| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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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. |
- Ahlén Bergman, Emma, et al.
(författare)
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Epigenetic methylation profiles of CD4 T cell signature loci from patients with urinary bladder cancer
- 2017
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Ingår i: Scandinavian Journal of Immunology. - : John Wiley & Sons. - 0300-9475 .- 1365-3083. ; 86:4, s. 264-264
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Urinary bladder cancer (UBC) is one of the most frequent cancer diseases with 380 000 new cases diagnosed worldwide and about 150 000 deaths yearly. To dissect the role of T helper (Th) cell responses in UBC we investigate the T helper cell subpopulations; Th1, Th2, Th17 and T regulatory cells (Tregs) and their lineage commitment in draining (sentinel) and non-draining lymph nodes and blood from patients subjected to transurethral resection of the bladder (TUR-B) and/or Cystectomy. By analyzing methylation in signature genes IFNG, IL13, IL17a and FOXP3 we measure the epigenetic stability of these T helper cells.In most patients IFNG is more demethylated in sentinel nodes compared to non-sentinel nodes and blood, suggesting a Th1 activation in nodes in contact with the tumor. Aside from that, the distribution of subpopulations in all tissues investigated is highly variable in between patients. All subsets are represented, although there seem to be no or little Th17 cells in nodes. After neoadjuvant treatment (given in between the TUR-B and cystectomy) a temporary increase in methylation of IFNG locus is seen in blood, which could suggest a translocation of activated Th cells from the blood to the tumor area, but also de novo synthesis of Th cells.By analyzing the intra-patient variations in distribution and relative amount of Th cell subpopulations in blood and sentinel nodes we hope to draw conclusions on differences in outcome. The long-term goal is to be able to identify which patients could respond well to immune modulatory treatments.
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| 4. |
- 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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| 5. |
- Hartana, Ciputra Adijaya, et al.
(författare)
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Detection of micrometastases by flow cytometry in sentinel lymph nodes from patients with renal tumours
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115:8, s. 957-966
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Stage is an important prognostic factor in renal tumours and dissemination to regional lymph nodes is associated with poor outcomes. Lymph nodes are routinely assessed by immunohistochemistry and microscopic evaluation, a time-consuming process where micrometastases might go undiagnosed. We evaluate an alternative method for detecting metastatic cells in sentinel nodes (SNs) by flow cytometry.METHODS: A total of 15 nodes from 5 patients diagnosed with renal tumours were analysed by flow cytometry. Staining for the intracellular marker cytokeratin 18 (CK18) with the surface markers carbonic anhydrase IX (CA9) and Cadherin 6 were used in flow cytometry analysis. Peripheral blood mononuclear cells (PBMCs) with the addition of known concentrations of cancer cell lines were analysed to investigate the sensitivity of micrometastasis detection.RESULTS: Stability of the assay was marked by low intra-assay variability (coefficient of variance ⩽16%) and low inter-assay variability (R(2)=0.9996-1). Eight nodes in four patients were positive for metastasis; six of them were considered being micrometastatic. These metastases were undetected by routine pathology and the patients were restaged from pN0 to pN1.CONCLUSIONS: Flow cytometry is able to detect micrometastases in lymph nodes of renal tumour patients that were undetected under H&E examination.
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| 6. |
- Hartana, C. A., et al.
(författare)
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Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer
- 2018
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Ingår i: Clinical and Experimental Immunology. - : WILEY. - 0009-9104 .- 1365-2249. ; 194:1, s. 39-53
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Tidskriftsartikel (refereegranskat)abstract
- Tissue-resident memory T (T-RM) cells are CD8(+) T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in T-RM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in T-RM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate T-RM cell phenotypes. We discovered that tumour T-RM cells have low DNA methylation in the PRF1 locus (329% methylation), which corresponds to increased numbers of perforin-expressing T-RM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour T-RM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that T-RM cells from tumours are not terminally exhausted. Moreover, a high number of T-RM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, T-RM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies T-RM cells as potential new targets for cancer immunotherapy.
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| 7. |
- Hartana, Ciputra Adijaya, et al.
(författare)
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Urothelial bladder cancer may suppress perforin expression in CD8+ T cells by an ICAM-1/TGFβ2 mediated pathway
- 2018
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- The immune system plays a significant role in urothelial bladder cancer (UBC) progression, with CD8+ T cells being capable to directly kill tumor cells using perforin and granzymes. However, tumors avoid immune recognition by escape mechanisms. In this study, we aim to demonstrate tumor immune escape mechanisms that suppress CD8+ T cells cytotoxicity. 42 patients diagnosed with UBC were recruited. CD8+ T cells from peripheral blood (PB), sentinel nodes (SN), and tumor were analyzed in steady state and in vitro-stimulated conditions by flow cytometry, RT-qPCR, and ELISA. Mass spectrometry (MS) was used for identification of proteins from UBC cell line culture supernatants. Perforin was surprisingly found to be low in CD8+ T cells from SN, marked by 1.8-fold decrease of PRF1 expression, with maintained expression of granzyme B. The majority of perforin-deficient CD8+ T cells are effector memory T (TEM) cells with exhausted Tc2 cell phenotype, judged by the presence of PD-1 and GATA-3. Consequently, perforin-deficient CD8+ T cells from SN are low in T-bet expression. Supernatant from muscle invasive UBC induces perforin deficiency, a mechanism identified by MS where ICAM-1 and TGFβ2 signaling were causatively validated to decrease perforin expression in vitro. Thus, we demonstrate a novel tumor escape suppressing perforin expression in CD8+ T cells mediated by ICAM-1 and TGFβ2, which can be targeted in combination for cancer immunotherapy.
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| 8. |
- Horwich, A, et al.
(författare)
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EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
- 2019
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
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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. |
- 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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| 11. |
- Jancke, Georg, et al.
(författare)
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Intravesical instillations and cancer-specific survival in patients with primary carcinoma in situ of the urinary bladder
- 2017
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 51:2, s. 124-129
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to evaluate the use of intravesical treatment and cancer-specific survival of patients with primary carcinoma in situ (CIS).MATERIALS AND METHODS: Data acquisition was based on the Swedish National Registry of Urinary Bladder Cancer by selecting all patients with primary CIS. The analysis covered gender, age, hospital type and hospital volume. Intravesical treatment and death due to bladder cancer were evaluated by multivariate logistic regression and multivariate Cox analysis, respectively.RESULTS: The study included 1041 patients (median age at diagnosis 72 years) with a median follow-up of 65 months. Intravesical instillation therapy was given to 745 patients (72%), and 138 (13%) died from bladder cancer during the observation period. Male gender [odds ratio (OR) = 1.56, 95% confidence interval (CI) 1.13-2.17] and treatment at county (OR = 1.65, 95% CI 1.17-2.33), university (OR =2.12, 95% CI 1.48-3.03) or high-volume (OR = 1.92, 95% CI 1.34-2.75) hospitals were significantly associated with higher odds of intravesical instillations. The age category ≥80 years had a significantly lower chance of receiving intravesical therapy (OR = 0.44, 95% CI 0.26-0.74) and a significantly higher risk of dying from bladder cancer (hazard ratio = 3.03, 95% CI 1.71-5.35).CONCLUSION: Significantly more frequent use of intravesical treatment of primary CIS was found for males and for patients treated at county, university and high-volume hospitals. Age ≥80 years was significantly related to less intravesical treatment and poorer cancer-specific survival.
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| 12. |
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| 13. |
- Kirrander, Peter, 1978-, et al.
(författare)
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The Swedish National Penile Cancer Register : Incidence, Tumour Characteristics, Management and Survival
- 2016
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Ingår i: BJU International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 117:2, s. 287-292
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess penile cancer incidence, stage distribution, adherence to guidelines, and prognostic factors in a population-based setting.PATIENTS AND METHODS: The population-based Swedish National Penile Cancer Register (NPECR) contains detailed information on tumour characteristics and management patterns. ● A total of 1678 men with primary squamous cell carcinoma of the penis identified in the NPECR between 2000 and 2012 were included in the study. RESULTS: The mean age-adjusted incidence of penile cancer was 2.1/100,000 men, remaining virtually unchanged during the study period. At diagnosis, 14% and 2% were clinically N+ and M+, respectively. Most patients were staged pTis (34%), pT2 (19%), or pT1 (18%), whereas stage was unavailable in 18%. Organ-preserving treatment was used in 71% of Tis-T1 tumours. In cN0 and ≥pT1G2 patients, 50% underwent lymph node staging, while 74% of cN1-3 patients underwent lymph node dissection. The overall 5-year relative survival was 82%. Men aged ≥40 years and those with pT2-3, G2-3 and N+ tumours had worse outcome.CONCLUSION: The incidence of penile cancer in Sweden is stable. Most men presented with localised disease, and the proportion of non-invasive tumours was high. During the period under study, adherence to guidelines was suboptimal. The overall 5-year relative survival was 82%. Older age, increasing tumour stage and grade, and increasing lymph node stage were associated with poorer survival.
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| 14. |
- Klinga, Gustaf, et al.
(författare)
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A retrospective evaluation of preoperative anemia in patients undergoing radical cystectomy for muscle-invasive urothelial urinary bladder cancer, with or without neoadjuvant chemotherapy
- 2016
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Ingår i: SpringerPlus. - : Springer. - 2193-1801. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (NAC) can be associated with anemia, which can lead to more perioperative blood transfusions (PBT). Usage of PBT is associated with worse oncological outcomes. We evaluated the prevalence of preoperative anemia (PA) and the effect on hemoglobin levels depending on surgery timing after NAC.METHODS: A retrospective single-center study with 240 consecutive patients undergoing radical cystectomy (RC) between 2001 and 2014 for muscle-invasive urothelial carcinoma (MIBC). Anemia was defined according to the WHO classification (male ≤ 130 g/L, female ≤ 120 g/L). Multivariable logistical regression was used to identify factors associated with PA and Pearson correlation for evaluating the change in hemoglobin levels depending on surgery timing.RESULTS: Overall, 128 (53.3 %) patients were anemic pre-RC and 87 (36.3 %) patients received NAC. In a multivariable analysis, age, receipt of NAC, female gender, and low BMI were independent predictors of PA. In patients receiving NAC, the time to surgery from the last NAC cycle was correlated with the change in hemoglobin levels between the initiation of NAC and surgery.CONCLUSIONS: PA was common in patients undergoing RC for MIBC. Receipt of NAC was found to be a strong predictor of PA.CLINICAL MESSAGE: The emerging treatment of cisplatin based neoadjuvant chemotherapy for muscle-invasive bladder cancer, confers an increased risk for preoperative anemia. In the management of this malignancy, preoperative anemia renders further attention and focus.
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| 15. |
- Krantz, David, et al.
(författare)
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Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer
- 2018
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 74:6, s. 688-692
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Tidskriftsartikel (refereegranskat)abstract
- Evidence indicates that neoadjuvant chemotherapy (NAC) may promote antitumour immune responses by activating T cells. The tumour-draining sentinel node (SN) is a key site to study tumour-specific T cell activation, being the primary immunological barrier against the tumour. In this prospective study, we set out to elucidate the effects of NAC on T cell subsets in the SNs of patients with muscle-invasive urothelial bladder cancer. We found that CD8+ effector T (Teff) cell exhaustion was reduced after NAC treatment, while cytotoxicity was increased. Additionally, in complete responders (CR patients), these cells were functionally committed effectors, as displayed by epigenetic analysis. In CD4+ Teffs, NAC treatment was associated with increased clonal expansion of tumour-specific SN-derived cells, as demonstrated by a specific cell reactivity assay. In contrast, we observed an attenuating effect of NAC on regulatory T cells (Tregs) with a dose-dependent decrease in Treg frequency and reduced effector molecule expression in the remaining Tregs. In addition, multicolour flow cytometry analysis revealed that CR patients had higher Teff to activated Treg ratio, promoting antitumoural T cell activation. These results suggest that NAC reinforces the antitumour immune response by activating the effector arm of the T cell compartment and diminishing the influence of suppressive Tregs.PATIENT SUMMARY: In this report, we analysed the effect of chemotherapy on immune cell subsets of 40 patients with advanced bladder cancer. We found that chemotherapy has a positive effect on immune effector T cells, whereas an opposite, diminishing effect was observed for immune-suppressive regulatory T cells. We conclude that chemotherapy reinforces the antitumour immune response in bladder cancer patients.
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| 16. |
- Liedberg, Fredrik, et al.
(författare)
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Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study
- 2019
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Ingår i: Bju International. - : Wiley. - 1464-4096 .- 1464-410X. ; 53:Suppl. 221, s. 20-20
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the association between hospital volume and overall survival (OS), cancer-specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1-T3 in Sweden between 1997 and 2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at >= 25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually. Results PSMAV in the highest tertile (>= 25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75-1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of >3 months after diagnosis. Conclusions The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.
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| 17. |
- Malmström, Per-Uno, et al.
(författare)
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Incidence, survival and mortality trends of bladder cancer in Sweden 1997–2016
- 2019
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 53:4, s. 193-199
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate trends in bladder cancer incidence, survival and mortality in Sweden from 1997–2016. Patients and methods: The Swedish National Registry of Urinary Bladder Cancer is a nation-wide quality register that started in 1997. It includes information on initial tumor characteristics and treatment; 41,097 new cases were registered up to 2016. Patients were stratified into four time periods. Deaths were monitored through the national death register. Overall and relative survival in time periods were studied with respect to differences in stage, age and gender. Results: The number of new cases increased by 38% for men and 39% for women from 1997 to 2016. The corresponding age-standardized incidence per 100,000 was less dramatic, with increases of 6% and 21%, respectively, and the increase was most evident in the oldest age group. The survival rate was stable until 2012, but thereafter a significant improvement occurred. The survival trends in stage-groups show that this improvement is found in all categories as well as irrespective of age and gender. The mortality rate during this period was stable for women, but showed a slight decrease for men. The main limitation of this study is the use of administrative data for defining some of the endpoints. Conclusion: The most recent Swedish bladder cancer statistics show an increased incidence, improved survival, but stable mortality. © 2019, © 2019 Acta Chirurgica Scandinavica Society.
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| 18. |
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| 19. |
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| 20. |
- Norkin, Maxim, et al.
(författare)
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Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 25:2, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.
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| 21. |
- Rosenblatt, Robert, et al.
(författare)
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Blood transfusions during neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer may have a negative impact on overall survival
- 2019
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 53, s. 35-36
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Several studies have demonstrated a decreased overall survival for patients with muscle-invasive bladder cancer (MIBC) receiving allogenic peri- and postoperative blood transfusions at cystectomy. However, the extent and the effect of blood transfusions given during neoadjuvant chemotherapy (NAC) has never been addressed. The purpose of the present study, was to assess the impact of blood transfusions given during NAC on survival in patients with MIBC undergoing NAC and radical cystectomy.Materials and Methods: A cohort of 120 consecutive patients with MIBC (cT2-T4aN0M0) undergoing NAC and radical cystectomy at four Swedish centers was retrospectively evaluated. Clinical and pathoanatomical data was obtained, including data SCANDINAVIAN JOURNAL OF UROLOGY 35 on administeredallogenic blood at consecutive time-intervals. Overall survival was analyzed by Kaplan-Meier plotting and Cox regression.Results: One third of the cohort (n ¼ 40) received blood transfusions during NAC-therapy. The five-year overall survival rates were significantly lower in this group compared to the non-transfused patients (39.7% and 58.9% respectively, p ¼ 0.047). In a univariate analysis, blood transfusions, nodal status and locally advanced tumor growth (pT >2), were negative prognostic factors for survival. In multivariate analysis, only pNx and pT >2 remained significant negative prognostic factors. In subgroup analysis of localized and non-disseminated patients only (n ¼ 96), blood transfused patients showed a 18,5% absolute risk increase compared to blood naïve patients (p¼ 0.197).Conclusions: This is the first time that the extent and the effect of allogenic blood transfusions during NAC is examined in MIBC. Data suggest that there may be an association between blood transfusion and poor pathological and oncological outcome. Firm conclusions are difficult to draw due to the limited number of study participants and the retrospective nature of the study.
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| 22. |
- Rosenblatt, Robert, et al.
(författare)
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Sentinel node detection in muscle-invasive urothelial bladder cancer is feasible after neoadjuvant chemotherapy in all pT stages, a prospective multicenter report
- 2017
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Ingår i: World journal of urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 35:6, s. 921-927
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine whether sentinel node detection (SNd) in muscle-invasive urothelial bladder cancer (MIBC) can be performed in patients undergoing neoadjuvant chemotherapy (NAC) and determine whether SNd is feasible in all pT stages, including pT0.BACKGROUND: Previous published series of SNd in MIBC have not included patients undergoing NAC, and systematic reports of pT0 patients w/wo NAC were absent. Translational immunological tumor research on MIBC focusing on SNd, in the era of NAC, requires technical feasibility. Additionally, SNd in MIBC requests further evaluations as a method for nodal staging.MATERIALS AND METHODS: Ninety-nine patients with suspected urothelial MIBC were prospectively selected from six urological centers. After TUR-B and primary staging, 65 MIBC patients qualified for radical cystectomy. Precystectomy staging was cT2a-T4aN0M0, including 47 NAC patients and 18 chemo-naïve patients. All 65 patients underwent intraoperative SNd by peritumoral injection of 80 Mbq Technetium and Geiger probe detection. Postcystectomy staging was pT0-T4aN0-N2M0. SNs were defined by two calculations, SNdef1 and SNdef2.RESULTS: Totally 1063 lymph nodes were removed (total SNs; 222-227). NAC patients with pT0 (n = 24) displayed a true positive detection in 91.7 % by either SNdef, with a median of 3.0 SNs. NACpT >0 patients had a true positive detection in 87 % (SNdef1) and 91.3 % (SNdef2). In a univariate analysis, patient group neither NAC nor tumor downstaging influenced detection rates, regardless of SN definition. In total eight patients, 4/22 metastatic nodes were SNs while 18/22 were non-SNs.CONCLUSIONS: Sentinel node detection in MIBC is feasible also in NAC patients, regardless of pT stage. SNd played no role in nodal staging.
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| 23. |
- Russell, Beth, et al.
(författare)
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Neoadjuvant chemotherapy for muscle invasive bladder cancer : a nationwide investigation on survival
- 2019
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 53:4, s. 206-212
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Randomised controlled trials (RCTs) have investigated the use of neoadjuvant chemotherapy (NAC) and its effect on survival patients with non-metastatic muscle-invasive bladder cancer (MIBC). However, these RCTs have limited external validity and generalisability and, therefore, the current study aims to use real world evidence in the form of observational data to identify the effect that NAC may have on survival, compared to the use of radical cystectomy (RC) alone.Materials and methods: The study cohort (consisting of 944 patients) was selected as a target trial from the Bladder Cancer Data Base Sweden (BladderBaSe). This study calculated 5-year survival and risk of bladder cancer (BC)-specific and overall death by Cox proportional hazard models for the study cohort and a propensity score (PS) matched cohort.Results: Those who had received NAC had higher 5-year survival proportions and decreased risk of both overall and BC specific death (HR = 0.71, 95% CI = 0.52-0.97 and HR = 0.67, 95% CI = 0.48-0.94), respectively, as compared to patients who did not receive NAC. The PS matched cohort showed similar estimates, but with larger statistical uncertainty (Overall death: HR = 0.76, 95% CI = 0.53-1.09 and BC-specific death: HR = 0.73, 95% CI = 0.50-1.07).Conclusion: Results from the current observational study found similar point estimates for 5-year survival and of relative risks as previous studies. However, the results based on real world evidence had larger statistical variability, resulting in a non-statistically significant effect of NAC on survival. Future studies with detailed validated data can be used to further investigate the effect of NAC in narrower patient groups.
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| 24. |
- Sherif, Amir, et al.
(författare)
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Immune responses to neoadjuvant chemotherapy in muscle invasive bladder cancer
- 2018
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Ingår i: Bladder cancer. - : IOS Press. - 2352-3727. ; 4:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- The secondary effects of chemotherapy, with bone marrow depression and risk of leukopenia, has traditionally been considered being detrimental for the immune system. However, growing evidence suggests a main role for chemotherapy in antitumor immunomodulation. With reference to cisplatin, which is the basis of neoadjuvant chemotherapy in muscle invasive bladder cancer, four different aspects of immunomodulation has thus far been described; increased MHC class I expression, recruitment and proliferation of effector cells, enhancement of tumor-lytic activity of cytotoxic effectors and downregulation of immunosuppressive actors in the microenvironment. Consequently, the role of chemotherapy in cancer is changing from a therapy solely aimed at inducing tumor cell death, to a potent inducer of immune responses and a potential future major partaker in cancer immunotherapy. This is a great opportunity for the urological community to broaden research in this field in order to increase knowledge, optimize and improve the neoadjuvant regimens of muscle invasive bladder cancer to ultimately improve patient outcome.
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| 25. |
- Sherif, Amir, et al.
(författare)
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Pilot study of adoptive immunotherapy with sentinel node-derived T cells in muscle-invasive urinary bladder cancer
- 2015
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 49:6, s. 453-462
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to determine by computed tomography (CT) whether treatment with tumor-draining lymph-node-derived expanded autologous T lymphocytes results in objective responses and/or improved survival in patients with metastatic urinary bladder cancer (UBC) and to record the toxicity of the treatment.MATERIALS AND METHODS: Eighteen patients with metastatic UBC were prospectively selected from two centers. The preoperative staging was T2-T4bN1-2 and/or M0-M1 or MX. Tumor-draining lymph nodes were harvested at intended cystectomy for the extraction of T lymphocytes. This was followed by expansion of the T lymphocytes in a cell culture, and subsequent reinfusion of these autologous tumor-specific T lymphocytes. Responses to therapy were evaluated by CT scans according to Response Evaluation Criteria In Solid Tumors (RECIST) and clinical follow-up, according to the research protocol.RESULTS: Nine out of 18 patients were treated. Treatment was feasible and safe. In two out of nine immunologically treated patients, objective responses were detected in terms of diminished or obliterated nodal metastases. When excluding three patients with disseminated osseous metastases plus one with a T4b tumor left in situ, a success rate of two out of six treated patients was seen. The two responders had survival times of 35 and 11 months, respectively. No toxicity was recorded.CONCLUSIONS: Infusion of expanded autologous tumor-specific T lymphocytes is feasible and safe, and objective responses according to RECIST were recorded. One objective responder to immunotherapy displayed notably long overall survival.
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