| 1. |
- Aljabery, Firas, et al.
(författare)
-
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
-
Ingår i: BJU International. - : Blackwell Publishing. - 1464-4096 .- 1464-410X. ; 126:5, s. 625-632
-
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.
|
|
| 2. |
- Mezheyeuski, Artur, et al.
(författare)
-
The ratio of CD8+ lymphocytes to CD68+CD163+ macrophages is prognostic in immunogenic tumors and predicts immunotherapy response
-
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.
|
|
| 3. |
- Micke, Patrick, et al.
(författare)
-
The prognostic impact of the tumour stroma fraction : A machine learning-based analysis in 16 human solid tumour types
- 2021
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 65
-
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.
|
|
| 4. |
- Mezheyeuski, Artur, et al.
(författare)
-
An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers
- 2023
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 88
-
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.
|
|
| 5. |
- Hedegaard, Jakob, et al.
(författare)
-
Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
-
Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
-
Tidskriftsartikel (refereegranskat)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
|
|
| 6. |
- Thulin, Helena, et al.
(författare)
-
Defecation disturbances after cystectomy for urinary bladder cancer
- 2011
-
Ingår i: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 108:2, s. 196-203
-
Tidskriftsartikel (refereegranskat)abstract
- What’s known on the subject? and What does the study add?Functional gastrointestinal symptoms and problems are common after radical cystectomy with urinary diversion. This study adds new important epidemiological data on this group of symptoms. OBJECTIVE: To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS: During their follow-up we attempted to contact all men and women aged 30–80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS: The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS: Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.
|
|
| 7. |
- Jahnson, Staffan, et al.
(författare)
-
Swedish National Registry of Urinary Bladder Cancer : no difference in relative survival over time despite more aggressive treatment
- 2016
-
Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 50:1, s. 14-20
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. MATERIALS AND METHODS: All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. RESULTS: The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. CONCLUSIONS: This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.
|
|
| 8. |
- Malmström, Per-Uno, et al.
(författare)
-
AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial
- 2010
-
Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 16:12, s. 3279-3287
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Immunotherapy with Bacillus Calmette-Guerin (BCG) instillation is recommended for high-risk, non-muscle invasive bladder cancer. Bacillus Calmette-Guerin is not effective in advanced tumors, and better alternatives are warranted. Immunostimulating gene therapy with adenoviral vectors expressing CD40 ligand (AdCD40L) has shown efficacy in tumor models. CD40 ligand stimulates systemic immunity and may be effective in local and invasive human disease.EXPERIMENTAL DESIGN: Patients with invasive bladder cancer scheduled for cystectomy or patients with T(a) tumors were enrolled in a phase I/IIa trial. Patients were treated with three cycles of intrabladder Clorpactin WCS-90 prewash, followed by AdCD40L instillation 1 week apart. Safety, gene transfer, immune effects, and antitumor responses were monitored.RESULTS: All eight recruited patients were treated as scheduled, and therapy was well tolerated. The main adverse effect was transient local pain during prewash. Postoperatively, urinary tract infections and one case of late septicemia with elevated potassium were reported. No adverse events were ascribed to vector therapy. Gene transfer was detected in biopsies, and bladders were heavily infiltrated with T cells. The effector marker IFN-gamma increased in biopsies, whereas levels of circulating T regulatory cells were reduced. Histologic evaluation indicated that AdCD40L therapy reduced the load of malignant cells.CONCLUSIONS: To our knowledge, this is the first report on immunogene therapy in bladder cancer and the first using AdCD40L in vivo. Local AdCD40L gene therapy was safe, boosted immune activation, and should be further evaluated as a single or an adjuvant therapy for urothelial malignancies.
|
|
| 9. |
- Malmström, Per-Uno, et al.
(författare)
-
Role of hexaminolevulinate-guided fluorescence cystoscopy in bladder cancer: critical analysis of the latest data and European guidance
- 2012
-
Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 46:2, s. 108-116
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL-FC has a role in improving detection of NMIBC and provide recommendations on situations for its use. Since the publication of the EAU guidelines and the European consensus statement, new evidence on the efficacy of HAL-FC in reducing recurrence of NMIBC, compared with white light cystoscopy (WLC), have been published. Material and methods. To consider whether these new trials have an impact on the expert guidelines and on clinical practice (e. g. supporting existing recommendations or providing evidence for a change or expansion of practice), a group of bladder cancer experts from Denmark, Finland, Norway and Sweden met to address the following questions: What is the relevance of the new data on HAL-FC for clinical practice in managing NMIBC? What impact do the new data have on European guidelines? How could HAL-FC be used in clinical practice? and What further information on HAL-FC is required to optimize the management of NMIBC? Results and conclusions. This article reports the outcomes of the discussion at the Nordic expert panel meeting, concluding that, in line with European guidance, HAL-FC has an important role in the initial detection of NMIBC and for follow-up of patients to assess tumour recurrence after WLC. It provides practical advice, with an algorithm on the use of this diagnostic procedure for urologists managing NMIBC.
|
|
| 10. |
- Bergengren, Oskar, et al.
(författare)
-
Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study
- 2023
-
Ingår i: Ejso. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 49:4, s. 868-874
-
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/).
|
|
