| 1. |
-
Overview of the JET results
- 2015
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Bozoky, Benedek, et al.
(författare)
-
Stabilization of the classical phenotype upon integration of pancreatic cancer cells into the duodenal epithelium
- 2021
-
Ingår i: Neoplasia. - : Elsevier. - 1522-8002 .- 1476-5586. ; 23:12, s. 1300-1306
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been defined that differ in prognosis. Cells of both subtypes can coexist in individual tumors; however, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the spatial tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall, and identify the duodenal epithelium as a distinct PDAC microniche. Materials and methods: We used serial multiplex quantitative immunohistochemistry (smq-IHC) for 24 proteins to phenotypically chart PDAC tumor cells in patients whose tumors infiltrated the duodenal epithelium. Additionally, we used a genetically engineered mouse model to study the PDAC cell phenotype in the small intestinal epithelium in a controlled genetic background. Result: We show that pancreatic cancer cells revert to non-destructive growth upon integration into the duodenal epithelium, where they adopt traits of intestinal cell differentiation, associated with phenotypical stabilization of the classical subtype. The integrated tumor cells replace epithelial cells in an adenoma-like manner, as opposed to invasive growth in the submucosa. Finally, we show that this phenomenon is shared between species, by confirming duodenal integration and phenotypic switching in a genetic PDAC mouse model. Discussion: Our results identify the duodenal epithelium as a distinct PDAC microniche and tightly link microenvironmental cue to cancer transcriptional subtypes. The phenomenon of "intestinal mimicry" provides a unique opportunity for the systematic investigation of microenvironmental influences on pancreatic cancer plasticity.
|
|
| 3. |
- Crippa, Stefano, et al.
(författare)
-
A tug-of-war in intraductal papillary mucinous neoplasms management : Comparison between 2017 International and 2018 European guidelines
- 2021
-
Ingår i: Digestive and Liver Disease. - : Elsevier. - 1590-8658 .- 1878-3562. ; 53:8, s. 998-1003
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 2017 International and 2018 European guidelines are the most recent guidelines for intraductal papillary mucinous neoplasms management.AIM: to evaluate the diagnostic accuracy of these guidelines in identifying malignant IPMN.METHODS: data from resected patients with IPMN were collected in two referral centers. Features of risk associated to cancerous degeneration described in International and European guidelines were retrospectively applied. Sensitivity, specificity, positive and negative predictive value in detecting malignant disease were calculated.RESULTS: the study includes 627 resected patients. European guidelines suggest resection in any patient with at least one feature of moderate-risk. International guidelines suggest that patients with moderate-risk features undergo endoscopic ultrasound before surgery. European guidelines had a higher sensitivity (99.2% vs. 83%) but a lower positive predictive value (59.5% vs. 65.8%) and Specificity (2% vs. 37.5%). European guidelines detected almost all malignancies, but 40% of resected patients had low-grade dysplasia. 297 patients underwent endoscopic ultrasound before surgery. 31/116 (26.7%) tumors radiologically classified as "worrisome features" were reclassified as "high-risk stigmata" by endoscopic ultrasound and 24/31 were malignant IPMN.CONCLUSIONS: European and International guidelines have a relatively low diagnostic accuracy, being European guidelines more aggressive. Endoscopic ultrasound can improve guidelines accuracy in patients with moderate-risk features.
|
|
| 4. |
- Garg, Neeraj, et al.
(författare)
-
Chemoselective Probe Containing a Unique Bioorthogonal Cleavage Site for Investigation of Gut Microbiota Metabolism
- 2018
-
Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773. ; 57:42, s. 13805-13809
-
Tidskriftsartikel (refereegranskat)abstract
- While metabolites derived from gut microbiota metabolism have been linked to disease development in the human host, the chemical tools required for their detailed analysis and the discovery of biomarkers are limited. A unique and multifunctional chemical probe for mass spectrometric analysis, which contains p-nitrocinnamyloxycarbonyl as a new bioorthogonal cleavage site has been designed and synthesized. Coupled to magnetic beads, this chemical probe allows for straightforward extraction of metabolites from human samples and release under mild conditions. This isolation from the sample matrix results in significantly reduced ion suppression, an increased mass spectrometric sensitivity, and facilitates the detection of metabolites in femtomole quantities. The chemoselective probe was applied to the analysis of human fecal samples, resulting in the discovery of four metabolites previously unreported in this sample type and confirmation of the presence of medically relevant gut microbiota-derived metabolites.
|
|
| 5. |
- Halttunen, Jorma, et al.
(författare)
-
Difficult cannulation as defined by a prospective study of the Scandinavian Association for Digestive Endoscopy (SADE) in 907 ERCPs
- 2014
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 49:6, s. 752-758
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The definition of a "difficult" cannulation varies considerably in reports of endoscopic retrograde cholangiopancreatography (ERCP). Aims. To define a difficult cannulation, which translates into higher risk of post-ERCP pancreatitis. Patients and methods. Prospective consecutive recording of 907 cannulations in Scandinavian centers done by experienced endoscopists. Inclusion: indication for biliary access in patients with intact papilla. Exclusion: acute non-biliary and chronic pancreatitis at time of procedure. Results. The primary cannulation succeeded in 74.9%, with median values for time 0.88 min (53 s), with two attempts and with zero pancreatic passages or injections. The overall cannulation success was 97.4% and post-ERCP pancreatitis (PEP) rate was 5.3%. The median time for all successful cannulations was 1.55 min (range 0.02-94.2). If the primary cannulation succeeded, the pancreatitis rate was 2.8%; after secondary methods, it rose to 11.5%. Procedures lasting less than 5 min had a PEP rate of 2.6% versus 11.8% in those lasting longer. With one attempt, the PEP rate was 0.6%, with two 3.1%, with three to four 6.1%, and with five and more 11.9%. With one accidental pancreatic guide-wire passage, the risk of the PEP was 3.7%, and with two passages, it was 13.1%. Conclusions. If the increasing rate of PEP is taken as defining factor, the wire-guided cannulation of a native papilla can be considered difficult after 5 min, five attempts, and two pancreatic guide-wire passages when any of those limits is exceeded.
|
|
| 6. |
- Haraldsson, Erik, et al.
(författare)
-
Endoscopic papillectomy and KRAS expression in the treatment of adenoma in the major duodenal papilla
- 2015
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 50:11, s. 1419-1427
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. The use of endoscopic papillectomy for resecting adenomas in the major duodenal papilla is increasing. This study focuses on the following three issues: Can endoscopic papillectomy be performed as a safe diagnostic and/or therapeutic procedure in biopsy-verified or suspected ampullary adenoma? Does expression of mutated KRAS in resected adenomatous tissue predict long-term outcome? What other factors may affect long-term outcome and should, therefore, be considered in decision making prior to endoscopic papillectomy? Material and methods. Thirty-six prospectively collected patients who underwent endoscopic papillectomy at Karolinska University Hospital between 2005 and 2014 were analyzed. Results. The rate of exact agreement between the histomorphological grading of the endoscopic biopsies and the papillectomy specimens was low (48%). Obstructive jaundice at presentation increased the risk of undetected adenocarcinoma (RR = 3.98; 95% CI = 1.46-10.85, p = 0.007). Lesions with malignancies were significantly larger (mean 30.6 mm) than those where only adenomas were found (mean 14.4 mm, p = 0.001). Mutated KRAS was detected in 9 of the 36 post-papillectomy specimens, including 4 of the 5 cases of ampullary adenocarcinoma. Eighteen cases were endoscopically cured after a mean follow-up period of 47 months (range 16-92 months). Conclusions. Endoscopic papillectomy is a valuable staging tool because of the limitations of endoscopic biopsy. Endoscopic papillectomy concomitantly offers a curative treatment for most patients with adenoma in the major duodenal papilla. Jaundice at presentation and large adenomas may indicate the presence of more advanced disease. Determination of mutated KRAS seems to be of limited value in predicting long-term outcome.
|
|
| 7. |
- Jain, Abhishek, et al.
(författare)
-
Comparison of two arylsulfatases for targeted mass spectrometric analysis of microbiota-derived metabolites
- 2021
-
Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 195
-
Tidskriftsartikel (refereegranskat)abstract
- Sulfation of metabolites is the second highest phase II modification in humans, which plays a critical role in the xenobiotics clearance process and gut microbiota-host co-metabolism. Besides the main function to remove xenobiotics from the body, sulfated metabolites have also been linked to inflammation, bacterial pathogenesis and metabolic disorders. A better understanding of how these metabolites impact the human body has turned into an important research area. Analytical methods for selective identification of this metabolite class are scarce. We have recently developed an assay utilizing the arylsulfatase from Helix pomatia due to a high substrate promiscuity combined with state-of-the-art metabolomics bioinformatic analysis for the selective identification of O-sulfated metabolites in human samples. This enzyme requires a multistep purification process as highest purity is needed for the developed mass spectrometric assay. In this study, we have utilized a new and recombinant overexpressed arylsulfatase (ASPC) for the selective identification of organic sulfate esters in human urine samples. We have compared the substrate conversion in urine samples and substrate specificity of this enzyme with purified arylsulfatase from Helix pomatia. Our analysis of urine samples revealed that both enzymes can be utilized for the selective analysis and discovery of sulfated metabolites with high promiscuity as demonstrated by equal hydrolysis of 108 substrates including sulfated conjugates of 27 metabolites of microbial origin. Importantly, we also identified 21 substrates in human urine samples that are exclusively hydrolyzed by ASPC and application of this enzyme increases the discovery of unknown sulfated metabolites with a higher scaffold diversity.
|
|
| 8. |
- Kourie, Mourad, et al.
(författare)
-
Autoimmune Pancreatitis Type 1 with Biliary, Nasal, Testicular, and Pulmonary Involvement: A Case Report and a Systematic Review
- 2023
-
Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:19
-
Forskningsöversikt (refereegranskat)abstract
- Introduction: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur at almost any anatomical site. It often presents as a multiorgan disease that may mimic malignancy, infection, or other immune-mediated conditions. Autoimmune pancreatitis (AIP) type 1 is the most prominent manifestation of IgG4-RD in the digestive tract, with common extra-pancreatic inflammation. We present the first patient with AIP and involvement of the testicles and nasal cavity. Patient and methods: A case of a patient with AIP type 1 and other organ involvement (bile ducts, testicles, nasal polyps, and lungs) is described. Additionally, a systematic review of AIP type 1 with testicular and nasal involvement was conducted. Results: The systematic review found two cases of AIP type 1 with testicular involvement and 143 cases with AIP type 1 with nasal cavity involvement. None of them had both testicular and nasal involvement. Conclusions: This is the first case of AIP type 1 with other organ involvement, including testicular and nasal involvement, to be described. The number of patients with nasal and testicular involvement described in the literature is low. Creating awareness of this rare clinical condition is necessary, especially due to the very effective available treatment with corticosteroids and rituximab.
|
|
| 9. |
- Lin, Weifeng, et al.
(författare)
-
Sensitive mass spectrometric analysis of carbonyl metabolites in human urine and fecal samples using chemoselective modification
- 2020
-
Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 145:11, s. 3822-3831
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolites with ketone or aldehyde functionalities comprise a large proportion of the human metabolome, most notably in the form of sugars. However, these reactive molecules are also generated through oxidative stress or gut microbiota metabolism and have been linked to disease development. The discovery and structural validation of this class of metabolites over the large concentration range found in human samples is crucial to identify their links to pathogenesis. Herein, we have utilized an advanced chemoselective probe methodology alongside bioinformatic analysis to identify carbonyl-metabolites in urine and fecal samples. In total, 99 metabolites were identified in urine samples and the chemical structure for 40 metabolites were unambiguously validated using a co-injection procedure. We also describe the preparation of a metabolite-conjugate library of 94 compounds utilized to efficiently validate these ketones and aldehydes. This method was used to validate 33 metabolites in a pooled fecal sample extract to demonstrate the potential for rapid and efficient metabolite detection over a wide metabolite concentration range. This analysis revealed the presence of six metabolites that have not previously been detected in either sample type. The constructed library can be utilized for straightforward, large-scale, and expeditious analysis of carbonyls in any sample type.
|
|
| 10. |
- Lohr, J-Matthias, et al.
(författare)
-
How to cannulate? A survey of the Scandinavian Association for Digestive Endoscopy (SADE) in 141 endoscopists
- 2012
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:7, s. 861-869
-
Tidskriftsartikel (refereegranskat)abstract
- Cannulation of the papilla vateri represents an enigmatic first step in endoscopic retrograde cholangiopancreaticography (ERCP). In light of falling numbers of (diagnostic) ERCP and novel techniques, e. g. short-wire system, we were interested in the approach novice and experienced endoscopist are taking; especially, what makes a papilla difficult to cannulate and how to approach this. We devised a structured online questionnaire, sent to all endoscopists registered with SADE, the Scandinavian Association for Digestive Endoscopy. A total of 141 responded. Of those, 49 were experienced ERCP-endoscopists (>900 ERCPs). The first choice of cannulation is with a sphincterotome and a preinserted wire. Both less experienced and more experienced endoscopists agreed on the criteria to describe a papilla difficult to cannulate and both would choose the needle-knife sphincterotomy (NKS) to get access to the bile duct. The less experienced used more "upward" NKS, whereas the more experienced also used the "downward" NKS technique. This survey provides us with a database allowing now for a more differentiated view on cannulation techniques, success, and outcome in terms of pancreatitis.
|
|
