Delaying BCG immunotherapy onset after transurethral resection of non-muscle-invasive bladder cancer is associated with adverse survival outcomes.

PURPOSE: This study was carried out to assess whether a prolonged time between primary transurethral resection of non-muscle-invasive bladder cancer (TURB) and implementation of bacillus Calmette-Guerin (BCG) immunotherapy (time to BCG; TTBCG) is associated with adverse oncological survival in patients with T1 high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data on 429 patients from 13 tertiary care centers with primary T1HG NMIBC treated with reTURB and maintenance BCG between 2001 and 2019 were retrospectively reviewed. Change-point regression was applied following Muggeo's approach. The population was divided into subgroups according to TTBCG, whereas the recurrence-free survival (RFS) and progression-free survival (PFS) were estimated with log-rank tests. Additionally, Cox regression analyses were performed. Due to differences in baseline patient characteristics, propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. RESULTS: The median TTBCG was 95 days (interquartile range (IQR): 71-127). The change-point regression analysis revealed a gradually increasing risk of recurrence with growing TTBCG. The risk of tumor progression gradually increased until a TTBCG of approximately 18 weeks. When the study population was divided into two subgroups (time intervals: ≤ 101 and > 101 days), statistically significant differences were found for both RFS (p = 0.029) and PFS (p = 0.005). Furthermore, in patients with a viable tumor at reTURB, there were no differences in RFS and PFS. After both PSM and IPW, statistically significant differences were found for both RFS and PFS, with worse results for longer TTBCG. CONCLUSION: This study shows that delaying BCG immunotherapy after TURB of T1HG NMIBC is associated with an increased risk of tumor recurrence and progression.

Oncological outcomes of laparoscopic versus open nephroureterectomy for the treatment of upper tract urothelial carcinoma: an updated meta-analysis.

BACKGROUND: During the past two decades, laparoscopic radical nephroureterectomy (LRNU) has been proposed as an alternative technique to open radical nephroureterectomy (ORNU) and has become increasingly accepted for the treatment of patients with upper tract urothelial carcinoma (UTUC). Nevertheless, the oncologic efficacy of LRNU remains controversial, especially for the treatment of locally advanced (T3/T4 and/or N+) UTUC. In this meta-analysis, we aimed to cumulatively compare the oncological outcomes of LRNU versus ORNU. MATERIALS AND METHODS: The present meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search was conducted of three electronic databases, namely, Medline, Embase, and Cochrane Library. Outcome measurements of cancer-specific survival (CSS), overall survival (OS), intravesical recurrence-free survival (IVRFS), and recurrence-free survival (RFS), including hazard ratios (HRs) and 95% confidence intervals (CIs), were extracted and pooled. RESULTS: Eighteen articles published from 2007 to 2020 were included in the final quantitative analysis. One study was a randomized controlled trial (RCT), and the remaining articles had a retrospective design. Among a total of 10,730 participants in the selected papers, 5959 (55.5%) and 4771 (44.5%) underwent ORNU and LRNU, respectively. The results of pooled analyses revealed no significant differences in CSS (HR 0.84, 95% CI 0.60-1.19, p = 0.33), OS (HR 0.84, 95% CI 0.62-1.13, p = 0.25), IVRFS (HR 1.08, 95% CI 0.85-1.39, p = 0.52), and RFS (HR 1.09, 95% CI 0.94-1.25, p = 0.26) between LRNU and ORNU groups. Furthermore, the results of subgroup analyses for pT3/T4 and pTany N+ populations did not confirm any statistically significant differences between LRNU and ORNU in terms of any survival parameter. CONCLUSIONS: Our present meta-analysis of current evidence suggests that LRNU and ORNU have comparable oncological outcomes in patients with UTUC, even in those with locally advanced disease. Further multicenter RCTs with large sample sizes and uniform data regarding specific surgical procedures, such as bladder cuff excision, are required to establish definitive conclusions.

The Usefulness of Lymphadenectomy in Bladder Cancer-Current Status.

The purpose of this review is to present the current status of lymph node dissection (LND) during radical cystectomy in patients with bladder cancer (BCa). Despite the growing body of evidence of LND utility at the time of radical cystectomy (RC) in high-risk nonmuscle-invasive and muscle-invasive BCa (MIBC), therapeutic and prognostic value and optimal extent of LND remain unsolved issues. Recently published results of the first prospective, a randomized trial assessing the therapeutic benefit of extended versus limited LND during RC, failed to demonstrate survival improvement with the extended template. Although LND is the most accurate staging procedure, the direct therapeutic effect is still not evident from the current literature, limiting the possibility of establishing clear recommendations. This indicates the need for robust and adequately powered clinical trials.

Pain reduction methods during transurethral cystoscopy.

Transurethral cystoscopy (CS) is a common urological procedure, performed mostly for diagnostic but also for therapeutic purposes. Although CS is generally well tolerated, some patients describe the pain related to the procedure as high or even "unbearable". As a result, many patients fear and avoid both primary and/or follow-up cystoscopies. This may lead to uncontrolled progression of neoplastic disease. Therefore, it is crucial to maximally increase the comfort of the patient and to implement safe and effective analgesia before the procedure. Providing the patients with appropriate care during CS can encourage them to comply with diagnostic schedules and improve their prognosis. The aim of this review is to analyze the available literature on various methods of pain reduction during transurethral CS. The PubMed electronic database limited to English articles published until January 2021 was used in the process. Meta-analyses, systematic reviews, randomized controlled trials, clinical trials, prospective randomized studies, multicenter comparisons, reviews and retrospective comparisons were used. As a result, 65 articles were included in this review.

Analysis of age influence on oncological results and toxicity of BCG immunotherapy in non-muscle invasive bladder cancer.

PURPOSE: The aim of this study was to analyse the influence of age on the treatment outcome and toxicity in patients with T1HG non-muscle invasive bladder cancers treated with BCG immunotherapy. METHODS: Data from 637 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in two academic centres were retrospectively reviewed. Median follow-up was 57 months. Patients were divided into two groups: younger (< 70 years old) and older (≥ 70 years old). Additional analyses in subgroups of older (> 75 and > 80) patients were performed. Log-rank test, Cox regression analysis, and propensity score matching were performed to compare the groups. RESULTS: There were 389 patients below and 248 patients above or equal 70 years old. Recurrence-free, progression-free, and cancer-specific survival rates did not differ significantly between younger and older patients. Recurrence-free survival for younger and older patients were 55.4% vs 52.9%, progression-free survival 75.9% vs 76.6%, and cancer-specific survival were 87.5% vs 89.9% (all p > 0.05). Differences in the oldest subgroups also did not reach statistical significance. In both regression analysis and propensity score matching, no statistically significant associations of age with any of analysed end-points were found. Finally, there were no statistically significant differences between younger and older group in terms of moderate and severe complications occurrence (47.6% vs. 44.5%; p > 0.05) CONCLUSIONS: It was shown that increasing age was not associated with BCG immunotherapy oncological outcomes, or with BCG toxicity in T1HG non-muscle invasive bladder cancer.

Management of Intradiverticular Bladder Tumours: A Systematic Review.

The aim of this systematic review was to present available data on diagnostic and therapeutic options in intradiverticular bladder tumour cases. A literature search within the Medline database was conducted in March 2019 with combinations of the following search terms: bladder cancer, bladder tumour, bladder diverticulum, diverticulum, intradiverticular. Seventeen relevant articles were identified. Diagnostic and therapeutic options for intradiverticular bladder tumour follow the general management of bladder cancer patients. The most important differences include a higher rate of non-urothelial histology, higher rate of invasive cancers (stage T1 and higher), no stage T2 disease due to lack of a muscularis propria layer and potential role of partial cystectomy or diverticulectomy in the treatment. Among cystectomized patients, the survival is comparable to general bladder cancer patients after cystectomy. Data on accuracy of imaging and endoscopy in diagnosing intradiverticular bladder tumour are poor. There is no study comparing different treatment modalities in intradiverticular bladder tumour patients. Limitations of this review include low number and low evidence level of available studies, as well as low number and heterogeneity of enrolled subjects. Available literature data cannot be the basis for clinical recommendations in intradiverticular bladder tumour cases. While bladder cancer is the most common urinary tract malignancy and at least 1% of cases are intradiverticular, further research in this field is justified.

Polymorphisms of genes encoding cytokines predict the risk of high-grade bladder cancer and outcomes of BCG immunotherapy.

INTRODUCTION: The present study investigated the association of cytokines genes polymorphisms (IL-2, IL-8 and IL-18) and polymorphisms in genes encoding molecules related to the differentiation of Th17 subpopulation (IL-17 and IL-23R) with the risk of bladder cancer (BC) and response to BCG immunotherapy. MATERIAL AND METHODS: Altogether, 175 BC patients treated with BCG due to high-grade non-muscle invasive tumors and 207 healthy individuals were genotyped for the following polymorphisms: IL-17A-197G>A (rs2275913); IL-17F+7488T>C (rs763780); IL-23Rc.309C>A (rs10889677);IL-23Rc.1142G>A (rs11209026); IL-2-330T>G (rs2069762), IL-8-251A>T (rs4073), and IL-18-137G>C (rs187238) using the TaqMan SNP genotyping assays. RESULTS: The IL-23Rc.-309C>A[A] allele was associated with the risk of BC (OR: 1.42, p = 0.03). Moreover, heterozygocities for IL-17A-197G>A[GA] and IL-18-137G>C[GC] increased the risk of BC, as compared to both homozygotes (OR: 1.67, p = 0.01 and OR: 1.84, p = 0.008, respectively). The IL-18-137G>C[GC] heterozygous patients had the highest risk of tumor recurrence and progression, and the worst recurrence-free and progression-free survival. Homozygous IL-17A-197G>A[GG] patients presented the best recurrence-free survival, while IL-17A-197G>A[AA] patients had 1.8-fold higher risk of recurrence. CONCLUSIONS: The present study highlighted the importance of IL-17, IL-18, and IL-23R gene polymorphisms for BC susceptibility and BCG immunotherapy outcomes. It may help to identify appropriate candidates for early radical treatment.

The Optimal Timing of Restaging Resection before Introduction of Bacillus Calmette-Guerin Immunotherapy in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer.

INTRODUCTION: The study aimed to analyze the influence of restaging transurethral resection of bladder tumor (reTURB) timing on outcomes in patients receiving Bacillus Calmette-Guerin (BCG) immunotherapy. MATERIAL AND METHODS: This retrospective study enrolled 491 patients with bladder cancer receiving BCG intravesical therapy between 1998 and 2016. All patients were followed up for at least 12 months and received at least 7 BCG instillations. The patients were analyzed in terms of recurrence free, progression free, and cancer specific survival (CSS). RESULTS: Median follow-up was 57 months (12-257 months). The risk for all analyzed clinical events was higher in patients who underwent reTURB after 6 weeks from primary TURB. After the change point of 57 days after primary resection, further delay was not associated with increased risk of recurrence and progression. The time limit for CSS was 76 days. With every 1 more day of time interval between TURB and reTURB, the risk of each clinical event in follow-up increased by 4%. CONCLUSIONS: There is no benefit of the reTURB performed after 8 weeks from primary TURB. Optimal timing of reTURB is from 2 to 6 weeks after initial TURB. However, even within this time frame, the sooner the procedure is performed, the risk of recurrence, progression, or cancer-specific death is lower.

Technical developments in transurethral resection of bladder tumours.

Bladder cancer is one of the most common malignancies worldwide. The transurethral resection of bladder tumour (TURB) remains the gold standard in both diagnostics and treatment. Because of the importance of TURB in bladder cancer management and the fact that TURB is one of the most commonly performed urologic procedures, it is the subject of continuous technological development. The latest advances in the field of endourology are aimed at increasing surgical accuracy and thus reducing the risk of bladder tumour recurrence and progression. However, despite the constant progress in technology and technique, there are still a lack of good quality data showing the superiority of any of the methods. The aim of this paper is to present available data on new technological developments in surgical technique of TURB. Advantages and disadvantages of currently available methods are discussed, and literature showing their effectiveness and safety is shown.

Should information about sexual health be included in education directed toward men with cardiovascular diseases?

BACKGROUND: Modifiable risk factors contribute to the pathogenesis of cardiovascular disease (CVD) and erectile dysfunction (ED). We aimed to compare the knowledge about the contribution of modifiable risk factors to the pathogenesis of CVD and ED. The impact of patients' having modifiable risk factors on the awareness of their negative influence on the development of CVD and ED was examined. METHODS: To this multicenter cohort study, we included 417 patients with CHD who had been hospitalized in the cardiology or cardiac surgery department during the previous six weeks and underwent cardiac rehabilitation in one of the five centers. Knowledge about modifiable risk factors was collected. ED was assessed by an abridged IIEF-5 questionnaire. Comparisons between groups were conducted using the Student's t-test, Mann-Whitney U test, and Kruskal-Wallis test. Relationships were analyzed with Spearman's rank correlation coefficient. RESULTS: The mean number of correctly identified risk factors for CVD was significantly higher than those for ED (3.71 ± 1.87 vs. 2.00 ± 1.94; p < .0001). Smoking was the most recognized risk factor both for CVD and ED. Dyslipidemia was least frequently identified as a risk factor for CVD. Sedentary lifestyle was the only risk factor whose incidence did not affect the level of patient knowledge. CONCLUSIONS: Cardiac patients with ED know more about risk factors for CVD than ED. It is necessary to include information about the negative impact of modifiable risk factors on sexual health into education programs promoting healthy lifestyles in men with cardiovascular diseases.

Influence of Transurethral Resection of Bladder Cancer on Sexual Function, Anxiety, and Depression.

The standard of care in non-muscle invasive bladder cancer consists of transurethral tumor resection. The aim of this study was to evaluate the influence of transurethral resection of bladder tumor (TURB) on the patients' self-reported depression, anxiety, sexual satisfaction, and erectile dysfunction. Psychological condition of 252 male patients who underwent TURB was prospectively evaluated. The Hospital Anxiety and Depression Scale (HADS), simplified International Index of Erectile Function (IIEF-5), and Sexual Satisfaction Questionnaires (SSQ) were administered to patients before and 10 days after tumor resection. We found that primary anxiety, depression, and erectile dysfunction were all worse in cancer patients than those in the general population, and all further worsened after tumor resection. The post-resection worsening was influenced by the operation and catheterization time, complications, and the tumor characteristics. Taxonomical analysis shows that the greatest risk of depression aggravation concerned patients who were younger, had a higher body mass index, and a medium-sized tumor. We conclude that transurethral resection of non-muscle invasive bladder cancer may adversely affect sexual function, anxiety, and depression. Patients should be informed about potential complications to prevent the abandonment of a follow-up. The findings of this study stress the role of personalized medicine pursued by a multidisciplinary medical team.

Are There Differences in Toxicity and Efficacy between Various Bacillus Calmette-Guerin Strains in Bladder Cancer Patients? Analysis of 844 Patients.

PURPOSE: To evaluate if there are differences in toxicity and efficacy between different Bacillus Calmette-Guerin (BCG) stains used for intravesical immunotherapy in patients with non-muscle invasive bladder cancer. METHODS: We retrospectively analysed a group of 844 patients who received TICE, RIVM and Moreau BCG strains. The allocation of the strain to each patient was random, stemming from differences in supply and distribution. The patients were analysed in terms of toxicity, recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS) and overall survival (OS). RESULTS: In the survival analysis, statistical significance was not reached in any tumour group for any clinical event. TICE caused more local and mild adverse effects and severe complications were mainly associated with RIVM strain. In a group in which the strain was changed during the course of the therapy, significantly more severe complications were observed and, in most of these cases, complications appeared right after the strain change. CONCLUSIONS: There were no differences in terms of RFS, PFS, CSS and OS after use of TICE, RIVM and Moreau strains. The complication profile differed statistically between used strains with TICE causing mostly mild complications. Also, strain change during the therapy course was associated with the increased risk of moderate to severe toxicity occurrence.

How different cystoscopy methods influence patient sexual satisfaction, anxiety, and depression levels: a randomized prospective trial.

PURPOSE: Bladder cancer (BC) is one of the most common cancers worldwide. BC diagnosis and surveillance is based on cystoscopy (CS). CS impact on patient's depression, anxiety, and sexual satisfaction (SS) is not sufficiently studied. There are no data on patient's comfort with flexible or rigid CS. METHODS: We prospectively evaluated pain perception (PP), depression, anxiety, and SS of 100 male patients who previously underwent at least one rigid CS in our department as surveillance after TURB procedure due to non-muscle-invasive BC and were scheduled for the next CS examination. The patients were randomized for flexible or rigid CS. Before CS, patients described their recalled rigid CS-related pain by NRS and fulfilled HADS and SS questionnaires. After CS, PP was re-evaluated immediately and HADS and SS within 7-10 days following the CS. RESULTS: The baseline scores include 5.2 ± 2.6 points for rigid CS recalled pain, 7.2 ± 3.0 points for HADS anxiety, 5.8 ± 3.5 for depression, and 27.8 ± 5.1 for SS. The flexible CS-related pain was approximately three times lower than the recalled pain level and also than the current rigid CS related (p < 0.001). Mean SS score was two points lowered after rigid CS (p < 0.001). One point decrease in anxiety level was observed after flexible CS (p < 0.001). Multivariate analysis supported the hypothesis of patients benefiting from flexible CS in terms of pain perception, anxiety symptoms, and SS. CONCLUSIONS: Our study demonstrates the superiority of flexible CS in terms of pain alleviation, and shifts in SS and anxiety levels.

The presence of prostate cancer at biopsy is predicted by a number of genetic variants.

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low-risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.

[Genetic and immunologic determinants of intravesical BCG therapy in non-muscle-invasive urothelial bladder cancer]. / Genetyczne i immunologiczne uwarunkowania odpowiedzi na dopecherzowa terapie BCG w raku urotelialnym pecherza moczowego nienaciekajacym blony miesniowej

Bladder cancer (BCA) is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin) is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines - IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland.

BACKGROUND: The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20-fold). The geographical and ethnic extent of this recurrent allele has not yet been determined. METHODS: We assayed for the presence of the G84E mutation in 3,515 prostate cancer patients and 2,604 controls from Poland and estimated the odds ratio for prostate cancer associated with the allele. RESULTS: The G84E mutation was detected in 3 of 2,604 (0.1%) individuals from the general population in Poland and in 20 of 3,515 (0.6%) men with prostate cancer (Odds ratio [OR] = 5.0; 95% CI: 1.5-16.7; P = 0.008). The allele was present in 4 of 416 (1.0%) men with familial prostate cancer (OR = 8.4, 95% CI: 1.9-37.7; P = 0.005). CONCLUSIONS: The G84E mutation predisposes to prostate cancer in Poland, but accounts for only a small proportion of cases. We expect that the G84E founder mutation might be present in other Slavic populations.

The clinical significance of lymphangiogenesis in renal cell carcinoma.

BACKGROUND: The formation of lymphatic vessels (lymphangiogenesis) occurs in tumor tissues and is crucial for tumor development and progression in some cancers. Lymphangiogenesis and its clinical effect on renal cell carcinoma have been less thoroughly investigated in comparison with angiogenesis. The aim of this study was to evaluate the role of lymphangiogenesis as a prognostic factor in renal cell carcinoma (RCC). MATERIAL AND METHODS: The expression of peritumoral/intratumoral lymphatics was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 133 patients with clear cell carcinoma. Patients were divided into 3 groups depending on postoperative follow-up: I) patients without metastases, II) patients with metastases during follow-up, and III) patients with metastases during the operation. Peritumoral lymphatics (PTL) and intratumoral lymphatics (ITL) were immunostained with a D2-40 antibody. RESULTS: The mean number of PTL present in each group was I=14.1, II=10.6, III=12.1. The mean number of ITL present in each group was I=0.7, II=2.3, III=2.3. The 3 groups showed statistically significant differences only in the case of ITL. A mean count of ITL ≥1 is significantly associated with an increased risk of regional lymph node involvement and distant metastasis. Patients with expression ITL >0.2 and PTL ≤15.2 had a significantly shorter cancer-specific survival. CONCLUSIONS: The number of ITL showed an association with more aggressive cases of RCC and progression of disease. Therefore, the level of expression ITL, together with stage and histological grading, may provide valuable predictive information about the outcome of treatment.

Sentinel Lymph Node Techniques in Urologic Oncology: Current Knowledge and Application.

Lymph node (LN) metastases have a significant negative impact on the prognosis of urological malignancies. Unfortunately, current imaging modalities are insufficient when it comes to detecting micrometastases; thus, surgical LN removal is commonly used. However, there is still no established ideal lymph node dissection (LND) template, leading to unnecessary invasive staging and the possibility of missing LN metastases located outside the standard template. To address this issue, the sentinel lymph node (SLN) concept has been proposed. This technique involves identifying and removing the first group of draining LNs, which can accurately stage cancer. While successful in breast cancer and melanoma, the SLN technique in urologic oncology is still considered experimental due to high false-negative rates and lack of data in prostate, bladder, and kidney cancer. Nevertheless, the development of new tracers, imaging modalities, and surgical techniques may improve the potential of the SLN procedures in urological oncology. In this review, we aim to discuss the current knowledge and future contributions of the SLN procedure in the management of urological malignancies.

The influences of selected clotting and fibrinolysis factors on survival of patients with kidney tumors - a prospective study.

Introduction: Multiple studies suggest that cancer leads to activation of clotting and fibrinolysis pathways, elevating the risk of thromboembolic events. Kidney cancer is often complicated by clotting disorders. In this study, we hypothesized that preoperative clotting and fibrinolysis parameters are altered in healthy volunteers and kidney tumor patients. We also hypothesized that these differences may be associated with survival in patients who have undergone operations due to kidney tumors. Material and methods: In this study, 96 patients with kidney tumors and 30 healthy volunteers were recruited at a single university center. All patients were assessed for pre-operative serum concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI, total TFPI, full-length TFPI, truncated TFPI), plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), von Willebrand factor (vWF), clotting factor XIII A1 (FXIIIA1), D-dimers, and fibrinogen. Additionally, standard peripheral blood morphology was evaluated. Results: Malignant kidney tumors were diagnosed in 85 of 96 tumor patients. In patients with kidney tumors, there were statistically significantly higher concentrations of fibrinogen, D-dimers, TAT, PAF, TF, TFPI, vWF, FXIIIA1, and leukocyte counts compared to the control group. Statistically significant correlations were found between multiple parameters. This points to significant clotting system alterations. Cox stepwise hazard analysis showed that pre-operative fibrinogen and D-Dimer concentrations were significantly associated with survival. Conclusions: In patients with kidney tumors, multiple clotting and fibrinolysis parameters are significantly altered. Routine pre-operative measures should include determination of fibrinogen and D-dimer concentrations as these markers aid in prediction of survival probability.

Variation in the gene encoding the co-inhibitory molecule BTLA is associated with survival in patients treated for clear cell renal carcinoma - results of a prospective cohort study.

Introduction: The successful introduction of immune checkpoint blockade approaches to renal-cell carcinoma (RCC) treatment indicates the importance of molecules regulating the T cell response to RCC risk and progression. Material and methods: In this study, we evaluate the association of variations in the CTLA-4, BTLA and CD28 genes with overall survival (OS) of RCC patients and specifically clear cell RCC (ccRCC) patients. The following single nucleotide polymorphisms (SNPs) previously genotyped using the RFLP method or TaqMan SNP Genotyping Assays were analyzed: CTLA-4 gene: c.49A>G (rs231775), g.319C>T (rs5742909), g.*6230G>A (CT60; rs3087243), g.*10223G>T (Jo31; rs11571302); CD28 gene: c.17+3T>C (rs3116496), c.-1042G>A (rs3181098); BTLA gene: rs2705511, rs1982809, rs9288952, rs9288953, rs2705535 and rs1844089. Results: During long term observation (6.5 years) we discovered that possessing the A allele at BTLA rs1844089 SNP, together with advanced disease (stage ≥ 3, tumor grade > 3, tumor diameter ≥ 70 mm), is an independent risk factor of death which increases the hazard ratio (HR) of death by more than two-fold (HR = 2.21, 95% CI: 1.28-3.83). Furthermore, the OS of patients bearing this allele is 6 months shorter than for homozygous (GG) patients (42.5 vs. 48.2 months). Conclusions: Our results indicate for the first time that genetic variation within the gene encoding BTLA is significantly associated with overall survival in clear cell renal cell carcinoma patients.