| 1. |
- Krantz, David, et al.
(författare)
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IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity
- 2020
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Ingår i: Scandinavian Journal of Immunology. - : John Wiley & Sons. - 0300-9475 .- 1365-3083. ; 92:6
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Tidskriftsartikel (refereegranskat)abstract
- In the effort of developing new immunotherapies, the sentinel node (SN) has proven a promising source from which to harness an effective antitumour T cell response. However, tumour immune escape, a process in which regulatory T cells (Tregs) play a central role, remains a major limiting factor. Therefore, there is a clear need to increase the knowledge of Treg function and signalling in sentinel nodes. Here, we set out to explore whether the proteome in SN-resident T cells is altered by the tumour and to identify key proteins in SN T cell signalling, focusing on Tregs. Five patients with muscle-invasive urothelial bladder cancer were prospectively included. Mass spectrometry was performed on two patients, with validation and functional studies being performed on three additional patients and four healthy donors. At cystectomy, SN, non-SN lymph nodes and peripheral blood samples were collected from the patients and T cell subsets isolated through flow cytometry before downstream experiments. Proteomic analysis indicated that growth and immune signalling pathways are upregulated in SN-resident Tregs. Furthermore, centrality analysis identified the cytokine IL-16 to be central in the SN-Treg signalling network. We show that tumour-released factors, through activating caspase-3, increase Treg IL-16 processing into bioactive forms, reinforcing Treg suppressive capacity. In conclusion, we provide evidence that Tregs exposed to secreted factors from bladder tumours show increased immune and growth signalling and altered IL-16 processing which translates to enhanced Treg suppressive function, indicating altered IL-16 signalling as a novel tumour immune escape mechanism.
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- 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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| 4. |
- Abuhasanein, Suleiman, et al.
(författare)
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Do not throw out the baby with the bath water
- 2022
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Ingår i: Scandinavian Journal of Urology. - Abingdon, Oxfordshire, United Kingdom : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:3, s. 235-236
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Abuhasanein, Suleiman, et al.
(författare)
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Standardized care pathways for patients with suspected urinary bladder cancer: the Swedish experience
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:3, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To compare time intervals to diagnosis and treatment, tumor characteristics, and management in patients with primary urinary bladder cancer, diagnosed before and after the implementation of a standardized care pathway (SCP) in Sweden. Materials and methods Data from the Swedish National Register of Urinary Bladder Cancer was studied before (2011-2015) and after (2016-2019) SCP. Data about time from referral to transurethral resection of bladder tumor (TURBT), patients and tumor characteristics, and management were analyzed. Subgroup analyses were performed for cT1 and cT2-4 tumors. Results Out of 26,795 patients, median time to TURBT decreased from 37 to 27 days after the implementation of SCP. While the proportion of cT2-T4 tumors decreased slightly (22-21%, p < 0.001), this change was not stable over time and the proportions cN + and cM1 remained unchanged. In the subgroups with cT1 and cT2-4 tumors, the median time to TURBT decreased and the proportions of patients discussed at a multidisciplinary team conference (MDTC) increased after SCP. In neither of these subgroups was a change in the proportions of cN + and cM1 observed, while treatment according to guidelines increased after SCP in the cT1 group. Conclusion After the implementation of SCP, time from referral to TURBT decreased and the proportion of patients discussed at MDTC increased, although not at the levels recommended by guidelines. Thus, our findings point to the need for measures to increase adherence to SCP recommendations and to guidelines.
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| 6. |
- Ahlén Bergman, Emma, et al.
(författare)
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Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- 2018
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Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
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| 7. |
- Alvaeus, Julia, et al.
(författare)
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Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy
- 2020
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Ingår i: World journal of urology. - : Springer. - 0724-4983 .- 1433-8726. ; 38, s. 2207-2213
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the relationship between the number of tumour draining sentinel nodes (SNs) and pathoanatomical outcomes, in muscle-invasive bladder cancer (MIBC), in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).MATERIALS AND METHODS: In an ongoing prospective multicenter study, we included 230 patients with suspected urothelial MIBC from ten Swedish urological centers. All underwent TURb and clinical staging. From the cohort, 116 patients with urothelial MIBC; cT2-cT4aN0M0, underwent radical cystectomy (RC) and lymphadenectomy with SN-detection (SNd). 83 patients received cisplatin-based NAC and 33 were NAC-naïve. The number and locations of detected SNs and non-SNs were recorded for each patient. The NAC treated patients were categorized by pathoanatomical outcomes post-RC into three groups: complete responders (CR), stable disease (SD) and progressive disease (PD). Selected covariates with possible impact on SN-yield were tested in uni -and multivariate analyses for NAC-treated patients only.RESULTS: In NAC treated patients, the mean number of SNs was significantly higher in CR patients (3.3) and SD patients (3.6) compared with PD patients (1.4) (p = 0.034). In a linear multivariate regression model, the number of harvested nodes was the only independent variable that affected the number of SNs (p = 0.0004).CONCLUSIONS: The number of tumor-draining SNs in NAC-treated patients was significantly lower in patients with progressive disease.
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| 8. |
- 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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| 9. |
- Bobjer, Johannes, et al.
(författare)
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A population-based study on the effect of a routine second-look resection on survival in primary stage T1 bladder cancer
- 2021
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 55:2, s. 108-115
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the value of second-look resection (SLR) in stage T1 bladder cancer (BCa) with respect to progression-free survival (PFS), and also the secondary outcomes recurrence-free survival (RFS), bladder-cancer-specific survival (CSS), and cystectomy-free survival (CFS). Patients and methods The study included 2456 patients diagnosed with stage T1 BCa 2004-2009 with 5-yr follow-up registration in the nationwide Bladder Cancer Data Base Sweden (BladderBaSe). PFS, RFS, CSS, and CFS were evaluated in stage T1 BCa patients with or without routine SLR, using univariate and multivariable Cox regression with adjustment for multiple confounders (age, gender, tumour grade, intravesical treatment, hospital volume, comorbidity, and educational level). Results SLR was performed in 642 (26%) individuals, and more frequently on patients who were aged < 75 yr, had grade 3 tumours, and had less comorbidity. There was no association between SLR and PFS (hazard ratio [HR] 1.1, confidence interval [CI] 0.85-1.3), RFS (HR 1.0, CI 0.90-1.2), CFS (HR 1.2, CI 0.95-1.5) or CSS (HR 1.1, CI 0.89-1.4). Conclusions We found similar survival outcomes in patients with and patients without SLR, but our study is likely affected by selection mechanisms. A randomised study defining the role of SLR in stage T1 BCa would be highly relevant to guide current praxis.
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| 10. |
- Bobjer, Johannes, et al.
(författare)
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Bladder cancer recurrence in papillary urothelial neoplasm of low malignant potential (PUNLMP) compared to G1 WHO 1999: a population-based study
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Objective Papillary urothelial neoplasm of low malignant potential (PUNLMP) and stage TaG1 non-muscle invasive bladder cancer (NMIBC) represent separate categories in current WHO 1999 grade definitions. Similarly, PUNLMP and Ta low-grade are separate entities in the WHO 2004/2016 grading system. However, this classification is currently questioned by reports showing a similar risk of recurrence and progression for both categories. Patients and methods In this population-based study, risk estimates were evaluated in patients diagnosed with PUNLMP (n = 135) or stage TaG1 (n = 2176) NMIBC 2004-2008 with 5-year follow-up registration in the nation-wide Bladder Cancer Data Base Sweden (BladderBaSe). The risk of recurrence was assessed using multivariable Cox regression with adjustment for multiple confounders (age, gender, marital status, comorbidity, educational level, and health care region). Results At five years, 28/135 (21%) patients with PUNLMP and 922/2176 (42%) with TaG1 had local recurrence. The corresponding progression rates were 0.7% (1/135) and 4.0% (86/2176), respectively. A higher relative risk of recurrence was detected in patients with TaG1 tumours compared to PUNLMP (Hazard Ratio 1.6, 95% CI 1.2-2.0) at 5-year follow-up, while progression events were too few to compare. Conclusions The difference in risk of recurrence between primary stage TaG1 and PUNLMP stands in contrast to the recently adapted notion that treatment and follow-up strategies can be merged into one low-risk group of NMIBC.
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