RESUMO
BACKGROUND: The survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) after open or thoracoscopic upfront esophagectomy remained unclear. OBJECTIVE: The aim of this retrospective study was to compare overall survival between open and thoracoscopic esophagectomy for ESCC patients without neoadjuvant chemodatiotherapy (CRT). METHODS: The Taiwan Cancer Registry was investigated for ESCC cases from 2008 to 2016. We enrolled 2053 ESCC patients receiving open (n = 645) or thoracoscopic (n = 1408) upfront esophagectomy. One-to-two propensity score matching between the two groups was performed. Stage-specific survival was compared before and after propensity score matching. Univariate analysis and multivariate analysis were used to identify risk factors. RESULTS: After one-to-two propensity score matching, a total of 1299 ESCC patients with comparable clinic-pathologic features were identified. There were 433 patients in the open group and 866 patients in the thoracoscopic group. The 3-year overall survival of matched patients in the thoracoscopic group was better than that of matched patients in the open group (58.58% vs 47.62%, P = 0.0002). Stage-specific comparisons showed thoracoscopic esophagectomy is associated with better survival than open esophagectomy in patients with pathologic I/II ESCC. In multivariate analysis, surgical approach was still an independent prognostic factor before and after one-to-two propensity score matching. CONCLUSION: This propensity-matched study revealed that thoracoscopic esophagectomy could provide better survival than open esophagectomy in ESCC patients without neoadjuvant CRT.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Neoplasias Esofágicas/cirurgia , Estudos Retrospectivos , Esofagectomia/efeitos adversos , Terapia Neoadjuvante , Pontuação de PropensãoRESUMO
BACKGROUND: Fungal empyema is an uncommon disease and is associated with a high mortality rate. Surgical intervention is suggested in stage II and III empyema. However, there were no studies that reported the outcomes of surgery for fungal empyema. METHODS: This study is a retrospective analysis in a single institute. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. We separated the patients into a fungal empyema group and a bacterial empyema group according to culture results. We used 1:3 propensity score matching to reduce selection bias. RESULTS: There were 1197 empyema patients who received surgery. Of these, 575 patients showed positive culture results and were enrolled. Twenty-eight patients were allocated to the fungal empyema group, and the other 547 patients were placed in the bacterial empyema group. Fungal empyema showed significantly longer intensive care unit stay (16 days vs. 3 days, p = 0.002), longer median ventilator usage duration (20.5 days vs. 3 days, p = 0.002), longer hospital stay duration (40 days vs. 17.5 days, p < 0.001) and a higher 30-day mortality rate (21.4% vs. 5.9%, p < 0.001). Fungal empyema revealed significantly poorer 1-year survival rate than bacterial empyema before matching (p < 0.001) but without significant difference after matching. CONCLUSIONS: The fungal empyema patients had much worse surgical outcomes than the bacterial empyema patients. Advanced age and high Charlson Comorbidity Index score are independent predictors for poor prognosis. Prompt surgical intervention combined with the use of antifungal agents was the treatment choice for fungal empyema.
Assuntos
Empiema Pleural , Cirurgia Torácica Vídeoassistida , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Cirurgia Torácica Vídeoassistida/efeitos adversos , Empiema Pleural/tratamento farmacológico , Empiema Pleural/cirurgia , Empiema Pleural/microbiologia , BactériasRESUMO
BACKGROUND: For patients with locoregional esophageal squamous cell carcinoma (ESCC), survival outcomes among neoadjuvant chemoradiotherapy followed by operation (nCRT-OP), definitive chemoradiotherapy (dCRT), and esophagectomy alone remain controversial. PATIENTS AND METHODS: Information from the 2008-2016 Taiwan Cancer Registry was used. A total of 7637 cT1b-4, N0/+, M0 ESCC patients receiving nCRT-OP (n = 1955), dCRT (n = 4122), or esophagectomy alone (n = 1560) were included. Propensity score matching was performed to balance clinical variables among the three groups. Stage-specific overall survival was compared before and after propensity score matching. Univariable and multivariable analyses were performed to identify prognostic factors. RESULTS: Propensity score matching resulted in 1407 cases for comparison. The 5-year overall survival rates for matched patients treated via dCRT, nCRT-OP, and esophagectomy alone were 19.77%, 31.23%, and 30.52%, respectively (p < 0.001). On multivariable analysis, treatment modality was still an independent prognostic factor both before and after propensity score matching. nCRT-OP and esophagectomy alone were associated with significantly better overall survival than dCRT for locoregional ESCC patients. CONCLUSIONS: This propensity-matched study revealed that nCRT-OP and esophagectomy provided better survival than dCRT in cT1b-4, N0/+, M0 ESCC patients.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Quimiorradioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Esofagectomia , Humanos , Terapia Neoadjuvante , Prognóstico , Estudos RetrospectivosRESUMO
Pemetrexed is a folic acid inhibitor used as a second-line chemotherapeutic agent for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), which accounts for 85% of lung cancers. However, prolonged treatment with pemetrexed may cause cancer cells to develop resistance. In this study, we found increased expressions of BMI1 (B Lymphoma Mo-MLV insertion region 1 homolog) and Sp1 and a decreased expression of miR-145-5p was found in pemetrexed-resistant A400 cells than in A549 cells. Direct Sp1 targeting activity of miR-145-5p was demonstrated by a luciferase based Sp1 3'-UTR reporter. Changed expression of miR-145-5p in A400 or A549 cells by transfection of miR-145-5p mimic or inhibitor affected the sensitivity of the cells to pemetrexed. On the other hand, the overexpression of Sp1 in A549 cells caused the decreased sensitivity to pemetrexed, induced cell migratory capability, and epithelial-mesenchymal transition (EMT) related transcription factors such as Snail Family Transcriptional Repressor 1 and Zinc Finger E-Box Binding Homeobox 1. In addition, the overexpression of BMI1 in the A549 cells resulted in an increase in Sp1 and a decrease in miR-145-5p accompanied by the elevations of cell proliferation and EMT transcription factors, which could be reduced by the overexpression of miR-145-5p or by treatment with the Sp1 inhibitor of mithramycin A. In conclusion, the results of this study suggest that the downregulation of miR-145-5p by BMI1 overexpression could lead to the enhanced expression of Sp1 to induce the EMT process in pemetrexed-resistant NSCLC cells. These results suggest that increasing miR-145-5p expression by delivering RNA drugs may serve as a sensitizing agent for pemetrexed-resistant NSCLC patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Transição Epitelial-Mesenquimal/genética , Pemetrexede/farmacologia , Pemetrexede/metabolismo , Pemetrexede/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Proliferação de Células/genética , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismoRESUMO
Background and Objectives: This single-center study aimed to assess the role of laparoscopic greater curvature plication (LGCP) in bariatric surgery. Materials and Methods: Using data from our institution's prospectively maintained database, we identified adult patients with obesity who underwent either laparoscopic sleeve gastrectomy (LSG) or LGCP between January 2012 and July 2017. In total, 280 patients were enrolled in this study. Results: The body mass index was higher in the LSG group than in the LGCP group (39.3 vs. 33.3, p < 0.001). Both groups achieved significant weight loss during the 3-year follow-up (p < 0.001). The weight-reduction rate was higher in the LSG group than in the LGCP group 6, 12, and 24 months postoperatively (p = 0.001, 0.001, and 0.012, respectively). The reoperation rate of the LGCP group was higher than that of the LSG group (p = 0.001). No deaths were recorded in either group. Conclusions: Although both the LGCP and LSG groups achieved significant weight loss over three years, the LGCP group demonstrated a lower weight-reduction rate and a higher reoperation rate than the LSG group. Thus, it is necessary to reassess the role of LGCP in bariatric surgery, particularly when LSG is a feasible alternative.
Assuntos
Cirurgia Bariátrica , Gastroplastia , Laparoscopia , Obesidade Mórbida , Adulto , Índice de Massa Corporal , Gastrectomia , Humanos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
The l-type amino acid transporter 1 (LAT1) is a membranous transporter that transports neutral amino acids for cells and is dysregulated in various types of cancer. Here, we first observed increased LAT1 expression in pemetrexed-resistant non-small cell lung cancer (NSCLC) cells with high cancer stem cell (CSC) activity, and its mRNA expression level was associated with shorter overall survival in the lung adenocarcinoma dataset of the Cancer Genome Atlas database. The inhibition of LAT1 by a small molecule inhibitor, JPH203, or by RNA interference led to a significant reduction in tumorsphere formation and the downregulation of several cancer stemness genes in NSCLC cells through decreased AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) activation. The treatment of the cell-permeable leucine derivative promoted AKT/mTOR phosphorylation and reversed the inhibitory effect of JPH203 in the reduction of CSC activity in pemetrexed-resistant lung cancer cells. Furthermore, we observed that LAT1 silencing caused the downregulation of programmed cell death 1 ligand 1 (PD-L1) on lung cancer cells. The PD-L1+/LAT1+ subpopulation of NSCLC cells displayed great CSC activity with increased expression of several cancer stemness genes. These data suggest that LAT1 inhibitors can serve as anti-CSC agents and could be used in combination with immune checkpoint inhibitors in lung cancer therapy.
Assuntos
Antígeno B7-H1/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Benzoxazóis/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Transportador 1 de Aminoácidos Neutros Grandes/química , Transportador 1 de Aminoácidos Neutros Grandes/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Pemetrexede/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Tirosina/análogos & derivados , Tirosina/farmacologiaRESUMO
BACKGROUND: The therapeutic strategies for clinical stage T1-3N2 (cT1-3N2) lung cancer are controversial. For operable tumors, treatment can vary by center, region, and continent. This study aimed to identify the optimal therapeutic method and type of surgical strategy for cT1-3N2 lung cancer. METHODS: This retrospective evaluation analyzed the records of 17,954 patients with cT1-3N2 lung cancer treated in 2010 through 2015 from the SEER database. The effects of different therapeutic methods and types of surgical strategies on overall survival (OS) were assessed. Univariate and multivariate analyses were performed using a Cox proportional hazards model. RESULTS: The 5-year OS rates were 27.7% for patients with T1N2 disease, 21.8% for those with T2N2 disease, and 19.9% for T3N2 disease. Neoadjuvant therapy plus operation (OP) plus adjuvant therapy, and OP plus adjuvant therapy, provided better 5-year OS rates than OP alone or concurrent chemoradiotherapy (34.1%, 37.7%, 29.3%, and 16.1%, respectively). In the T1N2, T2N2, and T3N2 groups, lobectomy provided better 5-year OS than pneumonectomy, sublobectomy, and no surgery. Both univariate and multivariate analyses showed that young age, female sex, well-differentiated histologic grade, adenocarcinoma cell type, neoadjuvant and adjuvant therapy, lobectomy, and T1 stage were statistically associated with better 5-year OS rates. CONCLUSIONS: In cT1-3N2 lung cancer, multimodal treatments tended to provide better 5-year OS than OP alone or concurrent chemoradiotherapy. In addition, lobectomy was associated with better survival than other operative methods.
Assuntos
Quimiorradioterapia Adjuvante/estatística & dados numéricos , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante/estatística & dados numéricos , Pneumonectomia/estatística & dados numéricos , Idoso , Quimioterapia Adjuvante/estatística & dados numéricos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/métodos , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Phototriggered drug delivery systems (PTDDSs) facilitate controlled delivery of drugs loaded on photoactive platform to the target region under light stimulation. The present study investigated the synthesis and efficacy of carbazole-coumarin (CC)-fused heterocycles as a PTDDS platform for the photocontrolled release of a chemotherapeutic agent, chlorambucil, in an in vitro model of human breast and leukemia cancer cells. CC-fused heterocycles were constructed using 4-hydroxycarbazole as the starting material, and further modification of these heterocycles yielded two CC derivatives. CC-7 with an additional - COOH group and CC-8 with the triphenylphosphonium (TPP) group, a mitochondria-targeting ligand introduced in the carbazole ring, dissolved in polar solvents and exhibited emission bands at 360 and 450 nm, respectively. The results indicate that visible light of 405 nm triggers the photolysis of the CC-drug conjugate and efficiently delivers the drug in both in vitro cancer cell models. Cytotoxicity evaluation indicates the suppression of proliferation of both types of cells treated with CC-8 under synergy effect combining drug potency and photosensitization. Further, the lower IC50 of CC-8 toward leukemia cells suggests the efficacy of the TPP ligand in increasing the bioavailability of CC-drug conjugates in leukemia treatment. Studies on mitochondria-targeting drug delivery systems are required for improving the performance of anticancer drugs.
Assuntos
Antineoplásicos/administração & dosagem , Carbazóis/química , Clorambucila/administração & dosagem , Cumarínicos/química , Preparações de Ação Retardada/química , Leucemia/tratamento farmacológico , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Clorambucila/farmacocinética , Clorambucila/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , LuzRESUMO
BACKGROUND: Current esophageal treatment guidelines suggest that, when more than 15 lymph nodes are detected, dissection should be done as the minimum requirement for staging in esophageal squamous cell carcinoma (ESCC) patients undergoing esophagectomy without induction chemoradiotherapy (CRT). However, for neoadjuvant CRT, there is limited information. We sought to clarify the role of lymphadenectomy in ESCC patients with and without neoadjuvant CRT. PATIENTS AND METHODS: Data on 3156 ESCC patients receiving esophagectomy with (group 1, n = 1399) and without (group 2, n = 1757) neoadjuvant CRT between 2008 and 2014 were collected from a national cancer registry in Taiwan. The impact of the resected lymph nodes on overall survival was assessed according to pathologic stages. A Cox regression model was used to identify prognostic factors for overall survival. RESULTS: Five-year overall survival rates were 35.6% for the entire group, 30.32% for group 1, and 39.55% for group 2 (p < 0.0001 for group 1 vs group 2). The best cutoff value was 21 lymph nodes in both group 1 and group 2. In group 1, the independent prognostic factors included age ≥ 54 years, clinical N status, y-pathologic T, y-pathologic N, y-pathologic stage, grade, location, margin status, esophagectomy (thoracoscopic vs open), and number of total resected lymph nodes (≤ 21 vs > 21). For group 2, the independent prognostic factors were gender, clinical stage, pathologic T, pathologic N, tumor length, grade, and margin status. CONCLUSIONS: Extent of lymphadenectomy was associated with survival in patients with neoadjuvant CRT followed by esophagectomy. The optimum lymphadenectomy should be modulated by pathologic stage.
Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/secundário , Carcinoma de Células Escamosas do Esôfago/terapia , Excisão de Linfonodo , Linfonodos/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Esofagectomia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasia Residual , Sistema de Registros , Fatores Sexuais , Taxa de Sobrevida , Carga Tumoral , Adulto JovemRESUMO
Epidermal growth factor receptor (EGFR) mutations have been identified in approximately 55% of lung cancer patients in Taiwan. Gefitinib (Iressa) and Erlotinib (Tarceva) are the first-generation targeting drugs to patients with EGFR gene mutants a work by inhibiting tyrosine kinase activity. However, resistance in EGFR-mutated patients to first-generation tyrosine kinase inhibitor (TKI) therapy after 8-11 months of treatment has occurred. Betulinic acid (BetA) is a pentacyclic triterpenoid natural product derived from widespread plants. BetA has been reported to have a cytotoxic effect in several cancers. The purpose of this study is to investigate the effects and mechanisms of BetA on dampening EGFR TKI-resistance of lung cancer cells. Our study has demonstrated by MTT assay that combining BetA and an EGFR TKI increased the cytotoxicity against EGFR TKI-resistance lung cancer cells. Based on flow cytometry, combination treatments of BetA with an EGFR TKI enhanced Sub-G1 accumulation, induced apoptosis and induced mitochondrial membrane potential loss. Using western blotting, BetA and EGFR TKI combined treatments inhibited cell cycle related protein and triggered apoptosis- and autophagy- related protein expression. Taken together, our data suggests that a target therapy combining BetA with an EGFR TKI improves drug efficacy in EGFR TKI-resistant lung cancer cells.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Triterpenos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Triterpenos Pentacíclicos , Inibidores de Proteínas Quinases/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Triterpenos/administração & dosagem , Ácido BetulínicoRESUMO
BACKGROUND: Lung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC). METHODS: In this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS. RESULTS: Our results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24 h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP. CONCLUSIONS: We demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Chlorella/química , Neoplasias Pulmonares/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. Through immunoprecipitation analysis, we found that BMI1 did not interact with Hsp90α and that the downregulation of BMI1 by 17-DMAG was mediated by the inhibition of c-Myc and enhancement of zeste homolog 2 (EZH2) expression. The transcriptional and BMI1 promoter-binding activities of c-Myc in BCSCs were inhibited by 17-DMAG treatment. The overexpression of EZH2 attenuated the inhibitory effect of 17-DMAG on BMI1 and c-Myc expression. Furthermore, Hsp90α could be co-immunoprecipitated with c-Myc and EZH2 and bind to the BMI1 promoter. Treatment with 17-DMAG decreased the nuclear expression of EZH2 and c-Myc but not that of Hsp90α. In conclusion, our data suggested that Hsp90α could positively regulate the self-renewal of BCSCs by facilitating the nuclear translocation of c-Myc and EZH2 to maintain BMI1 expression.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Células-Tronco Neoplásicas/metabolismo , Complexo Repressor Polycomb 1/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Benzoquinonas/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Autorrenovação Celular/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lactamas Macrocíclicas/farmacologia , Ligação Proteica , Transporte Proteico , Proteínas Proto-Oncogênicas c-myc/genética , Transcrição GênicaRESUMO
BACKGROUND: The role of adjuvant chemoradiation in esophageal cancer has been underestimated in the literature. This study was undertaken to determine whether adjuvant chemoradiation improves survival compared with surgery alone. METHODS: Data of 1095 esophageal squamous cell carcinoma (ESCC) patients, including 679 in surgery alone group (group 1) and 416 in surgery followed adjuvant chemoradaition group (group 2), were obtained from the Taiwan Cancer Registry database. Propensity score matching (PSM) analysis was used to identify 147 well-balanced patients in each group for overall survival comparison. RESULTS: After PSM, the 3-year survival rates and median survival were 44.9% and 27.2 (95% confidence interval [CI]: 17.6-40.3) months in group 2, which is significantly higher than that in group 1 (28.1% and 18.2 [95% CI: 14.3-24.5] months, Pâ=â0.0043). In the multivariate survival analysis, pT3/4 stage (Hazard Ratio [HR]: 2.03, 95% CI: 1.38-2.97, Pâ<â0.001), pN+ stage (HR: 1.83, 95% CI: 1.31-2.57, Pâ=â0.0004), tumor length more than 32âmm (HR: 1.93, 95% CI: 1.33-2.79, Pâ<â0.001), R1/2 resection (HR: 1.75, 95% CI: 1.15-2.66, Pâ=â0.009), and adjuvant chemoradiation (HR: 0.57, 95% CI: 0.42-0.78, Pâ<â0.0001) were independent prognostic factors. Subgroup analysis suggested patients with pT3/4 stage, pN+ stage tumors, larger tumor size, poorly differentiated tumors, and R1/2 resections were more likely to demonstrate survival benefit from adjuvant chemoradiation. CONCLUSIONS: Compared with surgery alone, adjuvant chemoradiation provides a survival benefit to ESCC patients, especially those with pT3/4 stage, N+ tumors, larger tumor size, poorly differentiated tumors, and R1/2 resections.
Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/terapia , Esofagectomia , Idoso , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia Adjuvante/métodos , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Esofagectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pós-Operatórios/métodos , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Taiwan , Resultado do TratamentoRESUMO
BACKGROUND: Thoracoscopic lobectomy for primary lung cancer has become increasingly popular worldwide due to several advantages over open lobectomy including reduced pain, reduced length of hospital stay, and comparable oncologic outcomes. The costs of thoracoscopic versus conventional open lobectomy have been compared in several studies with variable results. We compared the costs of thoracoscopic versus open lobectomy in lung cancer patients in Taiwan. METHODS: Patients who underwent lobectomy for primary lung cancer from the Taiwan National Health Insurance Research Database (NHIRD) between 2004 and 2010 were identified. Patient characteristics, operative data, and costs for each part of the hospitalization for surgery and 30 days of care after discharge were analyzed. RESULTS: A total of 5366 patients with complete clinical data who underwent either conventional open lobectomy (n = 3166, 59 %) or thoracoscopic lobectomy (n = 2200, 41 %) for primary lung cancer were identified from the database. Compared with open lobectomy, thoracoscopic lobectomy was associated with younger age, less comorbidity, shorter anesthesia times, and reduced lengths of hospital stay. Total hospital costs, operative costs, and other costs were significantly higher in the thoracoscopic group. The 30-day after discharge costs were significantly lower in the thoracoscopic group. CONCLUSIONS: Thoracoscopic lobectomy for primary lung cancer in Taiwan was associated with higher total hospital costs but lower 30 days after discharge costs than open lobectomy. These differences may have resulted from higher operative and instrument costs in the thoracoscopic group.
Assuntos
Custos Hospitalares , Neoplasias Pulmonares/economia , Pneumonectomia/economia , Carcinoma de Pequenas Células do Pulmão/economia , Cirurgia Torácica Vídeoassistida/economia , Toracotomia/economia , Adenocarcinoma/economia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma de Células Grandes/economia , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma de Células Escamosas/economia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Comorbidade , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/cirurgia , Taiwan/epidemiologiaRESUMO
Transforming growth factor-ß (TGF-ß)-induced epithelial-mesenchymal transition is a critical process in the initiation of metastasis of various types of cancer. Chidamide is a class I histone deacetylase inhibitor with anti-tumor activity. This study investigated the effects of chidamide on TGF-ß-mediated suppression of E-cadherin expression in adenocarcinomic lung epithelial cells and the molecular mechanisms involved in these effects. Western blot analysis, confocal microscopy, Quantitative methyl-specific PCR and bisulfite sequencing were used to evaluate the effects of different treatments on chidamide ameliorating TGF-ß induced-E-cadherin loss. H3 acetylation binding to the promoter of E-cadherin was detected by chromatin immunoprecipitations (CHIP). We found that chidamide reduced the level of lung cancer cell migration observed using a Boyden chamber assay (as an indicator of metastatic potential). Chidamide inhibited TGF-ß-induced SMAD2 phosphorylation and attenuated TGF-ß-induced loss of E-cadherin expression in lung cancer cells by Western blotting and confocal microscopy, respectively. Quantitative methyl-specific PCR and bisulfite sequencing revealed that TGF-ß-enhanced E-cadherin promoter methylation was ameliorated in cells treated with chidamide. We demonstrated that histone H3 deacetylation within the E-cadherin promoter was required for TGF-ß-induced E-cadherin loss; cell treatment with chidamide increased the H3 acetylation detected by CHIP. Taken together, our results demonstrate that TGF-ß suppressed E-cadherin expression by regulating promoter methylation and histone H3 acetylation. Chidamide significantly enhanced E-cadherin expression in TGF-ß-treated cells and inhibited lung cancer cell migration. These findings indicate that chidamide has a potential therapeutic use due to its capacity to prevent cancer cell metastasis.
Assuntos
Aminopiridinas/farmacologia , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Fator de Crescimento Transformador beta/fisiologia , Células A549 , Antígenos CD , Caderinas/genética , Caderinas/metabolismo , Metilação de DNA , Ensaios de Seleção de Medicamentos Antitumorais , Epigênese Genética , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Fosforilação , Regiões Promotoras Genéticas , Processamento de Proteína Pós-TraducionalRESUMO
OBJECTIVE: To compare the perioperative outcomes of single-incision and multiple-incision thoracoscopic lobectomy and segmentectomy. BACKGROUND: Reports of single-incision thoracoscopic lobectomy and segmentectomy for lung cancer are limited, and a comparison between single-incision and multiple-incision thoracoscopic lobectomy or segmentectomy for lung cancer has not been previously reported. METHODS: From January 2005 to June 2013, a total of 233 patients with lung cancer underwent thoracoscopic lobectomy or segmentectomy via a single-incision or multiple-incision technique. A propensity-matched analysis, incorporating preoperative variables, was used to compare the short-term outcomes between single-incision and multiple-incision thoracoscopic lobectomy and segmentectomy. RESULTS: Overall, 50 patients underwent single-incision thoracoscopic pulmonary resections, including 35 lobectomies and 15 segmentectomies, and 183 patients underwent multiple-incision thoracoscopic lobectomy or segmentectomy between January 2005 and December 2011. Propensity matching produced 46 patients in each group. The length of hospital stay and the complication rate were not significantly different between the 2 groups. Single-incision thoracoscopic lobectomy and segmentectomy were associated with shorter operative time (P = 0.029), more numbers of lymph nodes (P = 0.032), and less intraoperative blood loss (P = 0.017) than with the multiple-incision approach. No in-hospital mortality occurred in either group. CONCLUSIONS: Single-incision thoracoscopic lobectomy and segmentectomy are feasible, and perioperative outcomes are comparable with those of the multiple-incision approach.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Toracoscopia/métodos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Carcinoma Pulmonar de Células não Pequenas/patologia , Conversão para Cirurgia Aberta , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Neoplasias Pulmonares/patologia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The prognostic value for the post-chemoradiation therapy (CRT) pathologic stage is uncertain. The purpose of this study was to compare the pathologic stage in patients undergoing esophagectomy with and without preoperative CRT for esophageal squamous cell carcinoma (ESCC). This study retrospectively reviewed the data from 2151 patients with ESCC who underwent esophagectomy with or without preoperative CRT between 2008 and 2011 in Taiwan. Patients were divided into 2 groups. Group A consisted of patients treated with primary surgery without prior treatments (n=1301), and group B consisted of patients receiving preoperative CRT followed by esophagectomy (n=850). In group A, 679 patients received surgery alone, 92 received postoperative chemotherapy, 416 received postoperative chemoradiation therapy, and 114 received postoperative radiation therapy. In group A, the 3-year survival rates by pathologic stage were 82.2% for stage 0, 67.6% for stage I, 50.7% for stage II, 21.5% for stage III, and 14.8% for stage IV (P<.001). In group B, the 3-year survival rates of post-CRT pathologic stages 0, I, II, III, and IV were 59.4%, 46.0%, 40.3%, 19.1%, and 8.2%, respectively (P<.001). In multivariate analysis, the pathologic T, N, and M were all independent prognostic factors in both group A (esophagectomy alone) and B (CRT plus esophagectomy). The current, 7th edition of the esophageal TNM staging system could adequately stratify prognostic groups in patients with squamous cell carcinoma who were treated with preoperative CRT and esophagectomy.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Taxa de Sobrevida , Adulto , Idoso , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , TaiwanRESUMO
BACKGROUND: Thoracoscopic lobectomy is a safe and effective procedure; however, the ways by which to incorporate this technically demanding procedure into residency training is still unknown. We reported on the outcomes of thoracoscopic lobectomies performed by a single thoracic resident, who was simultaneously undergoing training for both open and thoracoscopic lobectomies. PATIENTS AND METHODS: Between January 2010, and May 2011, data from 87 consecutive thoracoscopic lobectomies that were performed by a trainee surgeon (B.-Y.W.) were prospectively obtained. Data were grouped into the first 30 and subsequent 57 cases. Patient characteristics, operative data, complications, and surgical pathology were analyzed. RESULTS: The mean operating time in group 2 was significantly lower compared with group 1 (264.0 ± 45.9 min in group 1 vs. 197.5 ± 57.7 min in group 2; p<0.001). There were no mortalities in both the groups and no significant differences in postoperative complications. CONCLUSIONS: Thoracoscopic lobectomy can be taught to a nonexperienced thoracic resident during an open procedure without compromising the safety of patients. It appears that surgical performance reaches a plateau after the completion of 30 cases.
Assuntos
Educação Médica Continuada/métodos , Internato e Residência , Curva de Aprendizado , Pneumonectomia/educação , Toracoscopia/educação , Idoso , Competência Clínica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Segurança do Paciente , Pneumonectomia/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Análise e Desempenho de Tarefas , Toracoscopia/efeitos adversos , Fatores de TempoRESUMO
BACKGROUND: Empyema is a serious infection in pleural space. Finding out seasonal variations of empyema and its pathogens can help in providing preventive measures, and implicating future researches. METHODS: This study is a 10-year observational study in a single center. Patients with empyema thoracis receiving thoracoscopic decortication between January 2012 and December 2021 were included in the study. RESULTS: There were 1082 empyema patients enrolled in this study. No seasonal variation was noted (spring = 25.7 %, summer =25.5 %, autumn = 24.8 %, winter = 24.0 %). However, we observed seasonal variations in pathogens. Streptococcus species had slightly higher prevalence in winter and spring than summer and autumn (54.3 % vs. 45.7 %) without significant difference (p = 0.251). On the contrary, Staphylococcus species occurred more often in summer and autumn than winter and spring (61.5 % vs. 38.5 %) (p = 0.035). Klebsiella species were more likely found in autumn (34.9 %) (p = 0.050), and Pseudomonas species showed no peak prevalence in any season (p = 0.423). The incidence of Streptococcus species increased over the years. CONCLUSIONS: Although no seasonal variation was found in severe empyema patients requiring surgery, there were seasonal variations for the pathogens in Taiwan. The medical community should focus on Streptococcus species in winter and spring and Staphylococcus species in summer and autumn.
RESUMO
Background: The application of positron emission tomography/computed tomography (PET/CT) helps provide accurate clinical staging for lung cancer patients. However, the effects and trends in early-stage lung cancer remain unclear. The aim of this study was to compare differences between clinical stage I lung cancer patients who received PET/CT for staging and those who did not. Methods: Data were obtained from the Taiwan Society of Cancer Registry. There were 6587 clinical stage I lung cancer patients between 2009 and 2014 analyzed in this study. We compared the characteristics of the PET/CT and no PET/CT groups. After propensity score matching, it resulted in both groups having 2649 patients. We measured the overall survival rates of all clinical stage I lung cancer patients and the overall survival rates of patients with PET/CT and without PET/CT. Results: The 1-, 3-, and 5-year survival rates of all clinical stage I lung cancer patients were 97.2%, 88.2%, and 79.0%, respectively. Patients with a larger tumor size tended to receive PET/CT for staging (stage Ib: 38.25% vs. 27.82%, p < 0.0001) and a larger resection (lobectomy: 74.62% vs. 66.61%, p < 0.0001). The 5-year survival rates were 79.8% in the PET/CT group and 78.2% in the no PET/CT group after propensity score matching (p = 0.6528). Conclusions: For clinical stage I lung cancer in Taiwan, patients with larger tumor sizes tend to have PET/CT for staging. Although PET/CT provided more precise clinical staging, these patients still received larger resections and had more pathological migration. However, there was no overall survival rate benefit after PET/CT.