Chronic pancreatitis is a progressive fibroinflammatory disease primarily caused by a complex interplay of environmental and genetic risk factors. It might result in pancreatic exocrine and endocrine insufficiency, chronic pain, reduced quality of life, and increased mortality. The diagnosis is based on the presence of typical symptoms and multiple morphological manifestations of the pancreas, including pancreatic duct stones and strictures, parenchymal calcifications, and pseudocysts. Management of chronic pancreatitis consists of prevention and treatment of complications, requiring a multidisciplinary approach focusing on lifestyle modifications, exocrine insufficiency, nutritional status, bone health, endocrine insufficiency, pain management, and psychological care. To optimise clinical outcomes, screening for complications and evaluation of treatment efficacy are indicated in all patients with chronic pancreatitis.

Alcohol significantly contributes to pancreatitis, causing high global mortality and health burden. This study examines trends in alcohol-attributable pancreatitis (AAP) from 1990 to 2021 using Global Burden of Disease (GBD) 2021 data, focusing on demographic, temporal, and regional variations to inform policymaking.

AAP-related deaths and disability-adjusted life years (DALYs) were analyzed across 204 countries from 1990 to 2021, stratified by Sociodemographic Index (SDI), gender, and age groups. An age-period-cohort model assessed age-standardized DALY rates (ASDR), and decomposition analysis quantified impacts of population growth, aging, and epidemiological changes.

AAP-related DALYs rose from 401,700 in 1990 to 699,300 in 2021, though ASDR and ASMR showed declines globally. Burden increased notably in low and lower-middle SDI regions, especially among those under 40, while high SDI regions achieved better control. Males faced a disproportionately high burden due to alcohol consumption patterns, although some regions saw rising female burdens. Low-SDI areas suffered from limited healthcare, increasing alcohol use, and weak policies, with younger populations contributing significantly to rising burdens. Projections estimate 1.146 million DALYs annually by 2050, with males comprising over 90%. A GBD-AAP visualization platform was developed to present burden data and trends.

AAP exhibits significant regional and gender disparities. Targeted measures, including alcohol regulation, resource allocation, and public health education, are critical in low-SDI regions and among young males to mitigate AAP burden. The GBD-AAP platform offers valuable tool for targeted interventions.

Although acute pancreatitis is common and much is known about its management, further research could lead to targets identified for improvements in care. This study aimed to analyze factors, both medical and socioeconomic, associated with morbidity and mortality at a safety net hospital.

This was a retrospective review of patients with acute pancreatitis admitted between 2015 and 2022. Variables were collected from the electronic medical record and primary outcomes of interest were morbidity and mortality. Standard statistics were used for analysis.

Of the 404 patients that met inclusion criteria, the average age was 48 y, 46% were female, the majority were English speaking, most were Black, and the majority had public insurance. Four percent of patients died and 19.6% had a complication within 30 d. Most patients were admitted to medicine. Public insurance or self-pay status was associated with complications, as was presence of comorbidities and interventional radiology consultation. Surgery and interventional radiology consultation, among other factors, were associated with mortality. Thirty-nine percent of patients with gallstone pancreatitis underwent cholecystectomy. Many patients were started on antibiotics, and of those, 44.1% had no clear indication.

This study reveals novel factors associated with morbidity and mortality in patients with acute pancreatitis, as well as demonstrating that best practices are not uniformly practiced. The study provides further areas of study, including investigations into best pathways for consultations of services and admission service, interventions for at risk patients to improve morbidity and mortality, and how to reduce inappropriate antibiotic use.

Acute pancreatitis (AP) recurrence rates range from 11 to 36 % yet accurately predicting recurrent acute pancreatitis (RAP) and its progression to chronic pancreatitis (CP) after an initial episode remains challenging. Thus, this study explored the risk factors contributing to RAP and its progression to CP.

This retrospective study included patients with AP from three tertiary medical centers between January 2010 and December 2017. The patients were followed up for up to 60 months. The primary endpoint was the incidence of RAP and CP; risk factors influencing these outcomes were also identified.

Overall, 501 patients were included, of which 164 (32.7 %) experienced RAP, and 71 (14.2 %) progressed to CP. The leading causes of AP were alcohol consumption (43.1 %), gallstones (41.5 %) and hypertriglyceridemia (4.4 %). Multivariate Cox regression analysis revealed that smoking (HR, 4.09; 95 % CI, 2.752-6.078, p < 0.001), and organ failure after 48 h of hospitalization (HR, 3.52; 95 % CI, 1.22-10.19, p < 0.02) were significant risk factors for RAP. Significant risk factors for progression to CP included age over 60 years (HR, 5.29; 95 % CI, 1.25-22.47, p = 0.024), smoking (HR, 2.50; 95 % CI, 1.04-6.01, p = 0.04), alcohol consumption (HR, 8.79; 95 % CI, 2.06-37.43, p = 0.003), computed tomography severity index (CTSI) (HR, 1.22; 95 % CI, 1.04-1.44, p = 0.015), and recurrence of AP (HR, 70.69; 95 % CI, 2.61-1914.86, p = 0.011). In alcohol-induced RAP patients, ≥3 recurrences (HR, 4.18; 95 % CI, 1.75-9.98, p = 0.001) was significant risk factor for progression to CP.

Alcohol consumption was the predominant cause of AP and RAP. The severity of the initial AP episode was the key determinant for RAP, and RAP was the most significant risk factor for the progression to CP. Therefore, smoking and alcohol cessation are important to prevent the development of recurrent AP and CP during long-term follow-up.

Activation of type M2 macrophages has been implicated in the pathogenesis of chronic pancreatitis (CP). In a clinical pilot study, we investigated blood-based markers of macrophage activation at different stages of CP.

We performed a cross-sectional analysis of prospectively collected plasma samples from healthy controls and patients with suspected or definitive CP according to the M-ANNHEIM criteria. Plasma concentrations of soluble CD163 (sCD163), soluble CD206 (sCD206), and monocyte chemoattractant protein-1 (MCP-1) were analyzed using enzyme-linked immunosorbent assays. Group and pairwise comparisons of analytes were performed using regression models and area under the receiver operating curves (AUC-ROC).

In total, 73 subjects with CP (28 suspected CP and 45 definitive CP) and 40 controls were included. Compared to controls, the median plasma concentrations of sCD163 ( P  = 0.019) and sCD206 ( P  = 0.033) were elevated in patients with definitive CP. sCD206 was also elevated in patients with definitive CP ( P  = 0.042) compared to suspected CP. ROC analysis revealed the optimal sCD163 cutpoint to distinguish definitive CP from controls was 1.84 mg/mL (AUC-ROC 0.65; 95% confidence interval [CI], 0.54-0.77). The optimal sCD206 cutpoint to distinguish definitive CP from controls was 0.24 mg/mL (AUC-ROC 0.66; 95% CI, 0.54-0.78). MCP-1 concentrations showed no differences across subgroups.

Our study demonstrates that subjects with definitive CP, sampled during a clinically quiescent phase, exhibited increased levels of sCD163 and sCD206. This indicates the presence of activated M2 macrophages in patients with CP at advanced, but not early, clinical stages.

This review aims to summarize the role of endoscopic therapy in the management and outcomes of recurrent acute pancreatitis (RAP). RAP is a clinical entity characterized by repeated episodes of acute pancreatitis in the setting of a normal gland or chronic pancreatitis (CP). The aetiology of RAP can be identified in about 70% of cases; for the remaining cases, the term "idiopathic" (IRAP) is used. However, advanced diagnostic techniques may reduce the percentage of IRAP to 10%. Recognized causes of RAP are gallstone disease, including microlithiasis and biliary sludge, sphincter of Oddi dysfunction (SOD), pancreatic ductal abnormalities (either congenital or acquired) interfering with pancreatic juice or bile outflow, genetic mutations, and alcohol consumption. SOD, as a clinical entity, was recently revised in the Rome IV consensus, which only recognized type 1 dysfunction as a true pathological condition, while type 2 SOD was defined as a suspected functional biliary sphincter disorder requiring the documentation of elevated basal sphincter pressure to be considered a true clinical entity and type 3 was abandoned as a diagnosis and considered functional pain. Endoscopic therapy by retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) has been proven effective when a mechanical obstruction is found and can be removed. If an obstruction is not documented, few treatment options are available to prevent the recurrence of pancreatitis and progression toward chronic disease. In gallstone disease, endoscopic biliary sphincterotomy (EBS) is effective when a dilated common bile duct or biliary sludge/microlithiasis is documented. In type 1 SOD, biliary or dual sphincterotomy is generally successful, while in type 2 SOD, endotherapy should be reserved for patients with documented sphincter dysfunction. However, in recent years, doubts have been expressed about the real efficacy of sphincterotomy in this setting. When sphincter dysfunction is not confirmed, endotherapy should be discouraged. In pancreas divisum (PD), minor papilla sphincterotomy is effective when there is a dilated dorsal duct, and the success rate is the highest in RAP patients. In the presence of obstructive conditions of the main pancreatic duct, pancreatic endotherapy is generally successful if RAP depends on intraductal hypertension. However, despite the efficacy of endotherapy, progression toward CP has been shown in some of these patients, mainly in the presence of PD, very likely depending on underlying genetic mutations. In patients with IRAP, the real utility of endotherapy still remains unclear; this is because several unknown factors may play a role in the disease, and data on outcomes are few, frequently contradictory or uncontrolled, and, in general, limited to a short period of time.

The exocrine pancreas has a limited regenerative capacity, but to what extent all acinar cells are involved in this process is unclear. Nevertheless, the heterogenous nature of acinar cells suggests that cells exhibiting higher plasticity might play a more prominent role in acinar regeneration. In that regard, Stmn1 -expressing acinar cells have been identified as potential facultative progenitor-like cells in the adult pancreas. Here, we studied Stmn1-progeny under physiological conditions, during regeneration, and in the context of Kras G12D expression.

We followed the fate of Stmn1-progenies both under baseline conditions, following caerulein-induced acute or chronic pancreatitis, pancreatic duct ligation, and in the context of Kras G12D expression.

The Stmn1-lineage contributes to baseline acinar cell turnover under physiological conditions. Furthermore, these cells rapidly proliferate and repopulate the acinar compartment in response to acute injury in an ADM-independent manner. Moreover, acinar regeneration during chronic pancreatitis progression is in conjunction with a decline in the proliferative capacity of the Stmn1-lineage. Interestingly, newly generated acinar cells display increased susceptibility to additional injury during recurrent acute pancreatitis (RAP). Finally, given their inability to form ADMs, the Stmn1-lineage fails to form PanINs upon oncogenic Kras expression.

Our findings establish the Stmn1-lineage as a pivotal subpopulation for acinar tissue homeostasis and regeneration. The ability of these cells to restore acinar tissue in an ADM-independent manner distinguishes them as a critical regenerative population. This study presents a new paradigm for acinar regeneration and repair in the context of pancreatitis and neoplasia.

Pancreatitis, as a common exocrine pancreatic disease, poses a daunting challenge to patients' health and the medical system. Endoplasmic reticulum stress (ERS) plays an essential role in the pathologic process of pancreatitis. However, its mechanism is not fully understood. Therefore, this study was designed to deepen the understanding of the pathogenic mechanism of the disease by screening key ERS-related genes (ERSRGs) associated with pancreatitis. Pancreatitis mRNA data for GSE194331 (Normal: 32, Pancreatitis: 87) and pancreatitis GSE143754 (Normal: 9, Pancreatitis: 6) were downloaded from the GEO database and were used as a training and validation set, respectively. First, the training set GSE194331 was differentially expressed and intersected with the ERSRGs (n = 265) obtained from the MSigDB database to result in 42 differentially expressed ERSRGs (DE-ERSRGs). Subsequently, five candidate genes were further screened by PPI network and MCC and MCODE algorithms. However, according to the ROC curve results, AUC values of CCND1, BCL2, PIK3R1, and BCL2L1 were all greater than 0.6, indicating that they had good diagnostic performance, which was verified by the GSE143754 data set. Based on the GeneMANIA network, it was found that hub genes BCL2 and BCL2L1 may be the key factors in the regulation of mitochondrial metabolism. 24 differentially expressed pancreatitis-related genes (DE-PRGs) were found by difference analysis and Venn analysis. Hub genes BCL2 and PIK3R1 that were significantly correlated with 24 DE-PRGs were determined by Spearman analysis. ssGSEA algorithm was further used to reveal the significant correlation between these hub genes and the immune microenvironment of pancreatitis. The miRNA and lncRNA targeting hub genes were predicted using miRWalk, TargetScan, miRDB, and ENCORI databases, providing research directions for the mechanism of pancreatitis. Finally, the Network Analyst website was used to predict potential compounds associated with the hub gene. In conclusion, this study not only further supports the role of ERS in the development of pancreatitis but also provides a new perspective and direction for the development of biomarkers and mechanism of pancreatitis. At the same time, the results of this study provide a reliable research direction for the targeted treatment of pancreatitis.

Acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis are recognized as a continuum of pancreatic diseases. Recurrence increases the risk of progression to chronic pancreatitis. The aim of this study was to search for clinical features that may promote the progression of chronic pancreatitis in patients with recurrent acute pancreatitis.

We retrospectively reviewed patients with recurrent acute pancreatitis from Medical Information Mart for Intensive Care-IV database. They were divided into a training cohort and a validation cohort. A nomogram was constructed based on clinical features during the second hospitalization. The discrimination and calibration of the nomogram were evaluated using the concordance index, area under the time-dependent receiver operating characteristic curve, and calibration plots.

A total of 432 recurrent acute pancreatitis patients were evaluated, of which 93 (21.53%) were diagnosed with chronic pancreatitis later. Age, biliary pancreatitis, admission interval, alcohol dependence, lipase, and platelet were selected. The concordance index was 0.717 (95% confidence interval: 0.691-0.743) for the training cohort and 0.718 (95% confidence interval: 0.662-0.774) for the validation cohort. The area under the time-dependent receiver operating characteristic curve was >0.7 over 1000 days.

A nomogram was developed and validated to evaluate the transition from recurrent acute pancreatitis to chronic pancreatitis.

This review provides a comprehensive update on the diagnostic approaches to chronic pancreatitis (CP), emphasizing recent advancements in imaging techniques, biomarker research, and multivariable scoring systems. Despite substantial progress in these areas, current diagnostic algorithms have limitations, particularly for early and non-calcific CP. Traditional criteria have focused on classic diagnostic signs, but "minimal change" CP is increasingly recognized through advanced imaging and function tests. This article aims to guide clinicians in applying current methods and available strategies for CP diagnosis and outline research efforts in the field.

Acute pancreatitis (AP) and chronic pancreatitis (CP) are considered to be two separate pancreatic diseases in most studies, but some clinical retrospective analyses in recent years have found some degree of correlation between the two in actual treatment, however, the exact association is not clear. In this study, bioinformatics analysis was utilized to examine microarray sequencing data in mice, with the aim of elucidating the critical signaling pathways and genes involved in the progression from AP to CP. Differential gene expression analyses on murine transcriptomes were conducted using the R programming language and the R/Bioconductor package. Additionally, gene network analysis was performed using the STRING database to predict correlations among genes in the context of pancreatic diseases. Functional enrichment and gene ontology pathways common to both diseases were identified using Metascape. The hub genes were screened in the cytoscape algorithm, and the mRNA levels of the hub genes were verified in mice pancreatic tissues of AP and CP. Then the drugs corresponding to the hub genes were obtained in the drug-gene relationship. A set of hub genes, including Jun, Cd44, Epcam, Spp1, Anxa2, Hsp90aa1, and Cd9, were identified through analysis, demonstrating their pivotal roles in the progression from AP to CP. Notably, these genes were found to be enriched in the Helper T-cell factor (Th17) signaling pathway. Up-regulation of these genes in both AP and CP mouse models was validated through quantitative real-time polymerase chain reaction (qRT-PCR) results. The significance of the Th17 signaling pathway in the transition from AP to CP was underscored by our findings. Specifically, the essential genes driving this progression were identified as Jun, Cd44, Epcam, Spp1, Anxa2, Hsp90aa1, and Cd9. Crucial insights into the molecular mechanisms underlying pancreatitis progression were provided by this research, offering promising avenues for the development of targeted therapeutic interventions.

Necrotizing pancreatitis often demands intervention; contemporary management is directed by the step-up approach. Timing of intervention and specific approach is best directed by a multi-disciplinary team including advanced endosocpists, interventional radiologists, and surgeons with interest and experience managing this complex problem. The intervention is often a combination of percutaneous drainage, transluminal endoscopic approaches, and surgical debridement (minimally invasive or open). Goals of treatment are to evacuate solid infected necrosis, gain enteral access when needed, and to prevent recurrence-cholecystectomy in the setting of biliary pancreatitis. Experienced clinical judgment leads to optimal patient outcomes.

Increasing evidence has linked the Hippo pathway with the fibroinflammatory diseases. However, the detailed roles of key hippo components in pancreatic inflammatory diseases still remain unclear.

A series of genetic knockout mice were generated targeting the key components of Hippo pathway to examine the individual effects of YAP1 and TAZ on pancreatic inflammation. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence staining were performed to evaluate the pancreas tissue from mice with various genotypes. The therapeutic potential of a recently developed YAP1/TAZ inhibitor VT-104 was also evaluated in our mouse model.

Mice with acinar-specific knockout of YAP1/TAZ did not exhibit any histological abnormalities in the pancreas. LATS1/2 deficiency induced acinar to ductal metaplasia, immune cell infiltration, and fibroblast activation, which were rescued by the homozygous knockout YAP1, but not TAZ. Additionally, treatment with VT-104 also decreased pathological alterations induced by deletions of LATS1 and LATS2 in acinar cells.

Our findings highlight the critical role of YAP1 in modulating pancreatic inflammation and demonstrate that VT-104 holds therapeutic potential to mitigate pancreatitis-associated pathological manifestations. Further exploration is necessary to unravel the underlying mechanisms and translate these insights into clinical applications.

Recurrent acute pancreatitis (RAP) poses significant clinical challenges, with 32.3% developing to chronic pancreatitis within 5 years. The underlying microbial factors contributing to RAP remain poorly understood. This study aims to identify blood microbial signatures associated with RAP and explore the potential microbial predictors for RAP.

In this prospective cohort, 90 acute pancreatitis patients are classified into non-recurrent acute pancreatitis (NRAP, n=68) and RAP (n=22) groups based on the number of pancreatitis episodes. Microbial composition of blood samples is analyzed using 5-region (5R) 16S rRNA gene sequencing. Key microbial taxa and functional predictions are made. A random forest model is used to assess the predictive value of microbial features for RAP. The impact of Staphylococcus hominis (S. hominis) on RAP is further evaluated in an experimental mouse model.

Linear discriminant analysis effect size (LEfSe) analysis highlights significant microbial differences, with Paracoccus aminovorans, Corynebacterium glucuronolyticum and S. hominis being prominent in RAP. Functional predictions indicate enrichment of metabolic pathways in the RAP group. Random forest analysis identifies key microbial taxa with an AUC value of 0.759 for predicting RAP. Experimental validation shows that S. hominis exacerbates pancreatic inflammation in mice.

This study identifies distinct clinical and microbial features associated with RAP, emphasizing the role of specific bacterial taxa in pancreatitis recurrence. The findings suggest that microbial profiling could enhance the diagnosis and management of RAP, paving the way for personalized therapeutic approaches.

Retrospective studies and large databases, such as the OneFlorida Clinical Research Consortium, rely on International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes to identify patients with specificity. This study aimed to determine if ICD-10 codes for CP are overutilized.

Retrospective analysis was conducted for patients with ICD-10 codes K86.0 (alcohol-induced CP) and K86.1 (other CP) from February 2018 to February 2020. Data were extracted from the integrated electronic data repository. This study was approved by the institutional review board. The diagnosis of CP was defined as either being made by a gastroenterologist, proven by biopsy, or having characteristic findings on cross-sectional imaging with appropriate symptoms.

Five hundred four (37%) out of the 1360 patients had no evidence of CP. When broken down by diagnosis code, 41 of 176 charts (23.3%) with K86.0 and 461 of 1184 charts (38.6%) with K86.1 had no evidence of CP. Two hundred ninety-nine of these patients had either a single episode of acute pancreatitis, recurrent acute pancreatitis, or episode of acute necrotizing pancreatitis. Of note, 81 patients had no identifiable abdominal pathology.

Although the OneFlorida database makes multicenter research more accessible, it does not replace labor-intensive chart review given the propensity for overdiagnosis.

Increased systemic concentrations of YKL-40 are seen in various inflammatory conditions. We explored the relationship between the serum YKL-40 concentrations and subsequent disease severity in patients with acute pancreatitis (AP).

Consecutive adults with AP were prospectively enrolled, and classified as having mild, moderate or severe disease. On admission and 48 h later, C-reactive protein (CRP), YKL-40, interleukin-6 and 8 (IL-6, IL-8), and tumor necrosis factor alpha (TNF-α) concentrations were measured. Patients were also classified as those with low (<50 ng/mL, in the range seen in 30 age and sex-matched non-AP subjects), high (≥190 ng/mL, seen in most of the other inflammatory conditions), and intermediate YKL-40 (50-189 ng/mL).

Incidence of mild, moderate and severe AP among the 150 enrolled patients was 80 (53.3 %), 59 (39.3 %), and 11 (7.4 %), respectively. Both on admission and 48 h later, high YKL-40 (vs. intermediate or low) was strongly associated with higher odds of a more severe AP, independently of the concurrent IL-8 and TNF-α concentrations (OR around 3.5-4.0, or higher). On admission, the association was independent also of the concurrent CRP, whereas the association between the later concentrations and the outcome was conditional on CRP - uncertain at low, strong at high CRP. The high YKL-40 - outcome association at both time-points was conditional on concurrent IL-6: uncertain if IL-6 was low, strong if IL-6 was high.

Serum YKL-40 is a plausible candidate for further evaluation as an early biochemical indicator of subsequent AP severity, particularly if considered jointly with CRP and/or IL-6.

Recurrent acute and chronic pancreatitis (RAP, CP) are complex, progressive inflammatory diseases with variable pain experiences impacting patient function and quality of life. The genetic variants and pain pathways in patients contributing to most severe pain experiences are unknown. We used previously genotyped individuals with RAP/CP from the North American Pancreatitis Study II (NAPS2) of European Ancestry for nested genome-wide associated study (GWAS) for pain-severity, chronicity, or both. Lead variants from GWAS were determined using FUMA. Loci with p<1e-5 were identified for post-hoc candidate identification. Transcriptome-wide association studies (TWAS) identified loci in cis and trans to the lead variants. Serum from phenotyped individuals with CP from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED) was assessed for BDNF levels using Meso Scale Discovery Immunoassay. We identified four pain systems defined by candidate genes: 1) Pancreas-associated injury/stress mitigation genes include: REG gene cluster, CTRC, NEURL3 and HSF22. 2) Neural development and axon guidance tracing genes include: SNPO, RGMA, MAML1 and DOK6 (part of the RET complex). 3) Genes linked to psychiatric stress disorders include TMEM65, RBFOX1, and ZNF385D. 4) Genes in the dorsal horn pain-modulating BDNF/neuropathic pathway included SYNPR, NTF3 and RBFOX1. In an independent cohort BDNF was significantly elevated in patients with constant-severe pain. Extension and expansion of this exploratory study may identify pathway- and mechanism-dependent targets for individualized pain treatments in CP patients. PERSPECTIVE: Pain is the most distressing and debilitating feature of chronic pancreatitis. Yet many patients with chronic pancreatitis have little or no pain. The North American Pancreatitis Study II (NAPS2) includes over 1250 pancreatitis patients of all progressive stages with all clinical and phenotypic characteristics carefully recorded. Pain did not correlate well with disease stage, inflammation, fibrosis or other features. Here we spit the patients into groups with the most severe pain and/or chronic pain syndromes and compared them genetically with patients reporting mild or minimal pain. Although some genetic variants associated with pain were expressed in cells (1) of the pancreas, most genetic variants were linked to genes expressed in the nervous system cells associated with (2) neural development and axon guidance (as needed for the descending inhibition pathway), (3) psychiatric stress disorders, and (4) cells regulating sensory nerves associated with BDNF and neuropathic pain. Similar and overlapping genetic variants in systems 2 -4 are also seen in pain syndromes form other organs. The implications for treating pancreatic pain are great in that we can no longer focus on just the pancreas. Furthermore, new treatments designed for pain disorders in other tissues may be effective in some patient with pain syndromes from the pancreas. Further research is needed to replicate and extend these observations so that new, genetics-guided rational treatments can be developed and delivered.

Current knowledge on the fibro-inflammatory process underlying chronic pancreatitis originates from animal studies or human studies based on circulating biomarkers. To provide new insight into the underlying fibro-inflammatory processes, we simultaneously assessed fibrosis biomarkers in pancreatic fluid collections and the systemic circulation.

This prospective observational cross-sectional study included patients with acute and chronic pancreatitis undergoing drainage of pancreatic fluid collections, as well as 20 healthy controls (only serum levels). PRO-C3, PRO-C11 and PRO-C19 (markers of collagen formation), and C3M and C4M (markers of collagen degradation) were evaluated for both compartments (serum and fluid collection).

Forty-three patients were included: 26 with walled-off necrosis and 17 with pseudocyst. Serum levels of all 5 fibrosis biomarkers were elevated in patients as compared to controls (all P < 0.001). PRO-C3 levels were significantly higher in pancreatic fluid vs serum (280.6 vs 20.8 ng/mL, P < 0.001). In contrast, levels of C3M (20.5 vs 13.1 ng/mL, P = 0.003), PRO-C19 (64.9 vs 14.3 nM, P < 0.001), and C4M (55.6 vs 20.4 ng/mL, P < 0.001) were significantly higher in serum vs pancreatic fluid.

The high serum levels in patients suggest increased overall fibrotic activity in pancreatitis patients as compared to healthy controls. PRO-C3 elicited higher levels in the pancreatic fluid, indicating localized fibrotic activity.

Sphincter of Oddi disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurisation at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD.

Prospective cohort conducted at 14 US centres with 12 months follow-up. Patients undergoing first-time endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy for suspected SOD were eligible: pancreatobiliary-type pain with or without iAP. The primary outcome was defined as the composite of improvement by Patient Global Impression of Change (PGIC), no new or increased opioids and no repeat intervention. Missing data were addressed by hierarchal, multiple imputation scheme.

Of 316 screened, 213 were enrolled with 190 (89.2%) of these having a dilated bile duct, abnormal labs, iAP or some combination. By imputation, an average of 122/213 (57.4% (95% CI 50.4% to 64.4%)) improved; response rate was similar for those with complete follow-up (99/161, 61.5% (54.0% to 69.0%)); of these, 118 (73.3%) improved by PGIC alone. Duct size, elevated labs and patient characteristics were not associated with response. AP occurred in 37/213 (17.4%) at a median of 6 months post ERCP and was more likely in those with a history of AP (30.9% vs 2.9%, p<0.0001).

Nearly 60% of patients undergoing ERCP for suspected SOD improve, although the contribution of a placebo response is unknown. Contrary to prevailing belief, duct size and labs are poor response predictors. AP recurrence was common and like observations from prior non-intervention cohorts, suggesting no benefit of sphincterotomy in mitigating future AP episodes.

Pancreatic fibrosis (PF) is primarily distinguished by the stimulation of pancreatic stellate cells (PSCs) and excessive extracellular matrix deposition, which is the main barrier impeding drug delivery and distribution. Recently, nanomedicine, with efficient, targeted, and controllable drug release characteristics, has demonstrated enormous advantages in the regression of pancreas fibrotic diseases. Notably, paracrine signals from parenchymal and immune cells such as pancreatic acinar cells, islet cells, pancreatic cancer cells, and immune cells can directly or indirectly modulate PSC differentiation and activation. The intercellular crosstalk between PSCs and these cells has been a critical event involved in fibrogenesis. However, the connections between PSCs and other pancreatic cells during the progression of diseases have yet to be discussed. Herein, we summarize intercellular crosstalk in the activation of PSCs and its contribution to the development of common pancreatic diseases, including pancreatitis, pancreatic cancer, and diabetes. Then, we also examine the latest treatment strategies of nanomedicine and potential targets for PSCs crosstalk in fibrosis, thereby offering innovative insights for the design of antifibrotic nanomedicine. Ultimately, the enhanced understanding of PF will facilitate the development of more precise intervention strategies and foster individually tailored therapeutic approaches for pancreatic diseases.

The exocrine pancreas is the main source of digestive enzymes which are released from secretory vesicles of acinar cells into the small intestine. Enzymes, including amylases, proteases and lipases, degrade the ingested food and thus determine the nutritional substrate for the gut microbiota. Acute (AP) and chronic pancreatitis (CP) are associated with a transitional or progressive exocrine pancreatic dysfunction, we analysed in the present study how an experimental induction of pancreatitis in mouse models affects the colonic and duodenal microbiome composition. Evaluation by 16 S rRNA gene sequencing revealed specific microbiome changes in colonic as well as in duodenal samples in different models of AP and CP. Mild acute pancreatitis, which is associated with a transient impairment of pancreatic secretion showed only minor changes in microbial composition, comparable to the ones seen in progressive dysfunctional mouse models of CP. The strongest changes were observed in a mouse model of severe AP, which suggest a direct effect of the immune response on gut microbiome in addition to a pancreatic dysfunction. Our data indicate that highly dysbiotic microbiome changes during pancreatitis are more associated with the inflammatory reaction than with a disturbed pancreatic secretion.

Pancreatitis, characterized by abdominal pain and elevated pancreatic enzymes, remains a significant public health issue. This study aims to assess the awareness of the general population in the Eastern Province of Saudi Arabia regarding pancreatitis, focusing on symptoms, risk factors, and management.

A cross-sectional study was conducted using a structured questionnaire distributed to 446 participants through social media. Data were analyzed using descriptive statistics and Chi-square tests.

The study revealed that the most recognized symptoms of pancreatitis were abdominal pain, nausea, and vomiting. High-fat diets and genetic factors were the most commonly acknowledged risk factors. Medications and dietary changes were the most frequently known treatment methods. The overall knowledge level was 46%, with a significant difference in knowledge between healthcare and non-healthcare personnel. However, there were no significant differences in knowledge based on gender or income levels.

The study highlights a considerable gap in public awareness of pancreatitis, emphasizing the need for targeted educational initiatives. Enhanced public health campaigns could improve early detection and management, potentially reducing the disease burden in Saudi Arabia.

Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP.

Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors.

Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation ( P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001).

In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP.

Pancreatic stellate cells (PSCs) are critical mediators in chronic pancreatitis with an undefined role in acute pancreatitis (AP). PSCs consist of a heterogenous group of cells and are considered interchangeable with pancreatic fibroblasts. This study explored the heterogeneous nature of PSCs by characterizing pancreatic collagen-expressing fibroblasts (PCFs) via lineage tracing in mouse normal and AP pancreas and determining the effect of PCF depletion in AP.

Tandem dimer Tomato (tdTom+) PCFs in collagen type 1 (Col1)a2CreERtdTomato (Tom) mice receiving tamoxifen were characterized via fluorescence, Oil Red staining, and flow cytometry. AP was induced by cerulein, AP injury was assessed, and tdTom+ PCFs were monitored. The effect of PCF depletion on AP injury was evaluated in Col1a2CreERdiphtheria toxin A mice.

Approximately 13% of pancreatic cells in Col1a2CreERTom mice were labeled by tdTom (tdTom+ PCFs), which surrounded acini, ducts, and blood vessels, and stained with Oil Red, collagen type I, vimentin, and desmin. tdTom+ PCFs increased 2-fold during AP, correlating with AP score, amylase, and alpha-smooth muscle actin+ and Ki67+ staining. PCF depletion in Col1a2CreERdiphtheria toxin A mice receiving tamoxifen resulted in enhanced inflammation compared to control.

PCFs may constitute a subset of PSCs and can be activated during AP. PCF depletion aggravates AP, suggesting a protective role for PCFs.

Acute pancreatitis remains a serious public health problem, and the burden of acute pancreatitis is increasing. With significant morbidity and serious complications, appropriate and effective therapies are critical. Great progress has been made in understanding the pathophysiology of acute pancreatitis over the past two decades. However, specific drugs targeting key molecules and pathways involved in acute pancreatitis still require further study. Natural compounds extracted from plants have a variety of biological activities and can inhibit inflammation and oxidative stress in acute pancreatitis by blocking several signaling pathways, such as the nuclear factor kappa-B and mitogen-activated protein kinase pathways. In this article, we review the therapeutic effects of various types of phytochemicals on acute pancreatitis and discuss the mechanism of action of these natural compounds in acute pancreatitis, aiming to provide clearer insights into the treatment of acute pancreatitis.

Acute pancreatitis (AP) is increasing in incidence across the world, and in all age groups. Major changes in management have occurred in the last decade. Avoiding total parenteral nutrition and prophylactic antibiotics, avoiding overly aggressive fluid resuscitation, initiating early feeding, avoiding endoscopic retrograde cholangiopancreatography in the absence of concomitant cholangitis, same-admission cholecystectomy, and minimally invasive approaches to infected necrosis should now be standard of care. Increasing recognition of the risk of recurrence of AP, and progression to chronic pancreatitis, along with the unexpectedly high risk of diabetes and exocrine insufficiency after AP is the subject of large ongoing studies. In this review, we provide an update on important changes in management for this increasingly common disease.

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

To evaluate the long-term efficacy and cost-efficiency of blood purification (BP) in severe acute pancreatitis (SAP) through single-center data.

A total of 155 SAP patients were collected and followed up for 6 months. The participants were divided into control (49 cases) and BP group (106 cases) according to whether they received BP treatment or not. The primary outcomes were 6-month mortality, length of hospital stay, and hospitalization costs. Propensity score matching (PSM) analysis was performed based on various factors such as gender, age, etiology, SOFA score, JSS score, and creatinine value on day 1.

There were significant differences in all baseline data between BP and control groups (p<0.05). However, there was a significant difference in the mortality, length of hospital stay, hospital costs and infection aggravation rate the in outcome data for 6-months (all p<0.05). BP was not considered a death factor in any adjusted models, with p-values ranging from 0.81 to 0.93. The results of subgroup analysis after PSM showed that BP mode had no significant impact on prognostic indicators, but the length of ICU stay and total costs were significantly increased (all p<0.001). There was no significant difference in mortality among the cases that did not require early intervention after 6 months (p=0.487). However, the patients in BP group had longer ICU stays (p=0.001) and higher hospitalization costs (p<0.001) compared to the control group.

The utilization of BP therapy did not decrease the 6-month mortality in SAP patients. Additionally, BP therapy has a significant impact on the duration of ICU stay or hospitalization expenses. However, the effectiveness and cost-efficiency of this therapy are unsatisfactory, and early intervention does not enhance survival benefits. Furthermore, there was no substantial variation in survival benefits between continuous veno-venous hemofiltration (CVVH) alone and compound BP.

Pancreatic adenocarcinoma is one of the most lethal types of gastrointestinal cancer despite the latest medical advances. Its incidence has continuously increased in recent years in developed countries. The location of the pancreas can result in the initial symptoms of neoplasia being overlooked, which can lead to a delayed diagnosis and a subsequent reduction in the spectrum of available therapeutic options. The role of modifiable risk factors in pancreatic cancer has been extensively studied in recent years, with smoking and alcohol consumption identified as key contributors. However, the few screening programs that have been developed focus exclusively on genetic factors, without considering the potential impact of modifiable factors on disease occurrence. Thus, fully understanding and detecting the risk factors for pancreatic cancer represents an important step in the prevention and early diagnosis of this type of neoplasia. This review reports the available evidence on different risk factors and identifies the areas that could benefit the most from additional studies.

Acute pancreatitis is the leading cause of inpatient care among gastrointestinal conditions. Despite early intervention, one-third of patients experience recurrent acute pancreatitis (RAP). A comprehensive diagnostic approach is warranted to identify and treat underlying factors in order to prevent recurrence. RAP is most frequent among men aged 30-40, smokers, and in those with excessive alcohol consumption. To identify the etiology is paramount to stratify patients according to their individual risk of RAP and for predicting an eventual evolution to chronic pancreatitis. Although the initial management of acute pancreatitis is widely homogeneous according to established guidelines, there are no defined protocols to investigate RAP. In the present editorial article we propose a structured algorithm with precise recommendations to investigate the etiology RAP as part of routine clinical practice. Although there are relevant knowledge gaps in this disease, we believe that our guidance would contribute for a more homogenous diagnostic approach of RAP in clinical practice.

Patients with acute pancreatitis (AP) frequently experience hospital readmissions, posing a significant burden to healthcare systems. Acute peripancreatic fluid collection (APFC) may negatively impact the clinical course of AP. It could worsen symptoms and potentially lead to additional complications. However, clinical evidence regarding the specific association between APFC and early readmission in AP remains scarce. Understanding the link between APFC and readmission may help improve clinical care for AP patients and reduce healthcare costs.

To evaluate the association between APFC and 30-day readmission in patients with AP.

This retrospective cohort study is based on the Nationwide Readmission Database for 2016-2019. Patients with a primary diagnosis of AP were identified. Participants were categorized into those with and without APFC. A 1:1 propensity score matching for age, gender, and Elixhauser comorbidities was performed. The primary outcome was early readmission rates. Secondary outcomes included the incidence of inpatient complications and healthcare utilization. Unadjusted analyses used Mann-Whitney U and χ 2 tests, while Cox regression models assessed 30-day readmission risks and reported them as adjusted hazard ratios (aHR). Kaplan-Meier curves and log-rank tests verified readmission risks.

A total of 673059 patients with the principal diagnosis of AP were included. Of these, 5.1% had APFC on initial admission. After propensity score matching, each cohort consisted of 33914 patients. Those with APFC showed a higher incidence of inpatient complications, including septic shock (3.1% vs 1.3%, P < 0.001), portal venous thrombosis (4.4% vs 0.8%, P < 0.001), and mechanical ventilation (1.8% vs 0.9%, P < 0.001). The length of stay (LOS) was longer for APFC patients [4 (3-7) vs 3 (2-5) days, P < 0.001], as were hospital charges ($29451 vs $24418, P < 0.001). For 30-day readmissions, APFC patients had a higher rate (15.7% vs 6.5%, P < 0.001) and a longer median readmission LOS (4 vs 3 days, P < 0.001). The APFC group also had higher readmission charges ($28282 vs $22865, P < 0.001). The presence of APFC increased the risk of readmission twofold (aHR 2.52, 95% confidence interval: 2.40-2.65, P < 0.001). The independent risk factors for 30-day readmission included female gender, Elixhauser Comorbidity Index ≥ 3, chronic pulmonary diseases, chronic renal disease, protein-calorie malnutrition, substance use disorder, depression, portal and splenic venous thrombosis, and certain endoscopic procedures.

Developing APFC during index hospitalization for AP is linked to higher readmission rates, more inpatient complications, longer LOS, and increased healthcare costs. Knowing predictors of readmission can help target high-risk patients, reducing healthcare burdens.

Acute pancreatitis (AP) has a high incidence, and patients can develop recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) after AP.

We aimed to estimate the pooled incidence rates (IRs), cumulative incidences, and proportions of RAP and CP after AP.

A systematic review and meta-analysis of studies reporting the proportion of RAP and CP after AP.

The systematic search was conducted in three (PubMed, EMBASE, and CENTRAL) databases on 19 December 2023. Articles reporting the proportion of RAP or CP in patients after the first and multiple episodes of AP were eligible. The random effects model was used to calculate the pooled IR with 95% confidence intervals (CIs). The I 2 value assessed heterogeneity. The risk of bias assessment was conducted with the Joanna Briggs Institute Critical Appraisal Tool.

We included 119 articles in the quantitative synthesis and 29 in the IRs calculations. Our results showed that the IR of RAP in adult patients after AP was 5.26 per 100 person-years (CI: 3.99-6.94; I 2 = 93%), while in children, it was 4.64 per 100 person-years (CI: 2.73-7.87; I 2 = 88%). We also found that the IR of CP after AP was 1.4 per 100 person-years (CI: 0.9-2; I 2 = 75%), while after RAP, it increased to 4.3 per 100 person-years (CI: 3.1-6.0; I 2 = 76%). The risk of bias was moderate in the majority of the included studies.

Our results showed that RAP affects many patients with AP. Compared to patients with the first AP episode, RAP leads to a threefold higher IR for developing CP.

Our protocol was registered on PROSPERO (CRD42021283252).

HPSE2, the gene-encoding heparanase 2 (Hpa2), is mutated in urofacial syndrome (UFS), a rare autosomal recessive congenital disease attributed to peripheral neuropathy. Hpa2 lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase (Hpa1), yet it exhibits a high affinity toward HS, thereby inhibiting Hpa1 enzymatic activity. Hpa2 regulates selected genes that promote normal differentiation, tissue homeostasis, and endoplasmic reticulum (ER) stress, resulting in antitumor, antiangiogenic, and anti-inflammatory effects. Importantly, stress conditions induce the expression of Hpa2, thus establishing a feedback loop, where Hpa2 enhances ER stress which, in turn, induces Hpa2 expression. In most cases, cancer patients who retain high levels of Hpa2 survive longer than patients bearing Hpa2-low tumors. Experimentally, overexpression of Hpa2 attenuates the growth of tumor xenografts, whereas Hpa2 gene silencing results in aggressive tumors. Studies applying conditional Hpa2 knockout (cHpa2-KO) mice revealed an essential involvement of Hpa2 contributed by the host in protecting against cancer and inflammation. This was best reflected by the distorted morphology of the Hpa2-null pancreas, including massive infiltration of immune cells, acinar to adipocyte trans-differentiation, and acinar to ductal metaplasia. Moreover, orthotopic inoculation of pancreatic ductal adenocarcinoma (PDAC) cells into the pancreas of Hpa2-null vs. wild-type mice yielded tumors that were by far more aggressive. Likewise, intravenous inoculation of cancer cells into cHpa2-KO mice resulted in a dramatically increased lung colonization reflecting the involvement of Hpa2 in restricting the formation of a premetastatic niche. Elucidating Hpa2 structure-activity-relationships is expected to support the development of Hpa2-based therapies against cancer and inflammation.

The interleukin (IL) plays a role in the development of acute pancreatitis (AP). However, the specific IL in AP has not been fully revealed. Therefore, the association between prospective IL and AP was studied via Mendelian randomization (MR).

The HUGO Gene nomenclature committee (HGNC) database provided 47 interleukin related genes (ILRGs). ILRGs and differentially expressed genes (DEGs) from GSE194331 were overlapped to create differently expressed ILRGs (DE-ILRGs). The integrative epidemiology unit (IEU) open genome-wide association study (GWAS) database provided exposure and outcome datasets. Univariate MR (UVMR) analysis using MR-Egger, IVW, simple mode, and weighted mode was done. UVMR results were verified using sensitivity analysis. Drug prediction, MVMR analysis, and PPI network development were also performed.

Six DE-ILRGs were obtained. IL27 and IL1RN were substantially causally linked with AP by UVMR analysis (OR = 0.926, P < 0.001 and OR = 1.031, P = 0.023). Our sensitivity analysis showed the dependability of our results. Direct effect of IL27 was suggested by MVMR analysis. In the cytokine receptor binding pathway, IL27 and IL1RN interacted with IL36G and IL1R2. TAE-684, ARQ-680, and 12 other IL1RN and 14 IL27 medications were predicted.

IL1RN was identified as a risk factor for acute pancreatitis (AP), but IL27 was found to be a protective factor for AP.

Data on the incidence and clinical relevance of gallstones in patients with suspected acute alcoholic pancreatitis are lacking and are essential to minimize the risk of recurrent acute pancreatitis. The aim of this study was to assess the incidence of gallstones and the associated rate of recurrent acute pancreatitis in patients with presumed acute alcoholic pancreatitis.

Between 2008 and 2019, 23 hospitals prospectively enrolled patients with acute pancreatitis. Those diagnosed with their first episode of presumed acute alcoholic pancreatitis were included in this study. The term gallstones was used to describe the presence of cholelithiasis or biliary sludge found during imaging. The primary outcome was pancreatitis recurrence during 3 years of follow-up.

A total of 334 patients were eligible for inclusion, of whom 316 were included in the follow-up analysis. Gallstone evaluation, either during the index admission or during follow-up, was performed for 306 of 334 patients (91.6%). Gallstones were detected in 54 patients (17.6%), with a median time to detection of 6 (interquartile range 0-42) weeks. During follow-up, recurrent acute pancreatitis occurred in 121 of 316 patients (38.3%), with a significantly higher incidence rate for patients with gallstones compared with patients without gallstones (59% versus 34.2% respectively; P < 0.001), while more patients with gallstones had stopped drinking alcohol at the time of their first recurrence (41% versus 24% respectively; P = 0.020). Cholecystectomy was performed for 19 patients with gallstones (36%). The recurrence rate was lower for patients in the cholecystectomy group compared with patients who did receive inadequate treatment or no treatment (5/19 versus 19/34 respectively; P = 0.038).

Gallstones were found in almost one in every five patients diagnosed with acute alcoholic pancreatitis. Gallstones were associated with a higher rate of recurrent pancreatitis, while undergoing cholecystectomy was associated with a reduction in this rate.

The purpose of this study was to investigate the influencing factors for recurrent acute pancreatitis and construct the nomogram model to predict the risk of recurrent acute pancreatitis.

Patients diagnosed with acute pancreatitis in the Affiliated Hospital of Southwest Medical University were enrolled. We collected these patients' basic information, laboratory data, imaging information. Using Logistic regression and least absolute shrinkage and selection operator regression to select risk factor for Cross-Validation Criterion. To create nomogram and validated by receiver operator characteristic curve, calibration curves and decision curve analysis.

A total of 533 patients with acute pancreatitis were included, including 99 recurrent acute pancreatitis patients. The average age of recurrent acute pancreatitis patients was 49.69 years old, and 67.7% of them were male. At the same time, in all recurrent acute pancreatitis patients, hypertriglyceridemic pancreatitis is the most important reason (54.5%). Regression analysis and least absolute shrinkage and selection operator regression showed that smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis were identified and entered into the nomogram. The area under the receiver operator characteristic curve of the training set was 0.747. The calibration curve showed the consistency between the nomogram model and the actual probability.

In conclusion, some high-risk factors like smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis may predict recurrent pancreatitis and their incorporation into a nomogram has high accuracy in predicting recurrence.

Acute Pancreatitis (AP) is associated with high mortality and current treatment options are limited to supportive care. We found that blockade of activin A (activin) in mice improves outcomes in two murine models of AP. To test the hypothesis that activin is produced early in response to pancreatitis and is maintained throughout disease progression to stimulate immune cells, we first performed digital spatial profiling (DSP) of human chronic pancreatitis (CP) patient tissue. Then, transwell migration assays using RAW264.7 mouse macrophages and qPCR analysis of "neutrophil-like" HL-60 cells were used for functional correlation. Immunofluorescence and western blots on cerulein-induced pancreatitis samples from pancreatic acinar cell-specific Kras knock-in (Ptf1aCreER™; LSL-KrasG12D) and functional WT Ptf1aCreER™ mouse lines mimicking AP and CP to allow for in vivo confirmation. Our data suggest activin promotes neutrophil and macrophage activation both in situ and in vitro, while pancreatic activin production is increased as early as 1 h in response to pancreatitis and is maintained throughout CP in vivo. Taken together, activin is produced early in response to pancreatitis and is maintained throughout disease progression to promote neutrophil and macrophage activation.

Sphincter of Oddi Disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurization at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD.

Prospective cohort conducted at 14 U.S. centers with 12 months follow-up. Patients undergoing first-time ERCP with sphincterotomy for suspected SOD were eligible: pancreatobiliary-type pain with or without iAP. The primary outcome was defined as the composite of improvement by Patient Global Impression of Change (PGIC), no new or increased opioids, and no repeat intervention. Missing data were addressed by hierarchal, multiple imputation scheme.

Of 316 screened, 213 were enrolled with 190 (89.2%) of these having a dilated bile duct, abnormal labs, iAP, or some combination. By imputation, an average of 122/213 (57.4% [95%CI 50.4-64.4]) improved; response rate was similar for those with complete follow-up (99/161, 61.5%, [54.0-69.0]); of these, 118 (73.3%) improved by PGIC alone. Duct size, elevated labs, and patient characteristics were not associated with response. AP occurred in 37/213 (17.4%) at a median of 6 months post-ERCP and was more likely in those with a history of AP (30.9 vs. 2.9%, p<0.0001).

Nearly 60% of patients undergoing ERCP for suspected SOD improve, although the contribution of a placebo response is unknown. Contrary to prevailing belief, duct size and labs are poor response predictors. AP recurrence was common and like observations from prior non-intervention cohorts, suggesting no benefit of sphincterotomy in mitigating future AP episodes.Key Messages: WHAT IS ALREADY KNOWN ON THIS TOPIC: It is not clear if the sphincter of Oddi can cause abdominal pain (Functional Biliary Sphincter of Oddi Disorder) and idiopathic acute pancreatitis (Functional Pancreatic Sphincter of Oddi Disorder), and whether ERCP with sphincterotomy can ameliorate abdominal pain or pancreatitis.WHAT THIS STUDY ADDS: Using multiple patient-reported outcome measures, most patients with suspected sphincter of Oddi disorder improve after ERCP with sphincterotomy.Duct size, elevated pancreatobiliary labs, and baseline patient characteristics are not independently associated with response.There is a high rate of recurrent acute pancreatitis within 12 months of sphincterotomy in those with a history of idiopathic acute pancreatitis.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICY: Since a discrete population with a high (> 80-90%) response rate to sphincterotomy for suspected pancreatobiliary pain could not be identified, there is a need for additional observational and interventional studies that include phenotyping of patients using novel imaging or biochemical biomarkers.There remains a pressing need for quantitative nociceptive biomarkers to distinguish pancreatobiliary pain from other causes of abdominal pain or central sensitization.Discovery of blood-, bile-, or imaging-based biomarkers for occult microlithiasis and pancreatitis may be helpful in predicting who is likely to benefit from sphincterotomy.

More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling.

A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed.

Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP.

Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.