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1.
Jpn J Clin Oncol ; 54(2): 121-128, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-37952098

RESUMO

Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.


Assuntos
Carcinoma Adenoide Cístico , Carcinoma Mucoepidermoide , Neoplasias Pulmonares , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Neoplasias Pulmonares/patologia , Glândulas Salivares/patologia , Pulmão/patologia , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/cirurgia
2.
Jpn J Clin Oncol ; 53(5): 429-435, 2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-36655315

RESUMO

BACKGROUND: Pathological N2 (pN2) non-small cell lung cancer (NSCLC) is diverse; its treatment depends on the clinical N (cN) status. We aimed to determine the efficacy of upfront surgery for cN2pN2 NSCLC. METHODS: The study included 43 cN2pN2 NSCLC patients who underwent upfront surgery at the Shizuoka Cancer Center between 2002 and 2017. Survival outcome, focusing on cN2 status, was retrospectively investigated. Mediastinal lymph nodes were pre-operatively evaluated using computed tomography and positron emission tomography. Surgical eligibility criteria included single-station cN2. N2 with N1 and skip N2 were defined as N2 with and without ipsilateral hilar lymph node metastasis, respectively. A platinum-doublet regimen was used for adjuvant chemotherapy. Survival curves were analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model. RESULTS: Clinical-skip N2 and cN2 with N1 cases included 22 and 21 patients, respectively. Twenty-three patients received adjuvant chemotherapy. The median follow-up duration was 73 months. Clinical-skip N2 had a significantly better 5-year recurrence-free survival (RFS) than cN2 with N1 (58.3 vs 28.6%, P = 0.038) and was an independent favorable RFS predictor. Recurrence within 18 months occurred in 71% of cN2 with N1 cases. Five-year overall survival and RFS rates in patients receiving adjuvant chemotherapy vs those without adjuvant chemotherapy were 82.2 vs 41.9% (P = 0.019) and 56.5 vs 28.0% (P = 0.049), respectively. CONCLUSIONS: Clinical-skip N2 had an excellent prognosis, and upfront surgery was acceptable. Conversely, upfront surgery followed by chemotherapy is not recommended for cN2 with N1 patients because of early recurrence.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Estadiamento de Neoplasias , Mediastino/patologia , Prognóstico , Linfonodos/patologia
3.
Jpn J Clin Oncol ; 53(2): 161-167, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36461783

RESUMO

BACKGROUND: The importance of the stromal components in tumour progression has been discussed widely, but their prognostic role in small size tumours with lepidic components is not fully understood. Applying digital tissue image analysis to whole-slide imaging may enhance the accuracy and reproducibility of pathological assessment. This study aimed to evaluate the prognostic value of tumour components of lung adenocarcinoma by measuring the dimensions of the tumour consisting elements separately, using a machine learning algorithm. METHODS: Between September 2002 and December 2016, 317 patients with surgically resected, pathological stage IA adenocarcinoma with lepidic components were analysed. We assessed the whole tumour area, including the lepidic components, and measured the epithelium, collagen, elastin areas and alveolar air space. We analysed the prognostic impact of each tumour component. RESULTS: The dimensions of the epithelium and collagen areas were independent significant risk factors for recurrence-free survival (hazard ratio, 8.38; 95% confidence interval, 1.14-61.88; P = 0.037, and hazard ratio, 2.58; 95% confidence interval, 1.14-5.83; P = 0.022, respectively). According to the subgroup analysis when combining the epithelium and collagen areas as risk factors, patients with tumours consisting of both large epithelium and collagen areas showed significantly poor prognoses (P = 0.002). CONCLUSIONS: We assessed tumour components using a machine learning algorithm to stratify the post-operative prognosis of surgically resected stage IA adenocarcinomas. This method might guide the selection of patients with a high risk of recurrence.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Prognóstico , Neoplasias Pulmonares/patologia , Reprodutibilidade dos Testes , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
4.
Thorac Cardiovasc Surg ; 71(7): 589-594, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36736369

RESUMO

BACKGROUND: Pulmonary vein stump thrombosis may occur after left upper lobectomy (LUL) and is a potential risk factor for cerebral infarction. However, there are few reports on the role of pulmonary vein stump thrombosis in the development of cerebral infarction. We aimed to clarify the correlation between pulmonary vein stump thrombosis and cerebral infarction following LUL. METHODS: We evaluated 296 patients who underwent contrast-enhanced computed tomography (CT) after LUL for lung cancer at the Shizuoka Cancer Center Hospital in Shizuoka, Japan, between September 2002 and December 2015. The cerebral infarction in patients with pulmonary vein stump thrombosis was examined, and the risk factors for cerebral infarction were identified via a univariate analysis of the clinicopathological and surgical variables. RESULTS: Overall, 179 men and 117 women (median age: 68 years; range: 36-88 years) were included. The median observation period was 68 months. Pulmonary vein stump thrombosis occurred in 21 (7%) patients and cerebral infarction occurred in 15 (5%) patients. None of the 21 patients with pulmonary vein stump thrombosis developed cerebral infarction. Most cerebral infarctions (12/15) were diagnosed in the late phase (> 3 months). The pathological stage of cancer was found to be the only significant risk factor for cerebral infarction by the univariate analysis. CONCLUSION: Pulmonary vein stump thrombosis following LUL was not necessarily associated with cerebral infarction, including the late phase. A prospective observational study with contrast-enhanced chest CT would be required to investigate the risk factors for cerebral infarction in each phase of the postoperative period.


Assuntos
Neoplasias Pulmonares , Veias Pulmonares , Trombose Venosa , Masculino , Humanos , Feminino , Idoso , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Trombose Venosa/etiologia , Trombose Venosa/complicações , Infarto Cerebral/etiologia , Infarto Cerebral/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia
5.
Int J Clin Oncol ; 26(10): 1840-1846, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34165658

RESUMO

BACKGROUND: A significant number of non-small cell lung cancer (NSCLC) patients develop osteogenic metastases (OMs) and/or brain metastases (BMs) after surgery, however, routine chest computed tomography (CT) sometimes fails to diagnose these recurrences. We investigated the incidence of BMs and OMs after pulmonary resection and aimed to identify candidates who can benefit from brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in addition to CT. METHODS: We retrospectively reviewed medical records of 1099 NSCLC patients who underwent pulmonary resection between 2002 and 2013. Clinicopathological factors associated with OM and/or BM were investigated using univariate and multivariate analyses. RESULTS: Postoperative recurrence occurred in 344 patients (32.6%). OMs were diagnosed in 56 patients (5.6%) with 93% within 3 years. BMs were identified in 72 patients (6.6%) with 91.1% within 3 years. Multivariate analysis revealed that poorly differentiated tumor and the presence of pathological nodal metastases were significantly associated with postoperative BM (p = 0.037, < 0.001), preoperative serum carcinoembryonic antigen (CEA) level of 5 ng/mL or higher and the presence of pathological nodal metastases were significantly associated with OM (p = 0.034, < 0.001). The prevalence of OM and/or BM in 5 years was as high as 25.9% in patients with pathological nodal metastases. CONCLUSIONS: We identified significant predictive factors of postoperative BM and OM. Under patient selection, the effectiveness of intensive surveillance for the modes of recurrence should be investigated with respect to earlier detection, maintenance of quality of life, and survival outcomes.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Tomografia por Emissão de Pósitrons , Qualidade de Vida , Estudos Retrospectivos
6.
Jpn J Clin Oncol ; 50(4): 425-433, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-31926488

RESUMO

BACKGROUND: There is no standard therapeutic approach for local recurrence of non-small cell lung cancer (NSCLC) after complete resection. We investigated the outcomes of radiotherapy (RT) for patients with local recurrence. METHODS: We reviewed 46 patients who underwent curative-intent RT for local recurrence after lobectomy or pneumonectomy accompanied with mediastinal lymph node dissection between 2002 and 2014. We analyzed overall survival (OS), progression-free survival (PFS), local control, tumour response and the re-recurrence pattern. RESULTS: Among the 46 patients, 16 received concurrent chemotherapy. The median follow-up period was 48 months. The response rate was 91%. The 5-year OS and local control rates were 47.9 and 65.3%, respectively, and the 5-year PFS rate was 22.8%. Female sex and complete response to radiation were favourable prognostic factors. Of the 33 patients with recurrence after radiation, 32 (97%) had distant metastasis. CONCLUSIONS: Although RT for local recurrence has high efficacy, distant relapse after radiation remains a major issue. Therefore, combination systemic therapy for local recurrence at any site should be further investigated. Since it is difficult to achieve a radical cure for local recurrence using RT, further study, for the administration of post-operative adjuvant therapy, is recommended.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/cirurgia , Fatores de Risco , Resultado do Tratamento
7.
Respirology ; 25(8): 850-854, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31694070

RESUMO

BACKGROUND AND OBJECTIVE: The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values. METHODS: The medical records of patients with NSCLC who underwent thoracic surgery at our institution between January 2014 and January 2017 were retrospectively reviewed. Whole-exome sequencing with an Ion Proton system and gene expression profiling of fresh surgical specimens were performed. RESULTS: Among 367 patients with NSCLC, 62 (16.9%) were diagnosed with ILD. All samples were collected from primary tumours with a median TMB of approximately 2.1 (range: 0.1-64.4) mutation/Mb. Among 81 squamous cell carcinomas, we compared 27 tumours with concomitant ILD and 54 tumours without ILD. Univariate analyses revealed that tumours with concomitant ILD showed lower TMB values than those without ILD. Multivariate analysis revealed that concomitant ILD was significantly associated with low TMB values. Conversely, no difference was noted in the TMB value of adenocarcinoma between patients with and without ILD. CONCLUSION: Squamous cell carcinoma and adenocarcinoma with ILD do not have high TMB values. Therefore, considering the risk of severe pneumonitis, immune checkpoint inhibitors should not be used routinely against patients with NSCLC and ILD based on the expectation of high TMB values.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Doenças Pulmonares Intersticiais/genética , Neoplasias Pulmonares/genética , Mutação/genética , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/genética , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos
8.
Kyobu Geka ; 73(6): 403-405, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32475961

RESUMO

We evaluated postoperative pain intensity using the PainVision system for quantitative pain analysis and assessed the correlation with numerical rating scale( NRS) for subjective pain evaluation. Twelve patients were evaluated for both pain intensity by PainVision and values by NRS at 6, 24 and 48 hours following after thoracic surgery. The correlation coefficient between pain intensity and NRS values was 0.20, which suggested that degrees of pain measured by subjective and quantitative pain scales were not necessarily consistent. Assessing pains with both conventional subjective pain evaluation and quantitative pain intensity evaluation by PainVision is possibly useful in providing optimal postoperative pain management.


Assuntos
Dor Pós-Operatória , Procedimentos Cirúrgicos Torácicos , Humanos , Medição da Dor
9.
World J Surg ; 43(5): 1286-1293, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30675631

RESUMO

BACKGROUND: Despite the poor prognosis of recurrent esophageal squamous cell cancer (ESCC), long-term survival could be achieved in a subset of patients who successfully underwent surgical resection for recurrence. In this study, we investigated the outcomes of surgical resection for lymph node (LN) or pulmonary (PUL) recurrence in ESCC patients. METHODS: We retrospectively analyzed the outcomes of ESCC patients who underwent surgical resection between January 2008 and March 2015 for either LN or PUL recurrence after complete response (CR) by chemoradiotherapy or R0 esophagectomy. Every patient fulfilled the original institutional criteria: no recurrence at primary site; recurrence involving in only one organ; expectation of complete resection; and for PUL recurrence, no rapid growth with at least 2 months of observation. RESULTS: Among the 13 patients analyzed, surgical resection was performed in nine and four patients with LN and PUL recurrence, respectively. R0 resection was achieved in all patients with no fatal surgical complications. Mean duration from the day of the first CR/R0 to the recurrence was 809 (110-2575) days. Median recurrence-free survival following surgical resection for recurrence and overall survival following the first diagnosis of recurrence was 387 and 1297 days, respectively. CONCLUSION: Surgical resection for LN or PUL recurrence of ESCC according to our institutional criteria can be performed safely for selected patients.


Assuntos
Carcinoma de Células Escamosas do Esôfago/cirurgia , Excisão de Linfonodo , Recidiva Local de Neoplasia/cirurgia , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
BMC Cancer ; 16(1): 864, 2016 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-27821131

RESUMO

BACKGROUND: The majority of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Minimal information exists regarding genetic alterations in rebiopsy samples from Asian NSCLC patients who develop acquired resistance to EGFR-TKIs. METHODS: We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who had undergone rebiopsies after developing acquired resistance to EGFR-TKIs. We analyzed 27 practicable samples using a tumor genotyping panel to assess 23 hot-spot sites of genetic alterations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2), gene copy number of EGFR, MET, PIK3CA, FGFR1, and FGFR2, and ALK, ROS1, and RET fusions. Additionally, 34 samples were analyzed by commercially available EGFR mutation tests. RESULTS: Sixty-one patients underwent rebiopsy. Twenty-seven samples were analyzed using our tumor genotyping panel, and 34 samples were analyzed for EGFR mutations only by commercial clinical laboratories. Twenty-one patients (34 %) had EGFR T790M mutation. Using our tumor genotyping panel, MET gene copy number gain was observed in two of 27 (7 %) samples. Twenty patients received continuous treatment with EGFR-TKIs even after disease progression, and 11 of these patients had T790M mutation in rebiopsy samples. In contrast, only 10 of 41 patients who finished EGFR-TKI treatment at disease progression had T790M mutation. The frequency of T790M mutation in patients who received continuous treatment with EGFR-TKIs after disease progression was significantly higher than that in patients who finished EGFR-TKI treatment at disease progression (55 % versus 24 %, p = 0.018). CONCLUSIONS: The frequency of T790M mutation in this study was lower than that in previous reports examining western patients. These results suggest that continuous treatment with EGFR-TKI after disease progression may enhance the frequency of EGFR T790M mutation in rebiopsy samples.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Substituição de Aminoácidos , Biópsia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Códon , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Japão , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
11.
Surg Today ; 46(6): 699-704, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26525973

RESUMO

PURPOSE: The role of surgery for patients with non-small cell lung cancer (NSCLC) with clinical mediastinal lymph node metastasis (N2) remains controversial. We specified 4 criteria for performing initial surgery in these patients (single-station N2, non-bulky N2, N2 with regional mode of spread, and N2 without N1) and examined the outcomes to validate the treatment options. METHODS: Between September 2002 and December 2010, of 1290 patients who underwent complete resection for NSCLC, 808 patients underwent initial standard resection, including 779 patients with cN0-1 and 29 with cN2. We compared the outcomes, and evaluated patients with cN2-pN2. RESULTS: The median follow-up was 45.5 months (3-119 months). Seventy (9.0 %) and 24 (82.8 %) patients had p-N2 in the cN0-1 and cN2 groups, respectively (p < 0.0001). The 5-year disease-free survival (DFS) rates in the cN0-1 and cN2 groups were 73.3 and 50.6 %, respectively (p = 0.0053), and the 5-year overall survival (OS) rates were 81.3 and 71.1 %, respectively (p = 0.051). The 5-year DFS and OS of patients with cN2-pN2 were 52.5 and 72.6 %, respectively. CONCLUSIONS: Patients with clinical N2 disease based on our criteria represent a highly specific group with a favorable prognosis. Resection should therefore be the initial treatment for these patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Tomografia por Emissão de Pósitrons , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Kyobu Geka ; 69(10): 828-31, 2016 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-27586312

RESUMO

We retrospectively assessed the effectiveness and the safety of thoracic paravertebral block(PVB) in patients ineligible for epidural block (EP). Eleven PVB patients and 33 EP patients were enrolled. Postoperative pain was evaluated using a numerical rating scale (NRS). The mean NRS ± standard deviation at rest 24 and 48 hours after surgery were 1.36 ± 1.63 and 0.55 ± 1.03 in the PVB group and 1.07 ± 1.47 and 1.38 ± 1.31 in the EP group, respectively. There were no statistically significant differences in the NRS scores. Approximately 10% of the EP patients had complications such as hypotension, nausea and vomiting, or urinary retention. On the other hand, there were no adverse events in the PVB group. PVB can provide pain relief comparable to EP with a better side-effect profile. There were no technical complications associated with PVB. Thoracic PVB is an effective and safe method of postoperative analgesia for patients undergoing thoracic surgery with ineligibilities for EP.


Assuntos
Raquianestesia , Coluna Vertebral/efeitos dos fármacos , Procedimentos Cirúrgicos Torácicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Epidural , Raquianestesia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Cancer ; 120(10): 1471-81, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24700479

RESUMO

BACKGROUND: Integration of mutational profiling to identify driver genetic alterations in a clinical setting is necessary to facilitate personalized lung cancer medicine. A tumor genotyping panel was developed and the Shizuoka Lung Cancer Mutation Study was initiated as a prospective tumor genotyping study. This study reports the frequency of driver genetic alterations in Japanese lung adenocarcinoma patients, and clinicopathologic correlations with each genotype. METHODS: Between July 2011 and January 2013, 411 lung adenocarcinoma patients admitted to the Shizuoka Cancer Center were included in this study with their written informed consent. Surgically resected tissues, tumor biopsies, and/or body cavity fluids were collected and tested for 23 hotspot sites of driver mutations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2), gene amplifications in 5 genes (EGFR, MET, PIK3CA, FGFR1, and FGFR2), and ALK, ROS1, and RET fusions. RESULTS: Genetic alterations were detected in 54.3% (223 of 411) of all patients. The most common genetic alterations detected in this study were EGFR mutations (35.0%) followed by KRAS mutations (8.5%) and ALK fusions (5.0%). Concurrent genetic alterations were detected in 22 patients (5.4%), and EGFR mutations were observed in 16 patients as the most common partner for concurrent genetic alteration. Significantly more concurrent genetic alterations were observed in older patients. CONCLUSIONS: This is one of the largest reports of a prospective tumor genotyping study on Japanese patients with adenocarcinoma. These data suggest that mutational profiling data using a multimutational testing platform would be valuable for expanding the range of molecular-targeted therapeutics in lung cancer.


Assuntos
Adenocarcinoma/genética , Povo Asiático/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Proteínas ras/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Feminino , Genótipo , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas de Fusão Oncogênica/genética , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras) , Fumar/efeitos adversos , Fumar/epidemiologia
14.
J Vasc Surg ; 60(2): 490-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23958072

RESUMO

OBJECTIVE: This study tested to see if trehalose, a cytoprotective disaccharide, protects against spinal cord ischemia in a rabbit model. METHODS: The infrarenal aorta was mobilized in four groups of 10 rabbits. In groups I, II, and III, it was clamped proximally and distally for 20 minutes. In group I, the clamped aorta was infused at 2.5 L/min for 2 hours with lactated Ringer's (LR) solution. In group II, the clamped aorta was infused with 5% trehalose in LR. LR was administered intravenously (2.0 mL/min) in groups I and II starting 30 minutes before clamping. In group III, 5% trehalose in LR was infused intravenously only. Group IV was a sham-operated control group without aortic clamping. At 8, 24, and 48 hours after reperfusion, hind limb function was scored using the Tarlov score (paralysis = 0, perceptible joint movement = 1, good joint movement but unable to stand = 2, able to walk = 3, normal = 4). Histologic analysis and electron microscopy were performed on anterior horn cells. RESULTS: The Tarlov scores in groups I, II, and III were, respectively, 1.1 ± 1.4, 3.5 ± 0.5, and 2.9 ± 0.9 at 8 hours; 0.8 ± 1.2, 3.9 ± 0.3, and 2.9 ± 0.9 at 24 hours; and 0.6 ± 0.7, 3.9 ± 0.3, and 2.7 ± 0.9 at 48 hours after reperfusion. Group IV scores were normal (4 ± 0) at all assessments. These scores were higher in groups II and III than in group I (P < .01) at all assessments. Scores at 24 and 48 hours were higher in group II than in group III (P < .05). In group III, delayed paraparesis developed in one rabbit at 24 hours and in two more at 48 hours. Histopathologic analysis showed the number of normal neurons was higher in groups II (P < .0001), III (P = .006), and IV (P < .0001) vs group I. Electron microscopy confirmed preserved neuronal cell ultrastructure in rabbits with normal limb function. CONCLUSIONS: Transaortic trehalose infusion was protective against paraplegia, whereas intravenous trehalose reduced spinal cord ischemia. This study was preliminary and further studies are needed.


Assuntos
Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/prevenção & controle , Medula Espinal/efeitos dos fármacos , Trealose/farmacologia , Animais , Células do Corno Anterior/efeitos dos fármacos , Células do Corno Anterior/ultraestrutura , Citoproteção , Modelos Animais de Doenças , Esquema de Medicação , Infusões Intra-Arteriais , Infusões Intravenosas , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Paraparesia/fisiopatologia , Paraparesia/prevenção & controle , Paraplegia/fisiopatologia , Paraplegia/prevenção & controle , Coelhos , Medula Espinal/fisiopatologia , Medula Espinal/ultraestrutura , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo , Trealose/administração & dosagem
15.
BMC Cancer ; 14: 786, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25348872

RESUMO

BACKGROUND: Despite considerable recent progress in the treatment of lung adenocarcinoma, there has been little progress in the development of efficacious molecular targeted therapies for squamous cell lung cancer. In addition to the recent comprehensive genome-wide characterization of squamous cell lung cancer, it is also important to genotype this form of cancer. We therefore conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with thoracic malignancies. Here we report the results of genotyping in patients with squamous cell lung cancer. METHODS: Based on the biobanking system, in conjunction with the clinic and pathology lab, we developed a genotyping panel designed to assess 24 mutations in 10 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, HER2 and DDR2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 copy numbers, and EML4-ALK and ROS1 translocations, using pyrosequencing plus capillary electrophoresis, quantitative polymerase chain reaction (PCR) and reverse-transcription PCR, respectively. RESULTS: A total of 129 patients with squamous cell lung cancer and adenosquamous carcinoma were enrolled in this study between July 2011 and November 2012. We detected genetic alterations in 40% of all cases. Gene alterations included: EGFR mutations, 6%; KRAS mutations, 4%; PIK3CA mutations, 13%; NRAS mutations, 1%; KIF5b-RET fusion gene, 1%; EGFR copy number gain, 5%; PIK3CA copy number gain, 15%; and FGFR1 copy number gain, 5%. Twelve patients (9%) harbored simultaneous genetic alterations. Genetic alterations were detected more frequently in surgically-resected, snap-frozen samples than in formalin-fixed, paraffin-embedded samples (50% vs. 29%). In addition, patients aged ≤70 years old and never-smokers showed high frequencies of genetic alterations. CONCLUSIONS: This study represents one of the largest prospective tumor-genotyping studies to be performed in Asian patients with squamous cell lung cancer. These results suggest that incorporation of genetic profiling into lung cancer clinical practice may facilitate the administration of personalized cancer treatments in patients with squamous cell lung cancer.


Assuntos
Povo Asiático , Carcinoma Adenoescamoso/genética , Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Bancos de Espécimes Biológicos , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Variações do Número de Cópias de DNA , Feminino , Técnicas de Genotipagem , Humanos , Japão , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Risco
16.
Thorac Cardiovasc Surg ; 62(7): 588-92, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24590474

RESUMO

BACKGROUND: Little is known about the prognostic value of positive sputum cytology in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively examined the clinicopathological data of 30 patients who had undergone complete resection for NSCLC with positive sputum cytology between September 2002 and June 2011. RESULTS: Distant recurrence occurred significantly more frequently in the patients with adenocarcinoma (Ad) than in those with squamous cell carcinoma (p = 0.01). The most frequent metastatic site after surgery was the brain, occurring in five patients with Ad. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the 30 patients were 53 and 49%, respectively. In multivariate analyses, radiographic feature of pneumonic-type shadow and pathological N (pN) 1-2 status were the independent factors significantly correlated with poor DFS (p = 0.009, 0.001, respectively), whereas pN 1-2 status was the only independent factor significantly correlated with poor OS (p = 0.009). CONCLUSION: Surgical outcome for NSCLC with positive sputum cytology was unfavorable at our institution. Close surveillance after a curative resection is mandatory for those patients presenting with radiographic feature of pneumonic-type shadow as those with lymph node metastases because they are at high risk for recurrence.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia , Escarro/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
17.
Surg Today ; 44(3): 494-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24006127

RESUMO

PURPOSE: Interstitial lung disease (ILD) has been associated with primary lung cancer and an increased risk of postoperative acute exacerbation (AE). The effectiveness of 2-[18]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET) for staging lung cancer is well established. This study investigates the association of FDG uptake on PET in patients with AE of ILD. METHODS: The subjects of this retrospective study were 1309 patients with lung cancer, who underwent pulmonary resection at Shizuoka Cancer Center between September, 2002 and January, 2011. ILD was diagnosed with chest computed tomography in 95 patients, 81 of whom underwent (18)F-FDG PET before surgery. Six patients suffered from AE after surgery (AE group), while the remaining 75 (non-AE group) did not. We investigated the clinico-pathological findings and the results of FDG uptake on PET using the value of the I/M ratio, which is the ratio of the peak of standardized uptake value (SUV) of the ILD area to the mean SUV of the mediastinum. RESULTS: There was no significant difference in clinico-pathological findings, but a significance difference in the I/M ratio (P = 0.0102). CONCLUSION: The FDG uptake in PET may be a predictive factor for AE of ILD in patients who have undergone lung cancer surgery.


Assuntos
Progressão da Doença , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Humanos , Doenças Pulmonares Intersticiais/complicações , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Estudos Retrospectivos
18.
Artigo em Inglês | MEDLINE | ID: mdl-39008147

RESUMO

OBJECTIVE: The stair-climbing test (SCT) is used as a surrogate for cardiopulmonary exercise testing, which measures maximal oxygen uptake, and considered a useful method for assessing exercise capacity in thoracic surgery. This study aims to investigate whether the recovery time of percutaneous oxygen saturation (SpO2) after stair climbing is a predictor of postoperative complications after lobectomy. METHODS: We retrospectively identified 54 patients who performed SCT and underwent lobectomy between January 2015 and February 2023 at Shizuoka Cancer Center. The SpO2 recovery time was defined as the time required to recover from the minimum to resting value after stair climbing. The association between SpO2 recovery time and early postoperative pulmonary complications within 30 days after surgery was analyzed. RESULTS: Eleven patients (20.4%) had postoperative pulmonary complications (≥ Clavien-Dindo Classification Grade 2). The cutoff value of SpO2 recovery time obtained from the receiver operating characteristic curve analysis was 90 s [sensitivity, 81.8%; specificity, 72.1%; AUC, 0.77 (95% confidence interval, 0.64-0.90)]. The occurrence of postoperative pulmonary complications was 42.9% in the delayed recovery time (DRT; SpO2 recovery time ≥ 90 s) group and 6.1% in the non-DRT (SpO2 recovery time < 90 s) group (p = 0.002). DRT was a predictor of postoperative pulmonary complications (odds ratio, 11.60; 95% CI 2.19-61.80). CONCLUSIONS: DRT of SpO2 after stair climbing is a predictor of postoperative pulmonary complications following lobectomy in borderline patients who require exercise capacity assessment. SpO2 monitoring after stair climbing may be useful as one of the preoperative assessments in patients undergoing lobectomy.

19.
Gen Thorac Cardiovasc Surg ; 72(2): 127-133, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37395938

RESUMO

OBJECTIVE: Positive pleural lavage cytology (PLC +) is a poor prognostic factor for non-small cell lung cancer (NSCLC). However, data on the impact of intraoperative rapid diagnosis of PLC (rPLC) are lacking. Therefore, we evaluated the efficacy of rPLC before resection during surgery. METHODS: A total of 1,838 patients who underwent rPLC for NSCLC between September 2002 and December 2014 were studied retrospectively. We assessed the clinicopathological factors between rPLC findings and the impact on survival of patients with curative resection. RESULTS: The rPLC + status was observed in 96 (5.3%) among 1,838 patients. The rPLC + group had more unsuspected N2 (30%) than the rPLC- group (p < 0.001). The 5-year overall survival (OS) of patients who underwent lobectomy or more extensive resection with rPLC + , negative rPLC (rPLC-), and microscopic pleural dissemination (PD) and/or malignant pleural effusion (PE) were 67.3, 81.3, and 11.0%, respectively. In the rPLC + group, the prognosis of patients with pN2 was equal to that of pN0-1 (5-year OS: 77.9% vs. 63.4%, p = 0.263). Undetectable dissemination in the first evaluation immediately after starting surgery was found in 9% of rPLC + patients by additional evaluation of the thoracic cavity. CONCLUSIONS: Patients with rPLC + have more favorable survival than those with microscopic PD/PE after surgery. Curative resection should be performed in patients with rPLC + , even if N2 is detected during surgery. However, the rPLC + group often has N2 upstaging; therefore, systematic nodal dissection should be performed in rPLC + patients for exact staging. rPLC may contribute to preventing oversight PD by re-evaluation during surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Irrigação Terapêutica , Citologia , Estadiamento de Neoplasias , Prognóstico
20.
Clin Lung Cancer ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38762395

RESUMO

BACKGROUND: Although the positive rate of preresection pleural lavage cytology (PLC) is low, it is an important indicator of poor prognosis for non-small-cell lung cancer patients with frequent pleural dissemination (PD) recurrence. Thin-section computed tomography (TSCT) can reveal relationships between a primary tumor and the pleura at 1 to 2 mm intervals, and this is associated with visceral pleural invasion (VPI). However, its association with PLC remains unclear. Therefore, we aimed to improve PLC efficiency and predict PD recurrence by understanding the relationship between PLC and preoperative TSCT findings. PATIENTS AND METHODS: Between January 2014 and December 2018, we reviewed 978 patients with non-small-cell lung cancer who underwent PLC tests during complete resection surgery. Preoperative TSCT findings were evaluated, and factors with the highest specificity (proportion of patients with radiologically to pathologically diagnosed positive PLC) were investigated. We also evaluated their relationships with VPI and PD recurrence. RESULTS: PLC positive was identified in 55 (5.6%) of the 978 patients. The two TSCT findings predicting PLC results, "the absence of pleural findings," ie, tumor not attached to pleura or without pleural tag, and "consolidation-to-tumor ratio ≤0.5", had a specificity of 100% (95% confidence interval: 90.4%-100%); additionally, all cases with these findings were VPI negative and had no PD recurrence. And 24% of the cohort had either of these findings. CONCLUSION: The absence of pleural findings and/or consolidation-to-tumor ratio ≤0.5 of primary tumor on preoperative TSCT can predict PLC negativity with very high probability; therefore, PLC can be omitted for such patients.

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