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.

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

Wu H, Zou WB, Zhou DZ, Gu YT, Liao Z, Li ZS. Longer Leukocyte Telomere Length is Associated With an Increased Risk of Chronic Pancreatitis. Pancreas. 2017;46(8):e65-e66. doi:10.1097/MPA.0000000000000887
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
Sexton RE, Uddin MH, Bannoura S, et al. Connecting the Human Microbiome and Pancreatic Cancer [published correction appears in Cancer Metastasis Rev. 2022 Jun;41(2):333. doi: 10.1007/s10555-022-10037-3.]. Cancer Metastasis Rev. 2022;41(2):317-331. doi:10.1007/s10555-022-10022-w

Introduction

The clinical benefit of Proactive Therapeutic Drug Monitoring (TDM) for infliximab and other monoclonal antibodies in Inflammatory Bowel Disease (IBD) remains a subject of ongoing debate. This study aimed to assess the real-world impact of broadly applying proactive TDM in unselected, consecutive IBD patients receiving infliximab infusions (both induction and maintenance). We compared TDM-guided management decisions to those made by an IBD expert blinded to TDM results but fully informed otherwise.

Aims & Methods

Infliximab trough levels and anti-drug antibodies were assessed using a validated ELISA assay; Through levels above 10 mg/ml were considered therapeutic. Infliximab levels and antibodies were measured in 55 IBD patients (34 with Crohn’s Disease, 21 with Ulcerative Colitis) in 77 occasions: median age 42 years, median disease duration 8.5 years, mostly bio-exposed (58%) and mostly already on dose-escalated regimens (90%). Crohn’s Disease patients had mostly complicated (stricturing or penetrating) disease (74%), half had prior surgery (44%), 50% were smokers and 20% had perianal disease. Management decisions based on TDM were compared to those of a blinded expert. Patients were followed prospectively for clinical, biochemical, and endoscopic response, with endoscopic data available in 39 cases.

Results

Therapeutic infliximab levels were observed in 80% of samples and anti-drug antibodies were detected in only one patient. Following TDM-based adjustment showed most patients had clinical (80%), biologic (89%) and endoscopic (61%) improvement compared to baseline assessment. Concordance in decision making was achieved in 58% of occasions. Therapy was discontinued in 11 patients (blinded expert concurred in 3/11,27%), the same dose was maintained in 53 patients (agreement occurred in 36/53, 68%), and dose modification in 13 patients (agreement was seen in 6/13, 46%).

Conclusion

Excellent results were achieved in this difficult to treat group of IBD patients treated with iv infliximab, possibly aided by proactive TDM. Without proactive TDM a small but significant percentage of them would risk undertreatment, either by not optimizing or by staying on redundant therapy. Discrepancies between TDM-based decisions and expert clinical judgment suggest that TDM provides distinct and actionable information that may prevent both under- and overtreatment. Future studies should estimate the impact of proactive TDM in different clinical scenarios, mostly in patients with severe disease.

Disclosure

The authors have no conflicts of interest to declare

Introduction

Pancreatic fibrosis (PF) is a prominent histological feature of chronic pancreatitis and influences on vast majority of pancreatic disorders. So, PF early diagnosis gives a great opportunity to be a part of the strategy for preventing pancreatic diseases progression. It makes non-invasive PF assessment especially via biomarkers level measurement research perspective.

Aims & Methods

Aim was to evaluate the possibility of biomarkers levels measurement in PF grade assessment.
Methods. We measured interleukin-10 (IL-10) and interleukin-36 (IL-36), matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-9 (MMP-9), fibronectin (FN) and hyaluronic acid (HA) plasma levels from 165 patient who underwent surgery from April 2022 to February 2024 due to pancreatic tumors and advanced chronic pancreatitis. We included 69 (41.8%) male and 96 (58.2%) female patients, mean age was 57.91±13.5 (25-89). Serum levels of specified biomarkers were determined by enzyme immunoassay using commercial kits; data registration performed was carried out on a semi-automatic analyzer. PF morphological grade was assessed according to Klöppel & Maillet’s scoring system [1] and scaled into three grades: mild, moderate and severe PF.
This study was conducted within the healthcare research project “Assessment of pancreatic fibrosis as a prognostic factor for its diseases course” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department.

Results

Plasma FN (pFN) level was significantly (p=0.029) higher in patients with mild PF (pFN=110.7±72.7 μg/mL), than in patients with severe PF (pFN=74.9±32.8 μg/mL). The median pFN levels were significantly varied in groups with different grades of intralobular PF (p<0.05), but not in groups divided by perilobular PF grade (p>0.05). Moreover, pFN level significantly negatively correlated with PF integrative grade (Spearmen’s rho = -0.21, p=0.007). Regarding IL-10, IL36, MMP-1, MMP-9 and HA levels, there were no significant differences either in patients with different PF integrative grade, or in groups divided by perilobular and intralobular PF (p>0.05). We revealed no significant correlations between specified biomarkers levels and PF grade (p>0.05).

Conclusion

The FN serum level significantly decreased in patients with severe PF in contrast to patients with mild PF who had comparatively higher serum FN level. Oppositely, IL-10, IL36, MMP-1, MMP-9 and HA had shown no effect in PF grade assessment. It could be useful for noninvasive pancreatic fibrosis diagnosis and even for patients’ selection for advanced diagnostics.

References

1 Esposito I, Hruban RH, Verbeke C, et al. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club. Pancreatology. 2020;20(4):586-593. doi:10.1016/j.pan.2020.04.009