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  • 1.
    Aas, Kirsti
    et al.
    Consultant Urological Surgeon and Associate Professor, Akershus University Hospital, Norway; Faculty of Medicine, University of Oslo, Norway.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Consultant Urological Surgeon and Associate Professor, Norrlands University Hospital, Umeå, Sweden.
    Long-term patient follow-up should be routinely implemented in radiotherapy units to detect late adverse effects after cancer treatment2023In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 58, p. 30-31Article in journal (Other academic)
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  • 2. Abu-Ghanem, Yasmin
    et al.
    Fernandez-Pello, Sergio
    Bex, Axel
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Albiges, Laurence
    Dabestani, Saeed
    Giles, Rachel H.
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Kuusk, Teele
    Marconi, Lorenzo
    Merseburger, Axel S.
    Tahbaz, Rana
    Staehler, Michael
    Volpe, Alessandro
    Powles, Thomas
    Lam, Thomas B.
    Bensalah, Karim
    Limitations of Available Studies Prevent Reliable Comparison Between Tumour Ablation and Partial Nephrectomy for Patients with Localised Renal Masses: A Systematic Review from the European Association of Urology Renal Cell Cancer Guideline Panel2020In: European Urology Oncology, E-ISSN 2588-9311, Vol. 3, no 4, p. 423-442Article, review/survey (Refereed)
    Abstract [en]

    The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n = 11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies.

    Patient summary: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness.

  • 3.
    Abu-Ghanem, Yasmin
    et al.
    UCL Division of Surgical and Interventional Science, Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, London, United Kingdom.
    Powles, Thomas
    Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
    Capitanio, Umberto
    Division of Experimental Oncology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy.
    Beisland, Christian
    Department of Urology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
    Järvinen, Petrus
    Urology, Abdominal Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Stewart, Grant D.
    Department of Surgery, University of Cambridge, Cambridge, United Kingdom.
    Gudmundsson, Eirikur
    Department of Urology, Landspitali University Hospital, Reykjavik, Iceland.
    Lam, Thomas B.L.
    Academic Urology Unit, University of Aberdeen, Aberdeen, United Kingdom.
    Marconi, Lorenzo
    Department of Urology, Coimbra University Hospital, Coimbra, Portugal.
    Fernandéz-Pello, Sergio
    Department of Urology, Cabueñes University Hospital, Gijón, Spain.
    Nisen, Harry
    Urology, Abdominal Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Meijer, Richard P.
    Department of Oncological Urology, University Medical Centre Utrecht, Utrecht, Netherlands.
    Volpe, Alessandro
    Department of Urology, Maggiore della Carità Hospital, University of Eastern Piedmont, Novara, Italy.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Klatte, Tobias
    Department of Surgery, University of Cambridge, Cambridge, United Kingdom; Department of Urology, Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, United Kingdom.
    Bensalah, Karim
    Department of Urology, University Hospital of Rennes, Rennes, France.
    Dabestani, Saeed
    Division of Urological Cancers, Department of Translational Medicine, Central Hospital Kristianstad, Lund University, Lund, Sweden.
    Bex, Axel
    UCL Division of Surgical and Interventional Science, Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, London, United Kingdom; Department of Urology, Netherlands Cancer Institute, Amsterdam, Netherlands.
    Should patients with low-risk renal cell carcinoma be followed differently after nephron-sparing surgery vs radical nephrectomy?2021In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 128, no 3, p. 386-394Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether pT1 renal cell carcinoma (RCC) should be followed differently after partial (PN) or radical nephrectomy (RN) based on a retrospective analysis of a multicentre database (RECUR).

    Subjects: A retrospective study was conducted in 3380 patients treated for nonmetastatic RCC between January 2006 and December 2011 across 15 centres from 10 countries, as part of the RECUR database project. For patients with pT1 clear-cell RCC, patterns of recurrence were compared between RN and PN according to recurrence site. Univariate and multivariate models were used to evaluate the association between surgical approach and recurrence-free survival (RFS) and cancer-specific mortality (CSM).

    Results: From the database 1995 patients were identified as low-risk patients (pT1, pN0, pNx), of whom 1055 (52.9%) underwent PN. On multivariate analysis, features associated with worse RFS included tumour size (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14–1.39; P < 0.001), nuclear grade (HR 2.31, 95% CI 1.73–3.08; P < 0.001), tumour necrosis (HR 1.5, 95% CI 1.03–2.3; P = 0.037), vascular invasion (HR 2.4, 95% CI 1.3–4.4; P = 0.005) and positive surgical margins (HR 4.4, 95% CI 2.3–8.5; P < 0.001). Kaplan–Meier analysis of CSM revealed that the survival of patients with recurrence after PN was significantly better than those with recurrence after RN (P = 0.02). While the above-mentioned risk factors were associated with prognosis, type of surgery alone was not an independent prognostic variable for RFS nor CSM. Limitations include the retrospective nature of the study.

    Conclusion: Our results showed that follow-up protocols should not rely solely on stage and type of primary surgery. An optimized regimen should also include validated risk factors rather than type of surgery alone to select the best imaging method and to avoid unnecessary imaging. A follow-up of more than 3 years should be considered in patients with pT1 tumours after RN. A novel follow-up strategy is proposed.

  • 4. Abu-Ghanem, Yasmin
    et al.
    Powles, Thomas
    Capitanio, Umberto
    Beisland, Christian
    Järvinen, Petrus
    Stewart, Grant D.
    Gudmundsson, Eiríkur Orri
    Lam, Thomas B.
    Marconi, Lorenzo
    Fernandéz-Pello, Sergio
    Nisen, Harry
    Meijer, Richard P.
    Volpe, Alessandro
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Klatte, Tobias
    Dabestani, Saeed
    Bex, Axel
    The Impact of Histological Subtype on the Incidence, Timing, and Patterns of Recurrence in Patients with Renal Cell Carcinoma After Surgery: Results from RECUR Consortium2021In: European Urology Oncology, E-ISSN 2588-9311, Vol. 4, no 3, p. 473-482Article in journal (Refereed)
    Abstract [en]

    Background: Current follow-up strategies for patients with renal cell carcinoma (RCC) after curative surgery rely mainly on risk models and the treatment delivered, regardless of the histological subtype.

    Objective: To determine the impact of RCC histological subtype on recurrence and to examine the incidence, pattern, and timing of recurrences to improve follow-up recommendations.

    Design, setting, and participants: This study included consecutive patients treated surgically with curative intention (ie, radical and partial nephrectomy) for nonmetastatic RCC (cT1–4, M0) between January 2006 and December 2011 across 15 centres from 10 countries, as part of the euRopEan association of urology renal cell carcinoma guidelines panel Collaborative multicenter consortium for the studies of follow-Up and recurrence patterns in Radically treated renal cell carcinoma patients (RECUR) database project.

    Outcome measurements and statistical analysis: The impact of histological subtype (ie, clear cell RCC [ccRCC], papillary RCC [pRCC], and chromophobe RCC [chRCC]) on recurrence-free survival (RFS) was assessed via univariate and multivariate analyses, adjusting for potential interactions with important variables (stage, grade, risk score, etc.) Patterns of recurrence for all histological subtypes were compared according to recurrence site and risk criteria.

    Results and limitations: Of the 3331 patients, 62.2% underwent radical nephrectomy and 37.8% partial nephrectomy. A total of 2565 patients (77.0%) had ccRCC, 535 (16.1%) had pRCC, and 231 (6.9%) had chRCC. The median postoperative follow-up period was 61.7 (interquartile range: 47–83) mo. Patients with ccRCC had significantly poorer 5-yr RFS than patients with pRCC and chRCC (78% vs 86% vs 91%, p = 0.001). The most common sites of recurrence for ccRCC were the lung and bone. Intermediate-/high-risk pRCC patients had an increased rate of lymphatic recurrence, both mediastinal and retroperitoneal, while recurrence in chRCC was rare (8.2%), associated with higher stage and positive margins, and predominantly in the liver and bone. Limitations include the retrospective nature of the study.

    Conclusions: The main histological subtypes of RCC exhibit a distinct pattern and dynamics of recurrence. Results suggest that intermediate- to high-risk pRCC may benefit from cross-sectional abdominal imaging every 6 mo until 2 yr after surgery, while routine imaging might be abandoned for chRCC except for abdominal computed tomography in patients with advanced tumour stage or positive margins.

    Patient summary: In this analysis of a large database from 15 countries around Europe, we found that the main histological subtypes of renal cell carcinoma have a distinct pattern and dynamics of recurrence. Patients should be followed differently according to subtype and risk score.

  • 5.
    Abuhasanein, Suleiman
    et al.
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of surgery, Urology section, NU Hospital Group, Uddevalla, Region Västra Götaland, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Jerlström, Tomas
    Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden and Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Göteborg, Sweden.
    Kjölhede, Henrik
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Göteborg, Sweden.
    Do not throw out the baby with the bath water2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 3, p. 235-236Article in journal (Other academic)
  • 6.
    Abuhasanein, Suleiman
    et al.
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Surgery, Urology Section, NU Hospital Group, Trollhättan, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Jerlström, Tomas
    Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Göteborg, Sweden.
    Kjölhede, Henrik
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Göteborg, Sweden.
    Standardized care pathways for patients with suspected urinary bladder cancer: the Swedish experience2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 3, p. 227-232Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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  • 7.
    Adamo, Hanibal
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hägglöf, Christina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahl Scherdin, Tove
    Egevad, Lars
    Granfors, Torvald
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcomeManuscript (preprint) (Other academic)
    Abstract [en]

    Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of a tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ). To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, with distance to the tumor, and with tumor cell metastatic capacity.

    In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and a favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, the presence of metastases at diagnosis, and poor outcome. 

  • 8. Adolf, Katja
    et al.
    Wagner, Ludwig
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Ottosen, Peter
    Borre, Michael
    Birkenkamp-Demtröder, Karin
    Orntoft, Torben Falck
    Tørring, Niels
    Secretagogin is a new neuroendocrine marker in the human prostate.2007In: Prostate, ISSN 0270-4137, Vol. 67, no 5, p. 472-84Article in journal (Refereed)
  • 9. Adolfsson, Jan
    et al.
    Garmo, Hans
    Varenhorst, Eberhard
    Ahlgren, Göran
    Ahlstrand, Christer
    Andrén, Ove
    Bill-Axelson, Anna
    Bratt, Ola
    Damber, Jan-Erik
    Hellström, Karin
    Hellström, Magnus
    Holmberg, Erik
    Holmberg, Lars
    Hugosson, Jonas
    Johansson, Jan-Erik
    Petterson, Bill
    Törnblom, Magnus
    Widmark, Anders
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005.2007In: Scand J Urol Nephrol, ISSN 0036-5599, Vol. 41, p. 456-477Article in journal (Refereed)
  • 10.
    Ahlin, Rebecca
    et al.
    Department of Oncology, Division of Clinical Cancer Epidemiology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Nybacka, Sanna
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Josefsson, Andreas
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Sahlgrenska Cancer Center, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Stranne, Johan
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Steineck, Gunnar
    Department of Oncology, Division of Clinical Cancer Epidemiology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Box 423, Gothenburg, Sweden.
    Hedelin, Maria
    Department of Oncology, Division of Clinical Cancer Epidemiology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Box 423, Gothenburg, Sweden; Regional Cancer Center West, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    The effect of a phytoestrogen intervention and impact of genetic factors on tumor proliferation markers among Swedish patients with prostate cancer: study protocol for the randomized controlled PRODICA trial2022In: Trials, E-ISSN 1745-6215, Vol. 23, no 1, article id 1041Article in journal (Refereed)
    Abstract [en]

    Background: A high intake of phytoestrogens, found in soy, rye, and seeds, is associated with a reduced risk of a prostate cancer diagnosis. Previously, we found that the overall decreased risk of prostate cancer diagnosis in males with a high intake of phytoestrogens was strongly modified by a nucleotide sequence variant in the estrogen receptor-beta (ERβ) gene. However, we do not know if phytoestrogens can inhibit the growth of prostate cancer in males with established diseases. If there is an inhibition or a delay, there is reason to believe that different variants of the ERβ gene will modify the effect. Therefore, we designed an intervention study to investigate the effect of the addition of foods high in phytoestrogens and their interaction with the ERβ genotype on prostate tumor proliferation in patients with prostate cancer.

    Method: The PRODICA trial is a randomized ongoing intervention study in patients with low- and intermediate-risk prostate cancer with a Gleason score < 8, prostate-specific antigen (PSA) < 20, and scheduled for radical prostatectomy. The study is conducted at Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention consists of a daily intake of soybeans and flaxseeds (~ 200 mg of phytoestrogens) until the surgery, approximately 6 weeks. The aim is to recruit 200 participants. The primary outcome is the difference in the proliferation marker Ki-67 between the intervention and the control groups. The genotype of ERβ will be investigated as an effect-modifying factor. Secondary outcomes include, e.g., concentrations of PSA and steroid hormones in the blood.

    Discussion: The results of the PRODICA trial will contribute important information on the relevance of increasing the intake of phytoestrogens in patients with prostate cancer who want to make dietary changes to improve the prognosis of their cancer. If genetic factors turn out to influence the effect of the intervention diet, dietary advice can be given to patients who most likely benefit from it. Dietary interventions are cost-effective, non-invasive, and result in few mild side effects. Lastly, the project will provide basic pathophysiological insights which could be relevant to the development of treatment strategies for patients with prostate cancer.

    Trial registration. ClinicalTrials.gov NCT02759380. Registered on 3 May 2016.

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  • 11.
    Ahlin, Rebecca
    et al.
    Department of Oncology, Division of Clinical Cancer Epidemiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nørskov, Natalja P.
    Department of Animal and Veterinary Sciences, Aarhus University, AU-Foulum, Tjele, Denmark.
    Nybacka, Sanna
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Landberg, Rikard
    Department of Life Sciences, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden.
    Skokic, Viktor
    Department of Oncology, Division of Clinical Cancer Epidemiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Stranne, Johan
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Josefsson, Andreas
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Sahlgrenska Cancer Center, Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Steineck, Gunnar
    Department of Oncology, Division of Clinical Cancer Epidemiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Hedelin, Maria
    Department of Oncology, Division of Clinical Cancer Epidemiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Regional Cancer Center West, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Effects on serum hormone concentrations after a dietary phytoestrogen intervention in patients with prostate cancer: a randomized controlled trial2023In: Nutrients, E-ISSN 2072-6643, Vol. 15, no 7, article id 1792Article in journal (Refereed)
    Abstract [en]

    Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERβ genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERβ (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ.

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  • 12. Ahlén Bergman, Emma
    et al.
    Hartana, Ciputra Adijaya
    Johansson, Markus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden..
    Linton, Ludvig B
    Berglund, Sofia
    Hyllienmark, Martin
    Lundgren, Christian
    Holmström, Benny
    Palmqvist, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgery, Urology Section, Östersund County Hospital, Östersund, Sweden.
    Hansson, Johan
    Alamdari, Farhood
    Huge, Ylva
    Aljabery, Firas
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Winerdal, Malin E
    Krantz, David
    Zirakzadeh, A. Ali
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Unit of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Marits, Per
    Sjöholm, Louise K
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Winqvist, Ola
    Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients2018In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, article id 102Article in journal (Refereed)
    Abstract [en]

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

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

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

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  • 13. Ahlén Bergman, Emma
    et al.
    Hartana, Ciputra Adijaya
    Linton, Ludvig
    Winerdal, Malin E.
    Krantz, David
    Rosenblatt, Robert
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Stockholm South General Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lundgren, Christian
    Marits, Per
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, Ola
    Epigenetic methylation profiles of CD4 T cell signature loci from patients with urinary bladder cancer2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 264-264Article in journal (Other academic)
    Abstract [en]

    Urinary bladder cancer (UBC) is one of the most frequent cancer diseases with 380 000 new cases diagnosed worldwide and about 150 000 deaths yearly. To dissect the role of T helper (Th) cell responses in UBC we investigate the T helper cell subpopulations; Th1, Th2, Th17 and T regulatory cells (Tregs) and their lineage commitment in draining (sentinel) and non-draining lymph nodes and blood from patients subjected to transurethral resection of the bladder (TUR-B) and/or Cystectomy. By analyzing methylation in signature genes IFNG, IL13, IL17a and FOXP3 we measure the epigenetic stability of these T helper cells.

    In most patients IFNG is more demethylated in sentinel nodes compared to non-sentinel nodes and blood, suggesting a Th1 activation in nodes in contact with the tumor. Aside from that, the distribution of subpopulations in all tissues investigated is highly variable in between patients. All subsets are represented, although there seem to be no or little Th17 cells in nodes. After neoadjuvant treatment (given in between the TUR-B and cystectomy) a temporary increase in methylation of IFNG locus is seen in blood, which could suggest a translocation of activated Th cells from the blood to the tumor area, but also de novo synthesis of Th cells.

    By analyzing the intra-patient variations in distribution and relative amount of Th cell subpopulations in blood and sentinel nodes we hope to draw conclusions on differences in outcome. The long-term goal is to be able to identify which patients could respond well to immune modulatory treatments.

  • 14. Ahn, Jiyoung
    et al.
    Schumacher, Fredrick R
    Berndt, Sonja I
    Pfeiffer, Ruth
    Albanes, Demetrius
    Andriole, Gerald L
    Ardanaz, Eva
    Boeing, Heiner
    Bueno-de-Mesquita, Bas
    Chanock, Stephen J
    Clavel-Chapelon, Françoise
    Diver, W Ryan
    Feigelson, Heather Spencer
    Gaziano, J Michael
    Giovannucci, Edward
    Haiman, Christopher A
    Henderson, Brian E
    Hoover, Robert N
    Kolonel, Laurence N
    Kraft, Peter
    Ma, Jing
    Le Marchand, Loïc
    Overvad, Kim
    Palli, Domenico
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Stampfer, Meir
    Stram, Daniel O
    Thomas, Gilles
    Thun, Michael J
    Travis, Ruth C
    Trichopoulos, Dimitrios
    Virtamo, Jarmo
    Weinstein, Stephanie J
    Yeager, Meredith
    Kaaks, Rudolf
    Hunter, David J
    Hayes, Richard B
    Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3).2009In: Human molecular genetics, ISSN 1460-2083, Vol. 18, no 19, p. 3749-57Article in journal (Refereed)
    Abstract [en]

    Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17beta-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.

  • 15. Akre, Olof
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Lambe, Mats
    Bratt, Ola
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Mortality among men with locally advanced prostate cancer managed with noncurative intent: a nationwide study in PCBaSe Sweden2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 3, p. 554-563Article in journal (Refereed)
    Abstract [en]

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

  • 16.
    Alamdari, Farhood Iranparvar
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Adrenal metastasis in renal cell carcinoma: a recommendation for adjustment of the TNM staging system.2005In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, no 4, p. 277-282Article in journal (Refereed)
  • 17.
    Alamdari, Farhood Iranparvar
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry. Klinisk kemi.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Angiogenesis and other markers for prediction of survival in metastatic renal cell carcinoma.2007In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 1, p. 5-9Article in journal (Refereed)
  • 18. Albiges, Laurence
    et al.
    Powles, Tom
    Staehlerr, Michael
    Bensalan, Karim
    Giles, Rachel H.
    Horag, Milan
    Kuczyk, Markus A.
    Lam, Thomas B.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    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 Carcinoma2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, no 2, p. 151-156Article in journal (Refereed)
    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.

  • 19.
    Alcala, Karine
    et al.
    International Agency for Research on Cancer (IARC/WHO), Genomic Epidemiology Branch, 150 Cours Albert Thomas, Lyon, France.
    Mariosa, Daniela
    International Agency for Research on Cancer (IARC/WHO), Genomic Epidemiology Branch, 150 Cours Albert Thomas, Lyon, France.
    Smith-Byrne, Karl
    Cancer Epidemiology Unit, Oxford Population Health, University of Oxford, Oxford, United Kingdom.
    Nasrollahzadeh Nesheli, Dariush
    International Agency for Research on Cancer (IARC/WHO), Genomic Epidemiology Branch, 150 Cours Albert Thomas, Lyon, France.
    Carreras-Torres, Robert
    Group of Digestive Diseases and Microbiota, Institut d'Investigació Biomèdica de Girona-IDIBGI, Salt, Spain.
    Ardanaz Aicua, Eva
    Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Bondonno, Nicola P
    Danish Cancer Society Research Center, Copenhagen, Denmark; School of Biomedical Sciences, University of Western Australia, Royal Perth Hospital, Perth, Australia; Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.
    Bonet, Catalina
    Unit of Nutrition and Cancer, Catalan Institute of Oncology, ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute-(IDIBELL), l'Hospitalet de Llobregat, Barcelona, Spain.
    Brunström, Mattias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bueno-De-Mesquita, Bas
    Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
    Chirlaque, María-Dolores
    CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Christakoudi, Sofia
    Department of Epidemiology and Biostatistics, Imperial College London, Norfolk Place, St Mary's Campus, London, United Kingdom; MRC Centre for Transplantation, King's College London, London, United Kingdom.
    Heath, Alicia K
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Krogh, Vittorio
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, Milan, Italy.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Martin, Richard M
    Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
    May, Anne
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Melander, Olle
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Department of Emergency and Internal Medicine, Skåne University Hospital, Malmö, Sweden.
    Palli, Domenico
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
    Rodriguez-Barranco, Miguel
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria Ibs. GRANADA, Granada, Spain; Centro de Investigacion Biomedica en Red de Epidemiologia y Salud Publica, Madrid, Spain.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Cittàdella Salute e della Scienza University-Hospital, Turin, Italy.
    Stocks, Tanja
    Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Travis, Ruth C.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Vermeulen, Roel
    Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, Netherlands.
    Chanock, Stephen
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Purdue, Mark
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Weiderpass, Elisabete
    International Agency for Research on Cancer (IARC/WHO), Lyon, France.
    Muller, David
    Imperial College London, London, United Kingdom.
    Brennan, Paul
    International Agency for Research on Cancer (IARC/WHO), Genomic Epidemiology Branch, 150 Cours Albert Thomas, Lyon, France.
    Johansson, Mattias
    International Agency for Research on Cancer (IARC/WHO), Genomic Epidemiology Branch, 150 Cours Albert Thomas, Lyon, France.
    The relationship between blood pressure and risk of renal cell carcinoma2022In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 51, no 4, p. 1317-1327Article in journal (Refereed)
    Abstract [en]

    Background: The relation between blood pressure and kidney cancer risk is well established but complex and different study designs have reported discrepant findings on the relative importance of diastolic blood pressure (DBP) and systolic blood pressure (SBP). In this study, we sought to describe the temporal relation between diastolic and SBP with renal cell carcinoma (RCC) risk in detail. Methods: Our study involved two prospective cohorts: the European Prospective Investigation into Cancer and Nutrition study and UK Biobank, including >700 000 participants and 1692 incident RCC cases. Risk analyses were conducted using flexible parametric survival models for DBP and SBP both separately as well as with mutuality adjustment and then adjustment for extended risk factors. We also carried out univariable and multivariable Mendelian randomization (MR) analyses (DBP: ninstruments = 251, SBP: ninstruments = 213) to complement the analyses of measured DBP and SBP. Results: In the univariable analysis, we observed clear positive associations with RCC risk for both diastolic and SBP when measured ≥5 years before diagnosis and suggestive evidence for a stronger risk association in the year leading up to diagnosis. In mutually adjusted analysis, the long-term risk association of DBP remained, with a hazard ratio (HR) per standard deviation increment 10 years before diagnosis (HR10y) of 1.20 (95% CI: 1.10-1.30), whereas the association of SBP was attenuated (HR10y: 1.00, 95% CI: 0.91-1.10). In the complementary multivariable MR analysis, we observed an odds ratio for a 1-SD increment (ORsd) of 1.34 (95% CI: 1.08-1.67) for genetically predicted DBP and 0.70 (95% CI: 0.56-0.88) for genetically predicted SBP. Conclusion: The results of this observational and MR study are consistent with an important role of DBP in RCC aetiology. The relation between SBP and RCC risk was less clear but does not appear to be independent of DBP.

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  • 20.
    Alhashimi, Sara
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Synkron och metakron urotelial cancer hos patienter med muskelinvasiv urotelial cancer – med eller utan neoadjuvant kemoterapi.2021Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 21.
    Ali, Zaheer
    et al.
    BioReperia AB, Linköping, Sweden.
    Nilsson, Anna
    BioReperia AB, Linköping, Sweden.
    Vildevall, Malin
    BioReperia AB, Linköping, Sweden.
    Rizzo, Larissa
    BioReperia AB, Linköping, Sweden.
    Huge, Ylva
    Region Östergötland, Norrköping, Sweden.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Fahlgren, Anna
    BioReperia AB, Linköping, Sweden.
    Jensen, Lasse DE
    BioReperia AB, Linköping, Sweden.
    Abstract 6124: Translation of zebrafish tumor-derived xenograft-models for improved diagnosis and treatment planning in urinary bladder cancer patients2020In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 80, no 6 Supplement, p. 6124-6124Article in journal (Refereed)
    Abstract [en]

    Precision medicine in oncology aims to identify the most effective treatment for any given patient based on individualized analyses of patient material. Currently, precision medicine relies on sequencing of DNA or RNA to identify patient tumor-specific mutational profiles that may be coupled to drug response. These techniques, however, fail to reveal actionable mutations in approximately 85% of the cancer patients, and have not been established at all for many commonly used drugs including cisplatin-based treatments used in urinary bladder cancer. While mouse-PDX models can determine drug response rates with high accuracy in most patients and for most drugs, such techniques are too slow and expensive to be relevant for first line treatment planning. Urinary bladder cancer patients are often treated with cisplatin-containing combination therapy, with the hope of down-staging tumors before surgery. 60%, however, do not respond or even progress on this treatment, and these patients would benefit from immediate surgery upon diagnosis. To help identify non-responding patients, we show here that patient-derived tumor xenograft models can be established in zebrafish larvae (ZTX models) and that the resulting tumors exhibit differential responses to the two main cisplatin-containing treatments GC and MVAC.Preliminary results from the first 19 patients are presented. Two tumor biopsies were destroyed during transport and two did not allow isolation of sufficient viable cells for implantation. From the remaining 15 samples an average of 2,6 million cells with average viability of 53% were isolated and used to implant at least 60 2-days old larvae. All 15 samples implanted in the larvae and survived and/or grew exhibiting varying degrees of metastatic dissemination (average between 2 and 13 metastasized cells per embryo and model) within only three days from implantation. Four ZTX models exhibited different responses to GC and MVAC demonstrating that these treatments are not equally effective in all patients. Non-response in ZTX models was associated with tumors having re-appeared in the bladder upon radical cystectomy in all patients undergoing surgery prior to Dec. 5th 2019 (n=3). GC inhibited metastasis in all models (average 69% inhibition), whereas MVAC inhibited metastasis in 40% of the models (average 36% inhibition).In conclusion: The ZTX urinary bladder cancer platform presented here overcome limitations associated with long assay time and high cost of other functional models within precision medicine as well as the low hit-rate of actionable mutations associated with genomic techniques. ZTX models will therefore likely become a powerful method for functional precision medicine within oncology, in the near future.

  • 22. Aljabery, Firas
    et al.
    Liedberg, Fredrik
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Ströck, Viveka
    Hosseini, Abolfazl
    Gårdmark, Truls
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Jerlström, Tomas
    Malmström, Per-Uno
    Hagberg, Oskar
    Holmberg, Lars
    Treatment and prognosis of bladder cancer patients with other primary cancers: A nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe)2020In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 126, no 5, p. 625-632Article in journal (Refereed)
    Abstract [en]

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

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

    RESULTS: There were 38689 patients, of which 9804 (25%) had OPC. Those with synchronous OPC more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, CCI and T-stage, UBC-specific survival was similar to patients with UBC only, but overall survival was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis.

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

  • 23. Aljabery, Firas
    et al.
    Liedberg, Fredrik
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Ströck, Viveka
    Hosseini, Abolfazl
    Gårdmark, Truls
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Jerlström, Tomas
    Malmström, Per-Uno
    Holmberg, Lars
    Hagberg, Oskar
    Jahnson, Staffan
    Management and outcome of muscle-invasive bladder cancer with clinical lymph node metastases: a nationwide population-based study in the bladder cancer data base Sweden (BladderBaSe)2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 5, p. 332-338Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 24. Allen, N E
    et al.
    Key, T J
    Appleby, P N
    Travis, R C
    Roddam, A W
    Tjønneland, A
    Johnsen, N F
    Overvad, K
    Linseisen, J
    Rohrmann, S
    Boeing, H
    Pischon, T
    Bueno-de-Mesquita, H B
    Kiemeney, L
    Tagliabue, G
    Palli, D
    Vineis, P
    Tumino, R
    Trichopoulou, A
    Kassapa, C
    Trichopoulos, D
    Ardanaz, E
    Larrañaga, N
    Tormo, M-J
    González, C A
    Quirós, J R
    Sánchez, M-J
    Bingham, S
    Khaw, K-T
    Manjer, J
    Berglund, G
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Slimani, N
    Ferrari, P
    Rinaldi, S
    Riboli, E
    Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition.2008In: Br J Cancer, ISSN 1532-1827, Vol. 98, no 9, p. 1574-81Article in journal (Refereed)
  • 25. 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 University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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 nutrition2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, no 3, p. 635-644Article in journal (Refereed)
    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.

  • 26. Allen, Naomi E
    et al.
    Appleby, Paul N
    Roddam, Andrew W
    Tjønneland, Anne
    Johnsen, Nina Føns
    Overvad, Kim
    Boeing, Heiner
    Weikert, Steffen
    Kaaks, Rudolf
    Linseisen, Jakob
    Trichopoulou, Antonia
    Misirli, Gesthimani
    Trichopoulos, Dimitrios
    Sacerdote, Carlotta
    Grioni, Sara
    Palli, Domenico
    Tumino, Rosario
    Bueno-de-Mesquita, H Bas
    Kiemeney, Lambertus A
    Barricarte, Aurelio
    Larrañaga, Nerea
    Sánchez, Maria-José
    Agudo, Antonio
    Tormo, María-José
    Rodriguez, Laudina
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Bingham, Sheila
    Khaw, Kay-Tee
    Slimani, Nadia
    Rinaldi, Sabina
    Boffetta, Paolo
    Riboli, Elio
    Key, Timothy J
    Plasma selenium concentration and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).2008In: Am J Clin Nutr, ISSN 0002-9165, Vol. 88, no 6, p. 1567-1575Article in journal (Refereed)
  • 27. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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.2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, no 4, p. 982-987Article in journal (Refereed)
    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.

  • 28. Allen, Naomi E.
    et al.
    Travis, Ruth C.
    Appleby, Paul N.
    Albanes, Demetrius
    Barnett, Matt J.
    Black, Amanda
    Bueno-de-Mesquita, H. Bas
    Deschasaux, Melanie
    Galan, Pilar
    Goodman, Gary E.
    Goodman, Phyllis J.
    Gunter, Marc J.
    Heliovaara, Markku
    Helzlsouer, Kathy J.
    Henderson, Brian E.
    Hercberg, Serge
    Knekt, Paul
    Kolonel, Laurence N.
    Lasheras, Christina
    Linseisen, Jakob
    Metter, E. Jeffrey
    Neuhouser, Marian L.
    Olsen, Anja
    Pala, Valeria
    Platz, Elizabeth A.
    Rissanen, Harri
    Reid, Mary E.
    Schenk, Jeannette M.
    Stampfer, Meir J.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tangen, Catherine M.
    Touvier, Mathilde
    Trichopoulou, Antonia
    van den Brandt, Piet A.
    Key, Timothy J.
    Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies2016In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, no 11, article id djw153Article in journal (Refereed)
    Abstract [en]

    Background: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade. Methods: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. Results: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, P-heterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, P-trend <.001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, P-heterogeneity =.08). Conclusions: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

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  • 29.
    Alm, Ronja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Preoperative serum C-reactive protein (CRP) as a predictor of survival in urothelial muscle invasive bladder cancer in relation to neoadjuvant chemotherapy: A retrospective multi-center study2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 30.
    Almadalal, Tarik
    et al.
    Department of Surgery and Urology, Eskilstuna Country Hospital, Eskilstuna, Sweden.
    Sundqvist, Pernilla
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Harmenberg, Ulrika
    Department of Oncology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
    Hellström, Mikael
    Department of Radiology, Sahlgrenska Academy/Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
    Lindskog, Magnus
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Lindblad, Per
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lundstam, Svan
    Department of Urology and Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Clinical T1a Renal Cell Carcinoma, Not Always a Harmless Disease: A National Register Study2022In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 39, p. 22-28Article in journal (Refereed)
    Abstract [en]

    Background: T1a renal cell carcinoma (RCC) is typically considered a curable disease, irrespective of the choice of local treatment modality.

    Objective: To identify factors associated with the risk of local and distant recurrence, and overall survival (OS) in patients with primary nonmetastatic clinical T1a RCC.

    Design, setting, and participants: A population-based nationwide register study of all 1935 patients with cT1a RCC, diagnosed during 2005–2012, identified through The National Swedish Kidney Cancer Register, was conducted.

    Outcome measurements and statistical analysis: Outcome variables were recurrence (local or distant) and OS. Possible explanatory variables included tumor size, RCC type, T stage, surgical technique, age, and gender. Associations with disease recurrence and OS were evaluated by multivariable regression and Cox multivariate analyses, respectively.

    Results and limitations: Among 1935 patients, 938 were treated with radical nephrectomy, 738 with partial nephrectomy, and 169 with ablative treatments, while 90 patients had no surgery. Seventy-eight (4%) patients were upstaged to pT3. Local or metastatic recurrences occurred in 145 (7.5%) patients, significantly more often after ablation (17.8%). The risk of recurrence was associated with tumor size, upstaging, and ablation. Larger tumor size, disease recurrence, and older age adversely affected OS, whereas partial nephrectomy and chromophobe RCC (chRCC) were associated with improved survival. Limitations include register design and a lack of comorbidity or performance status data.

    Conclusions: Upstaging and recurrence occurred, respectively, in 4.0% and 7.5% of patients with nonmetastatic RCCs ≤4 cm. Tumor size upstaging and ablation were associated with the risk for recurrence, while tumor size and recurrence were associated with decreased OS. Patients with chRCC and partial nephrectomy had prolonged OS in a real-world setting.

    Patient summary: We studied factors that may influence the risk of disease recurrence and overall survival, in a large nationwide patient cohort having nonmetastatic renal cell carcinoma ≤4 cm. Tumor size, tumor type, and treatment were associated with the risk of recurrence and overall death. Partial nephrectomy prolonged overall survival.

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  • 31.
    Almdalal, Tarik
    et al.
    Department of Surgery and Urology, Eskilstuna Country Hospital, Eskilstuna, Sweden.
    Karlsson Rosenblad, Andreas
    Regional Cancer Centre Stockholm-Gotland, Stockholm, Sweden; Department of Medical Sciences, Division of Clinical Diabetology and Metabolism, Uppsala University, Uppsala, Sweden; Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Solna, Sweden.
    Hellström, Mikael
    Department of Radiology, Sahlgrenska Academy/Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
    Kjellman, Anders
    Department of Urology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lundstam, Sven
    Departments of Urology and Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sundqvist, Pernilla
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Predictive characteristics for disease recurrence and overall survival in non-metastatic clinical T1 renal cell carcinoma: results from the National Swedish Kidney Cancer Register2023In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 57, no 1-6, p. 67-74Article in journal (Refereed)
    Abstract [en]

    Objective: Patients with clinical T1 renal cell carcinoma (cT1RCC) have risks for recurrence and reduced overall survival despite being in the best prognostic group. This study aimed to evaluate the association of different treatments on disease recurrence and overall survival using clinical and pathological characteristics in a nation-wide cT1RCC cohort.

    Materials and methods: A total of 4,965 patients, registered in the National Swedish Kidney Cancer Register (NSKCR) between 2005 and 2014, with ≥ 5-years follow-up were identified: 3,040 males and 1,925 females, mean age 65 years. Times to recurrence and overall survival were analyzed with Kaplan-Meier curves, log-rank test, and Cox regression models.

    Results: Age, TNM-stage, tumor size, RCC-type, and performed treatment were all associated with disease recurrence. Patients selected for ablative treatments had increased risk for recurrent disease: hazard ratio (HR) = 3.79 [95% confidence interval (CI) = 2.69–5.32]. In multivariate analyses, age, gender, tumor size, RCC-type, N-stage, recurrence and performed treatment were all independently associated with overall survival. Patients with chRCC had a 41% better overall survival (HR = 0.59, 95% CI = 0.44–0.78; p < 0.001) than ccRCC. Patients treated with partial nephrectomy (PN) had an 18% better overall survival (HR = 0.83, 95% CI = 0.71–0.95, p < 0.001) than patients treated with radical nephrectomy.

    Conclusions: Age, gender, T-stage, tumor size, RCC type and treatment modality are all associated with risk of recurrence. Furthermore, age, male gender, tumor size, N-stage and recurrence are associated with reduced overall survival. Patients with chRCC, compared with ccRCC and pRCC patients, and PN compared with RN treated patients, had an advantageous overall survival, indicating a possible survival advantage of nephron sparing treatment.

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  • 32. Almquist, Martin
    et al.
    Johansen, Dorthe
    Björge, Tone
    Ulmer, Hanno
    Lindkvist, Björn
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Engeland, Anders
    Rapp, Kilian
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Selmer, Randi
    Diem, Guenter
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tretli, Steinar
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Manjer, Jonas
    Metabolic factors and risk of thyroid cancer in the Metabolic syndrome and Cancer project (Me-Can)2011In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 22, no 5, p. 743-751Article in journal (Refereed)
    Abstract [en]

    Objective  To investigate metabolic factors and their possible impact on risk of thyroid cancer. Methods  A prospective cohort study was conducted based on seven population-based cohorts in Norway, Austria, and Sweden, in the Metabolic syndrome and Cancer project (Me-Can). Altogether 578,700 men and women with a mean age of 44.0 years at baseline were followed for on average 12.0 years. Relative risk of incident thyroid cancer was assessed by levels of BMI, blood pressure, and blood levels of glucose, cholesterol, triglycerides, and by a combined metabolic syndrome (MetS) score. Risk estimates were investigated for quintiles, and a z score distribution of exposures was analyzed using Cox proportional hazards regression. Results  During follow-up, 255 women and 133 men were diagnosed with thyroid cancer. In women, there was an inverse association between glucose and thyroid cancer risk, with adjusted RR: 95% CI was 0.61 (0.41–0.90), p trend = 0.02 in the fifth versus the first quintile, and a positive association between BMI and thyroid cancer risk with a significant trend over quintiles. There was no association between the other metabolic factors, single or combined (Met-S), and thyroid cancer. Conclusion  In women, BMI was positively, while blood glucose levels were inversely, associated with thyroid cancer.

  • 33.
    Alvaeus, Julia
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    En undersökning av mängd och anatomisk fördelning av tumördränerande sentinel nodes vid muskelinvasiv urotelial blåscancer.2019Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 34.
    Alvaeus, Julia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Rosenblatt, Robert
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of UrologyKarolinska Institutet, Stockholm South General Hospital, Stockholm, Sweden.
    Johansson, Markus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Alamdari, Farhood
    Jakubczyk, Tomasz
    Holmström, Benny
    Hemdan, Tammer
    Huge, Ylva
    Aljabery, Firas
    Gabrielsson, Susanne
    Riklund, Katrine
    Winqvist, Ola
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy2020In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 38, p. 2207-2213Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the relationship between the number of tumour draining sentinel nodes (SNs) and pathoanatomical outcomes, in muscle-invasive bladder cancer (MIBC), in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).

    MATERIALS AND METHODS: In an ongoing prospective multicenter study, we included 230 patients with suspected urothelial MIBC from ten Swedish urological centers. All underwent TURb and clinical staging. From the cohort, 116 patients with urothelial MIBC; cT2-cT4aN0M0, underwent radical cystectomy (RC) and lymphadenectomy with SN-detection (SNd). 83 patients received cisplatin-based NAC and 33 were NAC-naïve. The number and locations of detected SNs and non-SNs were recorded for each patient. The NAC treated patients were categorized by pathoanatomical outcomes post-RC into three groups: complete responders (CR), stable disease (SD) and progressive disease (PD). Selected covariates with possible impact on SN-yield were tested in uni -and multivariate analyses for NAC-treated patients only.

    RESULTS: In NAC treated patients, the mean number of SNs was significantly higher in CR patients (3.3) and SD patients (3.6) compared with PD patients (1.4) (p = 0.034). In a linear multivariate regression model, the number of harvested nodes was the only independent variable that affected the number of SNs (p = 0.0004).

    CONCLUSIONS: The number of tumor-draining SNs in NAC-treated patients was significantly lower in patients with progressive disease.

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  • 35.
    Alvebro, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Jämförelse av skleroterapi med operation vidbehandling av hydrocele. En uppföljning på enrandomiserad kontrollerad studie2022Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 36.
    Andersson, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hexaminolevulinate-guided bladder tumor resection: impact on survival after radical cystectomy for muscle invasive urothelial bladder cancer: A retrospective multi-center study2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 37.
    Andersson Evelönn, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Köhn, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    DNA methylation status defines clinicopathological parameters including survival for patients with clear cell renal cell carcinoma (ccRCC)2016In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, no 8, p. 10219-10228Article in journal (Refereed)
    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.

  • 38.
    Andersson Evelönn, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Haider, Zahra
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Köhn, Linda
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    DNA methylation associates with survival in non-metastatic clear cell renal cell carcinoma2019In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 65Article in journal (Refereed)
    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.

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  • 39.
    Andersson, Nils
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Avstånd till sjukhus påverkar inte överlevnad vid T1 urinblåsecancer.2019Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 40.
    Andersson-Evelönn, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Vidman, Linda
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Källberg, David
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Liu, Xijia
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Combining epigenetic and clinicopathological variables improves prognostic prediction in clear cell Renal Cell CarcinomaManuscript (preprint) (Other academic)
  • 41.
    Andersson-Evelönn, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Vidman, Linda
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Källberg, David
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Liu, Xijia
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Combining epigenetic and clinicopathological variables improves specificity in prognostic prediction in clear cell renal cell carcinoma2020In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 18, no 1, article id 435Article in journal (Refereed)
    Abstract [en]

    Background: Metastasized clear cell renal cell carcinoma (ccRCC) is associated with a poor prognosis. Almost one-third of patients with non-metastatic tumors at diagnosis will later progress with metastatic disease. These patients need to be identified already at diagnosis, to undertake closer follow up and/or adjuvant treatment. Today, clinicopathological variables are used to risk classify patients, but molecular biomarkers are needed to improve risk classification to identify the high-risk patients which will benefit most from modern adjuvant therapies. Interestingly, DNA methylation profiling has emerged as a promising prognostic biomarker in ccRCC. This study aimed to derive a model for prediction of tumor progression after nephrectomy in non-metastatic ccRCC by combining DNA methylation profiling with clinicopathological variables.

    Methods: A novel cluster analysis approach (Directed Cluster Analysis) was used to identify molecular biomarkers from genome-wide methylation array data. These novel DNA methylation biomarkers, together with previously identified CpG-site biomarkers and clinicopathological variables, were used to derive predictive classifiers for tumor progression.

    Results: The “triple classifier” which included both novel and previously identified DNA methylation biomarkers together with clinicopathological variables predicted tumor progression more accurately than the currently used Mayo scoring system, by increasing the specificity from 50% in Mayo to 64% in our triple classifier at 85% fixed sensitivity. The cumulative incidence of progress (pCIP5yr) was 7.5% in low-risk vs 44.7% in high-risk in M0 patients classified by the triple classifier at diagnosis.

    Conclusions: The triple classifier panel that combines clinicopathological variables with genome-wide methylation data has the potential to improve specificity in prognosis prediction for patients with non-metastatic ccRCC.

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  • 42.
    Andréasson, Sara
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Regulatory T cells and Urinary BladderCancer. Characterization of Regulatory T cells in Peripheral Blood ofPatients with Muscle Invasive Urinary Bladder Cancer.2015Student thesis
  • 43. Ankarfeldt, Mikkel Z.
    et al.
    Ängquist, Lars
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Clinical Sciences in Malmö, Diabetes and Cardiovascular Diseases, Genetic Epidemiology, Lund University, Lund, Sweden.
    Jakobsen, Marianne U.
    Overvad, Kim
    Halkjær, Jytte
    Saris, Wim H. M.
    Astrup, Arne
    Sørensen, Thorkild I. A.
    Body characteristics, dietary protein and body weight regulation. Reconciling conflicting results from intervention and observational studies?2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 7, p. e101134-Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: Physiological evidence indicates that high-protein diets reduce caloric intake and increase thermogenic response, which may prevent weight gain and regain after weight loss. Clinical trials have shown such effects, whereas observational cohort studies suggest an association between greater protein intake and weight gain. In both types of studies the results are based on average weight changes, and show considerable diversity in both directions. This study investigates whether the discrepancy in the evidence could be due to recruitment of overweight and obese individuals into clinical trials. Subjects/Methods: Data were available from the European Diet, Obesity and Genes (DiOGenes) post-weight-loss weight-maintenance trial and the Danish Diet, Cancer and Health (DCH) cohort. Participants of the DCH cohort were matched with participants from the DiOGenes trial on gender, diet, and body characteristics. Different subsets of the DCH-participants, comparable with the trial participants, were analyzed for weight maintenance according to the randomization status (high or low protein) of the matched trial participants. Results: Trial participants were generally heavier, had larger waist circumference and larger fat mass than the participants in the entire DCH cohort. A better weight maintenance in the high-protein group compared to the low protein group was observed in the subgroups of the DCH cohort matching body characteristics of the trial participants. Conclusion: This modified observational study, minimized the differences between the RCT and observational data with regard to dietary intake, participant characteristics and statistical analysis. Compared with low protein diet the high protein diet was associated with better weight maintenance when individuals with greater body mass index and waist circumference were analyzed. Selecting subsets of large-scale observational cohort studies with similar characteristics as participants in clinical trials may reconcile the otherwise conflicting results.

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  • 44. Anttila, Tarja
    et al.
    Tenkanen, Leena
    Lumme, Sonja
    Leinonen, Maija
    Gislefoss, Randi Elin
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Thoresen, Steinar
    Hakulinen, Timo
    Luostarinen, Tapio
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Saikku, Pekka
    Dillner, Joakim
    Lehtinen, Matti
    Hakama, Matti
    Chlamydial antibodies and risk of prostate cancer.2005In: Cancer Epidemiology Biomarkers & Prevention, ISSN 1055-9965, Vol. 14, no 2, p. 385-9Article in journal (Refereed)
  • 45. Arkestal, Kurt
    et al.
    Mints, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Enocson, Anders
    Linton, Ludvig
    Marits, Per
    Glise, Hans
    Andersson, John
    Winqvist, Ola
    CCR2 upregulated on peripheral T cells in osteoarthritis but not in bone marrow2018In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 88, no 6, article id e12722Article in journal (Refereed)
    Abstract [en]

    Osteoarthritis (OA) is a condition affecting millions of patients around the world, causing pain and disability and often resulting in joint replacement surgery. The aetiology of OA has long been attributed to mechanical wear mainly due to the increased prevalence of OA in load bearing joints among older patients. However, recent studies reveal a complex molecular disease causality in which inflammation, nutritional deficit and angiogenesis lead to the destruction of the joint structure. The aim of this study was to examine chemokine receptor expression in peripheral blood and bone marrow in OA patients. We devised a protocol for extracting healthy bone marrow from patients undergoing hip arthroplasty due to coxarthrosis. Flow cytometry was used to determine the expression of 18 chemokine receptors on CD4 and CD8 T cells from bone marrow and blood from 7 osteoarthritis patients and peripheral blood from 9 healthy controls. We found a significantly increased fraction of CCR2 expressing CD4 and CD8 T cell in peripheral blood compared to healthy controls. Also, there was a significant decrease in CXCR3 (Th1) (P < 0.01) expressing T cells in peripheral blood from OA patients. Finally, multivariate analysis was used to separate T cell profiles from healthy controls and OA patients and demonstrate that the divergence of chemokine receptor expression occurs in the mature T cell subsets. In conclusion, we find increased CCR2 expression in peripheral blood from OA patients that possibly may be targeted in future clinical studies.

  • 46.
    Arnerlöv, Conny
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öhberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ghaffarpour, Ramin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Trippeldiagnostik säker vid symtomgivande rörlig njure: [Triple diagnostic can establish the diagnosis of symptomatic mobile kidney and nephropexy can give freedom of pain]2020In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 117, no 37, article id 20025Article in journal (Refereed)
    Abstract [en]

    Symtomatic mobile kidney is a rare condition and diagnosis is difficult. Typical symptoms are position dependent back-flank-abdominal pain with increase of pain when walking, jogging and lifting or other physical activities which increase the descent of the kidney. Triple diagnostic with typical pain history, an intravenous pyelography with a renal descent of ≥ 2 lumbar vertebral heights in the erect position, and an ultrasound with a positive pain provocation can establish the diagnosis of symptomatic mobile kidney. In our study nephropexy gives freedom of pain for 75% of patients and substantial relief for 15% of patients with severe pain.

  • 47.
    Aronsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ingen prognostisk betydelse av tidigare tonsillektomi hos patienter med muskelinvasiv blåscancer som har genomgått neoadjuvant kemoterapi och cystektomi.2021Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 48. Arthur, Rhonda
    et al.
    Moller, Henrik
    Garmo, Hans
    Holmberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Faculty of Medicine, Uppsala, Sweden.
    Malmstrom, Hakan
    Lambe, Mats
    Hammar, Niklas
    Walldius, Göran
    Robinson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Faculty of Medicine, Uppsala, Sweden.
    Jungner, Ingmar
    Van Hemelrijck, Mieke
    Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories2016In: Cancer Medicine, E-ISSN 2045-7634, Vol. 5, no 6, p. 1307-1318Article in journal (Refereed)
    Abstract [en]

    Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 mu g/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 mu g/L compared to PSA 4.0-9.9 mu g/L. Hypertriglyceridemia was also positively associated with PSA>20 mu g/L. Hyperglycemic men had a greater odds of intermediate-and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention.

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  • 49. Arthur, Rhonda
    et al.
    Møller, Henrik
    Garmo, Hans
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Holmberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Malmström, Håkan
    Lambe, Mats
    Hammar, Niklas
    Walldius, Göran
    Robinson, David
    Jungner, Ingmar
    Van Hemelrijck, Mieke
    Serum glucose, triglycerides, and cholesterol in relation to prostate cancer death in the Swedish AMORIS study2019In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 30, no 2, p. 195-206Article in journal (Refereed)
    Abstract [en]

    Purpose: Lifestyle-related conditions such as obesity are associated with prostate cancer progression, but the associations with hyperglycemia and dyslipidemia are unclear. This study, therefore, aims to examine the association of glucose, triglycerides, and total cholesterol with prostate cancer death. Methods: From the Swedish AMORIS cohort, we selected 14,150 men diagnosed with prostate cancer between 1996 and 2011 who had prediagnostic measurements of serum glucose, triglycerides, and total cholesterol. Multivariable Cox proportional hazards regressionmodels were used to determine the hazard ratios for death in relation to the aforementioned metabolic markers. Results: Using clinical cut-off points, a non-significant positive association was observed between glucose and prostate cancer death. When compared to those with glucose in the lowest quartile, those in the highest quartile had greater risk of prostate cancer death (HR 1.19; 95% CI 1.02-1.39). However, neither total cholesterol nor triglycerides were associated with prostate cancer death. Glucose and triglycerides were positively associated with overall, cardiovascular, and other deaths. Hypercholesterolemia was only associated with risk of CVD death. Conclusion: Our results suggest that glucose levels may influence prostate cancer survival, but further studies using repeated measurements are needed to further elucidate how glucose levels may influence prostate cancer progression.

  • 50.
    Asad, Danna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    A prospective evaluation of visual staging by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
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