RESUMO
INTRODUCTION/BACKGROUND: Samples from endobronchial ultrasound-guided fine needle aspiration (EBUS-TBNA) are frequently used for next generation sequencing (NGS) in patients with non-small cell lung cancer (NSCLC) to look for genetic driver mutations. The objective of the current study was to evaluate the performance of extended NGS panels using EBUS-TBNA samples in a real-world setting and identify factors associated with the success of NGS. MATERIALS AND METHODS: This study included all patients who underwent EBUS and were diagnosed with non-squamous NSCLC with mediastinal metastasis from 2016 to 2019 at the University of Pennsylvania. We reviewed demographic information, imaging studies, procedure reports, pathology and NGS reports. Logistic regression was used to analyze factors associated with the success of NGS panels. RESULTS: The success rates of NGS using EBUS-TBNA samples were 92.5%, and 91.5% for DNA and RNA NGS panels respectively. Samples from higher N stage (N2 and N3 lymph nodes) and with higher tumor cellularity (>25%) resulted in higher success rate for DNA NGS. The effect of tumor cellularity remained borderline significant after entering multivariable logistic regression. The short-axis diameter of the sampled lymph node on CT scan, FDG-avidity on PET CT and >3 EBUS passes per lymph node during the procedure were not associated with NGS success. CONCLUSION: Both DNA and RNA extended-panel NGS had high performance using EBUS-TBNA samples. Sampling more advanced nodal stations and obtaining samples with higher tumor cellularity were associated with higher success rate of DNA NGS. Other imaging or procedural factors did not affect NGS performance.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Broncoscopia/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
BACKGROUND: Pulmonary nodules suspicious for lung cancer are frequently diagnosed. Evaluating and optimizing the diagnostic yield of lung nodule biopsy is critical as innovation in bronchoscopy continues to progress. METHODS: This is a retrospective cohort study. Consecutive patients undergoing guided bronchoscopy for suspicious pulmonary nodule(s) between February 2020 and July 2021 were included. The cone-beam computed tomography (CBCT)+ radial endobronchial ultrasound (r-EBUS) group had their procedure using CBCT-derived augmented fluoroscopy along with r-EBUS. The CBCT+ ultrathin bronchoscope (UTB)+r-EBUS group had the same procedure but with the use of an ultrathin bronchoscope. The r-EBUS group underwent r-EBUS guidance without CBCT or augmented fluoroscopy. We used multivariable logistic regression to compare diagnostic yield, adjusting for confounding variables. RESULTS: A total of 116 patients were included. The median pulmonary lesion diameter was 19.5 mm (interquartile range, 15.0 to 27.5 mm), and 91 (78.4%) were in the peripheral half of the lung. Thirty patients (25.9%) underwent CBCT+UTB, 27 (23.3%) CBCT, and 59 (50.9%) r-EBUS alone with unadjusted diagnostic yields of 86.7%, 70.4%, and 42.4%, respectively ( P <0.001). The adjusted diagnostic yields were 85.0% (95% CI, 68.6% to 100%), 68.3% (95% CI, 50.1% to 86.6%), and 44.5% (95% CI, 31.0% to 58.0%), respectively. There was significantly more virtual navigational bronchoscopy use in the r-EBUS group (45.8%) compared with the CBCT+UTB (13.3%) and CBCT (18.5%) groups, respectively. CBCT procedures required dose area product radiation doses of 7602.5 µGym 2 . CONCLUSION: Compared with the r-EBUS group, CBCT + UTB + r-EBUS was associated with higher navigational success, fewer nondiagnostic biopsy results, and a higher diagnostic yield. CBCT procedures are associated with a considerable radiation dose.
Assuntos
Broncoscopia , Neoplasias Pulmonares , Humanos , Broncoscopia/métodos , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Fluoroscopia , Endossonografia/métodosRESUMO
BACKGROUND: Airway complications after lung transplantation are a difficult to treat clinical entity. A subset of these patients develop progressive distal airway stenosis (DAS) and a total loss of lobar airways. Stents may be placed to prevent continued obstruction. However, there is little data to suggest stent placement provides durable airway patency or a reduction in the need for further interventions. METHODS: A retrospective cohort study was conducted using patients with DAS who underwent a variety of interventions. Demographic information and complications were described using nonparametric methods. Lung function at 1 year and bronchoscopies per month were compared between stented and nonstented patients using a Mann-Whitney test. For patients treated with stenting, bronchoscopies per month were compared before and after stenting using a Wilcoxon signed-rank test. Airway patency was compared between stented and nonstented patients using the Fischer exact test. RESULTS: Eleven airways were identified as DAS phenotype, 5 of which were treated with stents. Within the stented airways, a trend toward an increase in bronchoscopies per month was seen after stent placement. Comparing the stented versus nonstented patients, there was no improvement in lung function, no reduction in bronchoscopies per month, and no difference in airway patency for stented patients. CONCLUSION: Patients with DAS phenotypes that were treated with endobronchial stenting did not require less airway intervention or have greater final airway patency compared with the nonstented airways. Among the stented patients, the need for airway manipulation did not decrease after stent placement.
Assuntos
Constrição Patológica/terapia , Transplante de Pulmão/efeitos adversos , Doenças Respiratórias/patologia , Stents/efeitos adversos , Adulto , Idoso , Obstrução das Vias Respiratórias/prevenção & controle , Broncoscopia/métodos , Broncoscopia/estatística & dados numéricos , Estudos de Casos e Controles , Falha de Equipamento/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Testes de Função Respiratória/métodos , Doenças Respiratórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Segurança , Resultado do TratamentoAssuntos
Broncoscopia/métodos , Quilotórax/diagnóstico por imagem , Anormalidades Linfáticas/diagnóstico por imagem , Linfografia/métodos , Quilotórax/patologia , Meios de Contraste/administração & dosagem , Fluoroscopia/métodos , Humanos , Anormalidades Linfáticas/patologia , Anormalidades Linfáticas/terapia , Masculino , Pessoa de Meia-Idade , Corantes de Rosanilina/administração & dosagem , Ducto Torácico/diagnóstico por imagem , Resultado do TratamentoRESUMO
RATIONALE: Transbronchial cryobiopsy is an emerging technique for obtaining biopsies of lung parenchyma. Despite limited evidence of its safety and efficacy in direct comparison with other available biopsy procedures, pulmonologists are integrating this technique into clinical practice with the hope of avoiding the risks of surgical lung biopsy. OBJECTIVES: To report the rate of severe complications and diagnostic outcomes immediately after introduction of transbronchial cryobiopsy into the clinical practice of a single-center, high-volume, interventional pulmonary group at a large academic medical center in the United States. METHODS: We conducted a retrospective review of a case series. RESULTS: Twenty-five consecutive patients underwent transbronchial cryobiopsy for a variety of indications over a period of 14 weeks. In the absence of a strict protocol, a variety of techniques were employed by four attending interventional pulmonologists and one advanced interventional pulmonology fellow to plan and complete the procedures. Three patients (12%) experienced serious hemorrhage immediately after biopsy, including one patient who survived a life-threatening bleed. Two procedures were complicated by an iatrogenic pneumothorax. One patient experienced hypercapnic respiratory failure shortly after the procedure. A definitive diagnosis was made with 14 cryobiopsies (56%). Another five biopsies (20%) contributed to a presumptive diagnosis achieved by multidisciplinary consensus. CONCLUSIONS: Transbronchial cryobiopsy may have diagnostic and safety limitations that are not yet well appreciated, given the state of the published medical literature. Major questions remain regarding the safest procedural protocol to be used when performing transbronchial cryobiopsy. Thorough planning and a high degree of caution are encouraged on first introduction of this technique into a clinical practice.
Assuntos
Biópsia/efeitos adversos , Criocirurgia/efeitos adversos , Hemorragia/etiologia , Pulmão/patologia , Pneumotórax/etiologia , Centros Médicos Acadêmicos , Biópsia/instrumentação , Biópsia/métodos , Broncoscopia/efeitos adversos , Criocirurgia/métodos , Humanos , Doença Iatrogênica , Pennsylvania , Pneumotórax/diagnóstico por imagem , Radiografia Torácica , Estudos RetrospectivosRESUMO
Cryotherapy is an evolving therapeutic and diagnostic tool used during bronchoscopy. Through rapid freeze-thaw cycles, cryotherapy causes cell death and tissue necrosis or tissue adherence that can be used via the flexible or rigid bronchoscope. This extreme cold can be used through the working channel of the bronchoscope via a specialized cryoprobe or directly with the use of spray cryotherapy. These properties allow for multiple bronchoscopic techniques, each with its own equipment and procedural, safety, and efficacy considerations. Bronchoscopic cryotherapy can be used in a variety of clinical scenarios, including the treatment of malignant and benign central airway obstruction and low-grade airway malignancy, foreign body removal or cryoextraction, endobronchial biopsy, and transbronchial biopsy. The bulk of the experience with bronchoscopic cryotherapy consists of uncontrolled case series of malignant central airway obstruction. There are also controlled data supporting the use of cryoadhesion for endobronchial biopsies, albeit with an increased risk of controllable bleeding. The use of cryoadhesion for transbronchial biopsies is an active area of investigation with limited controlled data. In addition, there are promising future directions using bronchoscopic cryotherapy, including chemosensitizing malignancy with cryotherapy and capitalizing on the synergy between cryotherapy and radiation.
Assuntos
Obstrução das Vias Respiratórias/terapia , Neoplasias Brônquicas/terapia , Broncoscopia , Crioterapia/métodos , Obstrução das Vias Respiratórias/etiologia , Biópsia/efeitos adversos , Neoplasias Brônquicas/patologia , Crioterapia/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The B and T lymphocyte attenuator (BTLA) is a recently identified member of the CD28 family of cell receptors. Initial reports demonstrated that mice deficient in BTLA expression were more susceptible to experimental autoimmune encephalomyelitis, indicating that BTLA was likely to function as a negative regulator of T cell activation. However, cross-linking of BTLA only resulted in a 2-fold reduction of IL-2 production, questioning the potency with which BTLA engagement blocks T cell activation. We established a model in which BTLA signaling could be studied in primary human CD4 T cells. We observed that cross-linking of a chimeric receptor consisting of the murine CD28 extracellular domain and human BTLA cytoplasmic tail potently inhibits IL-2 production and completely suppresses T cell expansion. Mutation of any BTLA tyrosine motifs had no effect on the ability of BTLA to block T cell activation. Only mutation of all four tyrosines rendered the BTLA cytoplasmic tail nonfunctional. We performed structure-function studies to determine which factors recruited to the BTLA cytoplasmic tail correlated with BTLA function. Using pervanadate as a means to phosphorylate the BTLA cytoplasmic tail, we observed both Src homology protein (SHP)-1 and SHP-2 recruitment. However, upon receptor engagement, we observed only SHP-1 recruitment, and mutations that abrogated SHP-1 recruitment did not impair BTLA function. These studies question whether SHP-1 or SHP-2 have any role in BTLA function and caution against the use of pervanadate as means to initiate signal transduction cascades in primary cells.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Inibidores do Crescimento/fisiologia , Fosfotirosina/química , Fosfotirosina/fisiologia , Receptores Imunológicos/fisiologia , Transdução de Sinais/imunologia , Motivos de Aminoácidos/genética , Animais , Antígenos CD28/genética , Antígenos CD28/fisiologia , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Dimerização , Inibidores do Crescimento/genética , Inibidores do Crescimento/metabolismo , Humanos , Interleucina-2/antagonistas & inibidores , Interleucina-2/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ativação Linfocitária/genética , Camundongos , Mutação , Fosfotirosina/genética , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Proteína Tirosina Fosfatase não Receptora Tipo 6 , Proteínas Tirosina Fosfatases/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/fisiologia , Transdução de Sinais/genética , Vanadatos/farmacologiaRESUMO
CTLA-4 and PD-1 are receptors that negatively regulate T-cell activation. Ligation of both CTLA-4 and PD-1 blocked CD3/CD28-mediated upregulation of glucose metabolism and Akt activity, but each accomplished this regulation using separate mechanisms. CTLA-4-mediated inhibition of Akt phosphorylation is sensitive to okadaic acid, providing direct evidence that PP2A plays a prominent role in mediating CTLA-4 suppression of T-cell activation. In contrast, PD-1 signaling inhibits Akt phosphorylation by preventing CD28-mediated activation of phosphatidylinositol 3-kinase (PI3K). The ability of PD-1 to suppress PI3K/AKT activation was dependent upon the immunoreceptor tyrosine-based switch motif located in its cytoplasmic tail, adding further importance to this domain in mediating PD-1 signal transduction. Lastly, PD-1 ligation is more effective in suppressing CD3/CD28-induced changes in the T-cell transcriptional profile, suggesting that differential regulation of PI3K activation by PD-1 and CTLA-4 ligation results in distinct cellular phenotypes. Together, these data suggest that CTLA-4 and PD-1 inhibit T-cell activation through distinct and potentially synergistic mechanisms.
Assuntos
Antígenos de Diferenciação/fisiologia , Antígenos de Superfície/fisiologia , Proteínas Reguladoras de Apoptose/fisiologia , Ativação Linfocitária/fisiologia , Linfócitos T/fisiologia , Antígenos CD , Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Antígeno CTLA-4 , Ativação Enzimática , Regulação da Expressão Gênica , Humanos , Técnicas In Vitro , Ácido Okadáico/farmacologia , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositóis/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosfoproteínas Fosfatases/antagonistas & inibidores , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Receptor de Morte Celular Programada 1 , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
OBJECTIVE: To review the history, development, and current applications of robotics in surgery. BACKGROUND: Surgical robotics is a new technology that holds significant promise. Robotic surgery is often heralded as the new revolution, and it is one of the most talked about subjects in surgery today. Up to this point in time, however, the drive to develop and obtain robotic devices has been largely driven by the market. There is no doubt that they will become an important tool in the surgical armamentarium, but the extent of their use is still evolving. METHODS: A review of the literature was undertaken using Medline. Articles describing the history and development of surgical robots were identified as were articles reporting data on applications. RESULTS: Several centers are currently using surgical robots and publishing data. Most of these early studies report that robotic surgery is feasible. There is, however, a paucity of data regarding costs and benefits of robotics versus conventional techniques. CONCLUSIONS: Robotic surgery is still in its infancy and its niche has not yet been well defined. Its current practical uses are mostly confined to smaller surgical procedures.