| 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. |
- Aljabery, Firas, et al.
(författare)
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Treatment and prognosis of bladder cancer patients with other primary cancers : A nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe)
- 2020
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Ingår i: BJU International. - : Blackwell Publishing. - 1464-4096 .- 1464-410X. ; 126:5, s. 625-632
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis.Patients And Methods: Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patient's characteristics, UBC tumour stage at diagnosis, and site of OPC.Results: There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis.Conclusions: OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.
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| 4. |
- Collins, Justin, et al.
(författare)
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Live streaming of robotic surgery from leading educational centres enables a global approach to surgical teaching
- 2016
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 195:4, s. E116-E116
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Following recently published EAU Policy on Live Surgical Events (LSE's) it is assured that live surgery will be ongoing at conferences in the immediate future. However, the panel reached >80% consensus view that performing at a home institution may be safer. The committee also identified issues with a ‘travelling surgeon’ performing complex surgery in an unfamiliar environment with a surgical team that is not experienced with the intricacies of surgeons techniques. LSE's from home institutions remove or minimize these negative aspects.
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| 5. |
- 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.
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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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| 6. |
- 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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| 7. |
- 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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| 8. |
- Hultman Patschan, Oliver, et al.
(författare)
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Use of bacillus Calmette-Guerin in stage T1 bladder cancer : long-term observation of a population-based cohort
- 2015
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 49:2, s. 127-132
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- 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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| 10. |
- 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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