RESUMEN
High grade non-muscle-invasive bladder tumours are treated with transurethral resection followed by recurrent intravesical instillations of Bacillus Calmette Guérin (BCG). Although most bladder cancer patients respond well to BCG, there is no clinical parameter predictive of treatment response, and when treatment fails, the prognosis is very poor. Further, a high percentage of NMIBC patients treated with BCG suffer unwanted effects that force them to stop treatment. Thus, early identification of patients in which BCG treatment will fail is really important. Here, to identify early stage non-invasive biomarkers of non-responder patients and patients at risk of abandoning the treatment, we longitudinally analysed the phenotype of cells released into the urine of bladder cancer patients 3-7 days after BCG instillations. Mass cytometry (CyTOF) analyses revealed a large proportion of granulocytes and monocytes, mostly expressing activation markers. A novel population of CD15+CD66b+CD14+CD16+ cells was highly abundant in several samples; expression of these markers was confirmed using flow cytometry and qPCR. A stronger inflammatory response was associated with increased cell numbers in the urine; this was not due to hematuria because the cell proportions were distinct from those in the blood. This pilot study represents the first CyTOF analysis of cells recruited to urine during BCG treatment, allowing identification of informative markers associated with treatment response for sub-selection of markers to confirm using conventional techniques. Further studies should jointly evaluate cells and soluble factors in urine in larger cohorts of patients to characterise the arms of the immune response activated in responders and to identify patients at risk of complications from BCG treatment.
Asunto(s)
Neoplasias de la Vejiga Urinaria , Administración Intravesical , Vacuna BCG/uso terapéutico , Humanos , Proyectos Piloto , Pronóstico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Background: Intra-vesical instillation of Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is an effective therapy for high-grade non-muscle invasive bladder cancer (NMIBC), which provokes a local immune response resulting in 70% of patients free of relapse after three years. Because non-responder patients usually have a bad prognosis, the early identification of treatment failure is crucial. We hypothesized that, if an effective immune response was taking place in the bladder, soluble factors would be released to the urine many days after BCG instillations. Methods: An extensive panel of cytokines and chemokines released into the urine seven days after every BCG instillation was screened in a cohort of NMIBC patients over three years. Results: The determinations of the urinary concentrations of cytokines, chemokines, and creatinine showed that increasing concentrations of C-X-C motif chemokine 10 (CXCL10) also known as interferon-inducible protein 10 (IP10) could be detected during the six-week induction cycle of BCG-treated patients released into the urine by CD14+ cells. In vitro, CXCL10 facilitated the recruitment of effector immune cells after the BCG-mediated upregulation of CXCR3 in both T- and natural killer (NK)-cells. Conclusions: The high concentrations of chemokine detected one week after the encounter with mycobacteria suggest that the CXCL10 axis might be related to the intensity of the immune anti-tumor response.
RESUMEN
OBJECTIVES: To evaluate the efficacy and safety of High Intensity Focused Ultrasound (HIFU) as salvage treatment after radical radiotherapy in prostate cancer (PC). METHODS: We reviewed the literature through databases and published articles that refer to this treatment between 2000 and 2010. We evaluated oncological results and adverse effects, compared with those published in conjunction with other therapies. RESULTS: We evaluated the different series, which include the results of the two devices currently available, all with their initial results and those that are in the process of dose adjustment. Generally, it can be said that the biggest problem of all is that initial morbidity is reduced as the surgeon gains experience with the treatment. We must stress the importance of the short series that are evaluated, especially in follow-up time and number of patients. Also, except for a recently published systematic review, no prospective studies are published. The results from different series are compared with existing literature regarding to other PC treatments. CONCLUSIONS: In spite of published results, the treatment with HIFU for prostate cancer recurrence after radiotherapy is an option that should be considered. Especially considering that, it is important to delay the development of the disease in these patients, and there are no other alternatives that have proven to be effective. Further research is needed to explore the use of HIFU in the treatment of PC. Anyway, it is essential to publish comparative prospective series and series with more patients and longer follow-up to draw definitive conclusions.
Asunto(s)
Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Próstata/cirugía , Terapia Recuperativa , Ultrasonido Enfocado Transrectal de Alta Intensidad , Diseño de Equipo , Humanos , Masculino , Neoplasias de la Próstata/radioterapia , Ultrasonido Enfocado Transrectal de Alta Intensidad/instrumentaciónRESUMEN
OBJETIVO: Evaluar la eficacia y seguridad de los Ultrasonidos de Alta Intensidad Focalizados (HIFU) como tratamiento de rescate tras radioterapia radical en el cáncer de próstata (CP). MÉTODOS: Se revisa la literatura a través de bases de datos y los artículos publicados que hacen referencia a este tratamiento entre el año 2000 y el 2010. Se han evaluado los resultados oncológicos, así como los efectos adversos, comparando con lo publicado en relación con otras terapias existentes. RESULTADOS: Se evalúan las distintas series publicadas, en las que se incluyen los resultados de los dos dispositivos disponibles en la actualidad, todas ellas con sus resultados iniciales y las que se encuentran en fase de ajuste de dosis. Se puede afirmar de forma general que el mayor problema de todas ellas resulta la morbilidad incial que se reduce según se gana en experiencia con el tratamiento. De forma generalizada, hay que resaltar la importancia de lo cortas que son las series evaluadas, sobre todo en tiempo de seguimiento y en número de pacientes. Asimismo, salvo una revisión sistemática recientemente publicada, no existe ningún estudio prospectivo con ninguno de los dos dispositivos. Todos los resultados de las distintas series publicadas son comparados con la literatura existente en relación a los distintos tratamientos del CP. CONCLUSIONES: A pesar de los resultados publicados, el tratamiento mediante HIFU en la recidiva del cáncer de próstata tras radioterapia es una opción que debe ser considerada. Sobre todo teniendo en cuenta que, en estos pacientes, es importante retrasar el desarrollo de la enfermedad y que no existen otras alternativas que hayan demostrado ser eficaces. Es necesaria una mayor investigación para explorar la utilización de HIFU en el tratamiento cel CP. En cualquier caso, es fundamental la publicación de series prospectivas comparativas y series con mayor número de pacientes y de más largo seguimiento para poder sacar conclusiones definitivas(AU)
OBJECTIVES: To evaluate the efficacy and safety of High Intensity Focused Ultrasound (HIFU) as salvage treatment after radical radiotherapy in prostate cancer (PC). METHODS: We reviewed the literature through databases and published articles that refer to this treatment between 2000 and 2010. We evaluated oncological results and adverse effects, compared with those published in conjunction with other therapies. RESULTS: We evaluated the different series, which include the results of the two devices currently available, all with their initial results and those that are in the process of dose adjustment. Generally, it can be said that the biggest problem of all is that initial morbidity is reduced as the surgeon gains experience with the treatment. We must stress the importance of the short series that are evaluated, especially in follow-up time and number of patients. Also, except for a recently published systematic review, no prospective studies are published. The results from different series are compared with existing literature regarding to other PC treatments. CONCLUSIONS: In spite of published results, the treatment with HIFU for prostate cancer recurrence after radiotherapy is an option that should be considered. Especially considering that, it is important to delay the development of the disease in these patients, and there are no other alternatives that have proven to be effective. Further research is needed to explore the use of HIFU in the treatment of PC. Anyway, it is essential to publish comparative prospective series and series with more patients and longer follow-up to draw definitive conclusions(AU)