| 1. |
- Bruins, Harman M, et al.
(författare)
-
The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer : a systematic review
- 2014
-
Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 66:6, s. 1065-1077
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19 793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.
|
|
| 2. |
- Gakis, Georgios, et al.
(författare)
-
EAU Guidelines on Primary Urethral Carcinoma
- 2013
-
Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 64:5, s. 823-830
-
Tidskriftsartikel (refereegranskat)abstract
- Context: The European Association of Urology (EAU) Guidelines Group on Muscle-Invasive and Metastatic Bladder Cancer prepared these guidelines to deliver current evidence-based information on the diagnosis and treatment of patients with primary urethral carcinoma (UC).Objective: To review the current literature on the diagnosis and treatment of patients with primary UC and assess its level of scientific evidence.Evidence acquisition: A systematic literature search was performed to identify studies reporting urethral malignancies. Medline was searched using the controlled vocabulary of the Medical Subject Headings database, along with a free-text protocol.Evidence synthesis: Primary UC is considered a rare cancer, accounting for <1% of all malignancies. Risk factors for survival include age, tumour stage and grade, nodal stage, presence of distant metastasis, histologic type, tumour size, tumour location, and modality of treatment. Pelvic magnetic resonance imaging is the preferred method to assess the local extent of urethral tumour; computed tomography of the thorax and abdomen should be used to assess distant metastasis. In localised anterior UC, urethra-sparing surgery is an alternative to primary urethrectomy in both sexes, provided negative surgical margins can be achieved. Patients with locally advanced UC should be discussed by a multidisciplinary team of urologists, radiation oncologists, and oncologists. Patients with noninvasive UC or carcinoma in situ of the prostatic urethra and prostatic ducts can be treated with a urethra-sparing approach with transurethral resection and bacillus Calmette-Guerin (BCG). Cystoprostatectomy with extended pelvic lymphadenectomy should be reserved for patients not responding to BCG or as a primary treatment option in patients with extensive ductal or stromal involvement.Conclusions: The 2013 guidelines document on primary UC is the first publication on this topic by the EAU. It aims to increase awareness in the urologic community and provide scientific transparency to improve outcomes of this rare urogenital malignancy.
|
|
| 3. |
- Hu, J., et al.
(författare)
-
The effects of chemotherapeutic drugs on human monocyte-derived dendritic cell differentiation and antigen presentation
- 2013
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 172:3, s. 490-499
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies indicate that chemotherapeutic agents may increase the anti-tumoral immune response. Based on the pivotal role of dendritic cells (DCs) in host tumour-specific immune responses, we investigated the effect of commonly used chemotherapeutic drugs dexamethasone, doxorubicin, cisplatin and irinotecan and glucocorticoids on monocyte-derived DCs (moDCs). Dexamethasone displayed the strongest inhibitory effect on DC differentiation. The effect of cisplatin and irinotecan was moderate, while only weak effects were noticed for doxorubicin. Surprisingly, when the functional consequence of chemotherapy-treated CD14+ monocytes and their capacity to activate CD4+ T responders cells were investigated, cisplatin-treated monocytes gave rise to increased T cell proliferation. However, dexamethasone, doxorubicin and irinotecan-pretreated monocytes did not stimulate any increased T cell proliferation. Further investigation of this observation revealed that cisplatin treatment during DC differentiation up-regulated significantly the interferon (IFN)- transcript. By contrast, no effect was evident on the expression of interleukin (IL)-1, tumour necrosis factor (TNF)-, IL-6 or IFN- transcripts. Blocking IFN- attenuated the cisplatin-enhanced T cell proliferation significantly. In conclusion, cisplatin treatment enhanced the immune stimulatory ability of human monocytes, a mechanism mediated mainly by the increased production of IFN-.
|
|
| 4. |
|
|
| 5. |
- Marits, Per, et al.
(författare)
-
The many flavors of tumor-associated B cells
- 2013
-
Ingår i: Oncoimmunology. - : Landes Bioscience. - 2162-4011 .- 2162-402X. ; 2:8, s. e25237-
-
Tidskriftsartikel (refereegranskat)abstract
- Little is known on the role of distinct B-cell subtypes in human malignancies. We have recently performed a multiplex characterization of B cells in patient-derived tumor-associated tissues, documenting the activation and antigen-driven differentiation of B cells in metastatic lymph nodes and neoplastic lesions. Here we discuss the role of B lymphocytes as antigen-presenting cells and catalysts of T cell-based immunotherapies in view of these findings.
|
|
| 6. |
- Porserud, Andrea, et al.
(författare)
-
The effects of a physical exercise programme after radical cystectomy for urinary bladder cancer. A pilot randomized controlled trial.
- 2014
-
Ingår i: Clinical Rehabilitation. - : Sage Publications. - 0269-2155 .- 1477-0873. ; 28:5, s. 451-459
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Assessment of feasibility and effects of an exercise training programme in patients following cystectomy due to urinary bladder cancer.Design: Single-blind, pilot, randomized controlled trial.Setting:University hospital, Sweden.Subjects: Eighteen patients (64-78 years), of 89 suitable, cystectomized due to urinary bladder cancer, were randomized after hospital discharge to intervention or control.Interventions: The 12-week exercise programme included group exercise training twice a week and daily walks. The control group received only standardized information at discharge.Main outcome measures: Trial eligibility and compliance to inclusion were registered. Assessments of functional capacity, balance, lower body strength and health-related quality of life (HRQoL) with SF-36.Results: Out of 122 patients 89 were eligible, but 64 did not want to participate/were not invited. Twenty-five patients were included, but 7 dropped out before randomization. Eighteen patients were randomized to intervention or control. Thirteen patients completed the training period. The intervention group increased walking distance more than the control group, 109 m (75-177) compared to 62 m (36-119) (P = 0.013), and role physical domain in SF-36 more than the control group (P = 0.031). Ten patients were evaluated one year postoperatively. The intervention group had continued increasing walking distance, 20 m (19-36), whereas the control group had shortened the distance -15.5 m (-43 to -5) (P = 0.010).Conclusions: A 12-week group exercise training programme was not feasible for most cystectomy patients. However, functional capacity and the role-physical domain in HRQoL increased in the short and long term for patients in the intervention group compared with controls.
|
|
| 7. |
- Rosenblatt, Robert, et al.
(författare)
-
Pathologic Downstaging Is a Surrogate Marker for Efficacy and Increased Survival Following Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Urothelial Bladder Cancer
- 2012
-
Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 61:6, s. 1229-1238
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Characterising responders to neoadjuvant chemotherapy (NAC) is important to minimise overtreatment and the unnecessary delay of definitive treatment of urothelial urinary bladder cancer.Objective: To assess the effect of NAC on tumour downstaging and overall survival.Design, setting, and participants: A total of 449 patients from the randomised prospective Nordic Cystectomy Trials 1 and 2 were analysed retrospectively. Eligible patients were defined as T2–T4aNXM0 preoperatively and pT0–pT4aN0−N + M0 postoperatively. The median follow-up time was 5 yr.Intervention: The experimental arm consisted of cisplatin-based NAC; the control arm consisted of cystectomy only.Measurements: The primary outcome was tumour downstaging defined as pathologic TNM less than clinical TNM. Different downstaging thresholds were applied: complete downstaging (CD) (pT0N0), noninvasive downstaging (NID) (pT0/pTis/pTaN0), and organ confinement (OC) (≤pT3aN0). Downstaging rates and nodal status were compared between the study arms using the chi-square test. Secondary outcome was overall survival (OS) stratified by treatment arm, downstaging categories, and clinical stages, analysed by the Kaplan-Meier method. The following covariates were tested as prognostic factors in univariate and multivariate analyses using the Cox regression method: age, sex, clinical stage, pN status, NAC, CD, NID, and OC.Results and limitations: Downstaging rates increased significantly in the NAC arm independent of the downstaging threshold. The impact was more prominent in clinical T3 tumours, with a near threefold increase in CD tumours. The combination of CD and NAC showed an absolute risk reduction of 31.1% in OS at 5 yr compared with CD controls. The combination of NAC and CD revealed a hazard ratio of 0.32 compared with 1.0 for the combination of no NAC and no CD. Limitations were the retrospective approach and uncertain clinical TNM staging.Conclusions: Survival benefits of NAC are reflected in downstaging of the primary tumour. Chemo-induced downstaging might be a potential surrogate marker for OS.
|
|
| 8. |
- Shah, Carl-Henrik, et al.
(författare)
-
Vascular endothelial growth factor receptor 2, but not S100A4 or S100A6, correlates with prolonged survival in advanced urothelial carcinoma
- 2014
-
Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 32:8, s. 1215-1224
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A major challenge in muscle-invasive urothelial carcinoma (UC) is to identify biomarkers that can predict disease prognosis and treatment response after cystectomy. Therefore, we analyzed the potential prognostic value of the proteins vascular endothelial growth factor receptor 2 (VEGFR2), S100A4, and S100A6 in UC.METHODS: Retrospective outcome data and tumor specimens from 83 cystectomy patients with histologically confirmed invasive UC were included. Expression levels of VEGFR2 (also called flk-1 and KDR), S100A4, and S100A6 were analyzed in primary tumor tissue by immunohistochemistry.RESULTS: Immunohistochemical staining and analysis of VEGFR2, S100A4, and S100A6 showed localization mainly in tumor cell cytoplasm. High VEGFR2 expression and low tumor category were independent variables associated with longer overall survival (OS) and disease-free survival, revealed by a bivariate Cox proportional hazards regression model (both P<0.001). In addition, the univariate log-rank test and the Cox model demonstrated that OS beyond 2 years was significantly greater among patients with low S100A6 expression than in those with high S100A6 expression (P = 0.017 and 0.022, respectively). Differences in tumor expression of S100A4 were not significantly associated with outcome.CONCLUSION: In this study, VEGFR2 expression was significantly correlated with risk of disease relapse and OS in a defined cohort of patients with UC of the bladder treated by cystectomy.
|
|
| 9. |
- Sherif, Amir M, et al.
(författare)
-
Sentinel node detection in renal cell carcinoma. A feasibility study for detection of tumour-draining lymph nodes.
- 2012
-
Ingår i: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 109:8, s. 1134-1139
-
Tidskriftsartikel (refereegranskat)abstract
- Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? This is the first presented results and second publication on detection of tumour-draining lymph nodes in human renal cell carcinoma. Techniques are displayed and tumour-draining patterns are presented. OBJECTIVE: • To evaluate the feasibility of performing sentinel node detection in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: • An open series of 13 arbitrarily selected patients with T1b-T3b RCC scheduled for radical nephrectomy at a single Tertiary Academic Centre were examined with different modalities of sentinel node detection. • Preoperative ultrasonography-guided injection of radioactive isotope, lymphoscintigram and single photon emission computed tomography/computed tomography, followed by intraoperative gamma-probe detection and Patent Blue detection, as well as postoperative scintigram of the main specimen were the planned interventions. • These investigations were performed in conjunction with intended open radical nephrectomy. RESULTS: • In 10 of the 13 patients sentinel node detection was achieved with 32 sentinel nodes displayed. • Radio-guided surgery using an intraoperative gamma-probe resulted in the highest realtive detection rate with detection of sentinel nodes in nine patients. • In total, nine metastatic sentinel nodes were detected in three patients. • One patient, preoperatively staged as N+, was restaged after sentinel node detection and histopathology as pN0. CONCLUSIONS: • Sentinel node detection in renal tumours is feasible although evaluation of different modes of detection needs further refinement and standardization. • All nodes preoperatively detected by routine computed tomography as suspicious metastatic lesions were confirmed as sentinel nodes, including two nodes considered as metastatic by preoperative routine imaging but ultimately staged as non-metastatic sentinel nodes.
|
|
| 10. |
- Winerdal, Malin E, et al.
(författare)
-
FOXP3 and survival in urinary bladder cancer
- 2011
-
Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 108:10, s. 1672-1678
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To investigate the possible impact of FOXP3 expression in T-cells, as well as in tumour cells, on long-term survival in patients with urinary bladder cancer (UBC) invading muscle.PATIENTS AND METHODS:In a retrospective study, tumour specimens from 37 patients cystectomized for T1-T4 UBC during 1999-2002 at the Karolinska University Hospital were examined by immunohistochemistry for tumour expression and/or infiltration of immune cells expressing FOXP3 as well as CD3. The results obtained were correlated with clinicopathological parameters, where the primary and secondary outcomes investigated were overall survival and progression-free survival, respectively.RESULTS:Infiltration of CD3(+) and FOXP3(+) lymphocytes (≥3 cells per high-power field) were both correlated with better survival, and this relationship persisted throughout the whole study period (all P < 0.05). Patients with FOXP3(+) tumour cells had decreased long-term survival compared to those patients with FOXP3(-) tumours (P < 0.05). Despite a limited amount of patient material, the results of the present study indicate that FOXP3 expression, in both lymphocytes and tumour cells, is an important prognostic factor in UBC.CONCLUSIONS:FOXP3 expression in UBC cells is associated with decreased long-term survival and thus may be a novel negative prognostic factor in UBC invading muscle. By contrast, the presence of FOXP3(+) tumour-infiltrating lymphocytes was correlated with a positive prognosis. Because FOXP3 is up-regulated upon activation in human T-cells, FOXP3 may serve more as an activation marker than as a regulatory T-cell indicator in this case. These results support the need for larger prospective studies aiming to confirm the results obtained and to examine the underlying mechanisms in detail.
|
|
