BACKGROUND:Venous thromboembolism (VTE) is a well-established sequela of acute necrotizing pancreatitis (ANP). No prior meta-analysis has comprehensively explored the pooled incidence of VTE in this patient population. METHODS:We performed a comprehensive literature search from inception to July 2025, to identify all studies reporting the incidence of VTE after an index episode of ANP. Two independent reviewers screened articles and extracted relevant variables. The random-effects model was used to calculate the pooled incidence and 95% confidence intervals (CI) of thrombosis in each anatomical location. Risk of bias assessment was done via the Newcastle-Ottawa Scale. The Higgins I2 index was used to assess heterogeneity, with I2 > 50% indicating significant heterogeneity. RESULTS:4243 patients across 24 studies were analysed. The pooled incidence of extremity DVT (eDVT) was 14% (95% CI: 4%-28%, I2 = 93.8%) across 6 studies and 4% (95% CI: 2-8%, I2 = 76.4%) for pulmonary embolism (PE) across 5. The pooled incidence for Splanchnic vein thrombosis (SVT) was 34% (95% CI: 26%-42%, I2 = 94.5%) with a higher SVT incidence of 53% (95% CI: 34%-72%, I2 = 86.1%) in the infected necrosis sub-group. The splenic vein was the commonly involved vein in the splanchnic system at 20% (95% CI: 12%-29%, I2 = 94.1%). CONCLUSION:There is a relatively high incidence of VTE in patients with pancreatic necrosis, with the incidence in some anatomical locations being of particular clinical importance. Prospective cohort studies are needed to better delineate subgroups at higher risk for thrombosis in this patient population and assess the risk/benefit of increased anticoagulation dosing.
BACKGROUND:Pain in chronic pancreatitis (CP) negatively impacts quality of life and healthcare utilization. This study characterized longitudinal analgesic prescribing trends, demographic differences, treatment pathways, and factors associated with opioid-related outcomes among patients with CP. METHODS:Using TriNetX, we identified adults with CP and assessed annual incidence and annual period prevalence of documented prescriptions from 2015 to 2024 for: NSAIDs/acetaminophen, opioids, benzodiazepines, neuropathic agents, and muscle relaxants. Treatment pathways and opioid-related outcomes were analyzed using Cox regression models adjusting for 39 covariates. RESULTS:Among 142,650 CP patients, the annual period prevalence of pain medication prescription increased from 41.24% to 58.80%, substantially exceeding the general population. NSAIDs/acetaminophen and opioid prescription prevalence showed the highest increases. Females exhibited higher use across all medication classes. Younger patients demonstrated higher initiation rates. Initial treatments mostly involved NSAIDs/acetaminophen and opioids, with frequent polypharmacy observed. 10% of patients developed opioid-related conditions, with significantly higher hazards among those with alcohol-related CP (opioid-related disorders: HR = 1.23, 95% CI 1.18-1.29, P < 0.001; opioid dependence: HR = 1.21, 95% CI 1.14-1.27, P < 0.001; opioid abuse: HR = 1.09, 95% CI: 1.02-1.18, p = 0.018) and those undergoing pancreatic surgery (opioid-related disorders: HR = 1.81, 95% CI 1.66-1.96, P < 0.001; opioid dependence: HR = 2.07, 95% CI: 1.89-2.27, p < 0.001). CONCLUSIONS:This large-scale analysis highlights substantial and increasing analgesic use in CP, marked by increasing opioid prescription burden, polypharmacy, and higher hazards of opioid-related disorders among patients with alcohol-related etiology or pancreatic surgery. These findings emphasize the need for more guideline-concordant, multimodal, and individualized pain management with careful monitoring of high-risk groups.
BACKGROUND:Pancreatic intraepithelial neoplasia (PanIN), a microscopic precursor of pancreatic ductal adenocarcinoma, cannot be directly visualized by conventional imaging. Secondary parenchymal and ductal changes-focal pancreatic parenchymal atrophy (FPPA), main pancreatic duct (MPD) abnormalities, and cystic lesions-have been proposed as indirect imaging findings (IIFs), but their diagnostic relevance remains uncertain. We investigated the association between specific IIFs and histopathologically confirmed malignant lesions in patients undergoing pancreatectomy without a detectable mass. METHODS:In this retrospective cohort study, 155 consecutive patients at two high-volume centers who underwent pancreatectomy for suspected high-grade PanIN between October 2018 and January 2026 were included. Preoperative imaging was reviewed to identify and map three IIF types (FPPA, MPD abnormalities, and cystic lesions) to surgical specimens, which were evaluated histopathologically. RESULTS:Of 155 patients, 94 (60.6%) had malignant lesions, including 77 (49.7%) high-grade PanIN, 14 (9.0%) invasive PDAC, and three (1.9%) non-invasive intraductal papillary mucinous carcinoma. Among 357 anatomical sites with IIFs, 125 (35.0%) contained malignancy. The positive predictive value increased with the number of overlapping IIF types: 20.7% for one, 38.5% for two, and 77.1% for three (p for trend < 0.001). Invasive PDAC occurred only at sites with multiple overlapping IIFs, in 5.2% and 14.6% of sites with two and three IIF types, respectively (p for trend < 0.001). CONCLUSIONS:A combination of IIFs was associated with a high-risk pancreatic phenotype linked to high-grade PanIN and early pancreatic cancer. Multiple IIFs may help identify patients who warrant further diagnostic evaluation and facilitate risk stratification.
BACKGROUND:Systemic inflammation is a key driver of progression in pancreatic ductal adenocarcinoma (PDAC). We aimed to externally validate the Systemic Inflammation Response Index (SIRI) and define its non-linear prognostic value in a large multicenter cohort. METHODS:We analyzed 672 patients with metastatic PDAC receiving first-line chemotherapy across 30 centers. SIRI was assessed using a validated cut-off (>2.3) and as a log-transformed continuous variable in multivariable Weibull accelerated failure-time models with restricted cubic splines. RESULTS:Patients with low SIRI (≤2.3) had longer median OS (14.0 vs 9.2 months; p < 0.001) and PFS (5.9 vs 3.9 months; p < 0.001) than those with high SIRI. High SIRI was associated with a lower objective response rate (25% vs 37%; p < 0.001). In multivariable analyses, higher SIRI independently predicted inferior OS and PFS (75th vs 25th percentile: HR 1.14 [95% CI 1.05-1.25], HR 1.11 [95% CI 1.03-1.21]) and poorer tumor response (OR 0.78; 95% CI 0.62-1.00). Higher SIRI correlated with greater hepatic tumor burden and cachexia. CONCLUSIONS:SIRI is a robust, independent prognostic marker in metastatic PDAC. Higher values identify a phenotype with inferior survival and poorer tumor response. An open-access web calculator is provided to illustrate and explore the nonlinear, continuous prognostic gradient of SIRI and its impact on outcome.
Background Amid global population aging, understanding the disease burden of pancreatic cancer and pancreatitis in adults ≥70 is essential. This study evaluates global, regional, and national burdens from 1990 to 2021. Methods Using Global Burden of Disease Study 2021 data, we analyzed age-standardized incidence, mortality, and DALYs for pancreatic cancer and pancreatitis among adults ≥70 across 204 countries, stratified by sex, SDI, and health system performance. We calculated estimated annual percentage changes and applied age-period-cohort modeling for risk factor assessment. Results From 1990 to 2021, pancreatic cancer incidence increased from 45.1 to 54.5 per 100,000, while pancreatitis decreased from 105.4 to 91.9. Pancreatic cancer burden increased universally, particularly in low-middle SDI regions. In contrast, pancreatitis burden declined in high-SDI regions but rose in low-middle SDI settings. Smoking accounted for 12.1% of pancreatic cancer DALYs, and high fasting plasma glucose for 29.2%, with the latter's role growing over time. Alcohol use represented 11.1% of pancreatitis DALYs. Conclusions Pancreatic cancer and pancreatitis show divergent global trajectories in older adults, driven by socioeconomic development, health system access, and modifiable risk factors. The rising pancreatic cancer burden requires strengthened prevention and early detection, especially in low-resource settings. Public health efforts should prioritize smoking cessation, glycemic control, and reduced alcohol use to mitigate disease impact in aging populations.
BACKGROUND:Intratumoral microbiota have been implicated in several cancers, including pancreatic cancer, but data on pancreatic neuroendocrine tumors (PNETs) remain limited. METHODS:We analyzed two complementary cohorts: a retrospective formalin-fixed paraffin-embedded cohort comprising 53 primary PNETs, 26 paired adjacent non-tumor tissues (ANTs), and 5 liver metastases assessed by fluorescence in situ hybridization (FISH); and a prospective subset of 25 paired fresh tumor-center and ANT samples analyzed by 16S rRNA gene sequencing. Taxonomic composition, alpha and beta diversity, differential abundance, predicted microbial functions, and associations with clinicopathological features and fasting serum lipids were evaluated. RESULTS:PNETs showed a higher frequency of detectable bacterial signals and greater microbial richness and diversity than ANTs. LEfSe identified 38 nominally differentially abundant taxa (P < 0.05; LDA > 2.5), including enrichment of Blautia, Rothia, and Ferrovibrio in tumors. Their combined abundance differentiated PNETs from ANTs with an area under the curve of 0.843. Exploratory functional inference suggested enrichment of 15 pathways in PNETs, including fatty acid and short-chain fatty acid biosynthesis pathways. Serum high-density lipoprotein levels were inversely associated with intratumoral microbial richness (Ace index: r = -0.497, P = 0.049). CONCLUSIONS:PNETs exhibited greater bacterial burden, microbial richness, and diversity than ANTs, with distinct taxonomic patterns and lipid-related associations. These exploratory findings warrant external validation in larger cohorts with rigorous low-biomass contamination control.
Background Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas present a broad spectrum of biological behavior, ranging from benign to malignant. Their management poses significant ethical dilemmas, particularly concerning diagnostic uncertainty, the risk of overdiagnosis and overtreatment, and resource allocation. Methods This qualitative study employed a constructivist approach to explore the ethical challenges faced by surgeons in managing IPMNs. Data were collected through focus group meetings (FGMs) with members of an expert working group at the Verona Evidence-Based Meeting on IPMNs (2020). Discussions were analyzed to identify key ethical concerns. Results The analysis highlighted several major ethical concerns: (1) decision-making under diagnostic uncertainty, (2) ethical challenges in patient communication, (3) overdiagnosis and over-surveillance due to defensive medicine and patient anxiety, (4) overtreatment through unnecessary surgery, and (5) issues of distributive justice in access to care and healthcare resource utilization. Participants emphasized the difficulty of balancing transparency with the need to minimize psychological distress in patients, as well as the challenge of applying international guidelines in diverse healthcare settings. Conclusions Ethical decision-making in IPMN management requires balancing the risks of malignancy with the potential harms of overtreatment, while also considering patient autonomy and resource limitations. Enhancing decision-support tools, improving surgeon training in communication, and refining clinical guidelines to incorporate ethical considerations may help address these challenges. Further research is needed to develop strategies for more individualized and patient-centered care.
BACKGROUND:Evidence on behavioral predictors of recurrence after first-episode of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is limited. We investigated the association between baseline current smoking status and post-discharge recurrence and whether this association varied over follow-up. METHODS:This multicenter retrospective cohort included patients with first-episode of HTG-AP hospitalized at three centers between January 2020 and March 2025. Smoking status was determined at the index hospitalization. Cox regression assessed time to first recurrence, and negative binomial regression assessed recurrence burden. Landmark and time-varying coefficient Cox models evaluated temporal variation in the association, with center-stratified and overlap-weighted analyses used for robustness. RESULTS:Among 311 patients, 111 were baseline current smokers and 84 experienced recurrence. Baseline current smoking status was associated with a higher cumulative recurrence probability (log-rank P = 0.009), an increased hazard of first recurrence (HR 3.00, 95% CI 1.69-5.33; P < 0.001), and greater recurrence burden (IRR 3.69, 95% CI 1.79-7.63; P < 0.001). No significant multiplicative interaction was observed between current smoking and current alcohol consumption, with an adjusted interaction term HR of 1.60 (95% CI: 0.49-5.29, P = 0.439). Current alcohol consumption was not independently associated with recurrence (center-stratified HR 0.75, 95% CI 0.44-1.29; P = 0.303). Landmark analysis showed no significant association within 6 months, whereas the association was evident thereafter. The time-varying coefficient Cox model indicated that the association was not constant over follow-up, and overlap weighting showed greater between-group differences during mid-to long-term follow-up. CONCLUSIONS:Baseline current smoking status was associated with higher recurrence risk and burden after first-episode of HTG-AP. The association appeared stronger during later follow-up, supporting its potential use as a simple behavioral marker for risk assessment and follow-up planning.
Background Acute pancreatitis (AP) frequently requires early fluid resuscitation to restore intravascular volume, preserve pancreatic perfusion, and prevent organ failure. However, the optimal fluid type and resuscitation strategy remain controversial. Methods We performed a component network meta-analysis (CNMA) of randomized controlled trials comparing fluids (normal saline [NS], lactated Ringer [LR], other balanced multi-electrolyte solutions [BMES], and naso-jejunal hydration solution [NJ]) and resuscitation strategies (aggressive vs. non-aggressive) in patients with new-onset AP. Primary endpoints were progression to moderately severe or severe AP, systemic inflammatory response syndrome (SIRS), and adverse events. Secondary endpoints included mortality, local complications, organ failure, and length of stay (LOS). Incremental component effects were expressed as incremental odds ratios (iOR) or mean differences (iMD). Certainty of evidence was evaluated using CINeMA and GRADE. Results Twelve trials (1,216 patients) were included. LR significantly reduced progression to moderately severe/severe AP (iOR 0.51; 95% CI 0.33; 0.79) and pancreatitis-related local complications (iOR 0.53; 95% CI 0.33; 0.85). BMES and LR reduced LOS by approximately 4 and 1 day, respectively, compared with NS. Aggressive resuscitation increased adverse events (iOR 3.35; 95% CI 1.52; 7.37). Heterogeneity and inconsistency were generally low for primary endpoints. Conclusions Balanced crystalloids, particularly LR, are associated with improved clinical outcomes compared with NS in early AP management, reducing disease progression, local complications, and hospital stay. Aggressive fluid regimens increase adverse events without a clear benefit. These findings support the preferential use of LR within a moderate, goal-directed resuscitation strategy, although the certainty of evidence was generally low to moderate due to risk of bias and imprecision.
BACKGROUND:Broader research and translational use of patient-derived organoids (PDOs) in pancreatic ductal adenocarcinoma (PDAC) remain constrained by complex and costly culture requirements. Here, we developed a conditional transgenic strategy to generate self-sustaining primary PDAC organoids and explored its feasibility for therapeutic evaluation. METHODS:We established a proof-of-concept PDAC organoid biobank (n = 10). Using a doxycycline-inducible lentiviral Tet-On system, we engineered organoids to express essential cytokines RSPO1 and WNT3A, enabling growth in supplement-depleted media. We then performed exploratory assessments of FOLFIRINOX-mimetic chemotherapy and EPHA2-targeted CAR-T cells in transgenic organoids, together with histopathological and clinicopathological co-analysis. RESULTS:Doxycycline-induced RSPO1/WNT3A expression rescued the impaired growth and passaging caused by exogenous cytokine depletion. In simplified media, transgenic organoids retained patient-specific histological and molecular features. Sensitivity to FOLFIRINOX-mimetic treatment and EPHA2 CAR-T cells varied among different patients, and the in vitro responses showed exploratory concordance with the corresponding clinical courses in a small subset. CONCLUSION:This conditional transgenic approach reduces culture complexity while preserving key phenotypic and functional characteristics of PDAC organoids, providing a feasible proof-of-concept platform for exploratory evaluation of chemotherapy and immunotherapy responses.
