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  • 1.
    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 universitet, Hälsoakademin.
    Is There Evidence for a Role of Propionibacterium acnes in Prostatic Disease?2009Ingår i: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 73, nr 2, s. 220-224Artikel, forskningsöversikt (Refereegranskat)
  • 2.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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)2019Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813Artikel i tidskrift (Refereegranskat)
    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.

  • 3.
    Andersson, Gunnel
    et al.
    Örebro universitet, Institutionen för klinisk medicin. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro universitet, Institutionen för klinisk medicin. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Sahlberg-Blom, Eva
    Örebro universitet, Institutionen för vårdvetenskap och omsorg.
    Pettersson, Nicklas
    Department of Public Health, O¨ rebro County Council, O¨ rebro, Sweden.
    Nilsson, Kerstin
    Örebro universitet, Institutionen för klinisk medicin. 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 study2005Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, nr 4, s. 301-307Artikel i tidskrift (Refereegranskat)
    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.

  • 4.
    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 cancer2008Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, nr 5, s. 2030-2034Artikel i tidskrift (Refereegranskat)
    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.

  • 5.
    Andrén, Ove
    Örebro universitet, Hälsoakademin.
    Natural history and prognostic factors in localized prostate cancer2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. Natural history of early, localized prostate cancer
    Öppna denna publikation i ny flik eller fönster >>Natural history of early, localized prostate cancer
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    2004 (Engelska)Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 291, nr 22, s. 2713-2719Artikel i tidskrift (Refereegranskat) 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.

    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Kirurgi, särskilt urologi
    Identifikatorer
    urn:nbn:se:oru:diva-15599 (URN)10.1001/jama.291.22.2713 (DOI)000221862300025 ()
    Tillgänglig från: 2011-05-18 Skapad: 2011-05-18 Senast uppdaterad: 2017-12-11Bibliografiskt granskad
    2. How well does the Gleason score predict prostate cancer death?: A 20-year followup of a population based cohort in Sweden
    Öppna denna publikation i ny flik eller fönster >>How well does the Gleason score predict prostate cancer death?: A 20-year followup of a population based cohort in Sweden
    Visa övriga...
    2006 (Engelska)Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 175, nr 4, s. 1337-1340Artikel i tidskrift (Refereegranskat) 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.

    Ort, förlag, år, upplaga, sidor
    Baltimore: Williams and Wilkins Co., 2006
    Nationell ämneskategori
    Medicin och hälsovetenskap Kirurgi Urologi och njurmedicin
    Forskningsämne
    Kirurgi, särskilt urologi
    Identifikatorer
    urn:nbn:se:oru:diva-5067 (URN)10.1016/S0022-5347(05)00734-2 (DOI)
    Tillgänglig från: 2009-01-26 Skapad: 2009-01-26 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    3. Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death
    Öppna denna publikation i ny flik eller fönster >>Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death
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    2005 (Engelska)Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 14, nr 6, s. 1424-1432Artikel i tidskrift (Refereegranskat) 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.

    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Kirurgi, särskilt urologi
    Identifikatorer
    urn:nbn:se:oru:diva-15600 (URN)10.1158/1055-9965.EPI-04-0801 (DOI)000229766600017 ()
    Tillgänglig från: 2011-05-18 Skapad: 2011-05-18 Senast uppdaterad: 2017-12-11Bibliografiskt granskad
    4. MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden
    Öppna denna publikation i ny flik eller fönster >>MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden
    Visa övriga...
    2007 (Engelska)Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 97, nr 6, s. 730-734Artikel i tidskrift (Refereegranskat) 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.

    Ort, förlag, år, upplaga, sidor
    London: Harcourt Publishers, 2007
    Nationell ämneskategori
    Medicin och hälsovetenskap Kirurgi Cancer och onkologi
    Forskningsämne
    Onkologi; Kirurgi, särskilt urologi
    Identifikatorer
    urn:nbn:se:oru:diva-5063 (URN)10.1038/sj.bjc.6603944 (DOI)
    Tillgänglig från: 2009-01-26 Skapad: 2009-01-26 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    5. Time trends and survival among men diagnosed with incidental prostate cancer in Sweden: a register-based study between 1970 and 2003
    Öppna denna publikation i ny flik eller fönster >>Time trends and survival among men diagnosed with incidental prostate cancer in Sweden: a register-based study between 1970 and 2003
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Kirurgi, särskilt urologi
    Identifikatorer
    urn:nbn:se:oru:diva-15601 (URN)
    Tillgänglig från: 2011-05-18 Skapad: 2011-05-18 Senast uppdaterad: 2017-10-17Bibliografiskt granskad
  • 6.
    Andrén, Ove
    et al.
    Örebro universitet, Institutionen för klinisk medicin.
    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 Sweden2006Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 175, nr 4, s. 1337-1340Artikel i tidskrift (Refereegranskat)
    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.

  • 7.
    Braide, Magnus
    et al.
    Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Delbro, Dick
    Örebro universitet, Institutionen för medicinska vetenskaper.
    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 osmolarity2016Ingår i: Peritoneal Dialysis International, ISSN 0896-8608, E-ISSN 1718-4304, Vol. 36, nr 3, s. 247-256Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    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 universitet, Institutionen för medicinska vetenskaper. 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)2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 4, s. 461-466Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    Böös, Malin
    et al.
    Department of Urology, Helsingborg Hospital, Helsingborg, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden.
    Jerlström, Tomas
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 universitet, Institutionen för medicinska vetenskaper. 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 cystectomy2019Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    Carlsson, Jessica
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma2019Ingår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 17, nr 5, s. 4566-4574Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    Carlsson, Jessica
    et al.
    Region Örebro län. Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Prostate cancer and inflammation: The role of miRNAs2013Ingår i: European Medical Journal Oncology, ISSN 2054-619X, s. 56-60Artikel, forskningsöversikt (Refereegranskat)
    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.

  • 12.
    Carlsson, Jessica
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för medicinska vetenskaper. 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 biopsies2018Ingår i: BMC Medical Research Methodology, ISSN 1471-2288, E-ISSN 1471-2288, Vol. 18, nr 1, artikel-id 161Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    Carlsson, Jessica
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Sundqvist, Pernilla
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 Carcinoma2019Ingår i: Applied immunohistochemistry & molecular morphology (Print), ISSN 1541-2016, E-ISSN 1533-4058Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    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 universitet, Institutionen för medicinska vetenskaper. 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 study2016Ingår i: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 34, nr 8, s. 1081-1086Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 cancer2018Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, nr 1, s. 40-47Artikel i tidskrift (Refereegranskat)
    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.

  • 16.
    Davidsson, Sabina
    et al.
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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
    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 universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    PD-L1 Expression in Men with Penile Cancer and its Association with Clinical Outcomes2019Ingår i: European Urology Oncology, E-ISSN 2588-9311, Vol. 2, nr 2, s. 214-221Artikel i tidskrift (Refereegranskat)
    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.

  • 17.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    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 universitet, Institutionen för hälsovetenskap och medicin.
    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 universitet, Institutionen för hälsovetenskap och medicin.
    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 cancer2011Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, nr 10, s. 2280-2287Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden; Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Örebro University Hospital, Örebro, Sweden .
    Andersson, Swen-Olof
    Örebro universitet, Institutionen för hälsovetenskaper. 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 universitet, Institutionen för medicinska vetenskaper.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016Ingår i: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, artikel-id 26Artikel i tidskrift (Refereegranskat)
    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.

  • 19.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Mölling, Paula
    Unemo, Magnus
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Rider, Jennifer R.
    Karlsson, Mats G.
    Andersson, Swen-Olof
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Elgh, Fredrik
    Andrén, Ove
    Örebro universitet, Institutionen för läkarutbildning.
    Söderquist, Bo
    Örebro universitet, Institutionen för läkarutbildning.
    Prevalence and typing of Propionibacterium acnes in prostate tissue obtained from men with prostate cancer and from health controlsManuskript (preprint) (Övrigt vetenskapligt)
  • 20.
    Delbro, Dick
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    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 universitet, Institutionen för naturvetenskap och teknik.
    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 rats2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 2, s. 139-142Artikel i tidskrift (Refereegranskat)
    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.

  • 21.
    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 study2004Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, nr 8, s. 2178-2185Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    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 failure2006Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 17, nr 6, s. 1695-1702Artikel i tidskrift (Refereegranskat)
    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.

  • 23.
    Erlandsson, Ann
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology, Örebro University Hospital, Örebro, Sweden; Department of Environmental and Life Sciences/Biology, Karlstad University, Karlstad, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 universitet, Institutionen för medicinska vetenskaper. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 cancer2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 2, s. 129-133Artikel i tidskrift (Refereegranskat)
    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.

  • 24.
    Erlandsson, Ann
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Davidsson, Sabina
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    M2 macrophages and regulatory T cells in lethal prostate cancer2019Ingår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, nr 4, s. 363-369Artikel i tidskrift (Refereegranskat)
    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.

  • 25. Fall, Katja
    et al.
    Strömberg, Fredrik
    Rosell, Johan
    Andrén, Ove
    Örebro universitet, Hälsoakademin.
    Varenhorst, Eberhard
    Reliability of death certificates in prostate cancer patients2008Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 42, nr 4, s. 352-357Artikel i tidskrift (Refereegranskat)
    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.

  • 26.
    Fored, C. M.
    et al.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    Ejerblad, E.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Fryzek, J. P.
    The International Epidemiology Institute, Rockville, MD, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
    Lambe, M.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Nyren, O.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Elinder, C. G.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    Socio-economic status and chronic renal failure: a population-based case-control study in Sweden2003Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 18, nr 1, s. 82-88Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Low socio-economic status is associated with the occurrence of several different chronic diseases, but evidence regarding renal disease is scant. To explore whether the risk of chronic renal failure varies by socio-economic status, we performed a population-based case-control study in Sweden.

    Methods: All native residents from May 1996 to May 1998, aged 18-74 years, formed the source population. Cases (n = 926) were incident patients with chronic renal failure in a pre-uraemic stage. Control subjects (n = 998) were randomly selected within the source population. Exposures were assessed at personal interviews and relative risks were estimated by odds ratios (OR) in logistic regression models, with adjustment for age, sex, body mass index (BMI), smoking, alcohol consumption and regular analgesics use.

    Results: In families with unskilled workers only, the risk of chronic renal failure was increased by 110% [OR = 2.1; 95% confidence interval (CI), 1.1-4.0] and 60% (OR = 1.6; 95% CI, 1.0-2.6) among women and men, respectively, relative to subjects living in families in which at least one member was a professional. Subjects with 9 years or less of schooling had a 30% (OR = 1.3; 95% CI, 1.0-1.7) higher risk compared with those with a university education. The excess risk was of similar magnitude regardless of underlying renal disease.

    Conclusions: Low socio-economic status is associated with an increased risk of chronic renal failure. The moderate excess was not explained by age, sex, BMI, smoking, alcohol or analgesic intake. Thus, socio-economic status appears to be an independent risk indicator for chronic renal failure in Sweden.

  • 27.
    Fored, C. M.
    et al.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    Ejerblad, E.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Fryzek, J. P.
    International Epidemiology Institute, Rockville, MD, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States.
    Dickman, P. W.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Signorello, L. B.
    International Epidemiology Institute, Rockville, MD, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States.
    Lipworth, L.
    International Epidemiology Institute, Rockville, MD, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States.
    Elinder, C. G.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden.
    Blot, W. J.
    International Epidemiology Institute, Rockville, MD, United States.
    McLaughlin, J. K.
    International Epidemiology Institute, Rockville, MD, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States.
    Zack, M. M.
    National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, United States .
    Nyren, O.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Acetaminophen, aspirin, and chronic renal failure2001Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 345, nr 25, s. 1801-1808Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect.

    Methods: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics.

    Results: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated.

    Conclusions: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.

  • 28.
    Fored, C. M.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Stockholm, Sweden.
    Nise, G.
    Division of Occupational Department of Renal Medicine, Huddinge University Hospital, Stockholm, Sweden.
    Ejerblad, E.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Fryzek, J. P.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    McLaughlin, J. K.
    The International Epidemiology Institute, Rockville, Maryland, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
    Elinder, C. G.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Renal Medicine, Huddinge University Hospital, Stockholm, Sweden.
    Nyren, O.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Absence of association between organic solvent exposure and risk of chronic renal failure: a nationwide population-based case-control study2004Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, nr 1, s. 180-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exposure to organic solvents has been suggested to cause or exacerbate renal disease, but methodologic concerns regarding previous studies preclude firm conclusions. We examined the role of organic solvents in a population-based case-control study of early-stage chronic renal failure (CRF). All native Swedish residents aged 18 to 74 yr, living in Sweden between May 1996 and May 1998, formed the source population. Incident cases of CRF in a pre-uremic stage (n = 926) and control subjects (n = 998), randomly selected from the study base, underwent personal interviews that included a detailed occupational history. Expert rating by a certified occupational hygienist was used to assess organic solvent exposure intensity and duration. Relative risks were estimated by odds ratios (OR) in logistic regression models, with adjustment for potentially important covariates. The overall risk for CRF among subjects ever exposed to organic solvents was virtually identical to that among never-exposed (OR, 1.01; 95% confidence interval [CI], 0.81 to 1.25). No dose-response relationships were observed for lifetime cumulative solvent exposure, average dose, or exposure frequency or duration. The absence of association pertained to all subgroups of CRF: glomerulonephritis (OR, 0.96; 95% CI, 0.68 to 1.34), diabetic nephropathy (OR, 1.02; 95% CI, 0.74 to 1.41), renal vascular disease (OR, 1.16; 95% CI, 0.76 to 1.75), and other renal CRF (OR, 0.92; 95% CI, 0.66 to 1.27). The results from a nationwide, population-based study do not support the hypothesis of an adverse effect of organic solvents on CRF development, in general. Detrimental effects from subclasses of solvents or on specific renal diseases cannot be ruled out.

  • 29.
    Franzén, Karin
    et al.
    Örebro universitet, Hälsoakademin. 2 Obstetrics and Gynaecology, Örebro County Council, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro universitet, Hälsoakademin. Urology, Örebro University Hospital, Örebro, Sweden; Centre for Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Andersson, Gunnel
    Örebro universitet, Hälsoakademin. Urology, Örebro University Hospital, Örebro, Sweden.
    Pettersson, Nicklas
    Department of Statistics, Stockholm University, Stockholm, Sweden.
    Nilsson, Kerstin
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Obstetrics and Gynaecology,Örebro County Council, Örebro, Sweden; Centre for Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Urinary incontinence in women is not exclusively a medical problem: a population-based study on urinary incontinence and general living conditions2009Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, nr 3, s. 226-232Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of the study was to analyse differences in general health and general living conditions between women with and without urinary incontinence (UI).

    MATERIAL AND METHODS: This cross-sectional population-based study was conducted in Orebro County, Sweden. A public health questionnaire, "Life and Health", was sent to a randomly selected sample of the population. The questionnaire consisted of 87 questions on broad aspects of general and psychiatric health. An additional questionnaire was enclosed for those respondents who reported experiencing UI. The data were analysed using binary logistic regression. The final study population constituted 4609 women, 1332 of whom had completed both questionnaires. The remaining 3277 had completed only the Life and Health questionnaire. Effect measures were odds ratios (ORs) with corresponding 95% confidence intervals (CIs).

    RESULTS: Statistically significant associations were found between UI and the occurrence of musculoskeletal pain (OR 1.45, 95% CI 1.20-1.76), fatigue and sleeping disorders (OR 1.59, 95% CI 1.30-1.95), feelings of humiliation (OR 1.29, 95% CI 1.12-1.50), financial problems (OR 1.36, 95% CI 1.11-1.66), and reluctance to seek medical care (OR 1.43, 95% CI 1.21-1.68).

    CONCLUSION: UI among women is commonly associated with a number of different psychosocial problems as well as an expressed feeling of vulnerability.

  • 30.
    Franzén, Karin M
    et al.
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Gunnel
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Odeberg, Jenny
    Swedish Council on Health Technology Assessment (SBU), Stockholm, Sweden.
    Midlöv, Patrik
    Center for Primary Health Care Research, Lund University, Malmö, Sweden.
    Samuelsson, Eva
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Stenzelius, Karin
    Department of Care Science, Malmö University, Malmö, Sweden.
    Hammarström, Margareta
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Surgery for urinary incontinence in women 65 years and older: a systematic review2015Ingår i: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 26, nr 8, s. 1095-1102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction and hypothesis: Urinary incontinence (UI) is common among the elderly, but the literature is sparse on the surgical treatment of UI among the elderly. This systematic review aims to assess the effectiveness of surgical interventions as treatment for urinary incontinence in the elderly population ≥65 years of age.

    Methods: Randomized controlled trials (RCT) and prospective nonrandomized studies (NRS) were included. The databases PubMed (NLM), EMBASE (Elsevier), Cochrane Library (Wiley), and Cinahl (EBSCO) were searched for the period 1966 up to October 2013. The population had to be ≥65 years of age and had to have undergone urethral sling procedures, periurethral injection of bulking agents, artificial urinary sphincter surgery, bladder injection treatment with onabotulinumtoxin A or sacral neuromodulation treatment. Eligible outcomes were episodes of incontinence/urine leakage, adverse events, and quality of life.

    The studies included had to be at a moderate or low risk of bias. Mean difference (MD) or standard mean difference (SMD)as well as risk difference (RD) and the 95 % CI were calculated.

    Results: Five studies-all on the suburethral sling procedure in women- that fulfilled the inclusion criteria were identified. The proportion of patients reporting persistent SUI after surgery ranged from 5.2 to 17.6 %. One study evaluating quality of life (QoL) showed a significant improvement after surgery. The complication rates varied between 1 and 26 %, mainly bladder perforation, bladder emptying disturbances, and de novo urge.

    Conclusion: The suburethral sling procedure improves continence as well as QoL among elderly women with SUI; however, evidence is limited.

  • 31.
    Frey, Janusz
    et al.
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Dorofte, Luiza
    Department of Pathology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sundqvist, Pernilla
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Malignant hydrocele: a rare manifestation of peritoneal carcinomatosis of colorectal origin as a transcoelomic spread into the scrotum - case report and literature overview2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 3, s. 232-235Artikel, forskningsöversikt (Refereegranskat)
  • 32. Furuland, Hans
    et al.
    Linde, Torbjörn
    Englund, Anders
    Örebro universitet, Hälsoakademin.
    Wikström, Björn
    Heart rate variability is decreased in chronic kidney disease but may improve with hemoglobin normalization2008Ingår i: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 21, nr 1, s. 45-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Cardiac autonomic function can be measured by heart rate variability (HRV). Dialysis patients have an abnormally low HRV and are at increased risk for sudden death. A reduction in HRV is associated with anemia. HRV was therefore measured in patients with chronic kidney disease (CKD) after hemoglobin normalization. Methods: Sixteen nondiabetic patients with CKD stage 4 (glomerular filtration rate 23.7 13.9 ml/min) and renal anemia received epoetin aiming at a hemoglobin level of 135-150 g/L. HRV was measured by 24-hour Holter electrocardiogram at baseline and after hemoglobin normalization and in a reference group consisting of 16 volunteers without impairment of renal function. Results: Hemoglobin level increased from 100.7 12.6 g/L to 142.4 7.2 g/L during the study. At baseline, HRV measured in the time domain as the standard deviation of all normal RR intervals in the entire 24-hour electrocardiogram (SDNN) was 116.3 39.2 ms compared with 147.5 27.2 ms in the reference group (p<0.05). The frequency domain measures low-frequency power and total power were 367.7 350.2 ms2 and 1,368.9 957.4 ms2 compared with 717.3 484.5 ms2 and 2,228.3 1142.4 ms2 (p<0.05) in the reference group. After hemoglobin normalization there was an increase in low-frequency power to 498.3 432.7 ms2 (p<0.05) and in total power to 1,731.0 1,069.4 ms2 (p<0.05) while SDNN remained at 120.9 33.8 ms (p=ns). Conclusions: CKD patients not yet on dialysis had a reduced HRV, indicating impaired autonomic function, compared with a reference group without impaired renal function. Hemoglobin normalization improved but did not fully normalize HRV. The clinical significance of this deserves further investigation. 

  • 33.
    Ghijselings, Lynn
    et al.
    Urology Department, Ghent University Hospital, Ghent University, Ghent, Belgium.
    Van De Putte, Dirk
    Colorectal Surgery, Ghent University Hospital, Ghent University, Ghent, Belgium.
    Hervé, François
    Urology Department, Ghent University Hospital, Ghent University, Ghent, Belgium; Urology Department, UCL University Hospital, Woluwe, Belgium.
    Goessaert, An-Sofie
    Urology Department, Ghent University Hospital, Ghent University, Ghent, Belgium.
    Beeckman, Dimitri
    Department of Public Health and Primary Care, Ghent University Hospital, Ghent University, Ghent, Belgium.
    Pattyn, Piet
    Urology Department, UCL University Hospital, Woluwe, Belgium.
    Everaert, Karel
    Urology Department, Ghent University Hospital, Ghent University, Ghent, Belgium.
    The OptiLUTS trial: improving care for therapy-resistant symptoms of the pelvis in Belgium2019Ingår i: Acta clinica Belgica, ISSN 1784-3286, s. 1-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction/Background: The management of therapy-resistant lower urinary tract symptoms (LUTS) and symptoms resulting from pelvic organ dysfunctions are subject to a high variability in the Belgian health-care centres. Practical guidelines and standardized patient clinical care pathways are often lacking and unadapted to the Belgian healthcare system.

    Objectives: The OptiLUTS trial aims to improve the multidisciplinary care of therapy-resistant symptoms of the pelvis in the Belgian healthcare setting.

    Project A aims for the improvement of knowledge of 2nd line treatments for LUTS among general practitioners. In project B a treatment algorithm for the overactive bladder syndrome and non-obstructive urinary retention will be developed specifically for Belgium. In Project C a patient customized sacral neuromodulation (SNM) care pathway will be set up.

    Methods: Part A: Explorative study among general practitioners by distribution of a questionnaire.

    Part B: Review of existing guidelines and use of the Delphi method to obtain expert consensus. Part C: A single center comparative study to compare outcomes before and after implementation of the SNM care pathway. Patients scheduled for the first stage of Interstim therapy™ will be included (N=100). Primary endpoints are the sensitivity and specificity of a new pelvic symptom assessment tool, the conversion to implant and explantation rates.

    Conclusion: There is a margin for improvement in the care process of patients with therapy-resistant symptoms of the pelvis in the Belgium healthcare system. In the OptiLUTs trial adapted guidelines and a clinical care pathway will be developed to standardize and increase the efficiency of care.

    Trial registration: Approval for the trial by the Ethics Committee of the Ghent University hospital: EC/2018/0244.

  • 34.
    Grabowska, Beata
    et al.
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ulvskog, Emma
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Oncology, University Hospital Örebro, Örebro, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Urology.
    Fiorentino, Michelangelo
    Department of Pathology, F. Addari Institute of Oncology, S. Orsola Hospital, Bologna, Italy.
    Giunchi, Francesca
    Department of Pathology, F. Addari Institute of Oncology, S. Orsola Hospital, Bologna, Italy.
    Lindblad, Per
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Sundqvist, Pernilla
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Clinical outcome and time trends of surgically treated renal cell carcinoma between 1986 and 2010: results from a single centre in Sweden2018Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 3, s. 206-212Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aims of this study were to create a cohort of retrospectively collected renal cell carcinoma (RCC) specimens to be used a basis for prognostic molecular studies, and to investigate the outcome and time trends in patients surgically treated for RCC in a single-centre cohort.

    MATERIALS AND METHODS: Patients undergoing surgery for RCC between 1986 and 2010 were included in the study. Medical records were reviewed, and the diagnostic tissue was re-evaluated according to a modern classification. The change in patient and tumour characteristics over time was analysed.

    RESULTS: The study included 345 patients. Smaller tumours, as indicated by primary tumour diameter, tumour (T) stage and American Joint Committee on Cancer (AJCC) stage, were found more frequently in later years compared to the early 1990s. No changes in the clinical outcome for the patients were seen among the time periods investigated. Increasing T stage, AJCC stage, primary tumour diameter and decreasing haemoglobin levels were associated with cancer-specific mortality in univariate analysis. A high calcium level was significantly associated with increased cancer-specific mortality (hazard ratio = 4.25, 95% confidence interval 1.36-13.28) in multivariate analysis.

    CONCLUSIONS: This study on patients who underwent surgery for RCC from 1986 to 2010 at a single institution in Sweden indicates that there has been a change in tumour characteristics of patients diagnosed with RCC over time. It was also shown that calcium levels were an independent prognostic factor for cancer-specific mortality in this cohort. This cohort could provide a valuable basis for further molecular studies.

  • 35.
    Han, Hedong
    et al.
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Ye, Chen
    Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China.
    Tang, Zhongjun
    Department of Ophthalmology, Minhang Hospital, Fudan University, Shanghai, China.
    Qin, Yingyi
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Ruan, Yiming
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    He, Jia
    Department of Health Statistics, Second Military Medical University, Shanghai, China; Tongji University School of Medicine, Shanghai, China.
    Clinical characteristics and outcomes of robot-assisted laparoscopic radical prostatectomy in HIV-positive patients: a nationwide population-based analysis2019Ingår i: International Urology and Nephrology, ISSN 0301-1623, E-ISSN 1573-2584Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To compare differences in clinical characteristics and outcomes between patients with and without human immunodeficiency virus (HIV) infection in light of robot-assisted laparoscopic radical prostatectomy (RALRP) as the most common surgical technique for prostate cancer. Previous data on perioperative complication rates of RALRP in HIV(+) patients are limited by small sample size.

    Methods: The National Inpatient Sample database from 2008 to 2014 was used to query prostate cancer patients who underwent RALRP. HIV(+) patients were identified through ICD9 codes 042, 043, 044, V08 and 079.53. Intraoperative and postoperative complications, rate of blood transfusion, in-hospital mortality, prolonged length of stay and total cost were compared by univariate, multivariate regression and 1:4 propensity score matched analyses.

    Results: Overall, 270,319 weighted patients undergoing RALRP were identified, among whom 546 (0.20%) patients were diagnosed with HIV. Patients with HIV were younger, less likely to be white and had more comorbidities. Multivariable regression analysis revealed that HIV(+) patients had significantly increased genitourinary complications (odds ratio [OR]: 3.31; 95% confidence interval [CI]: 1.03-10.68) and miscellaneous surgical events (OR 3.19; 95% CI 1.26-8.08). There were no differences in potentially life-threatening cardiac, respiratory and vascular events between patients with and without HIV after RALRP. Propensity score matched analysis yielded similar results.

    Conclusions: Our findings suggest that patients who underwent RALRP with HIV did not experience higher risk of potentially life-threatening postoperative complications. RALRP could be safely considered as a surgical treatment for HIV(+) patients with prostate cancer.

  • 36.
    Holmberg, Lars
    et al.
    Regional Cancer Center Uppsala/Örebro, Uppsala, Sweden; Division of Cancer Studies, Medical School, King’s College London, London, UK; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden .
    Bill-Axelsson, Anna
    Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology Karolinska Institute, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden .
    Steineck, Gunnar
    Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden; Division of Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg, Sweden .
    Garmo, Hans
    Regional Cancer Center Uppsala/Örebro, Uppsala, Sweden; Division of Cancer Studies, Medical School, King’s College London, London, UK .
    Palmgren, Juni
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Johansson, Eva
    Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden .
    Adami, Hans-Olov
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Johansson, Jan-Erik
    Center for Assessment of Medical Technology, Örebro, Sweden .
    Results from the scandinavian prostate cancer group trial number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting2012Ingår i: Journal of the National Cancer Institute. Monographs, ISSN 1052-6773, E-ISSN 1745-6614, Vol. 2012, nr 45, s. 230-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4), 347 men were randomly assigned to radical prostatectomy and 348 to watchful waiting. In the most recent analysis (median follow-up time = 12.8 years), the cumulative mortality curves had been stable over the follow-up. At 15 years, the absolute risk reduction of dying from prostate cancer was 6.1% following randomization to radical prostatectomy, compared with watchful waiting. Hence, 17 need to be randomized to operation to avert one death. Data on self-reported symptoms, stress from symptoms, and quality of life were collected at 4 and 12.2 years of median follow-up. These questionnaire studies show an intricate pattern of symptoms evolving after surgery, hormonal treatments, signs of tumor progression, and also from natural aging. This article discusses some of the main findings of the SPCG-4 study. The Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4) started in 1989 when radical prostatectomy was newly introduced in Scandinavia and when there was essentially no prostate-specific antigen (PSA) testing in asymptomatic men; such testing only became common at the end of the inclusion of the trial a decade later. However, the trial data continue to be important for several reasons. In many parts of the world, the clinical panorama of prostate cancer still resembles that in Sweden in the early 1990s. The trial results point to many of the issues that modern diagnosis and treatment have to solve. SPCG-4 is to date the only trial to inform about both forces of mortality and self-reported symptoms and quality of life in men after radical prostatectomy or watchful waiting two decades and more out after a primary diagnosis of prostate cancer. According to the protocol (http://www.roc.se/prostata/SPCG-4.pdf), the main trial data have been updated every 3 years since 2002 (1–6). In this presentation, we highlight some of the main findings with bearing on the topic of this conference and discuss some issues that have been raised when the trial results have been presented.

  • 37.
    Håkansson, Ulf
    et al.
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Kirrander, Peter
    Region Örebro län. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Uvelius, Bengt
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Baseckas, Gediminas
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Torbrand, Christian
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Organ-sparing reconstructive surgery in penile cancer: initial experiences at two Swedish referral centres2015Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, nr 2, s. 149-154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this study was to present early outcome data for patients treated for penile cancer with organ-sparing reconstructive surgery at two referral centres in Sweden.

    Material and methods: Oncological, cosmetic and functional outcome and complications were analysed retrospectively during the period 2011-2013. Twelve patients with non-invasive penile cancer were treated with glans resurfacing (GR), while 15 patients with invasive penile cancer underwent total glansectomy with neoglans reconstruction (TGN).

    Results: The 12 patients treated with GR had a median age of 66 years (range 35-83 years) and a median follow-up time of 16 months (range 4-40 months). All patients showed carcinoma in situ and negative surgical margins in the final pathology report. The 15 patients treated with TGN had a median age of 71 years (range 37-78 years) and the median follow-up time was 10 months (range 1-25 months). All patients had invasive penile cancer and the surgical margins were negative in all cases except one. Complications occurred in five of the 27 patients (18%), and in most cases these were minor and infection related. No recurrences were seen in either group during follow-up, and all patients except one, who had undergone GR, were satisfied with the functional and cosmetic results.

    Conclusions: GR and TGN seem to be oncologically safe procedures for treating carefully selected patients with penile cancer, and the functional and cosmetic results are promising. Based on these findings, the authors recommend that penile amputation should only be carried out in patients who are not suitable for organ-sparing reconstructive surgery.

  • 38.
    Iglesias-Gato, Diego
    et al.
    IVS, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Centre for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Cancer Society, Copenhagen, Denmark.
    Wikström, Pernilla
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Tyanova, Stefka
    Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
    Lavallee, Charlotte
    IVS, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Centre for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Cancer Society, Copenhagen, Denmark.
    Thysell, Elin
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Hägglöf, Christina
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Cox, Jürgen
    Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Stattin, Pär
    Departments of Surgery and Perioperative Sciences, Umeå University, Umeå, Sweden.
    Egevad, Lars
    Section of Urology, Department of Surgical Science, Karolinska Institutet, Stockholm, Sweden.
    Widmark, Anders
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Bjartell, Anders
    Department of Translational Medicine, Division of Urological Cancers, University of Lund, Lund, Sweden.
    Collins, Colin C.
    Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
    Bergh, Anders
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Geiger, Tamar
    Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
    Mann, Matthias
    Novo Nordisk Foundation Centre for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
    Flores-Morales, Amilcar
    IVS, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Centre for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Cancer Society, Copenhagen, Denmark.
    The Proteome of Primary Prostate Cancer2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 5, s. 942-952Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries.

    Objectives: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers for disease aggressiveness.

    Design, setting, and participants: Mass spectrometry was used for genome-scale quantitative proteomic profiling of 28 prostate tumors (Gleason score 6-9) and neighboring nonmalignant tissue in eight cases, obtained from formalin-fixed paraffin-embedded prostatectomy samples. Two independent cohorts of PCa patients (summing 752 cases) managed by expectancy were used for immunohistochemical evaluation of proneuropeptide-Y (pro-NPY) as a prognostic biomarker.

    Results and limitations: Over 9000 proteins were identified as expressed in the human prostate. Tumor tissue exhibited elevated expression of proteins involved in multiple anabolic processes including fatty acid and protein synthesis, ribosomal biogenesis and protein secretion but no overt evidence of increased proliferation was observed. Tumors also showed increased levels of mitochondrial proteins, which was associated with elevated oxidative phosphorylation capacity measured in situ. Molecular analysis indicated that some of the proteins overexpressed in tumors, such as carnitine palmitoyltransferase 2 (CPT2, fatty acid transporter), coatomer protein complex, subunit alpha (COPA, vesicle secretion), and mitogen-and stress-activated protein kinase 1 and 2 (MSK1/2, protein kinase) regulate the proliferation of PCa cells. Additionally, pro-NPY was found overexpressed in PCa (5-fold, p < 0.05), but largely absent in other solid tumor types. Pro-NPY expression, alone or in combination with the ERG status of the tumor, was associated with an increased risk of PCa specific mortality, especially in patients with Gleason score <= 7 tumors.

    Conclusions: This study represents the first system-wide quantitative analysis of proteome changes associated to localized prostate cancer and as such constitutes a valuable resource for understanding the complex metabolic changes occurring in this disease. We also demonstrated that pro-NPY, a protein that showed differential expression between high and low risk tumors in our proteomic analysis, is also a PCa specific prognostic biomarker associated with increased risk for disease specific death in patients carrying low risk tumors.

    Patient summary: The identification of proteins whose expression change in prostate cancer provides novel mechanistic information related to the disease etiology. We hope that future studies will prove the value of this proteome dataset for development of novel therapies and biomarkers. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 39.
    Ilicki, Jonathan
    et al.
    Department of Urology, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Krauss, Wolfgang
    Department of Radiology, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Andersson, Swen-Olof
    Region Örebro län. Department of Urology, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Partial Segmental Thrombosis of the Corpus Cavernosum: A Case Report and a Review of the Literature2012Ingår i: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 79, nr 3, s. 708-712Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Partial segmental thrombosis of the corpus cavernosum (PSTCC) is a rare urological condition characterized by a painful, firm mass in the proximal part of the corpus cavernosum. The underlying pathophysiology of this condition is not fully understood. We present a case diagnosed by magnetic resonance imaging with complete clinical recovery after conservative treatment and novel associated findings, such as excessive alcohol intake. We also review the previous cases of PSTCC and propose a two hit model explaining PSTCC's etiology. UROLOGY 79: 708-712, 2012.

  • 40.
    Jahnson, Staffan
    et al.
    Department of Urology, Örebro Medical Centre, Örebro, Sweden.
    Karlsson, Mats G.
    Department of Pathology, Örebro Medical Centre, Örebro, Sweden.
    Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally advanced bladder carcinoma2000Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 89, nr 3, s. 619-629Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma.

    Methods: The hospital records from all 173 patients treated with cystectomy for locally advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively reviewed. Three consecutive sections from biopsies taken before any treatment were stained using the standard immunohistochemical technique for p53, p21, and mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression and 10% or more for positive p21 and mdm2 expression.

    Results: Positive immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors (51%), and for mdm2 in only 16 tumors (9%). The only association found between immunostaining for the three antibodies was that most mdm2-positive tumors had positive p21 expression. Tumor mapping of regional immunostaining showed no association between immunostaining for p53 and p21. In a proportional hazards analysis, no association was found between the results of immunostaining for the three antibodies and treatment outcome.

    Conclusions: Positive or negative expression of p53, p21, or mdm2, or combinations of these, was not associated with cancer specific mortality after cystectomy for bladder carcinoma. There was no association between immunostaining for p21 and p53, whereas positive immunostaining for mdm2 was observed in a minority of the tumors. These results indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins and tumor suppressor proteins along the p53 pathway that are involved in tumor development and progression.

  • 41.
    Jakobsen, Jakob Kristian
    et al.
    Dept Urol, Aarhus Univ Hosp, Aarhus, Denmark.
    Krarup, Kim Predbjorn
    Dept Urol, Copenhagen Univ Hosp, Copenhagen, Denmark.
    Kirrander, Peter
    Region Örebro län. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Håkansson, Ulf
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Kaipia, Antti
    Dept Surg, Satakunta Cent Hosp, Pori, Finland.
    Perttila, Ilkka
    Dept Urol, Helsinki Univ Hosp, Helsinki, Finland.
    Axcrona, Karol
    Dept Surg, St Olavs Univ Hosp, Trondheim, Norway.
    Torkelsen, Tor Kristian
    Dept Urol, Haukeland Hosp, Bergen, Norway.
    Hilmarsson, Rafn
    Div Surg, Natl Univ Hosp Iceland, Reykjavik, Iceland.
    Jensen, Jorgen Bjerggaard
    Dept Urol, Aarhus Univ Hosp, Aarhus, Denmark.
    Penile cancer in Scandinavia: Current practice and future perspectives2016Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, nr 1, s. 90-92Artikel i tidskrift (Refereegranskat)
  • 42.
    Jarrick, Simon
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Lundberg, Sigrid
    Department of Nephrology, Danderyd University Hospital, Stockholm, Sweden; Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Welander, Adina
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, stockholm, Sweden.
    Carrero, Juan-Jesus
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Höijer, Jonas
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bottai, Matteo
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
    Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort Study.2019Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 30, nr 5, s. 866-876Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The clinical course of IgA nephropathy (IgAN) varies from asymptomatic nonprogressive to aggressive disease, with up to one in four patients manifesting ESRD within 20 years of diagnosis. Although some studies have suggested that mortality appears to be increased in IgAN, such studies lacked matched controls and did not report absolute risk.

    METHODS: We conducted a population-based cohort study in Sweden, involving patients with biopsy-verified IgAN diagnosed in 1974-2011; main outcome measures were death and ESRD. Using data from three national registers, we linked 3622 patients with IgAN with 18,041 matched controls; we also conducted a sibling analysis using 2773 patients with IgAN with 6210 siblings and a spousal analysis that included 2234 pairs.

    RESULTS: During a median follow-up of 13.6 years, 577 (1.1%) patients with IgAN died (10.67 per 1000 person-years) compared with 2066 deaths (0.7%) in the reference population during a median follow-up of 14.1 years (7.45 per 1000 person-years). This corresponded to a 1.53-fold increased risk and an absolute excess mortality of 3.23 per 1000 person-years (equaling one extra death per 310 person-years) and a 6-year reduction in median life expectancy. Similar increases in risk were seen in comparisons with siblings and spouses. IgAN was associated with one extra case of ESRD per 54 person-years. Mortality preceding ESRD was not significantly increased compared with controls, spouses, or siblings. Overall mortality did not differ significantly between patients with IgAN-associated ESRD and patients with ESRD from other causes.

    CONCLUSIONS: Patients with IgAN have an increased mortality compared with matched controls, with one extra death per 310 person-years and a 6-year reduction in life expectancy.

  • 43.
    Jerlström, Tomas
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Andersson, Gunnel
    Örebro University Hospital, Örebro, Sweden.
    Carringer, Malcolm
    Örebro University Hospital, Örebro, Sweden.
    Functional outcome of orthotopic bladder substitution: a comparison between the S-shaped and U-shaped neobladder2010Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 44, nr 4, s. 197-203Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To compare the functional outcome of two types of orthotopic bladder substitution, the S-shaped and the U-shaped neobladder, with respect to leakage, functional capacity and quality of life.

    MATERIAL AND METHODS: Between 1999 and 2007, 45 male patients with urinary bladder cancer were treated with cystectomy and orthotopic bladder substitution; 23 with the S-shaped bladder ad modum Schreiter and 22 with the U-shaped bladder ad modum Studer. Patients were followed up by a urologist and a specialized nurse (urotherapist) at 1, 3 and 6 months. At each visit the patient completed a voiding chart, a weighted pad test and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Differences between the groups in functional outcome and quality of life variables were analysed by Student's t test using SPSS software.

    RESULTS: Mean maximum bladder capacity increased over time. At 6 months, the S-bladder had a larger capacity than the U-bladder (525 ml vs 423 ml). Patients with an S-bladder had less urine leakage at all follow-ups, although this was statistically significant only at 6 months regarding day-time incontinence and at all visits regarding night-time incontinence. The mean urine leakage at 6 months was 7 g (day) and 30 g (night) in the S-bladder group and 50 g (day) and 250 g (night) in the U-bladder group. However, quality of life did not differ between the groups.

    CONCLUSION: The S-bladder had better bladder capacity and less leakage than the U-bladder, but these differences did not translate into differences in quality of life. The results should be confirmed in larger prospective studies.

  • 44.
    Jerlström, Tomas
    et al.
    Department of Urology, University Hospital, Örebro, Sweden.
    Gardmark, Truls
    Dept Surg & Urol, Danderyd Hosp, Danderyd, Sweden.
    Carringer, Malcolm
    Region Örebro län. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Holmang, Sten
    Dept Urol, Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Liedberg, Fredrik
    Dept Urol, Skåne Univ Hosp, Malmö, Sweden.
    Hosseini, Abolfazl
    Dept Mol Med & Surg, Urol Sect, Karolinska Inst, Stockholm, Sweden.
    Malmström, Per-Uno
    Dept Surg Sci, Uppsala Univ, Uppsala, Sweden.
    Ljungberg, Börje
    Dept Surg & Perioperat Sci Urol & Androl, Norrlands Univ Hosp, Umeå, Sweden.
    Hagberg, Oskar
    Reg Canc Ctr South, Lund, Sweden.
    Jahnson, Staffan
    Dept Clin & Expt Med, Div Urol, Linköping Univ Hosp, Linköping, Sweden.
    Urinary bladder cancer treated with radical cystectomy: Perioperative parameters and early complications prospectively registered in a national population-based database2014Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 48, nr 4, s. 334-340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Cystectomy combined with pelvic lymph-node dissection and urinary diversion entails high morbidity and mortality. Improvements are needed, and a first step is to collect information on the current situation. In 2011, this group took the initiative to start a population-based database in Sweden (population 9.5 million in 2011) with prospective registration of patients and complications until 90 days after cystectomy. This article reports findings from the first year of registration.

    Material and methods: Participation was voluntary, and data were reported by local urologists or research nurses. Perioperative parameters and early complications classified according to the modified Clavien system were registered, and selected variables of possible importance for complications were analysed by univariate and multivariate logistic regression.

    Results: During 2011, 285 (65%) of 435 cystectomies performed in Sweden were registered in the database, the majority reported by the seven academic centres. Median blood loss was 1000 ml, operating time 318 min, and length of hospital stay 15 days. Any complications were registered for 103 patients (36%). Clavien grades 1-2 and 3-5 were noted in 19% and 15%, respectively. Thirty-seven patients (13%) were reoperated on at least once. In logistic regression analysis elevated risk of complications was significantly associated with operating time exceeding 318 min in both univariate and multivariate analysis, and with age 76-89 years only in multivariate analysis.

    Conclusions: It was feasible to start a national population-based registry of radical cystectomies for bladder cancer. The evaluation of the first year shows an increased risk of complications in patients with longer operating time and higher age. The results agree with some previously published series but should be interpreted with caution considering the relatively low coverage, which is expected to be higher in the future.

  • 45.
    Jerlström, Tomas
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Ruoqing, Chen
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology.
    Ströck, Viveka
    Sahlgrenska Academy, Institute of Clinical Sciences, Gothenburg, Sweden; Sahlgrenska Academy, Institute of Clinical Sciences, Gothenburg, Sweden.
    Aljabery, Firas A. S.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Hosseini, Abolfazl
    Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Sherif, Amir
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Malmström, Per-Uno
    Department of Urology, Institute of Surgical Sciences, Uppsala, Sweden.
    Ullén, Anders
    PO Bäckencancer, Theme Cancer, Karolinska University Hospital and Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fall, Katja
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study2019Ingår i: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 46. Johansson, Eva
    et al.
    Bill-Axelson, Anna
    Holmberg, Lars
    Onelöv, Erik
    Johansson, Jan-Erik
    Örebro universitet, Hälsoakademin.
    Steineck, Gunnar
    Time, Symptom Burden, Androgen Deprivation, and Self-Assessed Quality of Life after Radical Prostatectomy or Watchful Waiting: The Randomized Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) Clinical Trial2008Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 55, nr 2, s. 422-432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Quality-of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer.

    OBJECTIVE: To evaluate how follow-up time, number of physical symptoms, and presence of androgen deprivation affected quality of life among men randomized to radical prostatectomy or watchful waiting.

    DESIGN, SETTING, AND PARTICIPANTS: The study group was composed of all 376 living men included in the Swedish part of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) between January 1, 1989, and February 29, 1996. Quality-of-life data were collected after a mean follow-up time of 4.1 yr.

    INTERVENTION: All patients were randomly assigned to radical prostatectomy or watchful waiting. Forty-five men were androgen deprived.

    MEASUREMENTS: Data of specific symptoms, symptom-induced stress, sense of well-being, and self-assessed quality of life were obtained by means of a questionnaire. Psychological symptoms were assessed using seven-point visual digital scales.

    RESULTS AND LIMITATIONS: In analyses stratified on the basis of the numbers of physical symptoms, anxiety and depressed mood were less common, and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group. As the number of physical symptoms increased, all psychological variables became worse and more prominent in the watchful waiting group. After a follow-up time of 6-8 yr, a significant decrease in quality of life (p=0.03) was seen in the watchful waiting group. Twenty-four percent of androgen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60% in the radical prostatectomy group. Eighty-eight percent of patients had clinically detected tumors.

    CONCLUSIONS: Androgen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting. The number of physical symptoms was associated with the level of quality of life. Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group (p=0.03).

  • 47.
    Kirrander, Peter
    et al.
    Region Örebro län.
    Andrén, Ove
    Region Örebro län.
    Windahl, Torgny
    Region Örebro län. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Dynamic sentinel node biopsy in penile cancer: initial experiences at a Swedish referral centre2013Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 111, nr 3B, s. E48-E53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study Type Therapy (case series) Level of Evidence4 What's known on the subject? and What does the study add? According to the current European Association of Urology Guidelines, dynamic sentinel node biopsy is the recommended approach to assess lymph node status in men with cN0 intermediate and high risk penile cancer. Nevertheless, most encouraging results derive from a limited number of studies. The present study shows a false-negative rate of 15%, comparable with or better than several previous studies. Nevertheless, the aim should be a false-negative rate of no more than 5%. We conclude that increased overall experience and the use of the complete modern dynamic sentinel node biopsy protocol are paramount to improve results.

    OBJECTIVE center dot To evaluate the false-negative rate and complication rate of dynamic sentinel node biopsy (DSNB) in penile cancer.

    PATIENTS AND METHODS center dot In this retrospective study, 58 unilaterally or bilaterally clinically lymph node negative (cN0) patients with penile cancer (57 squamous cell carcinomas and one malignant melanoma), scheduled for DSNB at the orebro University Hospital, Sweden, between 1999 and 2011, were analysed. center dot Preoperative ultrasonography and fine-needle aspiration cytology of suspicious nodes were not introduced until 2008. center dot Patients were assessed by lymphoscintigraphy using 99mtechnetium nanocolloid on the day before surgery and the dissection of sentinel nodes was aided by the lymphoscintigraphic images and intraoperative detection of radiotracer and patent blue dye. center dot The false-negative rate and complication rate were calculated per groin.

    RESULTS center dot Of the 58 patients, 32 (55%) underwent preoperative ultrasonography. center dot Two patients had positive fine-needle aspiration cytology and discontinued further DSNB protocol. Of the remaining 56 patients, all but one were bilaterally cN0 and hence 111 cN0 groins were assessed by lymphoscintigraphy. center dot In the 55 bilaterally cN0 patients, lymphoscintigraphy visualized a bilateral sentinel node in 34 (62%). center dot At surgery, all excised sentinel nodes were radioactive while 43% were additionally blue. In total, at least one sentinel node was harvested in 96 (86%) of the DSNB staged groins. center dot A positive sentinel node was found in 11 groins (bilaterally in three patients). During a median follow-up of 21 months, two false-negative cases emerged, producing a false-negative rate of 15%. Both false-negative cases occurred during the first half of the study. The complication rate was 10%. The majority of complications were minor and transient.

    CONCLUSIONS center dot DSNB is a minimally invasive staging tool in men with cN0 penile cancer, enabling early detection of metastatic disease and thus optimal care. center dot Our false-negative rate of 15% is comparable or even favourable in comparison with several previous studies, but far from the 5% or less that we aim for. The complication rate found is somewhat higher than previously reported. center dot With increased overall experience and the continued use of the complete DSNB protocol, we believe our results will improve and the complication rate will decrease.

  • 48.
    Kirrander, Peter
    et al.
    Örebro University Hospital.
    Sherif, A
    Friedrich, B
    Lambe, M
    Håkansson, U
    The swedish national penile cancer register: incidence, tumour characteristics, management and survivalManuskript (preprint) (Övrigt vetenskapligt)
  • 49.
    Kirrander, Peter
    et al.
    Region Örebro län. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Sherif, Amir
    Dept Surg & Perioperat Sci, Urol & Androl, Umeå Univ, Umeå, Sweden.
    Friedrich, Bengt
    Dept Surg & Perioperat Sci, Urol & Androl, Umeå Univ, Umeå, Sweden.
    Lambe, Mats
    Reg Canc Ctr Uppsala Orebro, Uppsala Univ, Uppsala, Sweden; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Håkansson, Ulf
    Dept Urol, Skåne Univ, Malmö, Sweden.
    Swedish National Penile Cancer Register: incidence, tumour characteristics, management and survival2016Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, nr 2, s. 287-292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To assess penile cancer incidence, stage distribution, adherence to guidelines and prognostic factors in a population-based setting.

    Patients and Methods: The population-based Swedish National Penile Cancer Register (NPECR) contains detailed information on tumour characteristics and management patterns. A total of 1 678 men with primary squamous cell carcinoma of the penis identified in the NPECR between 2000 and 2012 were included in the study.

    Results: The mean age-adjusted incidence of penile cancer was 2.1/100 000 men, remaining virtually unchanged during the study period. At diagnosis, 14 and 2% of the men had clinical N+ and M+ disease, respectively. Most men were staged pTis (34%), pT2 (19%), or pT1 (18%), while stage information was unavailable for 18% of the men. Organ-preserving treatment was used in 71% of Tis-T1 tumours. Of men with cN0 and >= pT1G2 disease, 50% underwent lymph node staging, while 74% of men with cN1-3 disease underwent lymph node dissection. The overall 5-year relative survival rate was 82%. Men aged >= 40 years and those with pT2-3, G2-3 and N+ tumours had worse outcomes.

    Conclusions: The incidence of penile cancer in Sweden is stable. Most men presented with localized disease, and the proportion of non-invasive tumours was high. During the period under study, adherence to guidelines was suboptimum. The overall 5-year relative survival rate was 82%. Older age, increasing tumour stage and grade, and increasing lymph node stage were associated with poorer survival.

  • 50.
    Kjolhede, Henrik
    et al.
    Dept Surg, Växjö Hosp, Lund Univ, Lund, Sweden.
    Bratt, Ola
    Dept Urol, Helsingborg Hosp, Lund Univ, Lund, Sweden.
    Gudjonsson, Sigurdur
    Dept Urol, Skåne Univ Hosp, Lund Univ, Lund, Sweden.
    Sundqvist, Pernilla
    Region Örebro län. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Liedberg, Fredrik
    Dept Urol, Skåne Univ Hosp, Lund Univ, Lund, Sweden.
    Simplified intraoperative sentinel-node detection performed by the urologist accurately determines lymph-node stage in prostate cancer2015Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, nr 2, s. 97-102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The reference standard for lymph-node staging in prostate cancer is currently an extended pelvic lymph-node dissection (ePLND), which detects most, but not all, regional lymph-node metastases. As an alternative to ePLND, sentinel-node dissection with preoperative isotope injection and imaging has been reported. The objective was to determine whether intraoperative sentinel-node detection with a simplified protocol can accurately determine lymph-node stage in prostate cancer patients.

    Materials and methods: Patients with biopsy-verified high-risk prostate cancer with tumour stage T2-3 were included in the study. All patients underwent both ePLND and sentinel-node detection. Tc-99m-marked nanocolloid was injected peritumourally by the operating urologist after induction of anaesthesia just before surgery. Sentinel nodes were detected both in vivo and ex vivo intraoperatively using a gamma probe. Sentinel nodes and metastases and their locations were recorded. Sensitivity and specificity were calculated.

    Results: At least one sentinel node was detected in 72 (87%) of the 83 patients. In 13 (18%) of these 72 patients sentinel nodes were detected outside the ePLND template. In six of these 13 patients, the Sentinel nodes from outside the template contained metastases, which proved to be the only metastases in two. For 12 patients the only metastatic deposit found was a micrometastasis (<= 2 mm) in a sentinel node. In the 72 patients with detectable sentinel nodes, pathological analysis of the sentinel node correctly categorized 71 and ePLND 70 patients.

    Conclusions: This protocol yielded results comparable to the commonly used technique of sentinel-node detection, but with more cases of non-detection.

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