Course Of Acute Pancreatitis Research Articles

New hormones to predict the severity of gallstone-induced acute pancreatitis.

Levels of the hormones ghrelin and leptin in rat models of acute pancreatitis (AP) have been investigated in several experimental studies. However, there are very few clinical studies addressing the connection between hormone levels and AP. A few recent studies investigating the changes in ghrelin and leptin levels in patients with AP have been reported; however, our study is the first clinical study to investigate the change of nesfatin-1 levels in patients with gallstone-induced AP. Forty patients were enrolled in this study, eight of which presented with severe AP. Two blood samples were obtained from each study patient. The first blood samples were obtained at patient admission to the hospital and the second was obtained at patient discharge. All samples were collected after at least 6 h of fasting. Plasma nesfatin-1, leptin, and ghrelin levels were measured. In all 40 patients, nesfatin-1 and leptin levels were higher at admission and had decreased at discharge. In contrast, the ghrelin levels at discharge were significantly higher than those at admission. Only the changes in these hormones in the mild AP group were significant. Levels of these hormones were altered during the course of gallstone-induced AP. These changes might be associated with the clinical outcomes of the disease. To clarify whether the magnitude of the change in hormone levels at AP onset can be used as a biomarkers to predict the severity of the disease requires further investigation.

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

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. 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. 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. 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.

The effect of enteral nutrition on adipokines in patients with acute pancreatitis.

The mechanism behind the beneficial effects of enteral nutrition (EN) for patients with acute pancreatitis (AP) is largely unknown. Adipokines, as mediators of metabolism and inflammation, may be a possible mechanism. The study aimed to investigate the effect of EN on adipokines early in the course of AP. Patients with AP were randomised to EN or nil-by-mouth (NBM). Blood samples were taken on the first 4 d of admission and adipokine concentrations for adiponectin, leptin, omentin, resistin and visfatin were determined by ELISA assays. A linear mixed model analysis was run to determine differences in adipokine concentrations between the two study groups. A total of thirty-two patients were included in the study. Omentin concentrations were significantly higher in patients who received EN compared with NBM across the first 4 d of admission (mean difference: 11·6 (95 % CI 1·0, 22·3) ng/ml; P = 0·033). Leptin concentrations were significantly higher in patients who received EN compared with NBM after adjusting for age, sex and BMI (mean difference: 2·3 (95 % CI 0·1, 4·5) ng/ml; P = 0·037). No significant difference in adiponectin, resistin or visfatin concentrations were observed between the two study groups. EN significantly increases omentin and leptin concentrations in AP. Future research should be directed towards understanding whether these adipokines are responsible for the therapeutic benefits of EN.

Effect of endogenous cholecystokinin on the course of acute pancreatitis in rats.

To examine the effects of pancreatic rest, stimulation and rest/stimulation on the natural course of recovery after acute pancreatitis. Acute hemorrhagic pancreatitis (AP) was induced in male rats by intraductal infusion of 40 μL/100 g body weight of 3% sodium taurocholate. All rats took food ad libitum. At 24 h after induction of AP, rats were divided into four groups: control (AP-C), pancreas rest (AP-R), stimulation (AP-S), and rest/stimulation (AP-R/S). Rats in the AP-C, AP-R and AP-S groups received oral administration of 2 mL/kg body weight saline, cholecystokinin (CCK)-1 receptor antagonist, and endogenous CCK release stimulant, respectively, twice daily for 10 d, while those in the AP-R/S group received twice daily CCK-1 receptor antagonist for the first 5 d followed by twice daily CCK release stimulant for 5 d. Rats without any treatment were used as control group (Control). Biochemical and histological changes in the pancreas, and secretory function were evaluated on day 12 at 24 h after the last treatment. Feeding ad libitum (AP-C) delayed biochemical, histological and functional recovery from AP. In AP-C rats, bombesin-stimulated pancreatic secretory function and HOMA-β-cell score were significantly lower than those in other groups of rats. In AP-R rats, protein per DNA ratio and pancreatic exocrine secretory function were significantly low compared with those in Control rats. In AP-S and AP-R/S rats, the above parameters recovered to the Control levels. Bombesin-stimulated pancreatic exocrine response in AP-R/S rats was higher than in AP-S rats and almost returned to control levels. In the pancreas of AP-C rats, destruction of pancreatic acini, marked infiltration of inflammatory cells, and strong expression of α-smooth muscle actin, tumor necrosis factor-α and interleukin-1β were seen. Pancreatic rest reversed these histological alterations, but not atrophy of pancreatic acini and mild infiltration of inflammatory cells. In AP-S and AP-R/S rats, the pancreas showed almost normal architecture. The favorable treatment strategy for AP is to keep the pancreas at rest during an early stage followed by pancreatic stimulation by promoting endogenous CCK release.

Predictors of critical acute pancreatitis: a prospective cohort study.

Critical acute pancreatitis (CAP) has recently emerged as the most ominous severity category of acute pancreatitis (AP). As such there have been no studies specifically designed to evaluate predictors of CAP. In this study, we aimed to evaluate the accuracy of 4 parameters (Acute Physiology and Chronic Health Evaluation [APACHE] II score, C-reactive protein [CRP], D-dimer, and intra-abdominal pressure [IAP]) for predicting CAP early after hospital admission. During the study period, data on patients with AP were prospectively collected and D-dimer, CRP, and IAP levels were measured using standard methods at admission whereas the APACHE II score was calculated within 24 hours of hospital admission. The receiver-operating characteristic (ROC) curve analysis was applied and the likelihood ratios were calculated to evaluate the predictive accuracy. A total of 173 consecutive patients were included in the analysis and 47 (27%) of them developed CAP. The overall hospital mortality was 11% (19 of 173). APACHE II score ≥11 and IAP ≥13 mm Hg showed significantly better overall predictive accuracy than D-dimer and CRP (area under the ROC curve—0.94 and 0.92 vs 0.815 and 0.667, correspondingly). The positive likelihood ratio of APACHE II score is excellent (9.9) but of IAP is moderate (4.2). The latter can be improved by adding CRP (5.8). In conclusion, of the parameters studied, APACHE II score and IAP are the best available predictors of CAP within 24 hours of hospital admission. Given that APACHE II score is rather cumbersome, the combination of IAP and CRP appears to be the most practical way to predict critical course of AP early after hospital admission.

HIV Infection in Patients With Acute Pancreatitis Is Associated With Worse In-Hospital Outcomes: A Nationwide Analysis

Introduction: The risk of acute pancreatitis (AP) in HIV-infected patients is high. The course of AP in this patient population is controversial due to the paucity of existing data. Furthermore, there have been no nationally representative studies examining this. In this study, we aimed to assess the national in-hospital outcomes among patients with AP and HIV. Methods: We analyzed the nationwide inpatient sample from 2007 to determine the in-hospital outcomes of AP among patients with and without HIV infection. Outcomes of interest included length of stay, total hospitalization costs, and severity of AP defined as development of local/systemic complications, or in-hospital death. Multivariate regression modeling was applied to evaluate the association between comorbid HIV and outcomes of interest. Weighted analysis adapted for survey data was performed using appropriate weights, strata and cluster variables. Total costs and length of stay were log transformed to attain normality for multivariate linear regression. Results: Among 72,297 admissions with a discharge diagnosis of AP, there were 1,181 (1.6%) with concomitant HIV infection. Patients with AP and HIV had higher mortality (5% vs. 2.5%; p<0.001), severe outcomes (31.3% vs. 18.0%; p<0.001), length of stay (8.8 days vs. 6.4 days; p<0.001), and total hospitalization charges ($50,640 vs. $38,496; p<0.001) compared with those without HIV. On multivariate regression, HIV infection independently predicted severe outcomes (odds ratio [OR]=1.20; CI 95%: 1.01-1.41), 2-fold longer length of stay (log transformed coefficient =2.02; CI 95%: 1.97-2.07), and 2-fold greater total hospital charges (log transformed coefficient =2.37; CI 95%: 2.28-2.45). Other independent predictors of severity included African-American race, increasing age, and higher Charlson comorbidity index. HIV infection was not independently associated with increased mortality in patients with AP (OR=1.42; CI 95%: 0.97-2.09). Conclusion: HIV-infected patients with AP-related hospitalizations were associated with greater severe in-hospital outcomes, longer hospital stay and increased total hospitalization costs compared with non-HIV patients in this national representative sample. Nonetheless, HIV did not increase in-hospital mortality in patients with AP. Further research is needed to better characterize the incidence and predictors of severe outcomes in HIV-infected patients with AP.

Does early ED CT scanning of afebrile patients with first episodes of acute pancreatitis ever change management?

Rising utilization of computed tomography (CT) imaging early in the course of acute pancreatitis (AP) has been recently reported. However, radiographic demonstration of the degree of necrosis or the presence of complications is not fully apparent within the first days of an acute attack. The objective of this study was to examine if CT scanning early in the course of disease (<48 h of symptoms) in afebrile patients with an emergency department (ED) diagnosis of first episode of AP revealed any unanticipated pathology that altered clinical management. A retrospective chart review of all adult patients with a first episode of AP without fever admitted to the medical ward through the ED of our community hospital from January 1, 2011 to May 31, 2012 was performed. In cases in which CT scans were performed, the record was reviewed to determine if any unexpected findings were uncovered or if patient care was altered by the CT report. Two hundred forty-eight patients were admitted with an ED diagnosis of AP; 26.2 % (n = 65) met inclusion criteria; 70.8 % (n = 46) received a CT scan within 48 h of symptom onset. No patient that underwent CT scanning had an unexpected finding (95 % CI, 0.923-1.0). Our results demonstrate that afebrile patients with first episodes of AP do not benefit from early abdominal CT imaging. These results support the ACR Appropriateness Criteria recommendation that CT is not indicated in the first 48 h after symptom onset in unequivocal cases of AP.

Severe acute pancreatitis: a possible role of intramyocardial cytokine production.

Several mechanisms are involved in the development of the local and systemic response in acute pancreatitis. Cardiovascular system may be affected throughout the clinical course of acute pancreatitis. The aim was to evaluate local myocardial cytokine production, as well as, functional and histological myocardial alterations in severe acute pancreatitis. The animals were divided into three groups: Group 1: control; Group 2: sham; Group 3: severe acute pancreatitis. Echocardiographic assessment of cardiac function, serum levels of amylase and cytokines (TNF-α, IL-6 and IL-10), and mRNA expression of TNF-α, IL-6 and TGF-β were measured. Myocardial tissue alterations were analysed by histological examination. The serum TNF-α and IL-10 levels were significant higher in AP 2h group. The mRNA IL-6 levels from group AP 2h were statistically higher. The mRNA TNF-α level from sham group and AP 2h were statistically lower. Significant changes in the left ventricular diameter were found in AP 2h and AP 12h groups. There were statistical changes for vacuolar degeneration, picnosis and loss of nucleus, and lymphocytes. We found cardiac and histological changes compatible with the inflammatory process triggered by SAP with the promotion of local myocardial cytokine production.

537 Impact of Vitamin D Supplementation on the Course, Severity, Complications and Outcome of Patients of Acute Pancreatitis With Vitamin D Deficiency

Background: Vitamin D (Vit D) is important hormone playing diverse role in calcium and bone metabolism. Recently its deficiency has been shown to be associated with poor outcome in critically ill patients as well as in patients with acute pancreatitis. Earlier, we had shown that Vit D deficiency is widely prevalent in patients with acute pancreatitis (AP) and its deficiency is more commonly associated with persistent organ failure. There is paucity of data on effect of Vit D supplementation on course of AP. Aim: Prospectively study effects of Vit D supplementation on course, severity, complications and outcome of patients of AP with Vit D deficiency. Methods: Eighty seven patients (58M; age 39.1±13.6 years) with AP andVitamin D deficiency admitted between January 2013 toOctober 2013were prospectively included (study group). The serum 25-hydroxy D3 levels were analysed at time of admission and all patients with Vitamin D levels of 0.05). Persistent organ failure developed in 62.1% patients in study group and this was significantly lower than control group (83.3%). The mortality rates were lower but not significantly different in study group as compared to control group (5.8% vs.16.6%; p>0.05). Development of acute fluid collections (p=0.29), need for radiological intervention (p= 0.24), or surgery (p=0.19) were similar in both the groups. Conclusions: Vit D replacement in patients of acute pancreatitis with Vitamin D deficiency seems to decrease the development of persistent organ failure. Further studies with larger sample size and randomization are needed to confirm these results.

Mo1340 Does the Site of Fluid Collection Alter the Clinical Course of Acute Pancreatitis? -A Prospective Observational Study

G A A b st ra ct s clear. Methods: Consecutive patients with symptomatic WOPN seen over last 7 months were prospectively included in the study. All the patients underwent EUS, MRI and abdominal ultrasoundwithin two days. On each of these investigations an attemptwas made to determine the site, size and the nature of contents of the WOPN. The echogenic material seen in the collection on EUS and abdominal ultrasound was considered as necrotic debris. On MRI, the hypo intense areas inside the collection on T2 weighted images were taken as solid debris. The solid debris was quantified by two independent observers for all three imaging modalities and the mean was taken as final value. Results: A total of 21 patients were included. There were 16 males (78.9%) and the mean age was 43.5 ± 11.13 years. The etiology was alcohol in 13 and gall stones in 6 patients. The imaging (EUS, MRI and abdominal ultrasound) was done at a mean of 12 ± 13.93 weeks of onset of abdominal pain. On EUS, 8 patients had a solid content of ≤10%, 11 had a content of 10-40% and 2 patients had a solid content of >40%. On MRI, 10 patients were noted to have a solid content of ≤10%, 9 patients had a solid content >10-40% and 2 had content of >40%. On abdominal ultrasound 9 patients had a content of ≤10% while nine patients had a solid content between 10-40%. WON could not be visualized on abdominal ultrasound in 3 patients, two of whom had a high content of solid debris on EUS/MRI. All patients in whom the collections were not visualized on abdominal ultrasound had presented within 6 weeks of onset of disease. All patients with disease duration of >6 weeks had WOPN well visualized on abdominal ultrasound. Conclusion: Trans abdominal ultrasound can help in diagnosis as well as characterization of majority of WOPN collections with comparable accuracy as that of EUS/MRI. However, collections early in the course of disease and with high content of solid debris may be difficult to evaluate on abdominal ultrasound.

Does the Presence of Obesity and/or Metabolic Syndrome Affect the Course of Acute Pancreatitis?

The incidence of acute pancreatitis (AP) is rising with increased prevalence of obesity, which exacerbates pancreatic injury. Metabolic syndrome (MS) is defined as a cluster condition of cardiovascular risk factors, including hyperglycemia, dyslipidemia, hypertension, and central obesity. We analyze if the presence of obesity and/or MS affects the course of pancreatitis. Data were collected from 140 patients with AP between January 2010 and February 2013. Anthropometric data, including body mass index and waist circumference, were measured. Biochemical tests were used including fasting glucose, triglyceride, low- and high-density lipoprotein cholesterol levels, and total cholesterol level. Atlanta criteria, Acute Physiology and Chronic Health Evaluation II, and Ranson scoring system were used to define severe AP. Patients were classified as having MS based on the International Diabetic Federation criteria. The mean body mass index was 30.15 kg/m(2). Sixteen (11.4%) patients had severe AP, whereas 124 (88.6%) patients had mild AP. We found that 62.8% of patients with AP fulfilled the criteria of MS (P = 0.000). Body weight can be used to predict clinical severity of AP with significant P value (P = 0.009). The presence of MS in patients with pancreatitis is noticeable, but it does not affect the course of disease severity, whereas obesity correlates with pancreatitis severity.

Endovascular treatment of pseudoaneurysms in pancreatitis.

IntroductionHaemorrhagic complications are commonly reported in the course of acute pancreatitis (AP). The most dangerous are pseudoaneurysms secondary to wall erosion of the vessels crossing the inflammation area.AimTo evaluate the efficacy of different embolisation techniques of pseudoaneurysms secondary to AP.Material and methodsThe treatment outcomes in 10 AP patients were analysed in a follow-up period of 1 to 10 months (most frequently: splenic or gastroduodenal artery aneurysms). A total of 12 endovascular procedures were performed (thrombin embolisation, coil embolisation or combined). The efficacy of aneurysm sac exclusion and the patency of the treated vessel were compared.ResultsThe follow-up examination on postprocedural day 7 revealed aneurysm refilling in 3 out of 11 cases. Three patients showed an occlusion of the aneurysm-parent vessel. One month after the procedures, involving 10 patients, a vessel occlusion was confirmed in 3 and aneurysm sac refilling in another 2 patients. Taking into consideration the type of the procedure performed, treatment failure in the form of sac refilling was observed in half of thrombin-based procedures, 25% of coil embolisations and 33% of sandwich technique procedures. Similar failure distribution was noted for vessel occlusion.ConclusionsIt seems that thrombin injection was least successful, whereas thrombin injection into the sac and implantation of coils into the aneurysm neck seems to be the optimal procedure, in respect to both the cost-effectiveness of the procedure and late outcomes.

Utility of the “Harmless Acute Pancreatitis Score” in predicting a non-severe course of acute pancreatitis: A pilot study in an Indian cohort

Several severity predictors have been tested for assessing acute pancreatitis (AP). The recently described harmless acute pancreatitis score (HAPS) could be an ideal predictor for Indian patients at the community level. We validate this system in the current study. This was a prospective pilot study conducted at a tertiary center from July 2010 to December 2011. Consecutive directly admitted patients over 18years with a documented first episode of AP were enrolled and followed for at least 12months after discharge/till death. HAPS was defined as absence of rebound abdominal tenderness, serum creatinine of <2mg/dL, and hematocrit of <43 for male and <39.6 for female patients at the time of admission; and it was considered positive if the patient fulfilled all three criteria. Study outcomes included total hospital stay, need for intensive care unit (ICU), ICU stay, development of local complications, organ failure, hospital-acquired infections (including infected necrosis), and in-hospital mortality. There were a total of 103 patients directly admitted with AP during the study period, out of which, 23 were excluded. Forty-seven (58.8%) patients were positive for HAPS. Of these, 44 (93.6%) had an eventual non-severe (mild) clinical course with odds ratio 17.6 (95% CI 4.5-68.3). Sensitivity, specificity, positive and negative predictive value, and receiver operating characteristics area under the curve of HAPS as a predictor of non-severe disease were 76.3 (66.9-86.4), 85.7 (78.0-96.8), 93.8 (88.5-98.6), 56.6 (45.4-73.6), and 84.8 (76.9-92.7) respectively. This study validated the utility of HAPS for directly admitted patients with AP in India. Large-scale multicenter community-based studies need to be performed.

Modern Approaches To Infusion Antibiotic Therapy In The Treatment Of Patients With Pancreonecrosis And Peritonitis

The results of a comprehensive treatment of 41 patients with necrotizing pancreatitis in hospital surgical department of Ivano-Frankivsk Central Clinical Hospital in the period from 2010 to 2013 are analyzed. Considering sensitivity of the detected microflora to antibiotics in the early period of the course of acute pancreatitis protected cephalosporins are recommended (avibactamom, tazobactam) combined with metronidazole. With the development of pancreatic necrosis advisable carbapenems are advisable: ertapenem, in severe condition – imipinem, cilastatin and meropenem.

Liver stiffness measured by transient elastography in patients with acute pancreatitis

BackgroundAlcohol abuse constitutes a risk factor for acute pancreatitis and liver cirrhosis, and cirrhosis in turn may delay the recovery from pancreatitis. We evaluated the occurrence and significance of liver fibrosis or cirrhosis in patients with acute pancreatitis by applying transient elastography (TE). MethodsTE was carried out in 78 patients with acute pancreatitis. Comparisons were made to the severity and recurrence of pancreatitis, to biological markers for fibrosis (APRI test), alcohol intake (AST/ALT ratio, AUDIT), and prothrombin time (TT-SPA). A cut-off value of ≥7.5 kilopascals (kPa) was set for increased liver stiffness, and ≥10 kPa for significant fibrosis. ResultsThe aetiology of pancreatitis was alcohol intake in 62 patients, gallstones in 11, idiopathic in 3, tumour in 1 and medication in 1. TE was successful in 64 out of 78 patients. The median TE value was 6.5 kPa (range 2.5–61.1); 22 (35%) had values ≥7.5 kPa and 7 (11%) ≥10 kPa. Values ≥7.5 were associated with older age, higher APRI ratio, and lower TT-SPA. It did not predict the length of hospitalization or the recurrence of pancreatitis. Increased AST/ALT ratio was associated with high TE values, whereas AUDIT values were not. Values ≥10 kPa seemed to indicate manifest cirrhosis, hepatitis or subsequent development of diabetes. ConclusionsTE values ≥7.5 kPa did not predict the length of hospital stay or recurrence of pancreatitis but there were some findings of impaired liver function. Values ≥10 kPa may indicate subsequent development of diabetes and a more severe course of acute pancreatitis.

Immunomodulatory therapies for acute pancreatitis.

It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3(rd) d to the 14(th) d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis.

Serum Leptin and Ghrelin Levels in Patients in the Early Stages of Acute Biliary Pancreatitis and Different Degrees of Severity

Acute pancreatitis (AP) is a potentially fatal disease. In animal experiments leptin and ghrelin were shown to modulate the course of AP. The aim of the study was to estimate the relationship between the severity of acute biliary pancreatitis (ABP) and serum levels of leptin and ghrelin in nonobese patients in the first seven days of the hospitalization. The study included nine patients with mild ABP (MABP), eleven patients with severe ABP (SABP) and twenty healthy controls, appropriately matched age, sex and weight. Serum concentrations of leptin and ghrelin were measured in patients on the first, third, fifth, and seventh days of hospitalization using leptin and ghrelin RadioImmunoAssay (RIA) kits. At admission and throughout the study the mean serum leptin concentration in SABP patients was higher than in the controls but without statistical significance. Serum ghrelin concentrations on admission were significantly lower in patients with ABP than in the controls. We observed steadily increasing serum ghrelin levels in both groups of the patients during the course of ABP. The results of our study do not support the role of leptin as a marker of the severity of ABP. On the other hand, rising serum ghrelin levels during the course of ABP may be a marker of recovery and an indicator of the healing process.

Acute pancreatitis in children and adolescents.

In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The etiology of acute pancreatitis in children is often drugs, infections, trauma, or anatomic abnormalities. Diagnosis is based on clinical symptoms (such as abdominal pain and vomiting), serum pancreatic enzyme levels, and imaging studies. Several scoring systems have been proposed for the assessment of severity, which is useful for selecting treatments and predicting prognosis. The basic pathogenesis of acute pancreatitis does not greatly differ between adults and children, and the treatments for adults and children are similar. In large part, our understanding of the pathology, optimal treatment, assessment of severity, and outcome of acute pancreatitis in children is taken from the adult literature. However, we often find that the common management of adult pancreatitis is difficult to apply to children. With advances in diagnostic techniques and treatment methods, severe acute pancreatitis in children is becoming better understood and more controllable.

The antioxidant profiles, lysosomal and membrane enzymes activity in patients with acute pancreatitis.

Oxidative stress and inflammatory mediators, such as IL-6, play an important role in the pathophysiology of acute pancreatitis. The study was aimed to assess the degree of the pro/antioxidative imbalance and estimate which antioxidant plays a role in the maintenance of pro/antioxidative balance during acute pancreatitis. The study was investigated in the blood of 32 patients with acute pancreatitis and 37 healthy subjects. IL-6 concentration as early marker of inflammation was determinated. The intensity of oxidative stress was assessed by TBARS concentration. To investigate antioxidative status, the GPx and Cu/Zn SOD activities and the levels of GSH, MT, SH groups, and TRAP were measured. The concentrations of Cu and Zn as ions participating in the maintenance of antioxidant enzymes stability and playing a role in the course of disease were determinated. The activities of GGT, AAP, NAG, and β-GD as markers of tissue damage were also measured. An increase in IL-6 concentration, which correlated with Ranson criteria, and an increase in GPx activity, levels of MT, TBARS, or GGT, and NAG activities in patients group compared to healthy subjects were demonstrated. A decrease in GSH level in patients group compared to control group was noted. The studies suggest that GPx/GSH and MT play the role of the first line of defence against oxidative stress and pro/antioxidant imbalance in the course of acute pancreatitis.

Regeneration from acute pancreatitis requires transcriptional silencing of NFATc1

Introduction: Tissue injury initiates a complex regenerative programme ensuring complete restoration of organ structure and function. Understanding the molecular key events in mediation and regeneration from pancreas injury is critical to develop novel therapeutic strategies. Recent evidence suggests important roles for developmental and inflammatory transcription factors in several steps of the regeneration process. Aims: To analyze whether and how the inflammatory transcription factor NFATc1 is involved in the course of acute pancreatitis. Methods: Caerulein and L-Arginin were used to induce acute pancreatitis in different pancreas specific transgenic mice models with differential expression of NFATc1. Mice were sacrificed at different time points after induction of acute pancreatitis to isolate pancreata for further analysis. Gene expression in mice tissue and acinar cell explants were determined by using RT-PCR, immunoblotting, immunofluorescence and immunohistochemical stainings. Local histone modifications on the NFATc1 promoter were investigated by ChIP analysis. Results: Caerulein mediated acute pancreatitis initiates acinar to ductal metaplasia, which goes along with activation of NFATc1 in metaplastic areas of the pancreas. Regeneration of the pancreas requires inactivation of NFATc1 by H3K27 trimethylation mediated by the Polycomb protein EZH2. While pharmacological or genetic inactivation of NFATc1 in mice accelerates pancreas regeneration, sustained activation of NFATc1 overcomes transcriptional silencing and fully prevents restoration of the organ. Conclusion: Our results provide evidence, that transcriptional silencing of NFATc1 by EZH2 is an inevitable prerequisite for sufficient regeneration from acute pancreatitis.