Gero Kramer

Vienna General Hospital, Wien, Vienna, Austria

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Publications (112)463.71 Total impact

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    ABSTRACT: In recent years, new therapeutic options have brought improvements in the treatment of metastatic, castration-resistant prostate cancer. Targeted Hormone Therapy (THT) represents a novel therapeutic component for which recent studies have shown a maximum benefit in the time between failure of androgen deprivation therapy (patient is metastatic and still pain-free) and prior to chemotherapy. Prostate cancer experts of the Austrian Society of Urology and Andrology (ÖGU), the Working Group for Urologic Oncology as part of the ÖGU, and the Professional Association of Austrian Urologists (BvU) have developed recommendations for the treatment of patients with asymptomatic or mildly symptomatic metastatic, castration-resistant prostate cancer. The definition of failure of classical hormonal therapy has been based on the guidelines of the German Society of Urology (Deutsche Gesellschaft für Urologie, DGU) and the European Association of Urology (EAU). Criteria for the initiation of treatment with hormonal or chemotherapy include: Castration resistance with increase of prostate-specific antigen (PSA) Evidence of metastases in imaging No or mild symptoms Quality of Life Index of the Eastern Cooperative Oncology Group (ECOG) 0-1 (ECOG 2 requires individualized decision) [1]. Treatment should only be initiated when all of these four criteria are applicable, with the age of the patient being no exclusion criterion. First-line therapies for these patients include abiraterone, enzalutamide, and docetaxel as well as radium-223. The manuscript refers only to treatment regimens available in Austria. Selection of the initial treatment option—starting with THT or chemotherapy—should be determined based on the individual patient characteristics. When using abiraterone or enzalutamide, re-staging within 3–6 months is recommended.
    No preview · Article · Feb 2016 · Wiener klinische Wochenschrift
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    ABSTRACT: Purpose: Blood levels of YKL-40 are elevated in various malignancies and other inflammatory diseases. Moreover, higher YKL-40 levels, have consequently been shown to correlate with poor prognosis in several cancers. The aim of this study was to investigate the prognostic value of circulating and tissue levels of YKL-40 in renal cell cancer (RCC). Patients and methods: Preoperative YKL-40 serum/plasma levels were determined in 222 surgically treated RCC patients, as well as in 35 controls. Postoperative serum samples were analysed in 19 of the 222 RCC cases. Moreover, gene expression levels were assessed in 101 RCC frozen tissue samples using quantitative RT real-time PCR. Finally, immunohistochemical analysis was done in 37 RCC cases to assess the tissue localization of YKL-40. Results were correlated with clinicopathological and follow-up data. Results: YKL-40 serum but not tissue gene expression levels were higher in RCC patients compared to controls (p= 0.050). Serum YKL-40 levels significantly increased following nephrectomy (p< 0.001). High circulating YKL-40 concentrations were independently associated with shorter survival in both serum and plasma cohorts. YKL-40 gene expression was not correlated with patients' prognosis. Conclusions: Preoperative elevated circulating levels of YKL-40 predict survival in patients treated with nephrectomy for RCC independently of determining from serum or plasma. Tumour cells do not seem to be the main source of elevated serum/plasma YKL-40 levels in RCC patients.
    No preview · Article · Oct 2015 · The Journal of urology

  • No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: AimHigh levels of fatty acid synthase have shown to correlate with the aggressiveness of prostate cancer. As [11C]acetate exhibits a close correlation with the level of fatty acid synthase, we aimed to assess whether the SUV in [11C]acetate PET serves as a suitable prognostic marker in patients with recurrent prostate cancer.Materials and Methods In 123 consecutive patients, examined between 2010 and 2014, the maximum standardized uptake value (SUVmax) of local recurrences as well as lymph node and bone metastases was measured. Choosing the spleen as a standard for relatively high physiological uptake, a ratio of tumor to spleen uptake (SUVts) was calculated for standardizing the uptake, too. The corresponding initial Gleason scores (GS) and serum-PSA levels around the time of the performed PET/CT for each patient were retrospectively collected and PSA doubling together with PSA velocity were determined. For further analysis patients were divided with regard to their initial Gleason score (≤3 + 4 and ≥ 4 + 3). The median of PSA velocity was calculated to separate patients with a high and low PSA velocity and Mann–Whitney U or Student's t-test were used, testing for significant differences. For correlation Spearmen-Rho test was used.ResultsPET was positive for recurrence in 82/123 patients. PSA was significantly higher in PET-positive than in negative patients (5.9 vs. 3.2 ng/ml; P = 0.006). Initial Gleason score did not differ in PET negative and positive patients (P = 0.3), whereas PSA velocity was markedly higher in PET positive patients (0.4 vs. 0.1 ng/ml/month; P = 0.01). Median SUVmax of PET positive patients was 5.23 (mean 5.78; range 0.9–16.8) and meadian SUVts was 0.78 (mean 0.84, range 0.14–2.50). SUVts was significantly higher in patients with high PSA velocity (SUVts 0.76 vs. 0.92; P = 0.009), whereas SUVmax failed statistical significance (5.4 vs. 6.3 ng/ml/month; P = 0.08). Patients with a high SUVmax proved to have a significantly higher median Gleason score compared to low uptake 8.0 vs. 7.0; P = 0.004). Vice versa both SUVmax (GS 6: 5.0; GS 7: 5.6; GS 8: 5.7; GS 9: 6.5; r = 0.30, P = 0.008) and SUVts (GS 6: 0.63; GS 7: 0.68; GS 8: 0.85; GS 9: 0.89; r = 0.30, P = 0.006) significantly correlated with Gleason score. Patients with a Gleason score ≤ 3 + 4 had a significantly lower SUVmax (4.8 vs. 5.7; P = 0.02) and SUVts (0.67 vs. 0.85; P = 0.02) as compared to a Gleason score ≥ 4 + 3.Conclusion[11C]acetate uptake demonstrated to correlate with initial Gleason score. Furthermore, patients with a high PSA velocity proved to have higher [11C]acetate uptake in tumor lesions. Prostate 9999: XX–XX, 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Aug 2015 · The Prostate
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    ABSTRACT: Tissue levels of the oncofetal protein insulin-like growth factor-II mRNA-binding protein-3 (IMP3) have been associated with poor prognosis in multiple human malignancies. However, its circulating levels have not yet been analyzed. Therefore, the aim of this study was to assess the prognostic value of both serum and tissue levels of IMP3 in prostate cancer (PC). IMP3 protein expression was analyzed in 124 PC and 13 benign prostate hyperplasia (BPH) patients using immunohistochemistry. Gene expression levels of IMP3 and its molecular target IGF2 were analyzed in 29 frozen and 26 paraffin embedded PC tissues using real-time PCR and immunohistochemistery. Serum IMP3 levels were assessed in 94 PC and 20 BPH patients as well as in 20 controls using ELISA. IMP3 immunostaining was present in 0% (0/13) of BPHs, 15% (15/101) of clinically localized PCs and 65% (15/23) of palliatively treated metastatic PCs (p<0.001). Accordingly, serum IMP3 concentrations were significantly higher in PC compared to BPH patients which were higher than those in controls (p<0.001 each). The highest concentrations were detected in metastatic PC patients (p=0.036). In patients who underwent radical prostatectomy high IMP3 serum levels were independently associated with poor cancer-specific survival. IMP3 gene and protein expressions were not correlated with those of IGF2. In conclusion, we found enhanced IMP3 levels in tissue and serum samples of PC patients compared to non-PC men. Moreover, IMP3 was associated with metastasis and PC-specific survival. The tumor promoting effect of IMP3 appears to be independent from its regulatory role on IGF2 in PC. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Oct 2014 · International Journal of Cancer
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    ABSTRACT: Objective To evaluate the benefit of docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line docetaxel.Patients and Methods We retrospectively reviewed the records of consecutive patients with mCRPC with a good response to first-line docetaxel [serum prostate specific antigen (PSA) decrease ≥50%; no clinical/radiological progression]. We analysed the impact of management at relapse (docetaxel rechallenge or non-taxane-based therapy) on PSA response, symptomatic response (performance status/pain/analgesic consumption), and overall survival (OS). We used multivariate stepwise logistic regression to analyse potential predictors of a favourable outcome.ResultsWe identified 270 good responders to first-line docetaxel. The median progression-free interval (PFI) was 6 months from the last docetaxel dose. At relapse, 223 patients were rechallenged with docetaxel (82.5%) and 47 received non-taxane-based therapy. There was no significant difference in median OS {18.2 [95% confidence interval (CI) 16.1-22.00] and 16.8 [95%CI 13.4-21.5] months, respectively, P = 0.35}. However, good PSA response and symptom relief/stable disease were more frequent on docetaxel rechallenge (40.4% vs 10.6%, P < 0.001 for PSA). A PFI of >6 months and added estramustine predicted a good PSA response and symptomatic response on docetaxel rechallenge but only a PFI of >6 months predicted longer OS. Haemoglobin (<13 g/dL) and pain were associated with reduced OS. Docetaxel rechallenge increased the incidence of grade ≥3 sensory neuropathy, nail disorders and asthenia/fatigue.Conclusions Docetaxel rechallenge is a management option for responders to docetaxel with a PFI of >6 months, but did not prolong survival. Potential benefits should be weighed against the risk of cumulative toxicity.
    No preview · Article · Jun 2014 · BJU International
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    ABSTRACT: Objective To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC).Patients and Methods We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality.ResultsOf the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3–4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols.ConclusionAC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3–4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings.
    No preview · Article · Jun 2014 · BJU International
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    ABSTRACT: YKL-40 is a novel inflammatory serum protein shown to be associated with the presence and prognosis of several malignancies. However, its prognostic relevance has not yet been analyzed in bladder cancer (BC). Therefore, the aim of this study was to assess the tissue, serum, and urinary levels of YKL-40 and their prognostic value in BC. YKL-40 gene expression levels were analyzed in frozen tissue samples of 91 patients with BC; YKL-40 concentrations were measured in 120 serum (101 patients with BC and 19 controls) and 154 urine samples (125 patients with BC and 29 controls). In 16 cases, corresponding serum samples collected before and after radical cystectomy were analyzed for YKL-40. Results were correlated with clinicopathological parameters and follow-up data. YKL-40 gene expressions and serum concentrations were higher in patients with BC compared with controls; however, urinary YKL-40 levels remained under the detection limit in both patients and controls. Higher tissue gene expressions and serum concentrations were associated with poor patients' survival in the univariable analysis (P = 0.037 and 0.022, respectively), but only high YKL-40 serum levels proved to be independent prognostic factors in BC (hazard ratio = 1.755, 95% CI: 1.014-3.039, P = 0.045). We found no significant difference between preoperative and postoperative serum concentrations of YKL-40. YKL-40 serum levels are associated with the presence of BC and poor patients' survival. The independent prognostic relevance of YKL-40 is of particular interest in patients with muscle-invasive BC treated with radical surgery. Our data suggest that BC tissue is not the main source of serum YKL-40 levels.
    Full-text · Article · May 2014 · Urologic Oncology

  • No preview · Article · Apr 2014 · European Urology Supplements
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    ABSTRACT: Objectives YKL-40 is a novel inflammatory serum protein shown to be associated with the presence and prognosis of several malignancies. However, its prognostic relevance has not yet been analyzed in bladder cancer (BC). Therefore, the aim of this study was to assess the tissue, serum, and urinary levels of YKL-40 and their prognostic value in BC. Methods and materials YKL-40 gene expression levels were analyzed in frozen tissue samples of 91 patients with BC; YKL-40 concentrations were measured in 120 serum (101 patients with BC and 19 controls) and 154 urine samples (125 patients with BC and 29 controls). In 16 cases, corresponding serum samples collected before and after radical cystectomy were analyzed for YKL-40. Results were correlated with clinicopathological parameters and follow-up data. Results YKL-40 gene expressions and serum concentrations were higher in patients with BC compared with controls; however, urinary YKL-40 levels remained under the detection limit in both patients and controls. Higher tissue gene expressions and serum concentrations were associated with poor patients’ survival in the univariable analysis (P = 0.037 and 0.022, respectively), but only high YKL-40 serum levels proved to be independent prognostic factors in BC (hazard ratio = 1.755, 95% CI: 1.014–3.039, P = 0.045). We found no significant difference between preoperative and postoperative serum concentrations of YKL-40. Conclusions YKL-40 serum levels are associated with the presence of BC and poor patients’ survival. The independent prognostic relevance of YKL-40 is of particular interest in patients with muscle-invasive BC treated with radical surgery. Our data suggest that BC tissue is not the main source of serum YKL-40 levels.
    Full-text · Article · Jan 2014
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    ABSTRACT: Objective: To determine if mammalian target of rapamycin (mTOR) inhibitor (everolimus or temsirolimus) rechallenge in the third- or fourth-line setting after sequential use of a vascular endothelial growth factor receptor (VEGF)-targeted agent and an mTOR inhibitor is a feasible and effective treatment strategy in patients with metastatic renal cell carcinoma (mRCC). Methods: Patients who received a VEGF-targeted agent, an mTOR inhibitor and rechallenge with a second mTOR inhibitor at 2 institutions (Hôpital Européen Georges-Pompidou and Vienna Medical School) between 30 March 2001 and 15 September 2011 were included. Analyses of radiographic images were performed according to the Response Evaluation Criteria in Solid Tumors, version 1.0, to determine the objective response rate and treatment duration (TD). Results: Twelve patients met the inclusion criteria. Following 1 or 2 VEGF receptor-tyrosine kinase inhibitors, 7 patients firstly received everolimus and 5 patients received temsirolimus. Irrespective of treatment sequence, 6 of 12 patients (50%) responded to everolimus and 4 of 12 patients (33%) responded to temsirolimus; 3 patients (25%) did not respond to either. Median TDs (95% confidence interval) for everolimus → temsirolimus and temsirolimus → everolimus sequences were 10.3 months (8.8-19.2 months) and 5.8 months (2.9-19.3 months), respectively. Conclusions: Despite the limited number of patients, this highlights the feasibility of utilizing mTOR rechallenge as an integral part of sequential treatment strategies in mRCC.
    No preview · Article · Jun 2013 · Oncology

  • No preview · Article · Mar 2013 · European Urology Supplements
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    ABSTRACT: In this study, we assessed the changes and prognostic relevance of syndecan-1 (SDC1) tissue and serum levels in bladder cancer (BC). SDC1 levels were analyzed in 213 samples (119 paraffin-embedded and 79 serum samples of BC patients and 15 controls) using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Results were correlated with clinicopathological characteristics and follow-up data, as well as previously determined serum levels of angiogenic factors (bFGF, endostatin, angiostatin, angiopoietin, VEGF, Tie2 and MMP-7). SDC1 staining was present in the cell membrane of normal bladder epithelium and non–muscle-invasive BC cells but was absent in a significant proportion of muscle-invasive carcinomas (P < .001). In contrast, stromal SDC1 expression was enhanced in muscle-invasive compared to non–muscle-invasive BCs (P = .001). Serum concentrations of the SDC1 ectodomain were higher in muscle-invasive BCs compared to controls or non–muscle-invasive carcinomas (P < .001 each). Lymph node–positive cases had the highest SDC1 serum concentrations (P < .001). SDC1 expression in stromal cells was independently associated with survival (hazard ratio = 2.034, 95% confidence interval 1.176-3.519, P = .011). SDC1 serum concentrations correlated with those of endostatin and MMP-7. Loss of SDC1 in tumor cells and the parallel increase of serum SDC1 ectodomain concentration in high-stage, high-grade BCs suggest the involvement of SDC1 shedding in BC progression. In addition, high preoperative SDC1 serum levels may help to identify patients with lymph node metastases, supporting therapeutic decision-making. Presence of SDC1 in tumor stroma is an independent risk factor for patient survival and may therefore be used to select patients for more aggressive therapy.
    Full-text · Article · Jan 2013 · Human pathology
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    ABSTRACT: Within the last two years the therapy of castration resistant prostate cancer (CRPC) has made major advances. Both the COU-AA-301 phase III trial and the TROPIC trial showed a survival benefit for patients after docetaxel failure treated with abiraterone or cabazitaxel, respectively. With rising interest for chemotherapeutic options and novel drugs, our goal was to review within the context of a multidisciplinary team the available evidence and explore the standards for medical treatment of prostate cancer outside of clinical trials. From this background, we are carefully evaluating the current treatment recommendations, based on the available evidence, and highlight potential future treatment options but also discuss important clinical topics like treatment until progression versus the advantage of chemo holidays and definition of particular patient subgroups. Additionally, we focus on novel molecular entities, which will most likely be available in the near future, such as MDV3100 and Sipuleucel T. The role and importance of palliation with radiotherapy and proactive medical management of pain is also discussed, as well as new options for bone directed therapy. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists.
    No preview · Article · Aug 2012 · Wiener klinische Wochenschrift
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    ABSTRACT: To assess the role and prognostic significance of angiostatin, basic fibroblast growth factor (bFGF), and tyrosine endothelial kinase (TEK/Tie2) in transitional cell bladder carcinoma. Angiostatin, bFGF, and TEK serum concentrations were measured in 82 bladder cancer patients and 20 age-matched healthy controls using enzyme-linked immunosorbent assay. Results were compared with clinicopathologic and follow-up data with the Mann-Whitney U test and Kaplan-Meier, univariate and multivariate Cox regression analyses. We found significantly decreased angiostatin and TEK serum levels and mildly elevated bFGF concentrations in samples of bladder cancer patients compared with controls (P < .001, P < .001, and P = .083, respectively). Furthermore, high TEK serum levels were correlated with poor disease-specific and metastasis-free survival in muscle-invasive bladder cancer (P = .013, P = .018), whereas angiostatin and bFGF concentrations did not show any correlation with patients' prognosis. Multivariate analysis revealed high TEK levels (<1.60 ng/mL) as borderline significant independent risk-factor of disease-specific survival (HR 1.83, 95% CI 0.97-3.44, P = .061) and metastasis-free survival (HR 2.65, 95% CI 0.93-7.55, P = .069). The characteristic differences in the circulating levels of angiostatin, TEK, and bFGF between patients and controls, suggest the presence of a tumor-induced proangiogenic milieu in bladder cancer. Serum TEK levels may contribute to a more reliable preoperative risk stratification in muscle-invasive bladder cancer and therefore may help to optimize therapeutic decisions.
    Full-text · Article · May 2012 · Urology

  • No preview · Article · Apr 2012 · The Journal of Urology
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    ABSTRACT: Multipotent mesenchymal stromal cells (MSCs) are found in a variety of adult tissues including human dermis. These MSCs are morphologically similar to bone marrow-derived MSCs, but are of unclear phenotype. To shed light on the characteristics of human dermal MSCs, this study was designed to identify and isolate dermal MSCs by a specific marker expression profile, and subsequently rate their mesenchymal differentiation potential. Immunohistochemical staining showed that MSC markers CD73/CD90/CD105, as well as CD271 and SSEA-4, are expressed on dermal cells in situ. Flow cytometric analysis revealed a phenotype similar to bone marrow-derived MSCs. Human dermal cells isolated by plastic adherence had a lower differentiation capacity as compared with bone marrow-derived MSCs. To distinguish dermal MSCs from differentiated fibroblasts, we immunoselected CD271(+) and SSEA-4(+) cells from adherent dermal cells and investigated their mesenchymal differentiation capacity. This revealed that cells with increased adipogenic, osteogenic, and chondrogenic potential were enriched in the dermal CD271(+) population. The differentiation potential of dermal SSEA-4(+) cells, in contrast, appeared to be limited to adipogenesis. These results indicate that specific cell populations with variable mesenchymal differentiation potential can be isolated from human dermis. Moreover, we identified three different subsets of dermal mesenchymal progenitor cells.
    Full-text · Article · Nov 2011 · Journal of Investigative Dermatology

  • No preview · Article · Sep 2011 · European Journal of Cancer

  • No preview · Article · Sep 2011 · European Journal of Cancer
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    ABSTRACT: First line treatment with temsirolimus is considered standard of care in poor risk patients with metastatic renal cell carcinoma. The role of temsirolimus in pretreated patients with any risk profile is unclear. The aim of this retrospective analysis was to investigate the impact of temsirolimus in patients who had progressed on various treatment lines. From April 2007 to July 2009, all patients who had progressed on receptor-tyrosine kinase-inhibitors, VEGF-antibodies and other agents were treated with temsirolimus (25 mg weekly). Physical examination, white blood cell count and chemistry were obtained weekly and tumor response was assessed every 12 weeks. Thirty patients with a median age of 68 years range (44-81) received treatment with temsirolimus. Most patients were categorized intermediate risk (60%) and the majority had three or more metastatic sites (56.7%). Temsirolimus was median the fourth (range 2-5) systemic treatment line. Grade 3 and 4 toxicities were rare and consisted of anemia, thrombocytopenia and hyperglycemia. Objective remission and stable disease were achieved in 13.3% and 60% of the patients, respectively. The median progression free survival was 4.9 months (2.93-6.81 95% CI). Temsirolimus appears feasible, safe and active in heavily pretreated patients.
    Full-text · Article · Jul 2011 · Acta oncologica (Stockholm, Sweden)

Publication Stats

2k Citations
463.71 Total Impact Points

Institutions

  • 2013-2015
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 2000-2015
    • Medical University of Vienna
      • • Department of Urology
      • • Universitätsklinik für Innere Medizin I
      • • Institut für Sozialmedizin
      Wien, Vienna, Austria
  • 1992-2009
    • University of Vienna
      • • Institute of Cancer Research
      • • Institute of Immunology
      Wien, Vienna, Austria
  • 2007
    • Atrium Medisch Centrum Parkstad
      Heerlen, Limburg, Netherlands