Introduction

Pancreatic cancer (PC) is characterized by an exceptionally aggressive biology and high tumor heterogeneity causing considerable variations in therapy response. Patient-derived organoids (PDOs) reflect parental tumor features and represent a powerful preclinical tool to predict drug response and harness personalized treatment. In clinical practice, PDO-guided selection of effective drugs may provide substantial benefit and improve outcomes.

Aims & Methods

We have derived >40 PDOs from treatment-naïve and pretreated PC patient primary tumor and metastases (after ultrasound-guided biopsy, endoscopic ultrasound-guided biopsy or surgical resection) with a reliable efficacy. PDO drug response was evaluated using a cytotoxicity assay. Using Jenks natural breaks classification method, we clustered response (AUC) for each drug and correlated it to patient response.

Results

The implementation of an automated pipetting system and the subsequent miniaturization of drug screenings significantly enhanced our process capacity, conferring the possibility to extend our panel to a second list of approved targeted substances and further reducing the time before pharmacotyping. The validity of our approach was assessed via re-pharmacotyping a set of PDOs. Following up our feasibility trial (Beutel, 2021), we validated the accuracy of our model on a greater number of PC patients. Our model allowed overall a successful drug-response prediction in naïve patients with an accuracy of 85.7% for both first and second-line regimens. Prediction power remained lower for pretreated patients, with a precision of 57.1% for subsequent lines. A trend was also observed towards a better performance of the system in prognosticating chemoresponsiveness vs unresponsiveness (89.5% vs 68.8%). Finally, the administration of a regimen predicted to be efficient translated into a significantly longer progression-free survival. The access to longitudinal biopsies allowed us to conduct whole exome sequencing on 14 PDOs to capture a comprehensive genetic profiling over the time of treatment, notably revealing a CHEK2-mutated patient who responded over time upon PARP inhibitor maintenance therapy, in line with our PDO-based response prediction, further highlighting the robustness of our method and algorithm.

Conclusion

Overall, we report a robust and clinically-relevant preclinical tool for drug response prediction, paving the way towards an PDO-based true precision medicine in clinical routine.

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

Pancreatic cancer (PC) accounts for 0.5 million new cases and 4.7% of the world's cancer-related deaths in 2020^1,2. Endoscopic ultrasound (EUS) guided Fine Needle Biopsies (FNB) are the current standard of care for confirming suspicious lesions, however the diagnostic accuracy is reported below 70%^3-5. Rapid on-site evaluation (ROSE) improves the diagnostic performances of biopsies via an on-site pathological assessment to reduce the number of needle passes, complication rates, and the need for additional procedures⁶. However, availability of an on-site pathologist is often not feasible. NovaScan has pioneered the use of an impedance spectroscopy biomarker for cancer detection in different tissues based on the Cole Relaxation Frequency (CRF). NovaScan has developed a ”smart ROSE” device that assesses PC presence in FNBs obtained during endoscopic procedures ex vivo, in real-time and on-site, without altering the tissue sample or affecting the workflow.

Aims & Methods

Data were collected in a double-blind, IRB approved study from a cohort of 21 patients (9 males, 12 females) undergoing EUS procedures for suspected pancreatic lesions at the Texas International Endoscopy Center. FNBs were performed with a 22 gauge biopsy from a transduodenal approach. Each biopsy sample was transferred onto a disposable strainer allowing for any excess fluid to drain. An electrode for scanning was placed onto the core samples for data collection with the "smart ROSE," a low cost, portable device that can be used in the operating room. The device measures impedance spectroscopy in the 1 kHz - 10 MHz frequency range and derives a bio impedance biomarker via custom-designed hardware. The assessment of the sample is completed in a few seconds and subsequently, the sample is flushed into a pathology jar to undergo the standard workflow for cytology. The algorithm for extracting the bioimpedance biomarker from the measurement was developed based on our previous preclinical study with transgenic (KPC) mice⁷; pancreas samples with a CRF biomarker below 1 MHz were considered noncancerous, while biomarker values above 1MHz or the absence of a biomarker reading were considered cancerous.

Results

PC assessment provided by nsCanary was validated against pathology outcomes for each biopsy sample. Findings showing a sensitivity of 80% and a specificity of 87.5% are reported in Table 1.

Conclusion

We believe the "smart ROSE" device will provide immediate feedback to the endoscopist on cancer presence and on sample adequacy. This device is intended to support the decision-making process by enabling clinicians to overcome the challenge of proving cancer presence during the first biopsy procedure, ultimately avoiding revisits and unnecessary trauma.

References

1. S. Kato and K. Honda. Use of biomarkers and imaging for early detection of pancreatic cancer. Cancers, 12(7):1965, 2020.
2. M. R. Young, N. Abrams, S. Ghosh, J. A. S. Rinaudo, G. Marquez, and S. Srivastava. Prediagnostic image data, artificial intelligence, and pancreatic cancer: a tell-tale sign to early detection. Pancreas, 49(7):882–886,2020.
3. S. Varadarajulu and M. B. Wallace. Applications of endoscopic ultrasonography in pancreatic cancer. Cancer Control, 11(1):15–22, 2004.
4. P. Michl et al. UEG position paper on pancreatic cancer. Bringing pancreatic cancer to the 21st century: Prevent, detect,and treat the disease earlier and better. UEG journal, 9(7):860–871, 2021
5. D. T. de Moura et al. Evaluation of endoscopic ultrasound fine-needle aspiration versus fine-needle biopsy and impact of rapid on-site evaluation for pancreatic masses. Endoscopy International Open, 8(06):E738–E747, 2020.
6. J. B. Klapman, R. Logrono, C. E. Dye, and I. Waxman. Clinical impact of on-site cytopathology interpretation on endoscopic ultrasound-guided fine needle aspiration. The American journal of gastroenterology, 98(6):1289–1294, 2003.
7. Bogdanowicz, Les, et al. Cole Relaxation Frequency: A Parameter for Pancreatic Cancer Detection. The American Journal of Gastroenterology 117(10S):p e24-e25, October 2022

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

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection.

Aims & Methods

Through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort, consisting of computerized histopathology data from all 28 pathology departments in Sweden during the period 1965-2017, we retrieved data on IPMN.
Each index case was matched to ≤5 general population controls.
Through Cox proportional hazards regression models, we estimated hazard ratios (HRs) for future gastrointestinal (GI) cancer precursors and death. In secondary analyses, full siblings were used as comparators.
We excluded IPMN patients with high-grade dysplasia (HGD) to avoid the risk of misclassification.
Outcome topography included esophagus, stomach, colon and rectum and outcome morphology included Barrett’s esophagus, gastric metaplasia, mucosa type 1-3, tubulous adenoma, sessile serrated polyp, tubulovillous adenoma and villous adenoma.

Results

A total of 117 patients with IPMN, 539 age- and sex-matched controls, and 122 siblings were included. Among patients with IPMN, the mean age at diagnosis was 68.3 years and 48% were female.
Compared to IPMN patients, sibling controls were slightly younger (mean 65.5 years).
Patients with IPMN were also more likely to have prior diabetes, chronic obstructive pulmonary disease, obesity, dyslipidemia, and alcohol-related disease.
Almost all IPMN cases (97%) had ≥3 healthcare visits within the last year before diagnosis.
A Charlson Comorbidity Index score of ≥3 was seen in 28% of IPMN cases, compared to in 11% of controls and 9% of siblings.
IPMN cases were at increased risk of earlier GI cancer precursors compared to controls from the general population (OR=6.67; 95%CI=3.45-14.29), but the association failed to reach statistical significance when we compared with siblings (OR=2.00; 95%CI=0.92-4.35).
Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI=0.34-10.55).
By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI=1.79-7.27)).
The most common cause of death in IPMN was pancreatic cancer (n=14; 45.2% of all deaths).
Pancreatic cancer was the cause of death in only two (2.7%) controls and one (7.7%) sibling.
Extrapancreatic cancers were found in eight (6.8%) IPMN patients, 21 (3.9%) controls and four (3.3%) siblings.

Conclusion

We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients.
Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN.

Disclosure

Dr Ludvigsson is coordinating a study on behalf of the Swedish IBD quality register (SWIBREG). This study has received funding from the Janssen corporation. Dr Ludvigsson has also received financial support from MSD to develop a paper reviewing national healthcare registers in China. Dr Vujasinovic and Dr Löhr have received lecture fees from Abbott and Viatris. Dr Vujasinovic and Dr Löhr have also received financial support for writing a scientific book from Viatris. All other authors declare that they have no conflicts of interest and nothing to declare.

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.