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  • 101. 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 bladder2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 2, p. 124-129Article in journal (Refereed)
    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.

  • 102. Jansson, K. Fredrik
    et al.
    Akre, Olof
    Garmo, Hans
    Bill-Axelson, Anna
    Adolfsson, Jan
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bratt, Ola
    Concordance of tumor differentiation among brothers with Prostate Cancer2012In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 62, no 4, p. 656-661Article in journal (Refereed)
    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.

  • 103. Jerlström, Tomas
    et al.
    Chen, Ruoqing
    Liedberg, Fredrik
    Andrén, Ove
    Ströck, Viveka
    Aljabery, Firas A S
    Hosseini, Abolfazl
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    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 study2019In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726Article in journal (Refereed)
    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.

  • 104. Jerlström, Tomas
    et al.
    Gårdmark, Truls
    Carringer, Malcolm
    Holmäng, Sten
    Liedberg, Fredrik
    Hosseini, Abolfazl
    Malmström, Per-Uno
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hagberg, Oskar
    Jahnson, Staffan
    Urinary bladder cancer treated with radical cystectomy: perioperative parameters and early complications prospectively registered in a national population-based database2014In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 48, no 4, p. 334-340Article in journal (Refereed)
    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.

  • 105. Jerlström, Tomas
    et al.
    Gårdmark, Truls
    Ströck, Viveka
    Aljabery, Firas A. -S.
    Hosseini, Abolfazl A.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    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 cancer2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, p. 34-35Article in journal (Other academic)
  • 106.
    Johansson, Maja
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. 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 University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Ragagnin, Gianna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Doverskog, Magnus
    Umecrine Cognit AB, Solna, Sweden.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    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 encephalopathy2015In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 309, no 5, p. G400-G409Article in journal (Refereed)
    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.

  • 107.
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Prostate cancer aetiology: epidemiological studies of the IGF- and one-carbon metabolism pathways2008Doctoral thesis, comprehensive summary (Other academic)
    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.

  • 108.
    Johansson, Mattias
    et al.
    International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Holmström, Benny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hinchliffe, Sally R
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stenman, Ulf-Håkan
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wiklund, Fredrik
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Combining 33 genetic variants with prostate-specific antigen for prediction of prostate cancer: longitudinal study2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 1, p. 129-137Article in journal (Refereed)
    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.

  • 109.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. 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 University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Genetic and plasma variation of insulin-like growth factor binding proteins in relation to prostate cancer incidence and survival2009In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 69, no 12, p. 1281-1291Article in journal (Refereed)
    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.

  • 110.
    Jonsson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forsberg, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    EVALUATION OF AIR MICRO BUBBLES IN DIALYSIS SYSTEMS IN VITRO2014In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 63, no 5, p. A61-A61Article in journal (Other academic)
  • 111.
    Jonsson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindmark, Lorentz
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundberg, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Formation of Blood Foam in the Air Trap During Hemodialysis Due to Insufficient Automatic Priming of Dialyzers2018In: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 42, no 5, p. 533-539Article in journal (Refereed)
    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.

  • 112.
    Josefsson, Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Prognostic markers in prostate cancer: studies of a watchful waiting cohort with long follow up2011Doctoral thesis, comprehensive summary (Other academic)
    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.

  • 113.
    Josefsson, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adamo, Hani
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Granfors, Torvald
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Laurent, Anna Engström
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome2011In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 179, no 4, p. 1961-1968Article in journal (Refereed)
    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.

  • 114.
    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 cancer2018In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 50, p. 29403-29413Article in journal (Refereed)
    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.

  • 115.
    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 Cancer2017In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, no 8, p. 849-858Article in journal (Refereed)
    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.

  • 116.
    Josefsson, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikstrom, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Egevad, Lars
    Granfors, Torvald
    Karlberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance2012In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, no 4, p. 247-257Article in journal (Refereed)
    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.

  • 117.
    Josefsson, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    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 University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillanceArticle in journal (Other academic)
    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.

  • 118.
    Josefsson, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Granfors, Torvald
    Egevad, Lars
    Karlberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    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 treatment2005In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 48, no 4, p. 577-583Article in journal (Refereed)
    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.

  • 119. Jäderling, Fredrik
    et al.
    Akre, Olof
    Aly, Markus
    Björklund, Johan
    Olsson, Mats
    Adding, Christofer
    Öberg, Michael
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. 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 surgery2019In: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 22, no 3, p. 391-398Article in journal (Refereed)
    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.

  • 120.
    Klinga, Gustaf
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    A retrospective evaluation of preoperative anemia in patients undergoing radical cystectomy for muscle-invasive urothelial urinary bladder cancer, with or without neoadjuvant chemotherapy2016In: SpringerPlus, E-ISSN 2193-1801, Vol. 5, article id 1167Article in journal (Refereed)
    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.

  • 121. Krantz, David
    et al.
    Hartana, Ciputra Adijaya
    Winerdal, Malin E
    Johansson, Markus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Alamdari, Farhood
    Jakubczyk, Tomasz
    Huge, Ylva
    Aljabery, Firas
    Palmqvist, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urology Section, Department of Surgery, Östersund County Hospital, Östersund, Sweden.
    Zirakzadeh, A Ali
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmström, Benny
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. 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 Cancer2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, no 6, p. 688-692Article in journal (Refereed)
    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.

  • 122. Kriegmair, Maximilian C.
    et al.
    Bertolo, Riccardo
    Karakiewicz, Pierre, I
    Leibovich, Bradley C.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    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 Relapse2018In: European Urology Oncology, ISSN 2588-9311, Vol. 1, no 6, p. 512-523Article, review/survey (Refereed)
    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.

  • 123. Kristiansen, Anna
    et al.
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Robinson, David
    Lissbrant, Ingela Franck
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Prognostic significance and biopsy characteristics of prostate cancer with seminal vesicle invasion on radical prostatectomy: a nationwide population-based study2017In: Pathology (Sydney), ISSN 0031-3025, E-ISSN 1465-3931, Vol. 49, no 7, p. 715-720Article in journal (Refereed)
    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.

  • 124. 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 carcinoma2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, p. 17-17Article in journal (Other academic)
    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.

  • 125. Ladyzynski, Piotr
    et al.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. European Society of Artificial Organs.
    Vienken, Jörg
    Malchesky, Paul S
    Jan Maria Wojcicki (1946-2013): scientist, organizer, friend2014In: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 38, no 4, p. 271-273Article in journal (Other academic)
  • 126.
    Lalos, Othon
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Berglund, Anna-Lena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bjerle, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Urodynamics in women with stress incontinence before and after surgery1993In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 48, no 3, p. 197-205Article in journal (Refereed)
    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.

  • 127. 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 University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lam, Thomas B L
    Systematic Review of Surgical Management of Nonmetastatic Renal Cell Carcinoma with Vena Caval Thrombus2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 2, p. 265-280Article, review/survey (Refereed)
    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.

  • 128.
    Laveborn, Emilie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindmark, Krister
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Skagerlind, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    NT-proBNP and troponin T levels differ after haemodialysis with a low versus high flux membrane2015In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 38, no 2, p. 69-75Article in journal (Refereed)
    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.

  • 129. Li, Weiqiang
    et al.
    Middha, Mridu
    Bicak, Mesude
    Sjoberg, Daniel D.
    Vertosick, Emily
    Dahlin, Anders
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rönn, Ann-Charlotte
    Stattin, Par
    Melander, Olle
    Ulmert, David
    Lilja, Hans
    Klein, Robert J.
    Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, no 6, p. 710-719Article in journal (Refereed)
    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.

  • 130.
    Lidgren, Anders
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Hypoxia inducible factor-1α in renal cell carcinoma2007Doctoral thesis, comprehensive summary (Other academic)
    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.

  • 131.
    Lidgren, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Klinisk kemi.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Glucose transporter-1 expression in renal cell carcinoma and its correlation with hypoxia inducible factor-1 alpha2008In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 101, no 4, p. 480-484Article in journal (Refereed)
    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.

  • 132. Liedberg, Fredrik
    et al.
    Hagberg, Oskar
    Aljabery, Firas
    Gårdmark, Truls
    Hosseini, Abolfazl
    Jahnson, Staffan
    Jancke, Georg
    Jerlström, Tomas
    Malmström, Per-Uno
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ströck, Viveka
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. 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 study2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410XArticle in journal (Refereed)
    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.

  • 133. Liedberg, Fredrik
    et al.
    Hagberg, Oskar
    Aljabery, Firas
    Gårdmark, Truls
    Hosseini, Abolfazl
    Jahnson, Staffan
    Jancke, Georg
    Jerlström, Tomas
    Malmström, Per-Uno
    Sherif, Amir
    Umeå University.
    Ströck, Viveka
    Häggström, Christel
    Umeå University. 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 study2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, p. 20-20Article in journal (Other academic)
    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.

  • 134. 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 study2015In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 4, p. 290-295Article in journal (Refereed)
    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.

  • 135. 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.2012In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, no 1, p. 14-8Article in journal (Refereed)
    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.

  • 136.
    Lindgren, Pierre
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    A pilot study investigation of muscle invasive bladder cancer and the national standard of treatment2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 137.
    Lindh, A.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sjöström, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Non-face-to-face treatment of stress urinary incontinence: predictors of success after 1 year2015In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 34, no S3, p. S443-S444Article in journal (Other academic)
  • 138.
    Lindh, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sjöström, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Non-face-to-face treatment of stress urinary incontinence: predictors of success after 1 year2016In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 27, no 12, p. 1857-1865Article in journal (Refereed)
    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.

  • 139. Lindskog, Magnus
    et al.
    Wahlgren, Thomas
    Sandin, Rickard
    Kowalski, Jan
    Jakobsson, Maria
    Lundstam, Sven
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    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 populations2017In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 35, no 9, p. 541.e15-541.e22Article in journal (Refereed)
    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. 

  • 140.
    Ljungberg, Borje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Nephron-Sparing Surgery Strategy: The Current Standard for the Treatment of Localised Renal Cell Carcinoma2011In: European urology. Supplement, ISSN 1569-9056, E-ISSN 1878-1500, Vol. 10, no 3, p. E49-E51Article in journal (Refereed)
    Abstract [en]

    Context: In the past few years, there has been a trend towards nephron-sparing surgery (NSS) strategies in renal cell carcinoma (RCC). The previous standard treatment-radical nephrectomy (RN)-has been abandoned, because a number of studies have shown similar oncologic outcomes after NSS for localised RCCs at least up to 7 cm. RN is recommended only in patients with locally advanced tumour growth; those who have an unfavourable tumour location; or for other clinical reasons, such as general health. Objective: The major advantage of NSS is the preservation of renal function. Evidence acquisition: Medical literature was retrieved from PubMed. Evidence synthesis: Already, one-fourth of patients in the current RCC population having tumours <4 cm in size have significantly impaired renal function diagnostic for stage 3 chronic kidney disease. Patients who have and those at risk for impaired renal function of the contralateral kidney have a higher risk for cardiovascular events and decreased overall mortality after RN. Conclusions: In general, NSS is currently advocated for patients with pT1 RCCs whenever technically feasible. This recommendation is based on the evidence that preserving kidney function in the long term results in reduced frequency of cardiovascular events and decreased overall mortality than after RN. Compared with RN, NSS has slightly higher complication rates but is a safe technique offering similar oncologic results. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 141.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Kidney cancer: a new nomogram predicting survival in renal cell carcinoma2010In: Nature reviews. Urology, ISSN 1759-4820, Vol. 7, no 8, p. 423-424Article in journal (Refereed)
  • 142.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Re: can partial nephrectomy preserve renal function and modify survival in comparison with radical nephrectomy?2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 3, p. 595-596Article in journal (Refereed)
  • 143.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    The role of metastasectomy in renal cell carcinoma in the era of targeted therapy2013In: Current Urology Reports, ISSN 1527-2737, Vol. 14, no 1, p. 19-25Article in journal (Refereed)
    Abstract [en]

    Despite contemporary innovations in systemic therapy and surgical treatment, renal cell carcinoma (RCC) remains the most lethal urologic malignancy. Still, around 20 % of patients with RCC present with metastases at diagnosis, and 40-50 % of those with localized advanced disease will ultimately progress to metastatic disease. Although the new, targeted therapy paradigms have changed the treatment of patients with advanced RCC and offer prolonged survival, cure is extremely uncommon in the absence of surgical resections. In this paper, the current role of metastasectomy is reviewed. Searches were carried out in the PubMed database and the Cochrane Library of Controlled Clinical Trials. While there is no randomized study available, recent large observational studies have better defined the prognosis of patients with metastatic RCC with or without metastasectomy. In multivariate analysis, independent predictive factors included male gender, disease-free interval > 1 year, single metastatic site and complete metastasectomy. Other reports from selected patient materials show 29-31 % 5-year overall survival rates. In patients with recurrent disease after resection of a lung metastasis, 60 % were able to undergo a subsequent resection, compared with 25 % with recurrent bone metastasis. Also, metastasectomy after initial systemic therapy gave partial or complete response in a majority of patients. In these patients, the median survival was 4.7 years and 21 % remained free of disease at last follow-up. Patients with metastatic renal cell carcinoma should be considered for multimodal therapy, including surgery of metastatic lesions. A proportion of patients will achieve long-term survival with aggressive surgical resection.

  • 144.
    Ljungberg, Börje
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Albiges, Laurance
    Abu-Ghanem, Yasmin
    Bensalan, Karim
    Dabestani, Saeed
    Montes, Sergio Fernandez-Pello
    Giles, Rachel H.
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Kuusk, Teele
    Lam, Thomas B.
    Marconi, Lorenzo
    Merseburger, Axel S.
    Powles, Thomas
    Staehler, Michael
    Tahbaz, Rana
    Volpe, Alessandro
    Bex, Axel
    European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 5, p. 799-810Article in journal (Refereed)
    Abstract [en]

    Context: The European Association of Urology Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC.

    Objective: To provide an updated RCC guideline based on standardised methodology including systematic reviews, which is robust, transparent, reproducible, and reliable.

    Evidence acquisition: For the 2019 update, evidence synthesis was undertaken based on a comprehensive and structured literature assessment for new and relevant data. Where necessary, formal systematic reviews adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were undertaken. Relevant databases (Medline, Cochrane Libraries, trial registries, conference proceedings) were searched until June 2018, including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm, systematic reviews, and meta-analyses. Where relevant, risk of bias (RoB) assessment, and qualitative and quantitative syntheses of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Clinical practice recommendations were developed and issued based on the modified GRADE framework.

    Evidence synthesis: All chapters of the RCC guidelines were updated based on a structured literature assessment, for prioritised topics based on the availability of robust data. For RCTs, RoB was low across studies. For most non-RCTs, clinical and methodological heterogeneity prevented pooling of data. The majority of included studies were retrospective with matched or unmatched cohorts, based on single- or multi-institutional data or national registries. The exception was for the treatment of metastatic RCC, for which there were several large RCTs, resulting in recommendations based on higher levels of evidence.

    Conclusions: The 2019 RCC guidelines have been updated by the multidisciplinary panel using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2019.

    Patient summary: The European Association of Urology Renal Cell Carcinoma Guideline Panel has thoroughly evaluated the available research data on kidney cancer to establish international standards for the care of kidney cancer patients.

  • 145.
    Ljungberg, Börje
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bensalah, Karim
    Canfield, Steven
    Dabestani, Saeed
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas
    Marconi, Lorenzo
    Merseburger, Axel S.
    Mulders, Peter
    Powles, Thomas
    Staehler, Michael
    Volpe, Alessandro
    Bex, Axel
    EAU Guidelines on Renal Cell Carcinoma: 2014 Update2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, no 5, p. 913-924Article in journal (Refereed)
    Abstract [en]

    Context: The European Association of Urology Guideline Panel for Renal Cell Carcinoma (RCC) has prepared evidence-based guidelines and recommendations for RCC management. Objectives: To provide an update of the 2010 RCC guideline based on a standardised methodology that is robust, transparent, reproducible, and reliable. Evidence acquisition: For the 2014 update, the panel prioritised the following topics: percutaneous biopsy of renal masses, treatment of localised RCC (including surgical and nonsurgical management), lymph node dissection, management of venous thrombus, systemic therapy, and local treatment of metastases, for which evidence synthesis was undertaken based on systematic reviews adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Relevant databases (Medline, Cochrane Library, trial registries, conference proceedings) were searched (January 2000 to November 2013) including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm. Risk of bias (RoB) assessment and qualitative and quantitative synthesis of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Evidence synthesis: All chapters of the RCC guideline were updated. For the various systematic reviews, the search identified a total of 10 862 articles. A total of 151 studies reporting on 78 792 patients were eligible for inclusion; where applicable, data from RCTs were included and meta-analyses were performed. For RCTs, there was low RoB across studies; however, clinical and methodological heterogeneity prevented data pooling for most studies. The majority of studies included were retrospective with matched or unmatched cohorts based on single or multi-institutional data or national registries. The exception was for systemic treatment of metastatic RCC, in which several RCTs have been performed, resulting in recommendations based on higher levels of evidence. Conclusions: The 2014 guideline has been updated by a multidisciplinary panel using the highest methodological standards, and provides the best and most reliable contemporary evidence base for RCC management. Patient summary: The European Association of Urology Guideline Panel for Renal Cell Carcinoma has thoroughly evaluated available research data on kidney cancer to establish international standards for the care of kidney cancer patients. 

  • 146.
    Ljungberg, Börje
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Campbell, Steven C.
    Section of Urologic Oncology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
    Cho, Han Yong
    Department of Urology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Korea.
    Jacqmin, Didier
    Service de Chirurgie Urologique, 1 Place de l’Hôpital, Strasbourg, France.
    Lee, Jung Eun
    Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
    Weikert, Steffen
    Department of Urology, Charité – University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
    Kiemeney, Lambertus A.
    Department of Epidemiology, Biostatistics and Health Technology Assessment, Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
    The epidemiology of renal cell carcinoma2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 4, p. 615-621Article, review/survey (Refereed)
    Abstract [en]

    Context: Kidney cancer is among the 10 most frequently occurring cancers in Western communities. Globally, about 270 000 cases of kidney cancer are diagnosed yearly and 116 000 people die from the disease. Approximately 90% of all kidney cancers are renal cell carcinomas (RCC). Objective: The causes of RCC are not completely known. We have reviewed known aetiologic factors.

    Evidence acquisition: The data provided in the current review are based on a thorough review of available original and review articles on RCC epidemiology with a systemic literature search using Medline.

    Evidence synthesis: Smoking, overweight and obesity, and germline mutations in specific genes are established risk factors for RCC. Hypertension and advanced kidney disease, which makes dialysis necessary, also increase RCC risk. Specific dietary habits and occupational exposure to specific carcinogens are suspected risk factors, but results in the literature are inconclusive. Alcohol consumption seems to have a protective effect for reasons yet unknown. Hardly any information is available for some factors that may have a high a priori role in the causation of RCC, such as salt consumption.

    Conclusions: Large collaborative studies with uniform data collection seem to be necessary to elucidate a complete list of established risk factors of RCC. This is necessary to make successful prevention possible for a disease that is diagnosed frequently in a stage where curative treatment is not possible anymore.

  • 147.
    Ljungberg, Börje
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Campbell, Steven C.
    Choi, Han Yong
    Jacqmin, Didier
    Lee, Jung Eun
    Weikert, Steffen
    Kiemeney, Lambertus A.
    Corrigendum to "The Epidemiology of Renal Cell Carcinoma" (vol 60, pg 615, 2011)2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 6, p. 1317-1317Article in journal (Refereed)
  • 148.
    Ljungberg, Börje
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Cowan, Nigel C
    Hanbury, Damian C
    Hora, Milan
    Kuczyk, Markus A
    Merseburger, Axel S
    Patard, Jean-Jacques
    Mulders, Peter F A
    Sinescu, Ioanel C
    EAU guidelines on renal cell carcinoma: the 2010 update2010In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 58, no 3, p. 398-406Article in journal (Refereed)
    Abstract [en]

    Context and objectives

    The European Association of Urology Guideline Group for renal cell carcinoma (RCC) has prepared these guidelines to help clinicians assess the current evidence-based management of RCC and to incorporate the present recommendations into daily clinical practice.

    Evidence acquisition

    The recommendations provided in the current updated guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials.

    Evidence synthesis

    A number of recent prospective randomised studies concerning RCC are now available with a high level of evidence, whereas earlier publications were based on retrospective analyses, including some larger multicentre validation studies, meta-analyses, and well-designed controlled studies.

    Conclusions

    These guidelines contain information for the treatment of an individual patient according to a current standardised general approach. Updated recommendations concerning diagnosis, treatment, and follow-up can improve the clinical handling of patients with RCC.

    Take Home Message

    This review of the 2010 European Association of Urology renal cell carcinoma guidelines is intended to help clinicians access knowledge of current evidence-based management according to a standardised general approach. Structured literature searches were carried out in different databases of systematic reviews and clinical trials. Grade of recommendation was assigned based on the underlying evidence.

  • 149.
    Ljungberg, Börje
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Gudmundsson, Eirikur
    Christensen, Stina
    Lundstam, Sven
    Practice patterns for the surgical treatment of T1 renal cell carcinoma: a nationwide population-based register study2014In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 48, no 5, p. 445-452Article in journal (Refereed)
    Abstract [en]

    Objective. Treatment of renal cell carcinoma (RCC) with radical nephrectomy (RN) induces chronic kidney disease more frequently compared with nephron-sparing surgery (NSS), which may have an impact on overall survival. Thus, NSS is recommended for RCCs up to 7 cm (T1). The aim of this study was to determine the extent to which these recommendations are implemented in clinical practice. Material and methods. Data were extracted from the Swedish National Kidney Cancer Register, a population-based register covering 98% of all RCCs in Sweden. In total, 3158 patients (1892 men, 1266 women) were primarily diagnosed with cT1N0M0 and treated surgically during 2005-2011. The administered treatments were evaluated between different hospitals as well as between the 21 independent healthcare counties. Results. In all, 742 patients were treated with NSS, 2339 with RN and 77 with minimally invasive ablative treatments. For cT1a RCC, patients treated with NSS increased from 22% in 2005 to 53% in 2011, and for cT1b from 2% to 10%. Nephron-sparing treatments for cT1a RCC were performed in 62% in university hospitals, 34% in intermediate- and 11% in low-volume hospitals. There was significant (p < 0.001) variation (31-67%) between the university hospitals and also for patient care in the 21 different counties (16-78%). There was an increased relative survival after NSS for T1a patients compared with RN. The register design by itself indicates limitations using data gathered from all Swedish hospitals. Conclusions. NSS was underutilized in many hospitals and a patient's chance of being offered NSS varied according to their place of residence. Patients with cT1a RCC treated with NSS had a significantly better relative survival than those treated with RN.

  • 150.
    Ljungberg, Börje
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Guomundsson, Eirikur
    Hellborg, Henrik
    Erikson, Stina
    Lundstam, Sven
    Reply from Authors re: Eric C. Umbreit, R. Houston Thompson. Metastatic Potential of the Small Renal Mass: Why Can't We Agree? Eur Urol 2011;60:983-52011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 5, p. 985-986Article in journal (Refereed)
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