| 1. |
- Aljabery, Firas
(författare)
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Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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. |
- Delbro, Dick, 1950-, et al.
(författare)
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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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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:2, s. 139-142
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Tidskriftsartikel (refereegranskat)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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| 3. |
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| 4. |
- Ekerhult, Teresa, et al.
(författare)
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Outcomes of reintervention after failed urethroplasty
- 2017
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 51:1, s. 68-72
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Urethroplasty is a procedure that has a high success rate. However, there exists a small subgroup of patients who require multiple procedures to achieve an acceptable result. This study analyses the outcomes of a series of patients with failed urethroplasty. Materials and methods: This is a retrospective review of 82 failures out of 407 patients who underwent urethroplasty due to urethral stricture during the period 1999-2013. Failure was defined as the need for an additional surgical procedure. Of the failures, 26 patients had penile strictures and 56 had bulbar strictures. Meatal strictures were not included. Results: The redo procedures included one or multiple direct vision internal urethrotomies, dilatations or new urethroplasties, all with a long follow-up time. The patients underwent one to seven redo surgeries (mean 2.4 procedures per patient). In the present series of patients, endourological procedures cured 34% (28/82) of the patients. Ten patients underwent multiple redo urethroplasties until a satisfactory outcome was achieved; the penile strictures were the most difficult to cure. In patients with bulbar strictures, excision with anastomosis and substitution urethroplasty were equally successful. Nevertheless, 18 patients were defined as treatment failures. Of these patients, nine ended up with clean intermittent self-dilatation as a final solution, five had perineal urethrostomy and four are awaiting a new reintervention. Complicated cases need centralized professional care. Conclusion: Despite the possibility of needing multiple reinterventions, the majority of patients undergoing urethroplasty have a good chance of successful treatment.
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| 5. |
- Ekerhult, Teresa, et al.
(författare)
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Sclerosis as a predictive factor for failure after bulbar urethroplasty: a prospective single-centre study.
- 2018
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1813 .- 2168-1805. ; 52:4, s. 302-308
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess whether sclerosis in histology following bulbar urethroplasty is a predictive factor for failure of surgery.Resected stricture specimens from 45 patients undergoing open urethroplasty with excision and anastomosis were collected prospectively during 2011-2014. Histopathological characteristics, including fibrosis (grade I-III), inflammation and sclerosis, were evaluated using different routine staining. These specimens were compared to normal urethral resection specimens from patients undergoing sex-correction surgery. The uropathologist who conducted the analyses was blinded to the study design.The outcomes of the histological classifications were as follows: 19 patients had grade I fibrosis, of whom three had failures; 13 patients had grade II fibrosis, without any failures; and the most severe fibrosis, grade III, including sclerosis, was found in 13 patients (11 with sclerosis), with failure in eight. Sclerosis was a significant risk factor for restricture when comparing patients with sclerosis and those without sclerosis, and likewise when adjusting for age, inflammation and stricture length.Histological findings of sclerosis in the resected urethral stricture specimen indicate a significantly higher risk for restricture after urethroplasty surgery.
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| 6. |
- Fall, Magnus, 1941, et al.
(författare)
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Classic Interstitial Cystitis: Unrelated to BPS
- 2015
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Ingår i: Current Bladder Dysfunction Reports. - : Springer Science and Business Media LLC. - 1931-7212 .- 1931-7220. ; 10:1, s. 95-102
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Tidskriftsartikel (refereegranskat)abstract
- When first recognized, more than one hundred years ago, the term interstitial cystitis (IC) was reserved for subjects with a special type of deep inflammation of the bladder wall. Later, the scope of IC widened, including all kinds of bladder pain syndromes (BPS), giving rise to a lot of confusion and difficulties in research as well as in clinical practice. Herein, recent progress in the understanding of the BPS/IC complex will be discussed, emphasizing the fact that the classic Hunner disease (BPS type 3C according to the European Society for the Study of Interstitial Cystitis (ESSIC) classification) is a well-defined condition that fulfills the requirements of the denomination interstitial cystitis. The paper will also discuss recent research on diagnostics, markers, genetics, and various types of remedies for classic IC. For the benefit of our patients, in BPS/IC, it is time for a final separation of the concepts BPS and IC. Classic IC is a well-defined entity with multiple unique characteristics, those characteristics having a potential for development of a specific rational, pharmacological, and surgical treatment algorithm if further investigated. BPS, on the other hand, seems to include a heterogenic composition of conditions calling for broad attempts to be more closely explored. © 2015, Springer Science+Business Media New York.
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| 7. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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The extracellular matrix proteoglycan versican is strongly expressed in the urothelium of healthy rats
- 2019
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 53:6, s. 431-434
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We have previously demonstrated protein expression of the extracellular matrix degrading protein ADAMTS5 in the nuclei of urothelial cells in healthy rats. The proteoglycan versican constitutes one of the main substrates for this protease. In this follow up study we investigated a potential co-localization of versican and ADAMTS5 in the urinary bladder wall. Material and Methods: The study was conducted with archive material (paraffin embedded bladder tissue from our previous study, i.e., 8 male Sprague-Dawley rats). Protein expression of versican was investigated by immunohistochemistry. Furthermore, the occurrence of versican mRNA was examined by in-situ hybridization. Results: Positive immunoreactivity for versican was evident in the urothelium but also, weakly, in the detrusor. This expression was localized only in the cytoplasm, leaving the nuclei devoid of reactivity. Interestingly, versican mRNA was only sparsely observed in the urothelial cells. Conclusions: We found by immunohistochemistry that the substrate for ADAMTS5, versican, was localized in the cytosol of urothelial cells. This demonstrates a difference regarding the expression of ADAMTS5, which was emphasized in the nuclei. This could imply an additional, non-enzymatic, function of ADAMTS5 in the urothelium.
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| 8. |
- Haghsheno, Mohammad-Ali, et al.
(författare)
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Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement.
- 2015
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1813 .- 2168-1805. ; 49:2, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. The aim of this study was to test whether lower urinary tract symptoms (LUTS) and urinary incontinence are associated with the metabolic syndrome (MetS). The association between LUTS and benign prostatic enlargement (BPE) was also investigated. Material and methods. A cross-sectional, representative risk factor analysis of LUTS, as measured by the International Prostate Symptom Score (IPSS), and urinary incontinence was conducted. Among 950 representative individuals, aged 69-81 years, the association between clinical, anthropometric, endocrine, metabolic and inflammatory factors on the one hand, as both major and minor aspects of MetS, and LUTS and urinary incontinence, on the other hand, was analysed. The prostate gland volume was measured in a subgroup of 155 randomly selected individuals and the association between LUTS and BPE was estimated. Results. No significant association was found between LUTS or urinary incontinence and the major aspects of the MetS. However, in a multivariate analysis, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. Furthermore, in a subgroup of 155 individuals, the prostate gland volume correlated positively with LUTS. Conclusions. The study did not show an association between LUTS or urinary incontinence and the major components of the MetS. However, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. The data confirm the general knowledge that BPE may be one of the causative factors of LUTS.
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| 9. |
- Hammarsten, Jan, et al.
(författare)
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A stage-dependent link between metabolic syndrome components and incident prostate cancer
- 2018
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Ingår i: Nature Reviews Urology. - : Springer Science and Business Media LLC. - 1759-4812 .- 1759-4820. ; 15:5, s. 321-333
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Forskningsöversikt (refereegranskat)abstract
- Metabolic syndrome is associated with increased cancer risk and progression at almost all sites, including the prostate in high-stage prostate cancer. However, several reports have described an inverse relationship between metabolic syndrome and its components and low-stage incident prostate cancer. Such anomalies in cancer research hamper efforts to fight cancer. Evidence suggests that metabolic syndrome and its components have two distinct effects in prostate cancer, concealing prostate cancer in low-stage disease and promoting progression to high-stage incident, nonlocalized, and lethal prostate cancer. The concealment of prostate cancer by metabolic syndrome and its components might be related to bias mechanisms that reduce PSA level and lead to a delayed diagnosis of low-stage prostate cancer, meaning that fewer men with metabolic syndrome are diagnosed with low-stage disease. The inverse link between metabolic syndrome and its components and low-stage incident prostate cancer might simply be the result of such bias and the shortcomings of the diagnostic procedure rather than being related to prostate cancer biology itself. The evidence summarized here supports the hypothesis that the link between metabolic syndrome and its components and incident prostate cancer is a two-way and stage-dependent one, a theory that requires further research. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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| 10. |
- Lekic, Zeljka, et al.
(författare)
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Striking decrease in blood loss with a urologist-assisted standardized multidisciplinary approach in the management of abnormally invasive placenta
- 2017
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Ingår i: Scandinavian Journal of Urology. - 2168-1805 .- 2168-1813. ; 51:6, s. 491-495
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to investigate the outcome of a standardized multidisciplinary approach using a modified surgical technique in the management of abnormally invasive placenta (AIP), with special reference to blood loss and the need for transfusion. Materials and methods: Data were collected retrospectively in women managed with a recently adopted multidisciplinary strategy using a modified surgical approach, involving a urologist (study group: 10 patients). Women managed before the introduction of this standardized management served as a control group (nine patients). Comparisons were made between the study group and the control group. The main outcome measures were blood loss and the need for transfusion in the two groups. Results: Standardized multidisciplinary management, involving a modified surgical technique performed by a urologist, decreased blood loss in the study group compared with the control group [median 1400 ml (range 400–3000 ml) vs median 8000 ml (2300–40000 ml); p <.001]. It also decreased postoperative complications and the need for transfusion of blood products. Conclusions: Standardized multidisciplinary management of patients with AIP, using a modified surgical technique, reduces the risks of massive obstetric hemorrhage, the need for massive transfusion and the risk of postoperative complications. Involving an experienced urologist appears to be of paramount importance in the management of AIP.
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