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- Dugic, A, et al.
(författare)
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The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
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- Ghorbani, P, et al.
(författare)
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Surgical Outcomes and Trends for Chronic Pancreatitis: An Observational Cohort Study from a High-Volume Centre
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Surgery for chronic pancreatitis (CP) is considered as a last resort treatment. The present study aims to determine the short- and medium-term outcomes of surgical treatment for CP with a comparison between duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD). The trends in surgical procedures were also examined. This was a retrospective cohort study of patients who underwent surgery for CP between 2000 and 2019 at the Karolinska University Hospital. One hundred and sixty-two patients were included. Surgery performed included drainage procedures (n = 2), DPPHR (n = 35), resections (n = 114, of these PD in n = 65) and other procedures (n = 11). Morbidity occurred in 17%, and the 90-day mortality was 1%. Complete or partial pain relief was achieved in 65% of patients. No significant difference in morbidity was observed between the DPPHR and PD groups: 17% vs. 20% (p = 0.728). Pain relief did not differ between the groups (62% for DPPHR vs. 73% for PD, p = 0.142). The frequency of performed DPPHR decreased, whereas the rate of PD remained unaltered. Surgical treatment for CP is safe and effective. DPPHR and PD are comparable regarding post-operative morbidity and are equally effective in achieving pain relief. Trends over time revealed PD as more commonly performed compared to DPPHR.
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- Hansson, MR, et al.
(författare)
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BIMODAL ERCP, A NEW WAY OF SEEING THINGS
- 2019
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Ingår i: GASTROINTESTINAL ENDOSCOPY. - : Elsevier BV. - 0016-5107. ; 89:6, s. AB249-AB250
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 39. |
- Hessmann, E, et al.
(författare)
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Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:3, s. 497-507
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Tidskriftsartikel (refereegranskat)abstract
- Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery.DesignGemcitabine metabolites were analysed in LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation.ResultsGemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2′,2′-difluorodeoxycytidine-5′-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2′,2′-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5′-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%.ConclusionsOur findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.
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| 45. |
- Khan, M, et al.
(författare)
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Adherence to European Guidelines for Treatment and Management of Pancreatic Exocrine Insufficiency in Chronic Pancreatitis Patients
- 2021
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- European evidence-based guidelines for the treatment and management of chronic pancreatitis (CP) have been made available following the harmonizing diagnosis and treatment of CP across Europe (HaPanEU) initiative by the United European Gastroenterology (UEG). The aim of this study was to evaluate adherence to the guideline recommendations in the management of patients with pancreatic exocrine insufficiency (PEI) at Karolinska University Hospital in Stockholm. UEG guideline recommendations were evaluated and categorized into 55 different quality indicators (QIs). Data from a retrospective cohort of CP patients being treated at Karolinska University Hospital were evaluated with regard to overall adherence as well as adherence to specific QIs. A total number of 118 patients out of 956 patients diagnosed with CP were eligible for inclusion with mean overall adherence of 61.9% to the defined QIs. A significant difference in mean overall adherence was shown between patients diagnosed with CP prior to 1 January 2016 and following 1 January 2016 (59.3% and 67.7% respectively, p = 0.004), with linear regression analysis also demonstrating improvement correlating to date of diagnosis (p = 0.002). In conclusion, diagnosis and treatment of PEI improved after the HaPanEU guidelines became available and is continuously improving; however, there is room for further improvement.
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| 49. |
- Kordes, M, et al.
(författare)
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Survival Benefits of Chemotherapy for Patients with Advanced Pancreatic Cancer in A Clinical Real-World Cohort
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Clinical outcomes of chemotherapy for patients with advanced pancreatic adenocarcinoma in a real-world setting might differ from outcomes in randomized clinical trials (RCTs). Here we show in a single-institution cohort of 595 patients that median overall survival (OS) of patients who received gemcitabine alone (n = 185; 6.6 months (95% CI; 5.5–7.7)) was the same as in pivotal RCTs. Gemcitabine/capecitabine (n = 60; 10.6 months (95% CI; 7.8–13.3)) and gemcitabine/nab-paclitaxel (n = 66; 9.8 months (95% CI; 7.9–11.8)) resulted in a longer median OS and fluorouracil/oxaliplatin/irinotecan (n = 31, 9.9 months (95% CI; 8.1–11.7)) resulted in a shorter median OS than previously reported. Fluorouracil/oxaliplatin (n = 35, 5.8 months (95% CI; 4.5–7)) and best supportive care (n = 206, 1.8 months (95% CI; 1.5–2.1)) could not be benchmarked against any RCTs. The degree of protocol adherence explained differences between real-world outcomes and the respective RCTs, while exposure to second-line treatments did not.
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| 50. |
- Lenggenhager, D, et al.
(författare)
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Commonly Used Pancreatic Stellate Cell Cultures Differ Phenotypically and in Their Interactions with Pancreatic Cancer Cells
- 2019
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Activated pancreatic stellate cells (PSCs) play a central role in the tumor stroma of pancreatic ductal adenocarcinoma (PDAC). Given the limited availability of patient-derived PSCs from PDAC, immortalized PSC cell lines of murine and human origin have been established; however, it is not elucidated whether differences in species, organ disease status, donor age, and immortalization alter the PSC phenotype and behavior compared to that of patient-derived primary PSC cultures. Therefore, a panel of commonly used PSC cultures was examined for important phenotypical and functional features: three primary cultures from human PDAC, one primary from normal human pancreas, and three immortalized (one from human, two from murine pancreas). Growth rate was considerably lower in primary PSCs from human PDAC. Basal collagen synthesis varied between the PSC cultures, and TGF-β stimulation increased collagen synthesis only in non-immortalized cultures. Differences in secretome composition were observed along with a divergence in the DNA synthesis, migration, and response to gemcitabine of PDAC cell lines that were grown in conditioned medium from the various PSC cultures. The findings reveal considerable differences in features and functions that are key to PSCs and in the interactions with PDAC. These observations may be relevant to researchers when selecting the most appropriate PSC culture for their experiments.
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