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1.
Journal of Forensic Medicine ; (6): 564-570, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1009388

RESUMEN

OBJECTIVES@#To establish a method for the simultaneous quantitative analysis of etomidate and its metabolite etomidate acid in blood, and to discuss its application value in actual cases.@*METHODS@#Acetonitrile precipitate protein method was used, and C18 column was selected. Gradient elution was performed with acetonitrile and 5 mmol/L ammonium acetate within 6 min. Electrospray ionization source in positive ion mode was used. The internal standard etomidate acid-d5 was obtained by etomidate-d5 alkaline hydrolysis reaction. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for quantitative analysis. The methodological verification was conducted.@*RESULTS@#Etomidate and etomidate acid in blood showed good linear relationship in the quantitative linear range (r>0.999), with the lower limit of quantification was 2.5 ng/mL and 7.5 ng/mL, respectively. The accuracy, precision, recovery rate, and matrix effect of the method met the professional verification standards. The practical application results showed that etomidate and etomidate acid could be detected in the blood of the abusers, and their mass concentrations ranged from 17.24 to 379.93 ng/mL.@*CONCLUSIONS@#The method established in this study can simultaneously quantify etomidate and etomidate acid in blood, which is simple and convenient to operate with accuracy. It can meet the detection needs of actual cases and provide technical support for law enforcement to crack down on etomidate abuse.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida , Etomidato , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida con Espectrometría de Masas , Acetonitrilos
2.
JTO Clin Res Rep ; 3(1): 100257, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34977823

RESUMEN

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

3.
Nat Commun ; 12(1): 6450, 2021 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-34750392

RESUMEN

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Supervivencia sin Enfermedad , Receptores ErbB/genética , Gefitinib/uso terapéutico , Genómica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico
4.
Chin Med J (Engl) ; 134(22): 2700-2709, 2021 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-34732663

RESUMEN

BACKGROUND: There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients. METHODS: A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients. RESULTS: After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy. CONCLUSION: Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Humanos , Inmunomodulación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Estadificación de Neoplasias , Puntaje de Propensión , Estudios Retrospectivos , Timalfasina
6.
Thorac Cancer ; 12(9): 1469-1488, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33787090

RESUMEN

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Inmunoterapia/efectos adversos , Neoplasias Pulmonares/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Periodo Perioperatorio
7.
Chinese Medical Journal ; (24): 2700-2709, 2021.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-921204

RESUMEN

BACKGROUND@#There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients.@*METHODS@#A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients.@*RESULTS@#After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy.@*CONCLUSION@#Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.


Asunto(s)
Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Inmunomodulación , Neoplasias Pulmonares/cirugía , Estadificación de Neoplasias , Puntaje de Propensión , Estudios Retrospectivos , Timalfasina
9.
J Clin Oncol ; 39(7): 713-722, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33332190

RESUMEN

PURPOSE: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% (P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (P = .316) and 5y DFS rates were 22. 6% and 23.2% (P = .928), respectively. CONCLUSION: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Gefitinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Vinorelbina/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioterapia Adyuvante , China , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Receptores ErbB/genética , Femenino , Gefitinib/efectos adversos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Tiempo , Vinorelbina/efectos adversos
10.
Lung Cancer ; 150: 164-171, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33186858

RESUMEN

OBJECTIVES: Health-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group. MATERIALS AND METHODS: In the phase III ADJUVANT trial, patients with completely resected, stage II-IIIA (N1-N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups. RESULTS: At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75-63509.05, p =  0.019; LCSS, 1.13, 1.04-1.22, p =  0.003; TOI, 88.39, 4.40-1775.05, p =  0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42-0.90, p =  0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43-0.93, p =  0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33-0.77, p =  0.001). CONCLUSION: Adjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II-IIIA (N1-N2), EGFR-mutant NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioterapia Adyuvante , Cisplatino/uso terapéutico , Receptores ErbB/genética , Gefitinib/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Estadificación de Neoplasias , Calidad de Vida , Vinorelbina/uso terapéutico
11.
J Thorac Dis ; 11(5): 2006-2023, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31285894

RESUMEN

BACKGROUND: To evaluate whether fat-free mass index (FFMI) could be predictive of prolonged air leak (PAL) complicating video-assisted thoracoscopic (VATS) lobectomy for non-small-cell lung cancer (NSCLC). METHODS: A retrospective study was conducted on the prospectively-maintained database in our institution between January 2015 and July 2017. The gender-specific median values of FFMI for males and females were applied as their respective cutoffs to stratify patients into low-FFMI group and high-FFMI group in initial univariable analyses. An effective multivariable logistic-regression analysis was then performed to demonstrate the predictive value of dichotomized FFMI. RESULTS: There were 1,091 surgical patients with NSCLC included (616 males and 475 females), with a PAL incidence of 14.6%. The median FFMI values among males and females were 17.3 and 14.6 kg/m2, respectively. PAL cases in both male (16.9±1.5 vs. 17.4±1.5 kg/m2; P=0.002) and female (14.0±0.9 vs. 14.6±1.1 kg/m2; P<0.001) groups had a significantly lower mean FFMI than that of non-PAL cases. The incidence of PAL was significantly increased in male patients with FFMI <17.3 kg/m2 (23.7% vs. 14.3%; P=0.003) and female patients with FFMI <14.6 kg/m2 (12.7% vs. 5.0%; P=0.003). Lower dichotomized FFMI was also significantly associated with prolonged time to air leak cessation and length of stay (LOS). Finally, multivariable logistic-regression analysis indicated that lower dichotomized FFMI [odds ratio (OR) =1.98; 95% confidence interval (CI): 1.33-2.96; P=0.001] could independently predict the occurrence of PAL. CONCLUSIONS: FFMI acts as an excellent categorical risk factor for PAL complicating VATS lobectomy and shows a much superior significance than body mass index (BMI) in terms of the prediction of PAL.

12.
Int J Surg ; 69: 32-42, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31319230

RESUMEN

OBJECTIVES: To evaluate prognostic significance of albumin-to-alkaline phosphatase ratio (AAPR) for patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC) by a propensity score-matching (PSM) analysis. METHODS: This PSM study was conducted on the prospectively-maintained database in our institution between December 2013 and March 2015. Overall survival analyses and further subgroup analyses were both performed to distinguish the differences in postoperative survival between patients stratified by an optimal cutoff of AAPR. Multivariable Cox proportional hazards regression models were established to determine the independent prognostic factors. RESULTS: There were 390 patients with operable NSCLCs included. An AAPR of 0.57 was identified as the optimal cutoff regarding to postoperative survival. Both overall survival (OS) and disease-free survival (DFS) in patients with AAPR≤0.57 were significantly shortened compared to those in patient with AAPR>0.57 (Log-rank P < 0.001). Patients with AAPR≤0.57 had significantly lower rates of OS and DFS than those of patients with AAPR>0.57 (P < 0.001). These differences still remained significant after subgroup analyses and PSM analyses. Multivariate analyses on the entire cohort and the PSM cohort commonly indicated that low preoperative AAPR could be an independent prognostic factor for unfavorable OS and DFS of resected NSCLCs. CONCLUSIONS: AAPR can serve as a novel risk stratification tool to refine prognostic prediction for surgical NSCLC. It may help surgeons to screen high-surgical-risk patients and further formulate individualized treatment schemes.


Asunto(s)
Fosfatasa Alcalina/sangre , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Puntaje de Propensión , Albúmina Sérica/análisis , Anciano , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos
13.
Thorac Cancer ; 10(3): 533-542, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30666800

RESUMEN

BACKGROUND: Approximately 8.3-15.9% of patients with clinical stage I non-small cell lung cancer are subsequently shown to have lymph node metastasis. However, the clinical characteristics of patients with lymph node metastasis in China are not fully understood. METHODS: This is a multicenter retrospective analysis of pathological T1 non-small cell lung cancer patients who underwent surgical resection from 2 January 2014 to 27 December 2017. Clinical and pathological information was collected with the assistance of the Large-scale Data Analysis Center of Cancer Precision Medicine-LinkDoc database. The clinical and pathological factors associated with lymph node metastasis were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 10 885 participants (51.6% women; 15.3% squamous cell carcinoma) were included in the analysis. The median age was 60.0 years (range 12.9-86.6 years). A total of 1159 patients (10.6%) had metastases in mediastinal nodes (N2), and 640 patients (5.9%) had metastasis in pulmonary lymph nodes (N1). Most patients had T1b lung cancer (4766, 43.8%). Of the patients, 3260 (29.9%) were current or former smokers. The univariate and multivariate analyses showed that younger age, squamous cell carcinoma, poor differentiation, larger tumor size, carcinoembryonic antigen level ≥5 ng/mL, and vascular invasion (+) were significantly associated with higher percentages of lymph node metastases (P < 0.001 for all). CONCLUSION: This real-world study showed the significant association of lymph node metastasis with age, tumor size, histology and differentiation, carcinoembryonic antigen levels, and status of vascular invasion. Female patients with T1a adenocarcinoma in the right upper lobe barely had lymph node metastasis.


Asunto(s)
Adenocarcinoma/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Metástasis Linfática , Pronóstico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , China/epidemiología , Femenino , Humanos , Modelos Logísticos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Masculino , Mediastino/patología , Persona de Mediana Edad , Estadificación de Neoplasias
14.
J Thorac Oncol ; 14(3): 503-512, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30521970

RESUMEN

INTRODUCTION: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized. METHODS: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted. RESULTS: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib. CONCLUSIONS: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored.


Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/secundario , Quimioterapia Adyuvante/efectos adversos , Gefitinib/efectos adversos , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/epidemiología , Análisis Espacio-Temporal , Adolescente , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Tasa de Supervivencia , Insuficiencia del Tratamiento , Adulto Joven
15.
World J Surg ; 43(3): 955-962, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30426188

RESUMEN

BACKGROUND: Controversy still exists in which subtype of non-small-cell lung cancer [squamous cell carcinoma (SCC) or adenocarcinoma] is more likely to have lymph node (LN) metastasis. The aim of this study is to compare the pattern of LN metastasis in two cohorts of matched patients surgically treated for SCC or adenocarcinoma. METHODS: A retrospective analysis of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy without preoperative treatment for lung SCC or adenocarcinoma was conducted in this study. Data for analysis consisted of age, gender, tumor size, lobe-specific tumor location, tumor location (peripheral or central), and pathologic findings. We conducted the propensity score-matched (PSM) analysis to eliminate potential bias effects of possible confounding factors. RESULTS: From January 2015 to December 2016 in our department, we finally included a total of 387 patients (including 63 patients with SCC and 324 patients with adenocarcinoma) for analysis. For the unmatched cohort, there was no sufficient evidence of significantly different number of positive LNs (P = 0.90) and rate of LN metastasis (P = 0.23) between SCC patients and adenocarcinoma patients. However, potential confounding factors, for example gender, tumor size, tumor location, tumor differentiation, and total number of dissected LNs, were significantly different between patients with SCC and those with adenocarcinoma. In the analysis of matched cohort after PSM analysis, those above confounding factors were comparable between the two groups. However, patients with adenocarcinoma had significantly more mean positive LNs (2.2 and 0.7; P = 0.008) and a higher rate of LN metastasis (53% and 29%; P = 0.016) than those with SCC. CONCLUSIONS: Lung adenocarcinoma had a higher risk of LN metastasis than SCC, suggesting that different therapeutic modalities may be indicated for the two different subtypes of lung cancer.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos
16.
Journal of Forensic Medicine ; (6): 581-585, 2019.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-985050

RESUMEN

Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry (GC-QTOF-MS). Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.


Asunto(s)
Humanos , Cromatografía Líquida de Alta Presión/métodos , Toxicología Forense/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Delitos Sexuales , Espectrometría de Masas en Tándem/métodos , Tiletamina/sangre , Zolazepam/sangre
17.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1010484

RESUMEN

Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC) worldwide. Protein phosphatase 2A (PP2A) dysfunction has been widely reported in a broad range of malignancies due to its distinctive role in miscellaneous cellular processes. However, it is poorly understood whether aberrant alterations of PP2A are involved in the network of oncogenic events in LSCC. Here, we detected a panel of PP2A-associated proteins using western blot in both laryngeal squamous cell carcinoma tissues and paired adjacent normal tissues from patients (Data S1). We found that phospho-PP2A/C (Y307), α4, cancerous inhibitor of protein phosphatase 2A (CIP2A), Akt, ezrin, phospho-ezrin (T567), 14-3-3, and focal adhesion kinase (FAK) showed increased expression levels in carcinoma tissues relative to normal tissues, while phospho-Akt (T308) showed decreased levels. Our study, thus, provides a rationale for targeting PP2A to develop novel therapies and proposes a combination of interrelated biomarkers for the diagnostic evaluation and prognosis prediction in LSCC.


Asunto(s)
Humanos , Autoantígenos/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Estudios de Casos y Controles , Proteínas del Citoesqueleto/metabolismo , Quinasa 1 de Adhesión Focal/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Laríngeas/metabolismo , Laringe/metabolismo , Proteínas de la Membrana/metabolismo , Fosforilación , Proteína Fosfatasa 2/metabolismo
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(5): 776-780, 2018 Sep.
Artículo en Chino | MEDLINE | ID: mdl-30378343

RESUMEN

OBJECTIVE: To develop a novel objective standardized endoscopic skill training and assessment system based on artificial intelligence technology. METHODS: By designing five basic skill parts of endoscopic operation including vision location, clamping, delivering, shearing and suturing, we achieved objective standardized indexes which gained automatically with image recognition and refined perception. RESULTS: With Huaxi intelligent endoscopic skill training system, the accurate rates of vision location, clamping, delivering, shearing and suturing were 90%, 95%, 99%, 90%, and 89%, respectively. The response and performance time were 8-10 s, <1 s, <1 s, 1-3 s, and <1 s, respectively. CONCLUSION: Huaxi intelligent endoscopic skill training and assessment system has preliminarily possessed the capability to assess the endoscopic skills of surgeons objectively.


Asunto(s)
Competencia Clínica , Endoscopía/educación , Inteligencia Artificial , Humanos
19.
J Thorac Dis ; 10(4): 2288-2294, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29850133

RESUMEN

BACKGROUND: Venous thromboembolism (VTE) remains a common complication after major thoracic surgery, especially resection of lung or esophagus cancer. This trial aims to explore the influence of preoperative usage of heparin on coagulation function of patients treated with video-assisted major thoracic surgery. METHODS: This prospective randomized control trial collected 91 patients who are diagnosed with lung or esophagus cancer intending to accept video-assisted neoplasm resection from June 2016 to May 2017 in West China Hospital, Sichuan University. After admission to hospital, the patients received heparin sodium (unfractionated heparin) 5,000 U twice a day before operation. The change of blood platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), international normalized ratio (INR) was collected and analyzed at the points of admission to hospital and post-operation. RESULTS: The mean value of all coagulation parameters (PLT, PT, APTT, TT, INR, FIB) were in normal range both before and after operation. Postoperative PLT and FIB were not significantly different from preoperative PLT and FIB respectively (P>0.05). Preoperative PT, APTT, and INR increased significantly compared to pre-operation respectively (P<0.05). Postoperative TT significantly decreased when compared to preoperative TT (P<0.05). Preoperative and postoperative abnormal rate of PT or APTT or TT or INR (number of abnormal cases/all cases) was not different significantly respectively (P>0.05). Postoperative mean drainage was 240 mL/d, mean time of hospital stay was 7.50 days, drainage tube was maintained for 4.22 days on average. CONCLUSIONS: All patients underwent video-assisted major thoracic surgery with preoperative use of heparin, there were significant differences in coagulation function after operation. However, mean values of all coagulation parameters stayed normal range clinically. In a word, the method showed no influence on coagulation function clinically.

20.
J Thorac Dis ; 10(1): 416-431, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29600074

RESUMEN

BACKGROUND: The purpose of our cohort study was to investigate the effects of pleural adhesions on perioperative outcomes in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC). METHODS: We performed a single-center retrospective analysis on the prospectively-maintained dataset at our unit from February 2014 to November 2015. Patients were divided into two groups (Group A: presence of pleural adhesions; Group B: absence of pleural adhesions) according to our grading system of pleural adhesions when entering the chest cavity. Demographic differences in perioperative outcomes between these two groups were initially estimated. A multivariate logistic-regression analysis was then performed to confirm the predictive value of the presence of pleural adhesions. RESULTS: A total of 593 NSCLC patients undergoing VATS lobectomy were enrolled. The conversion and postoperative morbidity rates were 3.2% and 29.2%, respectively. There were 154 patients with pleural adhesions (Group A) and 439 patients without pleural adhesions (Group B). Group A patients had significantly higher rates of conversion to thoracotomy (9.1% vs. 1.1%; P<0.001) and surgical complications (24.0% vs. 14.4%; P=0.006) than those of Group B patients. No significant difference was found in the overall morbidity and cardiopulmonary complication rates between these two groups. The presence of pleural adhesions was also significantly associated with the prolonged length of chest tube drainage (log-rank P<0.001) and length of stay (log-rank P=0.032). Finally, the presence of pleural adhesions was identified as an independent risk factor for conversion to thoracotomy [odds ratio (OR) =5.49; P=0.003] and surgical complications (OR =1.94; P=0.033) by multivariate logistic-regression analyses. CONCLUSIONS: Presence of pleural adhesions can predict conversion to thoracotomy and postoperative surgical complications in patients undergoing VATS lobectomy for NSCLC. Our study calls for an internationally accepted grading system for the presence of pleural adhesions to stratify the surgical risk.

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