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  • 751.
    Wang, Mojin
    et al.
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Wang, Rui
    Sichuan University, Peoples R China.
    Wang, Ziqiang
    Sichuan University, Peoples R China.
    Chen, Keling
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Zhou, Zongguang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    The PKA RI alpha/A-kinase anchoring proteins 10 signaling pathway and the prognosis of colorectal cancer2015In: Journal of Gastroenterology and Hepatology, ISSN 0815-9319, E-ISSN 1440-1746, Vol. 30, no 3, p. 496-503Article in journal (Refereed)
    Abstract [en]

    Background and AimPreviously study showed that the loss of the control of cAMP-dependent protein kinase A RI (PKA RI)/ A-kinase anchoring proteins 10 (AKAP10) signaling pathway initiate dysregulation of cellular healthy physiology leading to tumorigenesis. The aim of this study was to investigate the role of PKA RI/AKAP10 signaling pathway in colorectal cancer (CRC). MethodsThe AKAP10 expression at the mRNA and protein level have been analyzed in colon cancer cell lines, primary CRCs and matched normal mucosa samples, and compared in accordance with specific clinicopathological features of CRC. The correlation between expression of AKAP10 and PKA RI were also analyzed. ResultsCompared with HCT116 and SW480 cells, the AKAP10 was significantly upregulated in the colon cell line KM12C and its metastatic counterparts, KM12SM and KM12L4A. Moreover, the KM12SM and KM12L4A having high metastatic potentials displayed the elevated levels of AKAP10 compared with KM12C having poor metastatic potential. A notably higher level of AKAP10 expression was found in CRC tissues at both mRNA and protein levels. Increased expression of AKAP10 in CRC patients was positively associated with the depth of invasion and the grade of differentiation. Univariate survival analysis showed that the increased expression of AKAP10 was related to poorer survival. Cox multivariate regression analysis confirmed that AKAP10 was an independent predictor of the overall survival of CRC patients. PKA RI mRNA was also expressed at high levels in CRC. The correlation coefficient between mRNA expression of AKAP10 and PKA RI in CRC was 0.417. AKAP10mRNA overexpression was correlated significantly with PKA RI. ConclusionsOur data indicated that PKA RI/AKAP10 signaling pathway is associated with the progression and prognosis of CRC.

  • 752.
    Wang, Mo-Jin
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Nodin, Bjorn
    Lund University, Sweden.
    Meng, Wen-Jian
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Yu, Yong-Yang
    Sichuan University, Peoples R China.
    Wang, Cun
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    The prognostic factors and multiple biomarkers in young patients with colorectal cancer2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 10645Article in journal (Refereed)
    Abstract [en]

    The incidence of colorectal cancer (CRC) in young patients (less than= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.

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  • 753.
    Wang, Mo-Jin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Zhang, Hong
    University of Örebro, Sweden.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; .
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China.
    Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study2015In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 51, p. e2350-Article in journal (Refereed)
    Abstract [en]

    Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973 2011), and Linkoping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; P=0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CT, 0.106-1.192; P=0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.

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  • 754.
    Wang, Mo-Jin
    et al.
    Sichuan University, Peoples R China.
    Wang, Zi-Qiang
    Sichuan University, Peoples R China.
    Wang, Rui
    Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Letter: The elderly patients with colorectal cancer need careful multidisciplinary evaluation and optimizing comprehensive management in INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, vol 30, issue 5, pp 713-7142015In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 30, no 5, p. 713-714Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 755.
    Warntjes, Marcel Jan Bertus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tisell, Anders
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Modeling the Presence of Myelin and Edema in the Brain Based on Multi-Parametric Quantitative MRI2016In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, no 16Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to present a model that uses multi-parametric quantitative MRI to estimate the presence of myelin and edema in the brain. The model relates simultaneous measurement of R-1 and R-2 relaxation rates and proton density to four partial volume compartments, consisting of myelin partial volume, cellular partial volume, free water partial volume, and excess parenchymal water partial volume. The model parameters were obtained using spatially normalized brain images of a group of 20 healthy controls. The pathological brain was modeled in terms of the reduction of myelin content and presence of excess parenchymal water, which indicates the degree of edema. The method was tested on spatially normalized brain images of a group of 20 age-matched multiple sclerosis (MS) patients. Clear differences were observed with respect to the healthy controls: the MS group had a 79 mL smaller brain volume (1069 vs. 1148 mL), a 38 mL smaller myelin volume (119 vs. 157 mL), and a 21 mL larger excess parenchymal water volume (78 vs. 57 mL). Template regions of interest of various brain structures indicated that the myelin partial volume in the MS group was 1.6 +/- 1.5% lower for gray matter (GM) structures and 2.8 +/- 1.0% lower for white matter (WM) structures. The excess parenchymal water partial volume was 9 +/- 10% larger for GM and 5 +/- 2% larger for WM. Manually placed ROls indicated that the results using the template ROls may have suffered from loss of anatomical detail due to the spatial normalization process. Examples of the application of the method on high-resolution images are provided for three individual subjects: a 45-year-old healthy subject, a 72-year-old healthy subject, and a 45-year-old MS patient. The observed results agreed with the expected behavior considering both age and disease. In conclusion, the proposed model may provide clinically important parameters, such as the total brain volume, degree of myelination, and degree of edema, based on a single qMRI acquisition with a clinically acceptable scan time.

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  • 756.
    Wedin, Madelene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ahlner, Eva
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Falk, Annika
    Norrlands Univ Hosp, Sweden.
    Sandstrom, Asa
    Norrlands Univ Hosp, Sweden.
    Lindahl, Gabriel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Validation of the Lymphoedema Quality of Life Questionnaire (LYMQOL) in Swedish cancer patients2020In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226XArticle in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to validate a translated Swedish version of the lymphoedema-specific quality of life questionnaire (LYMQOL) in a cohort of Swedish cancer patients with secondary lymphoedema of the limbs after cancer treatment.

    Material and methods: We recruited 102 patients with lymphoedema of the arms or legs after cancer treatment who were visiting lymphoedema therapists at the departments of oncology at the university hospitals in Linköping and Umeå. The LYMQOL questionnaires were translated forward and backward from English to Swedish. Content and face validity were evaluated. The construct validity was assessed by comparing the LYMQOL with the Short Form Health Survey (SF-36) and the perceived degree of lymphoedema of the limbs, respectively. Reliability was determined through test-retest. The internal consistency was assessed by determining Cronbach’s alpha and by factor analysis.

    Results: The content and face validity assessments showed that LYMQOL was an easy, clear and not too long questionnaire to use for patients with lymphoedema. Construct validity was high in both versions when compared with the SF-36. The association between the degrees of perceived lymphoedema and the LYMQOL was only significant in the domains Function and Body Image in the arm version, whereas all domains in the leg version were significant. The reliability was good for the arm version (intra-class-correlation coefficients 0.53–0.87) and very good for the leg version (intra-class-correlation coefficients 0.78–0.90). The internal consistency was acceptable to excellent, with Cronbach’s alpha values between 0.79–0.93 (arm-version) and 0.87–0.94 (leg-version). The factor analysis confirmed the usefulness of the four domains in the LYMQOL versions.

    Conclusions: This study confirmed the validity of the Swedish version of LYMQOL and demonstrated that LYMQOL may be a simple and useful tool for use in clinical practice and scientific contexts for evaluating QoL in patients with lymphoedema of the limbs.

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  • 757.
    Weich, Rainer G.
    et al.
    Department of Plant Physiology, University of Lund, S-220 07 Lund, Sweden.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
    Vogel, Hans J.
    Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
    Jensén, Paul
    Department of Plant Physiology, University of Lund, S-220 07 Lund, Sweden.
    Phosphorus-31 NMR studies of cell wall-associated calcium-phosphates in Ulva lactuca1989In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 90, no 1, p. 230-236Article in journal (Refereed)
    Abstract [en]

    Phosphate concentrations in the range 0.1 to 2.0 millimolar induced the formation of extracellular amorphous calcium-phosphates in the cell wall of the marine macro algae Ulva lactuca when they were cultivated in light in seawater at 20°C. A broad resonance representing these compounds as well as resonances for extracellular orthophosphate and polyphosphates could be followed by 31P-nuclear magnetic resonance spectroscopy. The presence of the calcium-phosphate made the cells brittle and it inhibited the growth of the macro algae and caused mortality within 1 week. The formation of the calcium-phosphates was influenced by the external phosphate concentration, the extracellular pH and the nature and concentration of the external nitrogen source. Furthermore, no formation of these compounds was observed when Ulva lactuca was cultivated in the dark, at low temperatures (5°C) or in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The complex could be removed through washes with ethylenediaminetetraacetate; this treatment did not alter the intracellular pH or the orthophosphate and polyphosphate pools and it restored growth.

  • 758.
    Welander, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Brauckhoff, Michael
    Haukeland Hosp, Dept Surg, Norway; Univ Bergen, Dept Clin Sci, Norway.
    Brunaud, Laurent
    Department of Digestive, Hepato-Biliary and Endocrine Surgery, CHU Nancy - Hospital Brabois Adultes, University de Lorraine, France.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Activating FGFR1 mutations in sporadic pheochromocytoma2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 2, p. 482-489Article in journal (Refereed)
    Abstract [en]

    Pheochromocytomas are neuroendocrine tumors of the adrenal glands that cause hypertension. More than a third of the cases are associated with hereditary mutations in a growing list of susceptibility genes, some of which are also somatically altered in sporadic pheochromocytomas. However, for the majority of sporadic pheochromocytomas, a genetic explanation is still lacking. Here we investigated the genomic landscape of sporadic pheochromocytomas with whole-exome sequencing of 16 paired tumor and normal DNA samples, and discovered on average 33 non-silent somatic mutations per tumor. One of the recurrently mutated genes was FGFR1, encoding the fibroblast growth factor receptor 1, which was recently revealed as an oncogene in pilocytic astrocytoma and childhood glioblastoma. Including a subsequent analysis of a larger cohort, activating FGFR1  mutations were detected in three of 80 sporadic pheochromocytomas (3.8%). Gene expression microarray profiling showed that these tumors clustered with NF1- RET- and HRAS-mutated pheochromocytomas, indicating activation of the MAPK and PI3K-AKT signal transduction pathways. The results advance our biological understanding of pheochromocytoma and suggest that somatic FGFR1 activation is an important event in a subset of these tumors.

  • 759.
    Werner, Jonas
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Norrköping.
    Hägglund, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Ekstrand, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Waldén, Markus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Hässleholm-Kristianstad-Ystad Hospitals, Hässleholm, Sweden.
    Hip and groin time-loss injuries decreased slightly but injury burden remained constant in mens professional football: the 15-year prospective UEFA Elite Club Injury Study2019In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 53, no 9, p. 539-546Article in journal (Refereed)
    Abstract [en]

    Background Hip and groin injuries are common in men’s professional football, but the time-trend of these injuries is not known.

    Aim To investigate hip and groin injury rates, especially time-trends, in men’s professional football over 15 consecutive seasons.

    Study design Prospective cohort study.

    Setting Men’s professional football.

    Methods 47 European teams were followed prospectively for a varying number of seasons between 2001/2002 and 2015/2016, totalling 268 team seasons. Time-loss injuries and individual player exposure during training and matches were recorded. Injury rate was defined as the number of injuries/1000 hours and injury burden as the number of lay-off days/1000 hours. Time-trends for total hip and groin injuries and adductor-related injury rates were analysed using Poisson regression, and injury burden was analysed using a negative binomial regression model.

    Results Hip and groin injuries contributed 1812 out of 12 736 injuries (14%), with adductor-related injury as the most common of hip and groin injuries (n=1139, 63%). The rates of hip and groin injury and adductor-related injury were 1.0/1000 hours and 0.6/1000 hours, and these rates decreased significantly with on average 2% (Exp(b)=0.98, 95% CI 0.97 to 0.99, P=0.003) and 3% (Exp(b)=0.97, 95% CI 0.95 to 0.99, P<0.001) per season (year on year), respectively. The seasonal trend of hip and groin injury burden did not improve (Exp(b)=0.99, 95% CI 0.97 to 1.01, P=0.40).

    Conclusions Hip and groin injuries constitute a considerable part of all time-loss injuries in men’s professional football. Although there was a promising slight decreasing trend in the rates of hip and groin injury (as a category) and adductor-related injury (as a specific diagnosis), the injury burden remained at a consistent level over the study period.

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  • 760.
    West, Janne
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering.
    Collins, Rory
    Nuffield Department of Population Health, University of Oxford.
    Garratt, Steve
    UK Biobank, Spectrum Way, Adswood, Stockport, UK.
    Bell, Jimmy
    Research Centre for Optimal Health, University of Westminster, London, UK.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Advanced MR Analytics AB, Linköping, Sweden.
    Thomas, E. Louise
    Research Centre for Optimal Health, University of Westminster, London, UK.
    Feasibility of MR-based Body Composition Analysis in Large Scale Population Studies2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0163332Article in journal (Refereed)
    Abstract [en]

    Introduction

    Quantitative and accurate measurements of fat and muscle in the body are important for prevention and diagnosis of diseases related to obesity and muscle degeneration. Manually segmenting muscle and fat compartments in MR body-images is laborious and time-consuming, hindering implementation in large cohorts. In the present study, the feasibility and success-rate of a Dixon-based MR scan followed by an intensity-normalised, non-rigid, multi-atlas based segmentation was investigated in a cohort of 3,000 subjects.

    Materials and Methods

    3,000 participants in the in-depth phenotyping arm of the UK Biobank imaging study underwent a comprehensive MR examination. All subjects were scanned using a 1.5 T MR-scanner with the dual-echo Dixon Vibe protocol, covering neck to knees. Subjects were scanned with six slabs in supine position, without localizer. Automated body composition analysis was performed using the AMRA Profiler™ system, to segment and quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT) and thigh muscles. Technical quality assurance was performed and a standard set of acceptance/rejection criteria was established. Descriptive statistics were calculated for all volume measurements and quality assurance metrics.

    Results

    Of the 3,000 subjects, 2,995 (99.83 %) were analysable for fat, 2,828 (94.27 %) were analysable when fat and one thigh was included, and 2,775 (92.50 %) were fully analysable for fat and both thigh muscles. Reasons for not being able to analyse datasets were mainly due to missing slabs in the acquisition, or patient positioned so that large parts of the volume was outside of the field-of-view.

    Discussion and Conclusions

    In conclusion, this study showed that the rapid UK Biobank MR-protocol was well tolerated by most subjects and sufficiently robust to achieve very high success-rate for body composition analysis. This research has been conducted using the UK Biobank Resource.

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  • 761.
    West, Janne
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Thomas, E. Louise
    Department of Life Sciences Faculty of Science and Technology, University of Westminster, London, UK.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bell, Jimmy
    Department of Life Sciences Faculty of Science and Technology, University of Westminster, London, UK.
    Body Composition Analysis In Large Scale Population Studies using Dixon Water-Fat Separated Imaging2016Conference paper (Other academic)
    Abstract [en]

    Water-fat separated MRI, based on Dixon imaging techniques enables high soft-tissue contrast and the separation of fat and muscle compartments. This study investigate the feasibility and success-rate of one recently described method for MR data-acquisition and body composition analysis, in a large-scale population study. The first 1,000 subjects in the UK Biobank imaging cohort were scanned, quality assured and included for body composition analysis. Volumes of visceral adipose tissue, abdominal subcutaneous tissue, and thigh muscles were calculated. This study showed that the rapid MR-examination was sufficiently robust to achieve very high success-rate for body composition analysis. 

  • 762.
    West, Janne
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Linge, Jennifer
    Advanced MR Analytics AB, Linköping, Sweden.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Science & Engineering.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering.
    Bell, Jimmy
    Westminster University, London, UK.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Distribution Matters – Body Composition Profiling Associated with Prior Health Care Burden2017Conference paper (Refereed)
  • 763.
    West, Janne
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Spetz, Anna-Clara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Lindblom, Hanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Lindh Åstrand, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Automatic combined whole-body muscle and fat volume quantification using water-fat separated MRI in postmenopausal women2015In: International Society for Magnetic Resonance in Medicine Annual Meeting: Proceedings, 2015Conference paper (Other academic)
    Abstract [en]

    Quantitative and exact measurements of fat and muscle in the body are important when addressing some of the greatest health-challenges today. In this study whole-body combined regional muscle and fat volume quantification was validated in a group of postmenopausal women, where the body composition is changing. Twelve subjects were scanned with a 4-echo 3D gradient-echo sequence. Water and fat image volumes were calculated using IDEAL, and image intensity correction was performed. Subsequently, automatic tissue segmentation was established using non-rigid morphon based registration. Whole-body regional fat and muscle segmentation could be performed with excellent test-retest reliability, in a single 7-minutes MR-scan.

  • 764.
    West, Janne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Adv MR Analyt AB, Linkoping, Sweden.
    Thorell, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Sweden.
    Lindblom, Hanna
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Berin, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Spetz Holm, Anna-Clara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Lindh Åstrand, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Karlsson, Anette
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Adv MR Analyt AB, Linkoping, Sweden.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Adv MR Analyt AB, Linkoping, Sweden.
    Precision of MRI-based body composition measurements of postmenopausal women2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192495Article in journal (Refereed)
    Abstract [en]

    Objectives To determine precision of magnetic resonance imaging (MRI) based fat and muscle quantification in a group of postmenopausal women. Furthermore, to extend the method to individual muscles relevant to upper-body exercise. Materials and methods This was a sub-study to a randomized control trial investigating effects of resistance training to decrease hot flushes in postmenopausal women. Thirty-six women were included, mean age 56 +/- 6 years. Each subject was scanned twice with a 3.0T MR-scanner using a whole-body Dixon protocol. Water and fat images were calculated using a 6-peak lipid model including R2*-correction. Body composition analyses were performed to measure visceral and subcutaneous fat volumes, lean volumes and muscle fat infiltration (MFI) of the muscle groups thigh muscles, lower leg muscles, and abdominal muscles, as well as the three individual muscles pectoralis, latissimus, and rhomboideus. Analysis was performed using a multi-atlas, calibrated water-fat separated quantification method. Liver-fat was measured as average proton density fat-fraction (PDFF) of three regions-of-interest. Precision was determined with Bland-Altman analysis, repeatability, and coefficient of variation. Results All of the 36 included women were successfully scanned and analysed. The coefficient of variation was 1.1% to 1.5% for abdominal fat compartments (visceral and subcutaneous), 0.8% to 1.9% for volumes of muscle groups (thigh, lower leg, and abdomen), and 2.3% to 7.0% for individual muscle volumes (pectoralis, latissimus, and rhomboideus). Limits of agreement for MFI was within +/- 2.06% for muscle groups and within +/- 5.13% for individual muscles. The limits of agreement for liver PDFF was within +/- 1.9%. Conclusion Whole-body Dixon MRI could characterize a range of different fat and muscle compartments with high precision, including individual muscles, in the study-group of postmenopausal women. The inclusion of individual muscles, calculated from the same scan, enables analysis for specific intervention programs and studies.

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  • 765.
    Widmark, Anders
    et al.
    Umea Univ, Sweden.
    Gunnlaugsson, Adalsteinn
    Lund Univ, Sweden.
    Beckman, Lars
    Sundsvall Hosp, Sweden.
    Thellenberg-Karlsson, Camilla
    Umea Univ, Sweden.
    Hoyer, Morten
    Aarhus Univ Hosp, Denmark.
    Lagerlund, Magnus
    Kalmar Hosp, Sweden.
    Kindblom, Jon
    Univ Gothenburg, Sweden.
    Ginman, Claes
    Karlstad Cent Hosp, Sweden.
    Johansson, Bengt
    Orebro Univ, Sweden.
    Bjornlinger, Kirsten
    Ryhov Hosp, Sweden.
    Seke, Mihajl
    Cent Lasarettet, Sweden.
    Agrup, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fransson, Per
    Umea Univ, Sweden.
    Tavelin, Bjorn
    Umea Univ, Sweden.
    Norman, David
    Umea Univ, Sweden.
    Zackrisson, Bjorn
    Umea Univ, Sweden.
    Anderson, Harald
    Lund Univ, Sweden.
    Kjellen, Elisabeth
    Lund Univ, Sweden.
    Franzen, Lars
    Umea Univ, Sweden.
    Nilsson, Per
    Lund Univ, Sweden.
    Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial2019In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10196, p. 385-395Article in journal (Refereed)
    Abstract [en]

    Background Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RTPC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation. Methods In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) or conventional fractionated radiotherapy (78.0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1.338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5.0 years (IQR 3.1-7.0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1.002 (95% CI 0.758-1.325; log-rank p=0.99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0.057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0.0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1.00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0.14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity. Interpretation Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

  • 766.
    Wiik, Anna
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Lundberg, Tommy R.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Rullman, Eric
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Andersson, Daniel P.
    Karolinska Inst, Sweden.
    Holmberg, Mats
    Karolinska Univ Hosp, Sweden.
    Mandic, Mirko
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Brismar, Torkel B.
    Karolinska Inst, Sweden.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. AMRA Med AB, Linkoping, Sweden.
    Chanpen, Setareh
    Karolinska Univ Hosp, Sweden.
    Flanagan, John N.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Arver, Stefan
    Karolinska Univ Hosp, Sweden.
    Gustafsson, Thomas
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Muscle Strength, Size, and Composition Following 12 Months of Gender-affirming Treatment in Transgender Individuals2020In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 105, no 3, p. E805-E813Article in journal (Refereed)
    Abstract [en]

    Context. As many sports are divided in male/female categories, governing bodies have formed regulations on the eligibility for transgender individuals to compete in these categories. Yet, the magnitude of change in muscle mass and strength with gender-affirming treatment remains insufficiently explored. Objective. This study explored the effects of gender-affirming treatment on muscle function, size, and composition during 12 months of therapy. Design, settings, participants. In this single-center observational cohort study, untrained transgender women (TW, n = 11) and transgender men (TM, n = 12), approved to start gender-affirming medical interventions, underwent assessments at baseline, 4 weeks after gonadal suppression of endogenous hormones but before hormone replacement, and 4 and 12 months after treatment initiation. Main outcome measures. Knee extensor and flexor strength were assessed at all examination time points, and muscle size and radiological density (using magnetic resonance imaging and computed tomography) at baseline and 12 months after treatment initiation. Results. Thigh muscle volume increased (15%) in TM, which was paralleled by increased quadriceps cross-sectional area (CSA) (15%) and radiological density (6%). In TW, the corresponding parameters decreased by -5% (muscle volume) and -4% (CSA), while density remained unaltered. The TM increased strength over the assessment period, while the TW generally maintained their strength levels. Conclusions. One year of gender-affirming treatment resulted in robust increases in muscle mass and strength in TM, but modest changes in TW. These findings add new knowledge on the magnitude of changes in muscle function, size, and composition with cross-hormone therapy, which could be relevant when evaluating the transgender eligibility rules for athletic competitions.

  • 767.
    Winqvist, Maria
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Andersson, Per-Ola
    Boras Hosp, Sweden.
    Asklid, Anna
    Karolinska Inst, Sweden.
    Karlsson, Karin
    Lund Univ Hosp, Sweden.
    Karlsson, Claes
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Lauri, Birgitta
    Sunderby Hosp, Sweden.
    Lundin, Jeanette
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Mattsson, Mattias
    Uppsala Univ Hosp, Sweden.
    Norin, Stefan
    Karolinska Inst, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Rosenquist, Richard
    Karolinska Inst, Sweden.
    Spath, Florentin
    Umea Univ, Sweden.
    Hansson, Lotta
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Osterborg, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Long-term real-world results of ibrutinib therapy in patients with relapsed or refractory chronic lymphocytic leukemia: 30-month follow up of the Swedish compassionate use cohort2019In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, no 5, p. E208-E210Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 768.
    Winqvist, Maria
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Asklid, Anna
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Andersson, P. O.
    South Älvsborg Hospital, Sweden.
    Karlsson, Karin
    Skåne University Hospital, Sweden.
    Karlsson, Claes
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Lauri, Birgitta
    Sunderby Hospital, Sweden.
    Lundin, Jeanette
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Mattsson, Mattias
    University of Uppsala Hospital, Sweden.
    Norin, Stefan
    Karolinska University Hospital, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Faculty of Medicine and Health Sciences.
    Hansson, Lotta
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Osterborg, Anders
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 12, p. 1573-1580Article in journal (Refereed)
    Abstract [en]

    Ibrutinib, a Brutons tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine healthcare are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy amp;gt;= 10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richters transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.

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  • 769.
    Witt, Suzanne Tyson
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Bednarska, Olga
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Icenhour, Adriane
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jones, Michael P.
    Department of Psychology, Macquarie University, NSW, Australia.
    Elsenbruch, Sigrid
    Institute of Medical Psychology & Behavioral Immunobiology, Essen University Hospital, Essen, Germany.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Mayer, Emeran A.
    Department of Medicine, UCLA, Los Angeles, CA, United States of America.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 21, article id 101602Article in journal (Refereed)
    Abstract [en]

    Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

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  • 770.
    Woisetschläger, Mischa
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gimm, Oliver
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Johansson, K.
    Orebro Univ Hosp, Sweden; Orebro Univ Hosp, Sweden.
    Wallin, G.
    Orebro Univ Hosp, Sweden.
    Albert-Garcia, I
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Spångeus, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Dual energy 4D-CT of parathyroid adenomas not clearly localized by sestamibi scintigraphy and ultrasonography - a retrospective study2020In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 124, article id 108821Article in journal (Refereed)
    Abstract [en]

    Purpose: At present, the gold standard for diagnosing PAs includes ultrasonography of the neck and sestamibi scans of the parathyroid. The objective of this study was to evaluate scans performed in 4D-DECT (4D-dualenergy mode) at three different time points, in order to analyze spectral information from PAs, lymph nodes (LNs), and thyroid gland (Thy). Method: Fifteen patients (mean age: 57 +/- 18.9 years) with primary hyperparathyroidism, in which previous ultrasound and sestamibi scanning proved to be negative or equivocal, underwent 4D-DECT in three different phases. Hounsfield units (HU), dual-energy information (electron density [Rho], atomic number [Z], dual-energy index [DEW, and spectral information (keV) were determined. Results: For all energies, PAs exhibited significantly lower HU-values than the Thy in non-contrast images, and higher HU-values than LNs in the arterial phase (p amp;lt; 0.05). All three tissues differed significantly in HU in the venous phase at 90 kV, 150 kV, and mixed 0.8 images; the Thy showed significantly higher HU-values than PAs or LNs in non-contrast images at 90 kV, 150 kV, mixed 0.8 images, and [Rho] (p amp;lt; 0.05). LNs exhibited significantly lower HU-values than PAs and Thy in the arterial phase at 90 kV, 150 kV, mixed 0.8, Rho, Z, and DEI (p amp;lt; 0.05). With regards to spectral information, lower energies showed greater HU differences between the three tissues. During the venous phase, there were significant differences between all three tissues up to 100 keV (p amp;lt; 0.05). Conclusions: We identified significant differences in HU-values and spectral information between PAs, LNs, and Thy at different energies and contrast phases.

  • 771.
    Worley, G.
    et al.
    St Marks Hosp, England; Acad Inst, England; Imperial Coll London, England.
    Nordenvall, C.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Askari, A.
    St Marks Hosp, Acad Inst, England; Imperial Coll London, England.
    Pinkney, T.
    Univ Birmingham, England.
    Burns, E.
    St Marks Hosp, England, Acad Inst, England; Imperial Coll London, England.
    Akbar, A.
    St Marks Hosp, England, Acad Inst, England; Imperial Coll London, England.
    Olen, O.
    Karolinska Inst, Sweden; Sachs Children and Youth Hosp, Sweden.
    Ekbom, A.
    Karolinska Inst, Sweden.
    Bottai, M.
    Karolinska Inst, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Faiz, O.
    St Marks Hosp, Acad Inst, England; Imperial Coll London, England.
    Restorative surgery after colectomy for ulcerative colitis in England and Sweden: observations from a comparison of nationwide cohorts2018In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 20, no 9, p. 804-812Article in journal (Refereed)
    Abstract [en]

    AimA longstanding disparity exists between the approaches to restorative surgery after colectomy for patients with ulcerative colitis (UC) in England and Sweden. This study aims to compare rates of colectomy and restorative surgery in comparable national cohorts. MethodThe English Hospital Episode Statistics (HES) and Swedish National Patient Register (NPR) were interrogated between 2002 and April 2012. Patients with two diagnostic episodes for UC (age 15 years) were included. Patients were excluded if they had an episode of inflammatory bowel disease or colectomy before 2002. The cumulative incidences of colectomy and restorative surgery were calculated using the Kaplan-Meier method. ResultsA total of 98 691 patients were included in the study, 76 129 in England and 22 562 in Sweden. The 5-year cumulative incidence of all restorative surgery after colectomy in England was 33% vs 46% in Sweden (P-value amp;lt; 0.001). Of the patients undergoing restorative surgery, 92.3% of English patients had a pouch vs 38.8% in Sweden and 7.7% vs 59.1% respectively had an ileorectal anastomosis (IRA). The 5-year cumulative incidence of colectomy in this study cohort was 13% in England and 6% in Sweden (P-value amp;lt; 0.001). ConclusionFollowing colectomy for UC only one-third of English patients and half of Swedish patients underwent restorative surgery. In England nearly all these patients underwent pouches, in Sweden a less significant majority underwent IRAs. It is surprising to demonstrate this discrepancy in a comparable cohort of patients from similar healthcare systems. The causes and consequences of this international variation in management are not fully understood and require further investigation.

  • 772.
    Yakymenko, Olena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Schoultz, Ida
    Department of Medical Sciences, Faculty of Health and Medicine, Örebro University, Örebro, Sweden.
    Gullberg, Elisabet
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Almer, Sven
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden / GastroCentrum, Karolinska University Hospital, Stockholm, Sweden.
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wang, Arthur
    Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada..
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Campbell, Barry J.
    Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK.
    McKay, Derek M.
    Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 6, p. 677-684Article in journal (Refereed)
    Abstract [en]

    Objective: Infliximab is important in the therapeutic arsenal of Crohn’s disease (CD). However, its effect on mucosal barrier function is not fully understood. Adherent-invasive Escherichia coli (AIEC) are important in CD pathophysiology, but the transmucosal uptake routes are partly unknown. We investigated effects of infliximab on uptake of colon-specific AIEC HM427 across CD colonic mucosa.

    Materials and methods: Endoscopic biopsies from non-inflamed colon of seven patients with CD, before and after two infliximab infusions, and eight non-inflammation controls, were mounted in Ussing chambers. Paracellular permeability (51Cr-EDTA) and transmucosal passage of GFP-expressing HM427 were studied. Mechanisms of HM427 transepithelial transport were investigated in Caco-2 monolayers treated with TNF, in the presence of infliximab and/or endocytosis inhibitors.

    Results: Before infliximab treatment, colonic passage of HM427 [CD: 2475 CFU (450–3000); controls 1163(225–1950)] and 51Cr-EDTA permeability were increased in CD (p < .05), but were restored to control levels by infliximab (CD: 150 (18.8–1069)). In TNF-exposed Caco-2 monolayers HM427 transport and lipid rafts/HM427 co-localization was decreased by infliximab. The lipid raft inhibitor methyl-β-cyclodextrin decreased HM427 transport.

    Conclusion: Infliximab restored the colonic barrier to AIEC in CD; an effect partially mediated by blocking lipid rafts in epithelial cells. This ability likely contributes to infliximab’s clinical efficacy in colonic CD.

  • 773.
    Ydreborg, Karin
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Engstrand, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Larsson, Eva-Lena
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Hand function, experienced pain, and disability after distal radius fracture.2015In: The American journal of occupational therapy, ISSN 0272-9490, Vol. 69, no 1, article id 6901290030Article in journal (Refereed)
    Abstract [en]

    Objective: We sought to explore differences in range of motion (ROM), grip strength, and self-reported pain and disability over time after plate-fixation surgery for distal radius fracture.less thanbr /greater thanMethod: We used a prospective repeated-measures research design with four measure points for a study sample of 101 patients. The Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire; the Global Assessment Scale; and the Canadian Occupational Performance Measure were used to assess ROM, grip strength, and pain level.less thanbr /greater thanResults: ROM and grip strength improved over time. Pain improved until 6 mo after surgery but greatly deteriorated from 6 to 24 mo. Concurrently, overall discomfort (global index) from the wrist extensively improved from 12 to 24 mo. DASH score decreased 20.1 points from 6 wk to 6 mo and remained stable until 24 mo.less thanbr /greater thanConclusion: Even when ROM and grip strength were almost fully regained at 12 mo, pain at rest and during activity was still an issue at 24 mo.less thanbr /greater than (Copyright © 2015 by the American Occupational Therapy Association, Inc.)

  • 774.
    Yngman Uhlin, Pia
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Klingvall, Emma
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wilhelmsson, Maria
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jangland, Eva
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Obstacles and opportunities for achieving good care on the surgical ward: nurse and surgeon perspective2016In: Journal of Nursing Management, ISSN 0966-0429, E-ISSN 1365-2834, Vol. 24, no 4, p. 492-499Article in journal (Refereed)
    Abstract [en]

    Aim The purpose of this qualitative study was to explore and understand from the perspectives of nurses and surgeons the situations and processes that are important in the context of surgical care support or are obstacles to achieving good care. Background Medical advances and inpatients with multiple illnesses are on the increase. In addition, a high turnover of registered nurses has been identified. This contributes to an increasingly inexperienced nursing staff. Concurrently, studies have shown that patient safety and quality of care are linked to organisational structures and staffing education levels. Method Eight nurses and six surgeons from three hospitals were interviewed and data were analysed by systematic text condensation. Results This identified three themes: shifting focus away from the patients, emphasising good communication, and using the competence of the team. Conclusion This study contributes to a deeper understanding that many interruptions, insufficient communication and unused competence can be a threat to patient safety. Sweden has a high standard but this study elucidates that challenges remain to be resolved. Implications for nursing management The focus on patients can increase by a balance between direct/indirect patient work and administration and by the support of clinicians using their full professional competence.

  • 775.
    Yu, Nancy Y.
    et al.
    Karolinska Inst, Sweden.
    Iftimi, Adina
    Karolinska Inst, Sweden.
    Yau, Christina
    Univ Calif San Francisco, CA USA; Buck Inst Res Aging, CA USA.
    Tobin, Nicholas P.
    Karolinska Inst, Sweden.
    van t Veer, Laura
    Univ Calif San Francisco, CA USA.
    Hoadley, Katherine A.
    Univ N Carolina, NC 27515 USA.
    Benz, Christopher C.
    Buck Inst Res Aging, CA USA.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fornander, Tommy
    Karolinska Inst, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Czene, Kamila
    Karolinska Inst, Sweden.
    Esserman, Laura J.
    Univ Calif San Francisco, CA USA.
    Lindstrom, Linda S.
    Karolinska Inst, Sweden.
    Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer2019In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 5, no 9, p. 1304-1309Article in journal (Refereed)
    Abstract [en]

    Key PointsQuestionWhat is the long-term survival associated with tamoxifen therapy for postmenopausal patients with luminal A or luminal B subtype tumors? FindingsThis secondary analysis of the Stockholm Tamoxifen (STO-3) trial of 462 postmenopausal patients with lymph node-negative breast cancer found that patients with luminal A or luminal B tumor subtypes had a long-term risk of distant metastatic breast cancer and benefited from tamoxifen therapy for 15 years and 5 years after diagnosis, respectively. MeaningPatients with luminal A tumor subtype appeared to have a long-term benefit from tamoxifen therapy, and patients with luminal B subtype appeared to have an early benefit from therapy, when the risk of distant metastatic disease was high. This secondary analysis of the Stockholm Tamoxifen (STO-3) clinical trial, which was conducted from 1976 to 1990, assessed the long-term survival associated with tamoxifen therapy in postmenopausal patients with luminal A or B breast cancer tumor subtypes. ImportancePatients with estrogen receptor (ER)-positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood. ObjectiveTo compare the long-term survival from tamoxifen therapy for patients with luminal A or luminal B tumor subtype. Design, Setting, and ParticipantsSecondary analysis of patients from the Stockholm Tamoxifen (STO-3) trial conducted from 1976 to 1990, which randomized postmenopausal patients with lymph node-negative breast cancer to receive adjuvant tamoxifen or no endocrine therapy. Tumor tissue sections were assessed in 2014 using immunohistochemistry and Agilent microarrays. Only patients with luminal A or B subtype tumors were evaluated. Complete long-term follow-up data up to the end of the STO-3 trial on December 31, 2012, were obtained from the Swedish National registers. Data analysis for the secondary analysis was conducted in 2017 and 2018. InterventionsPatients were randomized to receive at least 2 years of tamoxifen therapy or no endocrine therapy; patients without recurrence who reconsented were further randomized to 3 additional years of tamoxifen therapy or no endocrine therapy. Main Outcomes and MeasuresDistant recurrence-free interval (DRFI) by luminal A and luminal B subtype and trial arm was assessed by Kaplan-Meier analyses and time-dependent flexible parametric models to estimate time-varying hazard ratios (HRs) that were adjusted for patient and tumor characteristics. ResultsIn the STO-3 treated trial arm, 183 patients had luminal A tumors and 64 patients had luminal B tumors. In the untreated arm, 153 patients had luminal A tumors and 62 had luminal B tumors. Age at diagnosis ranged from 45 to 73 years. A statistically significant difference in DRFI by trial arm was observed (log rank, Pamp;lt;.001 [luminal A subtype, n=336], P=.04 [luminal B subtype, n=126]): the 25-year DRFI for luminal A vs luminal B subtypes was 87% (95% CI, 82%-93%) vs 67% (95% CI, 56%-82%) for treated patients, and 70% (95% CI, 62%-79%) vs 54% (95% CI, 42%-70%) for untreated patients, respectively. Patients with luminal A tumors significantly benefited from tamoxifen therapy for 15 years after diagnosis (HR, 0.57; 95% CI, 0.35-0.94), and those with luminal B tumors benefited from tamoxifen therapy for 5 years (HR, 0.38; 95% CI, 0.24-0.59). Conclusions and RelevancePatients with luminal A subtype tumors had a long-term risk of distant metastatic disease, which was reduced by tamoxifen treatment, whereas patients with luminal B tumors had an early risk of distant metastatic disease, and tamoxifen benefit attenuated over time.

  • 776.
    Zardavas, Dimitrios
    et al.
    Breast Int Grp, Belgium.
    te Marvelde, Luc
    Canc Council, Australia.
    Milne, Roger L.
    Canc Council, Australia; Univ Melbourne, Australia.
    Fumagalli, Debora
    Breast Int Grp, Belgium.
    Fountzilas, George
    Aristotle Univ Thessaloniki, Greece.
    Kotoula, Vassiliki
    Aristotle Univ Thessaloniki, Greece.
    Razis, Evangelia
    Hygeia Hosp, Greece.
    Papaxoinis, George
    Hippokrateion Hosp, Greece.
    Joensuu, Heikki
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Moynahan, Mary Ellen
    Mem Sloan Kettering Canc Ctr, NY 10021 USA.
    Hennessy, Bryan T.
    Beaumont Hosp, Ireland; Royal Coll Surg, Ireland.
    Bieche, Ivan
    Curie Inst, France.
    Saal, Lao H.
    Lund Univ, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Iacopetta, Barry
    Univ Western Australia, Australia.
    Jensen, Jeanette Dupont
    Univ Southern Denmark, Denmark.
    OToole, Sandra
    Garvan Inst Med Res, Australia.
    Lopez-Knowles, Elena
    Garvan Inst Med Res, Australia; Royal Marsden NHS Trust, England; Inst Canc Res, England.
    Barbaraeschi, Mattia
    Santa Chiara Hosp, Italy.
    Noguchi, Shinzaburo
    Osaka Univ, Japan.
    Azim, Hatem A. Jr.
    Amer Univ Beirut, Lebanon.
    Lerma, Enrique
    Univ Autonoma Barcelona, Spain.
    Bachelot, Thomas
    Ctr Rech Cancerol Lyon, France.
    Wang, Qing
    Not Found:Linkoping Univ, Linkoping, Sweden.
    Perez Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    de Velde, Cornelis J. H. Can
    Leiden Univ, Netherlands.
    Rea, Daniel W.
    Univ Birmingham, England.
    Sabine, Vicky
    Univ Guelph, Canada.
    Bartlett, John M. S.
    Ontario Inst Canc Res, Canada.
    Sotiriou, Christos
    Univ Libre Bruxelles, Belgium.
    Michiels, Stefan
    Gustave Roussy, France; Univ Paris Saclay, France.
    Loi, Sherene
    Univ Melbourne, Australia.
    Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data2018In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 10, p. 981-+Article in journal (Refereed)
    Abstract [en]

    PurposePhosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data.Patients and MethodsAssociations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes.ResultsData from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P amp;lt; .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P amp;lt; .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P amp;lt; .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); amp;gt; 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS (P = .043), but not for the DDFS and OS end points.ConclusionIn this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors. (C) 2018 by American Society of Clinical Oncology

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  • 777.
    Zeidan, Youssef H.
    et al.
    Amer Univ Beirut, Lebanon.
    Habib, Joyce G.
    Fouad Khoury and Makassed Gen Hosp, Lebanon; Univ Libre Bruxelles, Belgium.
    Ameye, Lieveke
    Universite´Libre de Bruxelles, Brussels, Belgium.
    Paesmans, Marianne
    Universite´Libre de Bruxelles, Brussels, Belgium.
    de Azambuja, Evandro
    Univ Libre Bruxelles, Belgium.
    Gelber, Richard D.
    Harvard Med Sch, MA USA; Frontier Sci and Technol Res Fdn Inc, MA USA.
    Campbell, Ian
    Univ Auckland, New Zealand.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Gutierez, Jorge
    Clin Los Condes, Chile.
    Anderson, Michael
    Copenhagen Univ Hosp, Denmark; Danish Breast Canc Cooperat Grp, Denmark.
    Lluch, Ana
    Univ Valencia, Spain.
    Gnant, Michael
    Med Univ Vienna, Austria; Austrian Breast and Colorectal Canc Study Grp, Austria.
    Goldhirsch, Aron
    European Inst Oncol, Italy; Int Breast Canc Study Grp, Switzerland.
    Di Leo, Angelo
    Hosp Prato, Italy.
    Joseph, David J.
    Univ Western Australia, Australia; Edith Cowan Univ, Australia; Breast Canc Trials Australia and New Zealand, Australia.
    Crown, John
    St Vincents Univ Hosp, Ireland.
    Piccart-Gebhart, Martine
    Univ Libre Bruxelles, Belgium.
    Francis, Prudence A.
    Int Breast Canc Study Grp, Switzerland; Peter MacCallum Canc Ctr, Australia; Univ Melbourne, Australia; Univ Newcastle, Australia.
    Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial2018In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 101, no 2, p. 316-324Article in journal (Refereed)
    Abstract [en]

    Purpose: To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial. Methods and Materials: The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival. Results: We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P=.005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P=.02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT. Conclusion: Our analysis of the BIG02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks. (C) 2018 Elsevier Inc. All rights reserved.

  • 778.
    Zhang, Hong
    et al.
    University of Örebro, Sweden.
    Zhu, Zhen-Long
    Hebei Medical University, Peoples R China.
    Wang, Da-Wei
    Hebei Medical University, Peoples R China.
    Yang, Yan-Hong
    Hebei Medical University, Peoples R China.
    Wang, Hao
    Hebei Medical University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Upregulation of nucleoporin 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma2016In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 9, no 5, p. 8399-8404Article in journal (Refereed)
    Abstract [en]

    Nucleoporin 88 (Nup 88) is a component of the nuclear pore complexes (NPCs) that mediates nucleocytoplasmic trafficking of macromolecules, Nup 88 has been reported to be up-regulated in a wide variety of malignancies. Studies show that overexpression of this antigen is associated with the development, agressiveness, differentiation and prognosis in some tumours. Since no study has been carried out in the relationship between the Nup 88 expression and clinicopathological features in the patients with oral squamous cell carcinoma (OSCC), this study aimed to determine Nup 88 expression in OSCC and its clinicopathological significance. Nup 88 expression was examined by immunohistochemistry in 20 normal oral mucosa specimens and 83 OSCC tissues. The frequency of positive Nup 88 expression was gradually increased from normal oral mucosa (10%) to primary OSCC (40%, P=0.012). The Nup 88 positive rate in OSCC patient with nodal metastasis was significantly higher than those without nodal metastasis (64% vs. 21%, P=0.000085). The frequency of positive Nup 88 expression was significantly different between worse and better differentiation (80 vs. 27%, P=0.000024). Nup 88 expression was not related to the patients gender, age, location and tumour size (Pamp;gt;0.05). In conclusion, Nup 88 may play an important role in tumorigenesis in oral squamous cell carcinoma. Upregulation of Nup 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma.

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  • 779.
    Zhang, Ming-Ran
    et al.
    Sichuan University, Peoples R China; Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Xie, Tian-Hang
    Sichuan University, Peoples R China.
    Chi, Jun-Lin
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Yu, Yong-Yang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Prognostic role of the lymph node ratio in node positive colorectal cancer: a meta-analysis2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 45, p. 72898-72907Article in journal (Refereed)
    Abstract [en]

    The lymph node ratio (LNR) (i. e. the number of metastatic lymph nodes divided by the number of totally resected lymph nodes) has recently emerged as an important prognostic factor in colorectal cancer (CRC). However, the tumor node metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a meta-analysis to evaluate the prognostic role of the LNR in node positive CRC. A systematic search was performed in PubMed, Embase and the Cochrane Library for relevant studies up to November 2015. As a result, a total of 75,838 node positive patients in 33 studies were included in this meta-analysis. Higher LNR was significantly associated with shorter overall survival (OS) (HR = 1.91; 95% CI 1.71-2.14; P = 0.0000) and disease free survival (DFS) (HR = 2.75; 95% CI: 2.14-3.53; P = 0.0000). Subgroup analysis showed similar results. Based on these results, LNR was an independent predictor of survival in colorectal cancer patients and should be considered as a parameter in future oncologic staging systems.

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  • 780.
    Zhang, Xueli
    et al.
    Orebro Univ, Sweden; Soochow Univ, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Cao, Yang
    Orebro Univ, Sweden; Karolinska Inst, Sweden.
    Ye, Benchen
    Soochow Univ, Peoples R China.
    Peng, Qiliang
    Soochow Univ, Peoples R China.
    Liu, Xingyun
    Soochow Univ, Peoples R China.
    Shen, Bairong
    Soochow Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    CBD: a biomarker database for colorectal cancer2018In: Database: The Journal of Biological Databases and Curation, ISSN 1758-0463, E-ISSN 1758-0463, Vol. 2018, no 1 January 2018, article id bay046Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.

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  • 781.
    Zhang, Xueli
    et al.
    Orebro Univ, Sweden; Soochow Univ, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Shen, Bairong
    Soochow Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Potential Applications of DNA, RNA and Protein Biomarkers in Diagnosis, Therapy and Prognosis for Colorectal Cancer: A Study from Databases to AI-Assisted Verification2019In: Cancers, ISSN 2072-6694, Vol. 11, no 2, article id 172Article in journal (Refereed)
    Abstract [en]

    In order to find out the most valuable biomarkers and pathways for diagnosis, therapy and prognosis in colorectal cancer (CRC) we have collected the published CRC biomarkers and established a CRC biomarker database (CBD: http://sysbio.suda.edu.cn/CBD/index.html). In this study, we analysed the single and multiple DNA, RNA and protein biomarkers as well as their positions in cancer related pathways and protein-protein interaction (PPI) networks to describe their potential applications in diagnosis, therapy and prognosis. CRC biomarkers were collected from the CBD. The RNA and protein biomarkers were matched to their corresponding DNAs by the miRDB database and the PubMed Gene database, respectively. The PPI networks were used to investigate the relationships between protein biomarkers and further detect the multiple biomarkers. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were used to analyse biological functions of the biomarkers. AI classification techniques were utilized to further verify the significances of the multiple biomarkers in diagnosis and prognosis for CRC. We showed that a large number of the DNA, RNA and protein biomarkers were associated with the diagnosis, therapy and prognosis in various degrees in the CRC biomarker networks. The CRC biomarkers were closely related to the CRC initiation and progression. Moreover, the biomarkers played critical roles in cellular proliferation, apoptosis and angiogenesis and they were involved in Ras, p53 and PI3K pathways. There were overlaps among the DNA, RNA and protein biomarkers. AI classification verifications showed that the combined multiple protein biomarkers played important roles to accurate early diagnosis and predict outcome for CRC. There were several single and multiple CRC protein biomarkers which were associated with diagnosis, therapy and prognosis in CRC. Further, AI-assisted analysis revealed that multiple biomarkers had potential applications for diagnosis and prognosis in CRC.

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  • 782.
    Zhang, Xueli
    et al.
    Orebro Univ, Sweden; Soochow Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Shen, Bairong
    Soochow Univ, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Chromogranin-A Expression as a Novel Biomarker for Early Diagnosis of Colon Cancer Patients2019In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 12, article id 2919Article in journal (Refereed)
    Abstract [en]

    Colon cancer is one of the major causes of cancer death worldwide. The five-year survival rate for the early-stage patients is more than 90%, and only around 10% for the later stages. Moreover, half of the colon cancer patients have been clinically diagnosed at the later stages. It is; therefore, of importance to enhance the ability for the early diagnosis of colon cancer. Taking advantages from our previous studies, there are several potential biomarkers which have been associated with the early diagnosis of the colon cancer. In order to investigate these early diagnostic biomarkers for colon cancer, human chromogranin-A (CHGA) was further analyzed among the most powerful diagnostic biomarkers. In this study, we used a logistic regression-based meta-analysis to clarify associations of CHGA expression with colon cancer diagnosis. Both healthy populations and the normal mucosa from the colon cancer patients were selected as the double normal controls. The results showed decreased expression of CHGA in the early stages of colon cancer as compared to the normal controls. The decline of CHGA expression in the early stages of colon cancer is probably a new diagnostic biomarker for colon cancer diagnosis with high predicting possibility and verification performance. We have also compared the diagnostic powers of CHGA expression with the typical oncogene KRAS, classic tumor suppressor TP53, and well-known cellular proliferation index MKI67, and the CHGA showed stronger ability to predict early diagnosis for colon cancer than these other cancer biomarkers. In the protein-protein interaction (PPI) network, CHGA was revealed to share some common pathways with KRAS and TP53. CHGA might be considered as a novel, promising, and powerful biomarker for early diagnosis of colon cancer.

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  • 783.
    Zhang, Xueli
    et al.
    Orebro Univ, Sweden; Soochow Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Shen, Bairong
    Soochow Univ, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Novel MicroRNA Biomarkers for Colorectal Cancer Early Diagnosis and 5-Fluorouracil Chemotherapy Resistance but Not Prognosis: A Study from Databases to AI-Assisted Verifications2020In: Cancers, ISSN 2072-6694, CANCERS, Vol. 12, no 2, article id 341Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In general, early diagnosis for CRC and individual therapy have led to better survival for the cancer patients. Accumulating studies concerning biomarkers have provided positive evidence to improve cancer early diagnosis and better therapy. It is, however, still necessary to further investigate the precise biomarkers for cancer early diagnosis and precision therapy and predicting prognosis. In this study, AI-assisted systems with bioinformatics algorithm integrated with microarray and RNA sequencing (RNA-seq) gene expression (GE) data has been approached to predict microRNA (miRNA) biomarkers for early diagnosis of CRC based on the miRNA-messenger RNA (mRNA) interaction network. The relationships between the predicted miRNA biomarkers and other biological components were further analyzed on biological networks. Bayesian meta-analysis of diagnostic test was utilized to verify the diagnostic value of the miRNA candidate biomarkers and the combined multiple biomarkers. Biological function analysis was performed to detect the relationship of candidate miRNA biomarkers and identified biomarkers in pathways. Text mining was used to analyze the relationships of predicted miRNAs and their target genes with 5-fluorouracil (5-FU). Survival analyses were conducted to evaluate the prognostic values of these miRNAs in CRC. According to the number of miRNAs single regulated mRNAs (NSR) and the number of their regulated transcription factor gene percentage (TFP) on the miRNA-mRNA network, there were 12 promising miRNA biomarkers were selected. There were five potential candidate miRNAs (miRNA-186-5p, miRNA-10b-5, miRNA-30e-5p, miRNA-21 and miRNA-30e) were confirmed as CRC diagnostic biomarkers, and two of them (miRNA-21 and miRNA-30e) were previously reported. Furthermore, the combinations of the five candidate miRNAs biomarkers showed better prediction accuracy for CRC early diagnosis than the single miRNA biomarkers. miRNA-10b-5p and miRNA-30e-5p were associated with the 5-FU therapy resistance by targeting the related genes. These miRNAs biomarkers were not statistically associated with CRC prognosis.

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  • 784.
    Zhao, Senlin
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Hongcheng
    Shanghai Jiao Tong University, Peoples R China.
    Jiang, Weiliang
    Shanghai Jiao Tong University, Peoples R China.
    Mi, Yushuai
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Dongyuan
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    Shanghai Jiao Tong University, Peoples R China.
    Cheng, Dantong
    Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Wu, Shaohan
    Jiaxing Coll, Peoples R China.
    Yu, Yang
    Shanghai Jiao Tong University, Peoples R China.
    Liu, Xisheng
    Shanghai Jiao Tong University, Peoples R China.
    Cui, Weiyingqi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Zhang, Meng
    Fudan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Zhou, Zongguang
    Sichuan University, Peoples R China.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    Yan, Dongwang
    Shanghai Jiao Tong University, Peoples R China.
    miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGF beta-mediated epithelial to mesenchymal transition2017In: Molecular Cancer, ISSN 1476-4598, E-ISSN 1476-4598, Vol. 16, article id 12Article in journal (Refereed)
    Abstract [en]

    Background: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression. Methods: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGF beta pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC. Results: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGF beta signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/ Smad7/TGF beta in vitro and in vivo. Conclusion: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGF beta signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.

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  • 785.
    Zhou, Yin
    et al.
    Sichuan University, Peoples R China.
    Li, Yibo
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Chen, Keling
    Sichuan University, Peoples R China.
    Lyv, Zhaoying
    Sichuan University, Peoples R China.
    Huang, Dongmei
    Sichuan University, Peoples R China.
    Liu, Bin
    Sichuan University, Peoples R China.
    Xu, Zhicheng
    Sichuan University, Peoples R China.
    Xiang, Bo
    Sichuan University, Peoples R China.
    Jin, Shuguang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China.
    Inflammation and Apoptosis: Dual Mediator Role for Toll-like Receptor 4 in the Development of Necrotizing Enterocolitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 1, p. 44-56Article in journal (Refereed)
    Abstract [en]

    Background: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal mortality; effective interventions are lacking with limited understanding of the pathogenesis of NEC. The importance of Toll-like receptor 4 (TLR4) signaling in NEC is well documented; however, the potential mechanisms that regulate enterocyte inflammation and apoptosis remain unclear. The aim of this study was to characterize the role of TLR4-mediated inflammation and apoptosis in the development of NEC and to determine the major apoptotic pathways and regulators in the process. Methods: TLR4-deficient C57BL/10ScNJ mice and lentivirus-mediated stable TLR4-silent cell line (IEC-6) were used. NEC was induced by formula gavage, cold, hypoxia, combined with lipopolysaccharide in vivo or lipopolysaccharide stimulation in vitro. Enterocyte apoptosis was evaluated by TUNEL or Annexin analysis. The expression of TLR4, caspase3, caspase8, caspase9, Bip, Bax, Bcl-2, and RIP was detected by Western blot and immunofluorescence. Inflammatory factors such as tumor necrosis factor-a and interleukin-2 were examined by Luminex. Results: Defect of TLR4 led to suppressed enterocytes apoptosis both in vitro and in vivo; the expression of caspase3, caspase8, Bip, and Bax was decreased; and caspase9 and Bcl-2 were increased. NEC severity was attenuated in TLR4-deficient mice compared with wild-type counterparts, and enterocytes apoptosis was correlated with NEC severity. RIP and cytokine level of tumor necrosis factor-a and interleukin-2 were also decreased. Conclusions: TLR4-induced inflammation and apoptosis play a critical role in the pathogenesis of NEC. TLR4 inhibition, combined with extrinsic (caspase8) and/or endoplasmic reticulum stress (Bip) apoptosis signaling blockade could serve as a potential effective treating strategy for NEC.

  • 786.
    Zötterman, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Mirdell, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Horsten, Sandra
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Methodological concerns with laser speckle contrast imaging in clinical evaluation of microcirculation2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174703Article in journal (Refereed)
    Abstract [en]

    Background Laser Speckle Contrast Imaging (LSCI) is a non-invasive and fast technique for measuring microvascular blood flow that recently has found clinical use for burn assessment and evaluation of flaps. Tissue motion caused by for example breathing or patient movements may however affect the measurements in these clinical applications, as may distance between the camera and the skin and tissue curvature. Therefore, the aims of this study were to investigate the effect of frame rate, number of frames/image, movement of the tissue, measuring distance and tissue curvature on the measured perfusion. Methods Methyl nicotinate-induced vasodilation in the forearm skin was measured using LSCI during controlled motion at different speeds, using different combinations of frame rate and number of frames/image, and at varying camera angles and distances. Experiments were made on healthy volunteers and on a cloth soaked in a colloidal suspension of polystyrene microspheres. Results Measured perfusion increased with tissue motion speed. The relation was independent of the absolute perfusion in the skin and of frame rate and number of frames/image. The measured perfusion decreased with increasing angles (16% at 60, p = 0.01). Measured perfusion did not vary significantly between measurement distances from 15 to 40 cm (p = 0.77, %CV 0.9%). Conclusion Tissue motion increases and measurement angles beyond 45 decrease the measured perfusion in LSCI. These findings have to be taken into account when LSCI is used to assess moving or curved tissue surfaces, which is common in clinical applications.

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  • 787.
    Åkerberg, Daniel
    et al.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ansari, Daniel
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Factors influencing receipt of adjuvant chemotherapy after surgery for pancreatic cancer: a two-center retrospective cohort study2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 1, p. 56-60Article in journal (Refereed)
    Abstract [en]

    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 Linkoping, 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, pamp;lt;.001. Moreover, patients with severe postoperative complications (Clavien-Dindo grade amp;gt;= 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), pamp;lt;.001. Conclusions: Age, postoperative complications and the presence of lymph node metastases affect the likelihood of receiving adjuvant chemotherapy after PDAC surgery.

  • 788.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Paradigmskifte för gynekologisk cancer2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 50, p. 2271-Article in journal (Refereed)
    Abstract [sv]

    Med ökad förståelse för bakomliggande mekanismer har ett genombrott skett vad gäller behandling och förståelse av gynekologisk cancer. I år godkändes den första målriktade behandlingen vid gynekologisk cancer, och därmed blir individualiserad behandling en realitet.

  • 789.
    Åvall Lundqvist, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fujiwara, Keiichi
    Saitama Medical University, Japan.
    Seoud, Muhieddine
    Amer University of Beirut, Lebanon.
    Principles of chemotherapy2015In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 131, p. S146-S149Article in journal (Refereed)
    Abstract [en]

    n/a

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  • 790.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Classification of Endometrial Cancer2020In: Management of Endometrial Cancer / [ed] Mansoor R. Mirza, Cham: Springer, 2020, p. 3-6Chapter in book (Refereed)
    Abstract [en]

    Endometrial cancer is the most common malignancy of the female genital tract in the more developed regions of the world [1]. Stage of disease, i.e., the extent of tumor spread at the time of presentation, is the most significant prognostic parameter.

  • 791.
    Ödén, Jakob
    et al.
    Stockholm University and RaySearch Laboratories AB, Stockholm, Sweden.
    Toma-Dasu, Iuliana
    Stockholm University and Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Kjell
    RaySearch Laboratories AB, Stockholm, Sweden.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. The Skandion Clinic, Uppsala, Sweden.
    The influence of breathing motion and a variable relative biological effectiveness in proton therapy of left-sided breast cancer2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 11, p. 1428-1436Article in journal (Refereed)
    Abstract [en]

    Background: Proton breast radiotherapy has been suggested to improve target coverage as well as reduce cardiopulmonary and integral dose compared with photon therapy. This study aims to assess this potential when accounting for breathing motion and a variable relative biological effectiveness (RBE).

    Methods: Photon and robustly optimized proton plans were generated to deliver 50 Gy (RBE) in 25 fractions (RBE=1.1) to the CTV (whole left breast) for 12 patients. The plan evaluation was performed using the constant RBE and a variable RBE model. Robustness against breathing motion, setup, range and RBE uncertainties was analyzed using CT data obtained at free-breathing, breath-hold-at-inhalation and breath-hold-at-exhalation.

    Results: All photon and proton plans (RBE=1.1) met the clinical goals. The variable RBE model predicted an average RBE of 1.18 for the CTVs (range 1.14–1.21) and even higher RBEs in organs at risk (OARs). However, the dosimetric impact of this latter aspect was minor due to low OAR doses. The normal tissue complication probability (NTCP) for the lungs was low for all patients (<1%), and similar for photons and protons. The proton plans were generally considered robust for all patients. However, in the most extreme scenarios, the lowest dose received by 98% of the CTV dropped from 96 to 99% of the prescribed dose to around 92–94% for both protons and photons. Including RBE uncertainties in the robustness analysis resulted in substantially higher worst-case OAR doses.

    Conclusions: Breathing motion seems to have a minor effect on the plan quality for breast cancer. The variable RBE might impact the potential benefit of protons, but could probably be neglected in most cases where the physical OAR doses are low. However, to be able to identify outlier cases at risk for high OAR doses, the biological evaluation of proton plans taking into account the variable RBE is recommended.

  • 792.
    Örtenberg, Alexander
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Maria
    Linköping University, Department of Electrical Engineering, Computer Vision. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Science & Engineering. Linköping University, Faculty of Medicine and Health Sciences.
    Sandborg, Michael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Alm Carlsson, Gudrun
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Malusek, Alexandr
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    PARALLELISATION OF THE MODEL-BASED ITERATIVE RECONSTRUCTION ALGORITHM DIRA2016In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 169, no 1-4, p. 405-409Article in journal (Refereed)
    Abstract [en]

    New paradigms for parallel programming have been devised to simplify software development on multi-core processors and many-core graphical processing units (GPU). Despite their obvious benefits, the parallelisation of existing computer programs is not an easy task. In this work, the use of the Open Multiprocessing (OpenMP) and Open Computing Language (OpenCL) frameworks is considered for the parallelisation of the model-based iterative reconstruction algorithm DIRA with the aim to significantly shorten the code’s execution time. Selected routines were parallelised using OpenMP and OpenCL libraries; some routines were converted from MATLAB to C and optimised. Parallelisation of the code with the OpenMP was easy and resulted in an overall speedup of 15 on a 16-core computer. Parallelisation with OpenCL was more difficult owing to differences between the central processing unit and GPU architectures. The resulting speedup was substantially lower than the theoretical peak performance of the GPU; the cause was explained.

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