ABSTRACT
INTRODUCCIÓN: El 85% de los cánceres de pulmón son carcinomas de célula no pequeña (CPCNP) y la mayoría se diagnostican en estadios avanzados. La inmunoterapia ha cambiado el paradigma del tratamiento de estos tumores y la búsqueda de un marcador que seleccione a los pacientes. Actualmente PD-L1 es el biomarcador usado en la práctica clínica, aunque no es un marcador ideal. MATERIAL Y MÉTODOS: Revisión retrospectiva de 53 casos de CPCNP diagnosticados en el Hospital Universitario La Paz entre 2005 y 2007, con reclasificación de los tumores según la clasificación de la OMS 2015, estudio de PD-L1 con los clones 22C3 y 28-8 por dos observadores, valorando la concordancia entre patólogos y entre clones; y correlación de todos los datos estudiados con la supervivencia. RESULTADOS: Encontramos una prevalencia de expresión de PD-L1 en célula tumoral (TC) semejante a la literatura; una concordancia entre clones muy buena en la valoración de TC y de células inmunes (CCI 0,99-0,93; p < 0,001). Una concordancia interobservador muy buena en la evaluación de TC (CCI 0,902; IC 95%: 0,836-0,942; p < 0,001 para el clon 22C3 y CCI 0,927; IC 95%: 0,877-0,957; p < 0,001 para el clon 28-8); y discreta para las células inmunes (CCI 0,413; IC 95%: 0,163-0,613; p = 0,001 con el clon 22C3 y CCI 0,313; IC 95%: 0,053-0,534; p = 0,010 con el clon 28-8). Solo encontramos relación con el pronóstico en subtipo y grado histológico. CONCLUSIONES: Los clones de PD-L1 22C3 y 28-8 son equivalentes y hay buena concordancia interobservador en la valoración de las TC, pero no en la de células inmunes
INTRODUCTION: 85% of lung cancers are non-small cell carcinomas (NSCLC), the majority of which are diagnosed in an advanced stage. Immunotherapy has changed the treatment pattern for these tumors and created the need to find a marker for patient selection. Although not ideal, PD-L1 is the biomarker currently used in clinical practice. MATERIAL AND METHODS: Retrospective review by two pathologists of 53 cases of NSCLC from 2005 to 2007 in Hospital Universitario La Paz, using the WHO 2015 classification studying PD-L1 with clones 22C3 and 28-8. The consistency between observers and clones was assessed and all data studied were correlated with survival rates. RESULTS: We found a prevalence of PD-L1 expression in tumor cells (TC) similar to that previously reported in the literature and a very good consistency between clones in the evaluation of TC and immune cells (ICC 0.99-0.93, p<.001). Interobserver concordance was very good in the evaluation of TC (ICC 0.902, 95% CI: 0.836-0.942, p<.001 for clone 22C3 and ICC 0.927, 95% CI: 0.877-0.957, p<.001 for clone 28-8) and poor for immune cells (ICC of 0.413, 95% CI: 0.163-0.613, p=.001 with clone 22C3 and ICC of 0.313, 95% CI: 0.053-0.534, p=.010 with clone 28-8). Subtype and histological grade were the only variables related to prognosis. CONCLUSIONS: The clones of PD-L1 22C3 and 28-8 are equivalent and there is good interobserver consistency in the evaluation of TC but not in immune cells
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Small Cell Lung Carcinoma/metabolism , Small Cell Lung Carcinoma/surgery , Lung Neoplasms/metabolism , Lung Neoplasms/surgery , Biomarkers, Tumor/metabolism , Observer Variation , Survival Analysis , Retrospective Studies , Gene ExpressionABSTRACT
INTRODUCTION: 85% of lung cancers are non-small cell carcinomas (NSCLC), the majority of which are diagnosed in an advanced stage. Immunotherapy has changed the treatment pattern for these tumors and created the need to find a marker for patient selection. Although not ideal, PD-L1 is the biomarker currently used in clinical practice. MATERIAL AND METHODS: Retrospective review by two pathologists of 53 cases of NSCLC from 2005 to 2007 in Hospital Universitario La Paz, using the WHO 2015 classification studying PD-L1 with clones 22C3 and 28-8. The consistency between observers and clones was assessed and all data studied were correlated with survival rates. RESULTS: We found a prevalence of PD-L1 expression in tumor cells (TC) similar to that previously reported in the literature and a very good consistency between clones in the evaluation of TC and immune cells (ICC 0.99-0.93, p<.001). Interobserver concordance was very good in the evaluation of TC (ICC 0.902, 95% CI: 0.836-0.942, p<.001 for clone 22C3 and ICC 0.927, 95% CI: 0.877-0.957, p<.001 for clone 28-8) and poor for immune cells (ICC of 0.413, 95% CI: 0.163-0.613, p=.001 with clone 22C3 and ICC of 0.313, 95% CI: 0.053-0.534, p=.010 with clone 28-8). Subtype and histological grade were the only variables related to prognosis. CONCLUSIONS: The clones of PD-L1 22C3 and 28-8 are equivalent and there is good interobserver consistency in the evaluation of TC but not in immune cells.
Subject(s)
B7-H1 Antigen/analysis , Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/chemistry , Lung Neoplasms/chemistry , Adenocarcinoma/chemistry , Adenocarcinoma/classification , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Aged , Carcinoma, Non-Small-Cell Lung/classification , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/classification , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Female , Humans , Immunity, Cellular , Immunotherapy , Lung Neoplasms/classification , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Neoplasm Grading , Pathologists , Patient Selection , Prognosis , Retrospective StudiesABSTRACT
CLINICAL INTRODUCTION: A previously healthy 12-year-old boy presented with chest pain and dyspnoea. ECG (figure 1), echocardiogram (figure 2) and myocardial MRI (figure 3) were performed.Electromyography revealed mild proximal weakness. Blood tests showed creatine kinase 997â UI/L, aspartate transaminase 398â UI/L, alanine transaminase 293â UI/L and lactate deshidrogenase 1730â UI/L. Ophthalmology test showed diffuse loss of pigment in the retinal pigment epithelium. Myocardial biopsy was performed (figure 4). A cardiomyopathy was suspected. LAMP2 gene was sequenced, and a stop mutation was identified. QUESTION: What is the most likely diagnosis suggested based on the patient's tests and history? Danon's disease.Fabry's disease.Hypertrophic cardiomyopathy.Noonan's syndrome.Pompe's disease.
Subject(s)
Angina Pectoris/etiology , Dyspnea/etiology , Glycogen Storage Disease Type IIb/complications , Hypertrophy, Left Ventricular/etiology , Ventricular Dysfunction, Left/etiology , Biopsy , Child , DNA Mutational Analysis , Echocardiography , Electrocardiography , Glycogen Storage Disease Type IIb/diagnosis , Glycogen Storage Disease Type IIb/genetics , Humans , Hypertrophy, Left Ventricular/diagnosis , Hypertrophy, Left Ventricular/physiopathology , Lysosomal-Associated Membrane Protein 2/genetics , Magnetic Resonance Imaging , Male , Mutation , Stroke Volume , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left , Ventricular RemodelingABSTRACT
OBJECTIVES: The main challenge in treating bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the absence of an effective established treatment. We aimed to compare different potentially preventive treatments for BRONJ after dental extractions in zoledronic acid (ZA)-treated animals. We studied the local application of different combinations of adipose-derived stem cells (ASCs) with or without previous stimulation with bone morphogenetic protein 2 (BMP-2) and platelet-rich plasma (PRP) in rats. MATERIAL AND METHODS: Fifty-six male Wistar rats were treated with ZA for 9 weeks. Dental extractions were performed in the eighth week, and the animals were divided into 4 groups. In group 1 (n = 14), alveolar coverage with mucoperiosteal flap was performed. In group 2 (n = 14), PRP was applied over the sockets and covered with the flap. In group 3 (n = 15), allogeneic ASCs with PRP were applied and covered with the flap. In group 4 (n = 13), animals were treated with ASCs cultured with BMP-2, PRP, and flap coverage. Histologic, fluorescence, and radiologic studies of the maxillae were performed. RESULTS: ASC-treated animals showed lower frequency of osteonecrosis (14% vs 50%, p = 0.007) and greater bone turnover (p = 0.024) and osteoclast count (p = 0.045) than those not receiving the ASC treatment. CONCLUSIONS: In this high-risk model, ASC-based treatments seem to prevent BRONJ more effectively than mucosal flap with or without PRP. The combination of ASCs and PRP appears to be synergistic, and the addition of BMP-2 could further improve the results.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Imidazoles/therapeutic use , Platelet-Rich Plasma/metabolism , Adipocytes , Animals , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents/administration & dosage , Diphosphonates/administration & dosage , Disease Models, Animal , Imidazoles/administration & dosage , Male , Rats , Rats, Wistar , Stem Cells , Zoledronic AcidABSTRACT
Se presenta el caso de una paciente con diagnóstico previo de cirrosis biliar primaria (CBP) y hepatitis B crónica en fase de portador inactivo que, en tratamiento con ácido ursodesoxicólico, presentó elevación de las transaminasas, sin datos de reactivación de su hepatitis B crónica. Se realizó biopsia hepática en la que se observaron cambios compatibles con hepatitis autoinmune (HAI) sobreañadida. Las alteraciones analíticas respondieron al tratamiento con budesonida. Se realiza una revisión sobre la entidad clínica del síndrome de solapamiento CBP-HAI y las características especiales de esta paciente para alcanzar el diagnóstico y su tratamiento (AU)
We describe the case of a female patient with a previous diagnosis of primary biliary cirrhosis (PBC) and chronic hepatitis B in inactive phase who developed increased transaminase levels with no evidence of hepatitis B virus reactivation while receiving ursodeoxycholic acid treatment. A liver biopsy showed changes compatible with overlapping autoimmune hepatitis (AIH). Budesonide treatment achieved normalization of transaminase levels. We provide a review of PBC and AIH overlap syndrome and discuss the particular features of this case that led us to this diagnosis, as well as the treatment provided (AU)
Subject(s)
Humans , Liver Cirrhosis, Biliary/complications , Hepatitis B, Chronic/complications , Hepatitis, Autoimmune/complications , Disease Progression , Risk FactorsABSTRACT
We describe the case of a female patient with a previous diagnosis of primary biliary cirrhosis (PBC) and chronic hepatitis B in inactive phase who developed increased transaminase levels with no evidence of hepatitis B virus reactivation while receiving ursodeoxycholic acid treatment. A liver biopsy showed changes compatible with overlapping autoimmune hepatitis (AIH). Budesonide treatment achieved normalization of transaminase levels. We provide a review of PBC and AIH overlap syndrome and discuss the particular features of this case that led us to this diagnosis, as well as the treatment provided.
