ABSTRACT
Brain radiation necrosis (RN) is a subacute or late adverse event following radiotherapy, involving an exacerbated inflammatory response of the brain tissue. The risk of symptomatic RN associated with stereotactic radiosurgery (SRS) as part of the treatment of brain metastases (BMs) has been a subject of recent investigation. The activation of the signal transducer and activator of transcription 3 (STAT3) was shown in reactive astrocytes (RA) associated with BMs. Given that the pathophysiological mechanisms behind RN are not fully understood, we sought to investigate the role of STAT3 among other inflammatory markers in RN development. A mouse model of RN using clinical LINAC-based SRS was designed to induce brain necrosis with the administration of 50 Gy in a single fraction to the left hemisphere using a circular collimator of 5 mm diameter. Immunohistochemistry and multiplex staining for CD4, CD8, CD68, GFAP, and STAT3 were performed. For validation, eleven patients with BMs treated with SRS who developed symptomatic RN and required surgery were identified to perform staining for CD68, GFAP, and STAT3. In the mouse model, the RN and perinecrotic areas showed significantly higher staining for F4/80+ and GFAP+ cells, with a high infiltration of CD4 and CD8 T-lymphocytes, when compared to the non-irradiated cerebral hemisphere. A high number of GFAP+pSTAT3+ and F4/80+pSTAT3+ cells was found in the RN areas and the rest of the irradiated hemisphere. The analysis of human brain specimens showed that astrocytes and microglia were actively phosphorylating STAT3 in the areas of RN and gliosis. Phosphorylated STAT3 is highly expressed in the microglia and RA pertaining to the areas of brain RN. Targeting STAT3 via inhibition represents a promising strategy to ameliorate symptomatic RN in BM patients undergoing SRS.
ABSTRACT
Introducción Valorar la capacidad de la tomografía computarizada multidetector (TCMD) para identificar la localización de la perforación gastrointestinal (GI).Material y métodos Análisis retrospectivo de 98 pacientes con neumoperitoneo en la TCMD. Dos radiólogos expertos evaluaron la presencia o ausencia de signos radiológicos directos (extravasación del contraste oral; defecto focal de la pared; defecto focal en reconstrucciones multiplanares) e indirectos (aire libre supramesocólico; inframesocólico; supra- e inframesocólico; burbujas de gas adyacentes a la pared; líquido libre; engrosamiento parietal segmentario; trabeculación de la grasa; abscesos) de perforación para identificar su ubicación. Se determinó la concordancia kappa entre los radiólogos para identificar el lugar de la perforación y la presencia o ausencia de cada uno de los signos radiológicos; así como la correlación kappa de la localización detectada mediante TCMD y su confirmación o no en la intervención quirúrgica. Se calculó para cada signo radiológico su frecuencia, sensibilidad, especificidad, valor predictivo positivo (VPP) y negativo (VPN).Resultados Se diagnóstico correctamente el sitio de la perforación en un 80% de los casos. El índice kappa entre radiólogos para la localización fue excelente (0,919), variando para cada signo radiológico entre 0,5 y 1. La localización más frecuente de la perforación en la intervención quirúrgica (33,7%) y en la TCMD (40,8%) fue colon sigmoideo/recto. «Burbujas de gas adyacentes a la pared fue el signo con mayor S (91%) y el «engrosamiento parietal segmentario» el que tuvo un mayor VPP (90%).Conclusión La TCMD permite localizar las perforaciones gastrointestinales con una alta sensibilidad (80%) y excelente correlación interobservador (AU)
Introduction The purpose of this study was to evaluate the accuracy of multidetector computed tomography (MDCT) for locating the site of gastrointestinal tract perforations and to determine the most predictive signs in this diagnosis. Material and methods A total of 98 patients with pneumoperitoneum on MDCT were retrospectively analysed. Two experienced radiologists reviewed the presence or absence of direct signs (extravasation of oral contrast, focal defect in the bowel wall, focal defect with multiplanar reformations images) and indirect signs (free air in supramesocolic, inframesocolic, supramesocolic and inframesocolic compartments, concentration of extraluminal air bubbles adjacent to the bowel wall, extraluminal fluid, segmental bowel-wall thickening, perivisceral fat stranding, abscess) to identify the site of the perforation. The Kappa index was evaluated between radiologists to determine the site of perforation and for each predictive sign, as well as Kappa index between the site of perforation detected with MDCT and the site proven at surgery. The frequency, sensitivity, specificity and positive and negative predictive value (PPV and NPV, respectively) were calculated. Results The perforation site was identified correctly in 80.4% of cases. Kappa index between radiologists to identify the site was excellent (0.919), varying between 0.5-1.0 for each radiological sign. The most frequent site of perforation at surgery (33.7%) and in MDCT (40.82%) was the sigmoid colon/rectum. Concentration of extraluminal air bubbles adjacent to the bowel wall was the most sensitive (91%) sign and segmental bowel-wall thickening had the highest PPV (90%).Conclusion MDCT is useful for locating the site of GI perforation, with a high sensitivity (80%) and an excellent agreement between radiologists (AU)
Subject(s)
Humans , Intestinal Perforation/diagnosis , Multidetector Computed Tomography/methods , Diagnostic Imaging/methods , Pneumoperitoneum/complications , Retrospective Studies , Abdomen, Acute/etiologyABSTRACT
INTRODUCTION: The purpose of this study was to evaluate the accuracy of multidetector computed tomography (MDCT) for locating the site of gastrointestinal tract perforations and to determine the most predictive signs in this diagnosis. MATERIAL AND METHODS: A total of 98 patients with pneumoperitoneum on MDCT were retrospectively analysed. Two experienced radiologists reviewed the presence or absence of direct signs (extravasation of oral contrast, focal defect in the bowel wall, focal defect with multiplanar reformations images) and indirect signs (free air in supramesocolic, inframesocolic, supramesocolic and inframesocolic compartments, concentration of extraluminal air bubbles adjacent to the bowel wall, extraluminal fluid, segmental bowel-wall thickening, perivisceral fat stranding, abscess) to identify the site of the perforation. The Kappa index was evaluated between radiologists to determine the site of perforation and for each predictive sign, as well as Kappa index between the site of perforation detected with MDCT and the site proven at surgery. The frequency, sensitivity, specificity and positive and negative predictive value (PPV and NPV, respectively) were calculated. RESULTS: The perforation site was identified correctly in 80.4% of cases. Kappa index between radiologists to identify the site was excellent (0.919), varying between 0.5-1.0 for each radiological sign. The most frequent site of perforation at surgery (33.7%) and in MDCT (40.82%) was the sigmoid colon/rectum. Concentration of extraluminal air bubbles adjacent to the bowel wall was the most sensitive (91%) sign and "segmental bowel-wall thickening" had the highest PPV (90%). CONCLUSION: MDCT is useful for locating the site of GI perforation, with a high sensitivity (80%) and an excellent agreement between radiologists.