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Tumor spread through air spaces (STAS) is an invasive pattern of lung cancer that was recently described. In this study, we investigated the association between the extent of STAS and clinicopathological characteristics and patient outcomes in resected non-small cell lung cancers (NSCLCs). STAS has been prospectively described from 2008 and graded its extent with a two-tiered system (STAS I: <2500 µm [one field of ×10 objective lens] from the edge of tumor and STAS II: ≥2500 µm from the edge of tumor) from 2011 in Seoul National University Bundang Hospital. We retrospectively analyzed the correlations between the extent of STAS and clinicopathologic characteristics and prognostic significance in 1869 resected NSCLCs. STAS was observed in 765 cases (40.9%) with 456 STAS I (24.4%) and 309 STAS II (16.5%). STAS was more frequently found in patients with adenocarcinoma (ADC) (than squamous cell carcinoma), pleural invasion, lymphovascular invasion, and/or higher pathologic stage. In ADC, there were significant differences in recurrence free survival (RFS), overall survival (OS), and lung cancer specific survival (LCSS) according to the extent of STAS. In stage IA non-mucinous ADC, multivariate analysis revealed that STAS II was significantly associated with shorter RFS and LCSS (p < 0.001 and p = 0.006, respectively). In addition, STAS II was an independent poor prognostic factor for recurrence in both limited and radical resection groups (p = 0.001 and p = 0.023, respectively). In conclusion, presence of STAS II was an independent poor prognostic factor in stage IA non-mucinous ADC regardless of the extent of resection.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular , Neoplasias Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía , Supervivencia sin Progresión , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. METHODS: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. RESULTS: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. CONCLUSIONS: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
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Factor de Transcripción Activador 3/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Oxidorreductasas de Alcohol Dependientes de NAD (+) y NADP (+)/metabolismo , Polimorfismo de Nucleótido Simple , Factor de Transcripción Activador 3/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Sitios de Unión , Biomarcadores de Tumor/genética , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patología , Carcinoma de Células Grandes/cirugía , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Oxidorreductasas de Alcohol Dependientes de NAD (+) y NADP (+)/genética , Pronóstico , Regiones Promotoras Genéticas , Tasa de SupervivenciaRESUMEN
OBJECTIVES: Subsolid lung adenocarcinoma with cystic airspaces (LACA) is a unique manifestation of lung cancer. This study was conducted to establish a radiologic disease progression model of LACA and to explore its association with the clinical course and clinicopathologic features of LACA. MATERIALS AND METHODS: Sixty patients with LACA who underwent surgery at our center between 2004 and 2017 were retrospectively reviewed. The morphological changes of LACA over time on 98 serial computed tomography scans from 27 of 60 patients were tracked to establish a radiologic disease progression model. Associations between this model and the clinicopathologic characteristics of LACA were investigated. RESULTS: The following stepwise progression model of LACA was developed: in phase I, cystic airspaces (CAs) appear in the middle of non-solid nodules; in phase II, the CAs grow; in phase III, a solid component appears on the border of the CAs; and in phase IV, the solid component gradually surrounds the CAs and becomes thicker, and the CAs shrink. In total, 10 (17%), 33 (55%), and 17 (28%) LACA patients were classified as belonging to phases II, III, and IV at the time of surgery, respectively. More advanced phases were associated with higher pathologic T and N staging, lymphovascular invasion, visceral pleural invasion, spread through air spaces, and solid/micropapillary subtype. In the multivariate analysis, our model demonstrated a good discrimination capability for cancer recurrence risk. CONCLUSIONS: The stepwise disease progression model of LACA based on radiologic findings developed in this study represented its natural clinical course and clinicopathologic features well.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Quistes/diagnóstico por imagen , Quistes/patología , Progresión de la Enfermedad , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
In the original article there are errors in Fig. 3. Following is the corrected figure.
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BACKGROUND: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC). METHODS: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed. RESULTS: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54-0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13-4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08-1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10-3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41-1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11-6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17-2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12-6.88, p = 0.03, respectively). CONCLUSIONS: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas de Neoplasias/genética , Transferasas del Grupo 1-Carbono/genética , Pronóstico , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Variación Genética/genética , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Postoperative leakage after esophagectomy is associated with significant life-threatening complications. Recently, endoscopic vacuum therapy (EVT) was introduced and has been successfully used as a new treatment option. The purpose of this study was to evaluate the safety and efficacy of EVT for the management of postoperative leakage after esophagectomy. METHODS: A total of 22 patients were treated with either intraluminal or intracavitary EVT for the management of postoperative leakage from May 2012 to April 2018. The location of leakage was intrathoracic in 17 patients and cervical in five patients. The outcomes of EVT were analyzed retrospectively. RESULTS: Complete postoperative leakage closure was achieved in 19 of 22 patients. The median duration of EVT application was 14 days (range 2-103), and a median number of three EVT systems (range 1-14) were used. In 19 patients who were successfully managed with EVT, oral feeding was possible a median of 15 days after the first day of treatment. There were no cases of mortality related to postoperative leakage. CONCLUSIONS: EVT is a well-tolerated and effective therapeutic option for the treatment of various types of postoperative leakage after esophagectomy.
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Fuga Anastomótica/terapia , Endoscopía/métodos , Esofagectomía/efectos adversos , Terapia de Presión Negativa para Heridas/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC. METHODS: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated. RESULTS: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (Ptrend = 0.02) in tumor tissues. CONCLUSIONS: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.
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Adenocarcinoma/mortalidad , Carcinoma de Células Grandes/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/mortalidad , Neoplasias Pulmonares/mortalidad , Polimorfismo de Nucleótido Simple , Ubiquitina-Proteína Ligasas/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patología , Carcinoma de Células Grandes/cirugía , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: The aim of this study was to identify the factors predicting thoracic lymph node (LN) metastases for pulmonary resection from colorectal cancer (CRC). METHODS: The records of 160 patients who underwent pulmonary metastasectomy for CRC were retrospectively reviewed. Clinicopathologic factors were analyzed with chi-square test or t-test and logistic regression to identify predictable factors for LN metastases. RESULTS: Sixty patients (37.5%) underwent LN dissection during pulmonary metastasectomy, and LN metastases were found in five patients. Twenty-three patients had LN recurrence among the 100 patients (62.5%) without LN dissection during the follow-up period. Twenty-eight patients out of 160 (17.5%) had LN metastases. By multivariate analysis, the number of pulmonary metastasis and metastasis from colon cancers were independent factors predicting LN metastases. CONCLUSION: The number of pulmonary metastasis and metastasis from colon cancers were independent factors predicting LN metastases. LN sampling should be performed especially in cases with strong predictive factors to improve staging and help guide further treatment.
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Neoplasias Colorrectales/patología , Neoplasias Pulmonares/secundario , Ganglios Linfáticos/patología , Anciano , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Metastasectomía , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonectomía , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Propofol may help to protect against ischaemic acute kidney injury (AKI); however, research on this topic is sparse. OBJECTIVE: The current study aimed to investigate whether there were differences in the incidence of postoperative AKI after lung resection surgery between patients who received propofol-based total intravenous anaesthesia (TIVA) and those who received sevoflurane-based inhalational anaesthesia. DESIGN: A retrospective observational study. SETTING: A single tertiary care hospital. PATIENTS: Medical records of patients aged 19 years or older who underwent curative lung resection surgery for nonsmall cell lung cancer between January 2005 and February 2018 were examined. MAIN OUTCOME MEASURES: After propensity score matching, the incidence of AKI in the first 3 postoperative days was compared between patients who received propofol and those who received sevoflurane. Logistic regression analyses were also used to investigate whether propofol-based TIVA lowered the risk of postoperative AKI. RESULTS: The analysis included 2872 patients (1477 in the sevoflurane group and 1395 in the propofol group). After propensity score matching, 661 patients were included in each group; 24 (3.6%) of the 661 patients in the sevoflurane group developed AKI compared with 23 (3.5%) of the 661 patients in the propofol group (95% confidence intervals of difference in incidence -0.019 to 0.022, Pâ=â0.882). The logistic regression analyses revealed that the incidence of AKI was not different in the two groups (odds ratio 0.96, 95% confidence interval 0.53 to 1.71, Pâ=â0.882). CONCLUSION: In this retrospective study, no significant difference was found in the incidence of postoperative AKI after lung resection surgery between patients who received propofol-based TIVA and those who received sevoflurane-based inhalational anaesthesia. Considering the methodological limitation of this retrospective study, further studies are required to confirm these results.
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Lesión Renal Aguda/epidemiología , Anestesia General/métodos , Neumonectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Daño por Reperfusión/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Anciano , Anestesia General/efectos adversos , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/efectos adversos , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Incidencia , Riñón/irrigación sanguínea , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Puntaje de Propensión , Propofol/administración & dosificación , Propofol/efectos adversos , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & control , Estudios Retrospectivos , Sevoflurano/administración & dosificación , Sevoflurano/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: Perioperative positive fluid balance has negative effects on short-term outcomes, such as surgical complications, although the associations with postoperative mortality remain unclear. This study evaluated the associations of perioperative fluid balance (FB) with 30-day mortality and acute kidney injury (AKI) after postoperative intensive care unit (ICU) admission. METHODS: This retrospective study evaluated data from adult patients who were admitted to the ICU after surgery during 2012-2016. Weight-based cumulative FB (%) was calculated for 3 time periods [postoperative day (POD) 0 (24 h), 0-1 (48 h), and 0-2 (72 h)] and was categorized as positive (≥ 5%), mild to moderate positive (5-10%), severe positive (> 10%), normal (0-5%), or negative (< 0%). RESULTS: Data from 7896 patients were included in the analysis. The multivariable Cox regression model revealed that increased 30-day mortality was associated with positive FB groups (≥ 5%) compared to normal FB groups (0-5%) during 3 time periods [hazard ratio (HR) on POD 0 (24 h): 1.87, HR on POD 1 (48 h): 1.91, and HR on POD 2 (72 h): 4.62, all P < 0.05]. These trends were more evident in the severe positive FB group across the three time periods. Additionally, similar association was found for incidence of AKI during POD 0-2. CONCLUSION: Perioperative cumulative weight-based FB was positively associated with increased postoperative 30-day mortality or postoperative AKI in ICU patients; this association was consistent with the positive FB on POD 0 (24 h), 0-1 (48 h), and 0-2 (72 h).
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Lesión Renal Aguda/etiología , Unidades de Cuidados Intensivos , Equilibrio Hidroelectrolítico , Adulto , Anciano , Peso Corporal , Cuidados Críticos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios RetrospectivosRESUMEN
RegulomeDB is a new tool that can predict the regulatory function of genetic variants. We applied RegulomeDB in selecting putative functional variants and evaluated the relationship between these variants and survival outcomes of surgically resected non-small-cell lung cancer. Among the 244 variants studied, 14 were associated with overall survival (P < 0.05) in the discovery cohort and one variant (rs2257609 C>T) was replicated in the validation cohort. In the combined analysis, rs2257609 C>T was significantly associated with worse overall and disease-free survival under a dominant model (P = 2 × 10-5 and P = 0.001, respectively). rs2257609 is located in the SLC5A10 intron, but RegulomeDB predicted that this variant affected DRG2, not SLC5A10 expression. The expression level of SLC5A10 was not different with the rs2257609 genotype. However, DRG2 expression was different according to the rs2257609 genotype (Ptrend = 0.03) and was significantly higher in tumor than in non-malignant lung tissues (P = 1 × 10-5 ). Luciferase assay also showed higher promoter activity of DRG2 in samples with the rs2257609 T allele (P < 0.0001). rs2257609 C>T affected DRG2 expression and, thus, influenced the prognosis of early-stage non-small-cell lung cancer. This study was approved by the Institutional Review Broad of Kyungpook National University of Hospital (Approval No. KNUMC 2014-04-210-003).
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Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Unión al GTP/genética , Perfilación de la Expresión Génica/métodos , Neoplasias Pulmonares/patología , Polimorfismo de Nucleótido Simple , Proteínas de Transporte de Sodio-Glucosa/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Variación Genética , Humanos , Intrones , Neoplasias Pulmonares/genética , Masculino , Estadificación de Neoplasias , Pronóstico , Regiones Promotoras Genéticas , Análisis de SupervivenciaRESUMEN
OBJECTIVE: Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy. METHODS: This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection. ATM, RAD51, LKB1, H2AX, and SIRT1 expression levels were analyzed in resected tumor specimens via immunostaining and were used to classify patients and compare survival and responses to chemotherapy. RESULTS: SIRT1 expression correlated significantly with improved responses to platinum-based chemotherapy (odds ratio, 2.28; p = 0.024), progression-free survival (hazard ratio [HR], 0.74; p = 0.036), overall survival (HR, 0.63; p = 0.006), and tumor-bearing survival (HR, 0.62; p = 0.014). After adjusting for clinical variables, the HR of SIRT1 expression remained significant for overall survival (HR, 0.59; p = 0.039) but not for progression-free survival (HR, 0.74; p = 0.183). No prognostic stratification was observed for the other 4 markers. CONCLUSION: Patients with SIRT1-expressing NSCLC had superior responses to chemotherapy and longer survival durations than those with SIRT1-negative cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Sirtuina 1/biosíntesis , Sirtuina 1/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de la Ataxia Telangiectasia Mutada/biosíntesis , Proteínas de la Ataxia Telangiectasia Mutada/genética , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/efectos adversos , Terapia Combinada/métodos , Daño del ADN/efectos de los fármacos , Daño del ADN/genética , Reparación del ADN/genética , Supervivencia sin Enfermedad , Femenino , Histonas/biosíntesis , Histonas/genética , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Proteínas Serina-Treonina Quinasas/biosíntesis , Proteínas Serina-Treonina Quinasas/genética , Recombinasa Rad51/biosíntesis , Recombinasa Rad51/genética , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Propofol-based total intravenous anesthesia (TIVA) has been reported to improve long-term outcome following cancer surgery, when compared with inhalation agents. However, such investigational reports are still controversial, and no studies have been conducted in relation to non-small cell lung cancer (NSCLC) surgery. The present study aimed to compare the favorable effects of TIVA versus inhalation agents on recurrence-free survival and overall survival after curative resection of NSCLC. This retrospective cohort study examined medical records of the patients who were diagnosed with NSCLC and underwent curative resection at Seoul National University Bundang Hospital from August 2003 to July 2012. The primary outcome included the comparison of postoperative overall survival and recurrence-free survival in both groups. To balance the 2 groups for analysis, a propensity matching method was used, and stratified Cox proportional hazard models were used for statistical analysis. This study included 943 cases of NSCLC for final analysis, and the cases were divided into the TIVA group (n = 749) and inhalation group (n = 194). Propensity matching produced 196 patients in each group. The final analysis revealed no significant difference in the hazard ratio (HR) for recurrence between the TIVA and inhalation groups ( P = .233). The HR for death between the 2 groups was not significantly different either ( P = .551). In this study, we found no benefit of propofol-based TIVA for long-term oncologic outcome after NSCLC surgery, relative to inhalation agents.
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Anestesia Intravenosa/métodos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Statins are known for their anticancer effects, and many studies have shown the effectiveness of statins for cancer prevention and improvement of cancer-related long-term oncologic outcome. However, their effectiveness on recurrence or survival of non-small cell lung cancer (NSCLC) after curative resection remains unknown. This was a retrospective cohort study that assessed the medical records of patients who were diagnosed with NSCLC and treated with curative resection at a tertiary care hospital between August 2003 and July 2012. The primary outcome was the comparison of postoperative overall survival (OS) and recurrence-free survival (RFS) between the statin group of patients, who were administered statins at least 1 month before the surgery and continued it after the surgery, and the nonstatin group of patients, who were not administered statins. Propensity score (PS) matching was used to balance the 2 groups, and the analysis was performed using a Cox proportional hazards model. In total, 994 patients with NSCLC were included in the final analysis: 135 patients in the statin group and 859 patients in the nonstatin group. After PS matching, there was no significant difference in postoperative recurrence ( P = .862) or death ( P = .074) between the statin group and the nonstatin group. Similarly, there was no significant difference in postoperative RFS ( P = .862) and OS ( P = .072) between the 2 groups after PS matching. This study demonstrated that statin administration had no significant association with recurrence or survival after NSCLC treatment.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVES: This study evaluated the relationship between the maximum standardized uptake value (SUVmax) of preoperative positron emission tomography/computed tomography (PET/CT) and the characteristics of lung adenocarcinoma featuring ground-glass opacity nodules (GGN). METHODS: The association of the SUVmax of preoperative PET/CT with ground-glass opacity (GGO) proportion on CT, subtypes of adenocarcinoma (minimally invasive adenocarcinoma, invasive adenocarcinoma), predominant types of invasive adenocarcinoma, and size of the total and invasive components of pathology were evaluated in 190 patients who underwent resection for lung adenocarcinoma featuring GGN. RESULTS: The mean SUVmax of non-solid GGN and partly solid GGN were 0.53 and 1.32, respectively (P = 0.029). The mean SUVmax of the main masses in 38 patients with MIA and 152 with invasive adenocarcinoma were 0.86 and 1.36, respectively (P = 0.029). The mean SUVmax of acinar, lepidic, papillary, and solid tumors were 1.61, 0.87, 0.98, and 1.60, respectively. The mean SUVmax of invasive components measuring ≤10 mm, 11-20 mm, and >20 mm were 0.84, 1.66, and 2.09, respectively (P < 0.001). CONCLUSIONS: The SUVmax of lung adenocarcinoma featuring GGN can vary depending on the GGO proportion. A higher SUVmax can be expected in invasive adenocarcinoma than in MIA, and solid and acinar-predominant invasive adenocarcinoma showed a higher SUVmax.
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Adenocarcinoma/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Cuidados Preoperatorios/métodos , Radiofármacos/farmacocinética , Estudios RetrospectivosRESUMEN
BACKGROUND: This study was conducted to determine whether single-nucleotide polymorphisms (SNPs) in EMT-related genes may influence the prognosis of NSCLC after surgery. METHODS: There were 88 SNPs in EMT-related genes evaluated in a discovery set of 376 patients who underwent curative surgery for NSCLC. Significantly, 14 SNPs were evaluated in a validation set of 428 patients. Luciferase assay and RT-PCR were conducted to examine functional relevance of polymorphisms. RESULTS: Fourteen SNPs that were associated with survival outcomes in a discovery set were selected for validation. Among those, two SNPs (FOXF2 rs1711972A>C and HEYL rs784621G>A) were replicated in a validation study. In combined analysis, FOXF2 rs1711972 AC+CC genotype was associated with significantly better overall survival (OS) and disease-free survival (DFS) compared with AA genotype (adjusted hazard ratio [aHR] for OS = 0.67, 95% confidence interval [CI] 0.51-0.88, P = 0.004; and aHR for DFS = 0.77, 95% CI 0.62-0.95, P = 0.01). HEYL rs784621 AA genotype exhibited a significantly worse OS compared with GG+GA genotype (aHR for OS = 2.65, 95% CI 1.63-4.31, P = 8 × 10-5). FOXF2 rs1711972C allele had a significantly increased promoter activity than rs1711972A allele (P = 0.01), and HEYL rs784621A allele had a significantly lower promoter activity than rs784621G allele (P = 0.004). FOXF2 rs1711972A>C was significantly associated with increased FOXF2 mRNA expression. CONCLUSIONS: FOXF2 rs1711972A>C and HEYL rs784621G>A were associated with survival outcomes of surgically treated NSCLC. These SNPs may help to identify patients at high risk of poor disease outcomes.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Transición Epitelial-Mesenquimal , Factores de Transcripción Forkhead/genética , Neoplasias Pulmonares/patología , Polimorfismo de Nucleótido Simple , Proteínas Represoras/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patología , Carcinoma de Células Grandes/cirugía , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Single-incision thoracoscopic surgery (SITS) requires extensive time and practice to achieve satisfactory technical skills. The aim of this study was to evaluate the learning curves of SITS for primary spontaneous pneumothorax (PSP). METHODS: This study included a total of 274 consecutive patients who underwent PSP surgery by a single operator between May 2011 and February 2014. During this period, SITS was applied as a routine approach. Learning curves were made by the cumulative sum (CUSUM) method using the number of cases and four surgical technique-related factors, including operation time, postoperative complication, non-SITS rate, and ipsilateral PSP recurrence. RESULTS: Among the 274 patients, 16 patients who were presented with a previous 3-port wound scar or inadequate chest tube site before surgery were not eligible for SITS. Hence, SITS was attempted on 258 patients and performed successfully in 251 patients. For these successful SITS patients, the mean age was 22.9 ± 8.1 years, the mean operation time was 65.6 ± 22.2 min, the mean chest tube indwelling time was 1.5 ± 1.1 days, and the mean postoperative hospital stay was 1.7 ± 1.1 days. The mean operation time decreased from 84.0 to 47.6 min when a comparison was made between patients operated in the initial 6 months and the last 6 months of the study period. As revealed by the CUSUM technique, more than 50 % of the cases experienced an operation time of <70 min after the first 92 cases. After 57 cases, the postoperative complication rate was maintained at <5 %. The non-SITS rate was achieved to be lower than 5 % after 112 cases. The ipsilateral PSP recurrence rate was maintained at below 8 % after 102 cases. CONCLUSIONS: Although PSP is the most applicable scenario for the beginner of SITS, at least 100 cases of experience are needed to achieve optimal technical level.
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Competencia Clínica , Curva de Aprendizaje , Neumotórax/cirugía , Toracoscopía/métodos , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Recurrencia , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Reduced lung volumes are unavoidable after lung resection surgery. Magnesium sulphate (MgSO4) administration has been reported to reduce the requirement for neuromuscular blocking drugs and postoperative analgesics in surgical patients. OBJECTIVE: To investigate the effect of MgSO4 on pulmonary function after video-assisted thoracoscopic surgery (VATS). DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: A university tertiary care centre. PATIENTS: Sixty-six patients scheduled for pulmonary lobectomy or segmentectomy via VATS. INTERVENTION: Patients were allocated to one of two groups: the Mg (MgSO4 50âmgâkg intravenously for 10âmin, followed by a continuous infusion of 15âmgâkgâh during surgery) or the control (same volume of 0.9% saline). MAIN OUTCOME MEASURES: Pulmonary function tests [forced expiratory volume in 1âs (FEV1), forced vital capacity (FVC) and peak expiratory flow rate] were measured before surgery and at three time points after surgery (2, 24 and 48âh postoperatively) using a portable spirometer. Twelve months after surgery, pulmonary function test values were repeated at a regular outpatient follow-up visit. RESULTS: FEV1 at 24 (1.7â±â0.6 vs. 1.3â±â0.5âl, Pâ=â0.033) and 48âh (1.7â±â0.6 vs. 1.4â±â0.5âl, Pâ=â0.021) and FVC at 24 (2.0â±â0.8 vs. 1.6â±â0.6âl, Pâ=â0.038) and 48âh (2.2â±â0.8 vs. 1.7â±â0.7âl, Pâ=â0.008) after surgery were significantly greater in the Mg group. Patients in the Mg group required less rocuronium than those in the control group (64.2â±â19.9 vs. 74.9â±â20.3âmg, respectively; Pâ=â0.041). Consumption of postoperative patient-controlled analgesia was also significantly less at 24 and 48âh after surgery in the Mg group (Pâ=â0.022 and 0.015, respectively), although pain scores and rescue analgesics were comparable. Five patients in the control group were diagnosed with postoperative pneumonia using clinical and radiological criteria before discharge. FEV1 and FVC at 12 months after surgery were not different between the two groups. CONCLUSION: Intraoperative administration of MgSO4 improved pulmonary function and reduced the need for rocuronium and postoperative analgesics in patients who underwent VATS. TRIAL REGISTRATION: cris.nih.go.kr identifier: KCT0001410.
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Pulmón/efectos de los fármacos , Pulmón/fisiología , Sulfato de Magnesio/uso terapéutico , Dimensión del Dolor/efectos de los fármacos , Cirugía Torácica Asistida por Video/efectos adversos , Adulto , Anciano , Analgésicos/farmacología , Analgésicos/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Sulfato de Magnesio/farmacología , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/prevención & control , Respiración con Presión Positiva/métodos , Respiración con Presión Positiva/tendencias , Pruebas de Función Respiratoria/métodos , Pruebas de Función Respiratoria/tendencias , Cirugía Torácica Asistida por Video/tendenciasRESUMEN
PURPOSE: The aim of this retrospective, multicenter study was to develop a recurrence risk-scoring model in patients with curatively resected stage I lung adenocarcinoma (ADC). METHODS: Clinicopathologic and outcome data for a development cohort of 1,700 patients with pathologic stage I ADC from four institutions resected between January 2000 and December 2009 were evaluated. A phantom study was performed for correction of inter-institutional differences in positron emission tomography-standardized uptake value (PET-SUV). A nomogram for recurrence prediction was developed using Cox proportional hazards regression. This model was validated in a cohort of 460 patients in two other hospitals. The recurrence rate was 21.0 % for the development cohort and 22.1 % for the validation cohort. RESULTS: In multivariable analysis, three independent predictors for recurrence were identified: pathologic tumor size (hazard ratio [HR] 1.03, 95 % CI 1.017-1.048; p < 0.001), corrected PET-SUV (HR 1.08, 95 % CI 1.051-1.105; p < 0.001), and lymphovascular invasion (HR 1.65, 95 % CI 1.17-2.33; p = 0.004). The nomogram was made based on these factors and a calculated risk score was accorded to each patient. Kaplan-Meier analysis of the development cohort showed a 5-year recurrence-free survival (RFS) of 83 % (95 % CI 0.80-0.86) in low-risk patients and 59 % (95 % CI 0.54-0.66) in high-risk patients with the highest 30 percentile scores. The concordance index was 0.632 by external validation. CONCLUSIONS: This recurrence risk-scoring model can be used to predict the RFS for pathologic stage I ADC patients using the above three easily measurable factors. High-risk patients need close follow-up and can be candidates for adjuvant chemotherapy.