Pathophysiology and Biomarker Potential of Fatty Acid Ethyl Ester Elevation During Alcoholic Pancreatitis.

BACKGROUND & AIMS: The role of fatty acid ethyl esters (FAEEs) during human alcoholic pancreatitis is unknown. We compared FAEEs levels with their nonesterified fatty acids (NEFAs) precursors during alcohol intoxication and clinical alcoholic pancreatitis. The pathophysiology underlying FAEEs increase and their role as diagnostic biomarkers for alcoholic pancreatitis was investigated. METHODS: A prospective blinded study compared FAEEs, NEFAs, and ethanol blood levels on hospitalization for alcoholic pancreatitis (n = 31), alcohol intoxication (n = 25), and in normal controls (n = 43). Serum FAEEs were measured at admission for nonalcoholic pancreatitis (n = 75). Mechanistic cell and animal studies were done. RESULTS: Median FAEEs were similarly elevated during alcohol intoxication (205 nmol/L; 95% confidence interval [CI], 71.8-515 nmol/L, P < .001) and alcoholic pancreatitis (103.1 nmol/L; 95% CI, 53-689 nmol/L, P < .001) vs controls (1.7 nmol/L; 95% CI, 0.02-4.3 nmol/L) or nonalcoholic pancreatitis (8 nmol/L; 95% CI, 1.1-11.5 nmol/L). Alcoholic pancreatitis increased serum NEFAs (1024 ± 710 µmol/L vs 307 ± 185 µmol/L in controls, P < .05). FAEEs comprised 0.1% to 2% of the parent NEFA concentrations. FAEES correlated strongly with NEFAs independent of ethanol levels in alcoholic pancreatitis but not during alcohol intoxication. On receiver operating characteristic curve analysis for diagnosing alcoholic pancreatitis, the area under the curve for serum FAEEs was 0.87 (95% CI, 0.78-0.95, P < .001). In mice and cells, alcohol administration transiently increased all FAEEs. Oleic acid ethyl ester was the only FAEE with a sustained increase up to 24 hours after intraperitoneal oleic acid plus ethanol administration. CONCLUSIONS: The sustained, alcohol-independent, large (20- to 50-fold) increase in circulating FAEEs during alcoholic pancreatitis results from their visceral release and mirrors the 2- to 4-fold increase in parent NEFA. The large areas under the curve of FAEEs on receiver operating characteristic curve analysis supports their role as alcoholic pancreatitis biomarkers.

Hypophosphatemia Is More Common and Is Prognostic of Poorer Outcomes in Severe Alcoholic Pancreatitis.

OBJECTIVES: The aim of this study was to determine if hypophosphatemia is more common in patients with severe alcohol-induced acute pancreatitis (AAP). METHODS: This is a retrospective, single institution, cohort study that analyzed 147 patients admitted to the hospital for AAP. Multivariate logistic regression was used to determine if hypophosphatemia would be related to clinical outcomes of disease severity. RESULTS: Hypophosphatemia was more common in patients with severe AAP at admission; in addition, all patients with severe AAP (100%) eventually developed hypophosphatemia during admission, relative to those with mild (43%) and moderately severe (54%) AAP. The magnitude of the lowest phosphate measurement obtained during admission was lower in patients with severe AAP (mean, 1.5 mg/dL, standard deviation [SD], 0.5 mg/dL) relative to those with mild (mean, 2.6 mg/dL; SD, 0.9 mg/dL) and moderately severe (mean, 2.3 mg/dL; SD, 0.9 mg/dL) AAP (P < 0.001). Finally, patients who developed hypophosphatemia during admission were more likely to require intensive care unit admission (P < 0.001), vasopressors (P = 0.01), or intubation (P = 0.003). CONCLUSIONS: Hypophosphatemia is more common and of greater magnitude in patients admitted to the hospital with severe AAP. In addition, patients with severe AAP who develop hypophosphatemia during admission are more likely to have poorer clinical outcomes.

Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis.

BACKGROUND: IgG4-related disease (IgG4-RD) is a systemic inflammatory disease, which includes type 1 autoimmune pancreatitis (AIP). Interleukin-35 (IL-35) exhibits immunosuppressive effects in several autoimmune diseases. However, the expression of IL-35 had not been reported so far in type 1 AIP. We evaluated the association between IL-35 and several cytokines, which mediate the function of Tregs in type 1 AIP. METHODS: Plasma was collected from patients with type 1 AIP, alcoholic chronic pancreatitis (ACP), and healthy controls (HC) and assayed for cytokine expression. Total mRNA separated from peripheral blood was isolated from naïve Tregs (nTregs) and effector Tregs (eTregs). EBI3 and IL-12p35 gene expressions were tested in these cells by quantitative PCR. In addition, expression of IL-35 subunits in the pancreatic tissues of patients with type 1 AIP and ACP was analyzed by immunohistochemistry. RESULTS: IL-35 was significantly elevated in type 1 AIP (n = 32) plasma compared with ACP (n = 16) and HC (n = 22), but IL-27 was not. We also detected many cells expressing both EBI3 and IL-12p35 in type 1 AIP tissues. Moreover, in peripheral blood lymphocyte, the percentage of nTregs and eTregs of CD4+ T cells in patients with type 1 AIP (n = 14) compared with HC (n = 15) was significantly decreased and increased, respectively. There were no significant differences of gene expression in patients with type 1 AIP and HC. CONCLUSIONS: This study identified elevated expression of plasma IL-35 and tissue IL-35 subunits in patients with type 1 AIP. This might lead to inflammation suppression via activated eTregs. IL-35 might be associated with this anti-inflammatory role, especially against the Th2 response through several cytokines and the differentiation of Tregs in type 1 AIP.

Plasma level of soluble urokinase plasminogen activator receptor (suPAR) predicts long-term mortality after first acute alcohol-induced pancreatitis.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker associated with inflammatory and certain malignancies. Earlier we have shown that plasma suPAR (P-suPAR) predicts severity of acute alcohol-induced pancreatitis (AAP) on admission. Our aim was to investigate whether P-suPAR levels predict AAP recurrences or mortality during long-term follow-up after first AAP. METHODS: Eighty-three patients (median age 47.5, range 25-71 years) suffering their first AAP during 2001-2005 were recruited and followed prospectively for 9 years with a median follow-up time of 7.0 (range 0.3-9.8) years. P-suPAR was measured by enzyme-linked immunosorbent assay (ELISA) from the samples taken at follow-up visits. Survival was registered in November 2014. RESULTS: P-suPAR level on admission or after recovery of the first AAP did not predict the recurrence of AAP. However, higher P-suPAR measured after recovery of first AAP (3.6 vs. 2.9 ng/mL) predicted mortality during follow-up period (hazard ratio 1.48, p = .008). Cut-off value for P-suPAR indicating a higher risk for 10-year mortality resulted a value of ≥3.4 ng/mL. When adjusted for other covariates, P-suPAR above cut-off level retained its statistical significance as an independent factor. CONCLUSIONS: P-suPAR level on admission or after recovery of the first AAP does not predict the recurrence of AAP during long-term follow-up. However, P-suPAR ≥3.4 mg/mL measured after recovery from first AAP is associated with an increased risk of 10-year mortality as an independent factor. This can be used to detect patients with highest risk after AAP, in order to focus the preventive healthcare actions.

Serum levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in predicting the severity of acute pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) is a severe disease associated with significant morbidity and mortality. The overall outcome has improved, but specific treatment(s) remains elusive. The challenge is the early identification and treatment of patients who will develop severe acute pancreatitis. Therefore, the aim of the present study is to investigate plasma levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the initial phase of predicted severe acute pancreatitis. METHODS: Between June 2014 and January 2016, 64 patients with acute pancreatitis and 36 healthy individuals were included to study. Four blood samples, for serum TWEAK measurement, were taken from each individual in each group. The first measurement was taken from the admission blood sample. The subsequent three samples were taken at 12, 24, and 48 h after the hospital admission. RESULTS: Serum TWEAK levels were significantly higher in patients with acute pancreatitis when compared with healthy controls. TWEAK plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients. CONCLUSION: Serum TWEAK levels increase progressively with the severity of acute pancreatitis and TWEAK might be a novel early marker of severity in acute pancreatitis.

Plasma Level of Soluble Urokinase-type Plasminogen Activator Receptor Predicts the Severity of Acute Alcohol Pancreatitis.

OBJECTIVES: Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) are increased in various inflammatory and infectious diseases. We investigated the activation and prognostic value of plasma suPAR (P-suPAR) in patients experiencing their first acute alcohol pancreatitis (AAP). METHODS: From prospectively collected data, we measured P-suPAR concentrations in 104 patients with AAP during hospitalization and again after discharge. RESULTS: According to the revised Atlanta classification, pancreatitis was moderately severe in 29 (28%) and severe in 6 (6%) patients and these severities were combined for further analysis (non-mild AAP, n = 35; 34%). Median P-suPAR levels were significantly higher in patients with AAP during hospitalization than after discharge (4.8 vs 3.1 ng/mL; P < 0.001) and in non-mild compared to mild AAP (6.2 vs 4.2 ng/mL; P < 0.001). When the analysis was made 1 to 4 days after admission (n = 68), the area under the curve was 0.81 (95% confidence interval, 0.70-0.92). P-suPAR was found to be a better prognostic marker in AAP than C-reactive protein, hematocrit, or creatinine. CONCLUSIONS: P-suPAR concentrations are elevated in AAP and correlate with the severity of the disease. These results suggest that P-suPAR may have potential to serve as a novel prognostic marker for AAP severity on admission.

Early Prediction of Persistent Organ Failure by Serum Angiopoietin-2 in Patients with Acute Pancreatitis.

BACKGROUND: Biomarkers for the early prediction of the severity of acute pancreatitis (AP) are urgently needed for clinical management of the disease. Angiopoietin-2 (Ang-2), one of the autocrine peptides that reduce endothelial permeability, has been found to be associated with various diseases, including inflammatory disorders. AIMS: This study aimed to determine whether serum Ang-2 could serve as a noninvasive biomarker for the early prediction of persistent organ failure (POF) in acute pancreatitis. METHODS: A total of 120 AP patients were prospectively enrolled at Jinling Hospital. Serum samples were collected on admission. Clinical and laboratory data were recorded. Ang-2 levels were measured by enzyme-linked immunosorbent assay. RESULTS: A total of 37 patients developed POF and were classified as having severe AP (SAP). Ang-2 was significantly higher on admission in patients who developed POF than in those who did not (p < 0.001 for all). Furthermore, receiver operating characteristic (ROC) curve analysis revealed that Ang-2 could distinguish patients who developed POF from mild AP (MAP, area under ROC curve [AUC] = 0.88, 95 % CI 0.78-0.94) and moderately severe AP patients (MSAP, AUC = 0.74, 95 % CI 0.63-0.83). In addition, multivariate logistic regression showed that increased Ang-2 was an independent predictor of developing POF between subgroups with MSAP and SAP (OR 7.2, 95 % CI 2.7-19.4) and among all AP patients (OR 12.1, 95 % CI 4.8-30.3). CONCLUSIONS: Elevated serum Ang-2 levels on admission may be a promising biomarker for the prediction of POF in AP.

Serum Carbohydrate-Deficient Transferrin in Pancreatic Diseases of Different Etiologies.

BACKGROUND: The aim of this study was to find out whether pancreatic diseases invalidate the use of CDT for the detection of high alcohol intake and if CDT can distinguish between alcoholic and non-alcoholic pancreatitis. METHODS: The study was carried out on 110 patients with pancreatic diseases. Serum CDT was determined using the N Latex CDT test. RESULTS: The mean relative (%) and absolute (mg/L) CDT levels in acute and chronic pancreatitis were significantly higher than in controls and patients with primary pancreatic cancer. No significant difference was found in CDT concentrations between acute and chronic pancreatitis. The relative and absolute CDT concentrations in alcohol-induced pancreatitis were significantly higher compared to the controls and biliary-induced pancreatitis. CONCLUSIONS: Acute and chronic alcoholic pancreatitis, but not biliary pancreatitis, may affect CDT levels. Pancreatitis does not invalidate the use of CDT as a marker of alcohol abuse. CDT can be a useful test for distinguishing alcoholic from non-alcoholic pancreatitis. Changes in CDT level indicate disturbances in transferrin glycosylation in the course of alcoholic pancreatic diseases.

THE CONCENTRATION OF ACETYLCHOLINE AND THE LEVEL CHOLINESTERASE ACTIVITY IN THE SERUM OF PATIENTS WITH GASTRIC ULCER, DUODENAL ULCER AND ALCOHOLIC CHRONIC PANCREATITIS.

INTRODUCTION: There are a lot of pathogenic factors involved in development of polyetiologic diseases. Acetylcholine is known as first-order mediator and plays important role in development and maintenance of pathological processes. In this article we provide data on concentration of acetylcholine (Ah) in blood serum of patients with stomach ulcer (SU), duodenal ulcer (DU), alcoholic chronic pancreatitis (ACP) and control group.as well as activity of cholinesterase (Che). The aim of this study was to identify a role played by Ah in pathological process during a disease, that may complicate a course of the disease as poor prognostic factor. RESULTS AND DISCUSSION: We found that there are significant differences in Ah concentration and Che activity between SU, DU, ACP and control. In control group we divide concentration of Ah into three groups: low - 0.46 to 1.0 mlMol/l (60% of individuals), moderate - mlMol 02-1,5/I (30%) and high - more than 1.5 Ah mlMol/I (10%). CONCLUSION: We suppose that Che activity and Ah concentration depend on localization of pathological process. It is possible that there are hidden differences in Ah concentration and Che activity between GU and DU.

D-dimer, a Potential Marker for the Prediction of Severity of Acute Pancreatitis.

BACKGROUND: A number of experimental studies have been put forth suggesting an important role of the hemostatic system in acute pancreatitis (AP) in the recent past. However, meaningful studies on clinical values of parameters of the hemostatic system in predicting pancreatitis associated complications are still scarce. In the current investigation, we evaluated the role of D-dimer to predict the severity of acute pancreatitis on day 1 of admission to the hospital. METHODS: A total of 160 subjects (75 mild AP + 35 severe AP + 50 healthy controls) were examined in the study. Biochemical and hemostatic parameters were compared between various groups of subjects on day 1 and day 3 of admission to the hospital. RESULTS: Levels of prothrombin time (PT), fibrinogen, D-dimer, and C-reactive protein (CRP) were significantly higher in the severe AP group than in the mild AP group. Antithrombin III (AT III) levels were significantly lower in the severe AP group than in the mild AP group. D-dimer levels were 5 times higher than the reference limit in the severe group and 1.7 times higher than the reference limit in the mild group. This difference was statistically highly significant (< 0.0001). A positive correlation between D-dimer and CRP, D-dimer and fibrinogen, and between D-dimer and PT was recorded. CONCLUSIONS: Estimation of the levels of D-dimer on admission day provides an accurate method for the identification of patients who will develop systemic complications in the further course of AP.

Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis.

OBJECTIVES: Hypertriglyceridemia (HTG) represents a major health problem with prevalence exceeding 30% in the U.S. The present study aims to assess the effect of elevated serum triglyceride (TG) levels on the severity of acute pancreatitis (AP). METHODS: Prospectively enrolled AP patients were categorized into normal, mild, moderate, and severe/very severe categories based on their TG levels and compared in respect to demographics, comorbidities, and clinical outcomes. Multivariate analysis determined whether elevated TG levels were independently associated with persistent organ failure. RESULTS: Two hundred and one out of 400 AP patients had serum TGs measured within 72 h of presentation, of which 115 had normal TG levels and 86 HTG (20 mild, 41 moderate, and 25 severe/very severe). Patients with HTG were of younger age (44 vs. 52 years), predominantly male (65% vs. 45%), obese (57% vs. 34%), diabetic (38% vs. 17%), and developed more frequently persistent organ failure (40% vs. 17%) compared with those with normal TGs (P<0.02). The rate of persistent organ failure increased proportionally with HTG severity grades (17% when normal TGs, 30% in mild, 39% in moderate, and 48% in severe/very severe HTG, Ptrend<0.001). On multivariate analysis controlling for age, gender, body mass index, diabetes, and alcohol etiology, moderate HTG (odds ratio (OR), 2.6; P=0.04) and severe/very severe HTG (OR, 4.9; P=0.009) were independently associated with persistent organ failure. CONCLUSIONS: Elevated serum TGs in AP patients are independently and proportionally correlated with persistent organ failure regardless of etiology. TG-mediated lipotoxicity may be an attractive target to design novel interventions for severe AP.

Decreased serum platelet derived growth factor BB levels in acute and increased in chronic pancreatitis.

AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN). METHODS: Forty patients with mild AP, 40 patients with alcoholic CP, 33 patients with WOPN and 40 healthy subjects were examined. Serum concentrations of platelet derived growth factor BB (PDGF-BB), transforming growth factor ß-1 (TGFß-1), chemerin and high-mobility group box chromosomal protein 1 (HMBG1) were assayed by enzyme linked immunosorbent assay. RESULTS: Patients with mild AP and those with WOPN had significantly lower serum levels of PDGF-BB compared to healthy subjects (4.0 ± 0.61 ng/mL vs 6.2 ± 0.76 ng/mL, P = 0.027, and 1.60 ± 0.31 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001, respectively), while CP was associated with higher serum levels of PDGF-BB (12 ± 1.3 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001). Circulating TGFß-1 and chemerin levels were elevated in CP patients (57 ± 3.6 ng/mL vs 39 ± 3.6 ng/mL, P < 0.001 and 73 ± 7.2 ng/mL vs 48 ± 2.3 ng/mL, P < 0.001, respectively), but not in patients with AP and WOPN. No significant changes in serum HMBG1 levels were found either in patients with AP, WOPN or CP. CONCLUSION: The serum levels of some growth factors and cytokines differ significantly in AP, WOPN and CP. These data suggest that selected growth factors and cytokines may be considered as potential diagnostic biomarkers in patients with pancreatic diseases.

Total cholesterol level for assessing pancreatic insufficiency due to chronic pancreatitis.

BACKGROUND/AIMS: To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice. METHODS: A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups. RESULTS: The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052). CONCLUSIONS: Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.

YKL-40 and alcoholic liver and pancreas damage and disease in 86,258 individuals from the general population: cohort and mendelian randomization studies.

BACKGROUND: We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease. METHODS: We performed cohort and mendelian randomization in 86,258 individuals from the Danish general population, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738). RESULTS: Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein, and fibrinogen and with decreased albumin; coagulation factors II, VII, and X; and pancreatic amylase. The multifactorially adjusted hazard ratio for alcoholic liver cirrhosis comparing the 96%-100% vs 0%-33% YKL-40 percentile categories was 41 (95% CI 14-118). Corresponding ratios were 7.9 (5.1-12) for any alcoholic liver disease, 4.1 (1.7-10) for alcoholic pancreatitis, and 3.4 (1.9-6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations was associated with a multifactorially adjusted observational hazard ratio of 2.8 (2.4-3.3) for alcoholic liver cirrhosis and a corresponding genetic odds ratio of 1.1 (0.7-1.5). Corresponding risk estimates were 2.0 (1.8-2.2) observationally and 1.0 (0.8-1.1) genetically for any alcoholic liver disease, 1.4 (1.1-1.9) observationally and 1.1 (0.8-1.5) genetically for alcoholic pancreatitis, and 1.3 (1.1-1.6) observationally and 1.0 (0.8-1.3) genetically for any pancreatitis. Excessive alcohol consumption combined with YKL-40 concentrations in the top 5% was associated with 10-year risk of alcoholic liver cirrhosis of up to 7% in ever-smokers and 2% in never-smokers. CONCLUSIONS: YKL-40 concentration within the top 5% was a marker for alcoholic liver cirrhosis, with no evidence to support a causal relationship.

Hypertriglyceridemia is a risk factor for acute kidney injury in the early phase of acute pancreatitis.

OBJECTIVE: The aim of this study was to investigate the risk factors for acute kidney injury (AKI) in patients with acute pancreatitis (AP). METHODS: Patients with AP were retrospectively divided into AKI group and non-AKI group. To investigate the risk factors for AKI, logistic regression analysis was performed with demography, etiologies, and comorbidities. Mortalities of patients with different body mass indexes were compared. RESULTS: There were 43 patients with AKI and 202 patients without AKI. The risk factor for AKI in AP was hypertriglyceridemia (odds ratio, 2.964; 95% confidence interval, 1.485-5.915; P = 0.007). Forty-two patients developed AKI within the first 48 hours. The mortalities of normal weight, overweight, and obese groups in patients with AKI were 16.7%, 17.4%, and 62.5%, respectively. All the 4 patients who died in the non-AKI group were of normal weight. CONCLUSIONS: Hypertriglyceridemia is an independent risk factor for AKI in the early phase of AP. Obesity does not increase mortality of patients without AKI. We hypothesize that the role of pancreatic enzymes on triglyceride accumulated in renal may be an explanation for AKI in the early phase of AP.

Repeated transabdominal ultrasonography is a simple and accurate strategy to diagnose a biliary etiology of acute pancreatitis.

OBJECTIVES: Transabdominal ultrasonography (US) usually reveals diagnosis of biliary acute pancreatitis (AP). Guidelines suggest repeating US in AP patients without cause at first examination. This approach has been poorly investigated, as well as the accuracy of repeated US as compared with that of magnetic resonance cholangiopancreatography. This study aims at evaluating the diagnostic accuracy of repeated US for biliary AP. METHODS: The accuracy of each test for diagnosis of biliary AP was evaluated according to the final diagnosis. Comparison between tests was obtained by examining the areas under the receiver operating characteristic curves. RESULTS: Among 155 patients, the etiology was biliary in 52% and alcoholic in 20%. The accuracy of the first US alone and of the 2 combined examinations for a biliary etiology were 66% and 83%, respectively. Comparison of receiver operating characteristic curves showed a better performance of repeated US (difference between areas under the curve, 0.135; 95% confidence interval, 0.02-0.24; P = 0.021). Magnetic resonance cholangiopancreatography had high specificity (93%) but low sensitivity (62%), with 76% accuracy. The accuracy of the combination of the 2 US examinations and of elevated alanine transferase was 87%. CONCLUSIONS: Repeated US is effective for biliary AP diagnosis. The combination of repeated US examinations and biochemical tests seems an effective approach, whereas magnetic resonance cholangiopancreatography might be restricted to selected cases.

[Comparison of biohumoral and morphological parameters in acute pancreatitis].

INTRODUCTION: Acute pancreatitis occurs as a result of autodigestive activation of pancreatic proenzymes, within the parenchyma of the glands. OBJECTIVE: The goal of the work was to establish possible connection of etiology and severity of the acute pancreatitis and biohumoral parameters, ultrasound and CT. METHODS: The study included 273 patients with pancreatitis, classified by Ranson's score, according to degree of severity and etiology, whose biohumoral parameters were correlated with each other, and with the ultrasound and CT findings. RESULTS: The values of amylase and ALT were significantly higher in the severe form of pancreatitis and biliary etiology compared to etilic (p < 0.05).The ratio of AST/ALT was significantly higher in the group of etilic compared to biliary etiology (p < 0.05). LDH was significantly higher in the severe form group compared to moderate form of pancreatitis (p < 0.01). Cholesterol was significantly higher in the group of biliary compared to the group of etilic pancreatitis (p < 0.05). There was a negative low correlation between the value of calcium ions in the plasma and CT analysis (p = 0.05). Low degree negative correlation between the value of calcium ions and ultrasound analysis was established (p = 0.0001). CONCLUSION: There was a negative correlation between the level of ionized calcium in the blood and the degree of the acute pancreatitis by the Balthazar score. Mean value of alpha amylase, total value of cholesterol and ALT were significantly higher in the group of biliary compared to the group of etilic acute pancreatitis. The average values of the alpha amylase, LDH and ALT were significantly higher in the group of severe form of the acute pancreatitis compared to the group of moderate form. The ratio AST/ALT was significantly higher in the group of etilic than in the group of biliary pancreatitis.

Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of acute alcoholic pancreatitis.

The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset of alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated the ability of acinar cells to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and evaluated acinar cell necrosis in an animal model of AP and human samples. Rats were fed either an ethanol-containing or control diet for 14 weeks and killed 3 or 24 h after a single lipopolysaccharide (LPS) injection. Inflammasome components and necro-inflammation were evaluated in acinar cells by immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure enhanced acinar cell-specific production of TNFα, IL-6, MCP-1 and IL-10, as early as 3 h after LPS, whereas IL-18 and caspase-1 were evident 24 h later. Alcohol enhanced LPS-induced TNFα expression, whereas blockade of LPS signaling diminished TNFα production in vitro, indicating that the response of pancreatic acinar cells to LPS is similar to that of immune cells. Similar results were observed from acinar cells in samples from patients with acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased systemic levels of HMGB1 and LDH were observed, indicating that this strong systemic inflammatory response is associated with little pancreatic necrosis. These results suggest that TLR-4-positive acinar cells respond to LPS by activating the inflammasome and producing pro- and anti-inflammatory mediators during the development of mild, sub-clinical AP, and that these effects are exacerbated by alcohol injury.

Is alcoholic pancreatitis associated with enteroviral infection?

AIM: To investigate whether enteroviral infection might trigger acute pancreatitis in patients made susceptible due to high alcohol consumption. METHODS: Patients with alcohol-induced acute pancreatitis were analyzed for signs of simultaneous or preceding enteroviral infection. We studied the serum samples of 40 patients hospitalized for alcohol-induced acute pancreatitis and 40 controls recruited from an alcohol detoxification center. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus RNA and diagnose acute viremia. Immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) enteroviral antibodies were measured using enzyme immunoassay to detect subacute and previous infections. The samples were considered positive when the antibody titers were ≥ 15 IU. Furthermore, using RT-PCR, we studied pancreatic biopsy samples obtained during surgery from nine patients with chronic pancreatitis, one patient with acute pancreatitis and ten control patients with pancreatic carcinoma for evidence of persisting enteroviral RNA in the pancreatic tissue. RESULTS: No enterovirus RNA indicating acute viremia was detected by RT-PCR in the serum samples of any patient or control. A high incidence of positive antibody titers was observed in both study groups: IgM antibodies had positive titers in 5/40 (13%) vs 4/40 (10%), P = 0.723; IgG in 15/40 (38%) vs 19/40 (48%), P = 0.366; and IgA in 25/40 (63%) vs 33/40 (83%), P = 0.045, patients and controls, respectively. Ten (25%) patients had severe pancreatitis and two (5%) required treatment in intensive care. The median length of hospitalization was 7 d (range: 3-47 d). The severity of acute pancreatitis or the length of hospitalization was not associated with enteroviral IgM, IgG or IgA antibodies. Five pancreatic biopsy samples tested positive with RT-PCR, three (8%) in the control group and two (5%) in the patient group (P = 0.64). CONCLUSION: The rate of enteroviral infection is not increased in patients with alcohol-induced acute pancreatitis when compared to alcoholics with similar high alcohol use.