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- Tran, K. B., et al.
(författare)
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The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Tidskriftsartikel (refereegranskat)abstract
- Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 4. |
- Morgell, A, 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
- 2020
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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-labelled 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 TMAO. 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 pyloriand gastric cancer).Key pointsWe identified and quantified novel markers of IPMN cyst status and pancreatic cancer disease progression – including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products and TMAO.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.
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| 8. |
- Gaiser, RA, et al.
(författare)
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Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:12, s. 2186-2194
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Tidskriftsartikel (refereegranskat)abstract
- Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can progress to invasive pancreatic cancer. Associations between oncogenesis and oral microbiome alterations have been reported. This study aims to investigate a potential intracystic pancreatic microbiome in a pancreatic cystic neoplasm (PCN) surgery patient cohort.DesignPaired cyst fluid and plasma were collected at pancreatic surgery from patients with suspected PCN (n=105). Quantitative and qualitative assessment of bacterial DNA by qPCR, PacBio sequencing (n=35), and interleukin (IL)-1β quantification was performed. The data were correlated to diagnosis, lesion severity and clinical and laboratory profile, including proton-pump inhibitor (PPI) usage and history of invasive endoscopy procedures.ResultsIntracystic bacterial 16S DNA copy number and IL-1β protein quantity were significantly higher in IPMN with high-grade dysplasia and IPMN with cancer compared with non-IPMN PCNs. Despite high interpersonal variation of intracystic microbiota composition, bacterial network and linear discriminant analysis effect size analyses demonstrated co-occurrence and enrichment of oral bacterial taxa including Fusobacterium nucleatum and Granulicatella adiacens in cyst fluid from IPMN with high-grade dysplasia. The elevated intracystic bacterial DNA is associated with, but not limited to, prior exposure to invasive endoscopic procedures, and is independent from use of PPI and antibiotics.ConclusionsCollectively, these findings warrant further investigation into the role of oral bacteria in cystic precursors to pancreatic cancer and have added values on the aetiopathology as well as the management of pancreatic cysts.
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- Kurlinkus, B, et al.
(författare)
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In the Era of the Leeds Protocol: A Systematic Review and A Meta-Analysis on the Effect of Resection Margins on Survival Among Pancreatic Ductal Adenocarcinoma Patients
- 2020
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Ingår i: Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. - : SAGE Publications. - 1799-7267. ; 109:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- A positive resection margin is considered to be a factor associated with poor prognosis after pancreatic ductal adenocarcinoma resection. However, analysis of the resection margin is dependent on the pathological slicing technique. The aim of this systematic review and meta-analysis was to study the impact of resection margin on the survival of pancreatic ductal adenocarcinoma patients whose specimens were analyzed using the axial slicing technique. Material and Methods: A systematic search in the PubMed, Cochrane, and Embase datasets covering the time period from November 2006 to January 2019 was performed. Only studies with axial slicing technique (Leeds Pathology Protocol or Royal College of Pathology Protocol) were included in the final database. Meta-analysis between the marginal distance and survival was performed with the Inverse Variance Method in RevMan. Results: The systematic search resulted in nine studies meeting the inclusion criteria. The median survival for a resection margin 0 mm ranged from 12.3 to 23.4 months, for resection margin <0.5 mm 16 months, for resection margin <1 mm ranged from 11 to 27.5 months, for resection margin <1.5 mm ranged from 16.9 to 21.2 months, and for resection margin >2 mm ranged from 53.9 to 63.1 months. Five studies were eligible for meta-analysis. The pooled multivariable hazard ratio favored resection margin ⩾1 mm (hazard ratio: 1.32 and 95% confidence interval: 1.03–1.68, p = 0.03). Conclusion: Resection margins ⩾1 mm seem to lead to better survival in pancreatic ductal adenocarcinoma patients than resection margin <1 mm. However, there is not enough data to evaluate the effect of oncologic therapy or to analyze the impact of other resection margin distances on survival.
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