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1.
Cancer Sci ; 114(12): 4521-4534, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37806311

RESUMO

Epithelial-mesenchymal transition (EMT) promotes primary tumor progression toward a metastatic state. The role of tumor-associated macrophages (TAMs) in inducing EMT in lung squamous cell carcinoma (LUSC) remains unclear. We aimed to clarify the significance of TAMs in relation to EMT in LUSC. We collected 221 LUSC specimens from patients who had undergone surgery. Immunohistochemistry was performed to evaluate M1-like and M2-like TAM distribution and EMT by E-cadherin and vimentin staining. Human LUSC cell lines (H226 and EBC-1) and a human monocyte cell line (THP-1) were used for in vitro experiments. M2-like polarization of TAMs and EMT marker expression in LUSC cells were evaluated by western blotting. The biological behavior of LUSC cells was evaluated by migration, invasion, and cell proliferation assays. Immunohistochemical analysis showed that 166 (75.1%) tumors were E-cadherin-positive and 44 (19.9%) were vimentin-positive. M2-like TAM density in the tumor stroma was significantly associated with vimentin positivity and worse overall survival. Western blotting demonstrated higher levels of CD163, CD206, vascular endothelial growth factor, and transforming growth factor beta 1 (TGF-ß1) in TAMs versus unstimulated macrophages. Furthermore, increased TGF-ß1 secretion from TAMs was confirmed by ELISA. TAM-co-cultured H226 and EBC-1 cells exhibited EMT (decreased E-cadherin, increased vimentin). Regarding EMT-activating transcriptional factors, phosphorylated Smad3 and ZEB-family proteins were higher in TAM-co-cultured LUSC cells than in parental cells. TAM-co-cultured H226 and EBC-1 cells demonstrated enhanced migration and invasion capabilities and improved proliferation. Overall, the present study suggests that TAMs can induce EMT with increased metastatic potential and tumor cell proliferation in LUSC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Fator de Crescimento Transformador beta1 , Vimentina/metabolismo , Fator de Crescimento Transformador beta , Genes Homeobox , Macrófagos Associados a Tumor/metabolismo , Fator A de Crescimento do Endotélio Vascular , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Transição Epitelial-Mesenquimal , Caderinas/metabolismo , Neoplasias Pulmonares/metabolismo , Dedos de Zinco , Pulmão/patologia , Movimento Celular
2.
Surg Today ; 53(1): 135-144, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35780275

RESUMO

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Tegafur , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Uracila , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
3.
Surg Today ; 51(2): 322-326, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32535710

RESUMO

This study aimed to investigate the association between the volume-dependent parameters in 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) and a recurrence of thymic carcinoma. A retrospective chart review was performed based on our multi-institutional database to identify patients undergoing PET prior to resection of thymic carcinoma or neuroendocrine carcinoma between 1991 and 2018. The PET parameters (metabolic tumor volume and total lesion glycolysis) were evaluated retrospectively. The relevant factors were extracted and a survival analysis was performed using the Kaplan-Meier method. Sixteen patients were thus deemed to be eligible for analysis. The median follow-up period following resection was 2.65 years (range: 0.96-0.68 years). The recurrence-free survival was significantly longer in patients with a metabolic tumor volume < = 22.755 cm3 and with total lesion glycolysis < = 105.4006 g/mL (p = 0.001 and 0.001, respectively, by a log-rank test). The metabolic tumor volume and total lesion glycolysis may, therefore, be predictive of the postoperative recurrence of thymic carcinoma.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Timoma/diagnóstico por imagem , Timoma/cirurgia , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/cirurgia , Intervalo Livre de Doença , Fluordesoxiglucose F18 , Seguimentos , Glicólise , Humanos , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Recidiva , Estudos Retrospectivos , Timoma/metabolismo , Timoma/patologia , Neoplasias do Timo/metabolismo , Neoplasias do Timo/patologia , Fatores de Tempo
4.
Surg Today ; 51(4): 502-510, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32776294

RESUMO

PURPOSE: There are few data available on the outcomes of postoperative recurrent thymic carcinoma (TC) and thymic neuroendocrine carcinoma (TNEC). The aim of this study is to evaluate the treatment and survival in patients with recurrent TC and TNEC after undergoing surgical resection. METHODS: A retrospective chart review was performed using our multicenter database to identify patients with a postoperative recurrence of TC and TNEC from 1995 to 2018. The clinicopathological factors were reviewed and the survival outcomes were analyzed. RESULTS: Sixty patients were identified among 152 patients who underwent resection of TC and TNEC. The median follow-up period from the first recurrence was 14.8 months (range 0-144). The 5-year post-recurrence survival was 23% for the whole cohort. According to a univariable analysis, advanced stage [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.09-9.54], interval between primary surgery and recurrence (HR 0.97, 95% CI 0.95-0.99), any treatment for recurrence (HR: 0.27, 95% CI 0.13-0.58) and chemotherapy for recurrence (HR: 0.46, 95% CI 0.22-0.95) were significant factors related to post-recurrence survival. CONCLUSIONS: Chemotherapy rather than surgery appears to be the mainstay treatment for managing patients with postoperative recurrent TC and TNEC and it may also be considered in multidisciplinary management. Further studies with a larger sample size are required to confirm our findings.


Assuntos
Carcinoma Neuroendócrino/cirurgia , Recidiva Local de Neoplasia , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino/mortalidade , Terapia Combinada , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , Taxa de Sobrevida , Timoma/mortalidade , Neoplasias do Timo/mortalidade , Fatores de Tempo , Resultado do Tratamento
5.
Surg Today ; 49(4): 357-360, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30430264

RESUMO

Minimally invasive surgery (MIS) has occasionally been used for selected patients with thymoma, but there is little information on the MIS approach for thymic carcinoma. The aim of this study was to evaluate survival outcomes after MIS for early-stage (Masaoka stage I-II) thymic carcinoma and thymic neuroendocrine carcinoma. A retrospective chart review of the cases recorded in our multi-institutional database was performed to identify patients who underwent resection for thymic carcinoma between 1995 and 2017. MIS thymectomy was performed in 17 cases (VATS, n = 14; RATS, n = 3. male, 41%; median age, 72 years). The median follow-up period was 32.7 (range 7.4-106) months. The five-year overall survival and relapse-free survival rates were 84.4% and 77.8%, respectively. The present study demonstrated encouraging preliminary results regarding MIS for the treatment of early-stage thymic carcinoma and thymic neuroendocrine carcinoma. Further studies with a larger sample size are required to evaluate the indications for this surgery.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Timectomia/métodos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Timoma/mortalidade , Neoplasias do Timo/mortalidade
6.
BMC Pulm Med ; 17(1): 166, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-29202834

RESUMO

BACKGROUND: Previously reported prognostic tools for patients with resected non-small cell lung cancer (NSCLC) include factors found postoperatively, but not preoperatively. However, it would be important to predict patient prognosis before NSCLC resection. To suggest a novel preoperative prognostic tool, we evaluated the relationship of preoperative prognostic factors with the survival of patients with resected NSCLC. METHODS: We retrospectively reviewed the data of two independent cohorts of patients with completely resected NSCLC. To develop the prognostic index in one cohort, the overall survival (OS) was evaluated using the Cox proportional hazards model. We assessed the disease-free survival (DFS) and OS of three risk groups defined according to the prognostic index. Then, the prognostic index was validated in the other cohort. RESULTS: Seven independent risk factors for OS were selected: age ≥ 70 years, ever-smokers, vital capacity <80%, neutrophil-to-lymphocyte ratio ≥ 2.1, cytokeratin 19 fragment >normal limit, non-usual interstitial pneumonia (UIP) pattern, and UIP pattern. Three risk groups were defined: low-risk (36.9%), intermediate-risk (54.0%), and high-risk (9.1%). In the derivation cohort, the 5-year DFS rate was 77.8%, 58.8%, and 22.6% (P < 0.001), and the 5-year OS rate was 95.2%, 70.4%, and 28.9% (P < 0.001), respectively. Multivariate analyses showed that the prognostic index predicted DFS and OS, independent of pathological stage and tumor histology, in both derivation and validation cohorts. CONCLUSIONS: We developed and validated a simple preoperative prognostic index composed of seven variables, which may help clinicians predict prognosis before surgery in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Medição de Risco/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Intervalo Livre de Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/complicações , Queratina-19/sangue , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutrófilos , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Fumar , Taxa de Sobrevida , Capacidade Vital , Adulto Jovem
7.
World J Surg Oncol ; 15(1): 212, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29191241

RESUMO

BACKGROUND: Video-assisted thoracic surgery (VATS) plays an important role in thoracic surgery because it is less invasive. However, the existence of severe pleural adhesions may make VATS difficult and complicated. The aim of this study was to assess the utility of inspiration and expiration computed tomography (respiratory dynamic CT (RD-CT)) in evaluation of pleural adhesions preoperatively. METHODS: RD-CT was performed on 107 patients undergoing thoracotomies (both VATS and open). We assessed synchronous motion during respiration on RD-CT. Comparing the results of RD-CT and intraoperative findings, we assessed the utility of preoperative evaluation. RESULTS: A negative correlation between sliding score and adhesion grade was revealed. Sliding score in adhesion negative patients was significantly higher than that in adhesion positive patients (P < 0.0001). The sensitivity of RD-CT was 63.6%, specificity was 74.1%, and accuracy was 72%. Among 62 patients with a CT-Respiration Ratio of less than 0.65, the sensitivity of RD-CT was 77.8%, specificity was 86.8%, and accuracy was 85.5%. CONCLUSIONS: RD-CT may be clinically useful for detecting the presence of pleural adhesions. It can be adopted as one of the criteria for deciding the surgical approach.


Assuntos
Doenças Pleurais/diagnóstico por imagem , Cuidados Pré-Operatórios/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Aderências Teciduais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Conversão para Cirurgia Aberta , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/complicações , Respiração , Sensibilidade e Especificidade , Cirurgia Torácica Vídeoassistida/métodos , Aderências Teciduais/complicações
8.
Kyobu Geka ; 68(6): 421-5, 2015 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-26066871

RESUMO

Video-assisted thoracic surgery( VATS) has been utilized worldwide for treatment of thoracic disease in recent years. Then, in most VATS, the thoracoscope was handled by young surgeons consequently. In VATS, a role of the scopist is very important, because if there is no consensus of verticality and horizontality on the monitor among operator, assistant and scopist, it is difficult to perform the surgery smoothly. Therefore, it is important for young surgeons to improve their skills as scopist. However, there are few models of verticality and horizontality on the monitor and thoracoscope techniques of VATS. We present our consensus of verticality and horizontality on the monitor in the standard 3-ports VATS by right upper lobectomy and left upper lobectomy.


Assuntos
Pneumopatias/cirurgia , Cirurgia Torácica Vídeoassistida/instrumentação , Cirurgia Torácica Vídeoassistida/métodos , Humanos , Pneumonectomia/métodos , Toracoscópios
9.
Oncol Rep ; 47(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35169863

RESUMO

To improve the treatment strategy of immune­checkpoint inhibitors for non­small cell lung cancer (NSCLC), a comprehensive analysis of programmed death­ligand (PD­L)1 and PD­L2 expression is clinically important. The expression of PD­L1 and PD­L2 on both tumor cells (TCs) and tumor­infiltrating immune cells (ICs) was investigated, with respect to tumor­infiltrating lymphocytes (TILs) and M2 tumor­associated macrophages (TAMs), which are key components of the tumor microenvironment, in 175 patients with resected NSCLC. The TIL and M2 TAM densities were associated with the expression of PD­L1 on the two TCs (both P<0.0001) and ICs (both P<0.0001). The TIL and M2 TAM densities were also associated with the expression of PD­L2 on both TCs (P=0.0494 and P=0.0452, respectively) and ICs (P=0.0048 and P=0.0125, respectively). However, there was no correlation between the percentage of PD­L1­positive TCs and the percentage of PD­L2­positive TCs (r=0.019; P=0.8049). Meanwhile, tumor differentiation was significantly associated with the PD­L1 expression on TCs and ICs (P=0.0002 and P<0.0001, respectively). By contrast, tumor differentiation was inversely associated with the PD­L2 expression on both TCs and ICs (P=0.0260 and P=0.0326, respectively). In conclusion, the combined evaluation of PD­L1 and PD­L2 expression could be clinically important in the treatment strategy of immune­checkpoint inhibitors in patients with NSCLC. In particular, the evaluation of PD­L2 expression may be necessary for patients with PD­L1­negative NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Diferenciação Celular , Humanos , Linfócitos do Interstício Tumoral , Proteína 2 Ligante de Morte Celular Programada 1 , Microambiente Tumoral , Macrófagos Associados a Tumor
10.
Oncol Rep ; 48(5)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36102318

RESUMO

Tumor­associated macrophages (TAMs), particularly M2 macrophages, promote tumor progression, while Wnt genes encode a family of multi­functional glycoproteins that serve an important role in tumorigenesis. Immunohistochemical studies were performed to evaluate Wnt2b and Wnt5a expression in tumor and stromal cells in M2 and M1 TAMs and Ki­67 proliferation index in 160 consecutive patients with resected non­small cell lung cancer (NSCLC). Overall, 52 tumors (32.5%) were classified as tumoral Wnt2b­high (Wnt2b­positive tumor cells >30%) and 95 (59.4%) as stromal Wnt2b­high (Wnt2b­positive stromal cells >30%), while 75 (46.9%) were classified as tumoral Wnt5a­high (Wnt5a­positive tumor cells >30%) and 63 (39.4%) as stromal Wnt5a­high (Wnt5a­positive stromal cells >28%). The density of M2 TAMs was significantly higher in the tumoral (P=0.0024) and stromal Wnt2b­high groups (P=0.0054). The density of M2 TAMs was also significantly higher in the tumoral (P=0.0005) and stromal Wnt5a­high groups (P=0.0486). By contrast, no difference in stromal or islet M1 TAM density was observed in relation to tumoral or stromal Wnt2b or Wnt5a status. Furthermore, Ki­67 proliferation index was significantly higher in the tumoral (P=0.0121) and stromal Wnt2b­high (P=0.0019) and tumoral Wnt5a­high (P=0.0088) groups. Overall survival rate was significantly lower in the Wnt2b­high (P=0.0437), Wnt5a­high (P=0.0106) and M2 TAM­high (P=0.0060) groups. Wnt2b and Wnt5a expression in tumor and stromal cells may induce M2 TAMs to produce more aggressive behavior during tumor progression in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Glicoproteínas , Humanos , Imuno-Histoquímica , Antígeno Ki-67 , Neoplasias Pulmonares/patologia , Macrófagos Associados a Tumor , Proteínas Wnt/genética , Proteína Wnt-5a/genética
11.
Eur J Cardiothorac Surg ; 62(5)2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-35997576

RESUMO

OBJECTIVES: The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma. METHODS: Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I-III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan-Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS. RESULTS: The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15-2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96-0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00-1.07), smoking history (HR: 2.31, 95% CI: 1.35-3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32-4.00) were significantly associated with shorter OS. CONCLUSIONS: First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Mutação , Prognóstico
12.
Interact Cardiovasc Thorac Surg ; 33(2): 242-249, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34151358

RESUMO

OBJECTIVES: Although lymph node (LN) metastases are not uncommon in thymic carcinomas, preoperative LN evaluation, intraoperative lymph node dissection (LND) and postoperative outcomes remain unknown. The aim of this study was to elucidate the characteristics of and outcomes in patients with thymic carcinomas and thymic neuroendocrine carcinomas undergoing LND. METHODS: A retrospective chart review was performed using our multi-institutional database to identify patients who underwent resection and LND for thymic carcinoma or thymic neuroendocrine carcinoma between 1991 and 2018. An enlarged mediastinal LN was defined as having a short-axis diameter >1 cm. We assessed survival outcomes using the Kaplan-Meier analysis. RESULTS: N1-level LND was performed in 41 patients (54.6%), N2-level LND in 14 patients (18.7%) and both-level LND in 16 patients (21.3%). Pathological LN metastasis was detected in 20 patients (26.7%) among the 75 patients undergoing LND. There was a significant difference in the number of LN stations (P = 0.015) and metastasis factor (P = 0.0042) between pathologically LN-positive and pathologically LN-negative patients. The sensitivity of enlarged LNs on preoperative computed tomography was 18.2%. There was a tendency towards worse overall survival of pathologically N2-positive patients, although the difference was not statistically significant (P = 0.15). CONCLUSIONS: Preoperative CT appears to play a limited role in detecting pathological LN metastases. Our findings suggest that the significance of N1- and N2-level LND should be evaluated in prospective studies to optimize the postoperative management of patients with thymic carcinomas and neuroendocrine carcinomas.


Assuntos
Carcinoma Neuroendócrino , Timoma , Neoplasias do Timo , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/cirurgia , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Timoma/diagnóstico por imagem , Timoma/cirurgia , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia
13.
Lung Cancer ; 136: 136-144, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31499335

RESUMO

OBJECTIVES: PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) plays important roles in regulating the antitumor T cell response. However, the mechanistic and clinical significance of the effect of PD-L1 on TCs versus ICs remains unclear. On the other hand, tumor-associated macrophages (TAMs), M2 macrophages in particular, can promote tumor progression. METHODS: We evaluated PD-L1 expression on TCs and ICs using Ventana SP263 assay and the stromal M2 TAM distribution using CD163 staining in 160 consecutive patients with resected non-small cell lung cancer (NSCLC). RESULTS: PD-L1 expression on TCs and ICs was significantly higher in stromal M2 TAM-high group than in stromal M2 TAM-low group (p < 0.001 and p < 0.001, respectively). Regarding the clinical significance of PD-L1, PD-L1 expression on TCs was significantly associated with histology (p = 0.001), tumor differentiation (p < 0.001) and nodal status (p = 0.029). Furthermore, PD-L1 expression on ICs was significantly associated with histology (p < 0.001), tumor differentiation (p < 0.001), tumor status (p = 0.024), nodal status (p = 0.016), and pathologic stage (p = 0.004). The disease-free survival rate was significantly lower in patients with PD-L1-positive TC than in those with PD-L1-negative TC (p = 0.023), as well as in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p < 0.001). Furthermore, the overall survival rate was significantly lower in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p = 0.023). CONCLUSIONS: During tumor progression in NSCLC, the presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs. In patients with NSCLC, PD-L1 expression both on TCs and ICs was associated with malignant behaviors, which was more in case of ICs.


Assuntos
Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Expressão Gênica , Neoplasias Pulmonares/genética , Macrófagos/metabolismo , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Macrófagos/imunologia , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Microambiente Tumoral
14.
Exp Ther Med ; 18(6): 4490-4498, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31777551

RESUMO

Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment that can be polarized into different phenotypes, including tumor-inhibiting M1 macrophages and tumor-promoting M2 macrophages. To elucidate the biological and clinical significance of M2 TAMs in non-small-cell lung cancer (NSCLC), a comprehensive clinical assessment of the tissue distribution of M2 TAMs was performed. The tissue distribution of M2 TAMs was retrospectively analyzed using CD163 immunohistochemistry in 160 consecutive patients who underwent NSCLC resection. Tumor proliferation was evaluated via the Ki-67 proliferation index. The results revealed that the stromal density of M2 TAMs was significantly associated with the C-reactive protein (CRP) level (P=0.0250), the Ki-67 proliferation index (P=0.0090) and invasive size (P=0.0285). Furthermore, the stromal M2 TAM density was significantly associated with tumor differentiation (P=0.0018), lymph node metastasis (P=0.0347) and pathological stage (P=0.0412). The alveolar M2 TAM density was also significantly associated with the CRP level (P=0.0309), invasive size (P<0.0001), tumor differentiation (P=0.0192), tumor status (P=0.0108) and pathological stage (P=0.0110). By contrast, no association was observed between islet M2 TAM density and the aforementioned biological and clinical factors. In regards to prognosis, disease-free survival rate was significantly lower in patients with stromal M2 TAM-high tumors (P=0.0270) and in those with alveolar M2 TAM-high tumors (P=0.0283). Furthermore, the overall survival rate was also significantly lower in patients with stromal M2 TAM-high tumors (P=0.0162) and in those with alveolar M2 TAM-high tumors (P=0.0225). Therefore, during NSCLC progression, M2 TAMs may induce tumor cell aggressiveness and proliferation and increase metastatic potential, resulting in a poor prognosis in patients with NSCLC.

15.
Interact Cardiovasc Thorac Surg ; 28(3): 375-379, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137401

RESUMO

OBJECTIVES: Previous studies have suggested that a second malignancy often develops after resection of thymoma; however, it remains unknown whether this is applicable to thymic carcinoma. METHODS: A retrospective chart review was performed based on our multi-institutional database of resected thymic epithelial tumours between 1991 and 2016. A second malignancy was defined as newly diagnosed after thymic tumour resection. The cumulative incidence of and related death from a second malignancy after thymic and neuroendocrine carcinoma resections were estimated using a competing risk model and were compared to those of patients undergoing a thymoma resection. RESULTS: Two hundred and thirty-eight patients were identified (thymic carcinoma 59; thymoma 179). A second malignancy developed in 1 patient (1.7%) with thymic carcinoma and in 17 patients (9.5%) with thymoma. Deaths from second malignancies were noted in 7 patients with thymoma. There was a tendency towards a lower cumulative incidence of and a lower cumulative death from a second malignancy after thymic carcinoma resection (P = 0.139 and P = 0.20, respectively) than after thymoma resection. The cumulative incidence of a second malignancy in patients with thymic carcinoma was 2.8% at 5 years and at 10 years (8.0% at 5 years and 11.8% at 10 years in patients with thymoma). CONCLUSIONS: After resection of thymic and thymic neuroendocrine carcinoma, the probability of developing a second malignancy, as well as mortality from a second malignancy, is very low. A prospective study with a larger sample size is required to validate our results.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Timectomia/métodos , Timoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Timoma/diagnóstico , Adulto Jovem
16.
Ann Thorac Surg ; 106(4): e189-e191, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29733825

RESUMO

Thymoma is a common neoplasm in the anterior mediastinum but rarely arises from the middle mediastinum. We report 3 patients with thymoma that arose from the middle mediastinum. Surgical resections were performed with dissection of the azygos vein, which led to safe separation of the tumors from mediastinal structures. Although rare, thymoma should be included in the differential diagnosis for middle mediastinal tumors.


Assuntos
Mediastino , Timectomia/métodos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Adulto , Idoso , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Mediastinoscopia , Timoma/diagnóstico , Neoplasias do Timo/diagnóstico , Tomografia Computadorizada por Raios X
17.
Gen Thorac Cardiovasc Surg ; 66(8): 464-470, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29802566

RESUMO

OBJECTIVE: This study aimed to determine if the vessel interruption sequence during thoracoscopic lobectomy affects disease recurrence. METHODS: We retrospectively analyzed 187 consecutive patients who underwent video-assisted thoracoscopic surgery lobectomy with curative intent for non-small cell lung cancer between January 2007 and December 2013. Their clinicopathological, operative, and postoperative data were compared. Patients with minimally invasive adenocarcinoma were excluded. RESULTS: A total of 104 patients underwent total venous interruption before interruption of any artery branch (V-first), while 83 patients underwent some artery interruption first (non-V-first). Clinicopathological characteristic distributions were similar between both groups except for the resected lobe. Seven of 104 patients in the V-first group and 15 of 83 patients in the non-V-first group experienced disease recurrences. Among the 187 patients who underwent thoracoscopic lobectomy, overall survival tended to be longer in the V-first group than in the non-V-first group (P = 0.080). Furthermore, disease-free survival was significantly longer in the V-first group than in the non-V-first group (P = 0.019), particularly in stage I patients (P = 0.047). Multivariate analysis showed that vessel interruption sequence was a significant prognostic factor for poor disease-free survival, after adjusting for pathological stage and histology (hazard ratio 2.127; 95% confidence interval 1.009-4.481). There was no significant difference in intraoperative blood loss between both groups. CONCLUSIONS: Interrupting the pulmonary vein first may be associated with improved disease-free survival in patients undergoing thoracoscopic lobectomy for non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Veias Pulmonares/cirurgia , Cirurgia Torácica Vídeoassistida , Idoso , Perda Sanguínea Cirúrgica , Intervalo Livre de Doença , Feminino , Humanos , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Psicocirurgia , Estudos Retrospectivos
18.
J Cardiothorac Surg ; 12(1): 35, 2017 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-28526052

RESUMO

BACKGROUND: Long-acting ß2-adrenoceptor agonists have been shown to increase the risk of atrial arrhythmias in patients with stable chronic obstructive pulmonary disease. The aim of this study was to investigate whether perioperative long-acting ß2-adrenoceptor agonists treatment would increase the risk of postoperative atrial arrhythmias after lung cancer surgery in chronic obstructive pulmonary disease patients. METHODS: We retrospectively analyzed 174 consecutive chronic obstructive pulmonary disease patients with non-small-cell lung cancer who underwent lobectomy or segmentectomy. The subjects were divided into those with or without perioperative long-acting ß2-adrenoceptor agonists treatment. Postoperative cardiopulmonary complications were compared between the two groups. RESULTS: There were no statistically significant differences between the perioperative long-acting ß2-adrenoceptor agonists treatment group and the control group in the incidence of postoperative atrial arrhythmias (P = 0.629). In 134 propensity-score-matched pairs, including variables such as age, gender, comorbidities, smoking history, operation procedure, lung-cancer staging, and respiratory function, there were no significant differences between the two groups in the incidence of postoperative cardiopulmonary complications, including atrial arrhythmias. CONCLUSIONS: Perioperative administration of long-acting ß2-adrenoceptor agonists might not increase the incidence of postoperative atrial arrhythmias after surgical resection for non-small-cell lung cancer in chronic obstructive pulmonary disease patients.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Arritmias Cardíacas/etiologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Preparações de Ação Retardada , Feminino , Humanos , Incidência , Japão/epidemiologia , Neoplasias Pulmonares/complicações , Masculino , Pontuação de Propensão , Doença Pulmonar Obstrutiva Crônica/complicações
19.
Asian Cardiovasc Thorac Ann ; 24(2): 152-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26764199

RESUMO

BACKGROUND: It has recently been suggested that virtual-assisted lung mapping may enable safer and more reliable intraoperative navigation compared to conventional preoperative lung marking strategies. This study aimed to examine the relationship between emphysematous lungs and the intraoperative visibility of virtual-assisted lung mapping markings. METHODS: We retrospectively analyzed the data of 21 patients who underwent virtual-assisted lung mapping followed by lung resection between October 2013 and May 2015. The visibility of the intraoperative lung markings was graded. The degree of pulmonary emphysema was assessed by the percentage of low attenuation area on computed tomography. We elucidated the associations between the marking grade and other factors such as patient age or sex, pulmonary lobe mapped, marking operator, Brinkman index, and percentage of low attenuation area of the pulmonary lobe. RESULTS: In Spearman rank correlation analysis, there was no correlation between the Brinkman index and the percentage of low attenuation area (n = 26, r = -0.016, p = 0.937). In stepwise multivariate regression analysis, the marking grade correlated with the marking operator (p < 0.001) and the Brinkman index (p = 0.008), but not with patient age or sex, the pulmonary lobe mapped, or degree of pulmonary emphysema. CONCLUSION: The skill of the marking operator and the patient's smoking history had significant effects on the intraoperative visibility of markings made by virtual-assisted lung mapping, whereas emphysematous lungs did not affect the intraoperative visibility of lung markings.


Assuntos
Pontos de Referência Anatômicos , Broncoscopia , Neoplasias Pulmonares/patologia , Pulmão/patologia , Enfisema Pulmonar/patologia , Adulto , Idoso , Competência Clínica , Feminino , Humanos , Cuidados Intraoperatórios , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pneumonectomia , Valor Preditivo dos Testes , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/etiologia , Radiografia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Gravação em Vídeo
20.
Gen Thorac Cardiovasc Surg ; 63(12): 652-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26419246

RESUMO

OBJECTIVES: Inhaled corticosteroid (ICS) treatment has been shown to increase the risk of respiratory complications in patients with stable chronic obstructive pulmonary disease (COPD). However, the effects of perioperative ICS treatment on postoperative respiratory complications after lung cancer surgery have not been elucidated. The aim of this study was to investigate whether perioperative ICS treatment would increase the risk of postoperative respiratory complications after lung cancer surgery in patients with COPD. METHODS: We retrospectively analyzed 174 consecutive COPD patients with non-small-cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between January 2007 and December 2014. Subjects were grouped based on whether or not they were administered perioperative ICS treatment. Postoperative cardiopulmonary complications were compared between the groups. RESULTS: There were no statistically significant differences in the incidence of postoperative respiratory complications (P = 0.573) between the perioperative ICS treatment group (n = 16) and the control group (n = 158). Perioperative ICS treatment was not significantly associated with postoperative respiratory complications in the univariate or multivariate analysis (odds ratio [OR] = 0.553, 95% confidence interval [CI] = 0.069-4.452, P = 0.578; OR = 0.635, 95% CI = 0.065-6.158, P = 0.695, respectively). Kaplan-Meier analysis showed that there were no statistically significant differences in the postoperative respiratory complications-free durations between the groups (P = 0.566), even after propensity score matching (P = 0.551). CONCLUSION: There was no relationship between perioperative ICS administration and the incidences of postoperative respiratory complications after surgical resection for NSCLC in COPD patients.


Assuntos
Corticosteroides/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Pneumopatias/epidemiologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Complicações Pós-Operatórias/epidemiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/complicações , Métodos Epidemiológicos , Feminino , Humanos , Neoplasias Pulmonares/complicações , Masculino , Assistência Perioperatória/métodos , Pneumonia/epidemiologia , Atelectasia Pulmonar/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Respiração Artificial , Síndrome do Desconforto Respiratório/epidemiologia , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/terapia , Cirurgia Torácica Vídeoassistida , Traqueostomia
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