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Sökning: WFRF:(Aljabery Firas)

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1.
  • Jerlström, Tomas, et al. (författare)
  • No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy : a nation-wide register-based study
  • Ingår i: World Journal of Urology. - : Springer. - 0724-4983 .- 1433-8726. ; 38:2, s. 381-388
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking. Methods: We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not. Results: Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82–1.39) or mortality (OR 0.75 95% CI 0.36–1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30–0.81). Conclusion: This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.
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2.
  • Aljabery, F., et al. (författare)
  • 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
  • Ingår i: Scandinavian Journal of Urology. - : TAYLOR & FRANCIS LTD. - 2168-1805 .- 2168-1813. ; 53:5, s. 332-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To investigate the clinical management and outcome of patients with muscle-invasive bladder cancer with clinical lymph node involvement, using longitudinal nationwide population-based data. Methods: In the Bladder Cancer Data Base Sweden (BladderBaSe), treatment and survival in patients with urinary bladder cancer clinical stage T2-T4 N + M0 diagnosed between 1997 and 2014 was investigated. Patients ' characteristics were studied in relation to TNM classification, curative or palliative treatment, cancer-specific (CSS) and overall survival (OS). Age at diagnosis was categorised as <= 60, 61-70, 71-80 and >80 years, and time periods were stratified as follows: 1997-2001, 2002-2005, 2006-2010 and 2011-2014. Results: There were 786 patients (72% males) with a median age of 71 years (interquartile range = 64-79 years). The proportion of patients with high comorbidity increased over time. Despite similar low comorbidity, curative treatment was given to 44% and to 70% of those in older (>70 years) and younger age groups, respectively. Curative treatment decreased over time, but chemotherapy and cystectomy increased to 25% during the last time period. Patients with curative treatment had better survival compared to those with palliative treatment, both regarding CSS and OS in the whole cohort and in all age groups. Conclusions: The low proportion of older patients undergoing treatment with curative intent, despite no or limited comorbidity, indicates missed chances of treatment with curative intent. The reasons for an overall decrease in curative treatment over time need to be analysed and the challenge of coping with an increasing proportion of node-positive patients with clinically significant comorbidity needs to be met.
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3.
  • Aljabery, F., et al. (författare)
  • 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
  • Ingår i: Bju International. - : WILEY. - 1464-4096 .- 1464-410X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis. Patients And Methods Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patient's characteristics, UBC tumour stage at diagnosis, and site of OPC. Results There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis. Conclusions OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.
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4.
  • Alvaeus, Julia, et al. (författare)
  • Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy
  • 2019
  • Ingår i: World journal of urology. - : Springer. - 0724-4983 .- 1433-8726.
  • 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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5.
  • Hartana, C. A., et al. (författare)
  • Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer
  • 2018
  • Ingår i: ; 194:1, s. 39-53
  • 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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6.
  • Liedberg, F., et al. (författare)
  • Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study
  • 2019
  • Ingår i: Bju International. - : WILEY. - 1464-4096 .- 1464-410X. ; 124:3, s. 449-456
  • 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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7.
  • Malmström, P. U., et al. (författare)
  • Incidence, survival and mortality trends of bladder cancer in Sweden 1997–2016
  • 2019
  • Ingår i: Scandinavian Journal of Urology. - : TAYLOR & FRANCIS LTD. - 2168-1805 .- 2168-1813. ; 53:4, s. 193-199
  • 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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8.
  • Ottosson, Kristoffer, et al. (författare)
  • The increased risk for thromboembolism pre-cystectomy in patients undergoing neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer is mainly due to central venous access : a multicenter evaluation
  • 2020
  • Ingår i: ; 52:4, s. 661-669
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To investigate if patients receiving neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) had an increased risk of thromboembolic events (TEE) and to evaluate when these events occur on a timeline starting from 6 months pre-cystectomy, during NAC-administration and 60 months post-cystectomy.Methods: Two hundred and fifty five patients undergoing radical cystectomy during 2009–2014 at three Swedish cystectomy centers (Umeå, Linköping and Sundsvall) were in-detail reviewed retrospectively, using individual medical records. One hundred and twenty nine patients were ineligible for analysis. NAC patients (n = 67) were compared to NAC-naïve NAC-eligible patients (n = 59). The occurrence of TEE was divided into different periods pre-cystectomy and post-cystectomy. Statistical analyses included Chi-squared and logistical regression tests.Results: Significant associations were found between receiving NAC and acquiring a TEE during NAC therapy pre-cystectomy. All but one pre-cystectomy event was venous and all but one of the patients received NAC. 31% (14/45) of TEEs occurred pre-cystectomy. The incidence of TEEs pre-cystectomy in NAC-naive NAC-eligible patients was only 10% (2/20), whereas the incidence of TEEs in NAC patients occurred pre-cystectomy in 48% (12/25) and 11/12 incidents were detected during NAC therapy—this including 7/11 (64%) incidents affecting veins in anatomical conjunction with the placement of central venous access for chemotherapy administration.Conclusions: There is a significantly increased risk for TEE pre-cystectomy during chemotherapy administration in MIBC patients receiving NAC, compared to the risk in NAC-naïve NAC-eligible MIBC patients. In 64% of the pre-RC TEEs in NAC patients, there was a clinical connection to placement of central venous access.
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9.
  • Ahlén Bergman, Emma, et al. (författare)
  • Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
  • 2018
  • Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083. ; 10
  • 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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10.
  • Aljabery, Firas, et al. (författare)
  • M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer
  • 2018
  • Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 36:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTumor-associated macrophages (TAMs) constitute a subset of nonneoplastic cells in tumor stroma and influence cancer progression in solid tumors. The clinical significance of TAMs in urinary bladder cancer(UBC) is controversial.MethodsWe prospectively studied 103 patients with stage pT1–T4 UBC treated with cystectomy and pelvic lymph node dissection. Tumor sections were immunostained with M2-specific macrophage marker CD163 and proliferation marker Ki-67. The expression of these markers in cancer cells as well as macrophage infiltration (MI) in tumor stroma was analyzed in relation to clinical data and outcome.ResultsThe mean rate of CD163 and Ki-67 expressed by cancer cells were 35% and 78%, respectively. With borderline significance, MI was associated with lower rate of lymph node metastasis (P = 0.06). CD163 expression in cancer cells was proportional to MI (P<0.014). Patients with CD163-positive tumors and strong MI had significantly longer cancer-specific survival (CSS) (76 months), compared to patient with CD163-positive tumors and weak MI (28 months) (P = 0.02).ConclusionsM2-specific MI tends to be inversely correlated with LN metastasis and improved CSS in UBC. MI might have protective impact in CD163-positive tumors. Expression of CD163 in cancer cells is significantly correlated with MI and might have a tumor promoting impact.
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