Nonalcoholic fatty liver disease aggravates acute pancreatitis through bacterial translocation and cholesterol metabolic dysregulation in the liver and pancreas in mice

Background:Nonalcoholic fatty liver disease(NAFLD)is an independent risk factor for severe acute pancreatitis(AP).The underlying mechanism remains unclear.We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice.Methods:C57BL/6N mice were fed on a high-fat diet(HFD)to generate the NAFLD model,and mice in the control group were provided with a normal diet(ND).After being anesthetized with ketamine/xylazine,mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP,and sham operation(SO)was used as control.Serum amylase and Schmidt’s pathological score system were used to evaluate AP severity.Bacterial loads,total cholesterol level,and cholesterol metabolic-associated molecules[low-density lipoprotein receptor(LDLR)and ATP-binding cassette transporter A1(ABCA1)]were analyzed in the liver and pancreas.Results:Compared with the ND-AP group,mice in the HFD-AP group had severer pancreatitis,manifested with higher serum amylase levels and higher AP pathologic scores,especially the inflammation and hemorrhage scores.Compared with the HFD-SO group and ND-AP group,bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group.Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas,although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group.Conclusions:NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.

Alcoholic pancreatitis:New insights into the pathogenesisand treatment

Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis.

Alcoholic pancreatitis:Lessons from the liver

The association between alcohol consumption and pancreatitis has been recognized for over 100 years. Despite the fact that this association is well recognized, the mechanisms by which alcohol abuse leads to pancreatic tissue damage are not entirely clear. Alcohol abuse is the major factor associated with pancreatitis in the Western world. Interestingly, although most cases of chronic pancreatitis and many cases of acute pancreatitis are associated with alcohol abuse, only a small percentage of individuals who abuse alcohol develop this disease. This situation is reminiscent of the association between alcohol abuse and the incidence of alcoholic liver disease. The liver and the pancreas are developmentally very closely related. Even though these two organs are quite different, they exhibit a number of general structural and functional similarities. Furthermore, the diseases mediated by alcohol abuse in these organs exhibit some striking similarities. The diseases in both organs are characterized by parenchymal cell damage, activation of stellate cells, aberrant wound healing, and fibrosis. Because of the similarities between the liver and the pancreas, and the alcohol-associated diseases of these organs, we may be able to apply much of the knowledge that we have gained regarding the effects of alcohol on the liver to the pancreas.

Is alcoholic pancreatitis associated with enteroviral infection?

AIM: To investigate whether enteroviral infection might trigger acute pancreatitis in patients made susceptible due to high alcohol consumption. METHODS: Patients with alcohol-induced acute pan-creatitis were analyzed for signs of simultaneous or preceding enteroviral infection. We studied the serum samples of 40 patients hospitalized for alcohol-induced acute pancreatitis and 40 controls recruited from an alcohol detoxification center. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus RNA and diagnose acute viremia. Immuno-globulin G (IgG), immunoglobulin A (IgA) and immuno-globulin M (IgM) enteroviral antibodies were measured using enzyme immunoassay to detect subacute andprevious infections. The samples were considered posi-tive when the antibody titers were≥15 IU. Further-more, using RT-PCR, we studied pancreatic biopsy sam-ples obtained during surgery from nine patients with chronic pancreatitis, one patient with acute pancreatitis and ten control patients with pancreatic carcinoma for evidence of persisting enteroviral RNA in the pancreatic tissue. RESULTS: No enterovirus RNA indicating acute viremia was detected by RT-PCR in the serum samples of any patient or control. A high incidence of positive antibody titers was observed in both study groups: IgM antibod-ies had positive titers in 5/40 (13%) vs 4/40 (10%), P=0.723; IgG in 15/40 (38%) vs 19/40 (48%), P=0.366; and IgA in 25/40 (63%) vs 33/40 (83%), P=0.045, patients and controls, respectively. Ten (25%) patients had severe pancreatitis and two (5%) required treatment in intensive care. The median length of hos-pitalization was 7 d (range: 3-47 d). The severity of acute pancreatitis or the length of hospitalization was not associated with enteroviral IgM, IgG or IgA anti-bodies. Five pancreatic biopsy samples tested positive with RT-PCR, three (8%) in the control group and two (5%) in the patient group (P=0.64). CONCLUSION: The rate of enteroviral infection is not increased in patients with alcohol-induced acute pan-creatitis when compared to alcoholics with similar high alcohol use.

Alcoholic pancreatitis:A tale of spirits and bacteria

Alcohol is a major cause of chronic pancreatitis.About5%of alcoholics will ever suffer from pancreatitis,suggesting that additional co-factors are required to trigger an overt disease.Experimental work has implicated lipopolysaccharide,from gut-derived bacteria,as a potential co-factor of alcoholic pancreatitis.This review discusses the effects of alcohol on the gut flora,the gut barrier,the liver-and the pancreas and proposes potential interventional strategies.A better understanding of the interaction between the gut,the liver and the pancreas may provide valuable insight into the pathophysiology of alcoholic pancreatitis.

Hydroalcoholic extract of licorice(Glycyrrhiza glabra L.) root attenuates ethanol and cerulein induced pancreatitis in rats

Objective:To evaluate the therapeutic potential of hydroalcoholic extract of licorice root against ethanol and cerulein induced chronic pancreatitis in rats.Methods:The phytochemical profile of hydroalcoholic extract of licorice root was determined by high performance liquid chromatography(HPLC)and gas chromatography coupled to mass spectrometry(GC-MS).Chronic pancreatitis was induced in male albino Wistar rats by feeding them a diet containing ethanol(0%-36%of total calories)for 4 weeks and cerulein(20μg/kg b.wt,i.p.)thrice a week for 3 weeks.Lipase and amylase in serum,lipid peroxides and antioxidants including reduced glutathione,glutathione peroxidase,superoxide dismutase and catalase in pancreas were determined.Inflammatory response was measured by myeloperoxidase in the pancreas,caspase-1 and the concentrations of IL-1 as and liver was carried oαand IL-18 in serum.Moreover,histological evaluation of the pancreut.Results:Different flavonoids and saponins were identified in the hydroalcoholic extract of licorice root through HPLC and GC-MS.A marked increase in the levels of serum lipase,amylase,lipid peroxides,caspase-1,myeloperoxidase,IL-1 in the levels of antioxidants were observed after ethanoα,and IL-18 and a marked decrease l and cerulein administration.Treatment with hydroalcoholic extract of licorice root attenuated these changes.In addition,histological observation confirmed the protective effect of the extract in the pancreas and liver against inflammatory changes induced by ethanol and cerulein.Conclusions:The licorice root extract attenuates ethanol and cerulein induced pancreatitis in rats probably due to its antioxidant phytonutrients since ethanol and cerulein-induced production of reactive oxygen species contributes to severe inflammation in the pancreas.

Pathophysiology of severe gallstone pancreatitis:A new paradigm

Severe gallstone pancreatitis(GSP)refractory to maximum conservative therapy has wide clinical variations,and its pathophysiology remains controversial.This Editorial aimed to investigate the pathophysiology of severe disease based on Opie’s theories of obstruction,the common channel,and duodenal reflux and describe its types.Severe GSP might be a hybrid disease with pathology polarized between acute cholangitis with mild pancreatitis(biliary type)and necrotizing pancreatitis uncomplicated with biliary tract disease(pancreatic type),in which hepatobiliary and pancreatic lesion severity is inversely related to the presence or absence of impacted ampullary stones.Severe GSP is caused by stones that are persistently impacted at the ampulla with biliopancreatic obstruction(biliary type),and probably,stones that are either temporarily lodged at the duodenal orifice or passed into the duodenum,thereby permitting reflux of bile or possible duodenal contents into the pancreas(pancreas type).When the status of the stones and the presence or absence of impacted ampullary stones with biliopancreatic obstruction are determined,the clinical course and outcome can be predicted.Gallstones represent the main cause of acute pancreatitis globally,and clinicians are expected to encounter GSP more often.Awareness of the etiology and pathogenesis of severe disease is mandatory.

Does an association exist between chronic pancreatitis and liver cirrhosis in alcoholic subjects?

AIM: To study the possible association between chronic pancreatitis (CP) and liver cirrhosis (LC) of alcoholic etiology,after excluding any other causes.METHODS: One hundred and forty consecutive alcoholic patients were subdivided into three groups: CP (n = 53),LC (n = 57),and asymptomatic alcoholic (n = 30).Clinical,biochemical and morphological characteristics,Child-Pugh index,indocyanine green test,and fecal pancreatic elastase-1 test were assessed.RESULTS: In patients with cirrhosis,major clinical manifestations of CP such as pancreatic pain and steatorrhea,as well as imaging alterations of CP such as calcifications,duct dilation and pseudocysts were absent; insulin-dependent diabetes was present in 5.3% of cases,and elastase-1 test was altered in only 7%,and severely altered in none.In patients with CP,clinical characteristics of cirrhosis such as ascites,encephalopathy and gastrointestinal hemorrhage were present in one case,Child-Pugh grade > A in 5.7%,and altered indocyanine green test in 1.9% cases.In asymptomatic alcoholism,there was only a non-coincident alteration of elastase-1 test and indocyanine test in 14.8% and 10%,respectively,but other characteristics of cirrhosis or CP were absent.An inverse correlation (r = -0.746) between elastase-1 test and indocyanine test was found in alcoholic patients.CONCLUSION: There is a scarce coincidence in clinical and morphological alterations among patients with CP or LC of alcoholic etiology,but an inverse correlation between pancreatic and liver function tests.These findings support that these alcoholic diseases evolve in a different manner and have different etiopathogenesis.

Pathophysiology of alcoholic pancreatitis:An overview

Use of alcohol is a worldwide habit regardless of socio- economic background. Heavy alcohol consumption is a potential risk factor for induction of pancreatitis. The current review cites the updated literature on the alcohol metabolism, its effects on gastrointestinal and pancreatic function and in causing pancreatic injury, genetic predisposition of alcohol induced pancreatitis. Reports describing prospective mechanisms of action of alcohol activating the signal transduction pathways, induction of oxidative stress parameters through the development of animal models are being presented.

Autoimmune pancreatitis:Cornerstones and future perspectives

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

CD14 promoter polymorphism in Chinese alcoholic patients with cirrhosis of liver and acute pancreatitis

AIM: To investigate the relationship between genetic polymorphism of the CD14 promoter and the occurrence of alcoholic cirrhosis and alcoholic pancreatitis, and to challenge the conclusion made earlier that the patients with acute alcoholic pancreatitis and patients with alcoholic cirrhosis of liver are two different subpopulations.METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the polymorphism of CD14 gene and aldehyde dehydrogenase gene 2 (ALDH 2) in 335 alcoholic patients with different organ complications i.e., cirrhosis of liver (n = 100), acute pancreatitis (n = 100), esophageal cancer (n = 82) and avascular necrosis of hip joint (AVN) (n = 53)and 194 non-alcoholic controls in a Chinese group.RESULTS: The results showed that the carriage of T allele was not different among alcoholic patients with cirrhosis of liver, alcoholic patients with other complication and non-alcoholic controls. On the other hand, the carriage of the C allele was significantly more prevalent for alcoholic pancreatitis than for esophageal cancer (0.79 vs 0.60,P＜0.001), alcoholic AVN (0.79 vs 0.65, P＜0.025) and nonalcoholic controls (0.79 vs 0.68, P＜0.025). Furthermore,when only subjects with ALDH2 1-1 genotype were examined, the C allele frequency was significantly more prevalent for alcoholic pancreatitis than for alcoholic liver cirrhosis (0.82 vs 0.69, P＜0.025), esophageal cancer (0.82 vs 0.61, P＜0.01), alcoholic AVN (0.82 vs 0.64,P＜0.01) and non-alcoholic controls (0.82 vs 0.69, P＜0.05).CONCLUSION: The C allele may be associated with some mechanism, which is important in the pathogenesis of alcoholic pancreatitis, and that alcoholic patients with acute pancreatitis and cirrhosis of liver are probably two different subpopulations.

Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Computed tomographic differentiation between alcoholic and gallstone pancreatitis:Significance of distribution of infiltration or fluid collection

瞄准：评估各种各样的计算断层摄影术(CT ) 的实用性在区分尖锐胰腺炎的主要病原学的渗入或液体收集的调查结果包括分发。方法：我们考察了酒鬼的尖锐胰腺炎的 75 个相对严重的盒子(n = 43 ) 或胆汁的石头(n = 32 ) CT 上的病原学有渗入或液体收集。我们比较了胆汁的演算，和膨胀的胰腺的尺寸，分级的 CT，存在或缺席胰腺或胆汁管。我们也在每个组评估了度和渗入和液体收集的分发。结果：胰的尺寸不在醇基和石头组之间是不同的。醇基显示出比石头组分级的更高的 CT (P 【 0.05 ) 。胆汁的石头和管膨胀的存在在区分病原学是统计上重要的(P 【 0.05 ) 。醇基显示出胰腺的病理比在仅仅的石头组离开了的显著地突出的仙子腹分隔空间(P = 0.020 ) 。结论：含酒精的胰腺炎趋于形成更多的突出的仙子胰腺的变化比在相对严重的盒子中的胆石胰腺炎。这在左腹部的前面的方面上是明显的。尽管临床的历史和一些 CT 调查结果通常是病原学的一个主要决定因素，胰腺的病理可以有的仙子的这个模式在在暖昧的盒子中决定尖锐胰腺炎的病原学的一个辅助角色。

Chronic pancreatitis:Pain and computed tomography/magnetic resonance imaging findings

Chronic pancreatitis(CP)is a fibroinflammatory disease characterized by irreversible destruction of pancreatic tissue.With the development of the disease,it may lead to exocrine and/or endocrine insufficiency.CP is one of the common diseases that cause abdominal pain,which will not get permanent spontaneous relief as the disease evolves.The American College of Gastroenterology clinical guidelines recommend computed tomography or magnetic resonance imaging as the first-line examination for the diagnosis of CP.CP common imaging findings include pancreatic atrophy,irregular dilatation of the pancreatic duct,calcification of pancreatic parenchyma,pancreatic duct stones,etc.In clinical practice,whether any correlations between CP-induced abdominal pain patterns(no pain/constant/intermittent pain)and corresponding imaging findings present are not well known.Therefore,this review aims to comprehensively sort out and analyze the relevant information by collecting lots of literature on this field,so as to construct a cross-bridge between the clinical manifestations and imaging manifestations of CP patients.Also,it provides an imaging basis and foundation for the classification and diagnosis of abdominal pain types in clinical CP patients.

Polyvinyl alcohol and gelatin sponge particle embolization of splenic artery pseudoaneurysm complicating chronic alcoholic pancreatitis

AIM: To assess the effectiveness of and complications associated with polyvinyl alcohol (PVA) and gelatin sponge particles embolization of splenic artery pseudoaneurysm complicating chronic alcoholic pancreatitis.METHODS: A 42-year-old man with splenic artery pseudoaneurysm formation secondary to chronic alcoholic pancreatitis was admitted. We used PVA and gelatin sponge partides embo lization of splenic artery pseudoaneurysm by superselective embolization techniques.RESULTS: The splenic artery pseudoaneurysm was successfully controlled with splenic embolization. The patient was discharged in 9 d with complete recovery. CONCLUSION: This case confirms that superselective transcatheter embolization by PVA and gelatin sponge particles may represent an effective treatment for pseudoaneurysm caused by chronic alcoholic pancreatitis in the absence of other therapeutic alternatives.

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

A Deep Learning Framework for Mass-Forming Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma Classification Based on Magnetic Resonance Imaging

Pancreatic diseases, including mass-forming chronic pancreatitis (MFCP) and pancreatic ductal adenocarcinoma(PDAC), present with similar imaging features, leading to diagnostic complexities. Deep Learning (DL) methodshave been shown to perform well on diagnostic tasks. Existing DL pancreatic lesion diagnosis studies basedon Magnetic Resonance Imaging (MRI) utilize the prior information to guide models to focus on the lesionregion. However, over-reliance on prior information may ignore the background information that is helpful fordiagnosis. This study verifies the diagnostic significance of the background information using a clinical dataset.Consequently, the Prior Difference Guidance Network (PDGNet) is proposed, merging decoupled lesion andbackground information via the Prior Normalization Fusion (PNF) strategy and the Feature Difference Guidance(FDG) module, to direct the model to concentrate on beneficial regions for diagnosis. Extensive experiments inthe clinical dataset demonstrate that the proposed method achieves promising diagnosis performance: PDGNetsbased on conventional networks record an ACC (Accuracy) and AUC (Area Under the Curve) of 87.50% and89.98%, marking improvements of 8.19% and 7.64% over the prior-free benchmark. Compared to lesion-focusedbenchmarks, the uplift is 6.14% and 6.02%. PDGNets based on advanced networks reach an ACC and AUC of89.77% and 92.80%. The study underscores the potential of harnessing background information in medical imagediagnosis, suggesting a more holistic view for future research.