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  • 1.
    Alamdari, Farhood Iranparvar
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi. Urologi och andrologi.
    Ljungberg, Börje
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi. Urologi och andrologi.
    Adrenal metastasis in renal cell carcinoma: a recommendation for adjustment of the TNM staging system.2005Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, nr 4, s. 277-282Artikkel i tidsskrift (Fagfellevurdert)
  • 2.
    Alamdari, Farhood Iranparvar
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi. Urologi och andrologi.
    Rasmuson, Torgny
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi. Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
    Ljungberg, Börje
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi. Urologi och andrologi.
    Angiogenesis and other markers for prediction of survival in metastatic renal cell carcinoma.2007Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, nr 1, s. 5-9Artikkel i tidsskrift (Fagfellevurdert)
  • 3. 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 Carcinoma2019Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 2, s. 151-156Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 4. Allen, Naomi E
    et al.
    Appleby, Paul N
    Key, Timothy J
    Bueno-de-Mesquita, H B
    Ros, Martine M
    Kiemeney, Lambertus A L M
    Tjønneland, Anne
    Roswall, Nina
    Overvad, Kim
    Weikert, Steffen
    Boeing, Heiner
    Chang-Claude, Jenny
    Teucher, Birgit
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Palli, Domenico
    Sieri, Sabina
    Peeters, Petra
    Quirós, Jose Ramón
    Jakszyn, Paula
    Molina-Montes, Esther
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Wareham, Nick
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Ehrnström, Roy
    Ericson, Ulrika
    Gram, Inger Torhild
    Parr, Christine L
    Trichopoulou, Antonia
    Karapetyan, Tina
    Dilis, Vardis
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherrazzi, Guy
    Romieu, Isabelle
    Gunter, Marc J
    Riboli, Elio
    Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition2013Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, nr 3, s. 635-644Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.

  • 5. Allen, Naomi E
    et al.
    Roddam, Andrew W
    Sieri, Sabina
    Boeing, Heiner
    Jakobsen, Marianne Uhre
    Overvad, Kim
    Tjønneland, Anne
    Halkjær, Jytte
    Vineis, Paolo
    Contiero, Paolo
    Palli, Domenico
    Tumino, Rosario
    Mattiello, Amalia
    Kaaks, Rudolf
    Rohrmann, Sabine
    Trichopoulou, Antonia
    Zilis, Demosthenes
    Koumantaki, Yvoni
    Peeters, Petra H
    Bueno-de-Mesquita, H Bas
    Barricarte, Aurelio
    Rodríguez, Laudina
    Dorronsoro, Miren
    Sánchez, Maria-José
    Chirlaque, María Dolores
    Esquius, Laura
    Manjer, Jonas
    Wallström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. 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.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Bingham, Sheila
    Khaw, Kay-Tee
    Boffetta, Paolo
    Norat, Teresa
    Mouw, Traci
    Riboli, Elio
    A prospective analysis of the association between macronutrient intake and renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition.2009Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, nr 4, s. 982-987Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous case-control studies have suggested that a high intake of animal foods and its associated nutrients are associated with an increased risk of renal cell carcinoma, although data from prospective studies are limited. We report here on the relationship between macronutrient intake and renal cell carcinoma incidence among 435,293 participants enrolled in the European Prospective Investigation into Cancer and Nutrition. Cox proportional hazard models were used to examine the association of dietary intake of fat, protein, carbohydrate, fiber and cholesterol and risk of renal cell carcinoma adjusted for age, sex, center, height, body mass index, physical activity, education, smoking, menopausal status, alcohol and energy intake. During an average 8.8 years of follow-up, 507 renal cell carcinoma cases occurred. Risk of renal cell carcinoma was not associated with macronutrient intake, including nutrients derived from animal sources. Our results indicate that macronutrient intake is not associated with risk of renal cell carcinoma in this cohort of European men and women. (c) 2009 UICC.

  • 6.
    Andersson-Evelönn, Emma
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Haider, Zahra
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Köhn, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    DNA methylation associates with survival in non-metastatic clear cell renal cell carcinoma2019Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, artikkel-id 65Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress.

    Method: Diagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters.

    Results: The ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS5yr) p < 0.001 and cumulative incidence of progress (pCIP5yr) p < 0.001. An integrated genomic and epigenomic analysis in the ccRCCs, revealed significant correlations between the total number of genetic aberrations and total number of hypermethylated CpGs (R = 0.435, p < 0.001), and predicted mitotic age (R = 0.407, p < 0.001). We identified a promoter methylation classifier (PMC) panel consisting of 172 differently methylated CpGs accompanying progress of disease. Classifying non-metastatic patients using the PMC panel showed that PMC high tumors had a worse prognosis compared with the PMC low tumors (pCIP5yr 38% vs. 8%, p = 0.001), which was confirmed in non-metastatic ccRCCs in the publically available TCGA-KIRC dataset (pCIP5yr 39% vs. 16%, p < 0.001).

    Conclusion: DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.

  • 7. Bahi, R.
    et al.
    Pignot, G.
    Hammoudi, Y.
    Bensalah, K.
    Oger, E.
    Laguna, P.
    Barwari, K.
    Bessede, T.
    Rigaud, J.
    Roupret, M.
    Bernhard, J. C.
    Long, J. A.
    Zisman, A.
    Berger, J.
    Paparel, P.
    Lechevallier, E.
    Bertini, R.
    Salomon, L.
    Bex, A.
    Farfara, R.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Rodriguez, A. R.
    Patard, J. J.
    Ischemia is not an independent predictive factor of chronic renal failure after partial nephrectomy in a solitary kidney in patients without pre-operative renal insufficiency2015Inngår i: Progrès en urologie (Paris), ISSN 1166-7087, Vol. 25, nr 1, s. 27-33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To assess the influence of vascular clamping and ischemia time on long-term post-operative renal function following partial nephrectomy (PN) for cancer in a solitary kidney.

    Patients and methods: This is a retrospective study including 259 patients managed by PN between 1979 and 2010 in 13 centers. Clamping use, technique choice (pedicular or parenchymal clamping), ischemia time, and peri-operative data were collected. Pre-operative and last follow-up glomerular filtration rates were compared. A multivariate analysis using a Cox model was performed to assess the impact of ischemia on post-operative chronic renal failure risk.

    Results: Mean tumor size was 4.0 ± 2.3 cm and mean pre-operative glomerular filtration rate was 60.8 ± 18.9 mL/min. One hundred and six patients were managed with warm ischemia (40.9%) and 53 patients with cold ischemia (20.5%). Thirty patients (11.6%) have had a chronic kidney disease. In multivariate analysis, neither vascular clamping (P = 0.44) nor warm ischemia time (P = 0.1) were associated with a pejorative evolution of renal function. Pre-operative glomerular filtration rate (P < 0.0001) and blood loss volume (P = 0.02) were significant independent predictive factors of long-term renal failure.

    Conclusion: Renal function following PN in a solitary kidney seems to depend on non-reversible factors such as pre-operative glomerular filtration rate. Our findings minimize the role of vascular clamping and ischemia time, which were not significantly associated with chronic renal failure risk in our study.

  • 8. 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 Carcinoma2013Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 64, nr 5, s. 799-810Artikkel, forskningsoversikt (Fagfellevurdert)
    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.

  • 9. 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 Carcinoma2019Inngår i: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 9, artikkel-id 11Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 10. Bergerot, Cristiane Decat
    et al.
    Battle, Dena
    Bergerot, Paulo Gustavo
    George, Daniel J.
    Hammers, Hans J.
    Jonasch, Eric
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bex, Axel
    Dizman, Nazli
    Staehler, Michael D.
    Pal, Sumanta K.
    Frustration and distress during treatment for advanced renal cell carcinoma2018Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, nr 34, artikkel-id 47Artikkel i tidsskrift (Annet vitenskapelig)
  • 11. 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 Carcinoma2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 805-809Artikkel i tidsskrift (Fagfellevurdert)
    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. 

  • 12. 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.
    Staehler, Michael
    Volpe, Alessandro
    Powles, Thomas
    Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma2017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 5, s. 719-722Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The European Association of Urology Renal Cell Carcinoma (RCC) guidelines panel updated their recommendation on adjuvant therapy in unfavourable, clinically nonmetastatic RCC following the recently reported results of a second randomised controlled phase 3 trial comparing 1-yr sunitinib to placebo for high-risk RCC after nephrectomy (S-TRAC). On the basis of conflicting results from the two available studies, the panel rated the quality of the evidence, the harm-to-benefit ratio, patient preferences, and costs. Finally, the panel, including representatives from a patient advocate group (International Kidney Cancer Coalition) voted and reached a consensus to not recommend adjuvant therapy with sunitinib for patients with high-risk RCC after nephrectomy. Patient summary: In two studies, sunitinib was given for 1 yr and compared to no active treatment (placebo) in patients who had their kidney tumour removed and who had a high risk of cancer coming back after surgery. Although one study demonstrated that 1 yr of sunitinib therapy resulted in a 1.2-yr longer time before the disease recurred, the other study did not show a benefit and it has not been shown that patients live longer. Despite having been diagnosed with high-risk disease, many patients remain without recurrence, and the side effects of sunitinib are high. Therefore, the panel members, including patient representatives, do not recommend sunitinib after tumour removal in these patients.

  • 13. 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 Recommendations2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 849-851, artikkel-id S0302-2838(18)30624-9Artikkel i tidsskrift (Fagfellevurdert)
  • 14. 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 Carcinoma2016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 5, s. 875-876Artikkel i tidsskrift (Annet vitenskapelig)
  • 15. Bex, Axel
    et al.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    van Poppel, Hein
    Powles, Thomas
    The Role of Cytoreductive Nephrectomy: European Association of Urology Recommendations in 20162016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 6, s. 901-905Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patient summary: After the introduction of systemic targeted therapies, the use of nephrectomy in patients with metastatic renal cell carcinoma has declined. Currently, systemic therapy is offered to more patients first as a means to select those candidates that will likely benefit from removal of their primary tumour. Although studies consistently demonstrate a survival benefit after nephrectomy, most patients with poor risk metastatic disease are unlikely to benefit from surgery. Soon studies will report on the effect of nephrectomy in patients with metastatic disease at diagnosis.

  • 16.
    Blind, Per Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Bläckberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Carboxylic ester hydrolase: a serum marker of acute pancreatitis1987Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 2, nr 5, s. 597-603Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    By use of an enzyme-linked immunosorbent assay we established serum reference values of carboxylic ester hydrolase, a pancreatic secretory lipolytic enzyme, and explored to see if a raised serum level is indicative of acute pancreatitis. Postoperative elevation of carboxylic ester hydrolase was observed in seven out of ten patients who underwent pancreatic surgery. Serum levels of carboxylic ester hydrolase and amylase were determined in 129 patients admitted due to abdominal emergency conditions. Amylase was elevated in 27 patients, and in 20 of these raised carboxylic ester hydrolase levels affirmed the diagnosis acute pancreatitis. In five out of the seven patients with elevated amylase alone no etiologic factor of acute pancreatitis was found. Another 11 patients had raised carboxylic ester hydrolase levels without concomitant elevation of amylase. In all these patients, a likely cause of pancreatic inflammation was identifiable. Hence, a raised carboxylic ester hydrolase level, even in presence of normal amylase, could be indicative of acute pancreatic inflammation.

  • 17. Botteri, E.
    et al.
    Ferrari, P.
    Roswall, N.
    Tjonneland, A.
    Hjartaker, A.
    Huerta, J. M.
    Fortner, R. T.
    Trichopoulou, A.
    Karakatsani, A.
    La Vecchia, C.
    Pala, V.
    Perez-Cornago, A.
    Sonestedt, E.
    Liedberg, F.
    Overvad, K.
    Sanchez, M. J.
    Gram, I. T.
    Stepien, M.
    Trijsburg, L.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Johansson, M.
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Kuehn, T.
    Panico, S.
    Tumino, R.
    Bueno-de-Mesquita, H. B.
    Weiderpass, E.
    Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort2017Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, nr 10, s. 1963-1970Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35-70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits). Baseline alcohol intake was associated with a statistically nonsignificant increased risk of UCC (HR 1.03; 95% confidence interval (CI) 1.00-1.06 for each additional 12 g/day). HR in smokers was 1.04 (95% CI 1.01-1.07). Men reporting high baseline intakes of alcohol (>96 g/day) had an increased risk of UCC (HR 1.57; 95% CI 1.03-2.40) compared to those reporting moderate intakes (<6 g/day), but no dose-response relationship emerged. In men, an increased risk of aggressive forms of UCC was observed even at lower doses (>6 to 24 g/day). Average lifelong alcohol intake was not associated with the risk of UCC, however intakes of spirits>24 g/day were associated with an increased risk of UCC in men (1.38; 95% CI 1.01-1.91) and smokers (1.39; 95% CI 1.01-1.92), compared to moderate intakes. We found no association between alcohol and UCC in women and never smokers. In conclusion, we observed some associations between alcohol and UCC in men and in smokers, possibly because of residual confounding by tobacco smoking.

  • 18. Brannon, A Rose
    et al.
    Reddy, Anupama
    Seiler, Michael
    Arreola, Alexandra
    Moore, Dominic T
    Pruthi, Raj S
    Wallen, Eric M
    Nielsen, Matthew E
    Liu, Huiqing
    Nathanson, Katherine L
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Zhao, Hongjuan
    Brooks, James D
    Ganesan, Shridar
    Bhanot, Gyan
    Rathmell, W Kimryn
    Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns.2010Inngår i: Genes & cancer, ISSN 1947-6027, Vol. 1, nr 2, s. 152-163Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, but even within this classification, the natural history is heterogeneous and difficult to predict. A sophisticated understanding of the molecular features most discriminatory for the underlying tumor heterogeneity should be predicated on identifiable and biologically meaningful patterns of gene expression. Gene expression microarray data were analyzed using software that implements iterative unsupervised consensus clustering algorithms to identify the optimal molecular subclasses, without clinical or other classifying information. ConsensusCluster analysis identified two distinct subtypes of ccRCC within the training set, designated clear cell type A (ccA) and B (ccB). Based on the core tumors, or most well-defined arrays, in each subtype, logical analysis of data (LAD) defined a small, highly predictive gene set that could then be used to classify additional tumors individually. The subclasses were corroborated in a validation data set of 177 tumors and analyzed for clinical outcome. Based on individual tumor assignment, tumors designated ccA have markedly improved disease-specific survival compared to ccB (median survival of 8.6 vs 2.0 years, P = 0.002). Analyzed by both univariate and multivariate analysis, the classification schema was independently associated with survival. Using patterns of gene expression based on a defined gene set, ccRCC was classified into two robust subclasses based on inherent molecular features that ultimately correspond to marked differences in clinical outcome. This classification schema thus provides a molecular stratification applicable to individual tumors that has implications to influence treatment decisions, define biological mechanisms involved in ccRCC tumor progression, and direct future drug discovery.

  • 19. Buckland, G
    et al.
    Ros, M M
    Roswall, N
    Bueno-de-Mesquita, H B
    Travier, N
    Tjonneland, A
    Kiemeney, L A
    Sacerdote, C
    Tumino, R
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Gram, I T
    Weiderpass, E
    Skeie, G
    Malm, J
    Ehrnström, R
    Chang-Claude, J
    Mattiello, A
    Agnoli, C
    Peeters, P H
    Boutron-Ruault, M C
    Fagherazzi, G
    Clavel-Chapelon, F
    Nilsson, Lena Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Amiano, P
    Trichopoulou, A
    Oikonomou, E
    Tsiotas, K
    Sánchez, M J
    Overvad, K
    Quirós, J R
    Chirlaque, M D
    Barricarte, A
    Key, T J
    Allen, N E
    Khaw, K T
    Wareham, N
    Riboli, E
    Kaaks, R
    Boeing, H
    Palli, D
    Romieu, I
    Romaguera, D
    Gonzalez, C A
    Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study2014Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, nr 10, s. 2504-2511Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.

  • 20. Büchner, Frederike L
    et al.
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    Kampman, Ellen
    Egevad, Lars
    Overvad, Kim
    Raaschou-Nielsen, Ole
    Tjønneland, Anne
    Roswall, Nina
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Touillaud, Marina
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Boeing, Heiner
    Weikert, Steffen
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Sieri, Sabina
    Vineis, Paolo
    Tumino, Rosario
    Panico, Salvatore
    Vrieling, Alina
    Peeters, Petra H M
    van Gils, Carla H
    Lund, Eiliv
    Gram, Inger T
    Engeset, Dagrun
    Martinez, Carmen
    Gonzalez, Carlos A
    Larrañaga, Nerea
    Ardanaz, Eva
    Navarro, Carmen
    Rodríguez, Laudina
    Manjer, Jonas
    Ehrnström, Roy A
    Hallmans, Goran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Ljungberg, Borje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Allen, Naomi E
    Roddam, Andrew W
    Bingham, Sheila
    Khaw, Kay-Tee
    Slimani, Nadia
    Boffetta, Paolo
    Jenab, Mazda
    Mouw, Traci
    Michaud, Dominique S
    Kiemeney, Lambertus A L M
    Riboli, Elio
    Consumption of vegetables and fruit and the risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition2009Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, nr 11, s. 2643-2651Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous epidemiologic studies found inconsistent associations between vegetables and fruit consumption and the risk of bladder cancer. We therefore investigated the association between vegetable and fruit consumption and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Data on food consumption and complete follow-up for cancer occurrence was available for a total of 478,533 participants, who were recruited in 10 European countries. Estimates of rate ratios were obtained by Cox proportional hazard models, stratified by age at recruitment, gender and study centre, and adjusted for total energy intake, smoking status, duration of smoking and lifetime intensity of smoking. A calibration study in a subsample was used to control for dietary measurement errors. After a mean follow-up of 8.7 years, 1015 participants were newly diagnosed with bladder cancer. Increments of 100 g/day in fruit and vegetable consumption combined did not affect bladder cancer risk (i.e., calibrated HR = 0.98; 95%CI: 0.95-1.01). Borderline statistically significant lower bladder cancer risks were found among never smokers with increased consumption of fruit and vegetables combined (HR = 0.94 95%CI: 0.87-1.00 with increments of 100 g/day; calibrated HR = 0.92 95%CI 0.79-1.06) and increased consumption of apples and pears (hard fruit; calibrated HR = 0.90 95%CI: 0.82-0.98 with increments of 25 g/day). For none of the associations a statistically significant interaction with smoking status was found. Our findings do not support an effect of fruit and vegetable consumption, combined or separately, on bladder cancer risk. (c) 2009 UICC.

  • 21.
    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 nutrition2011Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, nr 12, s. 2971-2979Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 22.
    Canovic, Sead
    et al.
    Dept. of Applied Physics, Chalmers University of Technology, Fysikgränd 3, SE-412 96 Göteborg, Sweden.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Halvarsson, Mats
    Dept. of Applied Physics, Chalmers University of Technology, Fysikgränd 3, SE-412 96 Göteborg, Sweden.
    CVD TiC/alumina multilayer coatings grown on sapphire single crystals2011Inngår i: Micron, ISSN 0968-4328, E-ISSN 1878-4291, Vol. 42, nr 8, s. 808-818Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Multilayers of TiC/α-Al(2)O(3) consisting of three (1μm thick) alumina layers separated by thin (∼10nm) oxidized TiC layers have been deposited onto c-, a- and r-surfaces of single crystals of α-Al(2)O(3) by chemical vapour deposition (CVD). The aim of this paper is to describe and compare the detailed microstructure of the different multilayer coatings by using transmission electron microscopy (TEM). The general microstructure of the alumina layers is very different when deposited onto different surfaces of α-Al(2)O(3) single crystal substrates. On the c- and a-surfaces the alumina layers grow evenly resulting in growth of single crystal layers of TiC and alumina throughout the coating. However, when deposited on the r-surface the alumina layers generally grow unevenly. No pores are observed within the alumina layers, while a small number of pores are found at the interfaces below the TiC layers. The TiC and alumina layers grow epitaxially on the c- and a-surface substrates. On the r-surface, epitaxy is present only at some rare locations. The TiC layers were oxidized in situ for 2min in CO(2)/H(2) prior to the alumina layer deposition. For all three samples chemical analyses show that the whole TiC layer is oxidized. On the c- and a-surfaces the TiC layer was oxidized to an fcc TiCO phase. On the r-surface the oxidation stage resulted in a transformation of the initially deposited fcc TiC to a monoclinic TiCO phase, which appears to be a modified TiO structure with a high carbon content.

  • 23. Carter, J.
    et al.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hafizi, S.
    Sequence-specific epigenetic variation in the TNS3 gene promoter and its relation to Tensin3 expression in human kidney cancer2012Inngår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 279, s. 486-486Artikkel i tidsskrift (Annet vitenskapelig)
  • 24. Carter, Jessica A.
    et al.
    Gorecki, Dariusz C.
    Mein, Charles A.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hafizi, Sassan
    CpG dinucleotide-specific hypermethylation of the TNS3 gene promoter in human renal cell carcinoma2013Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 8, nr 7, s. 739-747Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tensin3 is a cytoskeletal regulatory protein that inhibits cell motility. Downregulation of the gene encoding Tensin3 (TNS3) in human renal cell carcinoma (RCC) may contribute to cancer cell metastatic behavior. We speculated that epigenetic mechanisms, e.g., gene promoter hypermethylation, might account for TNS3 downregulation. In this study, we identified and validated a TNS3 gene promoter containing a CpG island, and quantified the methylation level within this region in RCC. Using a luciferase reporter assay we demonstrated a functional minimal promoter activity for a 500-bp sequence within the TNS3 CpG island. Pyrosequencing enabled quantitative determination of DNA methylation of each CpG dinucleotide (a total of 43) in the TNS3 gene promoter. Across the entire analyzed CpG stretch, RCC DNA showed a higher methylation level than both non-tumor kidney DNA and normal control DNA. Out of all the CpGs analyzed, two CpG dinucleotides, specifically position 2 and 8, showed the most pronounced increases in methylation levels in tumor samples. Furthermore, CpG-specific higher methylation levels were correlated with lower TNS3 gene expression levels in RCC samples. In addition, pharmacological demethylation treatment of cultured kidney cells caused a 3-fold upregulation of Tensin3 expression. In conclusion, these results reveal a differential methylation pattern in the TNS3 promoter occurring in human RCC, suggesting an epigenetic mechanism for aberrant Tensin downregulation in human kidney cancer.

  • 25. 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)2019Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, nr 2, s. 261-264Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 26. 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)2019Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, nr 1, s. 14-20Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 27. 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 Analysis2019Inngår i: European Urology Focus, ISSN 1540-0085, E-ISSN 1788-618X, nr 5, s. 857-866Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 28. Dabestani, Saeed
    et al.
    Marconi, Lorenzo
    Hofmann, Fabian
    Stewart, Fiona
    Lam, Thomas B. L.
    Canfield, Steven E.
    Staehler, Michael
    Powles, Thomas
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bex, Axel
    Local treatments for metastases of renal cell carcinoma: a systematic review2014Inngår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 15, nr 12, s. E549-E561Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research.

  • 29. Dabestani, Saeed
    et al.
    Thorstenson, Andreas
    Lindblad, Per
    Harmenberg, Ulrika
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lundstam, Sven
    Renal cell carcinoma recurrences and metastases in primary non-metastatic patients: a population-based study2016Inngår i: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 34, nr 8, s. 1081-1086Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To present the occurrence of metastases and local recurrences in primary non-metastatic patients with renal cell carcinoma (RCC) in a contemporary Swedish population-based cohort. Between 2005 and 2009, a total of 4527 patients were included in the prospective National Swedish Kidney Cancer Register accounting for nearly all RCC patients in Sweden. Among M0 patients, 472 (13 %) had no follow-up data registered within 5-year follow-up time and were excluded from the analysis. In total, 939 (21 %) had distant metastases at presentation with a decrease from 23 to 18 % during the inclusion period. Of 3107 patients with follow-up data and with M0 disease, 623 (20 %) were diagnosed with a tumor recurrence during 5-year follow-up. Mean time to recurrence was 24 months (SD +/- A 20 months). Among these, 570 patients (92 %) were at primary diagnosis treated with radical nephrectomy, 23 patients (3.7 %) with partial nephrectomy and 12 patients (1.9 %) with minimally invasive treatments. The most frequent sites of metastases were lung (54 %), lymph nodes (22 %) and bone (20 %). The treatment of recurrence was in 50 % systemic treatments, while metastasectomy was performed in 17 % of the patients, out of which 68 % were with a curative intention. In this population-based study, 21 % of the patients had metastatic disease at presentation, with a decreasing trend over the study period. During 5-year follow-up, 20 % of the primary non-metastatic patients had recurrent disease. Of the patients with recurrence, half were given systemic oncological treatment and 17 % underwent metastasectomy.

  • 30.
    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.2009Inngår i: International Journal of Urological Nursing, ISSN 1749-771X, Vol. 3, nr 2, s. 64-68Artikkel i tidsskrift (Annet vitenskapelig)
    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.

  • 31.
    Degerman, Sofie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Tumkur Sitaram, Raviprakash
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The NBS1 gene is overexpressed and regulated by DJ-1 in clear cell renal cell carcinomaManuskript (preprint) (Annet vitenskapelig)
  • 32. Eichelberg, Christian
    et al.
    Junker, Kerstin
    Ljungberg, Börje
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Moch, Holger
    Diagnostic and prognostic molecular markers for renal cell carcinoma: a critical appraisal of the current state of research and clinical applicability.2009Inngår i: European urology, ISSN 1873-7560, Vol. 55, nr 4, s. 851-63Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: Earlier detection of renal cell carcinoma (RCC) and the recent expansion of treatment possibilities have positively influenced the outlook for patients with this disease. However, progression and treatment response are still not sufficiently predictable. Molecular markers could help to refine individual risk stratification and treatment planning, although they have not yet become clinically routine. OBJECTIVE: This review presents an overview of diagnostic and prognostic molecular markers for RCC and a subgrouping of these markers for different clinical issues. EVIDENCE ACQUISITION: Literature and recent meeting abstracts were searched using these terms: renal (cell) carcinoma, molecular/tumor markers, biopsy, blood, urine, disease progression/prognosis, immunohistochemistry, risk factors, and survival. Due to the resulting large number of articles, studies were subjectively selected according to the importance of a study on the field, number of investigated patients, originality, multivariate analyses performed, contrast with previously published data, actuality, and assumed clinical applicability of the described results. More then 90% of the selected studies originated from the past 10 yr; >50% of the articles were written in 2006 or later. EVIDENCE SYNTHESIS: These data were predominantly obtained via nonrandomized, retrospective, but often controlled studies. Thereby, the resulting level of evidence is 2A/2B. The broad spectrum of described molecular markers (MMs) for RCC consists of markers already extensively studied in other malignancies (eg, p53), as well as MMs typically associated with specific RCC-altered gene functions and pathways (eg, von Hippel-Lindau [VHL]). The main goal of using MMs is to refine the prediction of clinical end points like tumor progression, treatment response, and cancer-specific and/or overall survival. Further, MMs might facilitate the clinical work-up of undefined renal masses and prove to be more convenient tools for screening and follow-up in blood and urine. CONCLUSIONS: Presently, there are a number of promising MMs for diverse clinical questions, but the available data are not yet valid enough for routine, clinical application. We should comply with the demand for large multicenter prospective investigations, stratified for RCC type and treatment modalities, to lift the use of molecular markers in RCC to a practical level, thereby providing a better consultation for our patients regarding diagnosis, treatment, and follow-up.

  • 33. Escudier, Bernard
    et al.
    Osanto, Susanne
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Porta, Camillo
    Wagstaff, John
    Mulders, Peter
    Gore, Martin
    Bex, Axel
    Bellmunt, Joaquim
    Bracarda, Sergio
    Franklin, Alex
    Honoré, Per Hartvig
    Ravaud, Alain
    van Steijn, Jeanne
    Aziz, Zeba
    Akaza, Hideyuki
    Multidisciplinary management of metastatic renal cell carcinoma in the era of targeted therapies2012Inngår i: Cancer Treatment Reviews, ISSN 0305-7372, E-ISSN 1532-1967, Vol. 38, nr 2, s. 127-132Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The use of targeted agents to treat metastatic renal cell carcinoma (mRCC) has significantly extended progression-free and overall survival but raises issues relating to the long-term delivery of care and the sustained monitoring of efficacy and toxicities, certain of which have not previously been experienced. In this paper, an expert group of medical oncologists, urologists and oncology nurses and pharmacists review and make informal recommendations on the multidisciplinary management of mRCC in the light of progress made and problems that have arisen. Decentralisation of care, with a shift in emphasis from large to small hospitals and possibly to the community, may offer advantages of cost and convenience. However, the major responsibility for care should continue to lie with clinicians (either medical oncologists or urologists) with extensive experience in mRCC, assisted by specialist nurses, and working in centres with facilities adequate to monitor efficacy and manage toxicities. That said, the extended survival of patients emphasises the importance of compliance and the long-term prevention, detection and management of side effects. Much of this will take place in the community. There is therefore a need for multidisciplinary working to extend beyond specialist centres to include general practitioners, community nurses and pharmacists. Although this paper focuses on mRCC, many of the considerations discussed are also relevant to the management of more common solid tumours in the era of targeted therapy.

  • 34.
    Evelönn, Emma Andersson
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Köhn, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    DNA methylation status defines clinicopathological parameters including survival for patients with clear cell renal cell carcinoma (ccRCC)2016Inngår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, nr 8, s. 10219-10228Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epigenetic alterations in the methylome have been associated with tumor development and progression in renal cell carcinoma (RCC). In this study, 45 tumor samples, 12 tumor-free kidney cortex tissues, and 24 peripheral blood samples from patients with clear cell RCC (ccRCC) were analyzed by genome-wide promoter-directed methylation arrays and related to clinicopathological parameters. Unsupervised hierarchical clustering separated the tumors into two distinct methylation groups (clusters A and B), where cluster B had higher average methylation and increased number of hypermethylated CpG sites (CpGs). Furthermore, tumors in cluster B had, compared with cluster A, a larger tumor diameter (p = 0.033), a higher morphologic grade (p < 0.001), a higher tumor-node-metastasis (TNM) stage (p < 0.001), and a worse prognosis (p = 0.005). Higher TNM stage was correlated to an increase in average methylation level (p = 0.003) and number of hypermethylated CpGs (p = 0.003), whereas a number of hypomethylated CpGs were mainly unchanged. However, the predicted age of the tumors based on methylation profile did not correlate with TNM stage, morphological grade, or methylation cluster. Differently methylated (DM) genes (n = 840) in ccRCC samples compared with tumor-free kidney cortex samples were predominantly hypermethylated and a high proportion were identified as polycomb target genes. The DM genes were overrepresented by transcription factors, ligands, and receptors, indicating functional alterations of significance for ccRCC progression. To conclude, increased number of hypermethylated genes was associated with increased TNM stage of the tumors. DNA methylation classification of ccRCC tumor samples at diagnosis can serve as a clinically applicable prognostic marker in ccRCC.

  • 35. 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.2017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 3, s. 426-436Artikkel, forskningsoversikt (Fagfellevurdert)
    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.

  • 36. 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 risk2014Inngår i: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 35, nr 8, s. 1737-1744Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 37. 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 ancestry2016Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, nr 6, s. 1203-1214Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 38. Figueroa, Jonine D.
    et al.
    Ye, Yuanqing
    Siddiq, Afshan
    Garcia-Closas, Montserrat
    Chatterjee, Nilanjan
    Prokunina-Olsson, Ludmila
    Cortessis, Victoria K.
    Kooperberg, Charles
    Cussenot, Olivier
    Benhamou, Simone
    Prescott, Jennifer
    Porru, Stefano
    Dinney, Colin P.
    Malats, Nuria
    Baris, Dalsu
    Purdue, Mark
    Jacobs, Eric J.
    Albanes, Demetrius
    Wang, Zhaoming
    Deng, Xiang
    Chung, Charles C.
    Tang, Wei
    Bueno-De-Mesquita, H. Bas
    Trichopoulos, Dimitrios
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Clavel-Chapelon, Frangoise
    Weiderpass, Elisabete
    Krogh, Vittorio
    Dorronsoro, Miren
    Travis, Ruth
    Tjonneland, 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
    Kamat, Ashish M.
    Lerner, Seth P.
    Grossman, H. Barton
    Lin, Jie
    Gu, Jian
    Pu, Xia
    Hutchinson, Amy
    Burdette, Laurie
    Wheeler, William
    Kogevinas, Manolis
    Tardon, Adonina
    Serra, Consol
    Carrato, Alfredo
    Garcia-Closas, Reina
    Lloreta, Josep
    Schwenn, Molly
    Karagas, Margaret R.
    Johnson, Alison
    Schned, Alan
    Armenti, Karla R.
    Hosain, G. M.
    Andriole, Gerald, Jr.
    Grubb, Robert, III
    Black, Amanda
    Diver, W. Ryan
    Gapstur, Susan M.
    Weinstein, Stephanie J.
    Virtamo, Jarmo
    Haiman, Chris A.
    Landi, Maria T.
    Caporaso, Neil
    Fraumeni, Joseph F., Jr.
    Vineis, Paolo
    Wu, Xifeng
    Silverman, Debra T.
    Chanock, Stephen
    Rothman, Nathaniel
    Genome-wide association study identifies multiple loci associated with bladder cancer risk2014Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, nr 5, s. 1387-1398Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    andidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

  • 39. Fritz, Helena K.
    et al.
    Gustafsson, Anna
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ceder, Yvonne
    Axelson, Hakan
    Dahlback, Bjorn
    The Axl-Regulating Tumor Suppressor miR-34a Is Increased in ccRCC but Does Not Correlate with Axl mRNA or Axl Protein Levels2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 8, artikkel-id e0135991Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High expression of the receptor tyrosine kinase Axl is associated with poor prognosis in patients with Renal Cell Carcinoma (RCC), the most common malignancy of the kidney. The miR-34a has been shown to directly regulate Axl in cancer cells. The miR-34a is a mediator of p53-dependent tumor suppression, and low expression of miR-34a has been associated with worse prognosis in several cancers. Our aim was to elucidate whether miR-34a or the other members of the miR-34 family (miR-34b/c) regulate Axl in RCC.

  • 40. Fritz, Helena K. M.
    et al.
    Lindgren, David
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Axelson, Håkan
    Dahlbäck, Björn
    The miR(21/10b) ratio as a prognostic marker in clear cell renal cell carcinoma2014Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, nr 10, s. 1758-1765Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer in the adult kidney, and the prognosis of metastatic ccRCC remains poor with high mortality. In ccRCC, microRNAs (miRs) differentially expressed in tumour tissue have been identified and have been proposed to predict prognosis. The purpose of this study was to evaluate candidate miR markers identified from analysis of The Cancer Genome Atlas (TCGA) datasets in a large RCC cohort and to elucidate whether a ratio of miRs provided additional prognostic information. Experimental design: Deep sequencing data from TCGA datasets were analysed using biostatistical methods to identify candidate miRs that correlate with factors such as survival and stage of disease. Candidate miRs were analysed by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) in a cohort of 198 RCC tumours (ccRCC, n = 152) and 50 normal kidney samples. Results: Four candidate miRs (miR-10b, miR-21, miR-101 and miR-223) were selected from the TCGA analysis and analysed in our cohort. Of these, miR-21 and miR-10b were differentially expressed in RCC subtypes and in ccRCC nuclear grades. Individually, the two miRs demonstrated a non-significant trend to correlate with survival. Importantly, the ratio of miR-21/miR10b (miR(21/10b),) correlated significantly with disease severity and survival, a high miR(21/10b) being associated with poor prognosis (P = 0.0095). In particular, the miR(21/10b) was found to be an independent prognostic factor in metastasis-free patients (P = 0.016; confidence interval (CI) 1.201-5.736). Conclusions: We have shown that the miR(21/10b) ratio is an independent prognostic factor for M0 ccRCC patients, which could be useful to identify high-risk M0 patients who could benefit from increased surveillance.

  • 41. Fritz, Helena K. M.
    et al.
    Lindgren, David
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Axelson, Håkan
    Dahlbäck, Björn
    The miR21/10b ratio as a prognostic marker in metastasis-free clear cell renal cell carcinoma patients2014Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, s. S143-S144Artikkel i tidsskrift (Annet vitenskapelig)
  • 42. Fu, Yi-Ping
    et al.
    Kohaar, Indu
    Moore, Lee E.
    Lenz, Petra
    Figueroa, Jonine D.
    Tang, Wei
    Porter-Gill, Patricia
    Chatterjee, Nilanjan
    Scott-Johnson, Alexandra
    Garcia-Closas, Montserrat
    Muchmore, Brian
    Baris, Dalsu
    Paquin, Ashley
    Ylaya, Kris
    Schwenn, Molly
    Apolo, Andrea B.
    Karagas, Margaret R.
    Tarway, McAnthony
    Johnson, Alison
    Mumy, Adam
    Schned, Alan
    Guedez, Liliana
    Jones, Michael A.
    Kida, Masatoshi
    Hosain, G. M. Monawar
    Malats, Nuria
    Kogevinas, Manolis
    Tardon, Adonina
    Serra, Consol
    Carrato, Alfredo
    Garcia-Closas, Reina
    Lloreta, Josep
    Wu, Xifeng
    Purdue, Mark
    Andriole, Gerald L., Jr.
    Grubb, Robert L., III
    Black, Amanda
    Landi, Maria T.
    Caporaso, Neil E.
    Vineis, Paolo
    Siddiq, Afshan
    Bueno-de-Mesquita, H. Bas
    Trichopoulos, Dimitrios
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Severi, Gianluca
    Weiderpass, Elisabete
    Krogh, Vittorio
    Dorronsoro, Miren
    Travis, Ruth C.
    Tjonneland, Anne
    Brennan, Paul
    Chang-Claude, Jenny
    Riboli, Elio
    Prescott, Jennifer
    Chen, Constance
    De Vivo, Immaculata
    Govannucci, Edward
    Hunter, David
    Kraft, Peter
    Lindstrom, Sara
    Gapstur, Susan M.
    Jacobs, Eric J.
    Diver, W. Ryan
    Albanes, Demetrius
    Weinstein, Stephanie J.
    Virtamo, Jarmo
    Kooperberg, Charles
    Hohensee, Chancellor
    Rodabough, Rebecca J.
    Cortessis, Victoria K.
    Conti, David V.
    Gago-Dominguez, Manuela
    Stern, Mariana C.
    Pike, Malcolm C.
    Van Den Berg, David
    Yuan, Jian-Min
    Haiman, Christopher A.
    Cussenot, Olivier
    Cancel-Tassin, Geraldine
    Roupret, Morgan
    Comperat, Eva
    Porru, Stefano
    Carta, Angela
    Pavanello, Sofia
    Arici, Cecilia
    Mastrangelo, Giuseppe
    Grossman, H. Barton
    Wang, Zhaoming
    Deng, Xiang
    Chung, Charles C.
    Hutchinson, Amy
    Burdette, Laurie
    Wheeler, William
    Fraumeni, Joseph, Jr.
    Chanock, Stephen J.
    Hewitt, Stephen M.
    Silverman, Debra T.
    Rothman, Nathaniel
    Prokunina-Olsson, Ludmila
    The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease2014Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, nr 20, s. 5808-5818Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) >= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P-trend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.

  • 43. Granfors, Torvald
    et al.
    Tomic, Radisa
    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.
    Downstaging and survival benefits of neoadjuvant radiotherapy before cystectomy for patients with invasive bladder carcinoma.2009Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, nr 4, s. 293-299Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To compare the long-term outcomes of a series of patients treated with neoadjuvant radiotherapy combined with cystectomy against a later series of patients treated with immediate cystectomy. MATERIAL AND METHODS: A total of 187 consecutive patients, surgically treated with cystectomy due to cT1-3 transitional cell bladder carcinoma with (n=90) or without (n=97) neoadjuvant radiotherapy, was included in a retrospective analysis. The clinical stage at the primary bladder resection and the pathological reports after the cystectomy were re-evaluated and progression-free, disease-specific and overall survival were calculated. RESULTS: Seven of 97 (7%) patients treated without any neoadjuvant therapy had pT0 in the bladder specimen. In contrast, 51 of 90 patients (57%) treated with neoadjuvant radiotherapy downstaged to pT0. Among cT3 tumours none of 16 patients (0%) treated without radiotherapy downstaged to pT0, while 19 (56%) of 34 patients treated with radiotherapy did so. The progression-free survival was significantly longer for patients with pT0 than for those with a remaining tumour (pT1-4) in the cystectomy specimen (p<0.001). A high T stage correlated with adverse overall survival. Patients with cT3 tumours treated with neoadjuvant radiotherapy followed by cystectomy had significantly longer disease-specific survival time (p=0.007) than those undergoing cystectomy only. In a Cox regression analysis, cT stage as well as pT stage and occurrence of carcinoma in situ in the cystectomy specimens remained as independent prognostic factors. CONCLUSIONS: In this retrospective study neoadjuvant radiotherapy before the cystectomy resulted in significant downstaging of invasive bladder transitional cell carcinoma. This downstaging was most significant for patients with cT3 tumours leading to prolonged survival.

  • 44. Grimm, Marc-Oliver
    et al.
    Bex, Axel
    De Santis, Maria
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Catto, James W. F.
    Rouprêt, Morgan
    Hussain, Syed A.
    Bellmunt, Joaquim
    Powles, Tom
    Wirth, Manfred
    Van Poppel, Hendrik
    Safe Use of Immune Checkpoint Inhibitors in the Multidisciplinary Management of Urological Cancer: The European Association of Urology Position in 20192019Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 3, s. 368-380Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Immune checkpoint inhibitors (ICIs) are now used routinely to treat advanced or metastatic urothelial and renal cell carcinoma, among other cancers. Furthermore, multiple trials are currently exploring their role in adjuvant, neoadjuvant, and noninvasive (eg, high-grade non-muscle-invasive bladder cancer) settings. Consequently, urologists are increasingly confronted with patients who are on, have recently received, or will be treated with ICI therapy. The care of these patients is likely to be shared between urologists and medical oncologists, with additional occasional support of other medical specialties. Therefore, it is important that urologists have good knowledge of immune-related side effects. Here, we provide advice on prevention, early diagnosis, and clinical management of the most relevant toxicities to strengthen urologists' insight and, thus, role in the multidisciplinary management in the new immunotherapy era. Patient summary: Immune therapy is a common treatment for many patients with advanced cancer. We describe common side effects of this treatment, and advise how they are best prevented and managed.

  • 45. Gudmundsson, E. O.
    et al.
    Erikson, S.
    Hosseinnia, S.
    Lundstam, S.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Significant regional differences in the treatment of small renal cancers in Sweden2012Inngår i: European urology. Supplement, ISSN 1569-9056, E-ISSN 1878-1500, Vol. 11, nr 1, s. E135-E135Artikkel i tidsskrift (Annet vitenskapelig)
  • 46. Guomundsson, Eirikur
    et al.
    Hellborg, Henrik
    Lundstam, Sven
    Erikson, Stina
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Metastatic potential in renal cell carcinomas <= 7 cm: swedish kidney cancer quality register data2011Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, nr 5, s. 975-982Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Renal cell carcinoma(RCC) represents 2-3% of all malignancies and accounts for approximately 90% of all kidney malignancies. An increasing proportion of RCCs are discovered incidentally, and the average tumor diameter at diagnosis has decreased over the last few decades. Small RCCs have often been regarded by many as relatively harmless.

    Objective: The objective was to evaluate the incidence of local T-category distribution and lymph node and distant metastases in relation to tumor size in RCCs <= 7 cm in a nationally based patient population. Design, setting, and participants: Data were extracted from the National Swedish Kidney Cancer Register containing 3489 RCCs diagnosed between 2005 and 2008. This is a population-based registry including 99% of all RCCs diagnosed nationwide. The study included 2033 patients having a tumor <= 7 cm in diameter.

    Measurements: The size of the tumors was compared with sex, age, cause of diagnosis, Fuhrman grade, RCC type, and TNM category.

    Results and limitations: Most RCCs were discovered incidentally and incidence correlated inversely to tumor size. There were 887 (43%) patients with category T1a tumors, 836 (40%) with category T1b, 174 (8%) with T3a, 131 (6%) with T3b/c, and 12 (1%) patients had invasion of adjacent organs (T4). A total of 309 (15%) patients had lymph node and/or distant metastases. Of the 177 1- to 2-cm RCCs, category T3 tumors were identified in three patients and lymph node and/or distant metastases were identified in 8 (5%). Only for tumors <= 1 cm was there neither advanced stage nor metastasis. The occurrence of locally advanced growth, lymph node and distant metastases, and high tumor grade correlated to tumor size. Patients with Fuhrman grade III or IV had a fourfold greater risk of metastases than grades I or II.

    Conclusions: Lymph node and distant metastases occur even in small RCCs. Risk of metastases increases with tumor size. The data clearly show that small RCCs also have a malignant potential and should be properly evaluated and adequately treated. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.

  • 47. Gustafsson, Anna
    et al.
    Boström, Anna-Karin
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Axelson, Håkan
    Dahlbäck, Björn
    Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma.2009Inngår i: PloS one, ISSN 1932-6203, Vol. 4, nr 10, s. e7575-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The molecular biology of renal cell carcinoma (RCC) is complex and not fully understood. We have recently found that the expression of the receptor tyrosine kinase Axl in the RCC tumors independently correlates with survival of the patients. PRINCIPAL FINDINGS: Here, we have investigated the role of Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, in clear cell RCC (ccRCC) derived cells. The Axl protein was highly expressed in ccRCC cells deficient in functional von Hippel-Lindau (VHL) protein, a tumor suppressor gene often inactivated in ccRCC. VHL reconstituted cells expressed decreased levels of Axl protein, but not Axl mRNA, suggesting VHL to regulate Axl expression. Gas6-mediated activation of Axl in ccRCC cells resulted in Axl phosphorylation, receptor down-regulation, decreased cell-viability and migratory capacity. No effects of the Gas6/Axl system could be detected on invasion. Moreover, in ccRCC tumor tissues, Axl was phosphorylated and Gas6 gamma-carboxylated, suggesting these molecules to be active in vivo. SIGNIFICANCE: These results provide novel information regarding the complex function of the Gas6/Axl system in ccRCC.

  • 48. Gustafsson, Anna
    et al.
    Martuszewska, Danuta
    Johansson, Martin
    Ekman, Carl
    Hafizi, Sassan
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Dahlbäck, Björn
    Differential expression of Axl and Gas6 in renal cell carcinoma reflecting tumor advancement and survival2009Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 15, nr 14, s. 4742-4749Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Overexpression of the receptor tyrosine kinase Axl is implicated in several cancers. Therefore, we conducted this study to determine the expression of Axl and its ligand Gas6 in various renal cell carcinoma (RCC) types and in oncocytoma.

    EXPERIMENTAL DESIGN: Real-time quantitative reverse transcription-PCR was used to quantify tumor mRNA levels for Axl and Gas6 in a cohort (n = 221) of RCC patients. Serum levels of soluble sAxl and Gas6 proteins were measured using specific ELISA assays (n = 282). The presence of Axl protein in tumor tissue was evaluated by immunohistochemistry (n = 294). Results were correlated to tumor-associated variables, clinical biochemical tests, and patient survival.

    RESULTS: Tumor Axl mRNA levels correlated independently to survival when assessed against tumor stage and grade. In the study group, the median cancer-specific survival of all RCC patients during 307 months of follow-up was 55 months (confidence interval, +/-40.4). The 25% of patients with lowest tumor Axl mRNA levels had significantly better survival than the rest (P = 0.0005), with 70% of the patients still alive at the end of follow-up. In contrast, in patients with medium-high Axl mRNA, only 25% were alive at the end of follow-up. Tumor Gas6 mRNA levels correlated to survival, tumor-associated variables, and disease severity as did serum levels of soluble sAxl and Gas6 protein. However, no correlation between Axl protein in tumor tissue and survival was found.

    CONCLUSIONS: Axl and Gas6 expression in RCC are associated with tumor advancement and patient survival. In particular, low tumor Axl mRNA levels independently correlated with improved survival.

  • 49.
    Hedberg, Ylva
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Ljungberg, Börje
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Roos, Göran
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Landberg, Göran
    Retinoblastoma protein in human renal cell carcinoma in relation to alterations in G1/S regulatory proteins.2004Inngår i: International journal of cancer, ISSN 0020-7136, Vol. 109, nr 2, s. 189-93Artikkel i tidsskrift (Fagfellevurdert)
  • 50. Hosen, Ismail
    et al.
    Rachakonda, P. Sivaramakrishna
    Heidenreich, Barbara
    Sitaram, Raviprakash T.
    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.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Hemminki, Kari
    Kumar, Rajiv
    TERT promoter mutations in clear cell renal cell carcinoma2015Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, nr 10, s. 2448-2452Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We screened promoter region of the telomerase reverse transcriptase (TERT) for activating somatic mutations in 188 tumors from patients with clear cell renal cell carcinoma (ccRCC). Twelve tumors (6.4%) carried a mutation within the core promoter region of the gene. The mutations were less frequent in high grade tumors compared to low grade tumors [odds ratio (OR)=0.15, 95% confidence interval (CI)=0.03-0.72, p=0.02]. Multivariate analysis for cause specific survival showed statistically significant poor outcome in patients with TERT promoter mutations [hazard ratio (HR)=2.90, 95% CI=1.13-7.39, p=0.03]. A common polymorphism (rs2853669) within the locus seemed to act as a modifier of the effect of the mutations on patient survival as the noncarriers of the variant allele with the TERT promoter mutations showed worst survival (HR=3.34, 95% CI=1.24-8.98, p=0.02). We also measured relative telomere length (RTL) in tumors and difference between tumors with and without the TERT promoter mutations was not statistically significant. Similarly, no difference in patient survival based on RTL in tumors was observed. Our study showed a relatively low frequency of TERT promoter mutations in ccRCC. Nevertheless, patients with the mutations, particularly in the absence of the rs2853669 variant showed the worst disease-specific survival. Thus, it is possible that the TERT promoter mutations define a small subset of tumors with an aggressive behavior. What's new? The human telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of telomerase, a ribonucleoprotein complex that maintains genomic integrity. Activating somatic mutations in the promoter region of the TERT gene have been reported in many cancers. Here, the authors describe new TERT promoter mutations in clear cell renal cell carcinoma. Although present only in a proportion of the tumors, the TERT promoter mutations were independently associated with poor patient survival. The effect was enhanced by a common polymorphism within the core TERT promoter. The TERT promoter mutations may thus define a small subset of tumors with an aggressive behavior.

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