| 61. |
- Shirazi, L., et al.
(författare)
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Serum vitamin D (25OHD(3)) levels and the risk of different subtypes of breast cancer: A nested case-control study
- 2016
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Ingår i: Breast. - : Elsevier BV. - 0960-9776. ; 28, s. 184-190
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies regarding the association between serum 25-hydroxyvitamin D (25OHD(3)) and breast cancer risk have not been conclusive. The aim of this study was to investigate the potential association between pre-diagnostic serum 25OHD(3) levels and the risk of different subtypes of breast cancer. Materials and methods: The study was based on The Malmo Diet and Cancer Study recruiting 17,035 women from 1991 to 1996. A total of 764 incident breast cancers with matched controls were analysed for 25OHD(3) in samples collected at baseline, before diagnosis. A logistic regression analysis was used to calculate odds ratios with 95% confidence intervals for tertiles of 25OHD(3) in relation to different subtypes of breast cancer, i.e. defined according to tumour type, tumour size, lymph node involvement, histological grade, oestrogen receptor (ER) status, progesterone receptor (PgR) status, Ki67, cyclin D1 and p27. Results: As compared to the 1st tertile of 25OHD(3), the second tertile had a statistically significantly lower risk of ER negative tumours, PgR negative tumours and tumours with a high expression of Ki67, A similar pattern was seen in relation to large tumours (>= 21 mm), grade III tumours, and tumours with low p27 expression, but these associations did not reach statistical significance. The third tertile had a similar risk as the first tertile. Conclusions: We found that women with low levels of 25OHD(3), as compare to women in the middle tertile, had a high risk of breast tumours with an unfavourable prognosis.
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| 62. |
- Forsell, Karl, 1975-
(författare)
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Health hazards and cancer in relation to occupational exposures among Swedish seafarers
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis explores health hazards for seafarers in the Swedish merchant fleet, and occupational risks for lung cancer, mesothelioma and hematologic malignancy (HM). A special focus has been exposure to benzene and biomarker levels for work on product or chemical tankers during the mid-1990’ies.In a case report, we describe two cases of mesothelioma and two cases of lung cancer having worked in the engine room. Cumulative exposure to asbestos were up to 5 fibreyears. Other exposures were carcinogenic PAHs and nitroarenes. A web-based survey to active seafarers in the Swedish merchant fleet revealed noise, the risk of accidents, whole-body vibrations and ergonomic strain as main work environment problems. General health, work ability and safety climate were all rated high. Associations were found between lower airway symptoms and soot (PR 2.4, 95% CI 1.1-5.1) and between hearing impairment and noise exposure (PR 1.5; 95% CI 1.3–1.7). Iso-strain was especially common in the service department. Twenty-two percent of men and 45% of women had been subjected to harassments. The tanker study showed a geometric mean for benzene exposure of 0.45 mg/m3 (4hTWA) during a work shift, with a wide range (0.02-143 mg/m3). Correlations were found between exposure and benzene in alveolar air (p<0.0001), unmetabolised benzene in urine (p<0.0001) and ttMA in urine (p=0.0011). All biomarkers increased significantly during work (p<0.002). In a case-referent study with the observation period 1985 to 2014, the OR for HM was 1.32 (95% CI 0.86-2.02) if work on tankers had started before 1985 and with a cumulated tanker service of at least five years. If work on tankers had started after 1985, the OR was 0.85 (95% CI 0.51-1.43).In conclusion, health hazards in today’s seafaring relate to physical, chemical and psychosocial factors. Work on tankers with mixed open and closed cargo systems might have led to important benzene up-take. Possibly, the risk for HM for seafarers on tankers has decreased during the last decades.
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| 63. |
- Johansson, Patrik
(författare)
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Large scale integration and interactive exploration of cancer data – with applications to glioblastoma
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glioblastoma is the most common malignant brain tumor, with a median survival of approximately 15 months. The standard of care treatment consists of surgical resection followed by radiotherapy and chemotherapy, where chemotherapy only prolongs survival by approximately 3 months. There is therefore an urgent need for new approaches to better understand the molecular vulnerabilities of glioblastoma. To this end, we have conducted four interdisciplinary studies.In study 1 we develop a method for efficiently constructing and exploring large integrative network models that include multiple cohorts and multiple types of molecular data. We apply this method to 8 cancers from The Cancer Genome Atlas (TCGA) and make the integrative network available for exploration and visualization through a custom web interface.In study 2 we establish a biobank of 48 patient derived glioblastoma cell cultures called the Human Glioma Cell Culture (HGCC) resource. We show that the HGCC cell cultures represent all transcriptional subtypes, carry genomic aberrations typical of glioblastoma, and initiate tumors in vivo. The HGCC is an open resource for translational glioblastoma research, made available through hgcc.se.In study 3 we extend the analysis of HGCC cell cultures both in terms of number (to over 100) and in terms of data types (adding mutation, methylation and drug response data). Large-scale drug profiling starting from over 1500 compounds identified two distinct groups of cell cultures defined by vulnerability to proteasome inhibition, p53/p21 activity, stemness and protein turnover. By applying machine learning methods to the combined drug profiling and matched genomics data we construct a first network of predictive biomarkers.In study 4 we use the methods developed in study 1 applied to the data generated in studies 2 and 3 to construct an integrative network model of HGCC and glioblastoma data from TCGA. We present an interactive method for exploring this network based on searching for network patterns representing specific hypotheses defined by the user.In conclusion, this thesis combines the development of integrative models with applications to novel data relevant for translational glioblastoma research. This work highlights several potentially therapeutically relevant aspects, and paves a path towards more comprehensive and informative models of glioblastoma.
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| 64. |
- Björklund, Margereth, 1950-, et al.
(författare)
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Experiences of psychological flow as described by people diagnosed with and treated for head and neck cancer
- 2019
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Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 43, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe flow as experienced by people diagnosed with and treated for head and neck cancer. Method: A descriptive design based on a deductive qualitative content analysis was used to explain Csikszentmihalyi's flow theory from the perspective of people living with head and neck cancer. Interviews were conducted with seven participants diagnosed with and treated for different forms and stages of head and neck cancer. Results: Experiences of flow were associated with people's interests, skill levels and actions involving and creating both happiness and the feeling of something worth living for. Optimal flow was a state of consciousness in which mind and body work together, and the people were completely absorbed in an activity related to nature, hobbies or family. Microflow occurred as part of everyday life, relieving stress and anxiety and helping them to focus on their daily routines. This included humming, listening to the radio or watching TV. Conclusions: The peoples inner strength and desire to feel better made flow possible, and they used unknown skills that enhanced self-satisfaction. Managing self-care activities increased feelings of control, participation and enjoyment. This calls for person-centred care with a salutogenic approach based on the peoples own interests, skill levels and actions; what makes the person feel happy.
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| 65. |
- Lee, SangWook, et al.
(författare)
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Network analyses identify liver-specific targets for treating liver diseases
- 2017
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co-expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver-specific genes co-expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver-specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver-specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin-like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.
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| 66. |
- Nicholson, Brian D, et al.
(författare)
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Responsibility for follow-up during the diagnostic process in primary care : a secondary analysis of International Cancer Benchmarking Partnership data.
- 2018
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Ingår i: British Journal of General Practice. - : Royal College of General Practitioners. - 0960-1643 .- 1478-5242. ; 68:670, s. e323-e332
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unclear to what extent primary care practitioners (PCPs) should retain responsibility for follow-up to ensure that patients are monitored until their symptoms or signs are explained.AIM: To explore the extent to which PCPs retain responsibility for diagnostic follow-up actions across 11 international jurisdictions.DESIGN AND SETTING: A secondary analysis of survey data from the International Cancer Benchmarking Partnership.METHOD: The authors counted the proportion of 2879 PCPs who retained responsibility for each area of follow-up (appointments, test results, and non-attenders). Proportions were weighted by the sample size of each jurisdiction. Pooled estimates were obtained using a random-effects model, and UK estimates were compared with non-UK ones. Free-text responses were analysed to contextualise quantitative findings using a modified grounded theory approach.RESULTS: PCPs varied in their retention of responsibility for follow-up from 19% to 97% across jurisdictions and area of follow-up. Test reconciliation was inadequate in most jurisdictions. Significantly fewer UK PCPs retained responsibility for test result communication (73% versus 85%, P = 0.04) and non-attender follow-up (78% versus 93%, P<0.01) compared with non-UK PCPs. PCPs have developed bespoke, inconsistent solutions to follow-up. In cases of greatest concern, 'double safety netting' is described, where both patient and PCP retain responsibility.CONCLUSION: The degree to which PCPs retain responsibility for follow-up is dependent on their level of concern about the patient and their primary care system's properties. Integrated systems to support follow-up are at present underutilised, and research into their development, uptake, and effectiveness seems warranted.
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| 67. |
- Aljabery, Firas
(författare)
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Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.
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| 68. |
- Forsmark, A., et al.
(författare)
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Health Economic Analysis of Open and Robot-assisted Laparoscopic Surgery for Prostate Cancer Within the Prospective Multicentre LAPPRO Trial
- 2018
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 74:6, s. 816-824
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rapid adoption of robot-assisted laparoscopy in radical prostatectomy has preceded data regarding associated costs. Qualitative evidence regarding cost outcomes is lacking. Objective: This study assessed how costs were affected by robot-assisted laparoscopic prostatectomy (RALP) compared with open surgery. Design, setting, and participants: Cost analysis was based on the dataset of the LAPPRO (Laparoscopic Prostatectomy Robot Open) clinical trial, which is a prospective controlled, nonrandomised trial of patients who underwent prostatectomy at 14 centres in Sweden between September 2008 and November 2011. Currently, data are available from a follow-up period of 24 mo. Intervention: In the LAPPRO trial, RALP was compared with radical retropubic prostatectomy (RRP). Outcome measurements and statistical analysis: Costs per surgical technique were assessed based on resource variable data from the LAPPRO database. The calculation of average costs was based on mean values; Swedish currency was converted to purchasing power parity US dollar (PPP$). All tests were two-tailed and conducted at alpha = 0.05 significance level. Results and limitations: The cost analysis comprised 2638 men. Based on the LAPPRO trial data, RALP was associated with an increased cost/procedure of PPP$ 3837 (95% confidence interval: 2747-4928) compared with RRP. The result was sensitive to variations in caseload. Main drivers of overall cost were robotic system cost, operation time, length of stay, and sick leave. Limitations of the study include the uneven distribution between RALP and RRP regarding procedures in public/for-profit hospitals and surgeon/centre procedural volume. Conclusions: Based on the LAPPRO trial data, this study showed that RALP was associated with an increased cost compared with RRP in Swedish health care. There are many factors influencing the costs, making the absolute result dependent on the specific setting. However, by identifying the main cost drivers and/or most influential parameters, the study provides support for informed decisions and predictions. Patient summary: In this study, we looked at the cost outcome when performing prostatectomies by robot-assisted laparoscopic technique compared with open surgery in Sweden. We found that the robot-assisted procedure was associated with a higher mean cost. (C) 2018 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.
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| 69. |
- Loftås, Per, 1964-
(författare)
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Response to neoadjuvant treatment in rectal cancer surgery
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.
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| 70. |
- Lexomboon, Duangjai, 1965-, et al.
(författare)
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Consumption and direct costs of dental care for patients with head and neck cancer : A 16-year cohort study
- 2017
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Patients with head and neck (H&N) cancer are commonly treated with surgery and/or radiotherapy, which can increase the risk of oral infection, dental caries, and periodontal disease. The present study investigated dental care consumption and costs in patient with H&N cancer before and after the cancer diagnosis. Data from Swedish regional and national registers were used to follow up dental care utilization and dental procedure costs. The analysis included 2,754 patients who had been diagnosed with H&N cancer (exposed cohort) in Stockholm County, Sweden, during 2000–2012 and 13,036 matched persons without cancer (unexposed cohort). The exposed cohort was sub-grouped into irradiated and non-irradiated patients for analysis. The exposed cohort underwent a moderately higher number of dental procedures per year than the unexposed cohort in both the year of the cancer diagnosis and the year after cancer diagnosis; in addition, these numbers were higher in the irradiated than in the non-irradiated subgroup of the exposed cohort. Dental care consumption and costs in the exposed cohort declined over time but remained at a slightly higher level than in the unexposed cohort over the long term (more than two years). Examinations and preventive procedures accounted for most of the higher consumption in the short term (2 years) and at the longer term follow-up. Swedish national insurance subsidized costs for dental treatment, which were highest in the irradiated subgroup and lowest in the unexposed cohort. Direct costs to the patient, however, were similar among the groups. Swedish national health insurance protects patients with H&N cancer from high dental expenditures. Further studies on the cost-effectiveness of preventive dental care for patients are needed.
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