functions, regulates intracellular calcium [Ca2+]i levels, and has an anti-inflammatory role in acute pancreatitis. This study investigated the role of endogenous ghrelin in the expression of Cav 1.2 (L-type of Ca2+ channel) and Cav 2.2 (N-type of Ca2+ channel) in acute pancreatitis. For this purpose, acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) rat models were established. Cav 1.2 and Cav 2.2 expression was assessed by immunohistochemistry in the pancreatic tissues of rats; ghrelin, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) serum levels were detected using ELISA. Next, in AR42J cells with either knock-out or overexpression of ghrelin, Cav 1.2 and Cav 2.2 expression was examined using western blot analysis, and intracellular calcium [Ca2+]i was detected with confocal microscopy. In this study, the ghrelin serum level was highest in the ANP group and was higher in the AEP group than the normal group. Expression of Cav 1.2 and Cav 2.2 in the ANP and AEP groups was higher than in the respective control groups. The serum IL-1ß and TNF-α levels were significantly higher in the ANP group compared to the other groups. Cav 1.2 and Cav 2.2 expression and [Ca2+]i decreased in ghrelin knockdown AR42J cells but increased in ghrelin overexpressing cells. In conclusion, Cav 1.2 and Cav 2.2 expression increased in ANP. The [Ca2+]i level, which is mediated by Cav 1.2 and Cav 2.2 expression, is directly regulated by ghrelin in pancreatic acinar cells, and serum ghrelin levels may be involved in the severity of acute pancreatitis.

Hypernatremia and acute pancreatitis in chronic kidney disease: back to the salt mines. Questions.

BACKGROUND: Acute pancreatitis can be a life-threatening complication in patients with chronic kidney disease (CKD), especially in kidney transplant recipients. CASE DIAGNOSIS/TREATMENT: The patient was 7 years old when he received renal transplantation for CKD secondary to posterior urethral valves. Two years later, he presented with severe necrotizing pancreatitis (Ranson's score 5, Balthazar's score 8). Viral and genetic testing came back negative; pancreatitis was attributed to the patient's treatments (prednisone, trimethoprim-sulfamethoxazole, and everolimus). Twenty days later, necrotized pancreatic cysts had formed. Two drains were surgically inserted into the abdomen, and continuous cyst lavage was started with normal saline solution. Two days later, blood tests revealed severe hypernatremia and hypokalemia. We suspected unwanted peritoneal dialysis had occurred because of the high sodium chloride content and the absence of potassium in the normal saline solution being used for cyst lavage. We switched to a peritoneal dialysis solution for the lavage, leading to complete correction of hydroelectrolytic disorders. CONCLUSION: Acute pancreatitis is a frequent and potentially severe complication in CKD patients. It should be suspected in the presence of nonspecific symptoms, such as abdominal pain or vomiting. Rigorous monitoring of electrolytes is also mandatory for managing CKD patients with acute pancreatitis.