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1.
Respirology ; 29(5): 396-404, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38246887

RESUMEN

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.


Asunto(s)
Neoplasias Pulmonares , Linfadenopatía , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Estudios Prospectivos , Broncoscopía/métodos , Mediastino/patología , Biopsia Guiada por Imagen , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Linfadenopatía/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Instrumentos Quirúrgicos , Estudios Retrospectivos
2.
Cancer Sci ; 114(11): 4401-4412, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37732498

RESUMEN

Comprehensive genomic profiling (CGP) is implemented to detect actionable gene aberrations and design matched therapies. Although malignant thoracic tumors are commonly detected through respiratory endoscopy, it is questionable whether the small specimens obtained thereof are sufficient for CGP. Therefore, this study aimed to investigate the suitability of respiratory endoscopy for sampling primary and metastatic thoracic tumors for CGP. Patients whose specimens were collected through respiratory endoscopy and assessed by pathologists to determine their suitability for CGP at our institution between June 2019 and May 2022 were reviewed retrospectively. The suitability of each procedure as a sampling technique for CGP and, in the cases actually analyzed, the distribution of the detected gene aberration were assessed. In total, 122 patients were eligible for analysis; the median age was 61 (range, 29-86) years, and 71 (58.2%) patients were male. Primary intrathoracic tumors were found in 91 (74.6%) cases, including 84 (68.9%) primary lung cancers; the remaining thoracic metastases of extrathoracic origin included various types. The suitability rates of specimens obtained using conventional bronchoscopy with and without cryobiopsy, endobronchial ultrasound-guided transbronchial needle aspiration, and medical thoracoscopy were 82.8% (24/29), 70.4% (19/27), 72.9% (35/48), and 100% (18/18), respectively. Of the 96 cases judged suitable, 83 were subjected to CGP, and all but one were successfully analyzed. Finally, 47 (56.6%) patients had at least one actionable gene aberration and eight (9.6%) were treated with the corresponding targeted therapies. In conclusion, specimens obtained through respiratory endoscopy are suitable for CGP; medical thoracoscopy and cryobiopsy in conventional bronchoscopy are particularly useful.


Asunto(s)
Neoplasias Pulmonares , Neoplasias Torácicas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Neoplasias Torácicas/genética , Neoplasias Torácicas/diagnóstico , Broncoscopía/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Genómica , Neoplasias Pulmonares/patología
3.
Br J Cancer ; 129(12): 2003-2013, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37731022

RESUMEN

BACKGROUND: Delta-like ligand 3 (DLL3) is a therapeutic target in small-cell lung cancer (SCLC). However, how DLL3 expression status affects the tumor microenvironment (TME) and clinical outcomes in SCLC remains unclear. METHODS: This retrospective study included patients with postoperative limited-stage (LS)-SCLC and extensive-stage (ES)-SCLC treated with platinum and etoposide (PE) plus anti-programmed cell death ligand 1 (PD-L1) antibody. We investigated the relationship of DLL3 expression with TME, mutation status, tumor neoantigens, and immunochemotherapy. RESULTS: In the LS-SCLC cohort (n = 59), whole-exome sequencing revealed that DLL3High cases had significantly more neoantigens (P = 0.004) and a significantly higher rate of the signature SBS4 associated with smoking (P = 0.02) than DLL3Low cases. Transcriptome analysis in the LS-SCLC cohort revealed that DLL3High cases had significantly suppressed immune-related pathways and dendritic cell (DC) function. SCLC with DLL3High had significantly lower proportions of T cells, macrophages, and DCs than those with DLL3Low. In the ES-SCLC cohort (n = 30), the progression-free survival associated with PE plus anti-PD-L1 antibody was significantly worse in DLL3High cases than in DLL3Low cases (4.7 vs. 7.4 months, P = 0.01). CONCLUSIONS: Although SCLC with DLL3High had a higher neoantigen load, these tumors were resistant to immunochemotherapy due to suppressed tumor immunity by inhibiting antigen-presenting functions.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Ligandos , Microambiente Tumoral , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Etopósido/uso terapéutico , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética
4.
Jpn J Clin Oncol ; 53(9): 829-836, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37340759

RESUMEN

BACKGROUND: The use of endobronchial Watanabe spigots for intractable secondary pneumothorax in patients with cancer has not been adequate. This study aimed to investigate the use of endobronchial Watanabe spigots for intractable pneumothorax in patients with malignant tumors. METHODS: Consecutive patients with malignant tumors who underwent occlusion with an endobronchial Watanabe spigot for intractable pneumothorax associated with perioperative treatment or drug therapy at our institution between January 2014 and February 2022 were reviewed. RESULTS: Of the 32 cases in which an endobronchial Watanabe spigot was used, six were excluded; we thus evaluated 26 cases in which the chest tube was removed. Chest tubes were removed in 19 cases (73.1%) and could not be removed and required surgical treatment under general anesthesia in seven patients (26.9%), of which four (14.8%) underwent open-window thoracostomy. Half of the patients were treated with both an endobronchial Watanabe spigot and pleurodesis. Although thin-slice chest computed tomography revealed a fistula in 15 patients, the chest tube was removed in 11 (57.9%) patients. A significant difference was only observed in patients with a history of heavy smoking. CONCLUSIONS: The chest tube removal rate was comparable to those reported in previous studies. An endobronchial Watanabe spigot may be a useful treatment option for intractable cancer-related pneumothorax.


Asunto(s)
Embolización Terapéutica , Neoplasias , Neumotórax , Humanos , Neumotórax/terapia , Neumotórax/cirugía , Broncoscopía/métodos , Embolización Terapéutica/métodos , Tubos Torácicos
5.
Respirology ; 28(2): 152-158, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36288803

RESUMEN

BACKGROUND AND OBJECTIVE: The diagnostic yield of thin bronchoscopy with radial probe endobronchial ultrasound (rEBUS) of peripheral pulmonary lesions into which the rEBUS probe cannot be inserted is unsatisfactory. In such cases, adding ultrathin bronchoscopy may be an option. We evaluated the efficacy of sequential ultrathin bronchoscopy for peripheral pulmonary lesions into which the rEBUS probe could not be inserted during thin bronchoscopy. METHODS: In this multicentre prospective study, patients with peripheral pulmonary lesions ≤30 mm in diameter underwent rEBUS-guided transbronchial biopsy using a 4.0 mm diameter thin bronchoscope. In patients with lesions into which a rEBUS probe could not be inserted using that bronchoscope, bronchoscopy using a 3.0 mm diameter ultrathin bronchoscope was performed. RESULTS: A total of 342 patients were enrolled and 340 were analysed. Among them, 87 patients with lesions of a median longest diameter of 17.5 mm underwent thin bronchoscopy followed by ultrathin bronchoscopy. Of the 87 patients, the rEBUS probe was successfully inserted into the lesions via the ultrathin bronchoscope in 50 patients (57.5%). Of the 87 patients, the diagnostic yields of thin bronchoscopy and ultrathin bronchoscopy were 12.6% (11 of 87) and 41.4% (36 of 87), respectively (p < 0.001). CONCLUSION: Ultrathin bronchoscopy affords a higher diagnostic yield for lesions into which a rEBUS probe cannot be inserted via a thin bronchoscope.


Asunto(s)
Broncoscopía , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Estudios Prospectivos , Broncoscopios , Biopsia , Endosonografía
6.
Respiration ; 102(2): 143-153, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36543151

RESUMEN

BACKGROUND: Endobronchial ultrasound (EBUS)-guided intranodal forceps biopsy (IFB), a diagnostic bronchoscopic technique for intrathoracic lymphadenopathy, is performed following EBUS-guided transbronchial needle aspiration (TBNA). The current EBUS-IFB technique is complex and provides small sample volumes. We modified this technique to allow the use of standard-sized forceps. OBJECTIVES: The aim of this study was to assess the feasibility of the modified EBUS-IFB technique, which combines standard-sized forceps with standard EBUS-TBNA equipment. METHOD: This retrospective analysis included consecutive patients scheduled for EBUS-TBNA with attempted additional IFB between July 2020 and March 2021. The feasibility indices of IFB, technical success rate, diagnostic accuracy, and major complications were retrospectively investigated. We performed semi-quantitative evaluation of the histological specimens and univariable analyses to identify factors associated with IFB failure. RESULTS: During the study period, 295 patients underwent 307 EBUS-TBNAs; 195 cases were included in the analyses. Target lesions were mainly mediastinal lymph nodes (134 cases, 68.7%); the most frequent sites were #7 (61 cases) and #4R (50 cases). The median lesion size was 16.1 mm, the technical IFB success rate was 90.8%, and the diagnostic accuracy of the TBNA and IFB combination was 99.5%. One patient was lost to follow-up. Univariable analyses did not identify any factors involved in technical IFB failure. Major complications of pneumonia and pneumothorax occurred in 2 cases (1.0%). The median histological score was significantly higher in the IFB group than in the TBNA group (1.67 vs. 1.50, p = 0.032). CONCLUSIONS: Modified EBUS-IFB, combining standard-sized forceps with common EBUS-TBNA equipment, is feasible with few major complications.


Asunto(s)
Broncoscopía , Mediastino , Humanos , Estudios Retrospectivos , Estudios de Factibilidad , Broncoscopía/métodos , Ganglios Linfáticos/patología , Biopsia Guiada por Imagen , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos
7.
Eur Respir J ; 59(5)2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34625482

RESUMEN

BACKGROUND: Guide sheaths (GSs) have been widely used during radial probe endobronchial ultrasound-guided transbronchial biopsy (rEBUS-TBB) of peripheral pulmonary lesions. However, it remains unknown whether a GS enhances the diagnostic yield. We compared the diagnostic yields of small peripheral pulmonary lesions between rEBUS-TBB with and without a GS. METHODS: In eight institutions, patients with peripheral pulmonary lesions ≤30 mm in diameter were enrolled and randomised to undergo rEBUS-TBB with a GS (GS group) or without a GS (non-GS group) using a 4.0-mm thin bronchoscope, virtual bronchoscopic navigation and fluoroscopy. The primary end-point was the diagnostic yield of the histology specimens. RESULTS: A total of 605 patients were enrolled; ultimately, data on 596 (300 in the GS group and 296 in the non-GS group) with peripheral pulmonary lesions having a longest median diameter of 19.6 mm were analysed. The diagnostic yield of histological specimens from the GS group was significantly higher than that from the non-GS group (55.3% versus 46.6%; p=0.033). Interactions were evident between the diagnostic yields, procedures, lobar locations (upper lobe versus other regions; p=0.003) and lesion texture (solid versus part-solid nodules; p=0.072). CONCLUSIONS: The diagnostic yield for small peripheral pulmonary lesions afforded by rEBUS-TBB using a GS was higher than that without a GS.


Asunto(s)
Broncoscopía , Neoplasias Pulmonares , Biopsia/métodos , Broncoscopía/métodos , Endosonografía/métodos , Humanos , Biopsia Guiada por Imagen/métodos , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/patología , Ultrasonografía Intervencional
8.
Respiration ; 101(12): 1148-1156, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36327951

RESUMEN

BACKGROUND: Several factors have been reported to affect the diagnostic yield of bronchoscopy with radial endobronchial ultrasound (R-EBUS) for peripheral pulmonary lesions (PPLs). However, it is difficult to accurately predict the diagnostic potential of bronchoscopy for each PPL in advance. OBJECTIVES: Our objective was to establish a predictive model to evaluate the diagnostic yield before the procedure. METHOD: We retrospectively analysed consecutive patients who underwent diagnostic bronchoscopy with R-EBUS between April 2012 and October 2015. We assessed the factors that were predictive of successful bronchoscopic diagnosis of PPLs with R-EBUS using a multivariable logistic regression model. The accuracy of the predictive model was evaluated using the receiver operator characteristic area under the curve (ROC AUC). Internal validation was analysed using 10-fold stratified cross-validation. RESULTS: We analysed a total of 1,634 lesions; the median lesion size was 25.0 mm. Of these, 1,138 lesions (69.6%) were successfully diagnosed. In the predictive logistic model, significant factors affecting the diagnostic yield were lesion size, lesion structure, bronchus sign, and visible on chest X-ray. The predictive model consisted of seven factors: lesion size, lesion lobe, lesion location from the hilum, lesion structure, bronchus sign, visibility on chest X-ray, and background lung. The ROC AUC of the predictive model was 0.742 (95% confidence interval: 0.715-0.769). Internal validation using 10-fold stratified cross-validation revealed a mean ROC AUC of 0.734. CONCLUSIONS: The predictive model using the seven factors revealed a good performance in estimating the diagnostic yield.


Asunto(s)
Broncoscopía , Neoplasias Pulmonares , Humanos , Broncoscopía/métodos , Estudios Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X/métodos , Endosonografía/métodos , Pulmón/diagnóstico por imagen , Pulmón/patología
9.
BMC Pulm Med ; 22(1): 226, 2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35689261

RESUMEN

BACKGROUND: Cryobiopsy is an established technique that yields larger and higher-quality samples than does a forceps biopsy. However, it remains underutilised in the diagnosis of peripheral pulmonary lesions (PPLs), mainly because of difficulties in handling conventional cryoprobes. A recently introduced single-use cryoprobe with a smaller diameter and more flexibility than conventional ones may improve its diagnostic ability for PPLs. We conducted this prospective study to evaluate the feasibility of transbronchial cryobiopsy in the diagnoses of PPLs, using a new 1.7-mm cryoprobe. METHODS: The study included patients with PPLs less than 30 mm in diameter scheduled to undergo bronchoscopy. All the procedures were performed using a combination of virtual bronchoscopic navigation, radial endobronchial ultrasound (R-EBUS) and X-ray fluoroscopy, and all the samples were collected using the cryoprobe alone. Thereafter, we assessed the diagnostic outcomes and safety profiles. RESULTS: A total of 50 patients were enrolled and underwent cryobiopsy. The median lesion size was 20.8 mm (range, 8.2-29.6 mm), and the negative bronchus sign was seen in 34% of lesions. The diagnostic yield was 94% (95% confidence interval, 83.5-98.8%). A positive bronchus sign had a significantly higher diagnostic yield than did a negative bronchus sign (100% vs. 82.4%; P = 0.035). The yield was achieved regardless of other variables, including lesion size, location, and R-EBUS findings. The major complications were mild and moderate bleeding in 28% and 62% of patients, respectively. Pneumothorax was identified in one patient. CONCLUSION: Transbronchial cryobiopsy using the new 1.7-mm cryoprobe is a feasible procedure that has the potential to increase the diagnostic accuracy for PPLs. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCT1032200065. Registered July 8 2020, https://jrct.niph.go.jp/en-latest-detail/jRCT1032200065.


Asunto(s)
Broncoscopía , Neoplasias Pulmonares , Biopsia/métodos , Broncoscopía/métodos , Endosonografía/métodos , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Estudios Prospectivos
10.
Oncologist ; 24(8): 1033-e617, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31040252

RESUMEN

LESSONS LEARNED: In terms of efficacy and safety, good results were obtained with S-1 and paclitaxel (PTX) combination therapy.The findings suggest that S-1 and PTX combination therapy is a feasible treatment option in patients with previously treated non-small cell lung cancer. BACKGROUND: Although monotherapy with cytotoxic agents, including docetaxel and pemetrexed, is recommended for patients with previously treated advanced non-small cell lung cancer (NSCLC), its outcomes are unsatisfactory. S-1 is an oral fluoropyrimidine agent that consists of tegafur, 5- chloro-2, 4-dihydroxypyridine, and potassium oxonate. S-1 is approved for patients with gastric cancer in 7 Asian countries and 15 European countries. It is also approved for patients with eight type of cancers, including NSCLC, in Japan. We evaluated the efficacy and toxicity of S-1 and paclitaxel (PTX) combination therapy in patients with previously treated NSCLC. METHODS: Oral S-1 was administered thrice weekly on days 1-14 at 80, 100, and 120 mg/day in patients with body surface areas of <1.25, 1.25-1.5, and >1.5 m2, respectively. PTX was administered at 80 mg/m2 on days 1 and 8. Primary endpoint was response rate, and secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled, with response and disease control rates of 27.5% and 75.0%, respectively (Fig. 1). Median PFS and OS were 6.5 and 20.7 months, respectively. Grade 3/4 anemia and thrombocytopenia were seen in five (12%) and one (2%) patients, respectively. Febrile neutropenia occurred in three patients (7%). Common grade 3/4 nonhematological toxicities were stomatitis (5% of patients), diarrhea (7% of patients), and interstitial lung disease (one patient). No treatment-related deaths were observed. CONCLUSION: This S-1 and PTX cotherapy dose and schedule showed satisfactory efficacy, with mild toxicities, in patients with previously treated advanced NSCLC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Ácido Oxónico/administración & dosificación , Paclitaxel/administración & dosificación , Tegafur/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Anemia/inducido químicamente , Anemia/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Neutropenia Febril Inducida por Quimioterapia/etiología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ácido Oxónico/efectos adversos , Paclitaxel/efectos adversos , Supervivencia sin Progresión , Tegafur/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/epidemiología
11.
Oncologist ; 24(4): 459-e131, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30578309

RESUMEN

LESSONS LEARNED: Coadministration of S-1 and paclitaxel in elderly patients with advanced non-small cell lung cancer showed favorable efficacy.Coadministration of S-1 and paclitaxel in elderly patients with advanced non-small lung cancer showed tolerable toxicity. BACKGROUND: Although monotherapy with cytotoxic agents including docetaxel or vinorelbine are recommended for elderly patients with advanced non-small cell lung cancer (NSCLC), the outcome is not satisfactory. We evaluated the efficacy and safety of S-1 and paclitaxel (PTX) as a first-line cotreatment in elderly patients with advanced NSCLC. METHODS: Oral S-1 was administered on days 1-14 every 3 weeks at 80, 100, and 120 mg per day for patients with body surface area < 1.25 m2, 1.25-1.5 m2, and > 1.5 m2, respectively. PTX was administered at 80 mg/m2 on days 1 and 8. The primary endpoint was response rate, and secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Seventeen patients were enrolled with response and disease control rates of 47.1% and 88.2%, respectively. Median PFS and OS were 5.6 and 35.0 months, respectively. Hematological grade 3 or 4 toxicities included leukopenia (55.8%), neutropenia (52.9%), febrile neutropenia (11.8%), and anemia (11.8%). Nonhematological grade 3 toxicities included stomatitis (23.5%), diarrhea (5.9%), and interstitial lung disease (5.9%), and grade 5 toxicities included interstitial lung disease (5.9%). CONCLUSION: This S-1 and PTX cotherapy dose and schedule showed satisfactory efficacy with mild toxicities in elderly patients with advanced NSCLC.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Ácido Oxónico/administración & dosificación , Paclitaxel/administración & dosificación , Pronóstico , Tasa de Supervivencia , Tegafur/administración & dosificación
12.
Invest New Drugs ; 37(2): 291-296, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30121935

RESUMEN

This phase I study was aimed at determining the maximum tolerated dose (MTD) and recommended dose (RD) for oral S-1 plus paclitaxel combination therapy in elderly patients with non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients (age, >70 years) with stage III/IV NSCLC were treated with paclitaxel intravenously at four dose levels (DLs), 60, 70, 80, and 90 mg/m2, on day 1 and 8, and with S-1 (80 mg/m2) orally on days 1-14 every 3 weeks. MTD was defined as the dose at which two of the initial three patients experienced dose-limiting toxicities (DLTs). Three patients were added when the initial three patients experienced DLTs. The dose administered in three of the six patients with DLTs met the definition of MTD. The RD was defined as a dose 1 DL below the MTD. Fifteen patients including six on DL 1 and three each on DLs 2, 3, and 4 were enrolled. One patient experienced a DLT (febrile neutropenia) at DL 1. The remaining DLTs were noted at DL 4 (in one patient each): febrile neutropenia, grade (G) 3 skin rash, G3 diarrhea, G3 stomatitis, and G3 international normalized ratio (INR) elevation. The MTD of paclitaxel was 90 mg/m2. The RD for both S-1 and paclitaxel was 80 mg/m2 (DL 3). The response rate was 45.5% (8 of 15 patients achieved a partial response). In conclusion, the RD of both S-1 and paclitaxel was 80 mg/m2 in the combination therapy for chemotherapy-naïve patients with advanced NSCLC.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Dosis Máxima Tolerada , Ácido Oxónico/administración & dosificación , Paclitaxel/administración & dosificación , Pronóstico , Tegafur/administración & dosificación , Distribución Tisular
13.
Pathol Int ; 69(12): 721-726, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31724260

RESUMEN

We herein describe a rare case of low-grade endobronchial tumor that exhibited two distinct features of typical carcinoid and acinic cell carcinoma (ACC) by immunohistochemical and ultrastructure study. ACC was suspected on transbronchial biopsy. The resected specimen showed that the tumor surface comprised an acinic cell component (40% of the tumor), and the central area comprised typical carcinoid (60% of the tumor). The acinic cell component was positive for chromogranin A, synaptophysin and alpha-1-antichymotrypsin. Additionally, this component showed focal apical membranous staining for DOG1 and weak positivity for BCL10 and SOX10. Conversely, the carcinoid component was negative for all proteins except for chromogranin A and synaptophysin. Electron microscopy indicated zymogen-type granules (600-800 nm in diameter) in the acinic cell component, whereas neuroendocrine-type granules (200-300 nm in diameter) were observed in the carcinoid component. Nuclear NR4A3 immunostaining, which is highly specific for ACC of the salivary gland, was negative in this case. We conclude that the pulmonary carcinoid tumor with true zymogen-type granules could be seen but showed superficial similarities to ACC based on negative nuclear staining for NR4A3. Pulmonary carcinoids encompass a wide morphological spectrum and may exhibit prominent acinic cell differentiation.


Asunto(s)
Biomarcadores de Tumor/análisis , Tumor Carcinoide/diagnóstico por imagen , Carcinoma de Células Acinares/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Anciano , Tumor Carcinoide/patología , Carcinoma de Células Acinares/patología , Diferenciación Celular , Femenino , Humanos , Inmunohistoquímica , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/patología , Microscopía Electrónica , Vesículas Secretoras/patología , Tomografía Computarizada por Rayos X
15.
Invest New Drugs ; 36(5): 903-910, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29846848

RESUMEN

Background A global multicenter study demonstrated superiority of carboplatin + nab-paclitaxel (PTX) therapy compared to carboplatin + PTX in terms of response rate (RR) and non-inferiority in terms of progression free survival (PFS) and overall survival (OS) in untreated patients with stage IIIB/IV non-small cell lung cancer; no clinical findings have so far been reported on maintenance therapies with nab-PTX. The aim of this study was to determine the efficacy and safety of maintenance therapy with nab-PTX following carboplatin + nab-PTX combination therapy. Methods Carboplatin (AUC 6) was administered on Day 1; and nab-PTX 100 mg/m2 on Days 1, 8, and 15, and dosing was repeated in 4 courses of 4 weeks each. In patients with clinical response was observed at the end of the 4th course, nab-PTX maintenance therapy was repeated. Results Out of 39 patients included in the efficacy analysis, 19 (48.7%) patients completed the induction therapy and 15 (38.5%) were transitioned to maintenance therapy. The median PFS in the maintenance phase was 6.5 (90%CI 1.4-11.4) months. The median OS in 15 patients was 12.6 (95%CI: 7.4-not reached). Grade ≥ 3 toxicities observed in more than 5% of patients were neutropenia (55.0%), anemia (15.0%), and febrile neutropenia (5.0%), with no increase during the maintenance phase. Conclusions Although statistically significance was not demonstrated presumably due to a limited transition rate from induction to maintenance phase, nab-PTX was suggested to be a useful treatment option following the induction therapy with nab-PTX in patients with advanced NSCLC.


Asunto(s)
Albúminas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/administración & dosificación , Anciano , Anciano de 80 o más Años , Albúminas/efectos adversos , Anemia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Paclitaxel/efectos adversos
16.
Photodiagnosis Photodyn Ther ; 41: 103315, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36739957

RESUMEN

Photodynamic therapy (PDT) has been shown to be effective and safe in the treatment of malignant central airway stenosis. However, the laser dose for talaporfin PDT is unclear. We herein review cases where talaporfin PDT was used to treat malignant central airway stenosis. A total of 17 lesions were treated with talaporfin PDT at laser doses of 50-150 J/cm2. Improvement of airway stenosis was observed in all cases except for 1 lesion treated with a dose of 50 J/cm2. The results show that talaporfin PDT with 100 J/cm2 of laser dose is a feasible treatment for malignant central airway stenosis. (This is a secondary publication from the Journal of Japan Society for Laser Surgery and Medicine 2022; 43(1): 9-12.).


Asunto(s)
Fotoquimioterapia , Porfirinas , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Constricción Patológica/tratamiento farmacológico , Porfirinas/uso terapéutico , Rayos Láser
17.
Thorac Cancer ; 14(14): 1306-1310, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36929314

RESUMEN

Mucoepidermoid carcinoma (MEC) is a rare salivary gland tumor, accounting for 0.2% of all lung tumors. The standard treatment for MEC of the primary bronchus is surgery, although intraluminal bronchoscopic treatment has recently become an option. A 68-year-old man presented with an asymptomatic bronchial tumor in the right intermediate bronchus. The tumor was resected using a high-frequency snare (HFS) during bronchoscopy, and the specimen was pathologically diagnosed as low-grade MEC. A residual lesion was detected in the resected area by autofluorescence imaging. The tumor appeared to be localized within the subepithelial layer without metastases, and photodynamic therapy (PDT) was performed as a local treatment. The patient had no recurrence for 18 months. PDT is effective and safe for patients with centrally located early-stage lung cancer, but there are few reports of its use for rare tumors, such as MEC. In this case, PDT allowed for local control and avoided surgery, including bronchoplasty, for MEC. Combined treatment of tumor reduction by HFS and PDT of the residual lesion may be an optimal treatment for MEC of the bronchus.


Asunto(s)
Neoplasias de los Bronquios , Carcinoma Mucoepidermoide , Fotoquimioterapia , Masculino , Humanos , Anciano , Carcinoma Mucoepidermoide/tratamiento farmacológico , Carcinoma Mucoepidermoide/cirugía , Carcinoma Mucoepidermoide/patología , Neoplasias de los Bronquios/tratamiento farmacológico , Neoplasias de los Bronquios/cirugía , Neoplasias de los Bronquios/patología , Bronquios/patología , Broncoscopía/métodos
18.
Diagnostics (Basel) ; 13(6)2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36980372

RESUMEN

The presence of computed tomography bronchus sign (CT-BS) substantially increases the diagnostic yield of peripheral pulmonary lesions. However, the clinical significance of subdividing CT-BS remains controversial. We classified bronchus types on CT into six subtypes (CT-BS group I: types Ia-Ic with the bronchus connected within the lesion, group II: types IIa-IIc without connection) to clarify the differences in their characteristics and investigate the factors associated with diagnosis during radial endobronchial ultrasound (rEBUS)-guided bronchoscopy. In total, 1021 cases were analyzed. Our findings in diagnostic yields were that in CT-BS group I, penetrating type Ic was inferior to obstructed type Ia and narrowing type Ib (59.0% vs. 80.0% and 76.3%, p < 0.001, p = 0.004); in CT-BS group II, compressed type IIa showed no difference when compared with invisible type IIb and uninvolved type IIc (IIa: 52.8% vs. IIb: 46.3% and IIc: 35.7%, p = 0.253). Multivariable analysis revealed that bronchus type (types Ia and Ib vs. Ic) was a significant independent predictor of successful diagnosis in CT-BS group I (odds ratio, 1.78; 95% confidence interval, 1.04-3.05; p = 0.035), along with known factors such as rEBUS visualization. CT-BS subclassification may provide useful information regarding the bronchoscopic technique to facilitate accurate diagnosis.

19.
Thorac Cancer ; 14(10): 953-957, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36828806

RESUMEN

Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) have a poor prognosis and are often diagnosed at an inoperable advanced stage. Herein, we report a case of SMARCA4-UT diagnosed by endobronchial ultrasound-guided transbronchial cryobiopsy (EBUS-cryo). The patient was a 42-year-old man with a history of smoking. Chest computed tomography revealed a right upper lobe nodule and an enlarged #11s lymph node. Core tissues could not be obtained by EBUS-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis and mediastinal staging; hence, EBUS-guided intranodal forceps biopsy (EBUS-IFB) was performed. However, a detailed diagnosis beyond poorly differentiated carcinoma could not be obtained. Subsequent EBUS-cryo provided sufficient specimens for immunohistochemical and molecular evaluation and SMARCA4-UT was definitively diagnosed. Thus, EBUS-cryo could be of additional diagnostic value for uncommon tumors, such as SMARCA4-UT, conjointly with EBUS-IFB as well as EBUS-TBNA.


Asunto(s)
Neoplasias Pulmonares , Linfadenopatía , Masculino , Humanos , Adulto , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Broncoscopía/métodos , Mediastino/patología , Linfadenopatía/patología , Estadificación de Neoplasias , ADN Helicasas , Proteínas Nucleares , Factores de Transcripción
20.
Transl Lung Cancer Res ; 12(11): 2169-2180, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38090520

RESUMEN

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is recommended for nodal staging in non-small cell lung cancer (NSCLC). Although this method may rarely fail, reports on the causes are few. We therefore retrospectively investigated the factors causing failure of nodal staging by EBUS-TBNA. Methods: Consecutive patients who underwent EBUS-TBNA at National Cancer Center Hospital between January 2017 and December 2020 for systematic nodal staging in NSCLC were extracted. The nodal stages at diagnosis including EBUS-TBNA and at treatment were investigated separately, and unmatched cases were defined as failures. Factors associated with them were explored while dividing the cases into punctured and not-punctured groups. Results: Of the 264 patients, 21 (8.0%) failed the nodal staging: 10 (3.8%) in the punctured group and 11 (4.2%) in the not-punctured group. The latter was subdivided into the following three categories: (I) difficult-to-reach; (II) omission due to false-positive rapid on-site cytologic evaluation (ROSE) results; and (III) non-significant EBUS findings. The nodal staging failure rate was significantly higher in cases with driver oncogenes positive than in those negative (16.1% vs. 3.3%, P=0.026) for adenocarcinomas. Note that all cases categorized as non-significant EBUS findings involved various driver oncogenes. Conclusions: The present study demonstrated the risk of false positives with ROSE and the involvement of driver oncogenes as factors associated with nodal staging failure in NSCLC by EBUS-TBNA, in addition to limitations of the procedure itself, including sampling performance and reachability. Especially in adenocarcinoma patients with driver oncogenes, their nodal staging results should be interpreted cautiously.

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