RESUMEN
BACKGROUND: The prevalence of salvage surgeries after drug therapy for non-small cell lung cancer (NSCLC) has risen, mainly due to recent progress in molecular-targeted drugs and immune checkpoint inhibitors for NSCLC. While the safety and effectiveness of salvage surgery after drug therapy for NSCLC have been studied, its indications remain unclear. We aimed to identify the prognostic factors affecting survival in patients with advanced-stage (stages III-IV) NSCLC treated with salvage surgery after drug therapy. METHODS: A retrospective investigation was conducted on patients who received salvage surgery after drug therapy at four hospitals between 2007 and 2020. Salvage surgery was defined as surgery after drug therapy for local progression, tumor conversion to resectable status, and discontinuation of prior drug therapy owing to serious complications. RESULTS: Thirty-two patients received cytotoxic agents alone (n = 12 [38%]), tyrosine kinase inhibitors (TKIs; n = 16 [50%]), or immune checkpoint inhibitors (n = 4 [13%]) as prior drug therapy. In 11 (34%) and 21 (66%) patients, the clinical stage before treatment was III or IV, respectively. The median initial and preoperative serum carcinoembryonic antigen (CEA) levels were 10.2 (range, 0.5-1024) ng/mL and 4.2 (range, 0.6-92.5) ng/mL, respectively. Among the patients, 28 (88%) underwent lobectomy, 2 (6%) underwent segmentectomy, and 2 (6%) underwent wedge resection. Complete resection of the primary lesion was accomplished in 28 (88%) patients. Postoperative complications were documented in six (19%) patients. Mortality rates were 0% at 30 days and 3% at 90 days post-operation. The 5-year overall survival rate stood at 66%, while the 5-year progression-free survival rate was 21%. Multivariate analyses showed that prior TKI therapy and preoperative serum CEA level < 5 ng/mL were prognostic factors influencing overall survival (hazard ratio [95% confidence interval]: 0.06 [0.006-0.68] and 0.03 [0.002-0.41], respectively). The 5-year overall survival in the 11 patients with both favorable prognosticators was 100%. CONCLUSIONS: In this study, prior TKI therapy and preoperative serum CEA level < 5 ng/mL were favorable prognostic factors for overall survival in patients with NSCLC treated with salvage surgery. Patients with these prognostic factors are considered good candidates for salvage surgery after drug therapy.
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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/cirugía , Estudios Retrospectivos , Antígeno Carcinoembrionario , Inhibidores de Puntos de Control Inmunológico , Pronóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugíaRESUMEN
OBJECTIVES: Advances in drug therapy and radiotherapy for non-small cell lung cancer resulted in an increased number of salvage surgeries for initially unresectable tumors. This study aimed to evaluate the safety and efficacy of salvage surgery for non-small cell lung cancer. METHODS: We defined salvage surgery as (1) surgery for local recurrence/residual tumor after definitive chemoradiotherapy/radiotherapy (salvage surgery in a narrow sense) or (2) conversion surgery after non-surgical treatment. We retrospectively analyzed patients who underwent salvage surgery at four Keio University-affiliated hospitals. RESULTS: Forty-six patients were included. The initial clinical stage was I in 4 patients (9%), III in 19 (41%), and IV in 23 (48%). Initial treatment before salvage surgery was chemoradiotherapy in 10 patients (24%), radiotherapy in 4 (9%), and drug therapy in 32 (67%). Pneumonectomy, lobectomy, segmentectomy, and wedge resection were performed in 2 (4%), 37 (80%), 3 (7%), and 4 (9%) patients, respectively. Complete resection was achieved in 41 patients (89%). Postoperative complications occurred in 11 patients (24%). Initial chemoradiotherapy/radiotherapy was an independent predictor of postoperative complications (odds ratio 10, p = 0.03). The 30- and 90-day mortality rates were 0 and 2%, respectively. The 5-year overall and progression-free survival rates were 66 and 30%, respectively. CONCLUSION: The safety and efficacy of salvage surgery for non-small cell lung cancer were acceptable. Salvage surgery was a viable treatment option for selected patients with recurrent/residual tumors after non-surgical treatments.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioradioterapia/métodos , Progresión de la Enfermedad , Hospitales , Humanos , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Terapia Recuperativa/efectos adversos , Terapia Recuperativa/métodos , Resultado del TratamientoRESUMEN
Pulmonary epithelioid hemangioendothelioma (PEH) is a rare lung disease. This report describes the case of a 54-year-old female who underwent radical resection for bilateral multiple PEH nodules. Bilateral multiple nodular shadows were seen on the patient's chest X-rays during an annual health check. PEH was diagnosed based on a video-assisted thoracoscopic biopsy specimen. Thirty-two pulmonary nodules were resected through the bilateral transverse thoracosternotomy. The patient's postoperative recovery was uneventful, and she remains free of PEH recurrence 11 years after the surgery.
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Hemangioendotelioma Epitelioide/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Femenino , Hemangioendotelioma Epitelioide/diagnóstico , Humanos , Neoplasias Pulmonares/diagnóstico , Persona de Mediana EdadRESUMEN
OBJECTIVES: This investigation was conducted to assess the use of the intratumoral mRNA expression levels of nucleic acid-metabolizing enzymes as biomarkers of adjuvant chemotherapy for non-small cell lung cancer (NSCLC) using uracil-tegafur in a multi-institutional prospective study. MATERIALS AND METHODS: 236 patients with a completely resected NSCLC (adenocarcinoma and squamous cell carcinoma) of pathological stage IA (maximum tumor diameter of 2 cm or greater), IB, and II tumors were given a dose of 250 mg of uracil-tegafur per square meter of body surface area per day orally for two years after surgery. Intratumoral mRNA levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP) genes relative to an internal standard, ß-actin, were determined using laser-capture microdissection and fluorescence-based real time PCR detection systems. RESULTS AND CONCLUSION: Among 5-FU target enzymes, TS was the only one that showed a significant difference in the level of gene expression between the high and low gene expression groups, for both disease-free survival (DFS) and overall survival (OS), when patients were divided according to median values; 5-year DFS rates in high/low TS gene expression were 60.4% and 72.6%, respectively (p=0.050), 5-year OS rates were 78.1% and 88.6%, respectively (p=0.011). Cox's proportional hazard model indicated that the pathological stage and TS gene expression level were independent values for predicting DFS. The TS gene expression level was shown to be an independent predictive factor for DFS in stage I and II NSCLC patients who were treated with uracil-tegafur following surgery.
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Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Tegafur/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Japón , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Factores de Riesgo , Tegafur/farmacocinética , Resultado del TratamientoRESUMEN
The standard technique to evaluate the proteins present in epithelial lining fluid (ELF) is bronchoalveolar lavage (BAL). Bronchoscopic microsampling (BMS) method has been developed for humans as a less invasive alternative. We establish the usefulness of a rat bronchial microsampling (rBMS) to evaluate various proteins in ELF in lipopolysaccharide (LPS)-induced lung injury models in rats. In the first experiment of this study, we validate that whether the rBMS can obtain information from ELF in place of BAL. Tumor necrosis factor (TNF)-α concentrations were increased in the rBMS samples similar to BAL 1 and 3h after LPS instillation. In the second part of this study, a proteomic analysis of the rBMS, using the Protein Chip(R) system, revealed the presence of proteins whose molecular weights corresponded to TNF-related proteins in the LPS-treated rats. In rats treated with a TNF-α converting enzyme inhibitor, the concentrations of these proteins in rBMS decreased or disappeared. In the third experiment, rBMS was performed without tracheostomy at 6 and 24h after instillation of LPS, and a rat multiple cytokines assay system detected heterogeneous variations in the concentrations of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, TNF-αand interferon (IFN)-γ in ELF. The cytokine profile was significantly modified by pre-treatment with dexamethasone. This new rBMS technique could be used to measure TNF-α in LPS-induced acute lung injury (ALI) as well as for proteomic analysis, without sacrificing the rats. Furthermore, this procedure enables the serial collection of ELF, which would allow the examination of time-dependent cytokine variations in rat ALI model.
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Lesión Pulmonar Aguda/diagnóstico , Lavado Broncoalveolar/métodos , Broncoscopía/métodos , Citocinas/análisis , Factor de Necrosis Tumoral alfa/análisis , Proteínas ADAM/antagonistas & inhibidores , Proteína ADAM17 , Albúminas/análisis , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/metabolismo , Dexametasona/farmacología , Modelos Animales de Enfermedad , Lipopolisacáridos , Masculino , Proteoma/análisis , Ratas , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Traqueostomía/métodosRESUMEN
BACKGROUND: A signaling pathway of the small GTPase Rho and Rho-associated coiled-coil-forming protein kinase (ROCK), regulates the contraction of endothelial cells. We studied the effects of Y-27632, a specific ROCK inhibitor, to clarify the role of Rho/ROCK in the pathogenesis of ischemia-reperfusion lung injury in a rat model of single-lung transplantation (LTX). METHODS: We flushed 5 donor rat lungs with Euro-Collins solution, and 5 donor lungs with Euro-Collins + Y-27632, 0.03 mg/ml, and preserved the lungs for 6 h at 4°C before reperfusion for 4 h. The 5 rat recipients of Y-27632-treated lungs also received a 10-mg/kg bolus of Y-27632 i.p. 30 min before reperfusion. RESULTS: Pretreatment of the donor lungs and recipient rats with Y-27632 prominently suppressed the post-LTX edema, while the permeability index was only slightly decreased. The (1) numbers of neutrophils and macrophages, and (2) tumor necrosis factor (TNF)-α concentration, were significantly lower in the bronchoalveolar lavage fluid of treated than untreated lungs. CONCLUSIONS: Y-27632 (1) inhibited the migration of inflammatory cells into the alveolar space, (2) decreased the production of TNF-α, and (3) attenuated the edema after LTX. Endothelial Rho and ROCK may play an important role in the pathogenesis of post-LTX injury.
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Amidas/farmacología , Lesión Pulmonar/prevención & control , Trasplante de Pulmón/efectos adversos , Pulmón/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Daño por Reperfusión/prevención & control , Quinasas Asociadas a rho/antagonistas & inhibidores , Animales , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Quimiotaxis/efectos de los fármacos , Citoprotección , Modelos Animales de Enfermedad , Pulmón/enzimología , Pulmón/inmunología , Lesión Pulmonar/enzimología , Lesión Pulmonar/etiología , Lesión Pulmonar/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Infiltración Neutrófila/efectos de los fármacos , Permeabilidad , Edema Pulmonar/enzimología , Edema Pulmonar/prevención & control , Ratas Endogámicas Lew , Daño por Reperfusión/enzimología , Daño por Reperfusión/etiología , Daño por Reperfusión/inmunología , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo , Quinasas Asociadas a rho/metabolismoAsunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Neoplasias Pulmonares/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/secundario , Anciano , Resultado Fatal , Humanos , Inmunohistoquímica , Queratina-20/análisis , Queratina-7/análisis , Masculino , Proteínas Nucleares/análisis , Factor Nuclear Tiroideo 1 , Factores de Transcripción/análisisRESUMEN
OBJECTIVES: The purpose of our study was to describe our preliminary experience of evaluating mediastinal lymph node metastases with diffusion-weighted magnetic resonance (MR) imaging in patients with non-small cell lung cancer. MATERIALS AND METHODS: Forty-two consecutive patients with non-small cell lung cancer underwent preoperative diffusion-weighted MR imaging using a non-breath-hold short inversion time inversion recovery-echo planar imaging sequence with a high b value of 1000 s/mm2. An experienced thoracic radiologist prospectively evaluated each study for mediastinal lymph node metastases on a per-patient basis. On diffusion-weighted MR imaging, mediastinal lymph node metastasis was defined as a focus of low signal intensity at the site of a visible lymph node on corresponding T2-weighted image. The MR results were correlated with histopathologic findings. RESULTS: Diffusion-weighted MR imaging demonstrated mediastinal lymph node metastasis in 4 (80%) of 5 patients with pathologically proven metastasis and accurately identified 36 (97%) of 37 patients without mediastinal lymph node metastasis. Thus, 40 (95%) of 42 patients were accurately diagnosed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of diffusion-weighted MR imaging for mediastinal lymph node metastasis were 80%, 97%, 80%, 97%, and 95%, respectively. CONCLUSIONS: Our preliminary results show that diffusion-weighted MR imaging has a high negative predictive value for excluding mediastinal lymph node metastases from non-small cell lung cancer and has the potential to be a reliable alternative non-invasive imaging method for the preoperative staging of mediastinal lymph node in patients with non-small cell lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Imagen de Difusión por Resonancia Magnética , Neoplasias Pulmonares/diagnóstico , Ganglios Linfáticos/patología , Mediastino/patología , Adulto , Anciano , Anciano de 80 o más Años , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las PruebasAsunto(s)
Adenoma Pleomórfico/sangre , Adenoma Pleomórfico/diagnóstico por imagen , Enfermedades de la Médula Ósea/sangre , Enfermedades de la Médula Ósea/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Factor Estimulante de Colonias de Granulocitos/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Adenoma Pleomórfico/complicaciones , Anciano , Biomarcadores de Tumor/sangre , Enfermedades de la Médula Ósea/etiología , Diagnóstico Diferencial , Humanos , Hiperplasia/sangre , Hiperplasia/diagnóstico por imagen , Hiperplasia/etiología , Vértebras Lumbares/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Masculino , Radiofármacos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/secundarioRESUMEN
Extramedullary hematopoiesis predominantly occurs in the liver, spleen, and lymph nodes with hemolytic anemia. Occurrence with osteopetrosis tarda in the paravertebral region is very rare. We discuss the examination of the third known case of paravertebral extramedullary hematopoiesis arising with osteopetrosis tarda.
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Hematopoyesis Extramedular , Osteopetrosis/complicaciones , Osteopetrosis/diagnóstico por imagen , Anciano , Humanos , Masculino , RadiografíaRESUMEN
We hypothesized that the extent of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is modified with its initial passage through the liver. We tested this hypothesis by administering LPS, 5 mg/kg, or saline to 120 male Wistar rats via the portal vein (PV) or the inferior vena cava (IVC) over 1 h. Four experimental groups of rats were administered saline into the PV, saline into the IVC, LPS into the PV (LPS-PV group), and LPS into the IVC (LPS-IVC group), respectively. At 15 and 30 min after onset of 51Chromium-LPS infusion, the gamma counts in the liver were higher in the LPS-PV group than that in the LPS-IVC group. The ratio of 125Iodine-albumin counts in lung tissue to that in plasma per unit of weight (as an assessment of pulmonary microvascular permeability) at 240 min after onset of LPS stimulation, the accumulation of polymorphonuclear cell (assessed by myeloperoxidase activity) and the concentration of tumor necrosis factor alpha in the lung at 60 and 240 min after onset of LPS infusion, were higher in the LPS-IVC group than in the LPS-PV group. Significant differences in several factors indicative of inflammation and in the extent of LPS-induced ALI were observed after the onset of LPS infusion, depending on whether it was delivered via the PV or the IVC. These observations suggest that the entrapping of LPS during its initial passage through the hepatic circulation may attenuate LPS-induced ALI within 4 h of initiation of LPS stimulation.
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Endotoxinas/administración & dosificación , Hígado/patología , Síndrome de Dificultad Respiratoria/patología , Animales , Permeabilidad Capilar/efectos de los fármacos , Modelos Animales de Enfermedad , Endotoxemia/sangre , Endotoxemia/inducido químicamente , Endotoxemia/complicaciones , Endotoxinas/farmacocinética , Endotoxinas/farmacología , Agua Pulmonar Extravascular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Infusiones Intravenosas , Recuento de Leucocitos , Hígado/efectos de los fármacos , Hígado/metabolismo , Pulmón/efectos de los fármacos , Pulmón/enzimología , Pulmón/metabolismo , Masculino , Neutrófilos/efectos de los fármacos , Neutrófilos/enzimología , Neutrófilos/patología , Peroxidasa/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/metabolismo , Distribución Tisular , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Reexpansion of a collapsed lung increases the microvascular permeability and causes reexpansion pulmonary edema. Neutrophils and their products have been implicated in the development of this phenomenon. The small GTP-binding proteins Rho and its target Rho-kinase (ROCK) regulate endothelial permeability, although their roles in reexpansion pulmonary edema remain unclear. We studied the contribution of ROCK to pulmonary endothelial and epithelial permeability in a rabbit model of this disorder. Endothelial and epithelial permeability was assessed by measuring the tissue-to-plasma (T/P) and bronchoalveolar lavage (BAL) fluid-to-plasma (B/P) ratios with (125)I-labeled albumin. After intratracheal instillation of (125)I-albumin, epithelial permeability was also assessed from the plasma leak (PL) index, the ratio of (125)I-albumin in plasma/total amount of instilled (125)I-albumin. T/P, B/P, and PL index were significantly increased in the reexpanded lung. These increases were attenuated by pretreatment with Y-27632, a specific ROCK inhibitor. However, neutrophil influx, neutrophil elastase activity, and malondialdehyde concentrations in BAL fluid collected from the reexpanded lung were not changed by Y-27632. In endothelial monolayers, Y-27632 significantly attenuated the H(2)O(2)-induced increase in permeability and mitigated the morphological changes in the actin microfilament cytoskeleton of endothelial cells. These in vivo and in vitro observations suggest that the Rho/ROCK pathway contributes to the increase in alveolar barrier permeability associated with reexpansion pulmonary edema.
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Proteínas Serina-Treonina Quinasas/metabolismo , Edema Pulmonar/enzimología , Transducción de Señal , Citoesqueleto de Actina/metabolismo , Amidas/administración & dosificación , Animales , Líquido del Lavado Bronquioalveolar/química , Permeabilidad Capilar/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Inhibidores Enzimáticos/administración & dosificación , Péptidos y Proteínas de Señalización Intracelular , Elastasa de Leucocito/metabolismo , Masculino , Malondialdehído/análisis , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/metabolismo , Neutrófilos/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Edema Pulmonar/patología , Piridinas/administración & dosificación , Conejos , Transducción de Señal/efectos de los fármacos , Proteínas de Unión al GTP rho/metabolismo , Quinasas Asociadas a rhoRESUMEN
Tumor necrosis factor-alpha (TNF-alpha) has two forms with apparently different biological activities: a membrane-associated form and a soluble form. TNF-alpha-converting enzyme (TACE) mediates a cleavage of membrane-associated TNF-alpha to induce its bioactive soluble form. We hypothesized that inhibition of TACE might prevent TNF-alpha-induced tissue injury while preserving the benefits of TNF-alpha. In this study, we evaluated the role of TACE in acute inflammation using an inhibitor of the enzyme in a rat model of lung transplantation. Inbred Lewis rats underwent left lung isotransplantation, and the donor lungs were kept in Euro-Collins solution with or without the inhibitor. After 6 hours of ischemia, the left lung was transplanted into the recipient rat and reperfused for 4 hours. Inhibition of TACE significantly attenuated endothelial and alveolar septal damage, as assessed by radiolabeled albumin leakage after transplantation. The inhibition also attenuated neutrophil accumulation in the alveolar space and other histopathologic findings, including intercellular adhesion molecule-1 expression. In addition, significantly lower levels of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-1, high mobility group box-1, and soluble epithelial cadherin and decreased neutrophil elastase activity were observed in bronchoalveolar lavage fluid from the rats treated with the inhibitor. We conclude that TACE mediates a critical step in the development of post-transplantation lung injury.
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Inhibidores Enzimáticos/uso terapéutico , Enfermedades Pulmonares/inmunología , Trasplante de Pulmón/efectos adversos , Metaloendopeptidasas/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas ADAM , Proteína ADAM17 , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Cadherinas/inmunología , Quimiocinas/inmunología , Proteína HMGB1/inmunología , Enfermedades Pulmonares/prevención & control , Modelos Animales , Ratas , Ratas Endogámicas Lew , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Factor de Necrosis Tumoral alfa/efectos adversosRESUMEN
We examined the effects of prolonged hyperoxia (75% O(2)) on lung structure and collagen metabolism in the subacute phase of lung injury induced by continuous infusion of endotoxin (LPS) in a rat model. Experimental groups included control, endotoxin alone, endotoxin plus hyperoxia, and hyperoxia alone. Endotoxin-treated rats received a bolus of LPS (10 mg/kg i.v.) followed by 500 microg.kg(-1).day(-1) in continuous infusion for 10 days. The bronchoalveolar lavage (BAL) fluid/plasma albumin concentration ratio, an index of capillary permeability, and neutrophil and macrophage counts in BAL fluid were highest in the endotoxin plus hyperoxia group. On pathological examination, prolonged hyperoxia exacerbated destruction of the alveolar wall and caused most prominent emphysematous changes in the endotoxin plus hyperoxia group. Lung tissue hydroxyproline concentration was significantly decreased in the hyperoxia group and increased in the endotoxin group. The latent forms of MMP-2 and MMP-9 increased in BAL fluid of the endotoxin- and/or hyperoxia-treated groups, whereas the activities of collagenase and gelatinase, and the active form of MMP-2 were all increased in the hyperoxia-treated groups. Added to endotoxin, prolonged hyperoxia degraded collagen, the major structural component of basement membranes, and caused emphysematous changes associated with activation of collagenase and MMP-2. Our observations suggest that, in the subacute phase of endotoxin-induced lung injury, prolonged hyperoxia causes pulmonary emphysematous changes with persistent injury to the alveolar capillary barrier. Collagenase and MMP-2 activated by hyperoxia, together with MMP-9, may play prominent roles in disruption of the alveolar basement membranes and degradation of collagen lining the alveolar walls.
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Enfisema/etiología , Enfisema/patología , Hiperoxia/complicaciones , Enfermedades Pulmonares/inducido químicamente , Animales , Líquido del Lavado Bronquioalveolar , Recuento de Células , Colágeno/metabolismo , Colagenasas/metabolismo , Enfisema/metabolismo , Endotoxinas , Gelatinasas/metabolismo , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Edema Pulmonar/inducido químicamente , Edema Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley , Albúmina Sérica/metabolismoRESUMEN
OBJECTIVE: Acute lung injury induced by lung overstretch is associated with neutrophil influx, but the pathogenic role of neutrophils in overstretch-induced lung injury remains unclear. DESIGN: To assess the contribution of neutrophils, we compared the effects of noninjurious large tidal volume (Vt) ventilation on lungs in normal and neutrophil-depleted animals. SETTING: Research animal laboratory. SUBJECTS: Twenty-six male Japanese white rabbits. INTERVENTIONS: Animals were mechanically ventilated for 4 hrs with one of the three following protocols: large Vt (20 mL/kg), small Vt (8 mL/kg), and large Vt (20 mL/kg) with neutrophil depletion achieved by a single dose of vinblastine injection (0.75 mg/kg) intravenously 4 days before the experiment. MEASUREMENTS AND MAIN RESULTS: Large Vt ventilation produced alveolar neutrophil influx compared with low Vt (p =.002) without evidence of edema or increased epithelial permeability. The neutrophil influx was accompanied by increases in interleukin-8 in bronchoalveolar lavage fluid (p =.04). Immunohistochemistry of large Vt lungs showed increased interleukin-8 staining in bronchial epithelial cells, alveolar epithelium, alveolar macrophages, and smooth muscles of pulmonary vessels. Neutrophil depletion attenuated the interleukin-8 increase in the lung. Large Vt did not increase plasma interleukin-8 or tumor necrosis factor-alpha in plasma and bronchoalveolar lavage fluid. No expression of p-selectin or intercellular adhesion molecule-1 was observed. CONCLUSIONS: Cyclic overstretching of normal rabbit lungs with noninjurious large Vt produced neutrophil influx and interleukin-8 increase in bronchoalveolar lavage fluid. Production of pulmonary interleukin-8 by lung overstretch might require the interaction between resident lung cells and migrated neutrophils. This study suggests that large Vt ventilation potentiates the predisposed, subclinical lung injury, such as nosocomial pneumonia or aspiration of gastric contents.
Asunto(s)
Interleucina-8/biosíntesis , Neutrófilos/fisiología , Respiración Artificial , Animales , Receptores de Estiramiento Pulmonares/fisiología , Conejos , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/inmunologíaRESUMEN
Although neutrophil depletion can reduce the level of acute lung injury (ALI) induced by Escherichia coli endotoxin, that induced by live E coli cannot be attenuated even in neutropenia. This suggests that live E coli cause ALI by way of an mechanism independent of circulating neutrophil. Tumor necrosis factor-alpha (TNF-alpha), which is released from monocytes and macrophages, is a proinflammatory cytokine that is recognized as a central mediator of several forms of inflammation. In this controlled experimental study, we examined the effects of an adenosine-receptor agonist, 2-chloroadenosine (2CA), that has suppressive effects on various cell types and TNF-alpha, on endotoxin plus latex particles, and on ALI induced by live E coli in the neutropenic state. We studied 42 guinea pigs rendered neutropenic by means of intraperitoneal cyclophosphamide administration. Experimental groups consisted of (1) a saline-solution control group; (2) an endotoxin (0.2 mg/kg)-treated group; (3) a group treated with endotoxin plus 2CA (10 micro g/kg); (4) a group treated with latex (2 x 10(9)/kg); (5) a group exposed to endotoxin and latex; (6) a group exposed to endotoxin, latex, and 2CA; (7) a group exposed to E coli (2 x 10(9)/kg); and (8) a group exposed to E coli and 2CA. The injection of endotoxin alone in neutropenic animals did not increase the indexes of ALI (lung tissue/plasma ratio [T/P] and lung wet weight/dry weight ratio [W/D], calculated with the use of iodine 125-labeled albumin). In contrast, these indexes were increased in the endotoxin-and-latex groups compared with those of the control group. ALI in the endotoxin-and-latex group was attenuated by intravenous 2CA. The intravenous injection of live E coli also caused increases in T/P, W/D, and plasma TNF-alpha, but thse were limited by 2CA. In summary, ALI induced by latex particles added to endotoxin and live E coli in the neutropenic state was attenuated by 2CA, suggesting a partial contribution of various cell types or humoral mediators as a neutrophil-independent pathway in its pathogenesis.
Asunto(s)
2-Cloroadenosina/farmacología , Infecciones por Escherichia coli/inmunología , Escherichia coli , Enfermedades Pulmonares/tratamiento farmacológico , Neutropenia/inmunología , Enfermedad Aguda , Animales , Endotoxinas/farmacología , Cobayas , Inyecciones Intravenosas , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/microbiología , Microesferas , Neutropenia/microbiología , Organismos Libres de Patógenos Específicos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Tracheobronchial stenosis causes severe symptoms such as stridor or dyspnea. Patients who experience these symptoms with inoperable lesions require treatment for palliation of symptoms. In our institution, airway stent placements were performed in 88 patients. The clinical results of stenting for stenosis of the central airways are satisfactory for improvement of the quality of life. Insertion of airway stents and esophageal tubes could improve dysphagia and dyspnea in patients with esophagotracheal fistulas. Recently, several types of prostheses have become available for stenting of airways and each stent has specific features. Therefore it is important for effective and safe stenting to select the type of stent suitable for the condition of each patient.
Asunto(s)
Enfermedades Bronquiales/terapia , Stents , Estenosis Traqueal/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A 70-year-old man in whom nodular and reticular shadows had been noted on chest radiography since 1992 was admitted to our hospital with complaints of persistent cough and dyspnea on exertion in August, 2000. The definitive diagnosis of lung abnormalities was not confirmed by TBLB. He was re-admitted to our hospital to undergo a lung biopsy by video-assisted thoracoscopic surgery. Although desquamative interstitial pneumonia was diagnosed, respiratory failure developed rapidly after surgery. He responded well to high-dose steroid administration followed by maintenance therapy with a moderate dose of steroid, resulting in a considerable importance of the clinical condition associated with a significant decrease in the ground-glass opacities and infiltrative shadows. Although we could find no literature reporting acute exacerbation of DIP, our case demonstrates that DIP may also be acutely exacerbated when a severe insult is superimposed.
Asunto(s)
Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/patología , Pulmón/patología , Cirugía Torácica Asistida por Video/efectos adversos , Anciano , Antiinflamatorios/administración & dosificación , Biopsia , Humanos , Masculino , Metilprednisolona/administración & dosificación , Prednisolona/administración & dosificación , Quimioterapia por PulsoRESUMEN
BACKGROUND: Fibrin sealant is used in many kinds of surgical procedures. Although pasteurization is insufficient to remove human parvovirus (HPV) B19 from this plasma-derived product, the frequency of HPV B19 infection transmitted by its use has never been known. METHODS: Blood samples of 85 patients more than 20 years of age who had undergone pulmonary resection with fibrin sealant were obtained before and 12, 24, and 48 weeks after surgery. Anti-HPV B19 antibody IgG (HPV B19 IgG) and HPV B19 DNA were detected with these samples. RESULTS: In 56 (65.9%) of 85 patients, blood samples obtained before operation were positive for HPV B19 IgG. In these 56 patients, blood samples obtained 12 to 48 weeks after surgery were all negative for HPV B19 DNA by polymerase chain reaction (PCR). In 6 (20.7%) of 29 patients whose blood samples were negative for HPV B19 IgG before surgery, blood samples obtained 12 to 48 weeks after surgery were positive for HPV B19 DNA by PCR and also positive for HPV B19 IgG. In 5 of these 6 patients reticulocyte counts decreased to less than 10 x 10(9)/l 12 to 20 days after surgery. CONCLUSIONS: Epidemiologic evidence suggests that more than 20% uninfected persons were subsequently infected with HPV B19 by use of fibrin sealant during surgery.