Extent Of Pancreatic Necrosis Research Articles

Early detection of necrosis in low-enhanced pancreatic parenchyma using contrast-enhanced computed tomography was a better predictor of clinical outcomes than pancreatic inflammation: A multicentric cohort study of severe acute pancreatitis

ObjectivesWe aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis. MethodsPost-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis. ResultsIn total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59–0.70]; p < 0.001). In multivariable analysis, necrosis 30–50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01–4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04–7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity. ConclusionsThe degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation.

Laparoscopic necrosectomy for acute necrotizing pancreatitis: mesocolon-preserving approach and outcomes.

The surgical treatment of acute necrotizing pancreatitis has significantly evolved in recent years with the advent of enhanced imaging techniques and minimally invasive surgery. Various minimally invasive techniques, such as video-assisted retroperitoneal debridement (VARD) and endoscopic transmural necrosectomy (ETN), have been employed in the management of acute necrotizing pancreatitis and are often part of step-up approaches. However, almost all reported step-up approaches only employ a fixed minimally invasive technique prior to open surgery. In contrast, we implemented different minimally invasive techniques during the treatment of acute pancreatitis based on the extent of pancreatic necrosis. For acute necrotizing pancreatitis of the pancreatic bed with or without extension into the left retroperitoneum, we performed mesocolon-preserving laparoscopic necrosectomy for debridment. The quantitative indication for pancreatic debridment in our institute has been described previously. For acute necrotizing pancreatitis of the pancreatic bed with or without extension into the left retroperitoneum, mesocolon-preserving laparoscopic necrosectomy was performed for debridment. To safeguard the mesocolon, the pancreatic bed was entered via the gastrocolic ligament, and the left retroperitoneum was accessed via the lateral peritoneal attachments of the descending colon. Of the 77 patients requiring pancreatic debridment, 41 patients were deemed suitable for mesocolon-preserving laparoscopic necrosectomy by multiple disciplinary team and informed consent was acquired. Of these 41 patients, 27 underwent percutaneous drainage, 10 underwent transluminal drainage, and 2 underwent transluminal necrosectomy prior to laparoscopic necrosectomy. Two patients (4.88%) died of sepsis, three patients (7.32%) required further laparotomic necrosectomy, and five patients (12.20%) required additional percutaneous drainage for residual infection. Three patients (7.32%) experienced duodenal fistula, all of which were cured through non-surgical treatments. Nineteen patients (46.34%) developed pancreatic fistula that persisted for over 3weeks, with 17 being successfully treated non-surgically. The remaining two patients had pancreatic fistulas that lasted over 3months; an internal drainage procedure has been planned for them. No patient developed colonic fistula. Mesocolon-preserving laparoscopic necrosectomy proved to be safe and effective in selected patients. It can serve as a supplementary procedure for step-up approaches or as an alternative to other debridment procedures such as VARD, ETN, and laparotomic necrosectomy.

A selective anticoagulation policy for splanchnic vein thrombosis in acute pancreatitis is associated with favourable outcomes: experience from a UK tertiary referral centre.

There is a paucity of data on the incidence, risk factors, and treatment of splanchnic vein thrombosis (SVT) in acute pancreatitis (AP). All AP admissions between 2018 and 2021 across North East of England were included. Anticoagulation was considered in the presence of superior mesenteric vein/portal vein (SMV/PV) thrombus or progressive splenic vein thrombus (SpVT). The impact of such a selective anticoagulation policy, on vein recanalisation rates and bleeding complications were explored. 401 patients (median age 58) were admitted with AP. 109 patients (27.2%) developed SVT. The splenic vein in isolation was the most common site (n=46) followed by SMV/PV (n=36) and combined SMV/PV and SpVT (n=27). On multivariate logistic regression alcohol aetiology (OR 2.64, 95% CI [1.43-5.01]) and >50% necrosis of the pancreas (OR 14.6, 95% CI [1.43-383.9]) increased the risk of developing SVT. The rate of recanalization with anticoagulation was higher for PVT (66.7%; 42/63) than in SpVT (2/11; p=0.003). 5/74 of anticoagulated patients developed bleeding complications while 0/35 patients not anticoagulated had bleeding complications (p=0.4). The risk of SVT increases with AP severity and with extent of pancreatic necrosis. A selective anticoagulation policy for PVT and progressive SpVT in AP is associated with favourable outcomes with no increased risk of bleeding complications.

AXL and MERTK receptor tyrosine kinases inhibition protects against pancreatic necrosis via selectively limiting CXCL2-related neutrophil infiltration

BackgroundAcute pancreatitis (AP) was initiated within pancreatic parenchymal cells and sustained by uncontrolled inflammatory responses. AXL and MERTK receptor tyrosine kinases play a crucial role in negatively regulating the innate immunity. Therefore, this study aimed to investigate the role and underlying mechanism of AXL and MERTK in AP. MethodsExperimental AP was induced by ten hourly intraperitoneal administration of caerulein in global, hematopoietic- and pancreas-specific Axl and Mertk deficient mice. Pancreatitis severity was assessed biochemically and histologically. Pancreatic transcriptomics and pancreatic infiltrating immune cells were profiled. Some mice were given R428, an antagonist of AXL and MERTK. AXL and MERTK in peripheral leukocytes were measured by flow cytometry. FindingsThe levels of AXL and MERTK in pancreatic tissue and pancreatic CD45+ cells were dynamically altered at 6 h and 12 h after the 1st injection of caerulein. Global and hematopoietic-specific, but not pancreas-specific deletion of Axl and Mertk protected against pancreatic necrosis and trypsinogen activation. Pancreatic transcriptomic analysis revealed that differentially expressed gene signatures were mainly related to metabolic and inflammatory pathways. Furthermore, deletion or inhibition of Axl and Mertk selectively inhibited pancreatic neutrophil infiltration, which was primarily related to CXCL2 secreted by pro-inflammatory macrophages. Increased levels of MERTK in peripheral leukocytes were correlated with more severe form of AP. InterpretationOur findings reveal that specific AXL/MERTK antagonist may be a novel and potential early treatment for AP and the levels of MERTK in peripheral leukocytes may be a promising biomarker for predicting pancreatic severity in patients with AP. FundingNational Natural Science Foundation of China, Shanghai Natural Science Foundation, a Shanghai Young Talent Award and a Shanghai Young Orient Scholar Award. Research in contextEvidence before this studyAcute pancreatitis (AP) is a common inflammatory disorder of the exocrine pancreas, the severity of which was determined by the extent of pancreatic necrosis, with no targeted therapy. AP was initiated by signals within pancreatic parenchymal cells and sustained by uncontrolled innate immune responses. One of the three crucial regulatory roles for AXL and MERTK is to negatively regulate innate immune responses.Added value of this studyGlobal and hematopoietic-, but not pancreas-specific Axl and Mertk deficiency protected against pancreatitis, primarily pancreatic necrosis. Deletion of Axl and Mertk selectively inhibited pancreatic neutrophil infiltration that was related to CXCL2 secreted by pro-inflammatory macrophages. AXL and MERTK antagonist similarly reduced pancreatitis severity via limiting CXCL2-mediated pancreatic neutrophil infiltration. Higher levels of MERTK, but not AXL in peripheral leukocytes were correlated with more severe form of acute pancreatitis.Implications of all the available evidenceA specific AXL/MERTK antagonist may be a novel and potential early treatment for AP. The level of MERTK on peripheral leukocytes may be a promising biomarker for predicting disease severity in patients with AP.

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

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

Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study

Introduction. Patients could develop endocrine and exocrine pancreatic insufficiency after acute pancreatitis (AP), but the morbidity, risk factors and outcome remain unclear. The aim of the present study was to evaluate the incidence of endocrine and exocrine pancreatic insufficiency after AP and the risk factors of endocrine pancreatic insufficiency through a long-term follow-up investigation.&#x0D; Methods. Follow-up assessment of the endocrine and exocrine function was conducted for the discharged patients with AP episodes. Oral Glucose Tolerance Test (OGTT) and faecal elastase-1(FE-1) test were used as primary parameters. Fasting blood-glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin HBA1c, 2-h postprandial blood glucose (2hPG), Homa beta cell function index (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR) and FE-1 were collected. Abdominal contrast-enhanced computed tomography (CECT) was performed to investigate the pancreatic morphology and the other related data during hospitalization was also collected.&#x0D; Results. One hundred thirteen patients were included in this study and 34 of whom (30.1%) developed diabetes mellitus (DM), 33 (29.2%) suffered impaired glucose tolerance (IGT). Moreover, 33 patients (29.2%) developed mild to moderate exocrine pancreatic insufficiency with 100μg/g&lt;FE-1&lt;200μg/g and 7 patients (6.2%) were diagnosed with severe exocrine pancreatic insufficiency with FE-1&lt;100μg/g. The morbidity of DM and IGT in patients with pancreatic necrosis was significant higher than that in the non-pancreatic necrosis group (χ2 = 13.442,P = 0.001). The multiple logistic regression analysis showed that extent of pancreatic necrosis&lt;30% (P = 0.012, OR = 0.061) were the protective factors of endocrine pancreatic insufficiency. HOMA-IR (P = 0.002, OR = 6.626), Wall-off necrosis (WON) (P = 0.013, OR = 184.772) were the risk factors.&#x0D; Conclusion. The integrated morbidity of DM and IGT after AP was 59.25%, which was higher than exocrine pancreatic insufficiency. 6.2% and 29.2% of patients developed severe and mild to moderate exocrine pancreatic insufficiency, respectively. The extent of pancreatic necrosis&gt;50%, WON and insulin resistance were the independent risk factors of new onset diabetes after AP.

Comparative assessment of different methods of surgical treatment of nonbiliary necrotizing pancreatitis

Over the last decade, the issue of treatment of acute necrotizing pancreatitis has been requiring special attention because of the growth of this pathology worldwide and high mortality from it, especially with extended infected types of the disease. The aim of the research was to improve results of treatment of patients with nonbiliary necrotizing pancreatitis by optimizing of the surgical tactics, which depend on the extent of necrosis in the pancreas and peripancreatic fat. Materials and methods . The study analyzed results of treatment of 220 patients with acute nonbiliary necrotizing pancreatitis, who were hospitalized in the clinic from 2014 to 2016. The age of the patients ranged from 18 to 80 years, including patients under the age of 50, who accounted for 54 %. Comparison of qualitative features was carried out through analysis of conjugacy tables, using the χ² Pearson criterion (Pearson Chi-square). For four-field tables (for 1 degree of freedom), the Yates's correction was used. When comparing the groups, the level of statistical significance (P) was calculated. At P < 0.05, the differences were considered statistically significant. Results. The research argues that mortality depends not only on the extent of pancreatic necrosis, but also on the choice of method of surgical intervention. Use of puncture-draining operations under ultrasound control and lumbotomy made it possible to reduce postoperative mortality from lesser sac abscess from 6.5 % to 3.9 %, from retroperitoneal phlegmon – from 31.6 % to 15.8 %, and from their combination – from 60 % to 33.3 %. In cases of diffuse purulent peritonitis, mortality from laparostomy combined with the programmed sanitation of the abdominal cavity was 40 %; it included cases when carbapenem antibiotics (imipenem/cilastatin, and meropenem) were used in the complex treatment, accounting for 33.3 %, and cases of implementing laparostomy, sanitation, and drainage of the abdominal cavity, making 50 %. Conclusions. The more extensive use of puncture-draining operations under ultrasound control and lumbotomy, as well as laparostomy in combination with the programmed sanitation of the abdominal cavity, allowed to reduce mortality from 26.1 % to 12.1 %.

Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study

BackgroundPatients could develop endocrine and exocrine pancreatic insufficiency after acute pancreatitis (AP), but the morbidity, risk factors and outcome remain unclear. The aim of the present study was to evaluate the incidence of endocrine and exocrine pancreatic insufficiency after AP and the risk factors of endocrine pancreatic insufficiency through a long-term follow-up investigation.MethodsFollow-up assessment of the endocrine and exocrine function was conducted for the discharged patients with AP episodes. Oral Glucose Tolerance Test (OGTT) and faecal elastase-1(FE-1) test were used as primary parameters. Fasting blood-glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin HBA1c, 2-h postprandial blood glucose (2hPG), Homa beta cell function index (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR) and FE-1 were collected. Abdominal contrast-enhanced computed tomography (CECT) was performed to investigate the pancreatic morphology and the other related data during hospitalization was also collected.ResultsOne hundred thirteen patients were included in this study and 34 of whom (30.1%) developed diabetes mellitus (DM), 33 (29.2%) suffered impaired glucose tolerance (IGT). Moreover, 33 patients (29.2%) developed mild to moderate exocrine pancreatic insufficiency with 100μg/g<FE-1<200μg/g and 7 patients (6.2%) were diagnosed with severe exocrine pancreatic insufficiency with FE-1<100μg/g. The morbidity of DM and IGT in patients with pancreatic necrosis was significant higher than that in the non-pancreatic necrosis group (X2 = 13.442,P = 0.001). The multiple logistic regression analysis showed that extent of pancreatic necrosis<30% (P = 0.012, OR = 0.061) were the protective factors of endocrine pancreatic insufficiency. HOMA-IR (P = 0.002, OR = 6.626), Wall-off necrosis (WON) (P = 0.013, OR = 184.772) were the risk factors.ConclusionThe integrated morbidity of DM and IGT after AP was 59.25%, which was higher than exocrine pancreatic insufficiency. 6.2% and 29.2% of patients developed severe and mild to moderate exocrine pancreatic insufficiency, respectively. The extent of pancreatic necrosis>50%, WON and insulin resistance were the independent risk factors of new onset diabetes after AP.

Endothelial markers are associated with pancreatic necrosis and overall prognosis in acute pancreatitis: A preliminary cohort study

BackgroundEndothelial injury is believed to play an important role in the evolution of pancreatic microcirculatory dysfunction and pancreatic necrosis (PN) in patients with acute pancreatitis (AP). The aim of this study was to investigate the role of three endothelial markers (von Willebrand factor, vWF; E-selectin; endothelial protein C receptor, EPCR) in the early phase of AP, especially the relationship between endothelial markers and PN. MethodsFrom March 2015 to March 2016, 57 AP patients admitted within 72 h of symptom onset in our hospital were included for this study. Blood samples were taken on admission and the clinical characteristics and outcomes of these patients were recorded. The levels of vWF, E-selectin and EPCR were measured using ELISA for analysis and compared with other severity markers of AP. ResultsAll the three markers were significantly different in healthy control, mild, moderate and severe AP patients. Moreover, the endothelial markers, especially vWF, also showed significant difference in patients with different extent of PN, as well as those with or without MODS. Additionally, the levels of endothelial markers correlated well with other commonly used markers of AP severity. ConclusionElevated endothelium-related mediators (vWF, E-selectin and EPCR) appear to participate in the development of PN and may be a potential indicator of overall prognosis. Our results may help clinicians better understand the pathophysiological process of the development of PN.

Acute pancreatitis.

To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

Portosplenomesenteric Venous Thrombosis in Patients With Acute Pancreatitis Is Associated With Pancreatic Necrosis and Usually Has a Benign Course

Although there are some data on prevalence of portosplenomesenteric venous thrombosis (PSMVT) in patients with acute pancreatitis (AP), the progression of PSMVT in patients who have and have not received anticoagulants has not been studied systematically. We evaluated the prevalence and natural history of PSMVT in a well-defined cohort of individuals with AP. In a retrospective study, we analyzed data from the University of Pittsburgh Medical Center on 162 patients with a sentinel attack of AP from 2003-2010. Data were collected on patient demographics, clinical presentation, etiology, clinical course, and outcomes. One hundred twenty-two patients underwent contrast-enhanced computed tomography; the scans were reviewed to identify thromboses and/or narrowing of splanchnic veins (splenic, superior mesenteric, and portal). PSMVT was detected in 22 patients overall (14%; 18% among patients who underwent contrast-enhanced computed tomography). Median time to detection of PSMVT was 17 days (interquartile range, 11-40 days). PSMVT formed most frequently in the splenic vein (19 of 22, 86%), followed by portal (8 of 22, 36%) and superior mesenteric (6/22, 27%) veins. Development of PSMVT was associated with presence (21 of 22, 95%), location, and extent of pancreatic necrosis. Fifty-three percent of patients (21 of 40) with necrosis developed PSMVT. Anticoagulants were administered infrequently (6 of 22, 27%) and always for indications unrelated to PSMVT. Most patients with PSMVT developed collateral veins (19 of 22, 86%), and 27% (6 of 22) were found to have varices during endoscopic evaluation, but clot resolution was infrequent (2 of 22, 9%). No patient developed complications directly related to PSMVT. PSMVT develops in about half of patients with necrotizing AP and is rare in the absence of necrosis. Despite infrequent administration of anticoagulants, complications directly related to PSMVT are rare.

Maximum Extent of Pancreatic Necrosis and Not Site of Necrosis Guide the Therapeutic Modality in Severe Acute Pancreatitis

Maximum Extent of Pancreatic Necrosis and Not Site of Necrosis Guide the Therapeutic Modality in Severe Acute Pancreatitis

Changes in blood polyamine levels in human acute pancreatitis

Objective. Experimental studies have shown that pancreatic activation of polyamine catabolism occurs during the early stage of acute pancreatitis. Changes in pancreatic polyamines are reflected in the red blood cell (RBC) polyamine contents, correlating with the extent of pancreatic necrosis. The aim of this human study was to examine the changes in polyamine levels in the RBCs of patients with acute pancreatitis. Material and methods. Twenty-four patients with acute pancreatitis (7 alcoholic, 10 gallstone and 7 of unknown etiology) were recruited in the study. Eighteen patients with non-pancreatic acute abdominal diseases were included as controls, and 6 volunteers were studied as references. Blood samples were collected on admission and during hospitalization to assess polyamine levels. After clinical recovery, the patients revisited the clinic, and RBC polyamine levels were measured again. For comparison, plasma interleukin-6 (IL-6), IL-10 and C-reactive protein (CRP) were measured. Results. In acute pancreatitis patients, there was no difference in RBC polyamine levels on admission compared with those in controls or in volunteers. Putrescine levels on admission were higher in patients with pancreatic necrosis than in patients without necrosis, but there was no difference in spermidine and spermine levels. Patients with pancreatitis of unknown etiology had significantly higher levels of polyamines on admission and throughout hospitalization, but they also had more necrosis, which explained the difference in multivariate analysis. Spermidine and spermine levels increased after clinical recovery. RBC putrescine correlated with IL-6 and IL-10, and spermine correlated with CRP. Conclusions. The results of this study suggest that RBC polyamines change in human acute pancreatitis in several respects, as has been previously observed in experimental pancreatitis.

Free serum DNA is an early predictor of severity in acute pancreatitis

Objectives Cell-free DNA has been investigated as a diagnostic marker in many diseases, including acute conditions. Our hypothesis was that in acute pancreatitis free serum DNA correlates with the extent of pancreatic necrosis and that it may be an early marker of severity. Design and methods Free DNA was measured in sera from 30 patients with acute pancreatitis at admission, on the first, fourth and seventh day following admission. Results On the first day following admission patients who would develop severe pancreatitis had significantly higher serum DNA levels than those with mild disease (median 0.271 ng/μL vs. 0.059 ng/μL respectively; P < 0.001). This parameter showed very good characteristics as a potential severity predictor (area under ROC curve 0.97). Free serum DNA was in correlation with the extent of pancreatic necrosis. Conclusions Free serum DNA correlates with the extent of pancreatic necrosis and is a potential early marker of severe acute pancreatitis.

The Impact of Hospital-Acquired Infection on Outcome in Acute Pancreatitis

Little is known regarding the impact of hospital-acquired infection (HAI) in acute pancreatitis (AP). We conducted a population-based assessment of the impact of HAI on outcome in AP. Patient data were obtained from the Cardinal Health Clinical Outcomes Research Database, a large population-based data set. Cases with principal diagnosis by International Classification of Diseases, ninth revision, clinical modification 577.0 (AP) between January 2004 and January 2005 were identified. These cases were linked with recently reported HAI data collected by the Pennsylvania Health Care Cost Containment Council. Identification of HAI was based on definitions set forth by the National Nosocomial Infection Surveillance System. We conducted a 5:1 multivariate propensity-matched cohort study to determine the independent contribution of HAI to in-hospital mortality, length of stay (LOS), and hospital charges. From 177 participating hospitals, there were 11,046 AP cases identified. Eighty-two (0.7%) patients developed an HAI. Mortality in the overall AP population was 1.2% vs 11.4% among 405 matched non-HAI controls vs 28.4% among patients who developed HAI (chi(2) test, P < .0001). Fifteen percent of all deaths was associated with an HAI. Both average LOS and hospital charges were significantly increased among patients with HAI compared with matched non-HAI controls. We determined that HAI had a major impact on mortality in AP. Patients who developed HAI also had significantly increased LOS and hospital charges. These differences were not explained by increased disease severity alone. Reducing HAI is an important step to improving outcome in AP.

Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis

To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP). SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20 ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n=21) received no treatment after the SAP model was established; group B (n=20) was given IL-4 (8 microg/animal) intraperitoneally 0.5 h before the SAP model was established; group C (n=20) was given IL-4 (8 microg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r= -0.748, -0.827, -0.723; P<0.01). In the second series of experiments, no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model (P<0.01, P<0.05), but the expression of MCP was not influenced (P>0.05). The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model (P<0.05), but the expression of CD59 and MCP did not change (P>0.05). Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.

Diagnosis, assessment of severity and management of acute pancreatitis

Severe pancreatitis occurs in 20%?30% of all patients with acute pancreatitis. Pancreatic enzymes, cytokines and other active peptides, liberated from the inflamed pancreas, convert inflammation of the pancreas as a single-organ disease of the retroperitoneum to a multisystem disease. Determinations of pancreatic serum enzymes are still ?the golden standard? for diagnosis of the acute pancreatitis. Out of clinically significant pancreatic enzymes, pancreatic-amylase and lipase are suggested for routine clinical determination due to available methods for their measurement. The methods are simple, and the results may be obtained rather quickly without any special equipment. Maximal diagnostic accuracy is achieved by ?cut-off? values of 182 U/L for pancreatic-amylase and 656 U/L for lipase. Treatment of patients with acute pancreatitis is based on the initial assessment of disease severity. Early staging is based on the presence and degree of systemic failure (cardiovascular, pulmonary, and renal) and on the presence and extent of pancreatic necrosis. Individual clinical parameters and laboratory biomarkers, although sometimes helpful, are not sufficiently accurate to reliable assess the severity of an acute attack. Numeric grading systems with sensitivities of about 70% are commonly used today as indicators of organ failure and disease severity. Contrast material-enhanced computed tomography is used in addition to help evaluate local pancreatic morphology and the presence and extent of pancreatic necrosis. Out of all recently studied biochemical parameters for prognostic evaluation of acute pancreatitis patients, the measurement of C-reactive protein concentration appeared to be the parameter with the highest clinical accuracy. The best differentiation of moderate from severe acute pancreatitis forms is achieved by ?cut-off? CRP values of 126 mg/L, 48 hours from the onset of symptoms. For this reason, CRP measurement may be used as the alternative to computerized tomography. In compliance with the postulations for evidence- based medicine, the procedures related to diagnosis, prognosis and management of acute pancreatitis are classified into four categories: certain, probable, possible and inappropriate.

Acute pancreatitis in dogs

AbstractObjective:To summarize current information regarding severity assessment, diagnostic imaging, and treatment of human and canine acute pancreatitis (AP).Human‐based studies:In humans, scoring systems, advanced imaging methods, and serum markers are used to assess the severity of disease, which allows for optimization of patient management. The extent of pancreatic necrosis and the presence of infected pancreatic necrosis are the most important factors determining the development of multiple organ failure (MOF) and subsequent mortality. Considerable research efforts have focused on the development of inexpensive, easy, and reliable laboratory markers to assess disease severity as early as possible in the course of the disease. The use of prophylactic antibiotics, enteral nutrition, and surgery have been shown to be beneficial in certain patient populations.Veterinary‐based studies:The majority of what is currently known about naturally occurring canine AP has been derived from retrospective evaluations. The identification and development of inexpensive and reliable detection kits of key laboratory markers in dogs with AP could dramatically improve our ability to prognosticate and identify patient populations likely to benefit from treatment interventions. Treatment remains largely supportive and future studies evaluating the efficacy of surgery, nutritional support and other treatment modalities are warranted.Data sources:Current human and veterinary literature.Conclusions:Pancreatitis can lead to a life‐threatening severe systemic inflammatory condition, resulting in MOF and death in both humans and dogs. Given the similarities in the pathophysiology of AP in both humans and dogs, novel concepts used to assess severity and treat people with AP may be applicable to dogs.

A Prospective Evaluation of Pancreatic Exocrine Function in Patients with Acute Pancreatitis: Correlation with Extent of Necrosis and Pancreatic Endocrine Insufficiency

Aims: The aim of this prospective study was to assess pancreatic exocrine function in patients recovering from a first attack of acute pancreatitis, and to evaluate its relationship to severity of attack, extent of pancreatic necrosis and severity of pancreatic endocrine insufficiency. Methods: Between December 2000 and November 2001, 23 patients were prospectively evaluated. Pancreatic exocrine function was measured by the faecal elastase-1 test and insufficiency was classified as moderately impaired or severely impaired. Pancreatic necrosis was determined by contrast-enhanced CT scan, and its extent was categorised according to Balthazar’s classification. The severity of pancreatic endocrine insufficiency was categorised according to insulin dependence. Attacks were classified as mild (n = 16) or severe (n = 7) according to the Atlanta criteria. Results: Pancreatic exocrine insufficiency was significantly more frequent in patients recovering from severe attacks than mild (n = 6, 86% vs. n = 2, 13%; p = 0.002), and in those who developed pancreatic necrosis or pseudocyst than those who did not (6 of 7 patients vs. 2 of 16 patients, and 5 of 5 patients vs. 3 of 18 patients respectively; p = 0.002). The development of exocrine insufficiency correlated strongly with the extent of pancreatic necrosis (r = –0.754, p < 0.001), and the severity of pancreatic endocrine insufficiency (n = 4, r = –0.453, p = 0.03). Conclusion: Pancreatic exocrine insufficiency is a common occurrence in patients recovering from severe acute pancreatitis, and its severity correlates with the extent of pancreatic necrosis and the severity of concomitant pancreatic endocrine insufficiency.

Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis.

The risk factors predisposing to organ failure in patients with necrotizing pancreatitis remain unclear. The relationship between the extent of pancreatic necrosis, the presence of infection and the incidence of organ failure was analysed. In a retrospective review, the occurrence of pulmonary insufficiency, renal insufficiency, shock, sepsis/sepsis-like syndrome (SLS) and coagulopathy was evaluated in 273 patients with necrotizing pancreatitis, and a comparison was made between patients with sterile or infected necrosis. Additionally, the relation between the incidence of organ failure and extent of pancreatic parenchymal necrosis was investigated by classifying the patients into three groups according to the amount of necrotic tissue found by contrast-enhanced computed tomography (group 1, extent less than 30 per cent; group 2, 30-50 per cent; group 3, more than 50 per cent). Organ failure was more frequent in patients with infected necrosis than in those with sterile necrosis. Differences were found in the incidence of pulmonary insufficiency, sepsis/SLS and coagulopathy. Organ failure occurred more frequently in group 3 than in group 2 or 1 (95 versus 79 and 66 per cent; P = 0.0004). The extent of infected necrosis was not related to the incidence of organ failure (group 1, 88 per cent; group 2, 86 per cent; group 3, 96 per cent). However, there was a relation between the incidence of organ failure and the extent of sterile necrosis (group 1, 59 per cent; group 2, 74 per cent; group 3, 94 per cent; P = 0.0001). Multivariate analysis confirmed the presence of infection and the extent of necrosis as independent determinants of organ failure. The incidence of organ failure is determined by both bacterial infection and extent of necrosis. The incidence of organ failure is determined by the extent of necrotic parenchyma in patients with sterile necrosis. Infected necrosis is associated with a high incidence of organ failure irrespective of the extent of necrosis.