RESUMEN
OBJECTIVE: The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. METHODS: We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. RESULTS: Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033-1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054-1.344, respectively). These results were confirmed after the propensity score matching analysis. CONCLUSIONS: pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/cirugía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Masculino , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND AND OBJECTIVES: Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS). METHODS: We retrospectively collected data of surgically resected stage I and II adenocarcinoma. SELECTION CRITERIA: anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas. RESULTS: Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS. CONCLUSIONS: The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.
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Adenocarcinoma del Pulmón/patología , Adenocarcinoma Papilar/patología , Carcinoma de Células Acinares/patología , Bases de Datos Factuales , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/patología , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma Papilar/cirugía , Anciano , Carcinoma de Células Acinares/cirugía , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND/AIMS: At present, benefits of surgical resection and appropriate selection criteria in patients affected by both hepatic and pulmonary metastases of colorectal cancer (CRC) are under discussion. Our analysis focused on a surgical series of such patients and our final aim consisted in identifying potential prognostic factors. METHODS: Eighty-five patients undergoing resection of both hepatic and pulmonary metastases at 2 Healthcare Institutions from January 1993 to June 2015 were retrospectively reviewed as concerned clinical information, surgical notes and pathological features. Patient, treatment, and outcome variables were analyzed by use of log-rank tests, Cox regression, and Kaplan-Meier methods. RESULTS: Liver turned out as the first site of metastasis in 75% patients, lung in 13% patients, and both sites in 12% patients. Multiple hepatic metastases were detected in 67% patients and pulmonary metastases in 31% patients. Two hundred eighteen surgical interventions were performed (mean 2.56 for each patient). Overall survival (OS) rates at 3-, 5-, and 10-year follow-up from colorectal resection were 94, 79, and 38% respectively. Median OS was 8.31 years. Survival turned out significantly longer for patients with disease-free interval (DFI) exceeding 1 year between first metastasectomy and diagnosis of second metastases and in patients affected by metachronous pulmonary metastases. CONCLUSIONS: Surgical resection of both hepatic and pulmonary metastases of CRC represents a safe and effective treatment. It might lead to rewarding long-term survival rates in high selected patients. Shorter DFIs between first metastasectomy and diagnosis of second metastases can determine worse prognoses. In addition, poor outcomes could be predicted also for patients affected by synchronously detected pulmonary CRC metastases, although further confirmatory analyses are strongly required.
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Neoplasias Colorrectales/cirugía , Hepatectomía/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/cirugía , Neoplasias Primarias Múltiples/cirugía , Neumonectomía/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/secundario , Selección de Paciente , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a 18F-FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.
Asunto(s)
Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Enfermedades Pleurales/diagnóstico , Neoplasias Pleurales/diagnóstico , Anciano , Broncoscopía , Diagnóstico Diferencial , Endosonografía , Glucocorticoides/uso terapéutico , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Enfermedad Relacionada con Inmunoglobulina G4/patología , Linfadenopatía/diagnóstico , Linfadenopatía/etiología , Linfadenopatía/patología , Masculino , Mesotelioma Maligno , Enfermedades Pleurales/complicaciones , Enfermedades Pleurales/tratamiento farmacológico , Enfermedades Pleurales/patología , Derrame Pleural/etiología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisona/uso terapéuticoRESUMEN
BACKGROUND: Non-small cell lung cancer is the most common type of lung cancer. Surgery is proven to be the most effective treatment in early stages, despite its potential impact on quality of life. Pulmonary rehabilitation, either before or after surgery, is associated with reduced morbidity related symptoms and improved exercise capacity, lung function and quality of life. METHODS: We describe the study protocol for the open-label randomized controlled trial we are conducting on patients affected by primary lung cancer (stages I-II) eligible for surgical treatment. The control group receives standard care consisting in one educational session before surgery and early inpatient postoperative physiotherapy. The treatment group receives, in addition to standard care, intensive rehabilitation involving 14 preoperative sessions (6 outpatient and 8 home-based) and 39 postoperative sessions (15 outpatient and 24 home-based) with aerobic, resistance and respiratory training, as well as scar massage and group bodyweight exercise training. Assessments are performed at baseline, the day before surgery and one month and six months after surgery. The main outcome is the long-term exercise capacity measured with the Six-Minute Walk Test; short-term exercise capacity, lung function, postoperative morbidity, length of hospital stay, quality of life (Short Form 12), mood disturbances (Hospital Anxiety and Depression Scale) and pain (Numeric Rating Scale) are also recorded and analysed. Patient compliance and treatment-related side effects are also collected. Statistical analyses will be performed according to the intention-to-treat approach. T-test for independent samples will be used for continuous variables after assessment of normality of distribution. Chi-square test will be used for categorical variables. Expecting a 10% dropout rate, assuming α of 5% and power of 80%, we planned to enrol 140 patients to demonstrate a statistically significant difference of 25 m at Six-Minute Walk Test. DISCUSSION: Pulmonary Resection and Intensive Rehabilitation study (PuReAIR) will contribute significantly in investigating the effects of perioperative rehabilitation on exercise capacity, symptoms, lung function and long-term outcomes in surgically treated lung cancer patients. This study protocol will facilitate interpretation of future results and wide application of evidence-based practice. TRIAL REGISTRATION: ClinicalTrials.gov Registry n. NCT02405273 [31.03.2015].
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Carcinoma de Pulmón de Células no Pequeñas/rehabilitación , Neoplasias Pulmonares/rehabilitación , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a very rare and uninvestigated subtype of non-small cell lung cancer (NSCLC). METHODS: The aims of this study were to define the radiometabolic features (by (18)F-FDG PET/CT) in a bi-centric cohort of 49 PSC patients and to explore their relation with clinico-pathological characteristics and long-term survival results after surgical treatment. RESULTS: There were 40 males and 9 females aged 65.2 ± 10.47 years. Overall long-term survival was 26.7 % at 5 years. Mean and median values of SUVmax were 15.21 and 15, respectively (SD ±5.5). Performing an age-, gender- and staging-matched analysis comparing PSC Stage-I only with a cohort of Stage-I NSCLC (n = 93), we observed significantly higher SUVmax values in PSC group (15.11 vs 7.66, p = 0.001). CONCLUSIONS: No differences in terms of SUVmax were found with regard to tumour dimensions, histology (pure vs mixed, pleomorphic vs others), pathological stage and pattern of recurrence. P-stage, surgical radicality, vascular/lymphatic invasion but not SUVmax affected long-term survival in PSC.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Anciano , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Glucosa/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Cushing syndrome (CS) caused by bronchopulmonary carcinoids (BCs) is a very rare entity. The aim of this study was to revisit the features of a multicenter clinical series to identify significant prognostic factors. METHODS: From January 2002 to December 2013, the clinical and pathological data of 23 patients (treated in five different institutions) were retrospectively reviewed. Survival analysis was performed to explore the relative weight of potential prognostic factors. RESULTS: Median age and male/female ratio were 48 years and 14/9, respectively. Most (> 80%) of the patients presented with CS-related symptoms at diagnosis. Tumor location was peripheral in 13 patients (57%) and central in 10 (43%). All patients but two (treated with chemotherapy) underwent surgical resection with curative intent. Definitive cyto/histology was indicative of typical carcinoid (TC) in 16 cases (70%) and atypical carcinoid (AC) in 7 cases (30%). A complete remission of CS was obtained in 16 cases (70%). Lymph nodal involvement was detected in 11 cases (48%), with N2 disease occurring in 7 (â¼ 30% of all cases). Four patients (22%) experienced a relapse of the disease after radical surgery. Overall 5-year survival (long-term survival, LTS) was 60%, better in TCs when compared with AC (LTS: 66 v s. 48%, p = 0.28). Log-rank analysis identified ECOG performance status, cTNM and cN staging, pTNM and pN staging, persistence of CS and relapses (local p = 0.006; distant p = 0.001) as significant prognostic factors in this cohort of patients. CONCLUSION: BCs causing CS are characterized by a high rate of lymph-nodal involvement, a suboptimal prognosis (5-year survival = 60%, 66% in TCs) and a remarkable risk of relapse even after radical resection. Advanced stage, lymph-nodal involvement and the persisting of the CS after treatment correlate with a poor prognosis.
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Neoplasias de los Bronquios/complicaciones , Tumor Carcinoide/complicaciones , Síndrome de Cushing/etiología , Adulto , Neoplasias de los Bronquios/mortalidad , Neoplasias de los Bronquios/patología , Neoplasias de los Bronquios/terapia , Tumor Carcinoide/mortalidad , Tumor Carcinoide/secundario , Tumor Carcinoide/terapia , Quimioterapia Adyuvante , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/mortalidad , Femenino , Humanos , Italia , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía/métodos , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Toracotomía , Factores de Tiempo , Resultado del TratamientoRESUMEN
The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in establishing the potential risk of cancer, defining differential diagnosis and prognosis, predicting the response to treatment, and monitoring the disease progression. The existence of circulating soluble growth factor receptors (sGFRs) deriving from their membrane counterparts has stimulated the interest of researchers to investigate the use of such molecules as potential cancer biomarkers. But what are the origins of circulating sGFRs? Are they naturally occurring molecules or tumor-derived products? Among these, the epidermal growth factor receptor (EGFR) is a cell-surface molecule significantly involved in cancer development and progression; it can be processed into biological active soluble isoforms (sEGFR). We have carried out an extensive review of the currently available literature on the sEGFRs and their mechanisms of regulation and biological function, with the intent to clarify the role of these molecules in cancer (and other pathological conditions) and, on the basis of the retrieved evidences, speculate about their potential use in the clinical setting.
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Biomarcadores de Tumor/sangre , Receptores ErbB/sangre , Neoplasias/diagnóstico , Empalme Alternativo , Receptores ErbB/fisiología , Humanos , Modelos Biológicos , Neoplasias/sangre , Neoplasias/patología , Medicina de Precisión , Pronóstico , ARN Mensajero/metabolismoRESUMEN
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.
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Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Receptores ErbB/sangre , Neoplasias Pulmonares/diagnóstico , Anciano , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Detección Precoz del Cáncer , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana EdadRESUMEN
Pulmonary neuroendocrine tumors (pNETs) arise from bronchial mucosal cells known as enterochromaffin cells which are part of the diffuse neuroendocrine system. The pathological spectrum of pNETs ranges from low-/intermediate-grade neoplasms such as bronchial carcinoids (BCs), also known as typical or atypical carcinoids, to high-grade neoplasms as large-cell neuroendocrine carcinoma and small-cell lung cancer. The tumor biology of pNETs still represents a matter of open debate. The distinct features among the different pNETs include not only their pathologic characteristics but also their clinical behavior, epidemiology, treatment, and prognosis. In this sense, a correct pathological identification in the preoperative setting is a key element for planning the best strategy of care in pNETs and especially in BCs. Controversial results have been reported on the diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (F-18-FDG PET or PET/CT) in BCs. On the other hand, there is increasing evidence supporting the use of PET with somatostatin analogues (DOTA-TOC, DOTA-NOC, or DOTA-TATE) labeled with gallium-68 (Ga-68) in pNETs. Herein, we review the pertinent literature aiming to better define the current state of art of PET/CT in the detection and histological differentiation of pNETs with special emphasis on BCs.
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Neoplasias de los Bronquios/diagnóstico , Tumor Carcinoide/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias de los Bronquios/diagnóstico por imagen , Tumor Carcinoide/diagnóstico por imagen , Tumor Carcinoide/mortalidad , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Tumores Neuroendocrinos/diagnóstico por imagen , Octreótido/análogos & derivados , Compuestos Organometálicos , Sensibilidad y EspecificidadRESUMEN
Non-small-cell lung carcinoma (NSCLC) is the most common lung cancer and one of the pioneer tumors in which immunotherapy has radically changed patients' outcomes. However, several issues are emerging and their implementation is required to optimize immunotherapy-based protocols. In this work, we investigate the ability of the Bromodomain and Extra-Terminal protein inhibitors (BETi) to stimulate a proficient anti-tumor immune response toward NSCLC. By using in vitro, ex-vivo, and in vivo models, we demonstrate that these epigenetic drugs specifically enhance Natural Killer (NK) cell cytotoxicity. BETi down-regulate a large set of NK inhibitory receptors, including several immune checkpoints (ICs), that are direct targets of the transcriptional cooperation between the BET protein BRD4 and the transcription factor SMAD3. Overall, BETi orchestrate an epigenetic reprogramming that leads to increased recognition of tumor cells and the killing ability of NK cells. Our results unveil the opportunity to exploit and repurpose these drugs in combination with immunotherapy.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología , Células Asesinas Naturales , Proteína smad3/genética , Proteína smad3/metabolismo , Proteínas que Contienen BromodominioRESUMEN
The COVID-19 pandemic has had a significant impact on new cancer diagnoses. This study aims to evaluate the implications of the lockdown period on new lung cancer diagnoses in northern Italy. We compared 2020 with 2019 cancer registry data, reporting the variations by age, stage, and treatments. In 2020, 303 lung cancer cases were registered, 21 fewer than in 2019. Cases fell in men (-31 patients, 9.6%) but not in women (+10 patients, +3.1%). A significant drop in stage I from 19.8% to 12.9% (p < 0.05) and an increase in stage III (12.7% vs. 19.1%; p < 0.05) was observed. Histological confirmation dropped (70.1% vs. 60.1%; p < 0.05) while cytology increased (12% vs. 20.8%; p < 0.01). Surgery declined (28.7% vs. 21.5%; p < 0.05) but increased in stage III (19.5% vs. 25.9%; p = 0.46), while chemotherapy increased (17.6% vs. 34.3%; p < 0.01) for all stages. During the pandemic, new lung cancer diagnoses dropped only in men. The reorganization of health services has ensured a decrease in surgical interventions (due to the unavailability of operating rooms) counterbalanced by an increase in chemotherapy.
RESUMEN
Long non-coding RNAs (lncRNAs) are transcripts without coding potential that are pervasively expressed from the genome and have been increasingly reported to play crucial roles in all aspects of cell biology. They have been also heavily implicated in cancer development and progression, with both oncogenic and tumor suppressor functions. In this work, we identified and characterized a novel lncRNA, TAZ-AS202, expressed from the TAZ genomic locus and exerting pro-oncogenic functions in non-small cell lung cancer. TAZ-AS202 expression is under the control of YAP/TAZ-containing transcriptional complexes. We demonstrated that TAZ-AS202 is overexpressed in lung cancer tissue, compared with surrounding lung epithelium. In lung cancer cell lines TAZ-AS202 promotes cell migration and cell invasion. TAZ-AS202 regulates the expression of a set of genes belonging to cancer-associated pathways, including WNT and EPH-Ephrin signaling. The molecular mechanism underlying TAZ-AS202 function does not involve change of TAZ expression or activity, but increases the protein level of the transcription factor E2F1, which in turn regulates the expression of a large set of target genes, including the EPHB2 receptor. Notably, the silencing of both E2F1 and EPHB2 recapitulates TAZ-AS202 silencing cellular phenotype, indicating that they are essential mediators of its activity. Overall, this work unveiled a new regulatory mechanism that, by increasing E2F1 protein, modifies the non-small cell lung cancer cells transcriptional program, leading to enhanced aggressiveness features. The TAZ-AS202/E2F1/EPHB2 axis may be the target for new therapeutic strategies.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , Neoplasias Pulmonares/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo , Efrinas/genética , Efrinas/metabolismo , Línea Celular Tumoral , Pulmón/metabolismo , Regulación Neoplásica de la Expresión Génica/genéticaAsunto(s)
Osteosarcoma/patología , Neoplasias Pleurales/patología , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Femenino , Humanos , Inmunohistoquímica , Osteosarcoma/química , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/cirugía , Neoplasias Pleurales/química , Neoplasias Pleurales/diagnóstico por imagen , Neoplasias Pleurales/cirugía , Neumonectomía , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
PURPOSE: To evaluate the clinical relevance of subcentimetric lymph node biopsy via mediastinoscopy in patients with presumed ocular sarcoidosis (OS). METHODS: Retrospective study of consecutive patients who underwent biopsy via mediastinoscopy for suspected OS. The biopsy outcomes and clinical features of patients with subcentimetric nodes and of those with lymph nodes >1 cm were compared. RESULTS: A total of 67 patients with presumed OS were included. Forty-two patients (63%) had lymph nodes ≥1 cm in diameter, while 25(37%) showed subcentimetric lymph nodes. Biopsy was consistent with sarcoidosis in 83% of patients with lymph nodes ≥1 cm and in 76% of patients with subcentimetric lymph nodes (p = .60). Patients with OS who had subcentimetric lymph nodes had less lymphopenia (p = .01), lower lysozyme values (p = .03) and a longer diagnostic delay compared to those with larger lymph nodes. CONCLUSIONS: The biopsy of subcentimetric lymph nodes via mediastinoscopy may provide a histological diagnosis and reduce diagnostic delay.
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Endoftalmitis , Sarcoidosis , Biopsia , Diagnóstico Tardío , Humanos , Ganglios Linfáticos/patología , Estudios Retrospectivos , Sarcoidosis/diagnósticoRESUMEN
OBJECTIVE: To evaluate the influence of lung adenocarcinoma second predominant pattern on the maximal standard uptake value (SUVmax) and its prognostic effect in different histologic groups. METHODS: We retrospectively collected surgically resected pathologic stage I and II lung adenocarcinoma from nine European institutions. Only patients who underwent preoperative PET-CT and with available information regarding SUVmax of T (SUVmaxT) and N1 (SUVmaxN1) component were included. RESULTS: We enrolled 344 patients with lung adenocarcinoma. SUVmaxT did not show any significant relation according to the second predominant pattern (p = 0.139); this relationship remained nonsignificant in patients with similar predominant pattern. SUVmaxT influenced the disease-free survival in the whole cohort (p = 0.002) and in low- and intermediate-grade predominant pattern groups (p = 0.040 and p = 0.008, respectively). In the high-grade predominant pattern cohort and in the pathologic N1 cases, SUVmaxT lost its prognostic power. SUVmaxN1 did not show any significant correlation with predominant and second predominant patterns and did not have any prognostic impact on DFS. CONCLUSIONS: SUVmaxT is influenced only by the adenocarcinoma predominant pattern, but not by second predominant pattern. Concurrently, in high-grade predominant pattern and pN1 group the prognostic power of SUVmaxT becomes nonsignificant.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes. METHODS: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups. RESULTS: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008). CONCLUSIONS: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern.
Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patología , Adenocarcinoma del Pulmón/patología , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/cirugía , Masculino , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
Background: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. Methods: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.
RESUMEN
ABSTRACT: Solitary fibrous tumor of the pleura (SFTP) is a rare mesenchymal neoplasm. Preoperative diagnosis is usually difficult and based on radiological findings only. We report the imaging results observed in 5 patients with SFTP (2 malignant) obtained by 68Ga-DOTATOC PET/CT. At qualitative analysis, all tumors showed uptake of 68Ga-DOTATOC. Mean tumor SUVmax was 9.9 ± 5.7. The expression of SST2 (somatostatin receptors subtype 2) was confirmed by immunohistochemistry in 2 tumor samples, and by gene amplification of SST2 mRNA in all cases. These data suggest a diagnostic role of radioreceptor PET/CT in SFTP, and open novel potential treatment options in unresectable/metastatic disease.