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1.
  • Jonsson, Pär, et al. (författare)
  • Constrained randomization and multivariate effect projections improve information extraction and biomarker pattern discovery in metabolomics studies involving dependent samples
  • 2015
  • Ingår i: Metabolomics. - Springer. - 1573-3882. ; 11:6, s. 1667-1678
  • Tidskriftsartikel (refereegranskat)abstract
    • Analytical drift is a major source of bias in mass spectrometry based metabolomics confounding interpretation and biomarker detection. So far, standard protocols for sample and data analysis have not been able to fully resolve this. We present a combined approach for minimizing the influence of analytical drift on multivariate comparisons of matched or dependent samples in mass spectrometry based metabolomics studies. The approach is building on a randomization procedure for sample run order, constrained to independent randomizations between and within dependent sample pairs (e.g. pre/post intervention). This is followed by a novel multivariate statistical analysis strategy allowing paired or dependent analyses of individual effects named OPLS-effect projections (OPLS-EP). We show, using simulated data that OPLS-EP gives improved interpretation over existing methods and that constrained randomization of sample run order in combination with an appropriate dependent statistical test increase the accuracy and sensitivity and decrease the false omission rate in biomarker detection. We verify these findings and prove the strength of the suggested approach in a clinical data set consisting of LC/MS data of blood plasma samples from patients before and after radical prostatectomy. Here OPLS-EP compared to traditional (independent) OPLS-discriminant analysis (OPLS-DA) on constrained randomized data gives a less complex model (3 versus 5 components) as well a higher predictive ability (Q2 = 0.80 versus Q2 = 0.55). We explain this by showing that paired statistical analysis detects 37 unique significant metabolites that were masked for the independent test due to bias, including analytical drift and inter-individual variation.
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3.
  • Lundström, Karl-Johan, et al. (författare)
  • Small bowel obstruction and abdominal pain after robotic versus open radical prostatectomy
  • 2016
  • Ingår i: Scandinavian journal of urology. - 2168-1805 .- 2168-1813. ; 50:3, s. 155-159
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to examine whether intraperitoneal robot-assisted surgery leads to small bowel obstruction (SBO), possibly caused by the formation of intra-abdominal adhesions.Materials and methods: In total, 7256 men treated by intraperitoneal robot-assisted radical prostatectomy (RARP) and 9787 men treated by retropubic radical prostatectomy (RRP) in 2005-2012 were identified in the Prostate Cancer data Base Sweden (PCBaSe). Multivariable Cox proportional hazards models were used to calculate the risk of readmission for SBO, SBO-related surgery and admissions due to abdominal pain up to 5 years postoperatively.Results: During the first postoperative year, the risk of readmission for SBO was higher after RARP than after RRP [hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.14-3.25] but after 5 years there was no significant difference (HR 1.28, 95% CI 0.86-1.91), and there was no difference in the risk of SBO surgery during any period. The risk of admission for abdominal pain was significantly increased after RARP during the first year (HR 2.24, 95% CI 1.50-3.33) but not after 5 years (HR 1.23, 95% CI 0.92-1.63).Conclusion: Intraperitoneal RARP had an increased risk of SBO and abdominal pain in the short term during the first year, but not in the long term, compared to RRP.
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4.
  • Nilsson, Hanna, et al. (författare)
  • Incidence of groin hernia repair after radical prostatectomy : a population-based nationwide study
  • 2014
  • Ingår i: Annals of Surgery. - 0003-4932. ; 259:6, s. 1223-1227
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the incidence of groin hernia repair after radical prostatectomy for prostate cancer compared with the incidence in a control population without prostate cancer in a nationwide, population-based study.Background: Recent reports indicate an increase in the incidence of groin hernia repair after radical prostatectomy. Inadequate knowledge of the incidence of groin hernia in the general population makes this information hard to interpret.Methods: Information was retrieved from the Prostate Cancer Database (PCBaSe) and Swedish Hernia Register for events between 1998 and 2010. The incidence of groin hernia surgery was calculated for a group of men treated with radical prostatectomy (open and minimally invasive) and for a group treated with radiation therapy, and these were compared with the incidence in a control cohort of men matched for age and county of residence. Multivariate analysis was used to assess the hazard ratio (HR) of groin hernia repair according to age, tumor risk category, and Charlson Comorbidity Index.Results: A total of 28,608 cases and 105,422 controls were included in the study. Men treated with radical prostatectomy and radiation therapy had a significantly higher incidence of groin hernia repair than the control cohort: HR: 3.95 (95% confidence interval: 3.70-4.21) for retropubic prostatectomy, HR: 3.37 (95% confidence interval: 2.95-3.87) for minimally invasive prostatectomy, and HR: 1.84 (95% confidence interval: 1.66-2.04) for radiation therapy.Conclusions: An almost 4-fold increase in groin hernia repair was observed after radical prostatectomy compared with controls, and men who received radiation therapy had an almost 2-fold increase in incidence. As well as postoperative changes in the abdominal wall, increased vigilance for groin hernia seems to be important for the increased incidence of groin hernia repair seen after radical prostatectomy or radiation therapy for prostate cancer.
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5.
  • Adam, Meike, et al. (författare)
  • Functional Outcomes and Quality of Life After Radical Prostatectomy Only Versus a Combination of Prostatectomy with Radiation and Hormonal Therapy
  • 2017
  • Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 71:3, s. 330-336
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on patient-reported outcomes following multimodal therapy.Objective: To assess the impact of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency, and quality of life (QoL) after RP.Design, setting, and participants: Among 13 150 men who underwent RP from 1992 to 2013, 905 received RP + RT, 407 RP + ADT and 688 RP + RT + ADT.Outcome measurements and statistical analyses: Urinary function, sexual function, and overall QoL were evaluated annually using self-administered validated questionnaires. Propensity score-matched and bootstrap analyses were performed, and the distributions for all functional outcomes were analyzed as a function of time after RP.Results and limitations: Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (> 3 pads/24 h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received.Conclusions: Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment.Patient summary: Men with high-risk disease choosing surgery upfront should be counseled on the potential need for additional radiation and or androgen deprivation, and the potential net impairment of functional outcomes arising from multimodal treatment.
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6.
  • Adamo, Hanibal, et al. (författare)
  • Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
  • 2019
  • Ingår i: The Prostate. - WILEY. - 0270-4137 .- 1097-0045. ; 79:5, s. 435-445
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.
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7.
  • Adamo, Hanibal, et al. (författare)
  • Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of a tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ). To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, with distance to the tumor, and with tumor cell metastatic capacity.In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and a favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, the presence of metastases at diagnosis, and poor outcome. 
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8.
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9.
  • Adolfsson, Jan, et al. (författare)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 - Data from the national prostate cancer register in Sweden
  • 2007
  • Ingår i: Scandinavian Journal of Urology and Nephrology1967-01-01+01:002013-01-01+01:00. - Taylor & Francis. - 0036-5599. ; 41:6, s. 456-477
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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10.
  • Ahn, Jiyoung, et al. (författare)
  • Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3).
  • 2009
  • Ingår i: Human molecular genetics. - 1460-2083. ; 18:19, s. 3749-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17beta-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.
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