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PURPOSE: Ureteroenteric anastomosis after cystectomy is usually performed using the Bricker or Wallace technique. Deterioration of renal function is the most common long-term complication of urinary diversion (UD). To improve surgical care and optimize long-term renal function, we compared the Bricker and Wallace anastomotic techniques and identified risk factors for ureteroenteric strictures (UES) in patients after cystectomy. MATERIAL AND METHODS: Retrospective, monocentric analysis of 135 patients who underwent cystectomy with urinary diversion at the University Hospital Essen between January 2015 and June 2019. Pre- and postoperative renal function, relevant comorbidities, prior chemo- or radiotherapy, pathological findings, urinary diversion, postoperative complications, and ureteroenteric strictures (UES) were analyzed. RESULTS: Of all 135 patients, 69 (51.1%) underwent Bricker anastomosis and 66 (48.9%) Wallace anastomosis. Bricker and Wallace groups included 134 and 132 renal units, respectively. At a median follow-up of 14 (6-58) months, 21 (15.5%) patients and 30 (11.27%) renal units developed UES. We observed 22 (16.6%) affected renal units in Wallace versus 8 (5.9%) in Bricker group (p < 0.001). A bilateral stricture was most common in Wallace group (69.2%) (p < 0.001). Previous chemotherapy and 90-day Clavien-Dindo grade ≥ III complications were independently associated with stricture formation, respectively (OR 9.74, 95% CI 2-46.2, p = 0.004; OR 4.01, 95% CI 1.36-11.82, p = 0.013). CONCLUSION: The results of this study show no significant difference in ureteroenteric anastomotic techniques with respect to UES development regarding individual patients but suggest a higher risk of bilateral UES formation in patients undergoing Wallace anastomosis. This is reflected in the increased UES rate under consideration of the individual renal units.
Assuntos
Neoplasias da Bexiga Urinária , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Constrição Patológica/etiologia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
The detection of bulk micro-defects in Czochralski-grown silicon (Si) ã100ã wafers has significant importance in wafer quality control. Light Scattering Tomography (LST) is an industry standard technique for this purpose. This optical non-contact metrology requires destructive sample preparation: Samples have to be cleaved into half. One particular feature of the method is a dark field detection arrangement, which is achieved by separating the light detection part (microscope unit) from the illumination. Illumination is applied to the front surface of the sample, and the light scattered off of the defects is collected via the cleaved surface. The technique requires the perpendicularity of the cleaved surface to the front surface, which is fulfilled for Si(100) wafers. However, the nominally cleaved surface for Si(111) wafers is not perpendicular to the front surface but has an angle of 70.5°. This significant difference in cleavage results in the fact that Si(111) wafers cannot be measured by standard LST systems. Fortunately, the standard LST system can be modified by tilting the detection part under a proper angle allowing the measurements of Si(111) samples. In this article, we present this new technique in detail, showing the design and measurement capability of the new system. The measurement results are validated by a direct comparison to standard LST measurements on the same samples after proper sample preparation.
RESUMO
The detection of oxygen precipitates, voids, and other defects is critical for semiconductor wafer makers. One of the industry standard techniques for detecting these Bulk Micro-Defects (BMDs) is Semilab's Light Scattering Tomograph (LST) system. In this measurement, unpatterned wafers are nominally cleaved in half. Illumination is applied to the front surface of the sample, and the light scattered off of the defects is collected via the cleaved surface. This technique had been limited to the measurement of unpatterned wafers, but device makers show significant interest in measuring BMD distributions on patterned wafers using scattering-based techniques. A pattern on the surface of the wafer can cause significant scattering, making the standard LST technique unsuitable for this task. We present a solution for patterned wafer BMD measurements by an addition of a low-angle illumination unit to the standard LST system. This new illumination unit focuses the light into the bulk of the wafer via the cleaved surface, which enables measurement on patterned samples. The new system is called "light scattering tomograph enhanced by low-angle illumination." Excellent correlation was found between the detected defect densities obtained by the low-angle and the standard LST illumination mode.
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OBJECTIVES: The rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients. METHODS AND MATERIALS: MMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (nâ¯=â¯95), ABI (nâ¯=â¯140), or ENZA (nâ¯=â¯85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data. RESULTS: MMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (Pâ¯=â¯0.058 and Pâ¯=â¯0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (Pâ¯=â¯0.001) and ENZA (Pâ¯=â¯0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients' survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA. CONCLUSIONS: We confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.
Assuntos
Androstenos/uso terapêutico , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Docetaxel/uso terapêutico , Metaloproteinase 7 da Matriz/sangue , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Urachal cancer is a rare type of cancer, often following a clinically aggressive course. Due to its rarity, knowledge about its molecular background is still limited. In addition, no sufficiently reliable diagnostic markers are available. OBJECTIVES: The aim of the present study is to give an overview of our recent molecular projects on urachal cancer and to connect it with current literature in the field. MATERIALS AND METHODS: Three projects are introduced. The first project identified and validated diagnostic biomarkers in urachal adenocarcinomas compared to colorectal adenocarcinomas and primary adenocarcinomas of the bladder using various proteomic methods. In the second project, the most relevant differential diagnostic markers between urachal adenocarcinomas and colorectal adenocarcinomas compared to normal tissue (urachal remnants) were determined by analyzing a miRNA panel. Sequence analyses were performed in the third project. The focus was on molecular differences to colorectal adenocarcinomas and urothelial carcinomas. RESULTS AND CONCLUSIONS: We detected potential biomarker candidates for the immunohistochemical differential-diagnosis and generated a miRNA-based diagnostic scoring system with a potentially high differential-diagnostic significance. The sequence analyses data confirm the molecular autonomy of the urachal adenocarcinomas compared to other entities.
Assuntos
Adenocarcinoma , Neoplasias da Bexiga Urinária/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Diagnóstico Diferencial , Marcadores Genéticos , Humanos , Proteômica , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
BACKGROUND: In the last few years, significant progress has been achieved in the therapeutic options for advanced urothelial bladder cancer. OBJECTIVES: The aim of this work was to give an overview of the status and future perspective of the therapeutic options in this setting. Its focus is on the discussion of tissue-based therapy-predictive markers, which are evaluated through (molecular) pathology and thereby strengthening the role of pathology itself. MATERIALS AND METHODS: Current (clinical study) data, the literature, and our own expertise were considered and summarized in the areas of therapy prediction of platinum-based chemotherapy, immunotherapy, and other therapeutic approaches. RESULTS AND CONCLUSIONS: Molecular subtypes exhibit a predictive value both in platinum-based chemotherapy as well as in immunotherapy. However, further work is required to elucidate the predictive role of molecular subtypes in both settings. Changes in the DNA damage repair enzyme (DDR) genes, ERCC2, and ERBB2 as well as differences in the expression of EMMPRIN, survivin, and HMGA2 show promising results as further markers of chemotherapy efficacy. In the prediction of immunotherapy success, this mainly relates to the evaluation of the tumor mutation burden (TMB), tumor neoantigen burden (TNB), APOBEC signatures (MSig1; 3A/3B), and CD8-positive Teffector cell signature. When using the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib, which has not yet been approved in Germany, the evaluation of specific FGFR mutations and/or gene fusions by a companion diagnostic test is mandatory in the USA.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Biomarcadores Tumorais , Carcinoma de Células de Transição/patologia , Alemanha , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia , Proteína Grupo D do Xeroderma PigmentosoRESUMO
BACKGROUND: Tumors of the genitourinary system are common. In recent years, our understanding of their molecular background and therefore the number of potential predictive biomarkers has massively increased. OBJECTIVES: The aim of the current work is to give an overview of recent (molecular) developments and predictive biomarkers in urologic oncology and to give a perspective of what might become relevant in the future of the field. MATERIAL AND METHODS: We considered the recent literature and study data and combined it with our own expertise in tumors of the urinary system, kidneys, and prostate. RESULTS AND CONCLUSIONS: The molecular subtypes of muscle-invasive urothelial bladder cancer (MIBC) hold a predictive and prognostic significance and correlate with clinicopathological features. Immune therapy with checkpoint inhibitors (CPI) has a major role in urothelial carcinoma (UC), but also in renal cell carcinoma and a subgroup of prostate cancers. The first-line use in UC is restricted to PD-L1-"positive" cases (≥IC2/3, CPSâ¯≥ 10). Further predictive markers are currently under evaluation, while the predictive significance of tumor mutational burden (TMB) is under debate. In addition to a subgroup of renal cell carcinomas, a subgroup of prostate carcinomas with alterations in the DNA repair system might benefit from a customized therapy approach (PARP inhibitors, platin-containing chemotherapy). The multitude of potentially therapy-relevant molecular alterations and related predictive biomarkers calls for the implementation of sophisticated molecular analyses in daily routine. This will lead to an even more rapid dynamic in the field of genitourinary pathology.
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Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Biomarcadores , Biomarcadores Tumorais , Carcinoma de Células de Transição/patologia , Humanos , Masculino , Prognóstico , Neoplasias da Bexiga Urinária/patologiaRESUMO
Recently, a neuroendocrine-like molecular subtype has been discovered in muscle-invasive urothelial bladder cancer (BC). Chromogranin A (CGA) is a widely used tissue and serum marker in neuroendocrine tumors. Our aim was to evaluate serum CGA (sCGA) concentrations and their associations with clinical and follow-up data in BC and renal cell carcinoma (RCC). sCGA concentrations were analyzed in the following cohorts: (1) BC training set (n = 188), (2) BC validation set (n = 125), (3) RCC patients (n = 77), (4) healthy controls (n = 97). CGA immunohistochemistry and RT-qPCR analyses were performed in 20 selected FFPE and 29 frozen BC tissue samples. Acquired data were correlated with clinicopathological parameters including comorbidities with known effect on sCGA as well as with patients' follow-up data. sCGA levels were significantly higher in BC but not in RCC patients compared to healthy controls. High sCGA levels were independently associated with poor overall and disease-specific survival both in the BC training (P < 0.001, P = 0.002) and validation set (P = 0.009, P = 0.017). sCGA levels were inversely correlated with glomerulus filtrating rate (GFR) and linearly correlated with creatinine clearance and urea concentrations. These correlations were not related to the prognostic value of sCGA. Tissue CGA levels were low to absent independently of sCGA concentrations. Our results demonstrate elevated levels and an independent prognostic value for sCGA in BC but not in RCC. Despite the significant correlation between sCGA and GFR, the prognostic relevance of sCGA seems not related to impaired renal function or other comorbidities.
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Urachal cancer is a rare but aggressive disease. In addition to the non-glandular tumors, non-cystic urachal adenocarcinomas are nowadays distinguished from the primary cystic variant. (Immunohistochemical) markers are only of minor differential diagnostic value and, therefore, the diagnosis is primarily established in a multidisciplinary approach. The non-cystic variant accounts for the majority of cases (83%), is more common in men (63%), shows a median age at diagnosis of 51 years and has a 5-year survival rate of about 50%. In organ-confined disease, usually a partial cystectomy of the tumor in the bladder dome, including the median umbilical ligament and umbilicus, is performed. In advanced stages, systemic therapy is needed while 5fuorouracil (5-FU) containing regimes have been shown to be more effective. Due to the rarity of the tumor, targeted therapy approaches based on a biological rationale are becoming increasingly relevant. As molecular data are still sparse, we compiled and analyzed the largest urachal cancer cohort to date. In 31% of the cases, MAPK-/PI3K signaling pathway alterations were detected (especially in K-/NRAS) with implications for anti-EGFR therapy approaches. Further potentially therapeutic alterations were detected in FGFR1, MET, PDGFRA, and erbB2/HER2. Additionally, PD-L1 tumor cell expression (clone: 22C3) was demonstrated in 16% of cases, therefore making anti-PD-1/PD-L1 immuno-oncological approaches worth considering despite the absence of mismatch repair deficiency (MMR-d) and/or high microsatellite instability (MSI-h). Finally, urachal adenocarcinomas seem to be a distinct entity on the molecular level with closer resemblance to colorectal adenocarcinomas than to urothelial carcinomas.
Assuntos
Doenças Raras , Úraco/patologia , Neoplasias da Bexiga Urinária , Cistectomia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Doenças Raras/epidemiologia , Doenças Raras/metabolismo , Doenças Raras/patologia , Doenças Raras/terapia , Úraco/metabolismo , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
Urachal cancer is a rare but aggressive disease. In addition to the non-glandular tumors, non-cystic urachal adenocarcinomas are nowadays distinguished from the primary cystic variant. (Immunohistochemical) markers are only of minor differential diagnostic value and, therefore, the diagnosis is primarily established in a multidisciplinary approach. The non-cystic variant accounts for the majority of cases (83%), is more common in men (63%), shows a median age at diagnosis of 51 years and has a 5-year survival rate of about 50%. In organ-confined disease, usually a partial cystectomy of the tumor in the bladder dome, including the median umbilical ligament and umbilicus, is performed. In advanced stages, systemic therapy is needed while 5fuorouracil (5-FU) containing regimes have been shown to be more effective. Due to the rarity of the tumor, targeted therapy approaches based on a biological rationale are becoming increasingly relevant. As molecular data are still sparse, we compiled and analyzed the largest urachal cancer cohort to date. In 31% of the cases, MAPK-/PI3K signaling pathway alterations were detected (especially in K-/NRAS) with implications for anti-EGFR therapy approaches. Further potentially therapeutic alterations were detected in FGFR1, MET, PDGFRA, and erbB2/HER2. Additionally, PD-L1 tumor cell expression (clone: 22C3) was demonstrated in 16% of cases, therefore making anti-PD-1/PD-L1 immuno-oncological approaches worth considering despite the absence of mismatch repair deficiency (MMR-d) and/or high microsatellite instability (MSI-h). Finally, urachal adenocarcinomas seem to be a distinct entity on the molecular level with closer resemblance to colorectal adenocarcinomas than to urothelial carcinomas.
Assuntos
Adenocarcinoma , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-QuinasesRESUMO
Transitional cell carcinoma of the bladder can - in the majority of cases - be safely treated by transurethral resection and bladder preservation. In case of more aggressive and genetically instable tumors, the effect of radical cystectomy depends on tumor volume. If complete resection of invasive tumors is also possible, the additional effect of radical cystectomy seems to be marginal. In patients with favorable tumor location and acceptable prostate parameters, prostate-sparing surgery seems to be oncologically safe with good quality of life.
Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Carcinoma de Células de Transição/diagnóstico , Humanos , Recuperação de Função Fisiológica , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
BACKGROUND: Testosterone deficiency represents a significant health risk factor for men but the importance has so far been underestimated. Besides physiological and age-related reduction, acquired testosterone deficiency may also occur. Testosterone deficiency is a possible result of commonly occurring diseases or is itself the basis for development of different diseases. The scope of the present investigation was measurement of serum testosterone levels in different age groups. MATERIALS AND METHODS: Serum testosterone levels were determined in samples from 5,735 healthy men at the LADR laboratory MVZ Dr. Kramer & colleagues, Geesthacht under routine conditions. The frequency of testosterone deficiency was calculated in different age groups and compared using SPSS 19.0 software. RESULTS: Pathologically low testosterone levels (< 2.5 ng/ml) were found in 15.2 % of subjects while 37.4 % had a testosterone level lower than 3.5 ng/ml. Decreased testosterone levels were not associated with age. In addition the proportion of men with decreased serum testosterone levels was comparable in all age groups. The average serum testosterone level decreased slightly in all age groups during the period before midday. CONCLUSIONS: The data reveal high rates of testosterone deficiency in men independent of patient age. As decreased serum testosterone levels may be the consequence of several diseases and can be causally involved in the pathogenesis of further diseases, it is strongly recommended that serum testosterone measurement should be included in the diagnostic arsenal especially when symptoms, such as loss of libido, erectile dysfunction, lack of concentration, depression, lethargy, irritability and sleep disturbance are present.
Assuntos
Envelhecimento/sangue , Hipogonadismo/sangue , Hipogonadismo/epidemiologia , Testosterona/sangue , Testosterona/deficiência , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Early detection of metastases in muscle-invasive bladder cancer is crucial. Current imaging techniques provide only limited sensitivity for the detection of low volume metastases. Molecular markers and new rapid analysis techniques are therefore needed to improve metastasis detection sensitivity. High urinary matrix metalloproteinase 7 (MMP 7) levels were previously shown to be correlated with the presence of lymph node metastases. In the present study we applied a new innovative antibody-based electrical biochip technology for the quantitative detection of urinary MMP 7. MATERIALS AND METHODS: Preoperative urine samples were acquired from 30 bladder cancer patients (15xN0 and 15xN1-2) who underwent cystectomy because of muscle-invasive bladder cancer. In addition, urine samples of 15 age-matched healthy individuals were also collected. The MMP 7 analyses were performed using electrical biochip technology and a standard ELISA technique in parallel. RESULTS: Urinary MMP 7 concentrations measured by biochip technology were significantly higher in patients with metastatic bladder cancer compared to those with organ-confined cancer. The sensitivity for the detection of lymph node metastases was over 70 % using the biochip technology. CONCLUSIONS: These results confirm MMP 7 as a promising metastasis marker in bladder cancer. The new electrical biochip technology provides a rapid and reliable quantitative method for measurement of protein markers in urine.
Assuntos
Biomarcadores Tumorais/urina , Técnicas Biossensoriais/instrumentação , Condutometria/instrumentação , Imunoensaio/instrumentação , Urinálise/instrumentação , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/estatística & dados numéricos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/secundárioRESUMO
The question whether conventional cystoscopy should always be performed together with fluorescent diagnostic procedures remains to be answered. The current article presents the current literature dealing with this topic. Particularly for relevant carcinoma in situ lesions of the bladder there is no obvious advantage for photodynamic diagnostics compared to conventional cystoscopy with consistent use of urine cytology.
Assuntos
Carcinoma in Situ/diagnóstico , Carcinoma de Células de Transição/diagnóstico , Cistoscopia/métodos , Fármacos Fotossensibilizantes , Neoplasias da Bexiga Urinária/diagnóstico , Ácido Aminolevulínico/análogos & derivados , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/patologia , Fluorescência , Humanos , Gradação de Tumores , Valor Preditivo dos Testes , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Transurethral resection of transitional cell carcinoma of the bladder provides a definitive surgical treatment and supplies tissue for histological evaluation. Superficial low-grade carcinomas with a small risk of progression are treated properly with fulguration alone. To justify fulguration as a definitive treatment of papillary bladder tumours, one must be able to safely distinguish low-grade, noninvasive tumours from those that are high grade and potentially invasive. MATERIAL AND METHODS: A total of 160 patients with a transitional cell carcinoma at cystoscopy underwent transurethral resection of the tumour. The macroscopic appearance of the tumour, the aspect with bimanual palpation and the perioperative urine cytology were compared with the histological report. RESULTS: In our study we were able to safely distinguish low-grade tumours from high-grade tumours. All noninvasive tumours could be identified visually as such. CONCLUSION: Urologists skilled in the evaluation of urine cytology can distinguish low-grade noninvasive tumours of the bladder from high-grade and potentially invasive tumours by means of appearance at cystoscopy and perioperative urine cytology.
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Carcinoma de Células de Transição/patologia , Cistoscopia , Neoplasias da Bexiga Urinária/patologia , Urina/citologia , Carcinoma de Células de Transição/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Palpação , Valor Preditivo dos Testes , Prognóstico , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: Urinary bladder cancer represents a heterogeneous group of cancers regarding their clinical behaviour. For patients with muscle-invasive bladder cancer the 5-year disease-specific survival rate is only 50%. The main cause of death in this patient group is rapid metastatic progression following surgery. Clinicopathological features provide only limited information to predict disease progression in these patients. E-cadherin is a transmembrane glycoprotein critically involved in epithelial cell adhesion. Elevated circulating E-cadherin levels were shown to be correlated with progression of bladder cancer. MATERIAL AND METHODS: Plasma E-cadherin levels of 97 patients and 17 controls were analysed using an enzyme-linked immunosorbent assay, and results were compared with the clinical follow-up data. RESULTS: Plasma E-cadherin concentrations were significantly higher in patients than in controls (p<0.001). E-cadherin levels were not significantly correlated with clinicopathological parameters such as tumour stage (p=0.196), grade (p=0.570) and lymph node status (p=0.581). In a subgroup of patients treated by radical cystectomy, E-cadherin concentrations were higher in lymph node-positive cases; however, this correlation (p=0.100) failed to reach statistical significance. Furthermore, plasma E-cadherin levels were not able to predict disease-specific survival or metastasis-free survival (p=0.512 and p=0.197). CONCLUSIONS: Our results suggest that soluble E-cadherin levels are not able to predict patients' prognosis and underline the importance of external validation in prognostic marker research. Molecular markers predicting disease progression after radical cystectomy to identify high-risk patients and improve therapy decisions are still needed.
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Biomarcadores Tumorais/sangue , Caderinas/sangue , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
Urinary cytology is a non-invasive adjunct to cystoscopy in the diagnosis of bladder cancer. In order to assess the diagnostic accuracy of urinary cytology as an office-based method for clinically relevant high grade (G3) bladder cancer, three nationwide cytology survey tests were performed. Urine specimens from seven patients, three patients with high grade (G3) bladder cancer and four patients with urinary tract infections, were collected. A total of 1,000 cytology slides were produced from each urine specimen. Each set contained five slides (two malignant, three benign) which were sent to all participating German urologists. Three nationwide tests were performed from 1998-2000. The specimen sets were kept the same for the first and second test and in the third test two new slides were introduced. In addition to validity, the reliability was calculated for the first and second test as interobserver and intraobserver reliability according to Cohen's kappa statistics. Due to the change of two specimens in the third test in 2000 only sensitivity and specificity were calculated. A total of 335 urologists took part in the first survey test, 329 in the second and 292 in the third The sensitivity for G3 cytologies was 81.34% in the first, 87.08% in the second and 85.1% in the third survey test and the specificity was 85.87%, 83.58% and 89.15%, respectively. Interobserver reliability showed a weighted kappa value of 0.58 for the first and 0.59 for the second survey test. Calculation of intraobserver reliability was possible for 169 urologists taking part in the first and second survey test and showed a mean kappa value of 0.62. The results of the three nationwide urinary cytology tests indicate that urinary cytology has a high sensitivity in the detection of clinically relevant high grade bladder cancer. The kappa values achieved demonstrate a clear agreement of cytological diagnoses.
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Cistoscopia/estatística & dados numéricos , Citodiagnóstico/estatística & dados numéricos , Urinálise/estatística & dados numéricos , Urina/citologia , Neoplasias Urológicas/patologia , Neoplasias Urológicas/urina , Cistoscopia/métodos , Citodiagnóstico/métodos , Diagnóstico por Computador/métodos , Alemanha/epidemiologia , Humanos , Incidência , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Urinálise/métodos , Neoplasias Urológicas/epidemiologia , Urotélio/patologiaRESUMO
Urinary cytology is a basic adjunct to cystoscopy and transurethral resection in the diagnosis and characterization of high-grade urothelial carcinomas of the bladder. According to the new WHO classification the former tumor grading G1-3 for non-invasive carcinomas has been replaced by a separation into low-grade and high-grade urothelial carcinomas. An interesting question is where the former non-invasive G2 carcinomas will be positioned in this new classification. In a retrospective analysis we focused on 44 patients with pTaG2 and 17 patients with pT1G2 carcinomas and found that this group of tumors is cytologically heterogeneous but easily differentiated into low-grade and high-grade lesions. A cytometrical analysis significantly underlines the results of the cytological diagnostics. High-grade tumors show a higher recurrence and progression rate. Cytological diagnostics can therefore assist in differentiating low-grade from high-grade urothelial carcinomas.
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Carcinoma de Células de Transição/classificação , Carcinoma de Células de Transição/patologia , Classificação Internacional de Doenças , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/patologia , Urina/citologia , Adulto , Carcinoma de Células de Transição/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/urina , Adulto JovemRESUMO
Angiogenesis is a prerequisite for tumour growth and metastasis. Therefore, angiogenesis factors in bladder cancer, a common disease of the genitourinary tract, could serve as diagnostic tools, predictors of prognosis, and targets for therapy. Development of less invasive or noninvasive detection techniques, reliable prognostic markers, and individualized targeted therapy would have a significant impact on disease management. For this investigative goal, the utility of urine and blood is beneficial. Research in the field of angiogenesis and promising markers is currently evolving. In spite of the recent success of antiangiogenic agents in the oncological clinic, an optimal marker that will warrant substitution of the cystoscopic follow-up protocol in patients with urothelial neoplasms has not been identified yet. Despite this challenge, allocating more resources and attention to identifying such urine markers is justified to optimize the diagnostics and follow-up of urinary bladder cancer.