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Why ask for kRas in pancreatic cancer and what to ask for in cholangiocarcinoma?
1 Professor of Surgery Trinity College Dublin, Dublin, Ireland
2 Medizin. Hochschule Hannover, Hannover, Germany
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Driving the evolution of treatment goals in UC management: Long-term remission with mirikizumab (Eli Lilly and Company) (Complete Session)
1 University of Manchester, Manchester, United Kingdom
2 University of Porto, Porto, Portugal
3 Inselspital - Bern University Hospital, Bern, Switzerland
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When & for Whom: Intravenous vs Subcutaneous Therapies in IBD Maintenance (Celltrion) (Complete Session)
1 Hopital Saint-Antoine - APHP, Paris, France
2 Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany
3 Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
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Introduction
Pancreatic cancer remains a devastating disease with a poor prognosis, and liquid biopsy utilizing minimally invasive biofluids such as blood and duodenal juice has emerged as a promising approach for early detection. Our group has previously accumulated data on plasma- and duodenal fluid-based liquid biopsy, demonstrating potential clinical utility but also highlighting limitations in diagnostic sensitivity. This study aims to establish a robust cancer diagnostic and risk assessment method using plasma, duodenal juice, and pancreatic juice, while also charactering molecular abnormalities in resected tumors and surrounding tissues. To develop a novel clinical diagnostic framework, we comprehensively evaluated to cancer-associated genetic mutations in biofluids and compared these finding with tissue samples obtained via biopsy or surgical resection.
Aims & Methods
This multi-institutional study, initiated in 2021, focuses on developing a liquid biopsy platform for pancreatic cancer detection. Samples were collected as follows: plasma (n=224), duodenal juice (n=102), and pancreatic juice (n=85). Plasma was collected in 10 mL PAXgene Blood ccfDNA tubes (BD); cell-free DNA (cfDNA) was purified and concentrated to a 30 µL eluate. Duodenal fluid was collected through the endoscopic channel, and pancreatic juice was aspirated directly from the pancreatic duct using a catheter during ERP examination. Both fluid were each mixed with a preservation solution validated in a previous study. Digital PCR (dPCR) was performed to screen for KRAS G12/G13 and A59/Q61 mutations, followed by panel-based sequencing. For this study, we designed a Duplex UMI-based pancreatic cancer gene panel targeting 16 genes, including KRAS, TP53, CDKN2A, and SMAD4, to enable high sensitive detection of tumor-specific mutations.
Results
DPCR screening detected KRAS mutations in 75% of pancreatic juice samples and 50% of duodenal juice samples. Validation of the Duplex UMI-based target sequencing panel in a subset of samples (n=16) demonstrated that a minimum input of 20 ng of liquid-derived, non-genomic DNA was necessary to achieve concordance with mutations identified in matched tissue samples. Inputs below this threshold resulted in significantly reduced coverage and uniformity. Notably, duodenal and pancreatic juice exhibited superior sensitivity, reliably detecting tissue-confirmed mutations down to a minimum variant allele frequency (VAF) of 0.1%. Pancreatic juice not only captured a diverse spectrum of genetic alterations across multiple lesions but also identified mutations absent in corresponding tissue samples, suggesting its potential for detecting subclinical molecular changes. These findings underscore the complementary roles of different biofluids in capturing tumor heterogeneity.
Conclusion
Pancreatic juice-derived DNA shows exceptional promise for the accurate prediction of tumorous lesions, offering a powerful tool to prompt further diagnostic evaluation even in the absence of histological evidence. This approach could substantially enhance early detection and risk stratification in pancreatic cancer. Our ongoing study involves comprehensive analysis of all collected samples using the designed 16-gene panel. These efforts aim to establish liquid biopsy as a central component of pancreatic cancer diagnostics, supporting personalized treatment strategy and improving patient outcomes.
Disclosure
Y.O., K.T. and Y.M. receive funding form Hitachi High-Tech Corporation
DUPLEX UMI-ENHANCED HIGH-SENSITIVE LIQUID BIOPSY FOR PANCREATIC CANCER MUTATION DETECTION IN PANCREATIC JUICE AND DUODENAL FLUID
Yusuke Ono 1, Kenji Takahashi 2, Chiho Maeda 3, Mayumi Suzuki 3, Miyuki Mori 3, Hiroki Tanaka 4, Taito Itoh 4, Takuya Yamamoto 4, YUSUKE MIZUKAMI 1
1 Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan|||Asahikawa Medical University, Asahikawa, Japan|||Center for Intractable Diseases and ImmunoGenomics (CiDIG), National Institutes of Biomedical Innovation, Health and N
2 Asahikawa Medical University, Asahikawa, Japan|||Center for Intractable Diseases and ImmunoGenomics (CiDIG), National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
3 Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
4 Center for Intractable Diseases and ImmunoGenomics (CiDIG), National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
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Resmetirom and novel biomarkers
1 Charité Universitaetsmedizin Berlin, Dept of Hepatology & Gastroenterology, Berlin, Germany
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MULTI-OMICS ANALYSIS OF PERIANAL FISTULIZING CROHN'S DISEASE REVEAL NOVEL THERAPEUTIC TARGETS
1 Washington University in St. Louis, St. Louis, United States
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EFFICACY OF ADVANCED THERAPIES FOR THE TREATMENT OF REFRACTORY POUCHITIS IN PATIENTS WITH ILEAL-POUCH-ANAL ANASTOMOSIS (IPAA): A MULTICENTRE ITALIAN REAL-LIFE EXPERIENCE
Anna Maria Carvalhas Gabrielli 1, Rosanna Cannatelli 1, Francesca Ferretti 1, Alessandro Massari 1, Stefania Carmagnola 2, Edoardo Vincenzo Savarino 3, Luisa Bertin 3, Cristina Bezzio 4, Chiara Ricci 5, Irene Zammarchi 5, Simone Saibeni 6, Alice De Bernardi 6, Davide Giuseppe Ribaldone 7, Francesca De vita 7, Giovanni Maconi 1
1 Luigi Sacco University Hospital Gastroenterology Unit Biomed and Clinical Sciences, Milan, Italy
2 ASST Fatebenefratelli Sacco, Gastroenterology and Digestive Endoscopy Unit, Milan, Italy
3 University of Padua, Padua, Italy
4 Humanitas Research Hospital, Milano, Italy
5 Università degli Studi di Brescia, Brescia, Italy
6 ASST Rhodense, Rho, Italy
7 University of Turin, Turin, Italy
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