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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Archibugi, Livia, et al.
(författare)
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Gynecological and reproductive factors and the risk of pancreatic cancer : A case-control study
- 2020
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 20:6, s. 1149-1154
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: /Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a higher incidence in men compared to women, although the difference in known risk factors cannot explain this disparity completely. Reproductive and hormonal factors have been demonstrated in pre-clinical studies to influence pancreatic carcinogenesis, but the few published data on the topic are inconsistent. The aim was to investigate the role of reproductive and hormonal factors on PDAC occurrence in women.METHODS: We conducted a unicenter case-control study; PDAC cases were matched to controls by age with a 1:2 ratio. Risk factors were screened through questionnaires about gynecologic and medical history. Comparisons were made using Chi-square and Fisher's exact tests where appropriate for categorical variables and Student's t-test for continuous variables. Logistic regression was used to calculate Odds Ratios (ORs) and their 95% confidence intervals (CI). Multivariable logistic regression models were adjusted for potential confounders.RESULTS: 253 PDAC and 506 matched controls were enrolled. At logistic regression multivariable analysis adjusted for confounding factors, older age at menopause (OR:0.95 per year; 95% CI:0.91-0.98; p = 0.007), use of Oral Contraceptives (OR:0.52; 95% CI:0.30-0.89; p = 0.018), use of Hormonal Replacement Therapy (OR:0.31; 95% CI:0.15-0.64; p = 0.001), and having had two children (OR:0.57; 95% CI:0.38-0.84; p = 0.005) were significant, independent protective factors for the onset of PDAC.CONCLUSIONS: These data confirm some previous findings on menopause age and number of births while, to our knowledge, this is the first study to show a protective effect of HRT and OC use. The results collectively support the hypothesis that exposure to estrogens plays a protective role towards PDAC.
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| 4. |
- Kim, Hyeong Seok, et al.
(författare)
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Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas : An international multicenter study
- 2021
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Ingår i: Journal of hepato-biliary-pancreatic sciences. - : Wiley-Blackwell. - 1868-6974 .- 1868-6982.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms.METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients.RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255).CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.
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| 5. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 6. |
- Arnelo, Urban, et al.
(författare)
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Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia : a pilot study
- 2023
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 23:6, s. 704-711
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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.
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| 7. |
- Cárdenas-Jaén, Karina, et al.
(författare)
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Chronic use of statins and acetylsalicylic acid and incidence of post-endoscopic retrograde cholangiopancreatography acute pancreatitis : A multicenter, prospective, cohort study
- 2021
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Ingår i: Digestive Endoscopy. - : Wiley-Blackwell. - 0915-5635 .- 1443-1661. ; 33:4, s. 639-647
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP.METHODS: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated.RESULTS: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P = 0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94-2.99, P = 0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P = 0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49-2.13), P = 0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20 minutes, were risk factors.CONCLUSIONS: The use of statins or ASA is not associated with a lower risk or a milder course of PEP.
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| 8. |
- 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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| 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. |
- Haraldsson, Erik, et al.
(författare)
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Adenomatous neoplasia in the papilla of Vater endoscopic and/or surgical resection?
- 2022
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Ingår i: Surgical Endoscopy. - : Springer. - 0930-2794 .- 1432-2218. ; 36, s. 2401-2411
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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.
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