Renal cell carcinoma with intracardiac tumor thrombus extension: Radical surgery yields 2 years of postoperative survival in a single-center study over a period of 30 years.

Background: Renal cell carcinoma (RCC) with tumor thrombus extension into the right atrium (level IV) is a rare life-threatening clinical condition that can only be managed by means of a combined urological and cardiac surgical approach. The early and late outcomes of this radical treatment were analyzed in a large single-institution series over a period of 30 years. Methods: In 37 patients with RCC and intracardiac tumor thrombus extension, nephrectomy was performed followed by the extraction of the intracaval and intracardiac tumor thrombus under direct visual control during deep hypothermic circulatory arrest (DHCA). Recently, in 13 patients, selective aortic arch perfusion (SAAP) was instituted during DHCA. Results: In all patients, precise removal of the tumor thrombus was accomplished in a bloodless field. The mean duration of isolated DHCA was 15 ± 6 min, and 31.5 ± 10.2 min in the case of DHCA + SAAP, at a mean hypothermia of 22.7 ± 4°C. In-hospital mortality was 7.9% (3 patients). In Kaplan-Meier analysis, the estimated median survival was 26.4 months whereas the 5-year cancer-related survival rate was 51%. Conclusions: Despite its complexity, this extensive procedure can be performed safely with a generally uneventful postoperative course. The use of cardiopulmonary bypass with DHCA, with the advantage of SAAP, allows for a safe, precise, and complete extirpation of intracaval and intracardiac tumor mass. Late outcomes after radical surgical treatment in patients with RCC and tumor thrombus reaching up in the right atrium in our series justify this extensive procedure.

Investigation of ochratoxin A biomarkers in biological materials obtained from patients suffering from renal cell carcinoma.

Ochratoxin A (OTA) exposure can result in chronic renal diseases and cancer. The incidence of kidney, renal pelvis, and ureter malignant neoplasms in the Czech Republic is approximately 29.5 renal tumours per 100,000 inhabitants. The question arises whether mycotoxins are also involved in kidney disease and cancer. A sensitive validated analytical methodology, based on an immunoaffinity clean-up followed by HPLC with fluorescence detection, was developed to explore whether OTA accumulates in clear renal cell carcinoma-adenocarcinoma in Czech patients. Simultaneously, DNA-adducts and OTA metabolites were qualitatively analysed in tissues and urine. OTA was analysed in 33 kidney and tumour samples from 26 men and 7 women collected during nephrectomy from patients of the East Bohemian region from 2015 to 2017. OTA was found in 76% of the analysed samples. Its concentrations ranged from not detectable to 390 ng/kg with a median of 167 ng/kg in kidney samples and from not detectable to 430 ng/kg with a median of 122 ng/kg in tumour samples. Urinary OTA metabolites and DNA adducts were qualitatively analysed for the corresponding 20 patients. The presence of some OTA metabolites such as ochratoxin A hydroquinone and/or decarboxylated ochratoxin A hydroquinone correlate with the presence of OTA-DNA adducts.

Analyses of biomarkers of exposure to nephrotoxic mycotoxins in a cohort of patients with renal tumours.

The Czech Republic occupies the first place in the world in the frequency of renal and other urinary tract tumours, but their aetiology is unknown. To explore whether carcinogenic and nephrotoxic mycotoxins may contribute to kidney diseases in the Czech population, biomarkers of ochratoxin A (OTA) and citrinin (CIT) exposure were determined in biological specimens from a cohort of 50 patients with malignant renal tumours. Biomarker analyses in blood and urine samples used validated targeted methods for measuring OTA and CIT plus dihydrocitrinone (DH-CIT) after enrichment of analytes by specific immunoaffinity clean-up. OTA and CIT plus its metabolite DH-CIT were frequently detected in patient urine samples (OTA 62%; CIT 91%; DH-CIT 100%). The concentration ranges in urine were 1-27.8 ng/L for OTA, 2-87 ng/L for CIT and 2-160 ng/L for DH-CIT. The analyses of blood samples revealed also a frequent co-occurrence of OTA and CIT, in the ranges of 40-870 ng/L serum for OTA and 21-182 ng/L plasma for CIT. This first analysis of biomarkers in blood and urine samples of Czech patients revealed no major differences in comparison with published data for the general healthy Czech and European populations. Nonetheless, a frequent co-occurrence of CIT and OTA biomarkers in patient samples may be of interest with regard to potential interactions with other risk factors for renal disease.

The susceptibility to fosfomycin of Gram-negative bacteria isolates from urinary tract infection in the Czech Republic: data from a unicentric study.

BACKGROUND: Against a background of rapid increase of ß-lactamase-producing or multi-resistant pathogenic bacteria and the resulting lack of effective antibiotic treatment, some older antibiotics have been tested for new therapeutic uses. One of these is fosfomycin, to which according to studies these resistant bacteria are very sensitive. Our study was designed because there is no data on the fosfomycin susceptibility rate in the Czech Republic. METHOD: In this study from January 2013 to June 2014 3295 unique isolates of Gram-negative bacteria which had caused urinary tract infections were examined. The antibiotic susceptibility was measured by disk diffusion test. Both EUCAST and CLSI guidelines criteria (for fosfomycin only) were used for the antibiotic susceptibility evaluation. RESULTS: The most frequently tested bacterial isolates were Escherichia coli (51.3%, n = 1703), Klebsiella pneumoniae (19.4%, n = 643) and Proteus spp. (11.8%, n = 392). Among all isolates 29.0% (n = 963) were resistant to fluoroquinolones, 11.3% (n = 374) produced extended spectrum ß-lactamase and 4.2% (n = 141) produced AmpC ß-lactamase. The overall in vitro susceptibility was significantly higher for fosfomycin compared to the other tested per-oral antibiotics (nitrofurantoin, ampicillin, co-trimoxazole, ciprofloxacin and cefuroxime) against all tested Gram-negative rod isolates (excluding Morganella morgani and Acinetobacter spp. isolates). Fosfomycin also remained highly active against those isolates with extended spectrum ß-lactamase (ESBL) production (95.8% in Escherichia coli isolates and 85.3% in Klebsiella pneumoniae isolates), unlike other tested per-oral antibiotics, which showed significant (p < 0.0001) susceptibility decrease. CONCLUSION: We have confirmed in the Czech Republic the very high susceptibility to fosfomycin trometamol of urinary tract infection pathogens, particularly Gram-negative rods including those producing ß-lactamase.

Selective aortic arch perfusion enables to avoid deep hypothermic circulatory arrest for extirpation of renal cell carcinoma with tumour thrombus extension into the right atrium.

OBJECTIVES: Renal cell carcinoma with a tumour thrombus extending into the right heart chambers necessitates extensive combined urological and cardiac surgery. Maximum safety and exactness in extirpation of the caval and intracardiac thrombus is achieved under deep hypothermic circulatory arrest, at a price of its non-physiological burden and time constraints. We propose a simple surgical manoeuvre enabling selective arch perfusion allowing for a milder hypothermia and liberal interval of circulatory arrest. METHODS: On a routine cardiopulmonary bypass via median sternotomy, the dissection is extended along the aortic arch to identify the origins of the supra-aortic vessels. After standard aortic cross-clamping and cardioplegic cardiac arrest at moderate hypothermia, a second cross-clamp is applied at the aortic arch beyond the left carotid artery. A selective closed aortic arch perfusion is started while the extirpation of the tumour thrombus from the right atriotomy and abdominal cavotomy is being performed under conditions of circulatory arrest. RESULTS: Using selective aortic arch perfusion, successful and uncomplicated extirpation of voluminous caval and intracardiac tumour thrombi was accomplished in 3 presented patients. Unexpectedly difficult thrombus adhering to hepatic veins in 1 patient required 42 min of circulatory arrest. Postoperative courses were uneventful in all 3 patients. CONCLUSIONS: Second aortic cross-clamp to start selective closed aortic arch perfusion provides excellent surgical control of the operative field over a liberal time interval during circulatory arrest under milder hypothermia.

Magnetic resonance imaging in postprostatectomy radiotherapy planning.

PURPOSE: To investigate whether the use of magnetic resonance imaging (MRI) in prostate bed treatment planning could influence definition of the clinical target volume (CTV) and organs at risk. METHODS AND MATERIALS: A total of 21 consecutive patients referred for prostate bed radiotherapy were included in the present retrospective study. The CTV was delineated according to the European Organization for Research and Treatment of Cancer recommendations on computed tomography (CT) and T(1)-weighted (T(1)w) and T(2)-weighted (T(2)w) MRI. The CTV magnitude, agreement, and spatial differences were evaluated on the planning CT scan after registration with the MRI scans. RESULTS: The CTV was significantly reduced on the T(1)w and T(2)w MRI scans (13% and 9%, respectively) compared with the CT scans. The urinary bladder was drawn smaller on the CT scans and the rectum was smaller on the MRI scans. On T(1)w MRI, the rectum and urinary bladder were delineated larger than on T(2)w MRI. Minimal agreement was observed between the CT and T(2)w images. The main spatial differences were measured in the superior and superolateral directions in which the CTV on the MRI scans was 1.8-2.9 mm smaller. In the posterior and inferior border, no difference was seen between the CT and T(1)w MRI scans. On the T(2)w MRI scans, the CTV was larger in these directions (by 1.3 and 1.7 mm, respectively). CONCLUSIONS: The use of MRI in postprostatectomy radiotherapy planning resulted in a reduction of the CTV. The main differences were found in the superior part of the prostate bed. We believe T(2)w MRI enables more precise definition of prostate bed CTV than conventional planning CT.

Psychosocial implications and the duality of life outcomes for patients with prostate carcinoma after bilateral orchiectomy.

OBJECTIVES: The study presented focuses on patients' psychosocial status after a prostate cancer diagnosis that underwent a bilateral orchiectomy. METHODS: We evaluated the psychosocial implications of 89 patients with prostate cancer after performing castration and a bilateral orchiectomy. RESULTS: Patients suffered significantly more from sleep disorders during hospitalisation when compared to their time prior to an orchiectomy (p<0.0005). There were some increases in the severity of sleep disorder after discharge (level of evidence p<0.05). However, no additional medications for sleep disorders were required. Additionally, there was a significant reduction in the abuse of medication (p<0.001). Ten per cent of the patients were in the care of a psychologist or a psychiatrist before their diagnosis, and 21% asked for the help of a psychologist or a psychiatrist after having a bilateral orchiectomy. The occurrence of mood disorders is also very different than the occurrence of sleep disorders. Mood disorders occurred much less often after orchiectomy and discharge (p>0.085) compared with the period before surgery. Forty per cent of the patients had mood disorders before their operation, while only 37% still had these after discharge. There was a significant decrease in abuse of medication for anxiety. Twenty-four per cent of the patients took medication during hospitalisation, and only 10% continued after orchiectomy. CONCLUSIONS: The results of the study show that patients who were notified about their cancer diagnosis, particularly their health status, exhibited moderate stress and psychological impact.

Radical prostatectomy in high-grade prostate cancer, salvage and adjuvant radiotherapy.

INTRODUCTION: Prostate cancer with a Gleason score (GS) of 8-10 is linked to a higher risk of recurrence and progression. The aim of this paper is to evaluate treatment results of our high-risk patient cohort. PATIENTS AND METHODS: The cohort of 42 patients with radical prostatectomy (RP) specimen histology GS 8-10 was assessed. The patients were followed up after RP and radiotherapy (RT) was delivered in case of a biochemical relapse. Adjuvant radiotherapy (aRT) was delivered only in case of a positive surgical margin (PSM). The following parameters were evaluated: biochemical progression-free survival (BPFS), overall survival (OS) and cancer-specific survival (CSS). The second objective was to evaluate adverse effects of RP and RT. RESULTS: The median follow-up time was 88 months (18-168). RP led to BPFS in 16 patients (38%). Five patients with PSM underwent aRT and 20 underwent salvage radiotherapy (sRT). One patient died of myocardial infarction and 1 patient died of metastatic disease. Skeletal metastases were recorded in 2 patients. The BPFS in RP combinations with sRT or aRT was reached in 29 patients (69%). The OS and CSS in our cohort reached 95 and 98%, respectively. CONCLUSION: Management with aRT only in PSM was very effective, according to our retrospective study.

Calcium dobesilate for the treatment of erectile dysfunction in men with diabetes mellitus.

Calcium dobesilate has shown to improve endothelial function. This proof-of-concept clinical trial was done to check whether it may improve erectile dysfunction in diabetic men. Male diabetic patients with a diagnosis of erectile dysfunction were randomized to receive either calcium dobesilate 1 g twice per day or placebo for 6 weeks. The International Index of Erectile Function (IIEF) was chosen as the primary efficacy measurement. Statistical procedures included a pre-scheduled adaptive interim analysis to recalculate sample size. Relevant, but not significant differences in the mean change from baseline in the primary end-point (IIEF questions 3, 4 and 7) favouring dobesilate with respect to placebo were observed. Such differences reached statistical significance in some secondary end-points, including IIEF global as well as the erectile function and intercourse satisfaction domains' scores. Some patients experienced an important placebo effect. Results suggest that dobesilate may be of help to treat diabetic erectile dysfunction. Co-administration with phosphodiesterase inhibitors warrants further investigation.

Bi-weekly epirubicin, etoposide and low-dose dexamethasone for hormone-refractory prostate cancer.

BACKGROUND: Recent studies have demonstrated the efficacy and favorable toxicity profile of chemotherapy regimens given at lower doses and frequent intervals. The aim of our study was to evaluate the efficacy and toxicity of a bi-weekly chemohormonal regimen consisting of epirubicin, etoposide, and low-dose dexamethasone (EED) in patients with hormone-refractory prostate cancer (HRPC). METHODS: We treated a total of 32 patients who had failed hormonal therapy and antiandrogen withdrawal. Chemotherapy was given every 2 weeks and consisted of epirubicin (30 mg/m2 intravenously, day 1) and etoposide (50 mg/m2 orally, days 1-7). Dexamethasone (1.5 mg orally, every other day) was given continuously until disease progression. Twenty patients (63%) had received prior treatment with estramustine phosphate. Each patient's pain response was evaluated according to analgesic use. Toxicity was graded using the Common Toxicity Criteria (version 2.0). RESULTS: Prostate-specific antigen (PSA) levels showed a decline of 50% or greater in 16 of 32 patients (50%, 95% confidence interval [CI], 32-68%) with a median time to biochemical progression of 5 months (range, 4-9 months). The median survival for all patients was 10.5 months (range, 3-35 months). Four of 10 patients (40%) with measurable soft tissue lesions achieved partial response according to standard criteria. Eleven of 23 symptomatic patients (48%, 95% CI, 27-69%) experienced an improvement in pain with a median duration of 6 months. The regimen was tolerated well by the patients, with only four patients (12%) having grade 3 leukopenia. CONCLUSION: Chemohormonal EED regimen proved to be active and well-tolerated in patients with HRPC.