Introduction

Pancreatic cancer (PC) is one of the fatal malignant tumors, with a 5-year survival rate is approximately 6%, and is expected to become the second leading cause of cancer deaths by 2030. The poor prognosis of PC is associated with the tumour microenvironment, characterized by excessive fibrosis and extracellular matrix deposition, known as desmoplasia. PC’s highly desmoplastic property not only increases the malignancy of the tumor but also inhibits the penetration and diffusion of anti-cancer drugs, related to drug resistance. Chauhan et al. demonstrated that the angiotensin inhibitor (ASI), losartan reduced stromal collagen and hyaluronan production, thus improving the efficacy of chemotherapy in PC models. Several retrospective studies have reported that the ASI usage group showed higher overall survival (OS) and progression-free survival compared to the non-ASI usage group in PC patients. However, most of the previous studies on ASI in PC patients were based on retrospective data from single institutions. Recently, real-world big data study could explain this subject.

Aims & Methods

In this study, we aimed to conduct whether ASI use in PC patients improve OS using National Health Information Database of the National Health Insurance Service, which represents the entire Korean population. We assessed 209,723 participants for eligibility, diagnosed with pancreatic cancer between 2002 and 2020. A total of 64,219 PC patients were enrolled and divided into 3 groups [chronic ASI users with hypertension (HTN), n=13,239; non-ASI users with HTN, n=5,963; non-HTN group, n=45,017]. We performed propensity score matching to balance the baseline characteristics of the 3 groups and to reduce potential confounders using a logistic regression model with adjustment for the following: age; sex; region of residence (urban or rural); household income; underlying disease of HTN, diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic kidney disease or chronic pancreatitis; Charlson Comorbidity Index (0, 1 or ≥2); concurrent use of aspirin, metformin, statin; PC surgery type; radiotherapy; and chemotherapy.

Results

Multivariate analysis using Cox regression analysis for matched cohort presented ASI usage, female, younger, history of chronic pancreatitis, CCI ≥2, concurrent use of statin, and receiving distal pancreatectomy were significantly associated with longer OS. In addition, Kaplan-Meier curve for OS of 3 groups according to ASI usage showed that chronic ASI users presented significantly longer OS than non-ASI users and non-HTN group [Hazard ratio, chronic ASI users (control) versus non-ASI users 1.447; chronic ASI users (control) versus non-HTN group 1.518; P value < 0.001].

Conclusion

We found that the use of ASI after PC diagnosis is associated with longer survival in PC patients. Additional well-designed randomized controlled studies are needed to confirm these findings in the future.

References

1. Rahib, L., B. D. Smith, R. Aizenberg, A. B. Rosenzweig, J. M. Fleshman and L. M. Matrisian (2014). "Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States" Cancer Res 74(11): 2913-2921.
2. Encarnación-Rosado, J. and A. C. Kimmelman (2021). "Harnessing metabolic dependencies in pancreatic cancers." Nature Reviews Gastroenterology & Hepatology 18(7): 482-492.
3. Thomas, D. and P. Radhakrishnan (2019). "Tumor-stromal crosstalk in pancreatic cancer and tissue fibrosis." Molecular cancer 18: 1-15.
4. Chauhan, V. P., J. D. Martin, H. Liu, D. A. Lacorre, S. R. Jain, S. V. Kozin, T. Stylianopoulos, A. S. Mousa, X. Han, P. Adstamongkonkul, Z. Popović, P. Huang, M. G. Bawendi, Y. Boucher and R. K. Jain (2013). "Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels." Nat Commun 4: 2516.
5. Pinter, M. and R. K. Jain (2017). "Targeting the renin-angiotensin system to improve cancer treatment: Implications for immunotherapy." Sci Transl Med 9(410).

Introduction

Proton pump inhibitors (PPIs) are extensively prescribed due to the widespread diagnosis of gastro-oesophageal disease (GORD). ^1,2 Overutilisation of PPIs is common, and growing concerns over adverse events, inappropriate prescribing and unnecessary costs ^3,4 are driving exploration into the implementation of holistic management, including deprescription strategies¹.

Aims & Methods

We aimed to quantify healthcare professionals’ (HCPs) preferences on the management of GORD in the UK, and identify attributes perceived as enhancing or detracting from quality of care.
Attributes were derived from qualitative data gathered through 3 focus groups with gastroenterologists, pharmacists and general practitioners (GPs), and interviews with 4 GORD patients.
A discrete-choice experiment (DCE) was developed and administered via online survey (Jan–Apr 2025) to 38 HCPs. Respondents chose between paired hypothetical GORD management scenarios, varying by symptom severity, appointment frequency, treatment approach, information delivery method, and cost. Preferences were modelled using a multinomial conditional logit with effects coding. Marginal rates of substitution (MRS) were calculated to quantify trade-offs.

Results

74% of respondents were pharmacists (n=28) and 26% GPs (n=10). All had managed GORD patients in the past year, and 81% expressed concern over long-term PPI use.
A holistic approach combining PPIs with lifestyle modification was strongly preferred over PPI monotherapy (β=0.4244, p<0.001), representing the most influential driver of care quality. Lifestyle modification alone was also favoured over PPI monotherapy (β=0.1125), though this did not reach statistical significance (p=0.127).
Respondents expressed significant aversion to providing information via pamphlets compared to GP-led counselling (β=–0.1836, p=0.046), while no preference emerged between pharmacist- and GP-led counselling (β=0.0512, p=0.573). Neither appointment burden nor out-of-pocket costs significantly influenced decision-making.
Symptom severity was a notable driver: HCPs selected scenarios involving moderate symptoms over mild (β=0.2353, p=0.005), indicating increased urgency and prioritisation for moderate disease.
Analysis of MRS between attributes suggested that HCPs are willing to accept 4.4 additional appointments to manage moderate symptoms, rather than mild, and nearly 8 additional appointments to deliver combined holistic lifestyle and pharmacological therapy. This highlights a willingness to absorb appointment-related resource demands in favour of more comprehensive, effective care.

Conclusion

Concerns around long-term PPI use support a shift toward active GORD management and PPI deprescribing, with structured follow-up to monitor treatment response.
This interim analysis highlights a clear preference among HCPs for multimodal GORD management, particularly combining lifestyle modification with pharmacological treatment, and reinforces the importance of interactive clinician[BA1] -led patient education, which can promote compliance and improve outcomes. The willingness to accept 4.4 additional appointments reflects the value placed on ongoing monitoring and personalised care. However, this raises the question on the impact this may have on health services, and whether the integration of self-care into multimodal approaches developed with HCPs could be an alternative solution to be investigated. [LH2] These findings highlight the need for a system-wide shift toward guideline-informed, stepped-care models.
A further analysis on patient population preferences is under review.

References

1. Savarino E, Anastasiou F, Labenz J, Hungin APS, Mendive J. Holistic management of symptomatic reflux: rising to the challenge of proton pump inhibitor overuse. Br J Gen Pract. 2022; 72(724):541-544.
2. Hungin APS, Scarpignato C, Keefer L, Corsetti M, Anastasiou F, Muris JWM, Mendive JM, Kahrilas PJ. Review article: rethinking the "ladder" approach to reflux-like symptom management in the era of PPI "resistance" - a multidisciplinary perspective. Aliment Pharmacol Ther. 2022; 55(12):1492-1500.
3. Plehhova K, Wray J, Aluko P, Sutton S, McArdle J, Dawson A, Coyle C, Stevens RM. Prescribing practices for proton pump inhibitors among primary care physicians in England: an evaluation. BJGP Open. 2025.
4. Sosio J, McKee N, [BA1] [LH2] Gold R, Singson A, Boroda K. S579 PPI Stewardship: A Quality Improvement Tool to Improve Long-Term Prescribing Practices. Am J Gastroenterol. 2024; 119(10S): S400.

Disclosure

This study was funded by Reckitt Benckiser Healthcare Ltd.
K. Plehhova, and E. Horvath are employees of Reckitt.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we aim to carry out the first single-cell transcriptome analysis of PDAC metastatic microenvironment in matched primary tumor and liver metastasis tissues.

Aims & Methods

We collected synchronously resected PDAC primary tumors and matched liver metastases from four PDAC patients and performed single-cell RNA sequencing. We performed comparative analysis on both cellular composition and functional phenotyping between primary and metastatic tumors. We also performed trajectory analysis and cellular interactome analysis in the metastasis microenvironment.

Results

Epithelial cancer cells exhibited distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from primary tumor. We identified specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5⁺ cancer-associated fibroblasts, CCL18⁺ lipid-associated macrophages, S100A8⁺ neutrophils and FOXP3⁺ regulatory T cells. We also identified several new biomarkers associated with PDAC metastasis and poor prognosis, such as LITAF, SPRR1B, KLK7 and LGALS9. Cellular interactome analysis further revealed that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment.

Conclusion

Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis, which deepens our understanding of the mechanisms underlying the immunosuppressive microenvironment in metastatic PDAC and serves as a valuable resource for the design of novel targeted therapies.

Disclosure

No

Introduction

Volatile organic compounds (VOC) in stool samples may reflect functional activity of gut microbiome. Previous studies showed that gut flora may influence transient relaxations of lower esophageal sphincter through short-chain fatty acids production and thus - participate in pathogenesis of gastroesophageal reflux disease (GERD). However, the role of VOC in pathogenesis of GERD is poorly studied yet.

Aims & Methods

The aim of this study (FGMF-2025-0003) was to perform correlation analysis between concentrations of VOC in stool samples and GERD-Q score.
We enrolled willing to participate patients referred to perform multichannel 24-h pH-impedance recording (Ohmega, Laborie). According to the Lyon 2.0 criteria patients were allocated to the GERD or the control group. GERD-Q questionnaire was filled in by the participants on the same day as stool samples were collected. Thermo TSQ 8000 triple quadrupole mass-spectrometer (GC/MS) was used for the measurement of VOCs in stool samples were analyzed with. Correlation analysis (Spearman rank R) was performed between values of 80 VOCs in stool samples and the results of GERD-Q questionnaire.

Results

Data of 76 patients were eligible: 42 with GERD and 34 - of the control group. Participants in the GERD group were older (54.7±12.2 y.o. vs 46±14.9 y.o., P<0.05) and their BMI was greater (30.9±5.2 vs 27.2±6.5 kg/m², P<0.05). GERD-Q score was logically greater in GERD group (11.0±2.5 vs 5.2±1.2, p<0.01). Correlation analysis revealed significant correlations between GERD-Q score and concentrations of 2-methylbutyric acid (Spearman R =-0.31), caproic acid (0.34) and enantiic acid (0.396) in stool samples.

Conclusion

GERD-Q score positively correlates with concentrations of Caproic acid (0.34) and Enantiic acid (0.396) in stool samples and negatively – with 2-Methylbutyric acid. The data of this pilot study may serve as a basis for further research on the role of functional activity of gut microbiome in pathogenesis of GERD.

Introduction

Appropriate knowledge of surface features of colorectal polyps is necessary for their adequate management. Data are limited regarding the diagnostic value of surface pattern-based prediction of histology.

Aims & Methods

This nationwide observational cohort study aimed to compare the optical diagnosis based on Kudo’s pit pattern and the histologic result in case of colorectal polyps endoscopically removed during screening colonoscopies.
Data regarding Kudo’s pit pattern of the lesions (Kudo I-V), and the final histological results were obtained from clinical records of screening colonoscopies which were prospectively collected in the registry of Hungarian National Public Health Institute. The level of agreement was characterized by Cohen’s kappa coefficient. The feasibility of optical diagnostics to differentiate neoplastic and non-neoplastic lesions, as well as to identify submucosally invasive cancer (SMIC) were investigated. The potential effects of polyp size and location (left/right colon), and that of timing of colonoscopy (1st period between 2019 and 2021, and 2nd period between 2022 and 2023) were also evaluated.

Results

A total of 8289 polyps removed during screening colonoscopy were registered in the database between 2019 and 2023, from these 7187 were neoplastic (439 SMIC) and 1102 were non-neoplastic. Out of the 1095 serrated polyps 171 contained dysplasia. Non-neoplastic polyps had Kudo I pattern in 7.7%, Kudo II in 48.1%, Kudo III in 40.9%, Kudo IV in 3.2%, and Kudo V in 0.1% of the cases. Neoplastic lesions without submucosal invasion had Kudo I surface pattern in 2.0%, Kudo II in 7.5%, Kudo III in 71.2%, Kudo IV in 17.4%, and Kudo V in 1.7% of the cases, while in case of SMIC, the surface pattern was Kudo I in 0.2%, Kudo II in 0.7%, Kudo III in 15.7%, Kudo IV in 8.9%, and Kudo V in 74.5% of the cases.
Kudo I-II category showed moderate agreement with non-neoplastic lesions (κ=0.440), irrespective of lesion size and location, and timing of screening colonoscopy. The level of agreement was only slight for serrated lesions (κ=0.168). Kudo V category demonstrated substantial agreement (κ=0.722) with SMIC, irrespective of lesion size, location, and timing. SMICs could be identified based on Kudo V category with 74.5% sensitivity, 98.5% specificity, 73.0% positive and 98.6% negative predictive value.

Conclusion

This is the first real-world data obtained from screening colonoscopies of the Hungarian national colorectal screening program. Optical diagnosis might support the differentiation of neoplastic and non-neoplastic lesions and can be especially helpful in identifying SMICs that might require a different management approach.