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2.
N Engl J Med ; 390(19): 1756-1769, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38749033

RESUMEN

BACKGROUND: Standard treatment with neoadjuvant nivolumab plus chemotherapy significantly improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative treatment (i.e., neoadjuvant therapy followed by surgery and adjuvant therapy) with nivolumab may further improve clinical outcomes. METHODS: In this phase 3, randomized, double-blind trial, we assigned adults with resectable stage IIA to IIIB NSCLC to receive neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo every 3 weeks for 4 cycles, followed by surgery and adjuvant nivolumab or placebo every 4 weeks for 1 year. The primary outcome was event-free survival according to blinded independent review. Secondary outcomes were pathological complete response and major pathological response according to blinded independent review, overall survival, and safety. RESULTS: At this prespecified interim analysis (median follow-up, 25.4 months), the percentage of patients with 18-month event-free survival was 70.2% in the nivolumab group and 50.0% in the chemotherapy group (hazard ratio for disease progression or recurrence, abandoned surgery, or death, 0.58; 97.36% confidence interval [CI], 0.42 to 0.81; P<0.001). A pathological complete response occurred in 25.3% of the patients in the nivolumab group and in 4.7% of those in the chemotherapy group (odds ratio, 6.64; 95% CI, 3.40 to 12.97); a major pathological response occurred in 35.4% and 12.1%, respectively (odds ratio, 4.01; 95% CI, 2.48 to 6.49). Grade 3 or 4 treatment-related adverse events occurred in 32.5% of the patients in the nivolumab group and in 25.2% of those in the chemotherapy group. CONCLUSIONS: Perioperative treatment with nivolumab resulted in significantly longer event-free survival than chemotherapy in patients with resectable NSCLC. No new safety signals were observed. (Funded by Bristol Myers Squibb; CheckMate 77T ClinicalTrials.gov number, NCT04025879.).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia Neoadyuvante , Nivolumab , Humanos , Nivolumab/uso terapéutico , Nivolumab/efectos adversos , Nivolumab/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Anciano , Método Doble Ciego , Quimioterapia Adyuvante , Supervivencia sin Progresión , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Estadificación de Neoplasias , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neumonectomía
3.
Lung Cancer ; 177: 44-50, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36731290

RESUMEN

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is an established standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). However, of such patients who have received prior treatment with a first- or second-generation EGFR TKI, only approximately half are eligible for osimertinib therapy because its indication as second-line treatment and beyond is limited to metastatic NSCLC that is positive for the T790M resistance mutation of the EGFR gene. This study was initiated at the request of a dedicated network for patients with lung cancer in Japan. METHODS: We conducted a phase II study to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy. The primary end point was response rate (assessed by a central imaging reviewer). RESULTS: From August 2020 to February 2021, 55 patients from 15 institutions were enrolled in the study. The overall response for primary analysis was achieved in 16 patients (29.1 %; 95 % CI, 17.6-42.9), which exceeded the threshold response rate necessary for analysis. Stable disease was found in 16 patients (29.1 %), and progressive disease, in 18 (32.7 %). The median length of progression-free survival (PFS) was 4.07 months (95 % CI 2.10-4.30), and the rate of 12-month PFS was 17.3 %. CONCLUSIONS: Osimertinib demonstrated modest antitumor activity against progressive EGFR T790M-negative disease.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , 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 , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Genes erbB-1 , Platino (Metal)/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Mutación , Compuestos de Anilina/uso terapéutico , Compuestos de Anilina/efectos adversos
4.
Cancer Sci ; 113(12): 4327-4338, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36062851

RESUMEN

The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in patients with resected stage IB-IIIA non-small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)-IIIA NSCLC. Upon completing 1-4 cycles of adjuvant cisplatin-based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator-assessed disease-free survival, tested hierarchically first in patients with stage II-IIIA NSCLC whose tumors expressed programmed death-ligand 1 (PD-L1) on ≥1% of tumor cells, then in all randomized patients with stage II-IIIA NSCLC, and finally in the intention-to-treat (ITT) population (stage IB-IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all-randomized stage II-IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD-L1 tumor cells ≥1% stage II-IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease-free survival improvement with atezolizumab vs BSC was observed in the PD-L1 tumor cells ≥1% stage II-IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25-1.08), all-randomized stage II-IIIA (unstratified HR, 0.62; 95% CI, 0.35-1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34-1.10) populations. Atezolizumab-related grade 3/4 adverse events occurred in 16% of patients; no treatment-related grade 5 events occurred. Adjuvant atezolizumab showed disease-free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Cisplatino/uso terapéutico , Pueblos del Este de Asia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Anticuerpos Monoclonales Humanizados/uso terapéutico
5.
Oncol Ther ; 10(1): 253-262, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35246827

RESUMEN

INTRODUCTION: We describe the results of an exploratory analysis performed on the first head-to-head study (JapicCTI-194611) comparing two different intravenous (IV) neurokinin 1 (NK1) receptor antagonists, fosnetupitant and fosaprepitant, in combination with palonosetron (PALO) and dexamethasone (DEX) for the prevention of highly emetogenic chemotherapy (HEC)-induced nausea and vomiting (CINV). This analysis was performed to validate the findings of the primary analysis (previously published) utilizing a last observation carried forward (LOCF) approach for missing values for the efficacy endpoint of complete response (no emetic event and no rescue medication), while also evaluating the time periods encompassing the 0-168-hour (h) "extended overall phase" interval. METHODS: Patients scheduled to receive cisplatin-based chemotherapy were randomized 1:1 to fosnetupitant 235 mg or fosaprepitant 150 mg in combination with PALO 0.75 mg and DEX. Complete response rates were calculated and compared (stratified by age category and sex with a Mantel-Haenszel test) during the study's primary overall phase (0-120 h) and during additional time intervals of interest [acute (0-24 h), delayed (24-120 h), extended delayed (> 24-168 h), beyond delayed (120-168 h), and extended overall (0-168 h)]. RESULTS: A total of 785 patients were included (fosnetupitant N = 392, fosaprepitant N = 393). Complete response rates were numerically higher for fosnetupitant versus fosaprepitant for all time intervals and statistically significant for the extended overall phase. Complete response rates for fosnetupitant versus fosaprepitant during the overall, acute, delayed, extended delayed, beyond delayed, and extended overall phases were 75.5% vs. 71.0% (p = 0.1530), 93.9% vs. 92.6% (p = 0.4832), 77.0% vs. 72.8% (p = 0.1682), 74.7% vs. 68.4% (p = 0.0506), 86.7% vs. 81.7% (p = 0.0523), and 73.5% vs. 66.9% (p = 0.0450), respectively. CONCLUSION: In this exploratory analysis, fosnetupitant appeared to be more effective than fosaprepitant in preventing CINV associated with cisplatin-based HEC during the extended 7-day period following chemotherapy. INFOGRAPHIC.

6.
J Clin Oncol ; 40(2): 180-188, 2022 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-34793245

RESUMEN

PURPOSE: We evaluated the efficacy and safety of fosnetupitant (FosNTP) versus fosaprepitant (FosAPR) for preventing highly emetogenic chemotherapy-induced nausea and vomiting. This phase III study was the first head-to-head comparison between two different neurokinin-1 receptor antagonists in combination with palonosetron and dexamethasone. PATIENTS AND METHODS: Patients scheduled to receive cisplatin-based chemotherapy were randomly assigned 1:1 to FosNTP 235 mg or FosAPR 150 mg in combination with palonosetron 0.75 mg and dexamethasone. The primary end point was overall (0-120 hours) complete response (CR; no emetic event and no rescue medication) rate, stratified by sex and age category, to show the noninferiority of FosNTP to FosAPR (noninferiority margin, -10% for the difference in the overall CR rate). RESULTS: Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP [N = 392] v FosAPR [N = 393]) and were evaluated for efficacy and safety. The overall CR rate was 75.2% versus 71.0%, respectively (Mantel-Haenszel common risk difference, 4.1%; 95% CI, -2.1% to 10.3%), demonstrating noninferiority of FosNTP to FosAPR. The CR rates in the acute (0-24 hours), delayed (24-120 hours), and beyond delayed (120-168 hours) phases, and at 0-168 hours were 93.9% versus 92.6%, 76.8% versus 72.8%, 86.5% versus 81.4%, and 73.2% versus 66.9%, respectively. The incidence rates of treatment-related adverse events with FosNTP versus FosAPR were 22.2% versus 25.4%, whereas adverse events or treatment-related adverse events relevant to injection site reactions were 11.0% versus 20.6% (P < .001) and 0.3% versus 3.6% (P < .001), respectively. CONCLUSION: FosNTP demonstrated noninferiority to FosAPR, with a favorable safety profile and lower risk for injection site reactions. Thus, FosNTP is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.


Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Isoquinolinas/uso terapéutico , Morfolinas/uso terapéutico , Náusea/prevención & control , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Piridinas/uso terapéutico , Quinuclidinas/uso terapéutico , Vómitos/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Antieméticos/efectos adversos , Dexametasona/uso terapéutico , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Isoquinolinas/efectos adversos , Japón , Masculino , Persona de Mediana Edad , Morfolinas/efectos adversos , Náusea/inducido químicamente , Náusea/diagnóstico , Antagonistas del Receptor de Neuroquinina-1/efectos adversos , Piridinas/efectos adversos , Quinuclidinas/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Vómitos/inducido químicamente , Vómitos/diagnóstico
7.
Int J Clin Oncol ; 26(6): 1065-1072, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33660106

RESUMEN

INTRODUCTION: MET exon 14 skipping mutation, observed in 3-4% of non-small cell lung cancer (NSCLC), is emerging as a targetable alteration. In recent years, immune checkpoint inhibitors (ICI) have been effective in treating several NSCLCs. Our research aimed to investigate the characteristics of patients with NSCLCs harboring MET exon 14 mutations and their response to ICI in Japan. METHODS: Among the 1954 consecutive NSCLCs diagnosed at Saitama Cancer Center between 2010 and 2019, MET exon 14 skipping mutations were detected in 68 (3.5%) NSCLCs. We evaluated their characteristics such as programmed cell death ligand 1 (PD-L1) expression. RESULTS: Median age of patients with NSCLCs harboring MET exon 14 skipping mutations was 73 years. PD-L1 was highly expressed in 17 (70.8%) of the 24 patients examined. Seven patients received ICI monotherapy, and three out of seven had a remarkable treatment response, resulted in objective response rate (ORR) of 42.9% and progression-free survival of 24.7 months. Three patients with donor splice-site mutations showed a long-term treatment response, despite the fact that two with acceptor splice-site mutations demonstrated no response and experienced early disease progression with ICI monotherapy. CONCLUSION: Our results indicated that patients with NSCLCs harboring MET exon 14 mutations presented with a high rate of positive PD-L1 expression. ICI treatment showed a high ORR and long-term efficacy for NSCLCs harboring MET exon 14 mutations. Variants of MET exon 14 splice-site mutations may be associated with ICI response.

8.
Clin Lung Cancer ; 22(4): 376-380, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33612406

RESUMEN

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has recently been established as a standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC). However, only about one-half of patients who have received prior treatment with a first- or second-generation EGFR-TKI are eligible for osimertinib therapy because its indication in the second-line setting is limited to metastatic NSCLC positive for the T790M resistance mutation of EGFR. The dose-escalation part of a study in which patients received osimertinib at doses of 20 to 240 mg once daily after the development of resistance to first- or second-generation EGFR-TKIs revealed a response rate of 21% and a median progression-free survival of 2.8 months for individuals whose tumors were negative for EGFR T790M. We have now designed a phase II study of osimertinib for patients with EGFR mutation-positive NSCLC who develop isolated central nervous system progression (T790M-negative or unknown) after first- or second-generation EGFR-TKI therapy (cohort 1) or who develop systemic disease progression (T790M-negative) after first- or second-generation EGFR-TKI therapy and platinum-based chemotherapy (cohort 2). A total of 70 patients (cohort 1, n = 17; cohort 2, n = 53) will be enrolled in this study, which originated from a suggestion of a dedicated network for patients with lung cancer in Japan.


Asunto(s)
Acrilamidas/administración & dosificación , Compuestos de Anilina/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias del Sistema Nervioso Central/secundario , Estudios de Cohortes , Progresión de la Enfermedad , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Supervivencia sin Progresión , Estudios Prospectivos
9.
Immunotherapy ; 12(6): 373-378, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32314636

RESUMEN

Background: Tuberculosis (TB) is considered to be an adverse effect of treatment with immune checkpoint inhibitors. Methodology & results: Our case was a 75-year-old woman diagnosed with unresectable stage III non-small-cell lung cancer. After radical chemoradiotherapy was completed, durvalumab was initiated as a consolidation therapy. However, since chest CT showed appearances of infiltration shadows scattered in the periphery of the lungs after five doses of immunotherapy, duruvalumab was discontinued. 6 weeks later, the patient was aware of intermittent fever. Chest CT scan showed the appearance of a tree-in-bud pattern in the right lung. Acid-fast bacilli stain of sputum was positive and the PCR test was positive for Mycobacterium tuberculosis. Conclusion: Duruvalumab as PD-L1 blockade may activate TB.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Inmunoterapia/métodos , Neoplasias Pulmonares/terapia , Mycobacterium tuberculosis/fisiología , Tuberculosis Pulmonar/diagnóstico , Anciano , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/inmunología , Quimioradioterapia , Femenino , Humanos , Estadificación de Neoplasias , Tuberculosis Pulmonar/etiología
10.
Free Radic Biol Med ; 134: 200-214, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30639568

RESUMEN

The tumor microenvironment has previously been reported to be hypercapnic (as high as ~84 mmHg), although its effect on tumor cell behaviors is unknown. In this study, high CO2 levels, ranging from 5% to 15%, protected lung cancer cells from anticancer agents, such as cisplatin, carboplatin and etoposide, by suppressing apoptosis. The cytoprotective effect of a high CO2 level was independent of acidosis and was due to mitochondrial metabolic reprogramming that reduced mitochondrial respiration, as assessed by oxygen consumption, oxidative phosphorylation, mitochondrial membrane and oxidative potentials, eventually leading to reduced reactive oxidant species production. In contrast, high CO2 levels did not affect cisplatin-mediated DNA damage responses or the expression of Bcl-2 family proteins. Although high CO2 levels inhibited glycolysis, this inhibition was not mechanistically involved in high CO2-mediated reductions in mitochondrial respiration, because a high CO2 concentration inhibited isolated mitochondria. A cytoprotective effect of high CO2 levels on mitochondria DNA-depleted cells was not noted, lending support to our conclusion that high CO2 levels act on mitochondria to reduce the cytotoxicity of anticancer agents. High CO2-mediated cytoprotection was also noted in a 3D culture system. In conclusion, the hypercapnic tumor microenvironment reprograms mitochondrial respiratory metabolism causing chemoresistance in lung cancer cells. Thus, tumor hypercapnia may represent a novel target to improve chemosensitivity.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis , Resistencia a Antineoplásicos , Hipercapnia/fisiopatología , Neoplasias Pulmonares/patología , Mitocondrias/metabolismo , Microambiente Tumoral , Metabolismo Energético , Glucólisis , Humanos , Técnicas In Vitro , Neoplasias Pulmonares/tratamiento farmacológico , Mitocondrias/patología , Oxidación-Reducción , Fosforilación Oxidativa , Células Tumorales Cultivadas
11.
Intern Med ; 57(15): 2217-2221, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29526968

RESUMEN

We herein report a 42-year-old man with advanced lung adenocarcinoma and nivolumab-associated dermatomyositis. Nivolumab, an anticancer drug that is classified as an immune checkpoint inhibitor, often induces immune-related adverse events (irAEs). However, there have so far been no reports regarding nivolumab-associated dermatomyositis. This patient was diagnosed with dermatomyositis due to the presence of proximal muscle weakness with abnormal electromyography and magnetic resonance imaging findings; skin lesions, such as heliotrope rash, shawl sign, and periungual erythema; and an elevated serum aldolase level after nivolumab administration. It is important to consider drug-associated dermatomyositis in the differential diagnosis of patients presenting with skin lesions and muscle weakness after nivolumab treatment.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/efectos adversos , Dermatomiositis/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma del Pulmón , Adulto , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Debilidad Muscular/fisiopatología , Nivolumab
12.
J Gen Fam Med ; 18(6): 411-413, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29264074

RESUMEN

A 29-year-old man presented with sputum and cough, which were pointed out by his neighbors. A high-resolution chest computed tomography scan showed well-defined multiple centrilobular nodules and a tree-in-bud pattern. Chest auscultation revealed coarse crackles. He did not report any nasal sinus symptoms. We subsequently performed a video-assisted lung biopsy; the specimen confirmed diffuse panbronchiolitis. Subsequently, sinusitis was confirmed by an otolaryngologist. His symptoms gradually improved following treatment with erythromycin. We report a case of early-stage diffuse panbronchiolitis in a young patient, with multiple intralobular nodules, no bronchiectasis, and a good clinical course.

13.
Respir Med ; 129: 158-163, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28732824

RESUMEN

BACKGROUND: The clinicopathological characteristics of lung cancer with concomitant usual interstitial pneumonia (UIP) are insufficiently understood. This study aimed to elucidate a characteristic pathological feature of lung cancer that develops in patients with UIP, with a focus on the location of its onset. METHODS: We reviewed surgically obtained specimens, including 547 tumors from 526 patients who underwent lobectomy for lung cancer. Surveyed patients were classified into three groups: patients with UIP (UIP group), patients with lung pathology other than UIP (non-UIP group), and patients without any associated lung pathology (normal group). The histology as well as the lobe and location of the onset of lung cancer were compared among these groups. The peripheral location was subdivided into subpleural, inner and tumor involved centrally secondary to extension. RESULTS: The UIP group comprised 82 patients (male, 71 [87%]; mean age, 71 years; smoking rate, 94%), the non-UIP group comprised 334 patients (male, 267 [80%]; mean age, 69 years; smoking rate, 81%), and the normal group comprised 110 patients (male, 33 [30%]; mean age, 63; smoking rate, 29%). No statistical differences were noted in sex, mean age, or smoking index between the UIP and non-UIP groups. Compared with the non-UIP group, the frequency of squamous cell carcinoma (63% vs. 32%), lower lobe origin (76% vs. 32%), and subpleural location (24% vs. 5%) were significantly higher in the UIP group. CONCLUSIONS: Lung cancers in patients with UIP show a predilection for the subpleural region, where UIP is also thought to originate.


Asunto(s)
Carcinoma de Células Escamosas/patología , Fibrosis Pulmonar Idiopática/complicaciones , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Pulmón/anatomía & histología , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/epidemiología , Femenino , Humanos , Fibrosis Pulmonar Idiopática/clasificación , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/patología , Pulmón/patología , Pulmón/ultraestructura , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Fumar/epidemiología
14.
PLoS One ; 12(6): e0178979, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28582458

RESUMEN

Up-flow column percolation tests are used at laboratory scale to assess the leaching behavior of hazardous substance from contaminated soils in a specific condition as a function of time. Monitoring the quality of these test results inter or within laboratory is crucial, especially if used for Environment-related legal policy or for routine testing purposes. We tested three different sandy loam type soils (Soils I, II and III) to determine the reproducibility (variability inter laboratory) of test results and to evaluate the difference in the test results within laboratory. Up-flow column percolation tests were performed following the procedure described in the ISO/TS 21268-3. This procedure consists of percolating solution (calcium chloride 1 mM) from bottom to top at a flow rate of 12 mL/h through softly compacted soil contained in a column of 5 cm diameter and 30 ± 5 cm height. Eluate samples were collected at liquid-to-solid ratio of 0.1, 0.2, 0.5, 1, 2, 5 and 10 L/kg and analyzed for quantification of the target elements (Cu, As, Se, Cl, Ca, F, Mg, DOC and B in this research). For Soil I, 17 institutions in Japan joined this validation test. The up-flow column experiments were conducted in duplicate, after 48 h of equilibration time and at a flow rate of 12 mL/h. Column percolation test results from Soils II and III were used to evaluate the difference in test results from the experiments conducted in duplicate in a single laboratory, after 16 h of equilibration time and at a flow rate of 36 mL/h. Overall results showed good reproducibility (expressed in terms of the coefficient of variation, CV, calculated by dividing the standard deviation by the mean), as the CV was lower than 30% in more than 90% of the test results associated with Soil I. Moreover, low variability (expressed in terms of difference between the two test results divided by the mean) was observed in the test results related to Soils II and III, with a variability lower than 30% in more than 88% of the cases for Soil II and in more than 96% of the cases for Soil III. We also discussed the possible factors that affect the reproducibility and variability in the test results from the up-flow column percolation tests. The low variability inter and within laboratory obtained in this research indicates that the ISO/TS 21268-3 can be successfully upgraded to a fully validated ISO standard.


Asunto(s)
Metales Pesados/aislamiento & purificación , Contaminantes del Suelo/aislamiento & purificación , Suelo/química , Cloruro de Calcio/química , Técnicas de Química Analítica/métodos , Monitoreo del Ambiente , Guías como Asunto , Reproducibilidad de los Resultados
15.
Chemotherapy ; 62(3): 151-158, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28110331

RESUMEN

BACKGROUND: Exon 19 deletion (Del19) and exon 21 L858R substitution (L858R), which account for 90% of epidermal growth factor receptor (EGFR) mutations as common mutations, are associated with favorable outcomes with EGFR-tyrosine kinase inhibitors (TKIs) compared with other uncommon EGFR mutations in non-small-cell lung cancer (NSCLC). However, whether there are differences in overall survival (OS) between patients with these common EGFR mutations remains controversial. METHODS: The subjects studied were 74 NSCLC patients with common EGFR mutations treated with gefitinib or erlotinib. Using univariate and multivariate analyses, we retrospectively compared the clinicopahological characteristics of patients harboring Del19 with those harboring L858R. RESULTS: Compared with patients harboring L858R, EGFR-TKIs provided a significant OS benefit in patients harboring Del19 (p = 0.024), as well as favorable therapeutic responses (p = 0.045) and progression-free survival (PFS) benefits (p = 0.031). In multivariate analyses, Del19 was independently associated with PFS (p = 0.029) and OS (p = 0.009), whereas no parameters other than pleural dissemination at the initial treatment were associated with EGFR mutation types. CONCLUSION: Del19 and L858R have distinct prognostic implications and may require individual therapeutic strategies.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Receptores ErbB/genética , Neoplasias Pulmonares/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Supervivencia sin Enfermedad , Clorhidrato de Erlotinib/uso terapéutico , Exones , Femenino , Gefitinib , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Oportunidad Relativa , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/uso terapéutico , Estudios Retrospectivos , Eliminación de Secuencia
17.
J Hazard Mater ; 320: 326-340, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27565857

RESUMEN

Column percolation tests may be suitable for prediction of chemical leaching from soil and soil materials. However, compared with batch leaching tests, they are time-consuming. It is therefore important to investigate ways to shorten the tests without affecting the quality of results. In this study, we evaluate the feasibility of decreasing testing time by increasing flow rate and decreasing equilibration time compared to the conditions specified in ISO/TS 21268-3, with equilibration periods of 48h and flow rate of 12mL/h. We tested three equilibration periods (0, 12-16, and 48h) and two flow rates (12 and 36mL/h) on four different soils and compared the inorganic constituent releases. For soils A and D, we observed similar values for all conditions except for the 0h-36mL/h case. For soil B, we observed no appreciable differences between the tested conditions, while for soil C there were no consistent trends probably due to the difference in ongoing oxidation reactions between soil samples. These results suggest that column percolation tests can be shortened from 20 to 30days to 7-9days by decreasing the equilibration time to 12-16h and increasing the flow rate to 36mL/h for inorganic substances.

18.
Eur J Radiol ; 84(5): 986-92, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25676600

RESUMEN

PURPOSE: Airspace enlargement with fibrosis (AEF) has been identified pathologically as a smoking related change. We sought to identify the HRCT findings of AEF and search for distinguishing features from honeycombing. MATERIALS AND METHODS: 50 patients (47 males; mean age 69) were evaluated. All had undergone lobectomy for lung cancer and had confirmed AEF and/or usual interstitial pneumonia (UIP) by pathological evaluation. HRCT findings were first evaluated preresection for resected lobes, and then correlated with the subsequent pathological findings in the resection specimens. Three groups were devised: one with AEF alone to determine the HRCT findings of AEF, a second with AEF and UIP and third with UIP alone. HRCT features of AEF and honeycombing were compared. RESULTS: There were 11 patients (10 male; mean age 69) with AEF alone, 24 patients (22 male; mean age 69) with AEF and UIP, and 15 patients (15 male; mean age 68) with UIP alone. The HRCT on the AEF alone showed subpleural (but not abutting the pleura) multiple thin-walled cysts (MTWCs) in 7 and reticular opacities in 3. The HRCT in AEF and UIP showed MTWCs in 10, reticular opacities in 17; and honeycombing in 5. Among these 35 patients with the pathological finding of AEF (with or without UIP), 17 showed MTWCs. The maximum cyst wall thickness of MTWCs (mean 0.81 mm) was significantly thinner than that of honeycombing (mean 1.56 mm). MTWCs did not locate in lung base and was distant from the pleura. HRCT findings correlated with gross findings on both cysts and honeycombing. No MTWCs were seen in the 15 patients with UIP, 8 of 15 had honeycombing on CT. CONCLUSIONS: We confirmed that HRCT features of AEF were MTWCs and/or reticular opacities. MTWCs might be distinguished from those of honeycomb change. While we prefer the term MTWCs, these sorts of changes have probably been confused with/interpreted as honeycombing and/or empysema in the past.


Asunto(s)
Quistes/patología , Neoplasias Pulmonares/patología , Pulmón/patología , Fibrosis Pulmonar/patología , Fumar/efectos adversos , Tomografía Computarizada por Rayos X , Anciano , Quistes/diagnóstico por imagen , Femenino , Tejido de Granulación/patología , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Neumonectomía , Alveolos Pulmonares/patología , Fibrosis Pulmonar/diagnóstico por imagen , Reproducibilidad de los Resultados
19.
Intern Med ; 51(24): 3415-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23257531

RESUMEN

A 64-year-old woman presented with exertional dyspnea. The case was diagnosed as mixed connective tissue disease (MCTD) due to presence of swollen fingers, Raynaud's phenomenon, muscle weakness, positive anti-U1RNP antibody, pericarditis and interstitial pneumonia. Although the histology from a transbronchial lung biopsy (TBLB) indicated organizing pneumonia, corticosteroid therapy was postponed for two months at the patient's request. She died 8 weeks later from acute progressive interstitial pneumonia in spite of the administration of intravenous cyclophosphamide combined with prednisolone. The autopsy revealed exudative and organizing diffuse alveolar damage (DAD). Previous reports have shown that DAD is an extremely rare pulmonary complication in MCTD. This report presents a case of MCTD with acute respiratory failure. This case thus suggests that this therapy should be administered as soon as possible.


Asunto(s)
Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Insuficiencia Respiratoria/etiología , Autopsia , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Factores de Tiempo
20.
Intern Med ; 51(5): 491-5, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22382565

RESUMEN

A 49-year-old woman with a 20-year history of Sjögren's syndrome (SS) was incidentally found to have an abnormal chest X-ray along with dyspnea and desaturation. Chest CT findings showed multiple cystic shadows, ground glass opacity, and small nodule-like lymphocytic interstitial pneumonia (LIP), which have been previously reported. She was diagnosed by surgical lung biopsy to have mucosa-associated lymphoid tissue (MALT) lymphoma. It was difficult to detect the presence of lymphoma by the use of only CT findings. Pulmonary involvement of SS occurs in various forms so that SS patients with pulmonary involvement should undergo open biopsy to reach a definitive diagnosis.


Asunto(s)
Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/etiología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/etiología , Linfoma de Células B de la Zona Marginal/diagnóstico por imagen , Linfoma de Células B de la Zona Marginal/etiología , Síndrome de Sjögren/complicaciones , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Ciclofosfamida/administración & dosificación , Diagnóstico Diferencial , Doxorrubicina/administración & dosificación , Femenino , Humanos , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Persona de Mediana Edad , Prednisona/administración & dosificación , Radiografía Torácica , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificación
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