| 1. |
- 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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| 2. |
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| 3. |
- Mezheyeuski, Artur, et al.
(författare)
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An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression.Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations.Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy.Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types.
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| 4. |
- Mezheyeuski, Artur, et al.
(författare)
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The ratio of CD8+ lymphocytes to CD68+CD163+ macrophages is prognostic in immunogenic tumors and predicts immunotherapy response
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Immune cells in the microenvironment shape tumor development and progression. Through in situ analyses we assessed 15 immune cell classes in 352 colorectal cancers and identified a simpleprognostic signature based on the ratio of anti-tumoral CD8+ lymphocytes to tumor-supportiveCD68+CD163+ macrophages in the tumor microenvironment. The prognostic ability of this signature was superior to the state-of-art immune score and was also demonstrated in four other tumor types. Single-cell analyses identified these CD68+CD163+ macrophages as the source of complement C1q, and the ratio of CD8A to C1QA gene expression levels in bulk RNA predicted survival in five tumor types. In single cell analyses, RNA-based versions of the signature also predicted response to checkpoint inhibitor therapy. This supports broad clinical applicability of immune scores considering CD68+CD163+ macrophages as prognostic and predictive biomarkers in common cancers.
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| 5. |
- Micke, Patrick, et al.
(författare)
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The prognostic impact of the tumour stroma fraction : A machine learning-based analysis in 16 human solid tumour types
- 2021
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns.Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR (95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59 (1.49-8.62)) associations of the tumour stroma fraction with survival.Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance.
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| 6. |
- 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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| 7. |
- Abdul-Sattar Aljabery, Firas, et al.
(författare)
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Treatment and prognosis of patients with urinary bladder cancer 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. - : Wiley. - 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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| 8. |
- Ahlström, Håkan, et al.
(författare)
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Positron emission tomography in the diagnosis and staging of urinary bladder cancer
- 1996
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 37:2, s. 180-185
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Evaluation of positron emission tomography (PET) using (18)fl 18F-2-fluoro-2-deoxy-D-glucose (18FDG) and L-methyl-11C-methionine in the diagnosis and staging of urinary bladder carcinoma. MATERIAL AND METHODS: Twenty-three patients with biopsy-proven urinary bladder carcinoma were examined with PET after intravenous injection of 11C-methionine; 2 were also examined with 18FDG. The results from the PET investigations were compared with CT or MR findings and TNM classification before and after treatment. RESULTS: The urinary excretion of 18FDG prevented distinction of the primary tumour from the surrounding tracer. With 11C-methionine it was possible to detect 18/23 primary tumours. A trend was seen, suggesting that the higher the uptake values of 11C-methionine in the tumour, the greater the tumour stage. CONCLUSION: It is possible to visualize urinary bladder tumours larger than 1 cm in diameter with PET using (11)C-methionine, but the value of the method in the staging of the lesions is not superior to conventional methods.
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| 9. |
- Andersson, Gustav, et al.
(författare)
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Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival : validatory study of two independent patient cohorts
- 2014
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Ingår i: BMC Urology. - : BioMed Central (BMC). - 1471-2490. ; 14:1, s. 36-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.
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| 10. |
- Andersson, Lennart, et al.
(författare)
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Chairmen's summary
- 2008
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Ingår i: Scandinavian Journal of Urology and Nephrology, Supplementum. - : Informa UK Limited. - 0300-8886 .- 1651-2537 .- 0036-5599 .- 1651-2065. ; :218, s. 7-11
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Andersson, Marie, et al.
(författare)
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The diagnostic challenge of suspicious or positive malignant urine cytology findings when cystoscopy findings are normal : an outpatient blue-light flexible cystoscopy may solve the problem
- 2021
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 55:4, s. 263-267
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate whether outpatient blue-light flexible cystoscopy could solve the diagnostic challenge of positive or suspicious urine cytology findings despite normal white-light flexible cystoscopy results and normal findings on computerized tomography urography, in patients investigated for urothelial cancer.Material and methods: In a multicentre study, a total of 70 examinations were performed with the use of blue-light flexible cystoscopy (photodynamic diagnosis) after intravesical instillation of the fluorescence agent hexaminolevulinate. The examination started with a conventional white-light flexible cystoscopy and then the settings were switched to use blue light. Suspicious lesions were biopsied. Afterwards, the patients were interviewed regarding their experience of the examinations.Results: Bladder cancer was diagnosed in 29 out of 70 (41%) cases, among them 14/29 (48%) had malignant lesions seen only in blue light. The majority had carcinoma in situ (21/29). Normal findings were seen in 41 cases that underwent BLFC. During the further course, malignancy of the bladder was detected in six cases (9%) and malignancy of the upper urinary tract was detected in one case (1%). The majority of patients (93%) preferred the blue-light flexible cystoscopy performed at the outpatient clinic instead of the transurethral resection under general anaesthesia.Conclusion: Blue-light flexible cystoscopy at the outpatient clinic may be a useful tool to solve unclear cases of a malignant or suspicious urinary cytology suggestive of bladder cancer. The procedure was well tolerated by the patients.
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| 12. |
- Bergengren, Oskar, et al.
(författare)
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Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study
- 2023
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Ingår i: Ejso. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 49:4, s. 868-874
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population.Materials and methods: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary out-comes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models.Results: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multi -variable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0).Conclusion: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 13. |
- Beukers, Willemien, et al.
(författare)
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FGFR3, TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter Study
- 2017
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 197:6, s. 1410-1418
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Patients with nonmuscle invasive bladder cancer are followed with frequent cystoscopies. In this study FGFR3, TERT and OTX1 were investigated as a diagnostic urinary marker combination during followup of patients with primary nonmuscle invasive bladder cancer.Materials and Methods: In this international, multicenter, prospective study 977 patients with nonmuscle invasive bladder cancer were included. A total of 2,496 urine samples were collected prior to cystoscopy during regular visits. Sensitivity was estimated to detect concomitant recurrences. Kaplan-Meier curves were used to estimate the development of future recurrences after urinalysis and a negative cystoscopy.Results: Sensitivity of the assay combination for recurrence detection was 57% in patients with primary low grade, nonmuscle invasive bladder cancer. However, sensitivity was 83% for recurrences that were pT1 or muscle invasive bladder cancer. Of the cases 2% progressed to muscle invasive bladder cancer. Sensitivity for recurrence detection in patients with primary high grade disease was 72% and 7% of them had progression to muscle invasive bladder cancer. When no concomitant tumor was found by cystoscopy, positive urine samples were more frequently followed by a recurrence over time compared to a negative urine sample (58% vs 36%, p < 0.001). High stage recurrences were identified within 1 year after a positive urine test and a negative cystoscopy.Conclusions: Recurrences in patients with primary nonmuscle invasive bladder cancer can be detected by a combination of urine assays. This study supports the value of urinalysis as an alternative diagnostic tool in patients presenting with low grade tumors and as a means to identify high stage tumors earlier.
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| 14. |
- Boman, Karolina, et al.
(författare)
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Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer
- 2013
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Ingår i: BMC Urology. - : Springer Science and Business Media LLC. - 1471-2490. ; 13:April,8, s. 17-17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Low nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to be associated with poor prognosis in several cancer forms e.g. breast, ovarian, colorectal, prostate cancer and malignant melanoma. The aim of this study was to examine the prognostic impact of RBM3 expression in urinary bladder cancer.METHODS: Immunohistochemical RBM3 expression was examined in tumours from 343 patients with urothelial bladder cancer. Chi-square and Spearman's correlation tests were applied to explore associations between RBM3 expression and clinicopathological characteristics. The impact of RBM3 expression on disease-specific survival (DSS), 5-year overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analysis and Cox proportional hazards modelling.RESULTS: Reduced nuclear RBM3 expression was significantly associated with more advanced tumour (T) stage (p <0.001) and high grade tumours (p=0.004). Negative RBM3 expression was associated with a significantly shorter DSS (HR=2.55; 95% CI 1.68-3.86)) and 5-year OS (HR=2.10; 95% CI 1.56-2.82), also in multivariable analysis (HR=1.65; 95% CI 1.07-2.53 for DSS and HR=1.54; 95% CI 1.13-2.10 for 5-year OS). In patients with Ta and T1 tumours expressing reduced RBM3 levels, Kaplan-Meier analysis revealed a significantly shorter PFS (p=0.048) and 5-year OS (p=0.006).CONCLUSION: Loss of RBM3 expression is associated with clinically more aggressive tumours and an independent factor of poor prognosis in patients with urothelial bladder cancer and a potentially useful biomarker for treatment stratification and surveillance of disease progression.
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| 15. |
- Boman, Karolina, et al.
(författare)
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Membranous expression of podocalyxin-like protein is an independent factor of poor prognosis in urothelial bladder cancer
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 108:11, s. 2321-2328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Membranous expression of the anti-adhesive glycoprotein podocalyxin-like (PODXL) has previously been found to correlate with poor prognosis in several major cancer forms. Here we examined the prognostic impact of PODXL expression in urothelial bladder cancer. Methods: Immunohistochemical PODXL expression was examined in tissue microarrays with tumours from two independent cohorts of patients with urothelial bladder cancer: n = 100 (Cohort I) and n = 343 (Cohort II). The impact of PODXL expression on disease-specific survival (DSS; Cohort II), 5-year overall survival (OS; both cohorts) and 2-year progression-free survival (PFS; Cohort II) was assessed. Results: Membranous PODXL expression was significantly associated with more advanced tumour (T) stage and high-grade tumours in both cohorts, and a significantly reduced 5-year OS (unadjusted HR = 2.25 in Cohort I and 3.10 in Cohort II, adjusted HR = 2.05 in Cohort I and 2.18 in Cohort II) and DSS (unadjusted HR = 4.36, adjusted HR = 2.70). In patients with Ta and T1 tumours, membranous PODXL expression was an independent predictor of a reduced 2-year PFS (unadjusted HR = 6.19, adjusted HR = 4.60) and DSS (unadjusted HR = 8.34, adjusted HR = 7.16). Conclusion: Membranous PODXL expression is an independent risk factor for progressive disease and death in patients with urothelial bladder cancer.
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| 16. |
- Botling, Johan, et al.
(författare)
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Impact of thawing on RNA integrity and gene expression analysis in fresh frozen tissue
- 2009
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Ingår i: Diagnostic molecular pathology (Print). - 1052-9551 .- 1533-4066. ; 18:1, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks of fresh, unfixed human tissue represent a valuable source for gene expression analysis in translational research and molecular pathology. The aim of this study was to evaluate the impact of thawing on RNA integrity and gene expression in fresh frozen tissue specimens. Portions of snap frozen tonsil tissue, unfixed or immersed in RNAlater, were thawed at room temperature for 0 minute, 5 minutes, 30 minutes, 45 minutes, 1 hour, 3 hours, 6 hours, and 16 hours before RNA extraction. Additionally, tonsil tissue underwent repetitive freezing and thawing cycles. RNA integrity was analyzed by microchip gel electrophoresis and gene expression by quantitative real-time polymerase chain reaction for selected genes (FOS, TGFB1, HIF1A, BCL2, and PCNA). Minimal RNA degradation was detected after 30 minutes of thawing in unfixed samples. This degradation was accompanied by relevant changes in gene expression for FOS and BCL2 at 45 minutes. Modified primer design or the use of different housekeeping genes could not rectify the changes for FOS. Repetitive thawing cycles had similar effects on RNA integrity. The incubation of the tissue in RNAlater efficiently prevented RNA degradation. In conclusion, degradation of RNA in frozen tissue occurs first after several minutes of thawing. Already minimal decrease in RNA quality may result in significant changes in gene expression patterns in clinical tissue samples.
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| 17. |
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| 18. |
- Böös, Malin, et al.
(författare)
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Who should record surgical complications? : Results from a third-party assessment of complications after radical cystectomy
- 2019
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Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 53:5, s. 339-343
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In Sweden complications after radical cystectomy have been reported to the nationwide population-based Swedish Cystectomy Registry since 2011. Here, validation of the reporting was assessed in two healthcare regions.Materials and methods: Complications were ascertained from patient records by a third party not involved in the care delivered to 429 randomly selected patients from 949 who had undergone radical cystectomy since 2011 in four hospitals. Without knowledge of the outcome in the primary registration, post-operative complications within 90 days post-operatively were assessed by an independent review of patient charts, and the results were compared with the primary reports in the Swedish Cystectomy Registry.Results: The third-party assessment identified post-operative complications in 310 patients (72%). Low-grade complications (Clavien-Dindo I-II) were noted in 110 (26%) of the patients in the primary registration, but increased to 182 (42%) in the validation (p < 0.00001). High-grade complications (Clavien-Dindo III-V) were reported in 113 (26%) patients in the primary registration, but in 128 (30%) of the patients in the validation (p = 0.02). According to the third-party assessment, 18 patients (4%) had Clavien-Dindo grade IV complications and 12 (3%) died within 90 days of surgery (Clavien-Dindo grade V); corresponding values in the primary registration were 15 (3%) and 9 (2%), respectively. The readmission rate within 90 days increased from 27 to 32% in the validation (p < 0.00001).Conclusions: Compared with registry data, third-party assessment revealed more complications and readmissions after radical cystectomy. Hence such evaluation may improve the validity of reported complication data.
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| 19. |
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| 20. |
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| 21. |
- Carlsson, Jörgen, et al.
(författare)
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Conjugate chemistry and cellular processing of EGF-dextran
- 1999
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 313-321
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Tidskriftsartikel (refereegranskat)abstract
- Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.
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| 22. |
- Carlsson, Jörgen, et al.
(författare)
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EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides
- 2015
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Ingår i: Radiology and Oncology. - : Walter de Gruyter GmbH. - 1318-2099 .- 1581-3207. ; 49:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder canter and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.
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| 23. |
- Chan, Owen T. M., et al.
(författare)
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Association of MMP-2, RB and PAI-1 with decreased recurrence-free survival and overall survival in bladder cancer patients
- 2017
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:59, s. 99707-99721
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Tidskriftsartikel (refereegranskat)abstract
- Background: We previously reported an accurate urine-based bladder cancer (BCa)-associated diagnostic signature that can be used to non-invasively detect BCa. In this study, we investigated whether a component of this signature could risk stratify patients with BCa. Methods: Utilizing immunohistochemistry, we investigated angiogenin, MMP-2, p53, RB and PAI-1 expression from 939 patients with BCa. The expression levels were scored by assigning a proportion score and an intensity score to yield a total staining score for each protein. The expressions of each protein individually and as an aggregate were then correlated with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Results: Differential expressions of these markers were noted in BCa. With multivariate analysis in non-muscle invasive bladder cancer (NMIBC) age, tumor grade portended a worse PFS, while age, tumor grade, nodal status, MMP2, RB and PAI-1 expression portended a worse OS. As for multivariate analysis in muscle invasive bladder cancer (MIBC), age MMP-2 and RB were associated with a worse PFS, while age, nodal status, MMP-2, RB and PAI-1 were associated with a worse OS. Using Kaplan-Meier survival analysis, we noted a significant reduction in OS as more of the five biomarkers were expressed in a tumor. Thus, overall, high expressions of MMP-2, RB and/or PAI-1 in bladder tumors were markers of poor prognosis. Conclusion: Individually, MMP-2, RB and PAI-1, as well as in aggregate correlated with poor survival in patients with BCa. Thus, patients whose bladder tumors express these biomarkers may benefit from early radical treatment and/or neoadjuvant or adjuvant therapies.
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- D'Andrea, David, et al.
(författare)
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Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guerin immunotherapy for T1G3/HG bladder cancer
- 2021
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Ingår i: World journal of urology. - : Springer Nature. - 0724-4983 .- 1433-8726. ; 39:9, s. 3337-3344
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guerin (BCG) for T1G3/HG urinary bladder cancer (UBC).Materials and methods: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression.Results: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55).Conclusion: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.
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