| 51. |
- Dabestani, Saeed, et al.
(författare)
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Renal cell carcinoma recurrences and metastases in primary non-metastatic patients : a population-based study
- 2016
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Ingår i: World journal of urology. - New York, USA : Springer. - 0724-4983 .- 1433-8726. ; 34:8, s. 1081-1086
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To present the occurrence of metastases and local recurrences in primary non-metastatic patients with renal cell carcinoma (RCC) in a contemporary Swedish population-based cohort.Methods: Between 2005 and 2009, a total of 4527 patients were included in the prospective National Swedish Kidney Cancer Register accounting for nearly all RCC patients in Sweden. Among M0 patients, 472 (13 %) had no follow-up data registered within 5-year follow-up time and were excluded from the analysis.Results: In total, 939 (21 %) had distant metastases at presentation with a decrease from 23 to 18 % during the inclusion period. Of 3107 patients with follow-up data and with M0 disease, 623 (20 %) were diagnosed with a tumor recurrence during 5-year follow-up. Mean time to recurrence was 24 months (SD ± 20 months). Among these, 570 patients (92 %) were at primary diagnosis treated with radical nephrectomy, 23 patients (3.7 %) with partial nephrectomy and 12 patients (1.9 %) with minimally invasive treatments. The most frequent sites of metastases were lung (54 %), lymph nodes (22 %) and bone (20 %). The treatment of recurrence was in 50 % systemic treatments, while metastasectomy was performed in 17 % of the patients, out of which 68 % were with a curative intention.Conclusions: In this population-based study, 21 % of the patients had metastatic disease at presentation, with a decreasing trend over the study period. During 5-year follow-up, 20 % of the primary non-metastatic patients had recurrent disease. Of the patients with recurrence, half were given systemic oncological treatment and 17 % underwent metastasectomy.
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| 52. |
- Dahlin, Britt-Inger, et al.
(författare)
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Preoperative carbohydrate drink in a randomized study improves postoperative quality of life after urological surgery.
- 2009
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Ingår i: International Journal of Urological Nursing. - : Wiley Blackwell. - 1749-771X. ; 3:2, s. 64-68
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Recently, fast track treatment in surgery has been advocated. Fasting time has been cut down to attenuate preoperative discomfort as irritable and preoperative thirst. We accessed effects of preoperative carbohydrate drink on preoperative quality of life (QOL) including hospitalization time, drinking first day, gut emptying, and return to work. A total of 170 patients scheduled for nephrectomy or prostatectomy were randomized to carbohydrate drink or overnight fasting. Responses a modified QLQ-C30 questionnaire were collected before and one month after surgery. In patients treated with prostatectomy to the variables: did you worry, total health and total QOL improved, while most (19 of 30) variables were impaired. Nephrectomy patients had significantly fewer parameters with impaired QOL than prostatectomy (p = 0.01). There was significant weight loss despite surgical procedure (p < 0.001). When comparing the carbohydrate and control groups, there was no difference concerning age, sex and stages. After prostatectomy, only the QOL variable “worry” improved (p = 0.027) in the carbohydrate group. After nephrectomy, the carbohydrate group had less weight loss (p = 0.035) than controls and had improved QOL as: “short of breath” (p = 0.038), “feel tense” (p = 0.057), “worry” (p = 0.035), and “interfered social activities” (p = 0.024). There was no difference in hospitalization time, drinking 1st day, time to gut emptying, and return to normal activities between the groups, despite surgical procedure. Carbohydrate drink before surgery significantly improved QOL variables such as “worry”, “tense”, and “social activities”. Weight loss was significantly reduced compared with controls after nephrectomy. Thus, carbohydrate drinking before elective surgery improves postoperative QOL parameters, but not postoperative drinking and hospitalization time.
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| 53. |
- de Alwis, Roger, et al.
(författare)
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Identification and validation of NFIA as a novel prognostic marker in renal cell carcinoma
- 2023
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Ingår i: The journal of pathology. Clinical research. - : John Wiley & Sons. - 2056-4538. ; 9:4, s. 261-272
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Tidskriftsartikel (refereegranskat)abstract
- Prognostic tools are an essential component of the clinical management of patients with renal cell carcinoma (RCC). Although tumour stage and grade can provide important information, they fail to consider patient- and tumour-specific biology. In this study, we set out to find a novel molecular marker of RCC by using hepatocyte nuclear factor 4A (HNF4A), a transcription factor implicated in RCC progression and malignancy, as a blueprint. Through transcriptomic analyses, we show that the nuclear factor I A (NFIA)-driven transcription network is active in primary RCC and that higher levels of NFIA confer a survival benefit. We validate our findings using immunohistochemical staining and analysis of a 363-patient tissue microarray (TMA), showing for the first time that NFIA can independently predict poor cancer-specific survival in clear cell RCC (ccRCC) patients (hazard ratio = 0.46, 95% CI = 0.24–0.85, p value = 0.014). Furthermore, we confirm the association of HNF4A with higher grades and stages in ccRCC in our TMA cohort. We present novel data that show HNF4A protein expression does not confer favourable prognosis in papillary RCC, confirming our survival analysis with publicly available HNF4A RNA expression data. Further work is required to elucidate the functional role of NFIA in RCC as well as the testing of these markers on patient material from diverse multi-centre cohorts, to establish their value for the prognostication of RCC.
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| 54. |
- Eichelberg, Christian, et al.
(författare)
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Diagnostic and prognostic molecular markers for renal cell carcinoma : a critical appraisal of the current state of research and clinical applicability.
- 2009
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Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 55:4, s. 851-63
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Earlier detection of renal cell carcinoma (RCC) and the recent expansion of treatment possibilities have positively influenced the outlook for patients with this disease. However, progression and treatment response are still not sufficiently predictable. Molecular markers could help to refine individual risk stratification and treatment planning, although they have not yet become clinically routine. OBJECTIVE: This review presents an overview of diagnostic and prognostic molecular markers for RCC and a subgrouping of these markers for different clinical issues. EVIDENCE ACQUISITION: Literature and recent meeting abstracts were searched using these terms: renal (cell) carcinoma, molecular/tumor markers, biopsy, blood, urine, disease progression/prognosis, immunohistochemistry, risk factors, and survival. Due to the resulting large number of articles, studies were subjectively selected according to the importance of a study on the field, number of investigated patients, originality, multivariate analyses performed, contrast with previously published data, actuality, and assumed clinical applicability of the described results. More then 90% of the selected studies originated from the past 10 yr; >50% of the articles were written in 2006 or later. EVIDENCE SYNTHESIS: These data were predominantly obtained via nonrandomized, retrospective, but often controlled studies. Thereby, the resulting level of evidence is 2A/2B. The broad spectrum of described molecular markers (MMs) for RCC consists of markers already extensively studied in other malignancies (eg, p53), as well as MMs typically associated with specific RCC-altered gene functions and pathways (eg, von Hippel-Lindau [VHL]). The main goal of using MMs is to refine the prediction of clinical end points like tumor progression, treatment response, and cancer-specific and/or overall survival. Further, MMs might facilitate the clinical work-up of undefined renal masses and prove to be more convenient tools for screening and follow-up in blood and urine. CONCLUSIONS: Presently, there are a number of promising MMs for diverse clinical questions, but the available data are not yet valid enough for routine, clinical application. We should comply with the demand for large multicenter prospective investigations, stratified for RCC type and treatment modalities, to lift the use of molecular markers in RCC to a practical level, thereby providing a better consultation for our patients regarding diagnosis, treatment, and follow-up.
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| 55. |
- Escudier, Bernard, et al.
(författare)
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Multidisciplinary management of metastatic renal cell carcinoma in the era of targeted therapies
- 2012
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Ingår i: Cancer Treatment Reviews. - : Elsevier. - 0305-7372 .- 1532-1967. ; 38:2, s. 127-132
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Forskningsöversikt (refereegranskat)abstract
- The use of targeted agents to treat metastatic renal cell carcinoma (mRCC) has significantly extended progression-free and overall survival but raises issues relating to the long-term delivery of care and the sustained monitoring of efficacy and toxicities, certain of which have not previously been experienced. In this paper, an expert group of medical oncologists, urologists and oncology nurses and pharmacists review and make informal recommendations on the multidisciplinary management of mRCC in the light of progress made and problems that have arisen. Decentralisation of care, with a shift in emphasis from large to small hospitals and possibly to the community, may offer advantages of cost and convenience. However, the major responsibility for care should continue to lie with clinicians (either medical oncologists or urologists) with extensive experience in mRCC, assisted by specialist nurses, and working in centres with facilities adequate to monitor efficacy and manage toxicities. That said, the extended survival of patients emphasises the importance of compliance and the long-term prevention, detection and management of side effects. Much of this will take place in the community. There is therefore a need for multidisciplinary working to extend beyond specialist centres to include general practitioners, community nurses and pharmacists. Although this paper focuses on mRCC, many of the considerations discussed are also relevant to the management of more common solid tumours in the era of targeted therapy.
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| 56. |
- Fallara, Giuseppe, et al.
(författare)
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Recurrence pattern in localized RCC : results from a European multicenter database (RECUR)
- 2022
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 40:11, s. 494.e11-494.e17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern.Material and methods: This is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed.Results: After matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18–3.58, P-value = 0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01–1.16; P-value = .04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64–1.06; P-value = .14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study.Conclusions: The risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS.
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| 57. |
- Fernández-Pello, Sergio, et al.
(författare)
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A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:3, s. 426-436
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Forskningsöversikt (refereegranskat)abstract
- Context While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown. Objective To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC. Evidence acquisition Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken. Evidence synthesis The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03–1.92 and 1.41, 95% CI: 0.88–2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67–2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9–2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91–1.86). Sunitinib was associated with more Grade 3–4 adverse events than everolimus, although this was not statistically significant. Conclusions This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed. Patient summary We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.
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| 58. |
- Fernández-Pello, Sergio, et al.
(författare)
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Management of Sporadic Renal Angiomyolipomas : A Systematic Review of Available Evidence to Guide Recommendations from the European Association of Urology Renal Cell Carcinoma Guidelines Panel
- 2020
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 3:1, s. 57-72
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Forskningsöversikt (refereegranskat)abstract
- Context: Little is known about the natural history of sporadic angiomyolipomas (AMLs); there is uncertainty regarding the indications of treatment and treatment options. Objective: To evaluate the indications, effectiveness, harms, and follow-up of different management modalities for sporadic AML to provide guidance for clinical practice. Evidence acquisition: A systematic review of the literature was undertaken, incorporating Medline, Embase, and the Cochrane Library (from 1 January 1990 to 30 June 2017), in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No restriction on study design was imposed. Patients with sporadic AML were included. The main interventions included active surveillance, surgery (nephron-sparing surgery and radical nephrectomy), selective arterial embolisation, and percutaneous or laparoscopic thermal ablations (radiofrequency, microwaves, or cryoablation). The outcomes included indications for active treatment, AML growth rate, AML recurrence rate, risk of bleeding, post-treatment renal function, adverse events of treatments, and modalities of followup. Risk of bias assessment was performed using standard Cochrane methods. Evidence synthesis: Among 2704 articles identified, 43 were eligible for inclusion (zero randomised controlled trials, nine nonrandomised comparative retrospective studies, and 34 single-arm case series). Most studies were retrospective and uncontrolled, and had a moderate to high risk of bias. Conclusions: In active surveillance series, spontaneous bleeding was reported in 2% of patients and active treatment was undertaken in 5%. Active surveillance is the most chosen option in 48% of the cases, followed by surgery in 31% and selective arterial embolisation in 17% of the cases. Selective arterial embolisation appeared to reduce AML volume but required secondary treatment in 30% of the cases. Surgery (particularly nephron-sparing surgery) was the most effective treatment in terms of recurrence and need for secondary procedures. Thermal ablation was an infrequent option. The association between AML size and the risk of bleeding remained unclear; as such the traditional 4-cm cut-off should not per se trigger active treatment. In spite of the limitations and uncertainties relating to the evidence base, the findings may be used to guide and inform clinical practice, until more robust data emerge. Patient summary: Sporadic angiomyolipoma (AML) is a benign tumour of the kidney consisting of a mixture of blood vessels, fat, and muscle. Large tumours may have a risk of spontaneous bleeding. However, the size beyond which these tumours need to be treated remains unclear. Most small AMLs can be monitored without any active treatment. For those who need treatment, options include surgical removal of the tumour or stopping its blood supply (selective embolisation). Surgery has a lower recurrence rate and lower need for a repeat surgical procedure.
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| 59. |
- Figueroa, Jonine D., et al.
(författare)
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Genome-wide association study identifies multiple loci associated with bladder cancer risk
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:5, s. 1387-1398
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Tidskriftsartikel (refereegranskat)abstract
- andidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
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| 60. |
- Figueroa, Jonine D., et al.
(författare)
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Genome-wide interaction study of smoking and bladder cancer risk
- 2014
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 35:8, s. 1737-1744
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Tidskriftsartikel (refereegranskat)abstract
- Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 x 10(-5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 x 10(-7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 x 10-7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.
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