Introduction

Pancreatic fluid collection (PFC) often necessitates drainage or necrosectomy. Recently, minimally invasive endoscopic treatments have emerged as the first-line approach. However, limited data are available on the outcomes of such treatments in elderly patients.

Aims & Methods

This study aimed to evaluate the clinical outcomes of endoscopic treatment for PFC in elderly patients using a large-scale, multicenter cohort from Japan. This retrospective analysis included 349 patients who underwent endoscopic ultrasound-guided pancreatic fluid drainage (EUS-PFD) for PFC. The study cohort, derived from 11 institutions within the WONDERFUL study group between 2010 and 2021, was stratified into an elderly group (n = 54, aged ≥75 years) and a non-elderly group (n = 295). Treatment outcomes were compared between the two groups.

Results

The Charlson Comorbidity Index (CCI) of ≥2 was significantly more prevalent in the elderly group (28.4% vs. 10.1%, p < 0.001). No significant differences were observed between the groups in terms of gender, BMI, etiology of pancreatitis, or indications for treatment. PFC characteristics, including lesion proportion, size, morphology, and the prevalence of walled-off necrosis (WON), were comparable between the groups. However, pre-treatment white blood cell counts were significantly higher in the elderly group (10,250/μL vs. 8,060/μL, p= 0.003), and pre-treatment albumin levels were significantly lower (2.35 g/dL vs. 2.85 g/dL, p < 0.001). Clinical success rates of endoscopic treatment were similar between the elderly and non-elderly groups (82% vs. 87%, p = 0.29), as were rates of endoscopic necrosectomy (24.1% vs. 31.9%, p = 0.54), adverse events (16.7% vs. 17.6%, p = 0.99), surgical conversion (1.9% vs. 7.1%, p = 0.22), PFC recurrence (1.9% vs. 9.4%, p = 0.10), time to clinical success (41 days vs. 46 days, p = 0.49), number of endoscopic treatments (2 vs. 3, p = 0.19), and total treatment duration (86 minutes vs. 114 minutes, p = 0.54). However, the mortality rate was significantly higher in the elderly group (16.7% vs. 5.1%, p = 0.005). Multivariate analysis identified a statistically significant association between CCI ≥2 and mortality (odds ratio [OR]: 5.37, 95% confidence interval [CI]: 1.59–11.4, p = 0.007), while the elderly group showed a trend toward significance (OR: 3.31, 95% CI: 0.93–11.7, p = 0.06).

Conclusion

Elderly patients undergoing endoscopic treatment for PFC exhibited higher comorbidity burdens compared to their younger counterparts, as reflected by higher CCI scores. Despite comparable safety and clinical efficacy outcomes, mortality was significantly higher in the elderly cohort. These findings underscore the importance of comprehensive risk assessment, particularly considering systemic comorbidities, prior to initiating endoscopic treatment for PFC in elderly patients.

Introduction

Pancreatic fluid collections (PFCs) are significant local complications that can arise from acute pancreatitis, and its management often involves drainage, although the benefits of metal stents over plastic stents remain uncertain. This meta-analysis compared the efficacy and safety of metal stents versus plastic stents for endoscopic ultrasound (EUS)-guided drainage of PFCs.

Aims & Methods

We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing metal with plastic stents for drainage of PFCs. The odds ratio (OR) was used for binary outcomes and the mean difference (MD) for continuous outcomes with their respective 95% confidence interval (CI).

Results

This study included eight RCTs and over 500 patients. Procedure duration was shorter in the metal stent arm compared with the plastic stent arm (MD -10.63; 95%CI -16.12 to -5.15, p<0.001). However, there was no statistically significant difference between metal and plastic stents in clinical success (p=0.78), technical success (p=0.65), overall mortality (p=0.48), recurrence (p=0.23), number of interventions (p=0.85), need of necrosectomy (p=0.35), need of surgery (p=0.35), length of hospitalization (p=0.86), exocrine insufficiency (p=0.54), endocrine insufficiency (p=0.77), and AEs (p=0.36).

Conclusion

Metal stents for EUS-guided drainage of PFCs are associated with a shorter procedure duration. Besides that, it did not improve other clinically relevant outcomes in comparison with plastic stents.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) ranks among the most aggressive malignancies, with a five-year survival rate below 10%. Its poor prognosis stems from late diagnosis, rapid disease progression, and marked resistance to conventional therapies, largely driven by frequent KRAS and TP53 mutations. These genetic alterations disrupt multiple cellular processes, including intracellular calcium (Ca²⁺) signaling, which plays a critical role in tumor progression. Plasma membrane calcium ATPase isoform 4 (PMCA4) is a major regulator of cytosolic Ca²⁺ levels, essential for maintaining cellular homeostasis. Elevated expression of PMCA4 in PDAC has been associated with enhanced cell migration, apoptosis resistance, and poor clinical outcomes. PMCA4 localizes at focal adhesions, supporting motility and metastatic potential. Paradoxically, PMCA4 dysfunction can lead to Ca²⁺ overload, activating oncogenic pathways that drive cell proliferation and survival. The cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel, also modulates calcium homeostasis. CFTR deficiency or dysfunction impairs PMCA4 activity, while paradoxically inducing its overexpression, likely as a compensatory mechanism in response to altered Ca²⁺ signaling. This functional interaction between CFTR and PMCA4 is particularly relevant in pancreatic ductal epithelial cells, where both proteins co-localize at the apical membrane. Their coordinated function is crucial for regulating calcium and chloride transport, and its disruption may contribute to PDAC progression.

Aims & Methods

This study aim to investigate whether CFTR deficiency contributes to PMCA4 overexpression in PDAC cells and whether pharmacological restoration of CFTR function using Trikafta can normalize calcium signaling and modulate tumor cell behavior. Therefore we utilized both human pancreatic ductal organoids (hPOs) and the Capan-1 PDAC cell line to assess calcium and chloride transport. Intracellular calcium levels were measured using FURA-2-AM, and chloride efflux was monitored with MQAE dye. Immunofluorescence staining was employed to analyze the expression and localization of CFTR, PMCA4, SOX9, Vimentin, and α-SMA.

Results

We successfully cultured human pancreatic organoids from adult pancreas-derived stem cells using standard 3D culture conditions. Following the establishment of primary organoids, we performed the first passage to expand the culture. The organoids were then dissociated into single cells and plated onto 24 mm cover glasses for further analysis. Our experiments confirmed the expression of ductal markers in 2D human pancreatic organoids (hPOs) with the lack of mesenchymal markers Vimentin, and α-SMA. Immunofluorescent staining was visualized using a Zeiss LSM880 confocal microscope. Functional assays revealed that Capan-1 cells exhibited significantly reduced Ca²⁺ and Cl⁻ efflux compared to hPOs, indicating impaired CFTR and PMCA acitivty. Notably, treatment with Trikafta, a clinically approved CFTR modulator, successfully restored CFTR and PMCA4 activity in Capan-1 cells.

Conclusion

Our findings indicate that CFTR dysfunction contributes to the increased PMCA expression in PDAC cells, which can be ameliorated by Trikafta treatment. This study highlights the critical interplay between CFTR dysfunction and calcium homeostasis in pancreatic ductal adenocarcinoma (PDAC). These results underscore the relevance of epithelial ion transport pathways in PDAC pathophysiology and support further investigation of adjunctive approach in PDAC treatment.

Introduction

Neurofilaments are cytoskeletal proteins specific to neuronal tissue. As their blood levels rise following neuronal damage, they are increasingly being studied as the biomarkers for neuroaxonal injury in various conditions, such as Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, or type 2 diabetes mellitus (T2DM) related neuropathy. Pancreatic ductal adenocarcinoma (PDAC) is a malignant disease known for its poor prognosis, rapid spread, silent progression, and lack of effective diagnostic tools in its early stages. Perineural and/or endoneural invasion and neuronal damage are hallmarks of PDAC.

Aims & Methods

The aim of our study was to measure the levels of neurofilament light chain (NfL) in patients with PDAC, T2DM, chronic pancreatitis (ChP), and healthy controls. We used a Single Molecule Array (Simoa; Quanterix) to measure NfL levels in patients with PDAC (n=50, mean age 63.16 ± 8.8 years), T2DM (n=42, mean age 61.6 ± 8.4 years), ChP (n=30, mean age 56 ± 13.6 years), and healthy controls (n=46, mean age 54 ± 9.06 years).

Results

The following concentrations of NfL were obtained from the samples: PDAC: 30.31 ± 39.79 pg/ml, T2DM: 12.59 ± 10.19 pg/ml, ChP: 16.64 ± 13.78 pg/ml, Healthy controls:
7.93 ± 4.18 pg/ml. NfL levels were significantly different between PDAC and healthy controls (p < 0.001) and between T2DM and healthy controls (p < 0.001). Differences between other
groups were not significant. Further analysis confirmed age as a significant predictor of NfL levels (p < 0.001), indicating that NfL levels increase with age by 0.48 per year. We did not find a
significant impact of glycemic control (represented by glycated haemoglobin levels) or body mass index on NfL concentrations. Because of the correlation between age and NfL levels, we examined the relationship between age, diagnosis, and NfL levels using a statistical model comparison approach. After controlling for age, we found that PDAC and ChP showed significantly higher NfL levels compared to T2DM and healthy controls (p < 0.01). No significant differences were found between T2DM and healthy controls

Conclusion

This is the first study to date that evaluates serum levels of NfL in PDAC and chronic pancreatitis. The results support the possible role of NfL as a biomarker in certain non-neurological conditions. Elevated serum levels of NfL in PDAC and ChP suggest that this biomarker reflects neuronal damage, which is present in ChP and is a key feature of PDAC, even in the early stages of the disease.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that poses significant therapeutic challenges. In this regard, the identification of prognostic biomarkers is crucial to improve the prediction of clinical outcomes and guide therapeutic decisions. Tumour-associated autoantibodies (TAAbs) have been identified as prognostic biomarkers in several types of cancer, as they can be generated before the first clinically detectable signs of disease.

Aims & Methods

The aim of this study was to identify TAAbs that can be used as prognostic biomarkers in PDAC. 80 sera from patients with PDAC, divided into four groups according to disease stage, were included in the study: patients with premalignant lesions (n = 20), patients undergoing curative resection after diagnosis (CR) (n = 20), patients with unresectable advanced locoregional disease (LA) (n = 20) and patients with metastatic disease (MT) (n = 20). Sera from each group were analysed divided into 4 pools of 5 samples each using the HuProt Human Protreome microarray v4.0 (CDI Laboratories, Baltimore, MD). Candidate TAAbs with high specific reactivity in MT and/or LA samples were selected according to the following criteria: z-score ≥ 3 in at least 2/4 pools and fold-change > 1.2. The RNAseq data collected in the Human Protein Atlas were used to determine protein expression levels and prognostic value. The GSE15471, GSE28735 and GSE16515 databases were used to compare expression levels with those of healthy subjects without the disease.

Results

43 TAAbs demonstrated high levels of specific reactivity in samples from MT and/or LA patients. Of these highly recognised proteins, 15 were selected for showing notable levels of expression in tumour tissue from PDAC patients and prognostic capacity in some types of cancer. Of these 15, 2 proteins involved in tumour development were identified. Survival analyses showed that six of the 15 selected proteins were significantly associated with a worse prognosis in PDAC patients (p < 0.05). Finally, in the comparison with control tumour tissue, 5 proteins were identified with significantly higher expression in patients diagnosed with the disease (p < 0.05 in at least 2 of the cohorts used).

Conclusion

15 TAAbs have been identified as promising candidates for prognostic biomarkers in PDAC. Further validation studies are required to confirm their prognostic value and to develop a robust biomarker signature with potential for clinical application and market translation.

Introduction

The aetiology of acute pancreatitis remains elusive in 10-30% of patients after clinical, biological and morphological investigations. Endoscopic ultrasound has shown promise and is particularly effective in exploring the bilio-pancreatic region.

Aims & Methods

The aim of our study was to evaluate the contribution of endoscopic ultrasound to the aetiological diagnosis of unexplained acute pancreatitis.
This is a retrospective descriptive study of 89 patients who underwent endoscopic ultra sound for unexplained acute pancreatitis between January 2010 and January 2025.

Results

The mean age of our patients was 55 +/- 16.3 years, with extremes ranging from 17 to 89 years. The sex ratio (M/F) was 0.81, with a slight female predominance of 55.1%. A history of previous acute pancreatitis was found in 31.9% of cases, and 16.3% of patients had undergone cholecystectomy. The diagnostic yield in our study was 68%. Biliary origin was retained in 40.4% (n=36) of patients, 19 of whom underwent complementary ERCP at the same anaesthetic time. Neoplastic pathology was found in 32.5% of cases (n=30). Chronic pancreatitis was reported in 22.4% of patients (n=20). Two cases of pancreas divisum, one case of sphincter of Oddi dysfunction and one case of choledocele were found. In the remaining 32% of cases, the endoscopic ultrasound was normal and no cause could be found.

Conclusion

Endoscopic ultrasound is currently an indispensable tool in the etiological investigation of unexplained acute pancreatitis. In our study, the diagnostic efficiency was around 68%.

Introduction

Acute pancreatitis (AP) is a common gastrointestinal disorder with significant morbidity and mortality, particularly in severe cases (SAP). Early prediction of SAP is crucial for timely intervention and improved patient outcomes. Traditional scoring systems like Ranson, BISAP, and APACHE II have limitations in accuracy and timeliness. Machine learning (ML) has shown promise in enhancing SAP prediction, but the potential of advanced architectures like Transformer models remains unexplored. This study aims to develop a Transformer-based model for SAP prediction and compare its performance with traditional ML methods.

Aims & Methods

The primary aim of this study was to develop a Transformer-based prediction model for acute pancreatitis severity and evaluate its performance compared to traditional machine learning models. Retrospective data from 722 AP patients admitted to the Second Affiliated Hospital of Guilin Medical University between January 2020 and June 2024 were analyzed. Patient data included 24-hour admission laboratory indicators such as electrolytes, liver function, renal function, and inflammatory markers. To construct the prediction model, a comprehensive workflow was designed. Data preprocessing involved feature vectorization using One-Hot encoding, missing value imputation using the K-Nearest Neighbor (KNN) algorithm, normalization of feature values to a [0, 1] range, and handling class imbalance using Synthetic Minority Over-Sampling Technique (SMOTE). Feature selection was performed by dividing patients into SAP and MAP groups, identifying features with significant differences using non-parametric tests, and ranking features by their relevance through correlation analysis. Features causing a decline in AUC during incremental addition were removed to optimize the feature set. The Transformer model, leveraging self-attention mechanisms to process sequential data, was trained alongside traditional ML models (Logistic Regression, Decision Tree, Random Forest, and XGBoost). Five-fold cross-validation was used to prevent overfitting, and model performance was evaluated using metrics such as AUC, accuracy, precision, recall, F1 score, and specificity. SHAP analysis was employed to interpret the Transformer model's predictions, providing insights into the contribution of each feature to the model's output.

Results

The Transformer model outperformed traditional ML models (Table 1), achieving an AUC of 0.9662 and exceeding 0.90 in all metrics. It maintained robust performance even with minimal training data (AUC: 0.8437 at 5% training). SHAP analysis highlighted key predictors (calcium, amylase, basophil percentage, CO2 binding capacity), aligning with clinical relevance.

Table 1. Performance metrics comparison of different models.

Conclusion

The Transformer model demonstrated superior accuracy, generalizability, and interpretability for SAP prediction, particularly in small datasets. Its clinical utility is enhanced by SHAP-driven insights into key predictors. Retrospective design limits prospective validity; future work should validate the model in larger cohorts and integrate additional biomarkers. This study supports the potential of transformer in medical prediction to improve patient outcomes through timely interventions.

References

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