Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
Aktuelle Urol ; 2024 Apr 23.
Artículo en Alemán | MEDLINE | ID: mdl-38653467

RESUMEN

Urinary stones of the upper urinary tract can be considered a widespread public health concern due to their high incidence and prevalence and their health policy-related and financial implications. A significant proportion of newly diagnosed kidney stones are lower-pole stones, i.e., stones affecting the lower calyx group of the renal pelvicalyceal system. These are often diagnosed by chance, i.e., as incidental findings during ultrasound or CT scans performed for other reasons, or as "secondary stones" detected during the diagnostic work-up of symptomatic urinary stones in other locations. Residual disintegrates after extracorporeal shock-wave lithotripsy (ESWL) or endoscopic stone therapy constitute a further, quantitatively significant group. These incidentally discovered lower-pole stones are often characterised by their small size and lack of symptoms. It stands to reason that some of these small, asymptomatic lower-pole stones do not always remain small and asymptomatic, and that treatment tends to become more complex with increasing size. There has been an astonishing lack of published studies with a high level of evidence over the last 20 years to provide a conclusive and reproducible answer to the question posed in this review. Small, asymptomatic stones can be monitored. Symptomatic and rapidly growing stones should be treated. There is a lack of valid risk factors allowing an identification of subgroups that should be treated prophylactically at the asymptomatic stage. In active therapy, a 10-to-20-year-old principle still holds true today: a high stone-free rate in one therapy session is offset by an increased complication rate, with increasing miniaturisation in endourology (retrograde and percutaneous) and increasingly effective laser disintegration shifting this basic principle more and more in favour of flexible URS and (mini, micro) PCNL. The range of indications for ESWL is undoubtedly becoming smaller, and this also applies to lower-pole stones. The results of an ongoing prospective randomised study comparing the different treatment modalities, albeit with recruitment difficulties, are still pending.

2.
J Clin Pathol ; 76(2): 126-132, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34583948

RESUMEN

AIMS: Upper tract urothelial carcinoma (UTUC) is a rare malignancy with a poor prognosis which occurs sporadically or in few cases results from a genetic disorder called Lynch syndrome. Recently, examination of microsatellite instability (MSI) has gained importance as a biomarker: MSI tumours are associated with a better response to immunomodulative therapies. Limited data are known about the prevalence of MSI in UTUC. New detection methods using the fully automated Idylla MSI Assay facilitate analysis of increased patient numbers. METHODS: We investigated the frequency of MSI in a multi-institutional cohort of 243 consecutively collected UTUC samples using standard methodology (Bethesda panel), along with immunohistochemistry of mismatch repair (MMR) proteins. The same tumour cohort was retested using the Idylla MSI Assay by Biocartis. RESULTS: Using standard methodology, 230/243 tumours were detected as microsatellite stable (MSS), 4/243 tumours as MSI and 9/243 samples as invalid. In comparison, the Idylla MSI Assay identified four additional tumours as MSS, equalling 234/243 tumours; 4/243 were classified as MSI and only 5/243 cases as invalid. At the immunohistochemical level, MSI results were supported in all available cases with a loss in MMR proteins. The overall concordance between the standard and the Idylla MSI Assay was 98.35%. Time to result differed between 3 hours for Idylla MSI Assay and 2 days with the standard methodology. CONCLUSION: Our data indicate a low incidence rate of MSI tumours in patients with UTUC. Furthermore, our findings highlight that Idylla MSI Assay can be applied as an alternative method of MSI analysis for UTUC.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Colorrectales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/genética , Inestabilidad de Microsatélites , Repeticiones de Microsatélite , Neoplasias de la Vejiga Urinaria/genética
3.
Urologe A ; 60(9): 1211-1219, 2021 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-34398255

RESUMEN

A fundamental understanding of the physical properties is necessary for the application of lasers in medicine in order to be able to understand and appreciate the biological effect. The most important parameters are emission mode, wavelength of the laser and power output measured in watts. Pulsed lasers can be used for the treatment of stones and soft tissues, whereby in urology this essentially applies to the prostate gland and to a lesser extent also for the ureter, urethra, bladder and kidneys.


Asunto(s)
Láseres de Estado Sólido , Uréter , Urología , Humanos , Masculino , Próstata , Tulio
4.
Aktuelle Urol ; 2021 Apr 14.
Artículo en Alemán | MEDLINE | ID: mdl-33853160

RESUMEN

BACKGROUND: Immunostimulatory CpG oligodeoxynucleotides (CpG-ODN) have been verified as an effective antineoplastic agent for intravesical application in a murine orthotopic C57-BL6 /MB-49 urothelial cell carcinoma (UCC). To date, many details in the mode of action have remained unclear. Preceding studies pointed towards a Th1-weighted response. The aim of this work was to identify the local lymphocyte subsets in murine tumour-bearing bladders and to examine effects on the expression of Intercellular Adhesion Molecule 1 (ICAM-1) after treatment with CpG-ODN. MATERIAL AND METHODS: Different instillation schedules were applied in an established orthotopic C57-BL6 /MB49 UCC model. After 13 days, fresh frozen sections of the harvested bladders were immunohistochemically examined for the infiltration density of lymphocytes expressing CD 3, CD4, CD8 and CD19. In a second series of the same animal model, healthy and tumour-bearing bladders were exposed to CpG-ODN or PBS and later stained for the expression of ICAM-1. RESULTS: CpG-ODN instillation led to augmented T-cell infiltration (represented by CD3). Further T-cell subdifferentiation between T-helper cells (CD4) and cytotoxic T cells (CD 8a) did not show a perceptible variety between groups. The B-cell population (CD19) was found to decrease over the course of treatment. In the second series, treatment provoked a strong expression of ICAM-1 by infiltrating leukocytes, endothelial cells and particularly by the cancer cells themselves. DISCUSSION: The previously observed augmented lymphocyte density was classified as T-cell infiltration. The decline of the B-cell concentration over the course of treatment suggests a Th2 suppression in favour of a Th-1 polarisation. These findings support the assumption that a cell-mediated immune response is the mode of action underlying the antineoplastic CpG-ODN capacities. The marked upregulation of ICAM-1 expression, especially on tumour cells, suggests a crucial role of this membrane protein for the initiation and maintenance of anticancer immune response. CONCLUSION: CpG-ODN might be a prospective alternative to established instillation therapies. With a view to the current BCG shortage and the well-known toxicities, an amplification of the topic therapy armamentarium could be achievable. The now described capability of ICAM-1 induction on carcinoma cells and, by association, the reversal of escape strategies to cancer immunity may also make the agent interesting as an adjuvant for modern checkpoint inhibition.

5.
PLoS One ; 12(6): e0179602, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28632777

RESUMEN

PURPOSE: Genome-wide analyses revealed basal and luminal subtypes of urothelial carcinomas of the bladder. It is unknown if this subtyping can also be applied to upper tract urothelial carcinomas. MATERIALS AND METHODS: Tumor samples from 222 patients with upper tract urothelial carcinomas who were treated with radical nephroureterectomy were analyzed for the expression of seven basal/luminal immunohistochemical markers (CK5, EGFR, CD44, CK20, p63, GATA3, FOXA1). RESULTS: Hierarchical clustering revealed a basal-like subtype (enrichment of CK5, EGFR and CD44) in 23.9% and a luminal-like subtype (enrichment of CK20, GATA3, p63 and FOXA1) in 13.1% of the patients. In 60.8%, little to no markers were expressed, whereas markers of both subtypes were expressed in 2.2%. By using CK5 and CK20 as surrogate markers for the basal and luminal subtypes, we defined four subtypes of upper tract urothelial carcinomas: (i) exclusively CK20 positive and CK5 negative (CK20+/CK5-), (ii) exclusively CK5 positive and CK20 negative (CK20-/ CK5+), (iii) both markers positive (CK20+/CK5+) and (iv) both markers negative (CK20-/CK5-). A receiver-operator analysis provided the optimal cut-off values for this discrimination. An immunoreactive score >1 for CK5 and >6 for CK20 were defined as positive. In multivariate Cox's regression analysis, the CK20+/CK5- subtype was an independent negative prognostic marker with a 3.83-fold increased risk of cancer-specific death (p = 0.02) compared to the other three subtypes. CONCLUSIONS: Immunohistochemical subgrouping of upper tract urothelial carcinomas by analyzing CK5 and CK20 expression can be performed in a routine setting and can identify tumors with a significantly worse cancer-specific survival prognosis.


Asunto(s)
Carcinoma/patología , Queratina-20/metabolismo , Queratina-5/metabolismo , Neoplasias Urológicas/patología , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/metabolismo , Carcinoma/metabolismo , Carcinoma/mortalidad , Femenino , Humanos , Inmunohistoquímica , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/mortalidad , Urotelio/metabolismo
6.
J Endourol ; 31(1): 20-26, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27798969

RESUMEN

INTRODUCTION: Although ureteroscopy (URS) has been established as a viable treatment for stones in obese patients, its safety and success has not been fully elucidated. The current study describes the worldwide prevalence of obesity in patients with urolithiasis and examines trends in URS outcomes, safety, and efficacy. METHODS: This study utilized the Clinical Research Office of the Endourological Society (CROES) URS Global Study, which was a prospective, multicenter study including 11,885 patients treated with URS for urinary stones at 1 of 114 urology departments across 32 countries. The relationship between body mass index (BMI), diabetes, and creatinine, with retreatment, stone-free rates, complications, and long hospital stay, was examined with a multivariate logistic regression analyses. RESULTS: Of the 10,099 URS patients with BMI data, 17.4% were obese and 2.2% were super obese. Overall, 86.7% patients were stone free and 16.8% required retreatment. Higher BMI was associated with lower stone-free rates, and any deviation from normal weight was associated with higher retreatment rates. In multivariate analysis controlling for several variables including stone size, the association between BMI and lower stone-free rates with higher retreatment rates persisted. Intraoperative complications occurred in 518 (5.1%) patients, and 343 (3.4%) experienced a postoperative complication. Postoperative complications were more frequent in the underweight and super obese subjects, and there was no relationship between BMI and intraoperative complications. DISCUSSION: Although URS for stone disease was found to be an overall safe procedure for obese and super obese patients, efficacy of the procedure may be lower compared with normal-weight subjects and higher retreatment rates may be necessary.


Asunto(s)
Índice de Masa Corporal , Cálculos Ureterales/cirugía , Ureteroscopía/métodos , Cálculos Urinarios/cirugía , Urolitiasis/cirugía , Adulto , Anciano , Investigación Biomédica , Femenino , Humanos , Cooperación Internacional , Tiempo de Internación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/complicaciones , Complicaciones Posoperatorias/etiología , Prevalencia , Estudios Prospectivos , Retratamiento , Resultado del Tratamiento
7.
Biomarkers ; 21(7): 653-9, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27121394

RESUMEN

CONTEXT: Blood platelets may offer as RNA biomarker source for cancer as recently described for an oncogenic transcript in glioma patients and for PCA3 in prostate cancer (PCa) patients. OBJECTIVE: Here, we elaborated on this aspect for PCa. MATERIALS AND METHODS: PCA3 and other PCa-associated RNA markers were measured in platelets of PCa patients (cases) and healthy subjects (controls) in comparison to PCa cell lines by relative quantitative RT-PCR. RESULTS: The RNA markers displayed heterogeneous expression patterns in cell lines and platelets, however, without significant differences between cases and controls. DISCUSSION AND CONCLUSION: The data do not support platelets as a profitable RNA source for early detection of PCa. Nonetheless, certain PCa-derived RNA markers in platelets may merit further investigation as potential prognostic biomarkers for PCa.


Asunto(s)
Biomarcadores de Tumor/análisis , Plaquetas , Neoplasias de la Próstata/diagnóstico , ARN , Antígenos de Neoplasias/análisis , Estudios de Casos y Controles , Humanos , Masculino , Células Tumorales Cultivadas
8.
Anticancer Res ; 35(7): 4277-81, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26124390

RESUMEN

AIM: To analyze female gender as a possible age-dependent prognostic factor for overall (OS) and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UUTUC) after radical nephroureterectomy (RNU). PATIENTS AND METHODS: A total of 167 men and 101 women with UUTUC treated with RNU with bladder cuff resection at our clinic were retrospectively analyzed. Female patients were divided into pre- and post-menopausal groups and compared against male patients of the same age. We used a cut-off age of 59 years or more as a surrogate for the post-menopausal hormonal status of women. Kaplan-Meier analyses and multivariate Cox proportional hazards regression analyses were performed to analyze gender as a possible prognostic factor of OS and CSS. RESULTS: Women aged 59 years or more had a significantly worse CSS with an average of 231 months after RNU compared to 303 months for their male counterparts (p=0.011). Univariate Cox regression analysis showed a 2.44-fold higher risk of death (p=0.013), while multivariate analyses, adjusted for tumor stage and tumor grade, showed a 2.92-fold higher risk (p=0.011) of cancer-specific death for women aged 59 years or more. CONCLUSION: Female gender is an age-dependent prognostic factor for CSS for patients with UUTUC treated with RNU.


Asunto(s)
Carcinoma/patología , Sistema Urinario/patología , Neoplasias Urológicas/patología , Urotelio/patología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nefrectomía/métodos , Pronóstico , Estudios Retrospectivos
9.
Urol Int ; 95(4): 400-5, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25871980

RESUMEN

INTRODUCTION: We aimed at evaluating the incidence of lymphoceles, a common complication after radical retropubic prostatectomy (RRP), at a high volume centre, define risk factors and assess the clinical outcome. MATERIALS AND METHODS: 454 patients receiving RRP and pelvic lymph node dissection were assessed for postoperative lymphoceles using the ultrasound method. Findings were correlated to clinical parameters from a database (age, BMI, initial PSA, number of lymph nodes removed, prostate weight, duration of surgery, hospital stay, duration of catheterisation) and possible unconventional risk factors using meteorological data. RESULTS: Overall, 15.4% developed a lymphocele, 2.6% had a symptomatic lymphocele requiring treatment. The mean size of the lymphoceles requiring treatment was significantly higher (400 vs. 115 ml). Patients with lymphocele stayed longer in hospital. No correlation could be found between the clinical parameters and the risk for lymphoceles. Functional results in terms of urinary continence were similar. The assessment of meteorological risk factors showed a correlation of lymphoceles with air humidity. CONCLUSION: Lymphoceles are common after RRP, but few cases require intervention. There is no reliable clinical predictor for the risk of lymphocele development. Data sets have been published suggesting several risk factors but may be subject to statistical error like in the case of the meteorological predictors in this study.


Asunto(s)
Linfocele/epidemiología , Complicaciones Posoperatorias/epidemiología , Próstata/patología , Prostatectomía/efectos adversos , Neoplasias de la Próstata/cirugía , Medición de Riesgo/métodos , Anciano , Anciano de 80 o más Años , Alemania/epidemiología , Humanos , Incidencia , Laparoscopía , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática , Linfocele/diagnóstico por imagen , Linfocele/etiología , Masculino , Persona de Mediana Edad , Pelvis , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/secundario , Espacio Retroperitoneal , Estudios Retrospectivos , Factores de Riesgo , Ultrasonografía
10.
Urol Oncol ; 33(3): 110.e19-27, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25499923

RESUMEN

OBJECTIVES: Adjuvant immunotherapy of bladder cancer by instillation of bacillus Calmette-Guérin (BCG) is highly recommended within certain groups of non-muscle-invasive stages but only partially effective. Toll-like receptors (TLRs) TLR4 and TLR9 likely mediate BCG effects by triggering innate systemic immune cell responses. In addition, TLR4 and TLR9 expressed in bladder cancer cells may contribute to the outcome of BCG treatment. Here, we studied the expression and function of TLR4 and TLR9 in human bladder cancer cell lines. METHODS: TLR4 and TLR9 messenger RNA and protein levels were determined by real-time reverse transcription polymerase chain reaction and Western blot. Selected cell lines were analyzed with respect to cytokine induction, proliferation, and cell invasion after addition of BCG, TLR4-specific agonist lipopolysaccharide (LPS), or TLR9 agonist (CpG-oligodeoxynucleotide [ODN]). RESULTS: TLR4 and TLR9 were expressed quite heterogeneously in human bladder cancer cells. BCG caused induction of interleukin (IL)-6 or IL-8 in BFTC905 and T24 cells as representatives for TLR4-/TLR9-expressing cells. The study aimed to dissect TLR4- and TLR9-mediated effects. For functional analysis of TLR4 with LPS, we selected T24 and BFTC905 cells with high and undetectable TLR4 levels, respectively. For TLR9 analysis with CpG-ODN, we selected UMUC3 and RT112 cells with high and low TLR9 levels, respectively. Addition of LPS caused significant induction of TNFα and IL-6 messenger RNA in T24 cells but not in BFTC905 cells. Addition of CpG-ODN induced interferon ß (INFß), IL-8, tumor necrosis factor α (TNFα) and the angiogenic factors vascular endothelial growth factor-A and placental growth factor in UMUC3 cells; whereas in RT112 cells, induction of IL-8 and TNFα was noticed. Interestingly, addition of CpG-ODN significantly reduced cell viability and increased cell invasion in UMUC3 and RT112 cells. CONCLUSIONS: Our findings demonstrate that bladder cancer cell lines express functional TLR4 and TLR9 with possible effects on cancer progression and outcome of BCG-based immunotherapy.


Asunto(s)
Citocinas/metabolismo , Invasividad Neoplásica , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 9/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Vacuna BCG/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Quimioterapia Adyuvante , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunidad Innata , Inmunoterapia , Lipopolisacáridos/química , Oligodesoxirribonucleótidos/genética , ARN Mensajero/metabolismo
11.
BMC Urol ; 14: 85, 2014 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-25370343

RESUMEN

BACKGROUND: The causality of overactive bladder syndrome (OAB) is still not fully understood. Several studies indicate a significant increase of prostaglandin E2 (PGE2) in patients with OAB. However, in order to clarify whether these compounds can help to objectify the clinical diagnosis, further studies are needed. This prospective study aims to analyze PGE2 blood levels (sPGE2) in patients with OAB before and after botulinum toxin type A (BoNT-A) therapy. METHODS: Blood samples were obtained from 56 patients (52y, 18-87) with idiopathic OAB. sPGE2 levels were measured before and 4 weeks after BoNT-A treatment by enzyme linked immunosorbent assay (ELISA). 31 healthy persons with normal bladder function served as control group (59 y, 21-72). sPGE2 was set in relation to clinical data and the severity of OAB (wet/dry). The statistical data analysis was performed by using the non-parametric Mann-Whitney U test and paired t-test. RESULTS: Significant higher sPGE2 levels were detected in patients with OAB compared to members of the control group (2750 pg/ml vs. 1674 pg/ml, p < 0.005). Furthermore sPGE2 levels were increased in patients with OAB wet compared to OAB dry (p <0.01). In 30 patients sPGE2 levels decreased significantly after BoNT-A treatment compared to baseline (2995 pg/ml vs. 1486 pg/ml, p <0.005). Patients reported an average drug effect of 9 month (0-19); incontinence pads were needed significantly less frequent (p < 0.05). 3 patients reported no postoperative effect. sPGE2 increased in two patients compared to initial levels, a single patient showed a remotely decreased sPGE2. Six patients were treated repeatedly with BoNT-A after showing an sPGE2 re-rise. CONCLUSIONS: sPGE2-level is increased in patients with OAB. We could prove a significant decrease of sPGE2 after BoNT-A treatment. In this small cohort we could demonstrate a correlation between OAB and sPGE2, especially in the non-responder group. The use of sPGE2 as a biomarker in diagnostics and follow-up after therapy seems promising. To what extent sPGE2 can be useful as such needs to be examined prospectively in a larger population.


Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Dinoprostona/sangre , Fármacos Neuromusculares/uso terapéutico , Vejiga Urinaria Hiperactiva/sangre , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/diagnóstico , Adulto Joven
12.
BMC Urol ; 14: 20, 2014 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-24552585

RESUMEN

BACKGROUND: Only limited data are available on the outcome of tension-free obturator tape (TOT) procedures in overweight and obese women. We would like to verify the objective and subjective outcomes of TOT in women with a higher body mass index (BMI). METHODS: We evaluated the records of 116 patients who had undergone TOT, stratifying by BMI into normal weight (n = 31), overweight (n = 56), and obese (n = 29) groups. We compared pre- and postoperative evaluations, including subjective and objective outcome of TOT, complications, and quality of life assessed by validated questionnaires (ICIQ-SF and KHQ). RESULTS: The median follow-up was 21 months. There were no significant differences between different groups in terms of objective cure rate and subjective success, quality of life scores and postoperative complications. CONCLUSIONS: Our data demonstrate that TOT procedure is safe and effective. BMI did not influence the outcome of TOT procedures at a median of 21 months after surgery and represents no contraindication for continence surgery. The success of the outcome of TOT procedure in females and the occurrence of complications are not negatively affected by obesity.


Asunto(s)
Obesidad/diagnóstico , Obesidad/cirugía , Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/diagnóstico , Incontinencia Urinaria de Esfuerzo/cirugía , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Calidad de Vida/psicología , Recuperación de la Función , Estudios Retrospectivos , Resultado del Tratamiento , Incontinencia Urinaria de Esfuerzo/complicaciones
13.
BMC Cancer ; 13: 589, 2013 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-24325461

RESUMEN

BACKGROUND: Dovitinib (TKI-258) is a receptor tyrosine kinase (RTK) inhibitor targeting fibroblast growth factor receptor (FGFR) and further related RTKs. TKI-258 is under investigation as anticancer drug for the treatment of various cancers including bladder cancer with aberrant RTK signaling. Here, we analyzed the responses of ten human bladder cancer cell lines towards TKI-258 treatment in relation to the epithelial mesenchymal transition (EMT) status of the cells. METHODS: Expression of epithelial marker E-cadherin as well as mesenchymal markers N-cadherin and vimentin was determined by quantitative RT-PCR and Western-blot in RNA and protein extracts from the cultured cell lines. The cell responses were analyzed upon addition of TKI-258 by viability/proliferation (XTT assay) and colony formation assay for measurement of cell contact independent growth. RESULTS: The investigated bladder cancer cell lines turned out to display quite different EMT patterns as indicated by the abundance of E-cadherin or N-cadherin and vimentin. Protein and mRNA levels of the respective components strongly correlated. Based on E-cadherin and N-cadherin mRNA levels that were expressed approximately mutual exclusively, an EMT-score was calculated for each cell line. A high EMT-score indicated mesenchymal-like cells and a low EMT-score epithelial-like cells. Then, we determined the IC50 values for TKI-258 by dose response curves (0-12 µM TKI-258) in XTT assays for each cell line. Also, we measured the clonogenic survival fraction after adding TKI-258 (1 µM) by colony formation assay. We observed significant correlations between EMT-score and IC50 values (r = 0.637, p = 0.0474) and between EMT-score and clonogenic survival fraction (r = 0.635, p = 0.0483) as analyzed by linear regression analyses. CONCLUSIONS: In sum, we demonstrated that the EMT status based on E-cadherin and N-cadherin mRNA levels may be useful to predict responses towards TKI-258 treatment in bladder cancer.


Asunto(s)
Antineoplásicos/farmacología , Bencimidazoles/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Quinolonas/farmacología , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Antígenos CD/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Expresión Génica , Humanos , Concentración 50 Inhibidora , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal , Neoplasias de la Vejiga Urinaria , Vimentina/metabolismo
14.
J Urol ; 189(2): 568-73, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23260552

RESUMEN

PURPOSE: We analyzed the indications for and outcomes of percutaneous nephrolithotomy using upper pole access. MATERIALS AND METHODS: Between 2007 and 2009 prospective data were collected by the Clinical Research Office of the Endourological Society (CROES) from consecutive patients at 96 centers globally. Data on 4,494 patients were included in this analysis. Patients were divided into upper and lower pole access groups based on the location of percutaneous renal access. Preoperative characteristics and outcomes were compared between the 2 groups by univariate and multivariate tests. RESULTS: The upper pole access group had more staghorn stones (21.7% vs 15.5%, p <0.001) and a greater stone burden (mean ± SD 476 ± 390.5 vs 442 ± 344.9 mm(2), p = 0.091). Mean operative time was 92.4 ± 46.1 and 75.1 ± 41.3 minutes in the upper and lower pole groups, respectively (p <0.001). The stone-free rate was lower in the upper pole access group (77.1% vs 81.6%, p = 0.030). The overall complication rate was higher in the upper pole group with a higher incidence of hydrothorax (5.8% vs 1.5%) but a lower incidence of pelvic perforation (1.8% vs 3.2%). Mean hospital stay was longer in the upper pole group (p = 0.048). Success and complication rates were similar in upper pole access subgroups, defined as definitive (staghorn and isolated upper calyceal stones) and elective (pelvic, middle calyceal and lower pole stones) indications. CONCLUSIONS: Isolated upper pole access is indicated in a select group of patients with complex stones. Upper calyceal and staghorn stones are more commonly managed by upper pole access, which is associated with a higher complication rate and longer hospital stay as well as a lower stone-free rate due to procedure complexity.


Asunto(s)
Cálculos Renales/cirugía , Nefrostomía Percutánea/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
15.
Urol Int ; 87(4): 439-44, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22004911

RESUMEN

OBJECTIVES: Botulinum toxin A (BTX-A) injection into the detrusor muscle has changed therapy options for patients with overactive bladder (OAB). However, in some patients, therapy fails or the effects of BTX-A decrease. The aim of this prospective study was to evaluate the incidence of BTX-A antibodies (BTX-A Abs) after injection of BTX-A and its clinical relevance. METHODS: 31 patients (27 women, 4 men) were treated with BTX-A for OAB between January 2009 and August 2010. Eleven patients were treated once, 16 patients were treated twice and 4 patients were treated three times. Blood was collected before and 3 months after the BTX-A injection and BTX-A Abs were determined. RESULTS: In 5 patients (16%) BTX-A Abs were detectable after the BTX-A injection. The BTX-A Ab titer was clearly positive in 1 patient (3.2%). This patient showed complete failure of BTX-A therapy. In 4 patients (13%) BTX-A Abs were slightly positive after the first BTX-A injection. The second BTX-A injection showed no positive effects in only 1 patient with borderline BTX-A Ab titers; the second BTX-A injection was successful in 2 patients. CONCLUSIONS: The incidence of BTX-A Abs should be verified in nonresponders. More data are necessary to check the clinical relevance and risk of BTX-A Ab formation, especially in long-term follow-up, to optimize patient selection for this minimally invasive treatment option in OAB.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/inmunología , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/inmunología , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Administración Intravesical , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biomarcadores/sangre , Esquema de Medicación , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
16.
Strahlenther Onkol ; 187(6): 367-72, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21603993

RESUMEN

PURPOSE: To compare the accuracy of the robot-assisted needle positioning with that of the conventional template-guided method with the help of a prostate model in high dose rate (HDR) brachytherapy. MATERIALS AND METHODS: A prostate model of fresh porcine abdomen and special polyvinylchloride (PVC) sheets was developed. To verify the model, deviations from 311 needle placements of real prostate implants were analyzed. Second, the accuracy of the template-guided positioning versus robot-assisted positioning was measured with 20 needle insertions in the model. For robot-assisted positioning, different velocities (2.7, 5.4, 9.8 mm/s) of needle insertion were investigated. RESULTS: The average needle positioning accuracies of manual template guidance on the model closely resembled those of real patients (approximately 3 mm). The average needle positioning accuracy for the robot-assisted method on the prostate model was 1.8 ± 0.6 mm, at a velocity of 2.7 mm/s and, in comparison to the template-guided method (2.7 ± 0.7 mm), was statistically more precise (p < 0.001). At higher robotic velocities, the measured needle positioning accuracy showed no significant difference from that of the manual insertion procedure. CONCLUSION: By employing a prostate model, we showed for the first time that robot-assisted needle placement for HDR brachy-therapy is significantly more precise than the conventional method at a velocity of 2.7 mm/s. The robot-assisted needle positioning technique improves the degree of freedom by providing additional oblique insertion channels and could be potentially exploited not only for LDR but also for HDR brachytherapy.


Asunto(s)
Braquiterapia/métodos , Modelos Anatómicos , Neoplasias de la Próstata/radioterapia , Robótica/normas , Humanos , Masculino
17.
Anticancer Res ; 30(12): 5195-200, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21187512

RESUMEN

BACKGROUND: Reliable blood and urine markers for transitional cell carcinoma of the bladder (TCC) do not currently exist. The aim of this prospective study was the serological and immunohistochemical evaluation of CA19.9 and CEA in TCC and to assess the correlation with different TCC stages. PATIENTS AND METHODS: CA19.9 and CEA levels were prospectively determined in samples from 231 patients with TCC suspected bladder lesions, before transurethral tumor resection. Additionally, these serum parameters were determined in 11 patients with initial metastatic TCC. Immunohistochemical analysis on CA19.9 and CEA was performed in 83 patients. RESULTS: Neither CA19.9 nor CEA levels were significantly elevated in TCC patients. Patients with muscle-invasive TCC showed significantly higher levels of CEA (p = 0.008) and CA19.9 (p<0.001) compared to those with superficial TCC. Significantly higher levels were also evident with increasing grade of malignancy. Metastatic TCC showed significantly elevated CA19.9 levels compared to muscle invasive TCC as well as locally advanced (pT3/pT4/pN+) compared to localized TCC (pT2/pN0). Immunohistochemical staining revealed a strong correlation between CA19.9 serum levels and staining intensity. CONCLUSION: CEA and CA19.9 are not useful markers in primary diagnosis of TCC. However, in instances of elevated CEA and CA19.9 levels where gastrointestinal malignancy has been excluded, evidence of TCC should be sought. If elevated CEA and CA19.9 are present in TCC, serum levels correlate with tumor invasion and grade of malignancy.


Asunto(s)
Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma de Células Transicionales/sangre , Neoplasias de la Vejiga Urinaria/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/patología , Estudios de Casos y Controles , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/patología , Adulto Joven
19.
Urol Res ; 38(1): 41-6, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19943042

RESUMEN

One of the challenges of intracorporeal ureterolithotripsy is undesired stone migration. Stone-trapping devices have been designed to prevent this quite common phenomenon. These devices have to be effective in terms of ureteral obstruction and safe in terms of resistance to the action of commonly used lithotriptors. This work was conducted to evaluate the efficacy and safety of the recently approved Accordion stone-trapping device in vitro. In a rigid, submerged ureteral model with two different diameters (8 and 10 mm), artificial stones were positioned in direct contact with the engaged Accordion device. A defined number of pneumatic pulses of the LithoClast master at different performance levels was applied and the migration distance of the stone was measured after each single pulse. As a control, the same series was repeated without the stone-trapping device. Secondly, the Accordion device was exposed to a previously defined number of pneumatic or Ho:YAG-laser pulses, in direct contact with the lithotripsy probe, up to a total activation time of 2 min. At different time points, the device was controlled for damage and functionality. The mean stone migration distance without the Accordion device was between 39.2 and 52.8 mm and between 37.8 and 75.4 mm in the 8 and 10 mm tubes, respectively. In comparison, the stone or fragment travelling distance with the device was in the 0-2 mm range. This difference was highly significant. Both pneumatic and laser lithotriptor did not affect the functionality of the Accordion device. The Ho:YAG laser causes small perforations of the film without affecting the devices' stability. The Accordion device appears to be highly efficient and safe in vitro. Clinical trials will have to assess its value in endourological practice. Randomised comparative trials comparing different stone-trapping devices are needed.


Asunto(s)
Litotricia/instrumentación , Cálculos Ureterales/terapia , Diseño de Equipo
20.
Int J Urol ; 16(9): 718-22, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19659680

RESUMEN

OBJECTIVES: Current data on the prognostic impact of urinary collecting system (UCS) invasion by renal cell carcinoma (RCC) are highly conflicting. The aim of the present study was to assess incidence and long-term prognosis of RCC patients with and without UCS involvement. METHODS: We evaluated 780 patients who had undergone renal surgery between 1990 and 2005. The mean follow-up was 5.44 years. RESULTS: Sixty-seven patients (8.6%) demonstrated UCS invasion. These patients had a significant increase in the likelihood of cancer-related death (hazard ratio [HR] 1.9, 95% confidence interval: 1.4-2.7; P = 0.001). Their median 5-year tumor-specific survival rate was 61%, as opposed to 79% for patients without UCS invasion (P = 0.001). UCS invasion was significantly associated with tumor stage, grade, clinical symptoms, lymph node and visceral metastasis at diagnosis, but not with age, gender, histologic subtype or body mass index. However, by means of multivariate analysis, UCS invasion was disqualified as an individual prognostic marker for RCC. CONCLUSION: We do not advocate the inclusion of UCS invasion into upcoming Tumor-Nodes-Metastasis staging systems. In contrast, future research should focus on the prognostic role of novel molecular tumor markers and/or specific immunological characteristics of RCC patients.


Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Túbulos Renales Colectores/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Incidencia , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Urotelio/patología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...