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  • 1.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.

    Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.

    Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.

    Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

    List of papers
    1. PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Open this publication in new window or tab >>PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Show others...
    2015 (English)In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

    National Category
    Urology and Nephrology Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-120796 (URN)10.1186/s12894-015-0080-z (DOI)000359832000001 ()26294219 (PubMedID)
    Available from: 2015-08-25 Created: 2015-08-25 Last updated: 2017-05-17
    2. Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Open this publication in new window or tab >>Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
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    2017 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2017
    Keywords
    #BladderCancer, #blcsm, cystectomy, lymph node metastasis, prognostic factors, sentinel node
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-136947 (URN)10.1111/bju.13700 (DOI)000407781500011 ()27797436 (PubMedID)
    Note

    Funding agencies: County Council of Ostergotland, Linkoping, Sweden

    Available from: 2017-05-01 Created: 2017-05-01 Last updated: 2018-05-03
  • 2.
    Aljabery, Firas
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lindblom, Gunnar
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Skoog, Susann
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.2015In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

  • 3.
    Andersson, Ellen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs2017In: Clinical Practice, ISSN 2044-9038, E-ISSN 2044-9046, Vol. 14, no 3, p. 175-182Article in journal (Refereed)
    Abstract [en]

    Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.

  • 4.
    André, Malin
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Rules of Thumb and Management of Common Infections in General Practice2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis deals with problem solving of general practitioners (GPs), which is explored with different methods and from different perspectives. The general aim was to explore and describe rules of thumb and to analyse the management of respiratory and urinary tract infections (RTI and UTI) in general practice in Sweden. The results are based upon focus group interviews concerning rules of thumb and a prospective diagnosis-prescription study concerning the management of patients allocated a diagnosis of RTI or UTI. In addition unpublished data are given from structured telephone interviews concerning specific rules of thumb in acute sinusitis and prevailing cough.

    GPs were able to verbalize their rules of thumb, which could be called tacit knowledge. A specific set of rules of thumb was used for rapid assessment when emergency and psychosocial problems were identified. Somatic problems seemed to be the expected, normal state. In the further consultation the rules of thumb seemed to be used in an act of balance between the individual and the general perspective. There was considerable variation between the rules of thumb of different GPs for patients with acute sinusitis and prevailing cough. In their rules of thumb the GPs seemed to integrate their medical knowledge and practical experience of the consultation. A high number of near-patient antigen tests to probe Streptococcus pyogenes (Strep A tests) and C-reactive protein (CRP) tests were performed in patients, where testing was not recommended. There was only a slight decrease in antibiotic prescribing in patients allocated a diagnosis of RTI examined with CRP in comparison with patients not tested. In general, the GPs in Sweden adhered to current guidelines for antibiotic prescribing. Phenoxymethylpenicillin (PcV) was the preferred antibiotic for most patients allocated a diagnosis of respiratory tract infection.

    In conclusion, the use of rules of thumb might explain why current practices prevail in spite of educational efforts. One way to change practice could be to identify and evaluate rules of thumb used by GPs and disseminate well adapted rules. The use of diagnostic tests in patients with infectious illnesses in general practice needs critical appraisal before introduction as well as continuing surveillance. The use of rules of thumb by GPs might be one explanation for variation in practice and irrational prescribing of antibiotics in patients with infectious conditions.

    List of papers
    1. Asking for ’rules of thumb’: a way to discover tacit knowledge in general practice
    Open this publication in new window or tab >>Asking for ’rules of thumb’: a way to discover tacit knowledge in general practice
    2002 (English)In: Family Practice, ISSN 0263-2136, Vol. 19, no 6, p. 617-622Article in journal (Refereed) Published
    Abstract [en]

    Background. Research in decision-making has identified heuristics (rules of thumb) as shortcuts to simplify search and choice.

    Objective. To find out if GPs recognize the use of rules of thumb and if they could describe what they looked like.

    Methods. An explorative and descriptive study was set up using focus group interviews. The interview guide contained the questions: Do you recognize the use of rules of thumb? Are you able to give some examples? What are the benefits and dangers in using rules of thumb? Where do they come from? The interviews were transcribed and analysed using the templates in the interview guide, and the examples of rules were classified by editing analysis.

    Results. Four groups with 23 GPs were interviewed. GPs recognized using rules of thumb, producing examples covering different aspects of the consultation. The rules for somatic problems were formulated as axiomatic simplified medical knowledge and taken for granted, while rules for psychosocial problems were formulated as expressions of individual experience and were followed by an explanation. The rules seemed unaffected by the sparse objections given. A GP’s clinical experience was judged a prerequisite for applying the rules. The origin of many rules was via word-of-mouth from a colleague. The GPs acknowledged the benefits of using the rules, thereby simplifying work.

    Conclusion. GPs recognize the use of rules of thumb as an immediate and semiconscious kind of knowledge that could be called tacit knowledge. Using rules of thumb might explain why practice remains unchanged although educational activities result in more elaborate knowledge.

    Keywords
    Decision-making, focus groups, general practice, heuristics
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13634 (URN)10.1093/fampra/19.6.617 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2009-08-17
    2. Use of rules of thumb in the consultation in general practice: an act of balance between the individual and the general perspective
    Open this publication in new window or tab >>Use of rules of thumb in the consultation in general practice: an act of balance between the individual and the general perspective
    2003 (English)In: Family Practice, ISSN 0263-2136, Vol. 20, no 5, p. 514-519Article in journal (Refereed) Published
    Abstract [en]

    Background. Rules of thumb used by GPs could be considered as empirical evidence of intuition and a link between science and practice in general practice.

    Objective. The purpose of the present study was to analyse the description of the application of rules of thumb with regard to different situations in general practice.

    Methods. An explorative and descriptive study was started with focus group interviews. Four groups with 23 GPs were interviewed. The interviews were transcribed and analysed, and the rules and their application were classified by an editing analysis.

    Results. A specific set of rules of thumb was used for rapid assessment, when emergency and psychosocial problems were identified. When the main focus of the problems was identified as somatic or psychosocial, the GPs did not disregard the other aspects but described the use of rules in a simultaneous individualizing and generalizing process. The rules contained probability reasoning and risk assessment.

    Conclusion. Rules of thumb seemed to serve as a link between theoretical knowledge and practical experience and were used by the GPs in an act of balance between the individual and the general perspective.

    Keywords
    Consultation, focus groups, general practice, heuristics
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13635 (URN)10.1093/fampra/cmg503 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2018-09-01
    3. Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests
    Open this publication in new window or tab >>Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests
    Show others...
    2002 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 2374-4235, Vol. 34, no 12, p. 880-886Article in journal (Refereed) Published
    Abstract [en]

    A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000. As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections (n = 2899) in primary care were analyzed. Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours. Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic. Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis. The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used. In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels. In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed. The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines. However, the study indicates some areas for improvement. The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2002
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13636 (URN)10.1080/0036554021000026952 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2018-05-22
    4. The Use of CRP Tests in Patients with Respiratory Tract Infections in Primary Care in Sweden Can Be Questioned
    Open this publication in new window or tab >>The Use of CRP Tests in Patients with Respiratory Tract Infections in Primary Care in Sweden Can Be Questioned
    Show others...
    2004 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 36, no 3, p. 192-197Article in journal (Refereed) Published
    Abstract [en]

    A diagnosis-antibiotic prescribing study was performed in 5 counties in Sweden during 1 week in November in 2000 and 2002 respectively. As a part of the study, the use and results of C-reactive protein (CRP) tests in relation to duration of symptoms and antibiotic prescribing in 6778 patients assigned a diagnosis of respiratory tract infections were analysed. In almost half (42%) of the patients, a CRP test was performed. The majority of CRP tests (69%) were performed in patients assigned diagnosis upper respiratory tract infection, where the test is not recommended. Overall, there was a minor decrease in antibiotic prescribing when CRP was used (41%), in comparison to 44% of the patients where no CRP was performed (p<0.01). Patients assigned diagnoses implying a bacterial aetiology were prescribed antibiotics irrespective of result of CRP or length of symptoms before consultation. For patients assigned viral diagnoses, antibiotic prescribing increased with increasing duration of symptoms and increasing value of CRP. The use of CRP decreased antibiotic prescribing in patients assigned to viral diagnoses and with longstanding symptoms (p<0.001). However, 59% of the patients assigned viral diagnoses with CRP≥25 received antibiotics, which seems to indicate a misinterpretation of CRP and a non-optimal use of antibiotics.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13637 (URN)10.1080/00365540410019372 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2018-10-08
    5. Management of urinary tract infections in primary care: A repeated 1-week diagnosis-prescribing study in five counties in Sweden in 2000 and 2002
    Open this publication in new window or tab >>Management of urinary tract infections in primary care: A repeated 1-week diagnosis-prescribing study in five counties in Sweden in 2000 and 2002
    2004 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 36, no 2, p. 134-138Article in journal (Refereed) Published
    Abstract [en]

    A diagnosis-antibiotic prescribing study was performed in 5 counties in Sweden during 1week in November in the y 2000 and 2002, respectively. As part of the study, the characteristics and clinical management of patients who received diagnoses of urinary tract infections (UTIs) (n=1564) in primary care, were analysed. 85% of the visits were by women, and 74% of all consultations were diagnosed as lower UTIs. One or more diagnostic tests were performed in 98% of the women with suspected lower or recurrent UTIs and 95% were prescribed an antibiotic. The most commonly prescribed antibiotics for lower UTIs were trimethoprim followed by pivmecillinam and a quinolone. The study indicated a change in antibiotic prescribing with improved adherence to the national recommendations. There was an increase of prescribed nitrofurantoin and a decrease of prescribed quinolones to women with lower UTIs between the studied y. Furthermore, 3-d treatment with trimethoprim increased although the prescribed duration was mostly 7 d. In contrast to the guidelines, few urine cultures were performed. The study highlights the necessity of updating the guidelines for the management of lower UTIs in general practice.

    Keywords
    Urinary Tract Infections, Primary Care
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13638 (URN)10.1080/00365540410019075 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2009-06-09
  • 5.
    Bill-Axelson, Anna
    et al.
    University of Uppsala Hospital, Sweden .
    Holmberg, Lars
    University of Uppsala Hospital, Sweden Kings Coll London, England .
    Garmo, Hans
    University of Uppsala Hospital, Sweden Kings Coll London, England .
    Rider, Jennifer R.
    Brigham and Womens Hospital, MA USA Harvard University, MA USA Harvard University, MA 02115 USA .
    Taari, Kimmo
    University of Helsinki, Finland .
    Busch, Christer
    University of Uppsala Hospital, Sweden .
    Nordling, Stig
    University of Helsinki, Finland .
    Haggman, Michael
    University of Uppsala Hospital, Sweden .
    Andersson, Swen-Olof
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Spångberg, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Andren, Ove
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Palmgren, Juni
    Karolinska Institute, Sweden .
    Steineck, Gunnar
    Karolinska Institute, Sweden Sahlgrens Acad, Sweden .
    Adami, Hans-Olov
    Karolinska Institute, Sweden Harvard University, MA 02115 USA .
    Johansson, Jan-Erik
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, p. 932-942Article in journal (Refereed)
    Abstract [en]

    BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

  • 6.
    Björn, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Jakobsen Falk, Ingrid
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Vergote, Ignace
    Leuven Canc Inst, Belgium.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    ABCB1 Variation Affects Myelosuppression, Progression-free Survival and Overall Survival in Paclitaxel/Carboplatin-treated Ovarian Cancer Patients2018In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 123, no 3, p. 277-287Article in journal (Refereed)
    Abstract [en]

    The standard chemotherapy for ovarian cancer is paclitaxel/carboplatin. Patients often exhibit myelosuppressive toxicity, and the treatment response varies considerably. In this study, we investigated the previously reported SNPs 1199Gamp;gt;A (rs2229109), 1236Camp;gt;T (rs1128503), 2677Gamp;gt;T/A (rs2032582), 3435Camp;gt;T (rs1045642) in ABCB1, and 1196Aamp;gt;G (rs10509681) in CYP2C8 and their association with treatment-induced myelosuppression, progression-free survival (PFS) and overall survival (OS). From the phase III study, OAS-07OVA, 525 patients (All) treated with carboplatin and paclitaxel administered as Paclical (Arm A, n=260) or Taxol((R)) (Arm B, n=265) were included and genotyped using pyrosequencing. Genotype associations with myelosuppression, PFS and OS were investigated using anova, Kaplan-Meier analysis and Cox proportional hazard models. The most prominent finding was for the ABCB1 variant 3435TT, which was significantly associated with increased PFS in All (hazard ratio (HR) = 0.623), in Arm A (HR=0.590) and in Arm B (HR=0.627), as well as increased OS in All (HR=0.443) and in Arm A (HR=0.372) compared to the wild-type, 3435CC. For toxicity, the most interesting finding concerned the haplotype, including 1236TT, 2677TT and 3435TT, which was associated with higher neutrophil values in Arm B (p=0.039) and less neutrophil decrease in All (p=0.048) and in Arm B (p=0.021). It is noteworthy that the results varied depending on the treatment arm which indicates that the effects of ABCB1 variants vary with the treatment regimen. Our results reflect the contradictory results of previous studies, confirming that small variations in the composition of treatment regimens and patient populations may influence the interpretation of SNPs effects on treatment outcome.

  • 7.
    Carlsson, Per
    et al.
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Hedbrant, Johan
    System Analysis Group, Linköping University.
    Pedersen, Knud
    The Department of Urology, Ryhov County Hospital in Jönköping, Sweden.
    Varenhorst, Eberhard
    The Department of Urology, Norrköping County Hospital, Sweden.
    Gray, Darryl
    Sector of Clinical Epidemiology, Mayo Clinic, Rochester, USA.
    An evaluation of prostate cancer screening using a decision analytic model1993Report (Other academic)
    Abstract [en]

    As early prostate cancer is often asymptomatic, the disease is often not diagnosed until it has reached an advanced, incurable stage. However, if diagnosed when it is still confined to the prostate, prostate caner is potentially curable. At present, there are no completed prospective evaluations or other scientific evidence to suggest that prostate cancer mortality is reduced or that quality of life is increased either by curative treatment or by screening programmes. However, the potential effects of a screening programme can be modelled using decision analytic computer software.

    The aim of this project was to develop a model for comparing the expected quality-adjusted life expectancy for a group of men subjected to a programme of screening for prostate cancer to that of a control group with conventional case-finding, given limited empirical data on the effectiveness of both strategies.

    Due to limitations of existing data, the analysis was developed during the early stages of evaluating a prostate cancer screening programme. We wish to illustrate how an analytic tool such as this model can be used in the future.

    The model was functionally separated into two parts. The first part, the observation submodel, covers the first 6 years of the programme and classifies the screened population into different quality of life states, based on observed outcomes. The second part, the simulation submodel, predicts quality adjusted life-years for healthy participants and for prostate cancer patients who receiving curative treatment or expectant management. Data for the model were obtained from a pilot programme on screening for prostate cancer in which a randomly selected population sample has been screened by digital rectal examination in Norrköping Sweden in 1987 and 1990. The outcome evaluated in the model was quality-adjusted life expectancy for individuals in the cohort invited to the screening programme, compared to results for population controls.

    While the preliminary results identify some health benefits associated with screening, more accurate empirical data for a number of key variables could improve the evaluation. One feature of this model is that it combines solid, empirical data from the observation submodel with simulated results. When better empirical data on the actual consequences of different strategies are available, they can easily be analysed by using this model.

  • 8.
    Castiglione, Fabio
    et al.
    University of Leuven, Belgium; IRCCS Osped San Raffaele, Italy.
    Dewulf, Karel
    University of Leuven, Belgium.
    Hakim, Lukman
    University of Leuven, Belgium; Airlangga University, Indonesia.
    Weyne, Emmanuel
    University of Leuven, Belgium.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Russo, Andrea
    IRCCS Osped San Raffaele, Italy.
    Boeri, Luca
    IRCCS Osped San Raffaele, Italy.
    Bivalacqua, Trinity J.
    Johns Hopkins Medical Institute, MD 21205 USA.
    De Ridder, Dirk
    University of Leuven, Belgium.
    Joniau, Steven
    University of Leuven, Belgium.
    Albersen, Maarten
    University of Leuven, Belgium.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund University, Sweden.
    Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 6, p. 1032-1041Article in journal (Refereed)
    Abstract [en]

    Background: A medical treatment for urethral stricture (US) is not yet available. Objective: To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants: Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-beta 1 in the urethral wall. Intervention: One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis: Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations: US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p amp;lt; 0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34-55% smaller contractions than detrusor from sham rats (p amp;lt; 0.05). Corresponding values were 11-35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p amp;lt; 0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p amp;lt; 0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. Conclusions: Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. Patient summary: Stem cell therapy is effective for preventing urethral stricture in an experimental setting. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 9.
    Chen, Hui
    et al.
    Guangzhou Med Univ, Peoples R China; Jinan Univ, Peoples R China.
    Zeng, Jianwen
    Guangzhou Med Univ, Peoples R China.
    Zeng, Peng
    Guangzhou Med Univ, Peoples R China.
    Jiang, Chonghe
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Guangzhou Med Univ, Peoples R China.
    Xie, Keji
    Guangzhou First Peoples Hosp, Peoples R China.
    Lindström, Sivert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Repeat periods of electrical stimulation prolong the modulation of the micturition reflex in the rat2018In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 37, no 8, p. 2480-2486Article in journal (Refereed)
    Abstract [en]

    AimsMethodsThe aim of this study was to determine if the duration of the micturition reflex modulation could be prolonged by repeated periods of afferent stimulation in the decorticated rat. Eighteen female Sprague-Dawley rats were used for the study, 10 for intravesical electrical stimulation (IVES), and 8 for Ano-genital pudendal afferents stimulation. Repeated constant flow cystometries were performed with body-warm saline (0.06-0.1mL/min) at about 10min interval. The selected afferents were stimulated continuously for 5min at maximal intensity. The same stimulation was repeated six times with a pause of 5min between the stimulations. The mean threshold volume of cystometries performed during one hour before and each hour after the stimulation were compared. ResultsConclusionsAfter six periods of IVES, the micturition threshold volume decreased to its lowest value (62% of control) during the first hour and remained at 80% 4h later (n=10, Pamp;lt;0.01). Ano-genital afferent stimulation produced a corresponding increase in the micturition threshold volume. The long-lasting poststimulation effect was again observed for more than 5h. During the first hour the mean threshold volume increased to 211% of controls and it remained at about this level for the entire observation period (n=8, Pamp;lt;0.01). Repeated short periods of stimulation prolonged the modulatory effect well beyond the stimulation period. The findings provide experimental evidence supporting the clinical application of IVES and ano-genital stimulation for treatment of neurogenic urinary bladder dysfunction.

  • 10.
    Chen, Yun
    et al.
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden, Department of Physiology, University of Gothenburg, Box 432, SE 405 30 Gothenburg, Sweden.
    Lasaitiene, Daina
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Gabrielsson, Britt G.
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlsson, Lena M. S.
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Billig, Håkan
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Carlsson, Björn
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Marcussen, Niels
    Institute of Pathology, Aarhus Kommunehospital, Aarhus, Denmark.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, KC - Kirurgi- och onkologicentrum, Onkologiska kliniken.
    Friberg, Peter
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions2004In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, no 5, p. 1232-1243Article in journal (Refereed)
    Abstract [en]

    Lack of neonatal angiotensin II type I receptor (AT1) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT 1 receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, ~30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, a-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin a6 and caused relocalization of integrins a6 and a3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT1 receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and a-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.

  • 11.
    Coomans, Marijke
    et al.
    Leiden Univ, Netherlands.
    Dirven, Linda
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Aaronson, Neil K.
    Netherlands Canc Inst, Netherlands.
    Baumert, Brigitta G.
    Univ Hosp Bonn, Germany; Maastricht Univ, Netherlands; Maastricht Univ, Netherlands.
    van den Bent, Martin
    Erasmus MC Canc Inst, Netherlands.
    Bottomley, Andrew
    European Org Res Treatment Canc, Belgium.
    Brandes, Alba A.
    Azienda USL IRCCS Inst Neurol Sci, Italy.
    Chinot, Olivier
    Aix Marseille Univ, France.
    Coens, Corneel
    European Org Res and Treatment Canc Headquarters, Belgium.
    Gorlia, Thierry
    Univ Bonn, Germany; Univ Bonn, Germany.
    Herrlinger, Ulrich
    Grp Hop Pitie Salpetriere, France.
    Keime-Guibert, Florence
    Groupe Hôpital Pitié-Salpetrière, Paris, France.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Martinelli, Francesca
    Northwestern Univ, IL 60611 USA.
    Stupp, Roger
    Azienda Osped San Giovanni Addolorata, Italy.
    Talacchi, Andrea
    Univ Hosp, Switzerland; Univ Zurich, Switzerland.
    Weller, Michael
    Univ Hosp Heidelberg, Germany; German Consortium Translat Canc Res DKTK, Germany.
    Wick, Wolfgang
    Univ Amsterdam, Netherlands.
    Reijneveld, Jaap C.
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Taphoorn, Martin J. B.
    Leiden University Medical Center, Leiden, Netherlands; Haaglanden Medical Center, Den Haag, Netherlands.
    The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials2019In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 116, p. 190-198Article in journal (Refereed)
    Abstract [en]

    Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small. (C) 2019 Elsevier Ltd. All rights reserved.

  • 12.
    Danielsson, Gun
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Wijkstrom, Hans
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Nyberg, Tommy
    Karolinska Inst, Sweden; Univ Cambridge, England.
    Thulin, Helena
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bladder health in patients treated with BCG instillations for T1G2-G3 bladder cancer - a follow-up five years after the start of treatment2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 5-6, p. 377-384Article in journal (Refereed)
    Abstract [en]

    Objective: Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guerin (BCG) instillations. Materials and methods: Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients life. Results: In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being. Conclusion: Patients with bladder cancer T1G2-G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patients well-being. It is important to record the patients baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.

  • 13.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Bra lärobok – kan bli bättre2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, no 763Article, book review (Other academic)
  • 14.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Nu finns en ny svensk lärobok i njurmedicin2016In: Vaskulär Medicin, Vol. 32, no 41Article, book review (Other academic)
  • 15.
    Fernström, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Hylander Rössner, Britta
    Njurmedicinska kliniken, Karolinska universitetssjukhuset, Solna .
    Polycystisk njursjukdom (ADPKD)2015Other (Other academic)
    Abstract [sv]
    • Polycystisk njursjukdom (ADPKD) innebär att man i njurarna bildar ett fåtal till hundratals cystor i njurarna som slår ut den normala njurfunktionen och ökar buktrycket.
    • Orsakas av mutationer på PKD-1 och PKD-2-generna.
    • Ärvs autosomalt dominant.
    • Vanliga symtom är:- Tryckkänsla/smärta i buken- Njursten- Nedsatt urinkoncentrationsförmåga- Hypertoni- UVI- Hematuri- Uremiska symtom
    • Kan ge manifestationer extrarenalt- Levercystor- Pankreascystor- Intracerebrala aneurysm- Klaffvitium- Divertikulos- Bukväggsbråck
    • Diagnos sätts antingen på förekomst av cystor och ärftlighet för ADPKD eller enbart på förekomst av cystor (dock krävs då fler cystor).
    • Botande behandling annan än transplantation saknas.
    • Symtomlindrande behandling syftar till att minska mortalitet och morbiditet på grund av sjunkande njurfunktion.
    • Transplantation är indicerat om patienten är uremisk.
    • Nya behandlingar är under utveckling.
  • 16.
    Fuglsang, Katrine
    et al.
    Aarhus Univ Hosp, Denmark.
    Haldorsen, Ingfrid S.
    Haukeland Hosp, Norway.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lindahl, Gabriel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Roed, Henrik
    Univ Hosp, Denmark.
    Woie, Kathrine
    Haukeland Hosp, Norway.
    Pakarinen, Paivi
    Univ Helsinki, Finland.
    Thoroddsen, Asgeir
    Reykjavik Univ Hosp, Iceland.
    Anttila, Maarit
    Kuopio Univ Hosp, Finland.
    Blaakaer, Jan
    Odense Univ Hosp, Denmark.
    Cervical cancer staging, pretreatment planning, and surgical treatment in the Nordic countriesSurvey from the Surgical Subcommittee of the Nordic Society of Gynecological Oncology2018In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 97, no 10, p. 1178-1184Article in journal (Refereed)
    Abstract [en]

    IntroductionWomen with cervical cancer in the Nordic countries are increasingly undergoing pretreatment imaging by ultrasound, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) or computed tomography, or sentinel lymph node procedure. The present survey reports the influence of pretreatment imaging findings on the recorded clinical International Federation of Gynecology and Obstetrics (FIGO) stage in Nordic countries and its impact on treatment planning and preferred surgical approach in cervical cancer. Material and methodsThe Nordic Society of Gynecological Oncology Surgical Subcommittee developed a questionnaire-based survey that was conducted from 1 January to 31 March 2017. All the 22 Nordic Gynecological Oncology Centers (Denmark 5, Finland 5, Iceland 1, Norway 4, and Sweden 7) were invited to participate. ResultsThe questionnaires were returned by 19 of 22 (86.3%) centers. The median number (range) of women with cervical cancer treated at each center annually was 32 (15-120). In 58% (11/19) of the centers, imaging findings were reported to influence the clinical staging. MRI in combination with PET-CT was the preferred imaging method and the results influenced treatment planning. Robotic-assisted radical hysterectomy was the preferred surgical method in 72% (13/18) of the centers. Sentinel lymph node procedure was not routinely implemented in the majority of the Nordic centers. ConclusionMore than half of the Nordic Gynecological Oncology Centers already report a clinical FIGO stage influenced by pretreatment imaging findings. The trend in preferred treatment is robotic-assisted radical hysterectomy and the sentinel lymph node procedure is gradually being introduced.

  • 17.
    Geetha, Duvuru
    et al.
    Johns Hopkins University, Baltimore, MD, USA.
    Hruskova, Zdenka
    Charles University, Prague, Czech Republic .
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Hogan, Jonathan
    Hospital of the University of Pennsylvania, Philadelphia, USA.
    Morgan, Matthew D
    University of Birmingham, UK .
    Cavero, Teresa
    Hospital 12 de Octubre, Madrid, Spain .
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Seo, Philip
    John Hopkins University, Baltimore, USA.
    Manno, Rebecca L
    John Hopkins University, Baltimore, USA.
    Dale, Jessica
    University of Birmingham, Birmingham, UK.
    Harper, Lorraine
    University of Birmingham, UK.
    Tesar, Vladimir
    Charles University, Prague, Czech Republic .
    Jayne, David Rw
    Addenbrooke's Hospital, Cambridge, UK .
    Rituximab for treatment of severe renal disease in ANCA associated vasculitis2016In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 29, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    Background

    Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking.

    Methods

    We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m2. We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.

    Results

    A total 37 patients met the inclusion criteria. The median age was 61 years. (55–73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m2 (7–16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200–1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m2. Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed.

    Conclusions

    This study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.

  • 18.
    Hadimeri, Ursula
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Skaraborg Hosp, Sweden.
    Warme, Anna
    Univ Gothenburg, Sweden; Skaraborg Hosp, Sweden.
    Nasic, Salmir
    Skaraborg Hosp, Sweden.
    Fransson, Sven Göran
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Wigelius, Ann
    Umea Univ, Sweden.
    Stegmayr, Bernd
    Umea Univ, Sweden.
    Angiography and phlebography in a hemodialysis population: A retrospective analysis of interventional results2019In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, article id UNSP 0391398819863429Article in journal (Refereed)
    Abstract [en]

    Objective: To clarify the reasons and beneficial effects and duration of arteriovenous fistula patency after radiological interventions in arteriovenous fistula. The patients investigated were referred due to arteriovenous fistula access flow problems. Material and methods: In 174 patients, 522 radiological investigations and endovascular treatments such as percutaneous transluminal angioplasty were analyzed, retrospectively. All investigations were performed due to clinical suspicion of impaired arteriovenous fistula function. Results: Arterial stenosis was significantly more frequent among patients with diabetic nephropathy (p amp;lt; 0.001) and interstitial nephritis (p amp;lt; 0.001). According to the venous stenosis, the diagnosis did not affect the frequency (p = 0.22) or the degree (p = 0.39) of stenosis. The degree of stenosis prior to percutaneous transluminal angioplasty correlated significantly with the degree of remaining stenosis after intervention (p amp;lt; 0.001). Of the 174 patients, 123 (71%) performed a total of 318 investigations including percutaneous transluminal angioplasty. Repeated percutaneous transluminal angioplasty was performed significantly more often in patients with diabetic nephropathy. The median times to the first percutaneous transluminal angioplasty and to the subsequent percutaneous transluminal angioplasties were 9.5 and 5 months, respectively. Arteriovenous fistula in patients with diabetic nephropathy performed similar to most other diagnoses, although performing more percutaneous transluminal angioplasty/patient than most other diagnoses. Conclusion: Many patients could maintain long-term patency of arteriovenous fistula, including those with diabetic nephropathy, with repeated interventions; this motivates a closer follow-up for these patients. Clinically significant stenosis should be dilated as meticulously and as soon as possible. Occlusions of the arteriovenous fistula in most instances can be successfully thrombolyzed or dilated upon early diagnosis.

  • 19.
    Hemdan, Tammer
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Department of Surgical Sciences, Uppsala University, Uppsala.
    Segersten, Ulrika
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Emmprin expression predicts response and survival following cisplatin containing chemotherapy for bladder cancer: A validation study2015In: 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. © 2015 American Urological Association Education and Research, Inc.

  • 20.
    Holmar, Jana
    et al.
    1Tallinn University of Technology, Department of Biomedical Engineering, Tallinn, Estonia.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences.
    Luman, Merike
    North Estonia, Medical Centre, Centre of Nephrology,Tallinn, Estonia.
    Jankowski, Joachim
    RWTH Aachen University, Institute for Molecular Cardiovascular.
    Fridolin, Ivo
    1Tallinn University of Technology, Department of Biomedical Engineering, Tallinn, Estonia.
    Optical assesment of calcification markers during hemodialysis2015Conference paper (Other academic)
  • 21.
    Isnard Bagnis, Corinne
    et al.
    Université Pierre et Marie Curie, Paris, France..
    Crepaldi, Carlo
    Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo, Vicenza, Italy.
    Dean, Jessica
    Salford Royal Hospital, Salford, UK..
    Goovaerts, Tony
    Cliniques Universitaires St. Luc, Service de Néphrologie, Brussels, Belgium.
    Melander, Stefan
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nilsson, Eva-Lena
    Skåne University Hospital, Malmö.
    Prieto-Velasco, Mario
    Unidad de Nefrología, Complejo Asistencial Universitario de León, León, Spain.
    Trujillo, Carmen
    Unidad clínica de Gestión de Nefrología, Hospital Regional Carlos Haya, Malaga, Spain.
    Zambon, Roberto
    2Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo, Vicenza, Italy.
    Mooney, Andrew
    St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
    Quality standards for predialysis education: results from a consensus conference2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, no 7, p. 1058-1066Article in journal (Refereed)
    Abstract [en]

    This position statement was compiled following an expert meeting in March 2013, Zurich, Switzerland. Attendees were invited from a spread of European renal units with established and respected renal replacement therapy option education programmes. Discussions centred around optimal ways of creating an education team, setting realistic and meaningful objectives for patient education, and assessing the quality of education delivered.

  • 22.
    Jahnson, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Jedstrom, Tomas
    Orebro Univ Hosp, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Sherif, Amir
    Umea Univ Hosp, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the management of TaG3 tumours of the urinary bladder using nationwide population-based data in relation to the prevailing guidelines, patients characteristics, and outcome. Materials and methods: The Bladder Cancer Data Base Sweden (BladderBaSe), including data from the Swedish National Register for Urinary Bladder Cancer (SNRUBC), was used to study all patients with TaG3 bladder cancer diagnosed from 2008 to 2014. Patients were divided into the following management groups: (1) transurethral resection (TUR) only, (2) TUR and intravesical instillation therapy (IVIT), (3) TUR and second-look resection (SLR), and (4) TUR with both SLR and IVIT. Patient and tumour characteristics and outcome were studied. Results: There were 831 patients (83% males) with a median age of 74 years. SLR was performed more often on younger patients, on men, and less often in the Western and Uppsala/orebro Healthcare regions. IVIT was performed more often with younger patients, with men, in the Western Healthcare region, and less often in the Uppsala/orebro Healthcare region. Death from bladder cancer occurred in 6% of cases within a median of 29 months (0-84 months) and was lower in the TUR/IVIT and TUR/SLR/IVIT groups compared to the other two groups. Conclusion: In the present study, there was, according to the prevailing treatment guidelines, an under-treatment with SLR for older patients, women, and in some healthcare regions and, similarly, there was an under-treatment with IVIT for older patients. Cancer-specific survival and relative survival were lower in the TUR only group compared to the TUR/IVIT and TUR/SLR/IVIT groups.

  • 23.
    Jancke, Georg
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Aljabery, Firas
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gudjonsson, Sigurdur
    Landspitali Univ Hosp, Iceland.
    Sorenby, Anne
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Reply to Francesco Montorsi and Giorgio Gandaglias Letter to the Editor re: Georg Jancke, Firas Aljabery, Sigurdur Gudjonsson, et al. Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias?2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 2, p. E32-E33Article in journal (Other academic)
    Abstract [en]

    n/a

  • 24.
    Jancke, Georg
    et al.
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Liedberg, Fredrik
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Aljabery, Firas
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sherif, Amir
    Norrland University Hospital, Sweden.
    Strock, Viveka
    Sahlgrens University Hospital, Sweden.
    Malmstrom, Per-Uno
    Uppsala Akad Hospital, Sweden.
    Hosseini-Aliabad, Abolfazl
    Karolinska University Hospital, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Intravesical instillations and cancer-specific survival in patients with primary carcinoma in situ of the urinary bladder2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 2, p. 124-129Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate the use of intravesical treatment and cancer-specific survival of patients with primary carcinoma in situ (CIS). Materials and methods: Data acquisition was based on the Swedish National Registry of Urinary Bladder Cancer by selecting all patients with primary CIS. The analysis covered gender, age, hospital type and hospital volume. Intravesical treatment and death due to bladder cancer were evaluated by multivariate logistic regression and multivariate Cox analysis, respectively. Results: The study included 1041 patients (median age at diagnosis 72 years) with a median follow-up of 65 months. Intravesical instillation therapy was given to 745 patients (72%), and 138 (13%) died from bladder cancer during the observation period. Male gender [odds ratio (OR) = 1.56, 95% confidence interval (CI) 1.13-2.17] and treatment at county (OR = 1.65, 95% CI 1.17-2.33), university (OR =2.12, 95% CI 1.48-3.03) or high-volume (OR= 1.92, 95% CI 1.34-2.75) hospitals were significantly associated with higher odds of intravesical instillations. The age category amp;gt;80 years had a significantly lower chance of receiving intravesical therapy (OR = 0.44, 95% CI 0.26-0.74) and a significantly higher risk of dying from bladder cancer (hazard ratio = 3.03, 95% CI 1.71-5.35). Conclusion: Significantly more frequent use of intravesical treatment of primary CIS was found for males and for patients treated at county, university and high-volume hospitals. Age amp;gt;80 years was significantly related to less intravesical treatment and poorer cancer-specific survival.

  • 25.
    Jayne, David R. W.
    et al.
    Addenbrookes Hospital, England.
    Bruchfeld, Annette N.
    Karolinska University Hospital, Sweden.
    Harper, Lorraine
    University of Birmingham, England.
    Schaier, Matthias
    Heidelberg University, Germany.
    Venning, Michael C.
    Manchester Royal Infirm, England.
    Hamilton, Patrick
    Manchester Royal Infirm, England.
    Burst, Volker
    Uniklin Cologne, Germany.
    Grundmann, Franziska
    Uniklin Cologne, Germany.
    Jadoul, Michel
    Clin University of St Luc, Belgium.
    Szombati, Istvan
    Budai Irgalmasrendi Korhaz, Hungary.
    Tesar, Vladimir
    Charles University of Prague, Czech Republic.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Potarca, Antonia
    ChemoCentryx Inc, CA USA.
    Schall, Thomas J.
    ChemoCentryx Inc, CA USA.
    Bekker, Pirow
    ChemoCentryx Inc, CA USA.
    Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis2017In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 28, no 9, p. 2756-2767Article in journal (Refereed)
    Abstract [en]

    Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a amp;gt;= 50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, -4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%; P=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.

  • 26.
    Jensen, Gert
    et al.
    Univ Gothenburg, Sweden.
    Göransson, Lasse G.
    Stavanger Univ Hosp, Norway.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Furuland, Hans
    Univ Hosp, Uppsala, Sweden.
    Christensen, Jeppe H.
    Aalborg Univ Hosp, Denmark.
    Treatment of iron deficiency in patients with chronic kidney disease: A prospective observational study of iron isomaltoside (NIMO Scandinavia)2019In: Clinical Nephrology, ISSN 0301-0430, Vol. 91, no 4, p. 246-253Article in journal (Refereed)
    Abstract [en]

    Aims: Iron deficiency is common in patients with chronic kidney disease (CKD). Appropriate iron substitution is critical and intravenous iron is an established therapy for these patients. The objective of this study was to assess treatment routine, effectiveness, and safety of iron isomaltoside (Monofer (R), Pharmacosmos A/S, Holbaek, Denmark) in CKD patients in clinical practice. Materials and methods: This was a prospective observational study conducted in predialysis CKD patients treated with iron isomaltoside according to the product label and to routine clinical care. Results: The study included 108 patients with predialysis CKD: 22 were in stage 2 - 3, 41 in stage 4, and 45 in stage 5. The mean (standard deviation) age was 67 (15) years, and 55% of patients were male. The majority of patients (65%) received one iron isomaltoside treatment In patients with a baseline Hb amp;lt; 10 g/dL, the mean dose of iron isomaltoside in the study was lower than the estimated total iron requirement (567 mg versus 921 mg). A treatment response of Hb amp;gt;= 1 g/dL was achieved in 16/28 (57%) of patients, and the mean post-treatment Hb level was 10.5 g/dL. The probability of retreatment did not correlate with dose, but no dose administered was amp;gt; 1,000 mg. There were no serious adverse drug reactions. One nonserious adverse drug reaction - injection site discoloration - was reported, and the patient had an uneventful recovery. Conclusion: Iron isomaltoside shows a good effectiveness and safety profile in predialysis CKD patients. However, some patients did not receive adequate iron doses to allow for optimal correction of their iron deficiency anemia.

  • 27.
    Jiang, Chong-He
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Prolonged Modulation of the Micturition Reflex by Electrical Stimulation1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Intravesical electrical stimulation (IVES) has been used in treatment of patients with urinary bladder dysfunctions for more than four decades. While some investigators have reported excellent results others have observed less convincing effects or outright failures. The discrepancies may reflect differences in patient selection or stimulation procedure. A better theoretical understanding of the IVES working mechanism might help to improve the success rate of the treatment. The aims of the present study were to provide such information.

    Experiments were performed on adult female cats and rats under /alpha/-chloralose anesthesia. IVES was delivered by a catheter electrode in the bladder. At proper intensity and frequency, IVES evoked reflex detrusor contractions that were abolished by bilateral rhizotomy of sacral dorsal roots. Stimulation parameters and response characteristics revealed that bladder mechanoreceptor A/delta/ afferents were activated by the IVES, the same afferents that drive the normal micturition reflex.

    Five minutes of continues IVES at 20 Hz induced a prolonged, significant decrease in the micturition threshold volume of anesthetized rats. Similarly, selective bladder A/delta/ afferent stimulation induced a long-lasting enhancement of micturition reflex discharges in cats. A comparable prolonged inhibitory effect on the micturition reflex was demonstrated after ano-genital afferent stimulation. Both modulatory effects occurred without changes in response sensitivity of stimulated afferents. The IVES induced modulation was prevented by transient exposure of the bladder to a local anesthetic and by systemic administration of a glutamate NMDA receptor antagonist.

    In conclusion, IVES induces a prolonged modulation of the micturition reflex by an LTP like enhancement of excitatory synaptic transmission in the central micturition reflex pathway. The findings provide an experimental explanation for the neuronal mechanisms underlying the curative effect of IVES in patients with bladder evacuation problems.

    List of papers
    1. Intravesical electrical stimulation: an experimental analysis of the mechanism of action
    Open this publication in new window or tab >>Intravesical electrical stimulation: an experimental analysis of the mechanism of action
    1992 (English)In: Journal of Urology, ISSN 0022-5347, Vol. 148, no 3, p. 920-924Article in journal (Refereed) Published
    Abstract [en]

    The working mechanism of intravesical electrical stimulation (IVES) was evaluated in alpha-chloralose anaesthetized cats and rats. IVES involved a direct activation of bladder mechanoreceptor afferents of the A delta type and as a consequence a central reflex activation of the detrusor. The detrusor response was abolished by bilateral transection of the S1-S3 dorsal roots and by intravesical instillation of lidocaine. The optimal stimulation frequency was 20 Hz. The results offer a theoretical rationale for the use of IVES as treatment of weak detrusor contractility in man.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13504 (URN)
    Available from: 1999-02-25 Created: 1999-02-25
    2. Intravesical electrical stimulation induces a prolonged decrease in micturition threshold volume in the rat
    Open this publication in new window or tab >>Intravesical electrical stimulation induces a prolonged decrease in micturition threshold volume in the rat
    1996 (English)In: Journal of Urology, ISSN 0022-5347, Vol. 155, no 4, p. 1477-1481Article in journal (Refereed) Published
    Abstract [en]

    Purpose: Intravesical electrical stimulation (IVES) has been used clinically to treat patients with voiding disorders. The aim of the present experimental study was to obtain objective evidence of a modulation of the micturition reflex by intravesical electrical stimulation (IVES).

    Materials and Methods: Forty-one female rats, anesthetized by alpha-chloralose were used for the experiments. Intravesical electrical stimulation was given by a catheter electrode in the bladder (5 minutes of continuous stimulation at 20 Hz, 7 to 11 mA). The effect was evaluated by the change in cystometric micturition threshold volume.

    Results: The threshold volume of the micturition reflex decreased significantly to 82% of controls after IVES (p<0.001; n=31). The effect was reversible and lasted for about 1 hour. The decrease was prevented by a transient blockade of the bladder nerves during IVES.

    Conclusions: Intravesical electrical stimulation induced a prolonged modulation of the micturition reflex in anesthetized rats. The effect was due to activation of bladder mechanoreceptor afferents and remained long after the period of stimulation. It is proposed that the modulation was due to a prolonged enhancement of excitatory synaptic transmission in the central micturition reflex pathway. Such a modulation may underlie the curative effect of IVES in certain voiding disorders.

    Keywords
    stimulation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13505 (URN)10.1016/S0022-5347(01)66310-9 (DOI)
    Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2018-03-08
    3. Modulation of the micturition reflex pathway by intravesical electrical stimulation: An experimental study in the rat
    Open this publication in new window or tab >>Modulation of the micturition reflex pathway by intravesical electrical stimulation: An experimental study in the rat
    1998 (English)In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 17, no 5, p. 543-554Article in journal (Refereed) Published
    Abstract [en]

    Intravesical electrical stimulation (IVES) is used clinically to improve bladder evacuation in patients with inadequate micturition contractions. The procedure involves field stimulation of A bladder mechanoreceptor afferents resulting in a prolonged enhancement of the micturition reflex. The aim of the present experimental study in the rat was to identify the site for this neuromodulation, whether it was due to sensitization of bladder mechanoreceptors, to enhancement of transmission in the central micturition reflex pathway, or to improved effectiveness of the peripheral motor system of the bladder. The experiments were performed on female rats, anesthetized by -chloralose. Multi-unit afferent or efferent activity was recorded from bladder pelvic nerve branches during repeated cystometries before and after IVES. The specific antagonist CPPene was used to block central glutaminergic receptors of NMDA type. Micturition threshold volume decreased significantly after IVES. The afferent threshold volume, peak response, and pressure sensitivity were unchanged as were the peak efferent activity and bladder contractility. There was no efferent activity until just before the micturition contraction. The IVES-induced decrease in micturition threshold was blocked by prior administration of the NMDA (N-methyl-D-aspartic acid) antagonist CPPene (3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid). The findings indicate that the IVES-induced modulation of the micturition reflex is due to an enhanced excitatory synaptic transmission in the central micturition reflex pathway. The observed modulation may account for the clinical beneficial effect of IVES treatment.

    Keywords
    urinary bladder, electric stimulation, neuromodulation, bladder afferent, bladder efferent, micturition reflex, NMDA antagonist, rat
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13506 (URN)10.1002/(SICI)1520-6777(1998)17:5<543::AID-NAU11>3.0.CO;2-G (DOI)
    Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2017-12-13Bibliographically approved
    4. Optimal conditions for the long-term modulation of the micturition reflex by intravesical electrical stimulation: an experimental study in the rat
    Open this publication in new window or tab >>Optimal conditions for the long-term modulation of the micturition reflex by intravesical electrical stimulation: an experimental study in the rat
    1999 (English)In: BJU International, ISSN 1464-4096, Vol. 83, no 4, p. 483-487Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: To determine whether induced bladder contractions influence the modulation by intravesical electrical stimulation (IVES) of the micturition reflex in anaesthetized rats, and to identify the optimal IVES frequency and duration.

    MATERIALS AND METHODS: Seventy-six adult female rats, anaesthetized by alpha-chloralose. were divided into four groups to study the effect of: (i) IVES in combination with bladder contractions; (ii) bladder contractions alone; (iii) IVES frequency; and (iv) IVES duration. IVES was administered using a catheter electrode in the bladder. The effect of various IVES procedures was evaluated by determining the micturition threshold volume obtained from repeated cystometries before and after stimulation.

    RESULTS: Administering IVES with standard parameters induced a significant decrease in the micturition threshold volume for about an hour. There was no difference in outcome between IVES with the bladder filled and contracting during the stimulation or empty and not contracting. Imposed bladder contractions per se had no effect on the micturition threshold volume. IVES at low frequencies (< or = 20 Hz) had a better modulatory effect than higher frequencies and the optimum duration of IVES was 5 min.

    CONCLUSIONS: Evoked bladder contractions did not improve the IVES-induced modulation of the micturition reflex. These findings might help to improve the clinical application of the IVES procedure.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13507 (URN)
    Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2009-05-20
    5. Prolonged increase in micturition threshold volume by anogenital afferent stimulation in the rat
    Open this publication in new window or tab >>Prolonged increase in micturition threshold volume by anogenital afferent stimulation in the rat
    1998 (English)In: British Journal of Urology International, ISSN 1464-4096, Vol. 82, no 3, p. 483-487Article in journal (Refereed) Published
    Abstract [en]

    Objective

    To determine whether induced bladder contractions influence the modulation by intravesical electrical stimulation (IVES) of the micturition reflex in anaesthetized rats, and to identify the optimal IVES frequency and duration.

    Materials and methods

    Seventy-six adult female rats, anaesthetized by α-chloralose, were divided into four groups to study the effect of: (i) IVES in combination with bladder contractions; (ii) bladder contractions alone; (iii) IVES frequency; and (iv) IVES duration. IVES was administered using a catheter electrode in the bladder. The effect of various IVES procedures was evaluated by determining the micturition threshold volume obtained from repeated cystometries before and after stimulation.

    Results

    Administering IVES with standard parameters induced a significant decrease in the micturition threshold volume for about an hour. There was no difference in outcome between IVES with the bladder filled and contracting during the stimulation or empty and not contracting. Imposed bladder contractions per se had no effect on the micturition threshold volume. IVES at low frequencies (≤20 Hz) had a better modulatory effect than higher frequencies and the optimum duration of IVES was 5 min.

    Conclusions

    Evoked bladder contractions did not improve the IVES-induced modulation of the micturition reflex. These findings might help to improve the clinical application of the IVES procedure.

    Keywords
    bladder, electric stimulation, contraction, micturition reflex, rats
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13508 (URN)10.1046/j.1464-410x.1999.00947.x (DOI)
    Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2009-05-20
    6. Prolonged enhancement of the micturition reflex in the cat by repetitive stimulation of bladder afferents
    Open this publication in new window or tab >>Prolonged enhancement of the micturition reflex in the cat by repetitive stimulation of bladder afferents
    1999 (English)In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 517, no 2, p. 599-605Article in journal (Refereed) Published
    Abstract [en]
    1. Prolonged modulation of the parasympathetic micturition reflex was studied in cats anaesthetized by -chloralose. Reflex discharges were recorded from a thin pelvic nerve filament to the bladder and evoked by stimulation of the remaining ipsilateral bladder pelvic nerves or urethral branches of the pudendal nerve.

       

    2. Stimulation of bladder or urethral afferents at A intensity evoked micturition reflexes with a latency of 90-120 ms. Such reflexes were much enhanced following repetitive conditioning stimulation of the same afferents at 20 Hz for 5 min.

       

    3. The reflex enhancement lasted more than 1 h after the conditioning stimulation. The effect was not prevented by a preceding complete transection of the sympathetic supply to the bladder. A prolonged suppression of the reflex was obtained after conditioning stimulation of afferents in the dorsal clitoris nerves.

       

    4. It is proposed that the prolonged modulations of the micturition reflex represent physiological adaptive processes, which preserve a flawless function of the bladder during life. The observations provide a theoretical explanation for the beneficial effect of electric nerve stimulation in patients with voiding disorders.
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13509 (URN)
    Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2017-12-13Bibliographically approved
  • 28.
    Kaasinen, Eero
    et al.
    Hyvinkaa Hospital, Finland; Helsinki University Hospital, Finland.
    Wijkstrom, Hans
    Karolinska University, Sweden.
    Rintala, Erkki
    Helsinki University Hospital, Finland.
    Mestad, Oddvar
    University of Stavanger, Norway.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Malmstrom, Per-Uno
    University of Uppsala Hospital, Sweden.
    Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 5, p. 360-368Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to compare the long-term efficacy of BCG monotherapy to alternating therapy of mitomycin C (MMC) and BCG in patients with carcinoma in situ (CIS). Materials and methods: Between 1992 and 1997, 321 patients with CIS were randomized from Finland, Norway and Sweden in a prospective multicenter trial into two treatment groups. The alternating therapy comprised six weekly instillations of MMC 40 mg followed by 10 instillations of BCG (Connaught 120 mg) or MMC alternating monthly for 1 year. BCG monotherapy followed the same 6 + 10 schedule. Stratification was done by nationality and CIS category. Primary endpoints were time to first recurrence and time to progression. Secondary endpoints were disease-specific mortality and overall survival. The main statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model with the cumulative incidence and Kaplan-Meier analyses. Results: The median follow-up time was 9.9 years (maximum 19.9 years) in the BCG group and 8.9 years (maximum 20.3 years) in the alternating group. The risk of recurrence was significantly lower in the BCG group than in the alternating group (49 vs 59% at 15 years, respectively; hazard ratio 0.74, 95% confidence interval 0.54-1.00, p = 0.048). There were no significant differences in the other endpoints. Patients who progressed after 2 years were particularly prone to dying from bladder carcinoma. Younger patients performed worse than older ones. Conclusions: BCG monotherapy including monthly maintenance was effective and better than the alternating therapy. The risk of dying from bladder carcinoma after progression was high.

  • 29.
    Klaff, Rami
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Disease-Specific Survival in Prostate Cancer Patients: Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction

    Prostate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary.

    Aims

    • To explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I)
    • To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II)
    • To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III)
    • To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV)

    Material and methods

    The study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men.

    Result and conclusions

    The long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.

    List of papers
    1. The Long-term Disease-specific Mortality of Low-risk Localized Prostate Cancer: A Prospective Population-based Register Study Over Two Decades
    Open this publication in new window or tab >>The Long-term Disease-specific Mortality of Low-risk Localized Prostate Cancer: A Prospective Population-based Register Study Over Two Decades
    2016 (English)In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 91, p. 77-82Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE To identify prognostic factors, and to estimate the long-term disease-specific and annual disease-specific mortality rates of low-risk prostate cancer patients from the early prostate-specific antigen (PSA) era. PATIENTS AND METHODS We studied data extracted from the Southeast Region Prostate Cancer Register in Sweden, on 1300 patients with clinically localized low-risk tumors, T1-2, PSA level amp;lt;= 10 mu g/L and Gleason scores 2-6 or World Health Organization Grade 1, diagnosed 1992-2003. The Cox multivariate regression model was used to evaluate factors predicting survival. Prostate cancer death rates per 1000 person-years were estimated for 4 consecutive follow-up time periods: 0-5, 5-10, 10-15, and 15+ years after diagnosis. RESULTS During the follow-up of overall survivors (mean 10.6 years; maximum 21.8 years), 93 patients (7%) died of prostate cancer. Cancer-specific survival was 0.98 (95% confidence interval [CI] 0.97-0.99), 0.95 (95% CI 0.93-0.96), 0.89 (95% CI 0.86-0.91), and 0.84 (95% CI 0.80-0.88), 5, 10, 15, and 20 years after diagnosis. The 5-year increases in cancer-specific mortality were statistically significant (P amp;lt;. 001). Patients with PSA amp;gt;= 4 mu g/L managed initially with watchful waiting and those aged 70 years or older had a significantly higher risk of dying from their prostate cancer. CONCLUSION The long-term disease-specific mortality of low-risk localized prostate cancer is low, but the annual mortality rate from prostate cancer gradually increases. This indicates that some tumors slowly develop into lethal cancer, particularly in patients 70 years or older with a PSA level amp;gt;= 4 mu g/L. (C) 2016 Elsevier Inc.

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE INC, 2016
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:liu:diva-129173 (URN)10.1016/j.urology.2016.01.033 (DOI)000375901500023 ()26879734 (PubMedID)
    Available from: 2016-06-13 Created: 2016-06-13 Last updated: 2017-11-28
    2. Clinical characteristics and quality-of-life in patients surviving a decade of prostate cancer with bone metastases
    Open this publication in new window or tab >>Clinical characteristics and quality-of-life in patients surviving a decade of prostate cancer with bone metastases
    Show others...
    2016 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 6, p. 904-913Article in journal (Refereed) Published
    Abstract [en]

    Objective To describe characteristics and quality-of-life (QoL), and to define factors associated with long-term survival in a subgroup of patients with prostate cancer with M1b disease. Patients and Methods The study was based on 915 patients from a prospective randomised multicentre trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Long-term survival was defined as patients having an overall survival of &gt;= 10 years, and logistic regression models were constructed to identity clinical predictors of survival. QoL during follow-up was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - C30 version 1 (EORTC-C30) ratings. Results In all, 40 (4.4%) of the 915 men survived for &gt;10 years. Factors significantly associated with increased likelihood of surviving for &gt;10 years in the univariate analyses were: absence of cancer-related pain; Eastern Cooperative Oncology Group (ECOG) performance status of &lt;2; negligible analgesic consumption; T-category of 1-2; prostate-specific antigen (PSA) level of &lt;231 mu g/L; and a Soloway score of 1. In the multivariate analyses, ECOG performance status of &lt;2, PSA level of &lt;231 mu g/L, and Soloway score of 1, were all independent predictors of long-term survival. All subscales of the EORTC-C30 were higher in this group than for patients with short survival, but slowly declined over the decade. Conclusion A subgroup of patients with prostate cancer with M1b disease and certain characteristics showed a positive long-term response to androgen-deprivation therapy with an acceptable QoL over a decade or more. Independent predictors of long-term survival were identified as ECOG performance status of &lt;2, limited extent of bone metastases (Soloway score of 1), and a PSA level of &lt;231 mu g/L at the time of enrolment.

    Place, publisher, year, edition, pages
    WILEY-BLACKWELL, 2016
    Keywords
    prostate cancer; bone metastases; long-term survival; quality-of-life
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-128927 (URN)10.1111/bju.13190 (DOI)000376009800015 ()26033416 (PubMedID)
    Available from: 2016-06-09 Created: 2016-06-07 Last updated: 2017-05-02
    3. Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases
    Open this publication in new window or tab >>Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases
    Show others...
    2016 (English)In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 5, no 3, p. 407-414Article in journal (Refereed) Published
    Abstract [en]

    Approximately 15% of men with hormone naive metastatic prostate cancer primarily fail to respond to androgen deprivation treatment (ADT). The reason why the response to ADT differs in this subgroup of men with prostate cancer remains unclear. The aim of this study was to describe the characteristics of these men and to thereby define predictors of early ADT failure in prostate cancer patients with bone metastases. The study was based on 915 men from the prospective randomized multicenter trial (no. 5) conducted by the Scandinavian Prostate Cancer Group comparing parenteral estrogen with total androgen blockade. Early ADT failure was defined as death from metastatic prostate cancer within 12months after the start of ADT. Multivariate logistic regression models were applied to identify clinical predictors of early ADT failure. Ninety-four (10.3%) men were primarily nonresponders to ADT. Independent predictors of early ADT failure were poor Eastern Cooperative Oncology Group performance status (PS), analgesic consumption, low hemoglobin, and high Soloway score (extent of disease observed on the scan), in where patients with poor PS and/or high analgesic consumption had a threefold risk of early ADT failure. Not significantly factors related to early ADT failure were age, treatment, cardiovascular comorbidity, T category, grade of malignancy, serum estrogen level, and SHBG at enrolment. We analyzed characteristics of a subgroup of patients who primarily failed to respond to ADT. Four independent clinical predictors of early ADT failure could be defined, and men exhibiting these features should be considered for an alternative treatment.

    Place, publisher, year, edition, pages
    WILEY-BLACKWELL, 2016
    Keywords
    Androgen deprivation treatment; bone metastases; clinical predictors; early failure; prostate cancer
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-127443 (URN)10.1002/cam4.594 (DOI)000373203000003 ()26765317 (PubMedID)
    Note

    Funding Agencies|Ferring AB Malmo, Sweden; Ferring Laegemidler A/S Copenhagen, Denmark; Pharmacia AB, Uppsala, Sweden; Schering-Plough AB, Stockholm, Sweden

    Available from: 2016-04-30 Created: 2016-04-26 Last updated: 2017-11-30
    4. Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients
    Open this publication in new window or tab >>Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients
    Show others...
    2016 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 5, p. 352-359Article in journal (Refereed) Published
    Abstract [en]

    Objective: The aim of this study was to investigate the impact of bone metastasis on survival and quality of life (QoL) in men with hormone-naive prostate cancer. Materials and methods: The study included 900 patients from a randomized trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Extent of bone metastasis was categorized according to a modified Soloway score: score 1, n=319; score 2, n = 483; and score 3, n = 98 patients. The primary outcome measurements were mean differences in QoL and overall survival. Results: QoL rating scales showed a decrease with increasing extent of bone metastasis (p amp;lt; 0.001). The mean global health status decreased from 64.4 to 50.5 for Soloway score 1 and 3, respectively. Following adjustment for performance status, analgesic consumption, grade of malignancy, alkaline phosphatase, prostate-specific antigen, haemoglobin and global health status, Soloway score 2 and 3 had a 47% [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.21-1.80] and 78% (HR 1.78 95%, CI 1.32-2.42) increased mortality, respectively, compared to Soloway score 1. Independent predictive factors of mortality were assessed. Conclusions: Patient grouping based on three categories of extent of bone metastasis related to performance status, haemoglobin and global health status at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.

    Place, publisher, year, edition, pages
    TAYLOR & FRANCIS LTD, 2016
    Keywords
    Androgen deprivation treatment; bone metastasis; extent of disease; hormone-naive; predictors of survival; prostate cancer
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:liu:diva-132207 (URN)10.1080/21681805.2016.1209689 (DOI)000384068000005 ()27603423 (PubMedID)
    Note

    Funding Agencies|Ferring AB, Malmo, Sweden; Ferring Laegemidler A/S, Copenhagen, Denmark; Pharmacia AB, Uppsala, Sweden; Schering-Plough AB, Stockholm, Sweden

    Available from: 2016-11-01 Created: 2016-10-21 Last updated: 2017-08-09
  • 30.
    Klaff, Rami
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Faculty of Medicine and Health Sciences.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sandblom, Gabriel
    Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Hospital, Huddinge, Sweden.
    The Long-term Disease-specific Mortality of Low-risk Localized Prostate Cancer: A Prospective Population-based Register Study Over Two Decades2016In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 91, p. 77-82Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To identify prognostic factors, and to estimate the long-term disease-specific and annual disease-specific mortality rates of low-risk prostate cancer patients from the early prostate-specific antigen (PSA) era. PATIENTS AND METHODS We studied data extracted from the Southeast Region Prostate Cancer Register in Sweden, on 1300 patients with clinically localized low-risk tumors, T1-2, PSA level amp;lt;= 10 mu g/L and Gleason scores 2-6 or World Health Organization Grade 1, diagnosed 1992-2003. The Cox multivariate regression model was used to evaluate factors predicting survival. Prostate cancer death rates per 1000 person-years were estimated for 4 consecutive follow-up time periods: 0-5, 5-10, 10-15, and 15+ years after diagnosis. RESULTS During the follow-up of overall survivors (mean 10.6 years; maximum 21.8 years), 93 patients (7%) died of prostate cancer. Cancer-specific survival was 0.98 (95% confidence interval [CI] 0.97-0.99), 0.95 (95% CI 0.93-0.96), 0.89 (95% CI 0.86-0.91), and 0.84 (95% CI 0.80-0.88), 5, 10, 15, and 20 years after diagnosis. The 5-year increases in cancer-specific mortality were statistically significant (P amp;lt;. 001). Patients with PSA amp;gt;= 4 mu g/L managed initially with watchful waiting and those aged 70 years or older had a significantly higher risk of dying from their prostate cancer. CONCLUSION The long-term disease-specific mortality of low-risk localized prostate cancer is low, but the annual mortality rate from prostate cancer gradually increases. This indicates that some tumors slowly develop into lethal cancer, particularly in patients 70 years or older with a PSA level amp;gt;= 4 mu g/L. (C) 2016 Elsevier Inc.

  • 31.
    Klaff, Rami
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Varenhorst, Eberhard
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Berglund, Anders
    EpiStat, Sweden.
    Olov Hedlund, Per
    Karolinska Institute, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sandblom, Gabriel
    Karolinska Institute, Sweden.
    Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 5, p. 352-359Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to investigate the impact of bone metastasis on survival and quality of life (QoL) in men with hormone-naive prostate cancer. Materials and methods: The study included 900 patients from a randomized trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Extent of bone metastasis was categorized according to a modified Soloway score: score 1, n=319; score 2, n = 483; and score 3, n = 98 patients. The primary outcome measurements were mean differences in QoL and overall survival. Results: QoL rating scales showed a decrease with increasing extent of bone metastasis (p amp;lt; 0.001). The mean global health status decreased from 64.4 to 50.5 for Soloway score 1 and 3, respectively. Following adjustment for performance status, analgesic consumption, grade of malignancy, alkaline phosphatase, prostate-specific antigen, haemoglobin and global health status, Soloway score 2 and 3 had a 47% [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.21-1.80] and 78% (HR 1.78 95%, CI 1.32-2.42) increased mortality, respectively, compared to Soloway score 1. Independent predictive factors of mortality were assessed. Conclusions: Patient grouping based on three categories of extent of bone metastasis related to performance status, haemoglobin and global health status at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.

  • 32.
    Lindqvist, Emma
    et al.
    Highland Hospital, Sweden.
    Wedin, Madelene
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Lymphedema after treatment for endometrial cancer - A review of prevalence and risk factors2017In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 211, p. 112-121Article, review/survey (Refereed)
    Abstract [en]

    Lymphedema is one of the least studied complications of cancer treatment and a chronic condition with a substantial impact on health-related quality of life (HQoL). Lymphedema of the legs (LLL) constitutes a common adverse side effect of lymphadenectomy LA in gynecologic cancer treatment. Primary treatment of endometrial cancer (EC) comprises hysterectomy and bilateral salpingo-oophorectomy. Pelvic and para-aortic lymphadenectomy is recommended in prognostic high risk groups of EC. This review summarizes the published literature concerning the prevalence of LLL after treatment for EC, methods used for measuring LLL, risk factors and HQoL impact. The main findings are that the reported prevalence of LLL varies significantly between 0% and 50%. This is due to a lack of a generally accepted standardization of terminology in assessment of lymphedema. The studies use different methods to assess and grade lymphedema and often the methodology used for determining LLL is poorly described and lacks baseline measurement. Lymphadenectomy, number of lymph nodes removed, and radiation therapy seems to increase the risk for LLL. All studies dealing with HQoL show that women with LLL have impaired HQoL. The level of evidence in the published studies is generally low. Consequently it is difficult to make clear-cut conclusions about the true prevalence or determination of risk factors. More prospective longitudinal or randomized trials with LLL as the primary outcome are necessary before conclusions can be drawn regarding prevalence of LLL and risk factor determination in EC. An internationally accepted standardization for terminology and methodology in lymphedema in research is needed. (C) 2017 Elsevier B.V. All rights reserved.

  • 33.
    Loftås, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Response to neoadjuvant treatment in rectal cancer surgery2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.

    Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.

    Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.

    Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.

    Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.

    List of papers
    1. EXPRESSION OF FXYD-3 IS AN INDEPENDENT PROGNOSTIC FACTOR IN RECTAL CANCER PATIENTS WITH PREOPERATIVE RADIOTHERAPY
    Open this publication in new window or tab >>EXPRESSION OF FXYD-3 IS AN INDEPENDENT PROGNOSTIC FACTOR IN RECTAL CANCER PATIENTS WITH PREOPERATIVE RADIOTHERAPY
    Show others...
    2009 (English)In: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, ISSN 0360-3016, Vol. 75, no 1, p. 137-142Article in journal (Refereed) Published
    Abstract [en]

    Purpose: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables. Methods and Materials: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immumohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36). Results: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0.02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to he increased compared with normal mucosa regardless of RT. Conclusion: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer.

    Keywords
    FXYD-3, Rectal cancer, Radiotherapy, Prognosis, Immunohistochemistry
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20598 (URN)10.1016/j.ijrobp.2008.10.076 (DOI)
    Available from: 2009-09-16 Created: 2009-09-15 Last updated: 2016-11-24
    2. FXYD-3 expression in relation to local recurrence of rectal cancer
    Open this publication in new window or tab >>FXYD-3 expression in relation to local recurrence of rectal cancer
    Show others...
    2016 (English)In: Radiation Oncology Journal, ISSN 2234-1900, Vol. 34, no 1, p. 52-58Article in journal (Refereed) Published
    Abstract [en]

    Purpose: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer.

    Materials and Methods: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81).

    Results: Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without.

    Conclusion: Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.

    Place, publisher, year, edition, pages
    Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea, 2016
    Keywords
    Rectal cancer, Human FXYD3 protein, Local recurrence
    National Category
    Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-132758 (URN)10.3857/roj.2016.34.1.52 (DOI)27104167 (PubMedID)
    Available from: 2016-11-23 Created: 2016-11-23 Last updated: 2016-12-07Bibliographically approved
    3. Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer
    Open this publication in new window or tab >>Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer
    2016 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 42, no 6, p. 801-807Article in journal (Refereed) Published
    Abstract [en]

    Background: Pathological complete response (pCR) after neoadjuvant therapy in rectal cancer is correlated with improved survival. There is limited knowledge on the incidence of pCR at a national level with uniform guidelines. The aim of this prospective register-based study was to investigate the incidence and outcome of pCR in relation to neoadjuvant therapy in a national cohort. Method: All patients abdominally operated for rectal cancer between 2007 and 2012 (n = 7885) were selected from The Swedish Colorectal Cancer Register. Twenty-six per cent (n = 2063) had neoadjuvant therapy with either long or short course radiotherapy with amp;gt;4 weeks delay with the potential to achieve pCR. The primary endpoints were pCR and survival in relation to neoadjuvant therapy. Results: Complete eradication of the luminal tumor, ypTO was found in 161 patients (8%). In 83% of the ypTO the regional lymph nodes were tumor negative (ypTONO), 12% had 1-3 positive lymph nodes (ypTON1) and 4% had more than three positive lymph nodes (ypTON2). There was significantly greater survival with ypTO compared to ypT+ (hazard ratio 0.38 (C.I 0.25-0.58)) and survival was significantly greater in patients with ypTONO compared to ypT0N1-2 (hazard ratio 0.36 (C.I 0.15-0.86)). In ypTO, cT3-4 tumors had the greater risk of node-positivity. The added use of chemotherapy resulted in 10% ypTO compared to 5.1% in the group without chemotherapy (p amp;lt; 0.00004). Conclusion: Luminal pathological complete response occurred in 8%, 16% of them had tumor positive nodes. The survival benefit of luminal complete response is dependent upon nodal involvement status. (C) 2016 Elsevier Ltd. All rights reserved.

    Place, publisher, year, edition, pages
    ELSEVIER SCI LTD, 2016
    Keywords
    Rectal cancer; Complete response; Lymph nodes; Neoadjuvant treatment
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-130432 (URN)10.1016/j.ejso.2016.03.013 (DOI)000379559300007 ()27146960 (PubMedID)
    Available from: 2016-08-07 Created: 2016-08-05 Last updated: 2017-05-02
  • 34.
    Lood, Yvonne
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden.
    Aardal-Eriksson, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Webe, C.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden.
    Ekman, Bertil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Relationship between testosterone in serum, saliva and urine during treatment with intramuscular testosterone undecanoate in gender dysphoria and male hypogonadism2018In: Andrology, ISSN 2047-2919, E-ISSN 2047-2927, Vol. 6, no 1, p. 86-93Article in journal (Refereed)
    Abstract [en]

    Long-term testosterone replacement therapy is mainly monitored by trough levels of serum testosterone (S-T), while urinary testosterone (U-T) is used by forensic toxicology to evaluate testosterone doping. Testosterone in saliva (Sal-T) may provide additional information and simplify the sample collection. We aimed to investigate the relationships between testosterone measured in saliva, serum and urine during standard treatment with 1,000mg testosterone undecanoate (TU) every 12th week during 1year. This was an observational study. Males with primary and secondary hypogonadism (HG; n=23), subjects with gender dysphoria (GD FtM; n=15) and a healthy control group of men (n=32) were investigated. Sal-T, S-T and U-T were measured before and after TU injections. Sal-T was determined with Salimetrics((R)) enzyme immunoassay, S-T with Roche Elecsys((R)) testosterone II assay and U-T by gas chromatography-mass spectrometry. Sal-T correlated significantly with S-T and calculated free testosterone in both controls and patients (HG men and GD FtM), while Sal-T to U-T showed weaker correlations. Trough values of Sal-T after 12months were significantly higher in the GD FtM group (0.77 +/- 0.35nmol/L) compared to HG men (0.53 +/- 0.22nmol/L) and controls (0.46 +/- 0.15nmol/L), while no differences between S-T and U-T trough values were found. Markedly elevated concentrations of salivary testosterone, 7-14days after injection, were observed, especially in the GD FtM group. This study demonstrates that Sal-T might be a useful clinical tool to monitor long-term testosterone replacement therapy and might give additional information in forensic cases.

  • 35.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Etikprövningsnämnder måste kunna granska kvalitet2015Other (Other (popular science, discussion, etc.))
    Abstract [sv]

    Det kan vara oetiskt att inte forska, men dålig forskning är oetisk forskning. Etikprövningsnämnderna bör inte bara granska etiska aspekter utan även kvaliteten på klinisk forskning. Det skriver Johnny Ludvigson, senior professor vid Linköpings universitet, i en replik på inläggen av Hugo Lagercrantz och Nils Erik Sahlin om etiska tillstånd vid kliniska studier.

  • 36.
    Lundin, Ulrika
    Linköping University, The Department of Physics, Chemistry and Biology.
    Biomarker Discovery in Diabetic Nephropathy by Targeted Metabolomics2008Independent thesis Advanced level (degree of Master (Two Years)), 20 points / 30 hpStudent thesis
    Abstract [en]

    Diabetic nephropathy is a chronic kidney disease and one of the more severe complications from diabetes mellitus type 2. The glomerular and tubular dysfunctions usually lead to end stage renal disease and the treatments of these patients (dialysis, kidney transplants) are a huge economic burden for the society. Due to an epidemiologic increase of type 2 diabetes, conventional diagnostic markers like creatinine and albumin are not sufficient, since they are only able to identify already existing kidney damage. With targeted metabolomics, the analysis of small molecules produced from metabolism, this project aimed at finding novel and more sensitive metabolic biomarkers from several different classes of metabolites. The different assays were performed with flow injection analysis, high performance liquid chromatography, gas chromatography and mass spectrometry, and with principal component analysis and discriminant analysis, up-and down-regulated metabolites could be identified and their respective biochemical pathways, if possible, explained. In diabetics significantly elevated concentrations of very long chain fatty acids (impaired peroxisomal β-oxidation), urinary sugars and acylcarnitines in plasma could be recognized. Markers indicating kidney damage included significantly increased plasma concentrations of asymmetric dimethylarginine (inhibition of nitric oxide synthase resulting in decreased endothelial functionality) and histamine (indication of uremic pruritus). Oxidative stress was also found to be a potential prognostic marker as indicated by the raised methionine-sulfoxide to methionine ratio in nephrotic patients. To summarize, this project succeeded in identifying metabolic biomarkers both for diabetes type 2 and nephropathy, which in the future might become important tools in slowing down progression or diagnosing these diseases.

  • 37.
    Malmstrom, Per-Uno
    et al.
    Uppsala Univ, Sweden.
    Gardmark, Truls
    Danderyd Hosp, Sweden; Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Hosseini-Aliabad, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Aljabery, Firas
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Incidence, survival and mortality trends of bladder cancer in Sweden 1997-2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate trends in bladder cancer incidence, survival and mortality in Sweden from 1997-2016. Patients and methods: The Swedish National Registry of Urinary Bladder Cancer is a nation-wide quality register that started in 1997. It includes information on initial tumor characteristics and treatment; 41,097 new cases were registered up to 2016. Patients were stratified into four time periods. Deaths were monitored through the national death register. Overall and relative survival in time periods were studied with respect to differences in stage, age and gender. Results: The number of new cases increased by 38% for men and 39% for women from 1997 to 2016. The corresponding age-standardized incidence per 100,000 was less dramatic, with increases of 6% and 21%, respectively, and the increase was most evident in the oldest age group. The survival rate was stable until 2012, but thereafter a significant improvement occurred. The survival trends in stage-groups show that this improvement is found in all categories as well as irrespective of age and gender. The mortality rate during this period was stable for women, but showed a slight decrease for men. The main limitation of this study is the use of administrative data for defining some of the endpoints. Conclusion: The most recent Swedish bladder cancer statistics show an increased incidence, improved survival, but stable mortality.

  • 38.
    Marklund, Helén
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Spångberg, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Edéll-Gustafsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Sleep and health-related quality of life in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction compared to the general population and patients with inguinal hernia2010In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 44, no 5, p. 304-314Article in journal (Refereed)
    Abstract [en]

    Abstract Objective. To determine whether there are differences in the quantity and quality of sleep, including sleep efficiency and insomnia, and health-related quality of life (HRQoL) between patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO), men from the general population and patients with inguinal hernia. Material and methods. The designs were descriptive and comparative. The groups consisted of 239 patients aged 45-80 years who were referred to urological departments with LUTS suggestive of benign prostatic obstruction. The comparison groups consisted of 213 randomly selected men from the general population, stratified according to age and geographical region, and 200 patients with inguinal hernia. The setting was one university and two general hospitals. The method was self-administered questionnaires about demography, comorbidity, sleep and health-related quality of life. Further, patients with LUTS answered questions about urinary symptoms and disease-specific quality of life. Results. The prevalence of insomnia was 40%, 26% and 19% and the prevalence of sleep efficiency < 85% was 49%, 38.5% and 31% in the LUTS, general population and hernia groups, respectively. The median number of nocturnal micturitions was 2, 1 and 1. In the LUTS group (n = 216), 47% had IPSS 8-19 and 44% had >/= 20 points. The HRQoL was significantly impaired in patients with LUTS compared with one or both of the comparison groups (p values < 0.05). Conclusions. Patients with LUTS suggestive of BPO had significantly impaired sleep, a higher prevalence of insomnia and significantly impaired HRQoL compared with one or both of the comparison groups.

  • 39.
    Marklund-Bau, Helén
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Urology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Sleep and quality of life in men with lower urinary tract symptoms: and their partners2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aims: The overall aim was to determine how lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) affect sleep, health related quality of life and disease specific quality of life, and how the men’s urinary symptoms affect their partners.

    Subjects and methods: In papers I–II, a descriptive design with a pre-test and post-test was used and in papers III-IV the design was descriptive and comparative. The method was self-administered questionnaires. In papers I- II: The questionnaires were translated in the ethnographic mode. In paper I the reliability of the questionnaire was tested in 122 patients with LUTS/ BPO. The disease specific quality of life was studied before and after intervention in 572 consecutive patients with BPO, aged 45-94 yrs. In paper II, the partner specific quality of life was studied in partners to men with BPO before and after TURP. The reliability and the responsiveness of the questionnaire were tested in two groups with 51 partners each. Papers III-IV: A study of 239 men with LUTS, aged 45-80 yrs, and their partners (n=126) who were compared to randomly selected men from the population (n=213) and their partners (n=131). The men had an extra control group, men with inguinal hernia (n=200). Sleep and health related quality of life was studied in both men and their partners. The partners’ specific quality of life was also studied and the men with LUTS answered questions about urinary symptoms and disease specific quality of life.

    Results: Papers I-II: All the tested questionnaires showed an acceptable reliability and responsiveness. I: Before and after intervention the prevalence of urinary incontinence was 46 % and 16 % respectively. II: Partners were affected by the patients’ BPO symptoms before and improved after the patients TURPs. III: Most sleep variables were significantly impaired in men with LUTS compared to one or both of the control groups. The men with LUTS had a significantly higher prevalence of insomnia (40 %) than both control groups and significantly lower sleep efficiency (49 %) than men with hernia. The men with LUTS were significantly impaired in most domains of the health related quality of life compared to men in the population. IV: There were no significant differences between the two partner groups regarding the quantity and quality of sleep or the health related quality of life.

    Conclusions: All tested questionnaires showed an acceptable reliability and responsiveness.

    The prevalence of urinary incontinence before and after intervention was higher than earlier reported.

    Men with LUTS had significantly poorer sleep quality, reduced sleep efficiency and a higher prevalence of insomnia than men in the population and men with inguinal hernia.

    The HRQOL is impaired in men with LUTS compared to men in the population and men with inguinal hernia.

    Partners are affected by the patients’ symptoms, and it is emotional rather than practical aspects that affect them most.

    Partners of men with LUTS did not differ significantly from partners in the population with regard to sleep and health related quality of life.

    List of papers
    1. Bothersome urinary symptoms and disease-specific quality of life in patients with benign prostatic obstruction: High prevalence of urinary incontinence before and after intervention
    Open this publication in new window or tab >>Bothersome urinary symptoms and disease-specific quality of life in patients with benign prostatic obstruction: High prevalence of urinary incontinence before and after intervention
    2007 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 1, p. 32-41Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Firstly, to describe self-reported urinary symptoms and bothersomeness, including disease-specific quality of life (QOL), in patients with symptomatic benign prostatic obstruction (BPO) before and 6 months after intervention. Secondly, to identify factors which predict disease-specific QOL. Thirdly, to develop and test the reliability of an instrument to evaluate incontinence, the Linköping Incontinence Questionnaire (LIQ). Finally, to translate and test the reliability of Swedish versions of the International Prostate Symptom Score, including the bother question, the American Urological Association Symptom Problem Index (SPI) and the Benign Prostatic Hyperplasia Impact Index.

    Material and methods: Disease-specific QOL was studied in 572/720 consecutively treated patients using structured questionnaires. The reliability of the instruments was tested in 122 patients with lower urinary tract symptoms (LUTS) or BPO.

    Results: The frequency and weak stream items of the SPI were among those that best explained the patients' disease-specific QOL both before and after intervention. Before and after intervention the prevalence of urinary incontinence, assessed using the LIQ instrument, was 46% and 16%, respectively. Symptoms and disease-specific QOL improved most in the surgery group, intermediately in the transurethral incision of the prostate/transurethral microwave thermotherapy group and least in the drug therapy group.

    Conclusions: The frequency and weak stream items of the SPI were the factors that best explained disease-specific QOL. The prevalence of incontinence before and after intervention was higher than that previously

    Place, publisher, year, edition, pages
    Taylor & Francis, 2007
    Keywords
    Benign prostatic obstruction, benign prostatic hyperplasia, disease-specific quality of life, interventions, lower urinary tract symptoms, predicting factors, treatment, urinary incontinence, urinary symptoms
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:liu:diva-15942 (URN)10.1080/00365590601068926 (DOI)
    Available from: 2008-12-17 Created: 2008-12-17 Last updated: 2017-12-14Bibliographically approved
    2. A Swedish version of a quality of life questionnaire for partners of men with symptoms suggestive of benign prostatic obstruction
    Open this publication in new window or tab >>A Swedish version of a quality of life questionnaire for partners of men with symptoms suggestive of benign prostatic obstruction
    2008 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 42, no 2, p. 126-131Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Little is known about the quality of life experienced by the partners of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). The aims of this study were to translate a specific quality of life questionnaire for partners to patients with benign prostatic enlargement (BPE)/BPO to swedish and to test its reliability and responsiveness. A secondary aim was to evaluate the impact the patients' urinary symptoms have on their partners' specific quality of life.

    Material and methods: This study was conducted using two groups: a reliability partner group; and a responsiveness/evaluation partner group. Both groups consisted of the partners of patients on the waiting list for transurethral resection of the prostate (TURP). The reliability of the quality of life questionnaire for the partners of men with BPE/BPO was tested in 51 partners, with a test-retest interval of 5 weeks. The partners' specific quality of life and the responsiveness of the questionnaire were evaluated in 51 partners by administering the questionnaire before and 3 months after the patient's TURP.

    Results: At the test-retest, the Spearman's rank correlation coefficient for each question varied between 0.59 and 0.86 and Cronbach's was 0.80. Partners were affected by the patients' BPO symptoms. Compassion, worry about cancer and worry about an operation were the aspects of the specific quality of life that affected most partners (92%, 77% and 65%, respectively), whereas effects on spare time and household activities affected fewer partners: 35% and 24%, respectively. The specific quality of life among partners improved significantly after the patient's TURP.

    Conclusions: The Swedish version of a partner-specific quality of life questionnaire for men with LUTS suggestive of BPE/BPO had an acceptable reliability and responsiveness. Partners are affected by the patients' symptoms, and it is emotional rather than practical aspects which most affect them.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2008
    Keywords
    Benign prostatic enlargement; benign prostatic obstruction; lower urinary tract symptoms; transurethral resection of the prostate; partner; quality of life; questionnaire; urinary symptoms
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:liu:diva-15943 (URN)10.1080/00365590701725698 (DOI)
    Available from: 2008-12-17 Created: 2008-12-17 Last updated: 2017-12-14Bibliographically approved
    3. Sleep and health-related quality of life in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction compared to the general population and patients with inguinal hernia
    Open this publication in new window or tab >>Sleep and health-related quality of life in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction compared to the general population and patients with inguinal hernia
    2010 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 44, no 5, p. 304-314Article in journal (Refereed) Published
    Abstract [en]

    Abstract Objective. To determine whether there are differences in the quantity and quality of sleep, including sleep efficiency and insomnia, and health-related quality of life (HRQoL) between patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO), men from the general population and patients with inguinal hernia. Material and methods. The designs were descriptive and comparative. The groups consisted of 239 patients aged 45-80 years who were referred to urological departments with LUTS suggestive of benign prostatic obstruction. The comparison groups consisted of 213 randomly selected men from the general population, stratified according to age and geographical region, and 200 patients with inguinal hernia. The setting was one university and two general hospitals. The method was self-administered questionnaires about demography, comorbidity, sleep and health-related quality of life. Further, patients with LUTS answered questions about urinary symptoms and disease-specific quality of life. Results. The prevalence of insomnia was 40%, 26% and 19% and the prevalence of sleep efficiency < 85% was 49%, 38.5% and 31% in the LUTS, general population and hernia groups, respectively. The median number of nocturnal micturitions was 2, 1 and 1. In the LUTS group (n = 216), 47% had IPSS 8-19 and 44% had >/= 20 points. The HRQoL was significantly impaired in patients with LUTS compared with one or both of the comparison groups (p values < 0.05). Conclusions. Patients with LUTS suggestive of BPO had significantly impaired sleep, a higher prevalence of insomnia and significantly impaired HRQoL compared with one or both of the comparison groups.

    Place, publisher, year, edition, pages
    Informa Healthcare, 2010
    Keywords
    Benign prostatic hyperplasia, Benign prostatic obstruction, Disease specific quality of life, Health related quality of life, Inguinal hernia, Insomnia, Lower urinary tract symptoms, Population, Sleep disorders, Sleep quality
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:liu:diva-15944 (URN)10.3109/00365599.2010.488246 (DOI)000283129200005 ()20476852 (PubMedID)
    Available from: 2008-12-17 Created: 2008-12-17 Last updated: 2017-12-14Bibliographically approved
    4. Sleep and specific quality of life (QOL) in partners of men with lower urinary tract symptoms (LUTS) compared with partners to men from the population
    Open this publication in new window or tab >>Sleep and specific quality of life (QOL) in partners of men with lower urinary tract symptoms (LUTS) compared with partners to men from the population
    2008 (English)Article in journal (Refereed) Submitted
    Abstract [en]

    Objective: To determine whether there are significant differences in sleep, partner specific and health related quality of life between partners of men with LUTS suggestive of benign prostatic obstruction (BPO) and partners of men from the population. Secondly, to identify factors related to the specific quality of life in partners of men with LUTS and the sleep efficiency.

    Subjects and methods: The study designs were descriptive and comparative. The subjects were partners of men with LUTS suggestive of BPO (n=126) referred to departments of urology at one university and two general hospitals and partners (n=131) of randomly selected men from the general population. Self-administered questionnaires about demography, comorbidity, sleep, sexuality, partner specific and health related quality of life were used.

    Results: Partners to men with LUTS suggestive of BPO were significantly more affected in all variables measuring partner specific quality of life compared to partners from the population. The most impaired aspects were compassion and worry about an operation or cancer.

    In logistic regression, the only explanatory factors were having a partner belonging to the LUTS group for impaired partner specific quality of life and having a bed partner for high sleep efficiency.

    There were no significant differences between the two groups regarding the quantity andquality of sleep or the health related quality of life.

    Conclusions: The partner specific quality of life was impaired in partners of men with LUTS suggestive of BPO. Sleep and health related quality of life did not differ between partners of men with LUTS and partners in the population.

    Keywords
    Benign prostatic hyperplasia, Insomnia, Lower urinary tract symptoms, Partner, Quality of life, Sleep disorders
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:liu:diva-15945 (URN)
    Available from: 2008-12-17 Created: 2008-12-17 Last updated: 2009-08-19Bibliographically approved
  • 40.
    Marklund-Bau, Helén
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Urology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Edéll-Gustafsson, Ulla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Nursing Science.
    Spångberg, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Urology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    A Swedish version of a quality of life questionnaire for partners of men with symptoms suggestive of benign prostatic obstruction2008In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 42, no 2, p. 126-131Article in journal (Refereed)
    Abstract [en]

    Objectives: Little is known about the quality of life experienced by the partners of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). The aims of this study were to translate a specific quality of life questionnaire for partners to patients with benign prostatic enlargement (BPE)/BPO to swedish and to test its reliability and responsiveness. A secondary aim was to evaluate the impact the patients' urinary symptoms have on their partners' specific quality of life.

    Material and methods: This study was conducted using two groups: a reliability partner group; and a responsiveness/evaluation partner group. Both groups consisted of the partners of patients on the waiting list for transurethral resection of the prostate (TURP). The reliability of the quality of life questionnaire for the partners of men with BPE/BPO was tested in 51 partners, with a test-retest interval of 5 weeks. The partners' specific quality of life and the responsiveness of the questionnaire were evaluated in 51 partners by administering the questionnaire before and 3 months after the patient's TURP.

    Results: At the test-retest, the Spearman's rank correlation coefficient for each question varied between 0.59 and 0.86 and Cronbach's was 0.80. Partners were affected by the patients' BPO symptoms. Compassion, worry about cancer and worry about an operation were the aspects of the specific quality of life that affected most partners (92%, 77% and 65%, respectively), whereas effects on spare time and household activities affected fewer partners: 35% and 24%, respectively. The specific quality of life among partners improved significantly after the patient's TURP.

    Conclusions: The Swedish version of a partner-specific quality of life questionnaire for men with LUTS suggestive of BPE/BPO had an acceptable reliability and responsiveness. Partners are affected by the patients' symptoms, and it is emotional rather than practical aspects which most affect them.

  • 41.
    Marklund-Bau, Helén
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Urology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Edéll-Gustafsson, Ulla
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Spångberg, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Urology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Bothersome urinary symptoms and disease-specific quality of life in patients with benign prostatic obstruction: High prevalence of urinary incontinence before and after intervention2007In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 1, p. 32-41Article in journal (Refereed)
    Abstract [en]

    Objectives: Firstly, to describe self-reported urinary symptoms and bothersomeness, including disease-specific quality of life (QOL), in patients with symptomatic benign prostatic obstruction (BPO) before and 6 months after intervention. Secondly, to identify factors which predict disease-specific QOL. Thirdly, to develop and test the reliability of an instrument to evaluate incontinence, the Linköping Incontinence Questionnaire (LIQ). Finally, to translate and test the reliability of Swedish versions of the International Prostate Symptom Score, including the bother question, the American Urological Association Symptom Problem Index (SPI) and the Benign Prostatic Hyperplasia Impact Index.

    Material and methods: Disease-specific QOL was studied in 572/720 consecutively treated patients using structured questionnaires. The reliability of the instruments was tested in 122 patients with lower urinary tract symptoms (LUTS) or BPO.

    Results: The frequency and weak stream items of the SPI were among those that best explained the patients' disease-specific QOL both before and after intervention. Before and after intervention the prevalence of urinary incontinence, assessed using the LIQ instrument, was 46% and 16%, respectively. Symptoms and disease-specific QOL improved most in the surgery group, intermediately in the transurethral incision of the prostate/transurethral microwave thermotherapy group and least in the drug therapy group.

    Conclusions: The frequency and weak stream items of the SPI were the factors that best explained disease-specific QOL. The prevalence of incontinence before and after intervention was higher than that previously

  • 42.
    Marklund-Bau, Helén
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Urology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Spångberg, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Urology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Urology in Östergötland.
    Edéll-Gustafsson, Ulla
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Sleep and specific quality of life (QOL) in partners of men with lower urinary tract symptoms (LUTS) compared with partners to men from the population2008Article in journal (Refereed)
    Abstract [en]

    Objective: To determine whether there are significant differences in sleep, partner specific and health related quality of life between partners of men with LUTS suggestive of benign prostatic obstruction (BPO) and partners of men from the population. Secondly, to identify factors related to the specific quality of life in partners of men with LUTS and the sleep efficiency.

    Subjects and methods: The study designs were descriptive and comparative. The subjects were partners of men with LUTS suggestive of BPO (n=126) referred to departments of urology at one university and two general hospitals and partners (n=131) of randomly selected men from the general population. Self-administered questionnaires about demography, comorbidity, sleep, sexuality, partner specific and health related quality of life were used.

    Results: Partners to men with LUTS suggestive of BPO were significantly more affected in all variables measuring partner specific quality of life compared to partners from the population. The most impaired aspects were compassion and worry about an operation or cancer.

    In logistic regression, the only explanatory factors were having a partner belonging to the LUTS group for impaired partner specific quality of life and having a bed partner for high sleep efficiency.

    There were no significant differences between the two groups regarding the quantity andquality of sleep or the health related quality of life.

    Conclusions: The partner specific quality of life was impaired in partners of men with LUTS suggestive of BPO. Sleep and health related quality of life did not differ between partners of men with LUTS and partners in the population.

  • 43.
    McAdoo, Stephen P.
    et al.
    Imperial Coll London, England.
    Tanna, Anisha
    Imperial Coll London, England.
    Hruskova, Zdenka
    Gen University Hospital, Czech Republic; Charles University of Prague, Czech Republic.
    Holm, Lisa
    Skånes University Hospital, Sweden.
    Weiner, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Arulkumaran, Nishkantha
    Imperial Coll London, England.
    Kang, Amy
    Imperial Coll London, England.
    Satrapova, Veronika
    Gen University Hospital, Czech Republic; Charles University of Prague, Czech Republic.
    Levy, Jeremy
    Imperial Coll London, England.
    Ohlsson, Sophie
    Skånes University Hospital, Sweden.
    Tesar, Vladimir
    Gen University Hospital, Czech Republic; Charles University of Prague, Czech Republic.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Pusey, Charles D.
    Imperial Coll London, England.
    Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients2017In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 92, no 3, p. 693-702Article in journal (Refereed)
    Abstract [en]

    Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such double-positive cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies.

  • 44.
    Mossberg, Maria
    et al.
    Lund University, Sweden.
    Stahl, Anne-lie
    Lund University, Sweden.
    Kahn, Robin
    Lund University, Sweden.
    Kristoffersson, Ann-Charlotte
    Lund University, Sweden.
    Tati, Ramesh
    Lund University, Sweden.
    Heijl, Caroline
    Lund University, Sweden.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Leeb-Lundberg, L. M. Fredrik
    Lund University, Sweden.
    Karpman, Diana
    Lund University, Sweden.
    Cl-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles2017In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 28, no 8, p. 2472-2481Article in journal (Refereed)
    Abstract [en]

    The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial micro vesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (Pamp;lt;0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation.

  • 45.
    Patrick, Matthew T.
    et al.
    Univ Michigan, MI 48109 USA.
    Stuart, Philip E.
    Univ Michigan, MI 48109 USA.
    Raja, Kalpana
    Univ Michigan, MI 48109 USA; Morgridge Inst Res, WI 53715 USA.
    Gudjonsson, Johann E.
    Univ Michigan, MI 48109 USA.
    Tejasvi, Trilokraj
    Univ Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hosp, MI 48105 USA.
    Yang, Jingjing
    Univ Michigan, MI 48109 USA; Emory Univ, GA 30322 USA.
    Chandran, Vinod
    Univ Toronto, Canada.
    Das, Sayantan
    Univ Michigan, MI 48109 USA.
    Callis-Duffin, Kristina
    Univ Utah, UT 84132 USA.
    Ellinghaus, Eva
    Christian Albrechts Univ Kiel, Germany.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Esko, Tonu
    Univ Tartu, Estonia; Broad Inst and Harvard, MA 02142 USA.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    Kang, Hyun M.
    Univ Michigan, MI 48109 USA.
    Krueger, Gerald G.
    Univ Utah, UT 84132 USA.
    Lim, Henry W.
    Henry Ford Hosp, MI 48202 USA.
    Rahman, Proton
    Mem Univ, Canada.
    Rosen, Cheryl F.
    Univ Toronto, Canada.
    Weidinger, Stephan
    Univ Med Ctr Schleswig Holstein, Germany.
    Weichenthal, Michael
    Univ Med Ctr Schleswig Holstein, Germany.
    Wen, Xiaoquan
    Univ Michigan, MI 48109 USA.
    Voorhees, John J.
    Univ Michigan, MI 48109 USA.
    Abecasis, Goncalo R.
    Univ Michigan, MI 48109 USA.
    Gladman, Dafna D.
    Univ Toronto, Canada.
    Nair, Rajan P.
    Univ Michigan, MI 48109 USA.
    Elder, James T.
    Univ Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hosp, MI 48105 USA.
    Tsoi, Lam C.
    Univ Michigan, MI 48105 USA.
    Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 4178Article in journal (Refereed)
    Abstract [en]

    Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that occurs in similar to 30% of psoriasis patients. Currently, no systematic strategy is available that utilizes the differences in genetic architecture between PsA and cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here, we introduce a computational pipeline for predicting PsA among psoriasis patients using data from six cohorts with amp;gt;7000 genotyped PsA and PsC patients. We identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic markers. Among the top 5% of our PsA prediction we achieve amp;gt;90% precision with 100% specificity and 16% recall for predicting PsA among psoriatic patients, using conditional inference forest or shrinkage discriminant analysis. Combining statistical and machine-learning techniques, we show that the underlying genetic differences between psoriasis subtypes can be used for individualized subtype risk assessment.

  • 46.
    Patschan, Oliver
    et al.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Holmang, Sten
    Sahlgrens University Hospital, Sweden.
    Hosseini, Abolfazl
    Karolinska University Hospital, Sweden.
    Jancke, Georg
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Liedberg, Fredrik
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Ljungberg, Borje
    Umeå University, Sweden.
    Malmstrom, Per-Uno
    Akad University Hospital, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Second-look resection for primary stage T1 bladder cancer: a population-based study2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 4, p. 301-307Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to evaluate the use of second-look resection (SLR) in stage T1 bladder cancer (BC) in a population-based Swedish cohort. Materials and methods: All patients diagnosed with stage T1 BC in 2008-2009 were identified in the Swedish National Registry for Urinary Bladder Cancer. Registry data on TNM stage, grade, primary treatment and pathological reports from the SLR performed within 8weeks of the primary transurethral resection were validated against patient charts. The endpoint was cancer-specific survival (CSS). Results: In total, 903 patients with a mean age of 74years (range 28-99 years) were included. SLR was performed in 501 patients (55%), who had the following stages at SLR: 172 (35%) T0, 83 (17%) Ta/Tis, 210 (43%) T1 and 26 (5%) T2-4. The use of SLR varied from 18% to 77% in the six healthcare regions. Multiple adjuvant intravesical instillations were given to 420 patients (47%). SLR was associated with intravesical instillations, age younger than 74 years, discussion at multidisciplinary tumour conference, G3 tumour and treatment at high-volume hospitals. Patients undergoing SLR had a lower risk of dying from BC (hazard ratio 0.62, 95% confidence interval 0.45-0.84, pamp;lt;.0022). Five-year CSS rates were as follows, in patients with the indicated tumours at SLR (p=.001): 82% in those with T1, 90% in T0, 90% in Ta/Tis and 56% in T2-4. Conclusions: There are large geographical differences in the use of SLR in stage T1 BC in Sweden, which are presumably related to local treatment traditions. Patients treated with SLR have a high rate of residual tumour but lower age, which suggests that a selection bias affects CSS.

  • 47.
    Patschan, Oliver
    et al.
    Skåne University Hospital, Sweden.
    Holmang, Sten
    Sahlgrens University Hospital, Sweden.
    Hosseini, Abolfazl
    Karolinska University Hospital, Sweden.
    Liedberg, Fredrik
    Skåne University Hospital, Sweden.
    Ljungberg, Borje
    Northern University Hospital, Sweden.
    Malmstrom, Per-Uno
    Akad University Hospital, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Use of bacillus Calmette-Guerin in stage T1 bladder cancer: Long-term observation of a population-based cohort2015In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 2, p. 127-132Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to analyse the rate of use of bacillus Calmette-Guerin (BCG) at a population-based level, and the overall mortality and bladder cancer mortality due to stage T1 bladder cancer in a national, population-based register. Materials and methods. In total, 3758 patients with primary stage T1 bladder cancer, registered in the Swedish Bladder Cancer Register between 1997 and 2006, were included. Age, gender, tumour grade and primary treatment in the first 3-6 months were registered. High-volume hospitals registered 10 or more T1 tumours per year. Date and cause of death were obtained from the National Board of Health and Welfare Cause of Death Register. Results. BCG was given to 896 patients (24%). The use of BCG increased from 18% between 1997 and 2000, to 24% between 2001 and 2003, and to 31% between 2004 and 2006. BCG was given more often to patients with G3 tumours, patients younger than 75 years and patients attending high-volume hospitals. BCG treatment, grade 2 tumours and patient age younger than 75 years were associated with lower mortality due to bladder cancer. Hospital volume, gender and year of diagnosis were not related to bladder cancer mortality. However, selection factors might have affected the results since comorbidity, number of tumours and tumour size were unknown. Conclusions. Intravesical BCG is underused at a population-based level in stage T1 bladder cancer in Sweden, particularly in patients 75 years or older, and in those treated at low-volume hospitals. BCG should be offered more frequently to patients with stage T1 bladder cancer in Sweden.

  • 48.
    Pippias, Maria
    et al.
    University of Amsterdam, Netherlands.
    Stel, Vianda S.
    University of Amsterdam, Netherlands.
    Areste-Fosalba, Nuria
    University Hospital Virgen Macarena, Spain.
    Couchoud, Cecile
    Agence Biomed, France.
    Fernandez-Fresnedo, Gema
    University Hospital Marques de Valdecilla, Spain.
    Finne, Patrik
    University of Helsinki, Finland; Finnish Registry Kidney Disease, Finland.
    Heaf, James G.
    University of Copenhagen, Denmark.
    Hoitsma, Andries
    Radboud University of Nijmegen, Netherlands.
    De Meester, Johan
    Dutch Speaking Belgian Renal Registry NBVN, Belgium.
    Palsson, Runolfur
    Landspitali, Iceland; Fac Med, Iceland; University of Iceland, Iceland.
    Ravani, Pietro
    University of Calgary, Canada; University of Calgary, Canada.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Traynor, Jamie P.
    Meridian Court, Scotland.
    Reisaeter, Anna V.
    National Hospital Norway, Norway.
    Caskey, Fergus J.
    Southmead Hospital, England; University of Bristol, England.
    Jager, Kitty J.
    University of Amsterdam, Netherlands.
    Long-term Kidney Transplant Outcomes in Primary Glomerulonephritis: Analysis From the ERA-EDTA Registry2016In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 100, no 9, p. 1955-1962Article in journal (Refereed)
    Abstract [en]

    Background We evaluated the 15-year kidney allograft survival in patients with primary glomerulonephritis and determined if the risk of graft loss varied with donor source within each glomerulonephritis group. Methods Using data from the European Renal Association-European Dialysis and Transplant Association Registry, Kaplan-Meier, competing risk, and Cox regression analyses were performed on adult, first kidney transplant recipients during 1991 to 2010 (n = 14 383). Follow-up was set to December 31, 2011. Adjustments for pretransplant dialysis duration, sex, country, and transplant era were made. Death-adjusted graft survival was assessed in patients with glomerulonephritis and compared with those with autosomal dominant polycystic kidney disease (ADPKD), in which the native kidney disease cannot recur. Additionally, death-adjusted graft survival was compared between living and deceased donor transplants within each glomerulonephritis group. Results All glomerulonephritides had a 15-year death-adjusted graft survival probability above 55%. The 15-year risk of death-adjusted graft failure compared to ADPKD ranged from 1.17 (95% confidence interval [95% CI], 1.05-1.31) for immunoglobulin A nephropathy to 2.09 (95% CI, 1.56-2.78) for membranoproliferative glomerulonephritis type II. The expected survival benefits of living over deceased donor transplants were not present in membranoproliferative glomerulonephritis type I (adjusted hazard ratios [HRa], 1.08; 95% CI, 0.73-1.60) or type II (HRa, 0.90; 95% CI, 0.32-2.52) but present in immunoglobulin A nephropathy (HRa, 0.74; 95% CI, 0.59-0.92), membranous nephropathy (HRa, 0.47; 95% CI, 0.29-0.75), and focal segmental glomerulosclerosis (HRa, 0.69; 95% CI, 0.45-1.06). Conclusions This large European study shows favorable long-term kidney graft survival in all primary glomerulonephritides, although this remains lower than graft survival in ADPKD, and confirms that the reluctance to use living donors in some primary glomerulonephritides remains unfounded. These data will further inform prospective renal transplant recipients and donors during pretransplant counselling.

  • 49.
    Prieto-Velasco, Mario
    et al.
    Complejo Asistencial Universitario de León, León, Spain .
    Isnard Bagnis, Corinne
    Université Pierre et Marie Curie, Paris France .
    Dean, Jessica
    Department of Clinical Health Psychology, Salford Royal Hospital, Salford, UK.
    Goovaerts, Tony
    Cliniques Universitaires St. Luc, Brussels, Belgium .
    Melander, Stefan
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Mooney, Andrew
    St James’s University, Leeds, UK .
    Nilsson, Eva-Lena
    Skåne Universitetssjukhus, Malmö .
    Rutherford, Peter
    Baxter-Gambro Renal, Zurich, Switzerland.
    Trujillo, Carmen
    Hospital Regional Carlos Haya, Malaga, Spain.
    Zambon, Roberto
    Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo,Vicenza, Italy.
    Crepaldi, Carlo
    Unità Operativa di Nefrologia, Dialisi e Trapianto, Ospedale San Bortolo,Vicenza, Italy.
    Predialysis education in practice: a questionnaire survey of centres with established programmes.2014In: BMC research notes, ISSN 1756-0500, Vol. 7, p. 730-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is growing evidence that renal replacement therapy option education (RRTOE) can result in enhanced quality of life, improved clinical outcomes, and reduced health care costs. However, there is still no detailed guidance on the optimal way to run such programmes. To help address this knowledge gap, an expert meeting was held in March 2013 to formulate a position statement on optimal ways to run RRTOE. Experts were selected from units that had extensive experience in RRTOE or were performing research in this field. Before the meeting, experts completed a pilot questionnaire on RRTOE in their own units. They also prepared feedback on how to modify this questionnaire for a large-scale study.

    METHODS: A pilot, web-based questionnaire was used to obtain information on: the renal unit and patients, the education team, RRTOE processes and content, how quality is assessed, and funding.

    RESULTS: Four nurses, 5 nephrologists and 1 clinical psychologist (9 renal units; 6 EU countries) participated. Nurses were almost always responsible for organising RRTOE. Nephrologists spent 7.5% (median) of their time on RRTOE. Education for the patient and family began several months before dialysis or according to disease progression. Key topics such as the 'impact of the disease' were covered by every unit, but only a few units described all dialysis modalities. Visits to the unit were almost always arranged. Materials came in a wide variety of forms and from a wide range of sources. Group education sessions were used in 3/9 centres. Expectations on the timing of patients' decisions on modality and permanent access differed substantially between centres. Common quality assurance measures were: patient satisfaction, course attendance, updated materials. Only 1 unit had a dedicated budget.

    CONCLUSIONS: There were substantial variations in how RRTOE is run between the units. A modified version of this questionnaire will be used to assess RRTOE at a European level.

  • 50.
    Sari, Funda
    et al.
    Antalya Training and Research Hospital, Turkey.
    Didem Yalcin, Arzu
    Antalya Training and Research Hospital, Turkey.
    Esra Genc, Gizem
    Akdeniz University, Turkey.
    Sarikaya, Metin
    Antalya Training and Research Hospital, Turkey.
    Bisgin, Atil
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Cetinkaya, Ramazan
    Antalya Training and Research Hospital, Turkey.
    Gumuslu, Saadet
    Akdeniz University, Turkey.
    Autosomal Dominant Polycystic Disease is Associated with Depressed Levels of Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand2016In: Balkan Medical Journal, ISSN 2146-3123, E-ISSN 2146-3131, Vol. 33, no 5, p. 512-516Article in journal (Refereed)
    Abstract [en]

    Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by multiple, large renal cysts and impaired kidney function. Although the reason for the development of kidney cysts is unknown, ADPKD is associated with cell cycle arrest and abundant apoptosis of renal tubular epithelial cells. Aims: We asked whether serum-soluble TNF-related apoptosis-inducing ligand (sTRAIL) might underlie ADPKD. Study Design: Case-control study. Methods: Serum sTRAIL levels were measured in 44 patients with ADPKD and 18 healthy volunteers. The human soluble TRAIL/Apo2L ELISA kit was used for the in vitro quantitative determination of sTRAIL in serum samples. Results: Mean serum sTRAIL levels were lower in patients with ADPKD as compared to the control group (446.9 +/- 103.1 and 875.9 +/- 349.6 pg/mL, pamp;lt;0.001). Serum sTRAIL levels did not differ among stages of renal failure in patients with ADPKD. There was no correlation between serum sTRAIL levels and estimated glomerular filtration rate in patients with ADPKD (pamp;gt;0.05). Conclusion: Our results show that ADPKD patients have depressed sTRAIL levels, indicating apoptosis unrelated to the stage of chronic renal failure.

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