BACKGROUND/AIM:The management of patients with clear cell renal cell carcinoma (ccRCC) includes prognosis assessment based on TNM classification and biochemical markers. This approach stratifies patients with advanced ccRCC into groups of favorable, intermediate, and poor prognosis. The aim of the study was to improve prognosis estimation using microRNAs involved in the pathogenesis of ccRCC. PATIENTS AND METHODS:The study was based on a histologically-verified set of matched ccRCC FFPE tissue samples (normal renal tissue, primary tumor, metastasis, n=20+20+20). The expression of 2,549 microRNAs was analyzed using the SurePrint G3 Human miRNA microarray kit (Agilent Technologies). Prognostic value of significantly deregulated microRNAs was further evaluated on microRNA expression and clinical data of 475 patients obtained from TCGA Kidney Clear Cell Carcinoma (KIRC) database. RESULTS:There were 13 up-regulated and 6 down-regulated microRNAs in tumor tissues compared to control tissues. Among them, survival analysis revealed those with prognostic significance. Patients with high expression of miR-21, miR-27a, miR-34a, miR-106b, miR-210, and miR-342 showed significantly unfavorable outcome. The opposite was observed for miR-30e, patients with low expression had significantly shorter survival. CONCLUSION:The inclusion of these microRNAs in a prognostic panel holds the potential to enhance stratification scoring systems, on which the treatment of ccRCC patients is based.

Background/Aim: Enzalutamide (ENZ) and abiraterone acetate with prednisone (AAP) represent novel hormonal therapies used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The aim of the study was to assess the long-term outcome of mCRPC patients treated with ENZ or AAP in real-life clinical practice. Patients and Methods: The outcomes of 337 mCRPC patients treated with ENZ or AAP were retrospectively analysed. Results: Median radiographic progression-free (rPFS) and overall survival (OS) of patients treated in the first line (pre -chemotherapy) was 13.89 (95% CI=12.40-16.80) and 31.02 (95% CI=24.27-37.44) months vs. 10.97 (95% CI=8.97-14.82) and 26.57 (95% CI=15.97-33.92) months for those treated in the second line (post-chemotherapy). We found inferior survival for patients with synchronous metastases, high Gleason score (GS) and visceral metastases. Conclusion: The efficacy of both ENZ and AAP in mCRPC patients is herein confirmed. Synchronous metastases, high GS and visceral metastases were identified as significant adverse prognostic factors.

BACKGROUND:The anticancer properties of metformin have been suggested in numerous experimental studies and several retrospective clinical studies show that its use is associated with improved outcome of patients with cancer. However, limited data are available for patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. The aim of this retrospective study was to assess the impact of the metformin use on survival of mRCC patients treated with sunitinib or pazopanib.METHODS:Clinical data from 343 patients with mRCC treated with sunitinib or pazopanib in the first line were analyzed. Progression-free survival (PFS) and overall survival (OS) were compared according to the use of metformin.RESULTS:The median PFS and OS for patients using metformin was 31.1 (95% CI 20.6-35.1) and 51.6 (95% CI 44.7-NR) months compared to 9.3 (95% CI 8.0-12.0) and 22.4 (95% CI 19.4-26.8) months for patients not using metformin (p<0.0001 and p=0.0002, respectively). Cox multivariate analysis shows that the use of metformin remains a significant factor for PFS (HR=0.55 [95% CI 0.343-0.883], p=0.013) and also for OS (HR=0.45 [95% CI 0.256-0.794], p=0.006).CONCLUSION:The present study results suggest that the use of metformin was associated with favorable outcome of mRCC patients treated with sunitinib or pazopanib.

Background/Aim: The treatment of advanced clear cell renal cell carcinoma (ccRCC) is based on stratification of patients according to prognosis (favorable, intermediate, and poor). The aim of the study was to improve prognostication by biomarkers involved in angiogenesis. Patients and Methods: The study group consisted of 20 patients who underwent surgery for ccRCC. Gene expression analysis was peformed on a set of matched (primary tumor, metastasis, n=20+20) FFPE tissue samples. An additional analysis was done on expression data of 606 patients obtained from the TCGA Kidney Clear Cell Carcinoma (KIRC) database. Quantitative estimation of mRNA of selected genes (TaqMan human Angiogenesis Array, 97 genes) was performed by a real-time RT-PCR method with TaqMan® arrays. Results: Using the Cox regression model, 4 genes (PDGFB, FGF4, EPHB2 and BAI1) were identified whose expression was related to progression-free interval (PFI). Further analysis using the Kaplan Meier method conclusively revealed the relationship of BAI1 expression to prognosis (both datasets). Patients with higher BAI1 expression had significantly shorter PFI and overall survival. Conclusion: We showed that tumor tissue BAI1 expression level is a prognostic marker in ccRCC. Therefore, this gene might be involved in a prognostic panel to improve scoring systems on which the management of metastatic ccRCC patients is based.

Introduction In men with ≥pT1G2 cN0, penile cancer lymph node sampling is recommended with either (1) scintigraphically labelled Dynamic sentinel lymph node biopsy (DSLNB) or (2) modified inguinal lymph node dissection (MILND). Although DSLNB is a minimally invasive technique, the false negative rate can be about 10%, and a further operative procedure is required if positive. Open MILND is a diagnostic and therapeutic option but has a much higher morbidity. A potential compromise is the technique of LND-VEILND (video endoscopic inguinal LND) that can be combined with ICG florescence marking of sentinel lymph node (SLN). We present a pilot study of ICG-VEILND. The aim was to validate the applicability of a combination ICG marking of SLN in VEILND (to increase probability to excise SLN) and determine the optimal timing and dosage of ICG. Materials and Methods 15 patients with VEILND (24 groins) underwent ICG application with fluorescence near-infrared (NIR 803⟶830 nm) detection. ICG is applied subcutaneously adjacent to the penile cancer or residual stump of penis or suprapubic region (in a history of total penectomy: 5 cases). The dose of 1.25 mg (ICG) was applied in one case with invisible SLN, the dose of 2.5 mg in 1 mL in 8 cases, and 5 mg in the remaining 6 patients (10 groins). Results Failure of marking SLN with ICG occurred in 25.0% of cases (6/24): due to application of 1.25 mg ICG, extensive metastasis to SLN, in 4 cases, the cause was unknown (16.7%, 4/24). In the short follow-up period, no local recurrence was seen in the pN0 ICG group. Conclusion Fluorescence infrared image with ICG dye increases the probability of removal of the SLN during VEILND. The dose of ICG is 2.5 (5) mg diluted in 1 ml and can be applied preoperatively even in the suprapubic region in men with a history of total penectomy, with an unexplainable failure of ICG marking in 16.7%.

Patients with metastatic renal cell carcinoma (mRCC) are often elderly and have various comorbidities, including cardiovascular diseases. Although these patients have extensive co-exposure to targeted therapy and cardiovascular drugs, the impact of this co-exposure on outcomes for patients with mRCC remains unclear. Our objective was to evaluate the association between the use of cardiovascular medication and survival of patients with mRCC. The study included 343 consecutive patients with mRCC treated with sunitinib or pazopanib in the first line. Clinical data obtained from the Renal Cell Carcinoma Information System (RENIS) clinical registry and hospital information systems were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were compared according to the use of common medications, including antihypertensives (i.e., β-blockers [BBs], angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and diuretics), acetylsalicylic acid (aspirin), statins, and proton pump inhibitors. The univariate Cox analysis evaluating the impact of the assessed comedications on patient survival revealed that only BBs were significantly associated with PFS (hazard ratio [HR] 0.533, p < 0.001) and OS (HR 0.641, p = 0.006). The median PFS and OS for users of BBs was 18.39 and 37.60 months versus 8.16 and 20.4 months for patients not using BBs (p < 0.001 and p < 0.001, respectively). The Cox multivariate analysis showed that the use of BBs was a significant factor for both PFS (HR 0.428, p = 0.001) and OS (HR 0.518, p = 0.001). The results of this retrospective study suggest that the use of BBs is associated with favorable outcomes for patients with mRCC treated with sunitinib or pazopanib in the first line.

Hlavni stanovisko prace: Přehledový clanek zabývajici se problematikou hereditarnich renalnich nadorových syndromů, jejich zakladni charakteristikou, manifestaci, diagnostikou, lecbou a dispenzarizaci, se zaměřenim na renalni karcinom. Major statement: Review dealing with hereditary renal cell carcinoma syndromes, their basic characteristics, presentation, diagnosis, treatment and surveillance focusing on renal cell carcinoma. Kolař J, Pitra T, Pivovarcikova K, Jaklova R, Zavoral T, Travnicek I, Sedlackova H, Prochazkova K, Vaněcek T, Hes O, Hora M. Hereditarni renalni nadorove syndromy. V poslednich letech dochazi ke zvysovani poctu definovaných hereditarnich nadorových syndromů, z nichž některe jsou spojeny s predispozici k rozvoji renalniho karcinomu. Na hereditarni renalni nadorový syndrom je třeba pomýslet u mladých jedinců s renalnim karcinomem, u pacientů s pozitivni rodinnou anamnezou nadorů ledvin, dale u renalnich lezi bilateralnich a multifokalnich a při výskytu extrarenalnich symptomů charakteristických pro některý ze syndromů. Mezi nejcastějsi hereditarni nadorove syndromy asociovane s renalnim karcinomem patři syndrom von Hippel‑Lindau, Birt‑Hogg‑Dube syndrom, hereditarni papilarni renalni karcinom, hereditarni leiomyomatoza a renalni karcinom, sukcinatdehydrogenaza deficientni renalni karcinom, komplex tuberozni sklerozy a Cowdenův syndrom. V souvislosti s hereditarnim renalnim karcinomem jsou popsany mutace v tumor supresorových genech (VHL, BAP1, PTEN, TSC1, TSC2) i v protoonkogenech (MET). V ramci jednotlivých syndromů se setkavame s rozdily ve stupni penetrance onemocněni, v histologii jednotlivých typů renalniho karcinomu, v jeho agresivitě a metastatickem potencialu, a tedy i v nasledne lecbě a dispenzarizaci.

Mlynarcik M, Travnicek I, Pitra T, Kacerovska D, Hora M. Raritni připad gigantických kondylomat (Buschke-Lowenstein) v urologicke praxi. Prezentujeme kazuistiku gigantických ziskaných kondylomat (Buschke-Lowenstein tumor). Leze způsobena infekci HPV (lidský papilomavirus) velikosti 25 cm byla řesena chirurgickou excizi ve spolupraci s plastickým chirurgem. Buschke-Lowenstein tumor je premaligni leze perigenitalni oblasti způsobujici lokalni destrukci tkani s maligni transformaci až v polovině připadů.

Kolař J, Pitra T, Pivovarcikova K, Travnicek O, Lepic F, Hes O, Hora M. Biopsie nadorů ledvin - indikace, provedeni, výsledky. Cil: Zhodnotit výsledky biopsie tumorů ledvin (BTL) provedených na nasem pracovisti a tyto nasledně porovnat s výsledky udavanými v literatuře. Material a metoda: Retrospektivni hodnoceni souboru pacientů, kteři podstoupili BTL v letech 2007-2019. Výsledky: Za casove obdobi I/2007-XII/2019 byla na nasem pracovisti provedena BTL u 200 nemocných - 128 mužů (64,0 %) a 72 žen (36,0 %). Průměrný věk pacientů byl 64,8 let (34-85 let). Ve větsině připadů se jednalo o biopsii pod CT kontrolou (n = 192; 96,0 %), minoritně pod kontrolou ultrasonografickou (n = 8; 4,0 %). Nejcastějsi indikaci k biopsii ledviny byla histologicka verifikace u metastatickeho onemocněni před urcenim systemove onkologicke lecby (n = 162; 81,0 %), dale histologicka verifikace nejasných lezi (n = 32; 16,0 %) a biopsie před radiofrekvencni ablaci (n = 6; 3,0 %). Inicialni biopsie byla diagnosticka u 165 pacientů (82,5 %). Histologicky byl nejcastěji nalezen světlobuněcný renalni karcinom (n = 107; 53,5 %), dale papilarni renalni karcinom (n = 19; 9,5 %), urotelialni karcinom (n = 15; 7,5 %) a chromofobocelularni renalni karcinom (n = 3; 1,5 %). Ostatni histologicke nalezy byly popisovany u 21 jedinců (10,5 %). Nediagnostických bylo 35 provedených biopsii (17,5 %); re‑biopsie byla provedena v 17 připadech, z toho 16× již byla diagnoza stanovena. U zbylých 18 pacientů nebyla biopsie opakovana (doslo k celkovemu zhorseni stavu (n = 6), re‑biopsie byla pacientem odmitnuta (n = 2), netrvalo již klinicke podezřeni z nadoroveho postiženi (n = 4) nebo byl indikovan chirurgický výkon, kdy histologicke vysetřeni bylo provedeno v ramci vysetřeni preparatu (n = 6)). Nejzavažnějsi komplikaci byl perirenalni hematom s nutnosti podani krevni transfuze (Clavien 2). Zavěr: Biopsie tumoru ledviny je bezpecna a spolehliva diagnosticka metoda. V nami hodnocenem souboru byla BTL v naproste větsině provaděna pod CT kontrolou. Nejcastějsi indikaci byla histologicka verifikace před onkologickou lecbou u metastatickeho onemocněni a převladajicim histologickým nalezem byl světlobuněcný renalni karcinom.