Introduction

Pancreatic ductal adenocarcinoma (PDAC) remains a challenge in oncology with an overall survival rate remaining about 10%. Surgery and adjuvant chemotherapy stands as only curative treatment options. Only a minority of patients are diagnosed with resectable disease. While traditional diagnostic modalities show limitations in detecting and monitoring pancreatic cancer, liquid biopsies is a relatively new, non-invasive and promising diagnostic method for early detection, molecular profiling, and observation. Despite previous published or ongoing research projects and studies, liquid biopsies and specifically cell-free DNA (cfDNA) alterations role in management of pancreatic cancer remains unverified.

Aims & Methods

The aim of our study was to evaluate the diagnostic value of liquid biopsies and alterations in cfDNA levels in patients with pancreatic cancer. This study was approved by the Kaunas Regional Bioethics Committee (Approval ID: BE-2-31). Patients with newly diagnosed and histologically confirmed pancreatic cancer and patients with chronic pancreatitis, admitted to the Department of Surgery at Lithuanian University of Health Sciences Hospital, Kaunas Clinics, between September 2022 and December 2023, and healthy volunteers (control group) were included. Blood samples were obtained from the patients before any treatment procedures commenced. cfDNA was extracted from the collected blood using the QIAmp Circulating Nucleic Acid Kit (Qiagen). The concentration and quality of the extracted cfDNA were determined using the Qubit™ 1X dsDNA High Sensitivity (HS) and Broad Range (BR) Assay Kits (ThermoFisher Scientific, Inc., Waltham, MA, USA). Mann-Whitney U-test and Kruskal-Wallis H-test were used to determine the differences in quantitative traits between the comparison groups, with results being presented in median (min – max). The predictive capability (diagnostic performance) of cfDNA to distinguish PDAC and chronic pancreatitis/healthy controls was investigated by means of the area under the ROC (Receiver-Operating Characteristics) curve (AUC).

Results

Sixty-five patients were included (47 patients with PDAC, 10 patients with chronic pancreatitis and 8 healthy controls). Levels of cfDNA were statistically significantly higher in PDAC patients (46.5 (4 - 768) ng/ml) compared to patients with chronic pancreatitis (23.4 (8.56 - 138.4) ng/ml) (p = 0.032) and healthy controls (19.75 (17.6 - 22.8) ng/ml) (p < 0.001). The cfDNA cut-off value distinguishing PDAC from chronic pancreatitis and healthy controls were determined to be 23,65 ng/ml (AUC = 0.716) and 22.9 ng/ml (AUC = 0.915), respectively. There were no differences in cfDNA levels concerning tumor localization, size, differentiation, spread, or survival rates (all p > 0.05).

Conclusion

Liquid biopsies and cfDNA level alterations offer promising opportunities for distinguishing pancreatic cancer from benign inflammatory diseases, such as chronic pancreatitis. However, additional experiments and studies are necessary for more comprehensive validation and clinical use.

Disclosure

This study was partially funded by Lithuanian University of Health Sciences Scientific fund and Lithuanian Future Biomedicine foundation.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease of the pancreas with a high mortality rate due to late diagnosis at an advanced stage for its asymptomatic progression. Chronic pancreatitis, one of the risk factors for the development of PDAC, complicates the diagnostic process as both conditions sometimes share overlapping clinical and pathological features. Identifying individuals at higher risk of developing the disease and detecting pancreatic cancer at an early, curable stage is critical to improving overall patient outcomes. This study investigates the potential of relative telomere length (RTL) in peripheral blood and microbiome composition as biomarkers for PDAC. These biomarkers could support a minimally invasive liquid biopsy approach for early diagnosis of PDAC, differentiation from chronic pancreatitis, and screening of high-risk individuals.

Aims & Methods

A total of 239 participants were enrolled in the study and were divided into four groups: patients with PDAC (n = 36), chronic pancreatitis (n = 60), type II diabetes mellitus (n = 91) and cancer-free individuals (n = 52). Peripheral blood samples were collected to estimate relative telomere length using the multiplex monochrome qPCR method. Stool samples from a subset comprising chronic pancreatitis patients (n = 13), PDAC patients (n = 12), and healthy controls (n = 7) were analysed using 16S rRNA sequencing for metataxonomic analysis of the gut microbiome.

Results

Microbiome analysis revealed dysbiosis in a subset of patients, with an overrepresentation of bacterial species such as Prevotella copri and Akkermansia muciniphila in chronic pancreatitis and PDAC patients. A trend towards reduced microbial diversity was observed in PDAC patients, with changes in bacterial composition already detectable in chronic pancreatitis patients. No significant differences were found in RTL between the PDAC and cancer-free patient groups, and the only risk factors associated with changes were age, gender and smoking.

Conclusion

The pilot findings suggest a general trend towards reduced microbial diversity in PDAC patients, with alterations in bacterial proportions already observed in individuals diagnosed with chronic pancreatitis. These data ptovide a basis for the development of non-invasive diagnostic strategies to improve early detection and clinical outcomes for patients with PDAC. However, relative telomere length has not been shown to be a reliable biomarker.

References

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Riquelme E, Zhang Y, Zhang L, et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019;178(4):795-806.e12. doi:10.1016/j.cell.2019.07.008
Antwi SO, Petersen GM. Leukocyte Telomere Length and Pancreatic Cancer Risk: Updated Epidemiologic Review. Pancreas. 2018;47(3):265-271. doi:10.1097/MPA.0000000000000995
Campa D, Felici A, Corradi C, et al. Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review. Mutagenesis. 2025;40(1):39-47. doi:10.1093/mutage/gead034
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Introduction

Surgery is the traditional treatment of traumatic pseudocysts, but with considerable morbidity and mortality. A minimally invasive management of these collections has been increasingly used. Objective: To analyze the outcome following endoscopic treatment of pancreatic pseudocysts caused by abdominal trauma and to study the integrity of the main pancreatic duct (MPD).

Aims & Methods

Patients with pancreatic fluid collections due to abdominal trauma and who underwent endoscopic therapy were studied. All were symptomatic with a persistent collection for more than 6 weeks. Opacification of the MPD allowed characterization according to Takishima Classification (I, II and III) which guided therapy. Endoscopic drainage was divided into: transpapillary (Takishima II and III without bulging), transmural (type I) or combined (type II or III with bulging).

Results

From January 2020 January 2025 51 patients (36 men, mean age of 35.2 years, range - 13.9 years) were identified who developed pancreatic collections after blunt or penetrating abdominal trauma., The average size of the collection was 14.3  5.2 cm. ERP was obtained in 47/51 (90%). Drainage was transmural in 13 (all type I), combined in 24 (type IIa (4), IIb (7) and III (13) and transpapillary in 10 (all type III without bulging). The remaining 4 were drained transmurally. The success of endoscopic treatment was 94% with a recurrence rate of 8%. Stent occlusion occurred in 6%. There were 9 complications, but no procedural-related deaths. Patients with penetrating trauma had more recurrences than those with blunt trauma (p = 0.01). Penetrating trauma conferred a relative risk for development of infection 0.25; (95% 0.07 - 0.88; p = 0.045).

Conclusion

Endoscopic treatment of pancreatic fluid collections that develop after pancreatic trauma is safe and effective and can be considered a first-choice alternative to surgical and/or percutaneous treatment. Pancreatography is useful in determining the best endoscopic approach.

Disclosure

​NO CONFLICT OF INTEREST

Introduction

Intraductal papillary mucinous neoplasms (IPMN) is one of the main pancreatic ductal adenocarcinoma precursors, characterized by a remarkable morphological and spatial heterogeneity. This phenotypical heterogeneity is reflected in IPMN prognosis, with gastric phenotype IPMNs being more often branch-duct and low-grade lesions. There is no biomarker to predict which lesion will progress, complexifying the clinical surveillance scheme. Infiltration of immune cells and fibroblasts in tumor microenvironment (TME) may play a role in this phenotypic heterogeneity.

Aims & Methods

The aim of the present study was to describe the molecular heterogeneity of IPMN lesions at a transcriptional level and their TME. All histological slides from 135 paraffin embedded (FFPE) surgical pancreatic resections for IPMN (2013-2023) were reviewed for selection of regions of morphological interest (ROI) depending on IPMN phenotype and dysplasia. A total of 420 morphologically homogeneous ROI were microdissected for RNA sequencing and 22 from mixed phenotype for DNA sequencing. Additionally, 127 regions adjacent to IPMN lesions were annotated for immunochemistry to quantify immune cell and fibroblast infiltration. Proliferation index was quantified for all microdissections by Ki67 immunostaining.

Results

Among the 135 resections, 49 (36%) were pure gastric, 54 (40%) pure intestinal, 6 (4%) pure pancreatobiliary (PB) and 26 (19%) displayed a mixed phenotype (2 or 3 different phenotypes within the same specimen). Out of the 420 microdissections, 181 were gastric (22% high grade), 195 intestinal (40% high grade) and 44 PB (all high grade). Unsupervised analysis showed an important overlap of gastric and PB phenotype in contrast with intestinal IPMNs. Samples from mixed phenotypes tended to cluster independently and 8 out of 22 showed a common clonal origin. In non-intestinal samples, HG lesions clustered in 2 groups, one purely composed of gastric phenotype and a distinct one composed of gastric and PB. In intestinal samples, HG samples poorly clustered suggesting a biological continuum. Indeed, genes overexpressed in intestinal samples were enriched for cell division and proliferation pathways and the ki67 was significantly higher in intestinal (mean 24% ± 16) compared to gastric samples (mean 6% ± 6.4, p<0.0001). Overexpressed genes in gastric samples were highly enriched in immune response pathways. In fact, TME CD4 and CD8 T cell infiltration was significantly higher in gastric and PB compared to intestinal samples and this, independently of grade of dysplasia. Yet, PB samples displayed a significantly higher TME infiltration of active fibroblasts, regulatory T cells, M2 macrophages and neutrophils compared to gastric and intestinal phenotypes.

Conclusion

Our findings highlight the transcriptomic and microenvironmental heterogeneity of IPMN phenotypes, with distinct molecular programs and immune landscapes associated with each subtype. While intestinal IPMN are characterized by a proliferative, immune-cold profile irrespective of dysplasia grade, gastric and PB lesions show marked immune infiltration, with PB lesions enriched in immunosuppressive cell populations. These results suggest that TME composition may contribute to the differential progression potential of IPMN subtypes and provide a rationale for phenotype-specific biomarkers and interception strategies.