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  • 1
    Keywords: CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; SURVIVAL ; CELL ; Germany ; IN-VIVO ; INHIBITION ; MICROSCOPY ; MODEL ; PERFUSION ; VIVO ; PROTEIN ; kidney ; MICROCIRCULATION ; REDUCTION ; TRANSPLANTATION ; RAT ; DAMAGE ; RECRUITMENT ; REJECTION ; FAILURE ; RECEPTORS ; chemokine ; ANTAGONIST ; inflammation ; endothelial cells ; ALLOGRAFT-REJECTION ; chemokines ; in vivo ; KIDNEY-TRANSPLANTATION ; ALLOGRAFT ; Allograft rejection ; ANTAGONIST VMIP-II ; Virokine ; vMIP-II
    Abstract: During rejection, leukocytes are recruited from the peripheral circulation into the graft leading to the damage of endothelial cells, capillary perfusion failure and graft loss. Chemokines play a pivotal role in the recruitment of leukocytes to the endothelium. Viral macrophage inflammatory protein-II (vMIP-II), a human herpes virus-8 DNA-encoded protein, is a broad-spectrum chemokine antagonist. The aim of the study was to prove the beneficial activity of vMIP-II treatment on acute rat kidney allograft damage. Heterotopic rat kidney transplantation was performed in the Fischer 344 to Lewis transplantation model and animals were treated with vMIP-II (2 x 15 A mu g or 100 A mu g/day) for 7 days. Rejection-induced damage was analyzed by histology, and microcirculatory changes within the graft were analyzed by in vivo microscopy. Viral macrophage inflammatory protein-II significantly improved acute glomerular damage and tubulointerstitial inflammation and lowered the extent of vascular and tubulointerstitial damage of the treated allografts. Functional microcirculation of peritubular capillaries was significantly improved in vivo, and the firm adherence of leukocytes was significantly reduced by vMIP-II treatment. The administration of the broad-spectrum antagonist vMIP-II improved acute renal allograft damage, mainly by a reduction in leukocyte recruitment with a subsequently improved renal cortical microcirculation in vivo
    Type of Publication: Journal article published
    PubMed ID: 20401660
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  • 2
    Keywords: SPECTROSCOPY ; MEN ; PREDICTION ; COIL ; DEFINITION ; ACTIVE SURVEILLANCE ; LOCAL STAGING ACCURACY
    Abstract: PURPOSE: To evaluate whether clinically significant prostate cancer (PCa) can be ruled out by high-spatial resolution T2-weighted endorectal MRI (eMRI) in a cohort of patients with biopsy-proven PCa. PATIENTS AND METHODS: A retrospective analysis was carried out for consecutive patients who underwent 1.5 Tesla eMRI for local staging before open radical prostatectomy. The cohort was dichotomized into patients with apparent or inapparent tumour on eMRI. The results were compared with final histopathology, and an analysis for presence of clinically significance PCa was performed. RESULTS: A total of 385 patients were included in the study; in 85 patients (22 %), no apparent lesion suspicious for PCa was detected on eMRI, still final pathology revealed clinically significant PCa in 61 of these patients (72 %). In contrast, 256 (85 %) of the 300 patients with apparent tumour in eMRI harboured clinically significant PCa. eMRI could not differentiate clinically significant from insignificant PCa in neither of the groups (p 〉 0.6). CONCLUSIONS: Presence of clinically significant cancer cannot be excluded by high-resolution 1.5 Tesla T2-weighted eMRI. The results of the study suggest that the role of T2-weighted eMRI for selecting patients suitable for AS is limited.
    Type of Publication: Journal article published
    PubMed ID: 23754478
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  • 3
    Keywords: CANCER ; EXPERIENCE ; COMPLICATIONS
    Abstract: PURPOSE: To test the hypothesis that MRI-TRUS fusion technique can increase the detection rate of prostate cancer (PC) in patients with previously negative biopsy. METHODS: Patient records of men with persisting suspicion for PC after previous negative biopsy having undergone either extensive transrectal prostate biopsies (MD Anderson protocol; MDA), transperineal saturation (STP) or magnetic resonance imaging (MRI)/transrectal ultrasound (TRUS) fusion transperineal biopsies (MTTP) in three consecutive time intervals were reviewed retrospectively. The respective approach was the standard for the above indication at these episodes. In Cambridge, 70 patients underwent MDA biopsies, 75 STP underwent biopsies and 74 patients underwent MTTP biopsies. In total, 164 MTTP patients with the same indication from Heidelberg were analysed as reference standard. In total, 383 men were included into analysis. Low-grade PC was defined as Gleason score 7 (3 + 4) or lower. RESULTS: Even though MTTP patients had significantly larger prostates, the overall cancer detection rate for PC was the highest in MTTP (24.2 % MDA, 41.3 % STP, 44.5 % MTTP, p = 0.027, Kruskal-Wallis test). The detection rate for clinically relevant high-grade PC was highest in MTTP; however, this did not reach statistical significance compared with MDA (23.5 % MDA, 12.9 % STP, 27.2 % MTTP, p = 0.25, Fischer's exact test). Comparing MTTP between Cambridge and Heidelberg, detection rates did not differ significantly (44.5 vs. 48 %, p = 0.58). There was a higher detection rate of high-grade cancer in Heidelberg. (36.3 vs. 27.2 %, p = 0.04). CONCLUSION: Patients whom are considered for repeat biopsies may benefit from undergoing MRI-targeted TRUS fusion technique due to higher cancer detection rate of significant PC.
    Type of Publication: Journal article published
    PubMed ID: 24917295
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  • 4
    Abstract: PURPOSE: To report the outcome and course of disease in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel followed by abiraterone acetate in a single center. METHODS: In this retrospective observational study, we reviewed the course of disease of all applicable patients with mCRPC treated with docetaxel followed by abiraterone at our center. We analyzed progression-free survival (PFS) of docetaxel and abiraterone treatments. We further searched for predictive factors for the duration of treatment response. RESULTS: Median PFS between initiation of androgen deprivation therapy and the diagnosis of mCRPC was 32 months. Median PFS on docetaxel treatment was 9 months. Median PFS on abiraterone treatment was 11 months. Patients with higher Gleason scores (GS) (8-10) at initial diagnosis had a significantly longer median PFS on docetaxel as compared to patients with GS 6-7, p = 0.01. We demonstrate a significant correlation between the PFS on docetaxel and PFS on abiraterone in the post-docetaxel setting (Kendall tau r = 0.32, p = 0.019) as well as a significant negative correlation between the PSA nadir under abiraterone treatment and the time to progression under abiraterone (Kendall tau r = -0.43, p = 0.007). CONCLUSIONS: High Gleason score appears to be predictive of duration of response to docetaxel. Interestingly, progression-free survival with abiraterone appears to be correlated with the duration of response with docetaxel, whereas PSA decline and low nadir appear to be predictive of response to abiraterone.
    Type of Publication: Journal article published
    PubMed ID: 25113804
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  • 5
    Keywords: ASSOCIATION ; OBESITY ; GLUCOSE ; HYPERTENSION ; MELLITUS ; METAANALYSIS ; ALL-CAUSE MORTALITY ; Nephrectomy ; PROSTATE-CANCER RISK
    Abstract: PURPOSE: To evaluate the influence of type 2 diabetes on cancer-specific outcome in patients undergoing surgery for localized renal cell carcinoma (RCC). METHODS: A total of 1,140 patients with localized RCC undergoing radical or partial nephrectomy were enrolled into this retrospective case-control study. Primary outcome was the cancer-specific survival comparing patients with and without type 2 diabetes at the time of surgery. Secondary outcomes were recurrence-free survival and metastases-free survival comparing the same groups. Additionally, the influence of accompanying factors on cancer-specific survival and overall survival of patients was evaluated in a multivariate analysis. Among 1,140 patients included in the analyses, 202 had diabetes at the time of surgery and 938 patients without diabetes served as control. RESULTS: The univariate comparisons between patients with and without diabetes regarding recurrence-free, metastases-free, and cancer-specific survival revealed no significant differences. Multivariate results demonstrate that age, BMI, and diabetes had no significant effect on cancer-specific hazard among participants. After adjustment of the factors in terms of overall survival, however, increased age, increased BMI, and type 2 diabetes at the time of surgery were independent risk factors for the occurrence of the event death. CONCLUSIONS: Type 2 diabetes and obesity at the time of surgery have no significant impact on cancer-specific and recurrence-free survival in patients with localized renal cancer.
    Type of Publication: Journal article published
    PubMed ID: 24370691
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  • 6
  • 7
    Abstract: PURPOSE: To establish consensus on follow-up (FU) after focal therapy (FT) in renal masses. To formulate recommendations to aid in clinical practice and research. METHODS: Key topics and questions for consensus were identified from a systematic literature research. A Web-based questionnaire was distributed among participants selected based on their contribution to the literature and/or known expertise. Three rounds according to the Delphi method were performed online. Final discussion was conducted during the "8th International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer" among an international multidisciplinary expert panel. RESULTS: Sixty-two participants completed all three rounds of the online questionnaire. The panel recommended a minimum follow-up of 5 years, preferably extended to 10 years. The first FU was recommended at 3 months, with at least two imaging studies in the first year. Imaging was recommended biannually during the second year and annually thereafter. The panel recommended FU by means of CT scan with slice thickness 〈/=3 mm (at least three phases with excretory phase if suspicion of collecting system involvement) or mpMRI. Annual checkup for pulmonary metastasis by CT thorax was advised. Outside study protocols, biopsy during follow-up should only be performed in case of suspicion of residual/persistent disease or radiological recurrence. CONCLUSIONS: The consensus led to clear FU recommendations after FT of renal masses supported by a multidisciplinary expert panel. In spite of the low level of evidence, these recommendations can guide clinicians and create uniformity in the follow-up practice and for clinical research purposes.
    Type of Publication: Journal article published
    PubMed ID: 27106492
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  • 8
    Keywords: CANCER ; Germany ; PROSTATE ; DISEASE ; HISTORY ; incidence ; NEW-YORK ; POPULATION ; RISK ; RISKS ; SITE ; SITES ; GENE ; GENES ; PATIENT ; kidney ; FAMILY ; MEMBER ; MEMBERS ; SUSCEPTIBILITY ; BREAST-CANCER ; etiology ; PROSTATE-CANCER ; SWEDEN ; DATABASE ; SIR ; familial risk ; NATIONWIDE ; FAMILY-CANCER DATABASE ; GUIDELINES ; GENOMIC MEDICINE ; TESTICULAR CANCER ; CELL TUMORS ; familial cancers,heritable cancer,clinical counseling,urology ; LINDAU-DISEASE
    Abstract: Familial risks for cancer are important for clinical counseling and understanding cancer etiology. The nationwide Swedish Family-Cancer Database includes all Swedes born in 1932 and later (0 to 68-year-old offspring) with their parents, totaling over 10.2 million individuals. Urological cancer cases were retrieved from the Swedish Cancer Registry up to year 2000. Standardized incidence ratios (SIR) and 95% confidence limits (CI) were calculated for age-specific familial risk in offspring by an exact proband status. The familial risks for offspring cancer were increased at all urological sites from concordant cancer in the parent and in a sibling proband. The highest SIRs by parent were for testicular and prostate cancer (4.26 and 2.45). When a sibling was affected, even kidney cancer (4.74) showed a high SIR. For kidney cancers, and also for prostate and testicular cancers, the SIRs were higher among siblings than among offspring and parents, which may indicate the involvement of recessive effects. Family members of patients with prostate cancer or von Hippel Lindau disease can expect organized clinical counseling, but family members of patients with other urological cancers are probably not counseled. Guidelines for clinical counseling or action level should be developed for all urological cancers because of the established familial risks. Urological cancers also offer a challenge to molecular geneticists attempting to identify the susceptibility genes underlying the familial clustering
    Type of Publication: Journal article published
    PubMed ID: 14615900
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  • 9
    Keywords: CANCER ; RISK ; TIME ; ANTIGEN ; SPECTROSCOPY ; MEN ; prostate cancer ; FEASIBILITY ; ultrasound ; COIL ; detection rate ; 1.5 T ; ROUTINE ; PSA ; TRUS ; MRI-guided biopsy ; Significant carcinoma
    Abstract: PURPOSE: To investigate the positive biopsy rate of MRI-guided biopsy (MR-GB) in a routine clinical setting, identify factors predictive for positive biopsy findings and to report about the clinical significance of the diagnosed tumors. METHODS: Patients with at least one negative trans-rectal-ultrasound-guided biopsy (TRUS-GB), persistently elevated or rising serum prostate specific antigen (PSA) and at least one lesion suspicious for PCa on diagnostic 1.5 Tesla endorectal coil MRI (eMR) were included. Biopsies were carried out using a 1.5 Tesla MRI and an 18 G biopsy gun. Clinical information and biopsy results were collected; logistic regression analysis was carried out. Definite pathology reports of patients with diagnosis of PCa and subsequent radical prostatectomy (RP) were analyzed for criteria of clinical significance. RESULTS: One hundred patients were included, mean number of previous biopsies was 2 (range 1-9), mean PSA at time of biopsy was 11.7 ng/ml (1.0-65.0), and mean prostate volume was 46.7 ccm (range 13-183). In 52/100 (52.0%) patients, PCa was detected. Out of 52 patients, 27 patients with a positive biopsy underwent RP, 20 patients radiation therapy, and 5 patients active surveillance. In total, 80.8% of the patients revealed a clinically significant PCa. In univariate regression analysis, only serum PSA levels were predictive for a positive biopsy result. Number of preceding negative biopsies was not associated with the likelihood of a positive biopsy result. CONCLUSIONS: MR-GB shows a high detection rate of clinically significant PCa in patients with previous negative TRUS-GB and persisting suspicion for PCa.
    Type of Publication: Journal article published
    PubMed ID: 21512807
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  • 10
    Keywords: EPIDEMIOLOGY ; MORTALITY ; RISK ; BREAST ; FRANCE ; UNITED-STATES ; EUROPE ; BODY-MASS INDEX ; AFRICAN MIGRANTS ; NEW-SOUTH-WALES
    Abstract: The large international variation in the incidence of prostate cancer (PC) is well known but the underlying reasons are not understood. We want to compare PC incidence and survival among immigrants to Sweden in order to explain the international differences. Cancer data were obtained from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for PC in first-degree immigrants by country of birth. The immigrants were classified into four groups by SIR and area of origin. Survival in PC was assessed by hazard ratio (HR) in the four groups. In some analyses, clinical stage of PC was assessed by the tumor, node, and metastasis classification. The SIR was 0.47 (95 % confidence interval 0.43-0.51) for immigrants with the lowest risk, constituting men from Turkey, Middle East, Asia, and Chile. The HR was 0.60 (0.45-0.81) for these men and it was 0.49 if they had stayed 20+ years in Sweden. The SIR in screening detected PC, T1c, was 0.55. Among these men, screening detected PC constituted 34.5 % of all PC, compared to 29.0 % among Swedes (p = 0.10). The results showed that the non-European immigrants, of mainly Middle East, Asian, and Chilean origin, with the lowest risk of PC, also had the most favorable survival in PC. As the available clinical features of PC at diagnosis or the distribution of known risk factors could not explain the differences, a likely biological mechanism through a favorable androgenic hormonal host environment is suggested as an explanation of the observed effects.
    Type of Publication: Journal article published
    PubMed ID: 23306784
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