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  • 51.
    Forsman, Ramona
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Common blood markers as possible predictors of response to neoadjuvant chemotherapy, in muscle-invasive urinary bladder cancer2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 52. Fossa, Sophie D.
    et al.
    Wiklund, Fredrik
    Klepp, Olbjorn
    Angelsen, Anders
    Solberg, Arne
    Dumber, Jan-Erik
    Hoyer, Morten
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ten- and 15-yr Prostate Cancer-specific Mortality in Patients with Nonmetastatic Locally Advanced or Aggressive Intermediate Prostate Cancer, Randomized to Lifelong Endocrine Treatment Alone or Combined with Radiotherapy: Final Results of The Scandinavian Prostate Cancer Group-72016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 4, p. 684-691Article in journal (Refereed)
    Abstract [en]

    Background: In high-risk prostate cancer (PCa), no study with observation times beyond 10 yr has demonstrated survival improvement after addition of prostatic radiotherapy (RAD) to endocrine treatment (ET) alone. Objective: To compare mortality rates in patients receiving ET alone versus ET + RAD. Design, settings, and participants: From 1996 to 2002, 875 Scandinavian patients with high-risk (90%) or intermediate PCa were randomized to ET or ET + RAD (The Scandinavian Prostate Cancer Group-7). After 3 mo with total androgen blockade in all patients, all individuals continued lifelong antiandrogen monotherapy. Those randomized to ET + RAD started prostate radiotherapy (70 Gy) at 3 mo. Outcome, measurements and statistical analysis: PCa-specific 15-yr mortality represented the primary endpoint. Assessment of the combination treatment effect and prognostic factors was performed in competing risk analyses and Cox proportional-hazard models. Intervention: RAD added to ET. Results and limitations: With a median observation time of 12 yr, the 15-yr PCa-specific mortality rates were 34% (95% confidence interval, 29-39%) and 17% (95% confidence interval, 13-22%) in the ET and ET + RAD arms respectively (p < 0.001). Compared with the ET arm, the median overall survival in the ET + RAD arm was prolonged by 2.4 yr. Treatment with ET alone, age >= 65 yr and increasing histology grade independently increased the risk of PCa-specific and overall mortality. Limitations include nonformal evaluation of comorbidity, the inability to calculate progression-free survival, and lack of information about salvage therapy and toxicity. Conclusions: In patients with nonmetastatic locally advanced or aggressive PCa, ET + RAD reduces the absolute risk of PCa-specific death by 17% at 15 yr compared with ET alone; the comparable 15-yr PCa-specific mortality rates being 17% and 34%. The results warrant a phase 3 study comparing ET + RAD with radical prostatectomy in high-risk PCa. Patient summary: Adding prostatic therapy to lifelong antiandrogen therapy halves the absolute risk of death from prostate cancer from 34% to 17% 15 yr after diagnosis. 

  • 53.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Jan-Erik
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Health-related quality of life 10 years after external beam radiotherapy or watchful waiting in patients with localized prostate cancer2009In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, no 2, p. 119-126Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate long-term randomized comparisons of patient-reported outcome of symptoms and health-related quality of life (HRQoL) in men with localized prostate cancer 10 years after external beam radiotherapy (RT) or watchful waiting (WW). Material and methods. Three-year HRQoL and specific symptoms in surviving patients recruited between 1986 and 1996 were previously evaluated in a randomized trial; definitive RT versus WW. Two questionnaires were used: the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the Prostate Cancer Symptom Scale (PCSS). The present study is a prolonged follow-up with the same cohorts. Results. Fifty-four of 72 eligible patients (75%) returned the questionnaires at the present follow-up. The median age was 77 years in the RT group and 78 years in the WW group. The median follow-up time from randomization was 10 years. No differences in HRQoL or bowel symptoms were measured between the RT and WW. Cognitive (RT) and physical function (WW) decreased between 4 years and 10years. Weak urinary stream differed between the RT and WW groups. Fatigue and nocturia were increased in the RT group, and erections decreased in the WW patients over time. No difference in erectile function was seen between the RT and WW groups (p=0.292). Conclusion. The pattern of urinary and bowel symptoms and sexual function was rather similar, independent of RT or WW. Treatment with RT had minimal influence on HRQoL, in comparison with that of WW, at 10-year follow-up.

  • 54.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Does one have a sexual life 15 years after external beam radiotherapy for prostate cancer? Prospective patient-reported outcome of sexual function comparison with age-matched controls2011In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 29, no 2, p. 137-144Article in journal (Refereed)
    Abstract [en]

    Background and purpose: We previously published research on 4- and 8-year follow-ups of patient-reported sexual function after conventional external beam radiotherapy (EBRT) for localized prostate cancer (LPC) compared with age-matched controls. The current study is a prolonged 15-year follow-up with the same cohorts.

    Material and methods: The cohort consisted of 29 men surviving from a group of 181 men treated between 1986 and 1989, and who were reported on previously. Of the originally reported 141 controls, 62 were eligible and 34 completed the questionnaires. Sexual function was assessed using two questionnaires, Prostate Cancer Symptom Scale (PCSS) and International Index of Erectile Function (IIEF-5).

    Results: Twenty-three patients (78%) and 13 controls (38%) were not sexually active. None of the patients and 14 controls had enough of an erection to perform intercourse. Seventeen patients (94%) and 14 controls (64%) had severe erectile dysfunction. Patients with clinical progression and who had received hormone treatment had decreased sexual desire. No significant differences were measured between patients without progression/hormone treatment and the controls.

    Conclusion: The sexual activity 15 years after EBRT for LPC was very low, as was the probability of achieving an erection. Patients with a progressive disease and treated with hormones reported worse sexual and erectile function. The LPC free men showed higher sexual activity, lower sexual bother, and better erectile function than the patients.

  • 55.
    Fridriksson, Jon Örn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Folkvaljon, Y
    Lundström, KJ
    Robinson, D
    Carlsson, S
    Stattin, P
    Long-term adverse effects after open retropubic and robot-assisted radical prostatectomyManuscript (preprint) (Other academic)
  • 56.
    Friðriksson, Jón Örn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Erik
    Adolfsson, Jan
    Lambe, Mats
    Bill-Axelson, Anna
    Carlsson, Stefan
    Hugosson, Jonas
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Rehospitalization after radical prostatectomy in a nationwide, population-based study2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 1, p. 112-119Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate readmission frequencies during the 90 days following radical prostatectomy and to assess readmission risk associated with potentially related variables.

    MATERIALS AND METHODS: Using the population-based, nationwide database Prostate Cancer data Base Sweden (PCBaSe), we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy (RP) as their primary treatment, and we used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load, and patient characteristics.

    RESULTS: During the 90 postoperative days, 2,317 (10%) of the 24,122 men identified were non-electively readmitted, specifically 10% after retropubic radical prostatectomy (RRP), 9% after robot-assisted RP (RALP) and 11% after laparoscopic RP (LRP). The range in the readmission frequency between hospitals was 0-35%. A higher risk of readmission was associated with early calendar period (2009-2011 vs. 2000-2002: odds ratio (OR), 0.71; 95% confidence interval (CI), 0.61-0.83), greater age (≥70 years vs. <60 years: OR, 1.17; 95% CI, 1.00-1.36), higher risk category (high vs. low-risk category: OR, 1.78; 95% CI, 1.57-2.03), high comorbidity (Charlson comorbidity index ≥3 vs. 0: OR, 1.77; 95% CI, 1.29-2.44), and low hospital surgical volume (≥150 vs. <30 RPs per year: OR, 0.70; 95% CI, 0.60-0.81).

    CONCLUSIONS: Readmission rates after different RP methods were similar, ranging from 9% to 11%, with a wide variation between hospitals. Readmission rates can be used as an indicator of perioperative care quality, but potential confounders need to be adjusted to avoid bias.

  • 57. Fu, Yi-Ping
    et al.
    Kohaar, Indu
    Moore, Lee E.
    Lenz, Petra
    Figueroa, Jonine D.
    Tang, Wei
    Porter-Gill, Patricia
    Chatterjee, Nilanjan
    Scott-Johnson, Alexandra
    Garcia-Closas, Montserrat
    Muchmore, Brian
    Baris, Dalsu
    Paquin, Ashley
    Ylaya, Kris
    Schwenn, Molly
    Apolo, Andrea B.
    Karagas, Margaret R.
    Tarway, McAnthony
    Johnson, Alison
    Mumy, Adam
    Schned, Alan
    Guedez, Liliana
    Jones, Michael A.
    Kida, Masatoshi
    Hosain, G. M. Monawar
    Malats, Nuria
    Kogevinas, Manolis
    Tardon, Adonina
    Serra, Consol
    Carrato, Alfredo
    Garcia-Closas, Reina
    Lloreta, Josep
    Wu, Xifeng
    Purdue, Mark
    Andriole, Gerald L., Jr.
    Grubb, Robert L., III
    Black, Amanda
    Landi, Maria T.
    Caporaso, Neil E.
    Vineis, Paolo
    Siddiq, Afshan
    Bueno-de-Mesquita, H. Bas
    Trichopoulos, Dimitrios
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Severi, Gianluca
    Weiderpass, Elisabete
    Krogh, Vittorio
    Dorronsoro, Miren
    Travis, Ruth C.
    Tjonneland, Anne
    Brennan, Paul
    Chang-Claude, Jenny
    Riboli, Elio
    Prescott, Jennifer
    Chen, Constance
    De Vivo, Immaculata
    Govannucci, Edward
    Hunter, David
    Kraft, Peter
    Lindstrom, Sara
    Gapstur, Susan M.
    Jacobs, Eric J.
    Diver, W. Ryan
    Albanes, Demetrius
    Weinstein, Stephanie J.
    Virtamo, Jarmo
    Kooperberg, Charles
    Hohensee, Chancellor
    Rodabough, Rebecca J.
    Cortessis, Victoria K.
    Conti, David V.
    Gago-Dominguez, Manuela
    Stern, Mariana C.
    Pike, Malcolm C.
    Van Den Berg, David
    Yuan, Jian-Min
    Haiman, Christopher A.
    Cussenot, Olivier
    Cancel-Tassin, Geraldine
    Roupret, Morgan
    Comperat, Eva
    Porru, Stefano
    Carta, Angela
    Pavanello, Sofia
    Arici, Cecilia
    Mastrangelo, Giuseppe
    Grossman, H. Barton
    Wang, Zhaoming
    Deng, Xiang
    Chung, Charles C.
    Hutchinson, Amy
    Burdette, Laurie
    Wheeler, William
    Fraumeni, Joseph, Jr.
    Chanock, Stephen J.
    Hewitt, Stephen M.
    Silverman, Debra T.
    Rothman, Nathaniel
    Prokunina-Olsson, Ludmila
    The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease2014In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 20, p. 5808-5818Article in journal (Refereed)
    Abstract [en]

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

  • 58. Gakis, Georgios
    et al.
    Witjes, J. Alfred
    Comperat, Eva
    Cowan, Nigel C.
    De Santis, Maria
    Lebret, Thierry
    Ribal, Maria J.
    Sherif, Amir M.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    EAU Guidelines on Primary Urethral Carcinoma2013In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 64, no 5, p. 823-830Article in journal (Refereed)
    Abstract [en]

    Context: The European Association of Urology (EAU) Guidelines Group on Muscle-Invasive and Metastatic Bladder Cancer prepared these guidelines to deliver current evidence-based information on the diagnosis and treatment of patients with primary urethral carcinoma (UC).

    Objective: To review the current literature on the diagnosis and treatment of patients with primary UC and assess its level of scientific evidence.

    Evidence acquisition: A systematic literature search was performed to identify studies reporting urethral malignancies. Medline was searched using the controlled vocabulary of the Medical Subject Headings database, along with a free-text protocol.

    Evidence synthesis: Primary UC is considered a rare cancer, accounting for <1% of all malignancies. Risk factors for survival include age, tumour stage and grade, nodal stage, presence of distant metastasis, histologic type, tumour size, tumour location, and modality of treatment. Pelvic magnetic resonance imaging is the preferred method to assess the local extent of urethral tumour; computed tomography of the thorax and abdomen should be used to assess distant metastasis. In localised anterior UC, urethra-sparing surgery is an alternative to primary urethrectomy in both sexes, provided negative surgical margins can be achieved. Patients with locally advanced UC should be discussed by a multidisciplinary team of urologists, radiation oncologists, and oncologists. Patients with noninvasive UC or carcinoma in situ of the prostatic urethra and prostatic ducts can be treated with a urethra-sparing approach with transurethral resection and bacillus Calmette-Guerin (BCG). Cystoprostatectomy with extended pelvic lymphadenectomy should be reserved for patients not responding to BCG or as a primary treatment option in patients with extensive ductal or stromal involvement.

    Conclusions: The 2013 guidelines document on primary UC is the first publication on this topic by the EAU. It aims to increase awareness in the urologic community and provide scientific transparency to improve outcomes of this rare urogenital malignancy.

  • 59. Gnanapragasam, V. J.
    et al.
    Bratt, O.
    Muir, K.
    Lees, L. S.
    Huang, H. H.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Lophatananon, A.
    The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study2018In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, article id 31Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer.

    Methods: We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality.

    Results: The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n =3D 20,586), C-index 0.77 vs. 074; radiotherapy (n =3D 11,872), C-index 0.73 vs. 0.69; and conservative management (n =3D 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001).

    Conclusions: This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

  • 60. Grabe, Magnus J.
    et al.
    Lundström, Karl-Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tailored perioperative antimicrobial prophylaxis in urological surgery: myth or reality?2017In: Current Opinion in Urology, ISSN 0963-0643, E-ISSN 1473-6586, Vol. 27, no 2, p. 112-119Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review The controversies surrounding perioperative antimicrobial prophylaxis (AMP) are about the use and especially misuse of antibiotics. The overall lack of evidence to facilitate a rational perioperative AMP policy in urological surgery and the postoperative infectious complications remain a challenge. Therefore, a basic tool to aid decision-making would be useful. A model based on the patients' risk factors, the level of contamination and grading of surgical procedures is discussed.

    Recent findings A series of studies have shown that infectious complications and healthcare-associated infections remain consistently at an average of 10%, with a great variation in frequency dependent on the patients' preoperative status and the type, severity and contamination level of the surgical procedure. Preoperative patient assessment and preparation are key factors for well tolerated surgery and recovery. Adherence to the guidelines appears to reduce both the prescription of antimicrobials and the total costs without risking the patient outcome. Several studies of a series of interventions such as cystoscopy, endoscopic stone surgery and selected clean-contaminated interventions give support to the model. Bacteriuria, upgrading the patient to the contaminated level, requires preoperative control.

    Summary The discussed model assists the urologists in decision-making on perioperative AMP and contributes to a responsible use of antibiotics.

  • 61. Granfors, Torvald
    et al.
    Tomic, Radisa
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Downstaging and survival benefits of neoadjuvant radiotherapy before cystectomy for patients with invasive bladder carcinoma.2009In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, no 4, p. 293-299Article in journal (Refereed)
    Abstract [en]

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

  • 62.
    Gref, Margareta
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Formler för enprovs plasmaclearance2000In: Njurarna och övre urinvägarna / [ed] Göran Granerus, Lund: Studentlitteratur , 2000, p. 57-64Chapter in book (Other academic)
  • 63. Grimm, Marc-Oliver
    et al.
    Bex, Axel
    De Santis, Maria
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Catto, James W. F.
    Rouprêt, Morgan
    Hussain, Syed A.
    Bellmunt, Joaquim
    Powles, Tom
    Wirth, Manfred
    Van Poppel, Hendrik
    Safe Use of Immune Checkpoint Inhibitors in the Multidisciplinary Management of Urological Cancer: The European Association of Urology Position in 20192019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, no 3, p. 368-380Article, review/survey (Refereed)
    Abstract [en]

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

  • 64. Gronlund, Eric
    et al.
    Johansson, Silvia
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Thellenberg, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ahnesjo, Anders
    Dose painting of prostate cancer based on Gleason score correlations with apparent diffusion coefficients2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 5, p. 574-581Article in journal (Refereed)
    Abstract [en]

    Background: Gleason scores for prostate cancer correlates with an increased recurrence risk after radiotherapy (RT). Furthermore, higher Gleason scores correlates with decreasing apparent diffusion coefficient (ADC) data from diffusion weighted MRI (DWI-MRI). Based on these observations, we present a formalism for dose painting prescriptions of prostate volumes based on ADC images mapped to Gleason score driven dose-responses.

    Methods: The Gleason score driven dose-responses were derived from a learning data set consisting of pre-RT biopsy data and post-RT outcomes for 122 patients treated with a homogeneous dose to the prostate. For a test data set of 18 prostate cancer patients with pre-RT ADC images, we mapped the ADC data to the Gleason driven dose-responses by using probability distributions constructed from published Gleason score correlations with ADC data. We used the Gleason driven dose-responses to optimize dose painting prescriptions that maximize the tumor control probability (TCP) with equal average dose as for the learning sets homogeneous treatment dose.

    Results: The dose painting prescriptions increased the estimated TCP compared to the homogeneous dose by 0–51% for the learning set and by 4–30% for the test set. The potential for individual TCP gains with dose painting correlated with increasing Gleason score spread and larger prostate volumes. The TCP gains were also found to be larger for patients with a low expected TCP for the homogeneous dose prescription.

    Conclusions: We have from retrospective treatment data demonstrated a formalism that yield ADC driven dose painting prescriptions for prostate volumes that potentially can yield significant TCP increases without increasing dose burdens as compared to a homogeneous treatment dose. This motivates further development of the approach to consider more accurate ADC to Gleason mappings, issues with delivery robustness of heterogeneous dose distributions, and patient selection criteria for design of clinical trials.

  • 65. Grotta, Alessandra
    et al.
    Bottai, Matteo
    Adami, Hans-Olov
    Adams, Swann Arp
    Akre, Olof
    Blair, Steven Noel
    Mariosa, Daniela
    Nyrén, Olof
    Ye, Weimin
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bellocco, Rino
    Trolle Lagerros, Ylva
    Physical activity and body mass index as predictors of prostate cancer risk2015In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 33, no 10, p. 1495-1502Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Physical activity and body mass index (BMI) are involved in prostate cancer etiology; possible biologic mechanisms include their effects on hormonal levels. Our aim was to investigate the relationship between physical activity, obesity, and prostate cancer.

    METHODS: We followed a cohort of 13,109 Swedish men for 13 years and investigated the association of self-reported physical activity and BMI at baseline with prostate cancer incidence. We further analyzed whether BMI could modulate effects of physical activity. Occupational, recreational, and total physical activity were analyzed in relation to overall, localized, and advanced prostate cancer.

    RESULTS: During the study follow-up, we observed a total of 904 cases of prostate cancer (429 localized, 407 advanced, and 68 unclassified). High levels of occupational physical activity were associated with a nonsignificantly decreased risk of overall (HR 0.81, 95 % CI 0.61-1.07), localized (HR 0.75, 95 % CI 0.51-1.12), and advanced (HR 0.85, 95 % CI 0.55-1.31) prostate cancer. We found no association between high BMI and risk of prostate cancer incidence: We observed, however, a significant interaction between BMI and leisure physical activity.

    CONCLUSION: No association was confirmed between total physical activity and localized or advanced prostate cancer. The highest, relative to the lowest, level of occupational physical activity tended to be linked to a lower risk of prostate cancer, with a suggested dose-response relationship. We found no association between high BMI and risk of prostate cancer incidence; however, our analyses suggested an interaction between BMI and physical activity during recreational time that merits further investigation in future studies.

  • 66. Gudmundsson, E. O.
    et al.
    Erikson, S.
    Hosseinnia, S.
    Lundstam, S.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Significant regional differences in the treatment of small renal cancers in Sweden2012In: European urology. Supplement, ISSN 1569-9056, E-ISSN 1878-1500, Vol. 11, no 1, p. E135-E135Article in journal (Other academic)
  • 67. Guomundsson, Eirikur
    et al.
    Hellborg, Henrik
    Lundstam, Sven
    Erikson, Stina
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Metastatic potential in renal cell carcinomas <= 7 cm: swedish kidney cancer quality register data2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 5, p. 975-982Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 68. Hadimeri, Henrik
    et al.
    Frisenette-Fich, Carsten
    Deurell, Sven-Ingemar
    Svensson, Lars
    Carlsson-Bjering, Lena
    Fernstrom, Anders
    Almroth, Gabriel
    Melander, Stefan
    Haarhaus, Mattias
    Andersson, Per-Olof
    Cassel, Agneta
    Mauritz, Nils-Johan
    Stahl-Nilsson, Agneta
    Wilske, Jan
    Nordstrom, Kataryna
    Oruda, Pavel
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Larsson, Annelie Inghilesi
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A fixed protocol for outpatient clinic routines in the care of patients with severe renal failure2013In: Renal failure, ISSN 0886-022X, E-ISSN 1525-6049, Vol. 35, no 6, p. 845-854Article in journal (Refereed)
    Abstract [en]

    Background: The primary aim of this study was to assess whether a fixed protocol, using a specially trained team, for intermediate follow-up to fulfillment of guideline targets is non-inferior to conventional follow-up in the care of uraemic patients. A secondary aim was to investigate possible impact on patient outcome.

    Methods: The cohort comprised 424 patients from seven centers. Inclusion criteria were either serum creatinine exceeding 200 mu mol/l or calculated clearance below 30 ml/min, representing CKD 4 or 5a. Six centers followed a standardized protocol (group 1). One center provided controls (group 2). The study design was prospective and interventional. The variables measured were blood hemoglobin, bicarbonate, calcium, phosphate, intact parathyroid hormone, albumin, renal function variables, blood pressure and RAAS blockade. The number of patients achieving the set goals was analyzed as a time trend to determine if the intervention resulted in an improvement.

    Results: At baseline, group 1 had significantly lower GFR and higher serum creatinine, calcium, phosphate, calcium x phosphate product and bicarbonate, lower mean arterial pressure (MAP), systolic blood pressures and less use of RAAS. During the intervention, group 1 improved in the direction of guidelines for blood hemoglobin, albumin, bicarbonate and MAP. Outcome of secondary endpoints gave a risk of death of 30% in both groups, while the risk of renal replacement therapy was higher in group 1.

    Conclusions: However, the time to renal replacement therapy was significantly shorter in the intervention group, indicating that other variables than guideline achievements are important for the patient.

  • 69. Hadimeri, Ursula
    et al.
    Smedby, Örjan
    Fransson, Sven-Göran
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hadimeri, Henrik
    Fistula diameter correlates with echocardiographic characteristics in stable hemodialysis patients2015In: NEPHROLOGY @ POINT OF CARE, ISSN 2059-3007, Vol. 1, no 1, p. E44-E48Article in journal (Refereed)
    Abstract [en]

    Aims and background: Left ventricular hypertrophy (LVH) is a common finding in hemodialysis patients. The aim of the present study was to investigate if the diameter of the distal radiocephalic fistula could influence left ventricular variables in stable hemodialysis patients.

    Methods: Nineteen patients were investigated. Measurements of the diameter of the arteriovenous (AV) fistula were performed in 4 different locations. The patients were investigated using M-mode recordings and measurements in the 2D image. Doppler ultrasound was also performed. Transonic measurements were performed after ultrasound investigation.

    Results: Fistula mean and maximal diameter correlated with left ventricular characteristics. Fistula flow correlated neither with the left ventricular characteristics nor with fistula diameters.

    Conclusions: The maximal diameter of the distal AV fistula seems to be a sensitive marker of LVH in stable hemodialysis patients.

  • 70.
    Hadimeri, Ursula
    et al.
    Skaraborg Hosp, Skövde, Sweden.
    Warme, Anna V. B.
    Skaraborg Hosp, Skövde, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A Single Treatment, Using Far Infrared Light, Increased Blood Flow and AV-Fistula Diameter2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no Suppl. 3, p. 258-258Article in journal (Other academic)
  • 71.
    Halin Bergström, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Järemo, Helena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adamo, Hanibal Hani
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Prostate tumors downregulate microseminoprotein-beta (MSMB) in the surrounding benign prostate epithelium and this response is associated with tumor aggressiveness2018In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 4, p. 257-265Article in journal (Refereed)
    Abstract [en]

    Background: Microseminoprotein-beta (MSMB) is a major secretory product from prostate epithelial cells. MSMB synthesis is decreased in prostate tumors in relation to tumor grade. MSMB levels are also reduced in the circulation and MSMB is therefore used as a serum biomarker for prostate cancer. We hypothesized that cancers induce a reduction in MSMB synthesis also in the benign parts of the prostate, and that the magnitude of this response is related to tumor aggressiveness. Reduced levels of MSMB in the circulation could therefore be a consequence of reduced MSMB expression not only in tumor tissue but also in the benign prostate tissue.

    Methods: MSMB expression was analyzed in prostatectomy specimens from 36 patients using immunohistochemistry and qRT-PCR. MSMB expression in the benign prostate tissue was analyzed in relation to Gleason score, tumor stage, and distance to the tumor. Furthermore, Dunning rat prostate tumors with different aggressiveness were implanted into the prostate of Copenhagen rats to study if this affected the MSMB expression in the tumor-adjacent benign rat prostate tissue.

    Results: In prostatectomy specimens, MSMB expression was reduced in prostate tumors but also in the tumor-adjacent benign parts of the prostate. The reduction in tumor MSMB was related to tumor grade and stage, and the reduction in the benign parts of the prostate to tumor grade, stage, and distance to the tumor. Implantation of Dunning cancer cells into the rat prostate resulted in reduced MSMB protein levels in the tumor-adjacent benign prostate tissue. Rapidly growing and metastatic MatLyLu tumors had a more pronounced effect than slow-growing non-metastatic G tumors.

    Conclusion: Our data suggest that aggressive prostate tumors suppress MSMB synthesis in the benign prostate and that this could explain why serum levels of MSMB are decreased in prostate cancer patients. This study suggests that markers for aggressive cancer can be found among factors altered in parallel in prostate tumors and in the adjacent benign tissue.

  • 72.
    Hammarsten, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Scherdin, Tove Dahl
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hagglöf, Christina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersson, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Granfors, Torvald
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    High Caveolin-1 Expression in Tumor Stroma Is Associated with a Favourable Outcome in Prostate Cancer Patients Managed by Watchful Waiting2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, article id e0164016Article in journal (Refereed)
    Abstract [en]

    In the present study we have investigated whether Caveolin-1 expression in non-malignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients managed by watchful waiting. Caveolin-1 was measured in prostate tissues obtained through transurethral resection of the prostate from 395 patients diagnosed with prostate cancer. The majority of the patients (n = 298) were followed by watchful waiting after diagnosis. Tissue microarrays constructed from malignant and non-malignant prostate tissue were stained with an antibody against Caveolin-1. The staining pattern was scored and related to clinicopathologic parameters and outcome. Microdissection and qRT-PCR analysis of Cav-1 was done of the prostate stroma from non-malignant tissue and stroma from Gleason 3 and 4 tumors. Cav-1 RNA expression was highest in non-malignant tissue and decreased during cancer progression. High expression of Caveolin-1 in tumor stroma was associated with significantly longer cancer specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were combined with Caveolin-1 in a Cox regression model. High stromal Caveolin-1 immunoreactivity in prostate tumors is associated with a favourable prognosis in prostate cancer patients managed by watchful waiting. Caveolin-1 could possibly become a useful prognostic marker for prostate cancer patients that are potential candidates for active surveillance.

  • 73. Hartana, C. A.
    et al.
    Ahlén Bergman, E.
    Broomé, A.
    Berglund, S.
    Johansson, M.
    Alamdari, F.
    Jakubczyk, T.
    Huge, Y.
    Aljabery, F.
    Palmqvist, K.
    Holmström, B.
    Glise, H.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, O.
    Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer2018In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, no 1, p. 39-53Article in journal (Refereed)
    Abstract [en]

    Tissue-resident memory T (TRM ) cells are CD8+ T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in TRM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in TRM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate TRM cell phenotypes. We discovered that tumour TRM cells have low DNA methylation in the PRF1 locus (32·9% methylation), which corresponds to increased numbers of perforin-expressing TRM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour TRM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that TRM cells from tumours are not terminally exhausted. Moreover, a high number of TRM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, TRM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies TRM cells as potential new targets for cancer immunotherapy.

  • 74. Hartana, Ciputra Adijaya
    et al.
    Kinn, Johan
    Rosenblatt, Robert
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Anania, Stefan
    Alamdari, Farhood
    Glise, Hans
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, Ola
    Detection of micrometastases by flow cytometry in sentinel lymph nodes from patients with renal tumours2016In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 115, no 8, p. 957-966Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Stage is an important prognostic factor in renal tumours and dissemination to regional lymph nodes is associated with poor outcomes. Lymph nodes are routinely assessed by immunohistochemistry and microscopic evaluation, a time-consuming process where micrometastases might go undiagnosed. We evaluate an alternative method for detecting metastatic cells in sentinel nodes (SNs) by flow cytometry.

    METHODS: A total of 15 nodes from 5 patients diagnosed with renal tumours were analysed by flow cytometry. Staining for the intracellular marker cytokeratin 18 (CK18) with the surface markers carbonic anhydrase IX (CA9) and Cadherin 6 were used in flow cytometry analysis. Peripheral blood mononuclear cells (PBMCs) with the addition of known concentrations of cancer cell lines were analysed to investigate the sensitivity of micrometastasis detection.

    RESULTS: Stability of the assay was marked by low intra-assay variability (coefficient of variance ⩽16%) and low inter-assay variability (R(2)=0.9996-1). Eight nodes in four patients were positive for metastasis; six of them were considered being micrometastatic. These metastases were undetected by routine pathology and the patients were restaged from pN0 to pN1.

    CONCLUSIONS: Flow cytometry is able to detect micrometastases in lymph nodes of renal tumour patients that were undetected under H&E examination.

  • 75.
    Haya, N
    et al.
    Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia.
    Baessler, K
    Charite, Beckenbodenzentrum Charite, Berlin, Germany.
    Christmann-Schmid, C
    Hosp Lucerne, Luzern, Switzerland.
    de Tayrac, R
    Caremeau Univ Hosp, Nimes, France.
    Dietz, V
    Catharina Hosp, Eindhoven, Netherlands.
    Guldberg, R
    Odense Univ Hosp, Ctr Clin Epidemiol, DK-5000 Odense, Denmark.
    Mascarenhas, T
    Hosp Sao Joao, Oporto, Portugal.
    Nüssler, Emil
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Ballard, E
    Royal Brisbane & Womens Hosp, QIMR Berghofer RBWH Stat Unit, Brisbane, Qld, Australia.
    Ankardal, M
    Hallands Sjukhus, Kungsbacka, Sweden.
    Boudemaghe, T
    Caremeau Univ Hosp, Nimes, France.
    Maher, C
    Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia.
    Prolapse and continence surgery in OECD countries2014In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 25, p. S98-S100Article in journal (Other academic)
  • 76. Hedlund, Per Olov
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Jan Erik
    Hagerman, Inger
    Henriksson, Peter
    Iversen, Peter
    Klarskov, Peter
    Mogensen, Peter
    Rasmussen, Finn
    Varenhorst, Eberhard
    Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer: Evaluation of cardiovascular events in a randomized trial2011In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 45, no 5, p. 346-353Article in journal (Refereed)
    Abstract [en]

    Objective. This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin (R)) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease. Material and methods. Nine-hundred and fifteen patients with T0-4, Nx, M1, G1-3, hormone- naive prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin (R)) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl (R)) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression. Results. There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p < 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036). Conclusions. Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e. g. avoidance of osteopenia and hot flushes and the low price, are given priority.

  • 77. Hemdan, Tammer
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jahnson, Staffan
    Hellstrom, Pekka
    Tasdemir, Ilker
    Malmstrom, Per-Uno
    Five-year results of nordic T1G2-3, a randomized trial comparing bcg with epirubicin and interferon alpha 2b2013In: Scandinavian journal of urology, ISSN 2168-1805, Vol. 47, no Suppl. 219, p. 19-20Article in journal (Other academic)
  • 78.
    Henriksson, Tobias
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Impact of home adress and distance to nearest urological unit on survival in invasive urinary bladder cancer2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 79.
    Holm, Alexander
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Patients’ perspective on prostate artery embolization2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 80.
    Holmberg, Benny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andersson, Christer
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    There is no benefit of atorvastatin for patients with severe renal impairment independent if they have DM or notArticle in journal (Other academic)
  • 81.
    Holmberg, Benny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brännström, M
    Bucht, B
    Crougneau, V
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dimeny, E
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ekspong, A
    Granroth, B
    Gröntoft, KC
    Hadimeri, H
    Ingman, B
    Isaksson, B
    Johansson, G
    Lindberger, K
    Lundberg, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mikaelsson, L
    Olausson, E
    Persson, B
    Welin, D
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wikdahl, AM
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Safety and efficacy of atorvastatin in patients with severe renal dysfunction2005In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, no 6, p. 503-510Article in journal (Refereed)
  • 82.
    Holmberg, Benny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cardiovascular conditions in hemodialysis patients may be worsened by extensive interdialytic weight gain2009In: Hemodialysis International, ISSN 1492-7535, E-ISSN 1542-4758, Vol. 13, no 1, p. 27-31Article in journal (Refereed)
    Abstract [en]

    The risk of death is increased for hemodialysis (HD) patients compared with age-matched healthy subjects, the main reason for this being cardiovascular conditions. This prospective study investigated whether the burden of interdialytic weight gain (IDWG) was of importance for cardiovascular end points and survival. A total of 97 HD patients were studied. The end points included death (reasons given), acute myocardial infarction, or coronary vascular intervention. The extent of ultrafiltration was measured at predefined follow-up points. The IDWG was calculated as ultrafiltration/body weight given in weight%. The burden of IDWG was analyzed. End points occurred in 77 (79%) of the patients during the 5-year study period. The extent of IDWG was higher in those with end points due to cardiovascular reasons (3.77 weight% vs. 3.19 P<0.001), cardiac reasons (P<0.001), congestive heart failure (P<0.01), aortic aneurysm, and intracerebral bleeding (P<0.024). To reduce the risk for cardiovascular events, it is important to avoid too extensive IDWG in HD patients.

  • 83.
    Holmlund, Dan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    On medical treatment for ureteral stone expulsion2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 2, p. 94-100Article in journal (Refereed)
    Abstract [en]

    There is evidence that α-adrenoceptor (α-AR) antagonists facilitate the passage of ureteric stones, but the mechanism behind this effect has not been established. If one accepts that it is the friction between a ureteral stone and the mucosa that hampers the passage of the stone, and that the passage traumatizes the mucosa, the aim of treatment must be to reduce this friction. Elevated pressure above an obstructing stone results in an increase in tension in the wall of the upper urinary tract, including the tension at stone level, which causes an increase in friction and ureteric colic. Reducing pressure, by low but adequate fluid intake, non-steroidal anti-inflammatory drugs (NSAIDs), or α-AR antagonists that reduce the friction and give pain relief, seems to be rational. When the stone is pressed downwards by a high pressure the mucosa forms a bar ahead of the stone. These factors reduce the ureteral lumen and hamper the passage of both urine and the stone. The swelling can be reduced by NSAIDs. Filling of the ureter ahead of the stone reduces the friction between the stone and the ureteral mucosa. Evacuation of the urine ahead of the stone by effective peristaltic activity increases this friction. α-AR antagonists that reduce peristalsis may therefore be used to reduce the friction and consequently allow the stones to pass more often and earlier. For very early stone expulsion, a combination of NSAIDs and α-AR antagonists may be useful. There is no evidence that spasm influences the passage of ureteral stones.

  • 84.
    Holmlund, Dan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ureteral stones: an experimental and clinical study of the mechanism of the passage and arrest of ureteral stones1968Doctoral thesis, monograph (Other academic)
  • 85.
    Holmström, Benny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Early diagnosis and treatment of prostate cancer: observational studies in the National Prostate Cancer Register of Sweden and the Västerbotten Intervention Project2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Prostate-specific antigen (PSA) testing has caused a steep increase in the incidence of prostate cancer, especially the incidence of localised low risk disease. In order to decrease the overdiagnosis accompanied by PSA testing, analysis of inherited genetic variants have been suggested as potential tools for clinical assessment of disease risk. With the aim of minimizing overtreatment and postpone side-effects of curative treatment for low risk prostate cancer, active surveillance, a treatment strategy with initial surveillance and deferred radical prostatectomy at the time of progression has evolved. 

    The aim of this thesis was to study the validity of PSA (paper I) and inherited genetic variants (paper II) for early diagnosis of prostate cancer, to assess the extent of PSA testing in Sweden (paper III), and to study the safety of deferred radical prostatectomy in localised low to intermediate risk prostate cancer (paper IV).

    The study designs were i) case-control studies nested within the Västerbotten intervention project (paper I and II), ii) observational study in the Cancer Register of Sweden (paper III), and iii) observational study in the NPCR Follow-up study (paper IV).

    PSA had a high validity in predicting a prostate cancer diagnosis with an area under the receiver operating characteristics (ROC) curve of 0.86 (95% CI, 0.84 to 0.88). A combined test, including PSA, the ratio of free to total PSA, and 33 single nucleotide polymorphisms (SNPs) in a genetic risk score, increased the area under curve to 0.87 (95% CI, 0.85 to 0.89). The estimated uptake of PSA testing among men aged 55 to 69 years increased from zero to 56% between 1997 and 2007 and there were large variations in the uptake of PSA testing between counties in Sweden. After a median follow-up time of eight years there was no significant difference in presence of any one or more adverse pathology features or prostate cancer specific mortality after primary compared to deferred radical prostatectomy in localised low to intermediate risk prostate cancer.

    Results from these studies indicate that PSA and the hitherto identified SNPs are not suitable biomarkers in single-test prostate cancer screening. It is possible to estimate the uptake of PSA testing on a population level. Initial surveillance and deferred radical prostatectomy represent a feasible treatment strategy in localised low to intermediate risk prostate cancer.

  • 86.
    Holmström, Benny
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Erik
    Egevad, Lars
    Adolfsson, Jan
    Johansson, Jan-Erik
    Hugosson, Jonas
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Outcome of primary versus deferred radical prostatectomy in the National Prostate Cancer Register of Sweden follow-up study2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 4, p. 1322-1327Article in journal (Refereed)
    Abstract [en]

    Purpose We assessed outcomes in terms of adverse pathology and prostate cancer specific mortality in men who underwent primary or deferred radical prostatectomy.

    Materials and Methods In the National Prostate Cancer Register of Sweden Follow-Up Study men 70 years old or younger at diagnosis with localized low to intermediate risk prostate cancer diagnosed from 1997 to 2002 were identified. Outcome in terms of adverse pathology, namely upgrading of Gleason score, positive surgical margins and extraprostatic extension, as well as prostate cancer specific mortality, was assessed in 2,344 men who underwent primary radical prostatectomy and 222 who underwent deferred radical prostatectomy after an initial period of surveillance.

    Results Upgrading of Gleason score in surgical specimens vs core biopsies was less frequent after primary (25%) vs deferred radical prostatectomy (38%), p <0.001. There was no significant difference in the percentage of men who underwent primary vs deferred radical prostatectomy for positive surgical margins (33% vs 24%) or extraprostatic extension (27% vs 25%), and there was no difference in any 1 or more of the 3 adverse pathology features (55% vs 56%). After a median followup of 8 years 0.7% of men in the primary radical prostatectomy group and 0.9% in the deferred radical prostatectomy group had died of prostate cancer.

    Conclusions There was no significant difference in the presence of any 1 or more adverse pathology features or in prostate cancer specific mortality after primary compared to deferred radical prostatectomy. However, longer followup is needed to conclusively evaluate the role of deferred radical prostatectomy.

  • 87.
    Holmström, Benny
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. International Agency for Research on Cancer (IARC), Lyon, France.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stenman, Ulf-Håkan
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Prostate specific antigen for early detection of prostate cancer: longitudinal study2009In: BMJ (Clinical research ed.), ISSN 1468-5833, Vol. 339, p. b3537-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate if prostate specific antigen test attains validity standards required for screening in view of recent prostate cancer screening trial results.

    DESIGN: Case-control study nested in longitudinal cohort.

    SETTING: Västerbotten Intervention Project cohort, Umeå, Sweden.

    PARTICIPANTS: 540 cases and 1034 controls matched for age and date of blood draw.

    MAIN OUTCOME MEASURE: Validity of prostate specific antigen for prediction of subsequent prostate cancer diagnosis by record linkage to cancer registry.

    RESULTS: Blood samples were drawn on average 7.1 (SD 3.7) years before diagnosis. The area under the curve for prostate specific antigen was 0.84 (95% confidence interval 0.82 to 0.86). At prostate specific antigen cut-off values of 3, 4, and 5 ng/ml, sensitivity estimates were 59%, 44%, and 33%, and specificity estimates were 87%, 92%, and 95%. The positive likelihood ratio commonly considered to "rule in disease" is 10; in this study the positive likelihood ratios were 4.5, 5.5, and 6.4 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. The negative likelihood ratio commonly considered to "rule out disease" is 0.1; in this study the negative likelihood ratios were 0.47, 0.61, and 0.70 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. For a cut-off of 1.0 ng/ml, the negative likelihood ratio was 0.08.

    CONCLUSIONS: No single cut-off value for prostate specific antigen concentration attained likelihood ratios formally required for a screening test. Prostate specific antigen concentrations below 1.0 ng/ml virtually ruled out a prostate cancer diagnosis during the follow-up. Additional biomarkers for early detection of prostate cancer are needed before population based screening for prostate cancer should be introduced.

  • 88.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Metabolic factors and risk of prostate, kidney, and bladder cancer2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Prostate cancer is the most common cancer in Sweden with around 10,000 new cases every year. Kidney and bladder cancer are less common with 1,000 and 2,000 new cases annually, respectively. The incidence of these cancer sites is higher in developed, than in developing countries, suggesting an association between lifestyle and cancer risk. The aims of this thesis were to investigate body mass index (BMI), blood pressure, and blood levels of glucose, total cholesterol, and triglycerides as risk factors for prostate, kidney, and bladder cancer. Furthermore, we aimed at assess probabilities of prostate cancer and competing events, all-cause death, for men with normal and high levels of metabolic factors.

    Material and methods: This thesis was conducted within the Metabolic Syndrome and Cancer project (Me-Can), a pooled cohort study with data from 578,700 participants from Norway, Sweden, and Austria. Data from metabolic factors were prospectively collected at health examinations and linked to the Cancer and Cause of Death registers in each country. 

    Results: High levels of metabolic factors were not associated with increased risk of prostate cancer, but high levels of BMI and blood pressure were associated with risk of prostate cancer death. The probability of prostate cancer was higher for men with normal levels of metabolic factors compared to men with high levels, but the probability of all-cause death, was higher for men with high levels than for those with normal levels. For both men and women, high levels of metabolic factors were associated with increased risk of kidney cancer (renal cell carcinoma). Furthermore, blood pressure for men and BMI for women were found as independent risk factors of kidney cancer. High blood pressure was associated with an increased risk of bladder cancer for men.

    Conclusions: High levels of metabolic factors were associated to risk of kidney and bladder cancer and to death from kidney, bladder, and prostate cancer. Compared to men with normal levels, men with high levels of metabolic factors had a decreased probability of prostate cancer but an increased probability of all-cause death.

  • 89.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Liedberg, Fredrik
    Hagberg, Oskar
    Aljabery, Firas
    Ströck, Viveka
    Hosseini, Abolfazl
    Gårdmark, Truls
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Malmström, Per-Uno
    Garmo, Hans
    Jahnson, Staffan
    Holmberg, Lars
    Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 9, article id e016606Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe).

    PARTICIPANTS: The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death.

    FINDINGS TO DATE: Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival.

    FUTURE PLANS: The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author.

  • 90.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Rapp, Kilian
    Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Manjer, Jonas
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Bjørge, Tone
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Ulmer, Hanno
    Med Univ Innsbruck, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria.
    Engeland, Anders
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Almqvist, Martin
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Concin, Hans
    Agcy Prevent & Social Med, Bregenz, Australia.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tretli, Steinar
    Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
    Nagel, Gabriele
    Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Metabolic factors associated with risk of renal cell carcinoma2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2, p. e57475-Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown that obesity and hypertension are associated with increased risk of renal cell carcinoma (RCC), but less is known about the association to other metabolic factors. In the Metabolic Syndrome and Cancer project (Me-Can) data on body mass index (BMI, kg/m2), blood pressure, and circulating levels of glucose, cholesterol, and triglycerides were collected from 560,388 men and women in cohorts from Norway, Austria, and Sweden. By use of Cox proportional hazard models, hazard ratios (HR) were calculated for separate and composite metabolic exposures. During a median follow-up of 10 years, 592 men and 263 women were diagnosed with RCC. Among men, we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 1.51, 95% CI 1.13-2.03), systolic blood pressure, (HR = 3.40, 95% CI 1.91-6.06), diastolic blood pressure, (HR = 3.33, 95% CI 1.85-5.99), glucose, (HR = 3.75, 95% CI 1.46-9.68), triglycerides, (HR = 1.79, 95% CI 1.00-3.21) and a composite score of these metabolic factors, (HR = 2.68, 95% CI 1.75-4.11). Among women we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 2.21, 95% CI 1.32-3.70) and the composite score, (HR = 2.29, 95% CI 1.12-4.68). High levels of the composite score were also associated with risk of death from RCC among both men and women. No multiplicative statistical or biological interactions between metabolic factors on risk of RCC were found. High levels of BMI, blood pressure, glucose and triglycerides among men and high BMI among women were associated with increased risk of RCC.

  • 91.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Clinical Sciences, Diabetes and Cardiovascular Diseases, Genetic Epidemiology, Lund University, Lund, Sweden.
    Garmo, Hans
    Holmberg, Lars
    Van Hemelrijck, Mieke
    Interpretation of conventional survival analysis and competing-risk analysis: an example of hypertension and prostate cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 6, p. 850-852Article in journal (Refereed)
  • 92.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Nagel, Gabriele
    Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
    Manjer, Jonas
    Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
    Bjørge, Tone
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Engeland, Anders
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
    Ulmer, Hanno
    Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
    Lindkvist, Björn
    Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
    Selmer, Randi
    Norwegian Institute of Public Health, Oslo, Norway.
    Concin, Hans
    Agency for Preventive and Social Medicine, Bregenz, Austria.
    Tretli, Steinar
    Institute of Population-based Cancer Research, The Cancer Registry of Norway, Oslo, Norway.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Competing risk analysis of metabolic factors and prostate cancerManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Men at risk of prostate cancer are also at risk of competing events but this has been ignored in most studies of metabolic aberrations and prostate cancer. The aim of this study was to assess probabilities of prostate cancer and prostate cancer death by use of competing risk analysis.

    Methods: In the Metabolic syndrome and Cancer project (Me-Can), data on body mass index, blood pressure, glucose, total cholesterol, and triglycerides were collected from 285 040 men. Probabilities of prostate cancer, prostate cancer death and competing events, i.e. all-cause death or death from other causes, respectively, were calculated for men with normal (bottom 84%) and high (top 16%) levels of each metabolic factor and a composite score based on all metabolic factors

    Results: During follow up, 5893 men were diagnosed with prostate cancer, 1013 men died of prostate cancer, and 26 328 men died of other causes. Men with high levels of metabolic factors had decreased probability of prostate cancer, similar probability of prostate cancer death, and increased probability of other causes of death compared to men with normal levels. After 1996, when prostate specific antigen was used for detection of prostate cancer, men up to 80 years with normal levels of metabolic factors had 13% probability of prostate cancer and 37% probability of death from all causes. For men with high levels of metabolic factors, corresponding probabilities were 12% and 47%.

    Conclusions: Men with metabolic aberrations had a decreased probability of prostate cancer but a substantially higher probability of death from all causes.

  • 93.
    Inkiläinen, Aapo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Styrke, Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Sundsvall Hospital, Sundsvall, Sweden .
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Strigård, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Occurrence of abdominal bulging and hernia after open partial nephrectomy: a retrospective cohort study2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 1, p. 54-58Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Abdominal bulging and incisional hernia are known sequelae after open partial nephrectomy (OPN) via a flank incision. Precise rates are not known. The aims of this study were to determine the rates of bulging and hernia after OPN, and to examine potential risk factors.

    MATERIALS AND METHODS: A retrospective review was undertaken of 197 consecutive patients operated on with OPN via a flank incision between 2004 and 2014. After exclusion, 184 patients remained. Medical records and radiological images from the preoperative work-up, and follow-up after surgery at 3, 12 and 24 months, were reviewed.

    RESULTS: A visible bulge was noted in 36 of the 184 patients at clinical examination. Only 20 cases (12%) remained at the last follow-up. Radiological changes interpreted as a bulge were initially seen in 50 patients, while only 35 (19%) remained at the last radiological examination. Clinical incisional hernia was reported in five patients (3%), and radiological hernia was seen in 10 patients (5%). Patients who developed a hernia had a higher body mass index (30 vs 26 kg/m(2), p = 0.02). Other demographic variables showed no significant correlation.

    CONCLUSIONS: Bulging is a common sequela after flank incision. The rate of incisional hernia after flank incision is comparable to rates after other forms of abdominal surgery. Further studies are required to evaluate the psychological and physiological effects of bulging, the pain and weakness caused, and the cosmetic embarrassment suffered by the patient.

  • 94.
    Iranparvar Alamdari, Farhood
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Renal cell carcinoma: factors of importance for follow-up and survival2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Renal cell carcinoma (RCC) is most lethal of the urological cancers, with more than 40% dying of the disease. About 30% of the patients have metastases at initial diagnosis and up to 40% undergoing nephrectomy for localized RCC develop metastasis. A follow-up protocol based on accurate prognostic variables allows identification of low and high risk patients and selection of those most likely to benefit from adjuvant therapy. I have studied a number of prognostic patient-related factors, including tumour stage and grade, angiogenetic factors and tumour markers, in order to improve follow-up guideline as well as to try to predict prognosis and clinical outcome for individual patients.

    Material and Methods: The studies are based on patients treated for RCC between 1982 and 2002. All patients eligible for surgery with or without metastasis were treated with nephrectomy and were followed according to a scheduled follow-up programme. Serum samples were collected after obtained informed consent. Multiple clinicopathological, laboratory variables and preoperative radiological examinations were analyzed.

    Results: Study I- After nephrectomy in 187 patients with non-metastatic RCC, 30% developed metastases during the follow-up. The risk for metastases was greater for more advanced stage and was adjusted by size and DNA ploidy. The median time to the diagnosis of metastases was 14.5 months. Metastases occurred in 43% of the patients within one year, within 2 years in 70% and 80% in 3 years. Patients with tumours less than 5 cm and diploid pT1>5cm and pT2 tumours survived longer than those with larger and aneuploid tumours. The 5-years survival rate for pT1, pT2, pT3 tumours were 95%, 87%, and 37% respectively. In pT3 tumours DNA ploidy had no relation to survival time.

    Study II and IV- The median survival time for patients with metastatic RCC was 7 months. Cytoreductive nephrectomy was associated with longer survival time. Factors including performance status (PS), number of metastatic sites, erythrocyte sedimentation rate (ESR), calcium in serum, vein invasion, capsule invasion had independent prognostic value with Cox multivariate analysis. Study III- The incidence of adrenal tumour involvement was 5.3 %, unaffected of RCC type, tumour location or side. Gender (male) and locally advanced tumours (pT3 > 5cm) were factors predicting adrenal involvement. The presence of adrenal involvement was a significant adverse prognostic variable, indicating a significantly shorter survival in patients both with and without distant metastases.

    Conclusion: Optimal follow-up guidelines are important from both medical and economic perspectives. The risk for progression depends mainly on stage, which in combination with other prognostic factors may allow more individualized and cost effective follow-up, in some cases by avoiding unnecessary examinations in a third of the patients. Cytoreductive nephrectomy in patients with good PS, metastases limited to one organ, low ESR, normal calcium and no vein invasion were factors associated to long survival time. Soluble angiogenic factors in serum gave no prognostic information. Ipsilateral adrenalectomy in conjunction with radical nephrectomy should be performed if an adrenal lesion cannot be cleared of suspicion during preoperative work up. Ipsilateral adrenal involvement is a highly adverse prognostic factor and should be staged as M1a in the TNM staging system.

  • 95.
    Jacobsen, Jan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Vascular endothelial growth factor in renal cell carcinoma2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background. Angiogenesis is essential for tumour growth. Vascular endothelial growth factor (VEGF) and its isoforms were investigated in relation to the clinical course in a large number of patients with renal cell carcinoma (RCC).

    Methods. RCC subtypes and behaviour were established by clinicopathological criteria and surveillance. VEGF expression was analysed in serum by enzyme-linked immuno-sorbent assay (ELISA) and in tumour tissue by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and Western blot (WB).

    Results. Serum VEGF (S-VEGF) was increased in RCC compared to control group. S-VEGF correlated with tumour stage and grade and was associated with survival in men but not in women. S-VEGF correlated with blood platelet counts, which were inversely correlated to increasing age in women, and they were decreased in chronically medicated patients, particularly in men. In contrast to S-VEGF, platelet counts associated with survival only in patients free of medication and chronic diseases. RT-PCR showed a correlation between VEGF121/VEGF165 mRNA and between VEGF165/VEGF-R1 mRNA. There was no association between different VEGF mRNA isoforms and S-VEGF. Conventional renal cell carcinoma (CRCC) had higher VEGF165, VEGF121, and VEGF-R1 mRNA levels compared with papillary renal cell carcinoma (PRCC). IHC VEGF staining was strong in kidney cortex. Kidney tumour showed a considerable variation in cytoplasmatic VEGF expression, which correlated with tumour size. Although, there was no difference in VEGF expression between the RCC types, VEGF expression was associated with survival only in CRCC. WB showed a strong protein expression of both VEGF189 and VEGF165 in kidney cortex. In kidney tumour, expression of VEGF189 varied the most, VEGF165 less so, and VEGF121 was rarely detected. Both CRCC and PRCC expressed low levels of VEGF189 and VEGF165 compared with kidney cortex. Chromophobe renal cell carcinoma (ChRCC) expressed VEGF189 levels comparable to those from kidney cortex, while VEGF165 was lower. In PRCC and ChRCC, VEGF189 levels correlated inversely with advancing tumour stage, and in PRCC, VEGF165 levels correlated inversely with increasing tumour size. VEGF189 was an independent prognostic factor for survival in patients with PRCC.

    Conclusions. S-VEGF has a stronger association to progression in RCC than platelet count. CRCC showed high levels of VEGF mRNA isoforms and VEGF-R1 mRNA compared to PRCC. VEGF mRNA isoforms expression decreased with advancing stage. IHC demonstrated VEGF expression in cell cytoplasm related to tumour growth, particular in CRCC. Different VEGF isoform patterns were found in different RCC types. Protein VEGF189 expression was associated with tumour stage and was an independent prognostic factor in PRCC. Protein VEGF165 expression was generally low and had no prognostic value. The trend for decreasing levels of VEGF isoforms in advanced tumour stages may indicate that angiogenic activity is an early event in tumour growth induced by VEGF, but that during later tumour progression the role of VEGF is less clear.

  • 96. Jahnson, S.
    et al.
    Hagberg, O.
    Holmang, S.
    Liedberg, F.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Malmstrom, P. U.
    Wijkstrom, H.
    Mansson, W.
    Higher excess mortality rate in women than in men with invasive bladder cancer2012In: European urology. Supplement, ISSN 1569-9056, E-ISSN 1878-1500, Vol. 11, no 1, p. E870-U832Article in journal (Other academic)
  • 97. Jahnson, Staffan
    et al.
    Gårdmark, Truls
    Hosseini, Abolfazl
    Jerlström, Tomas
    Liedberg, Fredrik
    Malmström, Per-Uno
    Rosell, Johan
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ströck, Viveka
    Häggström, Christel
    Holmberg, Lars
    Aljabery, Firas
    Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe)2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the management of TaG3 tumours of the urinary bladder using nationwide population-based data in relation to the prevailing guidelines, patients' characteristics, and outcome.

    Materials and methods: The Bladder Cancer Data Base Sweden (BladderBaSe), including data from the Swedish National Register for Urinary Bladder Cancer (SNRUBC), was used to study all patients with TaG3 bladder cancer diagnosed from 2008 to 2014. Patients were divided into the following management groups: (1) transurethral resection (TUR) only, (2) TUR and intravesical instillation therapy (IVIT), (3) TUR and second-look resection (SLR), and (4) TUR with both SLR and IVIT. Patient and tumour characteristics and outcome were studied.

    Results: There were 831 patients (83% males) with a median age of 74 years. SLR was performed more often on younger patients, on men, and less often in the Western and Uppsala/Örebro Healthcare regions. IVIT was performed more often with younger patients, with men, in the Western Healthcare region, and less often in the Uppsala/Örebro Healthcare region. Death from bladder cancer occurred in 6% of cases within a median of 29 months (0-84 months) and was lower in the TUR/IVIT and TUR/SLR/IVIT groups compared to the other two groups.

    Conclusion: In the present study, there was, according to the prevailing treatment guidelines, an under-treatment with SLR for older patients, women, and in some healthcare regions and, similarly, there was an under-treatment with IVIT for older patients. Cancer-specific survival and relative survival were lower in the TUR only group compared to the TUR/IVIT and TUR/SLR/IVIT groups.

  • 98. Jahnson, Staffan
    et al.
    Hosseini Aliabad, Abolfazl
    Holmäng, Sten
    Jancke, Georg
    Liedberg, Fredrik
    Ljungberg, Börje
    Department of Urology, Northern University Hospital, Umeå, Sweden.
    Malmström, Per-Uno
    Rosell, Johan
    Swedish National Registry of Urinary Bladder Cancer: no difference in relative survival over time despite more aggressive treatment2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 1, p. 14-20Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. MATERIALS AND METHODS: All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. RESULTS: The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. CONCLUSIONS: This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

  • 99. Jamshidi, Neema
    et al.
    Jonasch, Eric
    Zapala, Matthew
    Korn, Ronald L
    Brooks, James D
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Kuo, Michael D
    The radiogenomic risk score stratifies outcomes in a renal cell cancer phase 2 clinical trial2016In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 26, no 8, p. 2798-2807Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To characterize a radiogenomic risk score (RRS), a previously defined biomarker, and to evaluate its potential for stratifying radiological progression-free survival (rPFS) in patients with metastatic renal cell carcinoma (mRCC) undergoing pre-surgical treatment with bevacizumab.

    METHODOLOGY: In this IRB-approved study, prospective imaging analysis of the RRS was performed on phase II clinical trial data of mRCC patients (n = 41) evaluating whether patient stratification according to the RRS resulted in groups more or less likely to have a rPFS to pre-surgical bevacizumab prior to cytoreductive nephrectomy. Survival times of RRS subgroups were analyzed using Kaplan-Meier survival analysis.

    RESULTS: The RRS is enriched in diverse molecular processes including drug response, stress response, protein kinase regulation, and signal transduction pathways (P < 0.05). The RRS successfully stratified rPFS to bevacizumab based on pre-treatment computed tomography imaging with a median progression-free survival of 6 versus >25 months (P = 0.005) and overall survival of 25 versus >37 months in the high and low RRS groups (P = 0.03), respectively. Conventional prognostic predictors including the Motzer and Heng criteria were not predictive in this cohort (P > 0.05).

    CONCLUSIONS: The RRS stratifies rPFS to bevacizumab in patients from a phase II clinical trial with mRCC undergoing cytoreductive nephrectomy and pre-surgical bevacizumab.

    KEY POINTS: • The RRS SOMA stratifies patient outcomes in a phase II clinical trial. • RRS stratifies subjects into prognostic groups in a discrete or continuous fashion. • RRS is biologically enriched in diverse processes including drug response programs.

  • 100. Jan, Michael
    et al.
    Bonn, Stephanie E.
    Sjölander, Arvid
    Wiklund, Fredrik
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Erik
    Grönberg, Henrik
    Bälter, Katarina
    The roles of stress and social support in prostate cancer mortality2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 1, p. 47-55Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to evaluate the association between perceived stress, social support, disease progression and mortality in a nationwide population-based cohort of men with prostate cancer. Materials and methods: The study surveyed 4105 Swedish men treated for clinically localized prostate cancer regarding stress, grief, sleep habits and social support. Associations between these factors and mortality were assessed using multivariate Cox regression analysis. Results: Men with the highest levels of perceived stress had a statistically significantly increased rate of prostate cancer-specific mortality compared with men with low stress levels (hazard ratio 1.66, 95% confidence interval 1.05-2.63). Men with high stress levels also had a high frequency of grieving and sleep loss. They also had fewer people with whom to share their emotional problems and felt an inability to share most of their problems with partners, friends and family. Conclusions: This study contributes to the growing field of psychosocial quality of life research in men with prostate cancer. The findings show a significant association between prostate cancer-specific mortality and perceived stress in patients initially diagnosed with localized, non-metastatic prostate cancer. Significant associations between perceived stress and various psychosocial factors were also seen. The findings of this study could prove useful to target interventions to improve quality of life in men with prostate cancer.

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