RESUMO
BACKGROUND: The use of single lung transplantation (SLTx) for chronic obstructive pulmonary disease is often viewed as inferior therapy compared with bilateral lung transplantation (BLTx). We hypothesized from our experience that subpopulations of recipients with emphysema exist in which SLTx represents therapy that is equivalent to BLTx, therefore allowing more patients access to transplantation. METHODS: Consecutive patients undergoing LTx for emphysema between 1992 and 2012 at a single institution were identified and analyzed retrospectively. A similar cohort from the United Network of Organ Sharing (UNOS) national database was identified for comparison. Five-year survival in patients receiving SLTx and those receiving BLTx were compared using Kaplan-Meier survival curves and log-rank tests. RESULTS: Two hundred thirty-six patients meeting criteria were identified from our institution. Two hundred six underwent SLTx, and 30 underwent BLTx. Five-year survival for single-center SLTx (53.2% ± 3.6%) and BLTx (56.7% ± 10.2%) was not significantly different (p = 0.753). The national database included 7,256 patients meeting selection criteria, with 4,408 undergoing SLTx and 2,848 undergoing BLTx. Five-year survival among the national cohorts was lower for SLTx (46.4% ± 0.8%) compared with BLTx (55.9% ± 1.1%) (p < 0.0001). However, 5-year survival for our single-center SLTx experience (53.2% ± 3.6%) was comparable to the national BLTx cohort (55.9% ± 1.1%) (p = 0.539). CONCLUSIONS: Five-year survival after SLTx for emphysema was comparable to that for BLTx in cohorts from our institution and from the UNOS national database. Further study should focus on the mechanism behind these improved outcomes. Given the potential for a larger number of life-years saved, SLTx should continue to be considered a therapeutic option in appropriately selected patients with chronic obstructive pulmonary disease (COPD).
Assuntos
Transplante de Pulmão , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/cirurgia , Enfisema Pulmonar/mortalidade , Enfisema Pulmonar/cirurgia , Feminino , Humanos , Transplante de Pulmão/métodos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: Energy-based devices are used in virtually every operation. Our purposes were to describe causes of energy-based device complications leading to injury or death, and to determine if common mechanisms leading to injury or death can be identified. STUDY DESIGN: The FDA's Manufacturer and User Facility Device Experience (MAUDE) database was searched for surgical energy-based device injuries and deaths reported over 20 years (January 1994 to December 2013). Device-related complications were recorded and analyzed. RESULTS: We analyzed 178 deaths and 3,553 injuries. Common patterns of complications were: thermal burns, 63% (n = 2,353); hemorrhage, 17% (n = 642); mechanical failure of device, 12% (n = 442); and fire, 8% (n = 294). Events were identified intraoperatively in 82% (3,056), inpatient postoperatively in 9% (n = 351), and after discharge in 9% (n = 324). Of the deaths, 12% (n = 22) occurred after discharge home. Common mechanisms for thermal burn injuries were: direct application, 30% (n = 694); dispersive electrode burn, 29% (n = 657); and insulation failure, 14% (n = 324). Thermal injury was the most common reason for death (39%, n = 70). The mechanism for these thermal injuries was most frequently direct application (84%, n = 59, p < 0.001 vs all other mechanisms). Fires were most common with monopolar "Bovie" instruments (88%, n = 258, p < 0.001 vs all other devices) when they were used in head and neck operations (66%, n = 193, p < 0.001 vs all other locations). CONCLUSIONS: Complications due to energy-based devices occur from 4 main causes: thermal burn, hemorrhage, mechanical failure, and fire. Thermal direct application injuries are the most common reason for both injury and death.
Assuntos
Queimaduras/etiologia , Equipamentos e Provisões Elétricas/efeitos adversos , Falha de Equipamento , Complicações Intraoperatórias/etiologia , Hemorragia Pós-Operatória/etiologia , Queimaduras/mortalidade , Bases de Dados Factuais , Incêndios/estatística & dados numéricos , Humanos , Complicações Intraoperatórias/mortalidade , Hemorragia Pós-Operatória/mortalidade , Estados Unidos , United States Food and Drug AdministrationRESUMO
Paraplegia following complex aortic intervention relies on crude evaluation of lower extremity strength such as whether the patient can lift their legs or flex the ankle. Little attention has been given to the possible long-term neurologic sequelae following these procedures in patients appearing functionally normal. We hypothesize that mice subjected to minimal ischemic time will have functional and histological changes despite the gross appearance of normal function. Male mice underwent 3 min of aortic occlusion (n=14) or sham surgery (n=4) via a median sternotomy. Neurologic function was graded by Basso Motor Score (BMS) preoperatively and at 24h intervals after reperfusion. Mice appearing functionally normal and sham mice were placed on a walking beam and recorded on high-definition, for single-frame motion analysis. After 96 hrs, spinal cords were removed for histological analysis. Following 3 min of ischemia, functional outcomes were split evenly with either mice displaying almost normal function n=7 or near complete paraplegia n=7. Additionally, single-frame motion analysis revealed significant changes in gait. Histologically, there was a significant stepwise reduction of neuronal viability, with even the normal function ischemic group demonstrating significant loss of neurons. Despite the appearance of normal function, temporary ischemia induced marked cyto-architectural changes and neuronal degeneration. Furthermore high-definition gait analysis revealed significant changes in gait and activity following thoracic aortic occlusion. These data suggest that all patients undergoing procedures, even with short ischemic times, may have spinal cord injury that is not evident clinically.
Assuntos
Doenças da Aorta/complicações , Paraplegia/etiologia , Traumatismo por Reperfusão/complicações , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/etiologia , Análise de Variância , Animais , Membro Posterior/fisiopatologia , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Exame Neurológico , Fatores de TempoRESUMO
BACKGROUND: Paraplegia remains a devastating complication of aortic surgery, occurring in up to 20% of complex thoracoabdominal repairs. Erythropoietin (EPO) attenuates this injury in models of spinal cord ischemia. Upregulation of the beta-common receptor (ßcR) subunit of the EPO receptor is associated with reduced damage in murine models of neural injury. This receptor activates anti-apoptotic pathways including signaling transducer and activator of transcription 3 (STAT3). We hypothesized that spinal cord ischemia-reperfusion injury upregulates the ßcR subunit with a subsequent increase in activated STAT3. METHODS: Adult male C57/BL6 mice received an intraperitoneal injection of 0.5 mL of EPO (10 U/kg) or 0.9% saline after induction of anesthesia. Spinal cord ischemia was induced through sternotomy and 4-minute thoracic aortic cross-clamp. Sham mice underwent sternotomy without cross-clamp placement. Four groups were studied: ischemic and sham groups, each with and without EPO treatment. After 4 hours of reperfusion, spinal cords were harvested and homogenized. The ßcR subunit expression and STAT3 activation were evaluated by immunoblot. RESULTS: Ischemia reperfusion increased ßcR subunit expression in spinal cords of ischemia + saline and ischemia + EPO mice compared with shams (3.4 ± 1.39 vs 1.31 ± 0.3, p = 0.01 and 3.80 ± 0.58 vs 1.56 ± 0.32, p = 0.01). Additionally, both ischemic groups demonstrated increased STAT3 activation compared with shams (1.35 ± 0.14 vs 1.09 ± 0.07, p = 0.01 and 1.66 ± 0.35 vs 1.08 ± 0.17, p = 0.02). CONCLUSIONS: Ischemia-reperfusion injury induces EPO receptor ßcR subunit expression and early downstream anti-apoptotic signaling through STAT3 activation. Further investigation into the role of the ßcR subunit is warranted to determine tissue protective functions of EPO. Elucidation of mechanisms involved in spinal cord protection is essential for reducing delayed paraplegia.
Assuntos
Receptores da Eritropoetina/biossíntese , Traumatismo por Reperfusão/metabolismo , Isquemia do Cordão Espinal/metabolismo , Medula Espinal/irrigação sanguínea , Regulação para Cima , Animais , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/fisiologiaRESUMO
OBJECTIVES: C-terminal tensin-like (Cten) protein, a component of focal adhesions, contributes to cell motility and invasion in multiple human cancers. Epidermal growth factor can activate signal transducer and activator of transcription 3, and both contribute to invasion through focal adhesion interactions. We hypothesize that Cten may mediate invasion of lung cancer cells provided by epidermal growth factor via signal transducer and activator of transcription 3. METHODS: Four human non-small cell lung cancer cell lines were treated with epidermal growth factor to evaluate activation of the signal transducer and activator of transcription 3 pathway and induction of Cten expression. Chemical inhibition of signal transducer and activator of transcription 3 was used to evaluate the effect on epidermal growth factor-induced Cten expression. Protein expression was quantified by Western blot. H125 and A549 cells were transduced with short-hairpin RNA via lentiviral vector to knockdown expression of Cten. An in vitro transwell invasion assay was used to assess the effects of Cten knockdown on cell invasion (n = 3 for all experiments). RESULTS: Stimulation of lung cancer cells with epidermal growth factor activated the signal transducer and activator of transcription 3 pathway and induced expression of Cten in all cell lines. Signal transducer and activator of transcription 3 inhibition significantly reduced epidermal growth factor-induced expression of Cten in H125 (P < .0001), H358 (P = .006), and H441 (P = .014) cells in a dose-dependent manner. Knockdown of Cten expression resulted in significant decreases in cellular invasion in both H125 (P = .0036) and A549 (P = .0006) cells. CONCLUSIONS: These are the first findings in lung cancer to demonstrate that Cten expression mediates invasion of human lung cancer cells and is upregulated by epidermal growth factor via signal transducer and activator of transcription 3 pathway. Cten should be considered a potential therapeutic target for lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Neoplasias Pulmonares/metabolismo , Proteínas dos Microfilamentos/metabolismo , Fator de Transcrição STAT3/metabolismo , Ácidos Aminossalicílicos/farmacologia , Benzenossulfonatos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fator de Crescimento Epidérmico/farmacologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas dos Microfilamentos/genética , Invasividade Neoplásica , Interferência de RNA , Fator de Transcrição STAT3/antagonistas & inibidores , Transdução de Sinais , Tensinas , Fatores de Tempo , TransfecçãoRESUMO
OBJECTIVE: Paraplegia remains a devastating complication of complex aortic surgery. Erythropoietin (EPO) has been shown to prevent paraplegia after ischemia reperfusion, but the protective mechanism remains poorly described in the spinal cord. We hypothesized that EPO induces the CREB (cAMP [adenosine 3'5' cyclic monophosphate] response element-binding protein) pathway and neurotrophin production in the murine spinal cord, attenuating functional and cellular injury. METHODS: Adult male mice were subjected to 4 minutes of spinal cord ischemia via an aortic and left subclavian cross-clamp. Experimental groups included EPO treatment 4 hours before incision (n = 7), ischemic control (n = 7), and shams (n = 4). Hind-limb function was assessed using the Basso motor score for 48 hours after reperfusion. Spinal cords were harvested and analyzed for neuronal viability using histology and staining with a fluorescein derivative. Expression of phosphorylated (p)AKT (a serine/threonine-specific kinase), pCREB, B-cell lymphoma 2, and brain-derived neurotrophic factor were determined using immunoblotting. RESULTS: By 36 hours of reperfusion, EPO significantly preserved hind-limb function after ischemia-reperfusion injury (P < .01). Histology demonstrated preserved cytoarchitecture in the EPO treatment group. Cords treated with EPO expressed significant increases in pAKT (P = .021) and pCREB (P = .038). Treatment with EPO induced expression of both of the neurotrophins, B-cell lymphoma 2, and brain-derived neurotrophic factor, beginning at 12 hours. CONCLUSIONS: Erythropoietin-mediated induction of the CREB pathway and production of neurotrophins is associated with improved neurologic function and increased neuronal viability following spinal cord ischemia reperfusion. Further elucidation of EPO-derived neuroprotection will allow for expansion of adjunct mechanisms for spinal cord protection in high-risk thoracoabdominal aortic intervention.
Assuntos
Proteína de Ligação a CREB/metabolismo , Eritropoetina/farmacologia , Paraplegia/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Isquemia do Cordão Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Paraplegia/enzimologia , Paraplegia/fisiopatologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/fisiopatologia , Medula Espinal/enzimologia , Medula Espinal/fisiopatologia , Isquemia do Cordão Espinal/enzimologia , Isquemia do Cordão Espinal/fisiopatologia , Fatores de TempoRESUMO
Reconstruction of large chest wall defects after resection remains a significant undertaking. Obtaining a negative margin is of paramount importance for long-term survival. While reconstructing the chest wall, recreating a stable chest wall with adequate functional capacity and reasonable cosmesis are always the end goals. Morbidity from these procedures is significant, and mortality continues to hover around 5%. With continued advancement in reconstructive techniques and improved perioperative management, these procedures will continue to result in improved outcomes for patients.
Assuntos
Neoplasias Pulmonares/cirurgia , Parede Torácica/cirurgia , Toracoplastia/métodos , Humanos , Pneumonectomia/métodosRESUMO
BACKGROUND: Donor lungs acquired from victims of asphyxiation by hanging are not routinely used for lung transplantation because of the associated lung injury. Ex vivo lung perfusion (EVLP) is a technique to evaluate marginal donor lungs before transplantation. We report here our experience with the use of EVLP in donor lungs procured from victims of asphyxia by hanging. METHODS: Lungs from 5 donors who became brain dead secondary to hanging were evaluated by EVLP. Donor organs were perfused according to trial protocol. Donor lungs were accepted for transplantation if they maintained a PaO2 greater than or equal to 350 mm Hg, had a clear roentgenogram, and had no significant worsening of physiologic metrics. RESULTS: Perfused organs included single and double lung blocs, and all were perfused without technical incident. Three of the 5 donor organs evaluated met criteria for transplantation after 3 hours of EVLP and were transplanted. Donor organs rejected for transplantation showed either signs of worsening PaO2 or deterioration of physiologic metrics. There were no intraoperative complications in the patients who underwent transplantation, and all were alive at 30 days. CONCLUSIONS: We report here the successful use of EVLP to assess donor lungs acquired from victims of asphyxiation by hanging. The use of EVLP in this particular group of donors has the potential to expand the available donor pool. We demonstrate that EVLP is a viable option for evaluating the function of lung allografts before transplantation and would recommend that all donor lungs obtained from hanging victims undergo EVLP to assess their suitability for transplantation.
Assuntos
Asfixia , Transplante de Pulmão , Perfusão/métodos , Obtenção de Tecidos e Órgãos/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Suicídio , Adulto JovemRESUMO
BACKGROUND: Lung cancer stem cells (CSCs) are a subpopulation of cells that drive growth, invasiveness, and resistance to therapy. Inflammatory eicosanoids are critical to maintain this malignant subpopulation. Secretory phospholipase A2 group IIa (sPLA2) is an important mediator of the growth and invasive potential of human lung cancer cells and regulates eicosanoid production. We hypothesized that sPLA2 plays a role in the maintenance of lung CSCs. METHODS: Cancer stem cells from lung adenocarcinoma cell lines H125 and A549 were isolated using aldehyde dehydrogenase activity and flow cytometry. Protein and mRNA levels for sPLA2 were compared between sorted cells using Western blotting and quantitative reverse transcriptase-polymerase chain reaction techniques. Chemical inhibition of sPLA2 and short-hairpin RNA knockdown of sPLA2 were used to evaluate effects on tumorsphere formation. RESULTS: Lung CSCs were isolated in 8.9%±4.1% (mean±SD) and 4.1%±1.6% of H125 and A549 cells respectively. Both sPLA2 protein and mRNA expression were significantly elevated in the CSC subpopulation of H125 (p=0.002) and A549 (p=0.005; n=4). Knockdown of sPLA2 significantly reduced tumorsphere formation in H125 (p=0.026) and A549 (p=0.001; n=3). Chemical inhibition of sPLA2 resulted in dose-dependent reduction in tumorsphere formation in H125 (p=0.003) and A549 (p=0.076; n=3). CONCLUSIONS: Lung CSCs express higher levels of sPLA2 than the non-stem cell population. Our findings that viral knockdown and chemical inhibition of sPLA2 reduce tumorsphere formation in lung cancer cells demonstrate for the first time that sPLA2 plays an important role in CSCs. These findings suggest that sPLA2 may be an important therapeutic target for human lung cancer.
Assuntos
Adenocarcinoma/enzimologia , Neoplasias Pulmonares/enzimologia , Células-Tronco Neoplásicas , Fosfolipases A2 Secretórias/fisiologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , FenótipoRESUMO
BACKGROUND: Thymidine kinase 1 (TK1) is a biomarker elevated in several malignancies, including lung cancer. Up-regulation of TK1 is an early event in carcinogenesis and therefore a target for early cancer detection. We have developed a novel Enzyme Linked Immunosorbent Assay (ELISA) to detect TK1 in serum. MATERIALS AND METHODS: Forty patients with pulmonary nodules and 18 healthy individuals had their serum collected prior to surgery. All samples were analyzed using a radioassay and ELISA. RESULTS: TK1 was significantly elevated in all lung cancer samples. Patients with stage I (n=16) and stage II (n=17) disease had significantly higher TK1 levels than controls. The area under the curve was 0.792, using 4.9 nM TK1 as cut-off, for early-stage lung cancer. The sensitivity and specificity were 75.0 and 83.3, respectively. TK1 concentration was a more sensitive and accurate indicator of lung cancer than TK1 activity. CONCLUSION: TK1 is significantly elevated in serum from patients with stage I and stage II lung cancer as measured using the established ELISA. This novel TK1 ELISA is both sensitive and specific for the detection of early-stage and advanced lung cancer, and therefore may be an important tool in the management of this disease.
Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Nódulo Pulmonar Solitário/diagnóstico , Timidina Quinase/sangue , Idoso , Área Sob a Curva , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Nódulo Pulmonar Solitário/sangueRESUMO
Over the course of 2013, many important studies have been published affecting the care of thoracic surgery patients. Novel chemotherapeutics are being developed to target specific tumor mutations. The utilization of robotic-assisted surgery continues to expand within this exciting field as well. Improved data on endobronchial ultrasound staging and sublobar resections for non-small cell lung cancer as well as postoperative surveillance after esophagectomy have also been reported. This review summarizes important publications of the past year influencing the practice of thoracic surgery today.
Assuntos
Robótica/métodos , Cirurgia Torácica Vídeoassistida/métodos , Procedimentos Cirúrgicos Torácicos/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Esofagectomia/métodos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgiaRESUMO
OBJECTIVE: Dexmedetomidine, an α-2a adrenergic agonist, given pre- and postoperatively was previously shown to attenuate neuronal injury in a murine model of spinal cord ischemia-reperfusion. In the brain, α-2 agonists have been shown to induce the phosphorylation of cyclic AMP response-element binding protein (CREB), a transcription factor necessary for neuron survival. We hypothesized that the α-2a adrenergic agonist given preoperatively increases CREB-mediated neuroprotective proteins, attenuating neuronal injury and cytoarchitectural decay. METHODS: Mice (ie, C57BL/6 mice) underwent 5 minutes of aortic occlusion via median sternotomy. Mice received 25 µg/kg dexmedetomidine or equivalent normal saline at 24 hours, 12 hours, and 30 minutes preoperatively. Functional outcomes were recorded at 6 to 48 hours postoperatively when spinal cords were removed for histologic analysis. Spinal cords were examined for protein kinase B, CREB, B-cell lymphoma 2, and brain-derived neurotrophic factor following treatment alone or ischemia-reperfusion surgery. RESULTS: Following aortic occlusion, mice in the treatment group had preserved neurologic function at all time points (P < .05). Histologic analysis showed preserved cytoarchitecture and decreased neuronal injury in the treatment group when compared with ischemic controls. Additionally, analysis of spinal cord homogenate following surgery and pretreatment revealed a significant (P < .05) increase in B-cell lymphoma 2 and brain-derived neurotrophic factor expression and protein kinase B and CREB phosphorylation with α-2a adrenergic agonist pretreatment. CONCLUSIONS: Pretreatment with the α-2a agonist dexmedetomidine preserved neurologic function and attenuated neuronal injury following thoracic aortic occlusion in mice. This relationship was associated with an increased phosphorylation of protein kinase B and CREB and subsequent up-regulation of antiapoptotic factor B-cell lymphoma 2 and brain-derived neurotrophic factor. Thus, α-2a receptor agonism-induced CREB phosphorylation and contributes to dexmedetomidine's protective mechanism in the spinal cord following ischemia.