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Molecular biology of renal tumours in clinical use
Trávníček, Ivan ; Hora, Milan (advisor) ; Soukup, Viktor (referee) ; Veselý, Štěpán (referee)
Molecular biology of renal tumours in clinical use MUDr. Ivan Trávníček Summary Aim: To identify tissue biomarker that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC). Material and methods: Our study included 39 patients with mCRCC; these were selected from 119 patients who received sunitinib in our hospital between the years 2005 - 2012 according to inclusion criteria of the study. Patients were stratified into two groups based on their response to sunitinib treatment; non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies performed before the initiation of treatment, with those done between 3rd and 7th months of treatment. Histological samples of tumour tissue and healthy renal parenchyma, acquired during surgery of the primary tumour, were examined with immunohistochemistry to detect tissue biomarkers (mTOR, p53, VEGF, HIF1, HIF2, CAIX). The average levels of biomarker expression in both, tumour tissue, as well as in healthy renal parenchyma were compared between the two groups of patients. Results were evaluated using Student's T-test. Results: When considering the results of the group of responders, statistically significant differences in marker...
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Problems of renal tumours in patiens with terminal stadium of renal failure
Ürge, Tomáš ; Hora, Milan (advisor) ; Novák, Jaroslav (referee) ; Zachoval, Roman (referee) ; Morávek, Petr (referee)
Objective: Risk of renal carcinoma is minimal 10 x higher in group of patients in terminal stadium of renal failure (end stage kidney disease - ESKD). We have only some information about chromosomal changes in renal tubules, from which rise renal carcinoma, and about pathogenesis of renal carcinoma, which seems to be different from carcinoma in common population. Aim of the study: In clinical part we valorize characteristic signs of renal carcinoma in ESKD by using of statistic methods. In experimental part we can explain pathogenesis of this carcinoma by analysis of selective chromosomal aberations. Material, methods: In 2000 - 2007 were 184 patients with ESKD in care of transplant centre and nephrologic ambulation of Faculty hospital Plze_. In 15 patients we diagnose renal carcinoma. In this group we valorize: age, gender, causation of renal failure and dialysis duration. Age, gender and type of renal carcinoma we confront with carcinoma in common population. In experimental part we valorize numerical aberations in chromosome 7, 17 and Y of tubular epithelium using fluorescent hybridization in situ (FISH). Results: We have 15 patients in average age 55.7 ± 11.5 years, long of during dialyzation was 78 ± 54 months. We do not find dependence between causation of renal failure and genesis of renal...
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Non-invasive diagnosis of urothelial carcinoma of the urinary bladder by evaluation of cell-free DNA and microRNA in urine
Brisuda, Antonín ; Babjuk, Marek (advisor) ; Hora, Milan (referee) ; Broďák, Miloš (referee)
Bladder cancer represents the most common malignancy of the uropoetic tract. Its incidence has been stable in the last couple of years in the Czech Republic, worldwide rises though. A ratio of incidence and mortality is considerable in bladder cancer since it is highest out of all genitourinary malignancies. An early diagnosis and adequate treatment is therefor determinig for its prognosis. There are several commercialy available urine tests, none of them is recommended as a standard diagnostic tool in any indication though. Urine cytology, as a complement of invasive cystoscopy, remains the only widely used method with all its limitations. Cell-free nucleic acids in urine (urine supernatant) belong amongs potential tumour biomarkers. Cell-free urinary DNA (ucfDNA) is excreted by cells undergoing necrosis or apoptosis although it can also originate from living cells. Their level in urine or serum can thus indicate a presence of malignancy. Micro RNA (miRNA) are short non-coding sequences of RNA produced outside of nucleus. They bind to complementary sequences of mRNA thus affecting its translation and protein formation. As such they play an important role in cell division and cancerogenesis. In our study, we correlated levels of ucfDNA in controls and patients with urothelial carcinoma of different...
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Rare Tumours of the Kidney - Cystic Tumours of the Kidney
Pitra, Tomáš ; Hora, Milan (advisor) ; Fedorko, Michal (referee) ; Weibl, Peter (referee)
Aim: To quantify the occurrence of cystic tumours of the kidney in a population of patients with tumour of the kidney. Other goals of this study were to compare results of imaging studies with the results of final histology, to evaluate malignity rate in each Bosniak group and to evaluate the options of surgical treatment of cystic tumours of the kidney. The emphasis was placed to determine the benefits of magnetic resonance imaging in the diagnostic algorithm of cystic tumours of the kidney. Material and methods: All patients, who underwent surgery for the tumour of the kidney or cystic lesion of the kidney at our department in the time period 2009-17 were evaluated and patients with radiologically described cystic lesion of the kidney were included in the cohort. Lesions were classified according to CT imaging in the Bosniak categories. The unclear findings were in clinical study consulted with the radiologist. In case of uncertainties, MRI was indicated. Histological classification of all neoplasias was done according to the WHO classification 2016. The cohort of cystic lesions (n=247) was stratified into two groups. Categories Bosniak I-IIF (n=115), which were treated surgically not for suspicion of the malignity, but because of the size, localisation, clinical manifestation or were solved...
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Preoperative Diagnostic Methods in Prostate Cancer
Dolejšová, Olga ; Hora, Milan (advisor) ; Záleský, Miroslav (referee) ; Springer, Drahomíra (referee)
Preoperative diagnostic methods in prostate cancer Introduction: At present, the most attention in prostate cancer is focused on tumor markers and imagining methods, especially magnetic resonance and fusion methods in order to accurately identify carcinoma deposits and predict the biological behavior of the tumor. Accurate diagnosis allows choosing optimal therapeutic procedure. Aim: The aim of the study is to evaluate how preoperative diagnostic methods can help in designing an optimal treatment in a patient with prostate cancer. The main objective is to evaluate the use of the Prostate Health Index (PHI) in differentiating low-risk carcinoma from aggressive cancer. Another goal of the thesis is the use of imaging methods. I focused on the 3T magnetic resonance imaging in assessing invasion beyond the prostate and in high risk patiens on a new method of fusion magnetic resonance imaging and positron emission tomography for prediction of nodal involvement. Methodology: A total of 320 patients who underwent preoperative diagnosis using our investigated methods (PHI, MRI, choline PET / MRI) and subsequently radical prostatectomy were enrolled in the study. It allowed us to retrospectively assess these diagnostic tests. The PSA, % fPSA, -2proPSA, and PHI results overall were evaluated by statistical...
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Papillary Renal Cell Carcinoma
Procházková, Kristýna ; Hora, Milan (advisor) ; Macek, Petr (referee) ; Král, Milan (referee)
The Pilsen region suffers the highest incidence of kidney tumours worldwide. Approximately 240 new cases diagnosed as C64 (malignant renal tumours outside the pelvis) were recorded in this region of about 580,000 inhabitants in 2015. Clear renal cell carcinoma has long held first place as the most common tumour, with papillary renal cell carcinoma (pRCC) being the second most frequently operated kidney tumour at the Urology Department of the University Hospital in Pilsen. The 2016 WHO classification of kidney tumours recognizes officially only the stratification of pRCC to type 1 (pRCC1) and type 2 (pRCC2). Unfortunately, the current division does not correspond with knowledge derived from everyday practice. Most clinical trials involving pRCC do not differentiate between the subtypes, adhering only to the official type 1 and 2 divisions and the atypical papillary forms being excluded from their studies. We therefore have to face the question of whether the histological pRCC subtype affects the risk of recurrence, or death, in surgically treated patients. The aim of this dissertation work is to take into consideration also all other papillary types which differ from characterization of pRCC1 and pRCC2. The analyses of a group of patients with surgically treated and histologically verified pRCC at...
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Molecular biology of renal tumours in clinical use
Trávníček, Ivan ; Hora, Milan (advisor) ; Soukup, Viktor (referee) ; Veselý, Štěpán (referee)
Molecular biology of renal tumours in clinical use MUDr. Ivan Trávníček Summary Aim: To identify tissue biomarker that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC). Material and methods: Our study included 39 patients with mCRCC; these were selected from 119 patients who received sunitinib in our hospital between the years 2005 - 2012 according to inclusion criteria of the study. Patients were stratified into two groups based on their response to sunitinib treatment; non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies performed before the initiation of treatment, with those done between 3rd and 7th months of treatment. Histological samples of tumour tissue and healthy renal parenchyma, acquired during surgery of the primary tumour, were examined with immunohistochemistry to detect tissue biomarkers (mTOR, p53, VEGF, HIF1, HIF2, CAIX). The average levels of biomarker expression in both, tumour tissue, as well as in healthy renal parenchyma were compared between the two groups of patients. Results were evaluated using Student's T-test. Results: When considering the results of the group of responders, statistically significant differences in marker...
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Impact of Warm Ischemia on Renal Function - Clinical Model of Tumor Resection of Solitary Kidney
Stránský, Petr ; Hora, Milan (advisor) ; Broďák, Miloš (referee) ; Doležel, Jan (referee)
Objective: The aim of this work is to evaluate the effect of warm ischemia on renal function. Methods: Within a multicentric study, the data about tumor-affected solitary kidney were obtained from 9 urological centers in the Czech Republic. Patients were divided into groups according to the WIT (warm ischemia time). In each group the mean preoperative serum creatinine was determined, as well as on 3rd and 7th postoperative day and the lowest GF postoperatively. In each group the mean R.E.N.A.L. nephrometric score was determined. Results: The study compriese data totally of 97 patients. The open approach was chosen in 78 cases, in 16 cases laparoscopic approach was chosen. The robotic surgery was performed in 3 patients. PN with zero ischemia was performed in 29 patients (30%). Conclusion: Our findings confirm that non-clamping partial nephrectomy in a solitary kidney minimizes renal injury. For the non-clamping partial nephrectomy can be mainly indicated smaller exophyticall tumors without deep parenchymal invasion. Unfortunately, most of PN should be performed with vascular clamping, allowing precise closure of collecting system, vascular and parenchymal defect, especially for larger tumors with deep parenchymal invasion. According to our observation that WIT of 15 minutes for a kidney is safe. Clamping of...
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The role of infections in prostate cancer etiopathogenesis
Hrbáček, Jan ; Urban, Michael (advisor) ; Vonka, Vladimír (referee) ; Hora, Milan (referee)
Thesis summary A number of studies have addressed the role of genitourinary infections in prostate cancer (PC) pathogenesis since 1980's. Identification of an infectious agent responsible for prostatic carcinogenesis would make it possible to screen for and prevent the disease in exposed populations. In our project, we investigated the prevalence of antibodies to selected genit- ourinary pathogens in patients with histopathological evidence of PC and in men with benign prostatic hyperplasia. We were testing the hypothesis that PC patients would be more likely to harbor antibodies than controls. This would favor the in- fectious theory of PC initiation. In case of human papillomavirus (HPV), tissue ana- lyses were performed aimed at the detection of HPV DNA in prostatic tissue samples. To our knowledge, we were the first to look for a potential association between PC and Mycoplasma hominis/Ureaplasma urealyticum infection. Men with PC were more likely to have U. urealyticum antibodies. We analyzed the subset of PC patients to find whether infection may change PC biological behavior, with a null result. Other data obtained in our study support the negative findings from the majority of previously published studies. Besides the abovementioned results, an original contribution of this work lies in the...
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