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Article ; Online: Novel Insights Into Macrophage Diversity During the Course of Pancreatitis.

Allawadhi, Prince / Beyer, Georg / Mahajan, Ujjwal M / Mayerle, Julia

2021 Volume 161, Issue 6, Page(s) 1802–1805

MeSH term(s)	Humans ; Macrophages ; Pancreatitis
Language	English
Publishing date	2021-09-26
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2021.09.049
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Article ; Online: Reply.

Beyer, Georg / Mahajan, Ujjwal M / Lerch, Markus M / Mayerle, Julia

Gastroenterology

2018 Volume 154, Issue 6, Page(s) 1853–1854

Language	English
Publishing date	2018
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2018.03.061
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Article ; Online: The inhibition of YAP Signaling Prevents Chronic Biliary Fibrosis in the Abcb4

Ye, Liangtao / Ziesch, Andreas / Schneider, Julia S / Ofner, Andrea / Nieß, Hanno / Denk, Gerald / Hohenester, Simon / Mayr, Doris / Mahajan, Ujjwal M / Munker, Stefan / Khaled, Najib Ben / Wimmer, Ralf / Gerbes, Alexander L / Mayerle, Julia / He, Yulong / Geier, Andreas / Toni, Enrico N De / Zhang, Changhua / Reiter, Florian P

Aging and disease

2024 Volume 15, Issue 1, Page(s) 338–356

Abstract: Primary sclerosing cholangitis (PSC) represents a chronic liver disease characterized by poor prognosis and lacking causal treatment options. Yes-associated protein (YAP) functions as a critical mediator of fibrogenesis; however, its therapeutic ... ...

Abstract	Primary sclerosing cholangitis (PSC) represents a chronic liver disease characterized by poor prognosis and lacking causal treatment options. Yes-associated protein (YAP) functions as a critical mediator of fibrogenesis; however, its therapeutic potential in chronic biliary diseases such as PSC remains unestablished. The objective of this study is to elucidate the possible significance of YAP inhibition in biliary fibrosis by examining the pathophysiology of hepatic stellate cells (HSC) and biliary epithelial cells (BEC). Human liver tissue samples from PSC patients were analyzed to assess the expression of YAP/connective tissue growth factor (CTGF) relative to non-fibrotic control samples. The pathophysiological relevance of YAP/CTGF in HSC and BEC was investigated in primary human HSC (phHSC), LX-2, H69, and TFK-1 cell lines through siRNA or pharmacological inhibition utilizing verteporfin (VP) and metformin (MF). The Abcb4
MeSH term(s)	Mice ; Animals ; Humans ; Hepatic Stellate Cells ; Liver Cirrhosis/drug therapy ; Fibrosis ; Cholestasis/metabolism ; Bile Ducts ; Epithelium/metabolism
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625789-0
ISSN	2152-5250 ; 2152-5250
ISSN (online)	2152-5250
ISSN	2152-5250
DOI	10.14336/AD.2023.0602
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Article: ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma.

bioRxiv : the preprint server for biology

2024

Abstract: Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We ... ...

Abstract	Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor Pdx1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in mouse and human. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia (SPEM)-like identity in the pancreas. Ablation of
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.13.571566
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Article ; Online: Consensus definition of sludge and microlithiasis as a possible cause of pancreatitis.

Żorniak, Michal / Sirtl, Simon / Beyer, Georg / Mahajan, Ujjwal Mukund / Bretthauer, Katharina / Schirra, Jörg / Schulz, Christian / Kohlmann, Thomas / Lerch, Markus M / Mayerle, Julia

Gut

2023 Volume 72, Issue 10, Page(s) 1919–1926

Abstract: Objective: In up to 20% of patients, the aetiology of acute pancreatitis (AP) remains elusive and is thus called idiopathic. On more detailed review these cases can often be explained through biliary disease and are amenable to treatment. Findings range ...

Abstract	Objective: In up to 20% of patients, the aetiology of acute pancreatitis (AP) remains elusive and is thus called idiopathic. On more detailed review these cases can often be explained through biliary disease and are amenable to treatment. Findings range from biliary sludge to microlithiasis but their definitions remain fluid and controversial. Design: A systematic literature review (1682 reports, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) analysed definitions of biliary sludge and microlithiasis, followed by an online international expert survey (30 endoscopic ultrasound/hepatobiliary and pancreatic experts; 36 items) which led to definitions of both. These were consented by Delphi voting and clinically evaluated in a retrospective cohort of patients with presumed biliary pancreatitis. Results: In 13% of original articles and 19.2% of reviews, microlithiasis and biliary sludge were used synonymously. In the survey, 41.7% of experts described the term 'sludge' and 'microlithiasis' as identical findings. As a consequence, three definitions were proposed, agreed on and confirmed by voting to distinctly discriminate between biliary sludge (hyperechoic material without acoustic shadowing) and microlithiasis (echorich calculi of ≤5 mm with acoustic shadowing) as opposed to larger biliary stones, both for location in gallbladder and bile ducts. In an initial attempt to investigate the clinical relevance in a retrospective analysis in 177 confirmed cases in our hospital, there was no difference in severity of AP if caused by sludge, microlithiasis or stones. Conclusion: We propose a consensus definition for the localisation, ultrasound morphology and diameter of biliary sludge and microlithiasis as distinct entities. Interestingly, severity of biliary AP was not dependent on the size of concrements warranting prospective randomised studies which treatment options are adequate to prevent recurrence.
MeSH term(s)	Humans ; Pancreatitis/complications ; Pancreatitis/diagnostic imaging ; Retrospective Studies ; Prospective Studies ; Acute Disease ; Consensus ; Gallstones/complications
Language	English
Publishing date	2023-04-18
Publishing country	England
Document type	Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2022-327955
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Article ; Online: Pankreaskarzinom 2018 – reif für personalisierte Therapiekonzepte?

Simon, Ole / Beyer, Georg / Mahajan, Ujjwal M / Mayerle, Julia

Deutsche medizinische Wochenschrift (1946)

2018 Volume 143, Issue 15, Page(s) 1109–1112

Abstract: In Germany, an estimated 19 000 people will develop pancreatic carcinoma in 2018. The 5-year survival rate of all pancreatic carcinoma patients is very low at around 6 %, and the potentially curative operation is only possible in 15 - 20 % of patients. ... ...

Title translation	Pancreatic Cancer in the Year 2018 - Room for Precision Medicine?
Abstract	In Germany, an estimated 19 000 people will develop pancreatic carcinoma in 2018. The 5-year survival rate of all pancreatic carcinoma patients is very low at around 6 %, and the potentially curative operation is only possible in 15 - 20 % of patients. More frequent use and combination of systemic chemotherapeutic agents has led to improved life expectancy in recent years. In this article we will summarize recent therapeutic strategies depending on tumor status and current approaches to personalized medicine in pancreatic carcinoma.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Forecasting ; Germany ; Humans ; Neoplasm Staging ; Pancreatectomy/methods ; Pancreatic Neoplasms/mortality ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/therapy ; Precision Medicine/trends ; Survival Rate ; Treatment Outcome
Language	German
Publishing date	2018-07-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	200446-x
ISSN	1439-4413 ; 0012-0472
ISSN (online)	1439-4413
ISSN	0012-0472
DOI	10.1055/a-0542-4310
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Article ; Online: Impact of tumor size and location on endoscopic ultrasound-guided sampling of pancreatic neuroendocrine tumors: A recursive partitioning analysis.

Sirtl, Simon / Mahajan, Ujjwal M / Auernhammer, Christoph Josef / Dziadkiewicz, Piotr / Hohmann, Eric / Wójcik, Michał / Kos-Kudła, Beata / Hartleb, Marek / Knösel, Thomas / Schirra, Jörg / Mayerle, Julia / Schulz, Christian / Żorniak, Michał

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.

2022 Volume 22, Issue 5, Page(s) 644–650

Abstract: Background: Current guidelines provide weak recommendations to treat small (<2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus ... ...

Abstract	Background: Current guidelines provide weak recommendations to treat small (<2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus regarding the minimal size of pNET, which allows EUS-guided biopsy with high enough diagnostic accuracy for stratification. Methods: We conducted a retrospective, bicentric analysis of patients who had undergone EUS-guided pNET sampling in two tertiary care Endoscopy Units in Germany and Poland. Using a recursive partitioning of the tree-aided model, we aimed to stratify the probability of successful EUS-guided biopsy of pNET lesions according to their size and location. Results: In our pNET cohort, successful histological confirmation of a pNET diagnosis was achieved in 59/69 (85.5%) cases at the initial EUS-guided biopsy. In 41 patients with a pNET size less than 18.5 mm, the EUS-guided first biopsy was successful in 90.2%. In 16 of these patients with smaller lesions, EUS-guided sampling was 100% in very small (less than 11 mm) and extremely small lesions (less than 8 mm). The biopsy success rate was 100% in tail lesions in the size range between ≥5.95 and <8.1 mm but only 33.3% independent of the investigator in pancreatic head or body, with an error rate of 11.2% CONCLUSION: Using a recursive partitioning of the tree-aided stratification model, we demonstrate for the first time that in balancing risks and benefits, very small pNETs (<1 cm) in the tail of the pancreas should be sampled under EUS-guidance.
MeSH term(s)	Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Humans ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors/pathology ; Pancreatic Neoplasms/pathology ; Retrospective Studies
Language	English
Publishing date	2022-05-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2056680-3
ISSN	1424-3911 ; 1424-3903
ISSN (online)	1424-3911
ISSN	1424-3903
DOI	10.1016/j.pan.2022.04.014
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Article ; Online: Pancreatitis severity in mice with impaired CFTR function but pancreatic sufficiency is mediated via ductal and inflammatory cells-Not acinar cells.

Trapp, Simon / Aghdassi, Ali A / Glaubitz, Juliane / Sendler, Matthias / Weiss, Frank Ulrich / Kühn, Jens Peter / Kromrey, Marie-Luise / Mahajan, Ujjwal M / Pallagi, Petra / Rakonczay, Zoltán / Venglovecz, Viktória / Lerch, Markus M / Hegyi, Peter / Mayerle, Julia

Journal of cellular and molecular medicine

2021 Volume 25, Issue 10, Page(s) 4658–4670

Abstract: Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) are an established risk factor for cystic fibrosis (CF) and chronic pancreatitis. Whereas patients with CF usually develop complete exocrine pancreatic insufficiency, ... ...

Abstract	Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) are an established risk factor for cystic fibrosis (CF) and chronic pancreatitis. Whereas patients with CF usually develop complete exocrine pancreatic insufficiency, pancreatitis patients with CFTR mutations have mostly preserved exocrine pancreatic function. We therefore used a strain of transgenic mice with significant residual CFTR function (CFTR
MeSH term(s)	Acinar Cells/cytology ; Acinar Cells/metabolism ; Animals ; Chlorides/metabolism ; Cystic Fibrosis/complications ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Humans ; Inflammation/etiology ; Inflammation/metabolism ; Inflammation/pathology ; Male ; Mice ; Mice, Transgenic ; Mutation ; Pancreatic Ducts/metabolism ; Pancreatic Ducts/pathology ; Pancreatitis/etiology ; Pancreatitis/metabolism ; Pancreatitis/pathology ; Severity of Illness Index
Chemical Substances	CFTR protein, human ; Chlorides ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2021-03-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.16404
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Article ; Online: HLA-DRB1∗16 and -DQB1∗05 alleles are strongly associated with autoimmune pancreatitis in a cohort of hundred patients.

Goni, Elisabetta / Regel, Ivonne / Mahajan, Ujjwal Mukund / Amodio, Antonio / De Marchi, Giulia / Beyer, Georg / Zuppardo, Raffaella Alessia / Di Leo, Milena / Lanzillotta, Marco / Bonatti, Francesco / Kauke, Teresa / Dick, Andrea / Weiss, Frank Ulrich / Schönermarck, Ulf / Lerch, Markus M / Frulloni, Luca / Cavestro, Giulia Martina / Mayerle, Julia

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.

2022 Volume 22, Issue 4, Page(s) 466–471

Abstract: Background/objectives: Autoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. ... ...

Abstract	Background/objectives: Autoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. In our study, we aimed to investigate HLA alleles in a large European cohort of autoimmune pancreatitis (AIP) patients. Methods: Hundred patients with AIP, diagnosed and classified according to the International Consensus Diagnostic Criteria (ICDC), were prospectively enrolled in the study. Forty-four patients with chronic pancreatitis (CP) and 254 healthy subjects served as control groups. DNA was isolated from blood samples and two-digit HLA typing was performed with sequence-specific primer (SSP-) PCR. HLA allele association strength to AIP was calculated as odds ratio. Results: We uncovered a strong enrichment of HLA-DQB1 homozygosity in type 1 and type 2 AIP patients. Moreover, a significantly increased incidence of the HLA-DRB1∗16 and HLA-DQB1∗05 alleles and a concomitant lack of the HLA-DRB1∗13 allele was detected in AIP type 1 and type 2 patients. In contrast, the HLA-DQB1∗02 allele was underrepresented in the 'not otherwise specified' (NOS) AIP subtype. We detected no significant difference in the HLA-DRB3, HLA-DRB4 and HLA-DRB5 allele frequency in our cohort. Conclusions: Although AIP type 1 and type 2 are characterized by distinct histopathological characteristics, both subtypes are associated with the same HLA alleles, indicating that the disease might rely on similar immunogenic mechanisms. However, AIP NOS represented another subclass of AIP.
MeSH term(s)	Alleles ; Autoimmune Pancreatitis ; Gene Frequency ; Genetic Predisposition to Disease ; HLA-DRB1 Chains/genetics ; HLA-DRB4 Chains/genetics ; Haplotypes ; Humans
Chemical Substances	HLA-DRB1 Chains ; HLA-DRB4 Chains
Language	English
Publishing date	2022-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2056680-3
ISSN	1424-3911 ; 1424-3903
ISSN (online)	1424-3911
ISSN	1424-3903
DOI	10.1016/j.pan.2022.03.015
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Article: Pankreaskarzinom 2018 – reif für personalisierte Therapiekonzepte?

Simon, Ole / Beyer, Georg / Mahajan, Ujjwal M. / Mayerle, Julia

TumorDiagnostik & Therapie

2019 Volume 40, Issue 03, Page(s) 180–183

Abstract: Epidemiologie: Die 5-Jahres-Überlebensrate (5-JÜR) aller Pankreaskarzinompatienten liegt mit rund 6 % sehr niedrig und die potenziell kurative Operation ist nur bei 15 – 20 % der Erkrankten möglich. Durch häufigeren Einsatz und Kombination systemischer ... ...

Abstract	Epidemiologie: Die 5-Jahres-Überlebensrate (5-JÜR) aller Pankreaskarzinompatienten liegt mit rund 6 % sehr niedrig und die potenziell kurative Operation ist nur bei 15 – 20 % der Erkrankten möglich. Durch häufigeren Einsatz und Kombination systemischer Chemotherapeutika konnte in den letzten Jahren eine verbesserte Lebenserwartung erreicht werden. Resektables Stadium: Nach vollständiger operativer Resektion eines Pankreaskarzinoms trägt eine adjuvante Chemotherapie zur Verlängerung des Gesamtüberlebens bei. Mittel der Wahl sind Gemcitabin oder 5-Fluorouracil (5-FU) und Folinsäure (FS). Kürzlich konnte für die Kombination aus Gemcitabin und Capecitabin (Gem-Cap) eine signifikante Verlängerung des Gesamtüberlebens im Vergleich zur Gemcitabin-Monotherapie gezeigt werden. Für den Einsatz einer adjuvanten Radiochemotherapie gibt es derzeit keine Empfehlung. Borderline-resektables Stadium: Eine neoadjuvante Therapie hat bei Pankreaskarzinomen außerhalb klinischer Studien keinen Stellenwert. Eine Ausnahme stellen borderline-resektable Pankreaskarzinome dar. Fortgeschrittenes Stadium (M1): Patienten mit fortgeschrittenem oder metastasiertem Pankreaskarzinom profitieren von einer Chemotherapie. Für Patienten mit gutem ECOG-Status konnte kürzlich in 2 Phase-III-Studien eine signifikante Lebenszeitverlängerung durch die Kombination aus Gemcitabin plus nab-Paclitaxel (Gem-Nab) sowie durch das Kombinationsschema aus Folinsäure, 5-FU, Irinotecan und Oxaliplatin (FOLFIRINOX) gezeigt werden. In der Zweitlinie steht nanoliposomales Irinotecan oder Oxaliplatin kombiniert mit 5FU/FS (OFF) zur Verfügung. Personalisierte Therapien: Die molekulare Charakterisierung des Pankreaskarzinoms hat Fortschritte gemacht und bietet schon heute Ansätze zur personalisierten Medizin. Bei gutem ECOG-Status sollte vor Zweitlinientherapie eine MSI-H/dMMR-Analyse erfolgen, um den möglichen Einsatz einer Checkpoint-Inhibitor-Therapie zu evaluieren. Bei BRCA-Mutationen kann die Gabe von PARP-Inhibitoren vielversprechend sein.
Keywords	Bauchspeicheldrüsenkrebs ; personalisierte Medizin ; Chemotherapie/Onkologie ; pancreatic cancer ; personalized medicine ; chemotherapy/oncology
Language	German
Publishing date	2019-04-01
Publisher	© Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2072365-9
ISSN	1439-1279 ; 0722-219X
ISSN (online)	1439-1279
ISSN	0722-219X
DOI	10.1055/a-0870-8867
Database	Thieme publisher's database

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