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Immune checkpoint blockade targeting the PD-1/PD-L1 axis has recently demonstrated efficacy and promise in cancer treatment. Appropriate biomarker selection is therefore essential for improving treatment efficacy. However, the establishment of PD-L1 assay in pathology laboratories is complicated by the presence of multiple testing platforms using different scoring systems. Here we assessed the PD-L1 expression in 713 consecutive non-small cell lung carcinomas by four commercially available PD-L1 immunohistochemical assays, namely, 22C3, 28-8, SP142 and SP263. The analytical performances of the four assays and diagnostic performances across clinically relevant cutoffs were evaluated. The prevalence of PD-L1 (22C3) expression was 21% with a ≥50% cutoff and 56% with a ≥1% cutoff. High PD-L1 expression (using a ≥50% cutoff) was significantly associated with male sex (P = 0.001), ever smoking history (P < 0.001), squamous cell carcinoma (P = 0.001), large cell carcinoma (P < 0.001), lymphoepithelioma-like carcinoma (P = 0.006), sarcomatoid carcinoma (P < 0.001), mutant KRAS (P = 0.005) and wild-type EGFR (P = 0.003). Elevated PD-L1 expression was also significantly associated with shorter survival in patients with adenocarcinoma (log-rank P = 0.026) and remained an independent prognostic factor by multivariable analysis. Among the four assays, 22C3, 28-8 and SP263 were highly concordant for tumor cell scoring. With a cutoff of ≥50% (i.e., the threshold for first-line patient selection), inter-rater agreement was high among the three assays with percentage agreement >97%. In conclusion, three PD-L1 assays showed good analytical performance and a high agreement with each other, but not all cases were correctly classified using the same clinical cutoff. Further studies comparing the predictive value of these assays are required to address the interchangeability of these assays for clinical use.
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Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). METHODS: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results. RESULTS: NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial-mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/ß-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with ß-catenin and TCF4 to enhance the functions of ß-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction. CONCLUSIONS: FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Via de Sinalização Wnt , Animais , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Células HEK293 , Humanos , Camundongos Nus , Metástase Neoplásica , PrognósticoRESUMO
BACKGROUND: Previous studies have shown that the levels of 15-lipoxygenase 1 (15-LOX-1) and 15-LOX-2 as well as their metabolites 13-S-hydroxyoctadecadienoic acid (13(S)-HODE) and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) are significantly reduced in smokers with non-small cell lung carcinoma (NSCLC). Furthermore, animal model experiments have indicated that the reduction of these molecules occurs before the establishment of cigarette smoking carcinogen-induced lung tumors, and this suggests roles in lung tumorigenesis. However, the functions of these molecules remain unknown in NSCLC. METHODS: NSCLC cells were treated with exogenous 13(S)-HODE and 15(S)-HETE, and then the ways in which they affected cell function were examined. 15-LOX-1 and 15-LOX-2 were also overexpressed in tumor cells to restore these 2 enzymes to generate endogenous 13(S)-HODE and 15(S)-HETE before cell function was assessed. RESULTS: The application of exogenous 13(S)-HODE and 15(S)-HETE significantly enhanced the activity of peroxisome proliferator-activated receptor γ (PPARγ), inhibited cell proliferation, induced apoptosis, and activated caspases 9 and 3. The overexpression of 15-LOX-1 and 15-LOX-2 obviously promoted the endogenous levels of 13(S)-HODE and 15(S)-HETE, which were demonstrated to be more effective in the inhibition of NSCLC. CONCLUSIONS: This study has demonstrated that exogenous or endogenous 13(S)-HODE and 15(S)-HETE can functionally inhibit NSCLC, likely by activating PPARγ. The restoration of 15-LOX activity to increase the production of endogenous 15(S)-HETE and 13(S)-HODE may offer a novel research direction for molecular targeting treatment of smoking-related NSCLC. This strategy can potentially avoid side effects associated with the application of synthetic PPARγ ligands.
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Araquidonato 15-Lipoxigenase/biossíntese , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Hidroxieicosatetraenoicos/administração & dosagem , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Araquidonato 15-Lipoxigenase/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , PPAR gama/genéticaRESUMO
PURPOSE: To describe the use of cerebral oximetry to detect a lack of right cerebral perfusion resulting from a malpositioned catheter used for antegrade cerebral perfusion during deep hypothermic circulatory arrest (DHCA). The simple corrective surgical adjustment that followed averted a potentially serious complication. CLINICAL FEATURES: A 57-yr-old male with a type-A aortic dissection undergoing DHCA required antegrade cerebral perfusion for cerebral protection. Catheters were placed accordingly in the left common carotid and brachiocephalic arteries. Whereas frontal cerebral oximetry immediately improved on the left, it did not improve on the right. It was immediately suspected that the tip of the brachiocephalic cannula had advanced into the right subclavian artery, thus depriving the right common carotid artery of blood flow. The problem resolved upon slight withdrawal of the cannula. CONCLUSION: Vigilance in anesthesia should not stop during DHCA or cardiopulmonary bypass. Cerebral oximetry may provide important information leading to actions that improve brain protection. Vigilances proved important in this case where the cannula tip used for antegrade cerebral perfusion was advanced too far into the right subclavian artery.
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Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Encéfalo/metabolismo , Catéteres/efeitos adversos , Oximetria , Parada Circulatória Induzida por Hipotermia Profunda , Humanos , Masculino , Pessoa de Meia-Idade , Artéria SubcláviaRESUMO
Chest wall tumor resection can result in a large defect that can pose a challenge in reconstruction in restoring chest wall contour, maintaining respiratory mechanics, and improving cosmesis. Titanium plates were first introduced for treating a traumatic flail chest, which yielded promising results in restoring chest wall stability. Subsequently, the applications of titanium plates in chest wall reconstruction surgery were demonstrated in case reports and series. Our center has adopted this technique for a decade, and patients are actively followed up after operation. Here, we retrospectively analyze our 10-year experience of using titanium plates and other reconstruction approaches for chest wall reconstruction, in terms of clinical outcomes, complications, and reasons for reoperation to determine long-term safety and efficacy. Thirty-eight patients who underwent chest wall resection and reconstruction surgery were identified. Of these, 11 had titanium plate insertion, 11 had patch repair or flap reconstruction, and the remaining 16 had primary closure of defects. Chest wall reconstruction using titanium plate(s) and patch repair (with or without flap reconstruction) was associated with larger chest wall defects and more sternal resections than primary closure. Subgroup analysis also showed that reconstruction by the titanium plate technique was associated with larger chest wall defects than patch repair or flap reconstruction [286.80â cm2 vs. 140.91â cm2 (p = 0.083)]. There was no 30-day hospital mortality. Post-operative arrhythmia was more commonly seen following chest wall reconstruction compared with primary closure (p = 0.041). Furthermore, more wound infections were detected following the use of titanium plate reconstruction compared with the patch repair (with or without flap reconstruction) approach (p = 0.027). In conclusion, the titanium plate system is a safe, effective, and robust approach for chest wall reconstruction surgery, especially in tackling larger defect sizes.
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Low-grade fibromyxoid sarcomas (LGFMSs) are typically adult-onset tumors that arise from the extremities. Here, we report an exceptional case of primary thoracic LGFMS in an 8-year-old girl that resulted in mediastinal syndrome. In reporting this case, we discuss the clinical challenges, role of molecular profiling and review reported cases of pediatric thoracic LGFMSs.
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Spontaneous haemopneumothorax (SHP) can be life threatening and is an important cause for unexplained signs of significant hypovolaemia. There is still some debate relating to patient selection and timing of surgery, particularly in those who become stable following chest tube insertion without further blood loss. Review of the literature over the past decade in the management of SHP are presented and discussed. Surgery should be considered early in the management of SHP to reduce morbidity associated with continued haemorrhage and inadequate drainage. Lower postoperative complications and shorter hospital stay following video assisted thoracic surgery compared with thoracotomy have led to its increased acceptance as an alternative approach for SHP patients who are haemodynamically stable.
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Hemopneumotórax/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Tubos Torácicos , Hemorragia/cirurgia , Humanos , Hipovolemia/etiologia , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Toracotomia , Resultado do Tratamento , Raios XRESUMO
Shortly after repair of a type A aortic dissection, resternotomy was required because of tamponade. During the exploration, it was discovered that the source of bleeding was in the right pleura. Collapse of the right lung was requested. A double-lumen tube would have necessitated changing the endotracheal tube (ETT) in an unstable patient in the middle of surgery. Instead, a Coopdech endobronchial blocker was passed into the right lung through the lumen of the in situ ETT. To ensure that the blocker did not migrate into the trachea, it was deliberately passed through the Murphy eye of the ETT, which had been deliberately passed distally to almost touch the carina. This arrangement provided reliable right-lung collapse to facilitate right pleural hemostasis.
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Complicações Intraoperatórias/terapia , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Pulmão/fisiologia , Respiração Artificial/métodos , Idoso , Anestesia por Inalação , Estenose da Valva Aórtica/cirurgia , Procedimentos Cirúrgicos Cardíacos , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/cirurgia , Hemostasia , Humanos , Masculino , Pleura/patologia , ReoperaçãoRESUMO
Multiportal video-assisted thoracic surgery (VATS) for major lung resection causes less immunochemokine production compared to thoracotomy. Whether uniportal VATS is similarly associated with lower early postoperative circulating levels of immunochemokines compared to multiportal VATS have not been studied. Selected patients who received uniportal or multiportal VATS major lung resection were recruited. Blood samples were collected preoperatively and on postoperative days 1 and 3 for enzyme linked immunosorbent assay of serum levels of Tissue Inhibitor of Metalloproteinase (TIMP)-1, Insulin Growth Factor Binding Protein (IGFBP)-3, and Matrix Metalloproteinase (MMP)-9. A linear mixed-effects models were used to analyze the effects of uniportal VATS on the postoperative circulating chemokine levels. From March 2014 to April 2017, 68 consecutive patients consented for the prospective study and received major lung resection by either uniportal VATS (N = 29) or multiportal VATS (N = 39) were identified. Uniportal VATS major lung resection was associated with lower post-operative levels of TIMP-1 and MMP-9 compared to multiportal VATS after controlling for the effects of the corresponding baseline level and the time of follow-up measurement. No difference was observed for the level of IGFBP-3. Less immunochemokine disturbances was observed after uniportal VATS major lung resection compared to multiportal VATS.
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Quimiocinas/sangue , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Cirurgia Torácica Vídeoassistida/efeitos adversos , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimiocinas/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Neoplasias Pulmonares/cirurgia , Masculino , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Pneumonectomia/métodos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/imunologia , Estudos Prospectivos , Índice de Gravidade de Doença , Cirurgia Torácica Vídeoassistida/métodos , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
Anesthetic management for anterior mediastinal mass resection is often challenging. The main concern being that the tumor might, on reduction in muscle tone, cause circulatory and/or airway collapse. In the setting of pregnancy, the expected physiologic changes (eg, increased oxygen demand, decreased functional residual capacity, and aortocaval compression) may further increase the risks. The objective of this report is to present a challenging case of a pregnant woman undergoing an anterior mediastinal mass resection with the additional rare requirement for one-lung anesthesia, and to describe the perioperative considerations and the plan executed to ensure a successful outcome. A 30-year-old pregnant (23 weeks) patient with a large anterior mediastinal mass and evidence of significant cardiovascular and tracheobronchial compression presented for thymectomy requiring one-lung ventilation. Anesthesia consisted of preoperative preparation, thoughtful selection of vascular access sites, preservation of spontaneous ventilation until sternotomy was accomplished, use of bronchial blocker and readily reversible pharmacologic agents, availability of backup airway and oxygenation plans, standby high-frequency ventilation, and anticipation of postoperative respiratory difficulties. Surgical considerations included the possibility of extracorporeal membrane oxygenation and the need for lifting the thymoma to relieve the compression of the mediastinum. A methodical and multidisciplinary plan is described to mitigate the risk of cardiorespiratory collapse in the setting of anterior mediastinal mass resection. Backup measures in case of catastrophe, as well as careful consideration of the physiologic changes of pregnancy, must be taken into account.
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Anestesia/métodos , Neoplasias do Mediastino/cirurgia , Ventilação Monopulmonar/métodos , Complicações Neoplásicas na Gravidez/cirurgia , Timectomia/métodos , Adulto , Feminino , Humanos , GravidezRESUMO
Minimal invasive video-assisted thoracic surgery can be a safe alternative technique in the assessment, diagnosis and surgical resection of posterior mediastinal tumours. Video-assisted thoracic surgery may be particularly suited for the management of posterior mediastinal tumours as most are benign. Surgical technique continues to evolve from the classic 3-port access in order to tackle more complex tumours positioned at the apical and inferior recesses of the posterior mediastinum. The preoperative identification of dumbbell tumours is important to facilitate arrangements for a single-stage combined resection for both the intra-thoracic and intraspinal tumour. Results from Video-assisted thoracic surgery posterior mediastinal tumour resection are comparable with conventional surgical techniques in terms of symptomatic improvement, recurrence and survival. Video-assisted thoracic surgery approach has been shown to result in less post-operative pain, improved cosmesis, shorter hospital stay, and more rapid recovery and return to normal activities. In over a decade, video-assisted thoracic surgery has gradually matured and is now a promising therapeutic alternative to open approach. In certain selected patients, video-assisted thoracic surgery may be considered the standard of care for conditions of the posterior mediastinum. Recent developments in robotic surgery for the management of mediastinal tumours are promising, however, long-term results are pending.
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Neoplasias do Mediastino/cirurgia , Cirurgia Torácica Vídeoassistida , Humanos , Laminectomia , Imageamento por Ressonância Magnética , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Robótica , Neoplasias da Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Whether EGFR mutation occurs in lung squamous cell carcinoma (SCC) remains a controversial issue. Although numerous trials have shown positive response to tyrosine kinase inhibitors in SCC, these observations have not been well correlated with presence or absence of EGFR mutation. A complicating issue is that adenosquamous carcinoma, a mimic of SCC, frequently harbours EGFR mutations. We evaluated the EGFR mutation status of 191 cases initially diagnosed as SCC of lung origin in years 2000-2011, and performed a panel of markers including p40, p63, CK5/6, TTF-1, mucicarmine on the tissue microarray or tissue blocks from each case, to ascertain the squamous differentiation of each case. Four cases were found to have EGFR mutations, with three showing typical squamous morphological features and immunohistochemical profile on all available tumour blocks, and one reclassified as adenosquamous carcinoma. Mixed responses were noted for two of the patients with EGFR-mutated SCC treated with tyrosine kinase inhibitors. In conclusion, we report that a small subset of rigorously proven SCC harbours EGFR mutation. It also appears in our cohort that EGFR-mutated tumours, in the context of SCC, may have relatively poor response to tyrosine kinase inhibitors.
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Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos RetrospectivosRESUMO
With the advent of advanced technology in performing diagnostics for lung cancer, an incremental increase in the number of patients with oligometastatic disease is currently being managed with intent to cure. As treatment of selected types of patients with oligometastasis show favourable outcomes, the past notion of managing these patients palliatively is fast becoming extinct. Selection of patients based on established criterion together with surgical metastasectomy combined with multiple ablative techniques with or without systemic chemotherapy offers a reasonable rate of treatment success which provides basis for treating such patient population. As more evidence becomes available to suggest that the oligometastatic state of lung cancer does exist, and are potentially curable, a better understanding of the condition is necessary for clinicians, and surgeons to provide optimal care. In this review we present some of the clinical basis which may cause a paradigm shift in management of patients with oligometastatic lung disease.
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INTRODUCTION: Patients with pulmonary large-cell carcinoma (LCC) have poor prognosis and limited treatment options. The identification of clinically actionable molecular alterations helps to guide personalized cancer treatment decisions. PATIENTS AND METHODS: A consecutive cohort of 789 resected NSCLC cases were reviewed. Fifty-nine NSCLC cases lacking morphologic differentiation, accounting for 7.5% of all resected NSCLCs, were identified and further characterized by immunohistochemistry according to the 2015 WHO lung tumor classification. Molecular alterations were investigated by multiple technologies including target capture sequencing, immunohistochemistry, and fluorescence in situ hybridizations. RESULTS: Of 59 NSCLC cases lacking morphologic differentiation, 20 (33.9%) were reclassified as adenocarcinoma (LCC-AD), 14 (23.7%) as squamous cell carcinoma (LCC-SqCC), and 25 (42.4%) as LCC-Null. Approximately 92% of LCC-Null, 95% of LCC-AD, and 86% of LCC-SqCC harbored clinically relevant alterations. Alterations characteristic of adenocarcinoma (EGFR, KRAS, ALK receptor tyrosine kinase [ALK], ROS1, and serine/threonine kinase 11 [STK11]) were detected in the LCC-AD subgroup but not in LCC-SqCC, whereas squamous-lineage alterations (phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha [PIK3CA], SRY-box 2 [SOX2], fibroblast growth factor receptor 1 [FGFR1], and AKT1) were detected in the LCC-SqCC subgroup but not in the LCC-AD group. Although some LCC-Null tumors displayed a genetic profile similar to either adenocarcinoma or squamous-cell carcinoma, more than half of the LCC-Null group were completely devoid of recognizable lineage-specific genetic profiles. High programmed death ligand 1 expression and high frequency of cell cycle regulatory gene alterations were found in the LCC-Null group offering alternative options of targeted therapy. CONCLUSIONS: This comprehensive molecular study provided further insight into the genetic architecture of LCC. The presence of clinically actionable alterations in a majority of the tumors allowed personalized treatment to emerge.
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Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Grandes/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma de Pulmão/classificação , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Carcinoma de Células Grandes/classificação , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/classificação , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Epidemiological observations have demonstrated that ambient fine particulate matter with dp < 2.5 µm (PM2.5) as the major factor responsible for the increasing incidence of lung cancer in never-smokers. However, there are very limited experimental data to support the association of PM2.5 with lung carcinogenesis and to compare PM2.5 with smoking carcinogens. METHODS: To study whether PM2.5 can contribute to lung tumorigenesis in a way similar to smoking carcinogen 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) via 15-lipoxygenases (15-LOXs) reduction, normal lung epithelial cells and cancer cells were treated with NNK or PM2.5 and then epigenetically and post-translationally examined the cellular and molecular profiles of the cells. The data were verified in lung cancer samples and a mouse lung tumor model. RESULTS: We found that similar to smoking carcinogen NNK, PM2.5 significantly enhanced cell proliferation, migration and invasion, but reduced the levels of 15-lipoxygenases-1 (15-LOX1) and 15-lipoxygenases-2 (15-LOX2), both of which were also obviously decreased in lung cancer tissues. 15-LOX1/15-LOX2 overexpression inhibited the oncogenic cell functions induced by PM2.5/NNK. The tumor formation and growth were significantly higher/faster in mice implanted with PM2.5- or NNK-treated NCI-H23 cells, accompanied with a reduction of 15-LOX1/15-LOX2. Moreover, 15-LOX1 expression was epigenetically regulated at methylation level by PM2.5/NNK, while both 15-LOX1 and 15-LOX2 could be significantly inhibited by a set of PM2.5/NNK-mediated microRNAs. CONCLUSION: Collectively, PM2.5 can function as the smoking carcinogen NNK to induce lung tumorigenesis by inhibiting 15-LOX1/15-LOX2.
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Araquidonato 15-Lipoxigenase/química , Carcinogênese/patologia , Neoplasias Pulmonares/patologia , Material Particulado/efeitos adversos , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinogênese/induzido quimicamente , Carcinogênese/metabolismo , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Inibidores de Lipoxigenase/efeitos adversos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/etiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nitrosaminas/toxicidade , Prognóstico , Fumar/efeitos adversos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Localization of tiny lung nodules during video-assisted thoracic surgery (VATS) resection can be challenging. Real-time image-guided hookwire localization of the target lesions immediately followed by VATS lung resection in the hybrid operating theatre setting is an emerging approach. METHODS: We retrospectively reviewed our experience with this form of hybrid operating theatre image-guided VATS (iVATS) for lung nodules 1.5 cm or less, or soft in consistency. These patients were compared with matched cohort who received standard hookwire localization in the radiology department. RESULTS: From February 2014 to September 2017, lung nodules of indeterminate nature in 32 consecutive patients with mean size 9.1±4.6 mm underwent iVATS. All were accurately localized by hookwire and successfully resected. There was no postoperative mortality. There were 21 (66%) malignant lesions, all with adequate resection margins. Major outcomes were compared with a comparable cohort of 8 patients who received standard hookwire localization and VATS (sVATS) performed at separate departments operation suites. sVATS groups has significantly longer 'at-risk' period for pneumothorax progression and hookwire dislodgement (109.5±57.1 minutes for sVATS vs. 41.1±15.0 minutes for iVATS, P=0.011), and a higher risk of hookwire dislodgement (25% for sVATS vs. 0 for iVATS, P=0.036). CONCLUSIONS: Real-time image-guided hookwire localization in the hybrid theatre setting is an effective facilitator of VATS resection of tiny lung nodules in selected patients, and may have added advantages in terms of safety and localization accuracy over the conventional sVATS method.
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Three-dimensional (3D) printing has been gaining much attention in the medical field in recent years. At present, 3D printing most commonly contributes in pre-operative surgical planning of complicated surgery. It is also utilized for producing personalized prosthesis, well demonstrated by the customized rib cage, vertebral body models and customized airway splints. With on-going research and development, it will likely play an increasingly important role across the surgical fields. This article reviews current application of 3D printing in thoracic surgery and also provides a brief overview on the extended and updated use of 3D printing in bioprinting and 4D printing.
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OBJECTIVE: Major surgery is immunosuppressive and could have an impact on postoperative tumor immunosurveillance and recurrence in cancer patients. Low circulating levels of insulin growth factor binding protein (IGFBP)-3 have been linked to advance prostate and the development of colonic cancers. This prospective study examined the early postoperative circulating levels of IGFBP-3, matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1 in early stage non-small cell lung cancer (NSCLC) patients undergoing major lung resection by VATS versus thoracotomy. METHODS: Forty-two consecutive patients with resectable primary NSCLC were assigned to VATS or thoracotomy approach over a 7-month-period. Blood samples were collected preoperatively and postoperatively on days (POD) 1 and 3 for enzyme linked immunosorbent assay determination of IGFBP-3, MMP-9 and TIMP-1 levels in the serum. RESULTS: There were no demographic differences between the two groups. VATS lung resection was associated with lower levels of MMP-9 and TIMP-1 on POD1 (median 628 vs 1311ng/ml, p=0.009; and 131 vs 211ng/ml, p=0.004, respectively) but higher levels of IGFBP-3 on POD3 (1366 vs 1144ng/ml, p=0.02), when compared with the thoracotomy approach. There was no perioperative mortality. CONCLUSIONS: VATS major lung resection for NSCLC is associated with higher circulating levels of IGFBP-3, and lower levels of MMP-9 and TIMP-1, compared to the thoracotomy approach. The clinical relevance of these postoperative changes on tumor biology following lung resection for cancer warrants further investigation.
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Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimiocinas/sangue , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida , Idoso , Biomarcadores/sangue , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
Background Transcatheter aortic valve implantation has been established as a safe and effective treatment option for patients at high or prohibitive surgical risk. However, some patients may not be suitable for the transfemoral approach due to severe iliofemoral disease or aneurysmal disease of the thoracoabdominal aorta. The aim of this case series was to evaluate the feasibility and clinical outcomes of the transaortic approach. Methods From May 2015 to June 2016, 5 patients (mean age 78.4 ± 3.9 years) with severe symptomatic aortic stenosis underwent transaortic transcatheter aortic valve implantation after a heart team discussion. They were considered to be at high surgical risk and ineligible for the transfemoral approach due to iliofemoral or thoracoabdominal aortic disease. Results A CoreValve Evolut R was successfully deployed in all 5 patients. We performed 4 right mini-parasternal incisions and one J-incision partial sternotomy. None of the patients required permanent pacemaker implantation, one required reopening of the mini-parasternal incision for postoperative bleeding. Follow-up echocardiography one month after the procedure showed improvement in the mean aortic gradient (from 63.2 to 8.3 mm Hg) and aortic valve area (from 0.62 to 2.2 cm2). None of the patients had more than mild paravalvular leakage. There was no intraoperative or 30-day mortality. Conclusion Transaortic transcatheter aortic valve implantation is a safe and feasible option for patients with severe aortic stenosis who are considered unsuitable for transfemoral aortic valve implantation.
Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Aortografia , Ecocardiografia Transesofagiana , Estudos de Viabilidade , Feminino , Próteses Valvulares Cardíacas , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Fatores de Risco , Índice de Gravidade de Doença , Esternotomia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/instrumentação , Resultado do TratamentoRESUMO
OBJECTIVES: To report the first multicenter experience on the treatment of end-stage emphysema using an endobronchial valve (EBV) [Emphasys EBV; Emphasys Medical; Redwood City, CA]. DESIGN: Retrospective analysis from prospective multicenter registry. PATIENTS AND INTERVENTIONS: This is a study of the use of EBVs in the treatment of end-stage emphysema at nine centers in seven countries. Ninety-eight patients with mean FEV(1) of 0.9 +/- 0.3 L (30.1 +/- 10.7% of predicted) [+/- SD] and residual volume (RV) of 5.1 +/- 1.3 L (244.3 +/- 0.3% of predicted) were treated over a period of 20 months. Spirometry, plethysmography, and diffusing capacity of the lung for carbon monoxide (Dlco) and exercise tolerance testing were performed at 30 days and 90 days after the procedure. RESULTS: RV decreased by 4.9 +/- 17.4% (p = 0.025), FEV(1) increased by 10.7 +/- 26.2% (p = 0.007), FVC increased by 9.0 +/- 23.9% (p = 0.024), and 6-min walk distance increased by 23.0 + 55.3% (p = 0.001). There was a trend toward improvement in Dlco, but this did not reach statistical significance (17.2 +/- 52.0%, p = 0.063). Patients treated unilaterally showed a trend toward greater improvement than those treated bilaterally. A similar trend toward improvement was observed in patients who had one entire lobe treated compared to those with just one or two bronchopulmonary segments treated. Eight patients (8.2%) had serious complications in the first 90 days, including one death (1.0%). CONCLUSION: This multicenter analysis confirms that improvement in pulmonary function and exercise tolerance can be achieved in emphysematous patients using EBVs. Future efforts should be directed to determining how to select those patients who would benefit most from this procedure and the best endobronchial treatment strategy.