Publications by authors named "Maximilian Seles"

19 Publications

  • Page 1 of 1

T1G1 Bladder Cancer: Prognosis for this Rare Pathological Diagnosis Within the Non-muscle-invasive Bladder Cancer Spectrum.

Eur Urol Focus 2022 May 13. Epub 2022 May 13.

Department of Urology, Pitié Salpétrière Hospital, AP-HP, GRC no. 5, Oncotype-Uro, Sorbonne University, Paris, France.

Background: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum.

Objective: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum.

Design, Setting, And Participants: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018.

Outcome Measurements And Statistical Analysis: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution.

Results And Limitations: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results.

Conclusions: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines.

Patient Summary: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer.
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http://dx.doi.org/10.1016/j.euf.2022.04.014DOI Listing
May 2022

Benefit of Metastasectomy in Renal Cell Carcinoma: A Propensity Score Analysis.

Clin Genitourin Cancer 2022 08 24;20(4):344-353. Epub 2022 Mar 24.

Division of Haematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. Electronic address:

Introduction: To quantify the magnitude of benefit of metastasectomy as compared to medical treatment alone in patients with metastatic renal cell carcinoma (mRCC).

Patients And Methods: We therefore conducted a propensity score analysis of overall survival (OS) in 106 mRCC patients with metachronous metastasis, of whom 36 (34%) were treated with metastasectomy, and 70 (66%) with medical therapy alone.

Results: The most frequent metastasectomy procedures were lung resections (n = 13) and craniotomies (n = 6). Median time-to-progression after metastasectomy was 0.7 years (25th-75th percentile: 0.3-2.7). After a median follow-up of 6.2 years and 63 deaths, 5-year OS estimates were 41% and 22% in the metastasectomy and medical therapy group, respectively (log-rank P = .00007; Hazard ratio (HR) = 0.38, 95%CI: 0.21-0.68). Patients undergoing metastasectomy had a significantly higher prevalence of favorable prognostic factors, such as fewer bilateral lung metastases and longer disease-free intervals between nephrectomy and metastasis diagnosis. After propensity score weighting for these differences and adjusting for immortal time bias, the favorable association between metastasectomy and OS became much weaker (HR = 0.62, 95%CI: 0.39-1.00, P = .050). Propensity-score-weighted 5-year OS estimates were 24% and 20% in the metastasectomy and medical therapy group, respectively (log-rank P = .001). In exploratory analyses, the benefit of metastasectomy was confined to patients who achieved complete resection of all known metastases.

Conclusion: Within the limitations of an observational study, these findings support the concept of metastasectomy being associated with an OS benefit in mRCC patients. Metastasectomies not achieving complete resection of all known lesions are likely without OS benefit.
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http://dx.doi.org/10.1016/j.clgc.2022.03.010DOI Listing
August 2022

Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria.

Cancers (Basel) 2021 Oct 27;13(21). Epub 2021 Oct 27.

Department of Urology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend ( < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr-Sep) and an increase during the winter months (Oct-Mar) were observed ( < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec ( = 0.008) and Jan-Mar ( < 0.001) was significantly higher compared to the months of Jul-Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas ( < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.
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http://dx.doi.org/10.3390/cancers13215377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582382PMC
October 2021

Conservative Treatment of Upper Urinary Tract Urothelial Carcinoma: Con.

Eur Urol Open Sci 2021 Oct 6;32:35-37. Epub 2021 Sep 6.

Department of Urology, Medical University of Graz, Graz, Austria.

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http://dx.doi.org/10.1016/j.euros.2021.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429919PMC
October 2021

Prognostic relevance of ABO blood group system in non-metastatic renal cell carcinoma: An analysis of two independent European cohorts with long-term follow-up.

Urol Oncol 2021 10 9;39(10):736.e9-736.e16. Epub 2021 Jul 9.

Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. Electronic address:

Background: The ABO blood group system has been previously discussed as a risk factor to develop, as well as a prognostic factor in non-metastatic renal cell carcinoma (RCC). Controversial findings have been reported in different populations of RCC patients with rather short follow-up periods. In this study, we aimed to clarify the distribution and prognostic role of ABO blood groups upon 15 years of median follow-up in non-metastatic RCC patients.

Materials And Methods: We evaluated the distribution and prognostic significance of ABO blood group system in two independent cohorts (n = 405 and n = 1473) of non-metastatic RCC patients, who underwent curative (partial or total) nephrectomy between 1998 and 2012 at two tertiary academic centers. Cancer-specific survival, metastasis-free survival, as well as overall survival (OS) were assessed using the Kaplan-Meier method, univariable- and multivariable Cox regression models were applied, respectively.

Results: In the two cohorts, blood groups were not associated with any clinical endpoints (for cohort 2: Cancer-specific survival (HR = 1.233; 95%CI 0.998-1.523, P = 0.052), metastasis-free survival (HR = 1.161; 95%CI 0.952-1.416, P = 0.142) and OS (HR = 1.037; 95%CI 0.890-1.208, P = 0.641), respectively). Compared to 250.298 healthy blood-donors of the Styrian state, the distribution of blood groups was (624 (42.4%) versus 106.861 (42.7%) in group A, 191 (13%) vs. 34.164 (13.7%) in group B, 575 (39%) versus 93.579 (37.4%) in group O and 83 (5.6%) vs. 15.694 (6.3%), P = 0.467).

Conclusion: In this large study with the longest period of follow-up reported to date, the ABO blood group system could not be validated as a prognostic factor in predicting important clinical endpoints in non-metastatic RCC patients.
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http://dx.doi.org/10.1016/j.urolonc.2021.06.005DOI Listing
October 2021

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel.

Eur Urol 2021 04 6;79(4):480-488. Epub 2021 Jan 6.

Department of Urology, The Stokes Centre for Urology, Royal Surrey Hospital, Guildford, UK.

Background: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s.

Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression.

Design, Setting, And Participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel.

Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion.

Outcome Measurements And Statistical Analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves.

Results And Limitations: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review.

Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary.

Patient Summary: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule.
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http://dx.doi.org/10.1016/j.eururo.2020.12.033DOI Listing
April 2021

Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer.

Cancers (Basel) 2020 May 10;12(5). Epub 2020 May 10.

Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

POU3F3 adjacent non-coding transcript 1 (PANTR1) is an oncogenic long non-coding RNA with significant influence on numerous cellular features in different types of cancer. No characterization of its role in renal cell carcinoma (RCC) is yet available. In this study, PANTR1 expression was confined to human brain and kidney tissue and was found significantly up-regulated in clear-cell renal cell carcinoma tissue (ccRCC) compared to non-cancerous kidney tissue in two independent cohorts ( < 0.001 for both cohorts). In uni- and multivariate Cox regression analysis, ccRCC patients with higher levels of PANTR1 showed significantly poorer disease-free survival in our own respective cohort ( = 175, hazard ratio: 4.3, 95% confidence interval: 1.45-12.75, = 0.008) in accordance with significantly poorer overall survival in a large The Cancer Genome Atlas database (TCGA) cohort ( = 530, hazard ratio: 2.19, 95% confidence interval: 1.59-3.03, ≤ 0.001). To study the underlying cellular mechanisms mediated by varying levels of PANTR1 in kidney cancer cells, we applied siRNA-mediated knock-down experiments in three independent ccRCC cell lines (RCC-FG, RCC-MF, 769-P). A decrease in PANTR1 levels led to significantly reduced cellular growth through activation of apoptosis in all tested cell lines. Moreover, as angiogenesis is a critical driver in ccRCC pathogenesis, we identified that PANTR1 expression is critical for in vitro tube formation and endothelial cell migration ( < 0.05). On the molecular level, knock-down of PANTR1 led to a decrease in Vascular Endothelial growth factor A (VEGF-A) and cell adhesion molecule laminin subunit gamma-2 (LAMC2) expression, corroborated by a positive correlation in RCC tissue (for VEGF-A = 0.19, < 0.0001, for LAMC2 = 0.13, = 0.0028). In conclusion, this study provides first evidence that PANTR1 has a relevant role in human RCC by influencing apoptosis and angiogenesis.
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http://dx.doi.org/10.3390/cancers12051200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281347PMC
May 2020

Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors.

Genome Med 2020 02 28;12(1):23. Epub 2020 Feb 28.

Hutchison/MRC Research Centre, University of Cambridge, Cambridge, CB2 0QQ, UK.

Background: Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.

Methods: Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine.

Results: Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings.

Conclusions: These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.
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http://dx.doi.org/10.1186/s13073-020-00723-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048087PMC
February 2020

Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

Urol Oncol 2020 05 5;38(5):440-448. Epub 2019 Nov 5.

Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria.

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors.

Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points.

Materials And Methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018.

Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP.

Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.
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http://dx.doi.org/10.1016/j.urolonc.2019.10.002DOI Listing
May 2020

Prognostic value of B7-H1, B7-H3 and the stage, size, grade and necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma.

Cent European J Urol 2019 14;72(1):23-31. Epub 2019 Mar 14.

Department of Urology, Medical University of Graz, Graz, Austria.

Introduction: We compared the potential prognostic impact of B7-H1 and B7-H3 glycoprotein expressions with the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma (mccRCC) during a long term follow-up.

Material And Methods: We investigated 44 mccRCC patients, who underwent radical nephrectomy between 1995 and 2006 at a single tertiary academic center and received interferon therapy (IFNT) for at least three months. The SSIGN score was applied as a validated prediction outcome model. Representative tumor sections were immunostained with anti-B7-H3 and anti-B7-H1 antibodies. Hereafter, positive antigen-antibody reactions were measured using the Positive-Pixel-Count Algorithm of the Aperio-Technology Image Scope software.

Results: In total, 48% of patients were treated with cytoreductive nephrectomy and postoperative IFNT due to synchronous mccRCC, whereas 52% received IFNT after developing metachronous mccRCC. The SSIGN score was independently associated with a higher mortality risk. Patients with a SSIGN score ≤9 showed an extended 'nephrectomy to start of INFT'-interval (p = 0.02), less synchronous clinical metastases (p = 0.0002), as well as an increased median overall - (OS) or cancer-specific survival (CSS) (p = 0.01), respectively. Furthermore, B7-H3 expression levels of ≤16% were associated with an improved OS or CSS and correlated with a more frequent pathologic grade 1-2, as well as a longer 'nephrectomy to start of IFNT'-interval, respectively. B7-H1 expression patterns did not correlate with survival.

Conclusions: The SSIGN score demonstrated the best prognostic performance. In contrast, B7-H3 expression patterns showed a low association with histopathological parameters, but predicted the cut-off-dependent impaired survival and in the future may define a cut-off to indicate checkpoint-inhibitor treatment.
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http://dx.doi.org/10.5173/ceju.2018.1858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469004PMC
March 2019

MiR-371a-3p Serum Levels Are Increased in Recurrence of Testicular Germ Cell Tumor Patients.

Int J Mol Sci 2018 Oct 12;19(10). Epub 2018 Oct 12.

Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (β-subunit of human chorionic gonadotropin (β-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease ( = 0.014). In contrast, miR-367 levels were not different in these patient groups ( = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.
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http://dx.doi.org/10.3390/ijms19103130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213366PMC
October 2018

MicroRNAs Associated with Von Hippel-Lindau Pathway in Renal Cell Carcinoma: A Comprehensive Review.

Int J Mol Sci 2017 Nov 22;18(11). Epub 2017 Nov 22.

Research Unit of Non-Coding RNA and Genome Editing in Cancer, Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor. One of the major problems with RCC treatment strategies is inherent or acquired resistance towards therapeutic agents over time. The discovery of microRNAs (miRNAs), a class of small, non-coding, single-stranded RNAs that play a crucial role in post-transcriptional regulation, has added new dimensions to the development of novel diagnostic and treatment tools. Because of an association between Von Hippel-Lindau (VHL) genes with chromosomal loss in 3p25-26 and clear cell RCC, miRNAs have attracted considerable scientific interest over the last years. The loss of VHL function leads to constitutional activation of the hypoxia inducible factor (HIF) pathway and to consequent expression of numerous angiogenic and carcinogenic factors. Since miRNAs represent key players of carcinogenesis, tumor cell invasion, angiogenesis, as well as in development of metastases in RCC, they might serve as potential therapeutic targets. Several miRNAs are already known to be dysregulated in RCC and have been linked to biological processes involved in tumor angiogenesis and response to anti-cancer therapies. This review summarizes the role of different miRNAs in RCC angiogenesis and their association with the VHL gene, highlighting their potential role as novel drug targets.
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http://dx.doi.org/10.3390/ijms18112495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713461PMC
November 2017

Blood Platelet Volume Represents a Novel Prognostic Factor in Patients with Nonmetastatic Renal Cell Carcinoma and Improves the Predictive Ability of Established Prognostic Scores.

J Urol 2017 12 14;198(6):1247-1252. Epub 2017 Jul 14.

Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Purpose: The average size of blood platelets determined by mean platelet volume might represent a biologically meaningful parameter in carcinogenesis and potentially serve as a novel prognostic biomarker in renal cell carcinoma.

Materials And Methods: In this retrospective analysis of the records of 652 patients we evaluated the potential prognostic value of mean platelet volume and its ability to improve existing risk assessment tools used in adjuvant clinical trials in nonmetastatic renal cell carcinoma cases. Associations of mean platelet volume with baseline covariates and clinical outcomes (recurrence, and death from renal cell carcinoma and other causes) were assessed with the competing risk estimators of Kaplan-Meier, and Marubini and Valsecchi, respectively. Univariable and multivariable Cox proportional hazard models were constructed. The Harrell c-index was applied to test improvements in the predictive accuracy of the established Leibovich prognosis score.

Results: Small platelet volume was associated with large tumors (p = 0.043), high Fuhrman grade (p = 0.001), sarcomatoid components (p <0.0001), histological tumor necrosis (p = 0.044) and vascular invasion (p = 0.022). On univariable and multivariable analyses small platelet volume accurately predicted recurrent renal cell carcinoma (continuously and binary coded) and cancer specific survival. Adding mean platelet volume to the Leibovich prognosis score improved its discriminative performance (c-index = 0.83, p = 0.004).

Conclusions: Mean platelet volume represented a highly significant predictor of recurrence and cancer specific death in patients with renal cell carcinoma. This parameter improved the accuracy of the Leibovich prognosis score to better predict long-term outcomes in localized renal cell carcinoma cases after curative surgical resection.
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http://dx.doi.org/10.1016/j.juro.2017.07.036DOI Listing
December 2017

Critical evaluation of the potential prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio under consideration of C-reactive protein levels in clear cell renal cell carcinoma.

Br J Cancer 2017 01 1;116(1):85-90. Epub 2016 Dec 1.

Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 25, Graz A-8036, Austria.

Background: We investigated the prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio (dNLR) and original NLR in relation to the commonly used inflammation marker C-reactive protein (CRP) in a large cohort of patients with clear cell renal cell carcinoma (RCC).

Methods: Clinicopathological data from 587 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single tertiary academic center, were evaluated retrospectively. Patients were categorised according to a cutoff value derived from receiver operating curve analysis. Overall (OS), cancer-specific (CSS) as well as metastasis-free survival (MFS) were assessed using the Kaplan-Meier method and multivariate Cox proportional models were applied. Spearman's rank correlation coefficient tested the association between dNLR and other markers of the systemic inflammatory response.

Results: The significant correlation between pretreatment NLR and dNLR was strong (ρ=0.84), whereas between dNLR and CRP it was weak (ρ=0.18). In multivariate analyses, dNLR achieved independent predictor status regarding CSS (P=0.037) and MFS (P=0.041), whereas CRP was confirmed as independent predictor of OS (P=0.010), CSS (P=0.039) and MFS (P=0.005), respectively. The NLR failed to reach independent predictor status regarding OS, CSS and MFS when CRP was included into the multivariate model.

Conclusions: In the cohort studied, an elevated (⩾10.0) pretreatment CRP level and elevated dNLR (>2) were robust independent predictors of CSS and MFS. Our data suggest that CRP might be superior to both NLR and dNLR.
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http://dx.doi.org/10.1038/bjc.2016.393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220155PMC
January 2017

Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma.

Int J Mol Sci 2016 Apr 15;17(4):573. Epub 2016 Apr 15.

Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.

Renal cell carcinoma (RCC) represents a deadly disease with rising mortality despite intensive therapeutic efforts. It comprises several subtypes in terms of distinct histopathological features and different clinical presentations. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the genome which vary in expression levels and length and perform diverse functions. They are involved in the inititation, evolution and progression of primary cancer, as well as in the development and spread of metastases. Recently, several lncRNAs were described in RCC. This review emphasises the rising importance of lncRNAs in RCC. Moreover, it provides an outlook on their therapeutic potential in the future.
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http://dx.doi.org/10.3390/ijms17040573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849029PMC
April 2016

Is There a Role for Active Surveillance in Low-Risk Prostate Cancer?

Urol Int 2015 17;95(2):125-31. Epub 2015 Mar 17.

Department of Urology, Medical University of Graz, Graz, Austria.

Background: Active surveillance (AS) represents an expectant treatment strategy for clinically localized prostate cancer (PCa) with low-risk features.

Objective: The actual management as well as the pros and cons of AS were evaluated.

Methods: A systematic review of the recent literature was performed using the Medline databases.

Conclusions: Since a substantial number of men die with rather than from PCa, there is a considerable role for AS in carefully selected men. AS may also represent a strategy to reduce the burden of overtreatment rooted in intensified PSA testing. Facing the imprecision of risk stratification based on transrectal ultrasound-guided biopsy, accurate clinical staging represents a major medical challenge. Counseling and care require empathy as well as a profound understanding of the biology and the natural history of PCa.
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http://dx.doi.org/10.1159/000371895DOI Listing
June 2016

Sampling of the anterior apical region results in increased cancer detection and upgrading in transrectal repeat saturation biopsy of the prostate.

BJU Int 2016 Apr 14;117(4):592-7. Epub 2015 May 14.

Department of Urology, Medical University of Graz, Graz, Austria.

Objective: To evaluate whether biopsy cores taken via a transrectal approach from the anterior apical region of the prostate in a repeat-biopsy population can result in an increased overall cancer detection rate and in more accurate assessment of the Gleason score.

Patients And Methods: The study was a prospective, randomised (end-fire vs side-fire ultrasound probe) evaluation of 288 men by repeat transrectal saturation biopsy with 28 cores taken from the transition zone, base, mid-lobar, anterior and the anterior apical region located ventro-laterally to the urethra of the peripheral zone.

Results: The overall prostate cancer detection rate was 44.4%. Improvement of the overall detection rate by 7.8% could be achieved with additional biopsies of the anterior apical region. Two tumours featuring a Gleason score 7 could only be detected in the anterior apical region. In three cases (2.34%) Gleason score upgrading was achieved by separate analysis of each positive core of the anterior apical region. A five-fold higher cancer detection rate in the anterior apical region compared with the transition zone could be shown.

Conclusion: Sampling of the anterior apical region results in higher overall cancer detection rate in repeat transrectal saturation biopsies of the prostate. Specimens from this region can detect clinically significant cancer, improve accuracy of the Gleason Scoring and therefore may alter therapy.
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http://dx.doi.org/10.1111/bju.13108DOI Listing
April 2016

Utilization of bilateral infragluteal flaps for correction of overaggressive gluteal liposuction.

Ann Plast Surg 2014 Mar;72(3):270-3

From the *Section of Plastic and Reconstructive Surgery, General Hospital Linz; and †maz-Microsurgical Training and Research Center, Linz, Austria.

Liposuction continues to be one of the most frequently performed aesthetic surgical procedures. Typically, good results can be achieved. However, this procedure is not without any associated risks, such as infection, embolism, or contour deformities. These deformities are a feared sequelae and can result from faulty technique and will lead to decreased patient satisfaction. Methods for correction are limited but include repeat liposuction, lipofilling, or lifting procedures. We report a case of bilateral massive contour deformity after liposuction that we corrected with a novel technique using pedicled infragluteal flaps combined with a gluteal lifting procedure. The corrective operation resulted in a definitive improvement of the gluteal contour with great patient satisfaction.
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http://dx.doi.org/10.1097/SAP.0b013e318269e4abDOI Listing
March 2014

BMP-6 and BMPR-1a are up-regulated in the growth plate of the fractured tibia.

J Orthop Res 2013 Mar 23;31(3):357-63. Epub 2012 Oct 23.

Department of Paediatric and Adolescence Surgery, Medical University of Graz, Auenbruggerplatz 34, 8036 Graz, Austria.

Bone overgrowth is a known phenomenon occurring after fracture of growing long bones with possible long-term physical consequences for affected children. Here, the physeal expression of bone morphogenetic proteins (BMPs) was investigated in a fracture-animal model to test the hypothesis that a diaphyseal fracture stimulates the physeal expression of these known key regulators of bone formation, thus stimulating bone overgrowth. Sprague-Dawley rats (male, 4 weeks old), were subjected to a unilateral mid-diaphyseal tibial fracture. Kinetic expression of physeal BMP-2, -4, -6, -7, and BMP receptor-1a (BMPR-1a) was analyzed in a monthly period by quantitative real time-polymerase chain reaction and immunohistochemistry. On Days 1, 3, 10, and 14 post-fracture, no changes in physeal BMPs gene-expression were detected. Twenty-nine days post-fracture, when the fracture was consolidated, physeal expression of BMP-6 and BMPR-1a was significantly upregulated in the growth plate of the fractured and contra-lateral intact bone compared to control (p<0.005). This study demonstrates a late role of BMP-6 and BMPR-1a in fracture-induced physeal growth alterations and furthermore, may have discovered the existence of a regulatory "cross-talk" mechanism between the lower limbs whose function could be to limit leg-length-discrepancies following the breakage of growing bones.
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http://dx.doi.org/10.1002/jor.22238DOI Listing
March 2013
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