L Hertle

Universitätsklinikum Münster, Muenster, North Rhine-Westphalia, Germany

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Publications (187)420.6 Total impact

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    ABSTRACT: The goal of this work was to describe the change of treatment paradigms for metastatic renal cell carcinoma (mRCC) since 2006. We retrospectively investigated all mRCC patients who were treated with targeted therapy between June 2006 and June 2012 at the University of Münster. In all, 50 of 158 (31.6 %) patients were initially treated with immunotherapy. The most often used second line treatment after immunotherapy was sorafenib (29 patients, 58.0 %). The first line treatment chosen for therapy-naïve patients was sunitinib (68 patients, 63.0 %). There was no statistically significant difference between the two groups (572 vs. 554 days, p = 0.745). A total of 77 patients had synchronous metastasis (48.8 %), 55 of whom underwent cytoreductive nephrectomy. There was a significant survival benefit in favor of surgically treated patients (510 vs. 186 days, p = 0.002). After introduction of the new agents treatment paradigms have changed substantially. Immunotherapy is used only rarely. Cytoreductive nephrectomy may continue to be regarded as standard treatment until prospective data are available.
    Der Urologe 02/2014; · 0.46 Impact Factor
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    ABSTRACT: To evaluate the predictive value of tumor volume (TV), tumor percentage (TP), and number of tumor foci (NF) in patients with prostate cancer. The prognostic relevance of TV, TP, and NF as predictors of biochemical recurrence (BCR) following radical prostatectomy (RPE) is controversial. The cohort consisted of 758 referred subjects who underwent RPE between 2000 and 2005 at the University of Muenster. The mean time of follow-up was 62 months. TV, TP, and NF were estimated visually with the assistance of a pathologic mapping grid for embedded whole-mount RPE specimens. In addition, TV and TP were assessed in a categorized fashion by using quartiles as cutoff points. Subgroup analyses for high- and low-risk patients using univariate and multivariate Cox proportional hazard analyses for BCR were performed. TV, TP, and NF were strongly related to tumor stage, Gleason score, surgical margin status, and preoperative prostate-specific antigen (PSA). In univariate analysis, all pathologic parameters including TV, TP, and NF were predictive for BCR. In multivariate analysis, only TP, tumor stage, and PSA level were independent predictors. In subgroup analysis, TP was an independent predictor for BCR in the high-risk group but not in the low-risk group. TP, but not TV or NF, was found to be an independent predictor for BCR in patients after RPE. TP seems to be more relevant in high-risk patients (i.e., any of the following:>pT2, Gleason score>6, or PSA>20ng/ml).
    Urologic Oncology 12/2013; · 3.65 Impact Factor
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    ABSTRACT: Precise and complete coding of diagnoses and procedures is of value for optimizing revenues within the German diagnosis-related groups (G-DRG) system. The implementation of effective structures for coding is cost-intensive. The aim of this study was to prove whether higher costs can be refunded by complete acquisition of comorbidities and complications. Calculations were based on DRG data of the Department of Urology, University Hospital of Münster, Germany, covering all patients treated in 2009. The data were regrouped and subjected to a process of simulation (increase and decrease of patient clinical complexity levels, PCCL) with the help of recently developed software. In urology a strong dependency of quantity and quality of coding of secondary diagnoses on PCCL and subsequent profits was found. Departmental budgetary procedures can be optimized when coding is effective. The new simulation tool can be a valuable aid to improve profits available for distribution. Nevertheless, calculation of time use and financial needs by this procedure are subject to specific departmental terms and conditions. Completeness of coding of (secondary) diagnoses must be the ultimate administrative goal of patient case documentation in urology.
    Der Urologe 06/2012; 51(7):975-81. · 0.46 Impact Factor
  • O.A. Brinkmann, L. Hertle
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    ABSTRACT: Darstellung pathogenetischer Aspekte der interstitiellen Zystitis (IC) anhand der aktuell verfügbaren Literatur unter Berücksichtigung der Kriterien Evidenz-basierter Medizin (EBM). 346 Artikel der letzten 30 Jahre (peer-reviewed, zurückgehend bis 1969) wurden in einer MEDLINE-Recherche mittels der Stichworte “interstitial cystitis“ und “pathogenesis” oder “etiology” identifiziert. Darüber hinaus wurden Lehrbücher und Monographien zum Thema der Pathogenese bzw. der Ätiologie der IC mit Schwerpunkt auf dem histologischen Erscheinungsbild bzw. der Entzündung i. Allg. studiert. Nachfolgend wurden alle Arbeiten in Themengruppen untergliedert und ausgewertet. Nahezu alle Schritte der gesetzmäßigen Reaktion des Gefäßbindegewebes auf einen entzündlichen Reiz hin werden als möglicher Auslöser der IC-Entstehung angeführt. Bei einer “nur klinisch” definierten Erkrankung versagen die Techniken der Evidenzbasierten Medizin, weil Voraussetzungen zur statistischen Erfassung und Analyse nicht greifen. In der Regel enthalten die Publikationen zu diesem Thema keine Kontrollgruppe Gesunder bzw. an einer bakteriellen oder radiogenen Zystitis erkrankter Patienten. Hinzu kommt, dass die klinischen Kriterien zur Diagnosestellung der IC nicht allgemein akzeptiert sind. Bisher hat keine Arbeitsgruppe ein allgemein anerkanntes Tiermodell entwickeln können, in dem eine IC natürlicherweise entsteht oder induzierbar ist. Geradezu inflationär ist der Umgang mit dem Begriff der Pathogenese bzw. der Ätiologie der IC. 346/683 IC-Arbeiten (50,7%) verwenden diese Begriffe in ihrem Abstrakt. Ein seriöserer Umgang mit den Begriffen Ätiologie/Pathogenese wird daher dringend empfohlen. Keiner der dargestellten Faktoren hat in den Untersuchungen zeigen können, alleinige oder dominierende Ursache für die “IC” zu sein. Auch wenn einige der Faktoren eher Teil des Zirculus vitiosus sind als ihn zu initiieren, können für therapeutische Überlegungen zur Unterbrechung der Entzündungsreaktion genutzt werden. Für jeden der dargestellten Faktoren, gibt es nahezu gleich viele Arbeiten, die seine Bedeutung unterstreichen bzw. die Bedeutung in Frage stellen oder ganz ablehnen. Das Zugrundelegen des pathologisch-anatomischen Modells der (chronischen) Entzündung ermöglicht es, die z. T. widersprüchlichen Meinungen zu integrieren und hoffen Perspektiven für zukünftige Forschungsansätze zu finden. Ein Fortschritt im Verständnis dieser Erkrankung erscheint nur möglich, wenn unter Verwendung objektiv nachvollziehbarer Kriterien IC-Patienten in Untergruppen aufgeteilt werden können. Diese Untergruppen stellen die Voraussetzung für eine differenzierte Untersuchung der Genese wie auch der Therapiestrategien voraus. Pathogenic aspects of interstitial cystitis (IC) are reviewed on the basis of the current literature applying the criteria of evidence-based medicine (EBM). Three hundred forty-six peer-reviewed publications of the past 30 years were retrieved via MEDLINE employing the key words “interstitial cystitis and pathogenesis or etiology” and classified according to EBM criteria and subject categories. The papers were then reviewed and summarized and are discussed considering the theory of acute and chronic inflammatory responses. In the literature, nearly all steps of the normal inflammatory response are considered pathogenically important in development of the IC syndrome. Applying EBM criteria, all studies fail to meet the criteria for sound statistical evaluation and to demonstrate reproducibly a reliable pathogenic factor. Most publications report only small numbers of patients. Control groups are frequently lacking or too small. Clinically useful criteria for the diagnosis of IC are not properly defined. There is no commonly accepted animal model in which IC occurs naturally or can be artificially induced. Of the 683 IC papers studied, 346 (50.7%) deal with pathogenic or etiological aspects of IC. The inflationary use of the terms pathogenesis or etiology in one out of every two papers calls for more prudent application of terminology in the future. As yet, none of the published pathogenic factors was found to represent the main trigger of the IC syndrome. Some of them seem to be part of a vicious cycle of the inflammatory reaction present. Detailed knowledge of the process of chronic inflammation can lead to treatments that may interrupt an inflammatory response. This might contribute to solving the pathogenic issue of IC and could be helpful in designing further investigations. Advances in understanding the causes of IC require objective criteria to subclassify the heterogenous patient cohort presently referred to as IC syndrome. Such subclassifications are a predisposition for pathogenic investigations and determining future treatment strategies.
    Der Urologe 04/2012; 39(6):520-526. · 0.46 Impact Factor
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    ABSTRACT: In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.
    Der Urologe 04/2012; 51(4):500, 502-6. · 0.46 Impact Factor
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    ABSTRACT: Germ cell cancer (GCC) is curable in metastatic stages. The International Germ Cell Cancer Collaborative Group (IGCCCG) reports a poor prognosis subgroup with a 5-year survival of 48%. High-dose chemotherapy with PBSC transplantation (HD-PBSCT) in these patients showed promising results in phase II, but failed to show significant advantage in randomized trials. We report our monocenter series of all poor and selected intermediate prognosis germ cell tumor patients treated with multiple-course HD-PBSCT and secondary surgery of remaining tissue. We performed a retrospective analysis of our complete series of 44 patients (40 poor prognosis and 4 intermediate prognosis) treated by HD-PBSCT as part of first-line therapy from 1999 to 2010. The CR rate after up to four cycles of HD-PBSCT and radical resection of residual manifestations was 73%. The 3-year survival rate was 79.5% (median follow-up of 51.5 months; range: 7-143 months). Disease-related death rate was 16%. HD-PBSCT-related death did not occur. One patient died postsurgery. Multiple courses of HD-PBSCT with radical secondary surgery is safe and effective in poor prognosis metastatic GCC. Despite disappointing phase III studies it is of high interest to further study this field.
    Bone marrow transplantation 02/2012; 47(10):1321-5. · 3.00 Impact Factor
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    ABSTRACT: A number of new agents have been approved for systemic therapy of metastatic renal cell carcinoma (mRCC) recently. Thereby, prognostic factors may aid in predicting the effectiveness of various treatment modalities in individual cases. Aim of this study was to determine the value of human leukocyte antigen (HLA) class II characteristics in predicting response of mRCC to combined immunochemotherapy (ICT). A retrospective study of 29 patients with mRCC treated with ICT was performed: 17 patients (group A) with long-term remission and 12 (group B) with progressive disease after ICT. DNA was used for high resolution typing of HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, and -DQB1. Statistical evaluation started with Classification and Regression Trees analysis. The assignment of single alleles to the groups was then aggregated to create a classification on a patients' basis. Finally, the accuracy of this test algorithm was evaluated. HLA-DRB1 (DRB1*0301*0401*0402*0407*1101*1501=progression) was the strongest discriminator between the 2 groups. The test algorithm defined all patients with at least one of these DRB1 alleles to be progressive after ICT. Thus, 12 of 12 patients of group B could have been identified as progressive (sensitivity=100%). However, only 10 of 17 patients of group A would have been identified as responding (specificity=58%). Thus, the test had a positive and negative predictive value of 63% and 100%, respectively. Approximately 5% to 10% of all patients with mRCC are able to benefit from ICT with long-term remission. HLA class II characteristics may aid in identifying this small subgroup of patients with mRCC.
    Journal of immunotherapy (Hagerstown, Md.: 1997) 03/2011; 34(2):196-201. · 3.20 Impact Factor
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    ABSTRACT: To investigate prognostic markers in patients with metastatic renal cell carcinoma (mRCC) undergoing treatment with the tyrosine kinase inhibitors (TKIs) sorafenib (So) or sunitinib (Su). Eighty-three patients with mRCC, who were treated at our institution between 2006 and 2009, were evaluated prospectively. Clinical and laboratory parameters were investigated, as well as, treatment-related adverse events. Subclinical hypothyroidism was characterized by serum TSH above the upper limit of normal and both total triiodothyronine (T3) and thyroxine (T4) within normal limits. Clinical hypothyroidism was defined as low serum T3 and T4 together with elevated TSH. Thirty-one (37.3%) patients received So, and 52 (62.7%) were treated with Su. In univariate analysis, the ECOG status (P < 0.0001) as well as MSKCC criteria (P = 0.003) and response to therapy (P < 0.0001) were associated with progression-free survival (PFS). Twenty-one of 66 (31.8%) evaluable patients developed hypothyroidism during treatment. Of those patients, 8/21 (38.1%) were treated with So and 13/21 (61.9%) with Su. Response rate in this subgroup was 49.2%. Hypothyroidism was associated with a longer PFS (16.0 ± 0.8 months vs. 6.0 ± 0.8 months, P = 0.032). Most patients [16/21 (76.2%)] developed abnormal TSH values during the first 4 weeks of treatment. Hormone replacement with l-thyroxine did not have an influence on survival. In multivariate analyses, only the ECOG status (ECOG 0/1 vs. ECOG 2, P = 0.018) and hypothyroidism (P = 0.01) were independent prognostic parameters. The development of hypothyroidism during treatment might be useful as a predictor of PFS for mRCC patients undergoing treatment with targeted agents.
    World Journal of Urology 12/2010; 29(6):807-13. · 2.89 Impact Factor
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    ABSTRACT: The aim of the study was to investigate prospectively the prevalence of testosterone deficiency (TD) in patients with testicular germ-cell cancer (TGCC) using longitudinal data. A total of 376 TGCC patients were evaluated for serum testosterone levels before, during and after the following therapies: cisplatin-based polychemotherapy, carboplatin monotherapy, radiotherapy or surgery only. Complete serial hormone analyses were performed on 160 patients (age: 33.8±9.1years, mean±SD). All patients received treatment according to the guidelines of the 'German Testicular Cancer Study Group' and the 'European Germ Cell Cancer Consensus Group' or within studies performed by the 'European Organisation for Research and Treatment of Cancer' and the 'Deutsche Krebsgesellschaft'. Main outcome measurements were sexual hormone profiles over time. Statistical analysis of 1831 testosterone serum levels over time revealed a persistent TD in 23.9% of seminoma and 26.2% of non-seminoma patients. TD was associated with subnormal residual testicular volumes (<12mL). In conclusion, TD rates are high in testis cancer patients. This is present at primary diagnosis and most likely related to testicular dysgenesis or atrophy. Our longitudinal evaluation indicates that treatment modalities have minor influence and effect on the persistently high rates of TD in TGCC patients.
    International Journal of Andrology 11/2010; 34(5 Pt 2):e351-7. · 3.37 Impact Factor
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    ABSTRACT: The aim of the study was the determination of the negative predictive value of sextant core prostate biopsy. Prostate cancer was diagnosed in 126 patients by systematic ultrasound-guided sextant biopsy and was subsequently treated with radical prostatectomy. The prostatectomy specimens were examined histopathologically using the whole-mount section technique. 81 patients were diagnosed with unilateral and 45 with bilateral prostate cancer after biopsy. In 15/81 patients, the diagnosis of unilateral disease was confirmed by the whole-mount sections; 66 patients turned out to have bilateral disease. In 14/66 cases, the missed tumour foci were diminutive. In the remaining 52 patients, an erroneous diagnosis of unilateral prostate cancer had been made after biopsy, although the missed tumour foci were not diminutive. The negative predictive value of sextant core biopsy with respect to unilateral disease was 36%. An unexpectedly high number of tumour foci are missed by systematic ultrasound-guided sextant prostate biopsy.
    Anticancer research 05/2010; 30(5):1823-7. · 1.71 Impact Factor
  • L Hertle, A van Ophoven
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    ABSTRACT: We have conducted a prospective open-label study to examine the safety and efficacy of the long-term administration of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). Patients were stratified into 2 groups: an NIDDK group including patients fulfilling the NIDDK criteria for IC and a non-NIDDK group encompassing patients who presented the characteristic IC symptoms but met at least one of the NIDDK exclusion criteria. Amitriptyline was taken strictly at bedtime following an established self-titration protocol without a limitation of the maximum daily dosage. Patients reporting improvement in a global response assessment questionnaire were defined as treatment responders. Further efficacy measures included changes of pain and urgency, functional bladder capacity and frequency. Changes in the O'Leary-Sant IC index and rating of overall satisfaction with the therapeutic outcome are reported as well. The mean follow-up of the study was 19.0 +/- 12.5 months. The response rate was 64% (60 patients). Overall mean dosage was 55 mg (range: 12.5-150 mg). Side effects occurred in 79 patients (84%) (dry mouth: 79%, weight gain: 59%). Patient overall satisfaction with the therapeutic result was either excellent or good in 43 patients (46%). The drop-out rate was 31% (29 patients) after a mean treatment period of 6 weeks at a mean dosage of 70 mg. Non-response to treatment was the primary reason for drop-out in all cases, side effects contributed to drop-out in 25 patients (86%). The various IC symptoms improved statistically significant compared with baseline. Long-term administration of amitriptyline is a feasible, safe and effective treatment for IC provided that the drug is used judiciously to minimise adverse effects. The therapeutic response to amitriptyline was uniformly observed in patients fulfilling the NIDDK criteria and in those patients with the pure clinical diagnosis of IC.
    Aktuelle Urologie 01/2010; 41 Suppl 1:S61-5. · 0.47 Impact Factor
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    ABSTRACT: We examined papillary renal cell carcinoma prognostic variables and validated the 2002 UICC TNM staging system in a multicenter analysis. From 10 urological institutions in Germany followup data were collected on a total of 675 patients with papillary renal cell carcinoma. Central pathological review was done to validate external histopathological diagnoses. The Kaplan-Meier method was used to derive cumulative cancer specific and overall survival, and the log rank test was used to compare the curves of 2 or more groups. For multivariate analysis of prognostic factors Cox regression analysis was done. All proportional hazard assumptions were systemically verified using the Grambsch-Therneau test. Cancer specific survival was significantly related to TNM stage and histological grading on univariate and multivariate analyses. Five-year cancer specific survival in pT1b cases was significantly shorter than in pT1a cases (90.0% vs 98.3%, p = 0.017). No significant difference was found between pT1b and pT2 tumors. Patients with pT3 or greater disease were at high risk for metastasis (50.6%) while metastatic disease associated with pT2 or less tumors occurred in 7.8% (p <0.0001). After metastatic disease was present the prognosis was poor with 7.2% 5-year cancer specific survival. Age was associated with poor prognosis in the subgroup with pT3 or greater tumors on univariate analysis (p = 0.026) but not on multivariate analysis. In its current form the 2002 UICC TNM staging system is not applicable to papillary renal cell carcinoma. Clinical and radiological followup should be offered at frequent intervals to patients with venous thrombus and/or locally advanced disease. The role of age remains unclear but should not be underestimated in risk stratification after surgery.
    The Journal of urology 12/2009; 183(2):460-6. · 4.02 Impact Factor
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    ABSTRACT: For decades, advanced renal cancer was almost resistant to systemic therapy. Only a few patients with metastatic disease derived clinical benefit from immunotherapy after nephrectomy. Recent advances in understanding the molecular biology of advanced and metastatic renal cancer led to the development of several targeted agents that showed impressive anti-tumor efficacy and prolongation of progression-free survival. The integration of these drugs into clinical practice did not only revolutionize the management of renal cancer, but also created controversy about the necessity, patient selection for and timing of the extirpation of the primary tumor, as well as metastasectomy. Data from ongoing preclinical investigations, including basic science and translational research, are presented and carried forward into multimodal considerations to optimize clinical efficacy of concomitant surgical treatments in the era of targeted agents. In addition to these analyses, this article highlights available clinical data regarding the disputable importance of surgical treatment approaches and explores the need of multimodality treatment paradigms within interdisciplinary decision making.
    Expert Review of Anti-infective Therapy 07/2009; 9(6):763-71. · 2.07 Impact Factor
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    ABSTRACT: The endothelin axis consists of endothelin-1 (ET-1) and its two receptors, ET(A)- and ET(B)-receptor (ET(A)-R and ET(B)-R). In several tumor entities, the ET(A)-R plays a significant role as a drug target. In our study, we investigated whether inhibition of ET(A)-R with atrasentan leads to an antitumor effect in urinary bladder carcinoma as well. Twenty nude mice with thymic aplasia were subcutaneously administered 2 x 10(6) KU-19-19 bladder cancer cells in the right flank. Starting on the 22nd day after the injection, ten animals were treated with atrasentan (2.5 mg/kg BW intraperitoneally), and another ten animals were treated with placebo. During treatment, absolute tumor growth and relative growth rate over time were determined. After the end of treatment, the mitosis and necrosis rates, microvessel density, and receptor density in the tumor tissue were analyzed by immunohistochemistry. In addition, the expression intensities of ET-1, ET(A)-R, and ET(B)-R were evaluated semiquantitatively and compared between the groups. No significant differences between the active-treatment and placebo groups were detected, either with respect to absolute tumor growth (P = 0.333) or mitosis rate (P = 0.217). In the analysis of the necrosis rate and receptor density for ET(A)-R, a trend toward higher values in the active-treatment group (mean necrosis rate = 63.67%, receptor density: 1.417) than in the placebo group (mean necrosis rate = 46.25%, receptor density: 1.270) was found; however, neither difference was statistically significant (P = 0.08 and 0.219, respectively). ET(A)-R blockade with atrasentan in a bladder cancer xenograft model shows no significant antitumor effect.
    Journal of Cancer Research and Clinical Oncology 06/2009; 135(10):1455-62. · 2.91 Impact Factor
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    ABSTRACT: The vascular endothelial growth factors VEGF-C, VEGF-D and its receptor, VEGFR-3, are overexpressed in different malignancies and associated with lymph node metastasis and poor prognosis. We analysed these factors in clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma (RCC). The results were correlated with various clinicopathological parameters (CPP). We constructed a tissue microarray with tumor samples of 135 (81%) ccRCC and 31 (19%) pRCC. After immunohistochemical staining using polyclonal antibodies for VEGF-C, VEGF-D and VEGFR-3, a semiquantitative analysis was performed to determine the levels of expression. The results were compared between the two subgroups and were correlated with CPP. In the two subgroups the expression of VEGF-C was significantly correlated with that of VEGF-D (p<0.001). There was an increased expression of VEGF-C in 11% of ccRCC and 36% of pRCC (p=0.002). VEGF-D expression was positive by means of analysis in 22% of ccRCC and 42% of pRCC (p=0.039). There was no significant difference regarding the expression of VEGFR-3 between the subgroups (44% ccRCC and 61% pRCC, p=0.11). No correlation was found between the expression of the analysed parameters and CPP (TNM, grading, progression-free survival and overall survival) in either the entire group or in the two subgroups. In summary, ccRCC and pRCC show a different expression pattern of the analysed lymphangiogenic factors. Further studies are necessary to confirm these results and to determine whether the VEGF-C/VEGF-D/VEGFR-3-axis can play a role as a prognostic tool or a target for therapeutic intervention in renal cell carcinoma.
    Oncology Reports 10/2008; 20(4):721-5. · 2.30 Impact Factor
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    ABSTRACT: Our goal was to prospectively evaluate self-reported quality-of-life (QoL) during second-line therapy in 51 consecutive patients with cytokine-refractory kidney cancer treated with sorafenib or sunitinib. QoL was assessed by the EORTC QoL questionnaire QLQ-C30 at baseline and at weeks 4, 6, 10, 12 and 16. Global QoL deteriorated significantly during the first 4 weeks of treatment (P < 0.0001). Patients experienced a reduction of their role, cognitive, and social function (all P < 0.0001). In addition, fatigue (P < 0.0001), nausea/vomiting (P = 0.003), and pain (P < 0.0001) as well as dyspnoea (P < 0.0001), insomnia (P = 0.026), appetite loss (P = 0.013), and diarrhoea (P < 0.0001) increased significantly. After 16 weeks, fatigue (P < 0.0001), pain (P = 0.015), appetite loss (P = 0.002) and diarrhoea (P = 0.038) were still influenced by the therapy, while all functional scales recovered. Global QoL at baseline was predictive of overall response (P = 0.006) and progression free survival (PFS) (P < 0.0001). A better physical function at baseline, a better ECOG performance status, and a low risk profile according to MSKCC risk groups correlated with a longer PFS (all P < 0.0001). No significant differences regarding QoL were found between sorafenib and sunitinib during the study period. Second-line therapy with sorafenib or sunitinib does not adversely affect patients global QoL after 16 weeks of treatment. Evaluation of baseline QoL can help to further stratify patients into risk groups predicting overall response and PFS.
    Journal of Cancer Research and Clinical Oncology 08/2008; 135(1):61-7. · 2.91 Impact Factor
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    ABSTRACT: Recent studies have shown that intraductal prostate carcinoma (IDC-P) should be considered as a separate lesion distinct from prostatic intraepithelial neoplasia (PIN). The purpose of the present study was to analyze the genetic relationship between benign prostatic tissue, PIN, invasive cancer, IDC-P, and extracapsular tumor tissue to get further information about the role of IDC-P in the development of prostate cancer. One hundred five radical prostatectomy specimens were investigated immunohistochemically, 77 cases were analyzed by PCR for LOH of the tumor suppressor genes TP53 and RB1, and 11 cases of IDC-P and 10 cases of PIN were investigated using comparative genomic hybridization (CGH). At CGH analysis, IDC-P showed several chromosomal imbalances in contrast to PIN, where no changes were found. We could demonstrate a significant increase of LOH for TP53 or RB1 from benign tissue to PIN. LOH of both TP53 and RB1 were frequently found in IDC-P (52%), followed by extracapsular tumor tissue (44%), invasive cancer (24%), PIN (19%), and benign prostatic tissue (17%). Increased immunohistochemical expression was found in invasive cancer for TP53, RB1, and for PTEN. Decreased expression could be demonstrated in extracapsular tumor tissue and in IDC-P. Our results indicate that IDC-P in general follows the genetic pathway from normal epithelium over PIN lesion. IDC-P represents a separate prostatic lesion and should be graded as a poorly differentiated carcinoma.
    Genes Chromosomes and Cancer 08/2008; 47(7):565-72. · 3.55 Impact Factor
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    ABSTRACT: To present long-term results of a single-center series of patients undergoing bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer and to analyze the impact of pelvic lymph node metastasis and lymphovascular invasion on clinical outcome. Between 1986 and 2005 833 patients were treated with bilateral pelvic lymphadenectomy and radical cystectomy at our institution. 614 of them with valid clinical follow-up information and no neoadjuvant therapy could be evaluated. Disease-free and overall survival in the entire cohort was 56.7% and 49.5% at 5 years and 52.4% and 38.2% at 10 years, respectively. 28.1% of all patients had pelvic lymph node metastasis. We found organ-confined tumor stages (<or=pT2) in 43.8%. Patients with non-organ-confined tumor stages (>or=pT3) and positive pelvic lymph nodes had a significantly shorter overall survival than those without lymph node metastasis (P < 0.0001). In the subgroup of <or=pT2, the presence of pelvic lymph node metastasis did not show a statistically significant effect on overall survival (P = 0.618). The presence of lymphovascular invasion was associated with an impaired survival (P < 0.0001). In multivariate analysis, pathological tumor stage (P < 0.0001), lymph node stage (>or=pT3) (P = 0.004) and lymphovascular invasion (P = 0.001) were independent prognostic parameters. According to the present series, survival for patients with <or=pT2 does not depend on the lymph node stage. Lymphovascular invasion is an independent parameter of impaired survival and should be determined routinely in cystectomy specimens to identify patients, who may benefit from adjuvant systemic therapy.
    International Journal of Urology 05/2008; 15(7):607-11. · 1.73 Impact Factor
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    ABSTRACT: The German DRG (dose-related groups) system is updated each year by the institution dealing with the remuneration in hospitals (InEK). Once again, the German Spcoety for Urology has supported the adjustment process in a constructive manner. Analysis of the changes and their implications is highly significant for urology. This article describes and discusses the main changes in the system for the specialty of urology insofar as they concern the structure of the DRG system and the catalogues of diagnoses (ICD) and of procedures (OPS). The 2007 edition of the DRG system leads to numerous changes for urology. There are new OPS codes for partial resection of the kidney, treatment of urinary incontinence and radical resection in the pelvis minor. Additional payment for implantation of a prosthetic penis is divided with reference to the type of prosthesis. At DRG level, new DRG splits are found depending on the PCCL and patient age. Combination operations on the bladder and bowel and on the male genitalia are assigned to newly established DRGs. The changes described enhance the professional accuracy of the representations of urological care provision. New strategies designed to solve problems in representation have been established (e.g. multi-step interventions). Various problems persist, e.g. those of operations on the penis (DRG M03Z) and the need for more finely defined representation of laser treatment in urology. In the short term practicable solutions to the problem of improving the quality of representation are needed.
    Der Urologe 03/2008; 47(2):182-9. · 0.46 Impact Factor
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    ABSTRACT: It was the aim of this study to investigate the clinical differences between the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib as second-line treatment for cytokine-refractory kidney cancer patients. Twenty consecutive patients received continuous treatment of oral sorafenib at a dose of 400 mg twice daily in 6-week cycles. Sunitinib was administered to the remaining 20 patients at 50 mg once daily in repeated 6-week cycles consisting of daily therapy for 4 weeks, followed by a 2-week off-treatment period. We correlated best treatment responses and progression-free survival (PFS) with either TKI treatment. Adverse events were evaluated and differences were compared between both treatment groups. In the sorafenib group, 2 (10%) patients showed a partial response (PR) and 4 (20%) patients had progressive disease (PD) versus 6 (30%) PRs and 3 (15%) PDs in the sunitinib group, respectively (p = 0.195). The median PFS was 6.4 months for sorafenib and 7.4 months for sunitinib (p = 0.969). In contrast to gender, age and the number of prior cytokine therapy cycles, the Eastern Cooperative Oncology Group performance status (p = 0.024) and the Memorial Sloan-Kettering Cancer Center risk groups for second-line treatments (p = 0.015) were independent predictive parameters of PFS. Gastrointestinal symptoms were found to occur with greater frequency in the sunitinib group (p = 0.03). Both TKIs showed comparable clinical benefits. The Eastern Cooperative Oncology Group performance status and the Memorial Sloan-Kettering Cancer Center risk groups can help determine which patients might benefit from alternative drug treatments.
    Oncology 02/2008; 74(3-4):216-22. · 2.17 Impact Factor

Publication Stats

2k Citations
420.60 Total Impact Points

Institutions

  • 2002–2013
    • Universitätsklinikum Münster
      • • Gerhard-Domagk-Institut für Pathologie
      • • Klinik für Urologie
      Muenster, North Rhine-Westphalia, Germany
  • 1993–2012
    • University of Münster
      • Department of Urology
      Münster, North Rhine-Westphalia, Germany
  • 2004–2007
    • EUREGIO-KLINIK Albert-Schweitzer-Straße GmbH
      Nordhorn, Lower Saxony, Germany
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1993–1998
    • Johannes Gutenberg-Universität Mainz
      • Department of Urology
      Mainz, Rhineland-Palatinate, Germany