Ladislav Dusek

Masaryk University, Brünn, South Moravian, Czech Republic

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Publications (212)423.11 Total impact

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    ABSTRACT: The aim of this prospective observational cohort study was to evaluate long-term outcomes in patients with mild-to-moderate lumbar spinal stenosis (LSS) and to analyse the predictors of clinical outcomes.
    06/2014;
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    ABSTRACT: Data from the Czech national registry were analysed retrospectively to describe treatment outcomes for capecitabine and oxaliplatin (XELOX) regimen with bevacizumab versus 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimen with bevacizumab in the first-line therapy for metastatic colorectal cancer (mCRC).
    BMC Cancer 05/2014; 14(1):323. · 3.33 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) is the second most common cancer in Europe and its incidence is steadily increasing. This trend could be reversed through timely secondary prevention (screening). In the last twenty years, CRC screening programs across Europe have experienced considerable improvements (fecal occult blood testing; transition from opportunistic to population based program settings). The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates. Each year, approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy. Twenty years ago, the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000. Originally, this program was based on the guaiac fecal occult blood test (FOBT) offered by general practitioners, followed by colonoscopy in cases of FOBT positivity. The program has continuously evolved, namely with the implementation of immunochemical FOBTs and screening colonoscopy, as well as the involvement of gynecologists. Since the establishment of the Czech CRC Screening Registry in 2006, 2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program. The overall program expanded to cover 25.0% of the target population by 2011. However, stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation, which is currently being prepared.
    World Journal of Gastroenterology 04/2014; 20(14):3825-3834. · 2.55 Impact Factor
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    ABSTRACT: Patients aged 65 years and older represent the majority of patients with metastatic colorectal cancer (mCRC). However, this patient population is often underrepresented in clinical trials and probably undertreated in the clinical practice. We have analysed the outcomes of 3,187 mCRC patients treated with first-line bevacizumab based on data from the Czech national registry of mCRC patients aiming to compare the treatment efficacy and safety according to the age categories. In total, 2,126 (66.7%), 932 (29.2%), and 129 (4.0%) patients were aged <65 years, 65 to 75 years, and 75+ years, respectively. Median progression-free survival (PFS) was 11.4, 11.3, and 11.8 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.94). Median overall survival (OS) was 26.9, 27.5, and 25.1 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.73). Using multivariable Cox model for both PFS and OS, the patient age was not significantly associated with either PFS or OS. No increase in bevacizumab-related toxicity was observed among the elderly mCRC patients with the exception of hypertension, which was observed in 71 (3.3%), 34 (3.6%), and 10 (7.8%) patients aged <65 years, 65 to 75 years, and 75+ years, respectively. The results of the present study suggest similar outcome in terms of OS and PFS with bevacizumab-containing therapy in elderly mCRC patients fit for chemotherapy combined with targeted therapy compared to younger patients. Thus, chronological age should not be considered to represent a limitation in prescribing bevacizumab-containing therapy in mCRC patients.
    BMC Gastroenterology 03/2014; 14(1):53. · 2.11 Impact Factor
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Epidemiological data from national registries are growing worldwide, but are still unavailable in Eastern Europe. A PAH registry was initiated in January 2007 using a nationwide network of echocardiographic centers and four diagnostic centers that specialize in PAH. All patients aged above 18 years, diagnosed with PAH and monitored between January 2000 and December 2007 were included. Patients diagnosed with PAH between January and December 2007 were classified as incident. The survival analyses were performed up to the end of 2010. Prognostic factors at the time of diagnosis were identified using uni- and multivariable Cox proportional hazard models. Overall, 191 patients were included (100 prevalent cases, 91 incident cases). Patients were predominantly female (n = 125) and had a mean age of 51.9 +/- 16.9 years. Incident patients were significantly older at the time of diagnosis than prevalent patients (p < 0.001). Most patients (60.7%) had idiopathic PAH; 20.4% had PAH associated with congenital heart disease and 11.4% had PAH associated with connective tissue disease. Estimates of prevalence and incidence of PAH in adults were 22.4 cases per million and 10.7 cases per million per year, respectively. The 1-, 2- and 3-year survival rates in the incident PAH cohort were 89% (95% confidence intervals [CI] 83-95%), 78% (95% CI 70-87%) and 74% (95% CI 65-83%), respectively. Lower survival rates were significantly associated with higher age (hazard ratio [HR] 6.6 95% CI 1.4-30.9) and lower creatinine clearance (HR 3.3 95% CI 1.1-9.7). This is the first study in Eastern Europe to describe the prevalence, incidence and survival of patients with PAH from a national representative registry. This registry from the Czech Republic highlights that diagnosis of PAH is frequently made late in the disease continuum when patients have significant functional impairment.
    BMC Pulmonary Medicine 03/2014; 14(1):45. · 2.76 Impact Factor
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    ABSTRACT: The aim of the present study was to describe treatment outcomes for bevacizumab in combination with chemotherapy based on data from the Czech registry of targeted therapies for metastatic colorectal cancer (mCRC). In total, 4,487 patients with mCRC who received bevacizumab combined with chemotherapy in first line (n=3,990, 88.9%), second line (n=386, 8.6%), or third/higher line (n=111, 2.5%) had evaluable data and were included in the present retrospective analysis. The median progression-free survival (PFS) was 11.3 months (95% conficence interval [CI]=11.0-11.7 months), 9.5 months (95% CI=8.2-10.9 months), and 7.3 months (95% CI=5.9-8.7 months; p<0.001), and the median overall survival from the start of bevacizumab-containing therapy was 28.4 months (95% CI=27.1-29.8 months), 25.9 months (95% CI=19.4-32.4 months), and 15.0 months (95% CI=10.7-19.3 months; p<0.001), respectively. The data describe efficacy of bevacizumab with chemotherapy for different treatment lines in a large patient cohort.
    Anticancer research 02/2014; 34(2):949-54. · 1.71 Impact Factor
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    ABSTRACT: In this study, we aimed to describe the value of pelvic lymph node dissection (LND) after sentinel lymph node (SN) biopsy in early-stage cervical cancer. We performed a retrospective multicenter cohort study in 8 gynecological oncology departments. In total, 645 women with International Federation of Gynecology and Obstetrics stage IA to IIB cervical cancer of squamous, adeno, or adenosquamous histologic type who underwent SN biopsy followed by pelvic LND were enrolled in this study. Radioisotope tracers and blue dye were used to localize the sentinel node, and pathologic ultrastaging was performed. Among the patients with low-volume disease (micrometastases and isolated tumor cells) in the sentinel node, the overall survival was significantly better (P = 0.046) if more than 16 non-SNs were removed. No such significant difference in survival was detected in patients with negative or macrometastatic sentinel nodes. Our findings indicate that in patients with negative or macrometastatic disease in the sentinel nodes, an additional LND did not alter survival. Conversely, our data suggest that the survival of patients with low-volume disease is improved when more than 16 additional lymph nodes are removed. If in a prospective trial our data are confirmed, we would suggest a 2-stage operation.
    International Journal of Gynecological Cancer 01/2014; · 1.94 Impact Factor
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    ABSTRACT: Patients with lung cancer experience elevated risk of venous thromboembolism. Cancer patients with thrombosis have a shorter life expectancy and the occurrence of VTE worsens the quality of life and may delay, interrupt, or completely halt the cancer therapy. In a large cohort of lung cancer patients we monitored the incidence of venous thromboembolism and we identified groups of patients with the highest risk of venous thromboembolism suitable for antithrombotic prophylaxis, which could favourably affect their morbidity and mortality.
    The Scientific World Journal 01/2014; 2014:125706. · 1.73 Impact Factor
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    ABSTRACT: Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5-10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats.
    Frontiers in Pharmacology 01/2014; 5:44.
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    ABSTRACT: Objectives The aim of the present study was to describe the efficacy and safety of everolimus in the treatment of metastatic renal cell carcinoma (mRCC) after administration of 1 vs. 2 prior tyrosine kinase inhibitors (TKIs). Patients and methods A national renal information system database was used as the data source for the retrospective study. There were 483 patients who received everolimus as the second (n = 350) or the third (n = 112) targeted agent following TKIs. Results Median progression-free survival (PFS) from the start of everolimus in the second or the third line of targeted therapy was 6.1 months for both subgroups (P = 0.863). Median total PFS from the start of the first targeted agent to progression on the third targeted agent for patients receiving 3 lines of therapy with TKI-TKI-everolimus (n = 112) and TKI-everolimus-TKI (n = 27) sequences was 28.3 months vs. 31.3 months, respectively (P = 0.16), and there was no significant difference in overall survival. PFS on everolimus was associated with PFS on previous TKIs in patients receiving 1 but not 2 previous TKIs. Only 13% of 352 patients starting targeted therapy for mRCC in 2010 had received 3 sequential targeted agents by the data cutoff in March 2013. Conclusion PFS on everolimus correlated with PFS on TKIs in patients pretreated with 1 but not 2 TKIs. Everolimus can be deferred to the third line without loss of efficacy or increased toxicity. However, only a minority of patients with mRCC starting targeted treatment can be expected to receive third-line therapy.
    Urologic Oncology 01/2014; · 3.65 Impact Factor
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    ABSTRACT: The purpose of our study was to evaluate a possible correlation between genetic polymorphisms in ATM and TGFB1 genes and late toxicity of chemoradiotherapy for locally advanced cervical cancer. Fifty five patients with FIGO stage IIB and higher without a disease recurrence with a mean follow up of 6 years were included. Late toxicity was assessed by EORTC/RTOG late toxicity criteria. Univariate and multivariate logistic regression model was used for statistical analysis. Degree of association between polymorphisms and late toxicity of chemotherapy was assessed on the basis of phi-coefficient (φ) as well. We did not find any association between 5557G>A polymorphism in the ATM gene or single TGFB1 polymorphisms and late toxicity. TGFB1 compound homozygosity (-1552delAGG, -509C>T, L10P) was a significant predictive factor of grade III-IV and any grade of complications in both univariate and multivariate logistic regression analyses and statistical significance of association between polymorphisms and late toxicity of chemoradiotherapy was confirmed also by the evaluation of phi-coefficient (φ). We conclude that haplotypes instead of single nucleotide polymorphic sites in the genes may better characterize the individual radiosensitivity. Keywords: cervical cancer, radiotherapy, ATM, TGFB1, late toxicity.
    Neoplasma 01/2014; 61(1):70-6. · 1.57 Impact Factor
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    ABSTRACT: More than 90% of cases of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) is established as possible risk factor. To demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer. A total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy-confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Cobas and Lynear array HPV test. Cervical, anal, and concurrent cervical and anal HPV infections were detected in 82.6%, 48.3% and 42.4% of women in the study group, and in 28.0%, 26.0% and 8.0% of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections of the cervix and anus occurred 5.3-fold more often in the study group than in the control group. Any contact with the anus was the only significant risk factor for development of concurrent HPV infection. Concurrent anal and cervical HR HPV infection was found in nearly half of women with CIN 2+. The dominant genotype found in both anatomical locations was HPV 16. Any frequency and any type of contact with the anus were shown as the most important risk factor for concurrent HPV infection.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 11/2013; · 3.12 Impact Factor
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    ABSTRACT: The incidence and mortality of colorectal cancer (CRC) in the Czech Republic is significant. The National CRC Screening Program started in 2000 and was further enhanced in 2009. In 2010, the European Guidelines were introduced. The aim of the present trend study was to evaluate the quality of the Czech National Colorectal Cancer Screening Program using early performance and long-term impact indicators. The screening program has been assessed using data from three sources: the Czech National Cancer Registry, the Czech National Reference Centre, and the Czech CRC Screening Registry. The data were compared with a set of recommended quality control indicators. Between 2006 and 2010, a total of 1 881 299 fecal occult blood tests were performed, of which 87 397 were positive (4.6%). Until 2011, a total of 68 527 fecal occult blood test follow-up colonoscopies were performed. In addition, between 2009 and 2011, a total of 10 309 screening colonoscopies were performed. As a result, a total of 25 255 adenomas (32.0% rate) and 3379 CRCs (4.3% rate) were detected. A trend of cancer detection in earlier stages has been observed. The overall program coverage has increased to 22.7% of the target population in 2010. The majority of European guidelines' quality indicators for nonpopulation-based programs were implemented in the Czech National CRC Screening program. An improvement in program management was accompanied by an increase in coverage as well as other performance indicators.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 08/2013; · 2.21 Impact Factor
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    ABSTRACT: Using the data of 723 chronic myeloid leukemia (CML) patients in the chronic phase, we analyzed the prognostic value of the Sokal, Euro, and EUTOS scores as well as the level of BCR-ABL1 and the achievement of complete cytogenetic response (CCgR) at 3 months of imatinib therapy in relation to the so-called current survival measures: the current cumulative incidence (CCI) reflecting the probability of being alive and in CCgR after starting imatinib therapy; the current leukemia-free survival (CLFS) reflecting the probability of being alive and in CCgR after achieving the first CCgR; and the overall survival. The greatest difference between the CCI curves at 5 years after initiating imatinib therapy was observed for the BCR-ABL1 transcripts at 3 months. The 5-year CCI was 94.3% in patients with BCR-ABL1 transcripts ≤ 10% and 57.1% in patients with BCR-ABL1 transcripts > 10% (p=0.005). Therefore, the examination of BCR-ABL1 transcripts at 3 months may help in early identification of patients who are likely to perform poorly with imatinib. On the other hand, CLFS was not significantly affected by the considered stratifications. In conclusion, our results indicate that once the CCgR is achieved, the prognosis is good irrespective of the starting prognostic risks.
    American Journal of Hematology 06/2013; · 4.00 Impact Factor
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    ABSTRACT: PURPOSE: The study aimed to analyze the dose-volume profiles of 3-dimensional radiation therapy (3D-CRT) and intensity modulated RT (IMRT) in the treatment of prostate carcinoma and to specify the profiles responsible for the development of gastrointestinal (GI) toxicity. METHODS AND MATERIALS: In the period 1997 to 2007, 483 patients with prostate carcinoma in stage T1-3 N0 (pN0) M0 were treated with definitive RT. Two groups of patients were defined for the analysis: the 3D-CRT group (n=305 patients) and the IMRT group (n=178 patients). In the entire cohort of 483 patients, the median follow-up time reached 4.4 years (range, 2.0-11.7 years). The cumulative absolute and relative volumes of irradiated rectum exposed to a given dose (area under the dose-volume curve, AUC) were estimated. The receiver operating characteristic analysis was then used to search for the optimal dose and volume cutoff points with the potential to distinguish patients with enhanced or escalated toxicity. RESULTS: Despite the application of high doses (78-82 Gy) in the IMRT group, GI toxicity was lower in that group than in the group treated by 3D-CRT with prescribed doses of 70 to 74 Gy. Both RT methods showed specific rectal dose-volume distribution curves. The total AUC values for IMRT were significantly lower than those for 3D-CRT. Furthermore, IMRT significantly decreased the rectal volume receiving low to intermediate radiation doses in comparison with 3D-CRT; specific cutoff limits predictable for the level of GI toxicity are presented and defined in our work. CONCLUSIONS: Total area under the dose-volume profiles and specific cutoff points in low and intermediate dose levels have significant predictive potential toward the RT GI toxicity. In treatment planning, it seems that it is valuable to take into consideration the entire dose-volume primary distribution.
    International journal of radiation oncology, biology, physics 04/2013; · 4.59 Impact Factor
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    ABSTRACT: INTRODUCTION: ADAM33 is the candidate gene most commonly associated with asthma and airway hyperreactivity (AHR). AIM: The aim of this study was to determine whether level of AHR is associated with certain alleles or haplotypes of the ADAM33 gene in asthmatic children. METHODS: One hundred and nine asthmatic children and 46 controls from the general population were examined with spirometry before and after histamine and methacholine inhalation. All subjects were genotyped for single-nucleotide polymorphisms (SNPs) of the ADAM33 gene. Haplotypes were determined according to genotypes of the patient's parents. RESULTS: We found the three most frequent ADAM33 haplotypes (a1-3) were associated with the highest level of AHR to methacholine and histamine in 66% of asthmatic children. The paternally transmitted GGGCTTTCGCA haplotype was seen in 73.3% asthmatic children with serious AHR to methacholine challenge (paternal and maternal origin of haplotype 73.3% to 37.5, P=0.046) Significant differences in the relative frequency of paternal haplotypes with high levels of AHR to histamine were found (P=0.013). CONCLUSION: ADAM33 haplotypes (a1, a2, a3) are associated with severity of AHR and are significantly more often transmitted in the paternal line.
    Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 04/2013; · 0.99 Impact Factor
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    ABSTRACT: Individual variation in immune responses to herpesviruses was observed in various species. Here, associations between polymorphic molecular markers and life-long anti-EHV-1/4 antibody immune responses were analyzed in a model EHV-infected population of the Old Kladruber horses. Two-dimensional analysis including overall mean titers and titer dynamics expressed by differences between spring and autumn titers allowed identification of low-responders. 50 randomly selected microsatellites and nine single nucleotide polymorphisms in nine immunity-related candidate genes were genotyped. Due to differences (p<0.001) in antibody titers between two color varieties of Old Kladruber horses, separate association studies were performed in the two sub-populations by using the Fisher's exact test. In black horses, the interleukin 4 receptor and MxA protein coding genes, and the microsatellite TKY325 were associated with the responder status. In the grey population, the microsatellite TKY343 showed significant association with anti-EHV antibody responsiveness after Bonferroni corrections.
    Research in Veterinary Science 04/2013; · 1.77 Impact Factor
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    ABSTRACT: AIM: To evaluate the final best corrected visual acuity (BCVA) in patients with branch retinal vein occlusion (BRVO) treated with either (1) laser arteriolar constriction (ACo) or (2) the standard treatment recommended by the Branch Vein Occlusion Study Group (grid laser photocoagulation (GLP) or only observation (if indication criteria for GLP were not met). METHODS: 358 BRVOs were treated in three different ways: early ACo (n=133) performed ≤ 9 weeks after onset of BRVO, late ACo (n=62) performed > 9 weeks after onset and controls which included GLP and observation (n=163). The groups were further divided according to initial BCVA into: ≤ 0.1; 0.16-0.3 and ≥ 0.4. RESULTS: Based on the proportion of 1 year BCVA ≤ 0.1 as a risk category, the results of early ACo (3.8%) were significantly better than for the controls (22.7%, P<0.001) and late ACo (16.1%, P=0.006). The greatest difference in final BCVA was in patients with the worst initial VA (≤ 0.1). In the intermediate initial BCVA group 0.16-0.3, a significant difference was only found between the early ACo group and controls (P=0.007). There was no significant difference between any treatment group and prevalence of a final BCVA ≤ 0.1 for patients with an initial BCVA ≥ 0.4. CONCLUSIONS: Early ACo significantly reduces the prevalence of a final BCVA ≤ 0.1 in patients with BRVO and an initial BCVA ≤ 0.3 compared to controls (standard treatment treated with GLP or observed).
    Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 03/2013; · 0.99 Impact Factor

Publication Stats

2k Citations
423.11 Total Impact Points

Institutions

  • 1998–2014
    • Masaryk University
      • • Institute for Biostatistics and Analyses of Faculty of Medicine
      • • I. interní kardioangiologická klinika
      • • Department of Internal Medicine, Hematology and Oncology
      • • Fakulta Přírodovědecká
      Brünn, South Moravian, Czech Republic
  • 2001–2013
    • University Hospital Brno
      • • Department of Neurology
      • • Department of Internal Cardiology Medicine
      Brno, South Moravian Region, Czech Republic
    • Veterinary Research Institute, Brno
      Brünn, South Moravian, Czech Republic
  • 1990–2013
    • Charles University in Prague
      • Gynekologicko-porodnická klinika (1. LF)
      Praha, Hlavni mesto Praha, Czech Republic
  • 2012
    • Comenius University in Bratislava
      Presburg, Bratislavský, Slovakia
  • 2010–2012
    • Military University Hospital Prague
      Praha, Praha, Czech Republic
  • 2003–2011
    • Palacký University of Olomouc
      • Department of Hemato-Oncology
      Olomouc, Olomoucky kraj, Czech Republic
  • 1999–2011
    • Masaryk Memorial Cancer Institute
      Brünn, South Moravian, Czech Republic
  • 2007–2010
    • University Hospital Olomouc
      • • Department of Hemato-Oncology
      • • Department of Medical Genetics and Fetal Medicine
      Olomouc, Olomoucky kraj, Czech Republic