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  • 1.
    Abreu, Miguel Henriques
    et al.
    Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; Porto Comprehensive Cancer Center Raquel Seruca (PCCC), Porto, Portugal.
    Lillsunde-Larsson, Gabriella
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Bartosch, Carla
    Porto Comprehensive Cancer Center Raquel Seruca (PCCC), Porto, Portugal; Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; Cancer Biology & Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (CI-IPO-Porto)/Health Research Network (RISE@CI-IPO-Porto), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
    Ricardo, Sara
    Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, Porto, Portugal; 1H-TOXRUN - One Health Toxicology Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; Department of Pathology, Faculty of Medicine from University of Porto (FMUP), Porto, Portugal.
    Editorial: New molecular approaches to improve gynecological cancer management2023In: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 13, article id 1235035Article in journal (Other academic)
  • 2.
    Abuhasanein, Suleiman
    et al.
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Surgery, Urology Section, NU Hospital Group, Trollhättan, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Göteborg, Sweden.
    Kjölhede, Henrik
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Göteborg, Sweden.
    Standardized care pathways for patients with suspected urinary bladder cancer: the Swedish experience2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 3, p. 227-232Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To compare time intervals to diagnosis and treatment, tumor characteristics, and management in patients with primary urinary bladder cancer, diagnosed before and after the implementation of a standardized care pathway (SCP) in Sweden.

    MATERIALS AND METHODS: Data from the Swedish National Register of Urinary Bladder Cancer was studied before (2011-2015) and after (2016-2019) SCP. Data about time from referral to transurethral resection of bladder tumor (TURBT), patients and tumor characteristics, and management were analyzed. Subgroup analyses were performed for cT1 and cT2-4 tumors.

    RESULTS: Out of 26,795 patients, median time to TURBT decreased from 37 to 27 days after the implementation of SCP. While the proportion of cT2-T4 tumors decreased slightly (22-21%, p < 0.001), this change was not stable over time and the proportions cN + and cM1 remained unchanged. In the subgroups with cT1 and cT2-4 tumors, the median time to TURBT decreased and the proportions of patients discussed at a multidisciplinary team conference (MDTC) increased after SCP. In neither of these subgroups was a change in the proportions of cN + and cM1 observed, while treatment according to guidelines increased after SCP in the cT1 group.

    CONCLUSION: After the implementation of SCP, time from referral to TURBT decreased and the proportion of patients discussed at MDTC increased, although not at the levels recommended by guidelines. Thus, our findings point to the need for measures to increase adherence to SCP recommendations and to guidelines.

  • 3. Adolfsson, Jan
    et al.
    Garmo, Hans
    Varenhorst, Eberhard
    Ahlgren, Göran
    Ahlstrand, Christer
    Andren, Ove
    Örebro University, School of Health and Medical Sciences.
    Bill-Axelson, Anna
    Bratt, Ola
    Damber, Jan-Erik
    Hellström, Karin
    Hellström, Magnus
    Holmberg, Erik
    Holmberg, Lars
    Hugosson, Jonas
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Petterson, Bill
    Törnblom, Magnus
    Widmark, Anders
    Stattin, Pär
    Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005: Data from the national prostate cancer register in Sweden2007In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 6, p. 456-477Article in journal (Refereed)
    Abstract [en]

    Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer

  • 4.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska University Hospital, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.
    Matthiessen, P.
    School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Fang, X.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; .
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery.
    Lindgren, R.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Effect of beta-blocker therapy on early mortality after emergency colonic cancer surgery2019In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 106, no 4, p. 477-483Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery.

    METHODS: This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis.

    RESULTS: A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin.

    CONCLUSION: Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.

  • 5.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Matthiessen, Peter
    School of Medical Sciences, Örebro University, Örebro, Sweden; Division of Colorectal Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    The Relationship Between Severe Complications, Beta-Blocker Therapy and Long-Term Survival Following Emergency Surgery for Colon Cancer2019In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 43, no 10, p. 2527-2535Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Emergency surgery for colon cancer carries significant morbidity, and studies show more than doubled mortality when comparing elective to emergency surgery. The relationship between postoperative complications and survival has been outlined. Beta-blocker therapy has been linked to improved postoperative outcomes. This study aims to assess the impact of postoperative complications on long-term survival following emergency surgery for colon cancer and to determine whether beta-blockade can reduce complications.

    STUDY DESIGN: This cohort study utilized the prospective Swedish Colorectal Cancer Registry to identify adults undergoing emergency colon cancer surgery between 2011 and 2016. Prescription data for preoperative beta-blocker therapy were collected from the national drug registry. Cox regression was used to evaluate the effect of beta-blocker exposure and complications on 1-year mortality, and Poisson regression was used to evaluate beta-blocker exposure in patients with major complications.

    RESULTS: A total of 3139 patients were included with a mean age of 73.1 [12.4] of which 671 (21.4%) were prescribed beta-blockers prior to surgery. Major complications occurred in 375 (11.9%) patients. Those suffering major complications showed a threefold increase in 1-year mortality (adjusted HR = 3.29; 95% CI 2.75-3.94; p < 0.001). Beta-blocker use was linked to a 60% risk reduction in 1-year mortality (adjusted HR = 0.40; 95% CI 0.26-0.62; p < 0.001) but did not show a statistically significant association with reductions in major complications (adjusted IRR = 0.77; 95% CI 0.59-1.00; p = 0.055).

    CONCLUSION: The development of major complications after emergency colon cancer surgery is associated with increased mortality during one year after surgery. Beta-blocker therapy may protect against postoperative complications.

  • 6.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Matthiessen, Peter
    School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Fang, Xin
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Lindgren, Rickard
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    β-Blockade in Rectal Cancer Surgery: A Simple Measure of Improving Outcomes2020In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 271, no 1, p. 140-146Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To ascertain whether regular β-blocker exposure can improve short- and long-term outcomes after rectal cancer surgery.

    BACKGROUND: Surgery for rectal cancer is associated with substantial morbidity and mortality. There is increasing evidence to suggest that there is a survival benefit in patients exposed to β-blockers undergoing non-cardiac surgery. Studies investigating the effects on outcomes in patients subjected to surgery for rectal cancer are lacking.

    METHODS: All adult patients undergoing elective abdominal resection for rectal cancer over a 10-year period were recruited from the prospectively collected Swedish Colorectal Cancer Registry. Patients were subdivided according to preoperative β-blocker exposure status. Outcomes of interest were 30-day complications, 30-day cause-specific mortality, and 1-year all-cause mortality. The association between β-blocker use and outcomes were analyzed using Poisson regression model with robust standard errors for 30-day complications and cause-specific mortality. One-year survival was assessed using Cox proportional hazards regression model.

    RESULTS: A total of 11,966 patients were included in the current study, of whom 3513 (29.36%) were exposed to regular preoperative β-blockers. A significant decrease in 30-day mortality was detected (incidence rate ratio = 0.06, 95% confidence interval: 0.03-0.13, P < 0.001). Deaths of cardiovascular nature, respiratory origin, sepsis, and multiorgan failure were significantly lower in β-blocker users, as were the incidences in postoperative infection and anastomotic failure. The β-blocker positive group had significantly better survival up to 1 year postoperatively with a risk reduction of 57% (hazard ratio = 0.43, 95% confidence interval: 0.37-0.52, P < 0.001).

    CONCLUSIONS: Preoperative β-blocker use is strongly associated with improved survival and morbidity after abdominal resection for rectal cancer.

  • 7.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska University Hospital, Stockholm, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Matthiessen, Peter
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Effects of beta-blocker therapy on mortality after elective colon cancer surgery: a Swedish nationwide cohort study2020In: BMJ Open, E-ISSN 2044-6055, Vol. 10, no 7, article id e036164Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Colon cancer surgery remains associated with substantial postoperative morbidity and mortality despite advances in surgical techniques and care. The trauma of surgery triggers adrenergic hyperactivation which drives adverse stress responses. We hypothesised that outcome benefits are gained by reducing the effects of hyperadrenergic activity with beta-blocker therapy in patients undergoing colon cancer surgery. This study aims to test this hypothesis.

    DESIGN: Retrospective cohort study.

    SETTING AND PARTICIPANTS: This is a nationwide study which includes all adult patients undergoing elective colon cancer surgery in Sweden over 10 years. Patient data were collected from the Swedish Colorectal Cancer Registry. The national drugs registry was used to obtain information about beta-blocker use. Patients were subdivided into exposed and unexposed groups. The association between beta-blockade, short-term and long-term mortality was evaluated using Poisson regression, Kaplan-Meier curves and Cox regression.

    PRIMARY AND SECONDARY OUTCOMES: Primary outcome of interest was 1-year all-cause mortality. Secondary outcomes included 90-day all-cause and 5-year cancer-specific mortality.

    RESULTS: The study included 22 337 patients of whom 36.1% were prescribed preoperative beta-blockers. Survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and of higher comorbidity. Regression analysis demonstrated significant reductions in 90-day deaths (IRR 0.29, 95% CI 0.24 to 0.35, p<0.001) and a 43% risk reduction in 1-year all-cause mortality (adjusted HR 0.57, 95% CI 0.52 to 0.63, p<0.001) in beta-blocked patients. In addition, cancer-specific mortality up to 5 years after surgery was reduced in beta-blocked patients (adjusted HR 0.80, 95% CI 0.73 to 0.88, p<0.001).

    CONCLUSION: Preoperative beta-blockade is associated with significant reductions in postoperative short-term and long-term mortality following elective colon cancer surgery. Its potential prophylactic effect warrants further interventional studies to determine whether beta-blockade can be used as a way of improving outcomes for this patient group.

  • 8.
    Ahmad, Abrar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Askari, Shlear
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Befekadu, Rahel
    Örebro University Hospital. Department of Laboratory Medicine, Section for Transfusion Medicine.
    Hahn-Strömberg, Victoria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma2015In: Molecular Medicine Reports, ISSN 1791-2997, E-ISSN 1791-3004, Vol. 11, no 4, p. 2493-2503Article in journal (Refereed)
    Abstract [en]

    There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin-fixed paraffin-embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin-8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor. The present results may facilitate the identification of potential biomarkers of the disease in addition to drug targets.

  • 9.
    Ahmad, Abrar
    et al.
    Department of Clinical Research, Örebro University Hospital, Örebro, Sweden.
    Venizelos, Nikolaos
    Department of Clinical Research, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hahn-Strömberg, Victoria
    Department of Clinical Research, Örebro University Hospital, Örebro, Sweden; ; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
    Prognostic Effect of Vascular Endothelial Growth Factor +936C/T Polymorphism on Tumor Growth Pattern and Survival in Patients Diagnosed with Colon Carcinoma2016In: Journal of Tumor Research, Vol. 2, no 1, p. 1-6, article id 1000108Article in journal (Refereed)
    Abstract [en]

    Introduction: Vascular endothelial growth factor (VEGF) is considered as endothelial cell-specific mitogen that plays an important role in the process of angiogenesis, thereby affecting the prognosis of tumor as angiogenesis is a crucial phase in tumor growth and metastasis. Accordingly, we carried out a case-control study to assess whether VEGF rs3025039 polymorphism affects the growth pattern and susceptibility to colon carcinoma.

    Materials and methods: One hundred and fifty, formalin fixed paraffin embedded (FFPE) tissue samples from patients diagnosed with colon carcinoma and the same number of blood controls were used in the present study. VEGF +936 C>T (rs3025039) polymorphism was evaluated by pyrosequencing. Computer image analysis was used to analyse the growth pattern of the colon carcinoma tumor by using cytokeratin-8 stained slides.

    Results: A heterozygous genotype TC in rs3025039 polymorphism was found as a significantly protective genotype as compared to homozygous genotypes (CC and TT). However we found no significant correlation between investigated polymorphisms, tumor growth pattern, 5 years survival and other clinicopathological parameters.

    Conclusion: We concluded that the heterogenous genotype of VEGF rs3025039 polymorphism appears to be a protective factor for colon carcinoma that could be a useful marker in follow-up studies and may be a genetic determinant for colon carcinoma.

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  • 10.
    Akre [Fall], Katja
    et al.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Ekström, A. M.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Signorello, L B
    2International Epidemiology Institute, Rockville, USA.
    Hansson, L.-E.
    Mora Hospital, Mora.
    Nyrén, O.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Aspirin and risk for gastric cancer: a population-based case-control study in Sweden2001In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 84, no 7, p. 965-8Article in journal (Refereed)
    Abstract [en]

    While aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) are associated with gastric mucosal damage, they might reduce the risk for gastric cancer. In a population-based case-control study in 5 Swedish counties, we interviewed 567 incident cases of gastric cancer and 1165 controls about their use of pain relievers. The cases were uniformly classified to subsite (cardia/non-cardia) and histological type and information collected on other known risk factors for gastric cancer. Helicobacter pylori serology was tested in a subset of 542 individuals. Users of aspirin had a moderately reduced risk of gastric cancer compared to never users; odds ratio (OR) adjusted for age, gender and socioeconomic status was 0.7 (95% CI = 0.6-1.0). Gastric cancer risk fell with increasing frequency of aspirin use (P for trend = 0.02). The risk reduction was apparent for both cardia and non-cardia tumours but was uncertain for the diffuse histologic type. No clear association was observed between gastric cancer risk and non-aspirin NSAIDs or other studied pain relievers. Our finding lends support to the hypothesis that use of aspirin reduces the risk for gastric cancer.

  • 11.
    Akre [Fall], Katja
    et al.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm.
    Signorello, Lisa B.
    Engstrand, Lars
    Bergström, Reinhold
    Larsson, Sune
    Eriksson, Bengt I.
    Nyrén, Olof
    Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement2000In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 60, no 22, p. 6376-80Article in journal (Refereed)
    Abstract [en]

    Despite strong evidence of an association between Helicobacter pylori and gastric cancer, the benefit of eradicating H. pylori infection is unknown. Our aim was to test the hypothesis that exposure to high doses of antibiotics reduces risk for gastric cancer via possible eradication of H. pylori We conducted a nationwide case-control study nested in a cohort of 39,154 patients who underwent hip replacement surgery between 1965 and 1983. Such patients frequently receive prophylactic antibiotic treatment. During follow-up through 1989, we identified 189 incident cases of gastric cancer. For each case, three controls were selected from the cohort. Exposure data were abstracted from hospital records. Blood samples from a separate cohort undergoing hip replacement surgery were analyzed for anti-H. pylori IgG before and after surgery. Both long-term antibiotic treatment before surgery [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7] and prophylactic antibiotic treatment (OR, 0.7; 95% CI, 0.5-1.1) conferred a reduction in gastric cancer risk. The reduction appeared stronger after 5 years (OR, 0.6; 95% CI, 0.3-1.2) than during shorter follow-up after hip replacement (OR, 0.8; 95% CI, 0.4-1.7). There was an apparent decrease in risk with increasing body weight-adjusted doses of antibiotics (P = 0.13). However, the rate of H. pylori antibody disappearance was not strikingly higher in the cohort of patients undergoing hip replacement than in a control cohort. Our findings provide indirect support for the hypothesis that treatment with antibiotics at a relatively advanced age reduces the risk of gastric cancer.

  • 12.
    Albrow, Rebecca
    et al.
    Sch Canc & Enabling Sci, Univ Manchester, Manchester, England.
    Blomberg, Karin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kitchener, Henry
    Sch Canc & Enabling Sci, Univ Manchester, Manchester, England.
    Brabin, Loretta
    Sch Canc & Enabling Sci, Univ Manchester, Manchester, England.
    Patnick, Julietta
    NHS Canc Screening Programmes, Sheffield, England.
    Tishelman, Carol
    Med Management Ctr, Dept Learning Informat Management & Eth, Karolinska Inst, Stockholm, Sweden.
    Törnberg, Sven
    Regional Cancer Center, Dept Cancer Screening, Stockholm, Sweden.
    Sparen, Par
    Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Widmark, Catarina
    Med Management Ctr, Dept Learning Informat Management & Eth, Karolinska Inst, Stockholm, Sweden; Dept Qual & Patient Safety, Karolinska Univ Hosp, Stockholm, Sweden.
    Interventions to improve cervical cancer screening uptake amongst young women: A systematic review2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 4, p. 445-451Article, review/survey (Refereed)
    Abstract [en]

    Objectives. In view of declining screening uptake in young women, this review aims to summarise the available evidence relating to interventions designed to increase cervical screening uptake amongst women aged <= 35 years.

    Methods. Electronic databases were searched and further articles located by manual searches. Study designs employing a valid comparison group and including women aged <= 35 years published through 2012 were considered. Data was extracted on the uptake from either screening programme statistics or as reported by the study subjects. A narrative synthesis was undertaken for each category of interventions identified.

    Results. Ninety-two records were screened with 36 articles retrieved for further assessment. Four studies met the inclusion criteria, two of which evaluated more than one intervention. One of the studies evaluated the use of a modified invitation letter and reported no significant increase in uptake compared to a standard invitation. Three studies investigated the use of a reminder letter, with two reporting a positive effect on screening uptake in women aged 24-34. Three studies were included which supported the use of physician and telephone reminders. One study on HPV self-sampling reported a positive effect when compared with a reminder letter.

    Conclusions. There is a lack of randomised controlled trials designed to specifically address falling cervical screening uptake in amongst young women. Cervical screening programmes need to look beyond the use of invitation/reminders letters in this group of women to develop interventions which attempt to overcome as many barriers to uptake as possible.

  • 13.
    Alevroudis, Emmanouil
    et al.
    2nd Department of Radiology, Nuclear Medicine Unit, National and Kapodistrian University of Athens, General University Hospital Attikon, Athens, Greece.
    Spei, Maria-Eleni
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Chatziioannou, Sofia N.
    2nd Department of Radiology, Nuclear Medicine Unit, National and Kapodistrian University of Athens, General University Hospital Attikon, Athens, Greece; Nuclear Medicine Division, Biomedical Research Foundation Academy of Athens, 4 Soranou Efesiou St., Athens, Greece.
    Tsoli, Marina
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Kaltsas, Gregory
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece; Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Clinical utility of 18f-fdg pet in neuroendocrine tumors prior to peptide receptor radionuclide therapy: A Systematic Review and Meta-Analysis2021In: Cancers, ISSN 2072-6694, Vol. 13, no 8, article id 1813Article, review/survey (Refereed)
    Abstract [en]

    The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27–10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48–4.04 and HR:2.25; 95% CIs:1.55–3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.

  • 14.
    Alhamdow, Ayman
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Essig, Yona J.
    Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Krais, Annette M.
    Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Gustavsson, Per
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Region Stockholm, Centre for Occupational and Environmental Medicine, Stockholm, Sweden.
    Tinnerberg, Håkan
    School of Public Health and Community Medicine, Section of Occupational and Environmental Medicine, University of Gothenburg Sahlgrenska Academy, Göteborg, Sweden.
    Lindh, Christian H.
    Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Hagberg, Jessika
    Örebro University, School of Science and Technology. Department of Occupational and Environmental Medicine.
    Graff, Pål
    Department of Chemical and Biological Work Environment, STAMI, Oslo, Norway.
    Albin, Maria
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden; Region Stockholm, Centre for Occupational and Environmental Medicine, Stockholm, Sweden.
    Broberg, Karin
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer2020In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 77, no 7, p. 488-495Article in journal (Refereed)
    Abstract [en]

    Objectives: Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers.

    Methods: We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation ofF2RL3andAHRRusing pyrosequencing.

    Results: Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). n-ary sumation OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation ofF2RL3andAHRRin chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) forF2RL3_cg03636183, and -7.1 (-9.6 to -4.7) forAHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, n-ary sumation OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation ofAHRRCpG2.

    Conclusions: Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation ofF2RL3andAHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.

  • 15.
    Alhamdow, Ayman
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lindh, Christian
    Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Hagberg, Jessika
    Örebro University, School of Science and Technology. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Graff, Pål
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; National Institute of Occupational Health, Oslo, Norway.
    Westberg, Håkan
    Örebro University, School of Science and Technology. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Krais, Annette M.
    Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Albin, Maria
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden; Centre for Occupational and Environmental Medicine (CAMM), Stockholm County Council, Stockholm, Sweden.
    Gustavsson, Per
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine (CAMM), Stockholm County Council, Stockholm, Sweden.
    Tinnerberg, Håkan
    Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Broberg, Karin
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons2018In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 39, no 7, p. 869-878Article in journal (Refereed)
    Abstract [en]

    Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls, and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 μg/g creatinine) followed by chimney sweeps (0.34 μg/g creatinine) and controls (0.05 μg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1% and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B=-2.04; P<0.057, adjusted for smoking and age) and lower average AHRR methylation (B=-2.05; P<0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B=-0.81; P<0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.

  • 16.
    Ali, Imran
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Julin, Bettina
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Glynn, Anders
    The National Food Agency, Uppsala, Sweden.
    Högberg, Johan
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Berglund, Marika
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Jan-Erik
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Giovannucci, Edward
    Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston MA, United States; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston MA, United States.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Stenius, Ulla
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Åkesson, Agneta
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Exposure to polychlorinated biphenyls and prostate cancer: population-based prospective cohort and experimental studies2016In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 37, no 12, p. 1144-1151Article in journal (Refereed)
    Abstract [en]

    Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer.

  • 17.
    Aljabery, Firas
    et al.
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Biobank Research, Umeå University, Umeå, Sweden.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hosseini, Abolfazl
    Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Medicine, King´s College London, London, UK.
    Hagberg, Oskar
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Management and outcome of muscle-invasive bladder cancer with clinical lymph node metastases. A nationwide population-based study in the bladder cancer data base Sweden (BladderBaSe)2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 5, p. 332-338Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the clinical management and outcome of patients with muscle-invasive bladder cancer with clinical lymph node involvement, using longitudinal nationwide population-based data.

    Methods: In the Bladder Cancer Data Base Sweden (BladderBaSe), treatment and survival in patients with urinary bladder cancer clinical stage T2-T4 N + M0 diagnosed between 1997 and 2014 was investigated. Patients´ characteristics were studied in relation to TNM classification, curative or palliative treatment, cancer-specific (CSS) and overall survival (OS). Age at diagnosis was categorised as ≤60, 61-70, 71-80 and >80 years, and time periods were stratified as follows: 1997-2001, 2002-2005, 2006-2010 and 2011-2014.

    Results: There were 786 patients (72% males) with a median age of 71 years (interquartile range = 64-79 years). The proportion of patients with high comorbidity increased over time. Despite similar low comorbidity, curative treatment was given to 44% and to 70% of those in older (>70 years) and younger age groups, respectively. Curative treatment decreased over time, but chemotherapy and cystectomy increased to 25% during the last time period. Patients with curative treatment had better survival compared to those with palliative treatment, both regarding CSS and OS in the whole cohort and in all age groups.

    Conclusions: The low proportion of older patients undergoing treatment with curative intent, despite no or limited comorbidity, indicates missed chances of treatment with curative intent. The reasons for an overall decrease in curative treatment over time need to be analysed and the challenge of coping with an increasing proportion of node-positive patients with clinically significant comorbidity needs to be met.

  • 18.
    Aljabery, Firas
    et al.
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Biobank Research, Umeå University, Umeå, Sweden.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Urology, Gothenburg, Sweden.
    Hosseini, Abolfazl
    Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    MalmströmMalmström, Per-Uno
    Department ofSurgical Sciences, Uppsala University, Uppsala, Sweden.
    Hagberg, Oskar
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Medicine, King´s College London, London, UK.
    Treatment and prognosis of bladder cancer patients with other primary cancers: A nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe)2020In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 126, no 5, p. 625-632Article in journal (Refereed)
    Abstract [en]

    Objective: To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis.

    Patients And Methods: Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patient's characteristics, UBC tumour stage at diagnosis, and site of OPC.

    Results: There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis.

    Conclusions: OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.

  • 19.
    Alping, Peter
    et al.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
    Burman, Joachim
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Fink, Katharina
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden.
    Fogdell-Hahn, Anna
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro University, School of Medical Sciences. Department of Neurology.
    Hillert, Jan
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Langer-Gould, Annette
    Clinical and Translational Neuroscience, Southern California Permanente Medical Group, Kaiser Permanente, Pasadena, CA, USA.
    Lycke, Jan
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Petra
    Department of Clinical Sciences/Neurology, Lund University, Lund, Sweden.
    Salzer, Jonatan
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Svenningsson, Anders
    Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Stockholm, Sweden.
    Vrethem, Magnus
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Olsson, Tomas
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden.
    Frisell, Thomas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
    Cancer Risk for Fingolimod, Natalizumab, and Rituximab in Multiple Sclerosis Patients2020In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 87, no 5, p. 688-699Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Novel, highly effective disease-modifying therapies have revolutionized multiple sclerosis (MS) care. However, evidence from large comparative studies on important safety outcomes, such as cancer, is still lacking.

    METHODS: In this nationwide register-based cohort study, we linked data from the Swedish MS register to the Swedish Cancer Register and other national health care and census registers. We included 4,187 first-ever initiations of rituximab, 1,620 of fingolimod, and 1,670 of natalizumab in 6,136 MS patients matched for age, sex, and location to 37,801 non-MS general population subjects. Primary outcome was time to first invasive cancer.

    RESULTS: We identified 78 invasive cancers among treated patients: rituximab 33 (incidence rate [IR] per 10,000 person-years = 34.4, 95% confidence interval [CI] = 23.7-48.3), fingolimod 28 (IR = 44.0, 95% CI = 29.2-63.5), and natalizumab 17 (IR = 26.0, 95% CI = 15.1-41.6). The general population IR was 31.0 (95% CI = 27.8-34.4). Adjusting for baseline characteristics, we found no difference in risk of invasive cancer between rituximab, natalizumab, and the general population but a possibly higher risk with fingolimod compared to the general population (hazard ratio [HR] = 1.53, 95% CI = 0.98-2.38) and rituximab (HR = 1.68, 95% CI = 1.00-2.84).

    INTERPRETATION: In this first large comparative study of 3 highly effective MS disease-modifying therapies, no increased risk of invasive cancer was seen with rituximab and natalizumab, compared to the general population. However, there was a borderline-significant increased risk with fingolimod, compared to both the general population and rituximab. It was not possible to attribute this increased risk to any specific type of cancer, and further studies are warranted to validate these findings.

  • 20. Amundadottir, Laufey T.
    et al.
    Sulem, Patrick
    Gudmundsson, Julius
    Helgason, Agnar
    Baker, Adam
    Agnarsson, Bjarni A.
    Sigurdsson, Asgeir
    Benediktsdottir, Kristrun R.
    Cazier, Jean-Baptiste
    Sainz, Jesus
    Jakobsdottir, Margret
    Kostic, Jelena
    Magnusdottir, Droplaug N.
    Ghosh, Shyamali
    Agnarsson, Kari
    Birgisdottir, Birgitta
    Le Roux, Louise
    Olafsdottir, Adalheidur
    Blondal, Thorarinn
    Andresdottir, Margret
    Gretarsdottir, Olafia Svandis
    Bergthorsson, Jon T.
    Gudbjartsson, Daniel
    Gylfason, Arnaldur
    Thorleifsson, Gudmar
    Manolescu, Andrei
    Kristjansson, Kristleifur
    Geirsson, Gudmundur
    Isaksson, Helgi
    Douglas, Julie
    Johansson, Jan-Erik
    Örebro University, Department of Clinical Medicine.
    Bälter, Katarina
    Wiklund, Fredrik
    Montie, James E.
    Yu, Xiaoying
    Suarez, Brian K.
    Ober, Carole
    Cooney, Kathleen A.
    Gronberg, Henrik
    Catalona, William J.
    Einarsson, Gudmundur V.
    Barkardottir, Rosa B.
    Gulcher, Jeffrey R.
    Kong, Augustine
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    A common variant associated with prostate cancer in European and African populations2006In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 38, no 6, p. 652-658Article in journal (Refereed)
    Abstract [en]

    With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.

  • 21.
    Andersen, Christen Lykkegaard
    et al.
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark..
    Bjorn, Mads Emil
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark..
    McMullin, Mary Frances
    Dept Haematol, Queen Univ Belfast Antrim, Belfast, North Ireland.
    Harrison, Claire
    Dept Haematol, NHS Fdn Trust, London, England.
    Samuelsson, Jan
    Dept Internal Med, Stockholm South Hosp, Stockholm, Sweden..
    Ejerblad, Elisabeth
    Dept Hematol, Univ Uppsala Hosp, Uppsala, Sweden..
    Zweegman, Sonja
    Dept Hematol, Vrije Univ Med Ctr, Amsterdam, Netherlands..
    Fernandes, Savio
    Dept Haematol, Russells Hall Hosp, Dudley, England.
    Bareford, David
    Dept Haematol, Russells Hall Hosp, Dudley, England.
    Knapper, Steven
    Dept Haematol, Cardiff Univ, Cardiff, UK.
    Lofvenberg, Eva
    Hematol Ctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Linder, Olle
    Dept Med, Div Hematol, Örebro Univ Hosp, Örebro, Sweden..
    Andreasson, Bjorn
    Dept Hematol, NU Hosp Org, Uddevalla Hosp, Uddevalla, Sweden.
    Ahlstrand, Erik
    Örebro University Hospital. Dept Med, Div Hematol, Örebro University Hospital, Örebro, Sweden.
    Jensen, Morten Krogh
    Dept Hematol, Herlev Hosp, Herlev, Denmark.
    Bjerrum, Ole Weis
    Dept Hematol, Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    Vestergaard, Hanne
    Dept Hematol, Odense Univ Hosp, Odense, Denmark.
    Larsen, Herdis
    Dept Hematol, Dept Internal Med, Viborg Hosp, Viborg, Denmark.
    Klausen, Tobias Wirenfeldt
    Dept Hematol,Herlev Hosp, Herlev, Denmark.
    Mourits-Andersen, Torben
    Dept Hematol, Esbjerg Cent Hosp, Esbjerg, Denmark.
    Skov, Vibe
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Thomassen, Mads
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Kruse, Torben
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Gronbaek, Kirsten
    Dept Hematol, Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    Hasselbalch, Hans Carl
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark.
    Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat2014In: Leukemia Research, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 38, no 7, p. 816-821Article in journal (Refereed)
    Abstract [en]

    YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms.

  • 22.
    Andersson, Emilia
    et al.
    Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Internal Medicine, Division of Gastroenterology.
    van Nieuwenhoven, Michiel A
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Internal Medicine, Division of Gastroenterology.
    The effectiveness of the colorectal cancer referral pathway: identification of colorectal cancer in a Swedish region2021In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 56, no 5, p. 552-558Article in journal (Refereed)
    Abstract [en]

    Introduction: To shorten the time for diagnosis of suspected colorectal cancer (CRC), a standardized colorectal cancer referral pathway (CCRP) was introduced in Sweden in September 2016. However, the effects of the CCRP are still uncertain, and CRC is also found in patients undergoing a routine colonoscopy.

    Objective: To identify all CRC-cases in the Region orebro County and to investigate via which diagnostic pathway they were diagnosed. Furthermore, to investigate the reasons for and possible effect of not being included in the CCRP for cases found via colonoscopy.

    Methods: Review of medical records of patients with CRC referred to the department of surgery in the Region orebro County in 2016-2018 (n = 459).

    Results: In CRC-cases found through colonoscopy (n = 347), 37.5% were diagnosed via a routine waiting list and 62.5% within the CCRP. No difference in tumor stage or tumor grade was found between the two groups. The non-CCRP showed a longer time to diagnosis than the CCRP group (21.5 days, IQR 7-43 vs. 13 days, IQR 8-17 (p < .001), respectively). Non-rectal cancer was more common in the non-CCRP group (81.5% vs. 57.6%, p < .001). The non-CCRP group had lower median Hb-value (106, IQR 87-129 vs. 117, IQR 101-136, p = .001). 85% of the non-CCRP group was found to meet one or more CCRP referral criteria, with bleeding anemia being the dominant criterion to meet.

    Conclusion: The CCRP did not appear to improve prognostic outcomes for CRC-patients.

    ClinicalTrials.gov Identifier: NCT04585516

  • 23.
    Andersson, Karin M.
    et al.
    Örebro University, School of Medical Sciences. The Skandion Clinic, Uppsala, Sweden.
    Edvardsson, A.
    The Skandion Clinic, Uppsala, Sweden, Radiation Physics, Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Sweden.
    Hall, A.
    The Skandion Clinic, Uppsala, Sweden.
    Enmark, M.
    The Skandion Clinic, Uppsala, Sweden, Radiation Physics, Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Sweden.
    Kristensen, I.
    The Skandion Clinic, Uppsala, 752 37, Sweden, Radiation Physics, Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Sweden.
    Pencil beam scanning proton therapy of Hodgkin's lymphoma in deep inspiration breath-hold: A case series report2020In: Technical Innovations & Patient Support in Radiation Oncology, E-ISSN 2405-6324, Vol. 13, p. 6-10Article in journal (Refereed)
    Abstract [en]

    Background: Most patients with Hodgkin's lymphoma are young and have a favourable prognosis, therefore it is of high importance to decrease the radiation doses to normal tissues received during radiotherapy. A combination of proton therapy and deep inspiration breath-hold technique (DIBH) can improve the sparing effect and thereby reduce the risk of late effects.

    Case presentation: The two first patient cases treated with proton therapy in DIBH at the Skandion Clinic, Uppsala, Sweden, are presented here. Proton treatment plans were compared to photon plans based on doses to target and organs at risk. Several CT scans were acquired during the treatment course and inter breath-hold variations were evaluated based on anatomical distances and dosimetric comparisons.

    Conclusions: The results from our first patients treated with proton therapy in DIBH imply that the treatment strategy is robust and has the potential to reduce dose to normal tissue.

  • 24.
    Andersson, Patiyan
    et al.
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Kolaric, Aleksandra
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Kirrander, Peter
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderkvist, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Karlsson, Mats G
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    PIK3CA, HRAS and KRAS gene mutations in human penile cancer2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, p. 2030-2034Article in journal (Refereed)
    Abstract [en]

    Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways.

    Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors.

    Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.

    Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

  • 25.
    Andersson, Sonia
    et al.
    Department of Women's and Children's Health, Karolinska University Hospital and Institute, Stockholm, Sweden.
    Belkić, Karen
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Claremont Graduate University, Claremont, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, USA.
    Mints, Miriam
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Women's and Children's Health, Karolinska University Hospital and Institute, Stockholm, Sweden.
    Östensson, Ellinor
    Department of Women's and Children's Health, Karolinska University Hospital and Institute, Stockholm, Sweden.
    Acceptance of Self-Sampling Among Long-Term Cervical Screening Non-Attenders with HPV-Positive Results: Promising Opportunity for Specific Cancer Education2021In: Journal of Cancer Education, ISSN 0885-8195, E-ISSN 1543-0154, Vol. 36, no 1, p. 126-133Article in journal (Refereed)
    Abstract [en]

    This study aims to investigate acceptance of vaginal self-sampling for high-risk human papilloma virus (HPV) among long-term screening non-attenders at increased cervical cancer risk and to identify leverage points to promote screening adherence among these women. Forty-three long-term screening non-attenders performed home vaginal self-sampling for HPV, had positive HPV results, and subsequently attended gynecologic examination. Sixteen (37.2%) had high-grade cervical intraepithelial neoplasia (CIN2 or 3), and two had invasive cervical cancer. Forty-one of these women completed a questionnaire concerning Specific Knowledge about HPV, CIN, and cervical cancer, potential barriers to screening and views about self-sampling. Results were compared with 479 women treated for CIN2+ who attended gynecologic follow-up and also performed self-sampling. Significant multivariate predictors of long-term non-attender status compared with referents were low Specific Knowledge, high confidence in self-sampling, and potential barriers-refraining from activity to attend gynecologic examination, needing another's help to attend, and long travel time. Non-attenders citing fear/refraining from gynecologic examination as why they preferred self-sampling significantly more often had lowest Specific Knowledge compared with other non-attenders. All non-attenders could envision themselves doing self-sampling again while only 74% of referents endorsed this statement (p = 0.0003). We conclude that HPV self-sampling is an acceptable option for women at increased cervical cancer risk who have been long-term screening non-attenders. Educational outreach to enhance Specific Knowledge about HPV, CIN and cervical cancer is critical. Those non-attenders who explicitly avoid gynecologic examinations need special attention. Trial Registry: Clinicaltrials.gov NCT02750124.

  • 26.
    Andersson, Sonia
    et al.
    Department of Women's and Children's Health, Obstetrics‑Gynecology Division, Karolinska Institute, Stockholm, Sweden.
    Megyessi, David
    Department of Women's and Children's Health, Obstetrics‑Gynecology Division, Karolinska Institute, Stockholm, Sweden.
    Belkic, Karen
    Department of Oncology‑Pathology, Karolinska Institute, Stockholm, Sweden; School of Community/Global Health, Claremont Graduate University, Claremont CA, USA; Institute for Health Promotion & Disease Prevention Research, Keck School of Medicine, University of Southern California, Los Angeles CA, USA.
    Alder, Susanna
    Department of Women's and Children's Health, Obstetrics‑Gynecology Division, Karolinska Institute, Stockholm, Sweden.
    Östensson, Ellinor
    Department of Women's and Children's Health, Obstetrics‑Gynecology Division, Karolinska Institute, Stockholm, Sweden.
    Mints, Miriam
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Women's and Children's Health, Obstetrics‑Gynecology Division, Karolinska Institute, Stockholm, Sweden.
    Age, margin status, high-risk human papillomavirus and cytology independently predict recurrent high-grade cervical intraepithelial neoplasia up to 6 years after treatment2021In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 22, no 3, article id 684Article in journal (Refereed)
    Abstract [en]

    The present study aimed to identify the factors that independently contribute to disease recurrence among women first-time treated for high-grade cervical intraepithelial neoplasia (CIN) during 4-6 years of follow-up. Overall, 529 of 530 eligible patients participated; these patients all attended a 1st follow-up appointment similar to 6 months post-conization, at which time high-risk human-papillomavirus (HPV) testing, liquid-based cytology and colposcopy were performed. Full data on margin excision status, other aspects of initial treatment and comorbidity were obtained. At least one subsequent follow-up was attended by 88% of patients. A total of 22 recurrent cases were detected during follow-up. Detected recurrence was the outcome of focus for multiple logistic regression analysis, with odds ratios (OR) and 95% confidence intervals (CI) computed. Four significant independent risk factors were identified: Age 45 years or above (OR=3.5, 95% CI=1.3-9.9), one or both unclear or uncertain margins (OR=5.3, 95% CI=2.0-14.2), positive HPV at 1st follow-up (OR=5.8, 95% CI=2.0-16.8), and abnormal cytology at 1st follow-up (OR=3.9, 95% CI=1.4-11.0). Bivariate analysis revealed that persistent HPV positivity was associated with recurrence (P<0.01). These findings indicated that incomplete excision of the CIN lesion may warrant more intensive subsequent screening, regardless of early post-conization HPV findings. Although early post-conization positive HPV was a powerful, independent predictor of recurrent high-grade CIN, over one-third of the patients with detected recurrence had a negative early post-conization HPV finding. These patients returned for routine screening, at which time, in most cases, HPV status was positive, thus indicating the need for repeated HPV evaluation. Especially during the on-going pandemic, home vaginal self-sampling is recommended. Particular attention is required for women aged >= 45 years. In addition, although not statistically significant, relevant comorbidities, especially autoimmune conditions, warrant consideration in clinical decision-making. Women who have been treated for high-grade CIN are at risk for recurrent disease and progression to cervical cancer; therefore, they require careful, individualized follow-up to avoid these adverse consequences.

  • 27.
    Anderzen Carlsson, Agneta
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Leibring, Ingela
    Fear and coping during treatment for acute lymphatic leukemia: from the perspective of children 5-9 years old2018Conference paper (Refereed)
    Abstract [en]

    Background: The concept of fear can be defined as ”an unpleasant often strong emotion caused by expectation of danger”. It is reasonable to believe that fear and coping of fear, can vary during the course of treatment for ALL. The aim of the present study was to describe a longitudinal perspective on fear related to having ALL, based on children’s perspective, as well as to describe the strategies these children use when experiencing fear.

    Design: The study has a longitudinal descriptive qualitative design. Three girls and 10 boys, initially aged 5-9 were interviewed once to three times during their treatment period (approximately two months after the diagnosis, after one year and at the end of the 2.5-year long treatment). In total, 35 interviews were conducted. Data were analyzed using a matrix-based qualitative analysis method.

    Results: The children described fear of being subjected to needles and related to having a feeding tube, to remove adhesive tape and taking tablets, as well as fear related to the bodily changes caused by the ALL. Existential fears were most frequently mentioned at end of treatment. The children wanted to participate in their care. They used cognitive strategies, such as ”thinking the right way” and emotional strategies, such as crying out loud and kicking. The fears changed over time, but the fear of being subjected to needles remained for half of the children, but was less intense at the end of treatment. The strategies developed, and became more sophisticated over the treatment period.

    Conclusion: The fear changed throughout the course of treatment, and so did the strategies used. It is reasonable to believe that the need for support also vary, which is a topic for future research.

  • 28.
    Anderzen-Carlsson, Agneta
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Leibring, I.
    Karlstad University, Faculty of Health- Science and Technology- Department of Health Sciences- Nursing, Karlstad, Sweden.
    Fear and Coping During Treatment for Acute Lymphatic Leukemia - from the Perspective of Children 5-9 Years Old2018In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 65, no Suppl.2, p. S598-S598Article in journal (Other academic)
    Abstract [en]

    Background/Objectives: The concept of fear can be defined as ”an unpleasant often strong emotion caused by expectation of danger”. It is reasonable to believe that fear and coping of fear, can vary during the course of treatment for ALL. The aim of the present study was to describe a longitudinal perspective on fear related to having ALL, based on children's perspective, as well as to describe the strategies these children use when experiencing fear.

    Design/Methods: The study has a longitudinal descriptive qualitative design. Three girls and 10 boys, initially aged 5-9 were interviewed once to three times during their treatment period (approximately two months after the diagnosis, after one year and at the end of the 2.5-year long treatment). In total, 35 interviews were conducted. Data were analyzed using a matrix-based qualitative analysis method.

    Results: The children described fear of being subjected to needles and related to having a feeding tube, removing adhesive tape and taking tablets, as well as fear related to the bodily changes caused by the ALL. Existential fears were most frequently mentioned at the end of treatment. The children wanted to participate i n their care. They used cognitive strategies, such as ”thinking the right way” and emotional strategies, such as crying out loud and kicking. The fears changed over time, but the fear of being subjected to needles remained for half of the children, but was less intense at the end of treatment. The strategies developed, and became more sophisticated over the treatment period.

    Conclusions: The fear changed throughout the course of treatment, and so did the strategies used. It is reasonable to believe that the need for support also vary, which i s a topic for future research.

  • 29.
    Anderzen-Carlsson, Agneta
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital. University Health Care Research Center.
    Leibring, Ingela
    Karlstad University, Faculty of Health, Science and Technology, Institution for Health, Karlstad, Sweden.
    CHILDREN'S NARRATIVES OF SUPPORT FROM PARENTS WHEN EXPERIENCING FEAR RELATED TO ACUTE LYMPHOBLASTIC LEUKEMIA2022In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 69, no Suppl. 5, p. S528-S528, article id P067Article in journal (Other academic)
    Abstract [en]

    Background and Aims: Children diagnosed with Acute Lymphoblastic Leukemia (ALL) typically undergo intense treatment with frequent hospitalizations. Medical, as well as existential fears have been identified. It has also been found that children's coping strategies develop during their illness trajectory. The literature on what children with ALL find to be valuable support from parents when experiencing fear is sparse. Thus, the aim of this presentation is to describe what young children find to be important support from their parents when experiencing fear related to ALL.

    Methods: The study had a longitudinal descriptive qualitative design. Thirteen children (3 girls and 10 boys), initially 5-9 years old were interviewed once to three times during their treatment period (approximately 2 months after the diagnosis, after 1 year, and at end of treatment). Data were analyzed using a matrix-based qualitative analysis method.

    Results: The parents’ physical and emotional closeness was the most frequently reported support. It eased the children's medical and existential fears. The children also found it supportive when the parents facilitated for them to participate in their care and when the parents acted as their advocate. Other supportive measures were offering distraction, talking to the child about their fears, assisting the professionals in alleviating pain and fear, being playful and encouraging. Five children also appreciated when their parents restricted them, during medical procedures. The experiences of support varied between children and between different time points during treatment.

    Conclusions: Although being quite young, the children were able to describe what they found to be supportive when experiencing fear, or for preventing fear. The parental support had an impact on the child's emotional, social and physical wellbeing. Professionals should encourage parents to stay with their child, and offer support to the parents, so that they in turn can support their child.

  • 30.
    Anderzén-Carlsson, Agneta
    Örebro University, School of Health and Medical Sciences.
    Aktuell forskare om barn med cancer, deras rädsla och sättet den hanteras på2008In: Barnbladet, ISSN 0349-1994, Vol. 33, no 2, p. 45-46Article in journal (Other (popular science, discussion, etc.))
  • 31.
    Anderzén-Carlsson, Agneta
    Örebro University, School of Health and Medical Sciences.
    Att hantera rädsla hos barn med cancer2008In: Onkologi i Sverige, ISSN 1653-1582, Vol. 4, no 6, p. 14-20Article in journal (Other (popular science, discussion, etc.))
  • 32.
    Anderzén-Carlsson, Agneta
    Örebro University, Department of Health Sciences.
    Existentiella rädslor hos barn med cancer: föräldrars och vårdpersonals berättelser2007In: Omsorg: Nordisk tidsskrift for Palliativ Medisin, ISSN 0800-7489, Vol. 24, no 4, p. 33-39Article in journal (Other academic)
  • 33.
    Anderzén-Carlsson, Agneta
    et al.
    Örebro University, School of Health and Medical Sciences.
    Kihlgren, Annica
    Örebro University, School of Health and Medical Sciences.
    Sörlie, Venke
    Högskolan i Bodö.
    Embodied suffering: experiences of fear in adolescent girls with cancer2008In: Journal of Child Health Care, ISSN 1367-4935, E-ISSN 1741-2889, Vol. 12, no 2, p. 129-143Article in journal (Refereed)
    Abstract [en]

    Previously, fear in adolescents with cancer has been sparsely described from an emic perspective. The aim of this study was to illuminate fear in adolescents with personal experience of cancer. The participants were six adolescent girls between the age of 14 and 16 years who were no longer under active treatment for cancer but still went for regular check-ups. Open interviews were conducted. Data were analysed according to the phenomenological hermeneutic method. In the result one main theme was identified: `an embodied fear — a threat to the personal self'. This theme was built up by three separate but intertwined themes: `experiencing fear related to the physical body', `experiencing existential fear' and `experiencing fear related to the social self'. In the comprehensive understanding the fear was interpreted from youth cultural aspects as well as a holistic perspective. The importance of professionals taking the whole person and their situation into account when meeting the fear is underlined.

  • 34.
    Andrén, Ove
    et al.
    Örebro University, School of Health and Medical Sciences.
    Fall, Katja
    Andersson, Swen-Olof
    Rubin, Mark A.
    Bismar, Tarek A.
    Karlsson, M.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Mucci, Lorelei A.
    MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden2007In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 97, no 6, p. 730-734Article in journal (Refereed)
    Abstract [en]

    Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score >=7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

  • 35. Andrén, Ove
    et al.
    Garmo, H.
    Mucci, L.
    Andersson, Swen-Olof
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Fall, Katja
    Incidence and mortality of incidental prostate cancer: a Swedish register-based study2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, no 1, p. 170-173Article in journal (Refereed)
    Abstract [en]

    In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.

  • 36.
    Andrén, Ove
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Widmark, A.
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Fält, A.
    Ulvskog, E.
    Örebro University, School of Medical Sciences. Department of Oncology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Karlsson, C. Thellenberg
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Hjälm-Eriksson, M.
    Department of Oncology, Karolinska Institute, Stockholm, Sweden.
    Cabazitaxel followed by androgen deprivation therapy (ADT) significantly improves time to progression in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A randomized, open label, phase III, multicenter trial2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no Suppl. 5, article id 811PArticle in journal (Other academic)
  • 37.
    Arora, Manish
    et al.
    Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, USA; Cellular and Molecular Pathology Research Unit, Department of Oral Pathology and Oral Medicine, University of Sydney, Sydney, Australia; Population Oral Health, University of Sydney, Sydney, Australia.
    Weuve, Jennifer
    Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, USA; Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Fall, Katja
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Pedersen, Nancy L.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Mucci, Lorelei A.
    Department of Epidemiology, Harvard School of Public Health, Boston, USA; Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
    An exploration of shared genetic risk factors between periodontal disease and cancers: a prospective co-twin study2010In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 171, no 2, p. 253-9Article in journal (Refereed)
    Abstract [en]

    Biologic mechanisms underlying associations of periodontal disease with cancers remain unknown. The authors propose that both conditions share common genetic risk factors. They analyzed associations between baseline periodontal disease, measured by questionnaire-recorded tooth mobility, and incident cancers, identified by linkage with national registries, between 1963 and 2004 in 15,333 Swedish twins. The authors used co-twin analyses to control for familial factors and undertook analyses restricted to monozygotic twins to further control for confounding by genetic factors. They observed 4,361 cancer cases over 548,913 person-years. After adjustment for covariates, baseline periodontal disease was associated with increased risk of several cancers ranging from 15% for total cancer (proportional hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.01, 1.32) to 120% for corpus uterine cancer (HR = 2.20, 95% CI: 1.16, 4.18). Periodontal disease was also associated with increased risk of colorectal (HR = 1.62, 95% CI: 1.13, 2.33), pancreatic (HR = 2.06, 95% CI: 1.14, 3.75), and prostate (HR = 1.47, 95% CI: 1.04, 2.07) cancers. In co-twin analyses, dizygotic twins with baseline periodontal disease showed a 50% increase in total cancer risk (HR = 1.50, 95% CI: 1.04, 2.17), but in monozygotic twins this association was markedly attenuated (HR = 1.07, 95% CI: 0.63, 1.81). Similar patterns emerged for digestive tract cancers, suggesting that shared genetic risk factors may partially explain associations between periodontal disease and cancers.

  • 38.
    Axelrad, Jordan E.
    et al.
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, New York, USA .
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Sachs, Michael C.
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Erichsen, Rune
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Surgery, Randers Regional Hospital, Randers, Denmark.
    Pedersen, Lars
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Sørensen, Henrik Toft
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States.
    Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden2021In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, no 2, p. 297-308Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD).

    DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs).

    RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32).

    CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

  • 39.
    Babaki, Behrouz
    et al.
    KU Leuven, Leuven, Belgium.
    Guns, Tias
    KU Leuven, Leuven, Belgium.
    Nijssen, Siegfried
    KU Leuven, Leuven, Belgium; Universiteit Leiden, Ca Leiden, The Netherlands.
    De Raedt, Luc
    KU Leuven, Leuven, Belgium.
    Constraint-Based Querying for Bayesian Network Exploration2015In: Advances in Intelligent Data Analysis XIV: 14th International Symposium, IDA 2015, Saint Etienne, France, October 22 -24, 2015. Proceedings / [ed] Elisa Fromont, Tilj De Bie, Matthijs van Leeuwen, Cham: Springer International Publishing , 2015, Vol. 9385, p. 13-24Conference paper (Refereed)
    Abstract [en]

    Understanding the knowledge that resides in a Bayesian network can be hard, certainly when a large network is to be used for the first time, or when the network is complex or has just been updated. Tools to assist users in the analysis of Bayesian networks can help. In this paper, we introduce a novel general framework and tool for answering exploratory queries over Bayesian networks. The framework is inspired by queries from the constraint-based mining literature designed for the exploratory analysis of data. Adapted to Bayesian networks, these queries specify a set of constraints on explanations of interest, where an explanation is an assignment to a subset of variables in a network. Characteristic for the methodology is that it searches over different subsets of the explanations, corresponding to different marginalizations. A general purpose framework, based on principles of constraint programming, data mining and knowledge compilation, is used to answer all possible queries. This CP4BN framework employs a rich set of constraints and is able to emulate a range of existing queries from both the Bayesian network and the constraint-based data mining literature.

  • 40.
    Baban, Bayar
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, School of Medical Sciences, Faculty of Medicne and Health, Örebro University, Örebro, Sweden.
    Eklund, Daniel
    Örebro University, School of Medical Sciences.
    Tuerxun, Kedeye
    Örebro University, School of Medical Sciences.
    Alshamari, Muhammed
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology.
    Laviano, Alessandro
    Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, School of Medical Sciences, Faculty of Medicne and Health, Örebro University, Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences.
    Altered insulin sensitivity and immune function in patients with colorectal cancer2023In: Clinical Nutrition ESPEN, E-ISSN 2405-4577, Vol. 58, p. 193-200Article in journal (Refereed)
    Abstract [en]

    Background & aims: Insulin resistance and chronic inflammation have been reported in patients with cancer. However, many of the underlying mechanisms and associations are yet to be unveiled. We examined both the level of insulin sensitivity and markers of inflammation in patients with colorectal cancer for comparison to controls.

    Methods: Clinical exploratory study of patients with colorectal cancer (n = 20) and matched controls (n = 10). Insulin sensitivity was quantified using the hyperinsulinemic normoglycemic clamp and blood samples were taken for quantification of several key, both intra- and extracellular, inflammatory markers. We analysed the differences in these parameters between the two groups.

    Results: Patients exhibited both insulin resistance (M-value, patients median (Mdn) 4.57 interquartile range (IQR) 3.49-5.75; controls Mdn 5.79 (IQR 5.20-6.81), p = 0.049), as well as increased plasma levels of the pro-inflammatory cytokines IL-1b(patients Mdn 0.48 (IQR 0.33-0.58); controls Mdn 0.36 (IQR 0.29-0.42), p = 0.02) and IL-6 (patients Mdn 3.21 (IQR 2.31-4.93); controls Mdn 2.16 (IQR 1.50-2.65), p = 0.02). The latter is present despite an almost two to three fold decrease (p < 0.01) in caspase-1 activity, a facilitating enzyme of IL-1b production, within circulating immune cells.

    Conclusion: Patients with colorectal cancer displayed insulin resistance and higher levels of plasma IL-1b and IL-6, in comparison to matched healthy controls. The finding of a seemingly disconnect between inflammasome (caspase-1) activity and plasma levels of key pro-inflammatory cytokines in cancer patients may suggest that, in parallel to dysregulated immune cells, tumour-driven inflammatory pathways also are in effect.

  • 41.
    Baban, Bayar
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Inflammasome activation, colonic cancer and glucose metabolism2016In: Clinical Nutrition ESPEN, E-ISSN 2405-4577, Vol. 12, article id e37Article in journal (Refereed)
    Abstract [en]

    Objectives: To study the association between inflammasome activation (a potent initiator of inflammation acting via caspase-1 and maturation of interleukin-1β), colonic cancer and glucose metabolism.

    Methods: Five patients with colon cancer and ten matched controls without cancer were measured for insulin sensitivity using the hyperinsulinemic euglycemic clamp. For detection of inflammasome activation the caspase-1 activity, determined by detecting FLICA using flow cytometry, was measured in both monocytes and granulocytes at the start of, and at 120 minutes into the clamp. Descriptive and analytical statistics were performed using nonparametric methods by SPSS.

    Results: There was no difference in levels of insulin sensitivity between the two groups (p=0.09). The cancer patients had significantly lower levels of caspase-1 both in monocytes (p<0.05) and granulocytes (p<0.05) compared with the controls. However both patients and controls had significantly higher levels of both mono- and granulocyte caspase-1 activity at 120 minutes into the clamp as compared to at start (p<0.05). Patients showed an overall higher relative increase in caspase-1 during the clamp, however this finding did not reach statistical significance (monocytes; p=0.27, granulocytes; p=0.22).

  • 42.
    Back, Erik
    et al.
    Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.
    Häggström, Jenny
    Department of Statistics, Umeå School of Business, Economics and Statistics, Umeå University, Umeå, Sweden.
    Holmgren, Klas
    Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.
    Haapamäki, Markku M.
    Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.
    Matthiessen, Peter
    Örebro University, School of Medical Sciences. Department of Surgery.
    Rutegård, Jörgen
    Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.
    Rutegård, Martin
    Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
    Author response to: Permanent stoma prediction after anterior resection for rectal cancer: risk prediction scoring using preoperative variables2022In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 109, no 2, article id e40Article in journal (Other academic)
  • 43.
    Backman, Christian
    et al.
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Johansson, Ulf
    University Health Care Research Center, Örebro University Hospital, Örebro, Sweden.
    Hellgren, Mikko
    Örebro University, School of Medical Sciences. Örebro University Hospital. University Health Care Research Center.
    Knowledge in and support for standardised cancer care pathways among general practitioners and other physicians in Sweden2021In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 39, no 1, p. 17-22Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the expertise in and support of the implemented new method of cancer patient pathways (CPPs) among general practitioners (GPs) and other working physicians in Sweden.

    DESIGN: A survey in the form of 10 knowledge-based multiple-choice questions (MCQs) and two general questions about CPPs.

    SETTING: Physicians from two different regions in Sweden answered the survey between December 2018 and January 2019.

    SUBJECTS: GPs in primary care compared to other physicians. 155 participants completed the survey and the response rate was 65%.

    MAIN OUTCOME MEASURES: Physicians' self-estimated knowledge of CPPs in general and opinion of CPPs effect on mortality and morbidity. Their scores on 10 different MCQs. Scores were analysed in subgroups related to the physicians medical specialty and experience.

    RESULTS: A majority of all physicians (63%) felt that they had insufficient knowledge regarding the procedure of CPPs, and the average score from the MCQs was 3.8 out of 10 correct answers. The results showed that GPs performed significantly better than specialists from other disciplines.

    CONCLUSIONS: The low percentage of correctly answered MCQs shows that the information about the entry part of CPPs needs to be improved. The study demonstrates a support for the system with CPPs because the physicians believed in its' positive effects on morbidity and mortality, however, it also reveals a lack of self-estimated knowledge about the system with CPPs.

    Key points

    Cancer patient pathways (CPPs) is a newly implemented method in Sweden that aims to equalize cancer care and reduce the time to diagnosis and treatment.

    • The proficiency of when to initiate an investigation according to a specific CPP seems low. General practitioners (GPs) performed significantly better on knowledge-based questions than other specialists did.
    • Physicians rated their knowledge as insufficient regarding the procedure of CPPs.
    • A clear majority of physicians believed that CPPs promotes a lower mortality and morbidity in cancer.
  • 44. Bahmanyar, S.
    et al.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Hillert, J.
    Ekbom, A.
    Olsson, T.
    Cancer risk among patients with multiple sclerosis and their parents2009In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 72, no 13, p. 1170-1177Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. METHODS: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. RESULTS: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. CONCLUSIONS: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible).

  • 45.
    Banaem, Hossein Yousefi
    et al.
    Tehran University of Medical Science, Tehran, Iran.
    Ahmadian, Alireza
    Tehran University of Medical Science, Tehran, Iran.
    Saberi, Hooshangh
    Tehran University of Medical Science, Tehran, Iran.
    Daneshmehr, Alireza
    University of Tehran, Tehran, Iran.
    Khodadad, Davood
    Tehran University of Medical Science, Tehran, Iran.
    Brain tumor modeling: glioma growth and interaction with chemotherapy2011In: International Conference on Graphic and Image Processing (ICGIP) / [ed] Yi Xie & Yanjun Zheng, SPIE - International Society for Optical Engineering, 2011, Vol. 8285, article id 82851MConference paper (Refereed)
    Abstract [en]

    In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

  • 46.
    Banerjee, Antara
    et al.
    Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), 603103, Kelambakkam, Chennai, India.
    Deka, Dikshita
    Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), 603103, Kelambakkam, Chennai, India.
    Muralikumar, Makalakshmi
    Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), 603103, Kelambakkam, Chennai, India.
    Sun-Zhang, Alexander
    Department of Oncology-Pathology, Karolinska Institute, 171 77, Solna, Sweden.
    Bisgin, Atil
    InfoGenom R&D Laboratories, Cukurova Technopolis, Adana, Turkey; Medical Genetics Department of Medical Faculty, Cukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center), Cukurova University, Adana, Turkey.
    Christopher, Cynthia
    Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), 603103, Kelambakkam, Chennai, India.
    Zhang, Hong
    Örebro University, School of Medical Sciences.
    Sun, Xiao-Feng
    Division of Oncology, Department of Biomedical and Clinical Sciences, Linköping University, 581 83, Linköping, Sweden.
    Pathak, Surajit
    Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), 603103, Kelambakkam, Chennai, India.
    A concise review on miRNAs as regulators of colon cancer stem cells and associated signalling pathways2023In: Clinical and Translational Oncology, ISSN 1699-048X, E-ISSN 1699-3055, Vol. 25, p. 3345-3356Article, review/survey (Refereed)
    Abstract [en]

    Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes.

  • 47.
    Bartnikowska, Agnieszka
    et al.
    Radiotherapy Department, Oncology Center, Opole, Poland; Institute of Physics, Opole University, Opole, Poland.
    Cieślik, Grzegorz
    Radiotherapy Department, Oncology Center, Opole, Poland.
    Młodzik, Mateusz
    Radiotherapy Department, Oncology Center, Opole, Poland.
    Garcia-Argibay, Miguel
    Örebro University, School of Medical Sciences.
    Comparison of pre-treatment and in-vivo dosimetry for advanced radiotherapy of prostate cancer2022In: Reports of Practical Oncology and Radiotherapy, ISSN 1507-1367, Vol. 27, no 2, p. 189-197Article in journal (Refereed)
    Abstract [en]

    The usage of advanced radiotherapy techniques requires validation of a previously calculated dose with the precise delivery with a linear accelerator. This study aimed to review and evaluate new verification methods of dose distribution. Moreover, our purpose was to define an internal protocol of acceptance for in-vivo measurements of dose distribution. This study included 43 treatment plans of prostate cancer calculated using the Monte Carlo algorithm. all plans were delivered using the Volumetric Modulated arc Therapy (VMaT) technique of advanced radiotherapy by the linear accelerator elekta VersahD. The dose distribution was verified using: MatriXX, iViewDose, and in-vivo measurements. The verification also included recalculation of fluence maps of quality assurance plans in another independent algorithm. The acceptance criterion of 95% points of dose in agreement was found for pre-treatment verification using MatriXX; the average γ value was 99.09 ± 0.93 (sD) and 99.64 ± 0.35 (sD) for recalculation in the collapse cone algorithm. Moreover, using the second algorithm in the verification process showed a positive correlation ρ = 0.58, p < 0.001. however, verification using iViewDose in a phantom and in-vivo did not meet this γ-pass rate.Evaluation of gamma values for in-vivo measurements utilizing iViewDose software was helpful to establish an internal dosimetry protocol for prostate cancer treatments. We assumed value at a minimum of 50% points of the dose in agreement with the 3%/3 mm criterion as an acceptable compliance level. The recalculated dose distribution of Qa plans in regard to the collapse cone algorithm in the other treatment planning system can be used as a pre-treatment verification method used by a medical physicist in their daily work. The effectiveness of use in iViewDose software, as a pre-treatment tool, is still debatable, unlike the MatriXX device.

  • 48.
    Batyrbekova, Nurgul
    et al.
    Department of Biostatistics, Scandinavian Development Services AB.
    Aleman, Soo
    Karolinska Institute, Stockholm, Sweden.
    Lybeck, Charlotte
    Örebro University, School of Medical Sciences. Infectious Diseases.
    Montgomery, Scott
    Örebro University, School of Medical Sciences.
    Duberg, Ann-Sofi
    Örebro University, School of Medical Sciences.
    Hepatitis C virus infection and the temporal trends in the risk of liver cancer: a national register-based cohort study in Sweden2020In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, no 1, p. 63-70Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In many countries, including Sweden, the birth cohorts with the highest prevalence of hepatitis C virus (HCV) infection have now reached the ages with high risk of primary liver cancer (PLC). The aims were to investigate the temporal trends in PLC incidence and the relative risks of PLC among people diagnosed with HCV-infection between 1990 and 2015.

    METHODS: The HCV-cohort (n: 52,853) was compared with a matched non-HCV comparison-cohort (n: 523,649). Both the Cancer (CR) and Death registers (DR) were used for follow-up. The crude and age-standardised PLC incidence rates were calculated. The relative risk was estimated as standardized incidence ratios (SIR) and as hazard ratios (HR) using stratified Cox hazards regression.

    RESULTS: There were 1,609 with PLC-diagnosis in the HCV-cohort, the annual number increased continuously with the crude incidence rate reaching 4.56 per 1,000 person-years in 2013, while remaining low and stable in the comparison-cohort. In the HCV-cohort, the age-standardised PLC incidence rates per 1,000 person-years remained relatively constant at 2.64 (95% CI: 1.54, 3.75) in 2000 and 3.31 (2.51, 4.12) in 2014. The highest SIR was 73 (65.9, 79.5) among those infected for 35-40 years; and the highest HR was 65.9 (55.9, 77.6) for men and 62.2 (31.9, 121.1) for women.

    CONCLUSIONS: There was a considerable increase in PLC-incidence over time and an extremely high relative risk in the population with HCV-infection for more than 35 years.

    IMPACT: The national HCV-associated PLC-incidence should be monitored in future studies to evaluate the effect of DAA-treatment.

  • 49.
    Behrens, Thomas
    et al.
    Bremen Institute of Prevention Research & Social Medicine, Bremen, Germany; Institute of Prevention & Occupational Medicine of German Social Accidents Insurance, Bochum, Germany.
    Lynge, Elsebeth
    Inst Publ Hlth, Univ Copenhagen, Copenhagen, Denmark..
    Cree, Ian
    Inst Ophthalmol, University College London (UCL), London, England.
    Lutz, Jean-Michel
    National Institute for Cancer Epidemiology and Registration (NICER), Univ Zurich, Zurich, Switzerland.
    Eriksson, Mikael
    Dept of Oncology, Lund University Hospital, Lund, Sweden..
    Guenel, Pascal
    Centre de recherche en épidémiologie et santé des populations (CESP), French National Institute of Health and Medical Research (INSERM), Villejuif, France; Univ Paris Sud, Villejuif, France.
    Merletti, Franco
    Cancer Epidemiology Unit, Univ Turin, Piemonte, Italy; ll Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica (CPO), Piemonte, Italy.
    Morales-Suarez-Varela, Maria
    Dept of Prevention Medicine, Unit Public Health & Environmental Care, University Valencia, Valencia, Spain; CIBER Act Epidemiology & Public Health, Res Grp CIBER CB06, Valencia, Spain; Center Public Health Research CSISP, Valencia, Spain.
    Afonso, Noemia
    Med Oncol Serv, Inst Portugues Oncol Francisco Gentil, Oporto, Portugal.
    Stengrevics, Aivars
    Latvia Canc Registry, Riga, Latvia.
    Fevotte, Joelle
    Umrestte UCB Lyon 1 InVS Inrets, Lyon, France.
    Sabroe, Svend
    Dept Epidemiol, Univ Aarhus, Aarhus, Denmark..
    Llopis-Gonzalez, Agustin
    Dept Prevent Med, Unit Publ Hlth & Environm Care, Univ Valencia, Valencia, Spain; CIBER Act Epidemiol & Publ Hlth, Res Grp CIBER CB06, Valencia, Spain.
    Gorini, Giuseppe
    Environm & Occupat Epidemiol Unit, ISPO Canc Prevent & Res Inst, Florence, Italy.
    Hardell, Lennart
    Department of Oncology, Örebro University Hospital, Region Örebro län, Örebro, Sweden.
    Stang, Andreas
    Inst Clin Epidemiol, Univ Halle Wittenberg, Halle, Germany; Inst Med Informat Biometry & Epidemiol, Univ Duisburg Essen, Essen, Germany..
    Ahrens, Wolfgang
    Bremen Inst Prevent Res & Social Med, Bremen, Germany; Inst Med Informat Biometry & Epidemiol, Univ Duisburg Essen, Essen, Germany.
    Pesticide exposure in farming and forestry and the risk of uveal melanoma2012In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 23, no 1, p. 141-151Article in journal (Refereed)
    Abstract [en]

    Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries.

    Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression analyses and adjusted for several potential confounders.

    293 case and 3,198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilizers in forestry (OR = 8.93; 95% CI 1.73-42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye color.

    Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures.

  • 50.
    Bekele, Maheteme
    et al.
    St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.
    Jibril, Aisha
    St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.
    Seifu, Daniel
    Addis Ababa University, Addis Ababa, Ethiopia.
    Abebe, Markos
    Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
    Bekele, Abebe
    Addis Ababa University, Addis Ababa, Ethiopia.
    Tigneh, Wondemagegnhu
    Addis Ababa University, Addis Ababa, Ethiopia.
    Bokretsion, Yonas
    Addis Ababa University, Addis Ababa, Ethiopia.
    Karlsson, Christina
    Örebro University, School of Health Sciences.
    Karlsson, Mats
    Örebro University, School of Medical Sciences.
    Martini, Rachel
    Weill Cornell Medical College, New York NY, USA.
    Elemento, Olivier
    Weill Cornell Medical College, New York NY, USA.
    Yates, Clayton
    Tuskegee University, Tuskegee AL, USA.
    Ginter, Paula
    Weill Cornell Medical College, New York NY, USA.
    Newman, Lisa
    Weill Cornell Medical College, New York NY, USA.
    Davis, Melissa
    Weill Cornell Medical College, New York NY, USA.
    Gebregzabher, Endale Hadgu
    St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.
    Tumor and immune cell profiling in breast cancer using highly multiplexed imaging mass cytometry single-cell technology demonstrates tumor heterogeneity and immune phenotypic abnormality in Ethiopian women2020In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 80, no 21 Suppl., article id PO-087Article in journal (Other academic)
    Abstract [en]

    Background: Tumor heterogeneity represents a complex challenge to cancer treatment, disease recurrence, and patient survival. Imaging mass cytometry (IMC) is an emerging proteomic tool for cancer profiling in tumor tissue samples. IMC enables digital image analysis by multiplexed immunostaining of cells and proteins within tissue and preserves spatial relations within tumor environment. We have applied IMC based approach to study the heterogeneity of invasive breast carcinoma protein expression pattern in formalin fixed paraffin embedded tissues.

    Methods: A total of 10 region of interest (ROI) derived from 5 patients with primary invasive breast carcinoma representing three molecular subclasses (HR+/HER2-,HER2+/HR- and TNBC) were stained with a 30-marker IMC metal labeled antibody panel (α-SMA, EGFR, p53, CD33, CD16, CD163, CD11b, PDL1, CD31, CD45, D44,Vimentin, FoxP3, CD4, ECadherin, CD68, CD20, CD8a, Cytokeratin7, PD1, GranzymeB, Ki67, ColTypeI, CD3, CD45RO, HLADR, DARC & CD11c). Tissue imaging was done by quantifying the abundance of bound antibody with a Hyperion IMC. MCD Viewer was used for visualization purpose and to export raw 16-bit tiff images for segmentation on CellProfiler. Segmentation masks were combined with the individual tiff files to extract single-cell information from each individual image. HistoCAT was applied to perform unbiased clustering of cell populations using the PhenoGraph algorithm and clustered cell populations was overlaid on t-SNE plot. The relative marker expression was used to generate heat-maps and each cluster was manually assigned a phenotype based on its expression profile.

    Results: The t-SNE generated from each ROI revealed different distinct cell populations and we report the presence of diverse tumor and immune cell populations in our samples. The (min, max) number of PhenoGraph clustered tumor cell populations in HR+/HER2-, HER2+ and TNBC Cases were (5,8) (7,9) and (5,7) respectively. Similarly, the (min, max) number of PhenoGraph clustered immune cell populations in HR+/HER2-, HER2+ and TNBC Cases were (5,8) (7,9) and (5,7) respectively. We also document the presence of inter and intra-tumor heterogeniety in expression of PD1 and PDL1 in all the tumor subtypes studied. Additionally, we report a phenotypic abnormality in the immune cell populations identified with dual or triple markers expression of the canonical CD antigens of T-Cells, B-Cells and macrophages.

    Conclusion: The current study demonstrates high-dimensional visualization with the simultaneous analysis of epithelial, immune, and stromal components using IMC can be used to explore cell populations in tumor tissue to quantify tumor heterogeneity or identification of novel clustering patterns that has potential for translational research and clinical practice. Significance: This study presents the potential of Imaging Mass Cytometry and single cell analysis algorithms in multiplex high throughput tumor tissue studies.

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