RESUMO
BACKGROUND: The vascular division sequence in video-assisted thoracic surgery (VATS) lung resection is usually determined by the handling difficulty due to the limited surgical view through the scope. However, upfront pulmonary vein division is theoretically desirable to avoid tumor cells spreading by surgical manipulation. Epithelial-mesenchymal transition (EMT) is associated with poor prognosis and an increased number of circulating tumor cells. The purpose of this study is to evaluate the effect of vascular division sequence and EMT on postoperative recurrence. METHODS: We retrospectively investigated tissue microarrays of 282 lung adenocarcinomas surgically resected between 2001 and 2007. We excluded the cases with segmentectomy, wedge resection, dissemination, insufficient material for staining, or lack of medical records. The effect of vascular division sequence and clinicopathologic factors on recurrence was evaluated in 195 cases. RESULTS: The upfront pulmonary vein division (V-first) was performed in 60 patients, and the upfront pulmonary artery division (A-first) was performed in 135 patients. The recurrence was observed in 67 patients (13 in V-first and 54 in A-first). Epithelial-mesenchymal transition activation was observed in 104 patients. Multivariable analysis with 195 patients revealed that lymph node metastasis and pleural invasion were risk factors for the recurrence. The stratified multivariable analysis showed that vascular division sequence (A-first) was a risk factor only in the EMT-negative group (91 patients). In the EMT-negative subset, the 5-year relapse-free survival rate was significantly lower in the A-first group than the V-first group (72.6% vs. 92.2%, p = 0.0136). CONCLUSIONS: The upfront pulmonary artery division might be a risk factor in patients without EMT activation.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Prognóstico , Recidiva Local de Neoplasia , Neoplasias Pulmonares/patologia , Transição Epitelial-Mesenquimal/fisiologiaRESUMO
We describe a 69-year-old woman with primary lung cancer in the right lower lobe invasive to the left atrium (LA) via the pulmonary vein (PV). The tumor in the LA measured 30 × 26 mm, and to avoid critical embolism preoperative induction therapy was not performed. The patient underwent right thoracotomy under cardiopulmonary bypass (CPB), and the atrial septum was incised via the right atrium. The tumor was placed out of the LA, followed by lobectomy. For right lung tumors invading the LA, the bilateral trans-septal approach is useful for confirming the surgical margin.
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Átrios do Coração/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Toracotomia , Idoso , Ponte Cardiopulmonar , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Margens de Excisão , Invasividade Neoplásica , Resultado do TratamentoRESUMO
OBJECTIVES: Mounting evidence suggests that preoperative nutritional status can predict postoperative outcomes in patients with non-small cell lung cancer. However, a consensus on the optimal evaluation tool among the various nutritional assessment methods has not been reached. This study aimed at validating the predictive value of 3 nutritional scoring systems for clinical outcomes in patients with completely resected non-small cell lung cancer. METHODS: We retrospectively reviewed the preoperative data of 475 consecutive patients with completely resected non-small cell lung cancer to assess the following 3 albumin-based nutritional methods: prognostic nutritional index, controlling nutritional status score, and geriatric nutritional risk index. RESULTS: Receiver operating characteristic curves of the prognostic nutritional index, controlling nutritional status score, and geriatric nutritional risk index identified the optimal cutoff values for predicting the postoperative complications as 47, 2, and 101, respectively. Stratification of patients using these cutoff values indicated a higher postoperative complication rate in the malnutrition group than in the group with proper nutrition (P < .05 for all nutritional assessment methods). Additionally, patients with malnutrition exhibited significantly lower 5-year overall and recurrence-free survivals, regardless of the assessment method (P < .05 for all 3 nutritional assessment methods). Multivariate analyses showed that all 3 nutritional parameters were independent prognostic factors for overall survival after lung resection. CONCLUSIONS: The 3 nutritional assessment methods we used were found to have high predictive values for postoperative complications and survival. Preoperative nutritional conditioning may improve the postoperative outcomes in patients with resectable non-small cell lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Avaliação Nutricional , Estado Nutricional , Pneumonectomia , Complicações Pós-Operatórias , Idoso , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Avaliação Geriátrica/métodos , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Estadiamento de Neoplasias , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Prognóstico , Projetos de PesquisaRESUMO
A 76-year-old man was referred to our hospital because of an abnormal shadow on chest X-ray. His physical exams and laboratory data were not notable. Chest computed tomography (CT) showed 2 nodular lesions with clear margin in anterior mediastinum. The nodule at the left inferior pole of the thymus was 9 cm in diameter, and another one at the right inferior pole was 3.5 cm in diameter. We performed thymo-thymectomy by median sternotomy. Histological study revealed that the left tumor was type B2 thymoma and the other one was type A thymoma. Both were completely encapsulated without invasion, which means stage â by Masaoka's classification. The patient has showed no evidence of recurrence for 11 years following the surgery. This is the 1st case in Japan that reported synchronous multicentric thymoma with apparently different histology of type A and B2.
Assuntos
Timoma , Neoplasias do Timo , Idoso , Humanos , Japão , Masculino , Recidiva Local de Neoplasia , TimectomiaRESUMO
OBJECTIVES: Microscopic vessel invasion (MVI) and visceral pleural invasion (VPI) have been recently reported as poor prognostic factors of non-small cell lung cancer. Epithelial-mesenchymal transition (EMT) and cancer stemness (CS) are known malignant phenotypes that induce resistance to cancer therapy. We aimed to assess the prognostic significance of MVI and the correlations among VPI/MVI, EMT, CS, and treatment failure for recurrent tumor. MATERIALS AND METHODS: From 2002 to 2013, 1034 consecutive patients with pathological T1-4N0-2M0 lung adenocarcinoma underwent complete resection. Moreover, we established 206 tissue microarray (TMA) samples from 2002 to 2007. We then evaluated the prognostic impact of MVI, including conventional clinicopathological factors, and analyzed the VPI/MVI, EMT, CS, and treatment failure by TMA immunohistochemical staining. RESULTS: Among the 1034 cases, the proportion of patients with a 5-year overall survival (OS) period was 63.9% and 88.2% (MVI: +/-; p < .001). Multivariate analysis revealed that both MVI and VPI were independent predictors of OS (HR 1.57 and 1.47, respectively). Significant separation of the OS rate curves was observed among the 3 groups [VPI/MVI: both positive (2), either positive (1), and both negative (0)]. Among the 206 TMA cases, these 3 groups of VPI/MVI were significantly correlated with EMT and CS. The median time to progression after recurrence were 3.8, 8.9, and 15.9 months, respectively (VPI/MVI: 2/1/0; p = 0.016). CONCLUSION: MVI and VPI are significant prognostic factors of lung cancer, and they are correlated with EMT, CS, and treatment failure for recurrent tumor.
Assuntos
Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Transição Epitelial-Mesenquimal , Microvasos/patologia , Invasividade Neoplásica/patologia , Pleura/patologia , Adenocarcinoma de Pulmão/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , Falha de Tratamento , Resultado do TratamentoRESUMO
The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non-small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations. We treated VR cells by Src Family Kinase (SFK) inhibitors or gene silencing and examined cell viabilities. ATP-binding Cassette Sub-family B Member 1 (ABCB1) was highly expressed in VR cells. A pathway analysis and western blot analysis revealed the high expression of integrins ß1 and ß3 and the activation of FA pathway components, including Src family kinase (SFK) and AKT, in VR cells. SFK involvement in VRB resistance was confirmed by the recovery of VRB sensitivity in FYN knockdown A549 VR cells. Saracatinib, a dual inhibitor of SFK and ABCB1, had a synergistic effect with VRB in VR cells. In conclusion, ABCB1 is the primary cause of VRB resistance. Additionally, the FA pathway, particularly integrin, and SFK, are promising targets for VRB-resistant lung cancer. Further studies are needed to identify clinically applicable target drugs and biomarkers that will improve disease prognoses and predict therapeutic efficacies.
Assuntos
Trifosfato de Adenosina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos , Adesões Focais/patologia , Neoplasias Pulmonares/patologia , Transdução de Sinais/efeitos dos fármacos , Vinorelbina/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Feminino , Adesões Focais/efeitos dos fármacos , Adesões Focais/metabolismo , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Quinases da Família src/metabolismoRESUMO
BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically. RESULTS: By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63. CONCLUSIONS: DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.
Assuntos
Rejeição de Enxerto/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Isoanticorpos/metabolismo , Transplante de Pulmão , Pulmão/imunologia , Animais , Biomarcadores/metabolismo , Citometria de Fluxo , Rejeição de Enxerto/diagnóstico , Masculino , Ratos , Ratos Endogâmicos Lew , Baço/imunologiaRESUMO
Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF-1α-induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF-1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF-1α, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF-1α expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF-1-dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF-1α in A549 cells. HIF-1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF-1α, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF-1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF-1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.
Assuntos
Antígenos de Neoplasias/metabolismo , Anidrase Carbônica IX/metabolismo , Resistencia a Medicamentos Antineoplásicos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/terapia , Vimblastina/análogos & derivados , Células A549 , Idoso , Hipóxia Celular , Quimiorradioterapia , Feminino , Transportador de Glucose Tipo 1/metabolismo , Glicólise , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Vimblastina/farmacologia , Vimblastina/uso terapêutico , VinorelbinaRESUMO
BACKGROUND: The development of vessel-sealing devices will facilitate safety in video-assisted thoracoscopic surgery. Our objective was to evaluate the feasibility and safety of sealing pulmonary arteries with the Enseal tissue-sealing device. METHODS: Pulmonary arteries from beagle dogs (mean body weight 13.1 kg, range 10.5-15.4 kg) were divided into 3 groups according to the in-vivo sealing method used (Enseal, ligation, and proximal ligation plus distal Enseal) and extracted to evaluate the pressure tolerance up to 75 mm Hg at the sealed end. A left lower lobectomy was performed to evaluate chronic-phase durability of the sealed stumps in a survival model. Two or three branches of the pulmonary arteries in each dog were allocated to each of the 3 groups. After the scheduled survival period, the pulmonary arteries were sampled. RESULTS: Pressure tolerance at the sealed end was evaluated in 91 pulmonary artery sections. All sealed ends showed pressure tolerance >75 mm Hg. A left lower lobectomy was performed in 13 dogs in which 35 pulmonary artery sections had been allocated into the 3 groups. No sealing failure was found, and pathological findings showed healing and persistent hemostasis at all sealed ends of the pulmonary arteries after 2 and 4 weeks of the survival period. CONCLUSIONS: Pulmonary arteries sealed in vivo with the Enseal device showed pressure tolerance >75 mm Hg in the acute phase, and persistent hemostasis after 2 or 4 weeks. Pulmonary artery sealing with the Enseal device is feasible and safe in thoracic surgery settings.
Assuntos
Hemorragia/prevenção & controle , Técnicas Hemostáticas/instrumentação , Pneumonectomia/efeitos adversos , Artéria Pulmonar/cirurgia , Cirurgia Torácica Vídeoassistida/efeitos adversos , Animais , Pressão Arterial , Cães , Desenho de Equipamento , Hemorragia/etiologia , Ligadura , Modelos Animais , Artéria Pulmonar/fisiopatologiaRESUMO
OBJECTIVES: The purpose of this study was to use Hounsfield unit (HU) thresholds of computed tomography (CT) images to predict pathological lymph node metastasis and tumour invasiveness of cT1N0M0 lung adenocarcinoma on 3D evaluations. METHODS: Preoperative CT images of 211 lesions of surgically resected cT1N0M0 lung adenocarcinoma were retrospectively examined. The tumour size was calculated in 1D, 2D and 3D views. Tumours with -300 HU and over were defined as 'solid tumours', and those between -800 and -301 HU were defined as 'ground glass opacity tumours'. Tumours with -800 HU and over were assumed to be the whole tumour entity. The proportion of 'solid tumour' within the whole tumour entity was also calculated as the 'solid tumour ratio'. These were compared with pathological information. RESULTS: Solid tumour size and ratio were positively correlated with microscopic invasion to pleura, vessels and lymphatics in all dimensional evaluations. Pathological lymph node metastases were also well predicted by solid tumour size and ratio in all dimensional evaluations. The P-values for the receiver operating characteristic (ROC) curves of 1D, 1D ×2, 2D and 3D evaluations were: solid tumour size P = 0.013, 0.014 and 0.032; and solid tumour ratio 0.016, 0.0032 and <0.0001. In comparisons of 1D, 2D and 3D evaluations, 'solid tumour size' of the area under the curve (AUC) of ROC to detect pathological lymph node metastases was not significant. However, strikingly, the 3D solid tumour ratio was found to be significantly more accurate for the prediction of pathological lymph node metastases than the 1D and 2D solid tumour ratios on ROC evaluation (AUC: 1D 0.736, 2D 0.803 and 3D 0.882; P-values for the AUC comparisons were P = 0.013 for 3D versus 1D and P = 0.022 for 3D versus 2D). The correlations of subtypes of adenocarcinoma and the 3D solid tumour ratio were also investigated. Subtypes of adenocarcinoma were well correlated with the 3D solid tumour ratio. CONCLUSIONS: Preoperative 3D CT using threshold values of -800 and -300 HU was useful for predicting pathological lymph node metastases and tumour invasiveness of cT1N0M0 lung adenocarcinoma.
Assuntos
Adenocarcinoma/diagnóstico , Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias Pulmonares/diagnóstico , Estadiamento de Neoplasias , Adenocarcinoma/secundário , Adenocarcinoma de Pulmão , Idoso , Feminino , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Curva ROC , Estudos RetrospectivosRESUMO
The epithelial-mesenchymal transition (EMT) and cancer stemness (CS) are reported to be pivotal phenomena involved in metastasis, recurrence, and drug-resistance in lung cancer; however, their effects on tumor malignancy in clinical settings are not completely understood. The mutual association between these factors also remains elusive and are worthy of investigation. The purpose of this study was to elucidate the association between EMT and CS, and their effect on the prognosis of patients with lung adenocarcinoma. A total of 239 lung adenocarcinoma specimens were collected from patients who had undergone surgery at Kyoto University Hospital from January 2001 to December 2007. Both EMT (E-cadherin,vimentin) and CS (CD133, CD44, aldehyde dehydrogenase) markers were analyzed through immunostaining of tumor specimens. The association between EMT and CS as well as the patients' clinical information was integrated and statistically analyzed. The molecular expression of E-cadherin, vimentin, and CD133 were significantly correlated with prognosis (P = 0.003, P = 0.005, and P < 0.001). A negative correlation was found between E-cadherin and vimentin expression (P < 0.001), whereas, a positive correlation was found between vimentin and CD133 expression (P = 0.020). CD133 was a stronger prognostic factor than an EMT marker. Elevated CD133 expression is the signature marker of EMT and CS association in lung adenocarcinoma. EMT and CS are associated in lung adenocarcinoma. Importantly, CD133 is suggested to be the key factor that links EMT and CS, thereby exacerbating tumor progression.
Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Attenuation of ischemia reperfusion injury (IRI) is important in lung transplantation. Our group previously reported that ß2-adrenoreceptor agonist inhalation during the period before procurement successfully attenuated IRI in donated lungs after cardiac death. We therefore hypothesized that ß2-adrenoreceptor agonist inhalation during ex vivo lung perfusion (EVLP) after procurement might also have a protective effect. METHODS: Cardiac-dead beagles were left at room temperature for 210 minutes, and all lungs were subsequently procured and subjected to EVLP for 240 minutes. The beagles were allocated to 2 groups: the ß2 group (receiving an aerosolized ß2-adrenoreceptor agonist 20 minutes after initiation of EVLP; n = 7) and the control group (receiving an aerosolized control solvent at the same time point; n = 6). Physiologic data, including lung function, were evaluated during EVLP. RESULTS: The ß2 group showed significantly lower peak airway pressure and pulmonary artery pressure than the control group. Dynamic pulmonary compliance was higher, pulmonary vascular resistance (PVR) was lower, and the wet-to-dry lung weight ratio was lower in the ß2 group than in the control group. Cyclic adenosine monophosphate (cAMP) and total adenosine nucleotide (TAN) levels in lung tissue after EVLP were higher in the ß2 group than in the control group. The ß2 group also showed more cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. CONCLUSIONS: After procurement, ß2-adrenoreceptor agonist inhalation during EVLP attenuates lung injury in a canine model of organ donation after cardiac death.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Pulmão/irrigação sanguínea , Procaterol/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Animais , Cães , Técnicas In Vitro , Perfusão , Procaterol/uso terapêuticoRESUMO
Hypoxia-inducible factor 1 (HIF-1) plays a role in tumour metastases; however, the genes that activate HIF-1 and subsequently promote metastases have yet to be identified. Here we show that Ubiquitin C-terminal hydrolase-L1 (UCHL1) abrogates the von Hippel-Lindau-mediated ubiquitination of HIF-1α, the regulatory subunit of HIF-1, and consequently promotes metastasis. The aberrant overexpression of UCHL1 facilitates distant tumour metastases in a HIF-1-dependent manner in murine models of pulmonary metastasis. Meanwhile, blockade of the UCHL1-HIF-1 axis suppresses the formation of metastatic tumours. The expression levels of UCHL1 correlate with those of HIF-1α and are strongly associated with the poor prognosis of breast and lung cancer patients. These results indicate that UCHL1 promotes metastases as a deubiquitinating enzyme for HIF-1α, which justifies exploiting it as a prognostic marker and therapeutic target of cancers.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias/diagnóstico , Neoplasias/patologia , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular , Células NIH 3T3 , Metástase Neoplásica , Neoplasias/metabolismo , Prognóstico , Estabilidade Proteica , Regulação para CimaRESUMO
OBJECTIVES: Recently, paravertebral block (PVB) has been reported to be an effective analgesic modality for post-thoracotomy pain, but there is no consensus on how thoracic PVB can be more effective. Our hypothesis that intact pleura has a significant impact on the analgesic effectiveness of thoracic PVB was evaluated. METHODS: Data of patients who underwent general thoracic surgery [thoracotomy or video-assisted thoracic surgery (VATS)] and paravertebral catheterization at Nagara Medical Center between April 2010 and March 2013 were collected. To compare the frequency of non-steroidal anti-inflammatory drugs taken as well as the usage of rescue pain medications between patients with pleural disruption and those without, data were analysed after matching on propensity scores. Covariates for match estimation were age, sex, body mass index, American Society of Anesthesiologists score, diagnosis, operative details and local anaesthesia infused. RESULTS: There were 278 patients who underwent general thoracic surgery and paravertebral catheterization. The propensity score-matching process created 78 matched patients with pleural disruption and those without. Based on the propensity score matching, a significant increase in the frequency of non-steroidal anti-inflammatory drugs taken on postoperative day 1 and in the usage of rescue drugs was observed in patients with pleural disruption. CONCLUSIONS: According to our analysis, creating a sub-pleural space without pleural disruption is essential for quality thoracic PVB.
Assuntos
Analgésicos/uso terapêutico , Bloqueio Nervoso/métodos , Dor Pós-Operatória/terapia , Pleura/cirurgia , Doenças Torácicas/cirurgia , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cateterismo , Feminino , Seguimentos , Humanos , Masculino , Medição da Dor , Dor Pós-Operatória/diagnóstico , Estudos Retrospectivos , Vértebras Torácicas , Resultado do TratamentoRESUMO
BACKGROUND: Appropriate postoperative analgesia is crucial in fast-track surgery, which is a multimodal therapeutic strategy that aims toward enhanced postoperative recovery and shortened hospital stay. Paravertebral block (PVB) has been reported to be as effective as thoracic epidural blockade (TEB), but PVB is not often employed for video-assisted thoracoscopic surgery (VATS) for 2 reasons. First, TEB is still the gold standard for thoracic surgery, and second, thoracoscopic insertion of a PVB catheter is challenging. METHODS: In this retrospective observational study, 185 patients who underwent VATS and thoracoscopic paravertebral catheterization were analyzed. Postoperatively, the patients were continuously administered a local anesthetic (0.5% bupivacaine hydrochloride or 0.2% ropivacaine hydrochloride). Additionally, they were given an oral non-steroidal anti-inflammatory drug (NSAID) as needed. Intramuscular/intravenous pentazocine was administered as a rescue medication. The effect of pain control was measured in terms of the frequency of NSAID taken orally and the necessity for a rescue drug on postoperative days (POD) 0, 1, 2, and 3. RESULTS: The mean age of the 185 patients included in the study was 67 years (Confidence Interval: 66-69). The mean frequency of NSAID use was 0.67 (0-3), 1.59 (0-4), 1.43 (0-4), and 1.33 (0-4) on POD 0, 1, 2, and 3, respectively. 32 (17.3%) and 3 patients (1.6%) were administered a rescue medication on POD 0 and 1, respectively. The most common postoperative complication was nausea/vomiting, which occurred in 17 patients (9.1%). CONCLUSIONS: PVB may greatly contribute to enhanced recovery after thoracic surgery owing to effective analgesia and fewer side effects.
Assuntos
Amidas/administração & dosagem , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Cirurgia Torácica Vídeoassistida , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Feminino , Humanos , Tempo de Internação , Masculino , Medição da Dor , Estudos Retrospectivos , RopivacainaRESUMO
BACKGROUND: The hedgehog (Hh) signaling pathway is aberrantly activated in various cancers. Expression of the GLI family of genes, which encode for transcriptional factors of the Hh pathway, has not been fully assessed in clinical samples of advanced lung adenocarcinoma. In this study, we retrospectively evaluated the expression of the GLI family of genes in advanced stage lung adenocarcinoma samples and determined their relation to patient survival. METHODS: The levels of GLI1, GLI2, and GLI3 mRNA expression were measured by quantitative real-time polymerase chain reaction in surgically obtained tissue samples from stage II-IV lung adenocarcinoma patients (n = 102). Pairwise comparisons between all three GLI mRNA expression were performed, and after dichotomizing the patients into low and high expression groups according to each GLI mRNA expression level, survival curves were calculated and multivariate analyses were conducted. RESULTS: Significant positive correlation was found between GLI1 and GLI3 mRNA expression (P <0.001). Tumors with higher expression (upper 15%) of GLI1 or GLI3 mRNA were associated with poor survival in stage II-IV (5-year overall survival rates: GLI1 mRNA low, 41.7% vs. high, 20.0%, P = 0.0074; GLI3 mRNA low, 43.1% vs. high, 13.3%, P = 0.0062) and stage III-IV (5-year overall survival rates: GLI1 mRNA low, 34.0% vs. high, 0%, P = 0.0012; GLI3 mRNA low, 33.4% vs. high, 7.7%, P = 0.057) lung adenocarcinoma patients. GLI2 mRNA expression did not appear to have great clinical significance. Multivariate analysis revealed higher GLI1 mRNA expression as an independent factor for unfavorable patient survival (P = 0.0030, hazard ratio = 3.1, 95% confidence interval = 1.5-6.2), as well as tumor differentiation and stage. CONCLUSIONS: Expression of GLI1 and GLI3 mRNA was strongly correlated, and their overexpression, especially that of GLI1, was found to be predictive of aggressive tumor behavior. This study indicates that the Hh pathway may be a key oncogenic signaling network in tumor pathogenesis and, thus, a potential therapeutic target in advanced lung adenocarcinoma.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Proteína GLI1 em Dedos de Zinco , Proteína Gli2 com Dedos de Zinco , Proteína Gli3 com Dedos de ZincoRESUMO
PURPOSE: Analgesia following thoracotomy is routinely accomplished using epidural blockage performed by anesthesiologists. More effective pain control can be achieved with continuous paravertebral blockage performed by thoracic surgeons. We aimed to retrospectively analyze the efficacy of paravertebral blockage for managing post-thoracotomy pain. METHODS: The study included 125 patients who underwent continuous paravertebral blockage for the following types of thoracic surgery: video-assisted thoracoscopic surgery(n = 87), anterior axillary thoracotomy (n = 21), posterolateral thoracotomy (n = 16), and median sternotomy with additional left thoracotomy (n = 1). We retrospectively evaluated the analgesic effects of continuous paravertebral blockage by assessing whether a good cough effort could be performed and whether an additional painkiller was given as a rescue medication. RESULTS: About 115 patients could perform a good cough effort to expectorate sputum immediately after extubation in the operating room. Six patients tolerated postoperative pain well without any oral or rectal non-steroidal anti-inflammatory drugs (NSAIDs). For97 patients postoperative NSAIDs could control thoracotomy pain well. Twenty-two patients were given an additional painkiller stronger than NSAIDs. Three patients complained of nausea postoperatively. CONCLUSION: Adequate post-thoracotomy pain control was accomplished by continuous paravertebral blockage, with few complications.
Assuntos
Anestésicos Locais/administração & dosagem , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Cirurgia Torácica Vídeoassistida/efeitos adversos , Toracotomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/efeitos adversos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Esternotomia/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Choroidal melanoma is the most common primary malignant intraocular tumor in adults. And its metastatic spread has been considered to be hematogenous with the liver being the most common site, and a solitary pulmonary metastasis without hepatic involvement is quite rare. PRESENTATION OF CASE: We report the case of a 61-year-old woman with a solitary pulmonary metastasis from choroidal melanoma, which had been originally treated with enucleation 13 years ago. Video-assisted thoracoscopic surgery (VATS) right upper lobectomy was performed for the right upper lobe tumor, which was histopathologically confirmed to be metastatic choroidal melanoma. DISCUSSION: Our case is quite unusual in 2 points; firstly, a solitary pulmonary metastasis without hepatic involvement is rare. Secondly, this mode of metastasis with an exceptionally long disease-free period (13 years) is also rare. CONCLUSION: A pulmonary metastasis from choroidal melanoma is described with reference to relevant literature.
RESUMO
Patients with Sjögren's syndrome frequently have pulmonary involvement, but the involvement of nodular pulmonary lesions, including pulmonary amyloidosis, is rare. Most cases of pulmonary amyloidosis involve multiple nodules; solitary pulmonary nodular amyloidosis, as an associated condition of Sjögren's syndrome, is very rare.In our report, we present the case of an 80-year-old female with Sjögren's syndrome who was incidentally found to have a small solitary pulmonary nodule. The nodule showed high fluorodeoxyglucose uptake and contained areas of calcification. Because the probability that the nodular lesion was malignant could not be excluded, the tumor was excised using a thoracoscopic procedure; the final diagnosis was pulmonary nodular amyloidosis. Although most cases of pulmonary amyloidosis involve multiple nodules, amyloidosis should be considered in the differential diagnosis for a solitary pulmonary nodule in patients with Sjögren's syndrome.
Assuntos
Amiloidose/etiologia , Pneumopatias/etiologia , Síndrome de Sjogren/complicações , Nódulo Pulmonar Solitário/etiologia , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico , Amiloidose/cirurgia , Biópsia , Feminino , Humanos , Pneumopatias/diagnóstico , Pneumopatias/cirurgia , Nódulo Pulmonar Solitário/diagnóstico , Nódulo Pulmonar Solitário/cirurgia , Toracoscopia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Tracheo-innominate artery fistula (TIF) is a surgical emergency with high mortality rates. Reported incidence is 0.1%-1.0% after tracheostomy with peak incidence 3 days to 6 weeks post procedure. TIF is usually fatal once it bleeds. For the successful management of TIF, treatment should be initiated immediately with the special considerations kept in mind. We describe two cases of TIF, and its clinical characteristics are reviewed in accordance with relevant literature.