| 1. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 2. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 4. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 5. |
- Ansari, Daniel, et al.
(författare)
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Hemorrhage after Major Pancreatic Resection: Incidence, Risk Factors, Management, and Outcome.
- 2017
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Ingår i: Scandinavian Journal of Surgery. - : SAGE Publications. - 1799-7267 .- 1457-4969. ; 106:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- Hemorrhage is a rare but dreaded complication after pancreatic surgery. The aim of this study was to examine the incidence, risk factors, management, and outcome of postpancreatectomy hemorrhage in a tertiary care center. A retrospective observational study was conducted on 500 consecutive patients undergoing major pancreatic resections at our institution. Postpancrea-tectomy hemorrhage was defined according to the International Study Group of Pancreatic Surgery criteria. RESULTS: A total of 68 patients (13.6%) developed postpancreatectomy hemorrhage. Thirty-four patients (6.8%) had a type A, 15 patients (3.0%) had a type B, and the remaining 19 patients (3.8%) had a type C bleed. Postoperative pancreatic fistula Grades B and C and bile leakage were significantly associated with severe postpancreatectomy hemorrhage on multivariable logistic regression. For patients with postpancreatectomy hemorrhage Grade C, the onset of bleeding was in median 13 days after the index operation, ranging from 1 to 85 days. Twelve patients (63.2%) had sentinel bleeds. Surgery lead to definitive hemostatic control in six of eight patients (75.0%). Angiography was able to localize the bleeding source in 8/10 (80.0%) cases. The success rate of angiographic hemostasis was 8/8. (100.0%). The mortality rate among patients with postpancreatectomy hemorrhage Grade C was 2/19 (10.5%), and both fatalities occurred late as a consequence of eroded vessels in association with pancreaticogastrostomy. CONCLUSION: Delayed hemorrhage is a serious complication after major pancreatic surgery.Sentinel bleed is an early warning sign. Postoperative pancreatic fistula and bile leakage are important risk factors for severe postpancreatectomy hemorrhage.
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| 6. |
- Ansari, David, et al.
(författare)
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Pancreatic cancer and thromboembolic disease, 150 years after Trousseau.
- 2015
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Ingår i: HepatoBiliary surgery and nutrition. - 2304-3881. ; 4:5, s. 325-335
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Forskningsöversikt (refereegranskat)abstract
- The connection between pancreatic cancer and venous thrombosis has been discussed for almost 150 years. The exact pathophysiological mechanisms are still partly understood, but it is known that pancreatic cancer induces a prothrombotic and hypercoagulable state and genetic events involved in neoplastic transformation (e.g., KRAS, c-MET, p53), procoagulant factors [e.g., tissue factor (TF), platelet factor 4 (PF4), plasminogen activator inhibitor type 1 (PAI-1)], mucin production (e.g., through activation of P- and L-selectin) and pro-inflammatory factors [e.g., cytokines, cyclooxygenase-2 (COX-2)] may be implicated. Also pancreatitis, both acute and chronic, is associated with increased risk of venous thrombosis, but in this circumstance a direct inflammatory process may be more important. This article discusses the incidence, treatment and outcome of venous thromboembolism (VTE) complicating pancreatic disease, with special emphasis on new knowledge obtained during the last fifteen years.
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| 7. |
- Ansari, David, et al.
(författare)
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Portal Venous System Thrombosis After Pancreatic Resection
- 2013
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 37:1, s. 179-184
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Tidskriftsartikel (refereegranskat)abstract
- Portal venous system thrombosis (PVST) is a rare, potentially fatal complication after pancreatic resection. The aim of this study was to assess the incidence, presenting symptoms, management, and treatment of PVST in a large cohort of patients. Prospectively collected data on patients undergoing pancreatic resection between 1997 and 2009 were reviewed retrospectively. Preoperative and postoperative imaging were analyzed for the presence or absence of venous thrombi. All patients received standard thromboprophylaxis with low-molecular-weight heparin (LMWH). Of 516 pancreatic resections performed, 18 (3.5 %) were complicated by PVST. The most common clinical presentations were abdominal pain (n = 9) and ascites (n = 5) but never any alarm symptoms. Other symptoms were vague and nonspecific (e.g., weight loss, fatigue, fever). Total pancreatectomy was a risk factor compared to hemipancreatectomy (p < 0.01), whereas the underlying disease per se did not make any difference. The median interval between surgery and diagnosis of PVST was 105 days (range 1-1,440 days). PVST was at least a contributing factor in the postoperative deaths of two patients. LMWH therapy did not significantly affect survival. PVST remains a relatively infrequent complication after pancreatic resection. Because accurate diagnosis and timely intervention may reduce morbidity and mortality, the possibility of PVST should be considered in patients presenting with vague symptoms. Whether anticoagulant treatment is needed is still not clear; there were no obvious differences in outcome between treated and untreated patients.
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| 8. |
- Moshontz, Hannah, et al.
(författare)
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The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network
- 2018
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Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:4, s. 501-515
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Tidskriftsartikel (refereegranskat)abstract
- Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability.
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| 9. |
- Muus, Christoph, et al.
(författare)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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| 10. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 11. |
- Åkerberg, Daniel, et al.
(författare)
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Early postoperative fluid retention is a strong predictor for complications after pancreatoduodenectomy
- 2019
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Ingår i: HPB. - : Elsevier BV. - 1365-182X. ; 21:12, s. 1784-1789
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Tidskriftsartikel (refereegranskat)abstract
- Background: Perioperative fluid overload has been reported to increase complications after a variety of operative procedures. This study was conducted to investigate the incidence of fluid retention after pancreatic resection and its association with postoperative complications. Methods: Data from 1174 patients undergoing pancreatoduodenectomy between 2010 and 2016 were collected from the Swedish National Pancreatic and Periampullary Cancer Registry. Early postoperative fluid retention was defined as a weight gain ≥2 kg on postoperative day 1. Outcome measures were overall complications, as well as procedure-specific complications. Results: The weight change on postoperative day 1 ranged from −1 kg to +9 kg. A total of 782 patients (66.6%) were considered to have early fluid retention. Patients with fluid retention had significantly higher rates of total complications (p = 0.002), surgical complications (p = 0.001), pancreatic anastomotic leakage (p = 0.018) and wound infection (p = 0.023). Multivariable logistic regression confirmed early fluid retention as an independent risk factor for total complications (OR 1.46; p = 0.003), surgical complications (OR 1.49; p = 0.002), pancreatic anastomotic leakage (OR 1.48; p = 0.027) and wound infection (OR 1.84; p = 0.023). Conclusions: Fluid retention is common after elective pancreatic resection, and its associated with an increased rate of postoperative complications.
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| 12. |
- Åkerberg, Daniel, et al.
(författare)
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Factors influencing receipt of adjuvant chemotherapy after surgery for pancreatic cancer : a two-center retrospective cohort study
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:1, s. 56-60
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The addition of adjuvant chemotherapy after surgical resection has improved survival rates for patients with pancreatic ductal adenocarcinoma (PDAC). However, outside clinical trials, many operated patients still do not receive adjuvant chemotherapy due to clinical and tumor-related factors. The aim of this study was to investigate factors that may influence the receipt of adjuvant chemotherapy and the effect on long-term survival. Materials and methods: Patients undergoing macroscopically curative resection for PDAC at the University Hospitals in Lund and Linköping, Sweden, between 1 January 2007 and 31 December 2015, were retrospectively reviewed. Clinical and pathological data were compared between adjuvant and non-adjuvant chemotherapy groups and factors affecting chemotherapy receipt were analyzed by multiple logistic regression. Multivariable Cox regression analysis was performed to select predictive variables for survival. Results: A total of 233 patients were analyzed. Adjuvant chemotherapy was administered to 167 patients (71.7%). The likelihood of receiving adjuvant chemotherapy decreased with age, OR 0.91, 95% CI 0.86–0.95, p < .001. Moreover, patients with severe postoperative complications (Clavien–Dindo grade ≥ III) were less likely to receive adjuvant chemotherapy, OR 0.31, 95% CI 0.14–0.71, p = .005. The presence of lymph node metastases on histopathological reporting was associated with increased likelihood of initiating adjuvant chemotherapy, OR 2.19, 95% CI 1.09–4.40, p = .028. Adjuvant chemotherapy was an independent factor for prolonged survival on multivariable Cox regression analysis, HR 0.45 (95% CI 0.31–0.65), p < .001. Conclusions: Age, postoperative complications and the presence of lymph node metastases affect the likelihood of receiving adjuvant chemotherapy after PDAC surgery.
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| 13. |
- Åkerberg, Daniel, et al.
(författare)
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Re-evaluation of classical prognostic factors in resectable ductal adenocarcinoma of the pancreas
- 2016
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327. ; 22:28, s. 6424-6433
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma carries a poor prognosis with annual deaths almost matching the reported incidence rates. Surgical resection offers the only potential cure. Yet, even among patients that undergo tumor resection, recurrence rates are high and long-term survival is scarce. Various tumorrelated factors have been identified as predictors of survival after potentially curative resection. These factors include tumor size, lymph node disease, tumor grade, vascular invasion, perineural invasion and surgical resection margin. This article will re-evaluate the importance of these factors based on recent publications on the topic, with potential implications for treatment and outcome in patients with pancreatic cancer.
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| 14. |
- Ahorsu Kwasi, Daniel, et al.
(författare)
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De-mythifying mental health taboo: Can an educational programme in combination with workshops change the perspective towards mental health and help seeking behavior among university students in Hong Kong?
- 2019
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Ingår i: Proceedings of the 5th International conference on medical and Health Sciences. - Bhutan : Medical Education Centre for Research Innovation and Training, (MECRIT), and the Khesar Gyalpo University of Medical Sciences of Bhutan (KGUMSB).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Promotion of mental health contributes to enhancing the ability of a person to reach and maintain a positive psychosocial state of wellbeing. The degree of knowledge on mental health significantly affects the willingness of an individual to seek for help in case of emotional distress. Aims and objectives: A psychoeducation programme was implemented to de-mythify mental illness and promote help-seeking behavior in combination with group workshops focusing on relaxation and physical activities in tertiary education students in Hong Kong. Methodology: A mixed method approach was used. Quantitative data was collected using questionnaires based on the validated tools to assess mental health awareness and help-seeking behavior. Focus group interviews were carried out to collect additional information on the program impact. Results: A total of 64 students participated in the study (mean age of 23.4 ± 5.2 years). A significant increase in awareness of mental health was observed. While the mean score increased from pretest to posttest, the help-seeking behavior showed no significant difference. A total of 18 subjects participated in 2 focus group interviews. The themes identified included definition of mental health, attitudes related to good mental health, challenges when dealing with mental health, strategies to deal with mental health, strategies to help others and positive impact of the program. Conclusion: The implementation of the psychoeducational program increased mental health awareness, had a positive impact on the participants awareness on self-care and promoted knowledge on strategies for self-help and helping others.
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| 15. |
- Andersson, Bodil, et al.
(författare)
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Acute pancreatitis - costs for healthcare and loss of production.
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:12, s. 1459-1465
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Severity of acute pancreatitis (AP) can vary from a mild to a fulminant disease with high morbidity and mortality. Cost analysis has, however, hitherto been sparse. The aim of this study was to calculate the cost of acute pancreatitis, both including hospital costs and costs due to loss of production. Material and methods. All adult patients treated at Skane University Hospital, Lund, during 2009-2010, were included. A severity grading was conducted and cost analysis was performed on an individual basis. Results. Two hundred and fifty-two patients with altogether 307 admissions were identified. Mean age was 60 ± 19 years, and 121 patients (48%) were men. Severe AP (SAP) was diagnosed in 38 patients (12%). Thirteen patients (5%) died. Acute biliary pancreatitis was more costly than alcohol induced AP (p < 0.001). Total costs for treating mild AP (MAP) in patients ≤65 years old was lower (p = 0.001) and costs for SAP was higher (p = 0.024), as compared to older patients. The overall hospital cost and cost for loss of production was per person in mean €5,100 ± 2,400 for MAP and €28,200 ± 38,100 for SAP (p < 0.001). The costs for treating AP during the two-year-long study period were in mean €9,762 ± 19,778 per patient. Extrapolated to a national perspective, the annual financial burden for AP in Sweden would be ∼ €38,500,000; corresponding to €4,100,000 per million inhabitants. Conclusions. The costs of treating AP are high, especially in severe cases with a long ICU stay. These results highlight the need to optimize care and continue the identification and focus on SAP, in order to try to limit organ failure and infectious complications.
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| 16. |
- Andersson, Bodil, et al.
(författare)
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Fatal Acute Pancreatitis Occurring Outside of the Hospital: Clinical and Social Characteristics.
- 2010
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; Jul 1, s. 2286-2291
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mortality caused by acute pancreatitis in patients admitted to the hospital has been thoroughly investigated, but knowledge regarding outpatient fatalities is far from complete. The purpose of this study was to assess the incidence and clinical characteristics of patients who have died due to acute pancreatitis occurring outside the hospital. METHODS: Deaths caused by acute pancreatitis in the southern part of Sweden during 1994-2008 were identified at the Department of Forensic Medicine, Lund. A retrospective review of all cases was performed. RESULTS: A total of 50 patients were included, representing approximately 50 of 292 (17%) of all deaths due to acute pancreatitis in the region during this period of time. Median age was 54 (47-69) years and the majority-37 (74%)-were men. The main etiology was alcohol, seen in at least 35 (70%) patients. Twelve (24%) patients were obese. The duration of abdominal pain, in evaluable cases, was 3.0 (1.6-6.2) days. Profound signs of pancreatitis were seen in all patients; 35 (70%) had a necrotising disease according to histopathological examination. Pulmonary changes were common, e.g., bronchopneumonia, pleural effusion, or edema, and all but four had fatty liver. Massive intra-abdominal bleeding was seen in one patient. At least eight patients had a mental disorder, and three were homeless. CONCLUSIONS: Fatal acute pancreatitis occurring outside the hospital accounts for a substantial part of all deaths due to the disease. The incidence seems to decline, and no variation in season was seen. Alcohol was the predominant etiology. Many of the patients lived alone and in poor social conditions.
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| 17. |
- Andersson, Bodil, et al.
(författare)
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Surgical stress response after colorectal resection.
- 2013
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Ingår i: International Surgery. - 0020-8868. ; 98:4, s. 292-299
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The human body's response to surgery is correlated with the extent of tissue damage. The aim of the present study was to, over time, map out parameters concerning inflammation, metabolism, nutrition, breathing function, muscle strength, and well-being in elective colorectal surgery. Eighteen patients were prospectively included: colon resection (n = 9) and rectum resection/amputation (n = 9). Postoperative interleukin 10 (IL-10) rose more in the rectum surgery group on day 0 (P = 0.007) and day 3 (P = 0.025). Furthermore, significant differences between groups were detected regarding albumin, prealbumin, and total iron-binding capacity (TIBC). For albumin and TIBC, this difference was seen even on day 7. C-reactive protein, IL-6, IL-8, glucose, cortisol, insulin, pain, fatigue, nausea, grip strength, and forced expiratory volume in 1 second did not show any differences. No correlation was revealed between measured parameters and postoperative complications. Postoperative levels of IL-10, albumin, prealbumin, and TIBC may be used as determinants of surgical stress after colorectal surgery.
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| 18. |
- Andersson, Ellen, et al.
(författare)
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Tissue factor in predicted severe acute pancreatitis.
- 2010
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327. ; 16:48, s. 6128-6134
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Tidskriftsartikel (refereegranskat)abstract
- To study tissue factor (TF) in acute pancreatitis and evaluate the role of TF as a predictive marker of severity.
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| 19. |
- Andersson, Roland, et al.
(författare)
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Acute pancreatitis–can evidence-based guidelines be transferred to an optimized comprehensive treatment program?
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:10, s. 1220-1221
-
Tidskriftsartikel (refereegranskat)abstract
- Acute pancreatitis is a common cause of hospitalization and has an incidence of about 300 per 1,000,000 inhabitants. A majority of patients with acute pancreatitis have mild disease, with an absence of local and systemic complications [1]. The clinical, translational, and experimental research in the field of acute pancreatitis is enormous and various guidelines exist. The guidelines have improved, and now increasingly use evidence-based grading, although expert opinion is still part of numerous recommendations.A persistent problem, however, is the uptake of and compliance with these guidelines. For every guideline recommendation, we should need an implementation plan and an audit. This was pointed out in an editorial in the Scandinavian Journal of Gastroenterology in 2008 [2]. It is reasonable to assume that adherence to existing management recommendations improves clinical outcomes for patients with acute pancreatitis.
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| 20. |
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| 21. |
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| 22. |
- Andersson, Roland, et al.
(författare)
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Pancreatic cancer–the past, the present, and the future
- 2022
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 57:10, s. 1169-1177
-
Forskningsöversikt (refereegranskat)abstract
- Background: Pancreatic cancer has been and still is associated with a very poor prognosis. This is due to a lack of major breakthroughs with respect to early diagnosis, prognostication, prediction, as well as novel, targeted therapies. The benefits of surgery and chemotherapy are evident, but the fact that only some 10% of all patients have early, localized disease highlights the unmet need for new early detection methods. An improved understanding of tumor biology and the development of molecular markers detectable both in the circulation and in cancer tissues may underlie the development of new tools for optimizing both diagnosis and treatment. Material and methods: Review of the literature. Results and conclusion: If we do not improve precision oncology for pancreatic ductal adenocarcinoma, the prognosis will still remain dismal and the” burden” on society will increase substantially.
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| 23. |
- Andersson, Roland, et al.
(författare)
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Surveillance after resection of pancreatic ductal adenocarcinoma : How to do it and what are the benefits?
-
Ingår i: Scandinavian Journal of Surgery. - 1457-4969.
-
Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Surveillance following resection with curative intent of pancreatic cancer varies widely, and supporting evidence is limited. Recurrence is although frequent, not at least during the first 2 years. Surveillance may be costly, but evidence on how this influences overall survival is not fully elucidated. Methods, Results: There are reports implying that signs of biological recurrence (increasing CA 19-9) precede radiologically demonstrated recurrence by months. Conclusions: The possibility of initiating salvage therapy earlier is discussed, potentially based on improved future biomarker panels.
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| 24. |
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| 25. |
- Ansari, Daniel, et al.
(författare)
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Analysis of MUC4 Expression in Human Pancreatic Cancer Xenografts in Immunodeficient Mice.
- 2014
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Ingår i: Anticancer research. - 1791-7530. ; 34:8, s. 3905-3910
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Tidskriftsartikel (refereegranskat)abstract
- Mucin 4 (MUC4) is a cell surface glycoprotein that is overexpressed in most pancreatic tumors. The aim of the present study was to characterize MUC4 expression in experimental pancreatic cancer in order to clarify the correlation between MUC4 and pancreatic cancer histology in vivo.
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| 26. |
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| 27. |
- Ansari, Daniel, et al.
(författare)
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Artificial neural networks predict survival from pancreatic cancer after radical surgery.
- 2013
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Ingår i: The American Journal of Surgery. - : Elsevier BV. - 1879-1883 .- 0002-9610. ; 205:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Artificial neural networks (ANNs) are nonlinear pattern recognition techniques that can be used as a tool in medical decision making. The objective of this study was to develop an ANN model for predicting survival in patients with pancreatic ductal adenocarcinoma (PDAC).
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| 28. |
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| 29. |
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| 30. |
- Ansari, Daniel, et al.
(författare)
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Centrosomal Abnormalities in Pancreatic Cancer : Molecular Mechanisms and Clinical Implications
- 2018
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:3, s. 1241-1245
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Forskningsöversikt (refereegranskat)abstract
- The centrosome is the main microtubule-organizing center in human cells. It regulates normal cell-cycle progression and cell division. Aberrations in the number, structure and function of centrosomes have been found to drive genomic instability and tumorigenesis. Pancreatic cancer frequently displays centrosomal aberrations. Supernumerary and abnormal centrosomes are observed in the earliest stages of pancreatic tumor development, and the p53 pathway acts as an initial barrier to the proliferation of cells with extra centrosomes. In this review, we summarize recent advances in the understanding of centrosomal aberrations in pancreatic cancer, focusing on regulatory mechanisms and prospects for future anticancer treatment.
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| 31. |
- Ansari, Daniel, et al.
(författare)
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Chronic pancreatitis: potential future interventions.
- 2010
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 45:9, s. 1022-1028
-
Forskningsöversikt (refereegranskat)abstract
- Chronic pancreatitis is a common disorder of which the underlying pathogenic mechanisms still are incompletely understood. In the last decade, increasing evidence has shown that activated pancreatic stellate cells play a key role in the fibrosis development associated with chronic pancreatitis as well as pancreatic cancer. During pancreatic injury or inflammation, quiescent stellate cells undergo a phenotypic transformation, characterized by smooth muscle alpha-actin expression and increased synthesis of extracellular matrix proteins. Hitherto, specific therapies to prevent or reverse pancreatic fibrosis are unavailable. This review addresses current insights into pathological mechanisms underlying chronic pancreatitis and their applicability as concerns the development of potential future therapeutic approaches.
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| 32. |
- Ansari, Daniel, et al.
(författare)
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CODUSA - Customize Optimal Donor Using Simulated Annealing In Heart Transplantation.
- 2013
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3:May,30
-
Tidskriftsartikel (refereegranskat)abstract
- In heart transplantation, selection of an optimal recipient-donor match has been constrained by the lack of individualized prediction models. Here we developed a customized donor-matching model (CODUSA) for patients requiring heart transplantations, by combining simulated annealing and artificial neural networks. Using this approach, by analyzing 59,698 adult heart transplant patients, we found that donor age matching was the variable most strongly associated with long-term survival. Female hearts were given to 21% of the women and 0% of the men, and recipients with blood group B received identical matched blood group in only 18% of best-case match compared with 73% for the original match. By optimizing the donor profile, the survival could be improved with 33 months. These findings strongly suggest that the CODUSA model can improve the ability to select optimal match and avoid worst-case match in the clinical setting. This is an important step towards personalized medicine.
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| 33. |
- Ansari, Daniel, et al.
(författare)
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Comparison of MUC4 expression in primary pancreatic cancer and paired lymph node metastases.
- 2013
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:10, s. 1183-1187
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Mucin 4 (MUC4) is a transmembrane glycoprotein that is expressed in pancreatic ductal adenocarcinoma (PDAC), but not in normal pancreatic tissue. MUC4 has a proposed role in pancreatic tumor progression and metastasis. The purpose of this pilot study was to investigate MUC4 expression during PDAC metastasis by comparing the expression in the primary tumor and paired lymph node metastases from the same patient. Material and methods. Surgical specimens from 17 cases of primary PDAC and paired lymph node metastases were immunohistochemically analyzed for MUC4 expression. The modified histochemical score (H-score) was used for staining assessment. Results. Positive staining for MUC4 was detected in most primary and metastatic PDAC tumors (15/17 vs. 14/17). The concordance for MUC4 expression in primary tumors and corresponding lymph node metastases was 82%. In two cases, the primary tumor was MUC4-positive and the lymph node metastases were negative, while in one patient with a MUC4-negative primary tumor, the lymph node metastasis was positive. The distribution of H-score for expression of MUC4 significantly correlated (r = 0.615; p = 0.009) between primary tumors and paired metastatic lesions. Conclusions: MUC4 was observed in both primary and matched metastatic tumors with a high level of concordance, suggesting that MUC4 expression is retained following PDAC metastasis.
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| 34. |
- Ansari, Daniel, et al.
(författare)
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Diagnosis and management of duodenal perforations : a narrative review
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 54:8, s. 939-944
-
Forskningsöversikt (refereegranskat)abstract
- Duodenal perforation is a rare, but potentially life-threatening injury. Multiple etiologies are associated with duodenal perforations such as peptic ulcer disease, iatrogenic causes and trauma. Computed tomography with intravenous and oral contrast is the most valuable imaging technique to identify duodenal perforation. In some cases, surgical exploration may be necessary for diagnosis. Specific treatment depends upon the nature of the disease process that caused the perforation, the timing, location and extent of the injury and the clinical condition of the patient. Conservative management seems to be feasible in stable patients with sealed perforations. Immediate surgery is required for patients presenting with peritonitis and/or intra-abdominal sepsis. Minimally invasive techniques are safe and effective alternatives to conventional open surgery in selected patients with duodenal perforations. Here we review the current literature on duodenal perforations and discuss the outcomes of different treatment strategies.
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| 35. |
- Ansari, Daniel, et al.
(författare)
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Early-onset pancreatic cancer : a population-based study using the SEER registry
- 2019
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Ingår i: Langenbeck's Archives of Surgery. - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 404:5, s. 565-571
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Early-onset pancreatic cancer (< 50 years, EOPC) is uncommon and limited data exist on clinical presentation and long-term survival. The aim of this study was to compare outcomes between patients with EOPC and those with later-onset pancreatic cancer (≥ 50 years, LOPC) using a large population-based cohort. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with a microscopically confirmed pancreatic ductal adenocarcinoma for the period 2004 to 2016. Propensity score matching was used to compare overall survival (OS) and cancer-specific survival (CSS) between patients with EOPC and LOPC. The EOPC and LOPC patients were paired 1:1 on propensity scores based on gender, tumor location, tumor size, AJCC stage, and treatment details. Results: The overall cohort included 72,906 patients with pancreatic ductal adenocarcinoma, including 4523 patients with EOPC (6.2%). EOPC patients were diagnosed at a more advanced AJCC stage (p < 0.001) compared with LOPC patients and received significantly more treatment, including surgery (p < 0.001), radiation (p < 0.001), and chemotherapy (p < 0.001). Following propensity score matching, 3172 EOPC patients were matched to 3172 LOPC patients, alleviating any covariate differences between the groups. The matched analysis showed that EOPC was associated with poorer 5-year OS (6.1% vs 8.6%, p = 0.003) and 5-year CSS (6.7% vs 9.7%, p < 0.001). In multivariable Cox regression analysis, EOPC remained significantly associated with adverse OS and CSS. Subgroup analyses showed that EOPC was associated with adverse 5-year OS (17.7% vs 26.9%, p < 0.001) and 5-year CSS (18.9% vs 29.7%, p < 0.001) in operated patients. After multivariable analysis, EOPC remained significantly associated with OS and CSS. For patients that did not undergo surgery, the OS and CSS remained dismal without any significant differences between the groups. Conclusion: To our knowledge, this is the largest study to compare the outcome of EOPC vs LOPC, as well as the first to use propensity score matching methodology for this purpose. The findings demonstrate that EOPC is diagnosed at a later stage and the matched survival analysis demonstrated reduced OS and CSS. We suggest that pancreatic cancer in young patients may have a unique tumor biology, which may be of importance for risk stratification and patient counseling.
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| 36. |
- Ansari, Daniel, et al.
(författare)
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Fast-track surgery: procedure-specific aspects and future direction.
- 2012
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Ingår i: Langenbeck's Archives of Surgery. - : Springer Science and Business Media LLC. - 1435-2451 .- 1435-2443.
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Fast-track (FT) surgery can be defined as a coordinated perioperative approach aimed at reducing surgical stress and facilitating postoperative recovery. The objective of this review was to examine the literature on the procedure-specific application of FT surgery. DISCUSSION: The concept of FT rehabilitation has been applied mainly in colorectal surgery, but positive data have appeared also in other areas such as orthopedic, hepatopancreaticobiliary, urological, upper gastrointestinal, gynecological, thoracic, vascular, endocrine, breast, and pediatric surgeries. There is very little experience with comprehensive FT programs in cardiac surgery or trauma. Quantitative analysis from randomized trials and cohort studies suggest that FT is effective in reducing hospital stay without increased adverse events. Other benefits of the FT approach include a reduction in complications, ileus, fatigue, pain, and hospital expenses. However, despite clear benefits of FT care, implementation in daily practice has been slow. Further efforts must be undertaken to secure implementation in routine clinical practice. Standardized FT protocols should be provided on a procedure-specific basis.
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| 37. |
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| 38. |
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| 39. |
- Ansari, Daniel, et al.
(författare)
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Multimodal management of colorectal liver metastases and the effect on regeneration and outcome after liver resection.
- 2012
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521.
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Management of colorectal liver metastases (CRLM) has dramatically changed during the last decade and has now become more multimodal and aggressive, including the use of downstaging chemotherapy, portal vein embolization to increase the function of the liver remnant or both in combination. Radiofrequency ablation is also an option in CRLM, potentially combined with surgical resection. Results are quite convincing concerning the safety of liver resection also when performed following neoadjuvant chemotherapy. Sparing liver parenchyma in patients with bilobar liver metastatic disease subjected to liver resection may be possible without endangering surgical radicality. Sparing liver parenchyma when using neoadjuvant chemotherapy, a chemotherapy-free period of 6 weeks or more seems to positively affect liver regeneration. There is still the possibility to reresect recurrent liver lesions, though there seems to be a tendency toward fewer reresections following the use of adjuvant chemotherapy.
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| 40. |
- Ansari, Daniel, et al.
(författare)
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Neoadjuvant/Downstaging Radiochemotherapy in Marginally Resectable Pancreatic Cancer
- 2014
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Ingår i: Hepato-Gastroenterology. - 0172-6390. ; 61:136, s. 2387-2390
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is a challenging disease due to the low resection rate at the time of initial diagnosis. A relatively new classification of marginally resectable pancreatic cancer has emerged and there is some evidence that this subgroup of patients may benefit from neoadjuvant radiochemotherapy. The first major definition of marginally resectable pancreatic cancer was made at M. D. Anderson Cancer Center and published in 2006. This definition was purely anatomical and CT-based and only handles the relationship of the pancreatic tumor to its surrounding major vessels. Later on, two other subtypes have been added to this definition: suspicion or known metastasis in regional lymph nodes (N1 disease), or severe pre-existing medical comorbidities requiring prolonged evaluation or recovery and precluding immediate surgery. Other definitions (anatomical and CT-based) for marginally resectable pancreatic cancer have also been established. For systematic research on neoadjuvant therapy in marginally resectable pancreatic cancer, however, the lack of uniform definitions and randomized trials have been troublesome. Nevertheless, several small cohort studies have demonstrated that 40-80% of the marginally resectable patients could proceed to resection after neoadjuvant treatment and also reporting some promising effects on microscopic resection margins, lymph node status and survival.
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| 41. |
- Ansari, Daniel, et al.
(författare)
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Pancreatic cancer - cost for overtreatment with gemcitabine.
- 2013
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Ingår i: Acta Oncologica. - 1651-226X. ; 52:6, s. 1146-1151
-
Tidskriftsartikel (refereegranskat)abstract
- Gemcitabine has been the standard chemotherapeutic agent in pancreatic cancer. However, two-thirds of pancreatic tumors display low expression of human equilibrative nucleoside transporter 1 (hENT1), which mediates cellular entry of the drug, and do not respond to gemcitabine therapy. The objective was to determine the costs of gemcitabine overtreatment and the cost-effectiveness of hENT1 testing using a Swedish pancreatic cancer cohort. Material and methods. The study population included 87 patients that were diagnosed with pancreatic cancer during 2008-2010 at Skåne University Hospital, Lund. A detailed review of treatments, side effects and resource utilization was performed. The proportion of hENT1-low was estimated at two-thirds based on previous evaluations of tumor samples from the Radiation Therapy Oncology Group (RTOG) trial 9704, the German AIO Pancreatic Cancer Group (AIO-PK) trial 0104, the Low hENT1 and Adenocarcinoma of the Pancreas (LEAP) trial and the authors' own institution. The cost of the hENT1 test was estimated at €50-200. Results. Sixty patients received gemcitabine and the other 27 best supportive care. Drug administration and hospitalization were the main expenditures. Grade 3 and 4 toxicities occurred in 42%, the most common being neutropenia (18%). The hospital costs related to gemcitabine overtreatment amounted to €5358 per pancreatic cancer patient, corresponding to as much as one-third of the total treatment cost. The health economical costs amounted to €9449 per patient when including indirect costs. Using hENT1 testing to select patients for gemcitabine therapy would save €8.6 million in Sweden each year. Conclusion. Total costs related to gemcitabine overtreatment were high. Individualizing gemcitabine treatment is cost-saving and would reduce unnecessary treatment-related toxicity.
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| 42. |
- Ansari, Daniel, et al.
(författare)
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Pancreatic cancer : Disease dynamics, tumor biology and the role of the microenvironment
- 2018
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:5, s. 6644-6651
-
Forskningsöversikt (refereegranskat)abstract
- Pancreatic cancer is known for its propensity to metastasize. Recent studies have challenged the commonly held belief that pancreatic cancer is a stepwise process, where tumor cells disseminate late in primary tumor development. Instead it has been suggested that pancreatic tumor cells may disseminate early and develop independently and in parallel to the primary tumor. Circulating tumor cells can be found in most patients with pancreatic cancer, even in those with localized stage. Also, recent phylogenetic analyses have revealed evidence for a branched evolution where metastatic lineages can develop early in tumor development. In this Review, we discuss current models of pancreatic cancer progression and the importance of the tumor microenvironment, in order to better understand the recalcitrant nature of this disease.
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| 43. |
- Ansari, Daniel
(författare)
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Pancreatic Cancer - Early Detection, Prognostic Factors, and Treatment
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Pancreatic cancer is the fourth leading cause of cancer-related death. Only about 6% of patients are alive 5 years after diagnosis. One reason for this low survival rate is that most patients are diagnosed at a late stage, when the tumor has spread to surrounding tissues or distant organs. Less than 20% of cases are diagnosed at an early stage that allows them to undergo potentially curative surgery. However, even for patients with a tumor that has been surgically removed, local and systemic recurrence is common and the median survival is only 17-23 months. This underscores the importance to identify factors that can predict postresection survival. With technical advances and centralization of care, pancreatic surgery has become a safe procedure. The future optimal treatment for pancreatic cancer is dependent on increased understanding of tumor biology and development of individualized and systemic treatment. Previous experimental studies have reported that mucins, especially the MUC4 mucin, may confer resistance to the chemotherapeutic agent gemcitabine and may serve as targets for the development of novel types of intervention. Aim: The aim of the thesis was to investigate strategies to improve management of pancreatic cancer, with special reference to early detection, prognostic factors, and treatment. Methods: In paper I, 27 prospectively collected serum samples from resectable pancreatic cancer (n=9), benign pancreatic disease (n=9), and healthy controls (n=9) were analyzed by high definition mass spectrometry (HDMSE). In paper II, an artificial neural network (ANN) model was constructed on 84 pancreatic cancer patients undergoing surgical resection. In paper III, we investigated the effects of transition from a low- to a high volume-center for pancreaticoduodenectomy in 221 patients. In paper IV, the grade of concordance in terms of MUC4 expression was examined in 17 tissue sections from primary pancreatic cancer and matched lymph node metastases. In paper V, pancreatic xenograft tumors were generated in 15 immunodeficient mice by subcutaneous injection of MUC4+ human pancreatic cancer cell lines; Capan-1, HPAF-II, or CD18/HPAF. In paper VI, a 76-member combined epigenetics and phosphatase small-molecule inhibitor library was screened against Capan-1 (MUC4+) and Panc-1 (MUC4-) cells, followed by high content screening of protein expression. Results/Conclusion: 134 differentially expressed serum proteins were identified, of which 40 proteins showed a significant up-regulation in the pancreatic cancer group. Pancreatic disease link associations could be made for BAZ2A, CDK13, DAPK1, DST, EXOSC3, INHBE, KAT2B, KIF20B, SMC1B, and SPAG5, by pathway network linkages to p53, the most frequently altered tumor suppressor in pancreatic cancer (I). An ANN survival model was developed, identifying 7 risk factors. The C-index for the model was 0.79, and it performed significantly better than the Cox regression (II). We experienced improved surgical results for pancreaticoduodenectomy after the transition to a high-volume center (≥25 procedures/year), including decreased operative duration, blood loss, hemorrhagic complications, reoperations, and hospital stay. There was also a tendency toward reduced operative mortality, from 4% to 0% (III). MUC4 positivity was detected in most primary pancreatic cancer tissues, as well as in matched metastatic lymph nodes (15/17 vs. 14/17), with a high concordance level (82%) (IV). The tumor incidence was 100% in the xenograft model. The median MUC4 count was found to be highest in Capan-1 tumors. α-SMA and collagen extent were also highest in Capan-1 tumors (V). Apicidin (a histone deacetylase inhibitor) had potent antiproliferative activity against Capan-1 cells and significantly reduced the expression of MUC4 and its transcription factor HNF4α. The combined treatment of apicidin and gemcitabine synergistically inhibited growth of Capan-1 cells (VI).
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| 44. |
- Ansari, Daniel, et al.
(författare)
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Pancreatic cancer stroma : controversies and current insights
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:6-7, s. 641-646
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Forskningsöversikt (refereegranskat)abstract
- Pancreatic cancer is characterized by a dense stromal response. The stroma includes a heterogeneous mass of cells, including pancreatic stellate cells, fibroblasts, immune cells and nerve cells, as well as extracellular matrix proteins, cytokines and growth factors, which interact with the tumor cells. Previous research has indicated that stromal elements contribute to tumor growth and aggressiveness. However, recent studies suggest that some elements of the stroma may actually restrain the tumor. This review focuses on the complex interactions between the stromal microenvironment and tumor cells, discussing molecular mechanisms and potential future diagnostic and therapeutic approaches by targeting the stroma.
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| 45. |
- Ansari, Daniel, et al.
(författare)
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Pancreatic cancer: Translational research aspects and clinical implications.
- 2012
-
Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327. ; 18:13, s. 1417-1424
-
Tidskriftsartikel (refereegranskat)abstract
- Despite improvements in surgical techniques and adjuvant chemotherapy, the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%. This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes, proteins, microRNAs or epigenetic modifications. However, there are still major hurdles when translating investigational biomarkers into routine clinical practice. Furthermore, novel ways of secondary screening in high-risk individuals, such as artificial neural networks and modern imaging, will be discussed. Drug resistance is ubiquitous in pancreatic cancer. Several mechanisms of drug resistance have already been revealed, including human equilibrative nucleoside transporter-1 status, multidrug resistance proteins, aberrant signaling pathways, microRNAs, stromal influence, epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells. These factors must be considered when developing more customized types of intervention ("personalized medicine"). In the future, multifunctional nanoparticles that combine a specific targeting agent, an imaging probe, a cell-penetrating agent, a biocompatible polymer and an anti-cancer drug may become valuable for the management of patients with pancreatic cancer.
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| 46. |
- Ansari, Daniel, et al.
(författare)
-
Pancreatic cancer : Yesterday, today and tomorrow
- 2016
-
Ingår i: Future Oncology. - : Future Medicine Ltd. - 1479-6694 .- 1744-8301. ; 12:16, s. 1929-1946
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology.
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| 47. |
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| 48. |
- Ansari, Daniel, et al.
(författare)
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Pancreaticoduodenectomy - the transition from a low- to a high-volume center.
- 2014
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 49:4, s. 481-484
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Previous studies have identified a significant volume-outcome relationship for hospitals performing pancreaticoduodenectomy (PD). However, scant information exists concerning the effects of increased caseload of PD within the same hospital. Here, we describe the effects of becoming a high-volume provider of PD. Material and methods. The study group comprised 221 patients who underwent PD between 2000 and 2012. Hospital volume was allocated into three groups: low-volume (<10 PDs/year), years 2000-2004, n = 25; medium-volume (10-24 PDs/year), years 2005-2009, n = 86; and high-volume (≥25 PDs/year), years 2010-2012, n = 110. Results. The annual number of PDs increased from 5 in 2000 to 39 in 2012. The median operative duration decreased over the volume categories (p < 0.001). Intraoperative blood loss dropped (p < 0.001). The need for intraoperative blood transfusion was reduced (p < 0.001). Increasing hospital volume was associated with fewer reoperations (p = 0.041) and shorter postoperative length of stay (p = 0.010). There was a tendency toward reduced mortality: 4.0% for the low-volume period, 2.3% for the medium-volume period, and 0% for the high-volume period (p = 0.066). Conclusions. The transition from a low- to a high-volume center resulted in optimized outcomes for PD and 0% operative mortality, favoring the continued centralization of this high-risk operation.
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| 49. |
- Ansari, Daniel, et al.
(författare)
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Positron emission tomography in malignancies of the liver, pancreas and biliary tract - indications and potential pitfalls.
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:3, s. 259-265
-
Forskningsöversikt (refereegranskat)abstract
- Abstract Malignancies of the hepato-pancreatico-biliary (HPB) system are relatively common and generally characterized by a dismal prognosis. Positron emission tomography (PET) is a functional imaging technique that has emerged as an important modality in oncological decision-making. The principal radiopharmaceutical in PET imaging is the glucose analog (18)F-fluorodeoxyglucose, which is able to detect altered glucose metabolism in malignant tissue. PET is typically used in conjunction with computed tomography (CT), and previous studies have supported several uses of PET/CT in HPB malignancies, including staging, differential diagnostics and monitoring of treatment response and progress of disease. A review of PET/CT in the context of HPB malignancies will be presented, including indications and potential pitfalls.
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| 50. |
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