RESUMEN
BACKGROUND: Measurement of residual disease following neoadjuvant chemotherapy that accurately predicts long-term survival in locally advanced breast cancer (LABC) is an essential requirement for clinical trials development. Several methods to assess tumor response have been described. However, the agreement between methods and correlation with survival in independent cohorts has not been reported. PATIENTS AND METHODS: We report survival and tumor response according to the measurement of residual breast cancer burden (RCB), the Miller and Payne classification and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in 151 LABC patients. Kappa Cohen's coefficient (Ð) was used to test the agreement between methods. We assessed the correlation between the treatment outcome and overall survival (OS) and relapse-free survival (RFS) by calculating Harrell's C-statistic (c). RESULTS: The agreement between Miller and Payne classification and RCB classes was very high (Ð = 0.82). In contrast, we found a moderate-to-fair agreement between the Miller and Payne classification and RECIST criteria (Ð = 0.52) and RCB classes and RECIST criteria (Ð = 0.38). The adjusted C-statistic to predict OS for RCB index (0.77) and RCB classes (0.75) was superior to that of RECIST criteria (0.69) (P = 0.007 and P = 0.035, respectively). Also, RCB index (c = 0.71), RCB classes (c = 0.71) and Miller and Payne classification (c = 0.67) predicted better RFS than RECIST criteria (c = 0.61) (P = 0.005, P = 0.006 and P = 0.028, respectively). CONCLUSIONS: The pathological assessment of tumor response might provide stronger prognostic information in LABC patients.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Taxoides/uso terapéutico , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/patología , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Docetaxel , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasia Residual , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Carga TumoralRESUMEN
Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carboplatino/uso terapéutico , Terapia Neoadyuvante , Neoplasias Basocelulares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
BACKGROUND: Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting. PATIENTS AND METHODS: Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) 4 cycles followed by docetaxel 100 mg/m(2 )4 cycles [EC-T]) or HT (exemestane 25 mg daily 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging. RESULTS: Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT. CONCLUSIONS: Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante/efectos adversos , Adulto , Anciano , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Docetaxel , Epirrubicina/efectos adversos , Epirrubicina/uso terapéutico , Receptores ErbB/metabolismo , Femenino , Humanos , Queratina-18/metabolismo , Queratina-8/metabolismo , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Taxoides/efectos adversos , Taxoides/uso terapéutico , Resultado del TratamientoRESUMEN
UNLABELLED: Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of response to these drugs. EXPERIMENTAL DESIGN: Four cycles of doxorubicin (75 mg/m²) or docetaxel (100 mg/m²) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate - PCR + class I of 56 vs. 0%; P = 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.
Asunto(s)
Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/genética , Genes Relacionados con las Neoplasias , Taxoides/uso terapéutico , Adulto , Anciano , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Docetaxel , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Humanos , Persona de Mediana Edad , Análisis Multivariante , Resultado del TratamientoRESUMEN
OBJECTIVE: The meaning of biopsy C4d detection in heart allografts without dysfunction or morphologic changes suggesting antibody-mediated rejection (AMR) is not clear. The aim of this study was to search for an association between C4d detection in allograft biopsies of well-functioning hearts without changes suggestive of AMR, and clinical outcomes. METHODS: Endomyocardial protocol biopsies from 44 heart transplant patients with well-functioning grafts and without changes suggesting AMR were performed at 1 month and 1 year after transplantation and analyze the presence of C4d deposition using immunohistochemistry. Two-year follow-up was based on clinical parameters and echocardiographic information. Heart graft function was categorized as good vs. poor. The presence of C4d, using diverse schemes to graduate the extension of the deposition, was correlated with clinical graft outcomes. RESULTS: C4d deposition was observed in the capillary walls of 33 biopsies (37.5%; n = 25 patients; 56.8%). No biopsy had diffuse (>50%) immunostaining. Six patients presented with multifocal capillary C4d immunostaining in at least 1 biopsy. Capillary positivity for C4d (if focal or multifocal) showed no statistical association with cellular rejection or graft function. Perimyocytic C4d detection was neither associated with rejection nor graft outcome. CONCLUSION: Our work failed to demonstrate an association between C4d detection in protocol biopsies of heart grafts and clinical outcomes. The clinical utility of C4d staining in solid organ transplantation may vary by organ. Our results suggest that C4d did not have clinical utility in surveillance biopsies of well-functioning heart grafts without morphological changes suggesting AMR.
Asunto(s)
Complemento C4b/análisis , Rechazo de Injerto/patología , Trasplante de Corazón/inmunología , Fragmentos de Péptidos/análisis , Adolescente , Adulto , Biomarcadores/análisis , Biopsia , Capilares/inmunología , Capilares/patología , Niño , Preescolar , Femenino , Rechazo de Injerto/inmunología , Trasplante de Corazón/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Trasplante Homólogo/inmunología , Trasplante Homólogo/patología , Resultado del TratamientoRESUMEN
Objetivo: El Hospital Clínico San Carlos de Madrid, es el primer centro público español en disfrutar de la última tecnología en cuanto a cirugía se refiere: el robot Da Vinci®. La primera intervención fue llevada a cabo en nuestro servicio el nueve de octubre de 2006. Desde entonces, se han producido numerosos cambios que nos han permitido ir superando dificultades, hasta superar la curva de aprendizaje. Métodos: Durante el período comprendido entre el 9 de octubre de 2006 y el 30 de noviembre de 2007 hemos realizado 30 prostatectomías radicales con el robot Da Vinci®. La edad media de los pacientes es de 63 años (47-70 años) con riesgo quirúrgico según la Asociación Americana de Anestesia siempre inferior a III, un grado de Gleason entre 2 y 8 y PSA≤15 (3,5-15). El volumen prostático medio valorado por ecografía transrectal fue de 36cc (16-90cc). Resultados/Conclusiones: Se utilizaron 6 trócares y un neuoperitoneo de 15mmHg. La duración media del tiempo de ocupación de quirófano fue de 5,9 horas (4-14horas). Dos casos fueron reconvertidos a cirugía abierta y uno a laparoscopia. No se han producido complicaciones intraoperatorias severas. En el postoperatorio inmediato 2 pacientes presentaron plexopatía y artralgia, 1 infección de uno de los trócares y 2 hematomas por colocación del trócar. 16 pacientes requirieron transfusión (media 1 concentrado (0-4)). La sonda se retiró entre el 5º y 21º días (media 11 días). En lo referente a incontinencia: 10 presentan una continencia completa o incontinencia leve (0-1 absorbentes) y 5 incontinenciamoderada (2-5 absorbentes). La potencia sexual se mantiene en 3 pacientes y en el resto existen diferentes grados de disfunción (AU)
Objectives: Hospital Clínico San Carlos in Madrid is the first Spanish public centre using the latest surgical technology: the Da Vinci® robot. First operation was carried out in our department in October 9th 2006. Since then, numerous changes have happened which enabled us to overcome difficulties, to complete the learning curve. Methods: Between October 9th 2006 and November30th 2007 we performed 30 radical prostatectomies with the Da Vinci® robot. Mean patient age was 63 years (47-70 years) with an ASA (American society of anesthesia) risk below III in all cases, a Gleason score between 2 and 8 and a PSA ≤ 15 (3.5-15). Mean prostatic volume measured by transrectal ultrasound was 36 cc (16-90 cc). Results/Conclusions: Six trocars and a 15 mm Hg pneumoperitoneum were employed. Mean operative room occupation time was 5.9 hours (4-14 hours). Two cases were converted to open surgery and one to laparoscopy. No major intraoperative complications have happened. In the immediate post-operative period,2 patients presented plexopathy and arthralgia, 1 infection at the site of one trocar, and 2 haematomas at the site of trocar insertion. Sixteen patients required transfusion (mean 1 red blood cells unit (0-4)). Bladder catheter was retrieved between 5th and 21st post-operative days (mean 11 days). Regarding continence: 10 patients were completely continent or present mild incontinence (0-1 pad) and 5 had moderate incontinence (2-5 pads). Three patients preserve sexual potency, the rest show different grades of dysfunction (AU)
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Prostatectomía/métodos , Robótica/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Laparoscopía/métodos , Profilaxis Antibiótica/métodos , Protocolos Clínicos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Prostatectomía/tendencias , Ciprofloxacina/uso terapéutico , Enoxaparina/uso terapéutico , Complicaciones Posoperatorias/diagnóstico , Procedimientos Quirúrgicos Mínimamente Invasivos/tendenciasRESUMEN
Osteoarthritis (OA) is largely considered to be a non-inflammatory disease, although there is compelling evidence that subclinical inflammation is a common event, even in the absence of acute inflammatory flares. In this study we analyze, by means of CD5 and CD69 expression, the infiltration and early activation of CD5+cells, mostly lymphocytes, in both synovial membrane and synovial fluid from advanced OA patients and compare them with samples from patients with rheumatoid arthritis and healthy controls. The number of infiltrating CD5+ cells in both synovial membrane and synovial fluid from patients with advanced OA was significantly reduced as compared with rheumatoid arthritis patients. However, synovial membrane and synovial fluid CD5+ cells on OA exhibited a phenotype with evidence of recent activation comparable to that observed in RA.
Asunto(s)
Artritis Reumatoide/inmunología , Activación de Linfocitos/inmunología , Osteoartritis/inmunología , Líquido Sinovial/inmunología , Membrana Sinovial/inmunología , Anciano , Anciano de 80 o más Años , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Artritis Reumatoide/patología , Antígenos CD5/inmunología , Estudios de Casos y Controles , Separación Celular , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Lectinas Tipo C , Masculino , Persona de Mediana Edad , Osteoartritis/patología , Membrana Sinovial/patologíaRESUMEN
Skin metastases are infrequent manifestations of solid tumours. However, it is important to recognize them since they may be the first evidence of a neoplasia, or a sign of tumour progression or recurrence. Skin metastases from gastric adenocarcinomas are particularly rare, and represent 6% of the total in males and 1% in females. We report, here, the case of a patient diagnosed with gastric adenocarcinoma with extensive subcutaneous infiltration of the abdominal wall, resulting in an abdominal cuirass.
Asunto(s)
Adenocarcinoma/secundario , Neoplasias Cutáneas/secundario , Neoplasias Gástricas/patología , Femenino , Humanos , Persona de Mediana Edad , Piel/patologíaRESUMEN
No disponible
Asunto(s)
Femenino , Recién Nacido , Persona de Mediana Edad , Humanos , Adenocarcinoma/secundario , Neoplasias Cutáneas/secundario , Neoplasias Gástricas/patología , Piel/patologíaRESUMEN
OBJECTIVE: To evaluate the role of parvovirus B19 (B19), varicella zoster virus (VZV), and human herpes virus 6 (HHV-6) in the aetiopathology of giant cell arteritis (GCA). METHODS: Temporal artery biopsy specimens from 57 patients with GCA and 56 controls were investigated. DNA was obtained by biopsy, and quantitative real time polymerase chain reaction assay performed to establish the prevalence and viral load of B19, VZV, and HHV-6. Amplification of the human beta-globin gene was used as internal positive control. RESULTS: (a) B19 was detected in 31/57 (54%) patients (median viral load 45.2 (25th-75th centiles 0-180.2) copies/microg DNA) v 21/56 (38%) controls (median viral load 0 (0-66.7) copies/microg of DNA; p = 0.07 for DNA prevalence, p = 0.007 for viral load. Among 31 B19 positive samples, 21 (68%) patients with biopsy proven GCA had >10(2) B19 copies/microg of DNA v 5/21 (24%) controls; p = 0.001. (b) No significant difference was found for VZV (p = 0.94 for DNA prevalence; p = 0.76 for viral load) and HHV-6 (p = 0.89 for DNA prevalence; p = 0.64 for viral load) in the GCA group compared with controls. CONCLUSION: B19 may have a role in the aetiopathology of GCA, particularly in those patients with high viral load; no evidence was found for VZV and HHV-6.
Asunto(s)
Arteritis de Células Gigantes/virología , Herpesvirus Humano 3/aislamiento & purificación , Herpesvirus Humano 6/aislamiento & purificación , Infecciones por Parvoviridae/complicaciones , Parvovirus B19 Humano/aislamiento & purificación , Anciano , Anciano de 80 o más Años , ADN Viral/análisis , Femenino , Herpes Zóster/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Roseolovirus/complicaciones , Carga ViralRESUMEN
Tumor growth is a surface phenomenon of the molecular beam epitaxy universality class in which diffusion at the surface is the determining factor. This Letter reports experiments performed in mice showing that these dynamics can, however, be changed. By stimulating the immune response, we induced strong neutrophilia around the tumor. The neutrophils hindered cell surface diffusion so much that they induced new dynamics compatible with the slower quenched-disorder Edwards-Wilkinson universality class. Important clinical effects were also seen, including remarkably high tumor necrosis (around 80%-90% of the tumor), a general increase in survival time [the death ratio in the control group is 15.76 times higher than in the treated group (equivalent to a Cox's model hazard ratio of 0.85; 95% confidence interval 0.76-0.95, p=0.004)], and even the total elimination of some tumors.
Asunto(s)
Carcinoma de Ehrlich/inmunología , Carcinoma de Ehrlich/patología , Modelos Inmunológicos , Animales , División Celular/inmunología , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunologíaRESUMEN
No disponible
Asunto(s)
Humanos , Quistes Óseos/congénito , Neoplasias de Cabeza y Cuello/patología , Diagnóstico Diferencial , Biopsia con Aguja FinaRESUMEN
Describimos el caso de una paciente de 61 años diagnosticada de artritis reumatoide. Desarrolló hematuria masiva con expulsión de coágulos sanguíneos; una biopsia de la mucosa vesical reveló amiloidosis secundaria. La amiloidosis secundaria sintomática de la vejiga es muy rara. Solamente se han descrito 22 casos en la bibliografía. La mayoría de estos casos tenía enfermedades reumáticas, más frecuentemente artritis reumatoide (AR) y espondilitis anquilosante (EA). Creemos que es necesario tener en cuenta la posibilidad de amiloidosis secundaria de la vejiga cuando el reumatólogo se enfrente a un paciente con artritis reumatoide y hematuria macroscópica (AU)
We describe the case of a 61-year-old woman with a diagnosis of rheumatoid arthritis. She developed massive hematuria with expulsion of blood clots. Biopsy of the vesical mucosa revealed secondary amyloidosis. Symptomatic amyloidosis of the bladder is highly infrequent and only 22 cases have been reported in the literature. Most reported patients had rheumatic disease, especially rheumatoid arthritis and ankylosing spondylitis. The possibility of secondary amyloidosis of the bladder should be suspected in patients with rheumatoid arthritis and gross hematuria (AU)
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Hematuria/complicaciones , Hematuria , Amiloidosis/complicaciones , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/diagnóstico , Prednisona/uso terapéutico , Azatioprina/uso terapéutico , Vejiga Urinaria/cirugía , Vejiga Urinaria , BiopsiaRESUMEN
Propósito: Descripción de un caso de recidiva única mediastínica adenopática diagnosticada por PET de carcinoma epidermoide de pulmón estadio I. Material y métodos: Varón de 70 años, intervenido quirúrgicamente de carcinoma epidermoide de pulmón estadio I, presentando tras 28 meses, recidiva ganglionar única subcarinal, confirmada por PET y tratada con quimioterapia con reducción del 50 por ciento tras 2 ciclos de quimioterapia. Resultados: Se realiza una revisión de la literatura orientada a determinar los factores pronósticos moleculares en cáncer de pulmón no de células pequeñas en estadios precoces y a valorar la utilidad de la tomografía por emisión de positrones (PET-FDG) en el diagnóstico de enfermedad recurrente. Conclusiones: Aunque el PET-FDG puede ayudar en el diagnóstico de las recaídas locales asintomáticas, no se conocen aún las consecuencias del tratamiento precoz de las mismas ni la repercusión en la supervivencia o el pronóstico final. La determinación del grado de proliferación celular con Ki 67 y c-erb2 realizados inicialmente podrían aportar información acerca de las posibilidades de respuesta a la quimioterapia (AU)
Asunto(s)
Anciano , Masculino , Humanos , Tomografía Computarizada de Emisión , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Recurrencia Local de Neoplasia , Carcinoma de Células Escamosas/cirugía , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
BACKGROUND: The aims of this study have been to describe survival to oral cancer and to identify clinical variables with independent influence on its prognosis before treatment. METHODS: 94 oral cancer patients treated during 1991-99 entered the study. The variables considered were: age, sex, location of the lesion, clinical presentation, symptoms, TNM classification, months elapsed since treatment and ploidy pattern. A descriptive study of the data was performed, along with a survival analysis using Kaplan-Meier curves (log rank test for comparison among curves) and single and multivariate Cox regression. RESULTS: Multivariate analysis recognized a prognostic value for the age of the patient (OR = 1.06; CI95%: 1.02-1.09) and also for tumour size. Tumour stage resulted also selected, but its predictive value was lower than size's, so it was excluded from the predictive model. No statistically significant differences in terms of survival were identified on the rest of variables considered in the study. CONCLUSIONS: This study suggests the need for considering age and tumour size as the most relevant clinical variables for predicting survival to oral cancer at the time of diagnosis.
Asunto(s)
Neoplasias de la Boca/mortalidad , Medición de Riesgo , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Aneuploidia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Intervalos de Confianza , Diploidia , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Suelo de la Boca/patología , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Análisis Multivariante , Estadificación de Neoplasias , Oportunidad Relativa , Pronóstico , Modelos de Riesgos Proporcionales , Factores Sexuales , España/epidemiología , Tasa de Supervivencia , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/mortalidad , Neoplasias de la Lengua/patologíaRESUMEN
OBJECTIVE: To analyze the mechanisms involved in the characteristic hyperexpression of CD23 on peripheral blood B cells from patients with rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from patients with active disease and activated during 18 h with an anti-CD3 monoclonal antibody in the presence or absence of blocking antibodies to CD154 or CD40. PBMC were further purified by rosetting and CD23 expression was assessed on B cells by flow cytometry after double staining (CD19/CD23). Lymphocytes were also isolated from synovial fluid (SF). CD154 expression was analyzed on PB or SF CD4+ T cells after double staining (CD4/CD154) by flow cytometry at basal conditions and after different stimuli [anti-CD3 or phorbol myristic acetate (PMA) plus ionomycin]. Co-culture experiments between SF and PB cells were performed to analyze the involvement of the CD40-CD154 interaction on CD23 expression. CD154 and CD23 expression was also analyzed on synovial membrane by immunohistochemical techniques. RESULTS: A high proportion of activated CD23 B cells was detected in patients with RA. Blocking experiments with both anti-CD40 and anti-CD154 Mab showed a significant reduction in the proportion of PB B cells expressing CD23. Following activation with anti-CD3 Mab or PMA plus ionomycin, CD154 expression was mainly induced on PB CD4+ T cells. In co-culture experiments, SF T cells were more efficient than PB T cells in inducing CD40 dependent CD23 expression on PB B cells. In addition, CD4+ T cells from synovial membrane clearly expressed CD154. CONCLUSION: Our results establish a link between CD154-CD40 pathway and CD23 expression on PB B cells from patients with RA. T cells from the synovial microenvironment were active participants in this CD23 expression, presumably in the context of cell recirculation.
Asunto(s)
Artritis Reumatoide/inmunología , Linfocitos B/metabolismo , Receptores de IgE/biosíntesis , Anticuerpos Monoclonales/farmacología , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Antígenos CD40/inmunología , Ligando de CD40/biosíntesis , Ligando de CD40/inmunología , Humanos , Activación de Linfocitos/inmunología , Membrana Sinovial/citología , Membrana Sinovial/inmunologíaRESUMEN
OBJECTIVE: To evaluate the prognostic value of flow cytometric DNA quantification and immunohistochemical expression of c-erbB-2 and p53, and traditional clinicopathologic variables in stages I-II invasive epithelial ovarian cancer. METHODS: We retrospectively reviewed 77 cases of stages I-II ovarian cancer after comprehensive surgical staging. We recorded anthropometric data (age, menopausal status, weight loss, Karnofsky index) and pathologic variables (tumor size, bilaterality, capsular status, ascites, peritoneal cytology, histologic type, and grade). In 72 cases representative paraffin-embedded samples were available for DNA quantification and immunohistochemical evaluation of c-erbB-2 and p53 overexpression. Most women (87%) had received cisplatin-based adjuvant chemotherapy. RESULTS: The median follow-up was 90 months (range 50-148 months). The 6-year overall disease-free survival rate was 70% (95% confidence interval [CI] 60%, 81%), and overall global survival was 77% (95% CI 67%, 87%). Multivariable analysis using Cox stepwise regression identified DNA content (odds ratio [OR] 12.3; P <.001) and stage (OR 1.4, P =.09) as independent poor prognosis factors for relapse, and DNA content (OR 9.8, P <.001) as the main independent factor for survival. In stepwise discriminant analysis the combination of DNA content and stage provided a correct prediction of relapse in 78% of women. CONCLUSION: Flow cytometric DNA quantification was the main independent prognostic factor of relapse and survival in these women with stages I-II epithelial ovarian cancer.
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Carcinoma/diagnóstico , ADN de Neoplasias/análisis , Genes erbB-2/genética , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Ováricas/diagnóstico , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Registros Médicos , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Neoplasias Ováricas/mortalidad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , España/epidemiología , Análisis de SupervivenciaRESUMEN
OBJECTIVE: Since its discovery as a marker for prostate cancer, there have been many attempts to enhance the diagnostic efficacy of the prostate specific antigen (PSA). Among these are the studies that analyze the behavior of different forms of serum PSA bound to different antiproteases, such as alpha-1-antichymotrypsin, which forms the complexed PSA (PSA-c). This study analyzed the utility of PSA-c to enhance specificity without altering sensitivity in comparison to total PSA (PSA-t). METHODS: From September 1998 to March 1999, blood samples were obtained from 96 patients that had undergone a prostate biopsy due to a suspicion of prostate cancer. PSA-c, PSA-t (Technicon Immunol system, Bayer) and PSA-c/PSA-t ratio were analyzed in these patients. RESULTS: ROC curves were plotted and the optimal cutoffs were found for which the specificity was higher for PSA-c (44.6% [CI 95%, 32-57]) versus PSA-t (35.4% [CI 95%, 25-49]) and the PSA-c/PSA-t ratio (38.5% [CI 95%, 27-51]) while maintaining a similar sensitivity index (90%). PSA-c showed similar results for other values of sensitivity. CONCLUSIONS: PSA-c was found to improve specificity in comparison to PSA-t and PSA-c/PSA-t ratio. PSA-c determination could avoid unnecessary biopsies without altering sensitivity; i.e., the same number of prostate cancers will be detected.
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Adenocarcinoma/sangre , Adenocarcinoma/diagnóstico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Anciano , Humanos , Masculino , Valor Predictivo de las Pruebas , Curva ROC , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: Mutations in the TP53 gene are frequently detected in some types of malignant tumors (bladder, prostate, kidney, lungs, breast, colon and rectum). This study analyzed the utility of semi-quantitative determination of p53 in transitional cell carcinoma of the bladder by an immunohistochemical technique and evaluated the results at 5 years. METHODS/RESULTS: A prospective clinical cohort study was conducted on 81 patients. The study comprised two groups: nontumoral bladder tissue specimens from 20 patients (group I) and tissue specimens from 61 patients with bladder carcinoma (group II). In both groups the tissue specimens were obtained between November 1992 and November 1993, and during the follow-up period until July 1998. p53 expression was determined by a semi-quantitative method based on an immunohistochemical technique (NCL-p53-DO7, Novocastra). CONCLUSIONS: p53 oncoprotein was not found to be useful in the characterization of carcinoma of the urinary bladder.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/química , Proteínas de Neoplasias/análisis , Proteína p53 Supresora de Tumor/análisis , Neoplasias de la Vejiga Urinaria/química , Anciano , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Estudios de Seguimiento , Genes p53 , Humanos , Tablas de Vida , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVES: 1) To determine p53 expression in urinary wash cytology by immunohistochemistry in patients with superficial transitional cell carcinoma of the bladder and controls; 2) to correlate p53 in urinary wash cytology and anatomopathological characteristics of the bladder tumors analyzed; 3) to determine the utility of p53 expression in urinary wash cytology as a prognostic factor; and 4) to identify a subgroup of patients with superficial tumors of worse prognosis in order to improve control of the evolution of the tumor and treatment. METHODS: From 1993 to 1998, 141 cases were studied; 32 controls comprised group I and 109 (38 primary and 71 recurrence) patients with transitional cell carcinoma of the urinary bladder comprised group II. RESULTS: In group II, 29.5% were positive for p53 in urinary wash cytology, while no positive cases were found in group I. A total of 104 valid data were analyzed, which showed a higher percentage of p53-positive cases in grade III tumors (44.4%). Statistical analysis showed the percentage of p53-positive cases increased with tumor grade in a linear trend (p = 0.17). The recurrence rate in the p53-positive was 20% greater than in the p53-negative cases. Tumor progression was three times higher in the p53-positive than in the p53-negative patients. CONCLUSIONS: The application of biomolecular knowledge to cytology is a useful complement in follow-up of patients with superficial transitional cell carcinoma of the bladder and offers additional parameters to distinguish benign and malignant cells. Immunohistochemical determination of p53 in urinary wash cytology identifies patients with superficial tumors with a worse prognosis.