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  • 1
    Language: English
    In: Molecular diagnosis & therapy, February 2013, Vol.17(1), pp.1-8
    Description: Prostate cancer (PCa) screening and detection have changed dramatically since the introduction of serum prostate-specific antigen (PSA) testing. Despite the resulting improvement in early PCa detection and stage migration, in clinical practice the use of PSA testing may cause overdetection and ultimately overtreatment. As a consequence, novel biomarkers are needed to increase the specificity of PCa detection. The aim of this article is to present an overview of novel blood- and urine-based biomarkers that may optimize PCa detection, with improved identification of patients with significant PCa and avoidance of unnecessary prostate biopsies. A systematic and comprehensive PubMed search was performed using the MeSH search terms 'prostate cancer', 'biomarker', 'marker', and 'detection'. Results were restricted to the English language. Several blood- and urine-based biomarkers have the potential to improve prediction of the presence and/or significance of PCa. Ideally, biomarkers should be used in combination within multivariate models, leading to superior accuracy for prediction of any PCa or clinically significant PCa, compared with the use of a single marker.
    Keywords: Early Detection of Cancer -- Methods ; Prostatic Neoplasms -- Diagnosis
    ISSN: 11771062
    E-ISSN: 1179-2000
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  • 2
    In: BJU International, December 2012, Vol.110(11b), pp.E771-E777
    Description: Byline: Jens Bedke, Felix K.-H. Chun, Axel Merseburger, Marcus Scharpf, Kathrin Kasprzyk, David Schilling, Karl-Dietrich Sievert, Arnulf Stenzl, Stephan Kruck Keywords: renal cell cancer; systemic inflammation; biomarkers; CRP; WBC; threshold; predictive accuracy What's known on the subject? and What does the study add? White blood cell count and C-reactive protein are reliable prognostic RCC Biomarkers.Nevertheless, accepted cut-offs for risk stratifications are missing. Therefore, both parameters were re-evaluated and multivariable analyses revealed an optimal CRP breakpoint at 0.25mg/dL to be best to stratify patients at risk of cancer-specific mortality. However, this CRP-based prediction added no additional information compared to a clinico-pathological based model. Objective To re-evaluate the prognostic and predictive significance of the preoperative white blood cell (WBC) count and C-reactive protein (CRP) that independently predicts patient prognosis and to determine optimal threshold values for CRP. Patients and Methods From 1996 to 2005, 327 patients with surgery for clear cell renal cell carcinoma were retrospectively evaluated. Cox proportional hazard models were used, adjusted for the effects of tumour stage, size, Fuhrman grade and Karnofsky index, to evaluate the prognostic significance of WBC count and CRP and to identify threshold values. Identified thresholds were correlated with clinicopathological parameters and used to estimate cancer-specific survival. To prove any additional predictive accuracy of the identified threshold it was compared with a clinicopathological base model using the Harrell concordance index (c-index). Results In univariable analyses WBC count was a significant prognostic marker at a concentration of 9.5/I1/4L (hazard ratio [HR] 1.83) and 11.0/I1/4L (HR 2.09) and supported CRP values of 0.25mg/dL (HR 6.47, P 0.001) and 0.5mg/dL (HR 7.15, P 0.001) as potential threshold values. If adjusted by the multivariable models WBC count showed no clear breakpoint, but a CRP value of 0.25mg/dL (HR 2.80, P = 0.027) proved to be optimal. Reduced cancer-specific survival was proved for CRP 0.25mg/dL (median 69.9 vs 92.3 months). Median follow-up was 57.5 months with 72 (22%) tumour-related deaths. The final model built by the addition of CRP 0.25mg/dL did not improve predictive accuracy (c-index 0.877) compared with the clinicopathological base model (c-index 0.881) which included TNM stage, grading and Karnofsky index. Conclusions Multivariable analyses revealed that an optimal breakpoint of CRP at a value of 0.25mg/dL was best to stratify patients at risk of cancer-specific mortality, but CRP 0.25mg/dL added no additional information in the prediction model. Therefore we cannot recommend measuring CRP as the traditional parameters of TNM stage, grading and Karnofsky index are already of high predictive accuracy. CAPTION(S): Supporting info item Testosterone levels and percentage of biopsy affected by tumour. Linear regression between the variables testosterone and percentage of tumour representation in the biopsy sample is displayed (P 0.01). In our centre, the tumour burden in the biopsy is expressed as the percentage of tumour in each prostatic lobe, ranging from 〉0% to 100%. Thus, the percentage of tumour represented in the biopsy adding the two prostatic lobes ranges from 〉0% to 200%. Testosterone levels and progression risk. Tumours were subclassified depending on their D'Amico risk of progression: low risk, PSA 10, DRE [less than or equal to] T2a and Gleason score [less than or equal to]6; intermediate risk, PSA 10-20, DRE = T2b and Gleason score 7; high risk, PSA 〉 20 or DRE a[yen] T2c or Gleason score a[yen]8. Low risk, testosterone 470 [+ or -] 171 ng/dL; intermediate risk, testosterone 445 [+ or -] 151 ng/dL; high risk, testosterone 365 [+ or -] 162 ng/dL; P= 0.03. Supporting info item
    Keywords: Renal Cell Cancer ; Systemic Inflammation ; Biomarkers ; Crp ; Wbc ; Threshold ; Predictive Accuracy
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 3
    Language: English
    In: The Journal of Urology, April 2017, Vol.197(4), pp.e988-e988
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.juro.2017.02.2212 Byline: Raisa Sinaida Pompe, Philipp Gild, Felix K. Chun Author Affiliation: Hamburg, Germany Article Note: (footnote) Source of Funding: none
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 4
    Language: English
    In: The Journal of Urology, July 2016, Vol.196(1), pp.89-94
    Description: As life expectancy increases, oncologic outcome in elderly patients 75 years old or older is a salient topic requiring further investigation. We analyzed the records of 13,997 patients who underwent radical prostatectomy from 2006 to 2013. Known prognosticators were compared according to age at radical prostatectomy in 13,732 patients younger than 75 years vs 265 patients 75 years old or older. Univariate and multivariate Cox regressions were used to estimate the impact of age on biochemical recurrence-free, metastasis-free, cancer specific and overall survival. Median followup was 47.3 months. Compared to patients younger than 75 years those 75 years old or older had a higher pathological Gleason score (p 〈0.001) and were more likely to harbor a nonorgan confined tumor (p 〈0.001), have a positive surgical margin (p = 0.004) and positive lymph nodes (p = 0.028), and receive salvage androgen deprivation therapy (p = 0.002). Five-year biochemical recurrence-free, metastasis-free, cancer specific and overall survival rates were 64.2%, 84.7%, 98.4% and 91.3% in patients 75 years old or older, and 76.9%, 96.2%, 99.0% and 96.2%, respectively, in patients younger than 75 years. On univariate and multivariate analysis age 75 years or greater was associated with worse biochemical recurrence-free and metastasis-free survival. Patients 75 years old or older were more likely to die of other causes than cancer. Nevertheless, noncancer related mortality was low. Older patients who underwent radical prostatectomy had more advanced disease. Age itself is an independent predictor of worse biochemical recurrence-free and metastasis-free survival. Healthy and highly selected patients 75 years old or older in our sample showed good long-term overall survival. Therefore, older age in well selected men should not be a contraindication to radical prostatectomy, especially in patients harboring high risk disease.
    Keywords: Prostatic Neoplasms ; Prostatectomy ; Aged ; Aged, 80 and Over ; Outcome Assessment, (Health Care) ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 5
    Language: English
    In: International Journal of Cancer, June 15, 2013, Vol.132(12), p.2948(8)
    Keywords: Immunohistochemistry -- Analysis ; Prostate Cancer -- Prognosis ; Prostate Cancer -- Analysis ; Carcinoma -- Prognosis ; Carcinoma -- Analysis
    ISSN: 0020-7136
    Source: Cengage Learning, Inc.
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  • 6
    Language: English
    In: BJU International, Sept, 2012, p.E183(8)
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2012.10936.x/abstract Byline: Jan Schmitges(1)(3)(*), Quoc-Dien Trinh(3)(5)(*), Maxine Sun(3), Jens Hansen(1)(3), Marco Bianchi(7), Claudio Jeldres(3), Paul Perrotte(4), Roland Dahlem(2), Shahrokh F. Shariat(6), Felix K. Chun(2), Francesco Montorsi(7), Mani Menon(5), Margit Fisch(2), Markus Graefen(1), Pierre I. Karakiewicz(3) Keywords: dialysis; chronic renal insufficiency; perioperative complications; nephrectomy; renal cell carcinoma Study Type - Therapy (population cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Patients with renal failure more frequently harbour RCC due to predisposing factors such as cystic disease of the kidney. The benefit of nephrectomy might be outweighed by adverse perioperative events, however, which may be more prevalent in patients with end-stage renal disease (ESRD). In a population-based study focusing on patients after non-elective colorectal surgery, patients with ESRD had an increased risk of mortality and complications. To date, small-scale studies have reported complication rates in patients with ESRD after nephrectomy for RCC with conflicting results. However, no formal contemporary analysis has been compiled within a nephrectomy cohort of adequate size. The present population-based case-control study showed that patients with ESRD are at substantially higher risk of in-hospital mortality and in-hospital complications. Specifically, we demonstrated higher cardiac-related complications, transfusion and haemorrhage/haematoma rates in patients with ESRD than in others. Moreover, patients with ESRD are more likely to have prolonged length of stay in hospital, and incur higher hospital charges. Based on the findings of the present study, use of biopsy and active surveillance for small, carefully selected renal masses might be considered in patients with ESRD at high risk of morbidity and mortality after surgery. OBJECTIVE * To examine the effect of end-stage renal disease (ESRD) on six short-term nephrectomy outcomes. PATIENTS AND METHODS * The Nationwide Inpatient Sample was used to assess the rates of blood transfusions, intra-operative and postoperative complications, length of hospital stay (LOS) within the highest quartile (〉5 days), total hospital charges within the highest quartile (〉$33 391) and in-hospital mortality. * Propensity-based matching was performed to adjust for potential baseline differences between patients with ESRD and others. * Multivariable logistic regression analyses further adjusted for confounding variables. RESULTS * Overall, 46 225 patients underwent open radical, open partial, laparoscopic radical or laparoscopic partial nephrectomy for non-metastatic kidney cancer between 1998 and 2007. * Of those, 941 patients with ESRD were identified (2.0%). * For patients with ESRD and others, the following rates were recorded, respectively: blood transfusions, 17.4 vs 9.1% (P 0.001); intra-operative complications, 3.5 vs 3.3% (P= 0.81); postoperative complications, 19.2 vs 15.6% (P= 0.007); length of stay within the highest quartile, 55.4 vs 30.1% (P 0.001); total hospital charges within the highest quartile, 50.4 vs 26.3% (P 0.001); in-hospital mortality, 2.4 vs 0.5% (P 0.001). * In multivariable logistic regression analyses, patients with ESRD were more likely to receive a blood transfusion (odds ratio [OR]= 2.05, P 0.001), to experience any postoperative complication (OR = 1.25, P= 0.019), to have a LOS within the highest quartile (OR = 3.06, P 0.001), to have hospital charges within the highest quartile (OR = 3.10, P 0.001), and to die during hospitalization (OR = 4.85, P 0.001). CONCLUSIONS * Patients with ESRD are at substantially higher risk of adverse outcomes after nephrectomy. * Most importantly, the in-hospital mortality rate is fivefold higher. Author Affiliation: (1)Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf (2)Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany (3)Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center (4)Department of Urology, University of Montreal Health Center, Montreal, QC, Canada (5)Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI (6)Weill Medical College of Cornell University, New York, NY, USA (7)Department of Urology, Vita Salute San Raffaele University, Milan, Italy Correspondence: (*) Jan Schmitges, Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, 1058, rue St-Denis, Montreal, QC, Canada H2X 3J4. e-mail: janschmitges@gmx.de Article Note: (*) These authors contributed equally to this work. Accepted for publication 9 November 2011
    Keywords: Cancer -- Complications And Side Effects ; Cancer -- Patient Outcomes ; Cancer -- Analysis ; Chronic Kidney Failure -- Complications And Side Effects ; Chronic Kidney Failure -- Patient Outcomes ; Chronic Kidney Failure -- Analysis ; Mortality -- Analysis ; Cancer Metastasis -- Complications And Side Effects ; Cancer Metastasis -- Patient Outcomes ; Cancer Metastasis -- Analysis
    ISSN: 1464-4096
    Source: Cengage Learning, Inc.
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  • 7
    Language: English
    In: BJU International, Sept, 2012, p.E183(8)
    Keywords: Cancer -- Complications And Side Effects ; Cancer -- Patient Outcomes ; Cancer -- Analysis ; Chronic Kidney Failure -- Complications And Side Effects ; Chronic Kidney Failure -- Patient Outcomes ; Chronic Kidney Failure -- Analysis ; Mortality -- Analysis ; Cancer Metastasis -- Complications And Side Effects ; Cancer Metastasis -- Patient Outcomes ; Cancer Metastasis -- Analysis
    ISSN: 1464-4096
    Source: Cengage Learning, Inc.
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  • 8
    In: International Journal of Cancer, 01 August 2015, Vol.137(3), pp.553-559
    Description: Recent studies indicate frequent early PSA retesting unrelated of men's baseline PSA, which increases the harms of early detection especially among men with low PSA. The current study investigates the PCa incidence among men with baseline PSA 〈1.0 ng ml in order to adjust retest intervals for more targeted early detection. Between 1998 and 2012, 2,416 men with baseline PSA 〈1.0 ng ml were prospectively observed. Primary endpoint was PCa diagnosis. Negative predictive value (NPV) and number needed to screen (NNS) to detect one PCa were calculated. During a median follow‐up time of 12.1 years, 54 (2.2%) PCa were diagnosed with  = 26 (48.1%) among men with baseline PSA of 0.75 ≤ 1.0 ng ml (upper baseline PSA quartile). The 10‐year probability of being diagnosed with PCa increased significantly from 0.19% (baseline PSA 〈 0.40 ng ml) to 2.0% (baseline PSA 0.40 ≤ 0.56 ng ml), 2.5% (baseline PSA 0.56 ≤ 0.75 ng ml) over 4.4% (baseline PSA 0.75 ≤ 1.0 ng ml) (all values 〈0.0001), respectively. The frequency of Gleason ≥7 PCa increased from 1 (0.17%) to 8 (1.4%), 5 (0.8) over 11 (1.8%) in these groups. The 8‐year NPV for Gleason ≥ 7 PCa were 99.8 (baseline PSA 〈 0.40 ng ml), 99.8 (baseline PSA 0.40 ≤ 0.56 ng ml), 100 (baseline PSA 0.56 ≤ 0.75 ng ml) and 99.5 (baseline PSA 0.75 ≤ 1.0 ng ml), respectively. During 12 years, the numbers were 99.8, 98.6, 99.2, and 98.2, respectively. Therefore, due to the very low rate of Gleason ≥ 7 PCa, further screening might be omitted in men with baseline PSA 〈 0.4 ng ml. Between 0.4 and 1.0 ng ml, an 8‐year interval can be discussed. What's New? Whether prostate cancer screening based on levels of prostate‐specific antigen (PSA) is beneficial is uncertain, yet early PSA retesting is on the rise in some places, leading to increased detection of low‐risk disease that may never become life‐threatening. This study explores the possibility of improving early prostate cancer detection through the adjustment of PSA retest intervals. Men with baseline PSA below 1 ng ml were observed over an average of 12 years. A very low risk of prostate cancer was found for baseline values below 0.4 ng ml, suggesting that further screening for men with such low values could be waived.
    Keywords: Prostate Cancer ; Prostate Specific Antigen ; Psa Below 1 ; Screening Interval
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 9
    In: BJU International, September 2013, Vol.112(5), pp.623-637
    Description: Byline: Michael Rink, Evanguelos Xylinas, Quoc-Dien Trinh, Yair Lotan, Vitaly Margulis, Jay D. Raman, Margit Fisch, Richard K. Lee, Felix K. Chun, Joual Abdennabi, Christian Seitz, Armin Pycha, Alexandre R. Zlotta, Pierre I. Karakiewicz, Marko Babjuk, Douglas S. Scherr, Shahrokh F. Shariat, Keywords: smoking; gender; urothelial carcinoma; transitional cell carcinoma; upper urinary tract; radical nephroureterectomy; dose relationship; recurrence; survival Objective * To evaluate the gender-specific differential effects of smoking habits and cumulative smoking exposure on outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Patients and Methods * A total of 864 consecutive patients, comprising 553 (64%) men and 311 (36%) women, from five international institutions underwent RNU without neoadjuvant chemotherapy. * Smoking history included smoking status (current, former or never), quantity of cigarettes per day (CPD), smoking duration in years and years since smoking cessation. Cumulative smoking exposure was categorized as light short-term ([less than or equal to]19 CPD and [less than or equal to]19.9 years), moderate (all combinations except light short-term and heavy long-term), and heavy long-term (a[yen]20 CPD and a[yen]20 years). * Uni- and multivariable competing risk regression models were used to assess the associations with outcomes. Results * Overall, 244 (28.2%), 297 (34.4%) and 323 (37.4%) patients were never, former and current smokers, respectively. * There were no differences in smoking status, quantity and duration between the genders. * In female ever smokers, 30 (9.6%), 121 (38.9%) and 67 (21.5%) were light short-term, moderate and heavy long-term smokers, respectively. Compared with men, female current smokers were more likely to experience disease recurrence in univariable analysis (P = 0.013). * In heavy long-term smokers, female gender was significantly associated with disease recurrence (hazard ratio [HR] 1.7; P = 0.03) and cancer-specific mortality (HR 2.0; P = 0.009) in multivariable analysis that adjusted for standard clinico-pathological features. * In female patients only, smoking quantity, duration and cumulative exposure were associated with disease recurrence and cancer-specific mortality on multivariable analyses (P [less than or equal to] 0.025). Conclusions * The impact of smoking on UTUC outcomes after RNU is gender-specific. * Females who are current and heavy long-term smokers experience worse outcomes than their male counterparts. * Further research is needed to elucidate the molecular mechanisms underlying the gender-specific differential effect of smoking on UTUC outcomes.
    Keywords: Smoking ; Gender ; Urothelial Carcinoma ; Transitional Cell Carcinoma ; Upper Urinary Tract ; Radical Nephroureterectomy ; Dose Relationship ; Recurrence ; Survival
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 10
    Language: English
    In: BJU international, December 2015, Vol.116(6), pp.911-9
    Description: To investigate whether mortality is increased for patients with metastatic prostate cancer (mCaP) admitted over the weekend. Using the Nationwide Inpatient Sample (NIS) between 1998 and 2009, admitted patients with a diagnosis of prostate cancer and concomitant metastases were identified. Rates of in-hospital mortality, complications, use of imaging and procedures were assessed. Adjusted logistic regression models examined associations of mortality and complications. A weighted sample of 534,011 patients with mCaP was identified, including 81.7% weekday and 18.3% weekend admissions. Of these, 8.6% died after a weekday vs 10.9% after a weekend admission (P 〈 0.001). Patients admitted over the weekend were more likely to be treated at rural (17.8% vs 15.7%), non-teaching (57.6% vs 53.7%) and low-volume hospitals (53.4% vs 49.4%) (all P 〈 0.001) compared with weekday admissions. They presented higher rates of organ failure (25.2% vs 21.3%), and were less likely to undergo an interventional procedure (10.6% vs 11.4%) (all P 〈 0.001). More patients admitted over the weekend had pneumonia (12.2% vs 8.8%), pyelonephritis (18.3% vs 14.1%) and sepsis (4.5% vs. 3.5%) (all P 〈 0.001). In multivariate analysis, weekend admission was associated with an increased likelihood of complications (odds ratio [OR] 1.15, 95% confidence Interval [CI] 1.11-1.19) and mortality (OR 1.20, 95% CI 1.14-1.27). In patients with mCaP weekend admissions are associated with a significant increase in mortality and morbidity. Our findings suggest that weekend patients may present with more acute medical issues; alternatively, the quality of care over the weekend may be inferior.
    Keywords: Nationwide Inpatient Sample ; Admission ; Metastatic ; Mortality ; Prostate Cancer ; Weekend ; Hospitalization -- Statistics & Numerical Data ; Prostatic Neoplasms -- Epidemiology
    ISSN: 14644096
    E-ISSN: 1464-410X
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