Course Of Severe Acute Pancreatitis Research Articles

Tectoridin alleviates caerulein-induced severe acute pancreatitis by targeting ERK2 to promote macrophage M2 polarization

Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.

Dynamic Changes in Serum Cytokine Profile in Rats with Severe Acute Pancreatitis

Background and Objectives: Most published research has only investigated a single timepoint after the onset of severe acute pancreatitis (SAP), meaning that they have been unable to observe the relationship between the dynamic changes in cytokines and SAP progression. In this study, we attempted to reveal the relationship between dynamic changes in cytokine expression levels and SAP disease progression and the relationship between cytokines, using continuous large-scale cytokine detection. Materials and Methods: Seventy rats were randomly assigned to control (Con), sham operation (SO) and SAP groups. The SAP group was randomly allocated to five subgroups at 3, 6, 9, 12 and 15 h after the operation. In the SAP group, 5% sodium taurocholate was injected retrograde into the pancreatic bile duct. Animals in the SO group received a similar incision, a turning over of the pancreas. Control animals did not receive any treatment. We observed the survival, ascites fluid amount, pancreatic histopathological scores and serum amylase activity of SAP rats. We used the cytokine microarray to simultaneously detect 90 cytokines and the dynamic changes in one experiment and to analyze the correlation between cytokine expression and disease progression. Results: The mortality of SAP rats increased with an increase in time. Serum amylase activity, pancreatic histopathological scores and ascites fluid amount were time-dependent. Compared with normal rats, 69 cytokines in SAP rats were significantly changed for at least one timepoint, and 49 cytokines were significantly changed at different timepoints after SAP induction. The changes in inflammatory cytokines were significantly upregulated at 6 and 9 h and 12 h and then significantly decreased. Conclusions: The trend of cytokine expression in SAP rats was not consistent with the disease progression. The cytokine-cytokine receptor interaction and MAPK signal's dominant cytokines were always highly expressed at various time points over the course of SAP.

Identification of key microRNAs in exosomes derived from patients with the severe acute pancreatitis

ObjectiveExosomes have been identified as important carriers of various genetic materials, including microRNAs (miRNAs). Increasing evidence indicates that the course of severe acute pancreatitis (SAP) is associated with miRNAs transported by exosomes. We aimed to identify the signature miRNAs as biomarkers of SAP. MethodsWe obtained exosomes from the SAP patients’ blood. After separation, purification, and identification, we performed high-throughput sequencing and screened the differentially expressed(DE) miRNAs in the exosomes. Bioinformatics analysis was performed to identified the target genes of the miRNAs and the pathways enriched based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and selected the key miRNAs related to SAP. Total RNA was extracted from patient serum exosomes to detect the expression levels of the selected miRNAs in exosomes of three experimental groups (mild -, moderately severe -, and severe AP) and a control group, using Real-time quantitative polymerase chain reaction (RT-qPCR). Results272 DE miRNAs were identified between SAP and control group. Using bioinformatics analysis, we determined that the functions of the target genes were enriched in six signaling pathways including focal adhesion. Based on this, seven candidate signature miRNAs were selected: miR-603, miR-548ad-5p, miR-122–5p, miR-4477a, miR-192–5p, miR-215–5p, and miR-583. The RT-qPCR results of the seven miRNAs in the SAP group were consistent with the sequencing results. ConclusionExosome-derived miR-603, miR-548ad-5p, miR-122–5p, miR-4477a, miR-192–5p, miR-215–5p, miR-583 are positively correlated with SAP, which might provide new insights into the pathogenesis of SAP and serve as the biomarkers of SAP.

”Fulminant” acute pancreatitis: diagnosis, prognosis, treatment

Aim:improving the results treatment of patients with severe acute pancreatitis by early diagnosis fulminant course of the disease and development of individualized treatment tactics based on early surgical interventions with perioperative extracorporeal detoxificationMaterials and methods:In research analyzed the treatment of 232 patients with severe acute pancreatitis: 175 patients were evaluated retrospectively (control group), 57 were included in a prospective study (main group). The severity of the disease was studied using integral scales, necrosis of the pancreas (its localization, depth) and the prevalence of parapancreatitis (gradations according to Ishikawa et al.) - according to CT data. The tactics of treatment at the retrospective stage of the study was based on the current Clinical Recommendations, at the prospective stage - on the developed signs of a "fulminant" course of the disease and included early operations with perioperative extracorporeal detoxification.Results:Criteria for a fulminant course of severe acute pancreatitis were found in 41 (23%) of 175 and 24 (42%) of 57 patients. According to the scale values (APACHE II ≥ 16 Ranson ≥ 8, SOFA ≥ 7 points) in the first 48 hours from the onset of the disease, the presence of aseptic enzymatic peritonitis, the depth of necrosis in the region of the head and body of the pancreas ≥50%, intra-abdominal hypertension of the III-IV degree, significant differences with similar indicators in 134 and 33 patients with severe acute pancreatitis. With fulminant course in the control and main groups, all 5 patients who received only conservative treatment died, 33 (86.8%) and 9 (40.9%) after operations, χ2 = 13.32, p<0.001. Mortality in severe acute pancreatitis, excluding patients with fulminant course, was comparable in the groups, being 15.7% and 15.2%, χ2 = 0.450, p> 0.05.Conclusion:Patients with severe acute pancreatitis represent a heterogeneous group. The morphological substrate of "fulminant" pancreatitis is deep (more than 50%) necrosis with localization in the head and body of the pancreas and widespread parapancreatitis. The developed individualized approach to treatment allows predicting an unfavorable course in the first 48 hours after the onset of the disease. Early operations in the nature of detoxification, decompression and drainage interventions, with perioperative use of extracorporeal detoxification methods allowed to reduce mortality from 86.8% to 40.9%.

Hemorrhage complicating the course of severe acute pancreatitis.

Backgrounds/AimsThe course of severe acute pancreatitis (SAP) complicated by hemorrhage is associated with poor outcome.MethodsTwenty-four (13%) out of 183 cases of SAP had hemorrhagic complications- 12 intraabdominal & 12 intraluminal, 13 had major & 11 had minor and 16 had de-novo & 8 post-surgical bleeding. The mean duration of pancreatitis prior to bleeding was 27±27.2 days.ResultsPredictors of haemorrhage on univariate analysis were delayed admission (0.037), more than one organ failure (p=0.008), presence of venous thrombosis (p=0.033), infective necrosis (0.001) and systemic sepsis – bacterial (0.037) & fungal (p=0.032). On multivariate analysis infected necrosis (OR=11.82) and presence of fungal sepsis (OR=3.73) were the significant factors. Patients presenting with more than one organ failure and bacterial sepsis had borderline significance on multivariate analysis. Need for surgery (50% vs. 12.6%), intensive care stay (7.4±7.9 vs. 5.4±5.2 days) and mortality (41.7% vs. 10.7%) were significantly higher in patients who suffered haemorrhage. Seven of the 13 with major bleeding had pseudoaneurysms-4 were embolized, 4 needed surgery including 1 embolization failure. Seven with intraabdominal bleeding required surgical intervention, 2 had successful embolization and 3 had expectant management. CT severity index and surgical intervention, were significantly associated with intraabdominal bleeding. Organ failure, presence of pseudoaneurysm and surgical intervention were associated with major bleeding.ConclusionsHemorrhage in SAP was associated with increased morbidity and mortality. Infected necrosis accentuated the degradation of the vessel wall, which predispose to hemorrhage. Luminal bleeding may be indicative of erosion into the adjacent viscera by the pseudoaneurysm.

Dynamics of homeostasis in patients with acute pancreatitis, depending on the use of parenteral nutrition

The data of patients with severe acute pancreatitis (AP) who were treated for the period from 2014 to 2018 were analyzed. Patients who on the second day of intensive therapy experienced intestinal failure syndrome, which made it impossible to conduct early enteral nutrition, nutritional support began with a total parenteral nutrition (TPN). Depending on the type of mixture that was used as nutritional support, the patients were divided into subgroups: subgroup 1 (n = 22) - patients who received three-component mixtures in special TPN bags. Subgroup 2 (n = 20) - patients who received three-component mixtures with a high content of ω-3 fatty acids for TPN. Subgroup 3 (control) - patients (n = 25), in which the TPN consisted of separate modules of carbohydrates, amino acids and fats. It is shown that during severe AP accompanied by increased levels of cortisol in patients subgroups 1, 2 and 3 is 1.8, 1.7 and 1.9 times higher than normal, stress-induced hyperglycemia and hypoalbuminemia from the first day of the disease. Conducting modular TPN did not provide a protein-saving effect against the background of hypercatabolism caused by the course of severe acute pancreatitis. The addition of ω-3 FA in the composition of TPN by three-chamber bags contributed to a more rapid recovery of the level of total blood protein and albumin against the background of the course of severe AP. On the background of the nutritional support by TPN using the three-chambered bags of enriched ω-3 fatty acids, it has been registered normalization of neutrophil-leukocyte index at 7 days by reducing leukocytosis and a significant increase in blood levels of lymphocytes, a faster and more pronounced decrease in blood levels of CRP. It determined that in patients with severe AP 1 and 2 subgroups that received TPN using a three-chambered bags, the total period of hospital treatment (27,5 ± 2,7 days and 22.1 ± 0.8 days, respectively) was significantly less than in patients who underwent TPN using modular systems (35.5 ± 7.7 days) (p 1, 2 = 0.001, p1, 3 <0.001, p2, 3 <0.001).

Pigtail catheter drainage and surgery in severe acute pancreatitis.

Background and AimSevere acute pancreatitis is initially managed with conservative treatment. Patients who failed conservative management were effectively treated with pigtail drainage. Factors predicting surgery remain uncertain.MethodsA total of 58 patients with severe acute pancreatitis presenting to JIPMER Hospital were studied and managed with a step‐up approach. In this prospective observational study, patients were divided into three groups based on the final mode of treatment received: conservative, pigtail alone, and surgery groups.ResultsOf 58 patients, 30 patients were managed with conservative treatment, 20 patients with pigtail alone, and 8 patients underwent surgical treatment after pigtail failure. Overall sepsis reversal was achieved in 22 of 28 (78.5%) patients: 18 were in the pigtail alone group, and 4 were in surgery group, which was statistically significant (P = 0.03). Respiratory failure was the most common organ failure, 68.9%, and overall mortality was 8.62 in this study. On univariate analysis, absence of sepsis reversal within 2 weeks of pigtail insertion is a predictor of need of surgery. Other significant findings were higher catheter‐related complications in the surgery group (P = 0.01) and a 100% unimicrobial infection in the surgery group (P = 0.02). Overall mortality was 8.6%, which did not differ significantly between the groups.ConclusionThe step‐up approach avoided unnecessary intervention, and 52% patients recovered by conservative treatment alone. Sepsis reversal within 2 weeks of pigtail insertion can be used as a predictor of surgery in the early course of severe acute pancreatitis managed by the step‐up approach.

Diagnosis and stage-adapted treatment of acute pancreatitis

Acute pancreatitis is apotentially life-threatening disease, which is morphologically classified into interstitial edematous or necrotizing pancreatitis. According to the revised Atlanta classification, mild, moderate and severe clinical courses are differentiated regarding local and systemic complications as well as concomitant organ failure. In the initial disease phase, the therapeutic measures are focused on (aggressive) volume replacement, early enteral nutrition and adequate analgesia. Characteristic in the course of severe acute pancreatitis are abdominal necroses, which require individualized and interdisciplinary treatment with antibiotic therapy, drainage and definitive necrosectomy. Necrosectomy should be planned as a"step-up approach" using interventional-radiological, endoscopic and minimally invasive surgical procedures.

Evolving Techniques in Pancreatic Surgery.

Evolving Techniques in Pancreatic Surgery.

Acute pancreatitis complicated by rupture of abdominal aortic aneurysm.

Acute pancreatitis complicated by rupture of abdominal aortic aneurysm.

The role of Card9 overexpression in peripheral blood mononuclear cells from patients with aseptic acute pancreatitis.

Activated mononuclear cells are an early event in the course of severe acute pancreatitis (SAP). To date, the molecular mechanism triggering peripheral blood mononuclear cells (PBMCs) is poorly understood. The aim of this paper was to determine the potential role of Card9 in SAP. We collected data from 72 subjects between January 2013 and June 2014. Subsequently, PBMCs were isolated on day 1, 3 and 5 of pancreatitis. Immunofluorescence staining, quantitative real-time PCR, Western blotting, immunoprecipitation and ELISA were used to determine the role of Card9 in SAP. Microbial culture showed that SAP patients at the early period did not develop any bacteria and fungi infection. Card9 expression in SAP patients was higher than that in mild acute pancreatitis and volunteer healthy controls, up to the peak on day 1. The monocyte-derived cytokines interleukin (IL)-17, IL-1β, IL-6 and tumour necrosis factor-α mediated by the induction of Card9 markedly increased in SAP patients compared with the control group. Furthermore, the inducible formation of Card9-Bcl10 complex was found in PBMCs, which may be involved in nuclear factor kappa B (NF-κB) and p38 activation in SAP. Receiver operating characteristic curve indicated that Card9 levels had a high sensitivity of 87.5% and specificity of 67.7%, showing the close correlation with SAP patients. Card9 overexpression was firstly found in aseptic SAP, which may be played an important role in NF-κB and p38 activation in PBMCs. It also provided the new insights into therapeutic interventions by targeting monocytes activation in SAP patients.

A new combination therapy in severe acute pancreatitis--hyperbaric oxygen plus 3-aminobenzamide: an experimental study.

ObjectivesThis study was designed to evaluate effects of hyperbaric oxygen (HBO) plus 3-aminobenzamide (3-AB) cotreatment on tissue oxidative stress parameters (TOSp), tissue histopathology scores (THSc), and bacterial translocations (Bact-Trans) in an experimental model of severe acute pancreatitis (AP).MethodsSeventy-five Sprague-Dawley rats were randomized into 5 groups. Group 1 received sham. Severe AP was induced by intraductal taurocholate infusion and then group 2 received saline, group 3 received 3-AB, group 4 received 3-AB plus HBO, and group 5 received HBO. 3-Aminobenzamide (10 mg/kg per day, once daily, intraperitoneal) and saline (1 mL/kg) were started right after the induction, whereas HBO (2,8 atm pressure, BID, 90 minutes each) was started at the sixth hour. The rats were euthanized at the 54th hour, and TOSp, THSc, and Bact-Trans were studied.ResultsIn treatment groups 3 and 5, Bact-Trans (P < 0.05, P < 0.05), TOSp (P < 0.05, P < 0.05), and THSc (P < 0.001, P < 0.001) were significantly lower than controls. In addition to these findings, group 4 (cotreatment) showed the most significant effect on Bact-Trans and THSc (P < 0.001, P < 0.001) and also better in TOSp (P < 0.02).ConclusionsPoly(ADP-ribose) polymerase inhibition by 3-AB and HBO treatment alone was effective in the course of severe AP, and favorable with cotreatment because of the improved cascades of inflammatory process by different aspects.

Individualized early goal-directed therapy in systemic inflammation: is full utilization of preload reserve the optimal strategy?

In severe acute pancreatitis, the administration of fluids in the presence of positive fluid responsiveness is associated with better outcome when compared to guiding therapy on central venous pressure. We compared the effects of such consequent maximization of stroke volume index with a regime using individual values of stroke volume index assessed prior to severe acute pancreatitis induction as therapeutic hemodynamic goals. Prospective, randomized animal study. University animal research laboratory. Thirty domestic pigs. After randomization, fluid resuscitation was started 2 hours after severe acute pancreatitis induction and continued for 6 hours according to the respective treatment algorithms. In the control group, fluid therapy was directed by maximizing stroke volume index, and in the study group, stroke volume index assessed prior to severe acute pancreatitis served as primary hemodynamic goal. Within the first 6 hours of severe acute pancreatitis, the study group received a total of 1,935.8 ± 540.7 mL of fluids compared with 3,462.8 ± 828.2 mL in the control group (p < 0.001). Pancreatic tissue oxygenation did not differ significantly between both groups. Vascular endothelial function, measured by flow-mediated vasodilation before and 6 hours after severe acute pancreatitis induction, revealed less impairment in the study group after treatment interval (-90.76% [study group] vs -130.89% [control group]; p = 0.046). Further, lower levels of heparan sulfate (3.41 ± 5.6 pg/mL [study group] vs 43.67 ± 46.61 pg/mL [control group]; p = 0.032) and interleukin 6 (32.18 ± 8.81 pg/mL [study group] vs 77.76 ± 56.86 pg/mL [control group]; p = 0.021) were found in the study group compared with control group. Histopathological examination of the pancreatic head and corpus at day 7 revealed less edema for the study group compared with the control group (1.82 ± 0.87 [study group] vs 2.89 ± 0.33 [control group, pancreatic head]; p = 0.03; 2.2 ± 0.92 [study group] vs 2.91 ± 0.3 [control group, pancreatic corpus]; p = 0.025). Individualized optimization of intravascular fluid status during the early course of severe acute pancreatitis, compared with a treatment strategy of maximizing stroke volume by fluid loading, leads to less vascular endothelial damage, pancreatic edema, and inflammatory response.

Six cases of severe acute pancreatitis complicated with vancomycin-resistant enterococcus enteritis.

The objective of this study was to explore the clinical manifestations and possible mechanisms of vancomycin-resistant enterococcus (VRE)-induced severe enteritis and extraenteric disseminations. In six patients with severe acute pancreatitis (SAP) complicated with acute infectious diarrhea, VRE was confirmed by bacterial genotyping, minimum inhibitory concentration testing, and empiric linezolid treatment. Samples collected from stools and peripancreatic effusions were used to compare the genotypes of VRE by pulsed-field gel electrophoresis and multilocus sequence typing and to validate the suspected extraenteric disseminations caused by VRE. To further elucidate the mechanisms of VRE-inflicted enteric mucosal injury, in vitro infection of human intestinal Caco-2 cell line with VRE was performed followed by inflammatory cytokine assays and morphological characterization by electron microscopy. All six VRE strains isolated from stool samples caused severe enteritis in SAP patients. The same strains further inflicted significant damage and induced inflammatory reactions in Caco-2 cells. Homologous assays demonstrated high homology between samples from stool and peripancreatic effusions in two patients, indicating the occurrence of extraenteric disseminations. Alterations in drug resistance and virulence of enterococci, part of the symbiotic bacteria, during the course of SAP may cause inflammatory injuries to enteric epithelium, resulting in enteritis and extraenteric disseminations.

Efficacy of Continuous Regional Arterial Infusion With Low-Molecular-Weight Heparin for Severe Acute Pancreatitis in a Porcine Model

Administration of heparin or its derivatives has been proved to be beneficial in the treatment of severe acute pancreatitis (SAP). However, drugs administered by conventional intravenous way are difficult to reach the pancreatic tissue and may cause bleeding complications due to coagulation and microcirculatory disturbance following initiation of SAP. In this study, we aimed to assess the effects of low-molecular-weight heparin (LMWH) administered with continuous regional arterial infusion (CRAI) technique in a porcine model of SAP. Following baseline measurements, 18 animals were divided into three groups: CRAI group (LMWH infused through placed arterial catheter), venous group (LMWH infused through central venous catheter), and SAP control group. We used retrograde intraductal infusion of sodium taurocholate to induce SAP. Global hemodynamic profiles, urine output, systemic oxygenation, and inflammatory and serum biochemical parameters of the animals were studied. At the end of the experiment, histological examination of pancreas, intestine, and lung was performed. Continuous regional arterial infusion with LMWH remarkably stabilized hemodynamic profiles, improved systemic oxygenation and peripheral perfusion, alleviated histological injury of pancreas (especially for the necrosis scale), and downregulated inflammatory response when compared with the other two groups. Moreover, serum D-dimer level also decreased most significantly in the CRAI group (474 ± 144 vs. 664 ± 155 µg/L in the venous group and 945 ± 351 µg/L in the controls at the end), partly indicating ameliorated coagulation disorders in the study group. No bleeding complication was observed in the CRAI group, whereas two animals in the venous group presented gastrointestinal hemorrhage. Continuous regional arterial infusion with LMWH exhibits strong therapeutic effects in the course of SAP with great safety. Human studies using this novel therapy are required to assess these potential benefits in the clinical setting.

Leiden Mutation and the Course of Severe Acute Pancreatitis

Objective: to evaluate the impact of Leiden mutation on the course of severe acute pancreatitis. Subjects and methods. One hundred and twelve people were examined. Group 1 comprised 50 patients diagnosed with severe acute pancreatitis without coagulation factor V (Leiden) mutation. Group 2 included 42 patients with severe acute pancreatitis who were found to have Leiden mutation. Acute pancreatitis was first diagnosed in both groups. Group 3 consisted of 20 apparently healthy individuals (a control group). The severity of the underlying disease was determined in accordance with the clinical and laboratory parameters recommended by the I. I. Dzhanelidze Saint Petersburg Research Institute of Emergence Care. Results. This investigation revealed an association of Leiden mutation with trends in the development of acute pancreatitis. Group 2 exhibited a more severe disease: large focal pancreatic necrosis was twice more common and infectious complications developed more frequently; more aggressive and radical treatments were more often used. The patients with Leiden mutation had higher mortality rates (33% in the Leiden mutation group and 24% in the non-mutation group. Conclusion. The findings should be kept in mind in elaborating new diagnostic methods and principles in the treatment of the underlying disease and in the prevention of its complications in patients with severe acute pancreatitis. Key words: acute pancreatitis, Leiden mutation.

Sa1374 Hemorrhage Complicating the Course of Severe Acute Pancreatitis

Sa1374 Hemorrhage Complicating the Course of Severe Acute Pancreatitis

Effects of FTY720 and Rapamycin on Inflammation in Taurocholate-Induced Acute Pancreatitis in the Rat

This study aimed at T-cell inhibition by immunosuppressants to reduce cell damage and improve the course of severe acute pancreatitis (SAP). A taurocholate-induced SAP was used and 5 groups were compared: (1) rapamycin + FTY720, (2) rapamycin, (3) FTY720, (4) cortisol, and (5) control: sodium chloride. Drugs were applied intravenously at SAP induction; 6 hours later, rats were killed. Interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor α, platelet-activating factor, amylase, and lipase were measured in serum and myeloperoxidase tissue activity in pancreas, kidney, lung, liver, and spleen. Edema, inflammation, and necrosis were histologically determined in pancreas. CD4/CD8 immunohistochemistry was performed. Inflammation was ameliorated in all 4 treated groups. Necrosis development was suppressed by FTY720, FTY720 + rapamycin, and cortisol. IL-6 and IL-10 were significantly lower in these groups. Amylase was higher in all treatment groups compared to the controls except for the cortisol group. Tumor necrosis factor α, lipase, and myeloperoxidase activity were not affected by therapy. CD4+/CD8+ cells were significantly less in FTY720-treated pancreata. Rapamycin and FTY720 ameliorated the severity of SAP, which may be due to early suppression of helper T cells. FTY720 reduced the development of pancreatic necrosis. The combination of both immunosuppressants did not show advantage to treatment with FTY720 alone.

Intra-Abdominal Fungal Infections Complicating Acute Pancreatitis: A Review

Intra-abdominal infections of pancreatic or peripancreatic necrotic tissue complicate the clinical course of severe acute pancreatitis (SAP) and are associated with significant morbidity. Fungal infection of necrotic pancreatic tissue is increasingly being reported. The incidence of intra-abdominal pancreatic fungal infection (PFI) varies from 5% to 68.5%. Candida albicans is the most frequently isolated fungus in patients with necrotizing pancreatitis. Prolonged use of prophylactic antibiotics, prolonged placement of chronic indwelling devices, and minimally invasive or surgical interventions for pancreatic fluid collections further increase the risk of PFI. Computed tomography- or ultrasound-guided fine-needle aspiration of pancreatic necrosis is a safe, reliable method for establishing pancreatic infection. Amphotericin B appears to be the most effective antifungal treatment. Drainage and debridement of infected necrosis are also critical for eradication of fungi from the poorly perfused pancreatic or peripancreatic tissues where the antifungal agents may not reach to achieve therapeutic levels. Fungal infection adversely affects the outcome of patients with SAP and is associated with increased morbidity, although the mortality rate is not increased specifically because of PFI. Although antifungal prophylaxis has been suggested for patients on broad-spectrum antibiotics, no randomized controlled trials have yet studied its efficacy in preventing PFI.

Targeting P-selectin in acute pancreatitis

Importance of the field: Acute pancreatitis (AP) is a multifactorial disorder not fully understood yet. In particular, the pathogenetic pathways promoting a severe life-threatening course of AP are the subject of ongoing investigations. P-selectin has been shown to play a central role in the complex pathophysiology in AP as well as various other inflammatory conditions.Areas covered in this review: P-selectin function in AP is reviewed with focus on its dual function as a mediator of leukocyte recruitment and cell adhesion, which implies the unique effect of linking both inflammation and coagulation, especially in the progression from mild to severe necrotizing AP. Potential therapeutic aspects are discussed with regard to the clinical situation.What the reader will gain: A better understanding of the pathogenic role of P-selectin in AP and of the rationale for a therapeutic blockade.Take home message: P-selectin is a glycoprotein that mediates the adhesion of activated platelets and leukocytes to the vessel wall in various inflammatory conditions. Both pathophysiological steps are closely linked and play a key role in the course of severe AP. A treatment approach by inhibition of P-selectin could be of distinct interest as a therapeutic option in severe AP.