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Objectives: Research on acute pancreatitis (AP) has been ongoing for a long time. It is necessary to summarize and investigate the history of AP research., Methods: Publications related to AP research were retrieved from PubMed. Medical Subject Headings (MeSH) terms, countries, journals, and publication dates were analyzed. Co-occurrence analysis was conducted to illustrate the holistic trend in AP research. A dynamic bar graph, heat maps, and line charts were created to illustrate change trends of MeSH terms., Results: In total, 28,222 publications with 8558 MeSH terms were retrieved from 1941 to 2020. Among these, 16,575 publications with 7228 MeSH terms were from 2001 to 2020. The top 10 MeSH terms showed a considerable change from 1941 to 1970 but remained stable since the 1970s. Four clusters obtained from the co-occurrence analysis were "experiments on animals," "diagnosis and treatment," "prognosis and expectation," and "protein and enzyme." From 1941 to 2020, 33 MeSH terms with increasing trends (MH-I) and 15 MeSH terms with decreasing trends (MH-D) were selected to create a heat map (every decade). Meanwhile, 16 MH-I and 41 MH-D were selected to create the heat map from 2001 to 2020 (every 2 years)., Conclusion: Over the past 80 years, the pathogenesis, treatment, risk management, and experimental model were the main research highlights. Optimal supportive management, minimally invasive treatment, and prediction of prognosis are subjects of interest for clinical practitioners; signal transduction to identify a target for precise treatment is the focus of experimental research in AP., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic duct stenting using endoscopy or surgery is widely used for the management of benign and malignant pancreatic diseases. Endoscopic pancreatic stents are mainly used to relieve pain caused by chronic pancreatitis and pancreas divisum, and to treat pancreatic duct disruption and stenotic pancreaticointestinal anastomosis after surgery. They are also used to prevent postendoscopic retrograde cholangiopancreatography pancreatitis and postoperative pancreatic fistula, treat pancreatic cancer, and locate radiolucent stones. Recent advances in endoscopic techniques, such as endoscopic ultrasonography and balloon enteroscopy, and newly designed stents have broadened the indications for pancreatic duct stenting. In this review we outlined the types, insertion procedures, efficacy, and complications of endoscopic pancreatic duct stent placement, and summarized the applications of pancreatic duct stents in surgery., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Acute pancreatitis (AP) is a common digestive disease encountered in Emergency Departments that carries a heavy socioeconomic burden. This study was conducted to determine the global status of AP research. Articles related to AP published in 1999 to 2018 were retrieved from the Web of Science (WOS) database and the 20 highest-output countries or regions were determined based on the total number of publications. Correlation analysis of AP research output and the gross domestic product (GDP) of each country or region was conducted. The quantity and quality of research of these 20 highest-output countries were compared to the total output, outputs per capita, and average impact factor (IF). All annual data were analyzed using time-trend analysis. A keyword co-occurrence analysis was conducted to determine the highlights in AP research. In total, 17,698 publications were retrieved, and 16,461 papers (93.0%) of them were from the 20 highest-output countries. A significantly positive correlation was identified between AP research output and the GDP (R = 0.973, P < .001). The 5 highest-output countries were the USA (24.9%), China (12.3%), Germany (7.5%), Japan (6.7%), and the UK (6.1%). Finland ranked 1st in the number of publication per capita, the USA had the highest accumulated IF (25,432.758) and total citations (104,592), Switzerland had the highest average IF (6.723), and Netherland had the highest average citations (51.90). Genetic research and AP-related hyperglycemia were research highlights. Analysis of the global output of research of AP research showed signs of growth. Research output was positively correlated with GDP. For the most productive countries, research quality was stable. Although developing countries lagged behind in output per capita and quality, great progress has been made in the past 2 decades., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Whether pancreatic extracorporeal shock wave lithotripsy (ESWL) is safe for patients with autosomal dominant polycystic kidney disease (ADPKD) is unclear. A woman in her early 30s was admitted to our hospital because of intermittent upper abdominal pain and recurrent pancreatitis. The imaging results confirmed the diagnosis of pancreatic stones and ADPKD. We performed pancreatic ESWL using a third-generation lithotripter to pulverize the pancreatic stones. A maximum of 5000 shock waves was delivered per therapeutic session. A second session of ESWL was performed the next day. The patient developed no adverse events or complications related to pancreatic ESWL. Three years after treatment, the patient had developed no relapse of pancreatitis or abdominal pain. Shock waves do not lead to complications such as hematuria, cyst rupture, or deterioration of the inner bleeding of renal cysts. Multiple kidney cysts are not a contraindication for pancreatic ESWL.

Background: Pancreatitis is the most common complication of pancreatic extracorporeal shock wave lithotripsy (ESWL). There has been little research into effective prevention of post-ESWL pancreatitis. Therefore, we aimed to assess the efficacy of prophylactic rectal indometacin in preventing post-ESWL pancreatitis., Methods: In this double-blind, randomised, placebo-controlled trial done at Changhai Hospital (Shanghai, China), patients aged 18 years or older with chronic pancreatitis and pancreatic stones (>5 mm in diameter) who were eligible for treatment with ESWL were randomly allocated using a computer-generated randomisation table, in a 1:1 ratio, to receive 100 mg rectal indometacin or identical glycerin (placebo) suppositories 30 min before ESWL. Patients, endoscopists, and outcome assessors were masked to group allocation. The primary outcome was the incidence of post-ESWL pancreatitis within 24 h of ESWL, analysed by the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02797067., Findings: Between May 31, 2016, and June 26, 2019, 1370 patients were enrolled, with 685 patients randomly assigned to the rectal indometacin group and 685 patients to the placebo group. All patients received their allocated intervention and completed final follow-up, and were included in the intention-to-treat analysis. Post-ESWL pancreatitis occurred in 60 (9%) patients in the rectal indometacin group and 84 (12%) patients in the placebo group (relative risk 0·71, 95% CI 0·52-0·98; p=0·042). Transient adverse events occurred in 235 (34%) patients in the rectal indometacin group and 252 (37%) patients in the placebo group, with asymptomatic hyperamylasaemia being the most common (189 [28%] patients vs 197 [29%] patients). No difference was noted between groups in the incidence of other complications and transient adverse events., Interpretation: Pre-procedural administration of rectal indometacin is an efficacious and safe means of reducing the incidence of post-ESWL pancreatitis., Funding: Programs of Shanghai Municipal Government and the "Ten Thousand Plan"-National High Level Talents Special Support Plan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The carboxyl-ester lipase (CEL) gene contains a variable number of tandem repeats (VNTR) region. It remains unclear whether the number of repeats in the CEL VNTR is related to the risk of pancreatic diseases. The aim of this study was to investigate whether CEL VNTR length is associated with idiopathic chronic pancreatitis (ICP), alcoholic chronic pancreatitis (ACP), or pancreatic cancer in a cohort of Chinese patients., Methods: CEL VNTRs were genotyped in patients diagnosed with ICP (n = 771), ACP (n = 222), or pancreatic cancer (n = 263), and in healthy controls (n = 927). CEL VNTR lengths were determined using a screening method combining PCR and DNA fragment analysis., Results: Overall, the CEL VNTR lengths ranged from 5 to 22 repeats, with the 16-repeat allele ('normal' size, N) accounting for 73.82% of all observed alleles. The VNTR allele frequencies and genotype distributions were not significantly different between healthy controls and patients with ACP or pancreatic cancer. For the ICP group, allele frequencies did not differ significantly from the controls, while the frequency of the SS genotype (homozygosity for 5-15 repeats) was significantly higher in the patients (4.67%) than in the controls (1.94%) (p = 0.0014; OR = 2.47; 95% CI = 1.39-4.39)., Conclusions: There were no associations between the CEL VNTR length and ACP or pancreatic cancer. However, homozygosity for short VNTR lengths may confer susceptibility to ICP., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Over 90% of pancreatic stones are radiopaque and can be treated with endoscopy or surgery. However, radiolucent stones are different than radiopaque stones in nature and formation, and therefore, treatment varies. Case presentation: A 25-year-old woman was admitted because of recurrent acute pancreatitis. Imaging examinations confirmed the diagnosis of chronic pancreatitis (CP), and which revealed the existence of radiolucent stones. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and abundant protein-like radiolucent stones were extracted. Three 10F, 7-cm plastic stents were placed. However, the stents were completely occluded by radiolucent stones 1 month later. A nasopancreatic tube was then inserted and flushed regularly, but protein-like stones formed continuously. After multidisciplinary consultation, the following conservative treatment strategy was applied: 1) no more endotherapy; 2) a diet with 40% to 50% of calories from fat was recommended; 3) no pancreatic enzyme replacement therapy; and 4) regular exercise. The above advice aimed to stimulate the secretion of pancreatic fluid to achieve auto-flushing of the pancreatic duct and prevent protein-like stones from depositing. No acute pancreatitis recurred during the 5-year follow-up., Conclusions: This strategy was effective for auto-flushing the pancreatic duct in patients with radiolucent pancreatic stones after the main pancreatic duct stricture was resolved.

Objectives: This study aimed to investigate the frequency, predictors, and management of relapse of type 1 autoimmune pancreatitis (AIP) after steroid treatment., Methods: One hundred one patients with type 1 AIP receiving steroid as initial treatment were enrolled. Predictors were identified by multivariate analysis using Cox proportional hazards model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated., Results: Thirty-nine (41.1%) patients experienced relapse after steroid treatment during a median follow-up of 40 months. The cumulative rate of relapse reached a plateau at 57.6% (95% CI, 50.3%-64.9%) at 59 months. Without maintenance therapy (HR, 4.53; 95% CI, 1.35-15.17) and proximal bile duct involvement (HR, 2.10; 95% CI, 1.07-4.14) were identified as risk factors. Repeated steroid treatment with the same initial dose but longer induction and tapering duration was given to 87.2% patients with relapse and obtained response (97.1%) during a short-term follow-up (median, 19 months)., Conclusions: Relapses are common in type 1 AIP after steroid treatment. Without maintenance therapy and proximal bile duct involvement were risk factors. Repeated steroid treatment with longer duration is effective for relapse.

Competing Interests: None

Background: Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is the first-line therapy for large pancreatic duct stones. Although it is a highly effective and safe procedure for the fragmentation of pancreatic stones, it is still not complication-free. Just like endoscopic retrograde cholangiopancreatography (ERCP), pancreatitis is the most common complication. To date, nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be the only effective prophylactic medication for post-ERCP pancreatitis and the European, American and Japanese Society for Gastrointestinal Endoscopy guidelines have recommended prophylactic rectally administered indomethacin for all patients undergoing ERCP. Given the little research about effective prevention for post P-ESWL pancreatitis, we aim to determine whether rectally administered indomethacin can reduce post-ESWL-pancreatitis., Methods/design: The RIPEP study is a prospective, randomized, double-blinded, placebo-controlled trial. One thousand three hundred and seventy patients with chronic pancreatitis and pancreatic stones (>5 mm in diameter) treated with P-ESWL at Changhai Hospital will be randomly allocated to rectally administered indomethacin or placebo therapy before the procedure. The primary endpoint is the incidence of post-ESWL pancreatitis. Secondary endpoints include the severity of pancreatitis, occurrence rate of asymptomatic hyperamylasemia and other complications., Discussion: The RIPEP trial is designed to show that rectally administered indomethacin reduces the development and severity of post-ESWL pancreatitis and benefits patients treated with P-ESWL., Trial Registration: ClinicalTrials.gov, ID: NCT02797067 . Registered on 17 November 2016.

Background and Aims: Almost all studies on post-ERCP pancreatitis (PEP) have mainly involved patients with biliary diseases rather than chronic pancreatitis (CP), and the concept that CP seems to be a protective factor associated with PEP has not been studied in detail. The aim of this study was to determine the incidence of PEP in patients with CP at different clinical stages and to identify the predictive and protective factors of PEP in a large cohort., Methods: In this observational cohort study, medical records of patients with CP (CP group) and biliary diseases (BD group) in a tertiary hospital from January 2011 to May 2015 were examined. The difference in the incidence of PEP between CP group and BD group and the risk of PEP at different clinical stages of CP were calculated by the χ 2 test or the Fisher exact test. The predictive and protective factors for PEP were investigated by univariate and multivariate analysis., Results: In total, 2028 ERCP procedures were performed in 1301 patients with CP and 2000 procedures in 1655 patients with BD. The overall incidence of PEP in CP group (4.5%) was similar to that in the BD group (4.8%; P = .747). However, CP patients had significantly lower rates of moderate and severe attacks (0% vs 1.3%, P < .01). According to the M-ANNHEIM classification, the PEP incidences of CP at stages 0, I, II, III, and IV were 4.4%, 5.1%, 3.8%, 2.0%, and 2.0%, respectively. CP patients at stage Ia had the highest PEP incidence (8.0%) among all CP patients, significantly higher than that at stages Ib + Ic (3.9%) and II (3.8%). Female gender, history of acute pancreatitis, and prior PEP were independent risk factors of PEP, whereas extracorporeal shock wave lithotripsy was a protective factor., Conclusions: Compared with BD patients, CP patients had similar incidence of PEP overall but lower grades of severity. The incidence of PEP in CP patients decreased significantly with disease progression. (Clinical trial registration number: NCT02781987.)., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: SPINK1 (serine protease inhibitor, kazal-type, 1), which encodes human pancreatic secretory trypsin inhibitor, is one of the most extensively studied genes underlying chronic pancreatitis. Recently, based upon data from qualitative reverse transcription-PCR (RT-PCR) analyses of transfected HEK293T cells, we concluded that 24 studied SPINK1 intronic variants were not of pathological significance, the sole exceptions being two canonical splice site variants (i.e., c.87 + 1G > A and c.194 + 2T > C). Herein, we employed the splicing prediction tools included within the Alamut software suite to prioritize the 'non-pathological' SPINK1 intronic variants for further quantitative RT-PCR analysis., Results: Although our results demonstrated the utility of in silico prediction in classifying and prioritizing intronic variants, we made two observations worth noting. First, we established that most of the prediction tools employed ignored the general rule that GC is a weaker donor splice site than the canonical GT site. This finding is potentially important because for a given disease gene, a GC variant donor splice site may be associated with a milder clinical manifestation. Second, the non-pathological c.194 + 13T > G variant was consistently predicted by different programs to generate a new and viable donor splice site, the prediction scores being comparable to those for the physiological c.194 + 2T donor splice site and even higher than those for the physiological c.87 + 1G donor splice site. We do however provide convincing in vitro evidence that the predicted donor splice site was not entirely spurious., Conclusions: Our findings, taken together, serve to emphasize the importance of functional analysis in helping to establish or refute the pathogenicity of specific intronic variants.

Acute pancreatitis (AP) usually causes acute lung injury, which is also known as acute pancreatitis associated lung injury (APALI). This study aimed to investigate whether captopril pretreatment was able to protect lung against APALI via inhibiting angiotensin II (Ang II) production and suppressing Rho/ROCK (Rho kinase) pathway in rats. Severe AP (SAP) was introduced to rats by bile-pancreatic duct retrograde injection of 5% sodium taurocholate. Rats were randomly divided into three groups. In the sham group, sham operation was performed; in the SAP group, SAP was introduced; in the pre-cpl + SAP group, rats were intragastrically injected with 5 mg/kg captopril 1 hour prior to SAP induction. Pathological examination of the lung and pancreas, evaluation of pulmonary vascular permeability by wet/dry ratio and Evans Blue staining, detection of serum amylase, Western blot assay for Ang II receptor type 1 (AT1), RhoA, ROCK (Rho kinase), and MLCK (myosin light chain kinase) were performed after the animals were sacrificed at 24 hours. After the surgery, characteristic findings of pancreatitis were observed, accompanied by lung injury. The serum amylase, Ang II, and lung expression of AT1, RhoA, ROCK, and MLCK increased dramatically in SAP rats. However, captopril pretreatment improved the histological changes, reduced the pathological score of the pancreas and lung, inhibited serum amylase and Ang II production, and decreased expression of AT1, RhoA, ROCK, and MLCK in the lung. These findings suggest that captopril pretreatment is able to protect the lung against APALI, which is, at least partially, related to the inhibition of Ang II production and the suppression of the Rho/ROCK pathway., (Copyright © 2016. Published by Elsevier Taiwan.)

Background and Study Aim: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most common complication of ERCP. Somatostatin may inhibit pancreatic secretion and has been tested for PEP prophylaxis. However, the results of previous studies are inconsistent. The aim of the current study was to investigate whether somatostatin can reduce the incidence of PEP., Patients and Methods: The study was a multicenter, open-label, randomized controlled trial. A total of 908 patients with normal amylase levels who were undergoing ERCP were randomized to receive somatostatin 250 μg bolus injection before ERCP and 250 μg/hour intravenous infusion for 11 hours after ERCP (somatostatin group) or no somatostatin treatments (control group). The incidences of PEP and hyperamylasemia were compared in the two groups., Results: The full analysis set included 900 patients (445 in the somatostatin group, 455 in the control group). PEP developed in 34 patients (7.5 %) in the control group (95 % confidence interval [CI] 5.4 % - 10.3 %) and in 18 patients (4.0 %) in the somatostatin group (95 %CI 2.6 % - 6.3 %; P = 0.03). Hyperamylasemia occurred in 46 patients (10.1 %) in the control group (95 %CI 7.7 % - 13.2 %) and in 27 patients (6.1 %) in the somatostatin group (95 %CI 4.2 % - 8.7 %; P = 0.03). No perforation or death occurred during the study., Conclusions: This study showed that somatostatin was effective and safe for the prevention of PEP and hyperamylasemia in ERCP patients.(ClinicalTrials.gov number, NCT01431781)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To investigate the prevalence and risk factors of upper gastrointestinal bleeding (UGIB) in patients with severe acute pancreatitis (SAP)., Methods: Altogether 101 patients were admitted to the Department of Gastroenterology, Changhai Hospital, Second Medical Military Hospital from July 2006 to June 2010 due to SAP. Their prevalence and risk factors of UGIB were retrospectively analyzed., Results: In total, 18 (17.8%) patients developed UGIB and 13 received endoscopic examination, which yielded six cases of acute gastric mucosal lesions (AGML), five of peptic ulcers (PU) and two of pancreatic necrotic tissue invading the duodenal bulb and presenting as multilesion, honeycomb-like ulcer. The mortality rate of UGIB patients was much higher than that of non-UGIB patients (44.4% vs 10.8%, P = 0.0021). Univariate analysis revealed that the risk factors for UGIB included the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, computed tomography severity index (CTSI), Ranson score, arterial blood pH and PaO2 , serum blood urea nitrogen and creatinine concentrations, platelet count, shock, sepsis and organ failure, mechanical ventilation, heparinized continuous renal replacement therapy and total parenteral nutrition. Multivariate logistic regression revealed that APACHE II score and CTSI were significant risk factors while PaO2 was the protective factor for UGIB in SAP., Conclusions: UGIB is a common complication with poor prognosis due mainly to PU and AGML. Patients having SAP with high APACHE II scores and CTSI or low PaO2 should be considered to be at high risk for UGIB., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background: Autoimmune pancreatitis (AIP) is increasingly recognized as a unique subtype of pancreatitis. This study aimed to analyze the diagnosis and treatment of AIP patients from a tertiary care center in China., Methods: One hundred patients with AIP who had been treated from January 2005 to December 2012 in our hospital were enrolled in this study. We retrospectively reviewed the data of clinical manifestations, laboratory tests, imaging examinations, pathological examinations, treatment and outcomes of the patients., Results: The median age of the patients at onset was 57 years (range 23-82) with a male to female ratio of 8.1:1. The common manifestations of the patients included obstructive jaundice (49 patients, 49.0%), abdominal pain (30, 30.0%), and acute pancreatitis (11, 11.0%). Biliary involvement was one of the most extrapancreatic manifestations (64, 64.0%). Fifty-six (56.0%) and 43 (43.0%) patients were classified into focal-type and diffuse-type respectively according to the imaging examinations. The levels of serum IgG and IgG4 were elevated in 69.4% (43/62) and 92.0% (69/75) patients. Pathological analysis of specimens from 27 patients supported the diagnosis of lymphoplasmacytic sclerosing pancreatitis, and marked (>10 cells/HPF) IgG4 positive cells were found in 20 (74.1%) patients. Steroid treatment and surgery as the main initial treatments were given to 41 (41.0%) and 28 (28.0%) patients, respectively. The remission rate after the initial treatment was 85.0%. Steroid was given as the treatment after relapse in most of the patients and the total remission rate at the end of follow-up was 96.0%., Conclusions: Clinical manifestations, laboratory tests, imaging and pathology examinations in combination could increase the diagnostic accuracy of AIP. Steroid treatment with an initial dose of 30 or 40 mg prednisone is effective and safe in most patients with AIP.

Background & Aims: Nuclear factor-κB (NF-κB) is activated during early stages of pancreatitis. This transcription factor regulates genes that control many cell activities, including inflammation and survival. There is evidence that activation of NF-κB protects against pancreatitis, and, in other cases, that it promotes this disease. We compared the effects of NF-κB in different mouse models of pancreatitis to understand these complications., Methods: To model constitutive activation of NF-κB, we expressed a transgene that encodes its p65 subunit or the inhibitor of κB kinase (IKK)2 in pancreatic acinar cells of mice. We analyzed effects on pancreatic tissues and levels of NF-κB target genes in these mice and compared them with mice that did not express transgenic p65 or IKK2 (controls)., Results: Transgenic expression of p65 led to compensatory expression of the inhibitory subunit IKB-α and, therefore, no clear phenotype. However, p65 transgenic mice given injections of cerulein, to induce acute pancreatitis, had higher levels of NF-κB activity in acinar cells, greater levels of inflammation, and more severe outcomes than control mice. In contrast, constitutive expression of IKK2 directly increased the activity of NF-κB in acinar cells and induced pancreatitis. Prolonged activity of IKK2 (3 months) resulted in activation of stellate cells, loss of acinar cells, and fibrosis, which are characteristics of chronic pancreatitis. Co-expression of IKK2 and p65 greatly increased the expression of inflammatory mediators and the severity of pancreatitis, compared with control mice., Conclusions: The level of NF-κB activation correlates with the severity of acute pancreatitis in mice. Longer periods of activation (3 months) lead to chronic pancreatitis. These findings indicate that strategies to inactivate NF-κB might be used to treat patients with acute or chronic pancreatitis., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To study the potential value and specificity of plasma miR-216a as a marker for pancreatic injury., Methods: Two rat models were applied in this article: L-arginine-induced acute pancreatitis was used as one model to explore the potential value of plasma miR-216a for detection of pancreatic injury; nonlethal sepsis induced in rats by single puncture cecal ligation and puncture (CLP) was used as the other model to evaluate the specificity of plasma miR-216a compared with two commonly used markers (amylase and lipase) for acute pancreatitis. Plasmas were sampled from rats at indicated time points and total RNA was isolated. Real-Time Quantitative reverse transcriptase-polymerase chain reaction was used to quantify miR-216a in plasmas., Results: In the acute pancreatitis model, among five time points at which plasmas were sampled, miR-216a concentrations were significantly elevated 24 h after arginine administration and remained significantly increased until 48 h after operation (compared with 0 h time point, P < 0.01, Kruskal-Wallis Test). In the CLP model, plasma amylase and lipase, two commonly used biomarkers for acute pancreatitis, were significantly elevated 24 h after operation (compared with 0 h time point, P < 0.01 and 0.05 respectively, Pairwise Bonferroni corrected t-tests), while miR-216a remained undetectable among four tested time points., Conclusion: Our article showed for the first time that plasma miR-216a might serve as a candidate marker of pancreatic injury with novel specificity.

Unlabelled: There is no consensus whether octreotide can prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We performed a meta-analysis comparing octreotide with placebo in randomized controlled trials., Methods: : Electronic databases, including MEDLINE, EMBASE, Cochrane controlled trials register, the Cochrane Library, and the Science Citation Index updated to January 2007, were searched to retrieve relevant randomized controlled trials. Outcome measures were post-ERCP pancreatitis., Results: : Fifteen trials were identified, and statistical homogeneity was present among these selected trials. After all the trials were pooled, post-ERCP pancreatitis occurred in 7.0% of controls (92 of 1320) versus 5.5% of treated patients (72 of 1301), without statistical significance (odds ratio, 0.78; 95% confidence interval, 0.57-1.08). Subsequent sensitivity analyses and subgroup analyses also produced no significant effect. Only in large-scale trials (>200 cases) that octreotide could statistically, significantly prevent pancreatitis (odds ratio, 0.50; 95% confidence interval, 0.32-0.79)., Conclusions: : On the basis of current best evidence, octreotide cannot prevent post-ERCP pancreatitis.

Objectives: Since the introduction of endoscopic retrograde cholangiopancreatology (ERCP) in clinical use, pancreatitis has become a common complication of ERCP. Octreotide is an inhibitor of pancreatic enzyme secretions. Several studies have evaluated the effect of octreotide on the incidence of clinical pancreatitis after ERCP, but with different results. The aim was to determine the efficacy of prophylactic administration of octreotide for the prevention of post-ERCP pancreatitis (PEP) and hyperamylasemia., Methods: In this study, patients with scheduled ERCP were randomized to receive either octreotide (0.3 mg) via intramuscular injection or a placebo. The study was conducted in 12 digestive endoscopic units in China. Patients were randomized into two groups: an octreotide group (N = 414) and a control group (N = 418). In the octreotide group, octreotide (0.3 mg) was dissolved in 500 mL of 0.9% saline solution and administered by continuous intravenous infusion, beginning 1 h before endoscopic examination and continued for 6 h thereafter; 0.1 mg of octreotide was injected subcutaneously at 6 and 12 h after the intravenous injection was stopped. The control group was given a placebo intravenously. The end point was the development of acute pancreatitis., Results: The overall incidence of acute pancreatitis was 3.85%; this included 2.42% (10/414) in the octreotide group and 5.26% (22/418) in the control group (P = 0.046). The overall incidence of hyperamylasemia was 14.9%; 12.32% (51/414) in the octreotide group and 17.46% (73/418) in the control group (P = 0.041). No side effects were found., Conclusion: The results indicate that octreotide can prevent PEP and hyperamylasemia.

Background: One of the major causes of death in severe acute pancreatitis (SAP) is severe infection owing to bacterial translocation. Some clinical studies suggested that ecoimmunonutrition (EIN) as a new strategy had better treatment effect on SAP patients. But the experiment studies on the precise mechanism of the effect of EIN were less reported. In this study, we mainly investigated the effects of EIN on bacterial translocation in SAP model of dogs., Methods: SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in healthy hybrid dogs. The SAP dogs were supported with either parenteral nutrition (PN) or elemental enteral nutrition (EEN) or EIN. The levels of serum amylase, serum aminotransferase and plasma endotoxin were detected before and after pancreatitis induction. On the 7th day after nutrition supports, peritoneal fluid, mesenteric lymph nodes (MLN), liver, and pancreas were collected for bacterial culture with standard techniques to observe the incidence of bacterial translocation. Pathology changes of pancreas were analyzed by histopathologic grading and scoring of the severity of pancreas, and the degree of intestinal mucosal damage was assessed by measuring mucosal thickness, villus height, and crypt depth of ileum., Results: Compared with PN and EEN, EIN significantly decreased the levels of serum amylase, serum aminotransferase, plasma endotoxin, and the incidence of bacterial translocation. Furthermore, compared with the others, the histology scores of inflammation in pancreas and the ileum injury (ileum mocosa thickness, villus height, and crypt depth) were significantly alleviated by EIN (P < 0.05). Moreover, concerning liver function, the serum levels of alanine aminotransferase, aspartate aminotransferase and albumin were ameliorating significantly in the EIN group., Conclusion: Our results suggested that EIN could maintain the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in SAP dogs. Early EIN was safe and more effective treatment for SAP dogs.

Objective: To investigate the dynamic changes of mitogen-activated protein kinase (MAPK) signal transduction in rats with severe acute pancreatitis (SAP)., Methods: The SAP model was induced by infusing the bilio-pancreatic duct of 56 Sprague-Dawley rats with 5% sterile sodium taurocholate solution. The rats were randomly divided into seven groups: control group, 0.5 h postoperative group, 1 h group, 3 h group, 6 h group, 12 h group and 24 h group. Western blot analysis was used to determine the activities of p38 MAPK and c-Jun N-terminal kinase (JNK) in the pancreas and lungs., Results: In the rats of the control group, basal p38MAPK activity could be detected but not that of JNK. After SAP was induced, the p38MAPK activity in the pancreas increased markedly and peaked at 3 h, but in the lung it peaked at 6 h. The p38MAPK activity in the pancreas and lungs was significantly higher than the basal activity at the 24 h time point. The activity of INK was only increased at the 12 h point and was not detectable at 24 h., Conclusion: The MAPK signal transduction pathway, in particular p38MAPK, plays an important role in the pathogenesis of SAP.

Background: Endoscopic ultrasound-guided pancreatic duct (PD) drainage (EUS-PDD) is being increasingly performed as an alternative method to surgical drainage to achieve PD decompression after failed endoscopic retrograde pancreatography (ERP). However, no directly study has compared EUS-PDD with surgical PD drainage after failed ERP in patients with chronic pancreatitis. Methods: Consecutive patients who underwent EUS-PDD or longitudinal pancreaticojejunostomy after failed ERP were retrospectively identified from our endoscopy and medical information systems. The primary end point was the Izbicki pain score. The secondary end points were pain relief at the end of follow-up, procedure outcomes, adverse events, readmission, and reintervention. Results: A total of 21 patients (11 EUS-PDD, 10 surgical drainages) were analyzed. There were no significant differences in mean Izbicki pain score (EUS-PDD, 13.6 ± 10.1 vs. surgical drainage 10.7 ± 7.9, p = 0.483) or complete/partial pain relief (60%/30% vs. 70%/30%, p = 0.752) at the end of follow-up of the two groups. The rates of overall adverse events (27.3% vs. 30.0%, p = 0.893) and readmission (63.6% vs. 40.0%, p = 0.290) were similar in the two treatment groups, while patients in EUS-PDD group required more reinterventions (45.5% vs. 0%, p = 0.039) compared with patients in the surgery group. Conclusion: EUS-PDD showed comparable pain relief and safety to surgical PD drainage after failed ERP, with a higher rate of reintervention. The selection of EUS-PDD or surgical drainage may be appropriate based on an individualized strategy. [ABSTRACT FROM AUTHOR]

Objectives: As a serious complication of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) can lead to a prolonged course of interventional therapy. Most predictive models designed to identify such patients are complex or lack validation. The aim of this study was to develop a predictive model for the early detection of IPN in MSAP and SAP. Methods: A total of 594 patients with MSAP or SAP were included in the study. To reduce dimensionality, least absolute shrinkage and selection operator regression analysis was used to screen potential predictive variables, a nomogram was then constructed using logistic regression analysis. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical efficacy of the model. External data were also obtained to further validate the constructed model. Results: There were 476, 118, and 82 patients in the training, internal validation, and external validation cohorts, respectively. Platelet count, hematocrit, albumin/globulin, severity of acute pancreatitis, and modified computed tomography severity index score were independent factors for predicting IPN in MSAP and SAP. The area under the ROC curves were 0.923, 0.940, and 0.817, respectively, in the three groups. There was a good consistency between the actual probabilities and the predicted probabilities. DCA revealed excellent clinical utility. Conclusion: The constructed nomogram is a simple and feasible model that has good clinical predictive value and efficacy in clinical decision‐making for IPN in MSAP and SAP. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone‐type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein‐induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF‐κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti‐inflammatory and anti‐fibrotic therapeutic agent for CP. [ABSTRACT FROM AUTHOR]

Aims: The studies on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in pancreas divisum (PD) patients without chronic pancreatitis (CP) are rare. In this study, we aimed to evaluate the incidence of PEP in PD patients without CP and the risk and protective factors for PEP. Methods: Consecutive patients with symptomatic PD that underwent ERCP from January 2005 to December 2017 were retrospectively analyzed. The patients were divided into PD without CP group and CP group. The basic information and medical records of patients were collected. The risk and protective factors for PEP in PD patients without CP were analyzed by univariate logistic analysis. Results: A total of 89 ERCP procedures were performed in 51 PD patients without CP, and 249 procedures in 136 patients with CP. The incidence of PEP was significantly higher in PD patients without CP than those with CP (15.7% vs. 5.6%, p =.005). Female gender were independent risk factors for PEP, while dorsal duct stent placement was a protective factor. Conclusion: CP may be a protective factor against PEP in PD patients. Female was a risk factor for PEP in PD patients and dorsal duct stent placement was a preventive factor that reduced the incidence of PEP in PD patients without CP. [ABSTRACT FROM AUTHOR]

The article examines the use of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment of hepatobiliary and pancreatic diseases. It states the development of several non-invasive diagnostic methods such as magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and intraoperative cholangiography. An overview on the complications related to ERCP application, is also mentioned.

Chronic pancreatitis ( CP) is a progressive inflammatory disease typified by end-stage fibrosis. This disease can also increase the risk of pancreatic cancer. The associated diagnosis, pain and other complications further add to the burden of disease management. In recent years, significant progress has been achieved in identifying mi RNAs and their physiological functions, including mRNA repression and protein expression control. Given the extensive effort made on mi RNA research, a close correlation has been discovered between certain types of mi RNAs and disease progression, particularly for tissue fibrosis. Designing mi RNA-related tools for disease diagnosis and therapeutic treatments presents a novel and potential research frontier. In the current review, we discuss various mi RNAs closely interacting with CP, as well as the possible development of targeted mi RNA therapies in managing this disease. [ABSTRACT FROM AUTHOR]

Objective We aimed to identify the risk factors for predicting pancreatic infection in patients with severe acute pancreatitis ( SAP). Methods In all, 163 patients with SAP were included and divided into two groups based on the presence or absence of pancreatic infection. Their demographic and clinical characteristics, laboratory examination results, complications and treatment modalities were collected from their medical records. Variables were initially screened by univariate analysis and those with statistical significance were then filtered by multivariate analysis to determine the independent risk factors for pancreatic infection in SAP. Results Patients having SAP with pancreatic infection had a lower partial pressure of arterial carbon dioxide (Pa CO2), peripheral white blood cell count and alkaline phosphatase levels, together with a higher computed tomography severity index ( CTSI) than those without pancreatic infection, while their lactate dehydrogenase (LDH) levels and blood urea nitrogen were much higher. Pancreatic infection was also more common in patients receiving late fluid resuscitation than in those receiving early fluid resuscitation. Multivariate analyses revealed that increased LDH level, high CTSI, delayed fluid resuscitation and hypoxemia were independent risk factors for pancreatic infection in SAP. The sensitivity, specificity, positive and negative predictive values for a model combining the parameters in predicting pancreatic infection were 84%, 97%, 88% and 96%, respectively, with a cut-off value of 0.393, and the area under the receiver operating characteristic curve was 0.923. Conclusion Increased LDH, high CTSI, delayed fluid resuscitation and hypoxemia are independent risk factors for predicting pancreatic infection in patients with SAP. [ABSTRACT FROM AUTHOR]

Purpose: The diagnosis and treatment of secondary infection of pancreatic necrotic tissue remain a major challenge. The level of soluble triggering receptor expressed on myeloid cells (sTREM-1) in fine needle aspiration (FNA) fluid may be a good marker of infected necrosis. Methods: Patients with a clinical suspicion of secondary infection of necrotic tissue were enrolled. The serum levels of C-reactive protein, amylase, procalcitonin (PCT), and sTREM-1 and the fluid levels of sTREM-1, PCT, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and amylase were examined. When infected necrosis was defined, the first step was percutaneous or endoscopic drainage. If there was no improvement after 72 h, an open necrosectomy was performed. Results: In 30 patients with suspected infection, 18 patients were diagnosed as having secondary infection of necrotic tissue. The levels of sTREM-1 and PCT in FNA fluid were found to have the closest correlation with the diagnosis of infected necrosis [sTREM-1: area under the receiver operating characteristic curve (AUC) 0.972; 95% confidence interval (95%CI) 0.837-1.000; PCT: AUC 0.903; 95%CI 0.670-0.990, P > 0.05]. A fluid sTREM-1 cutoff value of 285.6 pg/ml had a sensitivity of 94.4% and a specificity of 91.7%. In a multiple logistic regression analysis, an sTREM-1 level of more than 285 pg/ml and a PCT level of more than 2.0 ng/ml in FNA fluid were independent predictors of infected necrosis. Conclusions: The fluid level of sTREM-1 will help in the rapid and accurate diagnosis of secondary infection of necrotic tissue in patients with severe acute pancreatitis (SAP). [ABSTRACT FROM AUTHOR]

Objective. Considerable false-negative endoscopic ultrasound guided fine needle aspiration (EUS-FNA) findings exist in chronic pancreatitis patients with focal pancreatic mass lesions. Our aim was to develop a prediction rule to stratify risk for pancreatic cancer in chronic pancreatitis patients with focal pancreatic mass lesions with prior negative EUS-FNA cytology. Material and methods. A total of 138 eligible consecutive patients were identified from three hospitals between January 2000 and May 2008. A final diagnosis of pancreatic mass lesions was confirmed histologically or verified by a follow-up of at least 12 months. A prediction rule was developed from a logistic regression model by using a regression coefficient-based scoring method, and then internally validated by using bootstrapping. Results. The rate of pancreatic cancer in the cohort was 18.1%. The prediction rule, which was scored from 0 to 10 points, comprised five variables: sex, mass location, mass number, direct bilirubin, and CA 19-9. Among the 87.7% of patients with low-risk scores (≤≤3), the risk of pancreatic cancer was 13.2%; by comparison, this risk was 52.9% ( p < 0.001) among the 12.3% of patients with high-risk scores (>3). If further invasive tests were used for patients with high risk, 36% of patients with pancreatic cancer would not be missed. The prediction rule had good discrimination (area under the receiver operating characteristic curve, 0.72) and calibration ( p == 0.96). Conclusions. The prediction rule can provide available risk stratification for pancreatic cancer in chronic pancreatitis patients with focal mass lesions with prior negative EUS-FNA cytology. Application of risk stratification may improve clinical decision making. [ABSTRACT FROM AUTHOR]

Background: The majority of literature on the precut technique is concerned with needle-knife sphincterotomy, whereas the comparison of transpancreatic sphincterotomy and needle-knife sphincterotomy has been rarely reported. Aim The aim of the study was to compare the success and the complication rates of transpancreatic sphincterotomy with needle-knife sphincterotomy.Methods: During May 2006 and April 2007, 3,178 consecutive endoscopic retrograde cholangiopancreatography (ERCP) procedures were performed in a prospective multicenter study on ERCP-related complications. From the files of these patients, data of cases undergoing precut sphincterotomy, including transpancreatic sphincterotomy and needle-knife sphincterotomy, were retrospectively extracted and analyzed.Results: Overall, 216 patients with precut sphincterotomy were identified; 140 cases received transpancreatic sphincterotomy, and 76 received needle-knife sphincterotomy. There was no significant difference in the initial and eventual success rates between transpancreatic and needle-knife sphincterotomy (82.9% vs. 90.8% and 90.0% vs. 90.8%, respectively). The overall incidences of complications and acute pancreatitis were not significantly different between the two groups (14.3% vs. 18.4% and 11.4% vs. 11.8%, respectively). [ABSTRACT FROM AUTHOR]

However, we found some problems with this study, which was incompatible with the European Society of Gastrointestinal Endoscopy (ESGE) guidelines for endoscopic treatment of chronic pancreatitis that were published in 2012 and 2018 [3][4], especially with regard to the treatment of dominant main pancreatic duct (MPD) strictures. According to the guidelines, refractory MPD strictures are defined as symptomatic dominant strictures that persist or relapse after 1 year of single pancreatic stent placement [3][4]. [Extracted from the article]

The article presents details of an e-video of a 42-year-old man with a history of necrotizing pancreatitis complicated by pancreatic fluid collections (PFCs) undergoing endoscopy thus diagnosing disconnected pancreatic duct syndrome (DPDS).

OBJECTIVE: To investigate the risk factors for postoperative pancreatitis following endoscopic retrograde cholangiography (ERC), endoscopic retrograde pancreatography (ERP), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (EST) and endoscopic biliary stenting. METHODS: Four hundred and twelve patients referred to the endoscopy unit were divided into seven groups: (i) double ducts (pancreatic duct and biliary duct) contrast media filling group (ERCP group); (ii) biliary duct contrast media filling group (ERC group); (iii) pancreatic duct contrast media filling group (ERP group); (iv) ERCP plus biliary stenting group (ERCP + stent group); (v) ERC plus stenting group (ERC + stent group); (vi) ERCP plus EST and stone extraction (SE) group (ERCP + EST + SE group); and (vii) ERC plus EST and SE group (ERC + EST + SE group). Differences in postoperative serum amylase at 4 and 24 h, as well as clinical symptoms, were compared among the different groups. RESULTS: The incidence of postoperative hyperamylasemia at 4 and 24 h was 17.7 and 4.4%, respectively. The overall incidence of postoperative acute pancreatitis was 3.9% and the ERP group had the highest incidence of postoperative acute pancreatitis among the seven groups. CONCLUSIONS: Repeated pancreatic duct contrast filling during ERCP manipulation is the main risk factor for postoperative pancreatitis and therapeutic ERCP, such as EST, stenting and SE, does not increase the incidence of postoperative pancreatitis. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is characterized by persistent inflammation and fibrosis of the pancreas. To date, no clinical therapy is available to reverse the inflammatory damage or pancreatic fibrosis associated with CP. This study systematically investigated the effect of Dasatinib, a multiple tyrosine kinases (TKs) inhibitor, on pancreatic fibrosis and inflammation in vivo and in vitro. We found that Dasatinib notably ameliorated pancreatic fibrosis and infiltration of macrophages in a model of caerulein-induced murine CP. Further RNA-seq and phosphoproteomic analysis and in vitro validation assays indicated that Dasatinib exerted a marked inhibition on the proliferation and activation of PSCs, which may be resulted from increased GSK3β-mediated β-catenin cytosol retention by inhibiting upstream multiple TKs (such as PDGFR and Src) and MAPK cascades (including ERK1/2 and p38 MAPK). In addition, Dasatinib significantly restrained both the M1 and M2 polarization of macrophages, and impeded its recruitment and crosstalk with PSCs. Our findings indicated that Dasatinib is a potential anti-inflammatory and anti-fibrotic therapeutic strategy for CP. [ABSTRACT FROM AUTHOR]