[Show abstract][Hide abstract] ABSTRACT: Aim. To retrospectively analyze patients treated by renal tumor and venous tumor thrombus (VVT) removal and to introduce a less stressful and safer surgical method without thoracotomy in Neves level 3 cases. Methods. From 2002 to 2011, 33 patients underwent surgery for renal cell cancer combined with tumor thrombus of the inferior vena cava. Preoperative symptoms, tumor-node-metastasis classification of tumors, thrombus extension classified by Neves and Zincke system, types of surgical interventions, complications, postoperative management, and survival results were analyzed. Results. Ten patients had level 1, 17 had level 2, and 6 had level 3 thrombi according to Neves and Zincke. In 5 patients with level 3 thrombi, the liver was mobilized without thoracotomy and in 1 patient endoluminal occlusion was utilized. There was no intraoperative mortality. The median survival time of 10 patients who died during follow-up period was 36.6 months (range, 0-121 months). Conclusion. Renal cell cancer complicated with tumor thrombus without metastasis can be curable by performing a complete resection. The thrombus level determines the surgical approach and method. Our results confirm that level 3 caval vein tumor thrombus can be safely surgically treated by laparotomy with liver mobilization. Thoracotomy, use of cardiopulmonal bypass, and hypothermic circulatory arrest can be avoided with adequate liver- and vascular surgery methods.
Croatian Medical Journal 06/2014; 55(3):265-70. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The primary testicular non-Hodgkin lymphoma, which has been first described in 1866, is a very uncommon type of urological neoplasia occuring mostly in the elderly ages. It only gives 5% of the testicular tumors, 2% of extranodal lymphomas, and barely 1% of all non-Hodgkin diseases. Patients with testicular non-Hodgkin lymphomas need prompt multidisciplinary aid because without treatment the outcome can be unfavorable. The authors discuss the attributes, diagnostic modalities and treatment options of the primary testicular non-Hodgkin lymphoma and present a case of a 68-year-old patient who underwent orchiectomy, chemo- and radiotherapy after having been diagnosed with the tumor. The follow-up PET-CT and cerebrospinal fluid analysis found no further sign of the disease, and complete remission has been achieved. Orv. Hetil., 2014, 155(2), 69-71.
[Show abstract][Hide abstract] ABSTRACT: The main objective of this retrospective study was to evaluate the influence of pathological experience in histological examination of prostate cancer (PCa) on preoperative understaging (UNS), undergrading (UNG), and upgrading (UPG).
Histopathological data of prostate biopsy (PB) and radical prostatectomy (RP) specimens of patients undergoing subsequent radical prostatectomy (n = 430) in our center were compared. Histological diagnoses of PB were provided either by corresponding academic pathology institute (Group 1: 322 patients) or by external (nonacademic) departments which had a lower number (≤100/year) of PCa histopathological evaluations (Group 2 108 patients). The rate of UNG, UPG, and UNS in both groups and also the effects of institutional learning curve were analyzed in terms of grading and staging.
Significant difference was detected between Group 1 and Group 2 in average preoperative Gleason score (GS) values and in the rate of well, moderately, and poorly differentiated cancers as well. There was also a significant difference in the rate of UNG (29.1 vs. 56.5 %, p < 0.0001). The mean preoperative and postoperative GS in Group 1 was significantly lower in the first 50 than in the last 50 patients, but the rates of UNG, UPG, and UNS did not differ significantly between the groups.
The experience of pathologists has direct influence on grading concordance and on UNG and UPG, between PB and RP specimen; however, it has no significant effect on complete preoperative understaging. The bigger pathological experience improves the sensitivity of the histological diagnostic process.
International Urology and Nephrology 08/2013; · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the role and prognostic significance of angiostatin, basic fibroblast growth factor (bFGF), and tyrosine endothelial kinase (TEK/Tie2) in transitional cell bladder carcinoma.
Angiostatin, bFGF, and TEK serum concentrations were measured in 82 bladder cancer patients and 20 age-matched healthy controls using enzyme-linked immunosorbent assay. Results were compared with clinicopathologic and follow-up data with the Mann-Whitney U test and Kaplan-Meier, univariate and multivariate Cox regression analyses.
We found significantly decreased angiostatin and TEK serum levels and mildly elevated bFGF concentrations in samples of bladder cancer patients compared with controls (P < .001, P < .001, and P = .083, respectively). Furthermore, high TEK serum levels were correlated with poor disease-specific and metastasis-free survival in muscle-invasive bladder cancer (P = .013, P = .018), whereas angiostatin and bFGF concentrations did not show any correlation with patients' prognosis. Multivariate analysis revealed high TEK levels (<1.60 ng/mL) as borderline significant independent risk-factor of disease-specific survival (HR 1.83, 95% CI 0.97-3.44, P = .061) and metastasis-free survival (HR 2.65, 95% CI 0.93-7.55, P = .069).
The characteristic differences in the circulating levels of angiostatin, TEK, and bFGF between patients and controls, suggest the presence of a tumor-induced proangiogenic milieu in bladder cancer. Serum TEK levels may contribute to a more reliable preoperative risk stratification in muscle-invasive bladder cancer and therefore may help to optimize therapeutic decisions.
[Show abstract][Hide abstract] ABSTRACT: Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.
Archives of Toxicology 04/2012; 86(9):1369-78. · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: What's known on the subject? and What does the study add? Insulin-like growth factor mRNA-binding protein 3 (IMP3) is an oncofetal protein found to be re-expressed in a series of human cancers including bladder cancer. In vitro analyses showed an invasion and proliferation promoting effect for IMP3. Further in vitro studies suggested that IMP3 is able to bind to the mRNAs of CD44 and insulin-like growth factor 2 (IGF2), enhancing their stability and expression. However, this molecular interaction has not yet been analysed in tumour samples. In the present study, we identified for the first time high IMP3 tissue protein expression as an independent predictor of poor patients' survival in muscle-invasive bladder cancer. Furthermore, there was no correlation between IMP3 and its molecular targets in bladder carcinoma specimens and concluded that the tumour-promoting effect of IMP3 is not related to its regulatory action on IGF2 and CD44.
To assess the prognostic value and molecular actions of the oncofetal protein insulin-like growth factor mRNA-binding protein 3 (IMP3) in muscle-invasive bladder cancer (BC).
IMP3 expression was analysed by immunohistochemistry, real-time polymerase chain reaction and Western blot analysis in 224 patients with BC. The molecular targets of IMP3; CD44, insulin-like growth factor 2 (IGF2) and its receptor the IGF1 receptor (IGF1-R) were also investigated. Expression levels were correlated with clinical follow-up data by using both univariate and multivariate Cox regression analyses.
IMP3 mRNA and protein levels were significantly elevated in high-stage and high-grade muscle-invasive BC. In muscle-invasive BC IMP3 protein but not gene expression proved to be an independent predictor of disease-specific (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.28-4.56, P = 0.004) and overall survival (HR 2.07, 95% CI 1.12-3.82, P = 0.020). The expression levels of IGF2 and CD44 showed no correlation with that of IMP3.
High IMP3 protein levels may identify patients with BC at high risk of disease progression and may therefore select patients for a more intensive therapy or for a strict follow-up. Its high expression in high-grade bladder carcinoma cells makes IMP3 for an attractive target for therapy. The tumour promoting effect of IMP3 is independent from its regulatory action on IGF2 and CD44 expression.
BJU International 04/2012; 110(6 Pt B):E308-17. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our aim was to evaluate the anal sphincter function following cystectomy with urinary diversion of Mainz pouch II.
Seventy-six patients were involved in our survey, and the cohort was for two groups divided. The first group was a retrospective review of 40 patients with examination of the state of continence. Comparative examinations on anal sphincter function and the quality of life survey were carried out. The second group consisting of 15 patients underwent a prospective investigation including rectal manometry in both the pre- and postoperative periods. Measurements of resting anal sphincter pressure (RASP), maximal anal closing pressure (MACP) and the function of the recto anal inhibitions reflex were taken.
In the first part of our investigation, 80% of the patients were considered as continent. There were no significant differences observed between RASP values in the cases of continent as well as of incontinent patients (79.2 ± 2 vs. 73.6 ± 68.4 mmHg, p = 0-53); however, the MACP values of the continent patients were significantly higher (204.3 ± 22.8 vs. 117.3 ± 14 mmHg, p = 0.001). In the course of the second experiment, both the RASP (86.3 ± 18.7 vs. 76.1 ± 13.9 mmHg p = 0.0049) and the MACP (232.2 ± 53.8 vs. 194.1 ± 74.5 mmHg, p = 0.0054) were detected as decreasing in the case of the incontinent group.
A decrease in rectal sphincter function is responsible for incontinence following Mainz pouch type II diversion, and this dysfunction can be correlated with the surgery. Ureterosigmoideostomy is therefore considered as a useful method of urinary diversion only in selected cases with proven good sphincter function.
International Urology and Nephrology 02/2012; 44(4):1013-20. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a considerable discrepancy between the number of identified occupational-related bladder cancer cases and the estimated numbers particularly in emerging nations or less developed countries where suitable approaches are less or even not known. Thus, within a project of the World Health Organisation Collaborating Centres in Occupational Health, a questionnaire of the Dortmund group, applied in different studies, was translated into more than 30 languages (Afrikaans, Arabic, Bengali, Chinese, Czech, Dutch, English, Finnish, French, Georgian, German, Greek, Hindi, Hungarian, Indonesian, Italian, Japanese, Kannada, Kazakh, Kirghiz, Korean, Latvian, Malay, Persian (Farsi), Polish, Portuguese, Portuguese/Brazilian, Romanian, Russian, Serbo-Croatian, Slovak, Spanish, Spanish/Mexican, Tamil, Telugu, Thai, Turkish, Urdu, Vietnamese). The bipartite questionnaire asks for relevant medical information in the physician's part and for the occupational history since leaving school in the patient's part. Furthermore, this questionnaire is asking for intensity and frequency of certain occupational and non-occupational risk factors. The literature regarding occupations like painter, hairdresser or miner and exposures like carcinogenic aromatic amines, azo dyes, or combustion products is highlighted. The questionnaire is available on www.ifado.de/BladderCancerDoc.
Frontiers in bioscience (Elite edition) 01/2012; 4:2809-22.
[Show abstract][Hide abstract] ABSTRACT: Follow-up and review of patients who underwent surgery for renal cell cancer combined with tumor thrombus of the inferior vena cava at the Department of Urology Semmelweis University, Budapest, Hungary.
From l998 to 2010 twenty one patients underwent surgery for renal cell cancer combined with tumor thrombus of the inferior caval vein. Preoperative symptoms, TNM classification of the tumors, types of surgical interventions, complications, postoperative management and survival results were involved in the analysis. Mean follow-up period was 39 months, ranging from 3 to 101 months.
In five cases of level 3 thrombi the liver was mobilized without thoracotomy, and endoluminar occlusion was applied in one case. Intraoperative mortality was 9,5%. Survival time of patients with distant metastases was 12.1 months (3-9). Three patients without metastases died in the follow up period, their survival time was 26.7 months ranging from 22 to 31 months. Eight patients (73%) were alive at the time of the last follow-up. The mean survival time was 5.6 years ranging from 39 to 101 months.
Our results support that level 3 caval vein tumor thrombus can be removed by less aggressive surgical approach and underline the benefit of the surgical intervention without thoracotomy.
Magyar Sebészet (Hungarian Journal of Surgery) 12/2011; 64(6):283-8.
[Show abstract][Hide abstract] ABSTRACT: Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins' specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin-4, claudin-7, and Ki-67 might be used as potential markers to differentiate low-grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome.
Journal of Histochemistry and Cytochemistry 11/2011; 59(11):1022-30. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.
Archives of Toxicology 09/2011; 86(2):195-203. · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The members of the claudin family are major integral transmembrane protein constituents of tight junctions. Normal and neoplastic tissues can be characterized by unique qualitative and quantitative distribution of claudin subtypes, which may be related to clinicopathological features. Differential diagnosis and prognosis of nonmuscle invasive tumor entities of urinary bladder epithelium are often challenging. The aim was to investigate the expression profile of claudins in inverted urothelial papillomas (IUPs), urothelial papillomas (UPs), papillary urothelial neoplasms of low malignant potential (PUNLMPs), and intraepithelial (Ta), low-grade urothelial cell carcinomas (LG-UCCs) in order to reveal potential prognostic and differential diagnostic values of certain claudins. Claudin-1, -2, -4, and -7 protein expressions detected by immunohistochemistry and clinical data were analyzed in 15 IUPs, 20 UPs, 20 PUNLMPs, and 20 LG-UCCs. UPs, PUNLMPs, and LG-UCCs showed significantly decreased claudin-1 expression in comparison to IUPs. LG-UCCs expressing claudin-4 over the median were associated with significantly shorter recurrence-free survival. PUNLMPs expressing claudin-1 over the median revealed significantly longer recurrence-free survival. High claudin-1 protein expression might help to differentiate IUP from UPs, PUNLMPs, and LG-UCCs. High claudin-4 expression may determine an unfavorable clinical course of LG-UCCs, while high claudin-1 expression in PUNLMP was associated with markedly better clinical outcome.
Journal of Histochemistry and Cytochemistry 08/2011; 59(10):932-41. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endostatin, the proteolytic fragment of collagen XVIII, is an inhibitor of angiogenesis and tumor growth. Interestingly, elevated circulating endostatin levels have been found to correlate with poor patients' prognosis in several cancers. The aim of this study was to assess the prognostic value of endostatin in bladder cancer (BC) and to gain insight into the mechanisms involved in its production. This retrospective study included a total of 337 patients with BC and 103 controls. Collagen XVIII gene expression was analyzed using real-time PCR (n = 82). Endostatin tissue localization was assessed by immunohistochemistry (n = 27). Endostatin serum (n = 87) and urine (n = 153) levels were determined by ELISA. In 12 cases, both serum and paraffinized tissue samples from the same patients were available. We found decreased collagen XVIII tissue expression and increased endostatin urine and serum concentration in samples of patients with BC compared to controls. High serum endostatin levels correlated with the presence of lymph node metastases and MMP-7 concentrations and were independently associated with poor metastasis-free and disease-specific survival. Immunohistochemical analysis revealed a strong endostatin staining in the wall of tumor associated blood vessels in superficial but not in muscle-invasive BCs. Based on these, we concluded that elevated endostatin levels in patients with BC are the consequence of enhanced extracellular matrix degradation and are independent from collagen XVIII expression. Furthermore, serum endostatin levels may provide prognostic information independent from histopathological parameters and may therefore help to optimize therapy decisions. Loss of endostatin expression in tumor associated blood vessels might represent an important step supporting tumor-induced angiogenesis.
International Journal of Cancer 08/2011; 130(12):2922-9. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.
Pharmacogenetics and Genomics 07/2011; 21(10):673-8. · 3.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer is the second leading cause of cancer death among men in developed countries. Estrogen receptor-alpha (ER-α), vitamin D receptor (VDR), and the calcium-sensing receptor (CaSR), partly through their effects on calcium levels are implicated in the proliferation and carcinogenesis in the prostate gland. VDR, ER-α and CaSR genes show polymorphisms in humans that appear to have clinical significance in many pathological conditions, such as prostate cancer. Our aim was to evaluate the role of ER-α (PvuII, XbaI), VDR (BsmI) and CaSR (A986S) gene polymorphisms and serum calcium levels in the pathogenesis of prostate cancer.
Two hundred four patients with prostate cancer and 102 healthy controls were recruited into a hospital-based case control study. After genotyping, the relationship between the individual genotypes and prostate cancer was investigated.
Both the ER-α XbaI and the VDR BsmI polymorphisms were significantly related to the risk of prostate cancer. An age adjusted logistic regression limited to controls and patients not receiving bisphosphonate therapy showed that higher corrected serum calcium and the VDR Bb/BB genotypes independently increased the risk of prostate cancer.
ER-α XbaI and VDR BsmI genetic polymorphisms had a significant association with the risk of prostate cancer. Both VDR BsmI genotypes and serum calcium levels were independently related to the risk of prostate cancer, suggesting an influence of VDR on the development of this malignancy.
The Canadian Journal of Urology 06/2011; 18(3):5710-6. · 0.74 Impact Factor