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  • 1.
    Adamo, Hanibal Hani
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Hammarsten, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Hägglöf, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Scherdin, Tove Dahl
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Egevad, Lars
    Stattin, Paer
    Halin Bergström, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome2019Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, nr 5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 2. Ahlén Bergman, Emma
    et al.
    Hartana, Ciputra Adijaya
    Johansson, Markus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden..
    Linton, Ludvig B
    Berglund, Sofia
    Hyllienmark, Martin
    Lundgren, Christian
    Holmström, Benny
    Palmqvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgery, Urology Section, Östersund County Hospital, Östersund, Sweden.
    Hansson, Johan
    Alamdari, Farhood
    Huge, Ylva
    Aljabery, Firas
    Riklund, Katrine
    Winerdal, Malin E
    Krantz, David
    Zirakzadeh, Ali A .
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Unit of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Marits, Per
    Sjöholm, Louise K
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Winqvist, Ola
    Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients.2018Ingår i: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, artikel-id 102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.

    RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.

    CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.

  • 3. Akre, Olof
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Lambe, Mats
    Bratt, Ola
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Mortality among men with locally advanced prostate cancer managed with noncurative intent: a nationwide study in PCBaSe Sweden2011Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, nr 3, s. 554-563Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 4. Albiges, Laurence
    et al.
    Powles, Tom
    Staehlerr, Michael
    Bensalan, Karim
    Giles, Rachel H.
    Horag, Milan
    Kuczyk, Markus A.
    Lam, Thomas B.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Marconi, Lorenzo
    Merseburger, Axel S.
    Volpe, Alessandro
    Abu-Ghanem, Yasmin
    Dabestani, Saeed
    Fernndez-Pello, Sergio
    Hofmann, Fabian
    Kuusk, Teele
    Tahbaz, Rana
    Bex, Axel
    Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 2, s. 151-156Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies.

    Patient summary: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naive). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria.

  • 5. Anand, Aseem
    et al.
    Morris, Michael J.
    Larson, Steven M.
    Minarik, David
    Josefsson, Andreas
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Helgstrand, John T.
    Oturai, Peter S.
    Edenbrandt, Lars
    Røder, Martin Andreas
    Bjartell, Anders
    Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide2016Ingår i: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 6, artikel-id 23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide.

    METHODS: Retrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy. Automated BSI, prostate-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall's tau (τ) was used to assess the correlation of BSI with other blood-based biomarkers. Concordance index (C-index) was used to evaluate the discriminating strength of automated BSI in predicting OS.

    RESULTS: Eighty mCRPC patients with baseline bone scans were included in the study. There was a weak correlation of automated BSI with PSA (τ = 0.30), with HgB (τ = -0.17), and with ALP (τ = 0.56). At baseline, the automated BSI was observed to be predictive of OS (C-index 0.72, standard error (SE) 0.03). Adding automated BSI to the blood-based model significantly improved the C-index from 0.67 to 0.72, p = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change alone (C-index 0.73), p = 0.041.

    CONCLUSIONS: The upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated with enzalutamide.

  • 6.
    Asad, Danna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    A prospective evaluation of visual staging by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 7.
    Asklund, Ina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Nyström, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sjöström, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Umefjord, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Samuelsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Mobile app for treatment of stress urinary incontinence: a randomized controlled trial2017Ingår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 36, nr 5, s. 1369-1376Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To evaluate the effect of a mobile app treatment for stress urinary incontinence (SUI) in women.

    METHODS: Randomized controlled trial, conducted 2013-2014 in Sweden. Community-dwelling adult women with ≥1 SUI episode/week recruited through our website and randomized to app treatment (n = 62) or control group (postponed treatment, n = 61). One participant from each group was lost to follow-up. Intervention was the mobile app Tät(®) with a treatment program focused on pelvic floor muscle training (PFMT), and information about SUI and lifestyle factors. Primary outcomes, 3 months after randomization: symptom severity (International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form [ICIQ-UI SF]); and condition-specific quality of life (ICIQ Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]).

    RESULTS: One hundred and twenty-three women were included (mean age 44.7), with moderate/severe SUI (97.5%, 120/123), mean ICIQ-UI SF score 11.1 (SD 2.8) and mean ICIQ-LUTSqol score 34.4 (SD 6.1) at baseline. At follow-up, the app group reported improvements in symptom severity (mean ICIQ-UI SF score reduction: 3.9, 95% confidence interval 3.0-4.7) and condition-specific quality of life (mean ICIQ-LUTSqol score reduction: 4.8, 3.4-6.2) and the groups were significantly different (mean ICIQ-UI SF score difference: -3.2, -4.3to -2.1; mean ICIQ-LUTSqol score difference: -4.6, -7.8 to -1.4). In the app group, 98.4% (60/61) performed PFMT at follow-up, and 41.0% (25/61) performed it daily.

    CONCLUSIONS: The mobile app treatment was effective for women with SUI and yielded clinically relevant improvements. This app may increase access to first-line treatment and adherence to PFMT.

  • 8. Assel, Melissa
    et al.
    Dahlin, Anders
    Ulmert, David
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Lilja, Hans
    Vickers, Andrew J.
    Association Between Lead Time and Prostate Cancer Grade: Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 6, s. 961-967Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening. Objective: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time. Design, setting, and participants: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3-10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available. Outcome measurements and statistical analysis: Multivariable logistic regression was used to predict high-grade (Gleason grade group >= 2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age. Results and limitations: The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10-1.16; p < 0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28-0.64; p < 0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation. Conclusions: Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa. Patient summary: Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis.

  • 9.
    Bandhede, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    The recurrence rate of urinary bladder cancer (TaG3- and carcinoma in situ tumors) in relation to lead times from first documented symptom to the first trans-urethral resection of bladder2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 10. Bekema, Hendrika J.
    et al.
    MacLennan, Steven
    Imamura, Mari
    Lam, Thomas B. L.
    Stewart, Fiona
    Scott, Neil
    MacLennan, Graeme
    McClinton, Sam
    Griffiths, T. R. Leyshon
    Skolarikos, Andreas
    MacLennan, Sara J.
    Sylvester, Richard
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    N'Dow, James
    Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma2013Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 64, nr 5, s. 799-810Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Context: Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3-T4N0M0. Objective: To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND.

    Evidence acquisition: Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

    Evidence synthesis: A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes.

    Conclusions: There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3-T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.

  • 11. Bergerot, Cristiane Decat
    et al.
    Battle, Dena
    Bergerot, Paulo Gustavo
    Dizman, Nazli
    Jonasch, Eric
    Hammers, Hans J.
    George, Daniel J.
    Bex, Axel
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Pal, Sumanta Kumar
    Staehler, Michael D.
    Sources of Frustration Among Patients Diagnosed With Renal Cell Carcinoma2019Ingår i: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 9, artikel-id 11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite numerous therapeutic advances in renal cell carcinoma (RCC), little is known about patients' perspectives on cancer care. An international survey was conducted to identify points of frustration associated with cancer care reported by patients with RCC. Data were obtained from an online survey, conducted from April 1 to June 15, 2017, through social media and patient networking platforms. This survey obtained baseline demographic, clinicopathologic, and treatment-related information. Open-ended questions accessed sources of frustration in cancer-related care and patients' suggestions for amelioration. Responses were categorized and reviewed by independent reviewers. A qualitative analysis was performed and the Kruskal-Wallis test was used to define associations between baseline characteristics and sources of frustration. Among 450 patients surveyed, 71.5% reported sources of frustration, classified as either emotional (48.4%) or practical (23.1%). The most common were fear of recurrence/progression (15.8%), distrust of their cancer care system (12.9%), and lack of appropriate information (9.8%). Female gender and non-clear cell histology were associated with both types of frustration, and older age was linked to practical sources of frustration. Patients suggested solutions included greater compassion among health care practitioners (20.7%), better access to information (15.1%) and research to improve their chances of being cured (14.7%). Sources of frustration related to emotional and practical causes were identified amongst patients with RCC. Certain demographic and clinical characteristics were associated with more sources of frustration. This study provides the first characterization of specific ways to improve the patient experience by addressing common frustrations.

  • 12. Berglund, Anders
    et al.
    Garmo, Hans
    Tishelman, Carol
    Holmberg, Lars
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lambe, Mats
    Comorbidity, treatment and mortality: a population based cohort study of prostate cancer in PCBaSe Sweden2011Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 185, nr 3, s. 833-840Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose

    We examined associations among comorbidity, treatment decisions and mortality in patients with prostate cancer.

    Materials and Methods

    A total of 77,536 men diagnosed with prostate cancer between 1997 and 2006 were identified in PCBaSe Sweden from the National Prostate Cancer Register of Sweden. Logistic, Cox and competing risk regression were used to assess associations among Charlson comorbidity index, treatment and mortality. The Charlson comorbidity index was categorized into no (0), mild (1) and severe comorbidity (2+).

    Results

    In men with low risk prostate cancer 5,975 of the 13,245 (45.1%) patients without comorbidity underwent radical prostatectomy compared to 256 of the 1,399 (18.9%) men with severe comorbidity. Following adjustment for age and period of diagnosis, radical prostatectomy was less likely to be offered to men with severe comorbidity (OR 0.48, 95% CI 0.41–0.55). In men with high risk prostate cancer, radiotherapy was more common (range 7.7% to 21.3%) than radical prostatectomy (range 3.0% to 11.2%) regardless of comorbidity burden. All cause and competing cause but not prostate cancer specific mortality were increased in men with severe comorbidity (all cause HR 1.99, 95% CI 1.93–2.05; competing cause sHR 2.66, 95% CI 2.56–2.78; prostate cancer specific sHR 0.98, 95% CI 0.93–1.03). The cumulative probability of prostate cancer death given no death from competing causes was significantly higher in men with severe comorbidity in all risk groups (p <0.01).

    Conclusions

    Comorbidity affects treatment choices, and is associated with all cause, competing cause and conditional prostate cancer specific mortality. An increased conditional prostate cancer specific mortality in men with severe comorbidity may reflect less aggressive treatment, impaired tumor defense, lifestyle factors and poor general health behavior.

  • 13.
    Berglund, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Eisemann, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lalos, Othon
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Personality characteristics of-A stress incontinent women: a pilot study1994Ingår i: Journal of Psychosomatic Obstetrics and Gynaecology, ISSN 0167-482X, E-ISSN 1743-8942, Vol. 15, nr 3, s. 165-170Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Personality traits were assessed by means of the Karolinska Scale of Personality (KSP) and the Eysenck Personality Inventory (EPI) in 45 genuine stress incontinent women and compared with a reference group of continent women in order to investigate the possible impact of this chronic condition on the personality. Women with stress incontinence of long duration scored significantly higher than controls on the KSP scales somatic anxiety, psychic anxiety, psychasthenia and suspicion and on the EPI lie-scale. These findings point to the importance of personality factors in chronic conditions such as urinary incontinence.

  • 14.
    Berglund, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Fugl-Meyer, Kerstin S.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Some Sexological Characteristics of Stress Incontinent Women1996Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 30, nr 3, s. 207-212Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Forty-four women with stress urinary incontinence (SUI) were interviewed in order to investigate sexual activities, sexual function and satisfaction one month before and one year after either one of two possible surgical interventions. The findings were related to sexual response cycle, size of urinary leakage, duration of incontinence and depression. There was no significant difference in sexual activity before and after surgery. One or two sexual dysfunctions within the desire, excitement, orgasmic and resolution phases were reported by the majority both before and after intervention independently of surgical method. Neither the magnitude of the leakage nor the duration of SUI influenced the sexual experiences significantly while continence after surgery promoted sexual desire. The discrepances between the prevalence of sexual dysfunctions and the relatively high level of sexual satisfaction as well as the non-influencing parameters indicate the complexity of human sexuality.

  • 15.
    Berglund, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lalos, Othon
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    The pre- and postsurgical nursing of women with stress incontinence1996Ingår i: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 23, nr 3, s. 502-511Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the present study was to evaluate subjective and objective methods used for the investigation of stress urinary incontinence (SUI) and to compare the outcome of two different surgical techniques regarding cure rate, postoperative nursing, bladder drainage and postoperative pain relief. The study included 45 women with SUI, randomized either to retropubic urethrocystopexy (n = 30) or pubococcygeal repair (n = 15). The assessment included medical history, gynaecological examination, urine analysis and culture, residual urine, pad test, frequency-continence charts, water urethrocystoscopy, continence test, and cystometry with micturition analysis. Moreover, Beck's Depression Inventory and the Eysenck Personality Inventory were used before surgery. One year after surgery no significant difference in subjective cure rate was found between the two surgical methods (73% vs. 80%, respectively). According to pad tests, 67% of the women in the urethrocystopexy group and 47% in the pubococcygeal repair group had ceased to leak urine. The bladder volume increased significantly in both groups. Sixty-three per cent of the women in the urethrocystopexy and 33% in the pubococcygeal repair group experienced severe to very severe postoperative pain. In these groups, significantly more dysphoric women were found as compared with the group of women with less postoperative pain. Furthermore, the women with more severe pain scored higher on the neuroticism scale. These findings indicate the importance of personality factors in the treatment and nursing of women with SUI.

  • 16.
    Bergman, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Studies on patients with ileal conduit diversion with special regard to renal infection1978Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The conditions for retrograde transport of urine and thereby bacteria in the urinary svstem of diverted patients (device and urinary tract) were studied with roentgeno­logical technigue. Back-flow from the urinary collecting device into the conduit occurred in a fifth of those patients who had a flat stoma. A nipple stoma of at least 2 cm height resisted back-flow better than any flat stoma.

    Ureteral reflux occurred to approximately 30 % of the ureters, both in the supine and erect body positions.The intraluminal pressure in the conduit was "low"

    (^12 cm H2O) in approximately 30 % when reflux occurred.

    The autopsy study showed a higher frequency of renal infections in diverted patients than in non-diverted controls. 5 of 11 patients who died more than 2 months after diversion, and without cancer at autopsy, were attributed to death from renal infection.

    There was a relationship between urographical abnormalities, recognized as associated with pyelonephritis, and raised serum antibody titers against E.coli and/or P.mirabilis.

    Most of the ”not normal" renal units deteriorated after the diversion operation.

    The variable "kidney area" was found to be "small" in a higher frequency after a long postoperative period than after a short one.

    Raised -serum antibody titers occurred in 35 % of the patients and were correlated to growth of the corresponding bacteria (E.coli and P.mirabilisrespectively) in the conduit urine. The frequency of raised antibody titers increased with the time after the diversion operation. After treatment with antibiotics of patients with bacteriuria and raised serum antibody titers, the titers were within normal limits («£512), or decreased significantly, in 22 of 25 patients. Serum antibody titer determinations against E.coli and P.mirabilisare suggested as complement to urinary cultures in the follow-up of diverted patients.

    The residual urine volume in the conduit was shown to be of importance for bacteriuria and raised titer against P.mirabilis.

    Some measures, which possibly may reduce bacteriuria and thereby pyelonephritis, are suggested. A nipple stoma of at least 2 cm height ought to be constructed at the operation. To obtain a low residual urine volume the conduit should be short and unobstructed. The urinary collecting device should be emptied often and connected to a uribag during the night.

  • 17. Berndt, Sonja I
    et al.
    Sampson, Joshua
    Yeager, Meredith
    Jacobs, Kevin B
    Wang, Zhaoming
    Hutchinson, Amy
    Chung, Charles
    Orr, Nick
    Wacholder, Sholom
    Chatterjee, Nilanjan
    Yu, Kai
    Kraft, Peter
    Feigelson, Heather Spencer
    Thun, Michael J
    Diver, W Ryan
    Albanes, Demetrius
    Virtamo, Jarmo
    Weinstein, Stephanie
    Schumacher, Fredrick R
    Cancel-Tassin, Geraldine
    Cussenot, Olivier
    Valeri, Antoine
    Andriole, Gerald L
    Crawford, E David
    Haiman, Christopher
    Henderson, Brian
    Kolonel, Laurence
    Le Marchand, Loic
    Siddiq, Afshan
    Riboli, Elio
    Travis, Ruth C
    Kaaks, Rudolf
    Isaacs, William
    Isaacs, Sarah
    Wiley, Kathleen E
    Gronberg, Henrik
    Wiklund, Fredrik
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Xu, Jianfeng
    Zheng, S Lilly
    Sun, Jielin
    Vatten, Lars J
    Hveem, Kristian
    Njølstad, Inger
    Gerhard, Daniela S
    Tucker, Margaret
    Hayes, Richard B
    Hoover, Robert N
    Fraumeni, Joseph F
    Hunter, David J
    Thomas, Gilles
    Chanock, Stephen J
    Large-scale fine mapping of the HNF1B locus and prostate cancer risk2011Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 20, nr 16, s. 3322-3329Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 × 10(-8) with the most significant association with rs4430796 (P = 1.62 × 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2)= 0.64), rs7405696 was also associated with risk (P = 9.35 × 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 × 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 × 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer.

  • 18. Bessa, Agustina
    et al.
    Maclennan, Steven
    Enting, Deborah
    Bryan, Richard
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Van Hemelrijck, Mieke
    Reply to Jon Mikel Inarritu, Daniele Castellani, and Jeremy YC Teoh's Letter to the Editor re: Agustina Bessa, Steven Maclennan, Deborah Enting, et al. Consensus in Bladder Cancer Research Priorities Between Patients and Healthcare Professionals Using a Four-stage Modified Delphi Method. Eur Urol 2019;76:260-12019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 2, s. E45-E46Artikel i tidskrift (Refereegranskat)
  • 19. Bex, Axel
    et al.
    Albiges, Laurence
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bensalah, Karim
    Dabestani, Saeed
    Giles, Rachel H.
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas B.
    Marconi, Lorenzo
    Merseburger, Axel S.
    Fernandez-Pello, Sergio
    Tahbaz, Rana
    Abu-Ghanem, Yasmin
    Staehler, Michael
    Volpe, Alessandro
    Powles, Thomas
    Updated European Association of Urology Guidelines for Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Clear-cell Renal Cell Carcinoma2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 805-809Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cytoreductive nephrectomy (CN) has been the standard of care in patients with metastatic clear-cell renal cancer who present with the tumour in place. The CARMENA trial compared systemic therapy alone with CN followed by systemic therapy. This article outlines the new guidelines based on these data.

    Patient summary: The CARMENA trial demonstrates that immediate cytoreductive nephrectomy should no longer be considered the standard of care in patients diagnosed with intermediate and poor risk metastatic renal cell carcinoma when medical treatment is required. However, the psychological burden poor risk patients experience hearing that removal of their primary tumour will not be beneficial, should be carefully considered. 

  • 20. Bex, Axel
    et al.
    Albiges, Laurence
    Staehler, Michael
    Bensalah, Karim
    Giles, Rachel H.
    Dabestani, Saeed
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas B.
    Marconi, Lorenzo
    Merseburger, Axel S.
    Fernández-Pello, Sergio
    Tahbaz, Rana
    Abu-Ghanem, Yasmin
    Volpe, Alessandro
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Escudier, Bernard
    Powles, Thomas
    A Joint Statement from the European Association of Urology Renal Cell Cancer Guidelines Panel and the International Kidney Cancer Coalition: The Rejection of Ipilimumab and Nivolumab for Renal Cancer by the Committee for Medicinal Products for Human Use Does not Change Evidence-based Guideline Recommendations2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 849-851, artikel-id S0302-2838(18)30624-9Artikel i tidskrift (Refereegranskat)
  • 21. Bex, Axel
    et al.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Comparing Everolimus to Sunitinib in Non-clear-cell Renal Cell Carcinoma2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 5, s. 875-876Artikel i tidskrift (Övrigt vetenskapligt)
  • 22. Bjartell, Anders
    et al.
    Bottai, Matteo
    Persson, Josefin
    Bratt, Ola
    Damber, Jan-Erik
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Akre, Olof
    Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort2016Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, nr 4, s. 255-259Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA)<20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR. Results: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. Conclusions: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram

  • 23.
    Bjelkedal, Malte
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    A Genealogical Study of Prostate Cancer in Västerbotten2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 24. Björklund, Johan
    et al.
    Folkvaljon, Yasin
    Cole, Alexander
    Carlsson, Stefan
    Robinson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Ryhov County Hospital, Jönköping, Sweden.
    Loeb, Stacy
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Akre, Olof
    Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy: a nationwide population-based study2016Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, nr 2, s. 302-306Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To assess 90-day postoperative mortality after robot-assisted laparoscopic radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) using nationwide population-based registry data. Patients and Methods We conducted a cohort study using the National Prostate Cancer Register of Sweden, including 22 344 men with localized prostate cancer of clinical stage T1-T3, whose prostate-specific antigen levels were <50 mu g/mL and who had undergone primary radical prostatectomy in the period 1998-2012. Vital status was ascertained through the Total Population Register. The rates for 90-day postoperative mortality were analysed using logistic regression analysis, and comparisons of 90-day mortality with the background population were made using standardized mortality ratios (SMRs). Results Of the 14 820 men who underwent RRP, 29 (0.20%) died, and of the 7 524 men who underwent RARP, 10 (0.13%) died. Mortality in the cohort during the 90-day postoperative period was lower than in an age-matched background population: SMR 0.57 (95% confidence interval [CI] 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method: RARP vs RRP odds ratio (OR) 1.14; 95% CI 0.46-2.81. Postoperative 90-day mortality decreased over time: 2008-2012 vs 1998-2007 OR 0.44; 95% CI 0.21-0.95, mainly because of lower mortality after RARP. Conclusion The 90-day postoperative mortality rates were low after RARP and RRP and there was no statistically significant difference between the methods. Given the long life expectancy among men with low-and intermediate-risk prostate cancer, very low postoperative mortality is a prerequisite for RP, which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared with the background population.

  • 25. Bonn, S. E.
    et al.
    Wiklund, F.
    Sjölander, A.
    Szulkin, R.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Holmberg, E.
    Grönberg, H.
    Bälter, K.
    Body Mass Index and Weight Change in Men with Prostate Cancer: Progression and Mortality2015Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, s. 141-142Artikel i tidskrift (Övrigt vetenskapligt)
  • 26. Bosco, Cecilia
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Nilsson, Per
    Gunnlaugsson, Adalsteinn
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Van Hemelrijck, Mieke
    Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events2017Ingår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 97, nr 5, s. 1026-1031Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa). Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age-and county-matched comparison cohort of PCa-free men (n = 46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression. Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis. Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.

  • 27.
    Bovinder Ylitalo, Erik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Thysell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jernberg, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lundholm, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Crnalic, Sead
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Egevad, Lars
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 5, s. 776-787Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. Objectives: To identify molecular subgroups of PC bone metastases of relevance for therapy.

    Design, setting, and participants: Fresh-frozen bone metastasis samples from men with CRPC (n = 40), treatment-naïve PC (n = 8), or other malignancies (n = 12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription–polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n = 77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n = 12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n = 284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation.

    Results and limitations: The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non–AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non–AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient.

    Conclusions: Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored. Patient summary: We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients.

  • 28.
    Brandt, Christopher
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Is ONE mildly to moderately elevated PSA test enough to initiate a full work-up for a suspected prostate cancer?2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 29. Bratt, Ola
    et al.
    Carlsson, Stefan
    Holmberg, Erik
    Holmberg, Lars
    Johansson, Eva
    Josefsson, Andreas
    Nilsson, Annika
    Nyberg, Maria
    Robinsson, David
    Sandberg, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Sandblom, Dag
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    The Study of Active Monitoring in Sweden (SAMS): A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer2013Ingår i: Scandinavian Journal of Urology, ISSN 2168-1805, Vol. 47, nr 5, s. 347-355Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.

  • 30. Bratt, Ola
    et al.
    Folkvaljon, Yasin
    Eriksson, Marie Hjälm
    Akre, Olof
    Carlsson, Stefan
    Drevin, Linda
    Lissbrant, Ingela Franck
    Makarov, Danil
    Loeb, Stacy
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Undertreatment of Men in Their Seventies with High-risk Nonmetastatic Prostate Cancer2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, nr 1, s. 53-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. Objective: To investigate how age and comorbidity affect treatment of men with HRnMPCa. Design, setting, and participants: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. Outcome measurements and statistical analysis: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. Results and limitations: The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0-1. Only 10% of men aged 75-80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009-2012 for patients aged 70-80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed. Conclusions: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy. Patient summary: We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy.

  • 31. Bruins, Harman M
    et al.
    Veskimae, Erik
    Hernandez, Virginia
    Imamura, Mari
    Neuberger, Molly M
    Dahm, Philip
    Stewart, Fiona
    Lam, Thomas B
    N'Dow, James
    van der Heijden, Antoine G
    Compérat, Eva
    Cowan, Nigel C
    De Santis, Maria
    Gakis, Georgios
    Lebret, Thierry
    Ribal, Maria J
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Witjes, J Alfred
    The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer: a systematic review2014Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 66, nr 6, s. 1065-1077Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19 793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.

  • 32.
    Büchner, Frederike L
    et al.
    The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Bueno-de-Mesquita, H Bas
    The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Ros, Martine M
    The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Kampman, Ellen
    Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
    Egevad, Lars
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Overvad, Kim
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Tjønneland, Anne
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
    Roswall, Nina
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
    Clavel-Chapelon, Françoise
    INSERM (Institut National de la Santé et de la Recherche Médicale), ERI 20/Université Paris-Sud, EA 4045, IFR 69/Institut Gustave-Roussy, Villejuif, France.
    Boutron-Ruault, Marie-Christine
    INSERM (Institut National de la Santé et de la Recherche Médicale), ERI 20/Université Paris-Sud, EA 4045, IFR 69/Institut Gustave-Roussy, Villejuif, France.
    Touillaud, Marina
    INSERM (Institut National de la Santé et de la Recherche Médicale), ERI 20/Université Paris-Sud, EA 4045, IFR 69/Institut Gustave-Roussy, Villejuif, France.
    Kaaks, Rudolf
    Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
    Chang-Claude, Jenny
    Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
    Boeing, Heiner
    German Institute of Human Nutrition, Potsdam-Rehbücke, Germany.
    Weikert, Steffen
    German Institute of Human Nutrition, Potsdam-Rehbücke, Germany.
    Trichopoulou, Antonia
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece.
    Naska, Ada
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece.
    Benetou, Vicky
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece.
    Palli, Domenico
    Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
    Sieri, Sabina
    Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
    Vineis, Paolo
    Cancer Epidemiology Department, University of Turin, Turin, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Unit, Department of Oncology, “Civile M.P. Arezzo” Hospital, Ragusa, Italy.
    Panico, Salvatore
    Department of Clinical and Experimental Medicine, Federico II University, Medical School, Naples, Italy.
    van Duijnhoven, Fränzel J B
    The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Peeters, Petra H M
    Department of Epidemiology and Public Health, Imperial College London, London, UK.
    van Gils, Carla H
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
    Lund, Eiliv
    Institute of Community Medicine, University of Tromso, Tromso, Norway.
    Gram, Inger T
    Institute of Community Medicine, University of Tromso, Tromso, Norway.
    Sánchez, Maria-José
    Andalusian School of Public Health and CIBER de Epidemiología y Salud Pública (CIBERESP), Granada, Spain.
    Jakszyn, Paula
    Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain.
    Larrañaga, Nerea
    Public Health Department of Gipuzkoa, Basque Government and CIBER de Epidemiologia y Salud Pública (CIBERESP), San Sebastian, Spain.
    Ardanaz, Eva
    Public Health Institute of Navarra and CIBER Epidemiología y Salud Pública (CIBERESP), Pamplona, Spain.
    Navarro, Carmen
    Epidemiology Department, Murcia Health Council and CIBER Epidemiología y Salud Pública (CIBERESP), Murcia, Spain.
    Rodríguez, Laudina
    Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain.
    Manjer, Jonas
    Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
    Ehrnström, Roy
    Department of Pathology, Malmö University Hospital, Lund University, Malmö, Sweden.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Key, Tim J
    Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
    Allen, Naomi E
    Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
    Khaw, Kay-Tee
    Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Cambridge, UK.
    Wareham, Nicholas
    Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Cambridge, UK.
    Slimani, Nadia
    International Agency for Research on Cancer, Lyon, France.
    Jenab, Mazda
    International Agency for Research on Cancer, Lyon, France.
    Boffetta, Paolo
    International Agency for Research on Cancer, Lyon, France.
    Kiemeney, Lambertus A L M
    Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
    Riboli, Elio
    Department of Epidemiology and Public Health, Imperial College London, London, UK.
    Variety in vegetable and fruit consumption and risk of bladder cancer in the European prospective investigation into cancer and nutrition2011Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, nr 12, s. 2971-2979Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent research does not show an association between fruit and vegetable consumption and bladder cancer risk. None of these studies investigated variety in fruit and vegetable consumption, which may capture different aspects of consumption. We investigated whether a varied consumption of vegetables and fruits is associated with bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Detailed data on food consumption and complete follow-up for cancer incidence were available for 452,185 participants, who were recruited from ten European countries. After a mean follow-up of 8.7 years, 874 participants were diagnosed with bladder cancer. Diet diversity scores (DDSs) were used to quantify the variety in fruit and vegetable consumption. Multivariable Cox proportional hazard models were used to assess the effect of the DDSs on bladder cancer risk. There was no evidence of a statistically significant association between bladder cancer risk and any of the DDSs when these scores were considered as continuous covariates. However, the hazard ratio (HR) for the highest tertile of the DDS for combined fruit and vegetable consumption was marginally significant compared to the lowest (HR = 1.30, 95% confidence interval: 1.00-1.69, p-trend = 0.05). In EPIC, there is no clear association between a varied fruit and vegetable consumption and bladder cancer risk. This finding provides further evidence for the absence of any strong association between fruit and vegetable consumption as measured by a food frequency questionnaire and bladder cancer risk.

  • 33. Carlsson, Sigrid
    et al.
    Drevin, Linda
    Loeb, Stacy
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Franck Lissbrant, Ingela
    Robinson, David
    Johansson, Eva
    Stattin, Pär
    Fransson, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Population-based study of long-term functional outcomes after prostate cancer treatment2016Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, nr 6B, s. E36-E45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median follow-up of 12 years (IQR 11-13).

    PATIENTS AND METHODS: In this nationwide, population-based study, we identified from the National Prostate Cancer Register, Sweden, 6,003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate specific antigen < 20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 who were ≤70 years at diagnosis. 1,000 prostate cancer-free controls were selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire.

    RESULTS: Responses were obtained from 3,937/6,003 cases (66%) and 459/1,000 (46%) controls. Twelve years post diagnosis, at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction or sexually inactive, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62%, 6% and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction, compared to control men. Radical prostatectomy was associated with increased risk of urinary incontinence (odds ratio; OR 2.29 [95% CI 1.83-2.86] and radiotherapy increased the risk of bowel dysfunction (OR 2.46 [95% CI 1.73-3.49]) compared to control men. Multi-modal treatment, in particular including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 [95 CI 1.76-7.95] for erectile dysfunction and OR 3.22 [95% CI 1.93-5.37] for urinary incontinence.

    CONCLUSION: The proportion of men who suffer long-term impact on functional outcomes after prostate cancer treatment was substantial.

  • 34. Carlsson, Stefan
    et al.
    Bratt, Ola
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Current routines for transrectal ultrasound-guided prostate biopsy: A web-based survey by the Swedish Urology Network2012Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, nr 6, s. 405-410Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. This study aimed to survey current Swedish practices for performing and handling transrectal ultrasound-guided prostate biopsies. Material and methods. A Swedish Urology Network (SUNe) was organized for the distribution of information, survey studies and research collaborations. A web-based questionnaire was distributed to the members in 2011. Results. In this first SUNe survey, 137 (91%) of the 151 members replied. All used antibiotic prophylaxis (84% ciprofloxacin, 12% trimethoprim-sulfamethoxazole), most commonly (63%) as a single dose of ciprofloxacin. Local anaesthesia was used by 87%. Half of the respondents only used a "side-fire" probe, whereas 17% always used an "end-fire" probe. Most (84%) routinely took 10 or more biopsy cores. About three-quarters started with the right base of the prostate and did not routinely take midline biopsies. More than one-third never or rarely sampled the anterior part of the prostate. There was great variability in how biopsy location was reported, but 71% considered a national standardized coordinate system desirable. Fine-needle aspiration was used occasionally by 39%, in more than 10% of cases by 6% and always by 2%. Most urologists mounted the biopsy cores on paper before fixation (78%), put only one core per jar (75%) and used flat-bottomed jars (70%). Conclusions. Most routines for handling of prostate biopsies, antibiotic prophylaxis, local anaesthesia and number of cores were uniform. However, there is still a need for standardization of the performance of ultrasound-guided biopsies. Although the method used to specify biopsy location varied greatly, most urologists would prefer a national standardized system.

  • 35. Crawley, Danielle
    et al.
    Garmo, Hans
    Rudman, Sarah
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala.
    Zethelius, Björn
    Holmberg, Lars
    Adolfsson, Jan
    Van Hemelrijck, Mieke
    Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer2018Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, nr 2, s. 209-216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

    Subjects and Methods: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate-(T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

    Results: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

    Conclusions: Men with T2DM were less likely to receive curative treatment for localized intermediate-and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under-nor overtreated.

  • 36. Dabestani, Saeed
    et al.
    Beisland, Christian
    Stewart, Grant D.
    Bensalah, Karim
    Gudmundsson, Eirikur
    Lam, Thomas B.
    Gietzmann, William
    Zakikhani, Paimaun
    Marconi, Lorenzo
    Fernandez-Pello, Sergio
    Monagas, Serenella
    Williams, Samuel Paul
    Torbrand, Christian
    Powles, Thomas
    Van Werkhoven, Erik
    Meijer, Richard
    Volpe, Alessandro
    Staehler, Michael
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bex, Axel
    Intensive Imaging-based Follow-up of Surgically Treated Localised Renal Cell Carcinoma Does Not Improve Post-recurrence Survival: Results from a European Multicentre Database (RECUR)2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, nr 2, s. 261-264Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The optimal follow-up (FU) strategy for patients treated for localised renal cell carcinoma(RCC) remains unclear. Using the RECUR database, we studied imaging intensity utilised in contemporary FU to evaluate its association with outcome after detection of disease recurrence. Consecutive patients with nonmetastatic RCC (n = 1612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Recurrence occurred in 336 patients. Cross-sectional (computed tomography, magnetic resonance imaging) and conventional (chest X-ray, ultrasound) methods were used in 47% and 53%, respectively. More intensive FU imaging (more than twofold) than recommended by the European Association of Urology (EAU) was not associated with improved overall survival (OS) after recurrence. Overall, per patient treated for recurrence remaining alive with no evidence of disease, the number of FU images needed was 542, and 697 for high-risk patients. The study results suggest that use of more imaging during FU than that recommended in the 2017 EAU guidelines is unlikely to improve OS after recurrence. Prospective studies are needed to design optimal FU strategies for the future.

    Patient summary: After curative treatment for localised kidney cancer, follow-up is necessary to detect any recurrence. This study illustrates that increasing the imaging frequency during follow-up, even to double the number of follow-up imaging procedures recommended by the European Association of Urology guidelines, does not translate into improved survival for those with recurrence.

  • 37. Dabestani, Saeed
    et al.
    Beisland, Christian
    Stewart, Grant D.
    Bensalah, Karim
    Gudmundsson, Eirikur
    Lam, Thomas B.
    Gietzmann, William
    Zakikhani, Paimaun
    Marconi, Lorenzo
    Fernandéz-Pello, Sergio
    Monagas, Serenella
    Williams, Samuel P.
    Powles, Thomas
    Van Werkhovenn, Erik
    Meijer, Richard
    Volpe, Alessandro
    Staehler, Michael
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Bex, Axel
    Increased use of cross-sectional imaging for follow-up does not improve post-recurrence survival of surgically treated initially localized RCC: results from a European multicenter database (RECUR)2019Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Modality and frequency of image-based renal cell carcinoma (R.C.C.) follow-up strategies are based on risk of recurrence. Using the R.E.C.U.R.-database, frequency of imaging was studied in regard to prognostic risk groups. Furthermore, it was investigated whether imaging modality utilized in contemporary follow-up were associated with outcome after detection of recurrence. Moreover, outcome was compared based on whether the assessment of potential curability was a pre-defined set of criteria's (per-protocol) or stated by the investigator. Materials and methods: Consecutive non-metastatic R.C.C. patients (n = 1,612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Leibovich or U.I.S.S. risk group, recurrence characteristics, imaging modality, frequency and survival were recorded. Primary endpoints were overall survival (O.S.) after detection of recurrence and frequency of features associated with favourable outcome (non-symptomatic recurrences and detection within the follow-up-programme). Results: Recurrence occurred in 336 patients. Within low, intermediate and high risk for recurrence groups, the frequency of follow-up imaging was highest in the early phase of follow-up and decreased significantly over time (p < 0.001). However, neither the image modality for detection nor >= 50% cross-sectional imaging during follow-up were associated with improved O.S. after recurrence. Differences between per protocol and investigator based assessment of curability did not translate into differences in O.S. Conclusions: As expected, the frequency of imaging was highest during early follow-up. Cross-sectional imaging use for detection of recurrences following surgery for localized R.C.C. did not improve O.S. post-recurrence. Prospective studies are needed to determine the value of imaging in follow-up.

  • 38. Dabestani, Saeed
    et al.
    Beisland, Christian
    Stewart, Grant D.
    Bensalah, Karim
    Gudmundsson, Eirikur
    Lam, Thomas B.
    Gietzmann, William
    Zakikhani, Paimaun
    Marconi, Lorenzo
    Fernandéz-Pello, Sergio
    Monagas, Serenella
    Williams, Samuel P.
    Torbrand, Christian
    Powles, Thomas
    Van Werkhoven, Erik
    Meijer, Richard
    Volpe, Alessandro
    Staehler, Michael
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Bex, Axel
    Long-term Outcomes of Follow-up for Initially Localised Clear Cell Renal Cell Carcinoma: RECUR Database Analysis.2018Ingår i: European urology focus, ISSN 2405-4569, artikel-id S2405-4569(18)30072-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Optimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols.

    OBJECTIVE: To analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes.

    DESIGN, SETTING, AND PARTICIPANTS: Nonmetastatic ccRCC patients treated with curative intent between 1 January 2006 and 31 December 2011, with at least 4 yr of FU, were included. Patient, tumour and recurrence characteristics, Leibovich score, and management and survival data were recorded. Isolated local, solitary, and oligometastatic (three or fewer lesions at a single site) recurrences were considered PC, while all others were probably incurable (PI).

    INTERVENTION: Primarily curative surgical treatment of ccRCC while at recurrence detection metastasectomy, systemic therapy, best supportive care, or observation.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence, time to recurrence (TTR), and OS were measured. Competing risk analysis, Kaplan-Meier, and Cox regression models were used.

    RESULTS AND LIMITATION: Of 1265 patients with ccRCC, 286 had a recurrence, with 131 being PC and 155 PI. Five-year cumulative risks of recurrence for low- (n=53), intermediate- (n=105), and high-risk (n=128) patients were, respectively, 7.2%, 23.2%, and 61.6%, of whom 52.8%, 37.1%, and 30.5% were PC, respectively. Median TTR was 25.0 for PC patients versus 17.3 mo for PI patients (p=0.004). Median OS was longer in PC compared with that in PI patients (p<0.001). Competing risk analysis showed highest risk of ccRCC-related death in younger and high-risk patients. Limitations were no data on comorbidities, retrospective cohort, and insufficient data excluding 12% of cohort.

    CONCLUSIONS: Low-risk group recurrences are rare and develop later. Treatment of recurrences with curative intent is disappointing, especially in high-risk patients. An age- and risk score-dependent FU approach is suggested.

    PATIENT SUMMARY: We analysed data from eight European countries, and found that the incidence of the kidney cancer recurrence and patient survival correlated with clinical factors known to predict cancer recurrence reliably and age. We conclude that these factors should be used to design follow-up strategies.

  • 39.
    Dahlin, Britt-Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Preoperative carbohydrate drink in a randomized study improves postoperative quality of life after urological surgery.2009Ingår i: International Journal of Urological Nursing, ISSN 1749-771X, Vol. 3, nr 2, s. 64-68Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Recently, fast track treatment in surgery has been advocated. Fasting time has been cut down to attenuate preoperative discomfort as irritable and preoperative thirst. We accessed effects of preoperative carbohydrate drink on preoperative quality of life (QOL) including hospitalization time, drinking first day, gut emptying, and return to work. A total of 170 patients scheduled for nephrectomy or prostatectomy were randomized to carbohydrate drink or overnight fasting. Responses a modified QLQ-C30 questionnaire were collected before and one month after surgery.

    In patients treated with prostatectomy to the variables: did you worry, total health and total QOL improved, while most (19 of 30) variables were impaired. Nephrectomy patients had significantly fewer parameters with impaired QOL than prostatectomy (p = 0.01). There was significant weight loss despite surgical procedure (p < 0.001). When comparing the carbohydrate and control groups, there was no difference concerning age, sex and stages. After prostatectomy, only the QOL variable “worry” improved (p = 0.027) in the carbohydrate group. After nephrectomy, the carbohydrate group had less weight loss (p = 0.035) than controls and had improved QOL as: “short of breath” (p = 0.038), “feel tense” (p = 0.057), “worry” (p = 0.035), and “interfered social activities” (p = 0.024). There was no difference in hospitalization time, drinking 1st day, time to gut emptying, and return to normal activities between the groups, despite surgical procedure.

    Carbohydrate drink before surgery significantly improved QOL variables such as “worry”, “tense”, and “social activities”. Weight loss was significantly reduced compared with controls after nephrectomy. Thus, carbohydrate drinking before elective surgery improves postoperative QOL parameters, but not postoperative drinking and hospitalization time.

  • 40. Damoiseaux, Jan
    et al.
    Heijnen, Ingmar
    Van Campenhout, Christel
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Fabien, Nicole
    Herold, Manfred
    van der Molen, Renate G.
    Egner, William
    Patel, Dina
    Plaza-Lopez, Aresio
    Radice, Antonella
    Rego de Sousa, Marie Jose
    Viander, Markku
    Shoenfeld, Yehuda
    An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice2018Ingår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 56, nr 10, s. 1759-1770Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Detection of anti-neutrophil cytoplasmic antibodies (ANCA) is important for the diagnosis of the ANCA-associated vasculitides (AAV). For AAV, especially ANCA directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are most relevant. ANCA with less well-defined specificities may, however, also be detected in other inflammatory and non-inflammatory conditions.

    Methods: A questionnaire, initiated by the European Autoimmunity Standardisation Initiative (EASI), was used to gather information on methods and testing algorithms used for ANCA in clinical laboratories of 12 European countries (EASI survey).

    Results: Four hundred and twenty-nine responses were included in the EASI survey analysis which revealed differences within countries and between countries. Laboratories overall were poor in adherence to international consensus on ANCA testing. Substantial variation was observed with respect to the use of ANCA indirect immunofluorescence (IIF) in the algorithm, application of distinct methods for MPO- and PR3-ANCA, the daily availability of new ANCA results, and interpretation of test results.

    Conclusions: Awareness of these differences may stimulate further harmonization and standardization of ANCA testing. This may be promoted by an update of the international ANCA consensus and the introduction of international standards.

  • 41. Danneman, Daniela
    et al.
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Robinson, David
    Bratt, Ola
    Loeb, Stacy
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-20122017Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, nr 1, s. 50-56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

  • 42. Danneman, Daniela
    et al.
    Drevin, Linda
    Robinson, David
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Gleason inflation 1998-2011: a registry study of 97 168 men2015Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 115, nr 2, s. 248-255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer. Patients and Methods: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed. Results: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned. Conclusions: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.

  • 43.
    Duchek, Milos
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Johansson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Jahnson, Staffan
    Mestad, Oddvar
    Hellström, Pekka
    Hellsten, Sverker
    Malmström, Per-Uno
    Bacillus Calmette-Guérin is superior to a combination of epirubicin and interferon-alpha2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study.2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 1, s. 25-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Bacillus Calmette-Guérin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed.

    OBJECTIVE: To compare BCG to the combination of epirubicin and interferon-alpha2b as adjuvant therapy of T1 tumours.

    DESIGN, SETTING, AND PARTICIPANTS: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr.

    MEASUREMENTS: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented.

    RESULTS AND LIMITATIONS: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p=0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p=0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination.

    CONCLUSIONS: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

  • 44. Duranton, Flore
    et al.
    Palma, Alfonso
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wauthier, Michel
    Torres, Armando
    Argilés, Angel
    Blood Pressure Seasonality in Hemodialysis Patients from Five European Cities of Different Latitudes2018Ingår i: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 43, nr 5, s. 1529-1538Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Climate influences the regulation of blood pressure (BP). Our objective was to precisely estimate BP seasonality in hemodialysis (HD) patients from five European cities with marked climate differences. Methods: Stable prevalent HD patients from 5 European facilities (Santa Cruz de Tenerife (Spain), Seville (Spain), Montpellier (France), Ottignies (Belgium), Umea (Sweden)) present over the years 1995-1999 were included in this historical longitudinal observational study. Individual monthly averages of pre-dialysis BP level were computed from all facility BP measurements (>90 000 observations). The association between BP level and location, seasons and meteorological measurements was analyzed by mixed models. Results: 261 patients were included and followed-up for a median duration of 2 years (6903 monthly observations). Pre-dialysis SBP and DBP were minimal in summer (July) and maximal in winter (November and December), and mean changes were respectively 4.2 [3.0;5.4] and 2.0 [1.3;2.7] mmHg. Seasonality was confirmed in 4 locations (P-season <= 0.0010.001 for SBP and DBP), but not in Umea (both P-season >0.05). Seasonal changes in DBP were larger in southern locations (P-interaction =0.02). BP level was associated with climate parameters: in a positive manner with humidity or rainfall, and inversely with sunshine duration or temperature. The effects of temperature and rainfall on DBP varied with latitude (P-interaction <0.02) and were greater in southern locations. Conclusion: BP varies with seasons and climate in different European areas and seasonality can be more important in southern locations. These changes in BP deserve attention as they may be responsible for a significant increase in cardiovascular risk which may be preventable.

  • 45. Erlandsson, Ann
    et al.
    Carlsson, Jessica
    Andersson, Sven-Olof
    Vyas, Chraig
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andrén, Ove
    Davidsson, Sabina
    Rider, Jennifer R.
    High inducible nitric oxide synthase in prostate tumor epithelium is associated with lethal prostate cancer2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 2, s. 129-133Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in lethal prostate cancer (PCa) by studying the iNOS immunoreactivity in tumor tissue from men diagnosed with localized PCa. Materials and methods: This study is nested within a cohort of men diagnosed with incidental PCa undergoing transurethral resection of the prostate (the Swedish Watchful Waiting Cohort). To investigate molecular determinants of lethal PCa, men who died from PCa (n = 132) were selected as cases; controls (n = 168) comprised men with PCa who survived for at least 10 years without dying from PCa during follow-up. The immunoreactivity of iNOS in prostate tumor epithelial cells and in cells of the surrounding stroma was scored as low/negative, moderate or high. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for lethal PCa according to iNOS category. Results: There was no association between iNOS immunoreactivity in stroma and lethal disease. However, when comparing high versus low/negative iNOS immunoreactivity in epithelial cells, the OR for lethal PCa was 3.80 (95% CI 1.45-9.97). Conclusion: Patients with localized PCa have variable outcomes, especially those with moderately differentiated tumors. Identifying factors associated with long-term PCa outcomes can elucidate PCa tumor biology and identify new candidate prognostic markers. These findings support the hypothesis that high iNOS in tumor epithelium of the prostate is associated with lethal disease.

  • 46. Fernández-Pello, Sergio
    et al.
    Hofmann, Fabian
    Tahbaz, Rana
    Marconi, Lorenzo
    Lam, Thomas B
    Albiges, Laurence
    Bensalah, Karim
    Canfield, Steven E
    Dabestani, Saeed
    Giles, Rachel H
    Hora, Milan
    Kuczyk, Markus A
    Merseburger, Axel S
    Powles, Thomas
    Staehler, Michael
    Volpe, Alessandro
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bex, Axel
    A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma.2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 3, s. 426-436Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    CONTEXT: While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown.

    OBJECTIVE: To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC.

    EVIDENCE ACQUISITION: Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken.

    EVIDENCE SYNTHESIS: The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03-1.92 and 1.41, 95% CI: 0.88-2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67-2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9-2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91-1.86). Sunitinib was associated with more Grade 3-4 adverse events than everolimus, although this was not statistically significant.

    CONCLUSIONS: This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed.

    PATIENT SUMMARY: We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.

  • 47.
    Ferry, Sven
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Urinary tract infections in primary health care in northern Sweden: epidemiological, bacteriological and clinical aspects1988Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The epidemiology of urinary tract infection (UTI) in the population of Vännäs (8 000 inhabitants) was studied during one year. The annual incidence increased from 0.5% in the first decade of life to more than 10% in the age group 90-100 years. Male UTI comprised only 13% of the episodes, increased after middle age and contributed 4 0% by > 80 years of age. At 17 PHC centres (PHCCs) a prevalence study (McPHC) of mainly uncomplicated UTI was performed. Most episodes were acutely symptomatic (lower 75%, upper 5%).

    Microscopy of wet-stained urinary sediment with a minimum of moderate amount of bacteria and/or 5 leukocytes per high power field (4 00 x) as breakpoint resulted in a desired high sensitivity (97%) and 86% efficacy in acutely symptomatic patients. Diagnosis of bacteriuria using Uricult dipslides yielded acceptable results with an overall efficacy of 88%. Nitrite test and Uriglox showed an unacceptable low mean sensitivity ofR56 and 69%, respectively. A positive nitrite, sediment or Uricult , when used in combination, was optimal in diagnosing UTI with a sensitivity of 98% in acutely symptomatic patients during their office visits.

    The average risk of drug resistance was 17% in the Vännäs study. Sensicult satisfactorily predicted drug sensitivity (93%) but not bacterial drug resistance (50%). Using Uricult with classification of bacteriuria by Gram-grouping, lactose and catalase reactions for targeting UTI therapy, according to local guidelines, resulted in a similar low risk (6 %) of prescribing drugs to which the organisms were resistagt as when using Sensicult (7%). This development of the Uricult method is simple and can be recommended for office practice in PHC.

    The spectrum of bacteria causing UTI and their drug resistance was more associated with the selection of patients, sex and age than with symptoms. The pattern of drug resistance was little influenced by UTI history and the mean pretherapy resistance for the seven drugs tested in McPHC was low (7%). Drug resistance was increased in failure (mean 24%) but not in early or repeated recurrence. In McPHC therapy resulted in 8% bacteriological failure and 12% early recurrence, irrespective of whether the bacteria were classified as sensitive or resistant in vitro to the drug given. Thus, in order to be of prognostic value for therapy of uncomplicated UTI, high-level breakpoints focusing more on peak urinary drug concentrations need to be studied.

    UTI symptoms in McPHC were eradicated in only 2/3 of the bacterio- logically cured episodes and in 1/3 of the failures at control 1-3 days posttherapy showing that symptoms are an unreliable indicator of UTI.

    From current literature, it seems unlikely that asymptomatic bacteriuria (ABU) plays a major role in the development of uremia due to chronic pyelonephritis. With the exception of ABU in pregnancy, therapy seems to yield no benefit. Omitting posttherapy bacteriuria controls in patients with symptoms eradicated, at least in women with uncomplicated UTI, would lead to considerable savings both for patients and the health care system.

  • 48. Figueroa, Jonine D.
    et al.
    Han, Summer S.
    Garcia-Closas, Montserrat
    Baris, Dalsu
    Jacobs, Eric J.
    Kogevinas, Manolis
    Schwenn, Molly
    Malats, Nuria
    Johnson, Alison
    Purdue, Mark P.
    Caporaso, Neil
    Landi, Maria Teresa
    Prokunina-Olsson, Ludmila
    Wang, Zhaoming
    Hutchinson, Amy
    Burdette, Laurie
    Wheeler, William
    Vineis, Paolo
    Siddiq, Afshan
    Cortessis, Victoria K.
    Kooperberg, Charles
    Cussenot, Olivier
    Benhamou, Simone
    Prescott, Jennifer
    Porru, Stefano
    Bueno-de-Mesquita, H. Bas
    Trichopoulos, Dimitrios
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Clavel-Chapelon, Françoise
    Weiderpass, Elisabete
    Krogh, Vittorio
    Dorronsoro, Miren
    Travis, Ruth
    Tjønneland, Anne
    Brenan, Paul
    Chang-Claude, Jenny
    Riboli, Elio
    Conti, David
    Gago-Dominguez, Manuela
    Stern, Mariana C.
    Pike, Malcolm C.
    Van den Berg, David
    Yuan, Jian-Min
    Hohensee, Chancellor
    Rodabough, Rebecca
    Cancel-Tassin, Geraldine
    Roupret, Morgan
    Comperat, Eva
    Chen, Constance
    De Vivo, Immaculata
    Giovannucci, Edward
    Hunter, David J.
    Kraft, Peter
    Lindstrom, Sara
    Carta, Angela
    Pavanello, Sofia
    Arici, Cecilia
    Mastrangelo, Giuseppe
    Karagas, Margaret R.
    Schned, Alan
    Armenti, Karla R.
    Hosain, G. M. Monawar
    Haiman, Chris A.
    Fraumeni, Joseph F., Jr.
    Chanock, Stephen J.
    Chatterjee, Nilanjan
    Rothman, Nathaniel
    Silverman, Debra T.
    Genome-wide interaction study of smoking and bladder cancer risk2014Ingår i: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 35, nr 8, s. 1737-1744Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 x 10(-5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 x 10(-7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 x 10-7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.

  • 49. Figueroa, Jonine D.
    et al.
    Middlebrooks, Candace D.
    Banday, A. Rouf
    Ye, Yuanqing
    Garcia-Closas, Montserrat
    Chatterjee, Nilanjan
    Koutros, Stella
    Kiemeney, Lambertus A.
    Rafnar, Thorunn
    Bishop, Timothy
    Furberg, Helena
    Matullo, Giuseppe
    Golka, Klaus
    Gago-Dominguez, Manuela
    Taylor, Jack A.
    Fletcher, Tony
    Siddiq, Afshan
    Cortessis, Victoria K.
    Kooperberg, Charles
    Cussenot, Olivier
    Benhamou, Simone
    Prescott, Jennifer
    Porru, Stefano
    Dinney, Colin P.
    Malats, Nuria
    Baris, Dalsu
    Purdue, Mark P.
    Jacobs, Eric J.
    Albanes, Demetrius
    Wang, Zhaoming
    Chung, Charles C.
    Vermeulen, Sita H.
    Aben, Katja K.
    Galesloot, Tessel E.
    Thorleifsson, Gudmar
    Sulem, Patrick
    Stefansson, Kari
    Kiltie, Anne E.
    Harland, Mark
    Teo, Mark
    Offit, Kenneth
    Vijai, Joseph
    Bajorin, Dean
    Kopp, Ryan
    Fiorito, Giovanni
    Guarrera, Simonetta
    Sacerdote, Carlotta
    Selinski, Silvia
    Hengstler, Jan G.
    Gerullis, Holger
    Ovsiannikov, Daniel
    Blaszkewicz, Meinolf
    Esteban Castelao, Jose
    Calaza, Manuel
    Martinez, Maria Elena
    Cordeiro, Patricia
    Xu, Zongli
    Panduri, Vijayalakshmi
    Kumar, Rajiv
    Gurzau, Eugene
    Koppova, Kvetoslava
    Bueno-De-Mesquita, H. Bas
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Clavel-Chapelon, Francoise
    Weiderpass, Elisabete
    Krogh, Vittorio
    Dorronsoro, Miren
    Travis, Ruth C.
    Tjonneland, Anne
    Brennan, Paul
    Chang-Claude, Jenny
    Riboli, Elio
    Conti, David
    Stern, Marianna C.
    Pike, Malcolm C.
    Van den Berg, David
    Yuan, Jian-Min
    Hohensee, Chancellor
    Jeppson, Rebecca P.
    Cancel-Tassin, Geraldine
    Roupret, Morgan
    Comperat, Eva
    Turman, Constance
    De Vivo, Immaculata
    Giovannucci, Edward
    Hunter, David J.
    Kraft, Peter
    Lindstrom, Sara
    Carta, Angela
    Pavanello, Sofia
    Arici, Cecilia
    Mastrangelo, Giuseppe
    Kamat, Ashish M.
    Zhang, Liren
    Gong, Yilei
    Pu, Xia
    Hutchinson, Amy
    Burdett, Laurie
    Wheeler, William A.
    Karagas, Margaret R.
    Johnson, Alison
    Schned, Alan
    Hosain, G. M. Monawar
    Schwenn, Molly
    Kogevinas, Manolis
    Tardon, Adonina
    Serra, Consol
    Carrato, Alfredo
    Garcia-Closas, Reina
    Lloreta, Josep
    Andriole, Gerald, Jr.
    Grubb, Robert, III
    Black, Amanda
    Diver, W. Ryan
    Gapstur, Susan M.
    Weinstein, Stephanie
    Virtamo, Jarmo
    Haiman, Christopher A.
    Landi, Maria Teresa
    Caporaso, Neil E.
    Fraumeni, Joseph F., Jr.
    Vineis, Paolo
    Wu, Xifeng
    Chanock, Stephen J.
    Silverman, Debra T.
    Prokunina-Olsson, Ludmila
    Rothman, Nathaniel
    Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry2016Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, nr 6, s. 1203-1214Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.

  • 50.
    Forsberg, Ulf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Medicin-geriatriska kliniken, Skellefteå lasarett.
    Jonsson, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Christofer
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Microemboli, developed during haemodialysis, pass the lung barrier and may cause ischaemic lesions in organs such as the brain2010Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 25, nr 8, s. 2691-2695Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The infused and returning fluid from HD devices contains air microbubbles that enter the patient without triggering any alarms. These small emboli pass the lung and may cause ischaemic lesions in organs supported by the arterial circuit, such as the brain.

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