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1.
Gan To Kagaku Ryoho ; 47(3): 537-539, 2020 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-32381941

RESUMEN

The first case is a 62-year-old female who complained of painful left axillary lymph node swelling. Six months later, a CT scan revealed multiple lung nodules. Biopsies of the axillary lymph node and lung showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph node and lung. ER(+), PgR(±), HER2(1+). Letrozole was administered, and effective control was achieved for 20 months. The second case is a 62-year-old female who presented with back pain. A CT scan revealed left axillary lymph node swelling and multiple osteolytic changes in the thoracolumbar spine and rib. Biopsies of the axillary lymph node and thoracic spine showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph nodule and bone. ER(+), PgR(+), HER2(1+). Fulvestrant and denosumab were administered. However, after 6 months, she discontinued the treatment. Our results suggested that effective control could be achieved through systemic therapy and local therapy was not necessary for Stage Ⅳ occult breast cancer.


Asunto(s)
Neoplasias de la Mama , Axila , Femenino , Humanos , Ganglios Linfáticos , Metástasis Linfática , Persona de Mediana Edad
2.
Surg Today ; 49(7): 601-609, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30734881

RESUMEN

PURPOSES: The purpose of this study was to review the clinical course of patients with recurrence after induction chemoradiotherapy followed by surgery (trimodality therapy) for locally advanced non-small cell lung cancer (LA-NSCLC) and to identify the factors associated with favorable clinical outcome after recurrence. METHODS: We analyzed the records of 140 patients with LA-NSCLC who were treated with trimodality therapy between 1999 and 2014. RESULTS: Recurrence developed after trimodality therapy in 48 patients. A yp-N positive status was associated with a high risk of recurrence (HR, 2.05; P = 0.048). Of the 45 of these patients able to be assessed retrospectively, 18 had oligometastatic recurrence and 20 underwent local treatment with curative intent. Local treatment was most frequently given to patients with oligometastatic recurrence (P < 0.001). The median post-recurrence survival (PRS) was 41.4 months, and the 2-year PRS rate was 62%. Patients who received local treatment showed better PRS (P = 0.009). The presence of liver metastasis (P = 0.008), bone metastasis (P = 0.041), or dissemination (P < 0.0001) were associated with worse PRS. CONCLUSION: The survival of patients who received aggressive local treatment for postoperative recurrence after trimodality therapy for LA-NSCLC was better than that of patients who did not.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Quimioterapia de Inducción , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/terapia , Neoplasias Óseas/secundario , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Terapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Neumonectomía , Estudios Retrospectivos , Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
3.
Surg Today ; 49(5): 443-450, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30617600

RESUMEN

PURPOSE: Suppressor of cytokine signaling-3 (SOCS3) is a negative feedback inhibitor of cytokine signaling with T-cell-mediated immunosuppressive effects on obliterative bronchiolitis (OB). In this study, we aimed to investigate the impact of T-cell-specific overexpression of SOCS3 using a murine heterotopic tracheal transplantation (HTT) model. METHODS: Tracheal allografts from BALB/c mice were subcutaneously transplanted into wild-type C57BL/6J (B6; WT) mice and SOCS3 transgenic B6 (SOCS3TG) mice. Tracheal allografts were analyzed by immunohistochemistry and quantitative polymerase chain reaction assays at days 7 and 21. RESULTS: At day 21, allografts in SOCS3TG mice showed significant amelioration of airway obstruction and epithelial loss compared with allografts in WT mice. The intragraft expression of IFN-γ and CXCL10 was suppressed, while that of IL-4 was enhanced in SOCS3TG mice at day 7. The T-bet levels were lower in SOCS3TG allografts than in WT allografts at day 7. CONCLUSION: We revealed that the overexpression of SOCS3 in T cells effectively ameliorates OB development in a murine HTT model by inhibiting the Th1 phenotype in the early phase. Our results suggest that the regulation of the T-cell response, through the modulation of SOCS expression, has potential as a new therapeutic strategy for chronic lung allograft dysfunction.


Asunto(s)
Obstrucción de las Vías Aéreas/genética , Obstrucción de las Vías Aéreas/inmunología , Obstrucción de las Vías Aéreas/terapia , Expresión Génica , Proteína 3 Supresora de la Señalización de Citocinas/genética , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Linfocitos T , Tráquea/trasplante , Trasplante Heterotópico , Aloinjertos , Animales , Bronquiolitis Obliterante/genética , Bronquiolitis Obliterante/inmunología , Bronquiolitis Obliterante/terapia , Enfermedad Crónica , Rechazo de Injerto/terapia , Tolerancia Inmunológica , Trasplante de Pulmón , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Modelos Animales
4.
Gan To Kagaku Ryoho ; 46(1): 154-156, 2019 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-30765672

RESUMEN

A 66-year-old woman underwent distal gastrectomy because of gastric cancer(stage ⅠB)and received no adjuvant chemotherapy. Eight years after the operation, computed tomography showed a small nodule in the right breast. Mammography did not reveal any abnormalities. Ultrasound sonography showed a diffuse and gradual non-mass-like low echoic lesion. Core needle biopsy indicated a malignancy. Partial resection of the right breast was performed to obtain a diagnosis. On postoperative histopathological examination, signet-ring cells were found in the tumor, and immunohistochemical analysis showed that both the breast tumor and the gastric carcinoma were MUC5AC-positive and MUC1-negative. We diagnosed this breast tumor as metastasis from gastric cancer. The patient has received chemotherapy with no subsequent metastatic tumors, and good control has been achieved for 21 months after the detection of the breast metastasis.


Asunto(s)
Neoplasias de la Mama , Neoplasias Gástricas , Anciano , Neoplasias de la Mama/secundario , Quimioterapia Adyuvante , Femenino , Gastrectomía , Humanos , Mamografía , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía
5.
Carcinogenesis ; 39(5): 719-727, 2018 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-29546323

RESUMEN

Epidermal growth factor receptor (EGFR) is a member of the ErbB (HER) family that is known to play important roles in the pathogenesis of various human cancers. Mutations of the EGFR gene are commonly found as oncogenic driver mutations and have been targeted for treatment of non-small cell lung cancer (NSCLC). Leucine-rich repeat and immunoglobulin-like domain protein-1 (LRIG1) is a cell-surface protein that is known as a negative regulator of the ErbB (HER) family. In this study, we first confirmed that the expression levels of LRIG1 were much lower in NSCLC than in non-malignant cells or tissues. Next, we focused on the effect of LRIG1 in NSCLC. For this purpose, we established clones stably overexpressing LRIG1, using EGFR-mutant (HCC827, HCC4011 and NCI-H1975) and wild-type (A549) cells. Transfection of LRIG1 was associated with a decrease in the expression and phosphorylation levels of EGFR in the HCC827, HCC4011 and NCI-H1975 cells. It was also associated with strong suppression of the cell proliferative, invasive, migratory and tumorigenic potential of the HCC827 cells. On the other hand, no such effects were observed in the A549 cells. In addition, LRIG1 also downregulated the expression and phosphorylation levels of other tyrosine kinase receptors, such as HER2, HER3, MET and IGF-1R, and prevented the epithelial-to-mesenchymal transition induced by TGF-ß in the HCC827 cells. These findings suggest that LRIG1 exerts important tumor-suppressive effects in EGFR-mutant NSCLC and has the potential to become a novel therapeutic target for EGFR-mutant NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Glicoproteínas de Membrana/genética , Mutación/genética , Células A549 , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo/genética , Transición Epitelial-Mesenquimal/genética , Receptores ErbB/genética , Humanos , Invasividad Neoplásica/genética , Fosforilación/genética , Proteínas Tirosina Quinasas Receptoras/genética
6.
Cancer Sci ; 109(5): 1493-1502, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29532558

RESUMEN

Human epidermal growth factor receptor 2 (HER2) plays an important role in the pathogenesis of various cancers. HER2 alterations have been suggested to be a therapeutic target in non-small-cell lung cancer (NSCLC), just as in breast and gastric cancers. We previously reported that the pan-HER inhibitor afatinib could be a useful therapeutic agent as HER2-targeted therapy for patients with NSCLC harboring HER2 alterations. However, acquired resistance to afatinib was observed in the clinical setting, similar to the case for other HER inhibitors. Thus, elucidation of the mechanisms underlying the development of acquired drug resistance and exploring means to overcome acquired drug resistance are important issues in the treatment of NSCLC. In this study, we experimentally established afatinib-resistant cell lines from NSCLC cell lines harboring HER2 alterations, and investigated the mechanisms underlying the acquisition of drug resistance. The established cell lines showed several unique afatinib-resistance mechanisms, including MET amplification, loss of HER2 amplification and gene expression, epithelial-to-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. The afatinib-resistant cell lines showing MET amplification were sensitive to the combination of afatinib plus crizotinib (a MET inhibitor), both in vitro and in vivo. The resistant cell lines which showed EMT or had acquired CSC-like features remained sensitive to docetaxel, like the parental cells. These findings may provide clues to countering the resistance to afatinib in NSCLC patients with HER2 alterations.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Receptor ErbB-2/genética , Afatinib , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Crizotinib , Docetaxel , Femenino , Amplificación de Genes , Humanos , Neoplasias Pulmonares/genética , Ratones , Células Madre Neoplásicas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-met/genética , Pirazoles/administración & dosificación , Pirazoles/farmacología , Piridinas/administración & dosificación , Piridinas/farmacología , Quinazolinas/administración & dosificación , Quinazolinas/farmacología , Taxoides/administración & dosificación , Taxoides/farmacología , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Surg Today ; 48(12): 1089-1095, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30022248

RESUMEN

PURPOSE: Inflammatory changes during lung ischemia-reperfusion injury (IRI) are related to the activation of the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Sprouty-related EVH1 (enabled/vasodilator-stimulated phosphoprotein homology 1)-domain-containing proteins (SPREDs) are known inhibitors of ERK1/2 signaling. The role of SPRED2 in lung IRI was examined in a left hilar clamp mouse model. METHODS: C57BL/6 wild-type (WT) and Spred2-/- mice were used in the left hilar clamp model. Experimental groups underwent 30 min of left hilar clamping followed by 1 h of reperfusion. U0126, an ERK1/2 inhibitor, was administered to Spred2-/- mice with reperfused lungs. RESULTS: The partial pressures of oxygen of the Spred2-/- mice after reperfusion were significantly worse than those of WT mice (p < 0.01). Spred2-/- mice displayed more severe injuries than WT mice with increased neutrophil infiltration observed by a histological evaluation and flow cytometry (p < 0.001). This severe inflammation was inhibited by U0126. In addition, the rate of ERK1 activation was significantly higher in the lungs of Spred2-/- mice after reperfusion than in WT mice according to a Western blot analysis (p < 0.05). CONCLUSION: The activation of the ERK1/2 signaling pathway influences the severity of lung IRI, causing inflammation with neutrophil infiltration. SPRED2 may be a promising target for the suppression of lung IRI.


Asunto(s)
Isquemia/etiología , Isquemia/genética , Pulmón/irrigación sanguínea , Sistema de Señalización de MAP Quinasas/genética , Sistema de Señalización de MAP Quinasas/fisiología , Daño por Reperfusión/etiología , Daño por Reperfusión/genética , Proteínas Represoras/deficiencia , Proteínas Represoras/fisiología , Animales , Modelos Animales de Enfermedad , Femenino , Isquemia/patología , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Terapia Molecular Dirigida , Infiltración Neutrófila , Daño por Reperfusión/terapia , Índice de Severidad de la Enfermedad
8.
Gan To Kagaku Ryoho ; 45(3): 498-500, 2018 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-29650917

RESUMEN

A 76-year-old female underwent breast-conserving surgery of the right breast and sentinel lymph node biopsy for primary breast cancer. Three years later, mammography and ultrasonography showed a small nodule in the right breast. There was nothing abnormal in the left breast. Three months later, she complained of a huge and rapid growing mass in the left breast. Malignant cells were obtained on fine needle aspiration biopsy in the right breast tumor. But it was not possible to diagnose whether the left breast tumor was benign or malignant on fine needle aspiration biopsy and needle biopsy. Bilateral mastectomy and sentinel lymph node biopsy of the right side were performed. Pathological diagnosis were squamous cell carcinoma of the right breast and spindle cell carcinoma of the left breast. Although the patient was treated with adjuvant chemotherapy, she had an early relapse with pleural, lung and bone metastases. The patient died approximately 8 months after operation. Spindle cell carcinoma presents many problems about therapy and prognosis. Further accumulation analysis is necessary.


Asunto(s)
Neoplasias de la Mama/patología , Anciano , Biopsia con Aguja Fina , Biopsia con Aguja , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos
9.
Circ J ; 81(3): 383-390, 2017 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-28100891

RESUMEN

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) are currently treated with combination therapy of PAH-targeted drugs. Reverse right ventricular (RV) remodeling after lung transplantation (LTx) in patients with end-stage PAH despite combination therapy of PAH-targeted drugs has not been fully elucidated.Methods and Results:A total of 136 patients, including 32 with PAH, underwent LTx from 1998 to 2014. We enrolled 12 consecutive patients with PAH treated with combination therapy of PAH-targeted drugs who underwent LTx and retrospectively analyzed the temporal and serial changes in hemodynamics and echocardiography before LTx and at 3 and 12 months after LTx. Before LTx, the RV was markedly dilated with substantially reduced RV fractional area change (RVFAC). At 3 months after LTx, pulmonary artery pressure, pulmonary vascular resistance and RV stroke work index were significantly decreased, while left ventricular stroke work index was increased. RV size assessed by echocardiography also significantly decreased and RVFAC improved. At 12 months after LTx, RVFAC was further increased and RV wall thickness was decreased significantly. CONCLUSIONS: Although severe RV dysfunction and dilation were observed in patients with end-stage PAH despite combination therapy of PAH-targeted drugs, RV function and morphology were improved after reduction of RV pressure load by LTx.


Asunto(s)
Antihipertensivos/administración & dosificación , Remodelación Atrial , Hipertensión Pulmonar , Trasplante de Pulmón , Adolescente , Adulto , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Niño , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/terapia , Masculino , Persona de Mediana Edad , Volumen Sistólico/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos
10.
Acta Med Okayama ; 71(3): 259-262, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28655947

RESUMEN

 Primary sternal chondrosarcoma is a rare malignant tumor that is refractory to chemotherapy and radiation. Effective therapy is radical resection of the tumor. We present two patients with primary sternal chondrosarcoma who underwent a radical resection of the lower half of the sternum and bilateral ribs, followed by reconstruction with 2 sheets of polypropylene mesh layered orthogonally. The patients have maintained almost the same pulmonary function as preoperative values, with stability of the chest wall. Although there are various ways to reconstruct the anterior chest wall, reconstruction with polypropylene mesh layered orthogonally is an easy-to-use and sufficient method.


Asunto(s)
Neoplasias Óseas/cirugía , Condrosarcoma/cirugía , Procedimientos de Cirugía Plástica/métodos , Costillas/cirugía , Esternón/cirugía , Mallas Quirúrgicas , Pared Torácica/cirugía , Anciano , Neoplasias Óseas/patología , Condrosarcoma/patología , Femenino , Humanos , Persona de Mediana Edad , Polipropilenos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Técnicas de Sutura , Resultado del Tratamiento
11.
Acta Med Okayama ; 71(2): 105-112, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28420891

RESUMEN

We retrospectively assessed the dual-time-point (DTP) F-18 FDG PET/CT findings of thymic epithelial neoplasms (TENs) and investigated the diagnostic capacity of PET/CT compared to that of CT for predicting carcinoma. We calculated the ratio of the standardized uptake value of the tumor and that of the aortic arch (T/M ratio) for both the 90-min early scan and the 2-h delayed scan in 56 TEN patients. We used a multivariate logistic regression (MLR) analysis to estimate the CT features of carcinoma. We compared the diagnostic capacities of PET/CT and chest CT using receiver operating characteristic (ROC) analyses. The ROC curve revealed that the appropriate cut-off T/M ratio value for the highest accuracy was 2.39 with 75.0% accuracy. The area under the curve (AUC) was 0.855. The statistical analyses for DTP scans of 35 TEN patients demonstrated 74.3% accuracy and 0.838 AUC for the early scan versus 82.9% and 0.825 for the delayed scan. The MLR analysis indicated that mediastinal fat infiltration was a predictor of carcinoma. The ROC curve obtained for the model yielded an AUC of 0.853. Delayed scanning could improve the diagnostic capacity for carcinoma. The T/M ratio and mediastinal fat infiltration are predictive of carcinoma with moderate diagnostic accuracy.


Asunto(s)
Neoplasias Glandulares y Epiteliales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias del Timo/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/clasificación , Neoplasias Glandulares y Epiteliales/patología , Valor Predictivo de las Pruebas , Radiofármacos , Estudios Retrospectivos , Método Simple Ciego , Neoplasias del Timo/clasificación , Neoplasias del Timo/patología , Tomografía Computarizada por Rayos X/métodos , Adulto Joven
12.
Surg Today ; 47(3): 399-401, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27324517

RESUMEN

In cadaveric lung transplantation (LTx), a donor lung with an inadequate donor left atrial cuff is considered a "surgically marginal donor lung". The donor pericardium is commonly applied to reconstruct the inadequate donor left atrial cuff; however, in some cases, the donor pericardium is inadvertently removed during the lung procurement. We devised an alternative technique for reconstruction to overcome the absence of pericardium in a donor lung with an inadequate atrial cuff, using a patch of the donor pulmonary artery (PA) in single lung transplantation. In a recent case of lung transplantation in which the donor pericardium had been removed, we harvested a segment of the right PA distal to the main PA of the donor and used a PA patch to repair the inadequate donor left atrial cuff. No vascular complications were encountered in the recipient, who remains in good health after the transplantation.


Asunto(s)
Atrios Cardíacos/cirugía , Trasplante de Pulmón/métodos , Arteria Pulmonar/trasplante , Donantes de Tejidos , Cadáver , Humanos , Márgenes de Escisión , Pericardio , Procedimientos de Cirugía Plástica/métodos , Obtención de Tejidos y Órganos/métodos , Resultado del Tratamiento
13.
Surg Today ; 47(5): 601-605, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27629155

RESUMEN

PURPOSE: Preservation of the middle lobe during lung surgery is traditionally avoided, because its presence in the hemithoracic cavity is considered a cause of complications. We report a series of lung cancer patients who underwent a secondary pulmonary resection with the preservation of the middle lobe to explore the complications and feasibility of these procedures. METHODS: We reviewed the clinical courses of six patients who underwent surgery for metachronous lung cancers. Five patients underwent right upper lobectomy, including one sleeve lobectomy, after having undergone prior right lower lobectomy. The remaining patient underwent a right lower lobectomy after having undergone a prior right upper lobectomy. RESULTS: There were no treatment-related deaths. One patient was readmitted for surgery to treat delayed air leakage progressing to pyothorax. One patient was treated for persistent air leakage. Two patients required intermittent drainage of pulmonary effusion, because of middle lobe atelectasis. The postoperative forced vital capacity and forced expiratory volume in 1 s were greater than the values predicted post-pneumonectomy in four evaluable patients. CONCLUSIONS: While postoperative complications after middle lobe-preserving surgery are manageable, their high incidence should be considered when performing this surgery.


Asunto(s)
Neoplasias Pulmonares/cirugía , Tratamientos Conservadores del Órgano/métodos , Neumonectomía/métodos , Complicaciones Posoperatorias , Anciano , Anciano de 80 o más Años , Fuga Anastomótica , Empiema Pleural , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derrame Pleural , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
14.
Int Heart J ; 58(4): 557-561, 2017 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-28690295

RESUMEN

Adverse cardiovascular events after lung transplantation (LT) increase the mortality in patients with pulmonary arterial hypertension (PAH). Long-term intravenous prostacyclin is the usual treatment in severe patients with PAH, but it may increase the risk of hemorrhage due to its antiplatelet aggregation effect or thrombocytopenia. We investigated the impact of length of intravenous prostacyclin therapy on acute adverse cardiovascular events including hemorrhagic complication after LT. We retrospectively compared the incidence of adverse events (death, intrathoracic hematoma and bleeding, cardiac congestion or shock, cerebral infarction and pulmonary embolism) within 30 days after LT between no/short-term (median 0.6 years, n = 13) and long-term (median 3.7 years, n = 15) intravenous prostacyclin groups. There were no differences in the dose of intravenous prostacyclin and pulmonary artery pressure between the two groups. Among 22 adverse events (0.8 ± 1.1 events/patient), 4 events occurred in the no/short-term intravenous prostacyclin group and 18 occurred in the long-term intravenous prostacyclin group. The event rate per patient in the long-term intravenous prostacyclin group (1.2 ± 1.3 events/patient) was significantly higher than that in the no/short-term intravenous prostacyclin group (0.3 ± 0.5 events/patient) (P < 0.05). Intrathoracic hematoma and bleeding was the most frequent adverse event (9 events, 41%). Preoperative long-term intravenous prostacyclin therapy increases acute adverse cardiovascular events after LT in patients with PAH.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Epoprostenol/administración & dosificación , Hipertensión Pulmonar/terapia , Trasplante de Pulmón/efectos adversos , Cuidados Preoperatorios/métodos , Enfermedad Aguda , Adolescente , Adulto , Antihipertensivos/administración & dosificación , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Relación Dosis-Respuesta a Droga , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/fisiopatología , Incidencia , Inyecciones Intravenosas , Japón/epidemiología , Masculino , Complicaciones Posoperatorias , Presión Esfenoidal Pulmonar/fisiología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Adulto Joven
15.
Breast Cancer Res ; 18(1): 73, 2016 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-27368476

RESUMEN

BACKGROUND: The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. METHODS: In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. RESULTS: The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144-4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881-12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738-2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059). CONCLUSIONS: Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Isoenzimas/metabolismo , Células Madre Neoplásicas/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Retinal-Deshidrogenasa/metabolismo , Adulto , Anciano , Familia de Aldehído Deshidrogenasa 1 , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Femenino , Estudios de Seguimiento , Expresión Génica , Humanos , Inmunohistoquímica , Isoenzimas/genética , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Pronóstico , Retinal-Deshidrogenasa/genética , Factores de Tiempo
16.
Cancer Sci ; 107(1): 45-52, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26545934

RESUMEN

Human epidermal growth factor receptor 2 (HER2) is a member of the HER family of proteins containing four receptor tyrosine kinases. It plays an important role in the pathogenesis of certain human cancers. In non-small-cell lung cancer (NSCLC), HER2 amplification or mutations have been reported. However, little is known about the benefit of HER2-targeted therapy for NSCLCs harboring HER2 alterations. In this study, we investigated the antitumor effect of afatinib, an irreversible epidermal growth factor receptor (EGFR)-HER2 dual inhibitor, in lung cancers harboring HER2 oncogene alterations, including novel HER2 mutations in the transmembrane domain, which we recently identified. Normal bronchial epithelial cells, BEAS-2B, ectopically overexpressing wild-type HER2 or mutants (A775insYVMA, G776VC, G776LC, P780insGSP, V659E, and G660D) showed constitutive autophosphorylation of HER2 and activation of downstream signaling. They were sensitive to afatinib, but insensitive to gefitinib. Furthermore, we examined the antitumor activity of afatinib and gefitinib in several NSCLC cell lines, and investigated the association between their genetic alterations and sensitivity to afatinib treatment. In HER2-altered NSCLC cells (H2170, Calu-3, and H1781), afatinib downregulated the phosphorylation of HER2 and EGFR as well as their downstream signaling, and induced an antiproliferative effect through G1 arrest and apoptotic cell death. In contrast, HER2- or EGFR-non-dependent NSCLC cells were insensitive to afatinib. In addition, these effects were confirmed in vivo by using a xenograft mouse model of HER2-altered lung cancer cells. Our results suggest that afatinib is a therapeutic option as a HER2-targeted therapy for NSCLC harboring HER2 amplification or mutations.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Quinazolinas/farmacología , Receptor ErbB-2/genética , Afatinib , Animales , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Femenino , Genes erbB-2 , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Eur Radiol ; 26(1): 114-21, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25991483

RESUMEN

OBJECTIVES: To retrospectively evaluate the safety of computed tomography (CT) fluoroscopy-guided short hook wire placement for video-assisted thoracoscopic surgery and the risk factors for pneumothorax associated with this procedure. METHODS: We analyzed 267 short hook wire placements for 267 pulmonary lesions (mean diameter, 9.9 mm). Multiple variables related to the patients, lesions, and procedures were assessed to determine the risk factors for pneumothorax. RESULTS: Complications (219 grade 1 and 4 grade 2 adverse events) occurred in 196 procedures. No grade 3 or above adverse events were observed. Univariate analysis revealed increased vital capacity (odds ratio [OR], 1.518; P = 0.021), lower lobe lesion (OR, 2.343; P =0.001), solid lesion (OR, 1.845; P = 0.014), prone positioning (OR, 1.793; P = 0.021), transfissural approach (OR, 11.941; P = 0.017), and longer procedure time (OR, 1.036; P = 0.038) were significant predictors of pneumothorax. Multivariate analysis revealed only the transfissural approach (OR, 12.171; P = 0.018) and a longer procedure time (OR, 1.048; P = 0.012) as significant independent predictors. CONCLUSION: Complications related to CT fluoroscopy-guided preoperative short hook wire placement often occurred, but all complications were minor. A transfissural approach and longer procedure time were significant independent predictors of pneumothorax. KEY POINTS: Complications related to CT fluoroscopy-guided preoperative short hook wire placement often occur. Complications are usually minor and asymptomatic. A transfissural approach and longer procedure time are significant independent predictors of pneumothorax.


Asunto(s)
Fluoroscopía/métodos , Enfermedades Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neumotórax/diagnóstico por imagen , Cuidados Preoperatorios/métodos , Suturas/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Japón/epidemiología , Enfermedades Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Neumotórax/epidemiología , Neumotórax/etiología , Cuidados Preoperatorios/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Cirugía Asistida por Computador/métodos , Cirugía Torácica Asistida por Video , Adulto Joven
18.
Int J Clin Oncol ; 21(2): 302-309, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26293333

RESUMEN

BACKGROUND: Increased expression of collagen XV has been reported in hepatocellular carcinogenesis in mice. The aim of this study was to confirm the previous murine findings in human hepatocellular carcinoma (HCC) specimens, along with the histopathological distribution of collagen XV in tumoral tissues. METHODS: Sixty-three primary HCC specimens were examined. Immunostaining of collagen XV and quantitative reverse transcriptional PCR of COL15A1, which encodes collagen XV, were performed. RESULTS: Positive staining of collagen XV was observed in all tumoral regions, regardless of differentiation level or pathological type of HCC, along the sinusoid-like endothelium, whereas collagen XV was not expressed in any non-tumoral region. The intensity score of collagen XV immunostaining and the mRNA value of COL15A1 were significantly correlated. COL15A1 expression in tumors was 3.24-fold higher than in non-tumoral regions. Multivariate analysis showed that COL15A1 expression was significantly higher in the absence of hepatitis virus and moderately differentiated HCC. CONCLUSIONS: COL15A1 mRNA was up-regulated in HCC and collagen XV was expressed along the sinusoid-like endothelium of HCC but not in non-tumoral regions, which implies that collagen XV contributes to the capillarization of HCC.


Asunto(s)
Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/patología , Colágeno/genética , Neoplasias Hepáticas/química , Neoplasias Hepáticas/patología , Anciano , Anciano de 80 o más Años , Carcinogénesis , Carcinoma Hepatocelular/irrigación sanguínea , Diferenciación Celular , Endotelio/química , Femenino , Humanos , Hígado/química , Neoplasias Hepáticas/irrigación sanguínea , Masculino , Persona de Mediana Edad , Neovascularización Patológica , ARN Mensajero/análisis
19.
Acta Med Okayama ; 70(6): 507-510, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28003678

RESUMEN

We present the case of a 65-year-old Japanese man diagnosed with chronic empyema (without a bronchopleural fistula) that occurred 7 months after he underwent an extrapleural pneumonectomy for right malignant pleural mesothelioma (MPM). Following thoracic drainage and irrigation for 1 month, we performed surgery by a thoracoscopic approach, in light of his general condition. We performed debridement and removal of the Gore-Tex polytetrafluoroethylene (PTFE) patch that had been used for the reconstruction of the diaphragm and the pericardium. The empyema had not relapsed when he died from recurrence of the MPM at 4 months after the thoracoscopic surgery. This patient's case suggests that thoracoscopic debridement and patch removal can be a therapeutic option for not only early-stage (exudative or fibrinopurulent) empyema but also late-stage (organized and chronic) empyema without a bronchopleural fistula, particularly for patients in poor general condition.


Asunto(s)
Desbridamiento/métodos , Empiema/cirugía , Neumonectomía/métodos , Toracoscopía/métodos , Anciano , Enfermedad Crónica/terapia , Humanos , Neoplasias Pulmonares/cirugía , Masculino
20.
Acta Med Okayama ; 70(5): 421-424, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27777440

RESUMEN

Stent placement is an essential treatment for airway diseases. Although self-expandable metallic stents and silicone stents are commonly applied for the treatment of airway diseases, these stents are unsuitable for the treatment of small airway diseases encountered in pediatric patients and lung transplant recipients with airway complications. Currently, only vascular balloon-expandable metallic stents are available for the treatment of small airway diseases; however, little research has been conducted on the use of these stents in this field. We have launched a prospective feasibility study to clarify the safety and efficacy of balloon-expandable metallic stents for the treatment of airway diseases.


Asunto(s)
Obstrucción de las Vías Aéreas/terapia , Enfermedades Bronquiales/terapia , Stents , Estenosis Traqueal/terapia , Niño , Protocolos Clínicos , Humanos
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