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  • 201.
    Nyström, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Unit of Research, Education and Development, Östersund.
    Asklund, Ina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Unit of Research, Education and Development, Östersund.
    Sjöström, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Unit of Research, Education and Development, Östersund.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Re: Treatment of stress urinary incontinence with a mobile app: factors associated with success2018In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 29, no 6, p. 925-925Article in journal (Other academic)
  • 202.
    Nyström, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Söderström, Lars
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Self-Management of Incontinence Using a Mobile App: Factors Associated with Completion and ImprovementManuscript (preprint) (Other academic)
  • 203.
    Nüssler, Emil Karl
    et al.
    Västerbottens County Council, The National Quality Register of Gynecological Surgery, Umeå, Sweden.
    Greisen, Susanne
    Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus N, Denmark.
    Kesmodel, Ulrik Schiøler
    Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus N, Denmark.
    Löfgren, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Bek, Karl Møller
    Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus N, Denmark.
    Glavind-Kristensen, Marianne
    Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus N, Denmark.
    Operation for recurrent cystocele with anterior colporrhaphy or non-absorbable mesh: patient reported outcomes2013In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 24, no 11, p. 1925-1931Article in journal (Refereed)
    Abstract [en]

    Introduction and hypothesis: The aim of this study was to compare patient reported outcomes and complications after repair of recurrent anterior vaginal wall prolapse in routine health care settings using standard anterior colporrhaphy or non-absorbable mesh.

    Methods: The study is based on prospective data from the Swedish National Register for Gynaecological Surgery. 286 women were operated on for recurrent anterior vaginal wall prolapse in 2008–2010; 157 women had an anterior colporrhaphy and 129 were operated on with a non-absorbable mesh. Pre-, and perioperative data were collected from doctors and patients. Patient reported outcomes were evaluated 2 months and 12 months after the operation.

    Results: After 12 months, the odds ratio (OR) of patient reported cure was 2.90 (1.34–6.31) after mesh implants compared with anterior colporrhaphy. Both patient- and doctor-reported complications were found more often in the mesh group. However, no differences in serious complications were found. Thus, an organ lesion was found in 2.3 % after mesh implant compared with 2.5 % after anterior colporrhaphy (p = 0.58). Two patients in the mesh group (1.2 %) were re-operated compared with 1 patient (0.6 %) in the anterior colporrhaphy group (p = 0.58). The infection rate was higher after mesh (8.5 %) than after anterior colporrhaphy (2.5 %; OR 3.19 ; 1.07–14.25).

    Conclusion: Implantation of synthetic mesh during operation for recurrent cystocele more than doubled the cure rate, whereas no differences in serious complications were found between the groups. However, mesh increased the risk of infection.

  • 204. O'Farrell, Sean
    et al.
    Sandström, Karin
    Garmo, Hans
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Lars
    Adolfsson, Jan
    Van Hemelrijck, Mieke
    Risk of thromboembolic disease in men with prostate cancer undergoing androgen deprivation2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 3, p. 391-398Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the risk of thromboembolic disease (TED) in men with prostate cancer (PCa) on androgen deprivation therapy (ADT) while accounting for known TED risk factors.

    MATERIALS AND METHODS: TED risk was assessed for 42,263 PCa men on ADT compared to a matched, PCa-free cohort of 190,930 men. Associations between ADT and deep venous thrombosis (DVT) or pulmonary embolism (PE) were analysed using multivariate Cox proportional hazard regression models. Previous PCa-related surgeries and the following proxies for disease progression: transurethral resection of the prostate, palliative radiotherapy and nephrostomy, were accounted for.

    RESULTS: Between 1997-2013, 11,242 PCa men received anti-androgen (AA) monotherapy, 26,959 gonadotropin-releasing hormone (GnRH) agonists, 1,091 combined androgen blockade, and 3,789 underwent orchiectomy. When accounting for previous surgeries and proxies of disease progression, GnRH agonist users and surgically castrated men were at increased TED risk versus the comparison cohort, HR: 1.67 (95% CI: 1.40-1.98) and 1.61 (95% CI: 1.15-2.28), respectively. Men on AA monotherapy were at decreased risk, HR for DVT: 0.49 (95% CI: 0.33-0.74). TED risk was highest among those who switched from AA to GnRH agonists, PE HR: 2.55 (95% CI: 1.76-3.70). This increased from 2.52 (95% CI: 1.54-4.12) in year one, to 4.05 (95% CI: 2.51-6.55) in year two.

    CONCLUSION: TED incidence among men on ADT increased with the duration of therapy and risk was highest for those who switched regimen, thus implicating roles for disease progression as well as ADT in propagating TED risk. Nonetheless, these findings support that only men with a relevant indication should receive systemic ADT.

  • 205.
    Ohlson, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nygren, Katarina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The magnitude of early castration-induced primary tumour regression in prostate cancer does not predict clinical outcome2006In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 49, no 4, p. 675-683Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: This study was designed to test whether early castration-induced short-term cellular changes in primary prostate tumours could predict clinical outcome in advanced disease. PATIENTS AND METHODS: Biopsies from 83 patients obtained before and within two weeks after surgical castration were investigated. Tumour epithelial cell apoptosis, proliferation, and prostate specific antigen (PSA) levels were quantified using immunohistochemistry, laser capture micro-dissection, and real time RT-PCR. Cellular effects were related to changes in serum PSA levels and clinical outcome. RESULTS: Decreased proliferation and PSA mRNA levels, and increased apoptosis were observed in most tumours. These early cellular responses were not correlated to each other and did not predict serum PSA response or cancer-specific survival. A nadir PSA level below 1 ng/ml predicted a longer cancer-specific survival after castration therapy. CONCLUSION: Castration therapy causes primary tumour regression in most patients with advanced prostate cancer, but these primary tumour effects are not predictive for systemic disease control. Studies of early changes in metastases during hormonal therapy will probably give more predictive information for clinical outcome than further studies in primary tumours.

  • 206. Ohmann, Erin L.
    et al.
    Loeb, Stacy
    Robinson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Jönköping County Council, Jönköping, Sweden.
    Bill-Axelson, Anna
    Berglund, Anders
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Nationwide, population-based study of prostate cancer stage migration between and within clinical risk categories2014In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 48, no 5, p. 426-435Article in journal (Refereed)
    Abstract [en]

    Objective. In countries with widespread prostate cancer screening there has been strong stage migration, but little is known about changes within clinical risk categories. Such data are important for the proper interpretation of studies that recruited cases in an earlier era. The purpose of this study was to examine stage migration between and within clinical risk categories. Material and methods. Using the population-based National Prostate Cancer Register (NPCR) of Sweden, changes in the distribution of prostate-specific antigen (PSA), Gleason score, tumor stage and volume overall between and within clinical risk categories were examined in 120 228 prostate cancer cases diagnosed from 1998 to 2011. Results. Between 1998 and 2011, there was a two-fold increase in the proportion of low-risk prostate cancer (stage T1/T2, Gleason score 2-6 and PSA < 10 ng/ml), from 14% to 28%, and more than a two-fold decrease in the proportion of metastatic disease, from 25% to 11%. The proportion of men in the low-risk category with T1c tumors increased two-fold, from 36% to 71%, and PSA levels between 4 and 6 ng/ml increased from 24% to 38%; T2 tumors decreased from 39% to 20% and PSA between 8 and 10 ng/ml decreased from 24% to 15%. The proportion of men with less than 25% of cores involved with cancer increased from 41% to 52% between 2003-2006 and 2007-2011. Conclusions. Low-risk cases today have substantially lower tumor volume and PSA levels than low-risk cases diagnosed in 1998, indicating that outcomes in studies that recruited cases in previous decades represent worst case scenarios.

  • 207. Olsson, Mats
    et al.
    Lindström, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Häggkvist, Benjamin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Adami, Hans-Olov
    Bälter, Katarina
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ask, Birgitta
    Rane, Anders
    Ekström, Lena
    Grönberg, Henrik
    The UGT2B17 gene deletion is not associated with prostate cancer risk2008In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 68, no 5, p. 571-575Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Deletion polymorphism of the UDP-glucuronosyltransferase 2B17 (UGT2B17) gene has been associated with an increased prostate cancer risk in two previous independent studies. Here we determine the risk in a large-scale population-based case-control study.

    METHODS: Genotyping was conducted with a 5'-nuclease activity assay to distinguish those with one or two UGT2B17 gene copies (ins/del and ins/ins) from individuals homozygous for the deletion (del/del) allele.

    RESULTS: In contrast to previous findings, no association between the UGT2B17 deletion polymorphism and prostate cancer risk was found. Furthermore the UGT2B17 gene deletion did not affect the risk for prostate cancer specific death.

    CONCLUSION: The UGT2B17 deletion polymorphism does not play a major role in prostate cancer susceptibility as previously indicated.

  • 208.
    Otsetov, Aleksandar
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Ge, Rongbin
    Wang, Zongwei
    Bechis, Seth
    Wu, Shulin
    Wu, Chin-Lee
    Harisinghani, Mukesh
    Tabatabaei, Shahin
    Olumi, Aria
    Higher body mass index is associated with methylation and suppression of 5-alpha reductase 2 in adult prostate tissues2014In: 2014 Annual Meeting Program Abstracts, New York: Elsevier, 2014, Vol. 191, no S4, article id e192Conference paper (Refereed)
  • 209.
    Otsetov, Alexander
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Influence of Age and Obesity on 5 alpha-Reductase 2 Gene Expression2016In: Current Bladder Dysfunction Reports, ISSN 1931-7212, Vol. 11, no 2, p. 140-145Article in journal (Refereed)
    Abstract [en]

    The most common non-malignant, age-related disease in men is the benign prostatic hyperplasia (BPH). Androgens and genetic predisposition play important roles in normal prostate growth and in BPH progression. However, accumulating evidence indicates that factors such as aging and obesity also can contribute to the BPH etiology. Management of BPH includes medical treatment or surgery. Currently, the drug therapy uses the alpha1-blockers and/or inhibitors of the 5-alpha reductase enzyme (5ARIs). Latest studies demonstrated that a fraction of patients (up to 30 %) are resistant to this therapy. This article reviews the new risk factors in BPH etiology as well as the mechanisms of resistance to 5ARI therapy.

  • 210.
    Ottosson, Kristoffer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Thromboembolism in muscle invasive urinary bladder cancer – a multicenter evaluation.2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 211. Ouzaid, Idir
    et al.
    Capitanio, Umberto
    Staehler, Michael
    Wood, Christopher G.
    Leibovich, Bradley C.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Van Poppel, Hendrik
    Bensalah, Karim
    Surgical Metastasectomy in Renal Cell Carcinoma: A Systematic Review2019In: European Urology Oncology, ISSN 2588-9311, Vol. 2, no 2, p. 141-149Article, review/survey (Refereed)
    Abstract [en]

    Context: The benefit of surgical metastasectomy (SM) for patients with metastatic renal cell carcinoma (mRCC) remains controversial because of the lack of high-level evidence on the role of SM in terms of survival benefit in the era of systemic therapy.

    Objective: To perform a systematic review of the literature on the role of SM in the treatment of mRCC and discuss key issues in the SM decision-making process.

    Evidence acquisition: A systematic search of the Embase and Medline databases was carried out and a systematic review of the role of SM in mRCC was performed. A total of 56 studies were finally included in the evidence synthesis.

    Evidence synthesis: All the studies included were retrospective and mostly non-comparative. Median overall survival (OS) ranged from 36 to 142 mo for those undergoing SM, compared to 8-27 mo for no SM. SM was associated with a lower risk of all-cause mortality compared to no SM (pooled adjusted hazard ratio 2.37, 95% confidence interval 2.03-2.87; p < 0.001). Morbidity and mortality were similar for SM and primary tumor surgery. The most important prognostic factor for OS was complete resection of metastases. Other prognostic factors included disease free-survival from nephrectomy, primary tumor features (T stage >= 3, high grade, sarcomatoid features, and pathological nodal status), the number of metastases, and performance status. Lung metastasectomy seemed to show the best survival benefit.

    Conclusions: Although no randomized clinical data are available, published studies support the role of SM in selected patients in the modern era. Complete SM allows sustained survival free of systemic treatment. Integration of SM and systemic therapy in a multimodal approach remains a valid option for some patients.

    Patient summary: Surgical resection of metastases originating from renal cell carcinoma may play a role in prolonging survival and avoiding systemic therapy when complete resection is achievable. This strategy is an option for selected patients with a limited number of metastases who still have good general health status.

  • 212. Paananen, Ilkka
    et al.
    Ohtonen, Pasi
    Perttilä, Ilkka
    Jonsson, Olof
    Edlund, Christer
    Wiklund, Peter
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Möller-Jensen, Klaus
    Jonsson, Eirikur
    Månsson, Wiking
    Functional results after orthotopic bladder substitution: a prospective multicentre study comparing four types of neobladder2014In: Scandinavian journal of urology, ISSN 2168-1813, Vol. 48, no 1, p. 90-98Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate enterocystometry, voiding pattern and urine leakage of four types of orthotopic bladder substitute. Material and methods: At eight urological departments, 78 consecutive men were studied: 66 with an ileal neobladder [30 Studer pouches (S), 24 Hautmann pouches (H) and 12 T-pouches (T)] and 12 with a right colonic [Goldwasser type (G)] neobladder. Enterocystometry, determination of residual urine, micturition protocol and 24 h pad weight test were performed 6 and 12 months postoperatively. Results: Colonic neobladders had higher pouch pressure at first desire, normal desire and strong desire than ileal neobladders (except at first and normal desire at 12 months) (p < 0.02) and contraction was present more often at both 6 and 12 months (p < 0.01 and p < 0.01). Compliance was good in all types of pouch. Intermittent self-catheterization was more common in H patients at 6 months (p = 0.033). All patients with colonic neobladders used pads during the day and night. In patients with ileal pouches 32% used pads during the day and 70% during the night at 12 months. Urine leakage was higher in patients with colonic bladders at 6 and 12 months during the day (mean/median of 98/31 ml and 82/16 ml versus 10/0 ml and 4/0 ml, p < 0.001). T-pouches had excellent day-time continence, but nocturnal leakage was high. Conclusions: The Hautmann pouch and the Studer pouch behaved similarly at enterocystometry and clinically, and continence was good in the majority of patients. The low number of patients with the other two types of pouch precludes definitive statements.

  • 213. Parker, C.
    et al.
    Heinrich, D.
    Helle, S. , I
    O'Sullivan, J. M.
    Fossa, S.
    Chodacki, A.
    Demkow, T.
    Logue, J.
    Seke, M.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johannessen, D. C.
    Nilsson, S.
    Hoskin, P.
    Bottomley, D.
    Solberg, A.
    James, N. D.
    Syndikus, I
    Wedel, S. A.
    Kliment, J.
    Cross, A.
    O'Bryan-Tear, C. G.
    Garcia-Vargas, J.
    Sartor, O.
    Overall survival benefit and impact on skeletal-related events for radium-223 chloride (Alpharadin) in the treatment of castration-resistant prostate cancer (CRPC) patients with bone metastases: A phase III randomized trial (ALSYMPCA)2012In: European urology. Supplement, ISSN 1569-9056, E-ISSN 1878-1500, Vol. 11, no 1, p. E130-U523Article in journal (Other academic)
  • 214. Parker, Christopher C.
    et al.
    Coleman, Robert E.
    Sartor, Oliver
    Vogelzang, Nicholas J.
    Bottomley, David
    Heinrich, Daniel
    Helle, Svein I.
    O'Sullivan, Joe M.
    Fosså, Sophie D.
    Chodacki, Aleš
    Wiechno, Paweł
    Logue, John
    Seke, Mihalj
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johannessen, Dag Clement
    Hoskin, Peter
    James, Nicholas D.
    Solberg, Arne
    Syndikus, Isabel
    Kliment, Jan
    Wedel, Steffen
    Boehmer, Sibylle
    Dall'Oglio, Marcos
    Franzén, Lars
    Bruland, Øyvind S.
    Petrenciuc, Oana
    Staudacher, Karin
    Li, Rui
    Nilsson, Sten
    Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, no 3, p. 427-435Article in journal (Refereed)
    Abstract [en]

    Background: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. Objective: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. Design, setting, and participants: Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving >= 1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk after the last study-drug injection, to 3 yr from the first injection. Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. Outcome measurements and statistical analysis: All adverse events (AEs) were collected until 12 wk after the last injection; subsequently, only treatment-related AEs were collected. Additional long-term safety was assessed by development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and secondary malignancies. Data analysis used descriptive statistics. Results and limitations: During treatment to 12 wk following the last injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 mo after the last injection. No other cases were observed. Limitations include short (3-yr) follow-up. Conclusions: Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns.

  • 215. Patschan, Oliver
    et al.
    Holmäng, Sten
    Hosseini, Abolfazl
    Jancke, Georg
    Liedberg, Fredrik
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Malmström, Per-Uno
    Rosell, Johan
    Jahnson, Staffan
    Second-look resection for primary stage T1 bladder cancer: a population-based study2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 4, p. 301-307Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study aimed to evaluate the use of second-look resection (SLR) in stage T1 bladder cancer (BC) in a population-based Swedish cohort.

    MATERIALS AND METHODS: All patients diagnosed with stage T1 BC in 2008-2009 were identified in the Swedish National Registry for Urinary Bladder Cancer. Registry data on TNM stage, grade, primary treatment and pathological reports from the SLR performed within 8 weeks of the primary transurethral resection were validated against patient charts. The endpoint was cancer-specific survival (CSS).

    RESULTS: In total, 903 patients with a mean age of 74 years (range 28-99 years) were included. SLR was performed in 501 patients (55%), who had the following stages at SLR: 172 (35%) T0, 83 (17%) Ta/Tis, 210 (43%) T1 and 26 (5%) T2-4. The use of SLR varied from 18% to 77% in the six healthcare regions. Multiple adjuvant intravesical instillations were given to 420 patients (47%). SLR was associated with intravesical instillations, age younger than 74 years, discussion at multidisciplinary tumour conference, G3 tumour and treatment at high-volume hospitals. Patients undergoing SLR had a lower risk of dying from BC (hazard ratio 0.62, 95% confidence interval 0.45-0.84, p < .0022). Five-year CSS rates were as follows, in patients with the indicated tumours at SLR (p = .001): 82% in those with T1, 90% in T0, 90% in Ta/Tis and 56% in T2-4.

    CONCLUSIONS: There are large geographical differences in the use of SLR in stage T1 BC in Sweden, which are presumably related to local treatment traditions. Patients treated with SLR have a high rate of residual tumour but lower age, which suggests that a selection bias affects CSS.

  • 216. Patschan, Oliver
    et al.
    Holmäng, Sten
    Hosseini, Abolfazl
    Liedberg, Fredrik
    Ljungberg, Börje
    Department of Urology, Northern University Hospital, Umeå, Sweden.
    Malmström, Per-Uno
    Rosell, Johan
    Jahnson, Staffan
    Use of bacillus Calmette-Guerin in stage T1 bladder cancer: long-term observation of a population-based cohort2015In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 2, p. 127-132Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to analyse the rate of use of bacillus Calmette-Guerin (BCG) at a population-based level, and the overall mortality and bladder cancer mortality due to stage T1 bladder cancer in a national, population-based register. Materials and methods. In total, 3758 patients with primary stage T1 bladder cancer, registered in the Swedish Bladder Cancer Register between 1997 and 2006, were included. Age, gender, tumour grade and primary treatment in the first 3-6 months were registered. High-volume hospitals registered 10 or more T1 tumours per year. Date and cause of death were obtained from the National Board of Health and Welfare Cause of Death Register. Results. BCG was given to 896 patients (24%). The use of BCG increased from 18% between 1997 and 2000, to 24% between 2001 and 2003, and to 31% between 2004 and 2006. BCG was given more often to patients with G3 tumours, patients younger than 75 years and patients attending high-volume hospitals. BCG treatment, grade 2 tumours and patient age younger than 75 years were associated with lower mortality due to bladder cancer. Hospital volume, gender and year of diagnosis were not related to bladder cancer mortality. However, selection factors might have affected the results since comorbidity, number of tumours and tumour size were unknown. Conclusions. Intravesical BCG is underused at a population-based level in stage T1 bladder cancer in Sweden, particularly in patients 75 years or older, and in those treated at low-volume hospitals. BCG should be offered more frequently to patients with stage T1 bladder cancer in Sweden.

  • 217. Perez-Cornago, Aurora
    et al.
    Appleby, Paul N.
    Pischon, Tobias
    Tsilidis, Konstantinos K.
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Kaaks, Rudolf
    Kuehn, Tilman
    Boeing, Heiner
    Steffen, Annika
    Trichopoulou, Antonia
    Lagiou, Pagona
    Kritikou, Maria
    Krogh, Vittorio
    Palli, Domenico
    Sacerdote, Carlotta
    Tumino, Rosario
    Bueno-de-Mesquita, H. Bas
    Agudo, Antonio
    Larranaga, Nerea
    Molina-Portillo, Elena
    Barricarte, Aurelio
    Chirlaque, Maria-Dolores
    Ramon Quiros, J.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University.
    Wareham, Nick
    Khaw, Kay-Tee
    Schmidt, Julie A.
    Gunter, Marc
    Freisling, Heinz
    Aune, Dagfinn
    Ward, Heather
    Riboli, Elio
    Key, Timothy J.
    Travis, Ruth C.
    Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study2017In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, article id 115Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths. Results: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P-heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P-heterogeneity = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P-heterogeneity = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96). Conclusions: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.

  • 218. Persson, Beata
    et al.
    Sjödin, Jan-Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Lars
    Windahl, Torgny
    The National Penile Cancer Register in Sweden 2000-20032007In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 4, p. 278-282Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This article reviews the first 4 years of operation of the National Penile Cancer Register (NPECR) in Sweden. The register was set up to gain knowledge about the incidence and primary treatment of penile cancer, including the use of and the frequency of lymph node dissection. The register elicits treatment disparities between regions, and aims to determine the impact of clinical practice guidelines introduced in Sweden.

    MATERIAL AND METHODS: All patients newly diagnosed with penile cancer after the year 2000 have been registered in the NPECR. A total of 454 patients were registered in the period 2000-2003.

    RESULTS: Registrations in the NPECR were almost complete, with 98.7% of cases registered in the National Cancer Register also being registered in the NPECR. At least 145 clinicians reported to the register. The annual incidence of penile cancer is 2.2/100 000 men. Squamous cell carcinoma accounts for 95% of the cases. The mean age at diagnosis was 65.5 years. Most tumours were classified as Tis, T1 or T2, each class representing 25-30% of the total number of diagnosed cases. Penis-preserving treatment was performed in 58% of the patients (Table I). The number of patients classified as > or = T1/G2-G3 was 206, and 101 of these patients (49%) underwent inguinal lymphadenectomy.

    CONCLUSIONS: We have introduced a population-based register in Sweden with almost complete registration, and this offers unique possibilities for further studies of both epidemiological and clinical aspects of penile cancer. The results obtained to date indicate that the primary treatment is done in many settings and that guidelines, e.g. to dissect lymph nodes, are not always followed.

  • 219.
    Peters, Bjorn
    et al.
    Skaraborg Hosp, Skövde, Sweden.
    Andersson, Yvonne
    Skaraborg Hosp, Skövde, Sweden.
    Hadimeri, Henrik
    Skaraborg Hosp, Skövde, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Molne, Johan
    Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Diagnostic Quality and the Influence of Histological Diagnosis on Complications in 1083 Native and Transplant Kidney Biopsies2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no Suppl. 3, p. 454-454Article in journal (Other academic)
  • 220.
    Peters, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Clinical and quality aspects of native and transplant kidney biopsies in Sweden2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Percutaneous kidney biopsies have been performed since 1944 to establish diagnoses and treatment. Risk factors based on a limited amount of data have shown age, blood pressure, kidney function and needle size as some risk factors for biopsy complications. Although the techniques of biopsy have improved over the years, it is still an invasive procedure and serious complications can occur.

    The overall aim of this thesis was to obtain a large series of data from biopsy procedures and to use these to bring further light on risk factors to help minimize the risk for patients and to optimize diagnostics. Specific aims were to clarify if different factors, such as gender, diagnoses, localization of biopsies, needle types and sizes, could be useful to help minimize complication risks in native kidney biopsies (Nkb) and transplant kidney biopsies (Txb). Another point to investigate was the value of the Resistive Index (RI) obtained at ultrasound before performing Txb.

    Materials and methods: A protocol for prospective multicentre registration of various factors and complications associated with Nkb and Txb was designed. Consecutive data were obtained from seven hospitals. All biopsies, except one computer tomography-guided Nkb, were performed using real-time ultrasound guidance and an automated spring-loaded biopsy device. For the biopsies 14- to 20- Gauge (G) needles were used. The kidney function level, i.e. estimated glomerular filtration rate (eGFR), was calculated using the Modification of Diet in Renal Disease (MDRD) formula (GFR in mL/min per 1.73m2). For statistical analyses the IBM SPSS Statistic 22 (Armonk, NY, USA) and OpenEpi (Open Source Epidemiologic Statistics for Public Health, www.OpenEpi.com) were used. Data were presented as Odds Ratio (OR), Risk Ratio (RR) and Confidence Intervals (CI). A two sided p-value of <0.05 was considered significant. In total 1299 consecutive biopsies (1039 native and 260 transplant kidneys) in 1178 patients (456 women and 722 men) were used for investigation. The median age of patients was 55 years (range 16 to 90 years). Major (require an intervention) and minor biopsy complications (no need of intervention) were registered.

    Results: The overall frequency of biopsy complications for Nkb was 8.8% (major 6.7%, minor 2.1%) and for Txb was 6.5% (major 3.8%, minor 2.7%); no death. Women had a higher risk for development of major (10.7% versus 4.7%, OR 2.4, CI 1.4-4.2) and overall biopsy complications (13.2% versus 6.5%, OR 2.2, CI 1.4-3.5) compared to men in Nkb. In Nkb, major complications were more common after biopsies from the right kidney in women versus men (10.8% vs 3.1%, OR 3.7, CI 1.5–9.5), in patients with lower versus higher BMI (25.5 vs 27.3, p=0.016) and for younger versus older age (44.8 vs 52.3 years, p=0.002). Lower (90 mmHg) compared to higher (98 mmHg) mean arterial pressure in Txb indicated a risk of major complications (p=0.039). Factors such as number of passes and kidney function did not influence complication rates. Biopsy needles of 16 G compared to 18 G showed more glomeruli per pass in Nkb (11 vs 8, p<0.001) and in Txb (12 vs 8, p<0.001). Sub-analysis revealed that 18 G 19 mm side-notch needles in Nkb resulted in more major (11.3% vs 3%, OR 4.1, CI 1.4-12.3) and overall complications (12.4% vs 4.8%, OR 2.8, CI 1.1-7.1) in women than in men. If the physician had performed less compared to more than four Nkb per year, minor (3.5% vs 1.4%, OR 2.6, CI 1.1-6.2) and overall complications (11.5% vs 7.4%, OR 1.6, CI 1.1-2.5) were more common. The localization of biopsy within the kidney (Nkb and Txb) was not a risk factor for complications. Patients with IgA-nephritis compared to patients with other diseases had a higher risk of major complications (11.7% vs 6.4 %, OR 1.8, CI 1.1–3.2). More major complications were found in Nkb if they had higher versus lower degree of glomerulosclerosis (31% vs 20 %, p=0.008) and in Txb if there was a higher versus lower degree of interstitial fibrosis (82% vs 33%, p<0.001). Re-biopsies (Nkb) were more common in patients with IgA-nephritis than those with other diseases (4.7% vs 1.3 %, OR 4, CI 1.5–11), in younger versus older age (42.6 vs 52.3 years, p=0.031), and in those with a higher versus lower degree of interstitial fibrosis (63% vs 34 %, p=0.046). In Txb, a RI≥0.8 compared to RI<0.8 predicted major (13.3% vs 3.2%, RR 4.2, CI 1.3-14.1) and overall biopsy complications (16.7% vs 5.3%, RR 3.2, CI 1.2-8.6). In the group <0.8, RI correlated with age (rs=0.28, p<0.001) and systolic blood pressure (rs=0.18, p=0.02). In the group ≥0.8, RI correlated with degree of interstitial fibrosis (rs=0.65, p=0.006) and systolic blood pressure (rs=0.40, p=0.03). The multiple regression analysis showed that the <0.8 RI group correlated only with age (p<0.001), whereas the ≥0.8 RI group correlated only with the degree of interstitial fibrosis (p=0.003).

    Conclusions: The present results motivate greater attention to be paid to the possibility of major side-effects after Nkb in women and biopsies from their right side, but as well in younger patients, and in those with lower BMI. This also applies for patients with presumptive IgA-nephritis and higher degree of glomerulosclerosis. In Txb, patients with higher degree of interstitial fibrosis had a greater risk of major complications. Moreover, the present data indicate that Nkb and Txb should be preferably taken with 16 G needles with 20 mm sample size. This results in better histological quality and there is a lower risk for major complications as compared to 18 G needles. The localization of biopsy within the kidney (Nkb and Txb) does not alter complication rates. For Nkb there were fewer complications if the physician had performed at least four biopsies per year. A RI≥0.8 in Txb indicates a greater risk for major and overall complications.

  • 221.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Departments of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Hadimeri, Henrik
    Mölne, Johan
    Nasic, Salmir
    Jensen, Gert
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Desmopressin (Octostim®) before a native kidney biopsy can reduce the risk for biopsy complications in patients with impaired renal function: a pilot study2018In: Nephrology (Carlton. Print), ISSN 1320-5358, E-ISSN 1440-1797, Vol. 23, no 4, p. 366-370Article in journal (Refereed)
    Abstract [en]

    AIM: To evaluate if the administration of desmopressin alters the risk for renal biopsy complications.

    METHODS: A multicenter registry containing 576 native kidney biopsies (NKb) with a serum creatinine above 150 µmol/L in 527 patients (372 men and 155 women, median age 61 years) was used. Most of the data were prospective. At one of the hospitals all biopsies with creatinine above 150 µmol/L received desmopressin before biopsies (NKb 204). These were compared to outcome of biopsy complications against other centres where desmopressin was not given (NKb 372). Fisher's exact test, χ2 analyses, univariate and multiple binary logistic regression were used. Data were given as Odds Ratio (OR) and Confidence Interval (CI). A two sided p-value of <0.05 was considered significant.

    RESULTS: In NKb with creatinine >150 µmol/L, those with desmopressin had less overall (3.4% versus 8.4%, OR 0.39, CI 0.17-0.90) whereas major or minor complications were not different. While desmopressin did not exhibit difference in complications in men, women received less major (0% versus 8.6%, p = 0.03) and overall complications (0% versus 12.1%, p = 0.006). A multiple logistic regression revealed that, after adjusting for BMI, age and sex, prophylaxis with desmopressin showed less major (OR 0.38, CI 0.15-0.96) and overall complications (OR 0.36, CI 0.15-0.85).

    CONCLUSION: Desmopressin given before a native kidney biopsy in patients with impaired renal function can reduce the risk for complications.

  • 222.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Mölne, Johan
    Hadimeri, Henrik
    Hadimeri, Ursula
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sixteen Gauge biopsy needles are better and safer than 18 Gauge in native and transplant kidney biopsies2017In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 58, no 2, p. 240-248Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Kidney biopsies are essential for optimal diagnosis and treatment.

    PURPOSE: To examine if quality and safety aspects differ between types and sizes of biopsy needles in native and transplant kidneys.

    MATERIAL AND METHODS: A total of 1299 consecutive biopsies (1039 native and 260 transplant kidneys) were included. Diagnostic quality, needle size and type, clinical data and complications were registered. Eight-three percent of the data were prospective.

    RESULTS: In native kidney biopsies, 16 Gauge (G) needles compared to 18 G showed more glomeruli per pass (11 vs. 8, P < 0.001) with less complications. Sub-analysis in native kidney biopsies revealed that 18 G 19-mm side-notch needles resulted in more major (11.3% vs. 3%; odds ratio [OR], 4.1; 95% confidence interval [CI], 1.4-12.3) and overall complications (12.4% vs. 4.8%; OR, 2.8; 95% CI, 1.1-7.1) in women than in men. If the physician had performed less compared to more than four native kidney biopsies per year, minor (3.5% vs. 1.4%; OR, 2.6; 95% CI, 1.1-6.2) and overall complications (11.5% vs. 7.4%; OR, 1.6; 95% CI, 1.1-2.5) were more common. In transplant kidney biopsies, 16 G needles compared to 18 G resulted in more glomeruli per pass (12 vs. 8, P < 0.001). No differences existed in frequency of biopsy complications. The localization of performing biopsies was not a risk factor to develop complications.

    CONCLUSION: Kidney biopsies taken by 16 G needles result in better histological quality and lower frequency of complications compared to 18 G. For native kidney biopsies the performer of the biopsy should do at least four biopsies per year.

  • 223.
    Peters, Björn
    et al.
    Department of Nephrology, Skaraborgs Hospital, Skövde, Sweden.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andersson, Yvonne
    Hadimeri, Henrik
    Mölne, Johan
    Increased risk of renal biopsy complications in patients with IgA-nephritis2015In: Clinical and Experimental Nephrology, ISSN 1342-1751, E-ISSN 1437-7799, Vol. 19, no 6, p. 1135-1141Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to investigate if specific clinical and histological findings can be related to biopsy complications to enable more closely monitoring patients at high risk.

    METHODS: Results from 1081 biopsies (994 patients, median age 54.5 years; 896 native and 185 transplant kidney biopsies) were included. Diagnostic quality, morphology, clinical data and complications were prospectively registered.

    RESULTS: In native kidney biopsies, the most common diagnosis was IgA-nephritis, while in transplant kidney biopsies it was rejection. Patients with IgA-nephritis had a higher risk of major complications (11.7 versus 6.4 %, Odds Ratio (OR) 1.8, Confidence Interval (CI) 1.1-3.2) when compared to patients with other diseases. In native kidney biopsies, patients who experienced major complications had higher degrees of glomerulosclerosis (31 versus 20 %, p = 0.008), whereas in transplant kidney biopsies, patients had higher degrees of interstitial fibrosis (82 versus 33 %, p < 0.001) when compared to patients without major complications. IgA-nephritis-patients had a higher risk of re-biopsies (4.7 versus 1.3 %, OR 4, CI 1.5-11) than patients with other diseases. Patients with native kidneys who needed re-biopsies were younger (42.6 versus 52.3 years, p = 0.031) and had a higher degree of interstitial fibrosis (63 versus 34 %, p = 0.046).

    CONCLUSIONS: Patients with IgA-nephritis have an increased risk of major biopsy complications. The risk of re-biopsies was higher in younger individuals and in patients with IgA-nephritis.

  • 224.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mölne, Johan
    Haux, Stina-Britta
    Hadimeri, Henrik
    High Resistive Index in transplant kidneys is a possible predictor for biopsy complicationsManuscript (preprint) (Other academic)
  • 225.
    Peters, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mölne, Johan
    Department of Pathology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Haux, Stina-Britta
    Department of Radiology, Skaraborg Hospital, Skövde, Sweden..
    Hadimeri, Henrik
    Department of Nephrology, Skaraborg Hospital, Skövde, Sweden..
    High Resistive Index in Transplant Kidneys Is a Possible Predictor for Biopsy Complications2016In: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 48, no 8, p. 2714-2717Article in journal (Refereed)
    Abstract [en]

    Background. Transplant kidney biopsies are performed to determine a histological diagnosis for specific patient treatment. The aim of this study was to investigate if Resistive Index (RI) could be a predictor for biopsy complications.

    Methods. In this study, 220 consecutive transplant kidney biopsies (136 men and 84 women; median age, 55.5 years) were prospectively included. RI (median, 0.7) was measured by use of ultrasound. Histological diagnoses and biopsy complications were registered. Biopsy needles were either 16- or 18-gauge. Biopsies were performed by radiologists and were carried out as an outpatient procedure (70%) or an inpatient procedure (30%). Usually three passes per biopsy were performed.

    Results. The overall complication rate was 6.8%, divided into major (4.5%) and minor (2.3%) complications. An RI >= 0.8 predicts major (13.3% versus 3.2%; risk ratio [RR], 4.2; confidence interval [CI], 1.3-14.1; P=.03) and overall biopsy complications (16.7% versus 5.3%; RR, 3.2; CI, 1.2-8.6; P=.04) compared with RI <0.8. In the group <0.8, RI correlated with age (r(s) = 0.28, P<.001) and systolic blood pressure (r(s) = 0.18, P=.02). In the group >= 0.8, RI correlated with degree of interstitial fibrosis (r(s) = 0.65, P=.006) and systolic blood pressure (r(s) = 0.40, P =.03). The multiple regression analysis showed that in the group <0.8, the RI correlated only with age (P<.001), whereas in the group >= 0.8, RI correlated only with the degree of interstitial fibrosis (P=.003).

    Conclusions. An RI >= 0.8 indicates greater risk for major and overall biopsy complications and should result in greater caution after biopsy.

  • 226. Pignot, G.
    et al.
    Bahi, R.
    Bensalah, K.
    Oger, E.
    Laguna, P.
    Barwari, K.
    Rigaud, J.
    Rouprêt, M.
    Bernhard, J.
    Long, J.
    Zisman, A.
    Berger, J.
    Paparel, P.
    Lechevallier, E.
    Bertini, R.
    Salomon, L.
    Bex, A.
    Farfara, R.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Rodriguez, A.
    Patard, J.
    L’Ischémie n’est pas un facteur d’insuffisance rénale chronique après néphrectomie partielle sur rein unique2014In: Progrès en urologie (Paris), ISSN 1166-7087, Vol. 24, no 13, p. 822-822Article in journal (Refereed)
    Abstract [en]

    Objectifs Déterminer l‘influence du clampage pédiculaire et de sa durée sur la fonction rénale à long terme après néphrectomie partielle (NP) pour cancer sur rein unique.

    Méthodes L’étude a inclus rétrospectivement 259 patients opérés par NP entre 1979 et 2010 dans 13 centres. L’utilisation d’un clampage, son type (pédiculaire ou parenchymateux), sa durée ainsi que les données pré-, intra- et postopératoires ont été recueillies. Les valeurs de débit de filtration glomérulaire (DFG) préopératoire et au dernier suivi ont été comparés. Une analyse multivariée selon le modèle de Cox a été réalisée afin de déterminer l’impact de l’ischémie sur le risque d’insuffisance rénale (IR) chronique postopératoire.

    Résultats La taille moyenne des tumeurs était de 4,0±2,3cm et le DFG préopératoire moyen de 60,8±18,9ml/min. Au total, 106 patients ont été opérés en ischémie chaude (40,9 %) et 53 en ischémie froide (20,5 %). Trente patients (11,6 %) ont évolué vers l’insuffisance rénale chronique. En analyse multivariée, ni le clampage pédiculaire (p=0,44), ni la durée d’ischémie chaude (p=0,1) n’étaient associés à une évolution vers l’insuffisance rénale. Les facteurs indépendants d’insuffisance rénale à long terme étaient le DFG préopératoire (p<0,0001) et les pertes sanguines (p=0,02).

    Conclusion La fonction rénale après NP sur rein unique apparaît principalement liée à des facteurs non modifiables et notamment le DFG préopératoire. Ce travail relativise l’importance du clampage pédiculaire et du temps d’ischémie qui n’étaient pas significativement liés au risque d’IR dans notre étude.

  • 227. Plym, Anna
    et al.
    Chiesa, Flaminia
    Voss, Margaretha
    Holmberg, Lars
    Johansson, Eva
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Uppsala University Hospital, Uppsala, Sweden.
    Lambe, Mats
    Work Disability After Robot-assisted or Open Radical Prostatectomy: A Nationwide, Population-based Study2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 1, p. 64-71Article in journal (Refereed)
    Abstract [en]

    Background: Robot-assisted radical prostatectomy (RARP) has been associated with reduced bleeding and shorter hospital stays than open retropubic radical prostatectomy (RRP), but it is unclear whether these differences translate into shorter absence from work. Objective: To investigate short-and long-term rates of work disability following RARP and RRP. Design, setting, and participants: We conducted a nationwide population-based cohort study of 2571 men of working age treated with RARP or RRP between 2007 and 2009 identified in the National Prostate Cancer Register of Sweden. Information about physician-certified sick leave and disability pension was retrieved from the Swedish Social Insurance Agency through 2012. Outcome measurements and statistical analysis: We used Cox regression to calculate time to return to work (RTW, or duration of sick leave) after surgery and used generalised estimating equations to analyse days lost from work (because of sick leave and disability pension) after RTW. Results and limitations: Men treated with RARP returned to work after a median of 35 d, whereas the corresponding time for RRP was 48 d (p < 0.001). The difference was seen early; within the first month, men treated with RARP returned to work nearly four times faster than men treated with RRP (adjusted relative RTW rate 3.76; 95% confidence interval [CI], 3.04-4.66). During a median of 3.6 yr after return to work, men treated with RARP lost fewer days from work per person-year than men treated with RRP-12 d versus 15 d-but the association was not statistically significant (p = 0.10). The adjusted rate ratio was 1.08 (95% CI, 0.82-1.42). One limitation is the nonrandomised design of this study. Conclusions: RARP was associated with a faster RTW compared with RRP, but the surgical method did not influence long-term rates of work disability in terms of days lost from work after RTW. Patient summary: We compared disease-related absence from work between two surgical methods for the removal of the prostate. Robot-assisted surgery was associated with a faster return to work compared with open surgery but did not influence absence from work in a long-term perspective. 

  • 228. Plym, Anna
    et al.
    Voss, Margaretha
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Uppsala University Hospital, Uppsala, Sweden.
    Lambe, Mats
    Reply from Authors re: Matthew T. Gettman. Assessing Work Disability After Radical Prostatectomy. Eur Urol 2016;70:72-3 The Challenge of Assessing Work Disability2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 1, p. 73-74Article in journal (Other academic)
  • 229. Porserud, Andrea
    et al.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tollbäck, Anna
    The effects of a physical exercise programme after radical cystectomy for urinary bladder cancer. A pilot randomized controlled trial.2014In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 28, no 5, p. 451-459Article in journal (Refereed)
    Abstract [en]

    Objective: Assessment of feasibility and effects of an exercise training programme in patients following cystectomy due to urinary bladder cancer.

    Design: Single-blind, pilot, randomized controlled trial.Setting:University hospital, Sweden.

    Subjects: Eighteen patients (64-78 years), of 89 suitable, cystectomized due to urinary bladder cancer, were randomized after hospital discharge to intervention or control.

    Interventions: The 12-week exercise programme included group exercise training twice a week and daily walks. The control group received only standardized information at discharge.

    Main outcome measures: Trial eligibility and compliance to inclusion were registered. Assessments of functional capacity, balance, lower body strength and health-related quality of life (HRQoL) with SF-36.

    Results: Out of 122 patients 89 were eligible, but 64 did not want to participate/were not invited. Twenty-five patients were included, but 7 dropped out before randomization. Eighteen patients were randomized to intervention or control. Thirteen patients completed the training period. The intervention group increased walking distance more than the control group, 109 m (75-177) compared to 62 m (36-119) (P = 0.013), and role physical domain in SF-36 more than the control group (P = 0.031). Ten patients were evaluated one year postoperatively. The intervention group had continued increasing walking distance, 20 m (19-36), whereas the control group had shortened the distance -15.5 m (-43 to -5) (P = 0.010).

    Conclusions: A 12-week group exercise training programme was not feasible for most cystectomy patients. However, functional capacity and the role-physical domain in HRQoL increased in the short and long term for patients in the intervention group compared with controls.

  • 230. Powles, Thomas
    et al.
    Albiges, Laurence
    Staehler, Michael
    Bensalah, Karim
    Dabestani, Saeed
    Giles, Rachel H.
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas B.
    Marconi, Lorenzo
    Merseburger, Axel S.
    Fernández-Pello, Sergio
    Tahbaz, Rana
    Volpe, Alessandro
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bex, Axel
    Updated European Association of Urology Guidelines: Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, no 3, p. 311-315Article in journal (Refereed)
    Abstract [en]

    The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naive advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. LBA5, ESMO 2017, 2017). These results change the frontline standard of care for this disease and have implications for the selection of subsequent therapies. For this reason the European Association of Urology RCC guidelines have been updated. Patient summary: The European Association of Urology guidelines will be updated based on the results of the phase III Checkmate-214 clinical trial. The trial showed superior survival for a combination of ipilimumab and nivolumab (IN), compared with the previous standard of care, in intermediate-and poor-risk patients with metastatic clear cell renal cell carcinoma. When IN is not safe or feasible, alternative agents such as sunitinib, pazopanib, and cabozantinib should be considered. Furthermore, at present, the data from the trial are immature in favourable-risk patients. Therefore, sunitinib or pazopanib remains the favoured agent for this subgroup of patients.

  • 231. Powles, Thomas
    et al.
    Staehler, Michael
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bensalah, Karim
    Canfield, Steven E.
    Dabestani, Saeed
    Giles, Rachel H.
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas
    Marconi, Lorenzo
    Merseburger, Axel S.
    Volpe, Alessandro
    Bex, Axel
    European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 5, p. 705-706Article in journal (Refereed)
    Abstract [en]

    The European Association of Urology renal cancer guidelines panel recommends nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of vascular endothelial growth factor-targeted therapy. New data have recently become available showing a survival benefit for cabozantinib.

  • 232. Powles, Thomas
    et al.
    Staehler, Michael
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bensalah, Karim
    Canfield, Steven E.
    Dabestani, Saeed
    Giles, Rachel
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas
    Marconi, Lorenzo
    Merseburger, Axel S.
    Volpe, Alessandro
    Bex, Axel
    Updated EAU Guidelines for Clear Cell Renal Cancer Patients Who Fail VEGF Targeted Therapy2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, no 1, p. 4-6Article in journal (Other academic)
  • 233. Price, Alison J
    et al.
    Travis, Ruth C
    Appleby, Paul N
    Albanes, Demetrius
    Barricarte Gurrea, Aurelio
    Bjørge, Tone
    Bueno-de-Mesquita, H Bas
    Chen, Chu
    Donovan, Jenny
    Gislefoss, Randi
    Goodman, Gary
    Gunter, Marc
    Hamdy, Freddie C
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. International Agency for Research on Cancer, Lyon, France.
    King, Irena B
    Kühn, Tilman
    Männistö, Satu
    Martin, Richard M
    Meyer, Klaus
    Neal, David E
    Neuhouser, Marian L
    Nygård, Ottar
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tell, Grethe S
    Trichopoulou, Antonia
    Tumino, Rosario
    Ueland, Per Magne
    Ulvik, Arve
    de Vogel, Stefan
    Vollset, Stein Emil
    Weinstein, Stephanie J
    Key, Timothy J
    Allen, Naomi E
    Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 6, p. 941-951Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear.

    OBJECTIVE: To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade.

    DESIGN, SETTING, AND PARTICIPANTS: A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incident PCa and subtype by stage and grade.

    RESULTS AND LIMITATIONS: Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], ptrend=0.018, for folate and 1.12 [95% CI, 1.01-1.25], ptrend=0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity<0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend=0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation.

    CONCLUSIONS: The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation.

    PATIENT SUMMARY: Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.

  • 234.
    Prytz, Isak
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    A quality report on the Swedish patient-flow model for macroscopic haematuria  - SVF (standardized care process)-macrohematuria for Norrlands university hospital (NUS)2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 235.
    Ramsauer, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Glucose degradation products in patients on hemodialysis: interventional studies2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Hemodialysis (HD) is the most frequently used treatment for end-stage renal disease. Despite all efforts to improve the outcomes, the mortality of patients on HD is still high, and this especially is related to cardiovascular diseases (CVD). Glucose degradation products accumulate in plasma and tissue as a result of oxidative stress in these patients. Such accumulation is strongly related to the risk of developing CVD. Tissue deposits of advanced glycation end products (AGE) can be easily assessed by a skin autofluorescence (SAF) technique. SAF is one of the strongest prognostic markers of mortality in HD patients. The aim of this thesis is to examine whether intervention on HD treatment can reduce the load of AGE of these patients.

    The aim of the first study was to investigate whether changes in SAF appear after a single HD session and if they might be related to changes in plasma AF. Skin and plasma AF (PAF) were measured before and after HD in 35 patients on maintenance HD therapy. Median dialysis time was 4 h (range 3-5.5). SAF was measured noninvasively with an AGE Reader, and plasma AF was measured before and after HD. The HD patients had on average a 65% higher SAF value than age-matched healthy persons (P < 0.001). PAF was reduced by 14% (P < 0.001), whereas SAF was not changed after a single HD treatment. No significant influence of the reduced PAF on SAF levels was found. This suggests that the measurement of SAF can be performed during the whole dialysis period and is not directly influenced by the changes in plasma AF during HD.

    In study 2 different dialysis filters were compared to clarify whether using a high-flux (HF) dialyzer favors plasma or SAF removal compared to low-flux (LF) dialyzer. Twenty-eight patients were treated with either an HF-HD or LF-HD but otherwise unchanged conditions in a cross-over design. SAF was measured non-invasively with an AGE reader before and after HD. PAF was determined as total and non-protein-bound fractions. Corrections for hemoconcentrations by volume changes were made using the change in serum albumin. Paired and non-paired statistical analyses were used. The different treatments did not change SAF after LF- and HF-dialysis. Total, free, and protein-bound PAF were reduced after a single LF-HD by 21%, 28%, and 17%, respectively (P<.001). After HF-HD total and free PAF was reduced by 5% and 15%, respectively (P<.001), while protein-bound values were unchanged. The LF-HD resulted in a more pronounced reduction of PAF than did HF-HD (P<.001). Serum albumin correlated inversely with PAF in HF-HD. There was no significant change in SAF after dialysis, either with LF or with HF dialysis. Although only limited reductions in PAF were observed, these were more pronounced when performing LF dialysis. These data are not in overwhelming support of the use of HF dialysis in the setting used in this study.

    In the third study the effect on SAF was investigated using either glucose-containing or glucose-free dialysate. SAF and PAF were measured in patients on HD during standard treatment with a glucose-containing dialysate (n=24). After that, the patients were switched to a glucose-free dialysate for a 2 week period, and new measurements were performed on PAF and SAF.

    There was an increase of pre-dialysis SAF measured at the beginning of the study compared with the values one month later (as in study 4). By comparing pre- and post-dialysis values there was a significant decrease of SAF only when using glucose-free dialysate. Free PAF decreased independently whether glucose-containing or glucose-free dialysate was used. The important finding was that increase in SAF seemed possible to slow down using glucose-free dialysate.

    Study 4 was performed to investigate whether there are seasonal variations in SAF on a HD population. SAF was measured non-invasively with an AGE Reader in patients on HD at different seasonal periods during one year such as February-May (N=31), May–August (N=28), August–March (N=25). SAF was measured before HD. Paired statistical analyses were performed between each two periods.  Unexpectedly there was at a median 6% increase in SAF during the winter (p=0.004) and a 11% decrease from 4.0 to 3.5 arbitrary units of the SAF during the summer (p<0.001). The study concluded that SAF shows seasonal variation. The cause of these changes could not be clarified. A beneficial effect may be due to extended exposure to sunlight during the summer and/or to different dietary intakes during the seasons.

    In conclusion, these interventional studies confirmed that PAF is lowered by dialysis. SAF was only decreased by HD when using glucose-free dialysate. SAF was not influenced by a single HD, with glucose-containing dialysate, independent of using HF or LF filters. These data favor glucose-free dialysate as a possible measure to slow down the progress of tissue AGE compared to glucose-containing dialysate. Longitudinal studies will help to clarify this issue further.

  • 236.
    Ramsauer, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nephrology, Skaraborgs Hospital, 541 58 Skövde, Sweden.
    Engels, Gerwin Erik
    Graaff, Reindert
    Sikole, Aleksandar
    Arsov, Stefan
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Skin- and Plasmaautofluorescence in hemodialysis with glucose-free or glucose-containing dialysate2017In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 18, article id 5Article in journal (Refereed)
    Abstract [en]

    Background: Haemodialysis (HD) patients suffer from an increased risk of cardiovascular disease (CVD). Skinautofluorescence (SAF) is a strong marker for CVD. SAF indirectly measures tissue advanced glycation end products(AGE) being cumulative metabolites of oxidative stress and cytokine-driven inflammatory reactions. The dialysatesoften contain glucose.

    Methods: Autofluorescence of skin and plasma (PAF) were measured in patients on HD during standard treatment(ST) with a glucose-containing dialysate (n = 24). After that the patients were switched to a glucose-free dialysate(GFD) for a 2-week period. New measurements were performed on PAF and SAF after 1 week (M1) and 2 weeks(M2) using GFD. Nonparametric paired statistical analyses were performed between each two periods.

    Results: SAF after HD increased non-significantly by 1.2% while when a GFD was used during HD at M1, a decreaseof SAF by 5.2% (p = 0.002) was found. One week later (M2) the reduction of 1.6% after the HD was not significant(p = 0.33). PAF was significantly reduced during all HD sessions. Free and protein-bound PAF decreased similarlywhether glucose containing or GFD was used. The HD resulted in a reduction of the total PAF of approximately15%, the free compound of 20% and the protein bound of 10%. The protein bound part of PAF correspondedto approximately 56% of the total reduction. The protein bound concentrations after each HD showed thelowest value after 2 weeks using glucose-free dialysate (p < 0.05). The change in SAF could not be related to achange in PAF.

    Conclusions: When changing to a GFD, SAF was reduced by HD indicating that such measure may hamperthe accumulation and progression of deposits of AGEs to protein in tissue, and thereby also the developmentof CVD. Glucose-free dialysate needs further attention. Protein binding seems firm but not irreversible.

  • 237.
    Ramsauer, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Graaff, Reindert
    Sikole, Aleksandar
    Trajceska, Lada
    Arsov, Stefan
    Hadimeri, Henrik
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Skin Autofluorescence, a Measure of Cumulative Metabolic stress and Advanced Glycation End Products, shows seasonal variations in dialysis patientsManuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic and oxidative stress and cytokine driven inflammatory reactions. AGEs are thought to contribute to the cardiovascular complications of hemodialysis patients. Skin autofluorescence (AF) is related to the tissue accumulation of AGE, and is one of the strongest prognostic markers on mortality in these patients. The content of AGE is high in barbecue food. Since the barbecue season in northern Sweden is between June and August a longitudinal study was performed to investigate whether there are seasonal variations in skin-AF on a hemodialysis (HD) in this population. Skin-AF was measured non-invasively with an AGE Reader (Diagnoptics Technologies BV, Groningen, The Netherlands) in patients on HD at different seasonal periods during one year such as February-May (N=29, 21 men/8 women), May – August (N=26, 19 m/7 w), August  – March  (N=24, 18 m/6 w). Skin-AF was measured before and after dialyses. Paired statistical analyses were performed between each two periods. A second analysis was performed including only the patients with measurements at all 4 points of time (n=23, 17m/6w).

    There was at a median 5.6% increase in skin-AF during the winter period (p=0.004) and a 10.6% decrease of the skin-AF during the summer (p<0.001). The study concluded that skin-AF shows seasonal variation. The cause of these changes could not be clarified. A beneficial effect may be due to extended exposure to sunlight during the summer and/or to different dietary intake during the seasons.

  • 238.
    Ramsauer, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Nephrology, Skaraborgs Hospital, Skövde.
    Graaff, Reindert
    Sikole, Aleksandar
    Trajceska, Lada
    Lundström, Sara
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Arsov, Stefan
    Hadimeri, Henrik
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Decreases During the Summer in Dialysis Patients2019In: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 43, no 2, p. 173-180Article in journal (Refereed)
    Abstract [en]

    Tissue advanced glycation end products (AGEs) are a measure of cumulative metabolic and oxidative stress and cytokine-driven inflammatory reactions. AGEs are thought to contribute to the cardiovascular complications of hemodialysis (HD) patients. Skin autofluorescence (SAF) is related to the tissue accumulation of AGEs and rises with age. SAF is one of the strongest prognostic markers of mortality in these patients. The content of AGEs is high in barbecue food. Due to the location in northern Sweden, there is a short intense barbecue season between June and August. The aim of this study was to investigate if seasonal variations in SAF exist in HD patients, especially during the barbecue season. SAF was measured noninvasively with an AGE Reader in 34 HD-patients (15 of those with diabetes mellitus, DM). Each time the median of three measures were used. Skin-AF was measured before and after each one HD at the end of February and May in 31 patients (22 men/9 women); the end of May and August in 28 (20 m/8 w); the end of August and March in 25 (19 m/6 w). Paired statistical analyses were performed during all four periods (n = 23, 17 m/6 w); as was HbA1c of those with DM. There was at a median 5.6% increase in skin-AF during the winter period (February-May, P = 0.004) and a 10.6% decrease in the skin-AF during the summer (May-August, P < 0.001). HbA1c in the DM rose during the summer (P = 0.013). In conclusion, skin-AF decreased significantly during the summer. Future studies should look for favorable factors that prevent skin-AF and subsequently cardiovascular diseases.

  • 239. Ravaud, Alain
    et al.
    Motzer, Robert J
    Pandha, Hardev S
    George, Daniel J
    Pantuck, Allan J
    Patel, Anup
    Chang, Yen-Hwa
    Escudier, Bernard
    Donskov, Frede
    Magheli, Ahmed
    Carteni, Giacomo
    Laguerre, Brigitte
    Tomczak, Piotr
    Breza, Jan
    Gerletti, Paola
    Lechuga, Mariajose
    Lin, Xun
    Martini, Jean-Francois
    Ramaswamy, Krishnan
    Casey, Michelle
    Staehler, Michael
    Patard, Jean-Jacques
    Ljungberg, Börje
    Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.2016In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 375, no 23, p. 2246-2254Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy.

    METHODS: In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety.

    RESULTS: The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects.

    CONCLUSIONS: Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674 .).

  • 240. Roberts, Neil A.
    et al.
    Hilton, Emma N.
    Lopes, Filipa M.
    Singh, Subir
    Randles, Michael J.
    Gardiner, Natalie J.
    Chopra, Karl
    Coletta, Riccardo
    Bajwa, Zunera
    Ha, Robert J.
    Yue, Wyatt W.
    Schaefer, Franz
    Weber, Stefanie
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stuart, Helen M.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Newman, William G.
    Woolf, Adrian S.
    Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder2019In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 95, no 5, p. 1138-1152Article in journal (Refereed)
    Abstract [en]

    Mutations in leucine-rich-repeats and immunoglobulin-likedomains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. There was no anatomical blockage of the outflow tract, consistent with a functional bladder outlet obstruction. Transcriptome analysis revealed differential expression of 12 known transcripts in addition to Lrig2, including 8 with established roles in neurobiology. Mice with homozygous mutations in either Lrig2 or Hpse2 had increased nerve density within the body of the urinary bladder and decreased nerve density around the urinary outflow tract. In a sample of 155 children with chronic kidney disease and urinary symptoms, we discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome, and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract.

  • 241.
    Robinson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Garmo, Hans
    Bill-Axelson, Anna
    Mucci, Lorelei
    Holmberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Use of 5 alpha-reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study2013In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 346, p. f3406-Article in journal (Refereed)
    Abstract [en]

    Objective To assess the association between 5 alpha-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk. Design Nationwide, population based case-control study for men diagnosed with prostate cancer in 2007-09 within the Prostate Cancer data Base Sweden 2.0. Setting The National Prostate Cancer Register, National Patient Register, census, and Prescribed Drug Register in Sweden, from which we obtained data on 5-ARI use before date of prostate cancer diagnosis. Participants 26 735 cases and 133 671 matched controls; five controls per case were randomly selected from matched men in the background population. 7815 men (1499 cases and 6316 controls) had been exposed to 5-ARI. 412 men had been exposed to 5-ARI before the diagnosis of a cancer with Gleason score 8-10. Main outcome measures Risk of prostate cancer calculated as odds ratios and 95% confidence intervals by conditional logistic regression analyses. Results Risk of prostate cancer overall decreased with an increasing duration of exposure; men on 5-ARI treatment for more than three years had an odds ratio of 0.72 (95% confidence interval 0.59 to 0.89; P<0.001 for trend). The same pattern was seen for cancers with Gleason scores 2-6 and score 7 (both P<0.001 for trend). By contrast, the risk of tumours with Gleason scores 8-10 did not decrease with increasing exposure time to 5-ARI (for 0-1 year of exposure, odds ratio 0.96 (95% confidence interval 0.83 to 1.11); for 1-2 years, 1.07 (0.88 to 1.31); for 2-3 years, 0.96 (0.72 to 1.27); for >3 years, 1.23 (0.90 to 1.68); P=0.46 for trend). Conclusions Men treated with 5-ARI for lower urinary tract symptoms had a decreased risk of cancer with Gleason scores 2-7, and showed no evidence of an increased risk of cancer with Gleason scores 8-10 after up to four years' treatment.

  • 242.
    Robinson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Ryhov County Hospital, 551 85 Jönköping, Sweden.
    Garmo, Hans
    Bill-Axelson, Anna
    Mucci, Lorelei
    Holmberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
    Use of 5α-reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study2013In: BMJ (Clinical Research Edition), ISSN 0959-8138, Vol. 346, article id f3406Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the association between 5α-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk.

    DESIGN: Nationwide, population based case-control study for men diagnosed with prostate cancer in 2007-09 within the Prostate Cancer data Base Sweden 2.0.

    SETTING: The National Prostate Cancer Register, National Patient Register, census, and Prescribed Drug Register in Sweden, from which we obtained data on 5-ARI use before date of prostate cancer diagnosis.

    PARTICIPANTS: 26,735 cases and 133,671 matched controls; five controls per case were randomly selected from matched men in the background population. 7815 men (1499 cases and 6316 controls) had been exposed to 5-ARI. 412 men had been exposed to 5-ARI before the diagnosis of a cancer with Gleason score 8-10.

    MAIN OUTCOME MEASURES: Risk of prostate cancer calculated as odds ratios and 95% confidence intervals by conditional logistic regression analyses.

    RESULTS: Risk of prostate cancer overall decreased with an increasing duration of exposure; men on 5-ARI treatment for more than three years had an odds ratio of 0.72 (95% confidence interval 0.59 to 0.89; P<0.001 for trend). The same pattern was seen for cancers with Gleason scores 2-6 and score 7 (both P<0.001 for trend). By contrast, the risk of tumours with Gleason scores 8-10 did not decrease with increasing exposure time to 5-ARI (for 0-1 year of exposure, odds ratio 0.96 (95% confidence interval 0.83 to 1.11); for 1-2 years, 1.07 (0.88 to 1.31); for 2-3 years, 0.96 (0.72 to 1.27); for >3 years, 1.23 (0.90 to 1.68); P=0.46 for trend).

    CONCLUSIONS: Men treated with 5-ARI for lower urinary tract symptoms had a decreased risk of cancer with Gleason scores 2-7, and showed no evidence of an increased risk of cancer with Gleason scores 8-10 after up to four years' treatment.

  • 243.
    Robinson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Garmo, Hans
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lindahl, Bertil
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Van Hemelrijck, Mieke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Adolfsson, Jan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bratt, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Lars
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ischemic heart disease and stroke before and during endocrine treatment for prostate cancer in PCBaSe Sweden2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 2, p. 478-487Article in journal (Refereed)
    Abstract [en]

    In observational studies of men with prostate cancer, men on endocrine treatment (ET) have had an increased risk of ischemic heart disease (IHD) and stroke. However, prostate cancer per se may increase risk of IHD and stroke and men on ET may have been at increased risk already prior to initiation of ET. We assessed the incidence of IHD and stroke in men with prostate cancer before and during different endocrine treatments. The hazard ratio (HR) of IHD and stroke in 39,051 men with prostate cancer vs. a matched control population without prostate cancer was assessed by use of Cox proportion hazard models. An increased risk was found among 30,883 men with prostate cancer who did not receive ET, with a HR of 1.08 (95% CI 1.00–1.18) for IHD and 1.10 (95%CI 1.00–1.21) for stroke. In 8,168 men who initiated ET during the observation period, the risk of IHD was significantly higher (p = 0.014), during ET (HR 1.40, 95% CI 1.17–1.67) compared with before initiation of ET (HR of 0.98, 95% CI 0.72–1.33), whereas no such increase was found for stroke. Regardless of treatment, men with prostate cancer had a small increase in risk of IHD and stroke and initiation of ET was associated with a further increase in risk of IHD. Our data underline the importance of a proper indication for ET because many men with low-risk prostate cancer currently receive ET.

  • 244. Robinson, David
    et al.
    Garmo, Hans
    Lissbrant, Ingela Franck
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Pettersson, Andreas
    Gunnlaugsson, Adalsteinn
    Adolfsson, Jan
    Bratt, Ola
    Nilsson, Per
    Stattin, Pär
    Prostate Cancer Death After Radiotherapy or Radical Prostatectomy: A Nationwide Population-based Observational Study2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, no 4, p. 502-511Article in journal (Refereed)
    Abstract [en]

    Background: There are no conclusive results from randomized trials on radiotherapy (RT) versus radical prostatectomy (RP) for prostate cancer. Numerous observational studies have suggested that RP is associated with a lower risk of prostate cancer death, but whether results have been biased due to limited adjustments for confounding factors is unknown.

    Objective: To compare the risk of prostate cancer death after RT versus RP.

    Design, setting, and participants: Nationwide population-based observational study of men in the Prostate Cancer data Base Sweden 3.0 who had undergone RT or RP between 1998 and 2012.

    Outcome measurements and statistical analysis: Prostate cancer deaths were compared. Hazard ratios (HRs) were calculated in Cox regression models, including clinical T stage, M stage, Gleason grade group, serum levels of prostate-specific antigen, proportion of biopsy cores with cancer, mode of detection, comorbidity, age, educational level, and civil status. Period analysis with left truncation was performed.

    Results and limitations: Primary treatment was RT or RP for 41 503 men. Treatment effect was associated with disease severity. In univariate analysis of RT versus RP, risk of prostate cancer death was higher after RT-low-and intermediate-risk cancer, HR 1.82 (95% confidence interval [CI]: 1.53-2.16), and high-risk cancer, HR 1.57 (95% CI: 1.33-1.85). After full adjustment in period analysis, this difference between the treatments was attenuated-low-and intermediate-risk cancer, HR 1.24 (95% CI: 0.97-1.58), and high-risk cancer, HR 1.03 (95% CI: 0.81-1.31). Confounding remained due to nonrandom allocation to treatment.

    Conclusions: In comparison with previous studies, the difference in prostate cancer mortality after RT and RP was much smaller.

    Patient summary: The difference in prostate cancer mortality after contemporary radiotherapy and radical prostatectomy was small in contrast to previous studies, indicating that potential side effects should be more emphasized when selecting treatment.

  • 245.
    Robinson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Ryhov County Hospital, Jönköping, Sweden .
    Garmo, Hans
    Department of Urology, Ryhov County Hospital, Jönköping, Sweden; Regional Cancer Centre, Uppsala University Hospital, Uppsala, Sweden.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Michaëlsson, Karl
    Uppsala, Sweden.
    Risk of Fractures and Falls during and after 5-alpha Reductase Inhibitor Use: A Nationwide Cohort Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0140598Article in journal (Refereed)
    Abstract [en]

    Background Lower urinary tract symptoms are common among older men and 5-alpha reductase inhibitors (5-ARI) are a group of drugs recommended in treating these symptoms. The effect on prostate volume is mediated by a reduction in dihydrotestosterone; however, this reduction is counterbalanced by a 25% rise in serum testosterone levels. Therefore, 5-ARI use might have systemic effects and differentially affect bone mineral density, muscular mass and strength, as well as falls, all of which are major determinants of fractures in older men. Methods We conducted a nationwide cohort study of all Swedish men who used 5-ARI by comparing their risk of hip fracture, any type of fracture and of falls with matched control men randomly selected from the population and unexposed to 5-ARI. Results During 1 417 673 person-years of follow-up, 10 418 men had a hip fracture, 19 570 any type of fracture and 46 755 a fall requiring hospital care. Compared with unexposed men, current users of 5-ARI had an adjusted hazard ratio (HR) of 0.96 (95% CI 0.91-1.02) for hip fracture, an HR of 0.94 (95% CI 0.90-0.98) for all fracture and an HR of 0.99 (95% CI 0.96-1.02) for falls. Former users had an increased risk of hip fractures (HR 1.10, 95% CI 1.01-1.19). Conclusion 5-ARI is safe from a bone health perspective with an unaltered risk of fractures and falls during periods of use. After discontinuation of 5-ARI, there is a modest increase in the rate of fractures and falls.

  • 246. Rodhe, Nils
    et al.
    Englund, Lars
    Mölstad, Sigvard
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Research and Development Unit, Jämtland County Council, Sweden.
    Bacteriuria is associated with urge urinary incontinence in older women2008In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 26, no 1, p. 35-39Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the association between bacteriuria and frequency and type of urinary incontinence in elderly people living in the community. Bacteriuria and urinary incontinence are common conditions and often coexisting in this population; the authors have previously reported the prevalence of bacteriuria to be 22.4% in women and 9.4% in men.

    DESIGN: Cross-sectional study.

    SETTING: The catchment area of a primary healthcare centre in a Swedish middle-sized town.

    SUBJECTS: Residents, except for those in nursing homes, aged 80 and over. Participation rate: 80.3% (431/537).

    MAIN OUTCOME MEASURES: Urinary cultures and questionnaire data on urinary incontinence.

    RESULTS: In women the OR for having bacteriuria increased with increasing frequency of urinary incontinence; the OR was 2.83 (95% CI 1.35-5.94) for women who were incontinent daily as compared with continent women. Reporting urge urinary incontinence increased the risk of having bacteriuria: 3.36 (95% CI 1.49-7.58) in comparison with continent women while there was no significant association between stress urinary incontinence and bacteriuria. The prevalence of bacteriuria among men was too low to make any meaningful calculations about the association between bacteriuria and frequency and type of incontinence.

    CONCLUSION: Bacteriuria is associated with more frequent leakage and predominantly with urge urinary incontinence. The causes of this association and their clinical implications remain unclear. There might be some individuals who would benefit from antibiotic treatment, but further studies are warranted.

  • 247. Rosen, Raymond C.
    et al.
    Wu, Frederick
    Behre, Hermann M.
    Porst, Hartmut
    Meuleman, Eric J. H.
    Maggi, Mario
    Romero-Otero, Javier
    Martinez-Salamanca, Juan I.
    Jones, Thomas Hugh
    Debruyne, Frans M. J.
    Kurth, Karl-Heinz
    Hackett, Geoff I.
    Quinton, Richard
    Ströberg, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Reisman, Yacov
    Pescatori, Edoardo S.
    Morales, Antonio
    Bassas, Lluis
    Cruz, Natalio
    Cunningham, Glenn R.
    Wheaton, Olivia A.
    Quality of Life and Sexual Function Benefits of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME)2017In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 14, no 9, p. 1104-1115Article in journal (Refereed)
    Abstract [en]

    Background: The benefits and risks of long-term testosterone administration have been a topic of much scientific and regulatory interest in recent years. Aim: To assess long-term quality of life (QOL) and sexual function benefits of testosterone replacement therapy (TRT) prospectively in a diverse, multinational cohort of men with hypogonadism. Methods: A multinational patient registry was used to assess long-term changes associated with TRT in middle-age and older men with hypogonadism. Comprehensive evaluations were conducted at 6, 12, 24, and 36 months after enrollment into the registry. Outcomes: QOL and sexual function were evaluated by validated measures, including the Aging Males' Symptom (AMS) Scale and the International Index of Erectile Function (IIEF). Results: A total of 999 previously untreated men with hypogonadism were enrolled at 25 European centers, 750 of whom received TRT at at least one visit during the period of observation. Patients on TRT reported rapid and sustained improvements in QOL, with fewer sexual, psychological, and somatic symptoms. Modest improvements in QOL and sexual function, including erectile function, also were noted in RHYME patients not on TRT, although treated patients showed consistently greater benefit over time in all symptom domains compared with untreated patients. AMS total scores for patients on TRT were 32.8 (95% confidence interval = 31.3-34.4) compared with 36.6 (95% confidence interval = 34.8-38.5) for untreated patients (P < .001). Small but significant improvements in IIEF scores over time also were noted with TRT. Approximately 25% of treated and untreated men also used phosphodiesterase type 5 inhibitors, with notable differences in the frequency of phosphodiesterase type 5 inhibitor prescription use according to physician specialty and geographic site location. Clinical Implications: TRT-related benefits in QOL and sexual function are well maintained for up to 36 months after initiation of treatment. Strengths and Limitations: The major strengths are the large, diverse patient population being treated in multidisciplinary clinical settings. The major limitation is the frequency of switching from one formulation to another. Conclusion: Overall, we confirmed the broad and sustained benefits of TRT across major QOL dimensions, including sexual, somatic, and psychological health, which were sustained over 36 months in our treatment cohort. Copyright (C) 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  • 248.
    Rosenblatt, Robert
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Stockholm South General Hospital, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Markus
    Alamdari, Farhood
    Sidiki, Alexander
    Holmström, Benny
    Hansson, Johan
    Vasko, Janos
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Marits, Per
    Gabrielsson, Susanne
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Winqvist, Ola
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Sentinel node detection in muscle-invasive urothelial bladder cancer is feasible after neoadjuvant chemotherapy in all pT stages, a prospective multicenter report2017In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 35, no 6, p. 921-927Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine whether sentinel node detection (SNd) in muscle-invasive urothelial bladder cancer (MIBC) can be performed in patients undergoing neoadjuvant chemotherapy (NAC) and determine whether SNd is feasible in all pT stages, including pT0.

    BACKGROUND: Previous published series of SNd in MIBC have not included patients undergoing NAC, and systematic reports of pT0 patients w/wo NAC were absent. Translational immunological tumor research on MIBC focusing on SNd, in the era of NAC, requires technical feasibility. Additionally, SNd in MIBC requests further evaluations as a method for nodal staging.

    MATERIALS AND METHODS: Ninety-nine patients with suspected urothelial MIBC were prospectively selected from six urological centers. After TUR-B and primary staging, 65 MIBC patients qualified for radical cystectomy. Precystectomy staging was cT2a-T4aN0M0, including 47 NAC patients and 18 chemo-naïve patients. All 65 patients underwent intraoperative SNd by peritumoral injection of 80 Mbq Technetium and Geiger probe detection. Postcystectomy staging was pT0-T4aN0-N2M0. SNs were defined by two calculations, SNdef1 and SNdef2.

    RESULTS: Totally 1063 lymph nodes were removed (total SNs; 222-227). NAC patients with pT0 (n = 24) displayed a true positive detection in 91.7 % by either SNdef, with a median of 3.0 SNs. NACpT >0 patients had a true positive detection in 87 % (SNdef1) and 91.3 % (SNdef2). In a univariate analysis, patient group neither NAC nor tumor downstaging influenced detection rates, regardless of SN definition. In total eight patients, 4/22 metastatic nodes were SNs while 18/22 were non-SNs.

    CONCLUSIONS: Sentinel node detection in MIBC is feasible also in NAC patients, regardless of pT stage. SNd played no role in nodal staging.

  • 249.
    Rosenblatt, Robert
    et al.
    Umeå University.
    Sandström, Gabriella
    Umeå University.
    Bahar, Maryam
    Umeå University.
    Asad, Danna
    Umeå University.
    Forsman, Ramona
    Umeå University.
    Johansson, Markus
    Shareef, Marwan
    Alamdari, Farhood
    Bergh, Anders
    Winqvist, Ola
    Sherif, Amir
    Umeå University.
    Blood transfusions during neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer may have a negative impact on overall survival2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, p. 35-36Article in journal (Other academic)
    Abstract [en]

    Introduction: Several studies have demonstrated a decreased overall survival for patients with muscle-invasive bladder cancer (MIBC) receiving allogenic peri- and postoperative blood transfusions at cystectomy. However, the extent and the effect of blood transfusions given during neoadjuvant chemotherapy (NAC) has never been addressed. The purpose of the present study, was to assess the impact of blood transfusions given during NAC on survival in patients with MIBC undergoing NAC and radical cystectomy.

    Materials and Methods: A cohort of 120 consecutive patients with MIBC (cT2-T4aN0M0) undergoing NAC and radical cystectomy at four Swedish centers was retrospectively evaluated. Clinical and pathoanatomical data was obtained, including data SCANDINAVIAN JOURNAL OF UROLOGY 35 on administeredallogenic blood at consecutive time-intervals. Overall survival was analyzed by Kaplan-Meier plotting and Cox regression.

    Results: One third of the cohort (n ¼ 40) received blood transfusions during NAC-therapy. The five-year overall survival rates were significantly lower in this group compared to the non-transfused patients (39.7% and 58.9% respectively, p ¼ 0.047). In a univariate analysis, blood transfusions, nodal status and locally advanced tumor growth (pT >2), were negative prognostic factors for survival. In multivariate analysis, only pNx and pT >2 remained significant negative prognostic factors. In subgroup analysis of localized and non-disseminated patients only (n ¼ 96), blood transfused patients showed a 18,5% absolute risk increase compared to blood naïve patients (p¼ 0.197).

    Conclusions: This is the first time that the extent and the effect of allogenic blood transfusions during NAC is examined in MIBC. Data suggest that there may be an association between blood transfusion and poor pathological and oncological outcome. Firm conclusions are difficult to draw due to the limited number of study participants and the retrospective nature of the study.

  • 250.
    Ruge, Toralph
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Carlsson, Axel C.
    Larsson, Tobias E.
    Carrero, Juan-Jesus
    Larsson, Anders
    Lind, Lars
    Arnlov, Johan
    Endostatin Level is Associated with Kidney Injury in the Elderly: Findings from Two Community-Based Cohorts2014In: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 40, no 5, p. 417-424Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to investigate the associations between circulating endostatin and the different aspects of renal dysfunction, namely, estimated (cystatin C) glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR). Methods: Two independent longitudinal community-based cohorts of elderly. ULSAM, n = 786 men; age 78 years; median GFR 74 ml/min/1.73 m(2); median ACR 0.80 mg/mmol); and PIVUS, n = 815; age 75 years; 51% women; median GFR; 67 ml/min/1.73 m(2); median ACR 1.39 mg/mmol. Cross-sectional associations between the endostatin levels and GFR as well as ACR, and longitudinal association between endostatin at baseline and incident CKD (defined as GFR <60 ml/min/1.73 m(2)) were assessed. Results: In cross-sectional regression analyses adjusting for age, gender, inflammation, and cardiovascular risk factors, serum endostatin was negatively associated with GFR (ULSAM: B-coefficient per SD increase -0.51, 95% CI (-0.57, -0.45), p < 0.001; PIVUS -0.47, 95% CI (-0.54, -0.41), p < 0.001) and positively associated with ACR (ULSAM: B-coefficient per SD increase 0.24, 95% CI (0.15, 0.32), p < 0.001; PIVUS 0.13, 95% CI (0.06-0.20), p < 0.001) in both cohorts. Moreover, in longitudinal multivariable analyses, higher endostatin levels were associated with increased risk for incident CKD defined as GFR < 60 ml/min/1.73 m(2) at re-investigations in both ULSAM (odds ratio per SD increase of endostatin 1.39 (95% CI 1.01-1.90) and PIVUS 1.68 (95% CI 1.36-2.07)). Conclusions: Higher circulating endostatin is associated with lower GFR and higher albuminuria and independently predicts incident CKD in elderly subjects. Further studies are warranted to investigate the underlying mechanisms linking endostatin to kidney pathology, and to evaluate the clinical relevance of our findings. (C) 2014 S. Karger AG, Basel

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