RESUMEN
OBJECTIVES: To evaluate the usefulness of integrated positron emission tomography and computed tomography (PET/CT) in staging mycosis fungoides (MF) and Sézary syndrome and to correlate PET/CT data with histopathologic diagnosis of lymph nodes (LNs). DESIGN: A single-center, prospective cohort analysis. SETTING: Academic referral center for cutaneous lymphoma. PATIENTS: Thirteen patients with MF and SS at risk for secondary LN involvement. Interventions Patients were clinically evaluated based on general physical examination, total body skin examination, and laboratory screening. They underwent integrated PET/CT followed by excisional biopsy of LNs. MAIN OUTCOME MEASURES: We used PET/CT to assess LN size and metabolic activity. Enlarged LNs were defined as axillary or inguinal LNs with a short axis 1.5 cm or larger; or cervical LN, with a short axis 1.0 cm or larger. We classified LN pathologic results according to National Cancer Institute (LN1-4) and World Health Organization (WHO 1-3) criteria. We quantified PET activity using standardized uptake value (SUV) and correlated with LN grade. RESULTS: Based on CT size criteria alone, only 5 patients had enlarged LNs, whereas PET revealed hypermetabolic LNs in all 13 patients. Six patients had LN1-3, and 7 had effacement of LN architecture by lymphoma cells (LN4). Of the 7 patients with LN4 nodes, 4 had SS, and 3 had tumorous MF. Two patients with LN4 nodes had inguinal LNs smaller than 1.5 cm and would have been assigned an N0 classification without the use of integrated PET/CT. Correlation of SUV with LN grade revealed that LN1-3 nodes were associated with a mean SUV of 2.7 (median SUV, 2.2; range, 2.0-4.7) and LN4 nodes were associated with a mean SUV of 5.4 (median SUV, 3.9; range, 2.1-11.8). Patients with large cell transformation had the highest SUVs. CONCLUSIONS: For staging MF and SS, PET/CT was more sensitive in detecting LN involved by lymphoma compared with CT data alone and thus may provide more accurate staging and prognostic information. The intensity of PET activity correlated with histologic LN grade.
Asunto(s)
Micosis Fungoide/diagnóstico , Síndrome de Sézary/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis Fungoide/diagnóstico por imagen , Micosis Fungoide/patología , Estadificación de Neoplasias/métodos , Proyectos Piloto , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Estudios Prospectivos , Síndrome de Sézary/diagnóstico por imagen , Síndrome de Sézary/patología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Tomografía Computarizada por Rayos XAsunto(s)
Servicios de Salud Comunitaria , Tuberculosis/prevención & control , Cambodia/epidemiología , Servicios de Salud Comunitaria/economía , Servicios de Salud Comunitaria/organización & administración , Suplementos Dietéticos , Terapia por Observación Directa , Abastecimiento de Alimentos , Humanos , Evaluación de Programas y Proyectos de Salud , Tuberculosis/economía , Tuberculosis/epidemiologíaRESUMEN
Tumor necrosis factor alpha (TNF-alpha) plays an important role in host containment of infection by Mycobacterium tuberculosis, one of the leading causes of death by an infectious agent globally. Using the pathogenic M. tuberculosis strain H37Rv, we present evidence that upon stimulation of monocytic cells by M. tuberculosis a unique TNF-alpha enhanceosome is formed, and it is distinct from the TNF-alpha enhanceosome that forms in T cells stimulated by antigen engagement or virus infection. A distinct set of activators including ATF-2, c-jun, Ets, Sp1, Egr-1 and the coactivator proteins CBP/p300 are recruited to the TNF-alpha promoter after stimulation with M. tuberculosis. Furthermore, the formation of this enhanceosome is dependent on inducer-specific helical phasing relationships between transcription factor binding sites. We also show that the transcriptional activity of CBP/p300 is potentiated by mycobacterial stimulation of monocytes. The identification of TNF-alpha regulatory elements and coactivators involved in M. tuberculosis-stimulated gene expression thus provides potential selective molecular targets in the modulation of TNF-alpha gene expression in the setting of mycobacterial infection.
Asunto(s)
Regulación de la Expresión Génica , Proteínas Inmediatas-Precoces , Mycobacterium tuberculosis/metabolismo , Proteínas Nucleares/metabolismo , Transactivadores/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Transcripción Activador 2 , Animales , Secuencia de Bases , Línea Celular , Cromatina/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteína p300 Asociada a E1A , Proteína 1 de la Respuesta de Crecimiento Precoz , Ensayo de Inmunoadsorción Enzimática , Fijadores/farmacología , Formaldehído/farmacología , Humanos , Luciferasas/metabolismo , Macrófagos/metabolismo , Ratones , Modelos Biológicos , Datos de Secuencia Molecular , Monocitos/microbiología , Plásmidos/metabolismo , Pruebas de Precipitina , Regiones Promotoras Genéticas , Unión Proteica , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-ets , Factor de Transcripción Sp1/metabolismo , Linfocitos T/metabolismo , Linfocitos T/microbiología , Factores de Tiempo , Factores de Transcripción/metabolismo , Transcripción Genética , Transfección , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteína Elk-1 con Dominio etsRESUMEN
Purified protein derivative (PPD) skin testing is used to identify persons infected with Mycobacterium tuberculosis (Mtb) and to assess cell-mediated immune responses to Mtb. However, lack of skin induration to intradermal injection of PPD or PPD anergy is observed in a subset of patients with active tuberculosis (TB). To investigate the sensitivity and persistence of PPD reactivity and its in vitro correlates during active TB disease and after successful chemotherapy, we evaluated the distribution of skin size induration after intradermal injection of PPD among 364 pulmonary TB patients in Cambodia. A subset of 25 pulmonary TB patients who had a positive skin reaction to mumps and/or candida antigens showed persistent anergy to PPD after successful completion of TB therapy. Strikingly, in vitro stimulation of T cells from persistently anergic TB patients with mumps but not PPD resulted in T cell proliferation, and lower levels of IL-2 and IFN-gamma and higher levels of IL-10 were detected in PPD-stimulated cellular cultures from PPD-anergic as compared with PPD-reactive pulmonary TB patients. These results show that anergy to PPD is antigen-specific and persistent in a subset of immunocompetent pulmonary TB patients and is characterized by antigen-specific impaired T cell proliferative responses and a distinct pattern of cytokine production including reduced levels of IL-2.