ABSTRACT
BACKGROUND: The etiology and the molecular basis of lung adenocarcinomas (LuADs) in nonsmokers are currently unknown. Furthermore, the scarcity of available primary cultures continues to hamper our biological understanding of non-smoking-related lung adenocarcinomas (NSK-LuADs). PATIENTS AND METHODS: We established patient-derived cancer cell (PDC) cultures from metastatic NSK-LuADs, including two pairs of matched EGFR-mutant PDCs before and after resistance to tyrosine kinase inhibitors (TKIs), and then performed whole-exome and RNA sequencing to delineate their genomic architecture. For validation, we analyzed independent cohorts of primary LuADs. RESULTS: In addition to known non-smoker-associated alterations (e.g. RET, ALK, EGFR, and ERBB2), we discovered novel fusions and recurrently mutated genes, including ATF7IP, a regulator of gene expression, that was inactivated in 5% of primary LuAD cases. We also found germline mutations at dominant familiar-cancer genes, highlighting the importance of genetic predisposition in the origin of a subset of NSK-LuADs. Furthermore, there was an over-representation of inactivating alterations at RB1, mostly through complex intragenic rearrangements, in treatment-naive EGFR-mutant LuADs. Three EGFR-mutant and one EGFR-wild-type tumors acquired resistance to EGFR-TKIs and chemotherapy, respectively, and histology on re-biopsies revealed the development of small-cell lung cancer/squamous cell carcinoma (SCLC/LuSCC) transformation. These features were consistent with RB1 inactivation and acquired EGFR-T790M mutation or FGFR3-TACC3 fusion in EGFR-mutant tumors. CONCLUSIONS: We found recurrent alterations in LuADs that deserve further exploration. Our work also demonstrates that a subset of NSK-LuADs arises within cancer-predisposition syndromes. The preferential occurrence of RB1 inactivation, via complex rearrangements, found in EGFR-mutant tumors appears to favor SCLC/LuSCC transformation under growth-inhibition pressures. Thus RB1 inactivation may predict the risk of LuAD transformation to a more aggressive type of lung cancer, and may need to be considered as a part of the clinical management of NSK-LuADs patients.
Subject(s)
ErbB Receptors , Lung Neoplasms , Adenocarcinoma of Lung , Drug Resistance, Neoplasm/genetics , ErbB Receptors/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Microtubule-Associated Proteins , Mutation , Protein Kinase Inhibitors/pharmacology , Retinoblastoma Binding Proteins , Ubiquitin-Protein LigasesABSTRACT
Introducción: los tumores neurogénicos son las masas del mediastino posterior más frecuentes. Aproximadamente el 10% de los localizados en el mediastino posterior tienen un componente intraespinal, a través de algún foramen vertebral. Siendo conocidos como tumores de Dumbbell o en reloj de arena. Reporte de caso: paciente con diagnóstico casual de tumor neurogénico en mediastino posterior con componente intraespinal (tumor en reloj de arena o Dumbell). El tratamiento quirúrgico se realizó conjuntamente en un mismo acto por parte del servicio de Neurocirugía y Cirugía Torácica. En un primer tiempo se llevó a cabo la laminectomía posterior, identificación de raíz dorsal izquierda afecta, ligadura y sección. Posteriormente, mediante videotoracoscopia por puerto único se realizó resección del tumor neurogénico por plano libre de afectación tumoral. Conclusión: el tratamiento quirúrgico en un solo acto de los tumores mediastínicos con componente intraespinal, ha demostrado ser seguro, eficaz y no aumentar las complicaciones intraoperatorias o postoperatoria
Introduction: neurogenic tumors are the most frequent masses of the posterior mediastinum. Approximately 10% of those located in the posterior mediastinum have an intraspinal component, through some vertebral foramen. They are known as dumbbell tumors. Clinical case: Patient with a diagnosis of neurogenic tumor in the posterior mediastinum with intraspinal component (dumbbell tumor). Surgical treatment was performed jointly in the same act by the Neurosurgery and Thoracic Surgery service. In a first time the posterior laminectomy, identification of left dorsal root affected, ligation and section was carried out. Subsequently, by single port video-assisted thoracoscopy, the neurogenic tumor was resected through a free plane of tumor involvement. Conclusion: surgical treatment in a single act of mediastinal tumors with intraspinal component has been shown to be safe, effective and does not increase intraoperative or postoperative complications
Subject(s)
Mediastinal Neoplasms/surgery , Laminectomy/methods , Thoracic Surgery, Video-Assisted/methods , Nervous System Neoplasms , Spinal Cord/pathology , Combined Modality Therapy/methodsABSTRACT
No disponible
Subject(s)
Humans , Pneumothorax/surgery , Pneumothorax/diagnosis , ThoracoscopyABSTRACT
INTRODUCTION: Ventriculoatrial and ventriculopleural shunts (VPS) are alternatives to ventriculoperitoneal shunts for draining cerebrospinal fluid from patients with hydrocephalus. VPS has seldom been used because of the risk of respiratory insufficiency due to pneumothorax or pleural effusion. However, valves are currently available with anti-siphon devices for use with standard shunting systems to prevent the development of pleural effusion. The aim of this study was to analyze outcome after VPS in eight patients in whom we used the new valves for avoiding overdrainage of cerebrospinal fluid. MATERIAL AND METHOD: Nine VPS procedures were performed in eight hydrocephalic patients between 1988 and 2000. We used differential pressure valves in eight procedures and a flow regulator valve in one. The externally adjustable Sophy valve was used in six cases. The indication for VPS was peritoneal adhesions in four cases, persistent ascites in two, ventriculoatrial valve obstruction in one, and infection of the peritoneal shunt (peritonitis) in one. The ninth case involved replacement of a previously obstructed valve. RESULTS: After a follow-up period of 22 months all shunts were functioning well and the only patient with symptoms of hydrocephalus was the one who required valve replacement at six months. No surgical morbidity or mortality was observed, and only one patient developed transitory signs of excessive cerebrospinal fluid drainage, which was corrected by regulating the magnetic valve gradient. The death of one patient 36 months after surgery was unrelated to pleural drainage. CONCLUSIONS: Valves newly designed to prevent overdrainage of cerebrospinal fluid give satisfactory results, such that VPS should be considered as an alternative to peritoneal drainage.
Subject(s)
Cerebrospinal Fluid Shunts/methods , Hydrocephalus/surgery , Postoperative Complications , Adolescent , Adult , Cerebrospinal Fluid Pressure , Cerebrospinal Fluid Shunts/adverse effects , Child , Child, Preschool , Humans , Male , Pleura/surgery , Pleural Effusion/prevention & control , Prostheses and Implants , Treatment OutcomeABSTRACT
INTRODUCCIÓN: La derivación ventriculoatrial y la ventriculopleural (DVP) son métodos alternativos a la derivación ventriculoperitoneal para el drenaje del líquido cefalorraquídeo (LCR) en pacientes con hidrocefalia. La DVP ha sido poco utilizada por su riesgo de insuficiencia respiratoria por neumotórax o derrame pleural; sin embargo, la presencia actual de válvulas con dispositivos antisifón para los sistemas de derivación estándar previene el desarrollo de estos derrames pleurales. El objetivo es analizar los resultados de nueve DVP en 8 pacientes con las nuevas válvulas de DVP para evitar el drenaje excesivo de LCR. MATERIAL Y MÉTODO: Entre 1988 y 2000 se han realizado nueve DVP en 8 pacientes con hidrocefalia. Ocho válvulas eran de presión diferencial y una, reguladora de flujo. Además, seis (el modelo Sophy) son programables externamente. La indicación de la DVP fue, en 4 casos, la presencia de adherencias peritoneales; en dos, la presencia de ascitis persistente, en uno la obstrucción de la válvula ventriculoatrial, y en el último, la infección de la derivación peritoneal por una peritonitis. El noveno caso corresponde al recambio de una válvula previa obstruida. RESULTADOS: Tras un seguimiento medio de 22 meses, todas las derivaciones funcionan de forma adecuada y ningún paciente presenta síntomas de hidrocefalia, excepto un caso que precisó recambio valvular por obstrucción de la misma a los 6 meses. No se presentó morbimortalidad asociada a la técnica quirúrgica. Sólo un paciente mostró síntomas transitorios de drenaje excesivo de LCR, lo que fue corregido regulando el gradiente de la válvula magnética. Un paciente falleció a los 36 meses por un procedimiento no relacionado con el drenaje pleural. CONCLUSIONES: El uso de válvulas de nuevo diseño designadas para prevenir el sobredrenaje de LCR presenta unos resultados satisfactorios, por lo que la DVP debe considerarse como una alternativa al drenaje peritoneal (AU)
Subject(s)
Child , Child, Preschool , Adolescent , Adult , Male , Humans , Postoperative Complications , Treatment Outcome , Prostheses and Implants , Pleura , Pleural Effusion , Cerebrospinal Fluid Shunts , Cerebrospinal Fluid Pressure , HydrocephalusABSTRACT
No disponible
Subject(s)
Humans , Sternum , Thoracotomy , Survival Rate , Treatment Outcome , Pneumonectomy , Prognosis , Registries , Lung NeoplasmsSubject(s)
Lipoma/complications , Myasthenia Gravis/complications , Thymus Neoplasms/complications , Female , Humans , MaleABSTRACT
No disponible
Subject(s)
Middle Aged , Adult , Male , Humans , Ribs , Osteosarcoma , Pneumothorax , Testicular Neoplasms , Muscle Neoplasms , Sarcoma, Small Cell , Neoplasms, Germ Cell and Embryonal , Pleural Neoplasms , Bone Neoplasms , Lung NeoplasmsSubject(s)
Granuloma/diagnosis , Lung Diseases/diagnosis , Female , Granuloma/pathology , Humans , Lung Diseases/pathology , Middle AgedABSTRACT
We describe a 41-year-old patient with adult-onset dermatomyositis who developed persistent pneumomediastinum and severe subcutaneous emphysema due to end-stage interstitial lung disease. The diagnosis of dermatomyositis was based on proximal muscle weakness, electromyographic findings of inflammatory myopathy, and positive findings on muscle biopsy. Low levels of creatine kinase elevation were found at the time of diagnosis (a form of dermatomyositis which has been associated with a poor prognosis). The patient had no signs of cutaneous vasculitis. Despite treatment with prednisone and azathioprine, she died of intercurrent gram-negative sepsis 15 months after the diagnosis of dermatomyositis.
