Introduction

Biliary stones are a leading cause of acute pancreatitis (AP). Endoscopic Retrograde Cholangiopancreatography (ERCP) is the standard of care when concomitant cholangitis or confirmed choledocholithiasis is present¹. However, spontaneous migration of biliary stones in the latter occurs in approximately 20% of cases², potentially exposing patients to the inherent risks of ERCP without a definitive therapeutic benefit.

Aims & Methods

This study aimed to identify predictors of spontaneous common bile duct stone clearance in patients with acute biliary pancreatitis. We conducted a retrospective cohort study of consecutive patients diagnosed with acute pancreatitis and confirmed choledocholithiasis, who subsequently underwent ERCP. Patients with a prior ERCP or concurrent acute cholangitis were excluded.

Results

Forty-four patients were included, 61.4% female with a mean age of 67±18 years. In 31.8% of cases, no stone was identified at ERCP, suggestive of spontaneous resolution. The median interval from admission to ERCP was 10 days and did not significantly differ between patients with and without stones (p=0.872). Serum levels of total bilirubin (2.5±2.0 vs. 2.3±2.9 mg/dL, p=0.825), AST (160±31 vs. 171±50 U/L, p=0.505), and alkaline phosphatase (267±135 vs. 210±70 U/L, p=0.187) were not significantly different between groups with and without stones at ERCP, respectively. Neither cholecystectomy status (p=0.722), common bile duct dilation on imaging (p=0.955), nor number of stones (p=0.829) correlated with spontaneous clearance. Interestingly, patients without lithiasis at ERCP had significantly smaller common bile duct stones on imaging compared to those with retained stones (5 ± 3 mm vs. 8 ± 5 mm, p=0.025). Stone size was an independent predictor of spontaneous resolution in the multivariate analysis (OR = 1.24; 95% CI: 1.01–1.52; p = 0.036), with a diameter ≥7 mm yielding a sensitivity of 63% and a specificity of 78.6% for predicting the presence of stones at ERCP.

Conclusion

Spontaneous passage of biliary stones is common in the context of acute biliary pancreatitis, particularly when their size is ≤7 mm. These findings support a risk-adapted strategy, in which Endoscopic Ultrasound may be employed to confirm choledocholithiasis immediately prior to ERCP in patients with small biliary stones.

References

1. Manes, G. et al. Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 51, 472–491 (2019).
2. Sperna Weiland, C. J. et al. Suspected common bile duct stones: reduction of unnecessary ERCP by pre-procedural imaging and timing of ERCP. Surg. Endosc. 37, 1194–1202 (2023).

Introduction

The consequences of chronic pancreatitis (CP) may not be exclusively limited to the pancreas or restricted to the gastrointestinal tract but could also be systemic. To date, the relationship between chronic pancreatitis and cardiovascular risk factors has not been studied extensively. We conducted a systematic review and meta-analysis to examine if the combination of chronic inflammatory changes may possibly place CP patients at risk for cardiovascular disease.

Aims & Methods

We systematically searched PubMed, Scopus, and Cochrane Register of Controlled Trials for observational studies that compared major cardiovascular outcomes in patients with chronic pancreatitis. The outcomes explored were: (1) acute coronary disease/myocardial infarction; (2) hypertension; (3) hyperlipidemia; and (4) diabetes mellitus. We computed odds ratio (OR) for binary endpoints, with 95% confidence intervals (CI). Heterogeneity was examined I² statistics; p values less than 0.10 and I² > 25% were considered significant for heterogeneity.

Results

Four observational studies comprising a total of 57,721 patients with chronic pancreatitis were included in this meta-analysis. The most consistent finding across studies was a significantly higher risk of diabetes mellitus in patients with chronic pancreatitis compared to a control group without chronic pancreatitis (OR 4.77; 95% CI 1.32–17.28; p=0.017; I²=100%). In contrast, no statistically significant associations were found between chronic pancreatitis and other cardiovascular outcomes, including cerebrovascular disease (OR 1.59; 95% CI 0.98–2.57; p=0.05; I²=99.4%), acute coronary syndrome/myocardial infarction (OR 1.35; 95% CI 1.00–1.82; p=0.049; I²=95.4%), hypertension (OR 0.52; 95% CI 0.30–7.61; p=0.608; I²=99.9%) or hyperlipidemia (OR 2.60; 95% CI 0.36–18.77; p=0.342; I²=100%).

Conclusion

The results of our meta-analysis suggest that chronic pancreatitis is not associated with increased risk of cardiovascular disease despite being associated with a higher risk of diabetes mellitus.

Introduction

Cadmium (Cd), a group 1 carcinogen, is linked to the development of pancreatic cancer, though its dose-response relationship, especially at low exposure levels, is not well-defined.

Aims & Methods

To investigate the relationship between Cd exposure and the risk of pancreatic cancer through a meta-analysis focusing on pooled relative risk, biomarker comparisons, and dose-response relationships.
Methods: This meta-analysis adhered to PRISMA guidelines and applied the PECO framework. A systematic search of key databases including PubMed, Cochrane Library, Web of Science, EMBASE, ScienceDirect, and ProQuest was carried out without language restrictions. Studies that met the predefined PECO criteria were chosen, extracting data on effect estimates such as hazard ratios, odds ratios, and relative risks (RR), along with Cd biomarker concentrations. Analyses involved pooled relative risks, standardized mean differences for biomarker comparisons, and dose-response relationships, utilizing random-effects meta-analysis and meta-regression. Statistical procedures were performed on R version 4.3.0.

Results

Cd exposure was significantly associated with an increased risk of pancreatic cancer, with a pooled RR of 1.42 (95% CI = 1.16–1.73). Subgroup analyses indicated sex-specific variations: men demonstrated a significant increase in pancreatic cancer risk), while the risk for women was not statistically significant. Dose-response analyses revealed that higher Cd biomarker levels correlated with greater pancreatic cancer risk (β = 0.610, p = 0.035).

Conclusion

Cd exposure is associated with an increased risk of pancreatic cancer, as confirmed by a dose-response relationship and elevated biomarker levels in cases. Cd exposure is a modifiable risk factor for pancreatic cancer, meriting further investigation.

References

1. The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2019;4(12):934-47.
2. Occupational Safety and Health Administration (OSHA). Cadmium - 1910.1027 Washington, D.C., U.S.: U.S. Department of Labor; [cited January 11, 2025]. Available from: https://www.osha.gov/laws-regs/regulations/standardnumber/1910/1910.1027.
3. Smereczański NM, et al. Current levels of environmental exposure to cadmium in industrialized countries as a risk factor for kidney damage in the general population: A comprehensive review of available data. Int J Mol Sci. 2023;24(9).
4. Djordjevic VR, et al. Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies. Environ Int. 2019;128:353-61.
5. Ojajärvi IA, et al. Occupational exposures and pancreatic cancer: A meta-analysis. Occup Environ Med. 2000;57(5):316-24.
6. Chen C, et al. Cadmium exposure and risk of pancreatic cancer: A meta-analysis of prospective cohort studies and case-control studies among individuals without occupational exposure history. Environ Sci Pollut Res Int. 2015;22(22):17465-74.
7. Farahmandian P, et al. Investigating the relationship between exposure to cadmium and the risk of pancreatic cancer: A systematic review and meta-analysis. J Isfahan Med Sch. 2023;41(715):260-9.

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

Endoscopic ultrasound (EUS) elastography has emerged as a valuable tool for assessing pancreatic tissue stiffness, aiding in the differentiation of normal pancreas, chronic pancreatitis (CP), and solid pancreatic masses, including pancreatic adenocarcinoma (PDAC) and cholangiocarcinoma (CC). The newly developed two-dimensional shear wave elastography (2D-SWE) provides real-time, quantitative elasticity maps with improved reproducibility. This study aims to evaluate the performance of 2D-SWE during EUS for differentiating normal pancreas, CP, and solid pancreatic tumors.

Aims & Methods

This prospective study included patients undergoing EUS for pancreatic evaluation. All 2D-SWE measurements were made using the Aplio i800 EUS ultrasound machine. Four groups were analyzed: (1) individuals with a normal pancreas, (2) patients with CP (based on Rosemont criteria), (3) patients with PDAC, and (4) patients with CC (all diagnoses confirmed histopathologically). 2D-SWE was performed during EUS using a linear-array echoendoscope. Quantitative elasticity values (kPa) were recorded for the normal pancreas, CP-affected tissue, and tumor lesions. The diagnostic performance of 2D-SWE was assessed using intraclass correlation coefficient (ICC), receiver operating characteristic (ROC) analysis, and pairwise statistical comparisons.

Results

A total of 30 patients were included (6 normal, 5 CP, 17 PDAC, 2 CC). The intra-observer reproducibility of SWE measurements was excellent (ICC = 0.89). Mean elasticity values significantly differed among groups, with PDAC showing the highest variability (mean SWE = 54.1 ± 45.7 kPa, median = 33.1), CC presenting elevated stiffness (mean SWE = 77.4 ± 11.0 kPa), CP showing heterogeneous values (mean SWE = 57.5 ± 52.3 kPa, median = 43.6), and normal pancreas showing the lowest stiffness (mean SWE = 7.5 ± 3.9 kPa, median = 6.2).
ROC analysis for distinguishing malignant solid tumors (PDAC + CC) from normal pancreas showed excellent diagnostic performance (AUC = 0.93). The optimal cutoff of 17.0 kPa yielded a sensitivity of 84.2%, specificity of 100%, positive predictive value (PPV) of 100%, negative predictive value (NPV) of 66.7%, and overall accuracy of 88%.
Pairwise t-tests confirmed a statistically significant difference between PDAC and normal pancreas (p = 0.0007), with trends observed for CC vs normal (p = 0.0605) and CP vs normal (p = 0.099). No statistically significant differences were observed among solid tumor subtypes (PDAC vs CC, PDAC vs CP, CC vs CP).

Conclusion

2D-SWE during EUS provides highly reproducible and quantitative elasticity values that reliably differentiate normal pancreas from solid pancreatic tumors. This method demonstrates excellent diagnostic performance, particularly in identifying PDAC, and shows promising trends for distinguishing CP and CC, supporting its clinical integration in EUS evaluation protocols.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic tumor that significantly affects its aggressiveness and treatment resistance. Cancer-associated fibroblasts (CAFs) are key components of the desmoplastic stroma and are now recognized as dynamic, heterogeneous cells that contribute to disease progression. While CAFs play a role in creating an immunosuppressive tumor microenvironment (TME), their precise impact on survival and cellular dynamics remains unclear. This study aims to provide an unbiased classification of CAF subtypes and investigate their functional relevance and dynamics in chronic pancreatitis (CP) and PDAC.

Aims & Methods

We conducted single-cell RNA sequencing (scRNA-seq) on 40,000 fibroblasts isolated from resected human CP and PDAC tissues. We clustered the CAFs and examined the driving genes for each subtype. Validating these subtypes involved immunohistochemistry (IHC)-multiplexing on tissue microarrays (TMA) from 126 PDAC and 66 CP patients. Additionally, we performed flow cytometry on human PDAC CAFs and utilized immunocytochemistry (ICC) with our newly identified markers.

Results

Our clustering revealed 11 distinct CAF subtypes. To facilitate future mechanistic experiments, we also analyzed the surface receptor signatures of these enriched subtypes. IHC multiplexing confirmed the existence of these subtypes, with End Stage inflammatory CAFs (iCAFs) (35.7% in PDAC vs. 56.6% in CP) and End Stage myofibroblastic CAFs (myCAFs) (35.3% in PDAC vs. 25.6% in CP) being the most prevalent. Flow cytometry results corroborated IHC findings. Notably, we identified a novel subtype, Lipofibroblast, in both PDAC and CP, with RNA velocity analysis indicating its ability to differentiate into other subtypes, driven by Periostin (POSTN).

Conclusion

The discovery of a novel Lipofibroblast subtype with differentiation potential highlights a new avenue for understanding CAF plasticity and therapeutic targeting in PDAC and CP.

Introduction

Acute pancreatitis (AP) is a common gastrointestinal disorder with significant morbidity and mortality in severe cases. Pre-existing comorbidities and newly developed complications, like heart failure may influence outcomes in AP patients.

Aims & Methods

This study aimed to evaluate the impact of pre-existing and newly developed cardiac conditions on in-hospital and post-discharge mortality in patients with acute pancreatitis. A single-center registry analysis of the Hungarian Pancreatic Study Group Acute Pancreatitis Registry was conducted at Semmelweis University, Budapest, Hungary, involving 1,316 patients diagnosed with acute pancreatitis between 2021-2024. Data on pre-existing chronic heart failure (CHF), atrial fibrillation (AF), stroke history, and newly developed acute heart failure (AHF) were collected. Electrocardiogram (ECG) findings, including QTc prolongation, were also analyzed. In-hospital mortality and post-discharge mortality within one year were assessed. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to quantify the strength of associations.

Results

Of the 1316 patients, 45% were female, the average age was 55.8 (range: 18-95) years, 8% had severe, 25% had moderate, and 65% had mild AP. Regarding cardiovascular background, pre-existing CHF and stroke history did not show a significant association with increased in-hospital mortality in AP (OR: 1.85, 95% CI: 0.63-5.44 and OR: 1.21, 95% CI: 0.36-4.02, respectively). Although AP patients with pre-existing AF had four-fold higher odds of in-hospital mortality (OR: 4.01, 95% CI: 1.92-8.34). Assessing in-hospital cardiovascular alterations, newly discovered AF was not significantly associated with increased in-hospital mortality (OR: 4.40, 95% CI: 0.97-20.02). Moreover, QTc prolongation on ECG was not significantly associated with in-hospital mortality (OR: 2.10, 95% CI: 0.61-7.25) or post-discharge mortality within one year after AP (OR: 1.65, 95% CI: 0.20-13.74). However, AP patients with newly developed AHF had a 25-times higher odds of in-hospital mortality (OR: 25.81, 95% CI: 12.13-54.98) and a 4-times higher odds for post-discharge mortality within one year (OR: 4.93, 95% CI: 1.01-24.26).

Conclusion

Pre-existing AF and newly developed AHF are significantly associated with increased in-hospital mortality in patients AP, moreover, newly developed AHF is also associated with increased post-discharge mortality within one year. These findings highlight the importance of cardiac monitoring and management in AP patients to improve outcomes.