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1.
Surg Endosc ; 36(4): 2312-2320, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-33881626

RESUMEN

BACKGROUND: Previous studies have reported the feasibility and efficacy of thoracoscopic anatomical sublobar resection under three-dimensional computed tomography (3DCT) simulation; however, its long-term outcomes have not been clearly established in primary lung cancer. This study aimed to evaluate the long-term outcomes of this technique. METHODS: We retrospectively reviewed data from 112 consecutive patients with selected clinical stage IA non-small cell lung cancer (NSCLC) who underwent thoracoscopic anatomical sublobar resection from 2004 to 2014. This procedure was planned using preoperative 3DCT simulation to ensure sufficient surgical margins and enabled tailor-made surgery for each patient. Patients who had predominantly ground glass opacity lung cancers underwent anatomical sublobar resection as a curative-intent resection. Other patients who were high-risk candidates for lobectomy underwent anatomical sublobar resection as a compromised limited resection. RESULTS: Of the 112 cases, 82 had a curative-intent resection, while 30 had a compromised limited resection. Recurrence occurred in only 2 cases (1.8%), both of which were in the compromised limited group. A second primary lung cancer was observed in 5 cases (4.5%). Of the 5 patients, 4 underwent surgery for a second cancer and had no recurrence. The 5-year overall survival, lung cancer-specific overall survival, and recurrence-free survival rates were 92.5%, 100%, and 98.2%, respectively, for all cases; 97.6%, 100%, and 100%, respectively, in the curative-intent group; and 75.8%, 100% and 92.6%, respectively, in the compromised limited group. CONCLUSIONS: Thoracoscopic anatomical sublobar resection under 3DCT simulation may be an acceptable alternative treatment in selected patients with NSCLC. TRIAL AND CLINICAL REGISTRY: Clinical registration number: IRB No. 2020-98 (Dated: 2020.6.30).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Estadificación de Neoplasias , Neumonectomía/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
2.
Surg Today ; 51(9): 1480-1487, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33611651

RESUMEN

PURPOSE: Few studies have so far focused on the preoperative presence of venous thromboembolism (VTE) in lung cancer patients undergoing surgery. In this study, we investigated the prevalence and risk factors for preoperative deep venous thrombosis (DVT) in patients scheduled to undergo lung cancer surgery. METHODS: Between June 2013 and December 2018, 948 consecutive patients underwent lung cancer surgery in Kindai University Hospital. Four patients did not undergo screening for DVT; thus, 944 patients were enrolled in this study. Preoperatively, venous ultrasonography of the lower extremities was performed in patients deemed at risk for DVT, and the prevalence and risk factors for preoperative DVT were examined. RESULTS: Ninety-one patients (9.6%) were diagnosed with preoperative DVT, and postoperative symptomatic pulmonary thromboembolism occurred in one patient (0.11%). A multivariable logistic regression analysis demonstrated that female sex, age ≥ 72 years, history of VTE, a Wells score ≥ 2 points, chronic obstructive pulmonary disease (COPD), and lower hemoglobin levels were significantly associated with preoperative DVT. CONCLUSION: Female sex, age ≥ 72 years, history of VTE, Wells score ≥ 2 points, COPD, and lower hemoglobin levels were identified to be independent risk factors for preoperative DVT. Monitoring for these risk factors and management considering them should help improve the outcomes after lung cancer surgery.


Asunto(s)
Neoplasias Pulmonares/cirugía , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Factores de Edad , Anciano , Femenino , Hemoglobinas/deficiencia , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Complicaciones Posoperatorias , Periodo Preoperatorio , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica , Embolia Pulmonar , Factores de Riesgo , Factores Sexuales , Resultado del Tratamiento , Ultrasonografía , Trombosis de la Vena/diagnóstico por imagen
3.
Surg Today ; 50(11): 1427-1433, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32409869

RESUMEN

PURPOSE: A high plasma level of either fibrinogen or D-dimer has been shown to correlate with a poor prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). The present study aimed to identify whether or not both markers combined had a superior prognostic value to either alone. METHODS: Of the 1344 patients who underwent surgical resection for NSCLC at our institution between January 2007 and December 2016, 1065 had preoperative plasma fibrinogen and D-dimer data available and were included in the analysis. RESULTS: The recurrence-free survival (RFS) and overall survival (OS) rates were similar for patients with high plasma levels of either or both fibrinogen (> 4.0 g/L) or D-dimer (> 1.0 µg/mL); therefore, these three groups were combined for a further analysis into a single group with high plasma levels of either or both proteins. The high-level group had significantly lower 5-year RFS (53% vs. 68%, p < 0.001) and 5-year OS (65% vs. 80%, p < 0.001) rates than patients with normal plasma levels of fibrinogen and D-dimer (control group). CONCLUSIONS: Our results suggest that preoperative tests for both plasma fibrinogen and D-dimer are necessary to identify patients with surgically resected NSCLC likely to have a poor RFS and OS.


Asunto(s)
Biomarcadores de Tumor/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Neoplasias Pulmonares/cirugía , Neumonectomía , Trombofilia/diagnóstico , Tromboembolia Venosa/diagnóstico , Anciano , Trastornos de la Coagulación Sanguínea/etiología , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Femenino , Fibrinólisis , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/mortalidad , Masculino , Periodo Preoperatorio , Pronóstico , Tasa de Supervivencia , Trombofilia/etiología , Tromboembolia Venosa/etiología
4.
Pestic Biochem Physiol ; 165: 104538, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32359560

RESUMEN

Imidacloprid is very effective in controlling Nilaparvata lugens Stål, which severely damages rice plants. Following heavy imidacloprid use, imidacloprid-resistant N. lugens, which showed cross-resistance to other neonicotinoids, appeared. We used the baculovirus/Sf9 expression system to express CYP6ER1 variants carrying A375del + A376G (del3) mutations, either with or without T318S mutation, which confer imidacloprid resistance in N. lugens. These CYP6ER1 variants metabolized imidacloprid but did not metabolize dinotefuran. Moreover, Drosophila expressing a CYP6ER1 variant carrying T318S + del3 mutations were resistant to imidacloprid, with a resistance ratio of 288.7, whereas the resistance ratio to dinotefuran was 3.6. These findings indicate that N. lugens has a low level of resistance to dinotefuran, and the increase of resistance is slow. We also studied the metabolism of other neonicotinoids, as well as sulfoxaflor and flupyradifurone, by CYP6ER1 variants carrying del3 mutations, either with or without the T318S mutation. Sulfoxaflor, was not metabolized by either CYP6ER1-del3 or CYP6ER1-T318Sdel3 variants. However, these variants did metabolize flupyradifurone. This study sheds light on the substrate selectivity of CYP6ER1 variants.


Asunto(s)
Hemípteros , Insecticidas , Animales , Resistencia a los Insecticidas , Neonicotinoides , Nitrocompuestos
5.
Pestic Biochem Physiol ; 159: 27-33, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31400781

RESUMEN

Imidacloprid has been used to control one of most serious pests, Bemisia tabaci. However, B. tabaci has developed imidacloprid resistance mainly by over-expressing CYP6CM1. It was reported that imidacloprid-resistant B. tabaci showed no or low level of cross-resistance against dinotefuran. Here, we expressed CYP6CM1 variants using Sf9/baculovirus and/or Drosophila S2 cells and showed that CYP6CM1 variants metabolized imidacloprid but not dinotefuran. In addition, we demonstrated that imidacloprid and pymetrozine competed for a CYP6CM1 variant more efficiently than dinotefuran, using a luminescent substrate competition assay. These results suggest that lack of metabolic activity of CYP6CM1 variants against dinotefuran caused no or low level of cross-resistance.


Asunto(s)
Guanidinas/metabolismo , Guanidinas/farmacología , Hemípteros/efectos de los fármacos , Hemípteros/metabolismo , Insecticidas/metabolismo , Insecticidas/farmacología , Neonicotinoides/metabolismo , Neonicotinoides/farmacología , Nitrocompuestos/metabolismo , Nitrocompuestos/farmacología , Animales , Hemípteros/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas/genética , Triazinas/metabolismo , Triazinas/farmacología
6.
Kyobu Geka ; 72(5): 363-366, 2019 May.
Artículo en Japonés | MEDLINE | ID: mdl-31268034

RESUMEN

BACKGROUND: Although malignant tumor with heterotopic ossification have often been reported, it is very rare in lung cancer. We report a case of primary lung adenocarcinoma with heterotopic ossification. CASE: A 43-year-old woman undergoing a health check was found an abnormal nodular lesion on chest X-ray. Chest computed tomography (CT) showed a calcified tumor, which was diagnosed adenocarcinoma by transbronchial biopsy. Right lower lobectomy and ND2a-2 lymph node dissection was done. Postoperative pathological examination identified the tumor as a bronchioloalveolar adenocarcinoma with other mixed subtypes, associated with ossification containing bone marrow tissue in the tumor. An immunohistochemical examination showed that cancer cells around the ossification expressed bone morphogenetic protein-2 and osteopontin, which generally induce and stimulate bone formation. CONCLUSION: This finding may serve to elucidate a probable mechanism for the heterotopic ossification observed in cancer lesions.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Osificación Heterotópica , Adenocarcinoma del Pulmón/complicaciones , Adulto , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Osificación Heterotópica/complicaciones , Tomografía Computarizada por Rayos X
7.
Kyobu Geka ; 72(7): 535-542, 2019 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-31296804

RESUMEN

Since 2004, over 300 patients have undergone thoracoscopic segmentectomy without mini-thoracotomy. Thoracoscopic segmentectomy is one of the most complicated surgeries. To perform the complex segmentectomies, pre-operative simulation and 3-dimensional multi-detector computed tomography( 3DCT) are both essential for safely performing operations and for securing adequate surgical margins. Comprehension of the intersegmental and intrasegmental veins to visualize the segmental border facilitates an easier parenchymal dissection. We describe our method and knack for creating an inflation-deflation line for lung segmentectomy that could especially be useful in thoracoscopic procedures for seg-mentectomy. The 5-year over overall survival, cancer specific survival and recurrence free survival rates were 91.8%( curative intent 98.1% versus compromised 74.6%), 100% and 98.1%( curative intent 100% versus compromised 93.3%). According to these technical aspects, our method of thoracoscopic segmentectomy is acceptable for selective patient.


Asunto(s)
Neumonectomía , Humanos , Neoplasias Pulmonares , Toracoscopía , Tomografía Computarizada por Rayos X
8.
Kyobu Geka ; 70(9): 750-754, 2017 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-28790240

RESUMEN

Cases of rescue after rupture of pyogenic liver abscess into the thorax are rare. Here, we report 2 cases of rescue in patients with acute empyema due to rupture of a suppurative abscess into the thorax. Case 1:A 61-year-old male had high fever of 39 °C and right abdominal pain. Thoracic computed tomography(CT) showed encapsulated pleural effusion in the right thorax and ring-like enhancement in the right liver. The diagnosis was acute empyema caused by rupture of liver abscess. The pathogenic bacteria were Streptococcus group. The drain was removed after 6 days and the patient was discharged 32 days after surgery without reefing the diaphragm. Case 2:A 74-year-old male had a high fever of 39 °C and right chest pain. CT showed encapsulated pleural effusion in the right thorax, but not in the lung, and a low density area in the posterior segment of the liver. The diagnosis was acute empyema caused by rupture of liver abscess. The pathogenic bacteria were Streptococcus group and Bacteroides. The drain was removed after 8 days and the patient was discharged 32 days after surgery without reefing the diaphragm. CONCLUSION: Pathogenic bacteria in a pyogenic liver abscess are usually Gram-negative rods, but recently have also been reported to be Streptococcus anginosus group( SAG). Coinfection with SAG and anaerobic bacteria occurs in elderly patients, compromised hosts, and patients with a severe malignant disease. Therefore, early drainage using surgical treatment regardless of reefing the diaphragm should be considered to control severe infection due to liver abscess rupture.


Asunto(s)
Empiema Pleural/etiología , Empiema Pleural/cirugía , Absceso Piógeno Hepático/complicaciones , Absceso Piógeno Hepático/cirugía , Anciano , Drenaje , Empiema Pleural/diagnóstico por imagen , Humanos , Absceso Piógeno Hepático/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Rotura Espontánea/diagnóstico por imagen , Rotura Espontánea/etiología , Rotura Espontánea/cirugía , Tomografía Computarizada por Rayos X
9.
Kyobu Geka ; 69(7): 499-502, 2016 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-27365059

RESUMEN

A 17-year-old man was admitted to our hospital for the abnormal chest shadow. Chest computed tomography(CT) demonstrated mediastinal tumor, measuring 13 cm in diameter with high serum level of alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG). The lesions were diagnosed as mixed germ cell tumors including a non-seminomatous malignant component by CT guided needle biopsy. After 5 courses of chemotherapy, the serum AFP and hCG were decreased almost normal level but the tumor size was not changed. Because it seemed to be difficult to get sufficient operating field with standard median sternotomy and patient wanted to treat funnel chest, we selected tumor resection with plastron approach. The tumor was completely resected with a good operation field by this procedure.


Asunto(s)
Tórax en Embudo/cirugía , Neoplasias del Mediastino/cirugía , Neoplasias de Células Germinales y Embrionarias/cirugía , Procedimientos de Cirugía Plástica/métodos , Procedimientos Quirúrgicos Torácicos/métodos , Adolescente , Antineoplásicos/administración & dosificación , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Biopsia con Aguja , Quimioterapia Adyuvante , Gonadotropina Coriónica/sangre , Terapia Combinada , Tórax en Embudo/etiología , Humanos , Biopsia Guiada por Imagen , Masculino , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/patología , Neoplasias de Células Germinales y Embrionarias/complicaciones , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/patología , Esternotomía/métodos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , alfa-Fetoproteínas/análisis
10.
Kyobu Geka ; 69(7): 511-5, 2016 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-27365062

RESUMEN

Extensive chest wall resection carries the risk of difficult reconstruction and surgical complications. We report our experience on chest wall reconstruction using titanium plates for a wide thoracic defect after tumor resection. A 74-year-old man was diagnosed with chondrosarcoma of the 6th rib on the right. He needed extensive chest wall resection because of skip lesions on 4th rib noted on operative inspection, leaving a defect measuring 33 × 20 cm. Reconstruction using 5 transverse titanium plates sandwiched between an expanded polytetrafluoroethylene patch and a polypropylene mesh sheet stabilized the chest wall. This reconstruction allowed successful separation from ventilatory support after operation. The postoperative course was uneventful, and he was discharged on postoperative day 20. The advantages of this form of reconstruction over conventional prostheses are rigidity, and stability and usability.


Asunto(s)
Placas Óseas , Condrosarcoma/cirugía , Procedimientos de Cirugía Plástica/métodos , Neoplasias Torácicas/cirugía , Procedimientos Quirúrgicos Torácicos/métodos , Pared Torácica/cirugía , Titanio , Anciano , Condrosarcoma/diagnóstico por imagen , Condrosarcoma/patología , Humanos , Masculino , Neoplasias Torácicas/diagnóstico por imagen , Neoplasias Torácicas/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
11.
Kyobu Geka ; 69(10): 811-7, 2016 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-27586310

RESUMEN

Introduction of spinal surgery into the operation of lung cancer has made extensive surgical treatment feasible with acceptable long-term survival. We report our experience on total en bloc total spondylectomy for lung cancer invading the spine. A 60-year-old man was diagnosed with lung adenocarcinoma of the apicodorsal segment of the left lobe with invasion of the 2nd and 3rd thoracic vertebral bodies. After induction chemoradiotherapy, we performed en bloc resection through a posterolateral thoracotomy in the right decubitus position and a posterior median approach in the prone position. The thoracic manipulation was done earlier, making it useful for the dissection of the prevertebral plane from the posterior mediastinum at the upper thoracic level in addition to confirmation of non-N2 disease. Vertebral stabilization was achieved with rod fixation and placement of a titanium mesh cage between the remaining vertebral bodies.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Pulmonares/cirugía , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma del Pulmón , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Imagen Multimodal , Neumonectomía , Toracotomía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
12.
Kyobu Geka ; 68(12): 1004-7, 2015 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-26555916

RESUMEN

We report a rare case of pulmonary lipomatous hamartoma. A 61-year-old male was referred to our hospital due to abnormal mass densities on a chest radiograph. Thoracic computed tomography (CT) revealed a tumor with a maximum diameter of 42 mm. Bronchoscopic examination indicated the presence of a tumor at the orifice of the lateral segmental bronchus which was obstructed by the tumor. Endobronchial lipoma, was suspected by transbronchial biopsy, and we carried out a left upper lobectomy to prevent obstructive pneumonia. The pathological diagnosis was lipomatous hamartoma.


Asunto(s)
Hamartoma/diagnóstico , Lipoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Broncoscopía , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Neumonectomía , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
13.
Kyobu Geka ; 68(6): 412-5, 2015 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-26066869

RESUMEN

A 26-year-old man was admitted because of an abnormal shadow on a chest roentgenogram. Computed tomography(CT) revealed a very large tumor in the anterior mediastinum and bilateral mediastinal lymphadenopathy. Examination of a CT-guided biopsy specimen revealed a yolk-sac tumor. The patient received 4 courses of bleomycin, etoposide, and cisplatin chemotherapy. After chemotherapy, the tumor was markedly reduced in size, but the lymphadenopathy remained. The patient underwent thoracoscopic biopsy of the mediastinal lymph nodes. Sarcoid nodules were found in all the biopsied nodes, and the lymphadenopathy was thought to be a sarcoid-like reaction associated with the germ cell tumor. Resection of the residual tumor was performed according to the treatment algorithm of the International Germ Cell Cancer Collaborative Group. There were no viable tumor cells in the resected tissue. The patient is free of recurrence and without any sign of generalized sarcoidosis 3 years after the surgery.


Asunto(s)
Neoplasias del Mediastino/patología , Neoplasias de Células Germinales y Embrionarias , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Humanos , Metástasis Linfática , Masculino , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias del Mediastino/cirugía , Imagen Multimodal , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/cirugía , Tomografía de Emisión de Positrones , Neoplasias Testiculares , Tomografía Computarizada por Rayos X
14.
Clin Lung Cancer ; 25(4): 384-388.e1, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38360496

RESUMEN

INTRODUCTION: Although the standard treatment for patients with resectable early-stage non-small-cell lung cancer (NSCLC) is pulmonary lobectomy, recent clinical trials have demonstrated the efficacy of anatomical segmentectomy for small-sized early-stage NSCLC measuring ≤2 cm. Segmentectomy is gaining attention as an alternative procedure to lobectomy for early-stage NSCLC. PATIENTS AND METHODS: In January 2024, we have initiated a randomized phase III trial in Japan to confirm the noninferiority of anatomical segmentectomy to lobectomy in patients with peripheral clinical stage IA3 pure-solid NSCLC (tumor measuring >2 cm and ≤3 cm; consolidation-to-tumor ratio = 1.0). We plan to enroll 520 patients from 61 institutions over a period of 5 years. The primary endpoint is overall survival, and the secondary endpoints include relapse-free survival, postoperative respiratory function, proportion of patients with respiratory failure and cerebrovascular disease, cumulative incidence of death from other diseases, cumulative incidence of local recurrence, proportion of patients who undergo segmentectomy, number of resected segments, operative time, blood loss, and adverse events. This trial has been registered in the UMIN Clinical Trials Registry under the code UMIN000052064. CONCLUSIONS: This trial will help establish a novel treatment strategy for patients with peripheral clinical stage IA3 pure-solid NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Neumonectomía , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neumonectomía/métodos , Japón , Masculino , Femenino , Anciano , Persona de Mediana Edad , Adulto , Tasa de Supervivencia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estudios de Seguimiento
15.
J Thorac Oncol ; 19(1): 71-79, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37666482

RESUMEN

INTRODUCTION: Approximately 10% of mutations in the EGFR gene in NSCLC are in-frame insertions in exon 20 (X20ins). These tumors usually do not respond to conventional EGFR tyrosine kinase inhibitors (TKIs). Several novel EGFR TKIs active for X20ins are in clinical development, including mobocertinib, which was recently approved by the U.S. Food and Drug Administration. However, acquired resistance during treatment with these TKIs still occurs as in the case of EGFR TKIs of earlier generations. METHODS: We chronically exposed murine pro-B-cell line cells transduced with the five most common X20ins (A763_Y764insFQEA, V769_D770insASV, D770_N771insSVD, H773_V774insNPH and H773_V774insH) to mobocertinib in the presence of N-ethyl-N-nitrosourea and searched for secondary EGFR mutations. We evaluated the efficacies of several EGFR X20ins inhibitors, including zipalertinib and sunvozertinib, against cells with acquired resistant mutations. RESULTS: All secondary mutations resulting in acquired resistance to mobocertinib were exclusively C797S in insFQEA and insSVD. However, in the case of other X20ins (insASV, insNPH, and insH), T790M or C797S secondary mutations contributed to acquired resistance to mobocertinib. The emergence of T790M was more frequent in cells treated with lower drug concentrations. Sunvozertinib exhibited good activity against resistant cells with T790M. Cells with C797S were refractory to all EGFR TKIs, except for erlotinib, which was active for insFQEA with C797S. CONCLUSIONS: T790M or C797S, depending on the original X20ins mutations, conferred acquired resistance to mobocertinib. Sunvozertinib may be the treatment of choice for patients with tumors resistant to mobocertinib because of T790M.


Asunto(s)
Genes erbB-1 , Neoplasias Pulmonares , Animales , Ratones , Resistencia a Antineoplásicos/genética , Receptores ErbB , Exones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico
16.
Eur J Cancer ; 201: 113951, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417299

RESUMEN

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.


Asunto(s)
Adenocarcinoma del Pulmón , Antineoplásicos , Neoplasias del Sistema Nervioso Central , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Japón , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/cirugía , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Mutación , Recurrencia , Sistema Nervioso Central/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos
17.
J Pestic Sci ; 48(1): 17-21, 2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36874638

RESUMEN

The species selectivity of class 2 dihydroorotate dehydrogenase (DHODH), a target enzyme for quinofumelin, was examined. The Homo sapiens DHODH (HsDHODH) assay system was developed to compare the selectivity of quinofumelin for fungi with that for mammals. The IC50 values of quinofumelin for Pyricularia oryzae DHODH (PoDHODH) and HsDHODH were 2.8 nM and >100 µM, respectively. Quinofumelin was highly selective for fungal over human DHODH. Additionally, we constructed recombinant P. oryzae mutants where PoDHODH (PoPYR4) or HsDHODH was inserted into the PoPYR4 disruption mutant. At quinofumelin concentration of 0.01-1 ppm, the PoPYR4 insertion mutants could not grow, but the HsDHODH gene-insertion mutants thrived. This indicates that HsDHODH is a substitute for PoDHODH, and quinofumelin could not inhibit HsDHODH as in the HsDHODH enzyme assay. Comparing the amino acid sequences of human and fungal DHODHs indicates that the significant difference at the ubiquinone-binding site contributes to the species selectivity of quinofumelin.

18.
Front Oncol ; 13: 1287088, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38023140

RESUMEN

For decades, lobectomy has been the recommended surgical procedure for non-small cell lung cancer (NSCLC), including for small-sized lesions. However, two recent pivotal clinical trials conducted by the Japanese Clinical Oncology Group/West Japan Oncology Group (JCOG0802/WJOG4607L) and the Cancer and Leukemia Group B (CALGB140503), which compared the survival outcomes between lobectomy and sublobar resection (the JCOG0802/WJOG4607L included only segmentectomy, not wedge resection), demonstrated the efficacy of sublobar resection in patients with early-stage peripheral lung cancer measuring ≤ 2 cm. The JCOG0802/WJOG4607L demonstrated the superiority of segmentectomy over lobectomy with respect to overall survival, implying the survival benefit conferred by preservation of the lung parenchyma. Subsequently, the JCOG1211 also demonstrated the efficacy of segmentectomy, even for NSCLC, measuring up to 3 cm with the predominant ground-glass opacity phenotype. Segmentectomy has become the standard of care for early-stage NSCLC and its indications are expected to be further expanded to include solid lung cancers > 2 cm. However, local control is still a major concern for segmentectomy for higher-grade malignant tumors. Thus, the indications of segmentectomy, especially for patients with radiologically pure-solid NSCLC, remain controversial due to the aggressive nature of the malignancy. In this study, we reviewed previous studies and discussed the efficacy of segmentectomy for patients with such tumors.

19.
Biomolecules ; 13(9)2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37759777

RESUMEN

Several clinical trials have been revolutionizing the perioperative treatment of early-stage non-small cell lung cancer (NSCLC). Many of these clinical trials involve cancer immunotherapies with antibody drugs that block the inhibitory immune checkpoints programmed death 1 (PD-1) and its ligand PD-L1. While these new treatments are expected to improve the treatment outcome of NSCLC patients after pulmonary resection, several major clinical questions remain, including the appropriate timing of immunotherapy (neoadjuvant, adjuvant, or both) and the identification of patients who should be treated with neoadjuvant and/or adjuvant immunotherapies, because some early-stage NSCLC patients are cured by surgical resection alone. In addition, immunotherapy may induce immune-related adverse events that will require permanent treatment in some patients. Based on this fact as well, it is desirable to select appropriate patients for neoadjuvant/adjuvant immunotherapies. So far, data from several important trials have been published, with findings demonstrating the efficacy of adjuvant atezolizumab (IMpower010 trial), neoadjuvant nivolumab plus platinum-doublet chemotherapy (CheckMate816 trial), and several perioperative (neoadjuvant plus adjuvant) immunotherapies (AEGEAN, KEYNOTE-671, NADIM II, and Neotorch trials). In addition to these key trials, numerous clinical trials have reported a wealth of data, although most of the above clinical questions have not been completely answered yet. Because there are so many ongoing clinical trials in this field, a comprehensive understanding of the results and/or contents of these trials is necessary to explore answers to the clinical questions above as well as to plan a new clinical trial. In this review, we comprehensively summarize the recent data obtained from clinical trials addressing such questions.

20.
JTCVS Open ; 14: 502-522, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37425462

RESUMEN

Objectives: Despite the prognostic impacts of preoperative fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography examination, fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography-based prognosis prediction has not been used clinically because of the disparity in data between institutions. By applying an image-based harmonized approach, we evaluated the prognostic roles of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters in clinical stage I non-small cell lung cancer. Methods: We retrospectively examined 495 patients with clinical stage I non-small cell lung cancer who underwent fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography examinations before pulmonary resection between 2013 and 2014 at 4 institutions. Three different harmonization techniques were applied, and an image-based harmonization, which showed the best-fit results, was used in the further analyses to evaluate the prognostic roles of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters. Results: Cutoff values of image-based harmonized fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters, maximum standardized uptake, metabolic tumor volume, and total lesion glycolysis were determined using receiver operating characteristic curves that distinguish pathologic high invasiveness of tumors. Among these parameters, only the maximum standardized uptake was an independent prognostic factor in recurrence-free and overall survivals in univariate and multivariate analyses. High image-based maximum standardized uptake value was associated with squamous histology or lung adenocarcinomas with higher pathologic grades. In subgroup analyses defined by ground-glass opacity status and histology or by clinical stages, the prognostic impact of image-based maximum standardized uptake value was always the highest compared with other fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters. Conclusions: The image-based fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography harmonization was the best fit, and the image-based maximum standardized uptake was the most important prognostic marker in all patients and in subgroups defined by ground-glass opacity status and histology in surgically resected clinical stage I non-small cell lung cancers.

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