Abstract Pancreatitis progresses from acute pancreatitis (AP) to chronic pancreatitis (CP) phases through dynamic immune cell transitions that determine disease resolution or fibrosis. In AP, rapid infiltration of neutrophils and M1-like macrophages drives tissue injury via cytokine storms, neutrophil extracellular traps (NETs), and inflammasome activation, while Th17 cells amplify inflammatory cascades. Resolution depends on phenotypic switching: M1-like macrophages transition to reparative M2-like states, regulatory T cells (Tregs) expand to suppress excessive inflammation, and dendritic cells shift from pro-inflammatory to regulatory functions. However, persistent injury disrupts this balance. In CP, macrophages become trapped in incomplete M2-like polarization, retaining pro-inflammatory features while acquiring pro-fibrotic functions. Pathogenic Th17 cells persist and directly activate pancreatic stellate cells (PSCs) via IL-17A and IL-22, whereas Tregs undergo functional failure and lose suppressive capacity. Concurrently, neutrophil activity becomes scattered and residual. Metabolic reprogramming fundamentally underpins these immune transitions. In AP, ketogenesis restrains macrophage hyperactivation and NLRP3 inflammasome signaling, while impaired fatty acid oxidation (FAO) and mitochondrial dysfunction in CP lock macrophages into glycolytic, pro-fibrotic phenotypes. Similarly, Th17 cells adopt glycolytic metabolism to sustain IL-17 production, whereas Treg suppressive function depends on intact oxidative phosphorylation, which is compromised in chronic disease. Iron overload and dysregulated neddylation further amplify oxidative stress and fibrotic signaling. These immune and metabolic alterations converge on PSC activation, establishing self-sustaining fibrotic loops. This review delineates the spatiotemporal dynamics of innate and adaptive immune cells across disease phases, emphasizing therapeutic opportunities targeting macrophage polarization, Th17/Treg balance, PSC-immune crosstalk, and metabolic checkpoints to interrupt AP-to-CP progression.
Abstract Objective: This study aims to systematically compare the epidemiological patterns and long-term trends of pancreatitis burden between China and the United States. Methods: Using the Global Burden of Disease (GBD) 1990–2023 data, we analyzed the burden of pancreatitis in China and the United States, including prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Temporal trends were assessed using Joinpoint regression and age–period–cohort (APC) analysis. Socioeconomic inequality was evaluated using the slope index of inequality (SII) and concentration index (CIX) based on socio-demographic index (SDI), while alcohol-attributable burden was quantified using the population attributable fraction (PAF) approach. Results: In 2023, China had 515,000 prevalent pancreatitis cases vs . 403,000 in the United States, but lower age-standardized prevalence (24.26 vs . 81.31), incidence (23.70 vs . 51.11), mortality (0.42 vs . 1.05), and DALY rates (13.10 vs . 35.99) per 100,000. From 1990 to 2023, the age-standardized burden declined more rapidly in China, with greater reductions in females, whereas the United States males had higher mortality and DALY rates than females. APC analysis showed pronounced age effects in both countries but declining cohort risks only in China. Pancreatitis burden was higher in high-SDI regions and alcohol-attributable burden remained higher in the United States than in China. Conclusions: China had a higher absolute number of pancreatitis cases but a lower and faster-declining age-standardized burden than the United States. Targeted prevention strategies addressing aging, alcohol-related risks, and socioeconomic disparities are needed.
Abstract Objective: Pancreatic cancer (PC) remains a major global health burden characterized by high mortality and substantial socioeconomic inequality. This study compared long-term trends, inequality patterns, and risk-factor transitions of PC burden in China and the United States from 1990 to 2023. Methods: Using Global Burden of Disease Study (GBD) 1990–2023 data, we analyzed incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of PC. Temporal trends were assessed using Joinpoint regression analysis, calculating annual percent changes (APCs) and average annual percent changes (AAPCs). Socioeconomic inequalities were evaluated using the slope index of inequality (SII) and concentration index (CIX). Population attributable fractions (PAFs) were used to quantify major risk factors. Results: In 2023, China had more cases than the United States (103,000 vs. 66,000) but lower age-standardized prevalence (4.51 vs. 11.19), incidence (5.13 vs. 10.53), mortality (4.97 vs. 9.56) and DALYs per 100,000. From 1990 to 2023, burden increased in both countries, although age-standardized DALYs declined slightly in China (AAPC −0.15%) and increased in the United States (0.12%). Burden peaked at 60–74 years in China and shifted to older ages in the United States. Sex differences diminished with age and became non-significant in the oldest age groups. Globally, the burden remained concentrated in high socio-demographic index (SDI) with widening inequality. High fasting plasma glucose surpassed tobacco use as the leading attributable risk factor in the United States and became a major contributor in China. Conclusions: China had a higher absolute burden but lower age-standardized rates (ASR) than the United States. The United States burden was more concentrated in older age groups, while the global burden remained concentrated in high-SDI regions with widening inequality. Rising high fasting plasma glucose underscores the need for metabolic risk management in PC prevention.
Abstract Objective: The China Pancreas Data Center (CPDC) was established in 2015 with the support of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association and initiated prospective data collection in 2017. This article reports contemporary real-world evidence on surgical outcomes during 2020–2021, with the objective of assessing and refining clinical practice in pancreatic cancer care in China. Methods: Patients who underwent surgical treatment recorded in CPDC between January 2020 and December 2021 were retrospectively reviewed. Systematic analysis of real-world data encompassing demographics, medical history, comorbidities, symptoms, perioperative assessment and management, surgical interventions, postoperative complications, pathological findings, and overall survival was performed. Results: A total of 6297 pancreatic cancer patients who underwent surgical treatment from 65 centers across China were enrolled for analysis during 2020–2021. The median age was 64 years, and the male-to-female ratio was 1.2:1. Abdominal pain and jaundice were the most common symptoms. Approximately 62.6% of patients presented with pancreatic head/neck tumors, and the distribution of disease stage (I–IV) was 32.5%, 44.7%, 18.7%, and 4.1%, respectively. Minimally invasive surgery was performed in 30.4% of patients, with a conversion rate of 24.9%. Postoperative complication rates by Clavien–Dindo (I–V) were 52.6%, 33.2%, 12.7%, 1.0%, and 0.6%, respectively. The predominant neoadjuvant and adjuvant chemotherapy regimen was nab-paclitaxel plus gemcitabine (AG). The cohort’s in-hospital, 30-, and 90-day mortality rates were 0.6%, 1.2%, and 3.1%, respectively. And 1-year, 2-year, and 3-year postoperative overall survival rates were 75.8%, 53.3%, and 42.0%, respectively. Conclusions: Surgical management of pancreatic cancer in China exhibited regional and center-based concentration. The adoption of minimally invasive pancreatic surgery, surgical safety metrics, and outcomes reported herein align with established benchmarks from international high-volume pancreatic centers. Establishment and promotion of nationwide benchmarks and standardized protocols for pancreatic surgery are warranted.
Abstract Objective: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with distinct tumor biology that drives rapid progression and poor therapeutic response. A prominent feature of PDAC is abnormal glycosylation, especially hypersialylation, which involves excessive sialic acid expression and contributes to tumor growth and immune evasion. Sialyltransferases (STs) mediate hypersialylation; however, the specific enzymes involved in PDAC progression remain unclear. This study aims to identify and characterize key sialyltransferases in PDAC. Methods: We integrated RNA sequencing data and clinical information from PDAC patients obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases databases. A six-gene prognostic model based on STs expression was developed using Least Absolute Shrinkage and Selection Operator regression and validated across independent PDAC cohorts. Bioinformatic analyses evaluated associations between ST expression and survival outcomes, immune infiltration, immune checkpoint expression, tumor mutational burden, and drug sensitivity. Single-cell RNA sequencing and multiplex immunofluorescence (mIHC) were employed to investigate interactions between ST-expressing tumor cells and immune cells. Functional validation was performed thourgh in vitro knockdown experiments to assess the effects of key ST on carbohydrate antigen (CA)19-9 synthesis in PDAC cells. Results: The STs-based prognostic model showed strong predictive power (area under the curve=0.797), with β-galactoside α-2,3-sialyltransferase 1 (ST3GAL1) contributing most significantly. ST3GAL1 was markedly overexpressed in PDAC compared to normal tissue and was associated with worse overall survival (hazard ratio: 1.45, P <0.001, 95% confidence interval: 1.21–1.75). High ST3GAL1 expression was linked to an immunosuppressive tumor microenvironment characterized by reduced CD8 + T cells, elevated neutrophil infiltration, and increased M2 macrophages. Single-cell analysis and mIHC confirmed a positive correlation between ST3GAL1 + tumor cells and neutrophil infiltration. Notably, ST3GAL1-driven α2,3-sialylation was critical for CA19-9 biosynthesis. Knockdown of ST3GAL1 in PDAC cell lines significantly decreased CA19-9 expression, highlighting its critical role in generating this key tumor biomarker Additionly, ST3GAL1 knockdown predominantly reduced CA19-9 expression and suppressed proliferation and migration in vivo and in vitro . Conclusion: Our integrative analysis highlights ST3GAL1 as a potential key prognostic ST in PDAC, associated with both an immunosuppressive tumor microenvironment and CA19-9 production.
Solid pseudopapillary neoplasm (SPN) of the Pancreas is a low-grade malignant pancreatic tumor characterized by low incidence and a predilection for young female patients. It exhibits unique histological and biological features, and its diagnosis and management differ significantly from those of more common pancreatic ductal adenocarcinoma and pancreatic cystic neoplasms, or the less common pancreatic neuroendocrine neoplasms. Surgical resection yields favorable outcomes for SPN; however, a minority of patients experience recurrence and metastasis. High-risk factors for recurrence and metastasis are increasingly being identified. To incorporate recent advances in the diagnosis and management of SPN and to advance the field, this review summarizes the highest level of evidence within the discipline, incorporating clinical expert experience. The goal is to summarize diagnostic and therapeutic strategies for SPN, thereby enhancing overall clinical outcomes.
Objective: Total pancreatectomy (TP) is an invasive surgery, resulting in pancreatic endocrine and exocrine dysfunction. With increasing indications for pancreatic neoplasms, including pancreatic ductal adenocarcinoma (PDAC), understanding long-term metabolic adaptation after TP is essential for survivorship care. Methods: We retrospectively analyzed 160 TP cases at Tohoku University Hospital between 2003 and 2024 and evaluated the prognosis. A subset of 20 long-term survivors (>10 years) underwent longitudinal assessment of nutritional parameters, body mass index (BMI), skeletal muscle index (SMI), and steatotic liver disease (SLD) preoperatively and at 3 to 6 months, 1, 5, and 10 years postoperatively. Results: PDAC patients (n = 87) had significantly worse survival than non-PDAC patients (n = 73) (10-year survival: 16.2% vs 70.7%; hazard ratio (HR), 6.92; P < .001). Serum albumin recovered within 3 to 6 months and remained stable for 10 years. BMI recovered in both sexes by 5 years, but muscle mass showed a striking sex disparity. Males regained preoperative SMI, while females suffered persistent loss (35.5-30.9 cm(2)/m(2) at 10 years). The new-onset SLD occurred far more frequently in females (37.5% at 3-6 months; 55.6% at 1 year) than males (0%-11.1%). Notably, the dramatic reduction of BMI and SMI was more frequently associated with the development of SLD after TP in females than in males. Conclusions: This is a pioneering study to describe the sex-specific long-term metabolic changes after TP. Females experienced persistent muscle loss and new-onset SLD after TP, highlighting the need for sex-specific long-term follow-up to improve quality of life and outcomes.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal digestive malignancies, with a 5-year survival rate <10%. Multimodal strategies are thus essential for improving prognosis. Recent advances in molecular biology and genomics have established targeted therapy as a pivotal approach to overcome limitations of conventional chemotherapy, stimulating extensive development of PDAC-targeted agents. This review synthesizes targeted therapeutics for PDAC reported between 2020 and 2025, analyzing literature from PubMed/MEDLINE, Scopus, and Cochrane Library. After systematic screening, 87 studies were categorized into 6 mechanistic classes. Although targeted agents demonstrate accelerated development, their clinical efficacy remains modest overall and typically requires chemotherapy combinations. Emerging research continues to elucidate PDAC pathogenesis, further refining targeted therapies with significant promise.
Objective:. Despite radical resection, postoperative recurrence of nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) remains common, particularly among high-risk patients. This study evaluates the adjuvant therapeutic potential of Qizhen Yiliu Formula (QZYL) in a multicenter real-world cohort. Methods:. We retrospectively analyzed patients with NF-PanNETs treated at 5 tertiary centers in China between 2010 and 2022. Patients were divided into QZYL and control groups based on receipt of QZYL as postoperative adjuvant therapy. Baseline differences were adjusted using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) sensitivity analysis. Three hundred and eighty-five eligible patients were analyzed, with 112 matched pairs. Results:. QZYL treatment was associated with longer recurrence-free survival (RFS) compared with controls (median: 78.0 vs 71.9 months; hazard ratio [HR] = 0.60, P = .027), with higher 24-, 36-, and 60-month RFS rates (90.92% vs 80.36%, 86.14% vs 70.07%, 64.97% vs 55.56%, respectively). Subgroup analyses demonstrated trends favoring QZYL across high-risk strata (Ki-67 index 10%–20%, tumor size ≥4 cm, lymph node metastasis, and pathological invasion), although statistical significance varied between PSM and IPTW analyses. Among patients receiving other adjuvant therapies, QZYL use was associated with improved outcomes (HR = 0.56, P = .070). Safety analysis indicated that QZYL did not increase the overall incidence of adverse events (P = .847) and was associated with a lower incidence among patients receiving other adjuvant therapies (P = .010). Conclusions:. QZYL use was associated with a reduced risk of postoperative recurrence in patients with high-risk NF-PanNET, suggesting its role in postoperative management. Prospective validation is warranted.
Pancreatic surgery is a highly challenging abdominal procedure with high morbidity, where nontechnical skills (NTS)—situational awareness, decision-making, communication, leadership—are critical to reducing adverse outcomes. However, traditional NTS training like didactic lectures and apprenticeships has limitations like high simulation costs and subjective assessments. This review synthesizes artificial intelligence (AI)’s role in transforming pancreatic surgical NTS training: it enhances situational awareness via real-time feedback and 3D reconstruction, improves decision-making through anatomical guidance and immersive simulations, optimizes communication by decoding team mental models, and fosters adaptive leadership. It emphasizes aligning AI with socio-technical system perspective to avoid cognitive dependence, aiming to boost surgeons’ NTS and elevate patient care.
In recent years, lifestyle and dietary transitions have driven a marked rise in hypertriglyceridemia as a cause of acute pancreatitis, particularly in Asian countries, including China, where hypertriglyceridemia now ranks as the second most common etiology. The relationship between triglycerides and acute pancreatitis is both complex and bidirectional, in that hypertriglyceridemia can precipitate acute pancreatitis and is linked to complications, greater disease severity, and poorer outcomes, while the onset of pancreatitis may itself elevate triglyceride levels further. This reciprocal interaction poses major challenges for diagnosis and prognostic evaluation when assessments rely solely on serum triglyceride concentrations. At present, there are no internationally consistent criteria for the diagnosis or prognostic assessment of hypertriglyceridemic acute pancreatitis. Therefore, elucidating the causal pathways and underlying mechanisms connecting triglycerides and pancreatitis is essential for improving diagnostic accuracy, refining risk stratification, and guiding the identification of therapeutic targets. This review synthesizes recent advances with a particular focus on causality and pathophysiological mechanisms, including cytotoxic effects of free fatty acids, microcirculatory disturbance, calcium overload, inflammatory response, oxidative stress, and genetic factors. It also highlights critical considerations regarding the development of standardized international diagnostic criteria. These include recognition of hypertriglyceridemia as an independent etiology, integration of the dynamics of free fatty acids into diagnostic algorithms, and clarification of the pathophysiological role of mild-to-moderate triglyceride elevations. By addressing these gaps, we aim to provide a foundation for consensus-building that will support more precise diagnosis and effective clinical management of this increasingly prevalent condition.
Objective:. Pancreatic ductal adenocarcinoma (PDAC) is characterized by early dissemination, rapid progression, and poor prognosis. Focal adhesion kinase (FAK) has been implicated in PDAC metastasis, but its downstream mediators remain incompletely defined. Choline kinase alpha (CHKα), a key enzyme in choline metabolism, has been recognized as a pro-metastatic factor. This study aims to investigate the regulatory mechanisms linking FAK to CHKα expression are not fully understood. Methods:. We employed correlation analysis, structural modeling, immunofluorescence, co-immunoprecipitation, and functional assays to investigate the role of STAT1 in the FAK-CHKα axis. The impact of CHKα inhibition was evaluated in vitro and in vivo. The anti-metastatic efficacy of CHKI-03, the CHKα inhibitor developed by our team, and reference compound RSM-932A were compared through intrasplenic injection liver metastasis model. Results:. STAT1 was identified as a critical mediator of the FAK-CHKα axis. FAK directly interacted with STAT1 and modulated its expression. Silencing STAT1 reduced CHKA expression at both mRNA and protein levels and attenuated FAK-driven cell migration and invasion. Chromatin immunoprecipitation (ChIP)-Atlas analysis revealed STAT1 binding at the CHKA locus, suggesting direct transcriptional regulation. In vivo, CHKI-03 effectively suppressed PDAC liver metastasis. Conclusion:. Our findings establish STAT1 as a key mediator in the FAK-CHKα axis, driving PDAC liver metastasis. Targeting CHKα with CHKI-03 offers a promising anti-metastatic therapeutic strategy with superior efficacy.
Objective:. Over the past 2 decades, the increasing prevalence of pancreatic diseases has established regenerative therapy for pancreatic cells as a key research focus. This study employs bibliometric analysis to assess the current state of pancreas regeneration research, identify key areas, and predict future trends. Over the past 2 decades, the rising prevalence of pancreatic diseases has positioned regenerative therapy for pancreatic cells as a critical area of research. This study utilizes bibliometric analysis to assess the current state of pancreas regeneration research, identify key focus areas, and forecast future trends. Methods:. A systematic search and evaluation were performed on the annual publication output, major contributing countries and regions, active institutions and authors, core journals, references, and keywords related to pancreas regeneration. This research aimed to comprehensively and objectively analyze the current state of research in this field, providing a basis for further exploration and understanding of pancreas regeneration. Relevant publications on pancreas regeneration from January 1, 2004, to August 15, 2024, were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric data were analyzed via HistCite, VOSviewer, CiteSpace, and the bibliometrix R package. HistCite and the bibliometrix R package integrate and classify diverse literature types, while VOSviewer and CiteSpace conduct visual analyses and illustrate the interactions among various bibliographic features. These 2 aspects jointly elucidate the development of pancreas regeneration. Results:. A total of 1027 articles from 69 countries/regions, authored by 5159 researchers and published in 494 journals, were identified. The United States had the highest number of publications on pancreas regeneration (n = 324, 31.5%), followed by China (n = 122, 11.9%), Germany (n = 105, 10.2%), India (n = 96, 9.3%), and Japan (n = 85, 8.3%). The 3 most prolific authors were Susan Bonner-Weir from Harvard Medical School (n = 10) and Alexandra E. Butler from the Royal College of Surgeons in Ireland (n = 10). Similarly, Patrick Collombat, affiliated with the National Institute of Health and Medical Research, has published 10 academic works. PLOS One published the greatest number of articles on pancreas regeneration (n = 32), followed by Diabetes (n = 25), Diabetologia (n = 22), Pancreas (n = 20), and Gastroenterology (n = 16). “Regeneration” was the most frequently mentioned keyword, whereas “diabetes,” “antioxidant activity,” and “identification” emerged as trending topics. Conclusion:. The United States has led in research on pancreas regeneration. Most research outputs are published in journals focused on pancreatic diseases and pathology, with a primary emphasis on β cells. Future research is expected to explore the molecular mechanisms of inflammation, the precise process of pancreas regeneration, and the mechanisms of pancreas regeneration related to diabetes. In addition, therapeutic strategies represent a crucial research dimension.
Objective::Patients with chronic pancreatitis commonly experience abdominal pain, anxiety, depression, reduced mobility, and difficulty performing daily activities or maintaining employment. These factors contribute to diminished quality-of-life and high healthcare utilization. This study aims to explore the relationship between specific quality-of-life domains among patients with chronic pancreatitis.Methods::A 55-item online survey was administered to patients with the diagnosis of chronic pancreatitis at 3 Mayo Clinic sites from December 26, 2023, to December 26, 2024. The survey included validated questions assessing demographic, clinical, and quality-of-life metrics using EuroQol 5-Dimension 5-Level instrument—a standardized assessment tool that evaluates 5 key health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.Results::Of the 298 patients with chronic pancreatitis who completed the survey, employed patients had decreased odds of reporting problems with mobility (odds ratio [OR] = 0.45, P < .05), self-care (OR = 0.26, P < .01), usual activities (OR = 0.47, P <.05), and anxiety/depression (OR = 0.41, P < .05). Similarly, older patients had decreased odds of reporting problems with self-care (OR = 0.91, P < .01), usual activities (OR = 0.96, P < .01), pain/discomfort (OR = 0.96, P < .01) and anxiety/depression (OR= 0.92, P < .01). However, Medicare patients had greater odds of reporting problems with self-care (OR = 5.54, P < .01) and pain/discomfort (OR = 2.58, P < .05). Conclusions::Chronic pancreatitis impacts multiple dimensions of quality-of-life beyond pain. The EuroQol 5-Dimension 5-Level tool enables comprehensive assessment of physical and mental health. Our findings highlight key associations between patient characteristics and quality-of-life domains, supporting the need for individualized, deficit-targeted interventions. These results also suggest a potential role for vocational rehabilitation in promoting functional recovery and enhancing overall well-being in individuals with chronic pancreatitis.
