| 1. |
- Aljabery, Firas
(author)
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Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
- 2017
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 2. |
- Altman, Daniel, et al.
(author)
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The genetic and environmental contribution to the occurrence of bladder pain syndrome: an empirical approach in a nationwide population sample.
- 2011
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In: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 59:2, s. 280-5
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aetiology of bladder pain syndrome (BPS) remains poorly understood, and a number of pathogenic mechanisms have been proposed. The importance of genetic factors for BPS is receiving growing attention, but data so far are of a preliminary nature. OBJECTIVE: To empirically assess the genetic and environmental contribution to BPS in a population-based sample of twins. DESIGN, SETTING, AND PARTICIPANTS: The study included >25 000 twins born between 1959 and 1985. Individuals with BPS were identified using latent class cluster analysis (LCCA) based on self-reported symptoms from a nationwide screening for complex diseases in the Swedish Twin Registry. By comparing monozygotic and dizygotic twins, we estimated twin similarity and the relative proportions of phenotypic variance resulting from genetic and environmental factors. MEASUREMENTS: Twin similarity was measured. RESULTS AND LIMITATIONS: The LCCA yielded an overall BPS prevalence of 1.1% and 2.4% for males and females, respectively. In males, the contribution of genetic effects to BPS could not be assessed because of the small number of concordant twin pairs. In women, twin similarity estimates indicated a genetic component for the aetiology of BPS, but genetic factors contributed less than one-third of the total variation in susceptibility to BPS. Nonshared environmental factors accounted for more than two-thirds of the variance, whereas early nongenetic factors shared within the family were of little or no consequence to the risk of developing BPS later in life. Use of self-reported symptoms to define the disease phenotype is a limitation of the study. CONCLUSIONS: The influence of environmental factors in the development of BPS in women is substantial, whereas genetic influences are of only modest importance for the possibility of developing the disease.
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| 3. |
- Andersson-Evelönn, Emma, 1983-
(author)
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DNA methylation as a prognostic marker in clear cell Renal Cell Carcinoma
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma worldwide. Metastatic ccRCC is correlated to poor prognosis whereas non-metastatic disease has a 5-year survival rate up to 90%. Due to increased accessibility to different types of diagnostic imaging the frequency of metastatic ccRCC at diagnosis has decreased since the beginning of the 21st century. This has led to an earlier detection of primary tumors before patients present symptoms. However, 20-30% of the non-metastatic patients at diagnosis will progress and metastasize within five years of primary nephrectomy. Identifying patients at high risk of tumor progression at an early stage after diagnosis is of importance to improve outcome and survival. Currently, in Sweden, the Mayo scoring system is used to divide tumors into low, intermediate or high risk for tumor progression.DNA methylation has been associated with tumor development and progression in different malignancies. In this thesis, Illumina Infinium HumanMeth27 BeadChip Arrays and Human Meth450K BeadChip Arrays have been used to evaluate the relationship between methylation and clinicopathological variables as well as ccRCC outcome in 45 and 115 patients.Our studies identified an association between higher level of promoter-associated DNA methylation and clinicopathological variables in ccRCC. There was a significant stepwise increase of average methylation from tumor-free tissue, via non-metastatic tumors to metastatic disease. Cluster analysis divided patients into two distinct groups that differed in average methylation levels, TNM stage, Fuhrman nuclear grade, tumor size, survival and tumor progression. We also presented two prognostic classifiers for non-metastatic tumors; the promoter methylation classifier (PMC) panel and the triple classifier. The PMC panel divided tumors depending on the methylation level, PMC low or PMC high, with significantly worse prognosis in the PMC high group. This data was verified in an independent, publically available cohort. The triple classifier was created using a combination of clinicopathological variables, previously identified CpGs biomarkers and a novel cluster analysis approach (Directed Cluster Analysis). The triple classifier had a higher specificity compared to the clinically used Mayo scoring system and predicted tumor progression with higher accuracy at a fixed sensitivity.The identification of two epigenetic classifiers that predicted outcome in non-metastatic ccRCC further establishes the role of DNA methylation as a prognostic marker. This knowledge can contribute to identification of patients with a high risk of tumor progression and can be of importance in the decision regarding adjuvant treatment post-nephrectomy.
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| 4. |
- Andreasson, Anders, et al.
(author)
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High revision rate following artificial urethral sphincter implantation.
- 2014
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In: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1813 .- 2168-1805. ; 48:6, s. 544-548
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Journal article (peer-reviewed)abstract
- Abstract Objective. In severe cases of stress urinary incontinence (SUI), with sphincter dysfunction, the artificial urinary sphincter AMS 800™ may be the last solution. The purpose of this study was to evaluate the outcome of surgical intervention for SUI with the AMS 800 in patients who were treated at Sahlgrenska University Hospital, Gothenburg. The primary aim of the study was to determine the complications related to the operation. Material and methods. A retrospective follow-up was done by reviewing medical records. The material comprised 97 men, who underwent their first AMS 800 implantation between May 1997 and June 2010 at Sahlgrenska University Hospital. Results. The revision rate was 28%, including an infection rate of 3% and an erosion rate of 7%. The mean follow-up for revised patients was 3 years. The median time until revision was 1 year. Seventy-five per cent of all patients were satisfied with the operation at 6 months' follow-up. Radical prostatectomy was the reason behind incontinence in 84% of patients in this series. Conclusion. The results clearly demonstrate a need for revision procedures in a considerable proportion of patients implanted with an AMS 800 device. Patient satisfaction was high, but although this operation has extremely low mortality it has its complications and the system will need to be replaced in time.
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| 5. |
- Colleen, S, et al.
(author)
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Urogenitalt trauma.
- 2012
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In: Urologi 2ed. eds: Damber JE, Peeker R.. - Lund, Sverige : Lund: Studentlitteratur. - 9789144075921
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Book chapter (other academic/artistic)
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| 7. |
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| 8. |
- Delbro, Dick, 1950-, et al.
(author)
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The extracellular matrix-degrading protein ADAMTS5 is expressed in the nuclei of urothelial cells in healthy rats
- 2018
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In: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:2, s. 139-142
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Journal article (peer-reviewed)abstract
- Objective: The aim of this study was to investigate whether protein expression of the extracellular matrix-degrading protease ADAMTS5 can be demonstrated in the urinary bladder of healthy rats, and, if so, to determine the localization of this enzyme. Materials and methods: The experiments were conducted with eight inbred male Sprague-Dawley rats. Immunohistochemistry was used to investigate the expression of ADAMTS5 in the urinary bladder. Negative controls were established by either excluding the primary antibody or applying the antibody after it had been preabsorbed with its immunogenic peptide. Confocal microscopy was used to visualize the distribution of ADAMTS5 in the urinary bladder tissue. Results: Immunoreactivity for ADAMTS5 was demonstrated in the urothelium and in the detrusor. This expression was localized not only in the cytoplasm, but also in the nuclei. Confocal microscopy corroborated these findings. Conclusion: Expression of ADAMTS5 was demonstrated in the cytoplasm as well as in the nuclei of the urothelium and detrusor cells, suggesting that it may play a role at the transcriptional level.
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| 9. |
- Demirci, Umit, et al.
(author)
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Urovaginal fistula formation after gynaecological and obstetric surgical procedures: Clinical experiences in a Scandinavian series.
- 2013
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In: Scandinavian journal of urology and nephrology. - : Informa UK Limited. - 1651-2065 .- 2168-1805 .- 2168-1813. ; 47:2, s. 140-144
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Journal article (peer-reviewed)abstract
- Abstract Objective. The aim of this retrospective study was to review what kinds of surgical procedures are most frequently complicated by urovaginal fistulae, to find out how they were diagnosed and managed, and to study the outcome after surgical reconstruction. Material and methods. Nineteen women who underwent fistula repair at Sahlgrenska University Hospital between 2003 and 2009 were retrospectively studied by reviewing the medical records. Results. For 17 of the 19 patients hysterectomy was the causative procedure. Fourteen patients developed vesicovaginal and five developed ureterovaginal fistula. Urethrocystoscopy was sufficient for the diagnosis in nearly 50% of the patients and when combined with methylene blue instillation 90% of all fistulae were found. Several patients sought medical advice due to vaginal leakage following gynaecological surgery without the doctor suspecting a fistula, and for these patients the diagnosis was delayed. Eighteen patients were operated on with an abdominal approach and one with a vaginal approach, in all cases a minimum of 3 months after primary surgery. The reconstruction technique included the interposition of vascularized tissue. None of the patients reported leakage or relapse at follow-up after fistula repair. Conclusions. Hysterectomy was the most common cause behind the formation of urovaginal fistulae. Misinterpretation of symptoms after gynaecological surgery was common even in cases where the symptoms were indicative of a urovaginal fistula. Delayed fistula repair after a minimum of 3 months, via the abdominal route and with the interposition of vascularized tissue, yielded an excellent final outcome.
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| 10. |
- Edlund, Christer, 1962, et al.
(author)
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Funktionella störningar av nedre urinvägarna.
- 2012
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In: Urologi , 2nd ed. / Jan-Erik Damber, Ralph Peeker (red.). - Lund : Studentlitteratur. - 9789144075921
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Book chapter (peer-reviewed)
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