RESUMEN
Antecedentes y objetivo Los niveles elevados de vitaminaB12 se han asociado a enfermedades oncohematológicas. Sin embargo, se desconoce la relevancia de su detección incidental en sujetos sin un diagnóstico previo de cáncer. El objetivo de este estudio es evaluar la relación de la hipercobalaminemia y el diagnóstico de un proceso tumoral y establecer los factores de riesgo. Material y métodos Estudio observacional retrospectivo de una cohorte de pacientes con hipercobalaminemia. Se comparó la incidencia de neoplasias con una cohorte de pacientes con vitaminaB12<1.000pg/ml. Resultados Se seleccionaron 4.800 sujetos con determinaciones de vitaminaB12: 345 (7,1%) presentaban niveles >1.000pg/ml. Se excluyeron 68 (28,4%) por administración exógena, 12 (5%) por datos insuficientes y 15 (3%) por una neoplasia activa, seleccionando 250 pacientes; mediana de seguimiento: 22 (RIQ: 12-39) meses. Se detectó: hepatopatía 59 (23,6%), 44 (18,2%) presentaron cáncer de órgano sólido y 17 (7,1%), hemopatía maligna. El tiempo medio desde la detección de hipercobalaminemia al diagnóstico fue de 10meses. La mediana hasta el diagnóstico fue mayor en el grupo de vitaminaB12 elevada (13 vs 51meses; p<0,001). La hipercobalaminemia (HR_ 11,8; IC95: 2,8-49,6; p=0,001) y el tabaquismo (HR: 4,0; IC95%: 2,15-7,59; p<0,001) resultaron predictores independientes. Conclusiones La detección incidental de niveles séricos de vitaminaB12 >1.000pg/ml es elevada. El diagnóstico de neoplasia órgano sólido y hematológica es frecuente durante el año siguiente de seguimiento, siendo la hipercobalaminemia y el tabaquismo factores predictores de un mayor riesgo de cáncer. (AU)
Background and objective Elevated serum levels of vitaminB12 have been associated with oncohematological diseases. However, the relevance of its incidental detection in subjects without a previous diagnosis of cancer is unknown. The aim of this study was to evaluate the relationship between incidental hypercobalaminemia (vitaminB12 >1000pg/mL) and the diagnosis of a tumor process in patients without a diagnosis and to establish the risk factors. Material and methods Retrospective observational study of a cohort of patients with hypercobalaminemia. The incidence of neoplasms was compared with a cohort of patients with vitaminB12 levels <1000pg/mL. Results Vitamin B12 determinations of 4800 subjects were selected. Of them, 345 (7.1%) had levels >1000pg/ml; 68 (28.4%) were excluded due to exogenous administration, 12 (5%) due to insufficient data, and 15 (3%) due to having an active neoplasia, selecting 250 patients, with a median follow-up of 22 (IQR: 12-39) months. Structural liver disease was detected in 59 (23.6%). 18.2% (44 patients) had solid organ cancer and 17 (7.1%) had malignant hemopathy. The average time from the detection of hypercobalaminemia to the diagnosis of cancer was about 10months. The median until the diagnosis of neoplasia was higher in the high vitaminB12 group (13 vs 51months; P<.001). Hypercobalaminemia (HR: 11.8; 95%CI: 2.8-49.6; P=.001) and smoking (HR: 4.0; 95%CI: 2.15-7.59; P<.001) were independent predictors of neoplasia in the multivariate analysis. Conclusions Incidental detection of serum vitaminB12 levels >1000pg/ml is high in the population. The diagnosis of solid organ and hematological neoplasia is frequent during the following year of follow-up, with hypercobalaminemia and smoking being predictors of a higher risk of cancer. (AU)
Asunto(s)
Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Vitamina B 12 , Neoplasias/diagnóstico , Neoplasias Hematológicas/diagnóstico , Estudios Retrospectivos , Estudios de CohortesRESUMEN
Antecedentes y objetivo Los niveles elevados de vitaminaB12 se han asociado a enfermedades oncohematológicas. Sin embargo, se desconoce la relevancia de su detección incidental en sujetos sin un diagnóstico previo de cáncer. El objetivo de este estudio es evaluar la relación de la hipercobalaminemia y el diagnóstico de un proceso tumoral y establecer los factores de riesgo. Material y métodos Estudio observacional retrospectivo de una cohorte de pacientes con hipercobalaminemia. Se comparó la incidencia de neoplasias con una cohorte de pacientes con vitaminaB12<1.000pg/ml. Resultados Se seleccionaron 4.800 sujetos con determinaciones de vitaminaB12: 345 (7,1%) presentaban niveles >1.000pg/ml. Se excluyeron 68 (28,4%) por administración exógena, 12 (5%) por datos insuficientes y 15 (3%) por una neoplasia activa, seleccionando 250 pacientes; mediana de seguimiento: 22 (RIQ: 12-39) meses. Se detectó: hepatopatía 59 (23,6%), 44 (18,2%) presentaron cáncer de órgano sólido y 17 (7,1%), hemopatía maligna. El tiempo medio desde la detección de hipercobalaminemia al diagnóstico fue de 10meses. La mediana hasta el diagnóstico fue mayor en el grupo de vitaminaB12 elevada (13 vs 51meses; p<0,001). La hipercobalaminemia (HR_ 11,8; IC95: 2,8-49,6; p=0,001) y el tabaquismo (HR: 4,0; IC95%: 2,15-7,59; p<0,001) resultaron predictores independientes. Conclusiones La detección incidental de niveles séricos de vitaminaB12 >1.000pg/ml es elevada. El diagnóstico de neoplasia órgano sólido y hematológica es frecuente durante el año siguiente de seguimiento, siendo la hipercobalaminemia y el tabaquismo factores predictores de un mayor riesgo de cáncer. (AU)
Background and objective Elevated serum levels of vitaminB12 have been associated with oncohematological diseases. However, the relevance of its incidental detection in subjects without a previous diagnosis of cancer is unknown. The aim of this study was to evaluate the relationship between incidental hypercobalaminemia (vitaminB12 >1000pg/mL) and the diagnosis of a tumor process in patients without a diagnosis and to establish the risk factors. Material and methods Retrospective observational study of a cohort of patients with hypercobalaminemia. The incidence of neoplasms was compared with a cohort of patients with vitaminB12 levels <1000pg/mL. Results Vitamin B12 determinations of 4800 subjects were selected. Of them, 345 (7.1%) had levels >1000pg/ml; 68 (28.4%) were excluded due to exogenous administration, 12 (5%) due to insufficient data, and 15 (3%) due to having an active neoplasia, selecting 250 patients, with a median follow-up of 22 (IQR: 12-39) months. Structural liver disease was detected in 59 (23.6%). 18.2% (44 patients) had solid organ cancer and 17 (7.1%) had malignant hemopathy. The average time from the detection of hypercobalaminemia to the diagnosis of cancer was about 10months. The median until the diagnosis of neoplasia was higher in the high vitaminB12 group (13 vs 51months; P<.001). Hypercobalaminemia (HR: 11.8; 95%CI: 2.8-49.6; P=.001) and smoking (HR: 4.0; 95%CI: 2.15-7.59; P<.001) were independent predictors of neoplasia in the multivariate analysis. Conclusions Incidental detection of serum vitaminB12 levels >1000pg/ml is high in the population. The diagnosis of solid organ and hematological neoplasia is frequent during the following year of follow-up, with hypercobalaminemia and smoking being predictors of a higher risk of cancer. (AU)
Asunto(s)
Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Vitamina B 12 , Neoplasias/diagnóstico , Neoplasias Hematológicas/diagnóstico , Estudios Retrospectivos , Estudios de CohortesRESUMEN
BACKGROUND AND OBJECTIVES: Elevated serum levels of vitamin B12 have been associated with oncohematological diseases. However, the relevance of its incidental detection in subjects without a previous diagnosis of cancer is unknown. The aim of this study was to evaluate the relationship between incidental hypercobalaminemia (vitamin B12â¯>â¯1000â¯pg/mL) and the diagnosis of a tumor process in patients without a diagnosis and to establish the risk factors. MATERIAL AND METHODS: Retrospective observational study of a cohort of patients with hypercobalaminemia. The incidence of neoplasms was compared with a cohort of patients with vitamin B12 levels <1000â¯pg/mL. RESULTS: Vitamin B12 determinations of 4800 subjects were selected. Of them, 345 (7.1%) had levels >1000â¯pg/mL. 68 (28.4%) were excluded due to exogenous administration, 12 (5%) due to insufficient data and 15 (3%) due to having an active neoplasia, selecting 250 patients, with a median follow-up of 22 (IQR 12-39) months. Structural liver disease was detected in 59 (23.6%). 18.2% (44 patients) had solid organ cancer and 17 (7.1%) had malignant hemopathy. The average time from the detection of hypercobalaminemia to the diagnosis of cancer was about 10 months. The median until the diagnosis of neoplasia was higher in the high vitamin B12 group (13 vs. 51 months pâ¯<â¯0.001). Hypercobalaminemia (HR 11.8; 95% CI 2.8-49.6; pâ¯=â¯0.001) and smoking (HR 4.0; 95% CI, 2.15-7.59; pâ¯<â¯0.001) were independent predictors of neoplasia in the multivariate analysis. CONCLUSIONS: Incidental detection of serum vitamin B12 levels >1000â¯pg/mL is high in the population. The diagnosis of solid organ and hematological neoplasia is frequent during the following year of follow-up, with hypercobalaminemia and smoking being predictors of a higher risk of cancer.
Asunto(s)
Neoplasias Hematológicas , Neoplasias , Humanos , Vitamina B 12 , Neoplasias/diagnóstico , Neoplasias/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
La activación de la señalización de Wnt/β‐catenina en células del linaje osteoblástico conduce a un aumento en la masa ósea a través de un mecanismo dual: por una parte, aumentando la osteoblastogénesis, y por otra, disminuyendo la os‐teoclastogénesis. El predominio de un mecanismo sobre otro depende del estado madurativo del osteoblasto en el que produzca la acumulación de β‐catenina. La activación de la señalización de Wnt/β‐catenina en células del linaje osteo‐clástico y sus posibles efectos en la regulación de la masa ósea es menos conocida. Estudios previos han demostrado que la ablación condicional de β‐catenina en los osteoclastos induce una disminución de la masa ósea asociada a un aumento de los osteoclastos, y este hecho se ha atribuido a un incremento de la osteoclastogénesis. Sin embargo, no se han evaluado otras posibilidades alternativas como que una disminución de la apoptosis normal de los osteoclastos pueda también contribuir al mayor número de los mismos. En este trabajo, para obtener información sobre este hecho, generamos ratones en los que la β‐catenina se eliminó selectivamente de las células del linaje de monocito/macrófago utilizando un alelo flanqueado de la β‐catenina (Catnbf) junto con la línea de deleción LisozimaMCre (LysMCre). El análisis tridimensional de los huesos de los ratones Catnbf/f; LysMrevelaron una disminución significativa del grosor de la cortical femoral, mientras que el hueso trabecular vertebral no se vio afectado. Este fenotipo se asoció con un mayor número de osteoclastos en la superficie ósea. El número de osteoclastos en los cultivos procedentes de los ratones Catnbf/f; LysMfuedos veces mayor que en los cultivos obtenidos de los ratones control. La administración de WNT3a atenuó la formación de osteoclastos inducida por M‐CSF y RANKL in vitro. Además, WNT3a promovió la apoptosis de osteoclastos, y este efecto fue contrarrestado, tanto por la presencia de DKK1 como por la ausencia de β‐catenina. En conjunto, estos resultados apoyan un efecto autónomo celular de la β‐catenina en el osteoclasto, y proporcionan evidencia convincente del papel proapoptótico de β‐catenina en estas células
The activation of Wnt/β‐catenin signaling in cells of the osteoblastic lineage leads to an increase in bone mass through a dual mechanism: increasing osteoblastogenesis and decreasing osteoclastogenesis. The predominance of one mechanism over another depends on the maturational state of the osteoblast in which β‐catenin accumulation occurs. The activation of Wnt/β‐catenin signaling in cells of the osteoclastic lineage and its possible effects on the regulation of bone mass is less known. Previous studies have shown that conditional ablation of β‐catenin in osteoclasts induces a decrease in bone mass associated with an increase in osteoclasts, and this fact has been attributed to an increase in osteoclastogenesis. However, other alternative possibilities have not been evaluated, such as that a decrease in the normal osteoclastapoptosis may also contribute to the greater number of osteoclasts. In this paper, to obtain information about this fact, we generated mice in which β‐catenin was selectively eliminated from cells of the monocyte/macrophage lineage usingan allele flanked by β‐catenin (Catnbf) together with the deletion line LisozimaMCre (LysMCre). The three‐dimensional analysis of the bones of the Catnbf/f;LysMmice revealed a significant decrease in the thickness of the femoral cortex, while the trabecular bone of the vertebrae was not affected. This phenotype was associated with a greater number ofosteoclasts on the bone surface. The number of osteoclasts in the cultures from the Catnbf/f;LysMmice was twice as high as in the cultures obtained from the control mice. The administration of WNT3a attenuated the osteoclast formation induced by M‐CSF and RANKL in vitro. In addition, WNT3a promoted apoptosis of osteoclasts, and this effect was counteracted, both by the presence of DKK1 and by the absence of β‐catenin. Taken together, these results support a cellular autonomous effect of β‐catenin in the osteoclast, and provide convincing evidence of the proapoptotic role of β‐cateninin these cells
