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1.
Acta Med Okayama ; 77(6): 671-674, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145943

RESUMO

A 74-year-old Japanese woman presented with a 45-year history of refractory asthma. She had been treated with inhaled corticosteroids, a long-acting ß2-agonist, and a long-acting muscarinic antagonist for 6 months. She also had a repeated viral infection. Her condition had been characterized as a refractory asthma associated with type 2 and non-type 2 traits. We began treatment with tezepelumab. The control of the patient's asthma symptoms and quality of life improved greatly within 1 month (changes in eosinophil count from 748 to 96 /µL, in FeNO from 32 to 17 ppb, in the Asthma Quality of Life Questionnaire score from 3.59 to 6.68, and in the Asthma Control Test score from 13 to 23). Tezepelumab was effective as an initial biologic agent for a patient with refractory asthma associated with type 2 and non-type 2 traits.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Humanos , Feminino , Idoso , Antiasmáticos/uso terapêutico , Qualidade de Vida , Asma/complicações , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico
2.
Eur Respir J ; 59(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34625482

RESUMO

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.


Assuntos
Broncoscopia , Neoplasias Pulmonares , Biópsia/métodos , Broncoscopia/métodos , Endossonografia/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/patologia , Ultrassonografia de Intervenção
3.
Jpn J Clin Oncol ; 51(8): 1269-1276, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34115855

RESUMO

BACKGROUND: In a phase I study, afatinib (30 mg/body daily) plus bevacizumab (15 mg/kg every 3 weeks) was well tolerated and showed favourable outcomes in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer. Herein, we report the 2-year progression-free survival, overall survival and safety profile of these patients. METHODS: Chemo-naïve patients with EGFR-mutant advanced non-small-cell lung cancer were enrolled. One group of patients received 40 mg afatinib daily and 15 mg/kg bevacizumab every 3 weeks (level 0) until disease progression or severe toxicity. Another group of patients received 30 mg afatinib daily and the same dose of bevacizumab (level 1). Dose-limiting toxicity was the primary endpoint, whereas long-term progression-free survival, overall survival and tolerability were secondary endpoints. Survival rates were estimated using the Kaplan-Meier method. RESULTS: The study included 19 patients (level 0: 5; level - 1: 14). Until the data cut-off date, seven patients continued the treatment, whereas 12 discontinued due to disease progression (n = 5) or toxicity (n = 7). The median PFS was 24.2 months, while the median overall survival was not reached. All patients developed adverse effects. Diarrhoea and skin rash were frequently observed as severe adverse events (grade 3). A secondary EGFR mutation (T790M) was detected in two patients after progression. CONCLUSIONS: Prolonged follow-up revealed that combination therapy with afatinib and bevacizumab might improve survival outcomes in EGFR-mutant advanced non-small-cell lung cancer patients and seems to be promising. TRIAL REGISTRATION: UMIN000015944.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Mutação , Afatinib/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento
4.
Acta Med Okayama ; 75(4): 431-437, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34511609

RESUMO

This study aimed to evaluate whether there are differences in the attitudes and practices of cancer pain manage-ment between medical oncologists and palliative care physicians. An online nationwide survey was used to collect responses from board-certified medical oncologists and palliative care physicians in Japan. The survey questionnaire comprised 30 questions. The differences in responses between medical oncologists and palliative care physicians were examined. Out of the 1,227 questionnaires sent, 522 (42.5%) were returned. After apply-ing the exclusion criteria, 445 questionnaires (medical oncologists: n = 283; palliative care physicians: n = 162) were retained for analysis. Among the questions about potential barriers to optimal cancer pain man-agement, both medical oncologists and palliative care physicians considered the reluctance of patients to take opioids due to fear of adverse effects as the greatest barrier. Significantly different ratings between medical oncologists and palliative care physicians were observed on 5 of the 8 questions in this area. Significantly differ-ent ratings were observed for all questions concerning pain specialists and their knowledge. For effective cancer pain management, it is important to account for differences in attitudes and practice between medical oncolo-gists and palliative care physicians.


Assuntos
Dor do Câncer/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Oncologia/métodos , Cuidados Paliativos/métodos , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Analgésicos Opioides/uso terapêutico , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
5.
Water Sci Technol ; 83(7): 1511-1521, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33843739

RESUMO

Acidic biotrickling filters (BTF) can be used for simultaneous removal of hydrogen sulfide (H2S) and siloxane from biogas. In this study, the performance of a BTF under different acidic pH conditions was investigated. The removal profile of H2S showed that 90% of H2S removal was achieved during the first 0.4 m of BTF height with down-flow biogas. Decamethylcyclopentasiloxane (D5) removal decreased from 34.5% to 15.6% when the pH increased from 0.88 to 3.98. Furthermore, the high partition coefficient of D5 obtained in under higher pH condition was attributed to the higher total ionic strength resulting from the addition of sodium hydroxide solution and mineral medium. The linear increase in D5 removal with the mass transfer coefficient (kL) indicated that the acidic recycling liquid accelerated the mass transfer of D5 in the BTF. Therefore, the lower partition coefficient and higher kL under acidic pH conditions lead to the efficient removal of D5. However, the highly acidic pH 0.9 blocked mass transfer of H2S and O2 gases to the recycling liquid. Low sulfur oxidation activity and low Acidithiobacillus sp. content also deteriorated the biodegradation of H2S. Operating the BTF at pH 1.2 was optimal for simultaneously removing H2S and siloxane.


Assuntos
Biocombustíveis , Sulfeto de Hidrogênio , Biodegradação Ambiental , Reatores Biológicos , Filtração , Concentração de Íons de Hidrogênio , Siloxanas
6.
Jpn J Clin Oncol ; 50(12): 1447-1453, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-32869100

RESUMO

OBJECTIVES: Immune checkpoint inhibitors offer longer survival than chemotherapy in several clinical trials for advanced non-small cell lung cancer. In subset analyses of clinical trials, immune checkpoint inhibitors extended survival in patients aged ≥65 years, but the effects in patients aged ≥75 years are controversial. We performed multicenter, collaborative and retrospective analyses of immune checkpoint inhibitor efficacy and safety in non-small cell lung cancer patients aged ≥75 years. METHODS: We retrospectively studied 434 advanced non-small cell lung cancer patients who received immune checkpoint inhibitors from December 2015 to December 2017, and retrospectively applied the Geriatric (G) 8 screening tool with medical records. RESULTS: Of the 434 patients who received immune checkpoint inhibitors, 100 were aged ≥75 years. Five patients with performance status 3 were omitted from the final analysis. Immune checkpoint inhibitors were given as a first-line treatment to 20 patients. The objective response rates, median progression-free survival rates and median survival times were 35.0%, 6.1 months and 10.7 months for first-line treatment, and 20.0%, 2.9 months and 14.7 months for second- or later-line treatments, respectively. The median modified G8 score was 11.0. The median survival time was longer in the high modified G8 (≥12.0) group than in the low modified G8 (≤11.0) group (18.7 vs. 8.7 months; P = 0.02). Likewise, the median survival time was 15.5 months (performance status 0-1) vs. 3.2 months (performance status 2) (P < 0.01). The grade ≥ 2 immune-related adverse events incidence was 36.8%. CONCLUSIONS: In this study, immune checkpoint inhibitors were effective and tolerable for patients aged ≥75 years. The modified G8 screening tool and performance status were associated with the outcome of older non-small cell lung cancer patients treated with immune checkpoint inhibitors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Avaliação Geriátrica , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/mortalidade , Masculino , Intervalo Livre de Progressão , Estudos Retrospectivos
7.
Jpn J Clin Oncol ; 49(8): 762-765, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31090906

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have demonstrated long survival for the treatment of advanced non-small cell lung cancer (NSCLC). However, the effect and safety of ICI rechallenge have not been fully evaluated. The aim of this study was to investigate the efficacy and safety of ICI rechallenge in NSCLC patients. METHODS: We defined 'rechallenge' as re-administration of ICIs for patients who were previously treated with ICIs and discontinued treatment for any reason, and received subsequent chemotherapy. We retrospectively analyzed the histories of 434 patients with advanced NSCLC who received ICIs from December 2015 to December 2017 at seven centers. RESULTS: A total of 317 patients discontinued the ICI treatment, and 14 patients (4.4%) received ICI rechallenge. All 14 patients discontinued the first ICI due to disease progression. Eight patients received the same kind of ICIs, and six patients received different ICIs. Median progression-free survival and overall survival were 1.5 months [95% confidence interval (CI): 0.8-2.6] and 6.5 months [95% CI: 1.4-19.0], respectively. The objective response rate was 7.1%, and the disease control rate was 21.4%. Two of three patients who achieved at least a stable disease, received radiotherapy between the first and second ICIs. Adverse events were not significantly different compared with the first ICIs. CONCLUSIONS: In this study, the effect of ICI rechallenge was limited. Careful consideration of the administration of ICI rechallenge is necessary. This report involved a small number of cases, so further large prospective studies are warranted to confirm the efficacy of ICI rechallenge and to investigate predictive markers to identify a patient population in which ICI rechallenge is effective.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
8.
Acta Med Okayama ; 73(2): 155-160, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31015750

RESUMO

We investigated the clinical characteristics of refractory asthma associated with the effectiveness of bronchial thermoplasty (BT). We retrospectively evaluated data from 10 patients who underwent BT between June 2016 and December 2017 at Okayama Medical Center. The following were measured before and 6 months post-BT: forced expiratory volume in 1.0 s (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) level, blood eosinophil counts (Eosi), Asthma Quality of Life Questionnaire (AQLQ) score, and preventive medication use. At baseline, the mean post-bronchodilator FEV1 was 80.9% of the predicted value (range 45.6-115.7%). All patients were being treated with moderate- or high-dose inhaled corticosteroids and long-acting ß2 agonists. The AQLQ improved from 4.26±1.67 at baseline to 5.59±0.94 at 6 months post-BT (p<0.05). The %FEV1, FeNO, IgE, and Eosi did not change significantly between baseline and 6 months post-BT. No severe complications were reported. BT was effective for non-allergic and non-eosinophilic in 3 patients, and allergic or eosinophilic in 4 patients. Their AQLQ improved by > 0.5 points post-BT. For both allergic and eosinophilic asthmatics following mepolizumab, BT was not useful. BT was effective for non-allergic and non-eosinophilic or allergic asthmatics, but insufficient for both allergic and eosinophilic following mepolizumab.


Assuntos
Asma/terapia , Termoplastia Brônquica/métodos , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento
9.
Acta Med Okayama ; 72(3): 319-323, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29926012

RESUMO

Although cisplatin-based chemotherapy shows a survival advantage compared to carboplatin for treating advanced non-small cell lung cancer, high-volume hydration and a long infusion time are necessary to avoid nephrotoxicity, and cisplatin-based chemotherapy has been difficult to administer in outpatient settings. A low-volume hydration method using mannitol or furosemide as forced diuresis was recently introduced, but there are no clear conclusions regarding which agent should be used. We describe our ongoing randomized phase II trial (the OLCSG1406 Study) evaluating the efficacy of forced diuresis. This study will clarify whether mannitol or furosemide is more suitable in cisplatin-based chemotherapy with low-volume hydration.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/efeitos adversos , Diuréticos/uso terapêutico , Furosemida/uso terapêutico , Rim/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Manitol/uso terapêutico , Adulto , Idoso , Protocolos Clínicos , Ingestão de Líquidos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
10.
Jpn J Clin Oncol ; 47(5): 434-437, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28334767

RESUMO

OBJECTIVE: Although endobronchial intubation during a bronchoscopic examination is useful for invasive procedures, it is not routine practice in Japan. The present study evaluated discomfort due to endobronchial intubation using fentanyl and midazolam sedation during bronchoscopy. METHODS: Thirty-nine patients were enrolled prospectively from November 2014 to September 2015 at Okayama University Hospital. Fentanyl (20 µg) was administered to the patients just before endobronchial intubation, and fentanyl (10 µg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire survey was administered 2 h after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: excellent (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also asked. Predefined parameters (blood pressure, heart rate, oxygen saturation and complications) were recorded. RESULTS: The enrolled patients included 22 males and 17 females; their median age was 70 (range: 28-88) years. The patients received a mean dose of 47.9 µg of fentanyl (range: 30-90 µg) and 2.79 mg of midazolam (range: 1-7 mg). In total, 28 patients (71.7%) agreed to undergo a second bronchoscopic examination; the mean levels of discomfort and for the re-examination were 2.07 points each. About 41% of the patients remembered the bronchoscopic examination. No severe complications were reported. CONCLUSION: Endobronchial intubation using fentanyl and midazolam sedation during an invasive bronchoscopic procedure might be recommended. CLINICAL TRIAL REGISTRATION: UMIN000015578 in the UMIN Clinical Trials Registry.


Assuntos
Broncoscopia/efeitos adversos , Fentanila/administração & dosagem , Intubação/efeitos adversos , Midazolam/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fentanila/farmacologia , Hemodinâmica/efeitos dos fármacos , Humanos , Japão , Masculino , Midazolam/farmacologia , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
11.
Jpn J Clin Oncol ; 46(9): 871-4, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27380809

RESUMO

OBJECTIVE: Although sedation with fentanyl and midazolam during bronchoscopic examination is widely accepted in the USA and Europe, it is not routine practice in Japan. The objective of the present study was to evaluate sedation with fentanyl and midazolam during bronchoscopy. METHODS: Thirty-seven patients were enrolled prospectively between November 2014 and July 2015 at Okayama University Hospital. Fentanyl (20 µg) was administered to the patients just before the examination, and fentanyl (10 µg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire was administered 2 hours after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: great (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also used. Predefined matters for investigation (e.g. blood pressure, heart rate, oxygen saturation and complications) were recorded. RESULTS: The enrolled patients included 13 males and 24 females; the median age was 67 (range: 31-87) years. The patients received a median dose of fentanyl of 45.4 µg (range: 30-100 µg) and midazolam of 2.56 mg (range: 1-10 mg). Twenty-six patients (70.2%) agreed to undergo a second bronchoscopic examination, and the average levels of discomfort and re-examination were 2.02 points for each. Only 37.8% of the patients remembered the bronchoscopic examination. No severe complications were reported. CONCLUSIONS: Sedation with fentanyl and midazolam during bronchoscopic examination should be recommended for use in Japan.


Assuntos
Fentanila/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia , Feminino , Hemodinâmica , Humanos , Pneumopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente , Estudos Prospectivos , Inquéritos e Questionários
12.
Jpn J Clin Oncol ; 46(6): 529-33, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27004902

RESUMO

OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration is of diagnostic value in hilar/mediastinal (N1/N2) lymph node staging. We assessed the utility of endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients with N1/N2 lymph nodes detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. METHODS: Fifty lung cancer patients with N1/N2 disease on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography underwent endobronchial ultrasound-guided transbronchial needle aspiration for pathological lymph nodes between November 2012 and April 2015. The diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration, lymph node site and size, number of needle passes and complications were evaluated retrospectively from patients' medical records. Malignancy was defined as a maximum standardized uptake value (SUVmax) >2.5. RESULTS: The median longest diameter of the 61 lymph nodes (29 subcarinal, 21 right lower paratracheal, 6 left lower paratracheal, 4 right hilar and 1 upper paratracheal) was 23.4 mm (range: 10.4-45.7); the median number of needle passes was 2 (range: 1-5). There were no severe complications. A definitive diagnosis was made by endobronchial ultrasound-guided transbronchial needle aspiration in 39 patients (31 adenocarcinomas, 3 small-cell carcinomas, 2 squamous-cell carcinomas, 3 large-cell neuroendocrine carcinomas). In the remaining 11 patients, the diagnosis was indefinite: insufficient endobronchial ultrasound-guided transbronchial needle aspiration material was collected in two patients and non-specific lymphadenopathy was confirmed by endobronchial ultrasound-guided transbronchial needle aspiration or thoracotomy in the other nine patients. The mean lymph node SUVmax was 7.09 (range: 2.90-26.9) and was significantly higher in true-positive than in false-positive nodes (P < 0.05, t-test). Non-specific lymphadenopathy was diagnosed by expert visual interpretation of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography images in five of the nine patients. CONCLUSION: Endobronchial ultrasound-guided transbronchial needle aspiration accurately diagnoses N1/N2 disease detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Fluordesoxiglucose F18/química , Neoplasias Pulmonares/diagnóstico , Linfonodos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adenocarcinoma/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Broncoscopia , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Grandes/diagnóstico por imagem , Carcinoma de Células Grandes/patologia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Masculino , Mediastino/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Estudos Retrospectivos , Toracotomia
13.
Int J Clin Oncol ; 21(1): 81-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26093520

RESUMO

OBJECTIVE: We previously reported the feasibility of short-term low-volume hydration in patients with advanced lung cancer who received cisplatin-based chemotherapy (Jpn J Clin Oncol 2013). We sought to determine the clinical usefulness of a more convenient hydration method, evaluating the safety and efficacy of shorter-term and lower-volume hydration. METHOD: Chemonaïve patients with advanced lung cancer who were ≤ 75 years and reserved an adequate renal function for cisplatin use (≥ 60 mg/m(2)) were eligible. An intravenously administered hydration of 1700 ml in ~3.5 h with 1500 ml of orally administered hydration was investigated. The primary endpoint was the proportion of patients without grade 2 or worse renal toxicity in the first cycle. RESULTS: A total of 45 patients were registered, all of whom were evaluable for renal toxicity. The median baseline creatinine score was 0.70 mg/dl, and the median cisplatin dose on day 1 was 75 mg/m(2). In the first cycle, one patient (2 %) developed grade 2 creatinine toxicity, and thus, the proportion of patients with less than grade 2 was 98 % (the lower limit of 95 % confidence interval; 93 %), which met the primary endpoint. Five patients (11 %) had grade 1 or greater nephrotoxicity, three of whom successfully recovered. The objective response rate was 24 % and median progression-free survival 5.8 months. CONCLUSION: This prospective study demonstrated the safety and efficacy of shorter-term lower-volume hydration.


Assuntos
Injúria Renal Aguda/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidratação/métodos , Neoplasias Pulmonares/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Adulto , Idoso , Cisplatino/administração & dosagem , Creatinina/sangue , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores Sólidos
14.
Cancer Sci ; 106(10): 1296-302, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26211743

RESUMO

Malignant mesothelioma is an aggressive and therapy-resistant neoplasm arising from mesothelial cells. Evidence suggests that the major pathology associated with asbestos-induced mesothelioma is local iron overload. In the present study, we induced iron-induced mesothelioma in rats based on previous reports. Ten Wistar rats were given ferric saccharate and nitrilotriacetate i.p. for 5 days a week. Five of the ten rats exhibited widespread mesotheliomas in the peritoneum and tunica vaginalis. The tumor cells showed positive immunostaining for calretinin, wilms tumor-1, podoplanin and the oxidative DNA marker 8-hydroxy-2'-deoxyguanosine. In three of the five rats with mesothelioma, array-based comparative genomic hybridization analysis identified a common chromosomal deletion mapped to the chromosomal 4q31 locus, which encompasses the TBXAS1 gene. Downregulation of the TBXAS1 gene was confirmed using quantitative PCR. TBXAS1 gene expression was also reduced in three of four human malignant pleural mesothelioma cell lines compared with normal bronchial epithelial cells. Immunohistochemistry revealed that TBXAS1 expression was weakly positive and positive in five and three out of eight human malignant mesothelioma samples, respectively. In conclusion, TBXAS1 gene expression was downregulated in rats with iron-induced mesothelioma. The relationship between iron overload and TBXAS1 downregulation should be pursued further.


Assuntos
Ferro/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Mesotelioma/induzido quimicamente , Mesotelioma/genética , Tromboxano-A Sintase/genética , 8-Hidroxi-2'-Desoxiguanosina , Animais , Biomarcadores Tumorais/metabolismo , Calbindina 2/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Deleção Cromossômica , Desoxiguanosina/análogos & derivados , Desoxiguanosina/genética , Regulação para Baixo , Compostos Férricos , Óxido de Ferro Sacarado , Ácido Glucárico , Humanos , Sobrecarga de Ferro/genética , Neoplasias Pulmonares/patologia , Masculino , Glicoproteínas de Membrana/metabolismo , Mesotelioma/patologia , Mesotelioma Maligno , Neoplasias Experimentais/etiologia , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Proteínas Nucleares/metabolismo , Fatores de Processamento de RNA , Ratos , Ratos Wistar
16.
Jpn J Clin Oncol ; 44(5): 501-5, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24646812

RESUMO

Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage IIIA. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (i) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (ii) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome.


Assuntos
Corticosteroides/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Candidemia/etiologia , Neutropenia Febril/complicações , Hipopituitarismo/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Choque Séptico/microbiologia , Adenoma/cirurgia , Corticosteroides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Candidemia/complicações , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Evolução Fatal , Neutropenia Febril/induzido quimicamente , Humanos , Hipofisectomia/efeitos adversos , Hipopituitarismo/complicações , Hipopituitarismo/etiologia , Neoplasias Pulmonares/complicações , Masculino , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Hipofisárias/cirurgia
17.
Exp Cell Res ; 319(4): 417-23, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23274758

RESUMO

The effectiveness of vandetanib, an agent that targets RET, VEGFR and EGFR signaling, against EGFR-mutant lung cancer cells with PTEN loss was investigated. Two EGFR mutant non-small cell lung cancer (NSCLC) cell lines, PC-9 (PTEN wild type) and NCI-H1650 (PTEN null), were used. We transfected an intact PTEN gene into H1650 cells and knocked down PTEN expression in PC-9 cells using shRNA. The effectiveness of gefitinib and vandetanib was assessed using a xenograft model. While PC-9 cells were more resistant to vandetanib than gefitinib, H1650 cells were more sensitive to vandetanib than gefitinib. Both gefitinib and vandetanib suppressed the activation of EGFR and MAPK in H1650 cells, although phosphorylated AKT levels were not affected. In an H1650 cell xenograft model, vandetanib was also more effective than gefitinib. Although PTEN-transfected H1650 cells did not show restoration of sensitivity to gefitinib in vitro, the xenograft tumors responded to gefitinib and vandetanib. Knockdown of PTEN in PC-9 cells caused resistance to gefitinib. In conclusion, vandetanib might be effective in NSCLC with EGFR mutations that lack PTEN expression. The contribution of PTEN absence to vandetanib activity in NSCLC cells harboring EGFR mutations should be further examined.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Genes erbB-1 , Neoplasias Pulmonares/tratamento farmacológico , PTEN Fosfo-Hidrolase/genética , Piperidinas/uso terapêutico , Quinazolinas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Feminino , Genes erbB-1/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Mutação/fisiologia , PTEN Fosfo-Hidrolase/deficiência , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/farmacologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Cureus ; 16(3): e55595, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38576679

RESUMO

We evaluated the usefulness of endobronchial ultrasonography with guide sheath (EBUS-GS) for the diagnosis of peripheral pulmonary lesions (PPLs) in Japan. We searched the PubMed/Medline database using the keywords "EBUS guide sheath" for Japanese studies on EBUS-GS published between January 2004 and August 2023. We included 32 original articles that evaluated the diagnostic yield of EBUS-GS for PPLs. Case reports and conference abstracts were excluded due to limited information available for quality assessment. The diagnostic yield of EBUS-GS was 73.6% for 2996 malignant lesions, 65.4% for 752 ground-glass nodules, 59.4% for 414 benign lesions, 61.3% for 1114 lesions of size ≤2 cm, and 75.6% for 1246 lesions of size >2 cm; it was 69.4% for lesions located in the upper lobe (n=793), 71.9% for the middle lobe/lingula (n=121), and 62.5% for the lower lobe (n=334). None of the patients experienced severe complications. In this review, EBUS-GS is effective for the diagnosis of malignant and benign PPLs. A multimodality approach is needed to further enhance its diagnostic performance.

19.
Intern Med ; 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38220189

RESUMO

Objective Airway stenting is an established procedure for treating various airway disorders. The AERO stent (Merit Medical Systems, South Jordan, UT, USA) is a fully covered self-expandable metallic stent approved for use in Japan in 2014. However, its effectiveness in treating malignant airway disorders in patients with a poor performance status remains unclear. Therefore, we investigated the safety and efficacy of the AERO stent in patients with malignant airway disorders and a poor performance status. Patients and Methods We retrospectively reviewed the medical records of all patients who underwent AERO stent placement at our institute between April 2016 and March 2022, and 21 patients underwent 25 procedures for malignant airway disorders. All AERO stenting procedures were performed using an over-the-wire delivery system with flexible and/or rigid bronchoscopy. Results Eighteen of the 21 patients (85.7%) had a poor general condition (Eastern Cooperative Oncology Group performance status 3 or 4). AERO stents were successfully placed in 23 of the 25 procedures and migrated in the remaining 2 cases. Complications occurred in 10 cases, with infection being the most common (3 cases). Fourteen patients (66.6%) showed an improvement in their performance status. In addition, 5 of the 6 intubated patients were extubated following AERO stenting, and 11 patients subsequently received anticancer treatment. Conclusion The placement of the AERO stent is useful in patients with a poor performance status, including those who are intubated and afflicted with malignant airway disorders.

20.
Jpn J Clin Oncol ; 43(11): 1110-4, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23997237

RESUMO

OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration is a new minimally invasive test for investigating mediastinal and hilar lymphadenopathy. It is sometimes difficult to distinguish between a recurrent malignant lymph node and lymphadenopathy due to sarcoidosis in patients who develop lymphadenopathy after surgery for a malignant tumor. METHODS: Between December 2009 and October 2012, we performed endobronchial ultrasound-guided transbronchial needle aspiration in 13 selected patients with a suspected recurrence in the mediastinum and/or hilum of the lung after surgical resection of a malignant tumor. We examined their medical records to obtain information on the diagnosis, the sizes of lymph nodes, the number of needle passes and other complications. RESULTS: Definitive diagnoses were made using endobronchial ultrasound-guided transbronchial needle aspiration in 10 patients (three lung adenocarcinomas, one prostate carcinoma, one renal cell carcinoma, one neuroendocrine tumor and four sarcoidosis). Pathological specimens showing non-caseating granulomas led to the diagnosis of sarcoidosis in four patients; their previous malignancies had been papillary adenocarcinoma of the thyroid, carcinoma of the gingiva, thymoma and bladder cancer, but no recurrences were observed. The median of the longest diameter in 15 lymph nodes was 22 mm (range 13-35), and the median number of needle passes was two times (range 1-5) without severe complications. CONCLUSIONS: Endobronchial ultrasound-guided transbronchial needle aspiration might be useful in differentiating between benign lymphadenopathy, including sarcoidosis, and cancer recurrence in patients with mediastinal or hilar lymphadenopathy after surgical resection of a malignant tumor.


Assuntos
Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfonodos/patologia , Doenças Linfáticas/etiologia , Recidiva Local de Neoplasia/diagnóstico , Sarcoidose Pulmonar/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Tumores Neuroendócrinos/secundário , Valor Preditivo dos Testes , Neoplasias da Próstata/patologia , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico por imagem
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