19 results on '"Annika Bergquist"'
Search Results
2. Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis
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Martine Walmsley, Vipul Jairath, Christoph Schramm, Michael Trauner, Christopher Ma, Gideon Hirschfield, Palak J Trivedi, Nasir Hussain, Olalekan Lee Aiyegbusi, Mette Vesterhus, Kris Kowdley, Cyriel Ponsioen, Annika Bergquist, Paula Hanford, Cynthia Levy, David Assis, and Christopher Bowlus
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Medicine - Abstract
Background Primary sclerosing cholangitis (PSC) is a progressive immune-mediated liver disease, for which no medical therapy has been shown to slow disease progression. However, the horizon for new therapies is encouraging, with several innovative clinical trials in progress. Despite these advancements, there is considerable heterogeneity in the outcomes studied, with lack of consensus as to what outcomes to measure, when to measure and how to measure. Furthermore, there has been a paradigm shift in PSC treatment targets over recent years, moving from biochemistry-based endpoints to histological assessment of liver fibrosis, imaging-based biomarkers and patient-reported outcome measures. The abundance of new interventional trials and evolving endpoints pose opportunities for all stakeholders involved in evaluating novel therapies. To this effect, there is a need to harmonise measures used in clinical trials through the development of a core outcome set (COS).Methods and analysis Synthesis of a PSC-specific COS will be conducted in four stages. Initially, a systematic literature review will be performed to identify outcomes previously used in PSC trials, followed by semistructured qualitative interviews conducted with key stakeholders. The latter may include patients, clinicians, researchers, pharmaceutical industry representatives and healthcare payers and regulatory agencies, to identify additional outcomes of importance. Using the outcomes generated from the literature review and stakeholder interviews, an international two-round Delphi survey will be conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting will be convened to ratify the COS and disseminate findings for application in future PSC trials.Ethics and dissemination Ethical approval has been granted by the East Midlands—Leicester Central Research Ethics Committee (Ref: 24/EM/0126) for this study. The COS from this study will be widely disseminated including publication in peer-reviewed journals, international conferences, promotion through patient-support groups and made available on the Core Outcomes Measurement in Effectiveness Trials (COMET) database.Trial registration number 1239.
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- 2024
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3. The Swedish initiative for the study of Primary sclerosing cholangitis (SUPRIM)Research in context
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Martin Cornillet, Christina Villard, Fredrik Rorsman, Antonio Molinaro, Emma Nilsson, Stergios Kechagias, Erik von Seth, and Annika Bergquist
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Primary sclerosing cholangitis ,Inflammatory bowel disease ,Liver transplantation ,Phenotype ,Outcome ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Despite more than 50 years of research and parallel improvements in hepatology and oncology, there is still today neither a treatment to prevent disease progression in primary sclerosing cholangitis (PSC), nor reliable early diagnostic tools for the associated hepatobiliary cancers. Importantly, the limited understanding of the underlying biological mechanisms in PSC and its natural history not only affects the identification of new drug targets but implies a lack of surrogate markers that hampers the design of clinical trials and the evaluation of drug efficacy. The lack of easy access to large representative well-characterised prospective resources is an important contributing factor to the current situation. Methods: We here present the SUPRIM cohort, a national multicentre prospective longitudinal study of unselected PSC patients capturing the representative diversity of PSC phenotypes. We describe the 10-year effort of inclusion and follow-up, an intermediate analysis report including original results, and the associated research resource. All included patients gave written informed consent (recruitment: November 2011–April 2016). Findings: Out of 512 included patients, 452 patients completed the five-year follow-up without endpoint outcomes. Liver transplantation was performed in 54 patients (10%) and hepatobiliary malignancy was diagnosed in 15 patients (3%). We draw a comprehensive landscape of the multidimensional clinical and biological heterogeneity of PSC illustrating the diversity of PSC phenotypes. Performances of available predictive scores are compared and perspectives on the continuation of the SUPRIM cohort are provided. Interpretation: We envision the SUPRIM cohort as an open-access collaborative resource to accelerate the generation of new knowledge and independent validations of promising ones with the aim to uncover reliable diagnostics, prognostic tools, surrogate markers, and new treatment targets by 2040. Funding: This work was supported by the Swedish Cancer Society, Stockholm County Council, and the Cancer Research Funds of Radiumhemmet.
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- 2024
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4. Treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis: a comprehensive review
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Annika Bergquist, Carl Jorns, and Christina Villard
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterised by persistent biliary inflammation resulting in fibrosis and multifocal strictures of the biliary tree. The course of disease is highly variable, ranging from asymptomatic disease to the development of end-stage biliary cirrhosis and an increased risk of biliary tract cancer (BTC), particularly cholangiocarcinoma (CCA).PSC is the most important risk factor for CCA in younger people, with a reported lifetime prevalence ranging from 6% to 13%. Perihilar CCA (pCCA), involving the hepatic duct bifurcation, is the most common CCA amounting to approximately 50% of all cases, whereas intrahepatic CCA (iCCA), located within the hepatic parenchyma, represents less than 10%.CCA is an aggressive tumour, and only a minority of patients are amenable to surgical resection with curative intent. Radical liver resection and liver transplantation are potentially curative therapeutic options in patients with PSC in the absence of metastatic or locally advanced disease. Liver transplantation with neoadjuvant chemoradiation could be considered in selected patients with unresectable pCCA and without pretreatment in patients with PSC with bile duct high-grade dysplasia. Recent reports demonstrating favourable outcomes in transplanted patients with small iCCA and patients with locally advanced disease following neoadjuvant therapy have challenged the previously described poor outcome in transplanted patients with iCCA.Treatment for CCA is challenged by the inherent difficulties in enabling an early diagnosis and thereby preventing an otherwise dismal prognosis. This comprehensive review aims to describe therapeutic considerations and challenges in patients with PSC-CCA.
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- 2024
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5. Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis
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Jeremy S. Nayagam, Tobias J. Weismüller, Piotr Milkiewicz, Karolina M. Wronka, Emil Bik, Christoph Schramm, Katja Fuessel, Taotao Zhou, Johannes Chang, Martti Färkkilä, Ylva Carlsson, Anastasia Lundman, Nora Cazzagon, Giorgia Corrà, Eirini Rigopoulou, George N. Dalekos, Aiva Lundberg Båve, Annika Bergquist, Karim Ben Belkacem, Marco Marzioni, Martina Mancinelli, Xavier Verhelst, Hanns-Ulrich Marschall, Michael A. Heneghan, and Deepak Joshi
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Primary sclerosing cholangitis ,Intrahepatic cholestasis of pregnancy ,Cholangiopathy ,Pruritus ,Ursodeoxycholic acid ,Bile acids ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes. Methods: We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used. Results: There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p = 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p = 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p = 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p = 0.84). Conclusions: Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype. Impact and implications: Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.
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- 2024
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6. Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis
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Younghun Han, Jinyoung Byun, Catherine Zhu, Ryan Sun, Julia Y. Roh, Heather J. Cordell, Hyun-Sung Lee, Vikram R. Shaw, Sung Wook Kang, Javad Razjouyan, Matthew A. Cooley, Manal M. Hassan, Katherine A. Siminovitch, Trine Folseraas, David Ellinghaus, Annika Bergquist, Simon M. Rushbrook, Andre Franke, Tom H. Karlsen, Konstantinos N. Lazaridis, The International PSC Study Group, Katherine A. McGlynn, Lewis R. Roberts, and Christopher I. Amos
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Science - Abstract
The genetic basis of primary sclerosing cholangitis has only been partially uncovered. Here, the authors perform a multitrait genome-wide association study to provide insight into the genetic etiology of primary sclerosing cholangitis risk and possible therapeutic drug targets.
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- 2023
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7. Development of a prognostic MRCP-score (DiStrict) for individuals with large-duct primary sclerosing cholangitis
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Aristeidis Grigoriadis, Kristina Imeen Ringe, Johan Bengtsson, Erik Baubeta, Cecilia Forsman, Nafsika Korsavidou-Hult, Fredrik Rorsman, Emma Nilsson, Nikolaos Kartalis, and Annika Bergquist
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Cholangitis sclerosing ,Cholangiopancreatography ,Magnetic resonance ,Bile ducts ,Prognosis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Magnetic resonance cholangiopancreatography (MRCP) is used for the diagnosis and follow-up of individuals with primary sclerosing cholangitis (PSC). The aim of our study is to develop an MRCP-score based on cholangiographic findings previously associated with outcomes and assess its reproducibility and prognostic value in PSC. Methods: The score (DiStrict score) was developed based on the extent and severity of cholangiographic changes of intrahepatic and extrahepatic bile ducts (range 0–8) on 3D-MRCP. In this retrospective, multicentre study, three pairs of radiologists with different levels of expertise from three tertiary centres applied the score independently. MRCP examinations of 220 consecutive individuals with PSC from a prospectively collected PSC-cohort, with median follow-up of 7.4 years, were reviewed. Inter-reader and intrareader agreements were assessed via intraclass correlation coefficient (ICC). After consensus, the prognostic value of the score was assessed using Cox-regression and outcome-free survival rates were assessed via Kaplan-Meier estimates. Harrell's C-statistic was calculated. Results: Forty patients developed outcomes (liver transplantation or liver-related death). Inter-reader agreement between experienced radiologists was good (ICC 0.82; 95% CI 0.74–0.87, and ICC 0.81; 95% CI 0.70–0.87, respectively) and better than the agreement for the pair of experienced/less-experienced radiologists (ICC 0.48; 95% CI 0.05–0.72). Agreement between radiologists from the three centres was good (ICC 0.76; 95% CI 0.57–0.89). Intrareader agreement was good to excellent (ICC 0.85–0.93). Harrell's C was 0.78. Patients with a DiStrict score of 5–8 had 8.2-fold higher risk (hazard ratio 8.2; 95% CI 2.97–22.65) of developing outcomes, and significantly worse survival (p
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- 2022
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8. Suppression of bile acid synthesis as a tipping point in the disease course of primary sclerosing cholangitis
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Peder Rustøen Braadland, Kai Markus Schneider, Annika Bergquist, Antonio Molinaro, Anita Lövgren-Sandblom, Marcus Henricsson, Tom Hemming Karlsen, Mette Vesterhus, Christian Trautwein, Johannes Roksund Hov, and Hanns-Ulrich Marschall
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Cholestasis ,Ursodeoxycholic acid ,Liver transplantation ,Liver transplantation-free survival ,Cholestatic liver disease ,7α-Hydroxy-4-cholesten-3-one ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Farnesoid X receptor (FXR) agonists and fibroblast growth factor 19 (FGF19) analogues suppress bile acid synthesis and are being investigated for their potential therapeutic efficacy in cholestatic liver diseases. We investigated whether bile acid synthesis associated with outcomes in 2 independent populations of people with primary sclerosing cholangitis (PSC) not receiving such therapy. Methods: Concentrations of individual bile acids and 7α-hydroxy-4-cholesten-3-one (C4) were measured in blood samples from 330 patients with PSC attending tertiary care hospitals in the discovery and validation cohorts and from 100 healthy donors. We used a predefined multivariable Cox proportional hazards model to evaluate the prognostic value of C4 to predict liver transplantation-free survival and evaluated its performance in the validation cohort. Results: The bile acid synthesis marker C4 was negatively associated with total bile acids. Patients with fully suppressed bile acid synthesis had strongly elevated total bile acids and short liver transplantation-free survival. In multivariable models, a 50% reduction in C4 corresponded to increased hazards for liver transplantation or death in both the discovery (adjusted hazard ratio [HR] = 1.24, 95% CI 1.06–1.43) and validation (adjusted HR = 1.23, 95% CI 1.03–1.47) cohorts. Adding C4 to established risk scores added value to predict future events, and predicted survival probabilities were well calibrated externally. There was no discernible impact of ursodeoxycholic acid treatment on bile acid synthesis. Conclusions: Bile acid accumulation-associated suppression of bile acid synthesis was apparent in patients with advanced PSC and associated with reduced transplantation-free survival. In a subset of the patients, bile acid synthesis was likely suppressed beyond a tipping point at which any further pharmacological suppression may be futile. Implications for patient stratification and inclusion criteria for clinical trials in PSC warrant further investigation. Lay summary: We show, by measuring the level of the metabolite C4 in the blood from patients with primary sclerosing cholangitis (PSC), that low production of bile acids in the liver predicts a more rapid progression to severe disease. Many people with PSC appear to have fully suppressed bile acid production, and both established and new drugs that aim to reduce bile acid production may therefore be futile for them. We propose C4 as a test to find those likely to respond to these treatments.
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- 2022
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9. EASL Clinical Practice Guidelines on sclerosing cholangitis
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Olivier Chazouilleres, Ulrich Beuers, Annika Bergquist, Tom Hemming Karlsen, Cynthia Levy, Marianne Samyn, Christoph Schramm, Michael Trauner, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, CCA - Cancer Treatment and Quality of Life, CCA - Cancer biology and immunology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
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Adult ,Hepatology ,Cholangitis, Sclerosing ,Humans ,Child ,Prognosis - Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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- 2022
10. Reply: Insurance should cover vancomycin for primary sclerosing cholangitis
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Christopher L. Bowlus, Lionel Arrivé, Annika Bergquist, Mark Deneau, Lisa Forman, Sumera I. Ilyas, Keri E. Lunsford, Mercedes Martinez, Gonzalo Sapisochin, Rachna Shroff, James H. Tabibian, and David N. Assis
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Hepatology - Published
- 2023
11. Reply: Living donor liver transplantation for people with PSC
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Lisa M. Forman, Gonzalo Sapisochin, David N. Assis, Lionel Arrivé, Annika Bergquist, Christopher L. Bowlus, Mark Deneau, Sumera I. Ilyas, Keri E. Lunsford, Mercedes Martinez, Rachna Shroff, and James H. Tabibian
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Hepatology - Published
- 2023
12. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma
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Christopher L. Bowlus, Lionel Arrivé, Annika Bergquist, Mark Deneau, Lisa Forman, Sumera I. Ilyas, Keri E. Lunsford, Mercedes Martinez, Gonzalo Sapisochin, Rachna Shroff, James H. Tabibian, and David N. Assis
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Hepatology - Published
- 2022
13. Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile
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Tom H. Karlsen, Guro Elisabeth Lind, Hege Marie Vedeld, Erik von Seth, Vemund Paulsen, Martti Färkkilä, Kim Andresen, Hilde Honne, Heidi D. Pharo, Kirsten Muri Boberg, Annika Bergquist, Marine Jeanmougin, Marit Mæhle Grimsrud, Trine Folseraas, Lars Aabakken, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Department of Medicine, University of Helsinki, and Gastroenterologian yksikkö
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Male ,medicine.medical_specialty ,endocrine system diseases ,Cholangitis, Sclerosing ,Malignancy ,DIAGNOSIS ,Gastroenterology ,Polymerase Chain Reaction ,digestive system ,Primary sclerosing cholangitis ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,parasitic diseases ,SURVEILLANCE ,medicine ,Biomarkers, Tumor ,Bile ,Humans ,Digital polymerase chain reaction ,In patient ,CYTOLOGY RISK-FACTORS ,DYSPLASIA ,Early Detection of Cancer ,Neoplasm Staging ,Hepatology ,Receiver operating characteristic ,business.industry ,fungi ,digestive, oral, and skin physiology ,BRUSH CYTOLOGY ,Methylation ,DNA Methylation ,Middle Aged ,medicine.disease ,digestive system diseases ,3. Good health ,Bile Duct Neoplasms ,ROC Curve ,Dysplasia ,030220 oncology & carcinogenesis ,3121 General medicine, internal medicine and other clinical medicine ,DNA methylation ,030211 gastroenterology & hepatology ,Female ,business ,BILIARY CYTOLOGY ,Follow-Up Studies - Abstract
Background and Aims Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. Approach and Results Droplet digital PCR (ddPCR) was used to analyze 344 bile samples from 273 patients with sporadic and PSC-associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77–0.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA ≤ 12 months following bile collection increased the accuracy for cancer detection, with a combined sensitivity of 100% (28/28) and a specificity of 90% (20/203). The specificity increased to 93% when only including patients with PSC with longtime follow-up (> 36 months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls (n = 23). Importantly, the bile samples from the CCA-PSC ≤ 12 patients, all positive for the biomarkers, included both early-stage and late-stage CCA, different tumor growth patterns, anatomical locations, and carbohydrate antigen 19-9 levels. Conclusions Using highly sensitive ddPCR to analyze robust epigenetic biomarkers, CCA in PSC was accurately detected in bile, irrespective of clinical and molecular features, up to 12 months before CCA diagnosis. The findings suggest a potential for these biomarkers to complement current detection and screening methods for CCA in patients with PSC.
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- 2022
14. Outcome after resection for perihilar cholangiocarcinoma in patients with primary sclerosing cholangitis: an international multicentre study
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F. Bartsch, J. Hagendoorn, R. Charco, Q.I. Molenaar, Hauke Lang, A. Sultana, F. Heid, J.I. Erdmann, Erik Schadde, G. Kazemier, H.Z. Malik, J. Rolinger, Stefan Buettner, C.L.M. Nota, Andrea Ruzzenente, M.C. Giglio, Mikhail Efanov, Shishir K. Maithel, P. Muiesan, M. Ravaioli, K.J. Roberts, I. Capobianco, Thomas M. van Gulik, J. van Vugt, Ruslan Alikhanov, Hannes Jansson, A. Andreou, Alfredo Guglielmi, Johann Pratschke, M. Malago, Moritz Schmelzle, E. de Savornin Lohman, Silvio Nadalin, Marjolein A P Ligthart, P.R. de Reuver, Bas Groot Koerkamp, S. W. M. Olde Damink, L.E. Nooijen, Francesca Ratti, S. van Laarhoven, C. Gomez-Gavara, B.M. Zonderhuis, C. Benzing, Matteo Serenari, Luca Aldrighetti, L.C. Franken, Annika Bergquist, Cornelis H. C. Dejong, Ernesto Sparrelid, Matteo Cescon, William R. Jarnagin, L.M. Quinn, Pim B. Olthof, J.N.M. IJzermans, Roberto Troisi, RS: NUTRIM - R2 - Liver and digestive health, Surgery, MUMC+: MA Heelkunde (9), Jansson, H., Olthof, P. B., Bergquist, A., Ligthart, M. A. P., Nadalin, S., Troisi, R, Groot Koerkamp, B., Alikhanov, R., Lang, H., Guglielmi, A., Cescon, M., Jarnagin, W. R., Aldrighetti, L., van Gulik, T. M., Sparrelid, E., Andreou, A., Bartsch, F., Benzing, C., Buettner, S., Capobianco, I., Charco, R., de Reuver, P. R., de Savornin Lohman, E., Dejong, C. H. C., Efanov, M., Erdmann, J. I., Franken, L. C., Giglio, M. C., Gomez-Gavara, C., Hagendoorn, J., Heid, F., Ijzermans, J. N. M., Kazemier, G., Maithel, S. K., Malago, M., Malik, H. Z., Molenaar, Q. I., Muiesan, P., Nooijen, L. E., Nota, C. L. M., Olde Damink, S. W. M., Pratschke, J., Quinn, L. M., Ratti, F., Ravaioli, M., Roberts, K. J., Rolinger, J., Ruzzenente, A., Schadde, E., Schmelzle, M., Serenari, M., Sultana, A., van Laarhoven, S., van Vugt, J. L. A., Zonderhuis, B. M., Troisi, R. I., CCA - Cancer Treatment and Quality of Life, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
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medicine.medical_specialty ,endocrine system diseases ,Cholangitis ,Cholangitis, Sclerosing ,030230 surgery ,HILAR CHOLANGIOCARCINOMA ,Gastroenterology ,digestive system ,Article ,Sclerosing ,Resection ,Primary sclerosing cholangitis ,Cholangiocarcinoma ,03 medical and health sciences ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,0302 clinical medicine ,Primary outcome ,Internal medicine ,Overall survival ,medicine ,Humans ,In patient ,Perihilar Cholangiocarcinoma ,Retrospective Studies ,Intrahepatic ,RISK ,Hepatology ,business.industry ,digestive, oral, and skin physiology ,Retrospective cohort study ,medicine.disease ,digestive system diseases ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Postoperative mortality ,030220 oncology & carcinogenesis ,Bile Ducts ,business ,Klatskin Tumor - Abstract
Contains fulltext : 245473.pdf (Publisher’s version ) (Open Access) BACKGROUND: Resection for perihilar cholangiocarcinoma (pCCA) in primary sclerosing cholangitis (PSC) has been reported to lead to worse outcomes than resection for non-PSC pCCA. The aim of this study was to compare prognostic factors and outcomes after resection in patients with PSC-associated pCCA and non-PSC pCCA. METHODS: The international retrospective cohort comprised patients resected for pCCA from 21 centres (2000-2020). Patients operated with hepatobiliary resection, with pCCA verified by histology and with data on PSC status, were included. The primary outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. RESULTS: Of 1128 pCCA patients, 34 (3.0%) had underlying PSC. Median overall survival after resection was 33 months for PSC patients and 29 months for non-PSC patients (p = .630). Complications (Clavien-Dindo grade ≥ 3) were more frequent in PSC pCCA (71% versus 44%, p = .003). The rate of posthepatectomy liver failure (21% versus 17%, p = .530) and 90-day mortality (12% versus 13%, p = 1.000) was similar for PSC and non-PSC patients. CONCLUSION: Median overall survival after resection for pCCA was similar in patients with underlying PSC and non-PSC patients. Complications were more frequent after resection for PSC-associated pCCA, with no difference in postoperative mortality.
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- 2021
15. Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma
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Dan Sun, Joana Dias, Helene Johansson, Martin Cornillet, Hans Glaumann, Otto Strauss, Hannes Jansson, Jesper B. Andersen, Colm J O'Rourke, Erik von Seth, Lena Berglin, Johan K. Sandberg, Espen Melum, Ernesto Sparrelid, Niklas K. Björkström, Iva Filipovic, Christine L. Zimmer, Ewa Ellis, Laura Hertwig, and Annika Bergquist
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Tumor microenvironment ,education.field_of_study ,Hepatology ,medicine.diagnostic_test ,medicine.medical_treatment ,Cell ,Population ,Immunotherapy ,Biology ,Mucosal-Associated Invariant T Cells ,Flow cytometry ,Cholangiocarcinoma ,medicine.anatomical_structure ,Immune system ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Bile Ducts, Extrahepatic ,medicine ,Cancer research ,Tumor Microenvironment ,Immunohistochemistry ,Cytotoxic T cell ,Humans ,education - Abstract
Background and Aims: Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra- and extrahepatic bile ducts with dismal prognosis and few nonsurgical treatments available. Despite recent success in the immunotherapy-based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal-associated invariant T (MAIT) cells are cytotoxic innate-like T cells highly enriched in the human liver, where they are located in close proximity to the biliary epithelium. Here, we aimed to comprehensively characterize MAIT cells in intrahepatic (iCCA) and perihilar CCA (pCCA). Approach and Results: Liver tissue from patients with CCA was used to study immune cells, including MAIT cells, in tumor-affected and surrounding tissue by immunohistochemistry, RNA-sequencing, and multicolor flow cytometry. The iCCA and pCCA tumor microenvironment was characterized by the presence of both cytotoxic T cells and high numbers of regulatory T cells. In contrast, MAIT cells were heterogenously lost from tumors compared to the surrounding liver tissue. This loss possibly occurred in response to increased bacterial burden within tumors. The residual intratumoral MAIT cell population exhibited phenotypic and transcriptomic alterations, but a preserved receptor repertoire for interaction with tumor cells. Finally, the high presence of MAIT cells in livers of iCCA patients predicted long-term survival in two independent cohorts and was associated with a favorable antitumor immune signature. Conclusions: MAIT cell tumor infiltration associates with favorable immunological fitness and predicts survival in CCA.
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- 2021
16. Development of a novel MRCP-score for patients with primary sclerosing cholangitis, and assessment of agreement and prognostic value
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Aristeidis Grigoriadis, Kristina Ringe, Johan Bengtsson, Erik Fridh Baubeta, Cecilia Forsman, Nafsika Korsavidou-Hult, Fredrik Rorsman, Emma Nilsson, Nikolaos Kartalis, and Annika Bergquist
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Hepatology - Published
- 2022
17. Cholangiocytes cleave surface CD100 from biliary infiltrating T cells and mediate pathogenic Th17 differentiation
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Xiaojun Jiang, Kari Otterdal, Brian K. Chung, Christopher Maucourant, Christine Zimmer, Sverre Holm, Daniel Geanon, Annika Bergquist, Tom Hemming Karlsen, Niklas Björkström, and Espen Melum
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Hepatology - Published
- 2022
18. Sa1438: TIME TO CHOLANGIOCARCINOMA IN PEDIATRIC ONSET PSC-IBD
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Batul Kaj-Carbaidwala, Johan M. Fevery, Douglas G. Adler, Annika Bergquist, Lissy De Ridder, Mark R. Deneau, Corinne Gower, Roger W. Chapman, Kate D. Lynch, Catherine A. Stedman, David Wilson, Uzma Shah, Harland S. Winter, and Jochen K. Lennerz
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Hepatology ,Gastroenterology - Published
- 2022
19. Effect of Simvastatin on the Prognosis of Primary Primary Sclerosing Cholangitis (PSC) (PiSCATIN)
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Annika Bergquist, Professor
- Published
- 2022
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