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  • 101.
    Häggström, Christel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Nagel, Gabriele
    Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
    Manjer, Jonas
    Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
    Bjørge, Tone
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Engeland, Anders
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
    Ulmer, Hanno
    Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
    Lindkvist, Björn
    Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
    Selmer, Randi
    Norwegian Institute of Public Health, Oslo, Norway.
    Concin, Hans
    Agency for Preventive and Social Medicine, Bregenz, Austria.
    Tretli, Steinar
    Institute of Population-based Cancer Research, The Cancer Registry of Norway, Oslo, Norway.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Competing risk analysis of metabolic factors and prostate cancerManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

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

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

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

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

  • 102.
    Inkiläinen, Aapo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Styrke, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Sundsvall Hospital, Sundsvall, Sweden .
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Strigård, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Occurrence of abdominal bulging and hernia after open partial nephrectomy: a retrospective cohort study2018Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 1, s. 54-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

  • 103.
    Iranparvar Alamdari, Farhood
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap.
    Renal cell carcinoma: factors of importance for follow-up and survival2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

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

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

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

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

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

  • 104.
    Jacobsen, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Vascular endothelial growth factor in renal cell carcinoma2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

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

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

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

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

  • 105. Jahnson, S.
    et al.
    Hagberg, O.
    Holmang, S.
    Liedberg, F.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Malmstrom, P. U.
    Wijkstrom, H.
    Mansson, W.
    Higher excess mortality rate in women than in men with invasive bladder cancer2012Inngår i: European urology. Supplement, ISSN 1569-9056, E-ISSN 1878-1500, Vol. 11, nr 1, s. E870-U832Artikkel i tidsskrift (Annet vitenskapelig)
  • 106. Jahnson, Staffan
    et al.
    Gårdmark, Truls
    Hosseini, Abolfazl
    Jerlström, Tomas
    Liedberg, Fredrik
    Malmström, Per-Uno
    Rosell, Johan
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ströck, Viveka
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Aljabery, Firas
    Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe)2019Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, nr 4, s. 200-205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

  • 107. Jahnson, Staffan
    et al.
    Hosseini Aliabad, Abolfazl
    Holmäng, Sten
    Jancke, Georg
    Liedberg, Fredrik
    Ljungberg, Börje
    Department of Urology, Northern University Hospital, Umeå, Sweden.
    Malmström, Per-Uno
    Rosell, Johan
    Swedish National Registry of Urinary Bladder Cancer: no difference in relative survival over time despite more aggressive treatment2016Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, nr 1, s. 14-20Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 108. Jamshidi, Neema
    et al.
    Jonasch, Eric
    Zapala, Matthew
    Korn, Ronald L
    Brooks, James D
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Kuo, Michael D
    The radiogenomic risk score stratifies outcomes in a renal cell cancer phase 2 clinical trial2016Inngår i: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 26, nr 8, s. 2798-2807Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

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

  • 109. Jan, Michael
    et al.
    Bonn, Stephanie E.
    Sjölander, Arvid
    Wiklund, Fredrik
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Holmberg, Erik
    Grönberg, Henrik
    Bälter, Katarina
    The roles of stress and social support in prostate cancer mortality2016Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, nr 1, s. 47-55Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 110. Jancke, Georg
    et al.
    Liedberg, Fredrik
    Aljabery, Firas
    Sherif, Amir
    Norrland University Hospital.
    Ströck, Viveka
    Malmström, Per-Uno
    Hosseini-Aliabad, Abolfazl
    Jahnson, Staffan
    Intravesical instillations and cancer-specific survival in patients with primary carcinoma in situ of the urinary bladder2017Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, nr 2, s. 124-129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The aim of this study was to evaluate the use of intravesical treatment and cancer-specific survival of patients with primary carcinoma in situ (CIS).

    MATERIALS AND METHODS: Data acquisition was based on the Swedish National Registry of Urinary Bladder Cancer by selecting all patients with primary CIS. The analysis covered gender, age, hospital type and hospital volume. Intravesical treatment and death due to bladder cancer were evaluated by multivariate logistic regression and multivariate Cox analysis, respectively.

    RESULTS: The study included 1041 patients (median age at diagnosis 72 years) with a median follow-up of 65 months. Intravesical instillation therapy was given to 745 patients (72%), and 138 (13%) died from bladder cancer during the observation period. Male gender [odds ratio (OR) = 1.56, 95% confidence interval (CI) 1.13-2.17] and treatment at county (OR = 1.65, 95% CI 1.17-2.33), university (OR =2.12, 95% CI 1.48-3.03) or high-volume (OR = 1.92, 95% CI 1.34-2.75) hospitals were significantly associated with higher odds of intravesical instillations. The age category ≥80 years had a significantly lower chance of receiving intravesical therapy (OR = 0.44, 95% CI 0.26-0.74) and a significantly higher risk of dying from bladder cancer (hazard ratio = 3.03, 95% CI 1.71-5.35).

    CONCLUSION: Significantly more frequent use of intravesical treatment of primary CIS was found for males and for patients treated at county, university and high-volume hospitals. Age ≥80 years was significantly related to less intravesical treatment and poorer cancer-specific survival.

  • 111. Jansson, K. Fredrik
    et al.
    Akre, Olof
    Garmo, Hans
    Bill-Axelson, Anna
    Adolfsson, Jan
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bratt, Ola
    Concordance of tumor differentiation among brothers with Prostate Cancer2012Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 62, nr 4, s. 656-661Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Genetic factors seem to be of greater importance in prostate cancer than in other forms of cancer. Studies have suggested familial concordance in survival, but the extent to which that is due to tumor characteristics is not known. Objective: We hypothesized that a brother of an index case with prostate cancer is at particularly increased risk of prostate cancer with the same tumor differentiation as the index case. Design, setting and participants: We identified 21 930 brothers of index cases with prostate cancer in the Prostate Cancer Data Base Sweden and followed them up for incidence of prostate cancer. Outcome measurements and statistical analysis: The relative risk of Gleason score-specific prostate cancer in the cohort of brothers was estimated by using the standardized incidence ratio (SIR) stratified by Gleason score of the index case. We estimated 95% confidence intervals (CIs) assuming a Poisson distribution. Results and limitations: Among brothers of index cases with Gleason score 8-10 cancer, the SIR was 2.53 (95% CI, 1.97-3.21) for a Gleason score 2-6 cancer and 4.00 (95% CI, 2.63-5.82) for a Gleason score 8-10 cancer. SIR for Gleason score 2-6 cancer among brothers decreased with time since the date of the index cases' diagnoses, whereas the risk of Gleason 8-10 cancer increased over time for brothers of index cases with Gleason 8-10 cancer (p for trend = 0.009). Conclusions: Brothers of men with high-grade prostate cancer are at particularly increased risk of high-grade prostate cancer. Likewise, there is a concordance of less malignant prostate cancers within families. These findings may have direct clinical relevance for counseling men with a family history of prostate cancer. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.

  • 112. Jerlström, Tomas
    et al.
    Chen, Ruoqing
    Liedberg, Fredrik
    Andrén, Ove
    Ströck, Viveka
    Aljabery, Firas A S
    Hosseini, Abolfazl
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Malmström, Per-Uno
    Ullén, Anders
    Gårdmark, Truls
    Fall, Katja
    No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study2019Inngår i: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking.

    METHODS: We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not.

    RESULTS: Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81).

    CONCLUSION: This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.

  • 113. Jerlström, Tomas
    et al.
    Gårdmark, Truls
    Carringer, Malcolm
    Holmäng, Sten
    Liedberg, Fredrik
    Hosseini, Abolfazl
    Malmström, Per-Uno
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hagberg, Oskar
    Jahnson, Staffan
    Urinary bladder cancer treated with radical cystectomy: perioperative parameters and early complications prospectively registered in a national population-based database2014Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 48, nr 4, s. 334-340Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. Cystectomy combined with pelvic lymph-node dissection and urinary diversion entails high morbidity and mortality. Improvements are needed, and a first step is to collect information on the current situation. In 2011, this group took the initiative to start a population-based database in Sweden (population 9.5 million in 2011) with prospective registration of patients and complications until 90 days after cystectomy. This article reports findings from the first year of registration. Material and methods. Participation was voluntary, and data were reported by local urologists or research nurses. Perioperative parameters and early complications classified according to the modified Clavien system were registered, and selected variables of possible importance for complications were analysed by univariate and multivariate logistic regression. Results. During 2011, 285 (65%) of 435 cystectomies performed in Sweden were registered in the database, the majority reported by the seven academic centres. Median blood loss was 1000 ml, operating time 318 min, and length of hospital stay 15 days. Any complications were registered for 103 patients (36%). Clavien grades 1-2 and 3-5 were noted in 19% and 15%, respectively. Thirty-seven patients (13%) were reoperated on at least once. In logistic regression analysis elevated risk of complications was significantly associated with operating time exceeding 318 min in both univariate and multivariate analysis, and with age 76-89 years only in multivariate analysis. Conclusions. It was feasible to start a national population-based registry of radical cystectomies for bladder cancer. The evaluation of the first year shows an increased risk of complications in patients with longer operating time and higher age. The results agree with some previously published series but should be interpreted with caution considering the relatively low coverage, which is expected to be higher in the future.

  • 114. Jerlström, Tomas
    et al.
    Gårdmark, Truls
    Ströck, Viveka
    Aljabery, Firas A. -S.
    Hosseini, Abolfazl A.
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ullén, Anders
    Malmström, Per-Uno
    Liedberg, Fredrik
    Jahnson, Staffan
    Carringer, Malcolm
    Significantly more downstaging in patients recieving preoperative (neoadjuvant and induction) chemotherapy prior to cystectomy for muscle-invasive bladder cancer2017Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, s. 34-35Artikkel i tidsskrift (Annet vitenskapelig)
  • 115.
    Johansson, Maja
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umecrine Cognit AB, Solna, Sweden.
    Agusti, Ana
    INCLIVA, Valencia, Spain.
    Llansola, Marta
    Centro Investigación Príncipe Felipe, Valencia, Spain.
    Montoliu, Carmina
    INCLIVA, Valencia, Spain.
    Strömberg, Jessica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Malinina, Evgenya
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ragagnin, Gianna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Doverskog, Magnus
    Umecrine Cognit AB, Solna, Sweden.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Felipo, Vicente
    Centro Investigación Príncipe Felipe, Valencia, Spain.
    GR3027 antagonizes GABA(A) receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy2015Inngår i: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 309, nr 5, s. G400-G409Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABA(A) receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABA(A) receptors by neurosteroids such as allopregnanolone and 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE.

  • 116.
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Prostate cancer aetiology: epidemiological studies of the IGF- and one-carbon metabolism pathways2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The aim of this thesis was to investigate the involvement of the insulin-like growth factor- and the one-carbon metabolism pathways in prostate cancer aetiology, studying both circulating biomarkers and genetic variation. Papers included in the thesis were conducted within the case-control study CAncer Prostate in Sweden (CAPS), and the two prospective studies European Prospective Investigation into nutrition and Cancer (EPIC), and Northern Sweden Health and Disease Cohort (NSHDC).

    In paper I, we investigated the relation between genetic variants of the IGF1 gene and prostate cancer risk within the CAPS study. We found that a common haplotype within the 3’ region of the IGF1 gene is associated with increased prostate cancer risk.

    In paper II, we investigated if the variants of the IGF1 gene that were associated with prostate cancer risk in paper I, are also associated with circulating levels of IGF1. Circulating levels of IGF1 were analysed in controls from the CAPS study and three haplotype tagging SNPs (htSNPs) were genotyped in subjects from the NSHDC study in which circulating IGF1 had previously been analysed. The genetic variants previously associated with increased prostate cancer risk were now also found to be associated with elevated levels of circulating IGF1. We concluded that variation in the 3’ region of the IGF1 gene affects prostate cancer risk by influencing circulating levels of IGF1.

    In paper III, we investigated if variants of the IGFBP1, IGFBP3 and IGFALS genes are associated with i) prostate cancer risk, ii) circulating concentrations of total and intact IGFBP3, and iii) prostate cancer-specific survival probability. In addition, we investigated if circulating concentrations of total and intact IGFBP3 are associated with prostate cancer-specific survival probability. No association between genetic variation and overall prostate cancer risk or survival was observed, but we found a strong association between elevated levels of intact IGFBP3 and increased risk of prostate cancer-specific death. We could, however, not exclude that this association was confounded by treatment or by the tumour.

    In paper IV, we investigated if circulating levels of folate and vitamin B12 are associated with prostate cancer risk within the EPIC study. We observed no associations between levels of folate, vitamin B12 and overall prostate cancer risk, but elevated levels of vitamin B12 were associated with increased risk of advanced stage disease.

    In paper V, we investigated if circulating levels of ten B-vitamins and related metabolites within the one-carbon metabolism pathway are associated with prostate cancer risk within the NSHDC study. Overall positive associations with prostate cancer risk were observed for levels of choline, vitamin B2 and vitamin B12, and inverse associations were observed for levels of homocysteine and MMA. We also observed a biologically plausible risk modification by smoking status on the association between vitamin B12 and risk; in non-smokers vitamin B12 was positively associated with risk, whereas the association between vitamin B12 and risk was inverse or null in ever/current-smokers.

    In summary, our results suggest that genetic variation of the IGF1 gene affects prostate cancer risk by affecting circulating levels of IGF1. The association between circulating concentrations of intact IGFBP3 and prostate cancer-specific survival is intriguing, but further studies are needed to conclude if this association is caused by confounding. We also observed associations between several factors of one-carbon metabolism and risk, but these associations were statistically week and require confirmation in other prospective studies.

  • 117.
    Johansson, Mattias
    et al.
    International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Holmström, Benny
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hinchliffe, Sally R
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stenman, Ulf-Håkan
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wiklund, Fredrik
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Combining 33 genetic variants with prostate-specific antigen for prediction of prostate cancer: longitudinal study2012Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, nr 1, s. 129-137Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to investigate if a genetic risk score including 33 common genetic variants improves prediction of prostate cancer when added to measures of prostate-specific antigen (PSA). We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort (NSHDC), a prospective cohort in northern Sweden. A total of 520 cases and 988 controls matched for age, and date of blood draw were identified by linkage between the regional cancer register and the NSHDC. Receiver operating characteristic curves with area under curve (AUC) estimates were used as measures of prostate cancer prediction. The AUC for the genetic risk score was 64.3% [95% confidence interval (CI) = 61.4-67.2], and the AUC for total PSA and the ratio of free to total PSA was 86.2% (95% CI = 84.4-88.1). A model including the genetic risk score, total PSA and the ratio of free to total PSA increased the AUC to 87.2% (95% CI = 85.4-89.0, p difference = 0.002). The addition of a genetic risk score to PSA resulted in a marginal improvement in prostate cancer prediction that would not seem useful for clinical risk assessment.

  • 118.
    Johansson, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. International Agency for Research against Cancer, Lyon, France.
    McKay, James D
    Rinaldi, Sabina
    Wiklund, Fredrik
    Adami, Hans-Olov
    Grönberg, Henrik
    Kaaks, Rudolf
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Genetic and plasma variation of insulin-like growth factor binding proteins in relation to prostate cancer incidence and survival2009Inngår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 69, nr 12, s. 1281-1291Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Binding proteins regulate bioavailability of insulin-like growth factor-I (IGF-I) in the circulation and affect apoptosis of tumor cells in the prostate. We analyzed genetic variation within genes coding for IGF binding proteins in relation to prostate cancer incidence and survival. We also investigated if circulating IGFBP3 affects prostate cancer-specific survival. MATERIALS AND METHODS: Eleven haplotype tagging SNPs and two single SNPs in the IGFBP1, IGFBP3, and IGFALS genes were genotyped within the CAncer Prostate in Sweden (CAPS) study including 2,774 cases and 1,736 controls. Plasma samples for analyses of total- and intact IGFBP3 levels were available for 1,521 cases and 909 controls. Complete follow-up of vital status was achieved by linkage to the Swedish Cause of Death Register. RESULTS: We found no clear association between the genetic variants and prostate cancer incidence or survival. The rare allele of the IGFBP3 SNP rs2854744 was associated with elevated plasma levels of total IGFBP3 (P(trend) = 9 x 10(-8)), but not intact IGFBP3 (P(trend) = 0.16). Elevated levels of total- (P(trend) = 0.03) and intact IGFBP3 (P(trend) = 6 x 10(-14)) were associated with increased risk of prostate cancer specific death. Treatment and tumor characteristics accounted for the association with total IGFBP3, whereas the association with intact IGFBP3 was attenuated, but still statistically significant in adjusted analysis (P(trend-adjusted) = 0.0004). Elevated intact IGFBP3 was also significantly associated with increased risk of prostate cancer-specific death among patients who were chemically or surgically castrated (P(trend-adjusted) = 0.0003), and among patients who had not been treated (P(trend-adjusted) = 0.02). CONCLUSIONS: Circulating levels of intact IGFBP3 measured after diagnosis is associated with increased risk of prostate cancer-specific death.

  • 119.
    Jonsson, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Forsberg, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    EVALUATION OF AIR MICRO BUBBLES IN DIALYSIS SYSTEMS IN VITRO2014Inngår i: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 63, nr 5, s. A61-A61Artikkel i tidsskrift (Annet vitenskapelig)
  • 120.
    Jonsson, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindmark, Lorentz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Karlsson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lundberg, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Formation of Blood Foam in the Air Trap During Hemodialysis Due to Insufficient Automatic Priming of Dialyzers2018Inngår i: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 42, nr 5, s. 533-539Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We were encouraged to investigate the reasons for large amounts of foam observed in bloodlines during hemodialysis (HD). Foam was visible in the venous air trap within the Artis Gambro dialysis device. Estimates of the extent of foam were graded (0no foam, 10extensive foam) by two persons that were blind to the type of dialyzer used. Thirty-seven patients were involved in the dialysis procedures. Consecutive dialyses were graded using dialyzers from Fresenius Medical Care (CorDiax dialyzers that were used for high flux HDFX80 and FX100, and for hemodiafiltrationFX1000). The extracorporeal circuit was primed automatically by dialysate using Gambro Artis software 8.15 006 (Gambro, Dasco, Medolla Italy, Baxter, Chicago, IL, USA). The priming volume recommended by the manufacturer was 1100 mL, whereas our center uses 1500 mL. Extensive amounts of blood foam were visual in the air traps. Although the manufacturer recommended extension of priming volume up to 3000 mL, this did not eliminate the foam. Microbubble measurement during HD revealed the air to derive from the dialyzers. When changing to PF210H dialyzers (Baxter) and using a priming volume of 1500 mL, the foam was significantly less (P<0.01). The extent of foam correlated with the size of the FX-dialyzer surface (P=0.002). The auto-priming program was updated to version 8.21 by the manufacturer and the extent of foam in the air trap using FX dialyzers was now reduced and there was no longer a difference between FX and PF dialyzers, although less foam was still visible in the venous air trap during several dialyses. In conclusion, this study urgently calls attention to blood foam development in the venous air trap when using Artis devices and priming software 8.15 in combination with Fresenius dialyzers. Updated auto-priming software (version 8.21) of Artis should be requested to reduce the extent of foam for the Fresenius dialyzers. Other interactions may also be present. We recommend further studies to clarify these problems. Meanwhile caution is warranted for the combined use of dialysis devices and dialyzers with incompatible automatic priming.

  • 121.
    Josefsson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Prognostic markers in prostate cancer: studies of a watchful waiting cohort with long follow up2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Prostate Cancer (PC) is a common and highly variable disease. Using current diagnostic methods, the prostate specific antigen (PSA) blood test and histological grading of prostate tissue needle biopsies, it is often difficult to evaluate whether the patient has a PC that requires active treatment or not. The absolute majority of all 10,000 cases of PCs diagnosed annually in Sweden have tumours graded as Gleason score (GS) 6-7 and a PSA value in blood below 10. Many of these are harmless and can be left without active treatment and hence spared problematic post-therapy side-effects, others are highly malignant and require early diagnosis and treatment. Better prognostic markers are needed and the aim of this study was to evaluate prognostic markers and to test if these markers could identify patients with indolent tumours.

    Methods: We have studied tumour material from 419 men consecutively diagnosed with PC at transurethral resection (1975-1990). The majority of these patients (295) had no metastasis at diagnosis and was not given any curative treatment and only hormonal treatment upon symptoms from metastatic progression. Standard histological sections and tissue microarrays (TMA) from these tumours and surrounding normal prostate tissue were stained and evaluated for cell proliferation (Ki67), blood vessels (endoglin and von Willebrand factor, vWf) and the extracellular matrix component hyaluronan (HA). An orthotopic rat PC model was used to explore hyaluronan staining, hyaluronic acid synthase (HAS)-1 mRNA levels and the effect of local HA treatment on tumour growth.

    Results: Tumour cell proliferation (Ki67) and the density of intra-tumoural endoglin stained blood vessels were independent prognostic markers (i.e. they added prognostic information to the conventional prognostic markers; clinical stage and GS). None of the GS 6 patients with low staining for both Ki67 and endoglin died of PC within 15 years of follow-up. High HA staining in the tumour epithelium and stroma was a negative prognostic marker of cancer specific survival but they were not independent of GS. High HA staining and high vascular density in the stroma of the surrounding morphologically normal prostate were prognostic for short cancer specific survival. Implantation of tumour cells in the normal rat prostate resulted in an increase in HA and HAS-1 mRNA levels in the prostate tissue surrounding prostate tumours. Concurrently intra-prostatic injection of HA also stimulated tumour growth.

    Conclusions: By evaluating both tumour cell proliferation (Ki67) and vascular density, it is possible to identify patients with very low risk of cancer specific death in the absence of active treatment. Prostate tumours influence the surrounding non-malignant prostate tissue, for example they cause an increased angiogenesis and synthesis of hyaluronan. Such responses can possibly be used to diagnose PC and to evaluate PC aggressiveness.

  • 122.
    Josefsson, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Adamo, Hani
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hammarsten, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Granfors, Torvald
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Laurent, Anna Engström
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome2011Inngår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 179, nr 4, s. 1961-1968Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome.

  • 123.
    Josefsson, Andreas
    et al.
    Sahlgrenska Cancer Center, Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Larsson, Karin
    Månsson, Marianne
    Björkman, Jens
    Rohlova, Eva
    Åhs, Daniel
    Brisby, Helena
    Damber, Jan-Erik
    Welén, Karin
    Circulating tumor cells mirror bone metastatic phenotype in prostate cancer2018Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, nr 50, s. 29403-29413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Circulating tumor cells (CTCs) are promising biomarkers in prostate cancer (PC) because they derive from primary tumor and metastatic tissues. In this study, we used quantitative real-time PCR (qPCR) to compare the expression profiles of 41 PC-related genes between paired CTC and spinal column metastasis samples from 22 PC patients that underwent surgery for spinal cord compression. We observed good concordance between the gene expression profiles in the CTC and metastasis samples in most of the PC patients. Expression of nine genes (AGR2, AKR1C3, AR, CDH1, FOLH1, HER2, KRT19, MDK, and SPINK1) showed a significant correlation between the CTC and metastasis samples. Hierarchical clustering analysis showed a similar grouping of PC patients based on the expression of these nine genes in both CTC and metastasis samples. Our findings demonstrate that CTCs mirror gene expression patterns in tissue metastasis samples from PC patients. Although low detection frequency of certain genes is a limitation in CTCs, our results indicate the potential for CTC phenotyping as a tool to improve individualized therapy in metastatic prostate cancer.

  • 124.
    Josefsson, Andreas
    et al.
    Sahlgrenska Cancer Center, Department of Urology, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Linder, Anna
    Flondell Site, Despina
    Canesin, Giacomo
    Stiehm, Anna
    Anand, Aseem
    Bjartell, Anders
    Damber, Jan-Erik
    Welén, Karin
    Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naïve Prostate Cancer2017Inngår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, nr 8, s. 849-858Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC).

    METHODS: PC patients presenting with a prostate specific antigen (PSA) >80 ng/ml and/or metastatic disease, intended for ADT were enrolled in the study. CTCs were analysed for expression of PSA prostate specific membrane antigen (PSMA) and epidermal growth factor receptor (EGFR) before and three months after ADT and related to progression.

    RESULTS: At inclusion, 46 out of 53 patients (87%) were CTC-positive with a sensitivity and specificity for distant metastases (M1) of 98% and 75%, respectively. In patients with M1-disease, EGFR-detection in CTC was an independent prognostic marker for progression-free survival, whereas PSA and alkaline phosphatase serum levels, Gleason score, or T-stage were not. EGFR-positive patients had significantly shorter time to progression (5 months) compared to EGFR-negative patients (11 months) (P < 0.05).

    CONCLUSIONS: In this explorative study, CTCs were detected in 98% of M1 patients and detection of EGFR in CTCs was strongly associated with poor outcome, which indicated that phenotypical analysis of CTC could be a promising prognostic marker of ADT-response in castration-naïve metastatic PC patients. Prostate 77:849-858, 2017. © 2017 Wiley Periodicals, Inc.

  • 125.
    Josefsson, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikstrom, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Egevad, Lars
    Granfors, Torvald
    Karlberg, Lars
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance2012Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, nr 4, s. 247-257Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The aim of this study was to explore whether vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting. Material and methods. From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975-1990, tissue microarrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and were followed by watchful waiting (n = 295). The TMAs were stained for Ki67, endoglin and factor VIII-related antigen (vWf).

    Results: In univariate Cox analyses, increased Ki67 index, endoglin vascular density and vWf vascular density were associated with shorter cancer-specific survival. Ki67 index and endoglin vascular density added independent prognostic information to clinical stage, estimated tumour size and Gleason score (GS) in multivariate Cox analysis. In GS 6 tumours, high Ki67 index and high endoglin vascular density identified patients with poor outcome. After 15 years of follow-up not a single man out of 34 men with low staining for both markers (35% of all GS 6 tumours) had died of prostate cancer, in contrast to 15 prostate cancer deaths among the remaining 63 men with GS 6 tumours (65% cumulative risk of prostate cancer death). vWf vascular density in benign areas was a prognostic marker in GS 6 and 7 tumours.

    Conclusions: Men with GS 6 tumours with both low Ki67 index and endoglin vascular density staining scores have a low risk of progression. Additional studies are needed to test whether these two markers can be applied to core biopsies to select patients suitable for surveillance.

  • 126.
    Josefsson, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Egevad, Lars
    Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
    Granfors, Torvald
    Department of Urology, Central Hospital Västerås, Västerås, Sweden.
    Karlberg, Lars
    Department of Urology, Central Hospital Västerås, Västerås, Sweden.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillanceArtikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Objectives: To explore if vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting.

    Methods: From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975-1990, tissue micro-arrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and was followed by watchful waiting (n=295). The TMAs were stained for Ki67, endoglin and factor VIII related antigen (vWf).

    Results: In univariate Cox analyses, increased Ki67 index, endoglin vascular density (v.d.) and vWf v.d. were associated with shorter cancer specific survival. : Ki67 index and endoglin v.d. added independent prognostic information to clinical stage, estimated tumour size and Gleason score (GS) in multivariate Cox analysis. In GS 6 tumours high Ki67 index and high endoglin v.d. indentified patients with poor outcome. After 15 years of follow-up not a single man out of 34 men with low staining for both markers (35% of all GS 6 tumours) had died of prostate cancer, in contrast to 15 prostate cancer deaths among the remaining 63 men with GS 6 tumours (65 % cumulative risk of prostate cancer death). vWf v.d. in benign areas was a prognostic marker in GS 6 and GS 7 tumours.

    Conclusions: Men with GS 6 tumours with both low Ki67 index and endoglin v.d. staining scores have a low risk of progression. Additional studies are needed to test if these two markers can be applied to core biopsies to select patients suitable for surveillance.

  • 127.
    Josefsson, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Granfors, Torvald
    Egevad, Lars
    Karlberg, Lars
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Tumor size, vascular density and proliferation as prognostic markers in GS 6 and GS 7 prostate tumors in patients with long follow-up and non-curative treatment2005Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 48, nr 4, s. 577-583Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To investigate the prognostic value of potential markers in localized, Gleason score 6 and 7 prostate cancer (PC).

    Methods: From a consecutive series of men with PC diagnosed at transurethral resection (1975-1990),. specimens from 132 patients without metastases, with Gleason score (GS) 6 (n = 80) or 7 (n = 52) tumors followed with watchful waiting were examined. The fraction of resected prostate tissue containing cancer, the micro-vessel density (v.d.) when stained for endoglin or von Willebrand factor (vWf), and the percentage of Ki-67 labeled tumor cells were measured using immunohistochemistry.

    Results: High levels of vWf v.d., endoglin v.d., and percent cancer of the TURP specimen were significantly associated with short cancer-specific survival in Kaplan-Meier analysis of all patients with GS 6 and 7 tumors. Interestingly, a combined estimate of percent cancer and vWF v.d. could be used to identify a large subset (50%) of GS 6 tumors with only a 2.5% risk of PC death within 15 years. None of the tested markers gave independent prognostic information for the GS 7 tumors.

    Conclusions: Estimates of tumor size and vascular density may identify a large proportion of non-aggressive GS 6, but not GS 7, tumors.

  • 128. Jäderling, Fredrik
    et al.
    Akre, Olof
    Aly, Markus
    Björklund, Johan
    Olsson, Mats
    Adding, Christofer
    Öberg, Michael
    Blomqvist, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Department of Urology, Karolinska University Hospital, Solna, Sweden.
    Nyberg, Tommy
    Wiklund, Peter
    Carlsson, Stefan
    Preoperative staging using magnetic resonance imaging and risk of positive surgical margins after prostate-cancer surgery2019Inngår i: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 22, nr 3, s. 391-398Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: It is unclear whether preoperative staging using Magnetic Resonance Imaging (MRI) reduces the risk of positive margins in prostate cancer. We aimed to assess the effect on surgical margins and degree of nerve sparing of a pelvic MRI presented at a preoperative MRI conference. Methods: Single institution, observational cohort study including 1037 men that underwent robot assisted radical prostatectomy between October 2013 and June 2015. Of these, 557 underwent a preoperative MRI combined with a preoperative MRI conference and 410 did not. With whole-mount prostate specimen histopathology as gold standard we assessed the ability of MRI in finding the index tumor and the sensitivity and specificity for extra prostatic extension. We calculated relative risks for positive surgical margins and non-nerve sparing procedure, adjusting for preoperative risk factors using stabilized inverse-probability weighting. Results: MRI detected the index tumor in 80% of the cases. Non-organ confined disease (pT3) at histology was present in the MRI and the non-MRI group in 42% and 24%, respectively. Rate of positive surgical margins comparing the MRI and non-MRI groups was 26.7% and 33.7%, respectively, relative risk 0.79 [95% CI 0.65-0.96], weighted relative risk (wRR) 0.69 [95% CI 0.55-0.86]. The wRR of extensive positive surgical margins was 0.45 [95% CI 0.31-0.67]. Undergoing MRI was also associated with an increased risk of being operated with a non-nerve sparing technique (wRR, 1.84 [95% CI 1.11-3.03]). Conclusions: Our study suggests that preoperative prostate MRI in combination with a preoperative MRI conference affects the degree of nerve-sparing surgery and reduces positive surgical margins.

  • 129.
    Kindgren, Victor
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    RISK OF INCARCERATION AFTER PRIMARY GROIN HERNIA SURGERY2019Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 130.
    Klinga, Gustaf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    A retrospective evaluation of preoperative anemia in patients undergoing radical cystectomy for muscle-invasive urothelial urinary bladder cancer, with or without neoadjuvant chemotherapy2016Inngår i: SpringerPlus, E-ISSN 2193-1801, Vol. 5, artikkel-id 1167Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (NAC) can be associated with anemia, which can lead to more perioperative blood transfusions (PBT). Usage of PBT is associated with worse oncological outcomes. We evaluated the prevalence of preoperative anemia (PA) and the effect on hemoglobin levels depending on surgery timing after NAC.

    METHODS: A retrospective single-center study with 240 consecutive patients undergoing radical cystectomy (RC) between 2001 and 2014 for muscle-invasive urothelial carcinoma (MIBC). Anemia was defined according to the WHO classification (male ≤ 130 g/L, female ≤ 120 g/L). Multivariable logistical regression was used to identify factors associated with PA and Pearson correlation for evaluating the change in hemoglobin levels depending on surgery timing.

    RESULTS: Overall, 128 (53.3 %) patients were anemic pre-RC and 87 (36.3 %) patients received NAC. In a multivariable analysis, age, receipt of NAC, female gender, and low BMI were independent predictors of PA. In patients receiving NAC, the time to surgery from the last NAC cycle was correlated with the change in hemoglobin levels between the initiation of NAC and surgery.

    CONCLUSIONS: PA was common in patients undergoing RC for MIBC. Receipt of NAC was found to be a strong predictor of PA.

    CLINICAL MESSAGE: The emerging treatment of cisplatin based neoadjuvant chemotherapy for muscle-invasive bladder cancer, confers an increased risk for preoperative anemia. In the management of this malignancy, preoperative anemia renders further attention and focus.

  • 131. Kohestani, Kimia
    et al.
    Wallström, Jonas
    Dehlfors, Niclas
    Sponga, Ole Martin
    Månsson, Marianne
    Josefsson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlsson, Sigrid
    Hellstrom, Mikael
    Hugosson, Jonas
    Performance and inter-observer variability of prostate MRI (PI-RADS version 2) outside high-volume centres2019Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Despite the growing trend to embrace pre-biopsy MRI in the diagnostic pathway for prostate cancer (PC), its performance and inter-observer variability outside high-volume centres remains unknown. This study aims to evaluate sensitivity of and variability between readers of prostate MRI outside specialized units with radical prostatectomy (RP) specimen as the reference standard.

    Materials and methods: Retrospective study comprising a consecutive cohort of all 97 men who underwent MRI and subsequent RP between January 2012 and December 2014 at a private hospital in Sweden. Three readers, blinded to clinical data, reviewed all images (including 11 extra prostate MRI to reduce bias). A tumour was considered detected if the overall PI-RADS v2 score was 3-5 and there was an approximate match (same or neighbouring sector) of tumour sector according to a 24 sector system used for both MRI and whole mount sections.

    Results: Detection rate for the index tumour ranged from 67 to 76%, if PI-RADS 3-5 lesions were considered positive and 54-66% if only PI-RADS score 4-5 tumours were included. Detection rate for aggressive tumours (GS >= 4 + 3) was higher; 83.1% for PI-RADS 3-5 and 79.2% for PI-RADS 4-5. The agreement between readers showed average values of 0.41 for PI-RADS score 3-5 and 0.51 for PI-RADS score 4-5.

    Conclusions: Prostate MRI evidenced a moderate detection rate for clinically significant PC with a rather large variability between readers. Clinics outside specialized units must have knowledge of their performance of prostate MRI before considering omitting biopsies in men with negative MRI.

  • 132. Krantz, David
    et al.
    Hartana, Ciputra Adijaya
    Winerdal, Malin E
    Johansson, Markus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Alamdari, Farhood
    Jakubczyk, Tomasz
    Huge, Ylva
    Aljabery, Firas
    Palmqvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Urology Section, Department of Surgery, Östersund County Hospital, Östersund, Sweden.
    Zirakzadeh, A Ali
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Holmström, Benny
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Winqvist, Ola
    Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 688-692Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Evidence indicates that neoadjuvant chemotherapy (NAC) may promote antitumour immune responses by activating T cells. The tumour-draining sentinel node (SN) is a key site to study tumour-specific T cell activation, being the primary immunological barrier against the tumour. In this prospective study, we set out to elucidate the effects of NAC on T cell subsets in the SNs of patients with muscle-invasive urothelial bladder cancer. We found that CD8+ effector T (Teff) cell exhaustion was reduced after NAC treatment, while cytotoxicity was increased. Additionally, in complete responders (CR patients), these cells were functionally committed effectors, as displayed by epigenetic analysis. In CD4+ Teffs, NAC treatment was associated with increased clonal expansion of tumour-specific SN-derived cells, as demonstrated by a specific cell reactivity assay. In contrast, we observed an attenuating effect of NAC on regulatory T cells (Tregs) with a dose-dependent decrease in Treg frequency and reduced effector molecule expression in the remaining Tregs. In addition, multicolour flow cytometry analysis revealed that CR patients had higher Teff to activated Treg ratio, promoting antitumoural T cell activation. These results suggest that NAC reinforces the antitumour immune response by activating the effector arm of the T cell compartment and diminishing the influence of suppressive Tregs.

    PATIENT SUMMARY: In this report, we analysed the effect of chemotherapy on immune cell subsets of 40 patients with advanced bladder cancer. We found that chemotherapy has a positive effect on immune effector T cells, whereas an opposite, diminishing effect was observed for immune-suppressive regulatory T cells. We conclude that chemotherapy reinforces the antitumour immune response in bladder cancer patients.

  • 133. Kriegmair, Maximilian C.
    et al.
    Bertolo, Riccardo
    Karakiewicz, Pierre, I
    Leibovich, Bradley C.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Mir, Maria C.
    Ouzaid, Idir
    Salagierski, Maciej
    Staehler, Michael
    van Poppel, Hendrik
    Wood, Christopher C.
    Capitanio, Umberto
    Systematic Review of the Management of Local Kidney Cancer Relapse2018Inngår i: European Urology Oncology, ISSN 2588-9311, Vol. 1, nr 6, s. 512-523Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Context: Management of locally recurrent renal cancer is complex.

    Objective: In this systematic review we analyse the available literature on the management of local renal cancer recurrence.

    Evidence acquisition: A systematic search (PubMed, Web of Science, CINAHL, Clinical Trials, and Scopus) of English literature from 2000 to 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

    Evidence synthesis: The search identified 1838 articles. Of those, 36 were included in the evidence synthesis. The majority of the studies identified were retrospective and not controlled. Local recurrence after thermal ablation (TA) may be managed with repeat TA. Alternatively, salvage nephrectomy is possible. However, a higher rate of complications should be expected than after primary nephrectomy. Salvage nephrectomy and TA represent treatment options for local recurrence after partial nephrectomy. Local retroperitoneal recurrence after radical nephrectomy is ideally treated with surgical resection, for which minimally invasive approaches might be applicable to select patients. For large recurrences, addition of intraoperative radiation may improve local control. Local tumour destruction appears to be more beneficial than systemic therapy alone for local recurrences.

    Conclusions: Management of local renal cancer relapse varies according to the clinical course and prior treatments. The available data are mainly limited to noncontrolled retrospective series. After nephron-sparing treatment, TA represents an effective treatment with low morbidity. For local recurrence after radical nephrectomy, the low-level evidence available suggests superiority of surgical excision relative to systemic therapy or best supportive care. As a consequence, surgery should be prioritised when feasible and applicable.

    Patient summary: In renal cell cancer, the occurrence and management of local recurrence depend on the initial treatment. This cancer is a disease with a highly variable clinical course. After initial organ-sparing treatment, thermal ablation offers good cancer control and low rates of complications. For recurrence after radical nephrectomy, surgical excision seems to provide the best long-term cancer control and it is superior to medical therapy alone.

  • 134. Kristiansen, Anna
    et al.
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Robinson, David
    Lissbrant, Ingela Franck
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Prognostic significance and biopsy characteristics of prostate cancer with seminal vesicle invasion on radical prostatectomy: a nationwide population-based study2017Inngår i: Pathology (Sydney), ISSN 0031-3025, E-ISSN 1465-3931, Vol. 49, nr 7, s. 715-720Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to evaluate the prognostic significance of seminal vesicle invasion (SVI, pT3b) compared with extraprostatic extension (EPE) alone (pT3a) after radical prostatectomy, and to correlate pre-operative biopsy pathology with SVI and EPE. The National Prostate Cancer Register includes all prostate cancers diagnosed in Sweden. We analysed 4063 cases with stage category pT3a and 1371 cases with pT3b at radical prostatectomy between 2000 and 2012. Associations between pT3a and pT3b and progression were evaluated and adjusted for year, age, biopsy grade and s-PSA. Needle biopsy findings in these stages were compared. Patients with pT3b (n = 1371) had a higher risk of death from prostate cancer (HR 2.3, 95% CI 1.5-3.3, p < 0.001) and death from any cause (HR 1.5, 95% CI 1.2-1.8, p < 0.001) than those with pT3a (n = 4063). They were also more likely to be treated with post-operative radiotherapy (HR 1.5, 95% CI 1.4-1.7, p < 0.001) or androgen deprivation therapy (HR 3.0, 95% CI 2.5-3.7, p < 0.001), indicating clinical progression. Yet, disease-specific survival of patients with stage pT3b was 94% after 6 years. Median cancer extent in pre-operative biopsies of pT3a and pT3b was 14 and 24 mm (p < 0.001), number of positive cores was four and five, (p < 0.001) and biopsy Gleason score was 8-10 in 11.6% and 27.3%, respectively (p < 0.001). SVI of prostate cancer is associated with worse outcome after radical prostatectomy than EPE alone. However, few patients with SVI die within 6 years from surgery, suggesting that radical prostatectomy may be curative in locally advanced cancers.

  • 135. Kroger Dahlin, Britt-Inger
    et al.
    Thurm, Mascha
    Winsö, Ola
    Ljungberg, Börje
    Patient's QoL after open kidney surgery in a randomized study of spinal versus epidural analgesia in patients with renal cell carcinoma2019Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, s. 17-17Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Objective: This study was aimed to evaluate the patients perspectives, before and one month after surgery in patients treated with open surgery for renal cell carcinoma (RCC). Can effective perioperative analgesia be part of a multimodal approach to minimize morbidity and improve postoperative management [1].

    Material and Methods: A total of 135 patients with RCC in all stages 2012-2015, were randomized to receive either spinal analgesia with clonidine, or epidural analgesia in addition to the general anesthesia: The patients were stratified according to surgical technique. Inclusion criteria: ASA score I-III, age >18 years, no chronic pain medication or cognitive disorders. The patients survey used was based on the EORTC QLQ-C30. Wilcoxon Signed Rank test and Mann-Whitney-U tests were used for statistical evaluation.

    Results: A majority of the patients (117 of 135, 86%) responded to the survey. Patients groups treated with partial nephrectomy or radical nephrectomy, had significantly reduced physical and social functioning while emotional functioning improved postoperatively compared with preoperatively. In both surgical groups the patients reported significant negative financial difficulties postoperatively. Similar results was achieved for patients treated with either spinal or epidural anesthesia. The epidural group of patients experienced more negative social functioning but had an improved global health. When comparing the surgical procedures there was no significant difference in the quality of life parameters. However when comparing the analgesic groups, spinal anesthesia had significantly better physical and social functioning after surgery while the patients in the epidural group reported better global health.

    Conclusion: Patients randomized to be treated with spinal analgesia with clonidine, had better physical and social functioning postoperatively than patients randomized to be treated with epidural analgesia.

  • 136. Ladyzynski, Piotr
    et al.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. European Society of Artificial Organs.
    Vienken, Jörg
    Malchesky, Paul S
    Jan Maria Wojcicki (1946-2013): scientist, organizer, friend2014Inngår i: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 38, nr 4, s. 271-273Artikkel i tidsskrift (Annet vitenskapelig)
  • 137.
    Lalos, Othon
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Berglund, Anna-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bjerle, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Urodynamics in women with stress incontinence before and after surgery1993Inngår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 48, nr 3, s. 197-205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pad test, cystometry and analysis of micturition were performed in 36 women with stress incontinence before and a year after operation with either retropubic urethrocystopexy (n = 22) or pubococcygeal repair (n = 14). There was no difference in the subjective cure rate between the two groups of women (77% and 79%, respectively). The pad test 1 year after operation showed that 59% of the women in the urethrocystopexy group and 43% of the women in the pubococcygeal repair group had stopped leaking urine. The bladder volume had increased in both groups and the intravesical pressure of the bladder filled to the maximum had increased in the pubococcygeal repair group. The functional length of the urethra, intravesical pressure at maximal urine flow, maximal urine flow rate and urethral conductance were not affected by either operation. Pad test was a more accurate test for an objective evaluation of urine leakage before operation than were the urodynamic investigation or continence tests.

  • 138. Lardas, Michael
    et al.
    Stewart, Fiona
    Scrimgeour, Duncan
    Hofmann, Fabian
    Marconi, Lorenzo
    Dabestani, Saeed
    Bex, Axel
    Volpe, Alessandro
    Canfield, Steven E
    Staehler, Michael
    Hora, Milan
    Powles, Thomas
    Merseburger, Axel S
    Kuczyk, Markus A
    Bensalah, Karim
    Mulders, Peter F A
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lam, Thomas B L
    Systematic Review of Surgical Management of Nonmetastatic Renal Cell Carcinoma with Vena Caval Thrombus2016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 2, s. 265-280Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    CONTEXT: Overall, 4-10% of patients with renal cell carcinoma (RCC) present with venous tumour thrombus. It is uncertain which surgical technique is best for these patients. Appraisal of outcomes with differing techniques would guide practice.

    OBJECTIVE: To systematically review relevant literature comparing the outcomes of different surgical therapies and approaches in treating vena caval thrombus (VCT) from nonmetastatic RCC.

    EVIDENCE ACQUISITION: Relevant databases (Medline, Embase, and the Cochrane Library) were searched to identify relevant comparative studies. Risk of bias and confounding assessments were performed. A narrative synthesis of the evidence was presented.

    EVIDENCE SYNTHESIS: The literature search identified 824 articles. Fourteen studies reporting on 2262 patients were included. No distinct surgical method was superior for the excision of VCT, although the method appeared to be dependent on tumour thrombus level. Minimal access techniques appeared to have better perioperative and recovery outcomes than traditional median sternotomy, but the impact on oncologic outcomes is unknown. Preoperative renal artery embolisation did not offer any oncologic benefits and instead resulted in significantly worse perioperative and recovery outcomes, including possibly higher perioperative mortality. The comparison of cardiopulmonary bypass versus no cardiopulmonary bypass showed no differences in oncologic outcomes. Overall, there were high risks of bias and confounding.

    CONCLUSIONS: The evidence base, although derived from retrospective case series and complemented by expert opinion, suggests that patients with nonmetastatic RCC and VCT and acceptable performance status should be considered for surgical intervention. Despite a robust review, the findings were associated with uncertainty due to the poor quality of primary studies available. The most efficacious surgical technique remains unclear.

    PATIENT SUMMARY: We examined the literature on the benefits of surgery to remove kidney cancers that have spread to neighbouring veins. The results suggest such surgery, although challenging and associated with high risk of complications, appears to be feasible and effective and should be contemplated for suitable patients if possible; however, many uncertainties remain due to the poor quality of the data.

  • 139.
    Laveborn, Emilie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Skagerlind, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    NT-proBNP and troponin T levels differ after haemodialysis with a low versus high flux membrane2015Inngår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 38, nr 2, s. 69-75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Brain natriuretic peptide (BNP), N-terminal-proBNP (NT-proBNP), and high sensitive cardiac troponin T (TnT) are markers that are elevated in chronic kidney disease and correlate with increased risk of mortality. Data are conflicting on the effect of biomarker levels by hemodialysis (HD).Our aim was to clarify to what extent HD with low-flux (LF) versus high-flux (HF) membranes affects the plasma levels of BNP, NT-proBNP, and TnT.

    METHODS AND MATERIALS: 31 HD patients were included in a crossover design, randomized to start dialysis with a LF-HD or HF-HD dialyzer. Each patient was his/her own control. The dialyses included in the study were the first treatments of two consecutive weeks with each mode of dialysis. Patients normally on hemodiafiltration (HDF) also performed a HDF the third week. Values after HD were corrected for extent of ultrafiltration.

    RESULTS: During LF-HD the biomarkers NT-proBNP and TnT increased (15 versus 6%, P ≤ .001) while there was a slight decrease in BNP (P<.05). During HF-HD the NT-proBNP, BNP and TnT levels decreased (P ≤ .01 for all). During HDF all three markers decreased (P<.01 for all). The rise in TnT during LF-HD correlated with dialysis vintage (months on HD, r = .407, P = .026), Kt/V-urea (r = .383, P = .037), HD time in hours/treatment (r = .447, P = .013) and inversely with residual urinary output (r = -.495, P = .005). The baseline levels of BNP and NT-proBNP correlated with blood pressure.

    CONCLUSIONS: Cardiac biomarkers increase slightly during LF-HD. A HF-HD eliminates the biomarkers and can mask increases caused by, e.g., myocardial infarction.

  • 140. Li, Weiqiang
    et al.
    Middha, Mridu
    Bicak, Mesude
    Sjoberg, Daniel D.
    Vertosick, Emily
    Dahlin, Anders
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Rönn, Ann-Charlotte
    Stattin, Par
    Melander, Olle
    Ulmert, David
    Lilja, Hans
    Klein, Robert J.
    Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 710-719Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging.

    Objective: To identify single nucleotide polymorphisms (SNPs) associated with death from prostate cancer.

    Design, setting, and participants: Blood samples from 11 506 men in Sweden were collected during 1991–1996. Of these, 1053 men were diagnosed with prostate cancer and 245 died from the disease. Stage and grade at diagnosis and outcome information were obtained, and DNA from all cases was genotyped.

    Outcome measurements and statistical analysis: A total of 6 126 633 SNPs were tested for association with prostate-cancer-specific survival time using a Cox proportional hazard model, adjusted for age, stage, and grade at diagnosis. A value of 1 × 10−6 was used as suggestive significance threshold. Positive candidate SNPs were tested for association with gene expression using expression quantitative trait locus analysis.

    Results and limitations: We found 12 SNPs at seven independent loci associated with prostate-cancer-specific survival time. One of 6 126 633 SNPs tested reached genome-wide significance (p < 5 × 10−8) and replicated in an independent cohort: rs73055188 (p = 5.27 × 10−9, per-allele hazard ratio [HR] = 2.27, 95% confidence interval [CI] 1.72–2.98) in the AOX1 gene. A second SNP reached a suggestive level of significance (p < 1 × 10−6) and replicated in an independent cohort: rs2702185 (p = 7.1 × 10−7, per-allele HR = 2.55, 95% CI = 1.76–3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1 expression levels, which is associated with biochemical recurrence of prostate cancer in independent cohorts. This association is yet to be validated in other ethnic groups.

    Conclusions: The SNP rs73055188 at the AOX1 locus is associated with prostate-cancer-specific survival time, and AOX1 gene expression level is correlated with biochemical recurrence of prostate cancer.

    Patient summary: We identify two genetic markers that are associated with prostate-cancer-specific survival time.

  • 141.
    Lidgren, Anders
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap.
    Hypoxia inducible factor-1α in renal cell carcinoma2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Hypoxia Inducible Factor-1α in Renal Cell Carcinoma

    Departments of Surgical and Perioperative Sciences, Urology and Andrology; Radiation Sciences, Oncology; Medical Biosciences, Pathology; and Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden

    Background: Renal cell carcinoma (RCC) accounts for approximately 2-3% of all human cancers. A distinguished feature of RCC is vascularisation and among the three dominating RCC types conventional RCC (cRCC) generally is more vascularised than papillary RCC (pRCC) and chromophobe RCC (chRCC). Angiogenesis is a critical step in tumour progression controlled by a balance involving molecules that have positive and negative regulatory activity. A balance distorted by metabolic stress such as hypoxia, acidosis, and inflammation. Hypoxia-Inducible Factor 1α (HIF-1α) is a key transcription factor in angiogenesis and tumour progression, targeting more than a 100 genes involved in vascular growth and regulation, iron metabolism and erythropoesis, collagen matrix formation, regulation of extracellular pH, glucose uptake and metabolism, proliferation, apoptosis, differentiation, and cell viability.

    Methods: Tumour tissue and corresponding kidney cortex from nephrectomised RCC patients was used in order to characterize HIF-1α expression and one of its target genes, Glucose Transporter 1 (GLUT-1). All tumour samples were thoroughly described regarding tumour type, TNM stage, nuclear grade, tumour size, vein invasion, and patient survival. Utilizing RT-PCR, Westen Blot and Tissue micro array (TMA) we studied HIF-1α mRNA and protein expression as well as GLUT-1 protein expression, correlating them to each other and clinicopathological parameters.

    Results: Using Western Blot, HIF-1α protein expression differed significantly between the different RCC types and kidney cortex. In cRCC, high expression of HIF-1α was an independent prognostic factor for favourable prognosis.

    TMA is a useful method to analyze HIF-1α protein expression in RCC. HIF-1α levels were significantly lower in locally aggressive cRCC and patients with high levels of HIF-1 tended to have a better prognosis.

    GLUT-1 levels were higher in cRCC than in other RCC types and for cRCC a correlation to HIF-1α was seen.

    HIF-1α mRNA levels were significantly lower in cRCC compared to other RCC types and kidney cortex. An inverse correlation between HIF-1α protein expression and mRNA levels was observed.

    Summary: These results demonstrate a discrepancy between RCC types, highlighting the need to separately evaluate biological events in different RCC types. Overexpression of HIF-1α protein is not necessarily all bad and translational regulation appears more critical than anticipated. Further studies are encouraged to clarify angiogenic pathways in RCC.

  • 142.
    Lidgren, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Patologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
    Rasmuson, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Glucose transporter-1 expression in renal cell carcinoma and its correlation with hypoxia inducible factor-1 alpha2008Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 101, nr 4, s. 480-484Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To evaluate transcription factor hypoxia inducible factor-1 alpha (HIF-1 alpha) activity, by analysing a target gene for HIF-1 alpha, glucose transporter-1 (GLUT-1), using a tissue microarray (TMA) in different types of renal cell carcinoma (RCC, a tumour with a variable clinical course, partly due to angiogenic activity), as angiogenesis is important for tumour progression and metastatic spread, and is activated by hypoxia.

    PATIENTS AND METHODS: GLUT-1 and HIF-1 alpha expressions were semiquantitatively analysed using immunohistological staining of a prepared TMA, using samples from 187 patients, including 148 with conventional, 26 with papillary and 13 with chromophobe RCC.

    RESULTS: GLUT-1 staining was found mainly in the cytoplasm. The tumours were subdivided into GLUT -1(LOW) and GLUT-1(HIGH), based on staining intensity. There was a significant difference in GLUT-1 expression between RCC types (P < 0.05). In conventional RCC, GLUT-1 had no correlation with clinicopathological variables. By contrast there was a correlation with tumour stage in papillary RCC. There was an insignificant trend to better survival of patients with GLUT-1(LOW) expression in both conventional and papillary RCC. GLUT-1 correlated significantly (P = 0.008) with HIF-1 alpha.

    CONCLUSIONS: Most patients with conventional RCC had GLUT-1(HIGH) staining and there was a significant correlation with HIF-1 alpha. In papillary RCC, GLUT-1 expression was associated with stage; GLUT-1 expression was significantly higher in conventional RCC than in papillary and chromophobe RCC. GLUT-1(LOW) in both papillary and conventional RCC appeared to correspond with a better prognosis.

  • 143. Liedberg, Fredrik
    et al.
    Hagberg, Oskar
    Aljabery, Firas
    Gårdmark, Truls
    Hosseini, Abolfazl
    Jahnson, Staffan
    Jancke, Georg
    Jerlström, Tomas
    Malmström, Per-Uno
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ströck, Viveka
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Sciences, Uppsala University, Uppsala.
    Holmberg, Lars
    Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study2019Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, nr 3, s. 449-456Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the association between hospital volume and overall survival (OS), cancer-specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of <3 months.

    PATIENTS AND METHODS: We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1-T3 in Sweden between 1997 and 2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at ≥25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually.

    RESULTS: PSMAV in the highest tertile (≥25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75-1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of >3 months after diagnosis.

    CONCLUSIONS: The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.

  • 144. Liedberg, Fredrik
    et al.
    Hagberg, Oskar
    Aljabery, Firas
    Gårdmark, Truls
    Hosseini, Abolfazl
    Jahnson, Staffan
    Jancke, Georg
    Jerlström, Tomas
    Malmström, Per-Uno
    Sherif, Amir
    Umeå universitet.
    Ströck, Viveka
    Häggström, Christel
    Umeå universitet. Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care in Sweden: a nationwide population-based study2019Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, s. 20-20Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Objective: To investigate the association between hospital volume on overall survival (OS), cancer-specific survival (CSS), and quality of care defined as use of extended lymphadenectomy, continent reconstruction, neoadjuvant chemotherapy and treatment delay less than 3 months.

    Materials and Methods: We used Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent radical cystectomy for primary invasive bladder cancer stage T1-T3 in Sweden 1997-2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level and neoadjuvant chemotherapy. PSMAV was either categorised in tertiles, dichotomised (at 25 or more cystectomies annually), or used as a continuous variable for every increase of 10 cystectomies annually.

    Results: PSMAV in the highest tertile (25 or more cystectomies annually) was associated with improved overall survival (HR 0.87, 95% CI 0.751.0), with a similar trend for cancer-specific survival (HR 0.87, 95% CI 0.731.04). With PSMAV as a continuous variable, overall survival was improved for every increase of 10 cystectomies annually (HR 0.95, 95% CI 0.900.99). Moreover, higher PSMAV was associated with increased use of extended lymphadenectomy, continent reconstruction and neoadjuvant chemotherapy, but also more frequently with a treatment delay of more than 3 months after diagnosis.

    Conclusions: The current study supports centralisation of radical cystectomy for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.

  • 145. Liedberg, Fredrik
    et al.
    Hagberg, Oskar
    Holmäng, Sten
    Hosseini Aliabad, Abolfazl
    Jancke, Georg
    Ljungberg, Börje
    Department of Urology, Norrland University Hospital, Umeå, Sweden.
    Malmström, Per-Uno
    Åberg, Hanna
    Jahnson, Staffan
    Local recurrence and progression of non-muscle-invasive bladder cancer in Sweden: a population-based follow-up study2015Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, nr 4, s. 290-295Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) in a large population-based setting.

    MATERIALS AND METHODS: Patients with bladder cancer (stage Ta, T1 or carcinoma in situ) diagnosed in 2004-2007 (n = 5839) in Sweden were investigated 5 years after diagnosis using a questionnaire. Differences in time to recurrence and progression were analysed in relation to age, gender, tumour stage and grade, intravesical treatment, healthcare region, and hospital volume of NMIBC patients (stratified in three equally large groups).

    RESULTS: Local bladder recurrence and progression occurred in 50 and 9% of the patients, respectively. The rate of local recurrence was 56% in the southern healthcare region compared to 37% in the northern region. A multivariate Cox proportional hazards model, adjusting for age, gender, tumour stage and grade, intravesical treatment, healthcare region and hospital volume, showed that recurrence was associated with TaG2 and T1 disease, no intravesical treatment and treatment in the southern healthcare region, but indicated a lower risk of recurrence in the northern healthcare region. Adjusting for the same factors in a multivariate analysis suggested that increased relative risk of progression correlated with older age, higher tumour stage and grade, and diagnosis in the Uppsala/Örebro healthcare region, whereas such risk was decreased by intravesical treatment (relative risk 0.72, 95% confidence interval 0.55-0.93, p = 0.012).

    CONCLUSIONS: The incidence of NMIBC recurrence and progression was found to be high in Sweden, and important disparities in outcome related to care patterns appear to exist between different healthcare regions.

  • 146. Liedberg, Fredrik
    et al.
    Holmberg, Erik
    Holmäng, Sten
    Ljungberg, Börje
    Malmström, Per-Uno
    Månsson, Wiking
    Nunez, Leyla
    Wessman, Catrin
    Wijkström, Hans
    Jahnson, Staffan
    Long-term follow-up after radical cystectomy with emphasis on complications and reoperations: a Swedish population-based survey.2012Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, nr 1, s. 14-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To evaluate outcome after radical cystectomy for primary bladder cancer in a large population-based material.

    MATERIAL AND METHODS: Between 1997 and 2002 all patients treated with radical cystectomy within 3 months after diagnosis of primary bladder cancer without distant metastasis were retrieved through the Swedish Bladder Cancer Registry. A follow-up questionnaire was distributed to all units where the primary registration of patients was performed. Follow-up data on recurrence date were retrieved from the patient charts and causes of death were obtained from the Swedish Cause of Death Registry until 2003.

    RESULTS: During the study period radical cystectomy was performed in 39 units in Sweden, of which only five units were considered high-volume hospitals performing 10 or more procedures annually. Mean blood loss was 2300 ml (median 2000 ml) and the 90-day mortality rate was 5.7%. Blood loss was higher in high-volume units than in hospitals with lower hospital volumes, but the 90-day mortality rates were similar. During a median follow-up of 3.5 years, 24% of the patients were submitted to a reoperation. Reoperation rates were significantly higher in patients who received a continent urinary diversion (29%) compared with an ileal conduit (22%, p < 0.015).

    CONCLUSIONS: Radical cystectomy was associated with a reoperation rate of 24% in Sweden during the study period. The reoperation rates were higher in patients receiving a continent cutaneous diversion or bladder substitution. Blood loss was higher in high-volume units; otherwise, surgical volume did not affect mortality rates, cancer-specific survival or reoperation rates.

  • 147.
    Lindgren, Pierre
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    A pilot study investigation of muscle invasive bladder cancer and the national standard of treatment2018Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 148.
    Lindh, A.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sjöström, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Samuelsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Non-face-to-face treatment of stress urinary incontinence: predictors of success after 1 year2015Inngår i: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 34, nr S3, s. S443-S444Artikkel i tidsskrift (Annet vitenskapelig)
  • 149.
    Lindh, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sjöström, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Samuelsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Non-face-to-face treatment of stress urinary incontinence: predictors of success after 1 year2016Inngår i: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 27, nr 12, s. 1857-1865Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION AND HYPOTHESIS: The objective was to determine predictors of long-term success in women with stress urinary incontinence (SUI) treated with a 3-month pelvic floor muscle training (PFMT) program delivered via the Internet or a brochure.

    METHODS: We included 169 women with SUI ≥1 time/week who completed the 1-year follow-up (n = 169, mean age 50.3, SD 10.1 years). Three outcome variables defined success after 1 year: Patient Global Impression of Improvement (PGI-I), International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF), and sufficient treatment. Using logistic regression, we analyzed data from the baseline, and from the 4-month and 1-year follow-ups, for potential predictors of success.

    RESULTS: Of the participants, 77 % (129 out of 169) were successful in ≥1 of the outcomes, 23 % (37 out of 160) were successful in all 3. Participants with successful short-term results were more likely to succeed in the corresponding outcome at 1 year than those without successful short-term results (adjusted odds ratios [ORs]: PGI 5.15, 95 % confidence interval [CI] 2.40-11.03), ICIQ-UI SF 6.85 (95 % CI 2.83-16.58), and sufficient treatment 3.78 (95 % CI 1.58-9.08). Increasing age predicted success in PGI-I and sufficient treatment (adjusted OR 1.06, 95 % CI 1.02-1.10, and 1.08, 95 % CI, 1.03-1.13 respectively). Compared with not training regularly, regular PFMT at 1 year predicted success for PGI and sufficient treatment (adjusted OR 2.32, 95 % CI 1.04-5.20, and 2.99, 95 % CI 1.23-7.27 respectively).

    CONCLUSION: The long-term success of a non-face-to-face treatment program for SUI with a focus on PFMT can be predicted by successful short-term results, increasing age, and the performance of regular PFMT after 1 year.

  • 150. Lindskog, Magnus
    et al.
    Wahlgren, Thomas
    Sandin, Rickard
    Kowalski, Jan
    Jakobsson, Maria
    Lundstam, Sven
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Harmenberg, Ulrika
    Overall survival in Swedish patients with renal cell carcinoma treated in the period 2002 to 2012: Update of the RENCOMP study with subgroup analysis of the synchronous metastatic and elderly populations2017Inngår i: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 35, nr 9, s. 541.e15-541.e22Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: This retrospective study investigated overall survival (OS) and factors influencing OS in Swedish patients with metastatic renal cell carcinoma (mRCC) during the pre- (2002-2005), early (2006-2008), and late (2009-2012) targeted therapy (TT) era. Methods: Three national Swedish registries identified patients with mRCC. Median OS was estimated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. Subgroup analysis was conducted for patients with synchronous metastases (Ml) and the elderly (aged >= 75 y). Results: A total of 4,217 patients with mRCC were identified, including 1,533 patients with Ml and 1,275 elderly patients. For patients with mRCC diagnosed in 2002 to 2005, 2006 to 2008, and 2009 to 2012, median OS was 10.0, 13.0, and 18.0 months. Similarly, median OS improved in the M1 and elderly populations. Elderly patients were less likely to be prescribed TT (>= 75 vs. <75 y): 18.3 vs. 63.5% (in 2006-2008) and 28.6% vs. 55.9% (in 2009-2012). Diagnosis of mRCC in 2009 to 2012, nephrectomy and TT prescription were associated with improved OS in the total mRCC, Ml, and elderly populations. Conclusion: This real-world study showed continued significant improvement in mRCC OS during the late TT era, including in Ml and elderly populations. TT should be considered for all patients with mRCC based on tolerability, regardless of age. 

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