Abstract In the 20th century early management of acute pancreatitis often included surgical intervention, despite overwhelming mortality. The emergence of high-quality evidence (randomized controlled ...trials and meta-analyses) over the past two decades has notably shifted the treatment paradigm towards predominantly non-surgical management early in the course of acute pancreatitis. The present evidence-based review focuses on contemporary aspects of early management (which include analgesia, fluid resuscitation, antibiotics, nutrition, and endoscopic retrograde cholangiopancreatography) with a view to providing clear and succinct guidelines on early management of patients with acute pancreatitis in 2017 and beyond.
Clinical reports on early immune dysregulation in acute pancreatitis (AP) are scarce. Herein we investigate the initial temporal development of selected biomarkers. Blood samples were taken at 0-24 ...and 25-48 h after onsets of AP were acquired. Mean values and temporal intermediate difference (delta-values) of IL-1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were calculated. Differences between severity groups, predictive capacity of the biomarkers and association with severe disease were analyzed. Paired comparison of samples (n = 115) taken at 0-24 and 25-48 h after onsets of AP showed a change over time for IL-1β, IL-6, IL-8 and IL-10 (
< 0.05) and a significant difference between severity groups after 24 h. In ROC-analysis an IL-6 cut-off level of 196.6 pg/mL could differentiate severe AP (sensitivity 81.9, specificity 91.3). The delta-values of IL-1β and IL-6 were significantly associated with severe outcomes (odds ratios 1.085 and 1.002, respectively). Data of this work demonstrate a distinct change in IL-1β, IL-8, IL-10 and IL-6 over the first 48 h after onset of AP. The temporal development of biomarkers can assist in the early stratification of the disease. Herein IL-1β and IL-6 were associated with severe disease, however the prognostic capacity of investigated biomarkers is low.
Abstract
Background
Most patients with acute pancreatitis (AP) experience mild, self-limiting disease with little or no need for hospital care. However, 20–25% of patients develop a more severe and ...potentially life-threatening condition with progressive systemic inflammatory response syndrome (SIRS) and multiorgan failure, resulting in high morbidity and mortality rates. Predicting disease severity at an early stage is important, as immediate supportive care has been demonstrated to reduce the incidence of SIRS and organ failure, improving patient outcome. Several studies have demonstrated elevated levels of heparin-binding protein (HBP) in patients with sepsis and septic shock, and HBP is believed to play a part in endothelial dysfunction leading to vascular leakage. As HBP levels increase prior to other known biomarkers, HBP has emerged as a promising early predictor of severe sepsis with organ dysfunction.
Methods
Patients admitted to Skåne University Hospital in Malmö between 2010 and 2013 fulfilling the criteria for AP were identified in the emergency department and prospectively enrolled in this study. The primary outcome was measured levels of HBP upon hospital admission in patients with confirmed AP. Correlations among HBP concentrations, disease severity and fluid balance were considered secondary endpoints. The correlation between HBP levels and fluid balance were analysed using Pearson correlation, and the ability of HBP to predict moderately severe/severe AP was assessed using a receiver operating characteristic (ROC) curve.
Results
The overall median HBP level in this study was 529 (307–898) ng/ml. There were no significant group differences in HBP levels based on AP severity. Fluid balance differed significantly between patients with mild versus moderately severe and severe pancreatitis, but we found no correlation between HBP concentration and fluid balance.
Conclusions
HBP levels are dramatically increased in patients with AP, and these levels far exceed those previously reported in other conditions. In this study, we did not observe any significant correlation between HBP levels and disease severity or the need for intravenous fluid. Additional studies on HBP are needed to further explore the role of HBP in the pathogenesis of AP and its possible clinical implications.
Respiratory failure worsens the outcome of acute pancreatitis (AP) and underlying factors might be early detectable.
To evaluate the prevalence and prognostic relevance of early pleuropulmonary ...pathologies and pre-existing chronic lung diseases (CLD) in AP patients.
Multicentre retrospective cohort study. Caudal sections of the thorax derived from abdominal contrast enhanced computed tomography (CECT) performed in the early phase of AP were assessed. Independent predictors of severe AP were identified by binary logistic regression analysis. A one-year survival analysis using Kaplan-Meier curves and log rank test was performed.
358 patients were analysed, finding pleuropulmonary pathologies in 81%. CECTs were performed with a median of 2 days (IQR 1-3) after admission. Multivariable analysis identified moderate to severe or bilateral pleural effusions (PEs) (OR = 4.16, 95%CI 2.05-8.45, p<0.001) and pre-existing CLD (OR = 2.93, 95%CI 1.17-7.32, p = 0.022) as independent predictors of severe AP. Log rank test showed a significantly worse one-year survival in patients with bilateral compared to unilateral PEs in a subgroup.
Increasing awareness of the prognostic impact of large and bilateral PEs and pre-existing CLD could facilitate the identification of patients at high risk for severe AP in the early phase and thus improve their prognosis.
During the last decade, neoadjuvant therapy (NAT) for pancreatic cancer has become more frequent. Pathological response and overall survival are promising; however, various post-operative ...complications have been reported. Our primary aim was to compare the complication scenario of patients receiving NAT in borderline resectable and locally advanced disease with those who had upfront pancreatic surgery (UFS) for primarily resectable cancer.
From the Swedish National Pancreatic and Periampullary Cancer Registry, patients resected for pancreatic ductal adenocarcinoma (PDAC) between 2010 and 2018 were identified. Data on patient characteristics, neoadjuvant therapy, post-operative complications and survival were obtained. Comparisons between groups as well as survival analysis were performed.
Within the total cohort of 13,948 patients, 1894 (median age 69 years, 51% men) were resected for PDAC. Among these, 112 (5.9%) patients received NAT followed by surgery. The patients who received NAT were younger (67 vs 70 years, p < .001), had a lower level of CA19-9 (47 vs 108, p = .001) and had to a larger extent vascular resection (58.9 vs 26.9%, p < .001) and total pancreatectomy performed (23.2 vs 9.1%, p < .001). No difference was found for major post-operative complications and there was no significant change in survival rate between the NAT and UFS groups (median 28 vs 26 months, p = .122).
When analyzing data from a national registry, no difference in post-operative complications was found between resected patients receiving UFS and NAT for PDAC. Also, the survival was equal between groups. NAT is a feasible treatment option for patients with potentially curable pancreatic cancer.
Acute pancreatitis is a common cause of hospitalization and has an incidence of about 300 per 1,000,000 inhabitants. A majority of patients with acute pancreatitis have mild disease, with an absence ...of local and systemic complications 1. The clinical, translational, and experimental research in the field of acute pancreatitis is enormous and various guidelines exist. The guidelines have improved, and now increasingly use evidence-based grading, although expert opinion is still part of numerous recommendations.A persistent problem, however, is the uptake of and compliance with these guidelines. For every guideline recommendation, we should need an implementation plan and an audit. This was pointed out in an editorial in the Scandinavian Journal of Gastroenterology in 2008 2. It is reasonable to assume that adherence to existing management recommendations improves clinical outcomes for patients with acute pancreatitis.
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.
For patients with moderate or severe AP, fast and efficient treatment of complications is a prerequisite to keep mortality as well as long-term morbidity levels low. There is a heterogeneity of ...MAFLD, and the clinical course is influenced by age, diet, alcohol intake, genetics/epigenetics and metabolic health status. CONFLICT OF INTEREST STATEMENT The authors have no conflicts of interest to declare.
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