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Pancreatic Neoplasms: HELP
Articles by Matthias J. Löhr
Based on 25 articles published since 2010
(Why 25 articles?)
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Between 2010 and 2020, M. Löhr wrote the following 25 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline [S3-guideline exocrine pancreatic cancer]. 2013

Seufferlein, T / Porzner, M / Becker, T / Budach, V / Ceyhan, G / Esposito, I / Fietkau, R / Follmann, M / Friess, H / Galle, P / Geissler, M / Glanemann, M / Gress, T / Heinemann, V / Hohenberger, W / Hopt, U / Izbicki, J / Klar, E / Kleeff, J / Kopp, I / Kullmann, F / Langer, T / Langrehr, J / Lerch, M / Löhr, M / Lüttges, J / Lutz, M / Mayerle, J / Michl, P / Möller, P / Molls, M / Münter, M / Nothacker, M / Oettle, H / Post, S / Reinacher-Schick, A / Röcken, C / Roeb, E / Saeger, H / Schmid, R / Schmiegel, W / Schoenberg, M / Siveke, J / Stuschke, M / Tannapfel, A / Uhl, W / Unverzagt, S / van Oorschot, B / Vashist, Y / Werner, J / Yekebas, E / Anonymous260779 / Anonymous270779 / Anonymous280779. ·Klinik für Innere Medizin I, Universitätsklinikum Ulm. · Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Kiel. · Klinik für Radioonkologie und Strahlentherapie, Charité Universitätsmedizin Berlin. · Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU München. · Institut für Allgemeine Pathologie, Klinikum rechts der Isar, TU München. · Strahlenklinik, Universitätsklinikum Erlangen. · Leitlinienprogramm Onkologie, Deutsche Krebsgesellschaft e. V., Berlin. · I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz. · Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen. · Klinik für Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes Homburg/Saar. · Klinik für Gastroenterologie, Endokrinologie und Stoffwechsel, Universitätsklinikum Gießen und Marburg. · Medizinischen Klinik und Poliklinik III, Klinikum der Universität München LMU. · Chirurgische Klinik, Universitätsklinikum Erlangen. · Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg. · Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf. · Klinik für Allgemeine Chirurgie, Thorax-, Gefäß- und Transplantationschirurgie, Universitätsmedizin Rostock. · AWMF-Institut für Medizinisches Wissensmanagement, Marburg. · Medizinische Klinik I, Klinikum Weiden. · Klinik für Allgemein-, Gefäß- und Viszeralchirurgie, Martin-Luther-Krankenhaus Berlin. · Klinik und Poliklinik für Innere Medizin A, Universitätsmedizin Greifswald. · Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm. · Institut für Pathologie, Marienkrankenhaus Hamburg. · Medizinische Klinik - Schwerpunkt Gastroenterologie, Endokrinologie, Infektiologie, Caritasklinikum Saarbrücken. · Institut für Pathologie, Universitätsklinikum Ulm. · Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, TU München. · Klinik für Strahlentherapie und Radioonkologie, Klinikum Stuttgart. · AWMF-Institut für Medizinisches Wissensmanagement, Berlin. · Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charité Universitätsmedizin Berlin. · Chirurgische Klinik, Universitätsmedizin Mannheim. · Abt. für Hämatologie und Onkologie, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum. · Institut für Pathologie, Universitätsklinikum Kiel. · Medizinische Klinik II, SP Gastroenterologie, Universitätsklinikum Gießen und Marburg. · Klinik für Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Dresden. · II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, TU München. · Medizinische Klinik, Klinikum der Ruhr-Universität Bochum. · Klinik für Chirurgie, Rotkreuzklinikum München. · Klinik für Strahlentherapie, Universitätsklinikum Essen. · Institut für Pathologie, Ruhr-Universität Bochum. · Chirurgische Klinik, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum. · Institut für Medizinische Epidemiologie, Biometrie und Informatik, Martin-Luther-Universität Halle-Wittenberg. · Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Würzburg. · Klinik für Allgemeine, Viszerale und Transplantationschirurgie, Universitätsklinikum Heidelberg. · Klinik für Allgemein-, Thorax- und Viszeralchirurgie, Klinikum Darmstadt. ·Z Gastroenterol · Pubmed #24338757.

ABSTRACT: -- No abstract --

2 Guideline European experts consensus statement on cystic tumours of the pancreas. 2013

Del Chiaro, Marco / Verbeke, Caroline / Salvia, Roberto / Klöppel, Gunter / Werner, Jens / McKay, Colin / Friess, Helmut / Manfredi, Riccardo / Van Cutsem, Eric / Löhr, Matthias / Segersvärd, Ralf / Anonymous3160750. ·Division of Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. Electronic address: marco.del-chiaro@karolinska.se. ·Dig Liver Dis · Pubmed #23415799.

ABSTRACT: Cystic lesions of the pancreas are increasingly recognized. While some lesions show benign behaviour (serous cystic neoplasm), others have an unequivocal malignant potential (mucinous cystic neoplasm, branch- and main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm). European expert pancreatologists provide updated recommendations: diagnostic computerized tomography and/or magnetic resonance imaging are indicated in all patients with cystic lesion of the pancreas. Endoscopic ultrasound with cyst fluid analysis may be used but there is no evidence to suggest this as a routine diagnostic method. The role of pancreatoscopy remains to be established. Resection should be considered in all symptomatic lesions, in mucinous cystic neoplasm, main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm as well as in branch duct intraductal papillary mucinous neoplasm with mural nodules, dilated main pancreatic duct >6mm and possibly if rapidly increasing in size. An oncological partial resection should be performed in main duct intraductal papillary mucinous neoplasm and in lesions with a suspicion of malignancy, otherwise organ preserving procedures may be considered. Frozen section of the transection margin in intraductal papillary mucinous neoplasm is suggested. Follow up after resection is recommended for intraductal papillary mucinous neoplasm, solid pseudo-papillary neoplasm and invasive cancer.

3 Review Reduced risk of pancreatic cancer associated with asthma and nasal allergies. 2017

Gomez-Rubio, Paulina / Zock, Jan-Paul / Rava, Marta / Marquez, Mirari / Sharp, Linda / Hidalgo, Manuel / Carrato, Alfredo / Ilzarbe, Lucas / Michalski, Christoph / Molero, Xavier / Farré, Antoni / Perea, José / Greenhalf, William / O'Rorke, Michael / Tardón, Adonina / Gress, Thomas / Barberà, Victor / Crnogorac-Jurcevic, Tatjana / Domínguez-Muñoz, Enrique / Muñoz-Bellvís, Luís / Alvarez-Urturi, Cristina / Balcells, Joaquim / Barneo, Luis / Costello, Eithne / Guillén-Ponce, Carmen / Kleeff, Jörg / Kong, Bo / Lawlor, Rita / Löhr, Matthias / Mora, Josefina / Murray, Lim / O'Driscoll, Damian / Peláez, Pablo / Poves, Ignasi / Scarpa, Aldo / Real, Francisco X / Malats, Núria / Anonymous5500850. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain. · Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. · National Cancer Registry Ireland, Cork, Ireland, and Institute of Health & Society, Newcastle University, UK. · Hospital Madrid-Norte-Sanchinarro, Madrid, Spain. · Department of Oncology, Hospital Ramón y Cajal, Madrid, Spain. · Hospital del Mar-Parc de Salut Mar, Barcelona, Spain. · Technical University of Munich, Munich, Germany. · Exocrine Pancreas Research Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain. · Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain. · The Royal Liverpool University Hospital, Liverpool, UK. · Centre for Public Health, Queen's University Belfast, Belfast, UK. · Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain. · Department of Gastroenterology, University Hospital Giessen and Marburg, Marburg, Germany. · Laboratorio de Genética Molecular, Hospital General Universitario de Elche, Elche, Spain. · Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. · Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. · Cirugía General y del Aparato Digestivo, Hospital Universitario de Salamanca, Salamanca, Spain. · Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Gastrocentrum, Karolinska Institutet, Stockholm, Sweden. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. ·Gut · Pubmed #26628509.

ABSTRACT: OBJECTIVE: Studies indicate an inverse association between ductal adenocarcinoma of the pancreas (PDAC) and nasal allergies. However, controversial findings are reported for the association with asthma. Understanding PDAC risk factors will help us to implement appropriate strategies to prevent, treat and diagnose this cancer. This study assessed and characterised the association between PDAC and asthma and corroborated existing reports regarding the association between allergies and PDAC risk. DESIGN: Information about asthma and allergies was collated from 1297 PDAC cases and 1024 controls included in the PanGenEU case-control study. Associations between PDAC and atopic diseases were studied using multilevel logistic regression analysis. Meta-analyses of association studies on these diseases and PDAC risk were performed applying random-effects model. RESULTS: Asthma was associated with lower risk of PDAC (OR 0.64, 95% CI 0.47 to 0.88), particularly long-standing asthma (>=17 years, OR 0.39, 95% CI 0.24 to 0.65). Meta-analysis of 10 case-control studies sustained our results (metaOR 0.73, 95% CI 0.59 to 0.89). Nasal allergies and related symptoms were associated with lower risk of PDAC (OR 0.66, 95% CI 0.52 to 0.83 and OR 0.59, 95% CI 0.46 to 0.77, respectively). These results were supported by a meta-analysis of nasal allergy studies (metaOR 0.6, 95% CI 0.5 to 0.72). Skin allergies were not associated with PDAC risk. CONCLUSIONS: This study shows a consistent inverse association between PDAC and asthma and nasal allergies, supporting the notion that atopic diseases are associated with reduced cancer risk. These results point to the involvement of immune and/or inflammatory factors that may either foster or restrain pancreas carcinogenesis warranting further research to understand the molecular mechanisms driving this association.

4 Review Pathology reporting of pancreatic cancer following neoadjuvant therapy: challenges and uncertainties. 2015

Verbeke, C / Löhr, M / Karlsson, J Severin / Del Chiaro, M. ·Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden; Department of Pathology & Cytology, Karolinska University Hospital, Hälsovägen, 141 86 Stockholm, Sweden. Electronic address: caroline.verbeke@ki.se. · Gastrocentrum, Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden. Electronic address: matthias.lohr@ki.se. · Department of Pathology & Cytology, Karolinska University Hospital, Hälsovägen, 141 86 Stockholm, Sweden. Electronic address: josefin.severin-karlsson@karolinska.se. · Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Hälsovägen, 141 86 Stockholm, Sweden. Electronic address: marco.del-chiaro@karolinska.se. ·Cancer Treat Rev · Pubmed #25434282.

ABSTRACT: An increasing number of studies investigate the use of neoadjuvant treatment for ductal adenocarcinoma of the pancreas. While a strong rationale supports this approach, study results are difficult to interpret and compare due to marked variance in multiple aspects of study design and performance. Divergence in pathology examination and reporting as a cause for heterogeneity and incomparability of study results has not been brought into this discussion yet, despite the fact that several key outcome measures for neoadjuvant treatment are pathology-based. This article discusses areas of controversy and difficulty regarding the evaluation of the extent of residual tumour tissue, grading of tumour regression and assessment of the margins, and explains the important clinical implications of the present uncertainty and divergence in pathology practice.

5 Review Early detection and prevention of pancreatic cancer: is it really possible today? 2014

Del Chiaro, Marco / Segersvärd, Ralf / Lohr, Matthias / Verbeke, Caroline. ·Marco Del Chiaro, Ralf Segersvärd, Matthias Löhr, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, 141 86 Stockholm, Sweden. ·World J Gastroenterol · Pubmed #25232247.

ABSTRACT: Pancreatic cancer is the 4(th) leading cause of cancer-related death in Western countries. Considering the low incidence of pancreatic cancer, population-based screening is not feasible. However, the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well established. In particular, individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5- to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic cancer. The aim of such a program is to reduce pancreatic cancer mortality through early or preemptive surgery. Considering the risk associated with pancreatic surgery, the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals, but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms, or early cancer. Currently, results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions, nor do they define the outcome of the surgical treatment of these lesions. For this reason, surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical trial. However, the acquisition of a deeper understanding of this complex area, together with the increasing request for screening and treatment by individuals at risk, will usher pancreatologists into a new era of preemptive pancreatic surgery. Along with the growing demand to treat individuals with precancerous lesions, the need for low-risk investigation, low-morbidity operation and a minimally invasive approach becomes increasingly pressing. All of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.

6 Article Immunohistochemical profiling of liver metastases and matched-pair analysis in patients with metastatic pancreatic ductal adenocarcinoma. 2019

Held, Thomas / Verbeke, Caroline S / Strobel, Oliver / Rutkowski, Wiktor / Villard, Christina / Moro, Carlos Fernández / Del Chiaro, Marco / Büchler, Markus / Heuchel, Rainer / Löhr, Matthias. ·Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany; Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: thomas.held@med.uni-heidelberg.de. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: c.s.verbeke@medisin.uio.no. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: oliver.strobel@med.uni-heidelberg.de. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: wiktor.rutkowski@stud.ki.se. · Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: christina.villard@sll.se. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: carlos.fernandez.moro@ki.se. · Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: marco.del.chiaro@ki.se. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: markus.buechler@med.uni-heidelberg.de. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: rainer.heuchel@ki.se. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden; Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: matthias.lohr@ki.se. ·Pancreatology · Pubmed #31542399.

ABSTRACT: BACKGROUND: The purpose of the current study was to investigate the immunohistochemical (IHC) profile of liver metastases (LM) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Expression of 15 IHC markers in liver biopsies from 77 patients with PDAC, who were diagnosed between 2010 and 2014, were evaluated. In a separate subgroup analysis (n = 12), paired samples (LM and primary tumor) from the same patient were investigated for IHC profile differences. RESULTS: LM samples were classified as pancreatobiliary-type (PB-type) in 72 patients (93.5%), intestinal-type (INT-type) in four patients (5.2%), and squamous in one patient (1.3%). There was no significant difference in overall survival (OS) between LM of the PB-type or INT-type (p = 0.097). In a multivariate analysis, age <70 years (p = 0.047), absence of SMAD4 mutation (p = 0.026), absence of CDX2 expression (p = 0.003), and well to moderate differentiation were significant prognostic factors for better OS in patients with LM (p = 0.031). Analysis of paired tissue samples from LM and the primary tumor revealed a difference in CDX2 (50% increase, p = 0.125) and SMAD4 (33% loss of SMAD4, p = 0.375). CONCLUSIONS: CDX2 expression and SMAD4 mutation indicate a poor outcome in patients with LM of PDAC. Matched-pair analysis revealed differences in distinct IHC marker expression.

7 Article Role of c-MET Inhibitors in Overcoming Drug Resistance in Spheroid Models of Primary Human Pancreatic Cancer and Stellate Cells. 2019

Firuzi, Omidreza / Che, Pei Pei / El Hassouni, Btissame / Buijs, Mark / Coppola, Stefano / Löhr, Matthias / Funel, Niccola / Heuchel, Rainer / Carnevale, Ilaria / Schmidt, Thomas / Mantini, Giulia / Avan, Amir / Saso, Luciano / Peters, Godefridus J / Giovannetti, Elisa. ·Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348-14336 Shiraz, Iran. firuzio@sums.ac.ir. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV, Amsterdam, The Netherlands. firuzio@sums.ac.ir. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV, Amsterdam, The Netherlands. p.che@vumc.nl. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV, Amsterdam, The Netherlands. b.elhassouni@vumc.nl. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV, Amsterdam, The Netherlands. m.j.n2.buijs@student.vu.nl. · Physics of Life Processes, Huygens-Kamerlingh Onnes Laboratory, Leiden University, 2333 CA, Leiden, The Netherlands. coppola@physics.leidenuniv.nl. · Division of Surgery, CLINTEC, Karolinska Institutet, SE-171, Stockholm, Sweden. matthias.lohr@ki.se. · Cancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, 56124 Pisa, Italy. niccola.funel@gmail.com. · Division of Surgery, CLINTEC, Karolinska Institutet, SE-171, Stockholm, Sweden. rainer.heuchel@ki.se. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV, Amsterdam, The Netherlands. ilaria187@gmail.com. · Cancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, 56124 Pisa, Italy. ilaria187@gmail.com. · Physics of Life Processes, Huygens-Kamerlingh Onnes Laboratory, Leiden University, 2333 CA, Leiden, The Netherlands. Schmidt@physics.leidenuniv.nl. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV, Amsterdam, The Netherlands. g.mantini@vumc.nl. · Metabolic syndrome Research center, Mashhad University of Medical Sciences, 91778-99191 Mashhad, Iran. AvanA@mums.ac.ir. · Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University, 00185, Rome, Italy. luciano.saso@uniroma1.it. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV, Amsterdam, The Netherlands. g.j.peters@vumc.nl. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1081 HV, Amsterdam, The Netherlands. e.giovannetti@vumc.nl. · Cancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, 56124 Pisa, Italy. e.giovannetti@vumc.nl. · Fondazione Pisana per la Scienza, 56017, Pisa, Italy. e.giovannetti@vumc.nl. ·Cancers (Basel) · Pubmed #31072019.

ABSTRACT: Pancreatic stellate cells (PSCs) are a key component of tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) and contribute to drug resistance. c-MET receptor tyrosine kinase activation plays an important role in tumorigenesis in different cancers including PDAC. In this study, effects of PSC conditioned medium (PCM) on c-MET phosphorylation (by immunocytochemistry enzyme-linked immunosorbent assay (ELISA)) and drug response (by sulforhodamine B assay) were investigated in five primary PDAC cells. In novel 3D-spheroid co-cultures of cyan fluorescence protein (CFP)-firefly luciferase (Fluc)-expressing primary human PDAC cells and green fluorescence protein (GFP)-expressing immortalized PSCs, PDAC cell growth and chemosensitivity were examined by luciferase assay, while spheroids' architecture was evaluated by confocal microscopy. The highest phospho-c-MET expression was detected in PDAC5 and its subclone sorted for "stage specific embryonic antigen-4" (PDAC5 (SSEA4)). PCM of cells pre-incubated with PDAC conditioned medium, containing increased hepatocyte growth factor (HGF) levels, made PDAC cells significantly more resistant to gemcitabine, but not to c-MET inhibitors. Hetero-spheroids containing both PSCs and PDAC5 (SSEA4) cells were more resistant to gemcitabine compared to PDAC5 (SSEA4) homo-spheroids. However, c-MET inhibitors (tivantinib, PHA-665752 and crizotinib) were equally effective in both spheroid models. Experiments with primary human PSCs confirmed the main findings. In conclusion, we developed spheroid models to evaluate PSC-PDAC reciprocal interaction, unraveling c-MET inhibition as an important therapeutic option against drug resistant PDAC.

8 Article Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches. 2019

Gomez-Rubio, Paulina / Piñero, Janet / Molina-Montes, Esther / Gutiérrez-Sacristán, Alba / Marquez, Mirari / Rava, Marta / Michalski, Christoph W / Farré, Antoni / Molero, Xavier / Löhr, Matthias / Perea, José / Greenhalf, William / O'Rorke, Michael / Tardón, Adonina / Gress, Thomas / Barberá, Victor M / Crnogorac-Jurcevic, Tatjana / Muñoz-Bellvís, Luís / Domínguez-Muñoz, Enrique / Balsells, Joaquim / Costello, Eithne / Yu, Jingru / Iglesias, Mar / Ilzarbe, Lucas / Kleeff, Jörg / Kong, Bo / Mora, Josefina / Murray, Liam / O'Driscoll, Damian / Poves, Ignasi / Lawlor, Rita T / Ye, Weimin / Hidalgo, Manuel / Scarpa, Aldo / Sharp, Linda / Carrato, Alfredo / Real, Francisco X / Furlong, Laura I / Malats, Núria / Anonymous2240962. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain. · Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. · Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain. · Department of Surgery, Technical University of Munich, Munich, Germany. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Hospital Universitaru Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Barcelona, Spain. · Universitat Auntònoma de Barcelona, Campus de la UAB, Barcelona, Spain. · Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and University Hospital, Stockholm, Sweden. · Department of Surgery, University Hospital 12 de Octubre, Madrid, Spain. · Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, United Kingdom. · Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom. · Department of Medicine, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain. · Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany. · Laboratorio de Genética Molecular, Hospital General Universitario de Elche, Elche, Spain. · Centre for Molecular Oncology, John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. · General and Digestive Surgery Department, Hospital Universitario de Salamanca, Salamanca, Spain. · Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. · Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, (Saale), Germany. · Cancer Data Registrars, National Cancer Registry Ireland, Cork, Ireland. · ARC-Net Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University Hospital Trust of Verona, Verona, Italy. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and University Hospital, Sweden. · Hospital Madrid-Norte-Sanchinarro and Spanish National Cancer Research Centre (CNIO), Madrid, Spain. · Rosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. · Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom. · Department of Oncology, Hospital Ramón y Cajal, Madrid, Spain. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. · PanGenEU Study Investigators (Additional file 1: Annex S1). ·Int J Cancer · Pubmed #30229903.

ABSTRACT: Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene-disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case-control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58-0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21-0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19-0.89, and OR = 0.73, 95%CI 0.53-1.00, respectively). Several inflammatory-related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.

9 Article Prediction of improved survival in patients with pancreatic cancer via IL-21 enhanced detection of mesothelin epitope-reactive T-cell responses. 2018

Meng, Qingda / Valentini, Davide / Rao, Martin / Liu, Zhenjiang / Xie, Shanshan / Morgell, Ann / Dodoo, Ernest / Löhr, Matthias / Rangelova, Elena / Del Chiaro, Marco / Ernberg, Ingemar / Maeurer, Markus. ·Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden. · Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden. · Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden. · Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. ·Oncotarget · Pubmed #29854291.

ABSTRACT: Most patients with pancreatic cancer present with extensive metastasis at diagnosis, with a 5-year survival rate of approximately 5%, despite chemotherapy and surgery. New treatment modalities are needed to improve survival. Mesothelin is a tumor-associated antigen (TAA) in patients with pancreatic cancer that could be used to gauge cellular immune responses directed against transformed cells since up to 100 percent of pancreatic ductal adenocarcinoma cells have been shown to strongly express mesothelin. A prospective, observational study was carried out in twenty-six, chemotherapy-naïve patients with resectable pancreatic ductal adenocarcinoma. Participants were between 48 and 81 years (median age: 64.5 years), 15 males and 11 females. All participants were clinically followed-up between 439 and 853 days post-surgery (n=14) or until death (n=12). Peripheral blood drawn on the day of surgery was stimulated with a mesothelin peptide pool (42 peptides, non-overlapping), individual mesothelin peptides, positive (anti-CD3 antibody, OKT3) and negative controls (medium) with or without adding IL-21. Kaplan-Meier estimators were used to gauge patients' survival pattern in relation to mesothelin-specific IFN-γ responses. A survival benefit was linked with IFN-γ responses to peptides corresponding to mature mesothelin (p=0.018) and targeted recognition of the mesothelin

10 Article Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives. 2018

Molina-Montes, E / Gomez-Rubio, P / Márquez, M / Rava, M / Löhr, M / Michalski, C W / Molero, X / Farré, A / Perea, J / Greenhalf, W / Ilzarbe, L / O'Rorke, M / Tardón, A / Gress, T / Barberà, V M / Crnogorac-Jurcevic, T / Domínguez-Muñoz, E / Muñoz-Bellvís, L / Balsells, J / Costello, E / Huang, J / Iglesias, M / Kleeff, J / Kong, Bo / Mora, J / Murray, L / O'Driscoll, D / Poves, I / Scarpa, A / Ye, W / Hidalgo, M / Sharp, L / Carrato, A / Real, F X / Malats, N / Anonymous1210933. ·Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group, Madrid, and CIBERONC, Spain. · Karolinska Institutet and University Hospital, Gastrocentrum, Stockholm, Sweden. · Technical University of Munich, Department of Surgery, Munich, Germany. · University of Heidelberg, Department of Surgery, Heidelberg, Germany. · Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, and CIBEREHD, Spain. · Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology, Barcelona, Spain. · University Hospital 12 de Octubre, Department of Surgery, Madrid, Spain. · Royal Liverpool University Hospital, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK. · Hospital del Mar-Parc de Salut Mar, Barcelona, Spain. · Queen's University Belfast, Centre for Public Health, Belfast, UK. · Instituto Universitario de Oncología del Principado de Asturias, Department of Medicine, Oviedo, and CIBERESP, Spain. · University Hospital of Giessen and Marburg, Department of Gastroenterology, Marburg, Germany. · General University Hospital of Elche, Molecular Genetics Laboratory, Elche, Spain. · Barts Cancer Institute, Centre for Molecular Oncology, Queen Mary University of London, London, UK. · University Clinical Hospital of Santiago de Compostela, Department of Gastroenterology, Santiago de Compostela, Spain. · Salamanca University Hospital, General and Digestive Surgery Department, Salamanca, Spain. · Martin-Luther-University Halle-Wittenberg, Department of Visceral, Vascular and Endocrine Surgery, Halle (Saale), Germany. · National Cancer Registry Ireland and HRB Clinical Research Facility, University College Cork, Cork, Ireland. · ARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy. · Madrid-Norte-Sanchinarro Hospital, Madrid, Spain. · Newcastle University, Institute of Health and Society, Newcastle upon Tyne, UK. · Ramón y Cajal University Hospital, Department of Oncology, IRYCIS, Alcala University, Madrid, and CIBERONC, Spain. · Spanish National Cancer Research Centre (CNIO), Epithelial Carcinogenesis Group, Madrid, Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, and CIBERONC, Spain. ·Int J Epidemiol · Pubmed #29329392.

ABSTRACT: Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

11 Article In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and 2018

El-Heliebi, Amin / Hille, Claudia / Laxman, Navya / Svedlund, Jessica / Haudum, Christoph / Ercan, Erkan / Kroneis, Thomas / Chen, Shukun / Smolle, Maria / Rossmann, Christopher / Krzywkowski, Tomasz / Ahlford, Annika / Darai, Evangelia / von Amsberg, Gunhild / Alsdorf, Winfried / König, Frank / Löhr, Matthias / de Kruijff, Inge / Riethdorf, Sabine / Gorges, Tobias M / Pantel, Klaus / Bauernhofer, Thomas / Nilsson, Mats / Sedlmayr, Peter. ·Institute of Cell Biology, Histology and Embryology, Medical University Graz, Austria; amin.elheliebi@medunigraz.at. · Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Science for Life Laboratory, Department of Biophysics and Biochemistry, Stockholm University, Solna, Sweden. · Institute of Cell Biology, Histology and Embryology, Medical University Graz, Austria. · Center for Biomarker Research in Medicine (CBmed); Graz, Austria. · Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria. · Devyser AB, Stockholm, Sweden. · Department of Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · ATURO, Urology Practice, Berlin, Germany. · Center for Digestive Diseases, Karolinska University Hospital and Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden. · Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, the Netherlands. ·Clin Chem · Pubmed #29301749.

ABSTRACT: BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and

12 Article [Nanoparticles for cancer therapy]. 2017

Löhr, Matthias / van der Wijngaart, Wouter / Fagerberg, Björn. ·Karolinska Institutet - CLINTEC K53 Stockholm, Sweden Karolinska Institutet - CLINTEC K53 Stockholm, Sweden. · Kungliga Tekniska Hogskolan - Dept. Micro och Nanosystems Stockholm, Sweden Kungliga Tekniska Hogskolan - Dept. Micro och Nanosystems Stockholm, Sweden. · Institutionen för medicin - Avdelningen för molekylär och klinisk medicin Göteborg, Sweden Institutionen för medicin - Avdelningen för molekylär och klinisk medicin Göteborg, Sweden. ·Lakartidningen · Pubmed #28675414.

ABSTRACT: Nanoparticles for cancer therapy Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history, there is a huge gap between the exciting experimental possibilities and data and clinical studies making use of it. Of the cell-containing nanoparticles, only one formulation using gene-directed enzyme prodrug therapy (GDEPT) with CYP2B1 and ifosfamide was used in early clinical studies. Of the cell-free nanoparticles, some drug-releasing (doxorubicin) ones are in clinical use for trans-arterial chemo-embolization (TACE) in liver tumors and metastasis. Using liposomes, both paclitaxel and irinotecan have been used in pancreatic cancer as the model indication. Nanoparticle-albumin-bound paclitaxel (NAB-paclitaxel) has also been developed and is now registered as a drug for first-line therapy of pancreatic cancer, as is the liposomal irinotecan. The novel nanoparticle formulations carry a big promise for even better performance, both in diagnosis and therapy; however, few of these has entered the clinic as of today.

13 Article Discrimination of pancreatic cancer and pancreatitis by LC-MS metabolomics. 2017

Lindahl, Anna / Heuchel, Rainer / Forshed, Jenny / Lehtiö, Janne / Löhr, Matthias / Nordström, Anders. ·Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. · grid.4714.6 · Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden. · Department of Molecular Biology, Umeå University, 90187 Umeå, Sweden. · grid.12650.30 ·Metabolomics · Pubmed #28413374.

ABSTRACT: INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer-related death in Europe with a 5-year survival rate of <5%. Chronic pancreatitis (CP) is a risk factor for PDAC development, but in the majority of cases malignancy is discovered too late for curative treatment. There is at present no reliable diagnostic marker for PDAC available. OBJECTIVES: The aim of the study was to identify single blood-based metabolites or a panel of metabolites discriminating PDAC and CP using liquid chromatography-mass spectrometry (LC-MS). METHODS: A discovery cohort comprising PDAC (n = 44) and CP (n = 23) samples was analyzed by LC-MS followed by univariate (Student's RESULTS: Glycocholic acid, N-palmitoyl glutamic acid and hexanoylcarnitine were identified as single markers discriminating PDAC and CP by univariate analysis. OPLS-DA resulted in a panel of five metabolites including the aforementioned three metabolites as well as phenylacetylglutamine (PAGN) and chenodeoxyglycocholate. CONCLUSION: Using LC-MS-based metabolomics we identified three single metabolites and a five-metabolite panel discriminating PDAC and CP in two independent cohorts. Although further study is needed in larger cohorts, the metabolites identified are potentially of use in PDAC diagnostics.

14 Article A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk. 2017

Gomez-Rubio, P / Rosato, V / Márquez, M / Bosetti, C / Molina-Montes, E / Rava, M / Piñero, J / Michalski, C W / Farré, A / Molero, X / Löhr, M / Ilzarbe, L / Perea, J / Greenhalf, W / O'Rorke, M / Tardón, A / Gress, T / Barberá, V M / Crnogorac-Jurcevic, T / Muñoz-Bellvís, L / Domínguez-Muñoz, E / Gutiérrez-Sacristán, A / Balsells, J / Costello, E / Guillén-Ponce, C / Huang, J / Iglesias, M / Kleeff, J / Kong, B / Mora, J / Murray, L / O'Driscoll, D / Peláez, P / Poves, I / Lawlor, R T / Carrato, A / Hidalgo, M / Scarpa, A / Sharp, L / Furlong, L I / Real, F X / La Vecchia, C / Malats, N / Anonymous3520902. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, and CIBERONC, Spain. · Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro," Department of Clinical Sciences and Community Health, University of Milan, Milan. · Unit of Medical Statistics, Biometry and Bioinformatics, National Cancer Institute, IRCCS Foundation, Milan. · Department of Epidemiology, Mario Negri Institute for Pharmacological Research-IRCCS, Milan, Italy. · Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Pompeu Fabra Univeristy (UPF), Barcelona, Spain. · Department of Surgery, Technical University of Munich, Munich. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Gastroenterology, Santa Creu i Sant Pau Hospital, Barcelona. · Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Barcelona. · Department of Medicine, Universitat Autònoma de Barcelona, Barcelona. · Network of Biomedical Research Centres (CIBER), Hepatic and Digestive Diseases and Epidemiology and Public Health, Madrid, Spain. · Gastrocentrum, Karolinska Institutet and University Hospital, Stockholm, Sweden. · Department of Gastroenterology, Parc de Salut Mar University Hospital, Barcelona. · Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain. · Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool. · Centre for Public Health, Queen's University Belfast, Belfast, UK. · Department of Medicine, University Institute of Oncology of Asturias, Oviedo, Spain. · Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany. · Molecular Genetics Laboratory, General University Hospital of Elche, Elche, Spain. · Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, UK. · General and Digestive Surgery Department, Salamanca University Hospital, Salamanca. · Department of Gastroenterology, Clinical University Hospital of Santiago de Compostela, Santiago de Compostela. · Department of Oncology, Ramón y Cajal Hospital, Madrid, and CIBERONC, Spain. · Research Programme, National Cancer Registry Ireland. · ARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital trust of Verona, Verona, Italy. · Clara Campal Integrated Oncological Centre, Sanchinarro Hospital, Madrid, Spain. · Institute of Health & Society, Newcastle University, UK. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, and CIBERONC. · Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain. ·Ann Oncol · Pubmed #28383714.

ABSTRACT: Background: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. Methods: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. Results: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. Conclusions: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

15 Article Survival Analysis and Risk for Progression of Intraductal Papillary Mucinous Neoplasia of the Pancreas (IPMN) Under Surveillance: A Single-Institution Experience. 2017

Del Chiaro, Marco / Ateeb, Zeeshan / Hansson, Marcus Reuterwall / Rangelova, Elena / Segersvärd, Ralf / Kartalis, Nikolaos / Ansorge, Christoph / Löhr, Matthias J / Arnelo, Urban / Verbeke, Caroline. ·Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet at Center for Digestive Diseases Karolinska University Hospital, Stockholm, Sweden. marco.del.chiaro@ki.se. · Pancreatic Surgery Unit, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet at Center for Digestive Diseases Karolinska University Hospital, Stockholm, Sweden. · Division of Radiology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden. ·Ann Surg Oncol · Pubmed #27822633.

ABSTRACT: PURPOSE: While surveillance of the majority of patients with IPMN is considered best practice, consensus regarding the duration of follow-up is lacking. This study assessed the survival rate and risk for progression of IPMN under surveillance. METHODS: All patients diagnosed with and surveyed for IPMN between January 2008 and December 2013 were identified and assigned to two groups: patients without indication for surgery (Group 1), and patients whose IPMN required surgery but were inoperable for general reasons (Group 2). Disease progression and survival data were compared between both groups. RESULTS: In total 503 patients were identified, of whom 444 (88.3%) were followed up. Group 1 included 395 patients, and Group 2 had 49. In Group 1, IPMN-specific 1-, 5-, and 10-year survival rates were 100, 100, and 94.2%, respectively. Four patients died of associated or concomitant pancreatic cancer, and 230 patients (58.2%) experienced disease progression. The 1-, 4-, 10-year cumulative risk for progression and for surgery was 11.2, 70.6, 97.5, and 2.9, 26.2, 72.1%, respectively. In Group 2, the 1-, 5-, 10-year IPMN-specific survival rate was 90.7, 74.8, and 74.8%, respectively. CONCLUSIONS: This study confirmed the safety of surveillance for patients with IPMN who do not require surgery. However, the risk for disease progression and for surgery increases significantly over time. The study results support International and European guidelines not to discontinue IPMN surveillance and validate the European recommendation to intensify follow-up after 5 years. The fairly good prognosis of patients whose IPMN requires surgery but cannot undergo resection suggests a relatively indolent disease biology.

16 Article Expansion of Tumor-reactive T Cells From Patients With Pancreatic Cancer. 2016

Meng, Qingda / Liu, Zhenjiang / Rangelova, Elena / Poiret, Thomas / Ambati, Aditya / Rane, Lalit / Xie, Shanshan / Verbeke, Caroline / Dodoo, Ernest / Del Chiaro, Marco / Löhr, Matthias / Segersvärd, Ralf / Maeurer, Markus J. ·Departments of *Laboratory Medicine, Division of Therapeutic Immunology ‡Microbiology, Tumor and Cell Biology, Karolinska Institute Departments of †Clinical Science, Intervention and Technology §Laboratory Medicine, Division of Pathology ∥Neurosurgery ¶CAST, Center for Allogeneic Stem Cell Transplantation, Karolinska Hospital, Stockholm, Sweden. ·J Immunother · Pubmed #26849077.

ABSTRACT: Generation of T lymphocytes with reactivity against cancer is a prerequisite for effective adoptive cellular therapies. We established a protocol for tumor-infiltrating lymphocytes (TILs) from patients with pancreatic ductal adenocarcinoma. Tumor samples from 17 pancreatic cancer specimens were cultured with cytokines (IL-2, IL-15, and IL-21) to expand TILs. After 10 days of culture, TILs were stimulated with an anti-CD3 antibody (OKT3) and irradiated allogeneic peripheral blood mononuclear cells. Reactivity of TILs against tumor-associated antigens (mesothelin, survivin, or NY-ESO-1) was detected by intracellular cytokine production by flow cytometry. Cytotoxicity was measured using a Chromium 51 release assay, and reactivity of TILs against autologous tumor cells was detected by INF-[gamma] production (ELISA). TIL composition was tested by CD45RA, CCR7, 4-1BB, LAG-3, PD-1, TIM3, and CTLA-4 marker analysis. TCR V[beta] was determined by flow cytometry and TCR clonality was gauged measuring the CDR3 region length by PCR analysis and subsequent sequencing. We could reliably obtain TILs from 17/17 patients with a majority of CD8(+) T cells. CD3(+)CD8(+), CD3(+)CD4(+), and CD3(+)CD4(-)CD8(-)[double-negative (DN) T cells] resided predominantly in central (CD45RA(-)CCR7(+)) and effector (CD45RA-CCR7-) memory subsets. CD8(+) TILs tested uniformly positive for LAG-3 (about 100%), whereas CD4(+) TILs showed only up to 12% LAG-3(+) staining and PD-1 showed a broad expression pattern in TILs from different patients. TILs from individual patients recognized strongly (up to 11.9% and 8.2% in CD8(+)) NY-ESO-1, determined by ICS, or mesothelin, determined respectively by TNF-[alpha] and IFN-[gamma] production. Twelve of 17 of CD8(+) TILs showed preferential expansion of certain TCR V[beta] families (eg, 99.2% V[beta]13.2 in CD8(+) TILs, 77% in the V[beta]1, 65.9% in the V[beta]22, and 63.3% in the V[beta]14 family). TCR CDR3 analysis exhibited monoclonal or oligoclonal TCRs, some of them (eg, CD8(+) V[beta]13.2) reacting strongly against autologous tumor defined by INF-[gamma] production or by cytotoxicity. We have optimized methods for generating pancreatic cancer–specific TILs that can be used for adoptive cellular therapy of patients with pancreatic cancer.

17 Article Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals. 2015

Capurso, Gabriele / Signoretti, Marianna / Valente, Roberto / Arnelo, Urban / Lohr, Matthias / Poley, Jan-Werner / Delle Fave, Gianfranco / Del Chiaro, Marco. ·Gabriele Capurso, Marianna Signoretti, Roberto Valente, Gianfranco Delle Fave, Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, 00199 Rome, Italy. ·World J Gastrointest Endosc · Pubmed #26240684.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasia, for which secondary prevention (i.e., screening) is advisable for high-risk individuals with "familiar pancreatic cancer" and with other specific genetic syndromes (Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.

18 Article Association between pancreatic intraductal papillary mucinous neoplasms and extrapancreatic malignancies. 2015

Marchegiani, Giovanni / Malleo, Giuseppe / D'Haese, Jan G / Wenzel, Patrick / Keskin, Muharrem / Pugliese, Luigi / Borin, Alex / Benning, Valentina / Nilsson, Linda / Oruc, Nevin / Segersvard, Ralf / Friess, Helmut / Schmid, Roland / Löhr, Matthias / Maisonneuve, Patrick / Bassi, Claudio / Ceyhan, Güralp O / Salvia, Roberto / Del Chiaro, Marco. ·Unit of Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. Electronic address: giovanni.marchegiani@ospedaleuniverona.it. · Unit of Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Department of Gastroenterology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Division of Gastroenterology, Department of Internal Medicine, Ege University, Izmir, Turkey. · Unit of General Surgery 2, Department of Surgery, IRCCS Policlinico San Matteo, Pavia, Italy. · Division of Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Division of Gastroenterology, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. ·Clin Gastroenterol Hepatol · Pubmed #25478920.

ABSTRACT: BACKGROUND & AIMS: The association between pancreatic intraductal papillary mucinous neoplasms (IPMNs) and extrapancreatic neoplasms (EPNs) is controversial. We performed a multicenter observational study to assess the incidence of EPNs after an IPMN diagnosis. METHODS: 1340 patients with IPMNs were evaluated from 2000 through 2013 at 4 academic institutions in Europe for development of EPN. To estimate the actual incidence of EPN, we excluded patients with an EPN previous or synchronous to the IPMN, and patients who had been followed for less than 12 months, resulting in a study population of 816 patients. The incidence of EPN was compared with sex-specific, age-adjusted European cancer statistics; the standardized incidence ratio (SIR), and the 5- and 10-year cumulative incidence rates were calculated. RESULTS: A total of 290/1340 patients had a history of EPN (prevalence of 21.6%). In this subgroup of patients, the IPMN was discovered incidentally in 241. Among the 816 patients included in the incidence analysis, 50 developed an EPN after a median time of 46 months from study enrollment. The incidence of any EPN was not greater in patients with than without IPMN with a SIR of 1.48 (95% confidence interval, 0.94-2.22) in males and of 1.39 (95% CI 0.90-2.05) in females. The 5- and 10-year cumulative incidence rates for development of EPN in patients with IPMN were 7.9% and 16.6% in men, and 3.4% and 23.1% in women. CONCLUSIONS: Patients with IPMN do not have a significantly higher incidence of EPNs than the general European population. It might not be necessary to screen patients with IPMN for EPN.

19 Article Comparison of preoperative conference-based diagnosis with histology of cystic tumors of the pancreas. 2014

Del Chiaro, Marco / Segersvärd, Ralf / Pozzi Mucelli, Raffaella / Rangelova, Elena / Kartalis, Nikolaos / Ansorge, Christoph / Arnelo, Urban / Blomberg, John / Löhr, Matthias / Verbeke, Caroline. ·Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden, marco.del-chiaro@karolinska.se. ·Ann Surg Oncol · Pubmed #24385209.

ABSTRACT: BACKGROUND: Diagnostic errors in the evaluation of cystic neoplasms of the pancreas (PCNs) are quite common. Few data are available regarding the impact of these errors on clinical management. The aim of this study was to determine the accuracy of a pancreatic multidisciplinary conference in diagnosing PCNs, to assess the potential risk of misdiagnosis, and to evaluate the clinical impact of these errors. METHODS: A retrospective consecutive series of patients undergoing surgery for PCNs at Karolinska University Hospital between 2004 and 2012 was analyzed. RESULTS: During the study period, a total of 141 patients had undergone pancreatic resection for PCN. The overall accuracy of the preoperative diagnosis was 60.9 %. The rate of concordance between preoperative diagnosis and histology was similar for asymptomatic and symptomatic lesions (62.8 vs. 59.1 %; p = NS). The rate of correct diagnosis increased over time (54.5 % in 2004-2006, 61.7 % in 2007-2012, 63.5 % in 2010-2012). Univariate analysis identified the location of the lesion (diffuse pancreatic involvement) and a mucinous nature of the lesion as factors conducive to a correct diagnosis. Reevaluation of the original indication for surgery in light of the exact diagnosis showed that a surgical procedure should not have been performed in 12 patients (8.5 %). CONCLUSIONS: This study confirms that diagnostic errors are fairly common in the preoperative assessment of PCNs, but the errors are clinically relevant in <10 % of patients.

20 Article 3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing. 2013

Longati, Paola / Jia, Xiaohui / Eimer, Johannes / Wagman, Annika / Witt, Michael-Robin / Rehnmark, Stefan / Verbeke, Caroline / Toftgård, Rune / Löhr, Matthias / Heuchel, Rainer L. ·CLINTEC, Karolinska Institutet, Stockholm 14186, Sweden. ·BMC Cancer · Pubmed #23446043.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance. METHODS: Several established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine. RESULTS: Comparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect. CONCLUSIONS: We developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance.

21 Article Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis. 2013

Hart, Phil A / Kamisawa, Terumi / Brugge, William R / Chung, Jae Bock / Culver, Emma L / Czakó, László / Frulloni, Luca / Go, Vay Liang W / Gress, Thomas M / Kim, Myung-Hwan / Kawa, Shigeyuki / Lee, Kyu Taek / Lerch, Markus M / Liao, Wei-Chih / Löhr, Matthias / Okazaki, Kazuichi / Ryu, Ji Kon / Schleinitz, Nicolas / Shimizu, Kyoko / Shimosegawa, Tooru / Soetikno, Roy / Webster, George / Yadav, Dhiraj / Zen, Yoh / Chari, Suresh T. ·Division of Gastroenterology and Hepatology, Mayo Clinic, , Rochester, Minnesota, USA. ·Gut · Pubmed #23232048.

ABSTRACT: OBJECTIVE: Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. DESIGN: 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. RESULTS: The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. CONCLUSIONS: AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.

22 Article Identification of serum biomarker signatures associated with pancreatic cancer. 2012

Wingren, Christer / Sandström, Anna / Segersvärd, Ralf / Carlsson, Anders / Andersson, Roland / Löhr, Matthias / Borrebaeck, Carl A K. ·Department of Immunotechnology, Lund University, Lund, Sweden. ·Cancer Res · Pubmed #22589272.

ABSTRACT: Pancreatic cancer is an aggressive disease with poor prognosis, due, in part, to the lack of disease-specific biomarkers that could afford early and accurate diagnosis. With a recombinant antibody microarray platform, targeting mainly immunoregulatory proteins, we screened sera from 148 patients with pancreatic cancer, chronic pancreatitis, autoimmune pancreatitis (AIP), and healthy controls (N). Serum biomarker signatures were derived from training cohorts and the predictive power was evaluated using independent test cohorts. The results identified serum portraits distinguishing pancreatic cancer from N [receiver operating characteristics area under the curve (AUC) of 0.95], chronic pancreatitis (0.86), and AIP (0.99). Importantly, a 25-serum biomarker signature discriminating pancreatic cancer from the combined group of N, chronic pancreatitis, and AIP was determined. This signature exhibited a high diagnostic potential (AUC of 0.88). In summary, we present the first prevalidated, multiplexed serum biomarker signature for diagnosis of pancreatic cancer that may improve diagnosis and prevention in premalignant diseases and in screening of high-risk individuals.

23 Article Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. 2011

Lonardo, Enza / Hermann, Patrick C / Mueller, Maria-Theresa / Huber, Stephan / Balic, Anamaria / Miranda-Lorenzo, Irene / Zagorac, Sladjana / Alcala, Sonia / Rodriguez-Arabaolaza, Iker / Ramirez, Juan Carlos / Torres-Ruíz, Raul / Garcia, Elena / Hidalgo, Manuel / Cebrián, David Álvaro / Heuchel, Rainer / Löhr, Matthias / Berger, Frank / Bartenstein, Peter / Aicher, Alexandra / Heeschen, Christopher. ·Clinical Research Programme, Stem Cells and Cancer Group, Spanish National Cancer Research Centre, Madrid 28029, Spain. ·Cell Stem Cell · Pubmed #22056140.

ABSTRACT: Nodal and Activin belong to the TGF-β superfamily and are important regulators of embryonic stem cell fate. Here we investigated whether Nodal and Activin regulate self-renewal of pancreatic cancer stem cells. Nodal and Activin were hardly detectable in more differentiated pancreatic cancer cells, while cancer stem cells and stroma-derived pancreatic stellate cells markedly overexpressed Nodal and Activin, but not TGF-β. Knockdown or pharmacological inhibition of the Nodal/Activin receptor Alk4/7 in cancer stem cells virtually abrogated their self-renewal capacity and in vivo tumorigenicity, and reversed the resistance of orthotopically engrafted cancer stem cells to gemcitabine. However, engrafted primary human pancreatic cancer tissue with a substantial stroma showed no response due to limited drug delivery. The addition of a stroma-targeting hedgehog pathway inhibitor enhanced delivery of the Nodal/Activin inhibitor and translated into long-term, progression-free survival. Therefore, inhibition of the Alk4/7 pathway, if combined with hedgehog pathway inhibition and gemcitabine, provides a therapeutic strategy for targeting cancer stem cells.

24 Article Inhibition of ankyrin-B expression reduces growth and invasion of human pancreatic ductal adenocarcinoma. 2010

Chen, Ying / Löhr, Matthias / Jesnowski, Ralf. ·Clinical Cooperation Unit Molecular Gastroenterology (G350), DKFZ, Heidelberg, Germany. ·Pancreatology · Pubmed #21042036.

ABSTRACT: BACKGROUND: In spite of the increasing knowledge of the molecular pathology of pancreatic ductal adenocarcinoma (PDAC), treatment of this tumor still remains an unresolved problem. Thus, the identification of 'novel' genes involved in pancreatic tumor progression is essential for early diagnosis and new treatment regimens of PDAC. Ankyrin-B (ANK2) was identified as being overexpressed in PDAC in a previous study by our group. ANK2 overexpression has been described in several tumors; however, the function of ANK2 in pancreatic carcinoma has not been elucidated. MATERIALS AND METHODS: In the present study, we confirmed ANK2 overexpression in PDAC and analyzed the effects of ANK2 knockdown in the pancreatic tumor cell line PANC-1. RESULTS: ANK2 silencing reduced the activity of FAK, ERK1/2 and p38. Decreased ANK2 expression restrained migration and invasive potential of PANC-1 cells. Moreover, silencing of ANK2 decreased the proliferation of the pancreatic tumor cells and reduced their tumorigenicity in vitro and in vivo. CONCLUSION: Our results demonstrate that silencing of ANK2 expression reduced the malignant phenotype of pancreatic cancer cells, indicating that ANK2 represents a potential target for therapy of pancreatic cancer.

25 Article Comparison of two different methods for CA19-9 antigen determination. 2010

Deinzer, Martina / Faissner, Ralf / Metzger, Tobias / Kaminski, Wolfgang E / Löhr, Mathias / Neumaier, Michael / Brinkmann, Thomas. ·Institute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany. martina.deinzer@onkologikum-labor.de ·Clin Lab · Pubmed #20857896.

ABSTRACT: BACKGROUND: This study was designed to investigate the clinical performance of the Access GI Monitor (Beckman Coulter) on the UniCel DxI 800, a method for CA19-9 antigen determination, and to compare with CA19-9 assay on the AxSYM system (Abbott). METHODS: 1,063 serum samples from unselected patients with different underlying diagnoses were tested with both methods. Passing-Bablok regression analysis and Bland Altman analysis was performed. In addition, using ROC analysis, the distribution of Access GI Monitor and AxSYM CA19-9 antigen levels was tested in patients with pancreatic cancer (n = 50), acute inflammatory disease (n = 20), and with chronic inflammation of the pancreatic gland (n = 18). Furthermore, four patients with pancreatic cancer were monitored individually in their courses of the disease (before, during, and after therapeutic procedures) to compare their CA19-9 values with regard to inter-method concordance. RESULTS: Passing-Bablok analysis showed a systematic difference with R = 0.93, slope 0.75, and intercept -1.0. Bland Altman analysis showed a wide scatter of relative differences between both methods, especially in the low end measuring range. In the selected group of patients with pancreatic diseases the analysis of concordance revealed 95.5 % agreement between both methods with a comparable area under the ROC curves (0.73 vs. 0.76). A clear concordance was found for all four selected patients. CONCLUSIONS: Although we found significant systematic measuring variations in the global analysis, the two different automated methods for the quantitative determination of CA19-9 antigen were comparable with respect to their clinical accuracy and applicability to support decision making in the management of pancreatic cancer.