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.

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.

Treatment of muscle-invasive urothelial cancer with nivolumab (CheckMate 274 study): a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper published in a medical journal that describes the results of a study called CheckMate 274. This study looked at a new treatment for muscle-invasive urothelial cancer, a type of cancer found in the urinary tract that has spread from the inner lining of the urinary tract or bladder and into the surrounding muscle wall where it can then spread to other parts of the body. The standard treatment for muscle-invasive urothelial cancer is surgery to remove affected parts of the urinary tract. However, cancer returns in more than half of people after this surgery. Adjuvant therapy is given to people after surgery with muscle-invasive urothelial cancer with a goal to reduce the risk of the cancer coming back; however, at the time this study started, there was no standard adjuvant treatment. WHAT HAPPENED IN THE STUDY?: In the CheckMate 274 study, researchers compared nivolumab with a placebo as an adjuvant treatment for people with muscle-invasive urothelial cancer. The aim of the study was to understand how well nivolumab worked to reduce the chance of the cancer returning after surgery. The study also looked at what side effects (unwanted or unexpected results or conditions that are possibly related to the use of a medication) people had with treatment. WHAT DO THE RESULTS MEAN?: The results showed that people who received nivolumab versus placebo: Survived longer before the cancer was detected again, including people who had programmed death ligand-1 (shortened to PD-L1) on their cancer cells. Survived longer before a secondary cancer outside of the urinary tract was detected. Experienced no differences in health-related quality of life (the impact of the treatment on a person's mental and physical health). Had similar side effects to the people who received nivolumab in other studies. Clinical Trial Registration: NCT02632409 (ClinicalTrials.gov).

The Variations' in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis.

Renal cell cancer is the most common type of kidney cancer in adults, and clear cell renal cell carcinoma (ccRCC) is the most diagnosed type. T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) belongs to immunological checkpoints that are key regulators of the immune response. One of the known TIM-3 ligands is galectin-9 (LGALS9). A limited number of studies have shown an association between TIM-3 polymorphisms and cancer risk in the Asian population; however, there is no study on the role of LGALS9 polymorphisms in cancer. The present study aimed to analyze the influence of TIM-3 and LGALS9 polymorphisms on susceptibility to ccRCC and patient overall survival (OS), with over ten years of observations. Using TaqMan probes, ARMS-PCR, and RFPL-PCR, we genotyped two TIM-3 single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four LGALS9 SNPs: rs361497, rs3751093, rs4239242, and rs4794976. We found that the presence of the rs10057302 A allele (AC + AA genotypes) as well as the rs4794976 T allele (GT + TT genotypes) decreased susceptibility to ccRCC by two-fold compared to corresponding homozygotes. A subgroup analysis showed the association of some SNPs with clinical features. Moreover, TIM-3 rs1036199 significantly influenced OS. Our results indicate that variations within TIM-3 and LGALS9 genes are associated with ccRCC risk and OS.

Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.

BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).

Determinants of survival in patients with bladder cancer undergoing radical cystectomy: The impact of serum creatinine level.

BACKGROUND: Bladder cancer is one of the most common cancers in Europe and is mostly found in men. Cystectomy is the treatment for invasive tumors that infiltrate the muscle of the bladder. This procedure is associated with a large number of complications. Eligibility for surgical treatment is important, because surgery may shorten the patient's life. The main prognostic factor is the severity of the disease, but less specific factors can be very helpful in selecting the form of treatment. OBJECTIVES: To identify and analyze factors affecting significantly the survival in patients undergoing radical cystectomy (RC). MATERIAL AND METHODS: A retrospective analysis of a group of 129 patients treated at the Department of Urology and Urological Oncology of University Hospital in Wroclaw (Poland) was carried out. Furthermore, information about the results of laboratory tests from the medical records (blood count, creatinine concentration, etc.) was obtained. The follow-up was performed twice during the postoperative period. The Kaplan-Meier method was used to determine overall survival (OS) curves and statistical significance was assessed using log-rank test. RESULTS: A statistically significant correlation between preoperative serum creatinine level and OS was found. The OS was significantly shorter in patients with higher serum creatinine levels (log-rank test; p = 0.002). The patients were divided into different groups to exclude the relationship between the elevated creatinine concentration and the local disease advancement. The analysis was performed in patients with and without hydronephrosis. In both groups, creatinine levels above the acceptable range were associated with a shorter survival. CONCLUSIONS: Due to the high perioperative mortality, mainly in patients with advanced disease, it is necessary to develop the qualification process for surgical treatment. The awareness of the relationship between elevated creatinine levels and worse prognosis seems to be helpful.

SNP-SNP Interaction in Genes Encoding PD-1/PD-L1 Axis as a Potential Risk Factor for Clear Cell Renal Cell Carcinoma.

PD-1/PD-L1 axis plays an important role in maintaining homeostasis and prevention from autoimmunity; however, in the tumor microenvironment, PD-1/PD-L1 interaction is responsible for the evasion of immune surveillance by tumor cells. We therefore hypothesized that single nucleotide polymorphisms (SNPs) in genes encoding PD-1 and PD-L1 molecules are associated with the development and outcome of renal cell carcinoma (RCC). Here we genotyped nine polymorphisms: five of PDCD1: rs36084323G>A, rs11568821G>A, rs2227981C>T, rs10204525G>A, rs7421861T>C and four of PD-L1: rs822335C>T, rs4143815G>C, rs4742098A>G, rs10815225G>C in 237 RCC patients (including 208 with clear cell RCC (ccRCC)) and 256 controls, with application of allelic discrimination method with use of TaqMan Assays. Interestingly, we found the SNP-SNP interaction between rs10815225 and rs7421861 polymorphisms associated with ccRCC risk. The rs7421861 TC genotype decreased the risk of ccRCC development compared to TT and CC genotypes in the group of rs10815225 GC + CC individuals (OR = 0.21, CI95% = 0.08; 0.54). While possessing of rs10815225 GC or CC genotype increased susceptibility to ccRCC when compared to rs10815225 GG genotype in individuals with rs7421861 TT or CC genotype (OR = 2.40, CI95% = 1.25; 4.61). In conclusion, genetic variants in PDCD1 and PD-L1 genes, especially taken together as SNP-SNP interactions, can be considered to be ccRCC risk factors.

Potential plasma biomarkers of bladder cancer identified by proteomic analysis: A pilot study.

BACKGROUND: Bladder cancer diagnosis and surveillance includes cystoscopy and cytology. New methods for the detection of bladder cancer are needed, because cystoscopy is invasive and expensive, and because urine cytology is not sensitive enough. OBJECTIVES: The aim of the study was to select potential plasma protein markers for bladder cancer which could be useful in developing a specific laboratory test to improve diagnosis and to establish treatment strategies in order to prevent the recurrence of the disease. MATERIAL AND METHODS: Plasma proteome maps were prepared based on 2-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), combined with image gel analysis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of plasma samples from patients with urothelial bladder cancer, and they were compared to normal samples. RESULTS: The analyses of bladder cancer plasma samples allowed us to distinguish 3 groups of proteins whose relative abundance differed from that in normal samples. The 1st one comprised modified forms of plasma transferrin, fibrinogen gamma and complement C3b, which were absent in normal plasma. The 2nd group comprised haptoglobin, alpha-2-macroglobulin, vitamin D-binding protein, and pigment epithelium-derived factor, which occurred in the cancerous samples in large quantities. The 3rd group consisted of 3 molecular forms of immunoglobulin M (IgM), the relative abundance of which was significantly lower in the cancerous plasma samples. CONCLUSIONS: The data indicated potential plasma biomarkers associated with inflammation, immunity and coagulation processes accompanying bladder cancer. They could be used for the development of a laboratory test(s) useful in clinical practice.

Uroplakins and their potential applications in urology.

INTRODUCTION: Urothelium is a highly specialized type of epithelium covering the interior of the urinary tract. One of the structures responsible for its unique features are urothelial plaques formed from glycoprotein heteropolymers, the uroplakins. Four types of uroplakins are known - UPIa, UPIb, UPII, UPIII. Herein we review the current status of knowledge about uroplakins and discuss their potential clinical applications. MATERIAL AND METHODS: A PubMed search was conducted to find original and review papers about uroplakins. RESULTS: Uroplakins can be detected in tissue, urine and blood. The process of urothelial plaque formation is complex and its disturbances resulting in incorrect plaque formation might be responsible for some pathological states. Additionally, uroplakins might be associated with other pathological processes i.e. urothelial cancer or infections of the urinary tract. CONCLUSIONS: Uroplakins as the end-product of urothelial cells have unique features and a complex structure. These glycoproteins can be involved in some diseases of the urinary tract and as such can be used as potential targets for intervention and markers of the disease.

Salvage local therapy for radiation-recurrent prostate cancer - where are we?

INTRODUCTION: Prostate cancer is the most frequent cancer among males in Europe and a leading cause of cancer deaths, with similar proportion in other developed countries. For more than twenty years, external-beam radiation therapy, alongside with radical prostatectomy, has been used as a primary radical therapeutic approach for localized prostate cancer. Yet, EBRT failures relate to 22-69% following curative radiotherapy (± androgen deprivation therapy). Additionally, a proportion of these men will have a biopsy-proven local recurrence. MATERIAL AND METHODS: The Medline and Web of Science databases were searched without a time limit during March 2016 using the terms 'prostate cancer' in conjunction with 'radiotherapy', 'recurrence', 'biochemical', 'salvage', 'brachytherapy', 'prostatectomy', 'HIFU', 'cryotherapy' and 'focal'. The search was limited to the English, Polish, German and Spanish literature. RESULTS: Currently, salvage treatment after failed radiotherapy includes radical prostatectomy, brachytherapy and ablative whole-gland therapies, such as cryotherapy and high intensity focused ultrasound. New approaches, so called focal salvage therapy, involve ablation of only the zone of recurrence in order to decrease tissue injury and therefore to diminish morbidity. CONCLUSIONS: At present no authoritative recommendations can be concluded because of the absence of randomized data with standardized definitions and protocols. Nevertheless, we believe that local salvage treatment should be at least considered in patients after biochemical relapse following radiotherapy.

Urological complications after renal transplantation - a single centre experience.

INTRODUCTION: Urological complications after renal transplantation occur in between 2.5% and 30% of all graft recipients. The aim of the study was to present 7 years of experience in urological treatment of patients with a transplanted kidney. We aimed to identify retrospectively late urological complications in renal transplant recipients at a single center and analyze the treatment modalities and their outcome. MATERIAL AND METHODS: Between January 2008 and December 2014, a total of 58 patients after KTX were treated in the Department of Urology because of post-transplant urological complications that occurred during follow-up at the Transplant Outpatient Department. Retrieved data were analysed in retrospectively. RESULTS: In the group of 38 patients with ureteral stenosis (Clavien grade III), 29 patients underwent endoscopy, 8 open surgical procedures and one both endoscopic and open operation. Ten patients were admitted with symptomatic lymphocoele (Clavien III), of which 9 were successfully treated with drainage and one with surgical marsupialization. Because of urolithiasis in the grafted kidney (Clavien grade III), 4 patients were treated with ureterorenoscopic lithotripsy (URSL) and one only with the extracorporeal shock wave lithotripsy (ESWL) procedure. Five urethral strictures plasties and one graftectomy because of purulent pyelonephritis were also conducted. The average age in the group of recipients who experienced urologic complications was similar (46.1 vs. 47.8) to those without complications. There was no vesicoureteral reflux or ureteral necrosis requiring surgical intervention, no graft loss and death related to urological complication and treatment. CONCLUSIONS: Most complications could be successfully treated with endourological procedures. The kidney function improved in the majority of patients.

Interdisciplinary Aspects of Primary Hyperparathyroidism: Symptomatology in a Series of 100 Cases.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder. Beside renal and skeletal complications, it has a wide variety of nonspecific symptoms from other organs that mimic other diseases and delay the diagnosis. In recent decades the clinical profile of PHPT has evolved to less symptomatic forms. OBJECTIVES: The aim of the study was to revise the symptomatology profile of PHPT in a single region, and to facilitate early PHPT diagnosis by encouraging interdisciplinary communication among medical professionals. MATERIAL AND METHODS: Data from 100 patients (94 women and 6 men, aged 57.1 ± 13.7 years) diagnosed with PHPT in the authors' center during the past decade were retrospectively analyzed. Biochemical conditions and clinical manifestations (renal, skeletal, cardiovascular, gastrointestinal and asymptomatic) were evaluated. RESULTS: Renal symptoms were present in 55% of the patients. In the course of unrecognized disease, seven lithotripsy procedures, seven surgical lithotomy procedures and two nephrectomies were performed. Osteoporosis/ /osteopenia was present in 66% and 10% of the study group, respectively. In 16% there were fragility fractures; in 10% brown tumors were present, and 55% of the PHPT patients were hypertensive. Gastrointestinal symptoms were present in 52%; pancreatitis was documented in 3%. PHPT was diagnosed incidentally in asymptomatic patients in 15% of the group. Mean serum Ca was 2.87 mmol/L (SD: 0.36), mean urine Ca was 15.97 mEq/24 h (SD: 7.89), mean serum PTH was 324 pg/mL (SD 425.21). The duration from the appearance of any symptom to the diagnosis varied from < 1 year (19%), 1-10 years (46%) to > 10 years (35%). CONCLUSIONS: PHPT is still diagnosed too late, after a period of untreated symptomatic disease. Multidisciplinary cooperation among specialists on the diagnostic level can help avoid late complications of unrecognized disease.

Review of current optical diagnostic techniques for non-muscle-invasive bladder cancer.

INTRODUCTION: Urinary bladder urothelial cell carcinoma is one of the most commonly diagnosed cancers in Europe. After prostate, lung and colon cancers, bladder cancer rates as the fourth most common cancer in men in the world. Urinary bladder cancer detection, treatment, and staging have traditionally been based on an endoscopic examination - cystoscopy. MATERIAL AND METHODS: A Medline, and Web of Science database search was performed on September 2015 without setting time limits, using the terms 'bladder cancer' in conjunction with 'cystoscopy', 'diagnosis', 'detection', 'fluorescence', 'blue-light', 'PDD', 'narrow band imaging', 'molecular imaging', 'optical coherence tomography' or 'confocal laser endomicroscopy'. RESULTS: The new imaging techniques can be classified according to their scope as macroscopic, microscopic, and molecular. Macroscopic techniques, such as narrow band imaging, are similar to white light cystoscopy; however, they help visualize even very minute lesions in the bladder mucosa by means of contrast enhancement. Microscopic imaging techniques, such as optical coherence tomography and confocal laser endomicroscopy, provide high-resolution cross-sectional views of vesicular tissues, which resemble images obtained by histopathological examination. Therefore, these are referred as 'optical biopsy'. Molecular imaging methods offer highly specific real-time visualization of cancer cells and their differentiation from healthy tissue, by combining optical imaging with fluorescent labeling of elements such as antibodies. CONCLUSIONS: In this article we present a review of studies and literature concerning modern optical diagnostic techniques for non-muscle-invasive bladder cancer. We present available technology with its advantages and disadvantages, and studies regarding its effectiveness.

Patient comfort during flexible and rigid cystourethroscopy.

INTRODUCTION: Cystourethroscopy (CS) is an endoscopic method used to visualize the urethra and the bladder. AIM: In this study, we prospectively evaluated pain in men undergoing cyclic cystoscopic assessment with rigid and flexible instruments after transurethral resection of bladder tumor (TURB). MATERIAL AND METHODS: One hundred and twenty male patients who were under surveillance after a TURB procedure due to urothelial cell carcinoma and who had undergone at least one rigid cystourethroscopy in the past were enrolled in the trial. Patients were prospectively randomized to age-matched groups for flexible (group F) or rigid (group R) CS. Patient's comfort was evaluated on an 11-grade scale, ranging from 0 (free from pain) to 10 points (unbearable pain). RESULTS: The patients described the pain during the previous rigid CS as ranging from 4 to 10 (mean: 6.8) in group F and from 0 to 10 (mean: 5.8) in group R. Group R patients described the pain during the current rigid CS as ranging from 0 to 10 (mean: 5.7). No mean change in the grade was observed between the two pain descriptions (no change 11 patients, weaker pain 25 patients, stronger pain 24 patients, gamma 0.51, p < 0.0001). Group F described the pain as 1 to 5 (mean: 2.1). In the case of flexible CS the pain experience was greatly lowered compared to the previous rigid CS. All flexible CS patients reported lowered pain (by 1 to 9 grades). Patients' age did not influence the comfort of the flexible CS or the change in pain level. CONCLUSIONS: Flexible CS is better tolerated than rigid cystoscopy by male patients regardless of patients' age.

Association of 3' nearby gene BTLA polymorphisms with the risk of renal cell carcinoma in the Polish population.

OBJECTIVE: T cells play an important role in antitumor immunity, and molecules regulating T-cell activity could influence cancer susceptibility. The distinct role of coinhibitory receptors in immunosurveillance has been considered. B- and T-lymphocyte attenuator (BTLA) is one of these receptors, which negatively regulate immune responses. The aim of this study was to investigate the association between BTLA gene polymorphisms and susceptibility to renal cell carcinoma (RCC) in the Polish population. METHODS: Altogether 282 patients with RCC and 480 healthy subjects were genotyped for the following polymorphisms: rs2705511, rs1982809, rs9288952, rs16859633, rs9288953, rs2705535, and rs1844089 using the TaqManSNP Genotyping Assays. RESULTS: Here, we found that the presence of rs1982809G allele (genotype GG+AG) is associated with increased risk of RCC (odds ratio = 1.38; 95% CI: 1.03-1.86; P = 0.03). In patients with clear-cell RCC (ccRCC) with high-grade (3 and 4) tumors, the frequency of rs1982809[GG] genotype was significantly higher as compared to those with low-grade (1 and 2) tumors and to the controls (0.14 vs. 0.06, P = 0.05 and 0.14 vs. 0.06, P = 0.04, respectively). Moreover, we have noticed the trend for overrepresentation of carriers of rs2705511C allele in patients with RCC as compared with the controls (0.51 vs. 0.44, P = 0.08) Haplotype rs2705511C/rs1982809G/rs9288952A/rs9288953T/rs2705535C/rs1844089G (CGATCG) increased the risk of RCC of 46% (odds ratio = 1.46; 95% CI: 1.08-1.96; Pcorrected = 0.05). CONCLUSION: Our results indicate that polymorphisms rs1982809 situated in 3' UTR nearby region of BTLA gene might be considered as low-penetrating risk factor for RCC, but results have to be confirmed in further studies.

How to lower postoperative complications after radical cystectomy - a review.

INTRODUCTION: Lowering morbidity and mortality after RC is subject of considerable interest. Lately, many evidence-based data on improvements in operative technique, anesthetic management, and patient care have been published. In this article, we present a review of literature on how to lower postoperative complications after RC. MATERIAL AND METHODS: The Medline, and Web of Science databases were searched without a time limit on February 2016 using the terms 'cystectomy' in conjunction with 'radical', 'bladder cancer', 'complications' or 'management'. Boolean operators (NOT, AND, OR) were also used in succession to narrow and broaden the search. The search was limited to the English, Polish and Spanish literature. RESULTS: Many complications may be avoided by appropriate patient selection and meticulous introduction of care protocols. CONCLUSIONS: RC as treatment free of complications, even in the hands of an experienced urologist, does not exist. A large number of complications are acceptable in the name of good long-term results. Optimum results are possible with proper surgical technique, good patients and urinary diversion selection and proper patient management in the pre-, peri, and postoperative period.

Pregnancy and delivery in a patient with a Studer orthotopic ileal neobladder.

Pregnancies in patients after cystectomy with urinary diversion, especially after the construction of a continent urinary reservoir, are rare. Experience in this field is limited and mainly concerns patients with congenital disorders, neurogenic diseases or trauma. In this paper, we report the outcome of pregnancy, delivery and the postpartum period in a 27-year old woman with a Studer ileal orthotopic neobladder after radical cystectomy, performed after the diagnosis of a malignant tumor at the age of 14.

Prostate and Bladder Cancer Coexistence in Patients Undergoing Radical Cystoprostatectomy.

BACKGROUND: According to the Polish National Cancer Registry, bladder cancer is the 4th most common cancer in the male population (7.0%), while prostate cancer takes 2nd place (14.0%). In the case of both cancer types, prognoses are precarious and depend on many factors, such as the size of the primary tumor, infiltration of regional lymph nodes, histological grade and occurrence of distant metastases. OBJECTIVES: The objective of this work is to verify the coincidence of prostate cancer and bladder cancer in patients who underwent radical cystoprostatectomy in Wroclaw Medical University, Department of Urology and Oncological Urology, as well as to indicate factors that may influence the peri- and post-operative course. MATERIAL AND METHODS: We have retrospectively reviewed patients who underwent radical cystoprostatectomy for muscular-invasive bladder cancer between 2009 and 2014, which comprised of 116 male patients. We managed to establish telephone and personal contact with the patients. RESULTS: Seventeen of the 116 patients were diagnosed with coincidental prostate cancer in post-operative histological examination (14.6%). This result is lower than in other series of cystoprostatectomy cases (range 23-68%). The mean age of patient was 68.9 years and the median was 69.5 years. Factors influencing the peri- and post-operative periods were not statistically significant. CONCLUSIONS: Serum PSA level and DRE should be performed more often on patients prepared for radical cystoprostatectomy. An accurate pre-operative assessment of cancer infiltration is required for both types of tumors. Complete resection of prostate prevents residual neoplasm infiltration. It is important to take into account the possibility of primary prostate tumor occurrence in patients qualified for radical cystectomy. The post-operative supervision should be focused not only on bladder carcinoma but on the prostate carcinoma, too.

[Uroplakins as markers of diseases of the urinary system]. / Uroplakiny jako markery chorób ukladu moczowego

An unique element of bladder urothelium is a multilayer membrane, which extends from the renal pelvis to the urethra. Urotelial membrane covers more than 90% of the inner portion of the bladder and is in direct contact with urine. Urothelium is composed of characteristic two-dimensional, asymmetric plaques, composed of uroplakins (UP), differentiated, hexagonally arranged proteins. The unique structure of the urothelial plaques determines the tightness, integrity and strength of the urothelium, prevent rupture of the walls of the bladder during the build-up of urine in the bladder and protects against the toxic ingredients. Uroplakins are tissue-specific, heterogeneous glycoproteins whose oligosaccharide part plays a specific role in the structure and function of urothelium. Disorders of normal expression of uroplakins are highly associated with the pathogenesis in infection and urinary tract malignancies, primary vesico-urinary reflux, hydronephrosis and renal impairment. The emergence of uroplakins in urine and / or plasma may have a potential role in the early detection of bladder tumors. In this paper, the structure and function of uroplakins types Ia, Ib, II, IIIa, their natural oligomerization into heterodimers, tetramers and hexamers, and the role in the construction of asymmetric and flexible urothelial epithelium is presented. We discuss the potential role of uroplakins in laboratory diagnosis of umbrella cell differentiation and in the screening analysis of urinary bladder disorders. The possibilities of using the knowledge of uroplakins in clinical settings as well as in modern strategies for treatment of infectious diseases and cancer of the urinary tract are highlighted.

Interferon alpha and metronomic cyclophosphamide for metastatic kidney cancer: a phase 2 study.

Metronomic chemotherapy has been tested only a few times in the treatment of metastatic kidney cancer. We have combined metronomically dosed cyclophosphamide (mCTX) with full dosed interferon alpha (IFN) in patients with disseminated clear cell cancer. Toxicity was mainly attributable to IFN treatment. We have noticed mainly hematological and general symptoms with only few grade 3 or 4 adverse events. No patient required mCTX withdrawal. In 30 patients evaluated for the response, clinical benefit (CB) (objective responses and stabilization of the disease ≥24 weeks) was observed in 40%. Median overall survival (OS) for the whole group was 13.2 months. Survival responders and nonresponders were 9.5 versus 28.9 months (P=0.001). Patients with a higher hemoglobin concentration and fibrinogen level <6 g/L had a higher probability of response. Responders also had different kinetics of fibrinogen than nonresponders. When assessed for clinical response, the combination of mCTX and IFN proved to be disappointing. In contrast, OS in patients with CBs proved to be long. It is crucial to properly select patients for whom some predictive markers can be used. The combination of metronomic chemotherapy with targeted therapies might be an interesting direction for further research.