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Kidney disease; Cancer Enfermedad renal; Cáncer Malaltia renal; Càncer Onco-nephrology is a new field of medicine which combines many aspects of kidney injury in cancer patients and cancers in patients with kidney disease. This connection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, numerous paraneoplastic syndromes and an increased rate cancers in dialysis and transplanted patients. The appropriate laboratory assessment of the kidney function allows to optimize chemotherapy and thus minimizes the risk of complications. This article focuses on acute kidney injury (AKI), chronic kidney disease (CKD), various electrolyte and acid-base disorders, the most common cancers after kidney transplantation and the kidney disorders associated with HSCT (hematopoietic stem cell transplantation). The possibility of the application of novel cancer therapy, such as cancer immunotherapy and proton therapy in transplant recipients was also discussed.

Background. The nuclear factor–κB transcription factors 1 and 2 (NFKB1 and NFKB2) are key components of the NF-κB pathway, which responds to inflammatory signals. Since the NFKB1/2 factors are activated via different inflammatory molecules, we aimed to check their expression levels in penile cancer (PC), penile dermatoses: lichen sclerosus (PLS) and zoon balanitis (ZB). Methods: Skin biopsies from altered and healthy looking foreskin were obtained from 59 (49 LS; early PLS: 13, moderate PLS: 32, severe PLS: 4; 6 PC; 4 ZB) and unchanged foreskin from 13 healthy control adult males undergoing circumcision. NFKB1/2 mRNA levels were quantified by qPCR. Results: The highest levels of NFKB1 and NFKB2 were observed in PC, ca. 22 and 3.5 times higher than in control, respectively. NFKB1 expression was correlated with PLS progression (rs = 0.667) and was ca. 20 times higher in advanced PLS than in controls and early PLS. Occurrence of micro-incontinence was associated with elevated NFKB1 levels in PLS. Conclusion: This is the first study regarding gene profiles of NFKB1/2 in PC and penile dermatoses. New drugs targeting modulation of canonical-activated NF–κB pathway should be studied and introduced to the treatment of PLS and PC apart from other treatments.

Introduction The aim of this article was to evaluate non-invasive tests, which were typically used in preoperative diagnosis of male patients with anterior urethral strictures in the assessment of the urethral resistance caused by urethral occlusion. Material and methods A total of 63 adult males with confirmed urethral stricture and aged below 55 years old were enrolled in the study. Data obtained from non-invasive tests such as uroflowmetry (UF), ultrasound examination (USG), and questionnaires such as from The International Prostatic Symptom Score (IPSS), and The Patient-Reported Outcome Measure for Urethral Stricture Surgery (USS-PROM) were analyzed. Results Among all analyzed non-invasive tests, bladder wall thickness (BWT) showed the highest correlation with the degree of urethral occlusion described as percentage of preserved urethral lumen (r = -0.70; p

BACKGROUND Urachal cancer gives metastases through the lymph nodes (LNs). No lymphadenectomy scheme in the case of this cancer exist, yet it is proposed as a staging procedure. An assessment of lymphatic outflow from the tumor site with the use of single-photon emission computed tomography/computed tomography (SPECT/CT) lymphangiography is possible for staging purposes. OBJECTIVES To perform the mapping of the LNs draining the lymph from urachal cancer with the use of radioisotope-based technique and to propose the lymphadenectomy template in case of urachal cancer. MATERIAL AND METHODS A prospective study was conducted in 5 patients with urachal cancer. The 99m-technetium (Tc-99m)-nanocolloid was injected during a cystoscopy prior to the surgery. Lymphangiography was performed using SPECT/CT. A radioactive LNs analysis with the use of a hand-held gamma-ray detection probe was conducted during the surgery and the sentinel lymph node (SLN) biopsy procedure was performed. An additional lymphadenectomy containing the lymphatic basin of identified radioactive LNs was performed. RESULTS In all cases lymphatic outflow from the urachal tumor to the LNs was present. Preoperative SPECT/CT allowed detecting the activity of the radiotracer in the common iliac region in all the studied patients. In 3 cases, bilateral lymphatic outflow, and in 2 cases, unilateral lymphatic outflow was observed. All preoperatively visualized LNs were found and excised with the use of a gamma-ray detection probe during a lymphadenectomy. In all cases, SLNs did not contain metastases. CONCLUSIONS Mapping of the LNs draining the lymph from urachal cancer with the use of radiotracer is possible. Lymphatic outflow in the case of this cancer can be both unilateral and bilateral. No recommendations about the extension of lymphadenectomy are proposed. We recommend individual assessment and treatment based on additional knowledge about lymphatic outflow. This allows for minimally invasive yet targeted treatment as an SLN basin lymphadenectomy.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer, with high mortality rates worldwide. The sonic hedgehog (SHH) molecular cascade is altered in various malignancies in tumorigenesis, and several SHH pathway inhibitors have been considered as potential anticancer drugs. The aim of the present study was to determine the expression profile of SHH signaling components and their target genes in ccRCC. Additionally, the present study examined the effects of SHH pathway inhibitory drugs (RU‑SKI43, cyclopamine and GLI‑antagonist 61) on cell viability, cell cycle progression, expression levels of SHH target genes and migration ability in 786‑O, ACHN and HK2 cells. The study also included paired tumor and normal samples from 62 patients with ccRCC. The mRNA levels in clinical samples and cell lines were measured via reverse transcription‑quantitative PCR. Cell viability was examined using a sulforhodamine B assay. Flow cytometry was used to investigate cell cycle progression and the migratory rate of cells was assessed using a wound healing assay. High mRNA levels of

Current screening and monitoring of prostate cancer (PCa) is insufficient, producing inaccurate diagnoses. Presence of the receptor for advanced glycation end-products (RAGE) is associated with signature characteristics of PCa development such as cell proliferation, anchorage-independent growth, angiogenesis, migration, invasion, and poor patient survival. Therefore, we developed a preclinical multimodal imaging strategy targeted at RAGE to diagnose and monitor PCa. In this work, RAGE-targeted multimodal nanoparticles (64Cu-Cy5-G4-CML) were synthesized and rendered functional for nuclear and optical imaging using previously established methods. The probe’s binding affinity and targeting specificity was assessed in androgen-dependent (LNCaP) and androgen-independent (DU145) prostate cancer cells using flow cytometry and confocal microscopy. In vivo PET-CT imaging was used to evaluate RAGE levels in DU145 and LNCaP xenograft models in mice. Then, tumors were excised post-imaging for histological staining and autoradiography to further assess RAGE levels and targeting efficiency of the tracer. Finally, RAGE levels from human PCa samples of varying Gleason Scores were evaluated using Western blot and immunohistochemical staining. PCa cell culture studies confirmed adequate RAGE-targeting with 64Cu-Cy5-G4-CML with KD between 360 and 540 nM as measured by flow cytometry. In vivo PET-CT images of PCa xenografts revealed favorable kinetics, rapid blood clearance, and a non-homogenous, enhanced uptake in tumors, which varied based on cell type and tumor size with mean uptake between 0.5 and 1.4%ID/g. RAGE quantification of human samples confirmed increased RAGE uptake corresponding to increased Gleason scoring. Our study has shown that RAGE-targeted cancer imaging is feasible and could significantly impact PCa management.

The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic profiles of urine samples collected at three time points: before transurethral resection of bladder tumor (TURBT), the day after the procedure and two weeks after TURBT. Collected samples were analyzed with the use of high-performance liquid chromatography hyphenated with time-of-flight mass spectrometry detection (HPLC-TOF/MS) and gas chromatography coupled with triple quadrupole mass spectrometry detection (GC-QqQ/MS, in a scan mode). Levels of metabolites selected in our previous study were assessed in order to confirm their potential to differentiate the healthy and diseased samples, regardless of the risk factors and individual characteristics. Hippuric acid, pentanedioic acid and uridine confirmed their potential for sample differentiation. Based on the results of statistical analysis for the paired samples (comparison of metabolic profiles of samples collected before TURBT and two weeks after), a set of metabolites belonging to nucleotide metabolism and methylation processes was also selected. Longitudinal studies proved to be useful for the evaluation of metabolic changes in bladder cancer.

The purpose of this study was to immunohistochemically validate the primary tumor PSMA expression in prostate cancer (PCa) patients imaged with [The study included 40 men with newly diagnosed treatment-naïve PCa imaged with [Eighty-three percent (33/40) of patients presented focal uptake of [Positive [

Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue microarrays containing 128 primary tumors from 72 PCa patients stained immunohistochemically for epithelial cell adhesion molecule (EpCAM), followed by validation in a cohort of 310 primary tumors from 209 PCa patients. In order to investigate the gene expression differences between tumors with low and high TSR, we applied multigene expression analysis (nCounter® PanCancer Progression Panel, NanoString) of 42 tissue samples. TSR scores were categorized into low (&lt, 1 TSR) and high (≥1 TSR). In the pilot cohort, 31 patients (43.1%) were categorized as low and 41 (56.9%) as high TSR score, whereas 48 (23.0%) patients from the validation cohort were classified as low TSR and 161 (77.0%) as high. In both cohorts, high TSR appeared to indicate the shorter time to biochemical recurrence in PCa patients (Log-rank test, p = 0.04 and p = 0.01 for the pilot and validation cohort, respectively). Additionally, in the multivariate analysis of the validation cohort, TSR predicted BR independent of other factors, i.e., pT, pN, and age (p = 0.04, HR 2.75, 95%CI 1.07–7.03). Our data revealed that tumors categorized into low and high TSR score show differential expression of various genes, the genes upregulated in tumors with low TSR score were mostly associated with extracellular matrix and cell adhesion regulation. Taken together, this study shows that high stroma content can play a protective role in PCa. Automatic EpCAM-based quantification of TSR might improve prognostication in personalized medicine for PCa.

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available “-omics” approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.

This study aimed to define patients with renal cell cancer and coexisting tumor thrombus in order to address concerns regarding survival and prognostic factors after radical surgery. Several prognostic factors for overall survival (OS) were assessed in patients treated surgically at five institutions from 2012 to 2018. Univariate and multivariate analyses were used to determine the independent risk factors of OS. A total of 142 patients were eligible for further analysis (mean age of 64.75 years, 56% males). Most patients presented with clear cell carcinoma (95%). The Mayo stage was predominantly 0–1 (88%). Distant visceral metastases at the time of diagnosis were present in 36 patients (25%), whereas nodal metastases were present in 24 patients (16.9%). During the follow-up period (mean of 32.5 months), the 3-year OS rate reached 68.2%. The majority of patients received no adjuvant treatment (n = 107). In a multivariable model predicting OS, regional lymph node status (p &lt, 0.001), distant metastases (p = 0.009), tumor grade (p = 0.002), duration of hospitalization (p = 0.016), and Clavien–Dindo grade (p = 0.047) were identified as independent prognostic factors. A subgroup of patients with specific clinicopathological factors may benefit most from the radical surgery, including patients without regional lymph node or distant metastases and with low tumor grades, whereas short hospitalization and low Clavien–Dindo grades represent additional independent prognostic factors.

Since varicocele is so common in infertile men, this study intends to analyse the relationships between varicocele and conventional semen characteristics, sperm nuclear DNA dispersion and oxidation-reduction potential (ORP) in semen. Varicocele-positive and varicocele-negative infertile men (study groups) showed significantly lower standard sperm parameters and higher sperm DNA fragmentation (SDF) and ORP in semen than healthy volunteers and subjects with proven fertility (control groups). A lower proportion of low SDF levels (0–15% SDF) and higher incidence of high SDF levels (&gt, 30% SDF), as well as a higher prevalence of high ORP values (&gt, 1.37 mV/106 sperm/mL), were found in the study groups vs. the control groups. Moreover, infertile men had significantly lower odds ratios (ORs) for low SDF levels and significantly higher ORs for high SDF levels and high ORP. SDF and ORP were negatively correlated with sperm number, morphology, motility and vitality. Furthermore, a significant positive correlation was found between SDF and ORP. The obtained results suggest that disorders of spermatogenesis may occur in varicocele-related infertility. These abnormalities are manifested not only by reduced standard semen parameters but also by decreased sperm DNA integrity and simultaneously increased oxidative stress in semen.

The present study is based on a retrospective analysis of Gallium-68 (68Ga)-labelled prostate-specific membrane antigen (68Ga-PSMA IT distant disease was found in 14/82 subjects (17.1%, 2 with intermediate-risk and 12 with high-risk PCa). No extraprostatic disease was found in low-risk PCa. SUVmax of primary tumours showed a weak but significant correlation with serum PSA values (r = 0.51, p

Bladder cancer (BCa) is ninth amongst the most common types of cancer in the human population worldwide. The statistics of incidence and mortality of BCa are alarming and the currently applied diagnostic methods are still not sensitive enough. This leads to a large number of undiagnosed BCa cases, usually among patients in the early stages of the disease. Despite the fact that many risk factors of BCa have been recognized, the pathomechanism of development of bladder cancer has not been fully explained yet. Therefore, in the present study, multiplatform urinary metabolomics has been implemented in order to scrutinize potential diagnostic indicators of BCa that might help to explain its pathomechanism and be potentially useful in diagnosis and determination of stage of the disease. Urine samples collected from muscle-invasive high grade BCa patients (n = 24) and healthy volunteers (n = 24) were matched in terms of most common BCa risk factors i.e. gender, age, BMI and smoking status. They were analyzed by high performance liquid chromatography coupled with time of flight mass spectrometry detection (HPLC-TOF/MS) using RP and HILIC chromatography, gas chromatography hyphenated with triple quadruple mass spectrometry detection (GC-QqQ/MS) in scan mode, and proton nuclear magnetic resonance (1H NMR). The six datasets obtained were submitted to univariate and multivariate statistical analyses. 17 metabolites significantly discriminated urinary profiles of BCa patients from urinary profiles of healthy volunteers. These metabolites are mainly involved in amino acid metabolism, pyrimidine and purine metabolism, as well as energy metabolism and might play a crucial role in the pathogenesis of BCa.

Clear cell renal cell carcinoma (ccRCC) is the most common and the most aggressive histopathological subtype of kidney cancer, with patients exhibiting high mortality rates for metastatic tumors. The Sonic Hedgehog (SHH) pathway serves a crucial role in embryonic development. The abnormal activity of SHH signaling is observed in a broad range of malignancies. However, its role in ccRCC is still undetermined. The aim of the present study was to assess the expression of the SHH pathway genes in ccRCC. Neoplastic and morphologically unchanged kidney tissues were obtained during radical nephrectomy from 37 patients with ccRCC. The SHH, PTCH1, SMO and GLI1 mRNA levels were assessed using the reverse transcription-quantitative PCR. Western blot analysis was used to assess the full-length and C-terminal SHH protein level. The mRNA levels of SHH, SMO and GLI1 were approximately 2-, 2,5- and 7-fold higher in ccRCC tissue compared with control kidney tissue, respectively. Correlational analysis between the mRNA levels of SHH pathway genes and patients' clinicopathological factors revealed decreased and increased mRNA levels of PTCH1 and SMO respectively, in tumor samples derived from older patients (age >62). Furthermore, the level of C-terminal SHH protein in ccRCC samples was significantly lower in a group of males compared with females. No correlation was exhibited between molecular data and patient survival. Western blot analysis indicated a ~3-fold higher level of SHH full-length protein, and a 4-fold lower level of the C-terminal SHH protein domain, in ccRCC tumor tissues compared with normal kidney samples. The current study indicated an involvement of the SHH pathway in ccRCC development.

Introduction The aim of this study is to validate the Polish version of the Urethral Stricture Surgery - Patient-Reported Outcome Measure (USS-PROM) by evaluating its psychometric properties. Material and methods Patients with urethral stricture scheduled for urethroplasty between 2014 and 2018 were prospectively enrolled. The results of the USS-PROM were obtained before the operation, and during follow-up visits. The original USS-PROM was translated into Polish and re-translated into English in accordance with the guidelines by Dawson et al. regarding the adaptation process. Psychometric assessment included internal consistency, test-retest reliability, criterion validity and responsiveness. Results One hundred twelve patients were included. 54 patients completed the USS-PROM both before and 3 months after the surgery and 39 of them completed the questionnaire 6 months after the surgery to evaluate the test-retest reliability. Cronbach's α for internal consistency of the lower urinary tract symptoms (LUTS) domain score was 0.87. The test-retest intraclass correlation coefficient was 0.82. Spearman's coefficients showed no correlation between USS-PROM's result and maximal urinary flow (Qmax) result before the surgery (rs = 0.13; p >0.05) and a positive correlation between USS-PROM's result and Qmax result at follow up: 3 months after (rs =- 0.56; p

Introduction Refractory idiopathic overactive bladder (RIOAB) is a common condition with a significant negative impact on quality of life. Intravesical injection of botulinum toxin A (BTX-A) is widely used as an intervention for these cases. In the standard method the drug solution is colorless. The addition of dye such as methylene blue (MB) facilitates visualization during the procedure and may have a beneficial effect. Aim To evaluate the injection of BTX-A with the addition of methylene blue (MB) against a standard method in the treatment of RIOAB. Material and methods In this 1-center, single-blinded, randomized controlled trial, we recruited 80 patients with RIOAB. A total of 39 were assigned to injection into the bladder wall of 100 U BTX-A with MB (in 9.5 ml normal saline + 0.5 ml MB), and 41 were assigned to BTX-A 100 U alone (in 10 ml normal saline). Cystoscopy with a submucosal injection of the solution was performed systematically, including the bladder triangle. Participants were assessed 6 and 12 weeks after the treatment using a Likert scale and OABSS questionnaire. Results Significant improvement was similar (result of 1 or 2 on the Likert scale) and was achieved in 66.7% and 69.2% after 6 weeks and in 63.9% and 64.1% after 12 weeks in the BTX-A + MB group and only-BTX-A group, respectively. There was a significant difference between the two groups (p = 0.049) in the total number of patients with complications: 2 (5.6%) vs. 9 (23.1%). Conclusions The addition of MB to BTX for treatment of RIOAB patients does not influence treatment efficacy, while it limits the risk of complications.

Cancer is one of the main cause of death in Western countries. Inflammation plays an important role in the pathogenesis of cancer. Nicotinamide (NA) - known for its anti-inflammatory properties - participates in the processes related to the cell cycle regulation and DNA repair, which are relevant in cancer development. This study aimed to investigate the nicotinamide metabolism alterations in bladder cancer.Blood and plasma samples of patients with bladder cancer were collected. Blood pyridine and adenine nucleotides concentration were measured using high performance liquid chromatography (HPLC). Plasma nicotinamide metabolites concentration were determined using high performance liquid chromatography - mass spectrometry (LC/MS).Our results indicated that the development of bladder cancer caused significant decrease in the concentration of N-methylnicotinamide (MetNA) (0.07 ± 0.02 vs 0.1 ± 0.03 µmol/l) and an increase in the concentration of N-methyl-2-pyridone-5-carboxamide (Met2PY) - one of the final nicotinamide metabolites: (1.1 ± 0.15 vs 0.7 ± 0.07 µmol/l) in comparison to the control. The association between the stage of cancer and the increase in both, Met2PY and Met4PY levels was observed. Blood ATP and NAD levels were significantly decreased in bladder cancer patients as compared to the control (970.8 ± 77.84 vs 1165.00 ± 57.76 µmol/l; 45.86 ± 2.98 vs 53.06 ± 2.28 µmol/l respectively).Bladder cancer development caused substantial changes in nicotinamide metabolism, such as decreased plasma MetNA and increased Met2PY concentration. Analysis of the nicotinamide and its metabolites concentrations - as new biomarkers - may allow to track the course of pathological processes in cancer.

Introduction and hypothesis Surgical treatment of stress urinary incontinence in women using a synthetic midurethral tape has become a standard procedure. One of the complications observed postoperatively are lower urinary tract symptoms (LUTS). The aim was to analyze the role of introital ultrasound in the identification of patients at risk for developing LUTS after surgical treatment using synthetic tape. Methods A group of 50 patients suffering from LUTS following anti-incontinence surgery using synthetic tape was included in this study. The patients with pelvic organ prolapse and coexisting overactive bladder-wet before surgery were excluded. The control group consisted of 50 patients after the same treatment without any complications and with a good outcome. Tape visualization was performed using introital two-dimensional ultrasound. The assessment of the Tape Index (T/U) enabled us to divide the study group into the two subgroups with the tape index value of 0.375 as a borderline. The correlation between the tape position and the occurrence of LUTS was evaluated using a Chi-squared test. Results In the group of patients suffering from LUTS, the tape was found to be closer to the bladder neck (the lower edge of the tape was more than 37.5% of the urethral length) and it was statistically significant (Chi-squared = 19.87, p