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Chromophobe Renal Cell Cancer
Kolář, Jiří ; Hora, Milan (advisor) ; Pivovarčíková, Kristýna (referee) ; Fedorko, Michal (referee)
Introduction: Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of RCC after clear cell RCC and papillary RCC. It is a relatively indolent subtype of RCC with approximately 5% risk of progression and development of metastases after surgical treatment. Predicting the clinical behaviour of chRCC by histologic features has so far proven to be challenging which is related to the lack of a validated grading system for this type of renal cancer. Historically, several grading schemes were proposed specifically for chRCC. However, none of them has proven useful in clinical practice. Two main histological subtypes of chRCC are known, namely classic and eosinophilic. Moreover, several aberrant histologic subtypes have been described, including adenomatoid microcystic pigmented, multicystic, neuroendocrine, papillary, oncocytic and small cell-like. It has been previously reported that both main subtypes of chRCC (classic and eosinophilic) have no differences in their prognosis. It is hypothesized that also these rare histological subtypes are not associated with differences in clinical outcomes. Nevertheless, this hypothesis has never been tested or confirmed by clinical data. Materials and methods: The aim of this thesis was to assess the impact of histologic diversity in chRCC...
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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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CA IX protein expression in urogenital tumors, mainly in renal clear cell carcinoma and urotelial carcinoma of lower urinary tract
Hyršl, Lubomír ; Babjuk, Marek (advisor) ; Pacík, Dalibor (referee) ; Hora, Milan (referee)
Except testicular tumors and prostate carcinoma, there is lack of tumor markers in urogenital tumors. Carbonic anhydrase IX protein (CA IX) is a cell membrane protein, which can be ectopically expressed in various human tumors. It is often expressed as a response of tumor cells to hypoxia, which escalates invasivity of the tumor. In consequence, CA IX was proposed as a marker of poor prognosis. Its presence was proved by immunohistochemistry in renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of urinary tract. We study CA IX as a possible tumor marker. Presence of CA IX protein in tumor tissue was examined by imunohistochemistry, in serum and urine CA IX concentrations by immunoprecipitation of CA IX followed by Western blotting in combination with enhanced chemiluminiscence or ELISA. From our results we proved positive concentrations of soluble CA IX (s-CA IX) in 74,3% serum and in 63,3% urine samples in RCC group. In TCC group s-CA IX was positive in 69,6 % urine samples. Serum concentrations were all negative in this group. There was rapid decrease of s-CA IX concentration in serum after surgical removal of tumor with half-time 1- 2 days. s-CA IX is not detectable in blood and urine in healthy volunteers. In these days s-CA IX is not suitable marker of RCC and TCC. Nevertheless,...
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Concurrent possibilities of minimallyinvasive surgical treatment of kidney tumours
Eret, Viktor ; Hora, Milan (advisor) ; Zachoval, Roman (referee) ; Minčík, Ivan (referee)
Minimally invasive surgery in the treatment of kidney tumours has developed since the beginning of the nineties. A lot of specialized or top laparoscopic urological centres so-called "centres of excellence" have been created since the first laparoscopic radical nephrectomy (LRN). These centres have thanks to the centralization of kidney tumour patients sufficient cohorts for evaluation of operative data, operative technique and oncological results. A lot of large studies have been published so far, showing comparable oncological results with open nephrectomy and advantages of miniinvasivity ( shorter hospitalization time, less analgesia requirements, better recovery and cosmetics). LRN is considered a standard of care in the treatment of cT1-2 (≤ 8cm) renal tumours in patients who are not candidates for nephron- sparing surgery. In our department in Plzeň, we have been performing LRN since January 2003. The majority of procedures has been performed by transperitoneal approach. The first LRN in the Czech Republic was done in April 1998 within XII. Conference of Czech Urologic Society by guesting prof. Clayman. We prefer transperitoneal to extraperitoneal approach in our department. The transperitoneal approach provides a larger working space, better anatomical and topographical orientation.We perform...
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Prostate Cancer Diagnostic Algorithm
Sedláčková, Hana ; Hora, Milan (advisor) ; Baxa, Jan (referee) ; Záleský, Miroslav (referee)
Prostate cancer diagnostic algorithm Aim: The aim of the study is to implement the latest scientific knowledge in the diagnosis of prostate cancer (PC). We focused on tumor markers, imaging methods, prostate biopsy methodology and we created a diagnostic algorithm based on a review of current literature in combination with our own experience. Material and methods: The algorithm is divided into several branches, which have been individually subjected to clinical studies. Due to the low sensitivity and specificity of PSA, prostate health index (PHI) was added to the first line of patient stratification. 787 patients were primarily examined and these subsequently underwent radical prostatectomy. PHI levels were compared with definitive staging and grading. Cut-off values for PC detection and high-risk stratification, including locally advanced PC were determined. Next, 320 patients underwent prostate biopsy followed by radical prostatectomy. The cohort was further divided into two subgroups, patients with GS = 6 and patients with GS > 6. The ability of PHI to distinguish between insignificant and significant prostate cancer was evaluated. In a multicentric study with 395 patients, PHI with additional markers (tPSA, PSAD) and multiparametric magnetic resonance imaging of prostate (mpMRI) was assessed....
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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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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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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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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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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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