| 1. |
- Ibarra, Cristian, et al.
(författare)
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BCG-induced cytokine release in bladder cancer cells is regulated by Ca2+ signaling
- 2019
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Ingår i: Molecular Oncology. - : WILEY. - 1574-7891 .- 1878-0261. ; 13:2, s. 202-211
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Tidskriftsartikel (refereegranskat)abstract
- Bacillus Calmette-Guerin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca2+ (calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca2+ response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca2+ signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.
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| 2. |
- Abdul-Sattar Aljabery, Firas, et al.
(författare)
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Management and outcome of muscle-invasive bladder cancer with clinical lymph node metastases. A nationwide population-based study in the bladder cancer data base Sweden (BladderBaSe)
- 2019
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Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 53:5, s. 332-338
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the clinical management and outcome of patients with muscle-invasive bladder cancer with clinical lymph node involvement, using longitudinal nationwide population-based data.Methods: In the Bladder Cancer Data Base Sweden (BladderBaSe), treatment and survival in patients with urinary bladder cancer clinical stage T2-T4 N + M0 diagnosed between 1997 and 2014 was investigated. Patients´ characteristics were studied in relation to TNM classification, curative or palliative treatment, cancer-specific (CSS) and overall survival (OS). Age at diagnosis was categorised as ≤60, 61-70, 71-80 and >80 years, and time periods were stratified as follows: 1997-2001, 2002-2005, 2006-2010 and 2011-2014.Results: There were 786 patients (72% males) with a median age of 71 years (interquartile range = 64-79 years). The proportion of patients with high comorbidity increased over time. Despite similar low comorbidity, curative treatment was given to 44% and to 70% of those in older (>70 years) and younger age groups, respectively. Curative treatment decreased over time, but chemotherapy and cystectomy increased to 25% during the last time period. Patients with curative treatment had better survival compared to those with palliative treatment, both regarding CSS and OS in the whole cohort and in all age groups.Conclusions: The low proportion of older patients undergoing treatment with curative intent, despite no or limited comorbidity, indicates missed chances of treatment with curative intent. The reasons for an overall decrease in curative treatment over time need to be analysed and the challenge of coping with an increasing proportion of node-positive patients with clinically significant comorbidity needs to be met.
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| 3. |
- Holmberg, Lars, et al.
(författare)
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Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations
- 2024
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Ingår i: BJU INTERNATIONAL. - : Blackwell Publishing. - 1464-4096 .- 1464-410X. ; 134:2, s. 229-238
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guerin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC).Patients and MethodsWe analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs.ResultsThe cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk.ConclusionsThese data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.
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| 4. |
- Hosseini, Abolfazl, et al.
(författare)
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Enhanced formation of nitric oxide in bladder carcinoma in situ and in BCG treated bladder cancer
- 2006
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Ingår i: Nitric oxide. - Orlando, Fla. : Academic Press. - 1089-8603 .- 1089-8611. ; 15:4, s. 337-343
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to analyze endogenous nitric oxide (NO) formation and NO-synthase (NOS) gene expression in the urinary bladder from patients with urinary bladder cancer and to investigate the relationship between local NO formation, treatment with Bacillus Calmette Guerin (BCG) and clinical stage in bladder cancer patients. One hundred and three patients with bladder cancer were studied. Endogenous formation of NO was measured in 72 patients, including 6 patients with BCG treated bladder cancer and 6 tumor free control subjects. iNOS expression was analyzed at transcriptional and protein level in biopsies from 31 patients with bladder cancer by real time polymerase chain reaction (PCR) and Western blot (WB), respectively. Three patients in this group had received BCG treatment. Eight biopsies from normal bladder served as control for PCR and WB analysis. Patients with carcinoma in situ (CIS) had higher iNOS expression (p<0.01) and NO formation (p<0.01) than control subjects and patients with papillary tumors without concomitant CIS. Markedly increased iNOS expression (p<0.05) and NO formation (p<0.001) were also found in patients treated with BCG as compared to the other groups. In conclusion, the presence of elevated NO concentration and iNOS expression in the urinary bladder from BCG treated patients and patients with CIS further supports the notion that NO may be an important factor in bladder cancer biology and that the BCG effect on superficial bladder cancer may partly be due to stimulation of local NO formation.
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| 5. |
- Hosseini, Abolfazl
(författare)
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Nitric oxide : a marker for inflammation in the lower urinary tract
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main aim of this work is to investigate the role of Nitric oxide (NO) as a diagnostic marker for inflammation in the lower urinary tract. NO exerts multiple modulating effects on inflammation and plays a key role in the regulation of immune responses. NO is formed enzymatically in vivo from Larginine by several NO synthases (NOS). Being a free radical, NO has a very short half live in biological systems. In contrast, NO in the gaseous phase is more stable, which makes it possible to measure NO in luminal structures such as the urinary bladder. We have developed a new method for measurement of luminal NO formation involving the insertion of a silicon catheter through the urethra. The balloon is filled with NOfree air, which is incubated in the urinary bladder for sampling of NO from the bladder or placed in the prostatic urethra for sampling of NO from the prostate. We observed an almost 20-fold increase in urinary bladder concentration of NO in patients with interstitial cystitis (IC), compared with control subjects. The NO concentration in the urinary bladder of patients with detrusor instability, outflow obstruction and bladder hypersensitivity was as low as in the asymptomatic control subjects suggesting that measurement of NO in air from the urinary bladder can differentiate between inflammatory and non-inflammatory lower urinary tract conditions. Patients with classic IC, who responded with a significant reduction in symptom score to cortisone treatment, also had a clear reduction in NO formation in the bladder in contrast to non-responders. There was also a significant correlation between changes in symptom score and NO formation in each individual patient. This implies that measurement of NO formation can be used also for evaluation of treatment response in lower urinary tract inflammatory disorders. In patients with chronic abacterial prostatitis/chronic pelvic pain syndrome only 32% had an elevated NO concentration in the prostatic urethra. These patients also had more than 10 leukocytes in the expressed prostatic secretion, while none of the patients with no signs of inflammation in the prostatic secretion had an elevated NO- formation. Thus, NO may be used to differentiate between inflammatory and non-inflammatory chronic abacterial prostatitis. The presence of inducible NOS and the NO formation was investigated in bladder cancer patients. We found increased NO formation in the urinary bladder in patients with Bacillus Calmette Guérin (BCG) treated bladder cancer and carcinoma in situ, suggesting that NO may be an important factor in bladder cancer biology and that the BCG effect in bladder cancer may be due to the stimulation of NO formation. In summary the use of NO as an objective marker may improve the diagnostics of lower urinary tract disorders.
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| 6. |
- Häggström, Christel, et al.
(författare)
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Cohort profile : The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)
- 2017
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Ingår i: BMJ Open. - London : BMJ Publishing Group Ltd. - 2044-6055. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe).PARTICIPANTS: The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death.FINDINGS TO DATE: Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival.FUTURE PLANS: The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author.
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| 7. |
- Häggström, Christel, et al.
(författare)
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Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer : A Swedish nationwide population-based cohort study
- 2019
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Ingår i: Cancer Medicine. - : WILEY. - 2045-7634. ; 8:5, s. 2196-2204
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC.Methods: We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period.Results: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29.Conclusion(s): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.
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| 8. |
- Jahnson, Staffan, et al.
(författare)
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Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe)
- 2019
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 53:4, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- 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/Örebro Healthcare regions. IVIT was performed more often with younger patients, with men, in the Western Healthcare region, and less often in the Uppsala/Örebro 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.
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| 9. |
- Jahnson, Staffan, et al.
(författare)
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Swedish National Registry of Urinary Bladder Cancer : no difference in relative survival over time despite more aggressive treatment
- 2016
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 50:1, s. 14-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. MATERIALS AND METHODS: All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. RESULTS: The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. CONCLUSIONS: This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.
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| 10. |
- Jahnson, Staffan, et al.
(författare)
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Thromboembolism in Muscle-Invasive Bladder Cancer : A Population-based Nationwide Study
- 2021
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Ingår i: Bladder Cancer. - : IOS Press. - 2352-3727 .- 2352-3735. ; 7:2, s. 161-171
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Routine VTE prophylaxis within 30 days of radical cystectomy (RC) for urinary bladder cancer (UBC) is used to protect from venous thromboembolism (VTE). However, randomized studies and nationwide population-based studies are lacking.OBJECTIVE: To study VTE and risk factors for VTE in muscle-invasive UBC in a nationwide population-based series, with a focus on the association with RC with and without chemotherapy.MATERIALS AND METHODS: We studied all patients with clinical stage T2-T4 UBC diagnosed 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe). Previous VTE events and risk factors for VTE were registered from 1987. Cox regression analyses and Kaplan-Meier curves were performed to study risk factors for VTE and cumulative incidence of VTE.RESULTS: In 9720 patients (71% males) with a median age of 74 years 546 (5.6%) had VTE after diagnosis. In Cox analyses controlling for patient's and tumour characteristics, and risk factors for VTE, VTE after diagnosis and first treatment date were associated with chemotherapy with or without RC. Cumulative incidence of VTE increased during 24 months after diagnosis and first treatment date. VTE were less common in patients with previous cardiovascular disease.CONCLUSION: VTE was commonly observed after 30 days from diagnosis and from first treatment date in patients with T2-T4 UBC, particularly after chemotherapy. The findings suggest that long-term intervention studies of benefit and possible harms of VTE prophylaxis after UBC should be undertaken.
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