Pancreatitis Patients Research Articles

Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study

ObjectiveTo investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP). MethodsWe performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups. ResultsIn total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10. ConclusionCP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP.

Prediction and evaluation of a nomogram model for recurrent acute pancreatitis.

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.

Immune-Enhancing Treatment among Acute Necrotizing Pancreatitis Patients with Metabolic Abnormalities: A Post Hoc Analysis of a Randomized Clinical Trial.

Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

MicroRNA Signatures for Pancreatic Cancer and Chronic Pancreatitis: Expression Profiling by NGS.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease due to the lack of early detection. Because chronic pancreatitis (CP) patients are a high-risk group for pancreatic cancer, this study aimed to assess the differential miRNA profile in pancreatic tissue of patients with CP and pancreatic cancer. MiRNAs were isolated from formalin-fixed paraffin-embedded pancreatic tissue of 22 PDAC patients, 18 CP patients, and 10 normal pancreatic tissues from autopsy (C) cases and processed for next-generation sequencing. Known and novel miRNAs were identified and analyzed for differential miRNA expression, target prediction, and pathway enrichment between groups. Among the miRNAs identified, 166 known and 17 novel miRNAs were found exclusively in PDAC tissues, while 106 known and 10 novel miRNAs were found specifically in CP tissues. The pathways targeted by PDAC-specific miRNAs and differentially expressed miRNAs between PDAC versus CP tissues and PDAC versus control tissues were the proteoglycans pathway, Hippo signaling pathway, adherens junction, and transforming growth factor-β signaling pathway. This study resulted in a set of exclusive and differentially expressed miRNAs in PDAC and CP can be assessed for their diagnostic value. In addition, studying the role of miRNA-target gene interactions in carcinogenesis may open new therapeutic avenues.

Genetic Factors Associated With Adverse Pregnancy Outcomes in Chronic Pancreatitis.

The effects of genetic factors on pregnancy outcomes in chronic pancreatitis (CP) patients remain unclear. We evaluated the impacts of clinical features and mutations in main CP-susceptibility genes ( SPINK1 , PRSS1 , CTRC , and CFTR ) on pregnancy outcomes in Chinese CP patients. This was a prospective cohort study with 14-year follow-up. The sample comprised female CP patients with documented pregnancy and known genetic backgrounds. Adverse pregnancy outcomes were compared between patients with and without gene mutations. Univariate and multivariate analyses were performed to determine the impact factors for adverse pregnancy outcomes. Totally, 160 female CP patients with a pregnancy history were enrolled; 59.4% of patients carried pathogenic mutations in CP-susceptibility genes. Adverse pregnancy outcomes occurred in 38 patients (23.8%); the prevalence of adverse outcomes was significantly higher in those harboring gene mutations than those without (30.5% vs 13.8%, P = 0.015). Notably, the rates of preterm delivery (12.6% vs 3.1%, P = 0.036) and abortion (17.9% vs 4.6%, P = 0.013) were remarkably higher in patients with gene mutations (especially SPINK1 mutations) than those without. In multivariate analyses, both CP-susceptibility gene mutations (odds ratio, 2.52; P = 0.033) and SPINK1 mutations (odds ratio, 2.60; P = 0.037) significantly increased the risk of adverse pregnancy outcomes. Acute pain attack during pregnancy was another risk factor for adverse pregnancy outcomes. Pathogenic mutations in CP-susceptibility genes, especially SPINK1 , were independently related to adverse pregnancy outcomes in CP patients. Significant attention should be paid to pregnant females harboring CP-susceptibility gene mutations (ClinicalTrials.gov: NCT06055595).

A Novel Serum Exosomal miRNA Signature in the Early Prediction of Persistent Organ Failure in Patients with Acute Pancreatitis.

Current study aims to investigate whether serum exosomal microRNAs (miRNAs) could be potential biomarkers in predicting APs with POF at early phase. Novel biomarkers are sorely needed for early prediction of persistent organ failure (POF) in acute pancreatitis (AP) patients. In the discovery stage, exosomal miRNAs were profiled in sera from APs with or without POF (5 vs. 5) using microarrays. POF-associated miRNA signatures then were assessed in training cohort (n=227) and further validated in three independent cohorts (n=516), including one nested case-control cohort. A total of 743 APs were recruited in this large-scale biomarker identification study with a nested case-control study. Data from the discovery cohort demonstrated that 90 exosomal miRNAs were significantly dysregulated in APs with POF compared with controls. One miRNA classifier (Cmi) comprising 3 miRNAs (miR-4265, 1208, 3127-5p) was identified in the training cohort, and was further evaluated in two validation cohorts for their predictive value for POF. AUCs for Cmi ranged from 0.88 to 0.90, which was statistically superior to AUCs of APACHE-II and BISAP, and outperformed BUN and creatinine in POF prediction across all cohorts (P<.05). Higher levels of Cmi indicated increased need for ICU admission, prolonged hospitalization, and elevated mortality rate, thus poor prognosis. In the nested case-control study, Cmi could help identify prediagnostic POF in post-ERCP pancreatitis cases within "golden hours" after ERCP with high efficacy. Serum exosomal Cmi may be an early predictor for POF in AP, even within "golden hours" after AP onset. ClinicalTrials.gov (NCT02602808).

Effects of High-Dose Vitamin C on Liver Function, Systemic Inflammatory and Immune Responses in Patients with Severe Acute Pancreatitis

The objective of this study was to explore the impact of high-dose vitamin C on severe acute pancreatitis patients. This study involved 76 hospital patients from November 2022 to November 2023, divided into two groups: a high-dose group (44 patients) receiving 10 g of vitamin C daily and a routine-dose group (32 patients) receiving 1 g daily. The study evaluated treatment effects, liver function, inflammation levels, and blood T-lymphocyte subsets and complications. At 14 days, the high-dose group showed better overall treatment effects, lower levels of liver enzymes and inflammatory markers, and higher levels of T lymphocytes, with no significant difference in complications compared to the routine-dose group. The findings suggest that high-dose vitamin C effectively improves liver function, reduces inflammation, and boosts immunity in severe acute pancreatitis patients.

Inhibition of the Alternative Complement Pathway May Cause Secretion of Factor B, Enabling an Early Detection of Pancreatic Cancer.

This study aims to elucidate the cellular mechanisms behind the secretion of complement factor B (CFB), known for its dual roles as an early biomarker for pancreatic ductal adenocarcinoma (PDAC) and as the initial substrate for the alternative complement pathway (ACP). Using parallel reaction monitoring analysis, we confirmed a consistent ∼2-fold increase in CFB expression in PDAC patients compared with that in both healthy donors (HD) and chronic pancreatitis (CP) patients. Elevated ACP activity was observed in CP and other benign conditions compared with that in HD and PDAC patients, suggesting a functional link between ACP and PDAC. Protein-protein interaction analyses involving key complement proteins and their regulatory factors were conducted using blood samples from PDAC patients and cultured cell lines. Our findings revealed a complex control system governing the ACP and its regulatory factors, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, adrenomedullin (AM), and complement factor H (CFH). Particularly, AM emerged as a crucial player in CFB secretion, activating CFH and promoting its predominant binding to C3b over CFB. Mechanistically, our data suggest that the KRAS mutation stimulates AM expression, enhancing CFH activity in the fluid phase through binding. This heightened AM-CFH interaction conferred greater affinity for C3b over CFB, potentially suppressing the ACP cascade. This sequence of events likely culminated in the preferential release of ductal CFB into plasma during the early stages of PDAC. (Data set ID PXD047043.).

Health Literacy Needs of Acute Pancreatitis Patients During the Diagnosis and Treatment Process Under the Lens of the Timing It Right Theory: A Qualitative Study.

The incidence and recurrence rate of acute pancreatitis (AP) continues to increase worldwide. The risk of AP attack and recurrence is closely related to the patient's health literacy. Previous studies have shown that AP patients had low levels of health literacy. Understanding patients' experience in AP's diagnosis and treatment process and their health literacy needs might significantly improve their health status. This study aims to understand the experience of acute pancreatitis (AP) patients in the diagnostic and treatment process and explore their health literacy needs at various phases of this process. This study utilized a qualitative approach based on Timing It Right theory. A purposive sampling strategy was employed to select 31 participants diagnosed with AP at various phases of the diagnosis and treatment process. These patients were selected from the Pancreatitis Treatment Centers of two tertiary hospitals in Eastern China. Subsequently, semi-structured in-depth interviews were conducted with the selected participants. The qualitative data was analyzed using the Colaizzi's method. The themes of AP patients' experiences and health literacy needs at various phases of the diagnosis and treatment process were presented as follows. 1. Diagnosis phase: inability to obtain disease information, psychological support seeking, and change unhealthy lifestyle; 2. Hospitalization phase: disease treatment information needs and medical professionals' healthcare. 3. Discharge Preparation phase: fear of recurrence, individualized healthy lifestyle instruction. 4. Home Recovery phase: self-management, continuous healthcare needs, and family support. AP patients' HL needs and health-related problems vary during the diagnosis and treatment process. Medical professionals should comprehend AP patients' changing needs and individual differences, provide continuous healthcare, and involve families in patient management. These factors support patients' long-term self-management and preserve their overall health.

Analysis of Risk Factors for Severe Acute Pancreatitis in the Early Period (

BackgroundSevere acute pancreatitis (SAP) has high mortality. Early identification of high-risk factors that may progress to SAP and active intervention measures may improve the prognosis of SAP patients. ObjectiveClinical data within 24 h after admission were retrospectively analyzed to provide an evidence for early screening of high-risk factors in patients with SAP. MethodsA review of clinical data of acute pancreatitis patients from January 1, 2018, to December 31, 2022, was conducted. We compared the clinical data of SAP and non-SAP patients, and a multivariable logistic regression model was used to identify the independent predictors of SAP. The receiver operating characteristic (ROC) curve of SAP was drawn for continuous numerical variables to calculate the optimal clinical cutoff value of each variable, and the predictive value of each variable was compared by the area under the ROC curve. ResultsBased on the multivariate logistic regression analysis of Age (odds ratio (OR), 1.032;95% confident interval (CI),1.018–1.046, p < 0.001), body mass index (BMI) (OR, 1.181; 95% CI,1.083–1.288, p < 0.001), Non-HTGAP (nonhypertriglyceridemic acute pancreatitis) (OR, 2.098; 95% CI,1.276–3.45, p = 0.003), white blood cell count (WBC) (OR,1.072; 95% CI,1.034–1.111, p < 0.001), procalcitonin (PCT) (OR, 1.060; 95% CI, 1.027–1.095, p < 0.001), serum calcium (Ca) (OR,0.121; 95% CI, 0.050–0.292, p < 0.001), computed tomography severity index (CTSI) ≥4 (OR,12.942;95% CI,7.267–23.049, p < 0.001) were identified as independent risk factors for SAP. The area under the ROC curve (AUC) and optimal CUT-OFF values of continuous numerical variables for predicting SAP were Age (0.6079,51.5), BMI (0.6,23.25), WBC (0.6701,14.565), PCT (0.7086, 0.5175), Ca (0.7787,1.965), respectively. ConclusionAge, BMI, non-HTGAP, WBC, PCT, serum Ca and CTSI≥4 have good predictive value for SAP.

Nomogram and Web Calculator Based on Lasso-Logistic Regression for Predicting Persistent Organ Failure in Acute Pancreatitis Patients.

Acute pancreatitis is a common gastrointestinal emergency. Approximately 20% of patients with acute pancreatitis develop organ failure, which is significantly associated with adverse outcomes. This study aimed to establish an early prediction model for persistent organ failure in acute pancreatitis patients using 24-hour admission indicators. Clinical data and 24-h laboratory indicators of patients diagnosed with acute pancreatitis from January 1, 2017 to January 1, 2022 in Shanxi Bethune Hospital were collected. Patients from 2017 to 2021 were used as the training cohort to establish the prediction model, and patients from 2021 to 2022 were used as the validation cohort. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve (AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group. A total of 1166 patients with acute pancreatitis were included, a total of 145 patients suffered from persistent organ failure from 2017 to 2021. Data were initially selected for 100 variables, and after inclusion and exclusion, 46 variables were used for further analysis. Two prediction models were established and nomogram was drawn respectively. After comparison, the prediction values of the two models were similar (The univariate model AUC was 0.867, 95% CI (0.834-0.9). The LASSO model AUC was 0.864, 95% CI (0.828-0.895)), and the model established by LASSO regression was more parsimonious. A web calculator was developed using the model established by LASSO. Predictive model including 6 risk indicators can be used to predict the risk of persistent organ failure in patients with acute pancreatitis.

Frequency of Gall Stones in Patients with Acute Pancreatitis at Tertiary Care Hospital of Karachi, Pakistan

Background: In developed countries, the adult population has a 20% incidence of gallstones, with a rise of 0.60 to 1.39% yearly. Our study aimed to determinethe frequency of gallstones in Acute Pancreatitis (AP) patients. Methods: A cross-sectional study was conducted atAbbasi Shaheed Hospital, Karachi, recruited all patients fulfilling inclusion criteria presented in the general surgery department from 3rd Oct 2020 to 3rd Oct 2021. After ethical approval and consent, a brief history was taken, and clinical examination, laboratory investigations, and ultrasound of the upper abdomenwere done to ascertain the frequency of gallstones. Results:A total of 93 patients diagnosed with APwere included in this study. Of these, 70 (50.6%) were male patients, and 23 (49.4%) were females,with a mean age of 40.752+11.764 years. The gallstones were found in 42 (45.2%) patients. Conclusion: The frequency of gallbladder stones was high in patients with AP. A prompt or a late diagnosis can directly affect a patient’s mortality and morbidity. Keywords: Abdomen, Acute Pancreatitis, Gallstones, Prevalence.

A retrospective study investigating the clinical significance of body mass index in acute pancreatitis.

Acute pancreatitis is an unpredictable and potentially fatal condition for which no definitive cure is currently available. Our research focused on exploring the connection between body mass index, a frequently overlooked risk factor, and both the onset and progression of acute pancreatitis. A total of 247 patients with acute pancreatitis admitted to Jiangsu Provincial Hospital of Chinese Medicine from January 2021 to February 2023 were retrospectively reviewed. After screening, 117 patients with complete height and body weight data were selected for detailed assessment. Additionally, 85 individuals who underwent physical examinations at our hospital during this period were compiled to create a control group. The study received ethical approval from the ethics committee of Jiangsu Province Hospital of Chinese Medicine (Ref: No.2022NL-114-02) and was conducted in accordance with the China Good Clinical Practice in Research guidelines. A significant difference in body mass index (BMI) was observed between the healthy group and acute pancreatitis (AP) patients (p < 0.05), with a more pronounced disparity noted in cases of hyperlipidemic acute pancreatitis (p < 0.01). A potential risk for AP was identified at a BMI greater than 23.56 kg/m2 (AUC = 0.6086, p < 0.05). Being in the obese stage I (95%CI, [1.11-1.84]) or having a BMI below 25.4 kg/m2 (95%CI, [1.82-6.48]) are identified as risk factors for adverse AP progression. Moreover, BMI effectively predicts the onset of acute edematous pancreatitis and acute necrotizing pancreatitis (AUC = 0.7893, p < 0.001, cut-off value = 25.88 kg/m2). A higher BMI correlates with increased recurrence rates within a short timeframe (r = 0.7532, p < 0.01). Elevated BMI is a risk factor for both the occurrence and progression of AP, and underweight status may similarly contribute to poor disease outcomes. BMI is crucial for risk prediction and stratification in AP and warrants ongoing monitoring and consideration.

Validity of Predictive Markers for Post ERCP Pancreatitis Patients: A Single Centre Study

Abstract: Endoscopic retrograde cholangiopancreatography (ERCP) is a proprietary procedure, endoscopic modality, and specialized procedure used to diagnose and treat disorders of the pancreatic and biliary systems. The incidence of reported post-ERCP complications varied among several studies including post ERCP pancreatitis (PEP), duodenal perforation, and cholangitis. In this study, the author would like to show certain intra procedural factors related to PEP incidence. This was a retrospective study of secondary data of patients undergoing ERCP procedures from 2017-2022 at Prof. Dr. R. D. Kandou Hospital, Manado. Length of procedure, cannulation on pancreatic duct, pancreatogram, double wire technique, and the use of certain common bile duct (CBD) stone retrieval techniques such as endoscopic papillary balloon dilatation (EPBD) were recorded and analyzed. The results showed that based on the analyzed data, the percentage of pancreas cannulation was 8%, pancreatogram 5%, double-wire technique 3%, and EPBD procedure 10%, Incidence rate of PEP in all ERCP procedures was 19%. Increased amylase/lipase enzymes were found in 13 of 24 patients (54%) who underwent cannulation; 8 of 16 patients (50%) who underwent pancreatogram; 4 of 9 patients (44%) who underwent double wire procedure; and 10 of 30 patients (33%) who underwent EPBD. This PEP could be caused by several risk factors during ERCP including cannulation, pancreatogram, double wire, and EPBD. Number of cannulation attempt could result in trauma to the ampulla. Pancreatogram could result in hydrostatic, chemical, and allergic injury. Any manipulation of the pancreas that caused trauma could trigger the incidence of PEP. Assessment of the occurrence of PEP was based on increases in lipase and amylase enzyme values by four times the normal value and tested 6 hours after procedure. We could reduce the incidence of PEP by providing prophylactic therapy before ERCP. In conclusion, PEP is the most common complication in ERCP procedures and can be risky in patients with high risk factors. In this study, factors that affecting the incidence of PEP are cannulation, pancreatogram, double wire and EPBD. Keywords: endoscopic retrograde cholangiopancreatography; pancreatitis; complications

Visceral Fat Predicts New-Onset Diabetes After Necrotizing Pancreatitis.

We aimed to estimate the incidence of new-onset diabetes (NOD) and identify risk factors for NOD in patients with necrotizing pancreatitis (NP). Necrotizing pancreatitis patients were reviewed for NOD, diagnosed >90 days after acute pancreatitis. Baseline demographics, comorbidities, clinical outcomes, computed tomography (CT) characteristics of necrotic collections, and CT-derived abdominal fat measurements were analyzed to identify predictors for NOD. Among 390 eligible NP patients (66% men; median age, 51 years; interquartile range [IQR], 36-64) with a median follow-up of 400 days (IQR, 105-1074 days), NOD developed in 101 patients (26%) after a median of 216 days (IQR, 92-749 days) from NP. Of the NOD patients, 84% required insulin and 69% developed exocrine pancreatic insufficiency (EPI). Age (odds ratio [OR], 0.98), male sex (OR, 2.7), obesity (OR, 2.1), presence of EPI (OR, 2.7), and diffuse pancreatic necrosis (OR, 2.4) were independent predictors. In a separate multivariable model assessing abdominal fat on CT, visceral fat area (highest quartile) was an independent predictor for NOD (OR, 3.01). New-onset diabetes was observed in 1 of 4 patients with NP, most within the first year and requiring insulin. Male sex, obesity, diffuse pancreatic necrosis, development of EPI, and high visceral adiposity identified those at highest risk.

Long-term follow-up study of necrotising pancreatitis: interventions, complications and quality of life

ObjectiveTo describe the long-term consequences of necrotising pancreatitis, including complications, the need for interventions and the quality of life.DesignLong-term follow-up of a prospective multicentre cohort of 373 necrotising pancreatitis patients...

A novel early cancer detection approach for pancreatic cancer.

613 Background: Pancreatic adenocarcinoma (PDAC) is commonly diagnosed at advanced stages, leading to high mortality rates. Earlier detection of PDAC is associated with improved long-term survival, but effective population-level screening is not available. There is therefore an urgent need to improve early detection of PDAC. Wholomics has developed a PDAC-specific proprietary early detection test, using cancer-specific molecular signatures in peripheral blood. Methods: We conducted a retrospective analysis of serum samples from the Amsterdam UMC Liquid Biopsy Center. Three cohorts were included in this study: 1) A cohort of healthy control subjects, 2) patients with a histopathologically confirmed diagnosis of PDAC spanning stages I through IV, and 3) patients with a confirmed diagnosis of chronic pancreatitis. Peripheral blood samples of cancer patients were taken before treatment or surgery. Wholomics used its proprietary technology to quantitatively analyse all serum specimens. Disease-specific molecular signatures were identified and used to develop computational biomarkers specific to both pancreatic pathologies (chronic pancreatitis and pancreatic cancer) and to pancreatic cancer individually. A comparative analysis was conducted employing multiple machine learning algorithms, which were subjected to a 10-fold cross-validation procedure. The accuracy, specificity and sensitivity of the best-performing algorithm is reported. Results: This retrospective study included 50 healthy controls, 12 patients with chronic pancreatitis, and 42 patients with pancreatic cancer (12 stage I, 15 stage II, 9 stage III, 6 stage IV). Applying Wholomics´ technology, an accuracy of 99.1% in differentiating the chronic pancreatitis and pancreatic cancer patients from the healthy controls was achieved. A specificity of 98.0% and a sensitivity of 100.0% were reached. Furthermore, pancreatic cancer patients and chronic pancreatitis patients were differentiated with 95.2% accuracy. Wholomics was also capable of differentiating between early stage (stages I and II) and late-stage (stages III and IV) pancreatic cancer with an accuracy of 100%. Conclusions: Taken together, this study demonstrates that disease-specific molecular signatures in peripheral blood can distinguish patients with PDAC from healthy individuals and patients with pancreatitis with very high accuracy. If validated in additional cohorts, this method could be evaluated as a screening test for PDAC to allow for early detection and improve patient outcomes.

Abstract C089: A novel role of p53 in pancreatic acinar cell identity

Abstract Pancreatitis is an inflammatory disease that affects acinar cells in the exocrine pancreas, and can be triggered by several factors, such as alcohol abuse, smoking and familial genetic alterations. Pancreatic injury associated with pancreatitis is characterized by inflammation, acinar cell death, and acinar-to-ductal metaplasia (ADM), a regenerative process in which metaplastic cells proliferate and re-differentiate into acinar cells. Recurrent pancreatitis can cause persistent ADM, impairing exocrine function and causing precancerous lesions known as pancreatic intraepithelial neoplasia (PanIN) that can initiate pancreatic ductal adenocarcinoma (PDAC), a nearly always fatal disease. Importantly, the lack of treatment options for pancreatitis patients reinforces the need for strategies that could resolve pancreatic damage and stop disease progression. We have recently shown that pancreatic cells harboring a hyperactive variant of p53 display increased resistance to developing acute pancreatitis induced by cerulein (a secretagogue which mimics cholecystokinin). Here, we show that p53 activation using the drug Nutlin-3a can repair the damage caused by cerulein-induced pancreatitis, and reduce the formation of PanIN lesions. This repair is achieved exclusively at low doses of Nutlin-3a, which cause a mild p53 activation, and is entirely dependent on the presence of the p53 gene. We have also identified novel p53 target genes relevant to acinar identity from ChIP-seq and RNA-seq data, and validated their dependence on p53 in mouse embryonic fibroblasts and in pancreatic precancerous lesions. Lastly, we have observed expression of p53 in the developing pancreas at embryonic day 15.5, indicating a potential function of p53 in pancreatic development. Our findings suggest a novel role of p53 in rescuing acinar cells from damage, and that p53 activation may be used as a treatment for pancreatitis and pancreatic cancer prevention. Citation Format: Jennifer J. Twardowski, Stephano S. Mello, Thomas I. Heist. A novel role of p53 in pancreatic acinar cell identity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C089.

Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis

BackgroundSevere acute pancreatitis (SAP) is a dangerous condition with a high mortality rate. Many studies have found an association between adipokines and the development of SAP, but the results are controversial. Therefore, we performed a meta-analysis of the association of inflammatory adipokines with SAP.MethodsWe screened PubMed, EMBASE, Web of Science and Cochrane Library for articles on adipokines and SAP published before July 20, 2023. The quality of the literature was assessed using QUADAS criteria. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to assess the combined effect. Subgroup analysis, sensitivity analysis and publication bias tests were also performed on the information obtained.ResultFifteen eligible studies included 1332 patients with acute pancreatitis (AP). Pooled analysis showed that patients with SAP had significantly higher serum levels of resistin (SMD = 0.78, 95% CI:0.37 to 1.19, z = 3.75, P = 0.000). The difference in leptin and adiponectin levels between SAP and mild acute pancreatitis (MAP) patients were not significant (SMD = 0.30, 95% CI: -0.08 to 0.68, z = 1.53, P = 0.127 and SMD = 0.11, 95% CI: -0.17 to 0.40, z = 0.80, P = 0.425, respectively). In patients with SAP, visfatin levels were not significantly different from that in patients with MAP (SMD = 1.20, 95% CI: -0.48 to 2.88, z = 1.40, P = 0.162).ConclusionElevated levels of resistin are associated with the development of SAP. Resistin may serve as biomarker for SAP and has promise as therapeutic target.

Long term opioid use after burn injury: a retrospective cohort study

BackgroundPatients who have survive a burn injury might be at risk of opioid dependence after discharge. This study examined the use of opioids in patients who suffer burn injury and explored factors associated with persistent opioid use after hospital discharge. MethodsThis retrospective cohort study compared adults admitted with a burn injury from 2009 to 2019 with two matched comparison cohorts from the general population and adults with a diagnosis of acute pancreatitis. Pre-admission prescription opioid use was determined, and a multivariable negative binomial regression analysis used to explore post-discharge opioid use. ResultsA total of 7147 burn patients were matched with 6810 pancreatitis patients and with 28 184 individuals from the general population. Pre-admission opioid use was higher in the burn and pancreatitis cohorts (29% and 40%, respectively) compared with the general population (17%). Opioid use increased in both burn and pancreatitis cohorts after discharge (41% and 53%, respectively), although patients with pancreatitis were at even higher risk of increased opioid use in an adjusted analysis (incidence rate ratio 1.43). Female sex, lower socioeconomic status, ICU admission, pre-injury opioid use, and a history of excess alcohol use were all associated with an increase in opioid prescriptions after discharge. ConclusionsOpioid use is high in those admitted with a burn injury or acute pancreatitis when compared with the general population, increasing further after hospital discharge. Female sex and socioeconomic deprivation are among factors that make increased opioid use more likely, although this phenomenon seems even more pronounced in those with acute pancreatitis compared with burn injuries.