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  • 1.
    Austin, Paul F
    et al.
    Division of Urology, Washington University in St. Louis, St. Louis Children’s Hospital, Missouri.
    Bauer, Stuart B
    Department of Urology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts.
    Bower, Wendy
    Pediatrics (Nephrology Section), Skejby University Hospital, Aarhus, Denmark.
    Chase, Janet
    The Children’s Centre, Cabrini Hospital, Melbourne, Australia.
    Franco, Israel
    New York Medical College, Valhalla, New York.
    Hoebeke, Piet
    Pediatric Urology and Nephrology, Gent University Hospital, Ghent, Belgium.
    Rittig, Søren
    Pediatrics (Nephrology Section), Skejby University Hospital, Aarhus, Denmark.
    Walle, Johan Vande
    Pediatric Urology and Nephrology, Gent University Hospital, Ghent, Belgium.
    von Gontard, Alexander
    Department of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg, Germany.
    Wright, Anne
    Pediatrics, Evelina Children’s Hospital, St Thomas’ Hospital, London, England.
    Yang, Stephen S
    Division of Urology, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, New Taipei.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The Standardization of Terminology of Lower Urinary Tract Function in Children and Adolescents: Update Report from the Standardization Committee of the International Children's Continence Society.2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 6, p. 1863-1865Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The impact of the original International Children's Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function.

    MATERIALS AND METHODS: A variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited.

    RESULTS: Following a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback.

    CONCLUSIONS: The present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children.

  • 2. Barker, G. M.
    et al.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Arnell, Kai
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Distal shunt obstruction in children with meningomyelocele after bladder perforation2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 176, no 4 Pt 2, p. 1726-1728Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We studied short-term complications and particularly the signs of shunt dysfunction after augmented bladder perforation in patients with myelomeningocele and ventriculoperitoneal shunts. MATERIALS AND METHODS: In our series of bladder augmentations in 27 patients with myelomeningocele and a ventriculoperitoneal shunt in the last 10 years (1994 to 2004) we noted 4 who were 8 to 16 years old at our institute with bladder perforation 2 to 5 years after augmentation. Three patients received a colonic augmentation and 1 received an ileal augmentation. One patient underwent surgery for small bowel obstruction 2 years after the primary operation, when a hole in the augmented bladder was identified and oversewn. The other 3 bladder perforations occurred spontaneously or after failure to catheterize. An additional patient with spontaneous perforation underwent auto-augmentation elsewhere. RESULTS: After primary open abdominal surgery and enterocystoplasty there was no sign of shunt dysfunction in any patient. Bladder perforation and leakage of free urine into the abdominal cavity occurred in 4 of the 5 patients. In those patients severe symptoms of shunt dysfunction, including headache and high intracranial pressure, were noted 2 to 7 days after perforation. In patient 1 there was only urine leakage into a small cavity close to the bladder and no acute signs of post-perforation shunt dysfunction. In all cases the shunt was externalized for 1 to 6 weeks without further complications. CONCLUSIONS: In patients with myelodysplasia who have bladder perforation and free urine in the abdominal cavity the peritoneum is chemically inflamed by urine. Resorption of cerebral liquor may be disturbed, leading to shunt dysfunction and high intracranial pressure. Therefore, it is important for the urologist to recognize and evaluate postoperative signs and symptoms of increased intracerebral pressure in patients with bladder perforation. If found, early computerized tomography of the brain is recommended.

  • 3. Berglund, Anders
    et al.
    Garmo, Hans
    Tishelman, Carol
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stattin, Pär
    Lambe, Mats
    Comorbidity, treatment and mortality: a population based cohort study of prostate cancer in PCBaSe Sweden2011In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 185, no 3, p. 833-840Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    We examined associations among comorbidity, treatment decisions and mortality in patients with prostate cancer.

    MATERIALS AND METHODS:

    A total of 77,536 men diagnosed with prostate cancer between 1997 and 2006 were identified in PCBaSe Sweden from the National Prostate Cancer Register of Sweden. Logistic, Cox and competing risk regression were used to assess associations among Charlson comorbidity index, treatment and mortality. The Charlson comorbidity index was categorized into no (0), mild (1) and severe comorbidity (2+).

    RESULTS:

    In men with low risk prostate cancer 5,975 of the 13,245 (45.1%) patients without comorbidity underwent radical prostatectomy compared to 256 of the 1,399 (18.9%) men with severe comorbidity. Following adjustment for age and period of diagnosis, radical prostatectomy was less likely to be offered to men with severe comorbidity (OR 0.48, 95% CI 0.41-0.55). In men with high risk prostate cancer, radiotherapy was more common (range 7.7% to 21.3%) than radical prostatectomy (range 3.0% to 11.2%) regardless of comorbidity burden. All cause and competing cause but not prostate cancer specific mortality were increased in men with severe comorbidity (all cause HR 1.99, 95% CI 1.93-2.05; competing cause sHR 2.66, 95% CI 2.56-2.78; prostate cancer specific sHR 0.98, 95% CI 0.93-1.03). The cumulative probability of prostate cancer death given no death from competing causes was significantly higher in men with severe comorbidity in all risk groups (p<0.01).

    CONCLUSIONS:

    Comorbidity affects treatment choices, and is associated with all cause, competing cause and conditional prostate cancer specific mortality. An increased conditional prostate cancer specific mortality in men with severe comorbidity may reflect less aggressive treatment, impaired tumor defense, lifestyle factors and poor general health behavior.

  • 4.
    Beukers, Willemien
    et al.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    van der Keur, Kirstin A.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    Kandimalla, Raju
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    Vergouwe, Yvonne
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands..
    Steyerberg, Ewout W.
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands..
    Boormans, Joost L.
    Erasmus MC, Dept Urol, Rotterdam, Netherlands..
    Jensen, Jorgen B.
    Aarhus Univ Hosp, Dept Urol, Aarhus, Denmark..
    Lorente, Jose A.
    Hosp del Mar, Serv Urol, Barcelona, Spain..
    Real, Francisco X.
    Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.;Spanish Natl Canc Res Centre CNIO, Canc Cell Biol Programme, Epithelial Carcinogenesis Grp, Madrid, Spain..
    Segersten, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Malats, Nuria
    Spanish Natl Canc Res Centre CNIO, Canc Cell Biol Programme, Epithelial Carcinogenesis Grp, Madrid, Spain..
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Dyrskjot, Lars
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    FGFR3, TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter Study2017In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 197, no 6, p. 1410-1418Article in journal (Refereed)
    Abstract [en]

    Purpose: Patients with nonmuscle invasive bladder cancer are followed with frequent cystoscopies. In this study FGFR3, TERT and OTX1 were investigated as a diagnostic urinary marker combination during followup of patients with primary nonmuscle invasive bladder cancer.

    Materials and Methods: In this international, multicenter, prospective study 977 patients with nonmuscle invasive bladder cancer were included. A total of 2,496 urine samples were collected prior to cystoscopy during regular visits. Sensitivity was estimated to detect concomitant recurrences. Kaplan-Meier curves were used to estimate the development of future recurrences after urinalysis and a negative cystoscopy.

    Results: Sensitivity of the assay combination for recurrence detection was 57% in patients with primary low grade, nonmuscle invasive bladder cancer. However, sensitivity was 83% for recurrences that were pT1 or muscle invasive bladder cancer. Of the cases 2% progressed to muscle invasive bladder cancer. Sensitivity for recurrence detection in patients with primary high grade disease was 72% and 7% of them had progression to muscle invasive bladder cancer. When no concomitant tumor was found by cystoscopy, positive urine samples were more frequently followed by a recurrence over time compared to a negative urine sample (58% vs 36%, p < 0.001). High stage recurrences were identified within 1 year after a positive urine test and a negative cystoscopy.

    Conclusions: Recurrences in patients with primary nonmuscle invasive bladder cancer can be detected by a combination of urine assays. This study supports the value of urinalysis as an alternative diagnostic tool in patients presenting with low grade tumors and as a means to identify high stage tumors earlier.

  • 5.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Norlén, Bo Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Norberg, Mona
    No increased prostate cancer incidence after negative transrectal ultrasound guided multiple biopsies in men with increased prostate specific antigen and/or abnormal digital rectal examination.2003In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 170, no 4 Pt 1, p. 1180-3Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We investigated the incidence of prostate cancer after negative transrectal ultrasound (TRUS) guided multiple biopsies. Our secondary aim was to calculate the sensitivity of the extended protocol used.

    MATERIALS AND METHODS: A cohort of 547 men with elevated prostate specific antigen and/or abnormal digital rectal examination but with results negative for prostate cancer on a mean of 9 TRUS guided biopsies was followed through record linkage to the national cancer Registry. The observed number of prostate cancers was compared with the expected number during the same calendar period in an age matched male population to determine the standardized incidence ratio. The sensitivity of TRUS with multiple biopsies after 5 years of followup was calculated. Relative survival was estimated if there was an excess death rate due to undiagnosed prostate cancer.

    RESULTS: We found 11 men diagnosed with prostate cancer. The expected number in the age standardized male population was 15, resulting in a standardized incidence ratio of 0.8 (95% CI 0.4 to 1.2). Five-year sensitivity of the extended protocol of TRUS guided biopsies was 95.2% (95% CI 93.5 to 96.4) and relative survival was more than 100%, indicating a selection of men deemed candidates for curative treatment.

    CONCLUSIONS: Men with clinical suspicion of prostate cancer who are examined by an extended protocol of TRUS guided biopsies negative for cancer do not have an increased incidence of prostate cancer within 6 years compared with an age matched male population. Five-year sensitivity of this protocol was high.

  • 6.
    Brandström, Per
    et al.
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Esbjörner, Elisabeth
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Herthelius, Maria
    Department for Clinical Science, Intervention and Technology, Karolinska University Hospital, Huddinge, Sweden.
    Holmdahl, Gundela
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sillén, Ulla
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Sixt, Rune
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Sjöberg, Ingrid
    Department of Pediatrics, Children's University Hospital, Lund, Sweden.
    Stokland, Eira
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Jodal, Ulf
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Hansson, Sverker
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    The Swedish reflux trial in children: I. Study design and study population characteristics2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 1, p. 274-279Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection. MATERIALS AND METHODS: Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle. RESULTS: During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy. CONCLUSIONS: Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.

  • 7.
    Brandström, Per
    et al.
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sixt, Rune
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Stokland, Eira
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Jodal, Ulf
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Hansson, Sverker
    Pediatric Uro-Nephrologic Center, The Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    The Swedish reflux trial in children: IV. Renal damage2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 1, p. 292-297Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We compared the development of new renal damage in small children with dilating vesicoureteral reflux randomly allocated to antibiotic prophylaxis, endoscopic treatment or surveillance as the control group. MATERIALS AND METHODS: Included in the study were 128 girls and 75 boys 1 to younger than 2 years with grade III-IV reflux. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. Febrile urinary tract infections were recorded during followup. Data analysis was done by the intent to treat principle. RESULTS: New renal damage in a previously unscarred area was seen in 13 girls and 2 boys. Eight of the 13 girls were on surveillance, 5 received endoscopic therapy and none were on prophylaxis (p = 0.0155). New damage was more common in children with than without febrile recurrence (11 of 49 or 22% vs 4 of 152 or 3%, p <0.0001). CONCLUSIONS: In boys the rate of new renal damage was low. It was significantly higher in girls and most common in the control surveillance group. There was also a strong association between recurrent febrile UTIs and new renal damage in girls.

  • 8. Carter, H Ballentine
    et al.
    Albertsen, Peter C
    Barry, Michael J
    Etzioni, Ruth
    Freedland, Stephen J
    Greene, Kirsten Lynn
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Kantoff, Philip
    Konety, Badrinath R
    Murad, Mohammad Hassan
    Penson, David F
    Zietman, Anthony L
    Early detection of prostate cancer: AUA Guideline2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 190, no 2, p. 419-426Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men.

    MATERIALS AND METHODS:

    A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥ 70).

    RESULTS:

    Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.

    CONCLUSIONS:

    The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence.

  • 9. Dellagrammaticas, D
    et al.
    Bryden, A A
    Collins, G N
    Regression of metastatic transitional cell carcinoma in response to tamoxifen.2001In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 165, no 5, article id 1631Article in journal (Refereed)
  • 10. Donovan, Michael J.
    et al.
    Khan, Faisal M.
    Fernandez, Gerardo
    Mesa-Tejada, Ricardo
    Sapir, Marina
    Zubek, Valentina Bayer
    Powell, Douglas
    Fogarasi, Stephen
    Vengrenyuk, Yevgen
    Teverovskiy, Mikhail
    Segal, Mark R.
    Karnes, R. Jeffrey
    Gaffey, Thomas A.
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hlavcak, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Freedland, Stephen J.
    Vollmer, Robin T.
    Albertsen, Peter
    Costa, Jose
    Cordon-Cardo, Carlos
    Personalized prediction of tumor response and cancer progression on prostate needle biopsy2009In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 182, no 1, p. 125-132Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To our knowledge in patients with prostate cancer there are no available tests except clinical variables to determine the likelihood of disease progression. We developed a patient specific, biology driven tool to predict outcome at diagnosis. We also investigated whether biopsy androgen receptor levels predict a durable response to therapy after secondary treatment. MATERIALS AND METHODS: We evaluated paraffin embedded prostate needle biopsy tissue from 1,027 patients with cT1c-T3 prostate cancer treated with surgery and followed a median of 8 years. Machine learning was done to integrate clinical data with biopsy quantitative biometric features. Multivariate models were constructed to predict disease progression with the C index to estimate performance. RESULTS: In a training set of 686 patients (total of 87 progression events) 3 clinical and 3 biopsy tissue characteristics were identified to predict clinical progression within 8 years after prostatectomy with 78% sensitivity, 69% specificity, a C index of 0.74 and a HR of 5.12. Validation in an independent cohort of 341 patients (total of 44 progression events) yielded 76% sensitivity, 64% specificity, a C index of 0.73 and a HR of 3.47. Increased androgen receptor in tumor cells in the biopsy highly significantly predicted resistance to therapy, ie androgen ablation with or without salvage radiotherapy, and clinical failure (p <0.0001). CONCLUSIONS: Morphometry reliably classifies Gleason pattern 3 tumors. When combined with biomarker data, it adds to the hematoxylin and eosin analysis, and prostate specific antigen values currently used to assess outcome at diagnosis. Biopsy androgen receptor levels predict the likelihood of a response to therapy after recurrence and may guide future treatment decisions.

  • 11. Elmer, Caroline
    et al.
    Blomgren, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Falconer, Christian
    Zhang, Anju
    Altman, Daniel
    Histological Inflammatory Response to Transvaginal Polypropylene Mesh for Pelvic Reconstructive Surgery2009In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 181, no 3, p. 1189-1195Article in journal (Refereed)
    Abstract [en]

    Purpose: We prospectively evaluated the histological inflammatory response to the large polypropylene transvaginal mesh used for pelvic organ prolapse surgery. Materials and Methods: Ten patients and 8 controls underwent vaginal punch biopsy sampling before surgery and patients also underwent it I year after pelvic reconstructive surgery using polypropylene mesh. Foreign body response to the mesh was assessed using a combination of histological, semiquantitative and computerized image based analysis. Results: Compared to preoperative histology there was a significant postoperative increase in macrophage and mast cell counts (p = 0.03 and 0.01) but no significant changes in the count of cells involved primarily in the infectious cell response or collagen density and the elastin area fraction at the mesh-tissue interface (p = 0.2 and 0.3, respectively). Three cases of mild granuloma formation and 2 of mild erosion were observed. There was no significant change in epithelial thickness when comparing preoperative and postoperative samples. Conclusions: When used for pelvic reconstructive surgery, macroporous monofilament polypropylene mesh induces a mild but persistent foreign body reaction.

  • 12. Frioriksson, Jon Om
    et al.
    Holmberg, Erik
    Adolfsson, Jan
    Lambe, Mats
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Carlsson, Stefan
    Hugosson, Jonas
    Stattin, Par
    Rehospitalization after Radical Prostatectomy in a Nationwide, Population Based Study2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 1, p. 112-119Article in journal (Refereed)
    Abstract [en]

    Purpose: We investigated hospital readmission frequency during the 90 days after radical prostatectomy and assessed the readmission risk associated with potentially related variables. Materials and Methods: Using the population based, nationwide PCBaSe (Prostate Cancer data Base Sweden) we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy as primary treatment. We used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load and patient characteristics. Results: During 90 postoperative days 2,317 of the 24,122 men (10%) identified were nonelectively readmitted, specifically 10% after retropubic, 9% after robot-assisted and 11% after laparoscopic radical prostatectomy. The range in readmission frequency among hospitals was 0% to 35%. Higher readmission risk was associated with the early calendar period (2009 to 2011 vs 2000 to 2002 OR 0.71, 95% CI 0.61-0.83), greater age (70 or greater vs less than 60 years OR 1.17, 95% CI 1.00-1.36), higher risk category (high vs low OR 1.78, 95% CI 1.57-2.03), high comorbidity (Charlson comorbidity index 3 or greater vs 0 OR 1.77, 95% CI 1.29-2.44) and low hospital surgical volume (150 or greater vs fewer than 30 radical prostatectomies per year OR 0.70, 95% CI 0.60-0.81). Conclusions: Readmission rates after different radical prostatectomy methods were similar, ranging from 9% to 11%, with wide variation among hospitals. Readmission rates can be used as an indicator of perioperative care quality but potential confounders must be adjusted to avoid bias.

  • 13.
    Hemdan, Tammer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Johansson, Robert
    Jahnson, Staffan
    Hellström, Pekka
    Tasdemir, Ilker
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Five year outcome of a randomized prospective study comparing bacillus Calmette-Guerin with epirubicin and interferon α 2b in patients with T1 bladder cancer2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 5, p. 1244-1249Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    In a multicenter, prospectively randomized study we evaluated the five-year outcome of bacillus Calmette-Guérin (BCG) alone compared to a combination of epirubicin and interferon α 2b in the treatment of patients with T1 bladder cancer.

    MATERIAL AND METHODS:

    The transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and cancer in situ. Follow-up entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to failure of the treatment and progression, cancer-specific survival, and prognostic factors.

    RESULTS:

    The study recruited 250 eligible patients.The five years recurrence-free survival were 38% in the combination arm and 59% in the BCG arm (p=0.001). The corresponding rates for the other endpoints were not significantly different; free of - progression 78 and 77%, - treatment failure 75 and 75% and cancer-specific survival 90 and 92%. The type of treatment, size and tumour status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of BCG therapy. Independent factor for treatment failure was remaining T1 stage at second resection.

    CONCLUSIONS:

    BCG therapy was more effective than the tested combination. Presently recommended management with second resection and three week maintenance BCG entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumours at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after BCG therapy.

  • 14.
    Hemdan, Tammer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Jahnson, Staffan
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 6, p. 1575-1581Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response.

    MATERIALS AND METHODS: Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry.

    RESULTS: Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p <0.001). The values for cancer specific survival were 76% and 56%, respectively (p <0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p = 0.23) or cancer specific survival (55% vs 51%, p = 0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials.

    CONCLUSIONS: Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression.

  • 15.
    Holmdahl, Gundela
    et al.
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Brandström, Per
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sillén, Ulla
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Stokland, Eira
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Jodal, Ulf
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    Hansson, Sverker
    Pediatric Uro-Nephrologic Center, Queen Silvia Children's Hospital, University of Gothenburg, Göteborg, Sweden.
    The Swedish reflux trial in children: II. Vesicoureteral reflux outcome2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 1, p. 280-285Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We compared reflux status in children with dilating vesicoureteral reflux treated in 3 groups, including low dose antibiotic prophylaxis, endoscopic therapy and a surveillance group on antibiotic treatment only for febrile urinary tract infection.

    MATERIALS AND METHODS: A total of 203 children 1 to younger than 2 years with grade III-IV reflux were recruited into this open, randomized, controlled trial. Endoscopic treatment was done with dextranomer/hyaluronic acid copolymer. The main end point was reflux status after 2 years. Data were analyzed by the intent to treat principle.

    RESULTS: Reflux status improved in all 3 treatment arms. Of patients in the prophylaxis, endoscopic and surveillance groups 39%, 71% and 47%, respectively, had reflux resolution or downgrading to grade I-II after 2 years. This was significantly more common in the endoscopic than in the prophylaxis and surveillance groups (p = 0.0002 and 0.0030, respectively). After 1 or 2 injections 86% of patients in the endoscopic group had no or grade I-II reflux but recurrent dilating reflux was seen in 20% after 2 years.

    CONCLUSIONS: Endoscopic treatment resulted in dilating reflux resolution or downgrading in most treated children. After 2 years endoscopic treatment results were significantly better than the spontaneous resolution rate or downgrading in the prophylaxis and surveillance groups. However, of concern is the common reappearance of dilating reflux after 2 years.

  • 16. Loeb, Stacy
    et al.
    Berglund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Stattin, Par
    Population Based Study of Use and Determinants of Active Surveillance and Watchful Waiting for Low and Intermediate Risk Prostate Cancer2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 190, no 5, p. 1742-1749Article in journal (Refereed)
    Abstract [en]

    Purpose: Prior studies have reported the underuse of deferred treatment (ie active surveillance or watchful waiting) for low risk prostate cancer in the United States. We examined contemporary trends in active surveillance and watchful waiting in the nationwide Swedish prostate cancer registry. We also examined factors associated with selection of deferred management, which might provide insight into the rational diffusion of this important management strategy. Materials and Methods: We identified 57,713 men with very low risk (T1c, Gleason 6 or less, prostate specific antigen less than 10 ng/ml, prostate specific antigen density less than 0.20 ng/ml/cc, 2 or fewer positive biopsy cores or less than 25% of cores positive), low risk (T1-T2, Gleason 6 or less, and prostate specific antigen less than 10 ng/ml) and intermediate risk prostate cancer (T1-T2, Gleason 7 and/or prostate specific antigen 10 to 20 ng/ml) in the PCBaSe (Prostate Cancer database Sweden) from 1998 to 2011. Subclassification of very low risk disease, and active surveillance vs watchful waiting was possible beginning in 2007. We examined primary treatment selection by risk group and used logistic regression to evaluate factors associated with deferred treatment. Results: Overall 13,272 (46%) men with low risk and 8,695 (30%) with intermediate risk prostate cancer chose deferred treatment. Since 2007, 59%, 41% and 16% of very low, low and intermediate risk prostate cancer, respectively, chose active surveillance. Age was by far the strongest determinant of deferred treatment. Education, marital status and comorbidity were significantly but weakly associated with deferring treatment. Conclusions: Deferred treatment for low and intermediate risk prostate cancer was frequently used in Sweden. Dissociating diagnosis from treatment in men with a low risk of progression can decrease the rate of overtreatment.

  • 17.
    Loeb, Stacy
    et al.
    NYU, Dept Urol & Populat Hlth, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Lambe, Mats
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden..
    Re: Editorial Comment on Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma2016In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 195, no 4, p. 1172-1173Article in journal (Refereed)
  • 18.
    Loskog, Angelica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Björkland, Anna
    Brown, Michael P.
    Korsgren, Olle
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Tötterman, Thomas H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Potent antitumor effects of CD154 transduced tumor cells in experimental bladder cancer2001In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 166, no 3, p. 1093-1097Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Current intravesical immunotherapy for bladder cancer with bacillus Calmette-Guerin instillations is standard treatment for patients with high risk superficial tumors but relapses are common. We evaluated the tumor vaccine concept in murine bladder cancer by comparing tumor cell transduction with genes coding for the immunostimulatory molecules CD154, interleukin (IL)-12 and CD80 to design a novel vaccination strategy.

    MATERIALS AND METHODS: Adenoviral vectors were used to transduce murine bladder cancer MB-49 cells with genes coding for CD154, IL-12 and CD80. Parental or transduced MB-49 cells were injected subcutaneously into syngeneic mice. The effects of transgene expression on tumorigenicity and the generation of protective immunological memory against challenge with parental tumor were studied.

    RESULTS: All 76 animals injected with parental MB-49 cells had tumors within 8 to 12 days. Tumor cell expression of CD154 combined with IL-12 completely inhibited tumor outgrowth with all 21 mice tumor-free and CD154 transduction alone was almost as effective with 33 of 35 tumor-free. IL-12 production by tumor cells delayed tumor outgrowth and 4 of 10 mice remained tumor-free. Over expression of CD80 had no effect on tumorigenicity. CD154 expressing tumors were rapidly infiltrated with large numbers of CD4+ and CD8+ T cells. Mice vaccinated 4 times with adenoviral CD154 transduced MB-49 cells were completely protected against challenge with parental tumor. Co-injection of CD154 modified cells with parental MB-49 cells retarded tumor growth.

    CONCLUSIONS: Our experimental results suggest that the potent antitumor effects of CD154 gene transduction should be considered for immunostimulatory gene therapy for bladder cancer.

  • 19.
    Loskog, Angelica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ninalga, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Paul-Wetterberg, Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    de la Torre, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Tötterman, Thomas H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines2007In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 177, no 1, p. 353-358Article in journal (Refereed)
    Abstract [en]

    Purpose: Immunotherapy has faced limited success, although many solutions have been proposed. Recently regulatory T cells have made a comeback in the immunological arena and the role of these cells in patients with cancer is in focus. It is under evaluation whether the immunological status of patients with cancer may affect their sensitivity to immunotherapy. We are developing immunostimulating gene therapy for treating bladder cancer. In this study we constructed an immunological profile of patients with bladder carcinoma to understand which obstacles must be circumvented. Materials and Methods: Biopsies and blood were used to identify immune cell populations by FACS®, histochemistry and proliferation assays, and cytokine production by polymerase chain reaction. Results: Results indicate that bladder carcinoma is a Tri dominated tumor, as shown by the infiltration of T-regulatory cells expressing FOXP3, and the presence of tumor necrosis factor-β and interleukin-10 mRNA copies. We further noted that circulating patient T cells were unresponsive to polyclonal T-cell activation compared to healthy donor cells. Moreover, CD4+CD25+ T cells were increased in patient blood and could suppress the expansion of allogeneic T cells from healthy donors. Conclusions: Patients with bladder carcinoma show an immunosuppressive regulatory profile, including nonresponsive T cells. Clinical protocols able to effectively counteract these mechanisms are warranted.

  • 20. Lottman, Henri B.
    et al.
    Margaryan, M.
    Bernuy, M.
    Grosz, A.
    Aigrain, Y.
    Lortat-Jacob, S.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Long-term effects of dextranomer endoscopic injections for treatment of urinary incontinence: an update of a prospective study of 31 patients2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 175, no 4, p. 1485-9Article in journal (Refereed)
    Abstract [en]

    PURPOSE: A prospective study was initiated 7 years previously to assess the efficacy of endoscopic dextranomer based implants for pediatric structural incontinence. Preliminary results revealed that at 3 years 50% of the patients were either dry or significantly improved. We report long-term results in the same cohort of patients. MATERIALS AND METHODS: A total of 33 children and adolescents 5 to 18 years old with severe incontinence due to sphincteric incompetence (exstrophy-epispadias complex in 13, neuropathic bladder in 16, bilateral ectopic ureter in 4) were enrolled. Of the patients 13 underwent 2 and 4 underwent 3 treatment sessions to achieve a definitive result. Mean injected volume was 3.9 ml (range 1.6 to 12) per session. At each evaluation patients were considered cured (dryness interval 4 hours), significantly improved (minimal incontinence requiring no more than 1 pad daily and no further treatment required) or treatment failures (no significant improvement). Videourodynamics were used to study the evolution of the bladder capacity, activity and compliance. A total of 31 patients were followed 3 to 7 years after the last injection. RESULTS: At 3 years after treatment 15 of 30 patients (50%) were dry or improved. One patient who had leakage after 3 years of dryness due to bladder deterioration subsequently underwent ileocystoplasty. At 4 years 12 of 25 patients (48%) were dry or improved. At 5 years 9 of 21 patients (43%) were dry, as were 4 of 11 (36%) at 6 years and 2 of 5 (40%) at 7 years of followup. The success rate according to pathological evaluation was comparable in neuropathic bladders (7 of 14, or 50%), exstrophy (3 of 6, or 50%) and epispadias (3 of 7, or 43%). Of 12 patients who underwent bladder neck plasty before the injection of bulking agent 7 (58%) were either dry or improved. The success rate was higher in males (13 of 23, or 57%) than in females (3 of 8, or 38%). Also, at puberty 2 males who were improved became dry. Bladder capacity increased in 12 of 18 initially small bladders and remained normal and stable in 9, while 4 initially dry patients had development of recurrent leakage secondary to bladder deterioration and underwent augmentation. Otherwise, there were no long-term side effects observed related to the injection of the bulking agent. CONCLUSIONS: Endoscopic treatment of severe organic urinary incontinence with dextranomer is durable for up to 7 years of followup in 40% of the patients.

  • 21. Lottmann, Henri B.
    et al.
    Margaryan, M.
    Lortat-Jacob, S.
    Bernuy, M.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Long-term effects of dextranomer endoscopic injections for the treatment of urinary incontinence: an update of a prospective study of 61 patients2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 176, no 4 Pt 2, p. 1762-6Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To treat sphincteric deficiency in children endoscopic bladder neck injections may avoid or salvage more complex procedures. A prospective study to assess the efficacy of bladder neck injections of dextranomer based implants (Deflux(R)) was done in a 7-year period in 61 patients. MATERIALS AND METHODS: From September 1997 to September 2004 we enrolled in the study 41 males and 20 females 5 to 18 years old with severe sphincteric incompetence, including exstrophy-epispadias in 26, neuropathic bladder in 27, bilateral ectopic ureters in 5, and miscellaneous in 3. Preoperative evaluation consisted of medical history, urine culture, urinary tract ultrasound and videourodynamics. This evaluation was repeated 6 months and 1 year after treatment, and yearly thereafter. Of the patients 17 underwent 2 and 4 underwent 3 treatment sessions to achieve a definitive result. At each evaluation the case was considered cured-a dryness interval of 4 hours between voids or CIC, significantly improved-minimal incontinence requiring no more than 1 pad daily and no further treatment required, and treatment failure-no significant, long lasting improvement. Videourodynamics were mainly useful to study the evolution of bladder capacity, activity and compliance. Followup after the last injection was 6 to 84 months (mean 28). RESULTS: Mean injected volume per session was 3.9 cc (range 1.6 to 12). Postoperative complications were temporary dysuria in 2 patients nonfebrile urinary tract infection in 10, orchid-epididymitis in 1 and urinary retention with pyelonephritis in 1. The incidence of dryness or improvement during followup was 79% (48 of 61 patients) at 1 month, 56% (31 of 55) at 6 months, 52% (24 of 46) at 1 year, 51% (18 of 35) at 2 years, 52% (16 of 31) at 3 years, 48% (12 of 25) at 4 years, 43% (9 of 21) at 5 years, 36% (4 of 11) at 6 years and 40% (2 of 5) at 7 years. The success rate according to pathological condition was similar in cases of neuropathic bladder and the exstrophy-epispadias complex (48% and 53%, respectively). The success rate in re-treated cases was 38%. After treatment a contracted bladder developed in 6 patients. Also, of the 35 patients with at least 2 years of followup an increase in capacity of at least 50% was observed in 12 of 18 with an initially small bladder. No side effects related to the substance were observed. CONCLUSIONS: Endoscopic treatment for pediatric severe sphincteric deficiency with dextranomer implant, a nontoxic, nonimmunogenic, nonmigratory synthetic substance, was effective up to 2 years in half of the patients. Subsequently at up to 7 years of followup a slow decrease in efficacy was observed and treatment remained beneficial in 40% of the patients.

  • 22. Lundholm, Carl
    et al.
    Norlen, Bo Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ekman, Peter
    Johansson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lagerkvist, Mikael
    Lindeborg, Torsten
    Olsson, Jan Olov
    Tveter, Kjell
    Wijkstrom, Hans
    Westberg, Ronny
    Malmstrom, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    A randomized prospective study comparing long-term intravesical instillations of mitomycin-c and BCG in patients with superficial bladder carcinoma1996In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 156, no 2, p. 372-376Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    We compared the efficacy and toxicity of long-term mitomycin C versus bacillus Calmette-Guerin (BCG) instillation in patients at high risk for recurrence and progression of superficial bladder carcinoma.

    MATERIALS AND METHODS:

    Our randomized comparison study included 261 patients with primary dysplasia, or stage Tis, stage T1, grade 3 and multiple recurrent stage Ta/T1, grade 1 or 2 disease. Mitomycin C (40 mg.) or Pasteur strain BCG (120 mg.) was instilled weekly for 6 weeks, then monthly for up to 1 year and every 3 months during year 2.

    RESULTS:

    After a median followup of 39 months 49% of the patients given BCG and 34% given mitomycin C were disease-free (p < 0.03), compared to 48 and 35%, respectively, of those with stage Ta or T1 disease, and 54 and 33%, respectively, of those with dysplasia or stage Tis tumor. Tumor progressed in 13% of patients, with no statistically significant difference observed regarding progression between the mitomycin C and BCG groups. Side effects were more common after BCG instillation, with 5 cases of severe side effects compared to 1 in the mitomycin C group. Treatment was stopped due to toxicity in 10% of the patients.

    CONCLUSIONS:

    The majority of patients tolerated long-term intravesical therapy well. BCG instillation was hampered by more frequent side effects. BCG was superior regarding recurrence prophylaxis, since patients given BCG had fewer recurrences and a significantly longer time to treatment failure compared to those treated with mitomycin C. No statistically significant difference was observed regarding progression.

  • 23. Lundstrom, Karl-Johan
    et al.
    Drevin, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carlsson, Stefan
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Loeb, Stacy
    Stattin, Par
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Nationwide Population Based Study of Infections after Transrectal Ultrasound Guided Prostate Biopsy2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 4, p. 1116-1122Article in journal (Refereed)
    Abstract [en]

    Purpose: Transrectal ultrasound guided biopsy is the gold standard for detecting prostate cancer but international reports suggest that increasing risks are associated with the procedure. We estimated incidence and risk factors for infection after prostate biopsy as well as 90-day mortality using a nationwide Swedish sample.

    Material and Methods: We performed a population based study of 51,321 men from PCBaSe between 2006 and 2011. Primary outcome measures were dispensed prescriptions of antibiotics for urinary tract infection and hospitalization with a discharge diagnosis of urinary tract infection. Multivariable logistic regression was used to examine risk factors for infection in men who underwent prostate biopsy.

    Results: During the 6 months before biopsy the background incidence of urinary tract infection was approximately 2%. Within 30 days after biopsy 6% of the men had a dispensed prescription for urinary tract antibiotics and 1% were hospitalized with infection. The strongest risk factors for an antibiotic prescription were prior infection (OR 1.59, 95% CI 1.45-1.73), high Charlson comorbidity index (OR 1.25, 95% CI 1.11-1.41) and diabetes (OR 1.32, 95% CI 1.17-1.49). Risk of an antibiotic prescription after biopsy decreased from 2006 to 2011 (OR 0.79, 95% CI 0.70-0.90) but the risk of hospital admission increased (OR 2.14, 95% CI 1.58-2.94). No significant increase was observed in 90-day mortality.

    Conclusions: Severe infections with hospitalization after prostate biopsy are increasing in Sweden. The risk of post-biopsy infection is highest in men with a history of urinary tract infection and those with significant comorbidities.

  • 24.
    Läckgren, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Sköldenberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Endoscopic Treatment With Stabilized Nonanimal Hyaluronic Acid/Dextranomer Gel is Effective in Vesicoureteral Reflux Associated With Bladder Dysfunction2007In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 177, no 3, p. 1124-1129Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Endoscopic injection of stabilized nonanimal hyaluronic acid/dextranomer gel is an established treatment for vesicoureteral reflux in children. We performed a subgroup analysis to assess this treatment in reflux associated with bladder dysfunction. MATERIALS AND METHODS: Of 308 consecutive children treated endoscopically with stabilized nonanimal hyaluronic acid/dextranomer gel for dilating vesicoureteral reflux 54 were observed retrospectively to have bladder dysfunction. Initial followup consisted of voiding cystourethrogram at 3 and 12 months after injection, with positive response defined as reflux grade 0 or I. At 7 to 12 years following treatment patient charts were checked for urinary tract infections and bladder dysfunction, and a followup survey (postal questionnaire) was administered. RESULTS: A positive response to therapy (cure) was observed in 45 children (83%) after 1 to 3 endoscopic treatments. Concurrently, bladder dysfunction had resolved in 32 patients (59%). After the last stabilized nonanimal hyaluronic acid/dextranomer gel implantation 45 patients (83%) were free of urinary tract infections. Questionnaire results were similar to chart based findings. Stabilized nonanimal hyaluronic acid/dextranomer gel implantation was well tolerated, with no associated complications. CONCLUSIONS: Endoscopic treatment with stabilized nonanimal hyaluronic acid/dextranomer gel appears to be similarly effective in patients with vesicoureteral reflux with and without bladder dysfunction. These data indicate that bladder dysfunction should not be considered a contraindication to endoscopic treatment for reflux.

  • 25.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Editorial Comment: Inconsistent lower urinary tract symptoms in children with enuresis. The Journal of Urology Sept; 180(3):1085-9; Discussion 1089-902008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 180, no 3, p. 1090-Article in journal (Other academic)
    Abstract
  • 26.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Effect of Laser Acupuncture for Monosymptomatic Nocturnal Enuresis on Bladder Reservoir Function and Nocturnal Urine Output EDITORIAL COMMENT2011In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 185, no 5, p. 1862-1862Article in journal (Other academic)
  • 27.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Oxybutynin, desmopressin and enuresis2001In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 166, no 6, p. 2459-62Article in journal (Refereed)
  • 28.
    Nevéus, Tryggve
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eggert, Paul
    Klinik für Allgemeine Pädiatrie der Christian-Albrechts-Universität, Kiel, Germany.
    Evans, Jonathan
    Nottingham University Hospitals National Health Service Trust Queens Medical Centre Campus, Nottingham, United Kingdom.
    Macedo, Antonio
    Pediatric Urology Section, Federal University of São Paulo, São Paulo, Brazil.
    Rittig, Søren
    Department of Pediatrics, Aarhus University Hospital, Skejby, Aarhus, Denmark.
    Tekgül, Serdar
    Section of Paediatric Urology, Department of Urology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
    Vande Walle, Johan
    Pediatric Nephrology Unit, Ghent University Hospital, Ghent, Belgium.
    Yeung, C. K.
    Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
    Robson, Lane
    Calgary, Alberta, Canada.
    Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children's Continence Society2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 183, no 2, p. 441-447Article, review/survey (Refereed)
    Abstract [en]

    PURPOSE: We provide updated, clinically useful recommendations for treating children with monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: Evidence was gathered from the literature and experience was gathered from the authors with priority given to evidence when present. The draft document was circulated among all members of the International Children's Continence Society as well as other relevant expert associations before completion. RESULTS: Available evidence suggests that children with monosymptomatic nocturnal enuresis could primarily be treated by a primary care physician or an adequately educated nurse. The mainstays of primary evaluation are a proper history and a voiding chart. The mainstays of primary therapy are bladder advice, the enuresis alarm and/or desmopressin. Therapy resistant cases should be handled by a specialist doctor. Among the recommended second line therapies are anticholinergics and in select cases imipramine. CONCLUSIONS: Enuresis in a child older than 5 years is not a trivial condition, and needs proper evaluation and treatment. This requires time but usually does not demand costly or invasive procedures.

  • 29. Robinson, David
    et al.
    Sandblom, Gabriel
    Johansson, Robert
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Stattin, Pär
    Mommsen, Sören
    Varenhorst, Eberhard
    Prediction of survival of metastatic prostate cancer based on early serial measurements of prostate specific antigen and alkaline phosphatase2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 1, p. 117-122Article in journal (Refereed)
    Abstract [en]

    Purpose: We determined how serial measurements of prostate specific antigen and alkaline phosphatase can be used to predict survival early in the course of hormone treated metastatic prostate cancer. Materials and Methods: The study was based on a prospective randomized trial of 915 patients with metastatic prostate carcinoma designed to compare parenteral estrogen (polyestradiol phosphate) vs total androgen blockade. We included 697 men who survived at least 6 months and had complete serial measurements of prostate specific antigen and alkaline phosphatase. Six models were constructed based on prostate specific antigen and alkaline phosphatase at start, and after 6 months of treatment, alkaline phosphatase flare and relative prostate specific antigen velocity. We constructed time dependent receiver operating characteristic curves with corresponding area under the curve to predict death from prostate cancer within 3 years. Results: The best variables to predict outcome were alkaline phosphatase at 6 months (AUC 0.79 for polyestradiol phosphate and 0.72 for total androgen blockade), alkaline phosphatase at baseline (AUC 0.70 for polyestradiol phosphate and total androgen blockade) and prostate specific antigen at 6 months (AUC 0.70 for polyestradiol phosphate and total androgen blockade). Prostate specific antigen and alkaline phosphatase levels 6 months after start of treatment give better prediction of survival than baseline levels. Conclusions: Alkaline phosphatase at start of treatment and alkaline phosphatase and prostate specific antigen after 6 months can be used to predict survival of hormone treated metastatic prostate cancer.

  • 30.
    Stattin, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandin, Fredrik
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Bratt, Ola
    Lund Univ, Dept Translat Med, Urol Canc Res Unit, Lund, Sweden.;Cambridge Hosp, Dept Urol, Cambridge, England..
    Lambe, Mats
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    The Risk of Distant Metastases and Cancer Specific Survival in Men with Serum Prostate Specific Antigen Values above 100 ng/ml2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 6, p. 1594-1600Article in journal (Refereed)
    Abstract [en]

    Purpose: Current EAU (European Association of Urology) guidelines state that prostate specific antigen 100 ng/ml or greater at diagnosis indicates metastatic disease. We examined the association of prostate specific antigen 100 ng/ml or greater at diagnosis with distant metastasis and prostate cancer specific survival. Material and Methods: A total of 15,635 men with prostate cancer diagnosed between 1998 and 2009 who were identified in PCBaSe (Prostate Cancer Data Base Sweden 2.0) were included in a population based registry study. Prostate cancer specific survival was compared among 3 groups, including 1,879 men with prostate specific antigen 100 ng/ml or greater and negative imaging (MO), 5,642 with distant metastases on imaging (M1) and prostate specific antigen 100 ng/ml or greater, and 3,828 with M1 and prostate specific antigen less than 100 ng/ml. A fourth group consisted of 4,286 men with prostate specific antigen 100 ng/ml or greater who had not undergone imaging (Mx). The latter men were not included in the assessment of survival. Results: Of 7,521 men with prostate specific antigen 100 ng/ml or greater who underwent imaging for staging 75% were classified with M1 disease. Only 59% of 3,527 men with prostate specific antigen 100 to 300 mg/ml had distant metastases on imaging. Five-year prostate cancer specific survival was 72% (95% CI 70-74) in men with prostate specific antigen 100 ng/ml or greater and MO, 24% (95% CI 23-25) in men with prostate specific antigen 100 ng/ml or greater and Ml, and 39% (95% CI 37-40) in men with prostate specific antigen less than 100 ng/ml and Ml. Conclusions: A fourth of men with prostate specific antigen 100 ng/ml or greater did not have distant metastases. They had twofold to threefold higher 5-year survival than men with distant metastases on imaging. Our findings strongly suggest that using prostate specific antigen 100 ng/ml or greater as an indicator of metastatic disease should be reconsidered.

  • 31. Stenberg, Å M
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, B S
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Lack of distant migration after injection of a 125iodine labeled dextranomer based implant into the rabbit bladder1997In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 158, no 5, p. 1937-1941Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    In recent years endoscopic treatment of stress incontinence and vesicoureteral reflux has been introduced. Reports of possible particle migration of the injected material to distant organs in humans and experimental animals have led to a search for biological nonmigration products. An implant found to have a good clinical effect in these conditions is dextranomer in hyaluronan. We performed this study in rabbits to investigate the possible migration of dextranomer particles.

    MATERIALS AND METHODS:

    125Iodine labeled dextranomer particles were injected into the submucosal space of rabbit bladders, and samples of blood and various tissues were examined for radioactivity at scheduled intervals during a 28-day period. Furthermore, whole body autoradiography was performed 1 day, and 1 and 4 weeks after injection.

    RESULTS:

    Radioactivity was found in blood samples and in all tissues but it remained at the background activity level except in the thyroid, where uptake representing free 125iodine was detected. In the bladder 41 and 45% of the injected dose remained within the bladder wall 1 day and 4 weeks, respectively, after injection. The remainder of the dose probably disappeared from the bladder wall by leakage into the urine shortly after deposition, as indicated by the finding of 10-fold higher urine radioactivity levels at day 1 than at day 28 after injection.

    CONCLUSIONS:

    No distant migration of dextranomer particles occurs after submucosal injection of such an implant in the rabbit bladder wall.

  • 32.
    Tammela, T L
    et al.
    Tampere Univ Hosp, Dept Urol, Tampere, Finland.; Univ Tampere, Tampere, Finland.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Ladjevardi, Sam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Taari, K
    Helsinki Univ Hosp, Helsinki, Finland.
    Isotalo, T
    Paijiat Hame Cent Hosp, Lahti, Finland.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    von Below, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lennernäs, B
    Univ Orebro, Dept Oncol, Orebro, Sweden.
    Tolf, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Axén, N
    LIDDS AB, Uppsala, Sweden.
    Gölander, C-G
    LIDDS AB, Uppsala, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer2017In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 198, no 6, p. 1333-1339Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate tolerability, safety and antitumor effects of a novel intra-prostatic depot formulation of antiandrogen 2-hydroxyflutamide (2-HOF in NanoZolid(®)) in men with localized prostate cancer (PCa).

    MATERIALS AND METHODS: Two clinical trials, LPC-002 and LPC-003, were conducted on a total of 47 men. The formulation was injected transrectally into the prostate with ultrasound guidance. In LPC-002 the effects on prostate specific antigen (PSA) and prostate volume (PV) were measured over 6 months on 24 patients. In LPC-003, antitumor effects were evaluated with histopathology, magnetic resonance imaging (MRI) including spectroscopy (MRS) during 6 or 8 weeks on 23 patients. In both studies, testosterone and 2-HOF in plasma were measured, as well as quality-of-life parameters.

    RESULTS: In LPC-002 (mean dose 690 mg) a reduction in PSA and PV was observed. The nadir values for PSA and PV were on average 24.9 % and 14.0 % below baseline, respectively. When increasing the dose in LPC-003 (920 mg and 1740 mg), the average PSA dropped 16 % and 23 %, respectively, after 6 and 8 weeks. MRI/MRS showed morphological changes and a global drop in metabolite concentrations following treatment indicating an antitumor response. The injections did not result in hormone related side effects. In total, three serious adverse events were reported, all resolved by oral antibiotic treatment.

    CONCLUSIONS: The intraprostatic injections of 2-HOF depot formulations indicated anti-tumor effects and proved safe and tolerable. However, for better anti-cancer effects higher doses and better dose distribution are suggested.

  • 33.
    Tibblin, Gösta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Welin, Lennart
    Bergström, Reinhold
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Norlén, Bo-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Adami, Hans-Olov
    The value of prostatic specific antigen in early diagnosis of prostate cancer: the study of men born in 19131995In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 154, no 4, p. 1386-1389Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We attempt to elucidate the performance of serum prostate specific antigen (PSA) as a screening test for prostate cancer. MATERIALS AND METHODS: We analyzed sera stored since 1980 in a nested case-control study. RESULTS: The 36 patients with prostate cancer had a markedly greater mean serum PSA level than did 68 subjects without cancer (22.71 versus 2.67, respectively, p < 0.0001). Among the controls 24% had a serum PSA of greater than 4.0 micrograms/l. A serum PSA value exceeding 4.0 micrograms/l. in 1980 was associated with a 20-fold excess risk of cancer between 1981 and 1986, and an 8-fold risk between 1987 and 1991. CONCLUSIONS: Diagnosis of clinically significant prostate cancer can be advanced substantially by serum PSA testing. However, the large number of high serum PSA values in men who remained free of clinical disease emphasizes the need for a more specific screening test.

  • 34.
    van Kessel, Kim E. M.
    et al.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Beukers, Willemien
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Lurkin, Irene
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Ziel-van der Made, Angelique
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    van der Keur, Kirstin A.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Boormans, Joost L.
    Erasmus MC, Dept Urol, Rotterdam, Netherlands..
    Dyrskjot, Lars
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Marquez, Mirari
    Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid, Spain..
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Real, Francisco X.
    Spanish Natl Canc Res Ctr, Epithelial Carcinogenesis Grp, Madrid, Spain.;Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain..
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malats, Nuria
    Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid, Spain..
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Van Criekinge, Wim
    MDxHealth Inc, Irvine, CA USA.;Univ Ghent, Lab Bioinformat & Computat Genom, Ghent, Belgium..
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Validation of a DNA Methylation-Mutation Urine Assay to Select Patients with Hematuria for Cystoscopy2017In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 197, no 3, p. 590-595Article in journal (Refereed)
    Abstract [en]

    Purpose: Only 3% to 28% of patients referred to the urology clinic for hematuria are diagnosed with bladder cancer. Cystoscopy leads to high diagnostic costs and a high patient burden. Therefore, to improve the selection of patients for cystoscopy and reduce costs and over testing we aimed to validate a recently developed diagnostic urine assay.

    Materials and Methods: Included in study were 200 patients from a total of 3 European countries who underwent cystoscopy for hematuria, including 97 with bladder cancer and 103 with nonmalignant findings. Voided urine samples were collected prior to cystoscopy. DNA was extracted and analyzed for mutations in FGFR3, TERT and HRAS, and methylation of OTX1, ONECUT2 and TWIST1. Logistic regression was used to analyze the association between predictor variables and bladder cancer.

    Results: Combining the methylation and mutation markers with age led to an AUC of 0.96 (95% CI 0.92e0.99) with 93% sensitivity and 86% specificity, and an optimism corrected AUC of 0.95. The AUC was higher for T1 or greater tumors compared to Ta tumors (0.99 vs 0.93). The AUC was also higher for high grade tumors compared to low grade tumors (1.00 vs 0.93). Overall negative predictive value was 99% based on the 5% to 10% prevalence of bladder cancer in patients with hematuria. This would lead to a 77% reduction in diagnostic cystoscopy.

    Conclusions: Analyzing hematuria patients for the risk of bladder cancer using novel molecular markers may lead to a reduction in diagnostic cystoscopy. Combining methylation analysis (OTX1, ONECUT2 and TWIST1) with mutation analysis (FGFR3, TERT and HRAS) and patient age resulted in a validated accurate prediction model.

  • 35. Vellekoop, Annelies
    et al.
    Loeb, Stacy
    Folkvaljon, Yasin
    Uppsala University Hospital, Regional Cancer Centre, Uppsala, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Population Based Study of Predictors of Adverse Pathology among Candidates for Active Surveillance with Gleason 6 Prostate Cancer2014In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, no 2, p. 350-357Article in journal (Refereed)
    Abstract [en]

    Purpose

    Approximately a third of prostate cancer cases with a Gleason score of 6 are upgraded at radical prostatectomy. We studied trends and predictors of upgrading and up staging among men with Gleason 6 prostate cancer who were potential candidates for active surveillance in a population based cohort.

    Materials and Methods

    From 2007 to 2011, 13,159 men were diagnosed with Gleason 6, clinical stage T1c/T2 prostate cancer in the NPCR (National Prostate Cancer Register of Sweden). Of these men 4,500 underwent radical prostatectomy, including 2,205 with data on the extent of prostate cancer in the biopsy cores. Logistic regression was used to examine variables associated with adverse pathology (defined as upgrading to Gleason 7 or greater, or up staging to pT3 or greater) in the full group and in potential candidates for active surveillance using 6 current published protocols.

    Results

    Among Swedish men with clinically localized Gleason 6 prostate cancer approximately 50% had adverse pathology at radical prostatectomy. Of the men who met the study inclusion criteria of 6 different active surveillance protocols, adverse pathology was present in 33% to 45%. Predictors of adverse pathology were older age, higher prostate specific antigen, prostate specific antigen density greater than 0.15 ng/ml/cm3, palpable disease and extent of cancer greater than 4 mm on biopsy. Larger prostate volume had an inverse relationship with adverse pathology.

    Conclusions

    More than a third of men meeting the most stringent active surveillance criteria had adverse pathology at radical prostatectomy in this population based cohort. Active surveillance programs should consider prostate specific antigen density and extent of cancer on biopsy for patient selection.

  • 36. Wallerstedt, Anna
    et al.
    Carlsson, Stefan
    Nilsson, Andreas E
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Nyberg, Tommy
    Steineck, Gunnar
    Wiklund, N Peter
    Pad use and patient reported bother from urinary leakage after radical prostatectomy2012In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 187, no 1, p. 196-200Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To better understand clinically significant definitions of urinary incontinence we investigated the relationship between urinary leakage and patient reported bother from urinary leakage.

    MATERIALS AND METHODS:

    A consecutive series of 1,411 men who underwent radical prostatectomy at Karolinska University Hospital, Stockholm, Sweden, from 2002 to 2006 were invited to complete a study specific questionnaire with questions on pad status, urinary leakage and bother from urinary leakage.

    RESULTS:

    Questionnaires were received from 1,179 men with a followup of greater than 1 year (median 2.2). Results showed that even a small amount of urinary leakage resulted in a high risk of urinary bother. Of 775 survivors 46 (6%) reporting 0 pads indicated moderate or much bother compared to 38 of 123 (31%) who reported using a security pad. When comparing the 2 groups, the risk of bother from urinary leakage was more than 5 times higher in the safety pad vs the 0 pad group (RR 5.2, 95% CI 3.5-7.7). As the number of pads increased, we noted a higher bother risk. Cross-tabulation of pad use and urinary leakage revealed wide variation in pad requirements despite the same answer to urinary leakage questions.

    CONCLUSIONS:

    If the definition of continence is based on pad use, for example safety pads, a certain number of men who report moderate or much bother from urinary leakage will be defined as continent. Our results also show that for each stated rate of urinary leakage men prove to have a major variation in the pad requirement.

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