| 1. |
- Morgell, Ann, et al.
(författare)
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Metabolic Characterization of Plasma and Cyst Fluid from Cystic Precursors to Pancreatic Cancer Patients Reveal Metabolic Signatures of Bacterial Infection
- 2021
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 20:5, s. 2725-2738
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5 year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insufficient approaches are currently available to determine whether a cyst is going to progress into pancreatic cancer. Recently, we used metabolomics approaches to identify candidate markers of disease progression in patients diagnosed with intraductal papillary mucinous neoplasms (IPMNs) undergoing pancreatic resection. Here, we enrolled an independent cohort to verify the candidate markers from our previous study with orthogonal quantitative methods in plasma and cyst fluid from serous cystic neoplasm and IPMN (either low- or high-grade dysplasia or pancreatic ductal adenocarcinoma). We thus validated these markers with absolute quantitative methods through the auxilium of stable isotope-labeled internal standards in a new independent cohort. Finally, we identified novel markers of IPMN status and disease progression - including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products, and trimethylamine-oxide. We show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. Overall, our findings are interesting per se, owing to the validation of previous markers and identification of novel small molecule signatures of IPMN and disease progression. In addition, our findings further fuel the provoking debate as to whether bacterial infections may represent an etiological contributor to the development and severity of the disease in pancreatic cancer, in like fashion to other cancers (e.g., Helicobacter pylori and gastric cancer).
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| 2. |
- Crippa, Stefano, et al.
(författare)
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A tug-of-war in intraductal papillary mucinous neoplasms management : Comparison between 2017 International and 2018 European guidelines
- 2021
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Ingår i: Digestive and Liver Disease. - : Elsevier. - 1590-8658 .- 1878-3562. ; 53:8, s. 998-1003
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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.
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| 3. |
- Holmberg, Marcus, et al.
(författare)
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Outcome after resection for invasive intraductal papillary mucinous neoplasia is similar to conventional pancreatic ductal adenocarcinoma
- 2021
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:7, s. 1371-1377
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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.
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| 4. |
- Johnson, Gavin, et al.
(författare)
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Curriculum for ERCP and endoscopic ultrasound training in Europe : European Society of Gastrointestinal Endoscopy (ESGE) Position Statement
- 2021
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Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 0013-726X .- 1438-8812. ; 53:10, s. 1071-1087
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Tidskriftsartikel (refereegranskat)abstract
- The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in ERCP and EUS.This curriculum is set out in terms of the prerequisites prior to training; recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1 Trainees should be competent in gastroscopy prior to commencing training. Formal training courses and the use of simulation in training are recommended. 2 Trainees should keep a contemporaneous logbook of their procedures, including key performance indicators and the degree of independence. Structured formative assessment is encouraged to enhance feedback. There should be a summative assessment process prior to commencing independent practice to ensure there is robust evidence of competence. This evidence should include a review of a trainee's procedure volume and current performance measures. A period of mentoring is strongly recommended in the early stages of independent practice. 3 Specifically for ERCP, all trainees should be competent up to Schutz level 2 complexity (management of distal biliary strictures and stones >10mm), with advanced ERCP requiring a further period of training. Prior to independent practice, ESGE recommends that a trainee can evidence a procedure volume of >300 cases, a native papilla cannulation rate of ≥80% (90% after a period of mentored independent practice), complete stones clearance of ≥85%, and successful stenting of distal biliary strictures of ≥90% (90% and 95% respectively after a mentored period of independent practice). 4 The progression of EUS training and competence attainment should start from diagnostic EUS and then proceed to basic therapeutic EUS, and finally to advanced therapeutic EUS. Before independent practice, ESGE recommends that a trainee can evidence a procedure volume of >250 cases (75 fine-needle aspirations/biopsies [FNA/FNBs]), satisfactory visualization of key anatomical landmarks in ≥90% of cases, and an FNA/FNB accuracy rate of ≥85%. ESGE recognizes the often inadequate quality of the evidence and the need for further studies pertaining to training in advanced endoscopy, particularly in relation to therapeutic EUS.
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| 5. |
- Valente, Roberto, et al.
(författare)
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The use of ace inhibitors influences the risk of progression of BD-IPMNs under follow-up
- 2022
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 22:4, s. 516-524
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chemoprevention's ability to slow down or prevent the progression of BD-IPMNs is extremely appealing. Aspirin (ASA), Ace Inhibitors/Angiotensin Receptor Blockers (ACEIs/ARBs) and Statins (STATs) are frequently prescribed drugs with a possible beneficial effect on different cancer types. Their effect on IPMNs is largely unknown.AIM: To evaluate the association between the use of ASA, ACEIs/ARBs and STATs and the risk of progression of BD-IPMNs in follow-up.MATERIALS AND METHODS: multicenter, retrospective cohort study on patients with presumed BD-IPMNs without relative or absolute indication for surgery. Pharmacological exposures and risk factors were collected. We identified clinically relevant progression (occurrence of radiological absolute or relative indication for surgery) and any progression (occurrence of clinically relevant progression OR any dimension increase OR the occurrence of new cysts).RESULTS: Overall 594 patients were included. ACEIs were associated with a lower occurrence of any progression (HR = 0.70; 95% CI 0.49-0.98, p = 0.04) and clinically relevant progression, HR = 0.42 (95% CI 0.20-0.88; p = 0.02). No significant effect was shown for factors associated with the occurrence of pancreas cancer such as smoking, alcohol consumption and 1st degree family history of pancreas cancer. Among pharmacological exposures, no convincing effect was shown for the chronic use of ASA, ARB and STAT.CONCLUSIONS: ACEIs might have an effect in slowing the progression of BD-IPMNs. ASA, STAT and ARBs show no convincing effect on the progression of BD-IPMNs. Further, prospective, and long-term multicenter studies are needed to verify such association and to define the potential underlying mechanisms.
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| 6. |
- Vehviläinen, Sini, et al.
(författare)
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Single-operator peroral pancreatoscopy in the preoperative diagnostics of suspected main duct intraductal papillary mucinous neoplasms : efficacy and novel insights on complications
- 2022
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Ingår i: Surgical Endoscopy. - : Springer. - 0930-2794 .- 1432-2218. ; 36, s. 7431-7443
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Tidskriftsartikel (refereegranskat)abstract
- Background: Distinguishing intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic cystic lesions is essential since IPMNs carry the risk of becoming malignant. Differentiating the main pancreatic duct involving IPMNs (MD-IPMNs) through conventional imaging is deficient. Single-operator peroral pancreatoscopy (SOPP) represents a promising method offering additional information on suspected lesions in the pancreatic main duct (MD). We aimed to determine the role of SOPP in the preoperative diagnostics of suspected MD-IPMNs and identify factors contributing to SOPP-related complications.Materials and Methods: In this primarily retrospective study, SOPPs were performed at three high-volume centers on suspected MD-IPMNs. Primary outcome was the clinical impact of SOPP to subsequent patient care. Additionally, we documented post-SOPP complications and analyzed several assumed patient- and procedure-related risk factors.Results: One hundred and one (101) SOPPs were performed. Subsequent clinical management was affected due to the findings in 86 (85%) cases. Surgery was planned for 29 (29%) patients. A condition other than IPMN explaining MD dilatation was found in 28 (28%) cases. In 35 (35%) cases, follow-up with MRI was continued. Post-SOPP pancreatitis occurred in 20 (20%) patients and one of them was fatal. A decrease in odds of post-SOPP pancreatitis was seen as the MD diameter increases (OR 0.714 for 1.0 mm increase in MD diameter, CI 95% 0.514–0.993, p = 0.045). Furthermore, a correlation between lower MD diameter values and higher severity post-SOPP pancreatitis was seen (TJT = 599, SE = 116.6, z = − 2.31; p = 0.020). History of pancreatitis after endoscopic retrograde cholangiopancreatography was a confirmed risk factor for post-SOPP pancreatitis. Conclusions between complications and other risk factors could not be drawn.Conclusion: SOPP aids clinical decision-making in suspected MD-IPMNs. Risk for post-SOPP pancreatitis is not negligible compared to non-invasive imaging methods. The risk for pancreatitis decreases as the diameter of the MD increases.
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| 7. |
- Marques, Filipe, et al.
(författare)
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New through-the-needle brush for pancreatic cysts assessment : a randomized control trial
- 2023
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Ingår i: iGIE. - : Elsevier BV. - 2949-7086.
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Tidskriftsartikel (refereegranskat)abstract
- AbstractObjectiveCurrent endoscopic ultrasound technologies (EUS) are suboptimal in the assessment of pancreatic cystic lesions (PCLs). We developed a new through-the- needle brush, the "loop brush", to improve the cellular yield, and thereby sensitivity,of EUS fine needle aspiration (EUS-FNA) of pancreatic cysts. In this study, we aim to evaluate its safety and efficacy.DesignWe performed an in-vivo randomized controlled trial in pigs using artificial cysts. In one group, the loop brush was deployed through a 22G EUS-FNA needle into the cysts. In the control group, cystic punction was performed with standard EUS- FNA. Loop brushes were visually inspected post-procedure. Cytological assessment, cell counting, and hemoglobin analysis were performed in samples from both groups.ResultsArtificial cysts (n=114) were punctured in six pigs, 57 in each group. Neither adverse events nor significant device malfunction occurred during loop brushing. Samples collected with the brush had non-detectable concentrations of hemoglobin in 72% (41/57) of cases, and 26% (16/57) had less than 0.6 g/dL, with no significant difference to the controls (p=0.32). Brushing cell counts were associated with significantly increased cell counts (11.7× median difference, p<.0001). Cytological smears were diagnostic in 77% of cases in the brushing group, while 54% in the control group (p=0.01, Fisher’s exact test; p=0.006, Chi-square test).ConclusionsThe new loop brush procedure appears to be safe, causing neither significant bleeding nor device malfunction. Samples obtained with the loop brush were suitable for cytological analysis and showed significantly higher cell yield than controls. Further clinical studies are warranted.
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| 8. |
- Baldaque-Silva, Francisco, et al.
(författare)
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A Nerve-Wracking Cyst
- 2021
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Ingår i: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 161:5, s. e12-e13
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Halimi, Asif, et al.
(författare)
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Isolation of pancreatic microbiota from cystic precursors of pancreatic cancer with intracellular growth and DNA damaging properties
- 2021
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Ingår i: Gut microbes. - : Taylor & Francis Group. - 1949-0976 .- 1949-0984. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.
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| 10. |
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