Publications by authors named "Ulla Roggenbuck"

30 Publications

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Cross-sectional analysis of pulsatile hemodynamics across the adult life span: reference values, healthy and early vascular aging: the Heinz Nixdorf Recall and the MultiGeneration Study.

J Hypertens 2019 12;37(12):2404-2413

Institute for Medical Informatics, Biometry, and Epidemiology.

Background: Pulsatile hemodynamics predict major cardiovascular events. We aimed to provide comprehensive population-based reference values and to compare different measures of pulsatile hemodynamics to define early vascular aging (EVA) as well as healthy vascular aging (HVA).

Methods: In 2721 participants from the population-based Heinz Nixdorf Recall Study and the associated MultiGeneration Study, free from diabetes, cardiovascular disease, and antihypertensive drugs, we performed high-fidelity radial tonometry, calibrated waveforms with brachial blood pressures and processed them with a validated transfer function, pulse wave analysis, and wave separation analysis. Aortic pulse wave velocity (aoPWV) was estimated with a validated regression formula. HVA was defined as the lowest, EVA as the highest age-specific decile of central pulse pressure (cPP), backward wave amplitude, and aoPWV.

Results: Overall, 56.4% of participants were female, age range 18-90 years. Brachial PP increased from middle age, whereas cPP increased across the entire adult life span. Wave reflections increased across all age groups, apart from a plateau in older male participants. Indices of wave reflection were higher in women than in men. AoPWV showed the most prominent rise with age in both sexes. EVA and HVA, defined by cPP and backward wave amplitude, differed mainly by hemodynamic variables. In contrast, EVA participants were characterized by a worse hemodynamic, anthropometric, metabolic, and inflammatory profile, if aoPWV was used to discriminate EVA and HVA.

Conclusion: Age-specific and sex-specific reference values for central pulsatile hemodynamics in a general white population cohort are provided and may be utilized to define HVA and EVA.
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December 2019

Experience with One-Stage Repair of Urethral Strictures Using the Augmented Anastomotic Repair Technique.

Urol Int 2018 2;100(4):386-396. Epub 2018 May 2.

Section of Reconstructive Urologic Surgery, Kliniken Essen-Mitte, Essen, Germany.

Introduction: We report the results of augmented anastomotic repair (AAR) in the treatment of anterior urethral strictures.

Material And Methods: In this retrospective study, we evaluated 71 consecutive patients who had undergone AAR between June 2004 and June 2013. Medical records were reviewed to identify early postoperative complications based on the Clavien-Dindo classification (CDC). Self-developed standardized questionnaires sent to the patients and referring urologists were used to collect data on late complications (>90) days. Stricture recurrence (SR) was defined as any postoperative endoscopic or open surgical intervention on the urethra. The influence of patient demographics, stricture characteristics, and operative procedure performed on the occurrence of SR was analyzed.

Results: Early postoperative complications were rare events (11.3%) with only one severe CDC complication. Late complications were reported in 46.5% cases. At a median follow-up of 17 months (range 3-114 months), however, 64 patients had no evidence of SR and required no further intervention, giving an overall success rate of 90.1%. Seven patients with SR had a higher body mass index, were older, and had been operated on by less experienced surgeon(s). Most SRs occurred within the first year after surgery.

Conclusions: AAR was an effective and safe operative technique that allowed one-stage repair in our patients with anterior urethral strictures who needed resection of the scarred urethra and otherwise were not suitable for primary anastomosis or simple substitution urethroplasty.
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January 2019

Value of Progression of Coronary Artery Calcification for Risk Prediction of Coronary and Cardiovascular Events: Result of the HNR Study (Heinz Nixdorf Recall).

Circulation 2018 02 15;137(7):665-679. Epub 2017 Nov 15.

Institute for Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Germany (N.L. R.E., S. Moebus, A.S., U.R., K.-H.J.).

Background: Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events.

Methods: In 3281 participants (45-74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed.

Results: We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1-Q3, 23-360] versus 8 [0-83], <0.0001; similar for hard/total cardiovascular events). Some progression algorithms added to the predictive value of baseline CT and risk assessment in terms of C-statistic or integrated discrimination index, especially for total cardiovascular events. However, CAC progression did not improve models including CAC and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CAC=CAC=0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CAC progressed from 1 to 399 to CAC≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC=400. Participants with CAC≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively).

Conclusions: CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk.
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February 2018

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

Genes (Basel) 2017 Jul 17;8(7). Epub 2017 Jul 17.

Department of Animal Physiology, University of Cologne, 50674 Cologne, Germany.

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the locus in a gene-based approach ( = 1.2 × 10; = 0.020). This was driven by the AD subsample. No association with was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.
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July 2017

Accelerated progression of coronary artery calcification in hypertension but also prehypertension.

J Hypertens 2016 11;34(11):2233-42

aInstitute for Medical Informatics, Biometry & Epidemiology bDepartment of Cardiology cInstitute of Clinical Chemistry and Laboratory Medicine, University Clinic Essen, Essen dDepartment of Cardiology, Krankenhaus Bethanien, Moers, Germany eDepartment of Epidemiology, Boston University, Massachusetts, USA fInstitute of Medical Sociology, University Clinic Düsseldorf, Düsseldorf gAlfried Krupp Hospital Essen, Essen hDiagnosticum, Mülheim iInstitute of Diagnostic and Interventional Radiology, University Witten/Herdecke, Witten, Germany *Nils Lehmann and Raimund Erbel contributed equally to the article.

Objective: To determine the role of hypertension for coronary artery calcification (CAC) progression.

Methods: The population-based Heinz Nixdorf Recall study recruited 4814 participants from a German urban population in 2000-2003. CAC was measured using electron-beam computed tomography at baseline and after 5 years. The present analyses refer to 3481 participants with repeat scan (coronary heart disease until 5 years excluded, age at baseline 45-74 years, and 53.1% women). Blood pressure (BP), Framingham risk factors, and antihypertensive medication were recorded at baseline. BP was staged according to Joint National Committee 7 guidelines. Participants under antihypertensive medication were classified as stage 2. CAC at 5 years was predicted from baseline using our dedicated, publicly available algorithm. CAC progression was accordingly classified as slow, expected, or rapid.

Results: Normotension was found in 20.5%, prehypertension in 27.2%, stage 1 hypertension in 15.8%, and stage 2 (ST2) in 36.5%. The frequency of rapid progression increases with BP stage (normotension: 16.7% to ST2: 21.1%, P = 0.004). Risk factor adjusted relative risk [RR (95% confidence interval), reference: normotension] of rapid progression was for prehypertension: 1.22 (0.98;1.51), stage 1: 1.29 (1.01;1.65), and ST2: 1.45 (1.17;1.79). Risk factor adjusted measures of CAC progression per 10 mmHg SBP were already elevated in women with BP below 140/90 mmHg: CAC onset, RR = 1.22 (1.07;1.40), rapid progression, RR = 1.17 (1.05;1.31), 5-year CAC progression, 6.7% (0.5;13.4). In men below 140/90 mmHg, only RR of rapid progression was considerably increased [RR = 1.11 (0.96;1.29)].

Conclusion: CAC progression, a sign of ongoing target organ damage, is already accelerated in prehypertensive patients, a substantial proportion of our urban population.
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November 2016

Noncoronary Measures Enhance the Predictive Value of Cardiac CT Above Traditional Risk Factors and CAC Score in the General Population.

JACC Cardiovasc Imaging 2016 10 20;9(10):1177-1185. Epub 2016 Jul 20.

Department of Cardiology, West-German Heart Center, University of Duisburg-Essen, Essen, Germany.

Objectives: The aim of this study was to determine whether noncoronary measures from cardiac computed tomography (CT) may enhance the prognostic value of this imaging technology.

Background: When cardiac CT is performed for quantification of coronary artery calcium (CAC) score, information on other cardiac and thoracic structures is available.

Methods: Participants without known cardiovascular disease from the prospective population based Heinz Nixdorf Recall study underwent noncontrast cardiac CT for CAC score quantification. From CT, epicardial adipose tissue (EAT) volume, left ventricular and left atrial (LA) axial area index, ascending and descending aortic diameters, as well as aortic valve, mitral ring, and thoracic aortic calcification (TAC) were assessed. Incident cardiovascular events included myocardial infarction, stroke, and cardiovascular death. The prognostic value of CT-derived parameters was assessed by Cox regression analysis, receiver operating characteristics, and net reclassification improvement.

Results: From 3,630 subjects (59 ± 8 years of age, 46% male), 241 (6.6%) developed a cardiovascular event during 9.9 ± 2.6 years of follow-up. In multivariable Cox regression analysis including Framingham Risk Score, CAC (as log[CAC + 1]), and CT parameters, LA index (hazard ratio [HR]: 1.22 [95% confidence interval [CI]: 1.05 to 1.41] per SD; p = 0.010) and EAT volume (HR: 1.15 [95% CI: 1.01 to 1.30] per SD; p = 0.031) were significantly associated with incident events. In addition, presence of TAC showed an elevated event rate (HR: 1.33 [95% CI: 0.97 to 1.81]; p = 0.08), whereas all other CT-derived parameters showed no relevant association. The LA index, EAT volume, and presence of TAC together improved the prediction of events over Framingham Risk Score and CAC in receiver operating characteristics analysis (area under the curve: 0.749 to 0.764; p = 0.011), and let to a significant net reclassification improvement (HR: 38.0%; 95% CI: 25.1% to 50.8%).

Conclusion: Assessment of LA index, EAT volume, and TAC from non-contrast-enhanced cardiac CT improves the prediction of incident hard cardiovascular events above CAC and established risk factors, indicating that quantification of these noncoronary measures may improve the prognostic value of this imaging technology.
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October 2016

Resting heart rate is an independent predictor of all-cause mortality in the middle aged general population.

Clin Res Cardiol 2016 Jul 23;105(7):601-12. Epub 2016 Jan 23.

Clinic of Cardiology, West-German Heart and Vascular Center Essen, University Clinic Essen, Essen, Germany.

Background: High resting heart rate (RHR) predicts cardiovascular outcomes in patients with vascular disease and heart failure. We evaluated the prognostic value of RHR in a large contemporary population-based, prospective cohort of individuals without known coronary artery disease.

Methods And Results: Resting heart rate (RHR) was determined in 4091 individuals (mean age 59.2 ± 7.7; 53 % women) from the Heinz Nixdorf RECALL study, of whom, 3348 were free of heart rate lowering medication. During 10.5 years of follow-up (median), 159 (3.9 %) individuals developed a coronary event and 398 (9.7 %) died of any cause. Persons without any event (n = 3603) had similar heart rates as persons with coronary events (69.5 ± 11 versus 69.9 ± 11 bpm, p = 0.51) but lower heart rates than persons who died (72.3 ± 13 bpm, p < 0.0001). In individuals without heart rate lowering medication, an increase in heart rate by 5 bpm was associated with an increased hazard ratio (HR) for all-cause mortality of 13 % in unadjusted analysis and also upon adjustment for traditional cardiovascular risk factors, including coronary artery calcification [full model: HR (95 % CI) 1.13 (1.07-1.20), p < 0.0001], but not for coronary events [HR 1.02 (0.94-1.11), p = 0.60]. In individuals without heart rate lowering medication, the HR (full model) for heart rate ≥70 versus <70 bpm with regard to all-cause mortality and coronary events was 1.68 (1.30-2.18), p < 0.0001, and 1.20 (0.82-1.77), p = 0.35. Analysis of the entire cohort revealed a continuous relationship of heart rate with all-cause mortality [HR for lowest to highest heart rate quartile 1.64 (1.22-2.22), p = 0.001, full model] but not with coronary events [HR 1.04 (0.65-1.66), p = 0.86].

Conclusions: In the general population without known coronary artery disease and heart rate lowering medication, elevated RHR is an independent risk marker for all-cause mortality but not for coronary events.
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July 2016

Progression of coronary artery calcification seems to be inevitable, but predictable - results of the Heinz Nixdorf Recall (HNR) study.

Eur Heart J 2014 Nov 25;35(42):2960-71. Epub 2014 Jul 25.

Institute for Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Hufelandstrasse 55, Essen D-45122, Germany.

Aim: Coronary artery calcification (CAC), as a sign of atherosclerosis, can be detected and progression quantified using computed tomography (CT). We develop a tool for predicting CAC progression.

Methods And Results: In 3481 participants (45-74 years, 53.1% women) CAC percentiles at baseline (CACb) and after five years (CAC₅y) were evaluated, demonstrating progression along gender-specific percentiles, which showed exponentially shaped age-dependence. Using quantile regression on the log-scale (log(CACb+1)) we developed a tool to individually predict CAC₅y, and compared to observed CAC₅y. The difference between observed and predicted CAC₅y (log-scale, mean±SD) was 0.08±1.11 and 0.06±1.29 in men and women. Agreement reached a kappa-value of 0.746 (95% confidence interval: 0.732-0.760) and concordance correlation (log-scale) of 0.886 (0.879-0.893). Explained variance of observed by predicted log(CAC₅y+1) was 80.1% and 72.0% in men and women, and 81.0 and 73.6% including baseline risk factors. Evaluating the tool in 1940 individuals with CACb>0 and CACb<400 at baseline, of whom 242 (12.5%) developed CAC₅y>400, yielded a sensitivity of 59.5%, specificity 96.1%, (+) and (-) predictive values of 68.3% and 94.3%. A pre-defined acceptance range around predicted CAC₅y contained 68.1% of observed CAC₅y; only 20% were expected by chance. Age, blood pressure, lipid-lowering medication, diabetes, and smoking contributed to progression above the acceptance range in men and, excepting age, in women.

Conclusion: CAC nearly inevitably progresses with limited influence of cardiovascular risk factors. This allowed the development of a mathematical tool for prediction of individual CAC progression, enabling anticipation of the age when CAC thresholds of high risk are reached.
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November 2014

Effect of smoking and other traditional risk factors on the onset of coronary artery calcification: results of the Heinz Nixdorf recall study.

Atherosclerosis 2014 Feb 3;232(2):339-45. Epub 2013 Dec 3.

Institute for Medical Informatics, Biometry & Epidemiology, University Clinic Essen, Germany. Electronic address:

Background: Coronary artery calcium (CAC) indicates coronary atherosclerosis and can be present in very early stages of the disease. The conversion from no CAC to any CAC reflects an important step of the disease process as cardiovascular risk is increased in persons even with mildly elevated CAC. We sought to identify risk factors that determined incident CAC>0 in men and women from an unselected general population with a special focus on the role of smoking.

Methods: All 4814 persons that were initially studied in the Heinz Nixdorf Recall Study were invited to participate in the follow-up examination after 5.1 ± 0.3 years. All traditional Framingham risk factors were quantified using standard techniques. Smokers were categorized in never, former and present smokers. The CAC scores were measured from EBCT using the Agatston method.

Results: Overall, out of 342 men and 919 women with zero CAC at baseline, 107 (31.3%) men and 210 (22.9%) women had CAC>0 at second examination. In multivariable analysis, age (OR estimate per 5 years: 1.34 (95%CI: 1.21-1.47)), LDL cholesterol (per 10 mg/dL: 1.05 (95%CI: 1.01-1.10)), systolic blood pressure (per 10 mmHg: 1.19 (95%CI: 1.11-1.28)) and current smoking (1.49 (95%CI: 1.04-2.15)) were independent predictors of CAC onset. The probability of CAC onset steadily increased with age from 23.3% (men) and 15.3% (women) at age 45-49 years to 66.7% (men) and 42.9% (women) at age 70-74 years. The difference in age-dependent conversion rates was quantified by years between reaching a given level of CAC onset probability. We found a consistent pattern with respect to smoking status: presently (formerly) smoking middle-aged men convert to positive CAC 10 (5) years earlier than never smokers, for women (middle-aged to elderly) this time span is 8 (5) years.

Conclusion: Several traditional CVD risk factors are associated with CAC onset during 5 years follow-up. CAC onset is accelerated by approximately 10 (5) years for present (former) compared to never smokers.
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February 2014

Association of obstructive sleep apnoea with subclinical coronary atherosclerosis.

Atherosclerosis 2013 Dec 24;231(2):191-7. Epub 2013 Sep 24.

Department of Pneumology, Ruhrlandklinik, West German Lung Center, University Clinic Essen, Tüschener Weg 40, D-45239 Essen, Germany. Electronic address:

Background: Accumulating evidence suggests a role of obstructive sleep apnoea (OSA) as a risk factor for coronary atherosclerosis. This study aimed i) to assess the prevalence of OSA in the general population and ii) to analyse the association of this disorder with traditional cardiovascular disease risk factors and subclinical coronary atherosclerosis.

Methods: In a cross-sectional analysis of the Heinz Nixdorf Recall study a subgroup of 1604 subjects (791 men, age 50-80 years) underwent OSA screening. Furthermore, coronary artery calcium (CAC) was measured. OSA was defined as apnoea-hypopnoea index (AHI) ≥ 15/h.

Results: OSA was observed in 29.1% of men and 15.6% of women. In a multiple linear regression analysis adjusted for risk factors AHI was associated with CAC in men aged ≤65 years (estimated log-transformed increase of CAC = 0.25, 95% confidence interval (CI) = -0.001-0.50, p = 0.051) and in women of any age (estimated log-transformed increase = 0.23, 95% CI = 0.04-0.41, p = 0.02). Doubling of the AHI was associated with a 19% increase of CAC in men aged ≤65 years and with a 17% increase in women of any age.

Conclusions: In the general population aged ≥50 years OSA is associated with subclinical atherosclerosis in men aged ≤65 years and in women of any age, independent of traditional cardiovascular risk factors.
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December 2013

Coronary atherosclerosis burden, but not transient troponin elevation, predicts long-term outcome in recreational marathon runners.

Basic Res Cardiol 2014 Jan 19;109(1):391. Epub 2013 Nov 19.

Clinic of Cardiology and Intensive Care Medicine, Bethanien Hospital Moers, Bethanienstrasse 21, 47441, Moers, Germany,

We determined the prognostic value of transient increases in high-sensitive serum troponin I (hsTnI) during a marathon and its association with traditional cardiovascular risk factors and imaging-based risk markers for incident coronary events and all-cause mortality in recreational marathon runners. Baseline data of 108 marathon runners, 864 age-matched controls and 216 age- and risk factor-matched controls from the general population were recorded and their coronary event rates and all-cause mortality after 6 ± 1 years determined. hsTnI was measured in 74 marathon finishers before and after the race. Other potential predictors for coronary events, i.e., Framingham Risk Score (FRS), coronary artery calcium (CAC) and presence of myocardial fibrosis as measured by magnetic resonance imaging-based late gadolinium enhancement (LGE), were also assessed. An increase beyond the 99 % hsTnI-threshold, i.e., 0.04 μg/L, was observed in 36.5 % of runners. FRS, CAC, or prevalent LGE did not predict hsTnI values above or increases in hsTnI beyond the median after the race, nor did they predict future events. However, runners with versus without LGE had higher hsTnI values after the race (median (Q1/Q3), 0.08 μg/L (0.04/0.09) versus 0.03 μg/L (0.02/0.06), p = 0.039), and higher increases in hsTnI values during the race (median (Q1/Q3), 0.05 μg/L (0.03/0.08) versus 0.02 μg/L (0.01/0.05), p = 0.0496). Runners had a similar cumulative event rate as age-matched or age- and risk factor-matched controls, i.e., 6.5 versus 5.0 % or 4.6 %, respectively. Event rates in runners with CAC scores <100, 100-399, and ≥400 were 1.5, 12.0, and 21.4 % (p = 0.002 for trend) and not different from either control group. Runners with coronary events had a higher prevalence of LGE than runners without events (57 versus 8 %, p = 0.003). All-cause mortality was similar in marathon runners (3/108, 2.8 %) and controls (26/864, 3.0 % or 5/216, 2.4 %, respectively). Recreational marathon runners with prevalent myocardial fibrosis develop higher hsTnI values during the race than those without. Increasing coronary artery calcium scores and prevalent myocardial fibrosis, but not increases in hsTnI are associated with higher coronary event rates. All-cause mortality in marathon runners is similar to that in risk factor-matched controls.
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January 2014

Comparison of early postoperative morbidity after robot-assisted and open radical cystectomy: results of a prospective observational study.

BJU Int 2014 Mar 12;113(3):458-67. Epub 2013 Nov 12.

Department of Urology, Paediatric Urology and Urological Oncology, Kliniken Essen-Mitte, Essen, Germany.

Objective: To evaluate early postoperative morbidity in patients undergoing either robot-assisted (RARC) or open radical cystectomy (ORC) for bladder cancer.

Patients And Methods: A total of 100 patients underwent RARC (between August 2009 and August 2012) and 42 underwent ORC (between October 2007 and July 2009) as treatment for bladder cancer. Data on the patients' peri-operative course were collected prospectively up to the 90th postoperative day for the RARC group and up to the 60th postoperative day for the ORC group. Postoperative complications were recorded based on the Clavien-Dindo classification system. Both groups were compared with regard to patient and tumour characteristics, surgical and peri-operative outcomes.

Results: The RARC and ORC groups were well matched with regard to age, body mass index, gender distribution, type of urinary diversion and pathological tumour characteristics (all P > 0.1), but patients in the RARC group had more serious comorbidities according to the Charlson comorbidity index (P = 0.034). Although surgical duration was longer in the RARC group (P < 0.001) the estimated blood loss was lower (P < 0.001) and transfusion requirement was less (P < 0.001). Overall 59 patients (59%) in the RARC group and 39 patients (93%) in the ORC group experienced postoperative complications of any Clavien-Dindo grade <90 days and <60 days after surgery, respectively (P < 0.001; relative risk reduction 0.36). Major complications (grades 3a-5) were also less frequent after RARC (24 [24%] vs 18 patients [43%]; P = 0.029) with a relative risk reduction of 0.44. In the subgroup of patients with an ileum conduit as a urinary diversion (RARC, n = 76 vs ORC, n = 31) the overall rate of complications (43 [57%] vs 28 [90%] patients; P < 0.001) and the rate of major complications (17 [22%] vs 15 [48%] patients; P = 0.011) were lower in the RARC group with relative risk reductions of 0.37 and 0.54, respectively.

Conclusions: A significant reduction in early postoperative morbidity was associated with the robotic approach. Despite more serious comorbidities and a 30-day longer follow-up in the RARC group, patients in the RARC group experienced fewer postoperative complications than those in the ORC group. Major complications, in particular, were less frequent after RARC.
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March 2014

Does changeover by an experienced open prostatic surgeon from open retropubic to robot-assisted laparoscopic prostatectomy mean a step forward or backward?

ISRN Oncol 2013 21;2013:768647. Epub 2013 Jan 21.

Department of Urology, Pediatric Urology and Urologic Oncology, Kliniken Essen-Mitte, Henricistra β e 92, 45136 Essen, Germany.

We assessed whether changeover from open retropubic [RRP] to robotic-assisted laparoscopic prostatectomy [RALP] means a step forward or backward for the initial RALP patients. Therefore the first 105 RALPs of an experienced open prostatic surgeon and robotic novice-with tutoring in the initial 25 cases-were compared to the most recent 105 RRPs of the same surgeon. The groups were comparable with respect to patient characteristics and postoperative tumor characteristics (all P > 0.09). The only disadvantage of RALP was a longer operating time; the advantages were lower estimated blood loss, fewer anastomotic leakages, earlier catheter removal, shorter hospital stay (all P < 0.04), and less major complications within 90 days postoperatively (P < 0.01). Positive surgical margin rates were comparable both overall and stratified for pT stage in both groups (all P < 0.08). In addition, an equivalent number of lymph nodes were removed (P > 0.07). Twelve months after surgery, patient reported continence and erectile function were comparably good (all P > 0.11). Our study indicates that an experienced open prostatic surgeon and robotic novice who switches to RALP can achieve favorable surgical results despite the initial RALP learning curve. At the same time neither oncological nor functional outcomes are compromised.
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February 2013

Tumour characteristics, oncological and functional outcomes in patients aged ≥ 70 years undergoing radical prostatectomy.

BJU Int 2013 Mar 5;111(3 Pt B):E24-9. Epub 2012 Sep 5.

Kliniken Essen-Mitte, Department of Urology, Paediatric Urology and Urological Oncology, Essen, Germany.

Unlabelled: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The marked increase in life expectancy in recent years calls for reconsideration of the decision-making process for the treatment of prostate cancer, a condition particularly affecting the elderly. To date the general approach in elderly patients has tended to be more conservative, not least as it is generally thought that prostate cancer in these patients is less biologically aggressive. The present data showed that patients aged ≥70 years had biologically more aggressive tumours significantly more often than those aged <70 years. Nevertheless, advanced age itself was not an independent predictor of survival after retropubic radical prostatectomy, whereas adverse prostate cancer features and severe comorbidities were.

Objective: To investigate the effect of advanced age (≥70 years) on prostate cancer characteristics, oncological and functional outcomes in patients undergoing retropubic radical prostatectomy (RP).

Patients And Methods: Between June 1997 and September 2009, 1636 patients underwent RP at one institution. Of these patients, 1225 were aged < 70 years and 411 ≥70 years. Both groups were compared for prostate cancer characteristics, oncological and functional outcomes. Multivariate analyses were used to estimate the effect of advanced age on overall survival (OS), cancer-specific survival (CSS), biochemical recurrence-free survival (BFS) and postoperative continence.

Results: The median (range) age of the patients aged ≥ 70 years was 72 (70-85) years and for those aged < 70 years was 64 (40-69) years (P < 0.001), respectively. The patients aged ≥ 70 years were assigned higher American Society of Anesthesiologists (ASA) classes (P < 0.001) reflecting a higher rate of severe comorbidities in this group. In the patients aged ≥ 70 years there were significantly more clinically palpable and pathologically non-organ-confined tumours (P= 0.030 and P= 0.026, respectively), and higher biopsy and RP Gleason scores (P= 0.002 and P= 0.004, respectively). Accordingly, patients aged ≥ 70 years presented with a higher proportion of high-risk prostate cancer, although the difference was not significant (P= 0.060). There were no differences between the groups for preoperative prostate-specific antigen level (P= 0.898), rate of pelvic lymph node dissection (P= 0.231), pN+ (P= 0.526) and R+ status (P= 0.590). Kaplan-Meier curves showed a significantly lower 10-year OS (67 vs 82%; P= 0.017) and a trend towards a lower 10-year CSS (70 vs 83%; P= 0.057) in patients aged ≥ 70 years. However, on multivariate analysis advanced age was not an independent predictor of OS (P= 0.102) or CSS (P= 0.195), whereas pN+ status (both P < 0.001), RP Gleason scores 8-10 (both P < 0.001) and ASA classes 3-4 (P= 0.037 and P= 0.028, respectively) were. The 2-year postoperative continence rates was comparable between the groups (International Continence Society [ICS] male incontinence symptom score 2.10 vs 2.01; P= 0.984). In multivariate analysis it depended only on the preoperative ICSmale incontinence symptom score (P < 0.001) but not on advanced age (P= 0.341).

Conclusions: Patients aged ≥ 70 years had biologically more aggressive and locally advanced tumours significantly more often than those aged < 70 years. However, advanced age itself was not an independent predictor of survival after RP. Rather, survival was associated with adverse prostate cancer features and severe comorbidities. Consequently, it seems unjustifiable to generally exclude elderly patients from RP, not least because surgery achieved excellent postoperative continence in this age group, too.
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March 2013

Subclinical coronary atherosclerosis predicts cardiovascular risk in different stages of hypertension: result of the Heinz Nixdorf Recall Study.

Hypertension 2012 Jan 28;59(1):44-53. Epub 2011 Nov 28.

Department of Cardiology, University Clinic Essen, Essen, Germany.

Prehypertension is a frequent condition and has been demonstrated to increase cardiovascular risk. However, the association with coronary atherosclerosis as part of target organ damage is not well understood. We investigated the cross-sectional relationship and longitudinal outcome between blood pressure categories and coronary artery calcification (CAC), quantified by electron beam computed tomography, in 4181 participants from the population-based Heinz Nixdorf Recall Study cohort. At baseline, we observed a continuous increase in calcium scores with increasing blood pressure categories. During a median follow-up period of 7.18 years, 115 primary end points (2.8%; fatal and nonfatal myocardial infarction) and 152 secondary end points (3.6%; stroke and coronary revascularization) occurred. We observed a continuous increase in age- and risk factor-adjusted secondary endpoints (hazard ratios [95% CI]) with increasing blood pressure categories (referent: normotension) in men: prehypertension, 1.80 (0.53-6.13); stage 1 hypertension, 2.27 (0.66-7.81); and stage 2 hypertension, 4.10 (1.27-13.24) and in women: prehypertension, 1.13 (0.34-3.74); stage 1 hypertension, 2.14 (0.67-6.85); and stage 2 hypertension, 3.33 (1.24-8.90), respectively, but not in primary endpoints. Cumulative event rates were determined by blood pressure categories and the CAC. In prehypertension, the adjusted hazard ratios for all of the events were, for CAC 1 to 99, 2.05 (0.80-5.23; P=0.13); 100 to 399, 3.12 (1.10-8.85; P=0.03); and ≥400, 7.72 (2.67-22.27; P=0.0002). Risk of myocardial infarction and stroke in hypertension but also in prehypertension depends on the degree of CAC. This marker of target-organ damage might be included, when lifestyle modification and pharmacotherapeutic effects in prehypertensive individuals are tested to avoid exposure to risk and increase benefit.
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January 2012

Cardiovascular risk factors in patients with uncontrolled and long-term acromegaly: comparison with matched data from the general population and the effect of disease control.

J Clin Endocrinol Metab 2010 Aug 12;95(8):3648-56. Epub 2010 May 12.

Department of Endocrinology, Institute for Medical Informatics, Biometry, and Epidemiology, West-German Heart Centre Essen, University Hospital of Essen, University of Duisburg-Essen, Department of Endocrinology, Hufelandstrasse 55, 45122 Essen, Germany.

Context: Data on cardiovascular risk in acromegaly are scanty and lack a clear correlation to epidemiological data.

Objective: Our aim was an evaluation of cardiovascular risk factors in patients with active acromegaly, a calculation of the Framingham risk score (FRS) compared with age- and gender-matched controls of the general population, and an evaluation of the effect of IGF-I normalization.

Design And Setting: We conducted a retrospective, comparative study at a university referral center.

Patients: A total of 133 patients with acromegaly (65 men, aged 45-74 yr) from the German Pegvisomant Observational Study were matched to 665 controls from the general population.

Main Outcome Measures: Risk factors were measured at baseline and after 12 months of treatment with pegvisomant (n=62).

Results: Patients with acromegaly had increased prevalence of hypertension, mean systolic and diastolic blood pressure (BP), history of diabetes mellitus and glycosylated hemoglobin (all P<0.001) and decreased high-density lipoprotein, low-density lipoprotein, and total cholesterol (all P<0.001). FRS was significantly higher in patients with acromegaly compared with controls (P<0.001). At 12 months, systolic BP (P=0.04) and glycosylated hemoglobin (P=0.02) as well as FRS (P=0.005) decreased significantly. IGF-I was normalized in 62% (41 of 62). In these patients, glucose and systolic and diastolic BP was significantly lower than in partially controlled patients.

Summary: We found an increased prevalence of cardiovascular risk factors in acromegalic patients compared with controls. Control of acromegaly led to a significant decrease of FRS, implying a reduced risk for coronary heart disease. This was most significant in those patients who completely normalized their IGF-I levels.

Conclusion: Disease control is important to reduce the likelihood for development of coronary heart disease.
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August 2010

Association of exercise capacity and the heart rate profile during exercise stress testing with subclinical coronary atherosclerosis: data from the Heinz Nixdorf Recall study.

Clin Res Cardiol 2009 Oct 20;98(10):665-76. Epub 2009 Aug 20.

Department of Cardiology, West-German Heart Center Essen, University Clinic Duisburg-Essen, Hufelandstrasse 55, Essen, Germany.

Background: Exercise capacity and heart rate profile parameters obtained from exercise stress testing as well as the subclinical coronary atherosclerosis burden from cardiac CT have been suggested to improve cardiovascular (CV) risk stratification beyond traditional risk factors (RF) in persons at risk of CV events.

Aim: To study the association of exercise stress-test variables with the coronary artery calcium (CAC) burden in relation to age, sex and traditional RF in subjects without known coronary artery disease from the general population.

Methods: In 3,163 subjects, CV and RF were measured, a bicycle stress test was performed and the electron beam CT-based CAC-Agatston score was quantified.

Results: Exercise capacity, chronotropic response and an abnormal HR recovery were significantly and inversely related to CAC scores in men and women in univariate unadjusted analysis. This association was diminished after adjustment for age and sex and further after adjustment for traditional risk factors. In multivariate analysis, chronotropic response in men [estimate (95% CI): 0.94 (0.91-0.97), P = 0.0005] and an abnormal HR recovery (<15 bpm after 1 min) in women [estimate: 1.34 (1.07-1.70), P = 0.013] but not exercise capacity remained associated with CAC independent of traditional RF. In subjects not taking lipid-lowering, antiarrhythmic or antihypertensive drugs, estimates for the observed associations were essentially unchanged. The clinical ability of these variables to predict a high CAC score was limited.

Conclusion: The strong inverse association of exercise capacity, chronotropic response and abnormal HR recovery during exercise stress testing with the CAC burden in unadjusted univariate analysis is largely influenced by age, sex and cardiovascular RFs. The degree, to which exercise stress-test variables and the CAC burden independently contribute to the prediction of cardiovascular events, remains to be shown.
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October 2009

The effect of age and risk factors on coronary and carotid artery atherosclerotic burden in males-Results of the Heinz Nixdorf Recall Study.

Atherosclerosis 2009 Aug 15;205(2):595-602. Epub 2009 Jan 15.

Clinic of Cardiology, West-German Heart Center, University Duisburg-Essen, Germany.

Background: Increased arterial intima-media thickness (IMT) and coronary artery calcification (CAC) are measures of subclinical arteriosclerosis burden. Little is known, however, whether risk factors have an impact differently on atherosclerosis in these distinct vascular territories in the same individuals.

Methods And Design: For 1620 men without coronary artery disease (CAD) and stroke, aged 45-75 years (59+/-8), IMT was measured 1cm proximal to the bulb in the common carotid artery (CCA). Both sides were measured and the average of the right and left artery were applied. Electron-beam CT was used to quantify coronary artery calcium (CAC). Cardiovascular risk factors were measured with standard techniques.

Results: IMT increased with age from 0.64+/-0.12mm in the lowest decade (45-54 years) up to 0.76+/-0.14mm in the highest decade (65-74 years) (p<0.0001). CAC and IMT showed a significant correlation across the cohort. Individual variation in the extent of IMT and CAC was, however, high (r=0.26, p<0.0001). Standard risk factors had a similar impact on IMT and CAC relative to 5 years of ageing, except for diabetes and HDL, which had a higher impact on IMT than on CAC. The effect of diabetes mellitus on IMT exceeded the effect of 5 years of ageing.

Conclusions: IMT may be more sensitive to the atherosclerotic impact of diabetes than CAC, while blood pressure showed a higher effect on CAC. Thus, cardiovascular risk factors seem to have a different atherosclerotic impact on carotid arteries compared with coronary arteries.
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August 2009

The incidence of lymph node metastases in prostate carcinoma depends not only on tumor characteristics but also on surgical performance and extent of pelvic lymphadenectomy.

Medicina (Kaunas) 2008 ;44(8):601-8

Department of Urology, Kliniken Essen-Mitte, Henricistrasse 92, 45136 Essen, Germany.

Objectives: The purpose of the present study was to determine whether predictions of the incidence of pelvic lymph node metastases in patients with similar prostate cancer characteristics are influenced by the extent of pelvic lymphadenectomy or surgical performance.

Material And Methods: Data from a prostate cancer database were analyzed to investigate associations between incidence of lymph node metastasis and preoperative prostate-specific antigen level, clinical stage, biopsy Gleason score, extent of pelvic lymphadenectomy, and surgical performance. Subgroups of patients with the same characteristics were formed, and a multivariate analysis was performed.

Results: Data of 668 patients with cT1-T2c prostate cancer who underwent radical retropubic prostatectomy with pelvic lymphadenectomy were analyzed. Lymph node metastases were found in 8.7% of these patients. In the subgroup of patients undergoing limited pelvic lymphadenectomy, 6.3% were affected compared with 14.7% of patients undergoing extended pelvic lymphadenectomy (P<0.0005). In the subgroups of patients with the same tumor characteristics (with only two exceptions), the impact of the extent of lymphadenectomy on the incidence of lymph node metastases was evident. The results of the multivariate analysis corroborated the influence of the extent of pelvic lymphadenectomy (P<0.03) and surgical performance (P<0.04) on the incidence of lymph node metastases.

Conclusions: The incidence of lymph node metastases was dependent not only on preoperative prostate-specific antigen level, clinical stage, and biopsy Gleason score but also to a large degree on surgical performance and the extent of pelvic lymphadenectomy. Our data suggest that a limited and/or not thoroughly performed pelvic lymphadenectomy results in failure to detect a relevant proportion of lymph node metastases.
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September 2010

Complications of pelvic lymphadenectomy in 1,380 patients undergoing radical retropubic prostatectomy between 1993 and 2006.

J Urol 2008 Mar 22;179(3):923-8; discussion 928-9. Epub 2008 Jan 22.

Department of Urology, Pediatric Urology and Urologic Oncology, Kliniken Essen-Mitte, Essen, Germany.

Purpose: We evaluated the perioperative complications associated with pelvic lymphadenectomy in patients undergoing radical retropubic prostatectomy. In particular the influence of the extent of pelvic lymphadenectomy and of other possible risk factors on the complication rate was examined.

Materials And Methods: All intraoperative and early postoperative complications in 1,380 patients who underwent radical retropubic prostatectomy were documented. Complications related to pelvic lymphadenectomy were described and evaluated statistically to explore the role of possible risk factors.

Results: Limited pelvic lymphadenectomy was performed in 867 patients and an extended procedure was done in 434. In 60 cases pelvic lymphadenectomy was not specified and in 19 pelvic lymphadenectomy was omitted. Intraoperative complications associated with pelvic lymphadenectomy were rare events (8 cases). Early postoperative complications included hemorrhage of the obturator artery in 1 patient, symptomatic lymphocele in 72, thromboembolic sequelae in 6 and lymphocele infection in 2. Lymphocele formation depended on the extent of pelvic lymphadenectomy (p <0.0001), the number of lymph nodes removed (p = 0.0038) and the operating surgeon (p = 0.0073). Thromboembolic events (p = 0.001) and re-interventions (p <0.0001) were more frequent in patients with a lymphocele. Multivariate analysis confirmed extended pelvic lymphadenectomy as an independent risk factor for lymphocele and re-intervention.

Conclusions: Pelvic lymphadenectomy is the cause of a relevant number of perioperative complications in patients undergoing radical retropubic prostatectomy. Lymphocele formation, and the associated re-interventions and thromboembolic sequelae account for by far the highest percent of these complications. In the current study lymphocele formation depended on the extent of pelvic lymphadenectomy, the number of lymph nodes removed and the operating surgeon.
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March 2008

Intraoperative and early postoperative complications of radical retropubic prostatectomy.

Urol Int 2007 ;79(3):217-25

Department of Urology, Kliniken Essen-Mitte, Essen, Germany.

Introduction: To determine the perioperative complications and morbidity of radical retropubic prostatectomy (RRP) and to analyze risk factors for observed complications.

Materials And Methods: Data of 1,000 patients undergoing RRP and pelvic lymphadenectomy (pLA) performed by different surgeons of the same hospital were collected. Uni- and multivariate analysis was performed to detect associations between intra- and postoperative complications and specific variables.

Results: Relevant intraoperative complications were observed in 28 cases and relevant postoperative complications in 187 cases requiring reoperations in 46 patients. Diverse minor postoperative complications occurred in 75 cases. The surgeon's experience and the operating time significantly influenced the incidence of intraoperative complications. Extended pLA was associated with significantly higher rates of lymphoceles and reoperations. The patients with lymphocele showed significantly higher rates of deep venous thrombosis (DVT), pulmonary embolism (PE) and reoperation and patients with DVT a higher incidence of PE and a higher rate of reoperations. The incidence of anastomotic strictures correlated significantly with postoperative urine retention.

Conclusions: RRP is a safe surgical procedure. In the hands of experienced urologic surgeons it is associated with lower incidences of severe intraoperative complications. A substantial proportion of postoperative complications are associated with pLA and its extension.
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November 2007

Subclinical coronary atherosclerosis is more pronounced in men and women with lower socio-economic status: associations in a population-based study. Coronary atherosclerosis and social status.

Eur J Cardiovasc Prev Rehabil 2007 Aug;14(4):568-74

Department of Medical Sociology, University Clinic Düsseldorf, West-German Heart Center Essen, University Duisburg-Essen, Germany.

Background: Social inequalities of manifest coronary heart diseases are well documented in modern societies. Less evidence is available on subclinical atherosclerotic disease despite the opportunity to investigate processes underlying this association. Therefore, we examined the relationship between coronary artery calcification as a sign of subclinical coronary atherosclerosis, socio-economic status and established cardiovascular risk factors in a healthy population.

Design: Cross-sectional.

Methods: In a population-based sample of 4487 men and women coronary artery calcification was assessed by electron beam computed tomography quantified by the Agatston score. Socio-economic status was assessed by two indicators, education and income. First, we investigated associations between the social measures and calcification. Second, we assessed the influence of cardiovascular risk factors on this association.

Results: After adjustment for age, men with 10 and less years of formal education had a 70% increase in calcification score compared with men with high education. The respective increase for women was 80%. For income the association was weaker (among men 20% higher for the lowest compared with the highest quartile; and among women 50% higher, respectively). Consecutive adjustment for cardiovascular risk factors significantly attenuated the observed association of socio-economic status with calcification.

Conclusions: Social inequalities in coronary heart diseases seem to influence signs of subclinical coronary atherosclerosis as measured by coronary artery calcification. Importantly, cumulation of major cardiovascular risk factors in lower socio-economic groups accounted for a substantial part of this association.
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August 2007

Subclinical coronary atherosclerosis and resting ECG abnormalities in an unselected general population.

Atherosclerosis 2008 Feb 13;196(2):786-94. Epub 2007 Mar 13.

Clinic of Cardiology, West-German Heart Center Essen, University Clinic Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.

Objectives: Exposure to cardiovascular (CV) risk factors may result in coronary atherosclerosis and myocardial disease, which is reflected in the extent of coronary artery calcification (CAC) and resting ECG abnormalities, respectively. We studied the association of CAC with ECG abnormalities in a general population without myocardial infarction or revascularization.

Methods: The total cohort of 4814 subjects (45-75 years) were randomly selected from the general population for the Heinz Nixdorf Recall Study, an ongoing study designed to assess the prognostic value of modern risk stratification methods. In addition to measuring standard risk factors, digitized resting ECGs and the EBT-based Agatston score were obtained. Subjects were separated into those without (n=1929) and with CV disease (CVD) or treated risk factors (tRF) (n=2558).

Results: In both groups, a positive CAC-score was more frequent and CAC-scores were higher in men and women with ECG abnormalities as compared to those with normal ECGs (p<0.05 each). In persons without CVD/tRF, a CAC > or =75th percentile was more frequent in those with LVH (42.4%) and QTc >440 ms (34.2%) as compared to normal ECGs (23.0%, p<0.01 for both). In persons with CVD/tRF, a CAC-score > or =75th percentile was found in subjects with A-Fib (46.3%), borderline-LVH (39.1%), ECG signs of MI (40.5%) and major ECG abnormalities (40.3%) versus 31.2% in those with normal ECGs (p<0.03 for all). In multivariate analysis, LVH (p=0.025) and major ECG abnormalities (p=0.04) remained independently associated with CAC in subjects without and with CVD/tRF, respectively.

Conclusions: ECG-based evidence of myocardial disease is often associated with an elevated CAC burden, suggesting a link between epicardial and myocardial manifestations of risk factor exposure. The association of CAC burden with different ECG abnormalities in different clinical groups may have implications for the interpretation of the resting ECG and CAC burden in risk stratification.
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February 2008

Disease progression and survival in patients with prostate carcinoma and positive lymph nodes after radical retropubic prostatectomy.

BJU Int 2006 May;97(5):985-91

Division of Urology, Paediatric Urology and Urologic Oncology, Kliniken Essen-Mitte, Germany.

Objective: To determine disease progression and survival in patients with lymph node-positive prostate carcinoma after ascending radical retropubic prostatectomy (RP) and pelvic lymphadenectomy with different forms of postoperative adjuvant treatment.

Patients And Methods: We analysed 82 patients with lymph node metastases at the time of surgery and who had a RP between 1993 and 2002. Data from clinical records and follow-up questionnaires were used. Overall survival, time to clinical disease progression and time to biochemical progression were used as endpoints to assess the outcome. Clinical progression was defined as documented local recurrence or distant metastases, and biochemical as an increase in prostate-specific antigen (PSA) of > or = 0.4 ng/mL. Variables analysed included PSA level, Gleason score before and after RP, clinical and pathological stage, number of positive lymph nodes and hormone therapy after RP. The statistical assessment included univariate regression analysis, and to analyse the distribution of clinical findings in different groups, Mantel-Haenszel statistics were used to test for differences in the numbers of patients. Survival and progression-free interval were assessed by Kaplan-Meier estimates and differences between groups calculated by log-rank statistics and Cox regression models.

Results: The median (range) follow-up was 55 (10-125) months. Adjuvant hormonal treatment was used in 77 patients, five of whom had immediate adjuvant radiotherapy, and nine delayed radiotherapy because of local progression or symptomatic bone metastases; five had no additional treatment. The rates for 5- and 10-year overall survival, clinical progression-free survival and biochemical progression-free survival were 84% and 79%, 83% and 77%, and 70% and 60%, respectively. Ten patients died (12%), eight (10%) of them from the cancer; bone metastases were detected in nine (11%). Local recurrences developed in three (4%) patients, 10 (12%) had a PSA increase of > or = 0.4 ng/mL alone and 58 (71%) had no signs of progression, but two died from other causes.

Conclusions: Most patients with prostate cancer who had RP and pelvic lymphadenectomy followed by adjuvant hormone therapy, and who had lymph node metastases at the time of surgery, had excellent overall and progression-free survival in the long term.
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May 2006

Migrations in clinical and pathological stage of prostatic carcinoma in patients undergoing radical prostatectomy in the period between 1993 and 2003.

Coll Antropol 2005 Dec;29(2):593-8

Clinic of Urology, Pediatric Urology and Urologic Oncology, Clinics of Essen-Mitte, Essen, Germany.

The aim of this study based on an analysis of personal material was to establish stage migration in a relatively large number of patients who had undergone radical retropubic ascendant prostatectomy (RRP). Between 01.07.1993. and 31.06.2003. RRP was performed in 801 patients at the urology department of the Kliniken-Essen-Mitte. Data regarding diagnostic workup, treatment and postoperative course were collected prospectively into a database. An analysis was made regarding clinical and pathological stage and numbers of patients with positive lymph nodes. During the observation period the number of radical prostatectomies increased significantly from 8 in 1993 to 130 in 2002. The number of organ-confined tumors increased continuously between 1997 and 2003. In contrast to this, advanced and metastatic tumors showed a continuous decrease from 76% in 1997 to 66% in 2002. Between 1994 and 2003 the number of T1c tumors increased by 20%. Introduction of systematic 12-cylinder biopsy (S12C) increased the detection of prostatic carcinoma by 38% and the number of diagnosed tumors of a lower clinical stage increased. These facts confirm a trend towards clinical and pathological stage migration resulting from extensive use of prostate specific antigen (PSA) and S12C biopsy in the diagnosis of prostatic carcinoma.
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December 2005

Vascular endothelial growth factor plasma levels are significantly elevated in patients with cerebral arteriovenous malformations.

Cerebrovasc Dis 2006 23;21(3):154-8. Epub 2005 Dec 23.

Department of Neurosurgery, University Children's Hospital, Essen, Germany.

Background: Since growth and de novo generation of cerebrovascular malformations were demonstrated, a strictly congenital model cannot be further supported as unique factor in the pathogenesis of cerebral arteriovenous malformations (AVMs). Vascular endothelial growth factor (VEGF) has previously been demonstrated to be highly expressed in AVMs by immunohistochemical methods. However, systemic VEGF levels have not been analysed previously. This study aimed to investigate VEGF plasma concentrations as a possible plasma marker for neovascularization in patients with cerebral AVMs compared to healthy controls.

Methods: The study included 17 patients with cerebral AVMs and 40 healthy controls. VEGF plasma concentrations were measured by a specific enzyme immuno-assay.

Results: VEGF plasma concentrations were significantly higher in patients with cerebral AVMs (mean 140.9 pg/ml, SD 148.5 pg/ml and median 63.0 pg/ml) compared to a healthy control group (mean 44.7 pg/ml, SD 36.4 pg/ml and median 35.0 pg/ml), p = 0.0003.

Conclusions: Our findings suggest that VEGF plasma concentrations might play a role in the pathogenesis of cerebral AVMs. Further studies are necessary and would contribute to an improved understanding of the pathogenesis of cerebral AVMs.
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May 2006

Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease.

Thyroid 2005 Sep;15(9):1047-54

Division of Endocrinology, Department of Medicine University of Duisburg-Essen, Essen, Germany.

Objective: After primary successful antithyroid drug treatment (ATDT), Graves' disease has a relapse rate of 30% to 50%. Previous studies have evaluated age, gender, goiter volume, smoking habits, and the presence of thyrotropin-receptor antibodies (TRAb) as predictive markers to facilitate an individualized patient management. Despite higher sensitivity and specificity of the new second generation human TSH-receptor assay, the predictive value of TRAb for relapse of hyperthyroidism is still controversial. In a recent prospective multicenter study we have previously shown that suppressed or low TSH values predict both early (persistence) and late relapse of Graves' disease. We now present a more detailed analysis of the predictive value of TSH and TRAb for recurrent hyperthyroidism.

Methods: Four weeks after withdrawal of ATDT, 96 patients were available for thyroid function tests, including a sensitive third-generation TSH assay and a second-generation recombinant TSH receptor assay. Relapse of Graves' disease was evaluated for a total follow-up of 2 years.

Results: Within 2 years, 47 of 96 patients (49%) developed relapse of hyperthyroidism. Nine patients relapsed within the first 4 weeks after withdrawal of ATDT and were thus considered to have persistent Graves' disease. Ten of 15 other patients with TSH levels below 0.3 mU/L without overt hyperthyroidism relapsed within 2 years. Twenty-five of 65 patients with normal TSH (0.3-3.0 mU/L) and 3 of 4 patients with TSH values above 3 mU/L also had recurrent hyperthyroidism. After ATDT cessation, TSH had a positive predictive value of 70% and a negative predictive value of 62% (specificity 85%) for relapse of Graves 'disease. Mean TRAb levels in the group of patients with relapse were significantly higher (11.1 IU/L +/- 0.17) than TRAb values in the remission group (4.5 IU/L +/- 0.6), p < 0.001. Using a cutoff value of 1.5 IU/L, TRAb had low positive and negative predictive values of 49% and 54%, respectively (specificity, 14%), but with a cutoff level of 10 IU/L, predictive values improved to 83% and 62%, respectively (specificity, 92%). Combination of TSH and TRAb determinations did not further improve prediction of relapse. Other factors such as gender, age, goiter volume, smoking habits, presence of thyroid-associated ophthalmopathy, and urinary iodine excretion did not show a significant influence on relapse rate.

Conclusion: Low TSH values 4 weeks after ATDT withdrawal predict relapse of Graves' disease, both early (persistence) and, to a lesser extend, within 2 years of follow-up. Also, TRAb above 10 IU/L found in a small subset of patients, correlated with a higher relapse rate.
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September 2005

Association study of the G-protein beta3 subunit C825T polymorphism with disease progression in patients with bladder cancer.

World J Urol 2005 Sep 8;23(4):279-86. Epub 2005 Nov 8.

Institut für Pharmakologie, Universitätsklinikum Essen, Germany.

The T-allele in the GNB3 C825T polymorphism has been associated with increased cell migration, a prerequisite for metastasis. In this study we investigated a potential association of the C825T-allele status and disease progression in patients with transitional cell carcinoma of the bladder (TCC). Genotyping of the GNB3 C825T polymorphism was performed in 389 patients with transitional cell carcinoma of the bladder and in 104 control subjects and clinical follow-up was worked up in 339 patients. Genotype distribution in 389 patients with bladder cancer was comparable to genotype distribution of the control group. There was no association of GNB3 C825T genotype with tumor stage or grade, but follow-up analysis in the subgroup of non-smokers revealed a shorter time to metastasis in 825T-allele carriers compared to individuals homozygous CC. The genotype of the GNB3 C825T polymorphism appears to influence the biological behavior of tumor disease in non-smoking TCC patients.
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September 2005

Population-based assessment of subclinical coronary atherosclerosis using electron-beam computed tomography.

Atherosclerosis 2006 Mar 11;185(1):177-82. Epub 2005 Jul 11.

Cardioangiologisches Centrum, Bethanien, Im Prüfling 23, D-60389 Frankfurt am Main, Germany.

Aims: Coronary artery calcification (CAC) is determined as a measure of the extent of coronary atherosclerosis and can be used for expanded cardiovascular risk stratification. It was our aim to establish reference CAC scores in a population-based unselected European cohort.

Methods And Results: The Heinz Nixdorf Recall study (HNR) recruited a total of 4814 participants aged 45-74 years. Cardiovascular risk factors and medications were recorded, and CAC was measured using electron-beam CT (EBCT). CAC score distribution was compared with previous studies in subjects who were self-referred, volunteered, or were physician-referred. Of the 4472 (92.9%) subjects free of clinical coronary artery disease, the CAC score was available in 4275 (95.3%) (2027 men, 2248 women). CAC scores were lower in particular in the higher age groups (> or = 60 years) in men than in the previous studies. Also, in most age groups (except the highest, 70-74 years), subjects with no cardiovascular medications had significantly lower CAC scores than subjects using cardiovascular medications.

Conclusions: The current report characterises the distribution of EBCT-derived CAC scores in a European unselected population. Compared with previous reports, CAC scores were lower in our cohort, in particular in subjects not receiving cardiovascular medications. Classification of the CAC score may underestimate true risk if previously published referral cohorts are used as the reference.
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March 2006

Relapse of Graves' disease after successful outcome of antithyroid drug therapy: results of a prospective randomized study on the use of levothyroxine.

Thyroid 2002 Dec;12(12):1119-28

Department of Medicine, Klinikum Luedenscheid, Luedenscheid, Germany.

Antithyroid drugs are effective in restoring euthyroidism in Graves' disease, but many patients experience relapse after withdrawal. Prevention of recurrence would therefore be a desirable goal. In a prospective study, patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and randomly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment. The levothyroxine group was randomized to continue or discontinue levothyroxine after 1 year. End points included relapse of overt hyperthyroidism. Of 346 patients with Graves' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were randomly assigned to receive levothyroxine (114 patients) or no treatment (controls, 111 patients). Of those not randomized, 39 patients showed early relapse within 4 weeks, 61 endogenous TSH suppression, 7 TSH elevation, and 14 had to be excluded. Dropout rate during the study were 13.3%. Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group (20% after 1 year, 32% after 2 years) and the randomized controls (18%, 24%), whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH (33%, 49%). Levothyroxine therapy did not influence TSH-receptor antibody, nor did it reduce goiter size. The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs (posttreatment TSH). The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker.
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December 2002