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The aim of this study was to analyze the correlation between past bacterial infections and the type and chemical composition of urinary stones experienced by human patients. Bacteria have been recognized to contribute to urinary stones; however, the role of uropathogens in the development of specific stones has not been extensively investigated. The detection of past bacterial infection (eleven different bacterial species) in urinary stones from 83 patients was made on a DNA level using polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) and correlated with the chemical composition of urinary stones measured using X-ray powder diffraction (XPRD) technique and their elemental composition by total reflection X-ray fluorescence (TXRF). In this study, two scenarios of urinary stones formation mediated by Proteus sp. or Escherichia coli are presented. The first one is associated with Proteus spp. which dominated in 84% of infectious urinary stones and is strongly correlated with struvite and calcium phosphate, in whose matrix additionally strontium, phosphorus, potassium, nickel and zinc are detected. The formation of these stones is closely correlated with urease activity. The second scenario for urinary stone mineralization is associated with E. coli identified in weddellite stones, in which matrix iron was detected. In conclusion, the statistical correlations of bacterial infections with crystalline and elemental composition showed that in mixed bacterial infections, one scenario dominated and excluded the second one.
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Infecciones Bacterianas/complicaciones , Electroforesis en Gel de Gradiente Desnaturalizante , Reacción en Cadena de la Polimerasa , Espectrometría por Rayos X , Cálculos Urinarios/química , Cálculos Urinarios/complicaciones , Difracción de Rayos X , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: In 2013, thiosulfate in urine has been proposed as promising prostate cancer (PCa) biomarker. However, a missing comparison with other proven PCa markers suggested a re-evaluation study. Therefore, together with the authors from the initial study, the diagnostic accuracy of thiosulfate was compared with that of urinary prostate cancer associated 3 (PCA3), serum prostate health index (Phi), and percent free prostate-specific antigen (%fPSA). Thiosulfate was further measured in a multicenter approach to exclude center-related biases. METHODS: Thiosulfate, calculated as ratio of thiosulfate to urinary creatinine (TS/Crea ratio), was measured in two cohorts in a total of 269 patients. In the retrospective study (n=160) PCA3, Phi, PSA, and %fPSA were compared with the TS/Crea ratio between patients with and without PCa according to the prostate needle biopsy results. The second prospective cohort included 109 patients from four centers. RESULTS: The median TS/Crea ratio was not statistically different between the patients with and without PCa. The receiver-operating characteristics showed that the TS/Crea ratio was unable to discriminate between patients with and without PCa in contrast to %fPSA, Phi, and PCA3. In all four centers, the low median TS/Crea ratios (<1 mmol/mol) in both patient cohorts were confirmed and thiosulfate was again not able to distinguish between them (p-values, 0.13-0.90). CONCLUSIONS: This study could not confirm the previously observed high median TS/Crea ratio in PCa patients in comparison to non-PCa patients. Thiosulfate subsequently failed as PCa biomarker while PCA3 and Phi showed the expected diagnostic improvement.
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Biomarcadores de Tumor/orina , Neoplasias de la Próstata/orina , Tiosulfatos/orina , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Malignant tumors of the kidney, which the most common is renal cell carcinoma (RCC) is diagnosed in Poland in more than 5,000 patients each year. Most cases of kidney cancer occurs after the age of 55 years. In men, the risk is 2 times higher than in women. Among the various histological subtypes of RCC, 5% of cases of chromophobe renal cell carcinoma (chRCC). The 1% is in combination with oncocytoma, creating a hybrid chromophobe renal cell carcinoma. The paper presents a case report of a patient operated on because of a kidney tumor - eosinophilic type of chromophobe cancer. During subsequent care of patients experienced a rare complication of this type of tumor, ie. metastasized to the paraaortic lymph nodes. Another surgery and radiotherapy were later stages of treatment. Discussed in the paper example of a patient with type eosinophilic chRCC indicate the variable nature and mileage as compared with typical of the tumor, thus requiring increased surveillance oncology. This requires a careful approach clinicians at the stage of diagnosis and then treatment and aftercare.
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Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/terapia , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia Adyuvante , Tomografía Computarizada por Rayos XRESUMEN
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.
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Polimorfismo de Nucleótido Simple , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Área Bajo la Curva , Biopsia , Tacto Rectal , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patologíaRESUMEN
This review contains the results of Polish (Central Europe) ethnomedical studies that describe the treatment of urinary tract diseases with wild and cultivated plants. The study includes only the plants that are used to treat the urinary tract, excluding prostate diseases. A review of the literature was carried out to verify the pharmacological use of the plants mentioned in the interviews. Based on this, the study reviews the pharmacological activities of all the recorded species and indicates their most important chemical compounds. Fifty-three species (belonging to 30 families) were selected for the study. The Compositae (eight species), Rosaceae (six species), and Apiaceae (six species) are the most common families used in the treatment of urinary diseases in Polish folk medicine. Both in vitro and in vivo studies have confirmed that many of these plant species have beneficial properties, such as diuretic, antihyperuricemic, antimicrobial, and anti-inflammatory activity, or the prevention of urinary stone formation. These effects are exerted through different mechanisms, for example, through the activation of bradykinin B2 receptors, inhibition of xanthine oxidase, or inhibition of Na+-K+ pump. Many plants used in folk medicine are rich in phytochemicals with proven effectiveness against urinary tract diseases, such as rutin, arbutin, or triterpene saponins.
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Radical cystectomy (RC) remains a mainstay surgical treatment for non-metastatic muscle-invasive and BCG-unresponsive bladder cancer. Various perioperative scoring tools assess comorbidity burden, complication risks, and cancer-specific mortality (CSM) risk. We investigated the prognostic value of these scores in patients who underwent RC between 2015 and 2021. Cox proportional hazards were used in survival analyses. Risk models' accuracy was assessed with the concordance index (C-index) and area under the curve. Among 215 included RC patients, 63 (29.3%) died, including 53 (24.7%) cancer-specific deaths, with a median follow-up of 39 months. The AJCC system, COBRA score, and Charlson comorbidity index (CCI) predicted CSM with low accuracy (C-index: 0.66, 0.65; 0.59, respectively). Multivariable Cox regression identified the AJCC system and CCI > 5 as significant CSM predictors. Additional factors included the extent of lymph node dissection, histology, smoking, presence of concomitant CIS, and neutrophil-to-lymphocyte ratio, and model accuracy was high (C-index: 0.80). The internal validation of the model with bootstrap samples revealed its slight optimism of 0.06. In conclusion, the accuracy of the AJCC staging system in the prediction of CSM is low and can be improved with the inclusion of other pathological data, CCI, smoking history and inflammatory indices.
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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.
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Proteínas de Homeodominio/genética , Mutación Puntual/genética , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/genética , Adulto , Anciano , Anciano de 80 o más Años , Predisposición Genética a la Enfermedad/etnología , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Linaje , Polonia/epidemiología , Factores de Riesgo , Población Blanca/genética , Población Blanca/estadística & datos numéricosRESUMEN
Metallothioneins (MTs) are highly conserved, small molecular weight, cysteine rich proteins. The major physiological functions of metallothioneins include homeostasis of essential metals Zn and Cu and protection against cytotoxicity of heavy metals. The aim of this study was to determine whether there is an association between the -5 A/G single nucleotide polymorphism (SNP; rs28366003) in core promoter region and expression of metallothionein 2A (MT2A) gene and metal concentration in prostate cancer tissues. MT2A polymorphism was determined by the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP) using 412 prostate cancer tissue samples. MT2A gene expression analysis was performed by real-time RT-PCR method. A significant association between rs28366003 genotype and MT2A expression level was found. The average mRNA level was found to be lower among minor allele carriers (the risk allele) than average expression among homozygotes for the major allele. Metal levels were analyzed by flamed atomic absorption spectrometer system. Highly statistically significant associations were detected between the SNP and Cd, Zn, Cu and Pb levels. The results of Spearman's rank correlation showed that the expressions of MT2A and Cu, Pb and Ni concentrations were negatively correlated. On the basis of the results obtained in this study, we suggest that SNP polymorphism may affect the MT2A gene expression in prostate and this is associated with some metal accumulation.
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Alelos , Regulación Neoplásica de la Expresión Génica , Metalotioneína/genética , Metales Pesados/metabolismo , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Anciano , Humanos , Masculino , Metalotioneína/biosíntesis , Persona de Mediana Edad , Zinc/metabolismoRESUMEN
To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation-isoprostanes (8-isoPGF(2)) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer's instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2-2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.
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Biomarcadores de Tumor/orina , Dinoprost/análogos & derivados , Neoplasias de la Próstata/orina , Anciano , Glucemia , Estudios de Casos y Controles , Dinoprost/orina , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tamaño de los Órganos , Estrés Oxidativo , Próstata/patología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Riesgo , Ácido Úrico/sangreRESUMEN
BACKGROUND: The aim of this study was to examine the level of thiosulfate in the urine of prostate cancer (PCa) patients and evaluate its usefulness in the diagnosis and monitoring of prostate malignant transformation. Thiosulfate is a naturally occurring product of hydrogen sulfide (H2S) metabolism. H2S is involved in many physiological and pathological processes including inflammation and tumorigenesis. METHODS: The determination of thiosulfate in the urine of PCa patients and healthy controls was performed by reverse-phased liquid chromatography using 2-chloro-1-methylquinolinium tetrafluoroborate as a derivatization reagent. Thiosulfate concentrations were normalized to urinary creatinine levels to compensate for variable diuresis. RESULTS: In the urine samples of PCa patients, the mean thiosulfate level was almost 50 times higher than in the control groups and five times higher than in the benign prostatic hyperplasia group. The level of thiosulfate did not correlate with the serum prostate-specific antigen (PSA) level or PSA density. Neither tumor stage nor tumor grade was associated with thiosulfate level. CONCLUSIONS: The results suggest that thiosulfate concentration in urine may be a good facilitator in the diagnostics of PCa. The predictive accuracy of this method is particularly valuable for the diagnosis of patients with low serum PSA level and negative digital rectal examination and transrectal ultrasound results.
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Antígeno Prostático Específico/orina , Neoplasias de la Próstata/orina , Tiosulfatos/orina , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Adulto JovenRESUMEN
Topoisomerase IIß binding protein 1 (TopBP1) is involved in cell survival, DNA replication, DNA damage repair and cell cycle checkpoint control. The biological function of TopBP1 and its close relation with BRCA1 prompted us to investigate whether alterations in the TopBP1 gene can influence the risk of breast cancer. The aim of this study was to examine the association between five polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 3'UTR region of the TopBP1 gene and breast cancer risk as well as allele-specific gene expression. Five hundred thirty-four breast cancer patients and 556 population controls were genotyped for these SNPs. Allele-specific TopBP1 mRNA and protein expressions were determined by using real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with breast cancer. Compared to homozygous common allele carriers, heterozygous and homozygous for the T variant had significantly increased risk of breast cancer (adjusted odds ratio = 3.81, 95% confidence interval: 1.63-8.34, p = 0.001). Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT or TT genotype. There was a significant association between the rs115160714 and tumor grade and stage. Most carriers of minor allele had a high grade (G3) tumors classified as T2-T4N1M0. Our study raises a possibility that a genetic variation of TopBP1 may be implicated in the etiology of breast cancer.
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Neoplasias de la Mama/genética , Proteínas Portadoras/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Regiones no Traducidas 3' , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Secuencia de Bases , Neoplasias de la Mama/patología , Proteínas Portadoras/metabolismo , Estudios de Casos y Controles , Proteínas de Unión al ADN/metabolismo , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Proteínas Nucleares/metabolismo , Oportunidad Relativa , Factores de RiesgoRESUMEN
Introduction: A positive surgical margin (PSM) in the radical prostatectomy (RP) specimen is associated with biochemical recurrence (BCR) and the need for adjuvant radiation therapy, and is an analysis of surgical procedure quality. We present data describing the identification, anatomy, and management of PSM after RP performed via an open operation and laparoscopically. The aim of the study was to compare assessment of RP (open vs. laparoscopic) in terms of analysis of PSM in postoperative histopathological tissue. Material and methods: Patients with pT1 to pT3b prostate cancer with detailed surgical margin parameters and BCR status were analysed. The patients were divided into groups depending on the stage of neoplastic disease and the choice of operative procedure. Results: In total, we obtained data from 140 PC patients. Positive surgical margins were confirmed in 11 cases treated with open surgery and in 7 cases treated with laparoscopic procedure. There was no statistically significant (p >0.05) relationship between the frequency of positive margins and the type of procedure. There was no statistically significant (p >0.05) relationship between the frequency of positive margins and the type of procedure in subgroups according to the Gleason score. There was a statistically significant (p <0.05) relationship between the clinical stage of the tumor and the type of margin. This particularly refers to tumours with stage T3b (more numerous in the group of open surgeries) and T2c (more numerous in the laparoscopic group). Conclusions: There was no statistically significant correlation between the type of surgery and the incidence of a positive surgical margin.
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BACKGROUND: The mRNA expression of genes coding enzymes involved in O-GlcNAcylation were analyzed in urine obtained from 176 bladder cancer (BC) patients and 143 healthy persons. METHODS: MGEA5 and OGT expression was measured by a real-time PCR assay. RESULTS: OGT expression was not detected in urine of healthy persons but it was found in 51.7% of BC samples. Positive expression of MGEA5 was found in urine of both healthy persons (47.1%) and BC patients (52.3%). Poorly differentiated BC (grade III) showed significantly lower MGEA5 expression than grade I tumors. Contrary, OGT transcript level was significantly higher in grade II and III in comparison to grade I BC. Moreover, there was significant difference in OGT expression between early bladder cancers and invasive or advanced bladder cancers. CONCLUSIONS: These results suggest that analysis of urinary content of MGEA5 and OGT may be useful for bladder cancer diagnostics.
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Antígenos de Neoplasias/genética , Biomarcadores de Tumor/genética , Regulación Enzimológica de la Expresión Génica/fisiología , Histona Acetiltransferasas/genética , Hialuronoglucosaminidasa/genética , N-Acetilglucosaminiltransferasas/genética , ARN Mensajero/orina , Neoplasias de la Vejiga Urinaria/genética , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias de la Vejiga Urinaria/enzimologíaRESUMEN
Implementation of ultrasonography (USG), computed tomography (CT) and magnetic resonance imaging (MRI) into abdominal cavity diagnostics enabled early detection of cT1 graded renal cancers. According to European Association of Urology (EAU) and Polish urological Association (PUA) recommended method of treatment is sparing resection of renal parenchyma with tumour-nephron-sparing surgery (NSS). In selected cases other methods such as thermal ablation (TA) or cryoablation can be introduced /1/. OBJECTIVES: To evaluate the results of treatment of cT1 renal tumours with the use of NSS and TA methods. MATERIAL AND METHODS: 140 patients with cT1 renal carcinoma were treated in 2nd Department of Urology of Medical University of Lodz between 2014 and 2017. Neuron-sparing surgery was performed in 56 cases (40%), while percutane-ous thermal ablation (TA) in 84 cases (60%). Demographic data, clinical data (lab results, Charlson index), nephrometry data (tumour size, location, R.E.N.A.L. score) post-operative data (Clavien-Dindo classifica-tion) were investigated. Histopathology results, Fuhrman malignancy grading, as total three-year survival of patients were evaluated. The following methods were used for statistical evaluation: Chi2, Fisher, W Shapiro-Wilk, U Mann-Whitney tests, Kaplan-Meier's curve and Cox model. The results were displayed in a form of median and upper and lower quartile values (25-75%). RESULTS: No statistical differences in gender nor left/right kidney location were observed. Patients, who underwent TA were at average 10 years older and had multiple comorbidities (median age for TA was 79, for NSS 68; median Charlson index for TA was 5 and for NSS was 3). TA patients had lesser haematological values (Hb, Ht). R.E.N.A.L. scoring demonstrated comparable nephrometry in both groups. NSS procedure was open laparotomy without temporary clamping of renal vessels. Surgical margins of resected tumours were negative. TA was performed with Cool-Tip Covidienequipment with the use of Cluster electrode and was ultraso-nography-guided. Post-treatment complications evaluated with the use of Clavien-Dindo classification were slightly more frequent for NSS method. Patients after NSS were discharged at average after 8.5 days and after TA after 3 days. Histopathological type and Fuhrman malignancy grading were comparable in both groups. TA treated patients' death risk was 9-fold of that observed in NSS treated patients. There was 1 death for each group in perioperative period. CONCLUSION: 1. NSS was associated with slightly higher side effect rate but resulted in prolonged survival. 2. TA was applied to elderly patients with comorbidities. Despite less invasive treatment this group had poorer/reduced survival. 3. Charlson Comorbidity Index (CCI) and the treatment method were relevant survival factors in patients treated due to cT1 renal cancer tumours.
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Bladder cancer (BC) is the most common urological malignancy and has a high incidence of recurrence. BC cells alter their nutrient uptake and metabolic pathways in order to continue the production of sufficient levels of ATP and metabolic intermediates for proliferation and survival. Changes in metabolic pathways regarding the rate of the enzymatic reaction and transport lead to differences in the content of natural isotopes (13C, 15N, 34S) between normal and cancerous tissues. The assessment of the stable isotopes of carbon, nitrogen, and sulfur in normal urothelium and bladder cancer samples was performed using Isotope Ratio Mass Spectrometry (IRMS). The natural abundance of 15N and 13C was decreased in bladder cancer samples when compared to normal urothelium. No significant correlation was observed in BC specimens depending on the tumor grade and stage. Samples derived from bladder tumors and normal urothelium had a different pattern of 15N and 13C isotope abundance. Decreased 13C natural isotopes in the normal urothelium of BC patients were significantly associated with a shorter DFS. Our results suggest that isotopic analysis of normal urothelium of BC patients can be used to predict bladder cancer recurrence.
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Despite being standard tools for decision-making, the European Organisation for Research and Treatment of Cancer (EORTC), European Association of Urology (EAU), and Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk groups provide moderate performance in predicting recurrence-free survival (RFS) and progression-free survival (PFS) in non-muscle-invasive bladder cancer (NMIBC). In this retrospective combined-cohort data-mining study, the training group consisted of 3570 patients with de novo diagnosed NMIBC. Predictors included gender, age, T stage, histopathological grading, tumor burden and diameter, EORTC and CUETO scores, and type of intravesical treatment. The models developed were externally validated using an independent cohort of 322 patients. Models were trained using Cox proportional-hazards deep neural networks (deep learning; DeepSurv) with a proprietary grid search of hyperparameters. For patients treated with surgery and bacillus Calmette-Guérin-treated patients, the models achieved a c index of 0.650 (95% confidence interval [CI] 0.649-0.650) for RFS and 0.878 (95% CI 0.873-0.874) for PFS in the training group. In the validation group, the c index was 0.651 (95% CI 0.648-0.654) for RFS and 0.881 (95% CI 0.878-0.885) for PFS. After inclusion of patients treated with mitomycin C, the c index for RFS models was 0.6415 (95% CI 0.6412-0.6417) for the training group and 0.660 (95% CI 0.657-0.664) for the validation group. Models for PFS achieved a c index of 0.885 (95% CI 0.885-0.885) for the training set and 0.876 (95% CI 0.873-0.880) for the validation set. Our tool outperformed standard-of-care risk stratification tools and showed no evidence of overfitting. The application is open source and available at https://biostat.umed.pl/deepNMIBC/. PATIENT SUMMARY: We created and validated a new tool to predict recurrence and progression of early-stage bladder cancer. The application uses advanced artificial intelligence to combine state-of-the-art scales, outperforms these scales for prediction, and is freely available online.
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Aprendizaje Profundo , Neoplasias de la Vejiga Urinaria , Inteligencia Artificial , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
We aimed at characterization of the patients undergoing radical cystectomy (RC) using the prognostic model (a modified pentafecta). In the multicenter retrospective study, we enrolled 304 patients with bladder cancer (pTis-4N0-2M0) who underwent RC between 2015 and 2020 in experienced centers. The definition of the pentafecta was as follows: no Clavien-Dindo grade III-V complications at 90 days and no long-term complications related to urinary diversion <12 months, negative surgical margins, ≥10 lymph nodes (LNs) resected, and no recurrence ≤12 months. RC-pentafecta achievement rate was 22% (n = 67), varying from 47% to 88% attainment rate for different pentafecta components, and was the lowest for sufficient LN yield. Both 12-month recurrence-free survival (RFS) and cancer-specific mortality were compromised in pentafecta failers compared with achievers (57.8% vs. 100% and 33.8% vs. 1.5%, respectively). The following were identified as crucial predictors of RC pentafecta achievement: modality of the surgery, type of urinary diversion, histological type of bladder cancer, advanced staging, and elevated preoperative serum creatinine. In conclusion, we found that the pentafecta achievement rate was low even in high-volume centers in patients undergoing cystectomy. The complexity of the procedure directly influenced the attainment rate, which in turn led to an increase in cancer-specific mortality rate among the pentafecta failers.
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BRIEF DESCRIPTION: The results demonstrate that the European Organisation for Research and Treatment of Cancer (EORTC) scale provides the best recurrence and progression prediction in comparison with European Association of Urology (EAU) and Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk scores among a mixed population of patients with non-muscle-invasive bladder who were treated with, or without, Bacillus Calmette-Guerin (BCG) and without any immediate postoperative chemotherapy. The study highlights the role of tumor diameter and extent in transition prediction. This retrospective cohort analysis of 322 patients with newly diagnosed non-muscle-invasive bladder cancer (NMIBC) assesses the concordance and accuracy of predicting recurrence and progression by EAU-recommended tools (EAU risk groups, EORTC, and CUETO). One-year and five-year c-indices ranged from 0.55 to 0.66 for recurrence and from 0.72 to 0.82 for progression. AUCROC of predictions ranged from 0.46 for 1-year recurrence risk based on CUETO groups, to 0.82 for 1-year progression risk based on EAU risk groups. Diameter (HR: 1.91; 95% CI: 1.39-2.61) and tumor extent (HR: 1.21; 95% CI: 1.01-1.46 for recurrence; HR: 3.1; 95% CI: 1.40-6.87 for progression) were shown to be significant predictors in multistate analysis. Lower accuracy of prediction was observed for patients treated with BCG maintenance immunotherapy. The EORTC model (overall c-index c = 0.64; 95% CI: 0.61-0.68) was superior to the EAU (P = .035; .62; 95% CI: 0.59-0.66) and CUETO (P < .001; c = 0.53; 95% CI: 0.50-0.56) models in predicting recurrence. The EORTC model (c = 0.82; 95% CI: 0.77-0.86) also performed better than CUETO (P = .008; c = 0.73; 95% CI: 0.66-0.81) but there was no sufficient evidence that it performed better than EAU (P = .572; c = 0.81; 95% CI: 0.77-0.84) for predicting progression. EORTC and CUETO gave similar predictions for progression in BCG-treated EAU high-risk patients (P = .48). We share anonymized individual patient data. In conclusion, despite moderate accuracy, EORTC provided the best recurrence and progression prediction for a mixed population of patients treated with, or without BCG, and without immediate postoperative chemotherapy.
Asunto(s)
Cistectomía/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Guías de Práctica Clínica como Asunto/normas , Medición de Riesgo/métodos , Medición de Riesgo/normas , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
PURPOSE: In patients with nephrolithiasis, oxidative stress, especially lipid peroxidation is observed. Moreover, various invasive methods [including extracorporeal shock wave lithotripsy (ESWL)] for treatment of nephrolithiasis may induce not only the oxidative stress, but they may modulate hemostasis. The study was aimed to evaluate the oxidative damages of lipids and proteins in patients with nephrolithiasis (before and after ureteroscopic lithotripsy - URSL). The aim of the present study was also determine selected parameters of hemostasis in these patients. METHODS: 56 patients with nephrolithiasis and 49 healthy participants were included: 30 men and 26 women (for patient group); 27 men and 22 women (for healthy group). We measured the level of selected typical two biomarkers of oxidative modification of lipids [such as the production of thiobarbituric acid reactive substances (TBARS) and isoprostane concentration (8-isoPGF2α)] and two biomarkers of oxidative damages of proteins (carbonylation and the level of thiol groups) in patients with nephrolithiasis (before and after URSL). The following parameters of hemostasis were measured: blood platelet count, the level of fibrinogen and D-dimer, and coagulation times (the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of plasma). RESULTS: Different levels of plasma lipid peroxidation were observed in patients with nephrolithiasis before URSL and after URSL. However, no such difference in the level of oxidative damage to plasma proteins was observed. In addition, the tested hemostasis parameters were not influenced by the presence of nephrolithiasis, nor by treatment with URSL. CONCLUSION: We suggest URSL does not induce the oxidative modifications of plasma proteins and does not change hemostatic parameters in patients with nephrolithiasis.