GC-MS based metabolomics strategy to distinguish three types of acute pancreatitis.

Acute pancreatitis (AP) is a progressive systemic inflammatory response with high morbidity and high mortality, which is mainly caused by alcohol, bulimia, gallstones and hyperlipidemia. The early diagnosis of different types of AP and further explore potential pathophysiological mechanism of each type of AP is beneficial for optimized treatment strategies and better patient's care. In this study, a metabolomics approach based on gas chromatography-mass spectrometry (GC-MS), and random forests algorithm was established to distinguish biliary acute pancreatitis (BAP), Hyperlipidemia acute pancreatitis (HLAP), and alcoholic acute pancreatitis (AAP), from healthy controls. The classification accuracies for BAP, HLAP, and AAP patients compared with healthy control, were 0.886, 0.906 and 0.857, respectively, by using 5-fold cross-validation method. And some special metabolites for each type of AP were discovered, such as l-Lactic acid, (R)-3-Hydroxybutyric acid, Phosphoric acid, Glycine, Erythronic acid, l-Phenylalanine, d-Galactose, l-Tyrosine, Arachidonic acid, Glycerol 1-hexadecanoate. Furthermore, associations between these metabolites with the metabolism of amino acids, fatty acids were identified. Our studies have illuminated the biomarkers and physiological mechanism of disease in a clinical setting, which suggested that metabolomics is a valuable tool for identifying the molecular mechanisms that are involved in the etiology of BAP, AAP, HLAP and thus novel therapeutic targets.

Significantly different clinical features between hypertriglyceridemia and biliary acute pancreatitis: a retrospective study of 730 patients from a tertiary center.

BACKGROUND: Unlike western world, gallstones and hypertriglyceridemia (HTG) are among the first two etiologies of acute pancreatitis (AP) in China. But yet, detailed differences in clinical features and outcomes between hypertriglyceridemia and biliary acute pancreatitis have not been well described. METHODS: This retrospective study enrolled 730 acute pancreatitis patients from July 1, 2013 to October 1, 2016 in Jinling Hospital. The causes of the study patients were defined according to specific diagnostic criteria. The clinical features and outcomes of patients with hypertriglyceridemia acute pancreatitis (HTG-AP) and biliary acute pancreatitis (BAP) were compared in terms of general information, disease severity, laboratory data, system complications, local complications, and clinical outcome. RESULTS: In the enrolled 730 AP patients, 305 (41.8%) were HTG-AP, and 425 (58.2%) were BAP. Compared to BAP, the HTG-AP patients were found to be younger, with higher body mass Index (BMI), and much higher proportion of diabetes, fatty liver and high fat diet. Besides that, HTG-AP patients had significantly higher C-reactive protein (CRP) (p<0.01) and creatinine (p = 0.031), together with more acute respiratory distress syndrome (ARDS) (p = 0.039), acute kidney injury (AKI) (p<0.001), deep venous thrombosis (p = 0.008) and multiple organ dysfunction syndrome (MODS) (p = 0.032) in systematic complications. As for local complications, HTG-AP patients had significantly less infected pancreatitis necrosis (p = 0.005). However, there was no difference in mortality, hospital duration and costs between the groups. CONCLUSION: HTG-AP patients were younger, more male, having high fat diet and with higher BMI compared to BAP patients. The prevalence of AKI/ARDS/DVT/MODS in HTG-AP patients was higher than BAP patients, while BAP patients had a greater possibility in development of infected pancreatitis necrosis (IPN). According to the multivariate analysis, only the complication of AKI was independently related with the etiology of HTG, however, BMI contributes to AKI, ARDS and DVT.

The Diagnostic Usefulness of Serum Total Bile Acid Concentrations in the Early Phase of Acute Pancreatitis of Varied Etiologies.

The most common causes of acute pancreatitis (AP) are biliary tract diseases with cholestasis and alcohol consumption. In 10%-15% of patients, etiology determination is difficult. Identification of the etiology allows for the implementation of adequate treatment. The aim of this study was to assess the utility of the serum concentrations of total bile acids (TBA) to diagnose AP etiology in the early phase of the disease. We included 66 patients with AP, admitted within the first 24 h from the onset of symptoms. TBA were measured in serum at 24, 48, and 72 h from the onset of AP, using an automated fifth generation assay. The bilirubin-to-TBA ratio (B/TBA) was calculated. TBA was highest on the first day of AP and decreased subsequently. In patients with biliary etiology, serum TBA was significantly higher compared to those with alcoholic and other etiologies. B/TBA was significantly higher in patients with alcoholic etiology. At admission, the cut-off values of 4.7 µmol/L for TBA and 4.22 for the B/TBA ratio allowed for a differentiation between biliary and other etiologies of AP with a diagnostic accuracy of 85 and 83%. Both TBA and B/TBA may help in the diagnosis of AP etiology in the early phase of AP.

Yinchenhao Decoction Protects Against Acute Liver Injury in Mice With Biliary Acute Pancreatitis by Regulating the Gut Microflora-Bile Acids-Liver Axis.

Background and Aims: Acute liver injury (ALI) often follows biliary acute pancreatitis (BAP), but the exact cause and effective treatment are unknown. The aim of this study was to investigate the role of the gut microflora-bile acids-liver axis in BAP-ALI in mice and to assess the potential therapeutic effects of Yinchenhao decoction (YCHD), a traditional Chinese herbal medicine formula, on BAP-ALI. Methods: Male C57BL/6 mice were allocated into three groups: negative control (NC), BAP model, and YCHD treatment groups. The severity of BAP-ALI, intrahepatic bile acid levels, and the gut microbiota were assessed 24 h after BAP-ALI induction in mice. Results: Our findings demonstrated that treatment with YCHD significantly ameliorated the severity of BAP-ALI, as evidenced by the mitigation of hepatic histopathological changes and a reduction in liver serum enzyme levels. Moreover, YCHD alleviated intrahepatic cholestasis and modified the composition of bile acids, as indicated by a notable increase in conjugated bile acids. Additionally, 16S rDNA sequencing analysis of the gut microbiome revealed distinct alterations in the richness and composition of the microbiome in BAP-ALI mice compared to those in control mice. YCHD treatment effectively improved the intestinal flora disorders induced by BAP-ALI. Spearman's correlation analysis revealed a significant association between the distinct compositional characteristics of the intestinal microbiota and the intrahepatic bile acid concentration. Conclusions: These findings imply a potential link between gut microbiota dysbiosis and intrahepatic cholestasis in BAP-ALI mice and suggest that YCHD treatment may confer protection against BAP-ALI via the gut microflora-bile acids-liver axis.

Invalidity of Tokyo guidelines in acute biliary pancreatitis: A multicenter cohort analysis of 944 pancreatitis cases.

BACKGROUND: There is a noteworthy overlap between the clinical picture of biliary acute pancreatitis (AP) and the 2018 Tokyo guidelines currently used for the diagnosis of cholangitis (AC) and cholecystitis (CC). This can lead to significant antibiotic and endoscopic retrograde cholangiopancreatography (ERCP) overuse. OBJECTIVES: We aimed to assess the on-admission prevalence of AC/CC according to the 2018 Tokyo guidelines (TG18) in a cohort of biliary AP patients, and its association with antibiotic use, ERCP and clinically relevant endpoints. METHODS: We conducted a secondary analysis of the Hungarian Pancreatic Study Group's prospective multicenter registry of 2195 AP cases. We grouped and compared biliary cases (n = 944) based on the on-admission fulfillment of definite AC/CC according to TG18. Aside from antibiotic use, we evaluated mortality, AC/CC/AP severity, ERCP performance and length of hospitalization. We also conducted a literature review discussing each criteria of the TG18 in the context of AP. RESULTS: 27.8% of biliary AP cases fulfilled TG18 for both AC and CC, 22.5% for CC only and 20.8% for AC only. Antibiotic use was high (77.4%). About 2/3 of the AC/CC cases were mild, around 10% severe. Mortality was below 1% in mild and moderate AC/CC patients, but considerably higher in severe cases (12.8% and 21.2% in AC and CC). ERCP was performed in 89.3% of AC cases, common bile duct stones were found in 41.1%. CONCLUSION: Around 70% of biliary AP patients fulfilled the TG18 for AC/CC, associated with a high rate of antibiotic use. Mortality in presumed mild or moderate AC/CC is low. Each of the laboratory and clinical criteria are commonly fulfilled in biliary AP, single imaging findings are also unspecific-AP specific diagnostic criteria are needed, as the prevalence of AC/CC are likely greatly overestimated. Randomized trials testing antibiotic use are also warranted.

Readmissions After Biliary Acute Pancreatitis: Analysis of the Nationwide Readmissions Database.

Background: Acute pancreatitis is a common inflammatory condition that involves the pancreas. Gallstones and alcohol are the most common etiologies in the USA. Cholecystectomy is the cornerstone procedure in the management of biliary acute pancreatitis (BAP). In this study, we examined the causes and predictors of readmissions following BAP based on the procedure performed. Methods: Using the Nationwide Readmissions Database (NRD) and the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD10-CM/PCS), we retrospectively studied BAP hospitalizations (2016 - 2018). The first hospitalization within the year was marked as index hospitalization. Index hospitalizations were categorized based on whether an endoscopic retrograde cholangiopancreatography (ERCP) and/or a cholecystectomy was performed into no procedure group, ERCP group, cholecystectomy group, and both procedures group. We subsequently identified readmissions within 30 days. Using this categorization, we studied reasons, rates, and predictors of readmissions. Results: A total of 127,318 index hospitalizations were included. The cholecystectomy group constituted the largest share of this cohort (43.5%). Using the no procedure group as a reference, analysis of the outcomes showed that the cholecystectomy group had the lowest inpatient mortality (adjusted odds ratio (aOR): 0.18, P < 0.001), while both procedures group had the highest total hospital charges (adjusted mean difference (aMD): 42,249, P < 0.001). Acute pancreatitis without necrosis or infection was the most frequent principal diagnosis for readmission (18.7%). Analysis of readmission predictors showed that both procedures group had the lowest risk for readmission (adjusted hazard ratio (aHR): 0.40, P < 0.001). Females were less likely to be readmitted compared to males (aHR: 0.82, P < 0.001) and elderly were less likely to be readmitted compared to young adults (aHR: 0.82, P < 0.001). Patients discharged against medical advice were more likely to be readmitted (aHR: 1.76, P < 0.001). Conclusion: Undergoing both ERCP and cholecystectomy for BAP resulted in significantly higher hospital charges with no additional mortality benefit. However, it decreased the readmission risk significantly. Acute pancreatitis without necrosis or infection was the most frequent reason for readmissions.

The impact of pregnancy on the outcome of biliary acute pancreatitis. / El impacto del embarazo en el desenlace de pancreatitis biliar aguda.

BACKGROUND AND OBJECTIVE: Acute pancreatitis is one of the most common gastrointestinal conditions requiring hospitalization. Even though its presentation during pregnancy is uncommon, it is a medical challenge. Currently, no studies compare the clinical outcomes between pregnant patients with acute pancreatitis and nonpregnant patients with acute pancreatitis. Our aim was to compare the characteristics and clinical outcomes of pregnant and nonpregnant women with acute pancreatitis. METHODS: We conducted a retrospective study that included all patients admitted to our hospital with acute pancreatitis over a 10-year period. Demographics, general characteristics, and clinical outcomes were evaluated and compared between pregnant and nonpregnant women with acute pancreatitis, at a ratio of 1:5. RESULTS: Over 10 years, 27 pregnant patients with acute pancreatitis were treated. Etiology was biliary in 96% and hypertriglyceridemia was the cause in 3.4% (1 patient). The mean patient age was 26.2 years (range 15-36 years). The main cause of acute pancreatitis was biliary disease (96%). Patients in the study group were in their first, second, or third trimester of pregnancy, at 7.4%, 33.3%, and 59.3%, respectively. In the comparison of pregnant versus nonpregnant patients with acute pancreatitis, there were no differences in age, hospital stay (7.37 vs. 10.8, P=.814), severity (severe 3.7% vs. 16.7%, P=.79), local complications (0% vs. 1.9%, P=.476), or mortality (0% vs. 1.9%, P=.476). CONCLUSIONS: The clinical evolution of both groups with biliary acute pancreatitis was similar, with low morbidity and mortality.

Management of biliary acute pancreatitis.

Acute pancreatitis is a frequent pathology with 11,000 to 13,000 new cases per year in France. A biliary origin (30 to 70% of the cases) should be suspected when alanine amino-transferases are elevated during the first 48 hours, and it is confirmed by the presence of gallstones at trans abdominal ultrasound. Abdominal computed-tomography scan is performed around the fifth day, and is repeated according to clinical and biological evolution. Management of acute biliary pancreatitis varies according to its severity, which should be assessed according to systemic inflammatory response syndrome and organ failures. For mild acute pancreatitis, cholecystectomy should be performed during in-hospital stay, before oral feeding. For moderately severe and severe acute pancreatitis, treatment is based on resuscitation, early enteral continuous feeding, and management of complications. Interval cholecystectomy is performed at a later stage. Endoscopic retrograde cholangiopancreatography with sphincterotomy should be performed in emergency when angiocholitis is associated, and in delayed emergency before oral feeding for persistent common bile duct stone. A common bile duct stone should be searched for during cholecystectomy and can be treated during the same surgical procedure if local conditions are adequate. Cholelithiasis is the most frequent cause of acute pancreatitis during pregnancy, and its diagnosis and the treatment have some particularities.

Recurrent biliary acute pancreatitis is frequent in a real-world setting.

BACKGROUND: Data about recurrent acute pancreatitis (RAP) are limited. AIMS: To evaluate the rate of RAP and associated factors. METHODS: Single-centre prospective study of consecutive patients at first episode of acute pancreatitis (AP) being followed-up. RESULTS: Of 266 consecutive AP patients, (47% biliary, 15.4% alcoholic, 14.3% idiopathic) 66 (24.8%) had RAP in a mean follow-up of 42 months; 17.9% of recurrences occurred within 30 days from discharge. Age, gender, smoking and severity of first AP were not associated with RAP risk. The rate of biliary RAP was 31.3% in patients who did not receive any treatment, 18% in those treated with ERCP only, 16% in those who received cholecystectomy only, and 0% in those treated both with surgery and ERCP. Patients with biliary AP who received cholecystectomy had a significantly longer time of recurrence-free survival and reduced recurrence risk (HR = 0.45). In patients with alcoholic AP, the rate of recurrence was lower in those who quit drinking (5.8% vs 33%; p = 0.05). The alcoholic aetiology was associated with a higher risk of having >2 RAP episodes. CONCLUSION: RAP occurs in about 25% of cases, and failure to treat biliary aetiology or quitting drinking is associated with increased recurrence risk.

Antithrombin III and D-dimer levels as indicators of disease severity in patients with hyperlipidaemic or biliary acute pancreatitis.

Objective To assess changes in anticoagulation and fibrinolytic systems between biliary and hyperlipidaemic acute pancreatitis (AP). Methods Patients with biliary or hyperlipidaemic AP were enrolled. Demographic and clinical data were collected, and antithrombin III (ATIII), protein C, protein S, and D-dimer levels were investigated. Results A total of 45 patients with biliary AP and 50 patients with hyperlipidaemic AP were included (68 with mild AP and 27 with moderately-severe AP). ATIII and protein C levels in the mild AP group were significantly higher, but prothrombin time and D-dimer were significantly lower, versus the moderately-severe AP group. ATIII and D-dimer were found to be risk factors for moderately-severe AP. ATIII could predict AP severity, particularly in patients with biliary AP. D-dimer was a sensitive and specific predictor for disease severity in patients with AP, particularly in patients with hyperlipidaemic AP. Conclusion ATIII and protein C levels decreased as severity of AP increased, particularly in cases of biliary AP. D-dimer levels increased with severity of AP, particularly in hyperlipidaemic AP. ATIII and D-dimer may be useful biomarkers for assessing AP severity in patients with biliary and hyperlipidaemic AP, respectively.

Analyzing and identifying risk factors for acute pancreatitis with different etiologies in pregnancy.

OBJECTIVE: To identify the risk factors of acute pancreatitis (AP) associated with different etiologies, in pregnancy (APP). METHODS: Forty-seven eligible patients were divided into two groups: biliary acute pancreatitis in pregnancy (BAPP, n = 31) and hypertriglyceridemic-induced pancreatitis in pregnancy (HAPP, n = 16). Multivariate analysis was utilized in identifying independent risk factors of BAPP and HAPP. RESULTS: The independent risk factors of BAPP included gallbladder stones (OR, 3.924; p = 0.007) and high-fat diet in pregnancy (OR, 4.878; p = 0.001). Hypertriglyceridemia (OR, 3.667; p = 0.035) was the only independent risk factor for HAPP. Based on the severity of AP, no significant differences in adverse outcomes were found between BAPP and HAPP. CONCLUSIONS: High-fat diet should be prohibited for gravida with biliary diseases. Compared to biliary tract stones, the study observed that gallstones were more likely to cause AP for pregnant women. Hypertriglyceridemic pregnant women were found to be more susceptible to AP.

Mean platelet volume in patients with biliary and non-biliary acute pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) is a systemic inflammatory disease. We aimed to detect whether there was a change of mean platelet volume (MPV) level on onset and remission patients with biliary and non-biliary acute pancreatitis. MATERIALS AND METHODS: In our emergency service patients diagnosed with biliary and nonbiliary AP were analyzed retrospectively. Laboratory results measured in onset and remission were recorded and compared. RESULTS: Total number of patients enrolled in our study was 331 (177 female). 194 cases were classified as biliary and 137 were as non-biliary AP. Average age and numbers of female patients of biliary cases were higher than that of nonbiliary cases. Initial MPV values were lower than remission values in all patients with AP. In biliary group initial MPV was 8.42 ± 1.04 and remission value was 8.71 ± 1.12. In nonbiliary group initial MPV was 8.07 ± 1.02 and remission value was 8.4 ± 1.06. In both groups on onset had lower mean MPV levels than those in remission (P = 0.0001 both of them). CONCLUSIONS: MPV values were higher than initial values in remission period in patients both of groups. MPV was lower in non-biliary AP group than biliary AP group that can be an indicator of early-onset infection.

Gallstone pancreatitis: a review.

Gallstone disease is the most common cause of acute pancreatitis in the Western world. In most cases, gallstone pancreatitis is a mild and self-limiting disease, and patients may proceed without complications to cholecystectomy to prevent future recurrence. Severe disease occurs in about 20% of cases and is associated with significant mortality; meticulous management is critical. A thorough understanding of the disease process, diagnosis, severity stratification, and principles of management is essential to the appropriate care of patients presenting with this disease. This article reviews these topics with a focus on surgical management, including appropriate timing and choice of interventions.

Long term outcome of acute pancreatitis in Italy: results of a multicentre study.

BACKGROUND: In Italy, no long-term studies regarding the natural history of acute pancreatitis have been carried out. AIM: To report the results of a follow-up on a large series of patients hospitalised for pancreatitis. METHODS: Data of 631 patients admitted to 35 Italian hospitals were retrospectively evaluated 51.7±8.4 months after discharge. RESULTS: The average recovery time after mild or severe pancreatitis was 28.2 and 53.4 days respectively. Fourteen sequelae were not resolved and 9 cases required late surgical intervention. Eighty patients (12.7%) had a second hospital admission. Of the patients with mild biliary pancreatitis, 67.9% underwent a cholecystectomy. The overall incidence of relapse was 12.7%. Mortality was 9.8% and no death was related to pancreatitis. Three patients died from carcinoma of the pancreas. CONCLUSION: Reported recovery time after an attack of pancreatitis was longer than expected in the mild forms. The treatment of sequelae was delayed beyond one year after discharge. The incidence of relapse of biliary pancreatitis in patients not undergoing a cholecystectomy was low, due to endoscopic treatment. Mortality from pancreatic-related causes is low, but there is an association with malignant pancreatic or ampullary tumours not diagnosed during the acute phase of the illness.