| 1. |
- Altincekic, Nadide, et al.
(författare)
-
Targeting the Main Protease (Mpro, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies
- 2024
-
Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 19:2, s. 563-574
-
Tidskriftsartikel (refereegranskat)abstract
- The main protease Mpro, nsp5, of SARS-CoV-2 (SCoV2) is one of its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) of four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. Z604 shows time-dependent binding. Its inhibitory effect is sensitive to reducing conditions. Starting with Z604, we synthesized and characterized 13 compounds designed by fragment growth strategies. Each compound was characterized by NMR and/or activity assays to investigate their interaction with Mpro. These investigations resulted in the four-armed compound 35b that binds directly to Mpro. 35b could be cocrystallized with Mpro revealing its noncovalent binding mode, which fills all four active site subpockets. Herein, we describe the NMR-derived fragment-to-hit pipeline and its application for the development of promising starting points for inhibitors of the main protease of SCoV2.
|
|
| 2. |
- Arnelo, Urban, et al.
(författare)
-
Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia : a pilot study
- 2023
-
Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 23:6, s. 704-711
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs.Methods: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis.Results: In total, 46 patients, 48% females, mean age (range) 67 years (45–82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas.Conclusion: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.
|
|
| 3. |
- Arnelo, Urban, et al.
(författare)
-
Single-operator pancreatoscopy is helpful in the evaluation of suspected intraductal papillary mucinous neoplasms (IPMN)
- 2014
-
Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 14:6, s. 510-514
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Even when advanced cross-sectional imaging modalities have been employed, endoscopic evaluation of intraductal papillary mucinous neoplasms (IPMN) is often required in order to assess the final character and extent of lesions. The current study addresses the use of SpyGlass single-operator peroral pancreatoscopy in suspected IPMN.DESIGN: A prospective, non-randomized exploratory cohort study.SETTING: Single-center.PATIENTS AND INTERVENTION: A prospective study-cohort of 44 consecutive patients in a single tertiary referral center who underwent ERCP and peroral pancreatoscopy, was prospectively collected between July 2007 and March 2013 because of a radiological signs of IPMN. These IPMN-findings were discovered incidentally in 44% of the cases.MAIN OUTCOME MEASUREMENTS: Diagnostic accuracy (specificity & sensitivity) and complications.RESULTS: The targeted region of the pancreatic duct was reached with the SpyGlass system in 41 patients (median age 65 years, 41% female). Three patients were excluded from analysis because of failed deep cannulation of the pancreatic duct. Brush cytology was taken in 88% and direct biopsies in 41%. IPMN with intermediate or high-grade dysplasia was the main final diagnosis (76%) in 22 patients who had surgery. Out of the 17 patients with a final diagnosis of MD-IPMN, 76% were correctly identified by pancreatoscopy. Of the 9 patients with a final diagnosis of BD-IPMN, the pancreatoscopy identified 78% of the cases correctly.The incidence of post-ERCP pancreatitis was 17%. Pancreatoscopy was found to have provided additional diagnostic information in the vast majority of the cases and to affect clinical decision-making in 76%.LIMITATIONS: Single-center study.CONCLUSIONS: Single-operator peroral pancreatoscopy contributed to the clinical evaluation of IPMN lesions and influenced decision-making concerning their clinical management. The problem of post-procedural pancreatitis needs further attention.
|
|
| 4. |
- Conway, Louis P., et al.
(författare)
-
Chemoselective probe for detailed analysis of ketones and aldehydes produced by gut microbiota in human samples
- 2019
-
Ingår i: Chemical Communications. - : ROYAL SOC CHEMISTRY. - 1359-7345 .- 1364-548X. ; 55:62, s. 9080-9083
-
Tidskriftsartikel (refereegranskat)abstract
- New strategies are required for the discovery of unknown bioactive molecules produced by gut microbiota in the human host. Herein, we utilize a chemoselective probe immobilized to magnetic beads for analysis of carbonyls in human fecal samples. We identified 112 metabolites due to femtomole analysis and an increased mass spectrometric sensitivity by up to six orders of magnitude.
|
|
| 5. |
- Correia, Mario S. P., et al.
(författare)
-
Investigation of the individual human sulfatome in plasma and urine samples reveals an age-dependency
- 2021
-
Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:55, s. 34788-34794
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolic microbiome interaction with the human host has been linked to human physiology and disease development. The elucidation of this interspecies metabolite exchange will lead to identification of beneficial metabolites and disease modulators. Their discovery and quantitative analysis requires the development of specific tools and analysis of specific compound classes. Sulfated metabolites are considered a readout for the co-metabolism of the microbiome and their host. This compound class is part of the human phase II clearance process of xenobiotics and is the main focus in drug or doping metabolism and also includes dietary components and microbiome-derived compounds. Here, we report the targeted analysis of sulfated metabolites in plasma and urine samples in the same individuals to identify the core sulfatome and similarities between these two sample types. This analysis of 27 individuals led to the identification of the core sulfatome of 41 metabolites in plasma and urine samples as well as an age effect for 15 metabolites in both sample types.
|
|
| 6. |
- El Jellas, Khadija, et al.
(författare)
-
Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis : How to Correctly Identify MODY8 Cases
- 2022
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:4, s. 1455-1466
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Maturity onset diabetes of the young, type 8 (MODY8) is associated with mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. Several diabetes cases and families have in recent years been attributed to mutations in CEL without any functional or clinical evidence provided. Objective: To facilitate correct MODY8 diagnostics, we screened 2 cohorts of diabetes patients and delineated the phenotype. Methods: Young, lean Swedish and Finnish patients with a diagnosis of type 2 diabetes (352 cases, 406 controls) were screened for mutations in the CEL gene. We also screened 58 Czech MODY cases who had tested negative for common MODY genes. For CEL mutation-positive subjects, family history was recorded, and clinical investigations and pancreatic imaging performed. Results: Two cases (1 Swedish and 1 Czech) with germline mutation in CEL were identified. Clinical and radiological investigations of these 2 probands and their families revealed dominantly inherited insulin-dependent diabetes, pancreatic exocrine dysfunction, and atrophic pancreas with lipomatosis and cysts. Notably, hereditary pancreatitis was the predominant phenotype in 1 pedigree. Both families carried single-base pair deletions in the proximal part of the CEL variable number of tandem repeat (VNTR) region in exon 11. The mutations are predicted to lead to aberrant protein tails that make the CEL protein susceptible to aggregation. Conclusion: The diagnosis of MODY8 requires a pancreatic exocrine phenotype and a deletion in the CEL VNTR in addition to dominantly inherited diabetes. CEL screening may be warranted also in families with hereditary pancreatitis of unknown genetic etiology.
|
|
| 7. |
- Haraldsson, Erik, et al.
(författare)
-
Adenomatous neoplasia in the papilla of Vater endoscopic and/or surgical resection?
- 2022
-
Ingår i: Surgical Endoscopy. - : Springer. - 0930-2794 .- 1432-2218. ; 36, s. 2401-2411
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Adenomatous neoplasia in the papilla of Vater needs to be resected in order not to progress. It can be challenging to distinguish between early ampullary malignant lesions and non-invasive adenomas, due to the overlap in symptoms and radiological findings. This retrospective study describes the different findings and treatment decisions taken prior to endoscopic and/or surgical resection of ampullary adenomatous lesions.Materials and methods: Patients treated with endoscopic and/or surgical resection for suspected or verified ampullary adenomatous neoplasia, between January 2006 and July 2018, where pre-interventional cross-sectional imaging could not discern an obvious invasive, malignant tumor, were included. Findings were compared against the final diagnosis of the histopathological analysis on the resected specimen.Results: In total, 172 met the inclusion criteria. Patients were treated with either surgical resection (n = 96), endoscopic papillectomy (EP) (n = 55) or both (n = 21). The final diagnosis was in 48% ampullary adenocarcinoma, and the remaining had either ampullary adenoma (38%) or non-neoplastic lesions (14%). In patients where symptoms and cross-sectional imaging were suspicious for malignancy, but with no tissue samples that confirmed neoplasia prior to surgical resection, only 47% had adenocarcinoma. The remaining had either adenoma (9%) or non-neoplastic lesions (44%). Adenocarcinoma was revealed in 27% of the patients where endoscopic biopsies had shown adenoma. Patients with adenoma, treated with EP, were cured in 59%. However, 28% were after EP sent for further surgery due to ductal invasion or a finding of adenocarcinoma.Conclusions: In patients with a suspicion of ampullary neoplasia on imaging, attempts should be made to get endoscopic tissue samples before deciding on a treatment strategy. If biopsies show ampullary adenoma, patients should be considered for EP, unless there are clear radiologic or endoscopic signs of malignancy. Patients with adenocarcinoma on endoscopic biopsies should undergo surgical resection.
|
|
| 8. |
- He, Fei, et al.
(författare)
-
FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner
- 2023
-
Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:10, s. 1628-1645
-
Tidskriftsartikel (refereegranskat)abstract
- Sex-driven immune differences can affect tumor progression and the landscape of the tumor microenvironment. Deeper understanding of these differences in males and females can inform patient selection to improve sex-optimized immunotherapy treatments. In this study, single-cell RNA sequencing and protein analyses uncovered a subpopulation of myeloid cells in pancreatic lesions associated with an immune-excluded tumor phenotype and effector T-cell exhaustion exclusively in females. This myeloid subpopulation was positively correlated with poor survival and genetic signatures of M2-like macrophages and T-cell exhaustion in females. The G-protein coupled receptor formyl peptide receptor 2 (FPR2) mediated these immunosuppressive effects. In vitro, treatment of myeloid cells with a specific FPR2 antagonist prevented exhaustion and enhanced cytotoxicity of effector cells. Proteomic analysis revealed high expression of immunosuppressive secretory proteins PGE2 and galectin-9, enriched integrin pathway, and reduced proinflammatory signals like TNFα and IFNγ in female M2-like macrophages upon FPR2 agonist treatment. In addition, myeloid cells treated with FPR2 agonists induced TIM3 and PD-1 expression only in female T cells. Treatment with anti-TIM3 antibodies reversed T-cell exhaustion and stimulated their ability to infiltrate and kill pancreatic spheroids. In vivo, progression of syngeneic pancreatic tumors was significantly suppressed in FPR2 knockout (KO) female mice compared with wild-type (WT) female mice and to WT and FPR2 KO male mice. In female mice, inoculation of tumors with FPR2 KO macrophages significantly reduced tumor growth compared with WT macrophages. Overall, this study identified an immunosuppressive function of FPR2 in females, highlighting a potential sex-specific precision immunotherapy strategy.
|
|
| 9. |
- Holmberg, Marcus, et al.
(författare)
-
Outcome after resection for invasive intraductal papillary mucinous neoplasia is similar to conventional pancreatic ductal adenocarcinoma
- 2021
-
Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:7, s. 1371-1377
-
Tidskriftsartikel (refereegranskat)abstract
- Background/objectives: Resections for intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Overall survival (OS) for conventional pancreatic ductal adenocarcinoma (PDAC) is well known but OS for invasive IPMN (inv-IPMN) is not as conclusive. This study aims to elucidate potential differences in clinicopathology and OS between these tumor types and to investigate if the raised number of resections have affected outcome.Methods: Consecutive patients ≥18 years of age resected for inv-IPMN and PDAC at Karolinska University Hospital between 2009 and 2018 were included. Clinicopathological variables were analyzed in multivariable regression models. Outcome was assessed calculating two-year OS, estimating OS using the Kaplan-Meier model and comparing survival functions with log-rank test.Results: 513 patients were included, 122 with inv-IPMN and 391 with PDAC. During the study period both the proportion resected inv-IPMN and two-year OS, irrespective of tumor type, increased (2.5%–45%; p < 0.001 and 44%–57%; p = 0.005 respectively). In Kaplan-Meier survival analysis inv-IPMN had more favorable median OS (mOS) compared to PDAC (33.6 months vs 19.3 months, p = 0.001). However, in multivariable Cox Regression analysis, tumor type was not a predictor for death, but so were resection period, tumor subtype and N-stage (all p < 0.001).Conclusion: In this large single center observational cohort study, inv-IPMN seemed to have favorable survival outcome compared to PDAC, but after adjusting for predictors for death this benefit vanished. The combination of a pronounced increase in resected inv-IPMN and a concurrent hazard abatement for death within 2 years during the study period proved to be a principal factor.
|
|
| 10. |
- Holmberg, Marcus, et al.
(författare)
-
Outcome after surgery for invasive intraductal papillary mucinous neoplasia compared to conventional pancreatic ductal adenocarcinoma : a swedish nationwide register-based study
- 2022
-
Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 23:1, s. 90-97
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical importance of intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Long-term survival after resection for invasive IPMN (inv-IPMN) compared to conventional pancreatic ductal adenocarcinoma (PDAC) is not thoroughly delineated.Objective: This study, based on the Swedish national pancreatic and periampullary cancer registry aims to elucidate the outcome after resection of inv-IPMN compared to PDAC.Methods: All patients ≥18 years of age resected for inv-IPMN and PDAC in Sweden between 2010 and 2019 were included. Clinicopathological variables were retrieved from the national registry. The effect on death was assessed in two multivariable Cox regression models, one for patients resected 2010–2015, one for patients resected 2016–2019. Median overall survival (OS) was estimated using the Kaplan-Meier method.Results: We included 1909 patients, 293 inv-IPMN and 1616 PDAC. The most important independent predictors of death in multivariable Cox regressions were CA19-9 levels, venous resection, tumour differentiation, as well as T-, N-, M-stage and surgical margin. Tumour type was an independent predictor for death in the 2016–2019 cohort, but not in the 2010–2015 cohort. In Kaplan-Meier survival analysis, inv-IPMN was associated with longer median OS in stage N0-1 and in stage M0 compared to PDAC. However, in stage T2-4 and stage N2 median OS was similar, and in stage M1 even shorter for inv-IPMN compared to PDAC.Conclusion: In this population-based nationwide study, outcome after resected inv-IPMN compared to PDAC is more favourable in lower stages, and similar to worse in higher.
|
|
| 11. |
- Kaur, Amanpreet, et al.
(författare)
-
Chemoselective bicyclobutane-based mass spectrometric detection of biological thiols uncovers human and bacterial metabolites
- 2023
-
Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 14:20, s. 5291-5301
-
Tidskriftsartikel (refereegranskat)abstract
- Sulfur is an essential element of life. Thiol-containing metabolites in all organisms are involved in the regulation of diverse biological processes. Especially, the microbiome produces bioactive metabolites or biological intermediates of this compound class. The analysis of thiol-containing metabolites is challenging due to the lack of specific tools, making these compounds difficult to investigate selectively. We have now developed a new methodology comprising bicyclobutane for chemoselective and irreversible capturing of this metabolite class. We utilized this new chemical biology tool immobilized onto magnetic beads for the investigation of human plasma, fecal samples, and bacterial cultures. Our mass spectrometric investigation detected a broad range of human, dietary and bacterial thiol-containing metabolites and we even captured the reactive sulfur species cysteine persulfide in both fecal and bacterial samples. The described comprehensive methodology represents a new mass spectrometric strategy for the discovery of bioactive thiol-containing metabolites in humans and the microbiome.
|
|
| 12. |
- Lin, Weifeng, et al.
(författare)
-
Chemoselective and Highly Sensitive Quantification of Gut Microbiome and Human Metabolites
- 2021
-
Ingår i: Angewandte Chemie International Edition. - : John Wiley & Sons. - 1433-7851 .- 1521-3773. ; 60:43, s. 23232-23240
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The microbiome has a fundamental impact on the human host's physiology through the production of highly reactive compounds that can lead to disease development. One class of such compounds are carbonyl-containing metabolites, which are involved in diverse biochemical processes. Mass spectrometry is the method of choice for analysis of metabolites but carbonyls are analytically challenging. Herein, we have developed a new chemical biology tool using chemoselective modification to overcome analytical limitations. Two isotopic probes allow for the simultaneous and semi-quantitative analysis at the femtomole level as well as qualitative analysis at attomole quantities that allows for detection of more than 200 metabolites in human fecal, urine and plasma samples. This comprehensive mass spectrometric analysis enhances the scope of metabolomics-driven biomarker discovery. We anticipate that our chemical biology tool will be of general use in metabolomics analysis to obtain a better understanding of microbial interactions with the human host and disease development.
|
|
| 13. |
- Lin, Weifeng, et al.
(författare)
-
Squaric acid as a new chemoselective moiety for mass spectrometry-based metabolomics analysis of amines
- 2021
-
Ingår i: RSC CHEMICAL BIOLOGY. - : Royal Society of Chemistry. - 2633-0679. ; 2:5, s. 1479-1483
-
Tidskriftsartikel (refereegranskat)abstract
- The investigation of microbiome-derived metabolites is important to understand metabolic interactions with their human host. New methodologies for mass spectrometric discovery of undetected metabolites with unknown bioactivity are required. Herein, we introduce squaric acid as a new chemoselective moiety for amine metabolite analysis in human fecal samples.
|
|
| 14. |
- Lübbe, Jeanne, et al.
(författare)
-
ERCP-guided cholangioscopy using a single-use system : nationwide register-based study of its use in clinical practice
- 2015
-
Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 0013-726X .- 1438-8812. ; 47:9, s. 802-807
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND STUDY AIMS: Single-operator peroral cholangioscopy enables direct visualization of duct lesions, biopsy, and therapeutic interventions in the biliary and pancreatic ductal systems. The aim of this study was to address the use and outcome of this technology in wider clinical practice.PATIENTS AND METHODS: A nationwide study of endoscopic retrograde cholangiopancreatography (ERCP) procedures, with or without cholangioscopy, was conducted. Procedures that were registered in the Swedish Registry for Gallstone Surgery and ERCP (GallRiks), between 2007 and 2012 were included. The primary outcome was ERCP-specific adverse events.RESULTS: Data from 36 352 ERCP procedures were analyzed, including 408 cholangioscopy procedures. Postprocedural adverse events were more prevalent when cholangioscopy was used (19.1 % vs. 14.0 %). Pancreatitis (7.4 % vs. 3.9 %) and cholangitis (4.4 % vs. 2.7 %) were ERCP-specific adverse events that were elevated in the cholangioscopy group. However, in multivariate analysis, the risks of intraprocedural and postprocedural adverse events were significantly increased in the cholangioscopy group whereas the risks of pancreatitis and cholangitis, when adjusted for confounders, were not.CONCLUSION: The single-operator peroral cholangioscopy technique is an advanced technique for intraluminal visual inspection, and for therapeutic intervention of the biliary and pancreatic ducts. However, there is a significantly increased risk of intra- and postprocedural adverse events. Thus, this method should preferably be performed at tertiary referral centers in carefully selected patients.
|
|
| 15. |
- Löhr, J.-Matthias, et al.
(författare)
-
Can our experience with surveillance for inherited pancreatic cancer help to identify early pancreatic cancer in the general population?
- 2024
-
Ingår i: Familial Cancer. - : Springer Nature. - 1389-9600 .- 1573-7292.
-
Forskningsöversikt (refereegranskat)abstract
- Screening of the general population for cancer is a matter of primary prevention reducing the burden of disease. Whilst this is successful for several cancers including breast, colon and prostate, the situation to screen and hence prevent pancreatic cancer is different. The organ is not as accessible to simple physical exam or biological samples (fecal or blood test). Neither exists a blood test such as PSA that is cost-effective. Reviewing the evidence from screening risk groups for pancreatic cancer, one must conclude that there is no rational at present to screen the general population, for a lack of appropriate tests.
|
|
| 16. |
- Regnér, Sara, et al.
(författare)
-
Nya riktlinjer för kronisk pankreatit
- 2020
-
Ingår i: Lakartidningen. - 0023-7205. ; 117
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Patients with chronic pancreatitis have an impaired quality of life and are at risk for several long-term complications. It is important to diagnose and treat these patients to minimize the effects of the disease. Clinical manifestations of chronic pancreatitis include a wide range of symptoms and patients are managed differenth between medical centers. In recent years, there have been improvements in knowledge about treatment and management of patients with chronic pancreatitis. This is a short report of the recently published Swedish guidelines for chronic pancreatitis, which are based on international guidelines as well as original publications and are related to the Swedish healthcare system.
|
|
| 17. |
- Vu Trung, Kien, et al.
(författare)
-
Endoscopic papillectomy for ampullary lesions of minor papilla
- 2024
-
Ingår i: Gastrointestinal Endoscopy. - 0016-5107. ; 99:4, s. 587-595.e1
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. Methods: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. Results: Propensity score–based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). Conclusions: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.
|
|
| 18. |
- Vujasinovic, Miroslav, et al.
(författare)
-
Gastrointestinal cancer precursor risk and mortality in pancreatic intraductal papillary mucinous neoplasms : a nationwide cohort study
- 2024
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708.
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN.Methods: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to <= 5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death.Results: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths).Conclusions: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.
|
|
| 19. |
- Vujasinovic, Miroslav, et al.
(författare)
-
The Role of Immunoglobulin G4 in Outcomes of Primary Sclerosing Cholangitis
- 2024
-
Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease that is characterized by an inflammatory and fibrotic process affecting bile ducts which eventually develops into liver cirrhosis and liver failure. The aim of this study was to investigate serum IgG subclass distribution in patients with PSC and its possible association with PSC outcomes.Patients and methods: We performed a retrospective analysis of 181 patients who had been diagnosed with PSC between January 1970 and December 2015 and followed at our outpatient clinic. Their demographic, immunological, and clinical characteristics were recorded and analyzed.Results: This study included 181 patients with PSC (120 males, 61 females). There was no association between IgGs and the development of autoimmune hepatitis, cirrhosis, cholangiocarcinoma, liver transplantation, inflammatory bowel disease, and colectomy. Patients with elevated IgG4 had statistically significant higher rates of cholangitis (p = 0.02) and endoscopic retrograde cholangiopancreatography (ERCP) (p = 0.009). High IgG4 values were observed in nine patients who underwent ERCP. In these nine patients, on average, IgG4 was evaluated 5 years after ERCP (min 3 days, max 11 years). Subanalysis considering only IgG4 values evaluated before ERCP showed no significant difference but remains significant if we consider IgG4 values after ERCP.Conclusion: Elevated IgG4 in our study showed a possible association with higher rates of cholangitis and ERCP among patients with primary sclerosing cholangitis. It seems that IgGs may be a useful tool for the prediction of outcomes in patients with PSC. A prospective study is necessary, especially to study the trends of IgGs values during disease as well as the role of possible seroconversion.
|
|
