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  • 1.
    Abuhasanein, Suleiman
    et al.
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Surgery, Urology Section, NU Hospital Group, Uddevalla, Sweden.
    Chaves, Vanessa
    Department of Surgery, Urology Section, NU Hospital Group, Uddevalla, Sweden.
    Mohsen, Ali Moustafa
    Department of Surgery, Urology Section, NU Hospital Group, Uddevalla, Sweden.
    Al-Haddad, Jasmine
    Department of Surgery, Urology Section, NU Hospital Group, Uddevalla, Sweden.
    Sunila, Merete
    Department of Surgery, Urology Section, NU Hospital Group, Uddevalla, Sweden.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Göteborg, Region Västra Götaland, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Swärd, Jesper
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Kjölhede, Henrik
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Göteborg, Region Västra Götaland, Sweden.
    Diagnostic value of repeated comprehensive investigation with CT urography and cystoscopy for recurrent macroscopic haematuria2024In: BJUI Compass, E-ISSN 2688-4526, Vol. 5, no 2, p. 253-260Article in journal (Refereed)
    Abstract [en]

    Objectives: To perform a descriptive analysis of a series of patients with recurrent macroscopic haematuria after a primary standard evaluation including computed tomography urography (CTU) and cystoscopy negative for urinary bladder cancer (UBC) and upper tract urothelial cancer (UTUC) and to identify potential factors associated with occurrence of recurrent macroscopic haematuria.

    Methods: All patients older than 50 years who underwent urological investigation for macroscopic haematuria with both cystoscopy and CTU 2015-2017 were retrospectively reviewed. A descriptive analysis of the primary and later investigations for recurrent macroscopic haematuria was performed. To investigate the association between explanatory variables and the occurrence of recurrent macroscopic haematuria, a Poisson regression analysis was performed.

    Results: A total of 1395 eligible individuals with primary standard investigation negative for UBC and UTUC were included. During a median follow-up of 6.2 (IQR 5.3-7) years, 248 (18%) patients had recurrent macroscopic haematuria, of whom six patients were diagnosed with UBC, two with prostate cancer, one with renal cell carcinoma and one had a suspected UTUC at the repeated investigation. Within 3 years, 148 patients (11%) experienced recurrent macroscopic haematuria, of whom two patients were diagnosed with low-grade UBC (TaG1-2), one with T2G3 UBC and one with low-risk prostate cancer. The presence of an indwelling catheter, use of antithrombotic medication, pathological findings at CTU or cystoscopy or history of pelvic radiotherapy were all statistically significant independent predictors for increased risk for recurrent macroscopic haematuria.

    Conclusion: In the case of recurrent macroscopic haematuria within 3 years of primary standard evaluation for urinary tract cancer, there was a low risk of later urological malignancies in patients initially negative for UBC and UTUC. Therefore, waiting 3 years before conducting another complete investigation in cases of recurrent macroscopic haematuria might be appropriate.

  • 2.
    Abuhasanein, Suleiman
    et al.
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of surgery, Urology section, NU Hospital Group, Uddevalla, Region Västra Götaland, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden and Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Göteborg, Sweden.
    Kjölhede, Henrik
    Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Department of Urology, Sahlgrenska University Hospital, Region Västra Götaland, Göteborg, Sweden.
    Do not throw out the baby with the bath water2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 3, p. 235-236Article in journal (Other academic)
  • 3.
    Ahlberg, M.
    et al.
    Uppsala University Hospital, Dept. of Surgical Science, Uppsala, Sweden.
    Garmo, H.
    Uppsala University Hospital, Dept. of Surgical Science, Uppsala, Sweden.
    Adami, H-O
    Karolinska Institute, Dept. of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Andrén, O.
    Örebro University, School of Medical Sciences. Dept. of Urology.
    Johansson, J-E
    Örebro University, Dept. of Urology, Örebro, Sweden.
    Steineck, G.
    Sahlgrenska Academy at the University of Gothenburg, Dept. of Oncology, Gothenburg, Sweden.
    Holmberg, L.
    Uppsala University Hospital, Dept. of Surgical Science, Uppsala, Sweden.
    Bill-Axelson, A.
    Uppsala University Hospital, Dept. of Surgical Science, Uppsala, Sweden.
    Time without PSA recurrence after radical prostatectomy as a predictor of prostate cancer death2022In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 81, no Suppl. 1, p. S286-S286, article id A0184Article in journal (Other academic)
    Abstract [en]

    Introduction & Objectives: Although surveillance after radical prostatectomy routinely includes repeated Prostate Specific Antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk for prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence 5 and 10 years after radical prostatectomy.

    Materials & Methods: Between 1989 and 1998, 14 urological centres in Scandinavia randomized patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial. Data was collected prospectively. All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible in our cohort. 4 patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3). We stratified by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3), and negative or positive surgical margins. We analysed the cumulative incidences and absolute differences in metastatic disease and prostate cancer death.

    Results: We analysed 302 patients with complete follow-up during a median of 18 years. Median preoperative PSA was 9.8 ng/ml and median age at inclusion was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12% respectively. The long-term probabilities were higher for pT≥3 vs. pT2 and for positive vs. negative surgical margins.

    Conclusions: Following radical prostatectomy, patients with Gleason score ≤3+4=7 without biochemical recurrence 5 years after radical prostatectomy had low risk of metastases and prostate cancer death independent of pT-stage and surgical margins. The risk of clinical progression decreased drastically the first 3 years after radical prostatectomy and after 10 years without biochemical recurrence, no patient was diagnosed with metastases or died from prostate cancer. Our study indicates that men with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy can stop follow-up earlier than 10 years after radical prostatectomy while men with adverse pathology should continue with at least 10 years follow-up

  • 4.
    Alexeyev, Oleg
    et al.
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Olsson, Jan
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Elgh, Fredrik
    Örebro University, School of Health and Medical Sciences.
    Is There Evidence for a Role of Propionibacterium acnes in Prostatic Disease?2009In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 73, no 2, p. 220-224Article, review/survey (Refereed)
  • 5.
    Aljabery, Firas
    et al.
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Biobank Research, Umeå University, Umeå, Sweden.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hosseini, Abolfazl
    Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Medicine, King´s College London, London, UK.
    Hagberg, Oskar
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Management and outcome of muscle-invasive bladder cancer with clinical lymph node metastases. A nationwide population-based study in the bladder cancer data base Sweden (BladderBaSe)2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 5, p. 332-338Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 6.
    Aljabery, Firas
    et al.
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Biobank Research, Umeå University, Umeå, Sweden.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Urology, Gothenburg, Sweden.
    Hosseini, Abolfazl
    Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    MalmströmMalmström, Per-Uno
    Department ofSurgical Sciences, Uppsala University, Uppsala, Sweden.
    Hagberg, Oskar
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Medicine, King´s College London, London, UK.
    Treatment and prognosis of bladder cancer patients with other primary cancers: A nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe)2020In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 126, no 5, p. 625-632Article in journal (Refereed)
    Abstract [en]

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

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

    Results: There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis.

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

  • 7.
    Almdalal, Tarik
    et al.
    Department of Surgery and Urology, Eskilstuna Country Hospital, Eskilstuna, Sweden.
    Karlsson Rosenblad, Andreas
    Regional Cancer Centre Stockholm-Gotland, Stockholm, Sweden; Department of Medical Sciences, Division of Clinical Diabetology and Metabolism, Uppsala University, Uppsala, Sweden; Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Solna, Sweden.
    Hellström, Mikael
    Department of Radiology, Sahlgrenska Academy/Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
    Kjellman, Anders
    Department of Urology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    Örebro University, School of Medical Sciences.
    Lundstam, Sven
    Departments of Urology and Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sundqvist, Pernilla
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Ljungberg, Börje
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Predictive characteristics for disease recurrence and overall survival in non-metastatic clinical T1 renal cell carcinoma: results from the National Swedish Kidney Cancer Register2023In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 57, no 1-6, p. 67-74Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 8.
    Almdalal, Tarik
    et al.
    Department of Surgery and Urology, Eskilstuna Country Hospital, Eskilstuna, Sweden.
    Sundqvist, Pernilla
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Harmenberg, Ulrika
    Department of Oncology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
    Hellström, Mikael
    Department of Radiology, Sahlgrenska Academy/Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
    Lindskog, Magnus
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Lindblad, Per
    Örebro University, School of Medical Sciences.
    Lundstam, Svan
    Department of Urology and Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ljungberg, Börje
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Clinical T1a Renal Cell Carcinoma, Not Always a Harmless Disease-A National Register Study2022In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 39, p. 22-28Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

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

  • 9.
    Andersson, Gunnel
    et al.
    Örebro University, Department of Clinical Medicine. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University, Department of Clinical Medicine. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Sahlberg-Blom, Eva
    Örebro University, Department of Nursing and Caring Sciences.
    Pettersson, Nicklas
    Department of Public Health, O¨ rebro County Council, O¨ rebro, Sweden.
    Nilsson, Kerstin
    Örebro University, Department of Clinical Medicine. Centre for Evidence Based Medicine and Assessment of Medical Technology, O¨ rebro, Sweden; Department of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Urinary incontinence - why refraining from treatment?: a population based study2005In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, no 4, p. 301-307Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate why persons with urinary incontinence (UI) refrain from seeking care and treatment.

    MATERIAL AND METHODS: A population-based study was undertaken in which a public health survey and a specific UI questionnaire were sent to 15 360 randomly selected residents (age 18-79 years) of Orebro County, Sweden. For all persons reporting UI, the expressed wish for treatment or no treatment was analyzed in relation to relevant variables from both inquiry forms using binary logistic regression analysis.

    RESULTS: The response rate was 64.5%. UI was reported by 2194 persons, 1724 of whom comprised the study population. A statistically significant association was found between the degree of UI and a desire for treatment. Persons who did not experience daily leakage and those who did not perceive the leakage as troublesome or having an affect on their daily life mostly stated that they did not desire treatment. Socioeconomic or other health-related factors were not associated with desiring or not desiring treatment for UI.

    CONCLUSIONS: Our results show that it is the perceived severity of UI that determines whether afflicted persons desire treatment or not. Other factors, relating to seeking healthcare in general, were not found to be of importance. Interventions to identify those in need of treatment for UI should primarily be directed towards those with severe symptoms.

  • 10.
    Andersson, Patiyan
    et al.
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Kolaric, Aleksandra
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Kirrander, Peter
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderkvist, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Karlsson, Mats G
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    PIK3CA, HRAS and KRAS gene mutations in human penile cancer2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, p. 2030-2034Article in journal (Refereed)
    Abstract [en]

    Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways.

    Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors.

    Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.

    Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

  • 11.
    Andreasson, A.
    et al.
    Sahlgrenska university hospital, Dept. of Urology, Göteborg, Sweden.
    Hällgren, A.
    Linköping university, Dept. of Biomedical and Clinical Sciences, Linköping, Sweden.
    Georgeoulas, P.
    Örebro University Hospital, Dept. of Urology, Örebro, Sweden.
    Forsberg, J.
    Linköping university, Dept. of Biomedical and Clinical Sciences, Linköping, Sweden.
    Fridriksson, J.
    Umeå University, Dept. of Surgical and Perioperative Sciences, Umeå, Sweden.
    Granåsen, G.
    Umeå University, Dept. of Public Health and Clinical Medicine, Umeå, Sweden.
    Lundström, K-J
    Umeå University, Dept. of Surgical and Perioperative Sciences, Umeå, Sweden.
    Resare, S.
    Norrland University Hospital, Dept. of Urology, Umeå, Sweden.
    Lönn, Backman B.
    Umeå University, Dept. of Nursing, Umeå, Sweden.
    Grabe, M.
    Lund university, Dept. of Translational Medicine, Lund, Sweden.
    Stattin, P.
    Uppsala university, Dept. of surgical sciences, Uppsala, Sweden.
    Stranne, J.
    Göteborg University, The Institute of Clinical Sciences, Göteborg, Sweden.
    Sundqvist, M.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Styrke, J.
    Umeå University, Dept. of Surgical and Perioperative Sciences, Umeå, Sweden.
    Fosfomycin versus Ciprofloxacin as transrectal prostatebiopsy antibiotic prophylaxis an open randomized controlled multicenter drug trial2023In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 83, no Suppl. 1, p. S180-S180, article id A0131Article in journal (Other academic)
    Abstract [en]

    Introduction & Objectives: Antibiotic prophylaxis are administered as a routine to decrease the risk for septic complications following transrectal prostate biopsy. Fosfomycin administered 1 h or more prior to biopsy has equal or better infectious complication rates as compared to Ciprofloxacin in both prospective and retrospective studies from countries with high rates of antibiotic resistance. The aim of this study was to investigate if Fosfomycin administered immediately prior to prostate biopsy was as effective as Ciprofloxacin in Sweden, a country with low rates of antibiotic resistance.

    Materials & Methods: A randomized, controlled, open, multicenter, non-inferiority-study including men of all ages undergoing transrectal prostate biopsy was performed in the urology departments of three Swedish hospitals. The total number of patients were planned for 3448, divided into low and high infection risk groups. The low-risk group was randomized to either one dose of Fosfomycin 3g or Ciprofloxacin 750mg before biopsy. The high-risk group was randomized to either two doses of Fosfomycin 3g prior to biopsy and one more 24 h after biopsy or Ciprofloxacin 500mg once prior to biopsy and then twice daily for three days. The drugs were administered orally. All patients had a rectal swab for culture before and after biopsy. The endpoint was hospitalisation due to urinary tract infection within 14 days from biopsy, follow-up was performed with a phone interview.

    Results: The safety board prematurely interrupted the study after 42 included patients due to an unusual high number of hospitalisations. Four out of 20 patients (20%), three in the low-risk group and one in the high-risk group, had been hospitalised due to urosepsis in the Fosfomycin group. One further patient described fever symptoms but did not seek health care. No patient in the Ciprofloxacin group (n=21) described symptoms of infection from the urinary tract. One patient was lost to follow-up. A one-sided binomial test showed a p-value of <0.001. Two of the four hospitalised patients had a positive blood culture for Pseudomonas Aeruginosa and one had a positive rectal swab culture for Pseudomonas species both before and after biopsy.

    Conclusions: The study does not support the use of Fosfomycin administered immediately prior to prostate biopsy. The results may have been affected by the unexpected high number of Pseudomonas infections, a bacteria where Fosfomycin often lack effect. If Fosfomycin is to be used it should be with caution if Pseudomonas has been seen in earlier cultures

  • 12.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences.
    Natural history and prognostic factors in localized prostate cancer2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects.

    The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden.

    Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer.

    The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment.

    Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.

    List of papers
    1. Natural history of early, localized prostate cancer
    Open this publication in new window or tab >>Natural history of early, localized prostate cancer
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    2004 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 291, no 22, p. 2713-2719Article in journal (Refereed) Published
    Abstract [en]

    Context Among men with early prostate cancer, the natural history without initial therapy determines the potential for survival benefit following radical local treatment. However, little is known about disease progression and mortality beyond 10 to 15 years of watchful waiting. Objective To examine the long-term natural history of untreated, early stage prostatic cancer. Design Population-based, cohort study with a mean observation period of 21 years. Setting Regionally well-defined catchment area in central Sweden (recruitment March 1977 through February 1984). Patients A consecutive sample of 223 patients (98% of all eligible) with early-stage (T0-T2 NX MO classification), initially untreated prostatic cancer. Patients with tumor progression were hormonally treated (either by orchiectomy or estrogens) if they had symptoms. Main Outcome Measures Progression-free, cause-specific, and overall survival. Results After complete follow-up, 39 (17%) of all patients experienced generalized disease. Most cancers had an indolent course during the first 10 to 15 years. However, further follow-up from 15 (when 49 patients were still alive) to 20 years, revealed a substantial decrease in cumulative progression-free survival (from 45.0% to 36.0%), survival without metastases (from 76.9% to 51.2%), and prostate cancer-specific survival (from 78.7% to 54.4%). The prostate cancer mortality rate increased from 15 per 1000 person-years (95% confidence interval, 10-21) during the first 15 years to 44 per 1000 person-years (95% confidence interval, 22-88) beyond 15 years of follow-up (P=.01). Conclusion Although most prostate cancers diagnosed at an early stage have an indolent course, local tumor progression and aggressive metastatic disease may develop in the long term. These findings would support early radical treatment, notably among patients with an estimated life expectancy exceeding 15 years.

    National Category
    Surgery
    Research subject
    Surgery esp. Urology Specific
    Identifiers
    urn:nbn:se:oru:diva-15599 (URN)10.1001/jama.291.22.2713 (DOI)000221862300025 ()2-s2.0-2642548279 (Scopus ID)
    Available from: 2011-05-18 Created: 2011-05-18 Last updated: 2023-12-08Bibliographically approved
    2. How well does the Gleason score predict prostate cancer death?: A 20-year followup of a population based cohort in Sweden
    Open this publication in new window or tab >>How well does the Gleason score predict prostate cancer death?: A 20-year followup of a population based cohort in Sweden
    Show others...
    2006 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 175, no 4, p. 1337-1340Article in journal (Refereed) Published
    Abstract [en]

    Purpose

    Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment.

    Materials and Methods

    We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death.

    Results

    Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%.

    Conclusions

    Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.

    Place, publisher, year, edition, pages
    Baltimore: Williams and Wilkins Co., 2006
    National Category
    Medical and Health Sciences Surgery Urology and Nephrology
    Research subject
    Surgery esp. Urology Specific
    Identifiers
    urn:nbn:se:oru:diva-5067 (URN)10.1016/S0022-5347(05)00734-2 (DOI)
    Available from: 2009-01-26 Created: 2009-01-26 Last updated: 2017-12-14Bibliographically approved
    3. Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death
    Open this publication in new window or tab >>Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death
    Show others...
    2005 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 14, no 6, p. 1424-1432Article in journal (Refereed) Published
    Abstract [en]

    alpha-Methylacyl CoA racemase (AMACR) is overexpressed in prostate cancer relative to benign prostatic tissue. AMACR expression is highest in localized prostate cancer and decreases in metastatic prostate cancer. Herein, we explored the use of AMACR as a biomarker for aggressive prostate cancer. AMACR protein expression was determined by immunohistochemistry using an image analysis system on two localized prostate cancer cohorts consisting of 204 men treated by radical prostatectomy and 188 men followed expectantly. The end points for the cohorts were time to prostate-specific antigen (PSA) failure (i.e., elevation > 0.2 ng/mL) and time to prostate cancer death in the watchful waiting cohort. Using a regression tree method, optimal AMACR protein expression cutpoints were determined to best differentiate prostate cancer outcome in each of the cohorts separately. Cox proportional hazard models were then employed to examine the effect of the AMACR cutpoint on prostate cancer outcome, and adjusted for clinical variables. Lower AMACR tissue expression was associated with worse prostate cancer outcome, independent of clinical variables (hazard ratio, 3.7 for PSA failure; P = 0.018; hazard ratio, 4.1 for prostate cancer death, P = 0.0006). Among those with both low AMACR expression and high Gleason score, the risk of prostate cancer death was 18-fold higher (P = 0.006). The AMACR cutpoint developed using prostate cancer-specific death as the end point predicted PSA failures independent of Gleason score, PSA, and margin status. This is the first study to show that AMACR expression is significantly associated with prostate cancer progression and suggests that not all surrogate end points may be optimal to define biomarkers of aggressive prostate cancer.

    National Category
    Surgery
    Research subject
    Surgery esp. Urology Specific
    Identifiers
    urn:nbn:se:oru:diva-15600 (URN)10.1158/1055-9965.EPI-04-0801 (DOI)000229766600017 ()
    Available from: 2011-05-18 Created: 2011-05-18 Last updated: 2017-12-11Bibliographically approved
    4. MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden
    Open this publication in new window or tab >>MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden
    Show others...
    2007 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 97, no 6, p. 730-734Article in journal (Refereed) Published
    Abstract [en]

    Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score >=7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

    Place, publisher, year, edition, pages
    London: Harcourt Publishers, 2007
    National Category
    Medical and Health Sciences Surgery Cancer and Oncology
    Research subject
    Oncology; Surgery esp. Urology Specific
    Identifiers
    urn:nbn:se:oru:diva-5063 (URN)10.1038/sj.bjc.6603944 (DOI)000249392100005 ()2-s2.0-34548565758 (Scopus ID)
    Available from: 2009-01-26 Created: 2009-01-26 Last updated: 2023-12-08Bibliographically approved
    5. Time trends and survival among men diagnosed with incidental prostate cancer in Sweden: a register-based study between 1970 and 2003
    Open this publication in new window or tab >>Time trends and survival among men diagnosed with incidental prostate cancer in Sweden: a register-based study between 1970 and 2003
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Surgery
    Research subject
    Surgery esp. Urology Specific
    Identifiers
    urn:nbn:se:oru:diva-15601 (URN)
    Available from: 2011-05-18 Created: 2011-05-18 Last updated: 2017-10-17Bibliographically approved
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  • 13.
    Andrén, Ove
    et al.
    Örebro University, Department of Clinical Medicine.
    Fall, Katja
    Franzén, Lennart
    Andersson, Swen-Olof
    Johansson, Jan-Erik
    Rubin, Mark A.
    How well does the Gleason score predict prostate cancer death?: A 20-year followup of a population based cohort in Sweden2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 175, no 4, p. 1337-1340Article in journal (Refereed)
    Abstract [en]

    Purpose

    Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment.

    Materials and Methods

    We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death.

    Results

    Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%.

    Conclusions

    Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.

  • 14.
    Bergengren, Oskar
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Belozerov, Alexej
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Bill-Axelson, Anna
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Garmo, Hans
    Regional Cancer Centre, Uppsala University Hospital, Uppsala, Sweden.
    Hagberg, Oskar
    Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Aljabery, Firas
    Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Jahnson, Staffan
    Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital and Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Söderkvist, Karin
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Ullén, Anders
    Genitourinary Oncology and Urology Unit, Department of Oncology-Pathology, Karolinska Institutet, And Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Public Health and Clinical Medicine, Northern Registry Centre, Umeå University, Sweden.
    Liedberg, Fredrik
    Institution of Translational Medicine, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Short term outcomes after robot assisted and open cystectomy: A nation-wide population-based study2023In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 49, no 4, p. 868-874Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population.

    MATERIALS AND METHODS: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary outcomes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models.

    RESULTS: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multivariable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0).

    CONCLUSION: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.

  • 15.
    Bobjer, Johannes
    et al.
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Hagberg, Oskar
    Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Aljabery, Firas
    Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Jahnson, Staffan
    Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Simoulis, Athanasious
    Institution of Translational Medicine, Lund University, Malmö, Sweden; Department of Clinical Pathology, Skåne University Hospital, Malmö, Sweden.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital and Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Public Health and Clinical Medicine, Northern Registre Centre, Umeå University, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Bladder cancer recurrence in papillary urothelial neoplasm of low malignant potential (PUNLMP) compared to G1 WHO 1999: a population-based study2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 1, p. 14-18Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Papillary urothelial neoplasm of low malignant potential (PUNLMP) and stage TaG1 non-muscle invasive bladder cancer (NMIBC) represent separate categories in current WHO 1999 grade definitions. Similarly, PUNLMP and Ta low-grade are separate entities in the WHO 2004/2016 grading system. However, this classification is currently questioned by reports showing a similar risk of recurrence and progression for both categories.

    PATIENTS AND METHODS: In this population-based study, risk estimates were evaluated in patients diagnosed with PUNLMP (n = 135) or stage TaG1 (n = 2176) NMIBC 2004-2008 with 5-year follow-up registration in the nation-wide Bladder Cancer Data Base Sweden (BladderBaSe). The risk of recurrence was assessed using multivariable Cox regression with adjustment for multiple confounders (age, gender, marital status, comorbidity, educational level, and health care region).

    RESULTS: At five years, 28/135 (21%) patients with PUNLMP and 922/2176 (42%) with TaG1 had local recurrence. The corresponding progression rates were 0.7% (1/135) and 4.0% (86/2176), respectively. A higher relative risk of recurrence was detected in patients with TaG1 tumours compared to PUNLMP (Hazard Ratio 1.6, 95% CI 1.2-2.0) at 5-year follow-up, while progression events were too few to compare.

    CONCLUSIONS: The difference in risk of recurrence between primary stage TaG1 and PUNLMP stands in contrast to the recently adapted notion that treatment and follow-up strategies can be merged into one low-risk group of NMIBC.

  • 16.
    Boström, Peter J.
    et al.
    Department of Urology, Turku University Hospital, Turku, Finland.
    Jensen, Jørgen Bjerggaard
    Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Arum, Carl-Jørgen
    Norwegian University of Science and Technology, Trondheim, Norway.
    Gudjonsson, Sigurdur
    Department of Urology, Landspitali University Hospital, Reykjavik, Iceland.
    Ettala, Otto
    Department of Urology, Turku University Hospital, Turku, Finland.
    Syvänen, Kari T.
    Department of Urology, Turku University Hospital, Turku, Finland.
    Clinical markers of morbidity, mortality and survival in bladder cancer patients treated with radical cystectomy: A systematic review2020In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 54, no 4, p. 267-276Article, review/survey (Refereed)
    Abstract [en]

    Context: Radical cystectomy and pelvic lymph node dissection (RC and PLND) are an essential part of the treatment paradigm in high risk bladder cancer. However, these patients have high rates of morbidity and mortality related both to the treatment and to the disease.

    Objective:To provide overview of current literature about clinical markers that can be used to predict and improve BC-patient outcomes at the time of RC and PLND and to study if they are properly validated.

    Evidence acquisition: A systematic literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria between January 1990 and October 2018 to identify English written original and review articles relevant to this topic. Prospective and retrospective studies were included.

    Evidence synthesis: There are several risk factors identified from non-randomised trials that can be improved before surgery to reduce perioperative mortality and morbidity. These include poor nutritional status, anaemia, renal function and smoking. Preoperative nomograms have also been developed to help decision-making and to inform patients about the risks of surgery. They can be used to estimate risk of postoperative mortality after RC and PLND with accuracy varying from 70 to 86%. These nomograms are largely based on retrospective data. Likewise, nomograms developed to calculate estimates about patient's overall and cancer specific survival have the same limitations.

    Conclusion: Clinical markers to predict morbidity, mortality and survival in patients with bladder cancer treated with RC and PLND may help to improve patient outcomes and treatment decision-making, but available data come from small retrospective trials and have not been properly validated. Prospective, multi-centre studies are needed to implement and disseminate predictive clinical markers and nomograms such that they can be utilised in treatment decision-making in daily practice.

  • 17.
    Braide, Magnus
    et al.
    Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Delbro, Dick
    Örebro University, School of Medical Sciences.
    Waniewski, Jacek
    Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland.
    Erythrocytes as volume markers in experimental pd show that albumin transport in the extracellular space depends on pd fluid osmolarity2016In: Peritoneal Dialysis International, ISSN 0896-8608, E-ISSN 1718-4304, Vol. 36, no 3, p. 247-256Article in journal (Refereed)
    Abstract [en]

    Background: Macromolecules, when used as intraperitoneal volume markers, have the disadvantage of leaking into the surrounding tissue. Therefore, Cr-51-labeled erythrocytes were evaluated as markers of intraperitoneal volume and used in combination with I-125-labeled bovine serum albumin to study albumin transport into peritoneal tissues in a rat model of peritoneal dialysis (PD).

    Methods: Single dwells of 20 mL of lactate-buffered filter-sterilized PD fluid at glucose concentrations of 0.5%, 2.5%, and 3.9% were performed for 1 or 4 hours. Tissue biopsies from abdominal muscle, diaphragm, liver, and intestine, and blood and dialysate samples, were analyzed for radioactivity.

    Results: The dialysate distribution volume of labeled erythrocytes, measured after correction for lymphatic clearance to blood, was strongly correlated with, but constantly 3.3 mL larger than, drained volumes. Erythrocyte activity of rinsed peritoneal tissue biopsies corresponded to only 1 mL of dialysate, supporting our utilization of erythrocytes as markers of intraperitoneal volume. The difference between the distribution volumes of albumin and erythrocytes was analyzed to represent the albumin loss into the peritoneal tissues, which increased rapidly during the first few minutes of the dwell and then leveled out at 2.5 mL. It resumed when osmotic ultrafiltration turned into reabsorption and, at the end of the dwell, it was significantly lower for the highest osmolarity PD fluid (3.9% glucose). Biopsy data showed the lowest albumin accumulation and edema formation in abdominal muscle for the 3.9% fluid.

    Conclusion: Labeled erythrocytes are acceptable markers of intraperitoneal volume and, combined with labeled albumin, provided novel kinetic data on albumin transport in peritoneal tissues.

  • 18.
    Brandi, Maria Luisa
    et al.
    FIRMO Foundation, Florence, Italy.
    Ariceta, Gema
    Department of Pediatric Nephrology, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain.
    Beck-Nielsen, Signe Sparre
    Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
    Boot, Annemieke M.
    Department of Pediatric Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
    Briot, Karine
    APHP, Department of Rheumatology, Cochin Hospital, Université de Paris, Paris, France.
    de Lucas Collantes, Carmen
    Department of Nephrology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Madrid, Spain.
    Emma, Francesco
    Division of Nephrology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
    Giannini, Sandro
    Department of Medicine, University of Padua, Padua, Italy.
    Haffner, Dieter
    Department of Pediatric Kidney, Liver and Metabolic Diseases, Children's Hospital, Hannover Medical School, Hannover, Germany.
    Keen, Richard
    Metabolic Unit, Royal National Orthopaedic Hospital NHS Trust, London, UK.
    Levtchenko, Elena
    Department of Pediatric Nephrology and Development and Regeneration, University Hospitals Leuven, University of Leuven, Leuven, Belgium.
    Mӓkitie, Outi
    Pediatric Endocrinology, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Nilsson, Ola
    Örebro University, School of Medical Sciences. Division of Pediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden; Department of Medical Sciences and Department of Pediatrics, University Hospital, Örebro, Sweden.
    Schnabel, Dirk
    Center for Chronic Sick Children, Pediatric Endocrinology, Charitè, University Medicine, Berlin, Germany.
    Tripto-Shkolnik, Liana
    Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel-Hashomer, Israel.
    Zillikens, M. Carola
    Department of Internal Medicine, Erasmus MC Bone Center - Erasmus University Medical Center, Rotterdam, The Netherlands.
    Liu, Jonathan
    Kyowa Kirin International, Marlow, UK.
    Tudor, Alina
    Kyowa Kirin International, Marlow, UK.
    Mughal, M. Zulf
    Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK; Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.
    Post-authorisation safety study of burosumab use in paediatric, adolescent and adult patients with X-linked hypophosphataemia: rationale and description2022In: Therapeutic advances in chronic disease, ISSN 2040-6223, Vol. 13, article id 20406223221117471Article in journal (Refereed)
    Abstract [en]

    Background: X-linked hypophosphataemia (XLH) is a rare, inherited, phosphate-wasting disorder that elevates fibroblast growth factor 23 (FGF23), causing renal phosphate-wasting and impaired active vitamin D (1,25(OH)2D) synthesis. Disease characteristics include rickets, osteomalacia, odontomalacia, and short stature. Historically, treatment has been oral phosphate and 1,25(OH)2D supplements. However, these treatments do not correct the primary pathogenic mechanism or treat all symptoms and can be associated with adverse effects. Burosumab is a recombinant human immunoglobulin G1 monoclonal antibody against FGF23, approved for treating XLH in several geographical regions, including Europe and Israel. Burosumab restores normal serum phosphate levels, minimising the clinical consequences of XLH. Safety data on long-term treatment with burosumab are lacking owing to the rarity of XLH. This post-authorisation safety study (PASS) aims to evaluate the safety outcomes in patients aged >1 year.

    Methods: The PASS is a 10-year retrospective and prospective cohort study utilising data from the International XLH Registry (NCT03193476), which includes standard diagnostic and monitoring practice data at participating centres. The PASS aims to evaluate frequency and severity of safety outcomes, frequency and outcomes of pregnancies in female patients, and safety outcomes in patients with mild to moderate kidney disease at baseline, in children, adolescents and adults treated with burosumab for XLH. It is expected that there will be at least 400 patients who will be administered burosumab.

    Results: Data collection started on 24 April 2019. The expected date of the final study report is 31 December 2028, with two interim reports.

    Conclusion: This PASS will provide data on the long-term safety of burosumab treatment for XLH patients and describe safety outcomes for patients receiving burosumab contrasted with those patients receiving other XLH treatments, to help inform the future management of XLH patients. The PASS will be the largest real-world safety study of burosumab.

    Registry identification: The International XLH Registry is registered with clinicaltrials.gov as NCT03193476 (https://clinicaltrials.gov/ct2/show/NCT03193476), and the PASS is registered with the European Union electronic Register of Post-Authorisation Studies as EUPAS32190 (http://www.encepp.eu/encepp/viewResource.htm?id=32191).

  • 19.
    Bratt, Ola
    et al.
    Department of Urology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Holmberg, Erik
    Regional Cancer Centre, Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Gothenburg, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Carlsson, Stefan
    Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Drevin, Linda
    Regional Cancer Centre, Uppsala-Örebro, Uppsala, Sweden.
    Johansson, Eva
    Department of Urology, Academic Hospital, Uppsala, Sweden.
    Josefsson, Andreas
    Department of Urology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nyberg, Maria
    Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sandberg, Jonas
    Department of Urology, Norrland University Hospital, Umeå, Sweden.
    Stattin, Pär
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Robinsson, David
    Department of Urology, Department of Urology, Jönköping County, Sweden.
    The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS)2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, no 4, p. 461-466Article in journal (Refereed)
    Abstract [en]

    Background: A systematic repeat biopsy is recommended for men starting on active surveillance for prostate cancer, but the optimal number and distribution of cores are unknown.

    Objective: To evaluate an extensive repeat transrectal biopsy with anterior sampling in men starting on active surveillance.

    Design, setting, and participants: Randomised multicentre trial. From 2012 to 2016, 340 Swedish men, aged 40-75 yr, with recently diagnosed low-volume Gleason grade group 1 prostate cancer were included.

    Intervention: Either an extensive transrectal biopsy with anterior sampling (median 19 cores) or a standard transrectal biopsy (median 12 cores).

    Outcome measurements and statistical analysis: Primary outcome measure: Gleason grade group >= 2 cancer. Secondary outcomes: Cancer in anteriorly directed biopsy cores and postbiopsy infection. Nonparametric statistical tests were applied.

    Results and limitations: Gleason grade group >= 2 cancer was detected in 16% of 156 men who had an extensive biopsy and in 10% of 164 men who had a standard biopsy, a 5.7% difference (95% confidence interval [CI]-0.2% to 13%, p = 0.09). There was a strong linear association between prostate-specific antigen (PSA) density and cancer in the anteriorly directed biopsy cores. The odds ratios for cancer in the anteriorly directed cores were for any cancer 2.2 (95% CI 1.3-3.9, p = 0.004) and for Gleason grade group >= 2 cancer 2.3 (95% CI 1.2-4.4, p = 0.015) per 0.1-ng/ml/cm(3) increments. Postbiopsy infections were equally common in the two groups. A limitation is that magnetic resonance imaging was not used.

    Conclusions: The trial did not support general use of the extensive transrectal repeat biopsy template, but cancer in the anteriorly directed cores was common, particularly in men with high PSA density. The higher the PSA density, the stronger the reason to include anterior sampling at a systematic repeat biopsy.

    Patient summary: This trial compared two different templates for transrectal prostate biopsy in men starting on active surveillance for low-risk prostate cancer. Cancer was often found in the front part of the prostate, which is not sampled on a standard prostate biopsy. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 20.
    Böös, Malin
    et al.
    Department of Urology, Helsingborg Hospital, Helsingborg, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden.
    Jerlström, Tomas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Beckman, Eva
    Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Bläckberg, Mats
    Department of Urology, Helsingborg Hospital, Helsingborg, Sweden.
    Brändstedt, Johan
    Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Kollberg, Petter
    Department of Urology, Helsingborg Hospital, Helsingborg, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Löfgren, Annica
    Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Malmström, Per-Uno
    Department of Urology, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Sahlén, Göran
    Department of Urology, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Sörenby, Anne
    Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Vikerfors, Anders
    Örebro University, School of Medical Sciences. Department of Urology.
    Åkesson, Anna
    Clinical Studies Sweden, Skåne University Hospital, Lund, Sweden.
    Liedberg, Fredrik
    Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Who should record surgical complications?: Results from a third-party assessment of complications after radical cystectomy2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 5, p. 339-343Article in journal (Refereed)
    Abstract [en]

    Objective: In Sweden complications after radical cystectomy have been reported to the nationwide population-based Swedish Cystectomy Registry since 2011. Here, validation of the reporting was assessed in two healthcare regions.

    Materials and methods: Complications were ascertained from patient records by a third party not involved in the care delivered to 429 randomly selected patients from 949 who had undergone radical cystectomy since 2011 in four hospitals. Without knowledge of the outcome in the primary registration, post-operative complications within 90 days post-operatively were assessed by an independent review of patient charts, and the results were compared with the primary reports in the Swedish Cystectomy Registry.

    Results: The third-party assessment identified post-operative complications in 310 patients (72%). Low-grade complications (Clavien-Dindo I-II) were noted in 110 (26%) of the patients in the primary registration, but increased to 182 (42%) in the validation (p < 0.00001). High-grade complications (Clavien-Dindo III-V) were reported in 113 (26%) patients in the primary registration, but in 128 (30%) of the patients in the validation (p = 0.02). According to the third-party assessment, 18 patients (4%) had Clavien-Dindo grade IV complications and 12 (3%) died within 90 days of surgery (Clavien-Dindo grade V); corresponding values in the primary registration were 15 (3%) and 9 (2%), respectively. The readmission rate within 90 days increased from 27 to 32% in the validation (p < 0.00001).

    Conclusions: Compared with registry data, third-party assessment revealed more complications and readmissions after radical cystectomy. Hence such evaluation may improve the validity of reported complication data.

  • 21.
    Carlsson, Jessica
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Christiansen, Jesper
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Davidsson, Sabina
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Giunchi, Francesca
    Department of Pathology, F. Addari Institute of Oncology, S. Orsola Hospital, Bologna, Italy.
    Fiorentino, Michelangelo
    Department of Pathology, F. Addari Institute of Oncology, S. Orsola Hospital, Bologna, Italy.
    Sundqvist, Pernilla
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma2019In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 17, no 5, p. 4566-4574Article in journal (Refereed)
    Abstract [en]

    Renal cell carcinoma (RCC) is the most commonly diagnosed renal tumor, consisting of ~3% of all malignancies worldwide. The prognosis of RCC can vary widely, and detecting patients at risk of recurrence at an early stage of disease may improve patient outcome. The factors presently used in a clinical setting cannot reliably predict the natural history of the disease. Therefore, there is a requirement to identify novel biomarkers that can aid in predicting patient outcome. Previous studies have indicated that microRNAs (miRNAs/miRs) are potential candidates as prognostic biomarkers for patients suffering from RCC. Consequently, the aims of the present study were to validate the potential of 3 of these miRNAs to predict the prognosis of patients with RCC, and to investigate the stability of endogenous control genes for miRNA studies in RCC tissues. The expression of 7 endogenous controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in formalin-fixed paraffin-embedded tumor and benign tissues from patients suffering from clear cell RCC (ccRCC). The analyses identified RNU48 and U47 as the most stable endogenous controls. The expression of miR-126, miR-21 and miR-10b was analyzed using RT-qPCR in renal tissues from 116 patients diagnosed with ccRCC. All three investigated miRNAs were differentially expressed between malignant and benign tissues. miR-126 and miR-10b were also differentially expressed between grades and stages of ccRCC. In a univariate, but not in a multivariate model, low expression of miR-126 was associated with shorter time to recurrence of the disease. The results of the present study indicate that of the 3 miRNAs investigated, the expression of miR-126 has the strongest potential as a prognostic biomarker for patients suffering from ccRCC.

  • 22.
    Carlsson, Jessica
    et al.
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Urology.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Prostate cancer and inflammation: The role of miRNAs2013In: European Medical Journal Oncology, ISSN 2054-619X, p. 56-60Article, review/survey (Refereed)
    Abstract [en]

    Approximately 15-20% of all human cancers are assumed to be a result of infection and chronic inflammation due to a constant supply of cytokines and reactive oxygen species, giving rise to genomic instability and a subsequent tumour development. In recent years, chronic inflammation has also been hypothesised to influence prostate carcinogenesis, since both acute and chronic inflammation is commonly seen in prostatic tissues. The signalling pathways involved in the immune response and tumour development are overlapping with each other, and it has been proposed that miRNAs are a possible link between the two processes. In this review, we are describing some of the miRNAs which could constitute a conceivable link between inflammation and prostate cancer.

  • 23.
    Carlsson, Jessica
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Medicine and Health, University Hospital, Örebro, Sweden.
    Fridfeldt, Jonna
    Department of Urology, Faculty of Medicine and Health, University Hospital Örebro, Örebro, Sweden; Örebro University, Örebro, Sweden.
    Giunchi, Francesca
    Department of Pathology, F. Addari Institute of Oncology S. Orsola Hospital, Bologna, Italy.
    Fiano, Valentina
    Cancer Epidemiology Unit-CERMS, Department of Medical Sciences, University of Turin and CPO-Piemonte, Turin, Italy.
    Grasso, Chiara
    Cancer Epidemiology Unit-CERMS, Department of Medical Sciences, University of Turin and CPO-Piemonte, Turin, Italy.
    Zelic, Renata
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
    Richiardi, Lorenzo
    Cancer Epidemiology Unit-CERMS, Department of Medical Sciences, University of Turin and CPO-Piemonte, Turin, Italy.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Medicine and Health, University Hospital Örebro, Örebro, Sweden.
    Pettersson, Andreas
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
    Fiorentino, Michelangelo
    Department of Pathology, F. Addari Institute of Oncology S. Orsola Hospital, Bologna, Italy.
    Akre, Olof
    Department of Medicine Solna, Karolinska Institute, and Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Quantity and quality of nucleic acids extracted from archival formalin fixed paraffin embedded prostate biopsies2018In: BMC Medical Research Methodology, E-ISSN 1471-2288, Vol. 18, no 1, article id 161Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues.

    METHODS: In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality.

    RESULTS: Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids.

    CONCLUSIONS: To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.

  • 24.
    Carlsson, Jessica
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Sundqvist, Pernilla
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Kosuta, Vezira
    Department of Urology, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Fält, Anna
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Giunchi, Francesca
    Molecular Pathology Laboratory, Department of Hematology-Oncology, Addarii Institute of Oncology, University of Bologna, Bologna, Italy.
    Fiorentino, Michelangelo
    Molecular Pathology Laboratory, Department of Hematology-Oncology, Addarii Institute of Oncology, University of Bologna, Bologna, Italy.
    Davidsson, Sabina
    Department of Urology, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    PD-L1 Expression is Associated With Poor Prognosis in Renal Cell Carcinoma2020In: Applied immunohistochemistry & molecular morphology (Print), ISSN 1541-2016, E-ISSN 1533-4058, Vol. 28, no 3, p. 213-220Article in journal (Refereed)
    Abstract [en]

    Programmed death ligand 1 (PD-L1) is a protein which, when interacting with its receptor programmed death 1, acts as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic value of PD-L1 expression in renal cell carcinoma (RCC) has been controversial. In this study, the prognostic value of PD-L1 expression in RCC was evaluated by analyzing PD-L1 immunoreactivity in tumor cells and tumor-infiltrating immune cells (TIICs) in 346 RCC patients with long-term follow-up. PD-L1 positivity in tumor cells was associated with higher World Health Organization nucleolar grade (P<0.001), recurrence (P=0.011), and death due to RCC (P=0.031). PD-L1 positivity in TIICs was associated with higher nucleolar grade (P<0.001), higher T-stage (P=0.031), higher N-stage (P=0.01), recurrence (P=0.007), and death due to RCC (P=0.001). A significant positive association of time to cancer-specific death with both PD-L1-positive tumor cells and TIICs were also found. The data indicate that RCC patients with PD-L1-positive tumor cells and TIICs are at significant risk for cancer progression and the expression may be used as a complementary prognostic factor in the management of RCC patients.

  • 25.
    Cerantola, Yannick
    et al.
    University Hospital of Lausanne, Lausanne, Switzerland.
    Valerio, Massimo
    University Hospital of Lausanne, Lausanne, Switzerland.
    Persson, Beata
    University Hospital of Örebro, Örebro, Sweden.
    Jichlinski, Patrice
    University Hospital of Lausanne, Lausanne, Switzerland.
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Hubner, Martin
    University Hospital of Lausanne, Lausanne, Switzerland.
    Kassouf, Wassim
    McGill University, Montreal, Canada.
    Muller, Stig
    Akershus University Hospital, Oslo, Norway.
    Baldini, Gabriele
    McGill University, Montreal, Canada.
    Carli, Francesco
    McGill University, Montreal, Canada.
    Naesheimh, Torvind
    University Hospital of Northern Norway, Tromsø, Norway.
    Ytrebo, Lars
    University Hospital of Northern Norway, Tromsø, Norway.
    Revhaug, Arthur
    University Hospital of Northern Norway, Tromsø, Norway.
    Lassen, Kristoffer
    University Hospital of Northern Norway, Tromsø, Norway.
    Knutsen, Tore
    University Hospital of Northern Norway, Tromsø, Norway.
    Aarsether, Erling
    University Hospital of Northern Norway, Tromsø, Norway.
    Wiklund, Peter
    Karolinska University Hospital, Stockholm, Sweden.
    Patel, Hitendra R H
    University Hospital of Northern Norway, Tromsø, Norway.
    Guidelines for perioperative care after radical cystectomy for bladder cancer: enhanced Recovery After Surgery (ERAS(®)) society recommendations2013In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 32, no 6, p. 879-887Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery.

    OBJECTIVES: The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group.

    EVIDENCE ACQUISITION: A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated.

    EVIDENCE SYNTHESIS: Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery.

    CONCLUSIONS: ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.

  • 26.
    Chavers, Blanche M.
    et al.
    Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, United States.
    Hårdstedt, Maria
    Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
    Gillingham, Kristen J.
    Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
    Hyperlipidemia in pediatric kidney transplant recipients treated with cyclosporine2003In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 18, no 6, p. 565-569Article in journal (Refereed)
    Abstract [en]

    Hyperlipidemia is a risk factor for cardiovascular disease in adult kidney transplant (Tx) recipients. We sought to determine the prevalence of, and the risk factors associated with, hyperlipidemia in pediatric kidney Tx recipients on cyclosporine (CsA). We identified 59 patients (mean age 8.2+/-5.7 years) transplanted between 1 January 1991 and 31 December 1993. Pre Tx, 34% had elevated total cholesterol [TC >200 mg/dl (5.17 mmol/l)]; 54% had elevated triglycerides [TG >200 mg/dl (2.26 mmol/L)]. Mean TG was higher pre Tx in dialysis (versus nondialysis) patients: 306 mg/dl (3.46 mmol/l) versus 228 mg/dl (2.58 mmol/l) ( P=0.04). Mean TC was higher in peritoneal dialysis than hemodialysis patients: 222 mg/dl (5.74 mmol/l) versus 169 mg/dl (4.37 mmol/l) ( P=0.03). Pre Tx and 3-year values correlated (TC, r=0.49, P=0.0008; TG, r=0.41, P=0.001); 3- and 5-year TC values correlated ( r=0.57, P=0.003). At 5 years post Tx, 41% of the recipients had elevated TC; 14% had elevated TG. Recipients with elevated TC had higher mean CsA concentrations at 1 year post Tx ( P=0.03). Recipients with elevated TG tended to receive more prednisone ( P=0.06). At 5 years post Tx, recipients had a high prevalence of hyperlipidemia. The identification and treatment of hyperlipidemia should be included in pediatric kidney Tx protocols. 

  • 27.
    Dabestani, Saeed
    et al.
    Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Thorstenson, Andreas
    Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute Solna, Stockholm, Sweden.
    Lindblad, Per
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Harmenberg, Ulrika
    Department of Oncology, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Ljungberg, Börje
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Lundstam, Sven
    Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Renal cell carcinoma recurrences and metastases in primary non-metastatic patients: a population-based study2016In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 34, no 8, p. 1081-1086Article in journal (Refereed)
    Abstract [en]

    Purpose: To present the occurrence of metastases and local recurrences in primary non-metastatic patients with renal cell carcinoma (RCC) in a contemporary Swedish population-based cohort.

    Methods: Between 2005 and 2009, a total of 4527 patients were included in the prospective National Swedish Kidney Cancer Register accounting for nearly all RCC patients in Sweden. Among M0 patients, 472 (13 %) had no follow-up data registered within 5-year follow-up time and were excluded from the analysis.

    Results: In total, 939 (21 %) had distant metastases at presentation with a decrease from 23 to 18 % during the inclusion period. Of 3107 patients with follow-up data and with M0 disease, 623 (20 %) were diagnosed with a tumor recurrence during 5-year follow-up. Mean time to recurrence was 24 months (SD ± 20 months). Among these, 570 patients (92 %) were at primary diagnosis treated with radical nephrectomy, 23 patients (3.7 %) with partial nephrectomy and 12 patients (1.9 %) with minimally invasive treatments. The most frequent sites of metastases were lung (54 %), lymph nodes (22 %) and bone (20 %). The treatment of recurrence was in 50 % systemic treatments, while metastasectomy was performed in 17 % of the patients, out of which 68 % were with a curative intention.

    Conclusions: In this population-based study, 21 % of the patients had metastatic disease at presentation, with a decreasing trend over the study period. During 5-year follow-up, 20 % of the primary non-metastatic patients had recurrent disease. Of the patients with recurrence, half were given systemic oncological treatment and 17 % underwent metastasectomy.

  • 28.
    Daouacher, Georgios
    et al.
    Department of Urology, Central Hospital of Karlstad, Karlstad, Sweden.
    von Below, Catrin
    Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
    Gestblom, Charlotta
    Department of Pathology, Central Hospital of Karlstad, Karlstad, Sweden.
    Ahlström, Håkan
    Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
    Grzegorek, Rafael
    Department of Urology, Central Hospital of Karlstad, Karlstad, Sweden.
    Wassberg, Cecilia
    Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
    Sörensen, Jens
    Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
    Waldén, Mauritz
    Department of Urology, Central Hospital of Karlstad, Karlstad, SwedenDepartment of Urology, Central Hospital of Karlstad, Karlstad, Sweden.
    Laparoscopic extended pelvic lymph node (LN) dissection as validation of the performance of [(11) C]-acetate positron emission tomography/computer tomography in the detection of LN metastasis in intermediate- and high-risk prostate cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 1, p. 77-83Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the accuracy of the radiopharmaceutical [(11) C]-acetate combined with positron emission tomography/computer tomography (acetate-PET/CT) in lymph node (LN) staging in newly diagnosed prostate cancer cases. A second aim was to evaluate the potential discriminative properties of acetate-PET/CT in clinical routine.

    PATIENTS AND METHODS: In a prospective comparative study, from July 2010 to June 2013, 53 men with newly histologically diagnosed intermediate- or high-risk prostate cancer underwent acetate-PET/CT investigation at one regional centre before laparoscopic extended pelvic LN dissection (ePLND) at one referral centre. The sensitivity, specificity and accuracy of acetate-PET/CT were calculated. Comparisons were made between true-positive and false-negative PET/CT cases to identify differences in the clinical parameters: PSA level, Gleason status, lymph metastasis burden and size, calculated risk of LN involvement, and curative treatment decisions.

    RESULTS: In all, 26 patients had surgically/histologically confirmed LN metastasis (LN+). Acetate-PET/CT was true positive in 10 patients, false positive in one, false negative in 16, and true negative in 26. The individual sensitivity was 38%, specificity 96%, and accuracy 68%. The acetate-PET/CT positive cases had significantly more involved LNs (mean 7.9 vs 2.4, P < 0.001) with larger cancer diameters (14.1 vs 4.9 mm, P = 0.001) and fewer eventually had treatment with curative intent (40% vs 94%, P <0.005), although we lack long-term outcome data.

    CONCLUSION: Acetate-PET/CT has too low a sensitivity for routine LN staging but the specificity is high. The acetate-PET/CT positive cases have a very high burden of LN spread.

  • 29.
    Daouacher, Georgios
    et al.
    Department of Surgery, Central Hospital of Karlstad , Värmland, Sweden.
    Waldén, Mauritz
    Department of Surgery, Central Hospital of Karlstad, Karlstad, Värmland, Sweden.
    A simple reconstruction of the posterior aspect of rhabdosphincter and sparing of puboprostatic collar reduces the time to early continence after laparoscopic radical prostatectomy2014In: Journal of endourology, ISSN 0892-7790, E-ISSN 1557-900X, Vol. 28, no 4, p. 481-486Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Incontinence is a drawback after radical prostatectomy for prostate cancer. Several surgical methods to improve continence have been described however with contradictory results.

    OBJECTIVE: To determine whether a modified surgical technique during laparoscopic radical prostatectomy (LRP) improves postoperative continence.

    PATIENTS AND METHODS: This is a prospective nonrandomized study with two consecutive series of 100 patients in each group. The first group from 2005 to 2008 underwent a standard LRP. The second group from 2009 to 2011 was subjected to a modified LRP by sparing of puboprostatic ligaments, including the preservation of arcus tendineous, and using a simple posterior tension-releasing suture adapting the urethra stump to the bladder before the anastomosis. The patients had the same preoperative work-up and comparable preoperative baseline characteristics. The 2-year follow-up of the patients included a continence questionnaire and International Prostate Symptom Score (IPSS). Urinary peak flow (Qmax) and post-void residual (PVR) volume were assessed at 3 months. Continence was defined as 0-1 pad/day.

    RESULTS: Only 99 patients were evaluated in each group. The patients had comparable operative characteristics. The continence rates after the modified technique vs the standard were 33% vs 16%, p=0.007 at 1 month; 66% vs 44%, p=0.002 at 3 months; 81% vs 67%, p=0.034 at 6 months; 92% vs 80%, p=0.024 at 12 months; and 95% vs 86%, p=0.05 at 2 years. No significant differences were found regarding voiding functions, the Qmax, the PVR volume, or the IPSS. Three patients developed urethral stricture in the standard group compared with none in the modified group. The negative margin rates were unchanged.

    CONCLUSIONS: The anterior preservation and posterior suture technique studied is a simple, safe, and efficient method to shorten the time to continence after LRP without adverse effects on voiding or compromising the margin rates.

  • 30.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ohlson, Anna-Lena
    Department of Laboratory Medicine, Pathology, University Hospital Örebro, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Giunchi, Francesca
    Department of Hematology-Oncology, Molecular Pathology Laboratory, Addarii Institute of Oncology, University of Bologna, Bologna, Italy.
    Rider, Jennifer R.
    Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.
    Fiorentino, Michelangelo
    Department of Hematology-Oncology, Molecular Pathology Laboratory, Addarii Institute of Oncology, University of Bologna, Bologna, Italy.
    FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer2018In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 40-47Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs ). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer.

    METHODS: Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area.

    RESULTS: In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart.

    CONCLUSIONS: Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established.

  • 31.
    Davidsson, Sabina
    et al.
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Giunchi, Francesca
    Molecular Pathology Laboratory, Addarii Institute of Oncology, Department of Specialist Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy.
    Harlow, Alyssa
    Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
    Kirrander, Peter
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rider, Jennifer
    Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
    Fiorentino, Michelangelo
    Molecular Pathology Laboratory, Addarii Institute of Oncology, Department of Specialist Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    PD-L1 Expression in Men with Penile Cancer and its Association with Clinical Outcomes2019In: European Urology Oncology, E-ISSN 2588-9311, Vol. 2, no 2, p. 214-221Article in journal (Refereed)
    Abstract [en]

    Background: It has been hypothesized that PD-L1 expression in tumor cells and tumor-infiltrating immune (TII) cells may contribute to tumor progression by inhibiting antitumor immunity.

    Objective: To investigate the association between PD-L1 expression in tumor cells and TII cells and clinical outcomes in penile cancer.

    Design, setting, and participants: A cohort of 222 men treated for penile squamous cell carcinoma (SqCC) at Örebro University Hospital between 1984 and 2008 with long-term follow-up (median 34 mo) was evaluated for PD-L1 expression in tumor cells and TII cells via immunohistochemistry.

    Outcome measurements and statistical analysis: Association between clinicopathological features and PD-L1 expression was estimated using χ2 and Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used.

    Results and limitations: We found that 32.1% of the tumors and 64.2% of the TII cells expressed PD-L1. Our data demonstrate that penile SqCC patients with PD-L1–positive tumor cells or TII cells are at significant risk of lower cancer-specific survival and that the prognostic value of PD-L1 expression was strongest for tumor cell positivity. The use of tissue microarrays rather than whole sections may be viewed as a limitation.

    Conclusions: Tumor PD-L1 expression independently identifies penile SqCC patients at risk of poor clinical outcomes.

    Patient summary: We investigated how many patients with penile cancer had tumors that manufactured PD-L1, a protein that decreases the ability of the immune system to fight cancer. We found that up to one-third of penile tumors make this protein. Patients whose tumors make PD-L1 have more aggressive penile cancer and worse clinical outcomes.

  • 32.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Greenberg, Larry
    Department of Environmental and Life Sciences/Biology, Faculty of Health, Science and Technology, Karlstad University, Karlstad, Sweden.
    Wijkander, Jonny
    Department of Health Sciences, Faculty of Health, Science and Technology, Karlstad University, Karlstad, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Erlandsson, Ann
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Environmental and Life Sciences/Biology, Faculty of Health, Science and Technology, Karlstad University, Karlstad, Sweden.
    Cutibacterium acnes Induces the Expression of Immunosuppressive Genes in Macrophages and is Associated with an Increase of Regulatory T-Cells in Prostate Cancer2021In: Microbiology Spectrum, E-ISSN 2165-0497, Vol. 9, no 3, article id e0149721Article in journal (Refereed)
    Abstract [en]

    Tumors and infectious agents both benefit from an immunosuppressive environment. Cutibacterium acnes (C. acnes) is a bacterium in the normal skin microbiota, which has the ability to survive intracellularly in macrophages and is significantly more common in prostate cancer tissue compared with normal prostate tissue. This study investigated if prostate cancer tissue culture positive for C. acnes has a higher infiltration of regulatory T-cells (Tregs) and if macrophages stimulated with C. acnes induced the expression of immunosuppressive genes that could be linked to an increase of Tregs in prostate cancer. Real-time PCR and enzyme-linked immunosorbent spot assay (ELISA) were used to examine the expression of immunosuppressive genes in human macrophages stimulated in vitro with C. acnes, and associations between the presence of C. acnes and infiltration of Tregs were investigated by statistically analyzing data generated in two previous studies. The in vitro results demonstrated that macrophages stimulated with C. acnes significantly increased their expression of PD-L1, CCL17, and CCL18 mRNA and protein (p <0.05). In the cohort, Tregs in tumor stroma and tumor epithelia were positively associated with the presence of C. acnes (P = 0.0004 and P = 0.046, respectively). Since the macrophages stimulated with C. acnes in vitro increased the expression of immunosuppressive genes, and prostate cancer patients with prostatic C. acnes infection had higher infiltration of Tregs than their noninfected counterparts, we suggest that C. acnes may contribute to an immunosuppressive tumor environment that is vital for prostate cancer progression.

    IMPORTANCE: In an immune suppressive tumor microenvironment constituted by immunosuppressive cells and immunosuppressive mediators, tumors may improve their ability to give rise to a clinically relevant cancer. In the present study, we found that C. acnes might contribute to an immunosuppressive environment by recruiting Tregs and by increasing the expression of immunosuppressive mediators such as PD-L1, CCL17, and CCL18. We believe that our data add support to the hypothesis of a contributing role of C. acnes in prostate cancer development. If established that C. acnes stimulates prostate cancer progression it may open up avenues for targeted prostate cancer treatment.

  • 33.
    Davidsson, Sabina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fiorentino, Michelangelo
    Mol Pathol Lab, Addarii Inst Oncol, Dept Hematol Oncol, Univ Bologna, Bologna, Italy; Sch Med, Dana Farber Canc Inst, Dept Pathol, Brigham & Womens Hosp & Adult Oncol, Harvard Univ, Boston MA, USA.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fang, Fang
    Sch Med, Channing Lab, Dept Med, Brigham & Womens Hosp, Harvard Univ, Boston MA, USA; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Mucci, Lorelei A.
    Sch Publ Hlth, Dept Epidemiol, Harvard Univ, Boston MA, USA; Sch Med, Channing Lab, Dept Med, Brigham & Womens Hosp, Harvard Univ, Boston MA, USA.
    Varenhorst, Eberhard
    Dept Urol, Linköping Univ Hosp, Linköping, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rider, Jennifer R.
    Dept Urol, Örebro Univ Hosp, Örebro, Sweden; Sch Med, Dana Farber Canc Inst, Dept Pathol, Brigham & Womens Hosp & Adult Oncol, Harvard Univ, Boston MA, USA.
    Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 10, p. 2280-2287Article in journal (Refereed)
    Abstract [en]

    Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. Methods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. Results: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). Conclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. Impact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease. Cancer Epidemiol Biomarkers Prev; 20(10); 2280-7. (C) 2011 AACR.

  • 34.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Messing Eriksson, Anna
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Faculty of Medicine and Health, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Swanholm, Per
    Department of Urology, Karlstad Central Hospital, Karlstad, Sweden.
    Lewin Lundh, Maria
    Department of Urology, Karlstad Central Hospital, Karlstad, Sweden.
    Widing, Carolina
    Department of Urology, Faculty of Medicine and Health, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Lindlöf, Christina
    Department of Urology, Faculty of Medicine and Health, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Fridfeldt, Jonna
    Department of Urology, Faculty of Medicine and Health, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Andersson, Sven-Olof
    Department of Urology, Faculty of Medicine and Health, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    Androgen deprivation therapy in men with prostate cancer is not associated with COVID-2019 infection2023In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 83, no 6, p. 555-562Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Androgens may play a role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and host responses as the virus is dependent on the androgen-regulated protein transmembrane serine protease 2 for cell entry. Studies have indicated that prostate cancer patients receiving androgen deprivation therapy (ADT) are at reduced risk of SARS-CoV-2 infection and serious complications compared with patients without ADT, but data are inconsistent.

    METHODS: A total of 655 prostate cancer patients who were under surveillance at two urology departments in Sweden on April 1, 2020 were included in the study as well as 240 patients with benign prostatic hyperplasia (BPH). At follow-up early in 2021, the participants completed a questionnaire containing information about symptoms compatible with coronavirus disease 2019 (COVID-19). Blood samples were also collected for the assessment of SARS-CoV-2 IgG antibodies (SARS-CoV-2 Total; Siemens). We used multivariable logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between ADT and the risk of SARS-CoV-2 infection.

    RESULTS: The cumulative incidence of SARS-CoV-2 seropositivity was 13.4% among patients receiving ADT and 10.4% among patients without ADT. After adjusting for potential confounders, we observed no differences in symptoms or risk of SARS-CoV-2 infection between patients with and without ADT (OR: 0.98; 95% CI: 0.52-1.85). Higher body mass index, Type 1 diabetes, and prostate cancer severity, defined by high Gleason score (8-10; OR: 2.06; 95% CI: 1.04-4.09) or elevated levels of prostate-specific antigen (>20 µg/l; OR: 2.15; 95% CI: 1.13-4.07) were associated with increased risk of SARS-CoV-2 infection. Overall, the risk of SARS-CoV-2 infection was not higher among men with prostate cancer than among men with BPH.

    CONCLUSIONS: Our results do not support the hypothesis that ADT use in prostate cancer patients reduces the risk or symptom severity of SARS-CoV-2 infection or that prostate cancer patients are at increased risk of COVID-19 compared with men without prostate cancer.

  • 35.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden; Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden .
    Andersson, Swen-Olof
    Örebro University, School of Health Sciences. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, article id 26Article in journal (Refereed)
    Abstract [en]

    Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.

    Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.

    Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.

    Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.

  • 36.
    Davidsson, Sabina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Mölling, Paula
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rider, Jennifer R.
    Karlsson, Mats G.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Elgh, Fredrik
    Andrén, Ove
    Örebro University, School of Medicine, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden.
    Prevalence and typing of Propionibacterium acnes in prostate tissue obtained from men with prostate cancer and from health controlsManuscript (preprint) (Other academic)
  • 37.
    Delanaye, Pierre
    et al.
    Department of Nephrology-Dialysis-Transplantation, University of Liège (ULg CHU), CHU Sart Tilman, Liège, Belgium; Department of Nephrology-Dialysis-Apheresis, Hopital Universitaire Caremeau, Nimes, France.
    Björk, Jonas
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden; Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden.
    Courbebaisse, Marie
    Physiology Department, Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris, Paris Descartes University, INSERM, Paris, France.
    Couzi, Lionel
    CHU de Bordeaux, Nephrologie - Transplantation - Dialyse, Université de Bordeaux, CNRS-UMR 5164 Immuno ConcEpT, France.
    Ebert, Natalie
    Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany.
    Eriksen, Björn O.
    Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsö, Norway.
    Dalton, R Neil
    The Wellchild Laboratory, Evelina London Children's Hospital, London, United Kingdom.
    Dubourg, Laurence
    Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon, France.
    Gaillard, Francois
    Renal Transplantation Department, Assistance Publique-Hôpitaux de Paris (AP-HP), France.
    Garrouste, Cyril
    Department of Nephrology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
    Grubb, Anders
    Department of Clinical Chemistry, Skåne University Hospital, Lund, Lund University, Sweden.
    Jacquemont, Lola
    Renal Transplantation Department, CHU Nantes, Nantes University, Nantes, France.
    Hansson, Magnus
    Function area Clinical Chemistry, Karolinska University Laboratory, Karolinska University Hospital Huddinge and Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
    Kamar, Nassim
    Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR -BMT, University Paul Sabatier, Toulouse, France.
    Lamb, Edmund J.
    Clinical Biochemistry, East Kent Hospitals University NHS Foundation Trust, Canterbury, United Kingdom.
    Legendre, Christophe
    Hôpital Necker, AP-HP & Université Paris Descartes, Paris, France.
    Littmann, Karin
    Department of Medicine Huddinge (MedH), Karolinska Institute, Huddinge, Sweden.
    Mariat, Christophe
    Service de Néphrologie, Dialyse et Transplantation Rénale, Hôpital Nord, CHU de Saint-Etienne, France.
    Melsom, Toralf
    Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsö, Norway.
    Rostaing, Lionel
    Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Hôpital Michallon, CHU Grenoble-Alpes, France.
    Rule, Andrew D.
    Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
    Schaeffner, Elke
    Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany.
    Sundin, Per-Ola
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Geriatric.
    Berg, Ulla
    Department of Clinical Science, Intervention and Technology, Division of Pediatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Åsling-Monemi, Kajsa
    Department of Clinical Science, Intervention and Technology, Division of Pediatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Selistre, Luciano
    Mestrado em Ciências da Saúde -Universidade Caxias do Sul Foundation CAPES, Brazil.
    Åkesson, Anna
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden; Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    Bökenkamp, Arend
    Department of Paediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
    Pottel, Hans
    Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
    Nyman, Ulf
    Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö, Sweden.
    Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment2022In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 88, no 5, p. 2118-2127Article in journal (Refereed)
    Abstract [en]

    AIM: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing METHODS: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14,804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR), and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision, and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age, and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages.

    RESULTS: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR<60 mL/min and at BMI [18.5-25[kg/m2 , all equations performed similarly and for BMI<18.5kg/m2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI≥25kg/m2 the bias of the CG increased with increasing BMI (+17.2mL/min at BMI≥40kg/m2 ). The four more recent equations also classified mGFR stages better than CG.

    CONCLUSIONS: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for GFR, age, and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.

  • 38.
    Delbro, Dick
    et al.
    Örebro University, School of Medical Sciences.
    Hallsberg, Lena
    Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Peeker, Ralph
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy. University of Gothenburg, Gothenburg, Sweden.
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Fall, Magnus
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Godtman, Rebecka Arnsrud
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    The extracellular matrix-degrading protein ADAMTS5 is expressed in the nuclei of urothelial cells in healthy rats2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 2, p. 139-142Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate whether protein expression of the extracellular matrix-degrading protease ADAMTS5 can be demonstrated in the urinary bladder of healthy rats, and, if so, to determine the localization of this enzyme.

    MATERIALS AND METHODS: The experiments were conducted with eight inbred male Sprague-Dawley rats. Immunohistochemistry was used to investigate the expression of ADAMTS5 in the urinary bladder. Negative controls were established by either excluding the primary antibody or applying the antibody after it had been preabsorbed with its immunogenic peptide. Confocal microscopy was used to visualize the distribution of ADAMTS5 in the urinary bladder tissue.

    RESULTS: Immunoreactivity for ADAMTS5 was demonstrated in the urothelium and in the detrusor. This expression was localized not only in the cytoplasm, but also in the nuclei. Confocal microscopy corroborated these findings.

    CONCLUSION: Expression of ADAMTS5 was demonstrated in the cytoplasm as well as in the nuclei of the urothelium and detrusor cells, suggesting that it may play a role at the transcriptional level.

  • 39.
    Dewitte, Marieke
    et al.
    Department of Clinical Psychological Science, Maastricht University, Maastricht, The Netherlands.
    Bettocchi, Carlo
    Policlinic, Urology Unit, University of Aldo Moro, Bari, Italy.
    Carvalho, Joanna
    Escola de Psicologia e Ciências da Vida, Universidade Lusófona de Humanidades e Tecnologias, Lisbon, Portugal.
    Corona, Giovanni
    Endocrinology Unit, Medical Department, Azienda USL, Maggiore-Bellaria Hospital, Bologna, Italy.
    Flink, Ida
    Örebro University, School of Law, Psychology and Social Work.
    Limoncin, Erika
    Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
    Pascoal, Patricia
    CICPSI, Faculdade de Psicologia, Universidade de Lisboa, Alameda da Universidade, Lisboa, Portugal; Universidade Lusófona de Humanidades e Tecnologias, Lisbon, Portugal; Faculdade de Psicologia e Ciências da Educação & CPUP, Universidade do Porto, Portugal.
    Reisman, Yacov
    Flare Health, Amstelveen, The Netherlands.
    Van Lankveld, Jacques
    Department of Clinical Psychology, Open University, Heerlen, The Netherlands.
    A Psychosocial Approach to Erectile Dysfunction: Position Statements from the European Society of Sexual Medicine (ESSM)2021In: Sexual Medicine, E-ISSN 2050-1161, Vol. 9, no 6, article id 100434Article, review/survey (Refereed)
    Abstract [en]

    INTRODUCTION: Although erectile dysfunction (ED) involves an interaction between physiological and psychological pathways, the psychosocial aspects of ED have received considerably less attention so far.

    AIM: To review the available evidence on the psychosocial aspects of ED in order to develop a position statement and clinical practice recommendations on behalf of the European Society of Sexual Medicine (ESSM).

    METHOD: A comprehensive, narrative review of the literature was performed.

    MAIN OUTCOME MEASURES: Specific statements and recommendations according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence criteria were provided.

    RESULTS: A multidisciplinary treatment, in which medical treatment is combined with a psychological approach, is preferred over unimodal treatment. There is increasing evidence that psychological treatments of ED can improve medical treatments, the patient's adherence to treatment, and the quality of the sexual relationship. The main components of psychological treatment of ED involve cognitive and behavioral techniques aimed at reducing anxiety, challenging dysfunctional beliefs, increasing sexual stimulation, disrupting sexual avoidance, and increasing intimacy and communication skills in a relational context. When applicable and possible, it is strongly recommended to include the partner in the assessment and treatment of ED and to actively work on interpartner agreement and shared decision-making regarding possible treatment options. To ensure a better integration of the biopsychosocial model into clinical practice, developing concrete treatment protocols and training programs are desirable.

    CONCLUSION: Because the psychosocial approach to ED has been underexposed so far, this position statement provides valuable information for clinicians treating ED. Psychological interventions on ED are based on existing theoretical models that are grounded in empirical evidence. However, the quality of available studies is low, which calls for further research. The sexual medicine field would benefit from pursuing more diversity, inclusivity, and integration when setting up treatments and evaluating their effect. Dewitte M, Bettocchi C, Carvalho J, et al. A Psychosocial Approach to Erectile Dysfunction: Position Statements from the European Society of Sexual Medicine (ESSM). Sex Med 2021;XX:XXXXXX.

  • 40.
    Drakeford, Paul Andrew
    et al.
    Department of Anaesthesiology, Intensive Care and Pain Medicine, Tan Tock Seng Hospital, Novena, Singapore.
    Tham, Shu Qi
    Department of Anaesthesiology, Intensive Care and Pain Medicine, Tan Tock Seng Hospital, Novena, Singapore.
    Kwek, Jia Li
    Department of Anaesthesiology, Intensive Care and Pain Medicine, Tan Tock Seng Hospital, Novena, Singapore.
    Lim, Vera
    Department of Anaesthesiology, Intensive Care and Pain Medicine, Tan Tock Seng Hospital, Novena, Singapore.
    Lim, Chien Joo
    Clinical Research & Innovation Office, Tan Tock Seng Hospital, Novena, Singapore.
    How, Kwang Yeong
    Department of General Surgery, Tan Tock Seng Hospital, Novena, Singapore.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery.
    Acute Kidney Injury within an Enhanced Recovery after Surgery (ERAS) Program for Colorectal Surgery2022In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 46, no 1, p. 19-33Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to determine the prevalence, risk factors, and outcomes of acute kidney injury (AKI) within an ERAS program for colorectal surgery (CRS).

    METHODS: This is a retrospective case-control study conducted from March 2016 to September 2018 at a single tertiary hospital in Singapore. All adult patients requiring CRS within our ERAS program were considered eligible. Exclusions were stage 5 chronic kidney disease or patients requiring a synchronous liver resection. The primary outcome was AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. Secondary outcomes included mortality, major complications, and hospital length of stay. Patient, surgical, and anaesthesia-related data were analysed to determine factors associated with AKI.

    RESULTS: A total of 575 patients were eligible for the study. Twenty patients were excluded from the study leaving 555 patients for analysis. Mean age was 67.8 (SD 11.4) years. Seventy-four patients met the criteria for AKI (13.4%: stage 1-11.2%, stage 2-2.0%, stage 3-0.2%). One patient required renal replacement therapy (RRT). Patients with AKI had a longer length of stay (median [IQR], 11.0 [5.0-17.0] days vs 6.0 [4.0-8.0] days; P < .001), more major complications (OR, 6.55; 95% CI, 3.00-14.35, P < .001), and a trend towards higher mortality at one year (OR, 1.44; 95% CI 0.48-4.30; p = 0.511. After multivariable regression analysis, factors associated with AKI were preoperative creatinine (OR, 1.01 per 10 µmol/l; 95% CI, 1.03-1.22; P = 0.01), robotic surgery vs open surgery (OR, 0.15; 95% CI, 0.06-0.39; P < 0.001), anaesthesia duration (OR, 1.38 per hour; 95% CI, 1.22-1.55; P < 0.001), and major complications (OR, 5.55; 95% CI, 2.63-11.70; P < 0.001).

    CONCLUSIONS: Within the present cohort, the implementation of an ERAS program for CRS was associated with a low prevalence of moderate to severe AKI despite a balanced intravenous fluid regimen. Patients having open surgery, longer procedures, and major complications are at increased risk of AKI.

  • 41.
    Edlund, Charlotta
    et al.
    The Public Health Agency of Sweden, Solna, Sweden.
    Ternhag, Anders
    The Public Health Agency of Sweden, Solna, Sweden; Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Solna, Sweden.
    Skoog Ståhlgren, Gunilla
    The Public Health Agency of Sweden, Solna, Sweden.
    Edquist, Petra
    The Public Health Agency of Sweden, Solna, Sweden.
    Östholm Balkhed, Åse
    Division of Infectious Diseases, Department of Biomedical and Clinical Sciences, Faculty of Medicine, Linköping University, Linköping, Sweden.
    Athlin, Simon
    Örebro University, School of Medical Sciences. Department of Infectious Diseases.
    Månsson, Emeli
    Department of Infectious Diseases and Centre of Clinical Research, Västmanland Hospital, Västerås, Sweden.
    Tempé, Maria
    Sundsvall Härnösand Regional Hospital, Sundsvall, Sweden.
    Bergström, Jakob
    The Public Health Agency of Sweden, Solna, Sweden.
    Giske, Christian G.
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Solna, Sweden; Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
    Hanberger, Håkan
    Division of Infectious Diseases, Department of Biomedical and Clinical Sciences, Faculty of Medicine, Linköping University, Linköping, Sweden.
    The clinical and microbiological efficacy of temocillin versus cefotaxime in adults with febrile urinary tract infection, and its effects on the intestinal microbiota: a randomised multicentre clinical trial in Sweden2022In: The Lancet - Infectious diseases, ISSN 1473-3099, E-ISSN 1474-4457, Vol. 22, no 3, p. 390-400Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Use of third-generation cephalosporins, such as cefotaxime, is associated with an increased risk of selection for antimicrobial resistance, so alternative antibiotics need to be considered. The aim of the present study was to evaluate intestinal colonisation with third-generation cephalosporin-resistant pathogens following use of temocillin-an alternative antibiotic to cefotaxime that is potentially less prone to disturbing the intestinal microbiota-in empirical treatment of febrile urinary tract infection (UTI).

    METHODS: We did a randomised, multicentre, superiority, open-label phase 4 trial in patients who had been admitted to inpatient care in 12 Swedish hospitals with suspected or diagnosed febrile UTI (complicated or uncomplicated). To meet inclusion criteria, a patient was required to have at least one sign or symptom of pyelonephritis (ie, flank pain; costovertebral angle tenderness; and changes to urinary frequency or urgency or dysuria), a fever of 38·0°C or higher, and a positive urine dipstick (for nitrites, white blood cells, or both). Participants were also required to have an indication for intravenous antibiotic treatment. Participants were randomly assigned (1:1) to receive either 2 g temocillin or 1-2 g cefotaxime, by local investigators opening consecutive sealed randomisation envelopes that were generated centrally in advance. Both drugs were administered intravenously every 8 h. The trial was open label for investigators and patients, but those doing the microbiological analyses were masked to the groups. Participants were treated with antibiotics for 7-10 days (or up to 14 days if they had bacteraemia), at least 3 days of which were on the study drug; at day 4 and later, participants who were showing improvement could be given an oral antibiotic (ciprofloxacin, ceftibuten, cefixime, or co-trimoxazole). Patients not showing improvement were regarded as having treatment failures. Rectal swabs were collected at three timepoints: at baseline (before the first dose), after the last dose of study drug, and 7-10 days after treatment stopped. The composite primary outcome was colonisation with Enterobacterales with reduced susceptibility to third-generation cephalosporins, or colonisation with toxin-producing Clostridioides difficile, or both, to evaluate disturbance of the intestinal microbiota. The study is registered in the EU Clinical Trials Register (EudraCT 2015-003898-15).

    FINDINGS: Between May 20, 2016, and July 31, 2019, 207 patients were screened for eligibility, of whom 55 patients were excluded. 152 participants were randomly assigned to groups: 77 (51%) patients received temocillin, 75 (49%) patients received cefotaxime. The composite primary endpoint was met by 18 (26%) of 68 participants receiving temocillin versus 30 (48%) of 62 patients receiving cefotaxime (risk difference -22% [95% CI -42% to -3%]), showing superiority of temocillin versus cefotaxime (ie, less disturbance of the intestinal microbiota). 43 adverse events were reported in 40 (52%) of 77 patients in the temocillin group, versus 46 adverse events in 34 (45%) of 75 patients in the cefotaxime group. Most events were of mild to moderate severity. 21 (27%) patients in the temocillin and 17 (23%) patients in the cefotaxime group had an adverse event that was considered to be associated with the study drug.

    INTERPRETATION: Temocillin was found to be less selective than cefotaxime of Enterobacterales with reduced susceptibility to third-generation cephalosporins, and it could therefore be a favourable alternative in the empirical treatment of febrile UTI. Use of this antibiotic could reduce hospital transmission and health-care-associated infections by these pathogens.

  • 42.
    Ejerblad, E.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fored, C. M.
    Karolinska Institutet, Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Lindblad, Per
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fryzek, J.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Dickman, P. W.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Elinder, C. G.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    McLaughlin, J. K.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Nyren, O.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Association between smoking and chronic renal failure in a nationwide population-based case-control study2004In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, no 8, p. 2178-2185Article in journal (Refereed)
    Abstract [en]

    For determining whether smoking is associated with an increased risk for chronic renal failure (CRF) overall and by type of renal disease, smoking data were analyzed from a nationwide population-based case-control study. Eligible as cases were native 18- to 74-yr-old Swedes whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women). A total of 926 cases (78% of all eligible) and 998 control subjects (75% of 1330 randomly selected subjects from the source population), frequency matched to the cases by gender and age within 10 yr, were included. A face-to-face interview and a self-administered questionnaire provided information about smoking habits and other lifestyle factors. Logistic regression models estimated odds ratios (OR) as measures of relative risk for disease-specific types of CRF among smokers compared with never-smokers. Despite a modest and nonsignificant overall association, the risk increased with high daily doses (OR among smokers of >20 cigarettes/d, 1.51; 95% confidence interval [CI], 1.06 to 2.15), long duration (OR among smokers for >40 yr, 1.45; 95% CI, 1.00 to 2.09), and a high cumulative dose (OR among smokers with >30 pack-years, 1.52; 95% CI, 1.08 to 2.14). Smoking increased risk most strongly for CRF classified as nephrosclerosis (OR among smokers with >20 pack-years, 2.2; 95% CI, 1.3 to 3.8), but significant positive associations were also noted with glomerulonephritis. This study thus suggests that heavy cigarette smoking increases the risk of CRF for both men and women, at least CRF classified as nephrosclerosis and glomerulonephritis.

  • 43.
    Ejerblad, E.
    et al.
    Department of Medical Epidemiology and Biostatistic Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Fored, C. M.
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Lindblad, Per
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute and Karolinsak University Hospital, Stockholm, Sweden; Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Fryzek, J.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    McLaughlin, J. K.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Nyren, O.
    Department of Medical Epidemiology and Biostatistic Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Obesity and risk for chronic renal failure2006In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 17, no 6, p. 1695-1702Article in journal (Refereed)
    Abstract [en]

    Few large-scale epidemiologic studies have quantified the possible link between obesity and chronic renal failure (CRF). This study analyzed anthropometric data from a nationwide, population-based, case-control study of incident, moderately severe CRF. Eligible as cases were all native Swedes who were aged 18 to 74 yr and had CRF and whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women) during the study period. A total of 926 case patients and 998 control subjects, randomly drawn from the study base, were enrolled. Face-to-face interviews, supplemented with self-administered questionnaires, provided information about anthropometric measures and other lifestyle factors. Logistic regression models with adjustments for several co-factors estimated the relative risk for CRF in relation to body mass index (BMI). Overweight (BMI>or=25 kg/m2) at age 20 was associated with a significant three-fold excess risk for CRF, relative to BMI<25. Obesity (BMI>or=30) among men and morbid obesity (BMI>or=35) among women anytime during lifetime was linked to three- to four-fold increases in risk. The strongest association was with diabetic nephropathy, but two- to three-fold risk elevations were observed for all major subtypes of CRF. Analyses that were confined to strata without hypertension or diabetes revealed a three-fold increased risk among patients who were overweight at age 20, whereas the two-fold observed risk elevation among those who had a highest lifetime BMI of >35 was statistically nonsignificant. Obesity seems to be an important-and potentially preventable-risk factor for CRF. Although hypertension and type 2 diabetes are important mediators, additional pathways also may exist.

  • 44.
    Ekman, Bertil
    et al.
    Department of Medical and Health Sciences, Section of Endocrinology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Bachrach-Lindström, Margareta
    Division of Nursing Sciences, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Lindström, Torbjörn
    Department of Medical and Health Sciences, Section of Endocrinology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Wahlberg, Jeanette
    Department of Medical and Health Sciences, Section of Endocrinology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Blomgren, Johan
    Internal Medicine County Hospital, Eksjö, Sweden.
    Arnqvist, Hans J.
    Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    A randomized, double-blind, crossover study comparing two- and four-dose hydrocortisone regimen with regard to quality of life, cortisol and ACTH profiles in patients with primary adrenal insufficiency2012In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Current guidelines on how to divide the daily cortisol substitution dose in patients with primary adrenal insufficiency (PAI) are controversial and mainly based on empirical data.

    OBJECTIVE: To assess how an equal dose of hydrocortisone (HC) given either four times daily or twice daily influence diurnal profiles of cortisol and ACTH, patient preferences and health-related quality of life (HRQoL). DESIGN: Double blind, crossover.

    METHODS: Fifteen patients with PAI (six women) were included. Capsules of HC or placebo were given at 07:00, 12:00, 16:00 and 22:00 h in 4-week treatment periods: either one period with four doses (10 + 10 + 5 + 5 mg) or one period with two doses (20 + 0 + 10 + 0 mg). Diurnal profiles of cortisol and ACTH were collected, and area under the curve (AUC) was calculated. Questionnaires were used to evaluate patient preferences and HRQoL.

    RESULTS: The four-dose regimen gave a higher serum cortisol before tablet intake in the morning (P = 0·027) and a higher 24-h cortisol(AUC) (P < 0·0001) compared with the two-dose period. In contrast, a lower median plasma ACTH in the morning before tablet intake (P = 0·003) and a lower 24-h ln(ACTH(AUC) ) were found during the four-dose period. The patients preferred the four-dose regimen (P = 0·03), and the HRQoL scores tended to be higher (high score indicates better HRQoL) for the four-dose period. In summary, a four-dose regimen gives increased availability of cortisol and an enhanced effect with a less elevated ACTH in the morning in comparison with a two-dose regimen but the effect on HRQoL remains inconclusive.

  • 45.
    Enblad, Anna Pia
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Bergengren, Oskar
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Johansson, Eva
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Garmo, Hans
    Regional Cancer Center Uppsala Örebro Region, Uppsala, Sweden; King’s College London, School of Cancer and Pharmaceutical Sciences, Translational Oncology and Urology Research (TOUR), London, UK.
    Bill-Axelson, Anna
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    PSA testing patterns in a large Swedish cohort before the implementation of organized PSA testing2020In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 54, no 5, p. 376-381Article in journal (Refereed)
    Abstract [en]

    Background: Organized PSA testing for asymptomatic men aged 50-74 years will be implemented in Sweden to reduce opportunistic testing in groups who will not benefit. The aim of this study was to describe the opportunistic PSA testing patterns in a Swedish region before the implementation of organized PSA testing programs.

    Method: We included all men in the Uppsala-orebro health care region of Sweden who were PSA tested between 1 July 2012 and 30 June 2014. Information regarding previous PSA testing, prostate cancer diagnosis, socioeconomic situation, surgical procedures and prescribed medications were collected from population-wide registries to create the Uppsala-orebro PSA cohort (UPSAC). The cohort was divided into repeat and single PSA testers. The background population used for comparison consisted of men 40 years or older, living in the Uppsala-orebro region during this time period.

    Results: Of the adult male population in the region, 18.1% had undergone PSA testing. Among men over 85 years old 21% where PSA tested. In our cohort, 62.1% were repeat PSA testers. Of men with a PSA level <= 1 mu g/l 53.8% had undergone repeat testing. Prostate cancer was found in 2.7% and 4.8% of the repeat and single testers, respectively.

    Conclusion: Every fifth man in the male background population was PSA tested. Repeated PSA testing was common despite low PSA values. As repeated PSA testing was common, especially among older men who will not be included in organized testing, special measures to change the testing patterns in this group may be required.

  • 46. Ennart, Henrik
    et al.
    Danielsson-Tham, Marie-Louise (intervjuobjekt)
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    ’’Låt inte barnen trilla köttbullar’’2023In: Svenska Dagbladet, ISSN 1101-2412, no 13 mars 2023Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Mer än 100 små barn har de senaste tolv åren fått svåra njurskador efter att ha smittats av ehec som kan finnas i rå köttfärs. Låt inte barnen vara med och trilla köttbullar, varnar Diana Karpman, specialist på njursjukdomar.

  • 47.
    Erlandsson, Ann
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden; Department of Environmental and Life Sciences/Biology, Karlstad University, Karlstad, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Sven-Olof
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Vyas, Chraig
    Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.
    Wikström, Pernilla
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.
    High inducible nitric oxide synthase in prostate tumor epithelium is associated with lethal prostate cancer2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 2, p. 129-133Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in lethal prostate cancer (PCa) by studying the iNOS immunoreactivity in tumor tissue from men diagnosed with localized PCa.

    MATERIALS AND METHODS: This study is nested within a cohort of men diagnosed with incidental PCa undergoing transurethral resection of the prostate (the Swedish Watchful Waiting Cohort). To investigate molecular determinants of lethal PCa, men who died from PCa (n = 132) were selected as cases; controls (n = 168) comprised men with PCa who survived for at least 10 years without dying from PCa during follow-up. The immunoreactivity of iNOS in prostate tumor epithelial cells and in cells of the surrounding stroma was scored as low/negative, moderate or high. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for lethal PCa according to iNOS category.

    RESULTS: There was no association between iNOS immunoreactivity in stroma and lethal disease. However, when comparing high versus low/negative iNOS immunoreactivity in epithelial cells, the OR for lethal PCa was 3.80 (95% CI 1.45-9.97).

    CONCLUSION: Patients with localized PCa have variable outcomes, especially those with moderately differentiated tumors. Identifying factors associated with long-term PCa outcomes can elucidate PCa tumor biology and identify new candidate prognostic markers. These findings support the hypothesis that high iNOS in tumor epithelium of the prostate is associated with lethal disease.

  • 48.
    Erlandsson, Ann
    et al.
    Örebro University, School of Medical Sciences. Department of Urology.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology.
    Lundholm, Marie
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Fält, Anna
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Andersson, Sven-Olof
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology.
    M2 macrophages and regulatory T cells in lethal prostate cancer2019In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 4, p. 363-369Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tregs) can contribute to cancer progression by suppressing the anti‐tumor immune response. This study investigated the number of CD163‐positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and Tregs.

    METHODS: were assessed using Spearman's rank-order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts.

    RESULTS: showed a significant correlation (P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23-3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis.

    CONCLUSIONS: Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as Tregs , promote an immunosuppressive environment.

  • 49.
    Erlandsson, Ann
    et al.
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Environmental and Life Sciences/Biology, Karlstad University, Karlstad, Sweden.
    Lundholm, Marie
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Watz, Johan
    Department of Environmental and Life Sciences/Biology, Karlstad University, Karlstad, Sweden.
    Bergh, Anders
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Petrova, Elitsa
    Department of Clinical Pathology and Cytology, Central Hospital Karlstad, Karlstad, Sweden.
    Alamdari, Farhood
    Department of Urology, Västmanlands Hospital, Västerås, Sweden.
    Helleday, Thomas
    Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Andren, Ove
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tarish, Firas
    Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.
    Infiltrating immune cells in prostate cancer tissue after androgen deprivation and radiotherapy2023In: International journal of immunopathology and pharmacology, ISSN 0394-6320, Vol. 37, article id 03946320231158025Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Androgen deprivation therapy (ADT) has long been a cornerstone in treatment of advanced prostate cancer (PCa), and is known to improve the results of radiotherapy (RT) for high-risk disease. The purpose of our study was to use a multiplexed immunohistochemical (mIHC) approach to investigate the infiltration of immune cells in PCa tissue after eight weeks of ADT and/or RT with 10 Gy.

    METHODS: From a cohort of 48 patients divided into two treatment arms, we obtained biopsies before and after treatment and used a mIHC method with multispectral imaging to analyze the infiltration of immune cells in tumor stroma and tumor epithelium, focusing on areas with high infiltration.

    RESULTS: Tumor stroma showed a significantly higher infiltration of immune cells compared to tumor epithelium. The most prominent immune cells were CD20+ B-lymphocytes, followed by CD68+ macrophages, CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells (Tregs), and T-bet+ Th1-cells. Neoadjuvant ADT followed by RT significantly increased the infiltration of all five immune cells. Numbers of Th1-cells and Tregs significantly increased after single treatment with ADT or RT. In addition, ADT alone increased the number of cytotoxic T-cells and RT increased the number of B-cells.

    CONCLUSIONS: Neoadjuvant ADT in combination with RT results in a higher inflammatory response compared to RT or ADT alone. The mIHC method may be a useful tool for investigating infiltrating immune cells in PCa biopsies to understand how immunotherapeutic approaches can be combined with current PCa therapies.

  • 50. Fall, Katja
    et al.
    Strömberg, Fredrik
    Rosell, Johan
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences.
    Varenhorst, Eberhard
    Reliability of death certificates in prostate cancer patients2008In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 42, no 4, p. 352-357Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the reliability of cause-of-death diagnoses among prostate cancer patients. MATERIAL AND METHODS: Information from death certificates obtained from the Swedish Death Register was compared with systematically reviewed medical records from the population-based Swedish Regional Prostate Cancer Register, South-East Region. In total, 5675 patients were included who had been diagnosed with prostate cancer between 1987 and 1999 and who had died before 1 January 2003. RESULTS: The proportion of prostate cancer cases classified as having died from prostate cancer was 3% higher in the official death certificates than in the reviewed records [0.03, 95% confidence interval (CI) 0.02 to 0.04]. Overall agreement between the official cause of death and the reviewed data was 86% (95% CI 85 to 87%). A higher accuracy was observed among men with localized disease (88%, 95% CI 87 to 89%), aged 60 years or younger at death (96%, 95% CI 93 to 100%), or who had undergone curative treatment (91%, 95% CI 88 to 95%). This study indicates a relatively high reliability of official cause-of-death statistics of prostate cancer patients in Sweden. CONCLUSION: Mortality data obtained from death certificates may be useful in the evaluation of large-scale prostate cancer intervention programmes, especially among younger patients with localized disease.

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