| 1. |
- Abrahamsson, Johan, et al.
(författare)
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Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder : Association with tumor stage, lymph node metastases, FDG-PET findings, and survival
- 2017
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Ingår i: Urologic Oncology. - : Elsevier BV. - 1078-1439. ; 35:10, s. 9-606
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are currently no methods in clinical use that can detect early systemic dissemination of urothelial tumor cells. Objective: To evaluate measurement of circulating tumor cells (CTCs) as a biomarker for disseminated disease in patients with advanced bladder cancer. Design, setting, and participants: Between March 2013 and October 2015, 88 patients were prospectively included in the study: 78 were scheduled for radical cystectomy (RC) ± perioperative chemotherapy and 10 treated with palliative chemotherapy. The CellSearch CTC test was further assessed in this context by investigating expression of epithelial cell adhesion molecule (EpCAM) in primary tumors obtained at cystectomy from an independent cohort of 409 patients. Outcome measurements and statistical analysis: Presence of CTCs was tested for association with tumor stage, lymph node metastases, metastatic disease on [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cancer-specific and progression-free survival. Results: CTCs were detected in 17/88 patients (19%). In 61 patients who underwent FDG-PET-computed tomography (CT), a statistically significant association with presence of CTCs was found for radiological metastatic disease but not for normal PET-CT results (12/35 [34%] vs. 2/26 [8%], P = 0.014). After a median follow-up time of 16.5 months (95% CI: 9.6-21.4), presence of CTCs was associated with an increased risk of progression among patients treated with RC with or without perioperative chemotherapy (n = 75, P = 0.049). A multivariate analysis adjusted for clinical tumor stage, clinical lymph node status, and age showed that CTCs were an independent marker of progression (n = 75; hazard ratio = 2.78; 95% CI: 1.005-7.69; P = 0.049) but not of cancer-specific death (P = 0.596). In 409 cystectomised patients, more than 392 (96%) of the bladder tumors expressed EpCAM. Conclusions: CTCs were present in 19% of patients with advanced urothelial tumors and were associated with metastatic disease on FDG-PET-CT and with increased risk of disease progression after RC. A significant portion of urothelial cancer cells do express EpCAM and can thus be identified using EpCAM-antigen-based CTC detection methods.
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| 2. |
- Bain, C. C., et al.
(författare)
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Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors
- 2013
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 6:3, s. 498-510
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages (m phi) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete m phi populations carry out these distinct functions or if resident m phi change during inflammation. We show here that most resident m phi in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII hi, but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int) cells is present in resting colon and it expands during experimental colitis. Ly6C(hi) CCR2(+) monocytes can give rise to all m phi subsets in both healthy and inflamed colon and we show that the CX3CR1int pool represents a continuum in which newly arrived, recently divided monocytes develop into resident CX3CR1 hi m phi. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory m phi. Phenotypic analysis of human intestinal m phi indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory m phi in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD.
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| 3. |
- Boström, Peter J., et al.
(författare)
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Clinical markers of morbidity, mortality and survival in bladder cancer patients treated with radical cystectomy : A systematic review
- 2020
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 54:4, s. 267-276
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Forskningsöversikt (refereegranskat)abstract
- Context: Radical cystectomy and pelvic lymph node dissection (RC and PLND) are an essential part of the treatment paradigm in high risk bladder cancer. However, these patients have high rates of morbidity and mortality related both to the treatment and to the disease.Objective:To provide overview of current literature about clinical markers that can be used to predict and improve BC-patient outcomes at the time of RC and PLND and to study if they are properly validated.Evidence acquisition: A systematic literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria between January 1990 and October 2018 to identify English written original and review articles relevant to this topic. Prospective and retrospective studies were included.Evidence synthesis: There are several risk factors identified from non-randomised trials that can be improved before surgery to reduce perioperative mortality and morbidity. These include poor nutritional status, anaemia, renal function and smoking. Preoperative nomograms have also been developed to help decision-making and to inform patients about the risks of surgery. They can be used to estimate risk of postoperative mortality after RC and PLND with accuracy varying from 70 to 86%. These nomograms are largely based on retrospective data. Likewise, nomograms developed to calculate estimates about patient's overall and cancer specific survival have the same limitations.Conclusion: Clinical markers to predict morbidity, mortality and survival in patients with bladder cancer treated with RC and PLND may help to improve patient outcomes and treatment decision-making, but available data come from small retrospective trials and have not been properly validated. Prospective, multi-centre studies are needed to implement and disseminate predictive clinical markers and nomograms such that they can be utilised in treatment decision-making in daily practice.
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| 4. |
- Burger, Maximilian, et al.
(författare)
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ICUD-EAU International Consultation on Bladder Cancer 2012: Non-Muscle-Invasive Urothelial Carcinoma of the Bladder
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:1, s. 36-44
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Forskningsöversikt (refereegranskat)abstract
- Context: Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach. Objective: To critically review the recent data on the management of NMIBC to arrive at a general consensus. Evidence acquisition: A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched. Evidence synthesis: The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies. Conclusions: Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 5. |
- Engilbertsson, Helgi, et al.
(författare)
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TURBT Can Cause Seeding of Cancer Cells into the Bloodstream.
- 2015
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 193:1, s. 53-57
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Tidskriftsartikel (refereegranskat)abstract
- TURBT is the initial diagnostic procedure in bladder cancer (BC). Hypothetically, tumor resection could induce seeding of cancer cells into the circulation and subsequent metastatic disease. The objective of this study was to ascertain whether TURBT induces measurable seeding of cancer cells into the vascular system.
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| 6. |
- Gudjonsson, Sigurdur, et al.
(författare)
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Can tissue microarray-based analysis of protein expression predict recurrence of stage Ta bladder cancer?
- 2011
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 1651-2065 .- 0036-5599. ; 45, s. 270-277
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Being able to predict the recurrence or progression of non-muscle-invasive bladder cancer would facilitate effective planning of treatments and follow-up. Biomarkers are needed that can supply prognostic information beyond that provided by clinical and pathological parameters. Tissue microarray (TMA)-based analysis of Ta bladder tumours was used to investigate the prognostic value of expression of several proteins involved in bladder carcinogenesis. Material and methods. Tumour tissue from 52 patients with Ta bladder cancer was investigated. At least three 0.6 mm punch cores from each tumour were placed in a paraffin array block. Tumour expression of tumour protein 53 (TP53), CDH1 (E-cadherin), proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX2), fibroblast growth factor receptor-3 (FGFR3) and epidermal growth factor receptor (EGFR) was quantified by immunohistochemistry (IHC) and correlated with time to recurrence. Median follow-up time was 3.1 years. Whole-section IHC analysis was performed to validate significant findings. Results. Of all patients, 69% (36/52) experienced recurrence. In univariate analysis, recurrence was associated with multifocality, number of earlier recurrences and a low quantity score for EGFR. In a multivariate model, a low EGFR quantity score was correlated with early recurrence (hazard ratio = 5.5, p = 0.003). However, whole-section IHC results for EGFR differed markedly from the TMA findings (κ = 0.07) and no association with time to recurrence was found (p = 0.65). Conclusions. Expression of EGFR measured by TMA-IHC, but not by whole-section IHC, was associated with early recurrence. The results suggest that the proteins assessed have no predictive value for recurrences. Concerns are raised regarding the methodology and generalization of results obtained with TMA-IHC.
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| 7. |
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| 8. |
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| 9. |
- Gudjonsson, Sigurdur, et al.
(författare)
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Incontinent urinary diversion.
- 2008
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Ingår i: BJU International. - 1464-4096. ; 102:9 Pt B, s. 1320-1325
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Tidskriftsartikel (refereegranskat)
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| 10. |
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| 11. |
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| 12. |
- Gudjonsson, Sigurdur
(författare)
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Recurrent Non-Muscle-Invasive Bladder Cancer
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A characteristic feature of non-muscle-invasive bladder cancer (NMIBC) is the high risk of recurrent disease after primary treatment. Although only a minority of cases eventually progress to a life-threatening muscle-invasive tumour, it is necessary to conduct long-term follow-up with repeated cystoscopies. In addition to the negative mental and physical impact that this has on the patient, the examinations and the treatments of recurrence, impose an economic burden on the health care system. This thesis deals with various aspects of recurrent NMIBC. Paper I describes the present study of the genetic relationship between primary and recurrent tumours which revealed that in some cases there are fewer genetic aberrations in the latter than in the former. This finding contradicts the existance of a direct monoclonal relationsship between a primary and a recurrent tumour, although those lesions do show remarkably similar gene expression, which suggests that both are derived from a common progenitor cell. Paper II reports findings demonstrating that the voided urine marker, UroVysion® assay is too insensitive to replace cystoscopy in the follow-up of NMIBC patients. The results discussed in Paper III imply that only patients at low risk of recurrence benefit from early intravesical chemotherapy, and this disagrees with the European Association of Urology, which currently recommends that this treatment be given to all patients with presumed NMIBC. Paper IV demonstrates that biopsies from non-tumourous areas of bladder and prostatic urethra offer only about 50% sensitivity for carcinoma in situ (CIS). Lastly, as outlined in Paper V, none of the gene markers studied by the tissue microarray technique (i.e, TP53, CDH1, FGFR3, COX2, EGFR) were found to be associated with recurrence, but concerns were raised regarding the reliability of this methodology.
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| 13. |
- Gudjonsson, Sigurdur, et al.
(författare)
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Should All Patients with Non-Muscle-Invasive Bladder Cancer Receive Early Intravesical Chemotherapy after Transurethral Resection? The Results of a Prospective Randomised Multicentre Study.
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 55, s. 773-780
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To decrease recurrences in non-muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours. OBJECTIVE: To study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: In this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80mg of epirubicin in 50ml of saline intravesically within 24h of TUR or no further treatment after TUR. MEASUREMENTS: The primary end point was time to first recurrence. RESULTS AND LIMITATIONS: A total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0-2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for those with a risk score of >/=3 were 81% and 85%, respectively (p=0.35). CONCLUSIONS: A single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.
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| 14. |
- Gudjonsson, Sigurdur, et al.
(författare)
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The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)
- 2012
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 110:2B, s. E41-E45
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (greater than= 2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.
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| 15. |
- Gudjonsson, Sigurdur, et al.
(författare)
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The Value of the UroVysion((R)) Assay for Surveillance of Non-Muscle-Invasive Bladder Cancer.
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 54:2, s. 402-408
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally followed by repeat cystoscopy and urine cytology. A fluorescence in situ hybridisation technique called UroVysion((R)) (UV) is now available for clinical diagnosis of urothelial cancer cells. The aim of the present study was to compare UV analysis with routine follow-up methods. METHODS: We studied an unselected cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in 2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay. The UV assay was evaluated with regards to sensitivity, specificity, and positive predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed. UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70% sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The specificity of UV was 95%. UV detected all six CIS cases in the study and was predictive in two additional patients who developed CIS within 1 yr of inclusion. Cytology was positive in four of those eight CIS cases and atypical in the other four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of patients with non-muscle-invasive bladder cancer, but it may be valuable as a supplement to traditional measures for detecting CIS. Before any conclusions can be drawn regarding the efficacy of novel markers of bladder cancer, they must be studied in bladder cancer patients undergoing endoscopic surveillance.
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| 16. |
- Gudjonsson, Sigurdur, et al.
(författare)
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Urothelial carcinoma of the upper urinary tract
- 2009
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Ingår i: Imaging in Oncological Urology. - London : Springer London. - 9781846285141 ; , s. 115-119
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 17. |
- Hautmann, Richard E., et al.
(författare)
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ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary Diversion
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:1, s. 67-80
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Forskningsöversikt (refereegranskat)abstract
- Context: A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications. Objective: To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD). Evidence acquisition: An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis. Evidence synthesis: Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%. Conclusions: RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 18. |
- Heidenblad, Markus, et al.
(författare)
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Tiling resolution array CGH and high density expression profiling of urothelial carcinomas delineate genomic amplicons and candidate target genes specific for advanced tumors.
- 2008
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Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 1:Jan 31
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Urothelial carcinoma (UC) is characterized by nonrandom chromosomal aberrations, varying from one or a few changes in early-stage and low-grade tumors, to highly rearranged karyotypes in muscle-invasive lesions. Recent array-CGH analyses have shed further light on the genomic changes underlying the neoplastic development of UC, and have facilitated the molecular delineation amplified and deleted regions to the level of specific candidate genes. In the present investigation we combine detailed genomic information with expression information to identify putative target genes for genomic amplifications. METHODS: We analyzed 38 urothelial carcinomas by whole-genome tiling resolution array-CGH and high density expression profiling to identify putative target genes in common genomic amplifications. When necessary expression profiling was complemented with Q-PCR of individual genes. RESULTS: Three genomic segments were frequently and exclusively amplified in high grade tumors; 1q23, 6p22 and 8q22, respectively. Detailed mapping of the 1q23 segment showed a heterogeneous amplification pattern and no obvious commonly amplified region. The 6p22 amplicon was defined by a 1.8 Mb core region present in all amplifications, flanked both distally and proximally by segments amplified to a lesser extent. By combining genomic profiles with expression profiles we could show that amplification of E2F3, CDKAL1, SOX4, and MBOAT1 as well as NUP153, AOF1, FAM8A1 and DEK in 6p22 was associated with increased gene expression. Amplification of the 8q22 segment was primarily associated with YWHAZ (14-3-3-zeta) and POLR2K over expression. The possible importance of the YWHA genes in the development of urothelial carcinomas was supported by another recurrent amplicon paralogous to 8q22, in 2p25, where increased copy numbers lead to enhanced expression of YWHAQ (14-3-3-theta). Homozygous deletions were identified at 10 different genomic locations, most frequently affecting CDKN2A/CDKN2B in 9p21 (32%). Notably, the latter occurred mutually exclusive with 6p22 amplifications. CONCLUSION: The presented data indicates 6p22 as a composite amplicon with more than one possible target gene. The data also suggests that amplification of 6p22 and homozygous deletions of 9p21 may have complementary roles. Furthermore, the analysis of paralogous regions that showed genomic amplification indicated altered expression of YWHA (14-3-3) genes as important events in the development of UC.
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| 19. |
- Holmer, Magnus, et al.
(författare)
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Extended lymph node dissection in patients with urothelial cell carcinoma of the bladder: can it make a difference?
- 2009
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 1433-8726 .- 0724-4983. ; 27, s. 521-526
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We compared extended and limited lymph node dissections performed during radical cystectomy with regard to impact on survival and time to recurrence in bladder cancer patients. METHODS: We analyzed 170 patients who underwent radical cystectomy for urothelial carcinoma between January 1997 and December 2005. From 1997 to 2000, 69 of the patients were subjected to limited lymph dissection that included perivesical nodes and nodes in the obturator fossa. In 2001-2005, the remaining 101 patients underwent extended lymph dissection that included perivesical nodes; nodes in the obturator fossa; the internal, external, and common iliac nodes; and the presacral nodes. RESULTS: Tumors penetrating the bladder wall (pT3 and pT4a) were more common in the extended than in the limited dissection group (48 and 33%, respectively). The median numbers of lymph nodes removed in the two groups were 37 and 8, respectively. Lymph node metastases were detected in 38% of the extended dissection patients but only in 17% of the limited dissection patients. There was no significant difference in survival or time to recurrence between the two groups. Subgroup analyses showed a significantly longer time to recurrence (HR 0.45, 95% CI 0.22-0.93; P = 0.032) in patients with non-organ-confined disease who underwent extended lymph node dissection. In a multivariate analysis adjusting for tumor stage, lymph node status, age, sex, and adjuvant chemotherapy, there was a significantly improved survival (HR 0.47, 95% CI 0.25-0.88; P = 0.018) and time to recurrence (HR 0.42, 95% CI 0.23-0.79; P = 0.007) in the patients with extended lymph node dissections. CONCLUSIONS: Extended lymph node dissection did not improve disease-specific survival, but was in multivariate analysis related to significantly improved disease-specific survival and prolonged time to recurrence in radical cystectomy patients. These results should be interpreted cautiously, since they might have been affected by stage migration and the shorter follow-up in the extended dissection group.
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| 20. |
- Holmkvist, Petra, et al.
(författare)
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A major population of mucosal memory CD4(+) T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.
- 2015
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:3, s. 545-558
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.87.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Jin, Yuesheng, et al.
(författare)
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Distinct mitotic segregation errors mediate chromosomal instability in aggressive urothelial cancers.
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:6, s. 1703-1712
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Chromosomal instability (CIN) is believed to have an important role in the pathogenesis of urothelial cancer (UC). The aim of this study was to evaluate whether disturbances of mitotic segregation contribute to CIN in UC, if these processes have any effect on the course of disease, and how deregulation of these mechanisms affects tumor cell growth. Experimental Design: We developed molecular cytogenetic methods to classify mitotic segregation abnormalities in a panel of UC cell lines. Mitotic instabilities were then scored in biopsies from 52 UC patients and compared with the outcome of tumor disease. Finally, UC cells were exposed in vitro to a telomerase inhibitor to assess how this affects mitotic stability and cell proliferation. Results: Three distinct chromosome segregation abnormalities were identified: (a) telomere dysfunction, which triggers structural rearrangements and loss of chromosomes through anaphase bridging; (b) sister chromatid nondisjunction, which generates discrete chromosomal copy number variations; and (c) supernumerary centrosomes, which cause dramatic shifts in chromosome copy number through multipolar cell division. Chromosome segregation errors were already present in preinvasive tumors and a high rate mitotic instability was an independent predictor of poor survival. However, induction of even higher levels of the same segregation abnormalities in UC cells by telomerase inhibition in vitro led to reduced tumor cell proliferation and clonogenic survival. Conclusion: Several distinct chromosome segregation errors contribute to CIN in UC, and the rate of such mitotic errors has a significant effect on the clinical course. Efficient tumor cell proliferation may depend on the tight endogenous control of these processes.
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