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1.
Cell Rep ; 39(2): 110673, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35417682

RESUMO

RNA activation (RNAa) is an uncharacterized mechanism of transcriptional activation mediated by small RNAs, such as microRNAs (miRNAs). A critical issue in RNAa research is that it is difficult to distinguish between changes in gene expression caused indirectly by post-transcriptional regulation and direct induction of gene expression by RNAa. Therefore, in this study, we seek to identify a key factor involved in RNAa, using the induction of ZMYND10 by miR-34a as a system to evaluate RNAa. We identify the positive transcription elongation factors CDK9 and DDX21, which form a complex with nuclear AGO and TNRC6A, as important transcriptional activators of RNAa. In addition, we find that inhibition of DDX21 suppresses RNAa by miR-34a and other miRNAs without inhibiting post-transcriptional regulation. Our findings reveal a strong connection between RNAa and release of paused Pol II, facilitating RNAa research by making it possible to separately analyze post-transcriptional regulation and RNAa.


Assuntos
Quinase 9 Dependente de Ciclina , RNA Helicases DEAD-box , MicroRNAs , RNA Polimerase II , Núcleo Celular/metabolismo , Quinase 9 Dependente de Ciclina/metabolismo , RNA Helicases DEAD-box/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , RNA Polimerase II/metabolismo , Ativação Transcricional
2.
Catheter Cardiovasc Interv ; 99(6): 1758-1765, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35253349

RESUMO

OBJECTIVES: This study aimed to examine whether the combination of excimer laser coronary atherectomy (ELCA) and drug-coated balloon (DCB) angioplasty can provide feasible clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) with 8-month and 2-year scheduled follow-up angiography. BACKGROUND: Intracoronary thrombus elevates the risk of interventional treatment in patients with STEMI and hampers drug absorption into the vasculature released from DCB. METHODS: Sixty-two patients with STEMI within 24 h after the onset of symptoms were enrolled in this prospective, single-center, single-arm study. RESULTS: The laser catheter was successfully crossed distal to the culprit lesion in all cases. No ELCA-related adverse events occurred. Bail-out stenting was required in two patients (3.2%) after adjunctive ballooning; thus, the remaining 60 patients were completed with DCB angioplasty without stenting. Scheduled angiography at 8 months and 2 years was completed in 100% and 85.2%, respectively, and minimal lumen diameters were 3.4 ± 0.5, 3.4 ± 0.6, and 3.4 ± 0.5 mm after the procedure, at 8 months and at 2 years, respectively. Binary restenosis was observed in five patients (8.1%) in whom target lesion revascularization was performed. The duration of dual antiplatelet therapy was 2.3 ± 2.2 months, and neither abrupt vessel closure, reinfarction, cardiac death nor major bleeding was observed. CONCLUSION: A combination of DCB angioplasty with ELCA is a feasible therapeutic option for STEMI.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35293580

RESUMO

OBJECTIVES: The aim of this study was to assess the clinical effects of a small ground-glass opacity (GGO) component of a radiologically nearly pure-solid tumour on tumour aggressiveness in patients with clinical stage IA non-small-cell lung cancer (NSCLC). METHODS: Data of 988 patients with clinical stage IA NSCLC who had a consolidation-to-tumour ratio of ≥0.75 on high-resolution computed tomography were retrospectively analysed. The cumulative incidence of recurrence (CIR) was compared between patients with GGO (nearly pure-solid, n = 297) and those without GGO (pure-solid, n = 691). RESULTS: In patients with clinical T1mi + T1a and T1b, the CIR was significantly higher in the pure-solid group than in the nearly pure-solid group (5-year CIR, 15.2% and 19.3% vs 0% and 6.4%; P < 0.001); however, this was not the case for patients with clinical T1c (5-year CIR, 23.1% vs 26.5%; P = 0.580). In the multivariable analysis, pure-solid tumours were independently associated with a higher CIR than nearly pure-solid tumours in patients with clinical T1mi + T1a + T1b (solid tumour size ≤2 cm; subdistribution hazard ratio, 3.25; 95% confidence interval, 1.59-6.63; P = 0.001) but not in those with clinical T1c tumours (2-3 cm; subdistribution hazard ratio, 0.67; 95% confidence interval, 0.39-1.13; P = 0.130). CONCLUSIONS: Nearly pure-solid tumours with a small GGO component influence tumour aggressiveness based on solid tumour size, with a threshold of 2 cm in patients with clinical stage IA NSCLC. For tumours sized 2-3 cm, nearly pure-solid tumours had a similar tumour aggressiveness as pure-solid tumours.

4.
Ann Transl Med ; 10(4): 196, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35280355

RESUMO

Background: Transfer RNA-derived fragments (tRFs) and transfer RNA halves (tiRNAs) have been shown to play crucial roles in gene regulation. This study aims to reveal the expression profiles of tRFs and tiRNAs and their possible biological roles in lung adenocarcinoma (LUAD). Methods: Five paired clinical lung adenocarcinoma tissues (LAT) and adjacent normal lung tissues (ANLT) were selected to analyze the expression of tRFs and tiRNAs. Six significantly expressed tRFs and tiRNAs were selected and validated by Quantitative Real-time PCR (qPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Results: The sequencing results showed that 109 tRFs and tiRNAs were differentially expressed between LAT and ANLT, out of which 60 were upregulated and 49 were downregulated. Compared with ANLT, lower expression levels of 3 tRF-1s (tRF-Ser-TGA-010, tRF-Arg-CCT-018, and tRF-Val-CAC-017) in LAT were verified by qPCR. Subsequently, the putative target genes of tRF-1s were analyzed by computational prediction and the top 10 significant results of GO and KEGG pathway enrichment analysis were presented. Conclusions: This study has revealed the landscape of tRF and tiRNA expression profiles in LUAD. Three newly found differentially expressed downregulated tRF-1s may be involved in the pathogenesis of LUAD and may serve as potential diagnostic biomarkers, or otherwise reconcile target genes for drug development.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35181001

RESUMO

OBJECTIVE: The aim of this study was to evaluate the role and effect of adjuvant chemotherapy based on epidermal growth factor receptor mutation status in patients with stage I lung adenocarcinoma. METHODS: Between 2010 and 2016, of 1901 patients with pathologic stage I (8th edition) non-small cell lung cancer, we identified 475 with high-risk (pT1c/T2a or positive for lymphovascular invasion) stage I lung adenocarcinoma who underwent lobectomy. We estimated propensity scores to adjust for confounding variables, including age, sex, Brinkman index, pulmonary functions, comorbidities, surgical approach, invasive component tumor size, visceral pleural, lymphatic, and vascular invasion, adenocarcinoma subtype, epidermal growth factor receptor mutation status, postoperative complications, and institution associated with the administration of adjuvant chemotherapy. The primary end point was recurrence-free survival. RESULTS: Of 292 patients without/unknown epidermal growth factor receptor mutation, 105 (36.0%) received adjuvant chemotherapy and 187 (64.0%) did not. In 69 pairs of patients who were propensity score matched, the 5-year recurrence-free survival was significantly better in those who underwent adjuvant chemotherapy (88.4%) than in those who did not (63.6%; P = .001). Of 183 patients with epidermal growth factor receptor mutation, 78 (42.6%) received adjuvant chemotherapy and 105 (57.4%) did not. In 49 pairs of propensity score-matched patients, there was no significant difference in the 5-year recurrence-free survival between those who underwent adjuvant chemotherapy (74.3%) and those who did not (80.5%; P = .573). CONCLUSIONS: The effect of adjuvant chemotherapy for high-risk stage I lung adenocarcinoma varied by epidermal growth factor receptor mutation status. Epidermal growth factor receptor mutation status may help to identify patients with high-risk stage I lung adenocarcinoma who may benefit from adjuvant chemotherapy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35150248

RESUMO

OBJECTIVES: Segmentectomy can provide oncologically acceptable results for small-sized non-small-cell lung cancer (NSCLC). However, in cases of NSCLC with pathological invasive characteristics such as lymphatic invasion (LY), vascular invasion (V), pleural invasion (PL) and/or lymph node metastasis, the feasibility of segmentectomy is not known. METHODS: The patients included in the study (i) underwent lobectomy or segmentectomy for NSCLC with invasive characteristics such as LY, V, PL or pathological lymph node metastasis; (ii) presented with a node-negative, solid component-predominant tumour (consolidation tumour ratio >50%) on preoperative computed tomography; (iii) had a whole-tumour size of 2 cm or less; and (iv) presented between January 2010 and December 2019 to one of the 3 institutions. Cumulative incidences of recurrence (CIRs) after segmentectomy and lobectomy were compared. RESULTS: A total of 321 patients were included. Segmentectomy and lobectomy were performed in 80 (24.9%) and 241 (75.1%) patients, respectively. There was no significant difference in CIR between segmentectomy (5-year CIR rate, 17.2%) and lobectomy patients (5-year CIR rate, 27.8%, P = 0.135). In the propensity score-matched cohort, there was no significant difference in CIR between segmentectomy (5-year CIR rate, 19.1%) and lobectomy patients (5-year CIR rate, 19.2%; P = 0.650). In the multivariable analysis using inverse probability of treatment weighting and surgical method, segmentectomy was not a significant predictor of worse CIR (P = 0.920). CONCLUSIONS: Segmentectomy is feasible for clinically early-stage NSCLC irrespective of the presence of LY, V, PL or lymph node metastasis.

7.
Asian Cardiovasc Thorac Ann ; : 2184923211072486, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040362

RESUMO

BACKGROUND: Part-solid lung adenocarcinoma appears as a heterogeneous subgroup, and its surgical management is controversial. This study aimed to elucidate whether preoperative carcinoembryonic antigen, a time-honored tumor marker, can be used as a prognostic factor that contributes to its management. METHODS: We retrospectively reviewed consecutive patients with clinical-T1a-cN0M0 part-solid adenocarcinoma who underwent surgical resection between January 2011 and December 2015 at two institutions. RESULTS: Overall, 288 patients were identified. The median age was 69 years with 176 patients (61%) being female. The median follow-up time was 5.6 years. Lymph node metastases were found in 6 (15%) of 41 patients with elevated carcinoembryonic antigen levels, while 10 (4.0%) of 247 patients had normal carcinoembryonic antigen levels (P = 0.016). The 5-year overall survival rates in patients with normal and elevated carcinoembryonic antigen levels were 96.9% and 87.2%, respectively (P = 0.006), and the 5-year relapse-free survival rates were 91.8% and 62.8%, respectively (P < 0.001). The multivariable analysis revealed that preoperative carcinoembryonic antigen level was a significant prognostic factor for relapse-free survival (hazard ratio [HR] = 2.92, 95% confidence interval [CI] = 1.63-5.25, P < 0.001). Among the patients with elevated carcinoembryonic antigen levels, the 5-year overall survival rates in those undergoing lobar resection and segmentectomy were 87.0% and 88.9%, respectively (P = 0.59), and the 5-year relapse-free survival rates were 61.7% and 66.7%, respectively (P = 0.84). CONCLUSIONS: Our data suggest that preoperative carcinoembryonic antigen level appears to be an important predictor of postoperative survival outcomes in early-stage part-solid adenocarcinoma. Further studies are required to optimize management of patients with elevated preoperative carcinoembryonic antigen levels, although segmentectomy appeared acceptable in those patients.

8.
Photodiagnosis Photodyn Ther ; 37: 102659, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34852311

RESUMO

BACKGROUND: Even if lung cancer is detected at an early stage, surgery may be difficult in patients with severe comorbidities, like interstitial pneumonia (IP). Radiation therapy cannot be performed due to the high risk of acute IP exacerbation. Therefore, an effective alternative, such as photodynamic therapy (PDT), is required. To prove that acute exacerbation is not induced after PDT in peripheral lung cancer, we investigated the effects of PDT on IP rat models. METHODS: Bleomycin (BLM) was administered intratracheally. Seven days after administration, left thoracotomy was performed. Talaporfin sodium was injected, and diode laser irradiation (664 nm, 150mW, 100J/cm2) was performed. Seven days after PDT, the whole blood and left lungs were collected. A total of 23 rats, comprising BLM + PDT (n = 4), BLM + non-PDT (n = 10), non-BLM + PDT (n = 2), non-BLM + non-PDT (n = 5), and two rats that died immediately after PDT were observed. Serum levels of Krebs von den Lungen-6, surfactant protein-D, lactate dehydrogenase, and serum C-reactive protein were measured. Fibrosis and macrophage scorings, and the ​​collagen fibers percentage were examined by staining with hematoxylin and eosin, Elastica van Gieson, anti-α smooth muscle antibody, and anti-CD68 antibodies. RESULTS: There was no remarkable difference in the values of each marker in fibrosis and macrophage scores with or without PDT. In case of death, fibrosis was mild, and PDT was not affected. CONCLUSIONS: In IP rat models, PDT did not induce lung fibrosis or acute exacerbation.


Assuntos
Doenças Pulmonares Intersticiais , Fotoquimioterapia , Fibrose Pulmonar , Animais , Bleomicina , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fotoquimioterapia/métodos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Ratos , Triazenos
9.
Ann Thorac Surg ; 113(4): 1317-1324, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34022215

RESUMO

BACKGROUND: Due to its invasiveness, the indications for "complex segmentectomy" for radiologically hypermetabolic (high maximum standard uptake value) non-small cell lung cancer (NSCLC) remain controversial. This study compared the outcomes after complex segmentectomy and lobectomy in these patients. METHODS: We retrospectively reviewed 717 patients with radiologically hypermetabolic (maximum standardized uptake value ≥2.5), clinical stage IA NSCLC who underwent complex segmentectomy (n = 61) or location-adjusted lobectomy (n = 656) at three institutions from 2010 to 2019. Postoperative outcomes were analyzed for all patients and their propensity score matched pairs. Factors affecting oncologic outcomes were assessed by Kaplan-Meier estimates and Cox proportional hazards regression analyses. RESULTS: The prognosis of patients undergoing complex segmentectomy was not significantly different from that of patients undergoing lobectomy (5-year cancer-specific survival rate, 89.9% vs 91.1%, P = .98; and 5-year recurrence-free interval rate, 83% vs 77.5%, P = .62) in the nonadjusted cohort. In 55 propensity score matched pairs, oncologic outcomes were not significantly different between patients undergoing complex segmentectomy (5-year cancer-specific survival, 89.9%; 5-year recurrence-free interval, 83%) and lobectomy (5-year cancer-specific survival, 83.6%; 5-year recurrence-free interval, 82.5%). Multivariable Cox regression analysis for recurrence-free interval revealed no significant differences between oncologic outcomes associated with complex segmentectomy and lobectomy (hazard ratio, 0.84; 95% confidence interval, 0.25 to 2.14; P = .74). CONCLUSIONS: Oncologic outcomes of complex segmentectomy and lobectomy were not significantly different for patients with radiologically hypermetabolic, clinical stage IA NSCLC patients. Complex segmentectomy can treat high maximum standardized uptake value, clinical stage IA lung cancers without compromising oncologic results.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Estudos Retrospectivos , Resultado do Tratamento
10.
Eur J Cardiothorac Surg ; 61(4): 751-760, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-34940847

RESUMO

OBJECTIVES: Indications of limited resection, such as segmentectomy, have recently been reported for patients with solid-predominant lung cancers ≤2 cm. This study aims to identify unfavourable prognostic factors using three-dimensional imaging analysis with artificial intelligence (AI) technology. METHODS: A total of 157 patients who had clinical N0 non-small cell lung cancer with a radiological size ≤2 cm, and a consolidation tumour ratio > 0.5, who underwent anatomical lung resection between 2011 and 2017 were enrolled. To evaluate the three-dimensional structure, the ground-glass nodule/Solid Automatic Identification AI software Beta Version (AI software; Fujifilm Corporation, Japan) was used. RESULTS: Maximum standardized uptake value (SUVmax) and solid-part volume measured by AI software (AI-SV) showed significant differences between the 139 patients with adenocarcinoma and the 18 patients with non-adenocarcinoma. Among the adenocarcinoma patients, 42 patients (30.2%) were found to be pathological upstaging. Multivariable analysis demonstrated that high SUVmax, high carcinoembryonic antigen level and high AI-SV were significant prognostic factors for recurrence-free survival (RFS; P < 0.05). The 5-year RFS was compared between patients with tumours showing high SUVmax and those showing low SUVmax (67.7% vs 95.4%, respectively, P < 0.001). The 5-year RFS was 91.0% in patients with small AI-SV and 68.1% in those with high AI-SV (P = 0.001). CONCLUSIONS: High AI-SV, high SUVmax and abnormal carcinoembryonic antigen level were unfavourable prognostic factors of patients with solid-predominant lung adenocarcinoma with a radiological size ≤2 cm. Our results suggest that lobectomy should be preferred to segmentectomy for patients with these prognostic factors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inteligência Artificial , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Imageamento Tridimensional , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
11.
J Interv Cardiol ; 2021: 5590109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393666

RESUMO

OBJECTIVES: We evaluated the thrombus-vaporizing effect of excimer laser coronary angioplasty (ELCA) in patients with ST-segment elevation myocardial infarction (STEMI) by optical coherence tomography (OCT). BACKGROUND: Larger intracoronary thrombus elevates the risk of interventional treatment and mortality in patients with STEMI. METHODS: A total of 92 patients with STEMI who presented within 24 hours from the onset and underwent ELCA following manual aspiration thrombectomy (MT) were analyzed. RESULTS: The mean baseline thrombolysis in myocardial infarction flow grade was 0.4 ± 0.6, which subsequently improved to 2.3 ± 0.7 after MT (p < 0.0001) and 2.7 ± 0.5 after ELCA (p=0.0001). The median residual thrombus volume after MT was 65.7 mm3, which significantly reduced to 47.5 mm3 after ELCA (p < 0.0001). Plaque rupture was identified by OCT in only 22 cases (23.9%) after MT, but was distinguishable in 36 additional cases after ELCA (total: 58 cases; 63.0%). Ruptured lesions contained a higher proportion of red thrombus than nonruptured lesions (75.9% vs. 43.3%, p=0.001). Significantly larger thrombus burden after MT (69.6 mm3 vs. 56.3 mm3, p < 0.05) and greater thrombus reduction by ELCA (21.2 mm3 vs. 11.8 mm3, p < 0.01) were observed in ruptured lesions than nonruptured lesions. CONCLUSIONS: ELCA effectively vaporized intracoronary thrombus in patients with STEMI even after MT. Lesions with plaque rupture contained larger thrombus burden that was frequently characterized by red thrombus and more effectively reduced by ELCA.


Assuntos
Trombose Coronária , Terapia a Laser , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Idoso , Angiografia Coronária , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Trombectomia , Tomografia de Coerência Óptica , Resultado do Tratamento
12.
Ann Surg Oncol ; 28(12): 7162-7171, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34218364

RESUMO

BACKGROUND: The optimal extent of lymph node dissection (LND) for hypermetabolic tumors that are associated with high rates of nodal disease, recurrence, or mortality has not been elucidated. METHODS: We reviewed 375 patients who underwent lobectomy with lymphadenectomy for clinical T2-3 N0-1 M0 hypermetabolic non-small cell lung cancer (NSCLC) [maximum standard uptake value (SUVmax) ≥ 6.60] via a multicenter database. Extent of LND was classified into systematic mediastinal LND (systematic LND) and lobe-specific mediastinal LND (lobe-specific LND). Postoperative outcomes after lobectomy with systematic LND (n = 128) and lobe-specific LND (n = 247) were analyzed for all patients and their propensity-score-matched pairs. RESULTS: Cancer-specific survival (CSS) and recurrence-free interval (RFI) of the systematic LND group were not significantly different from those of the lobe-specific LND group in the nonadjusted whole cohort. In the propensity-score-matched cohort (101 pairs), systematic LND dissected significantly more lymph nodes (20.0 versus 16.0 nodes, P = 0.0057) and detected lymph node metastasis more frequently (53.5% vs. 33.7%, P = 0.0069). Six (5.9%) patients in the systematic LND group had a metastatic N2 lymph node "in the systematic LND field" that lobe-specific LND could not dissect. The systematic LND group tended to have better prognosis than the lobe-specific LND group (5-year CSS rates, 82.6% versus 69.6%; 5-year RFI rates, 56.6% vs. 47.3%). CONCLUSIONS: Systematic LND was found to harvest more metastatic lymph nodes and provide better oncological outcome than lobe-specific LND in a cohort of hypermetabolic NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos
13.
Lung Cancer ; 158: 9-14, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34090182

RESUMO

OBJECTIVES: Lymphatic vessel invasion (Ly) plays a crucial role in pathological lymph node metastasis (pN), and we consider pN + Ly + disease to indicate a high affinity for the lymphatic system. This study evaluated the outcomes of patients with clinically node-negative (N0) non-small cell lung cancer (NSCLC) who presented with pN + with Ly+. MATERIALS AND METHODS: This retrospective study evaluated 1775 patients with clinically N0 stage I-III NSCLC who underwent R0 anatomical resection and systematic lymph node dissection at three institutions between January 2010 and December 2017. Patients were classified into four groups according to their pN and Ly statuses. Univariable and multivariable analyses were performed to identify factors associated with poor recurrence-free survival (RFS) and pN + Ly+. RESULTS: Kaplan-Meier curves revealed that the 5-year RFS rates were 90.8 % for pN-Ly- patients, 55.6 % for pN-Ly + patients, 63.4 % for pN + Ly- patients, and 41.3 % for pN + Ly + patients. Distant and lymph node recurrences were more common in the pN + Ly + group, relative to in the pN-Ly- and pN-Ly + groups (both p < 0.001). Multivariable analyses revealed that pN and Ly statuses were independently associated with RFS, while the solid tumor size and maximum standardized uptake value were independently associated with pN + Ly + status. The proportion of pN + Ly + disease was 17.2 % in patients with a solid-part size of > 1.80 cm and a SUVmax of > 3.55. CONCLUSION: pN and Ly statuses were independent prognostic factors in patients with clinically N0 stage I-III NSCLC. Diseases presenting with pN + with Ly + were associated with increased rates of distant and lymph node recurrence.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco
14.
Front Oncol ; 11: 622742, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34164334

RESUMO

OBJECTIVE: This study aimed to identify patients at a high risk of recurrence using preoperative high-resolution computed tomography (HRCT) in clinical stage I non-small cell lung cancer (NSCLC). METHODS: A total of 567 patients who underwent screening and 1,216 who underwent external validation for clinical stage I NSCLC underwent lobectomy or segmentectomy. Staging was used on the basis of the 8th edition of the tumor-node-metastasis classification. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method, and the multivariable Cox proportional hazards model was used to identify independent prognostic factors for RFS. RESULTS: A multivariable Cox analysis identified solid component size (hazard ratio [HR], 1.66; 95% confidence interval [CI] 1.30-2.12; P < 0.001) and pure solid type (HR, 1.82; 95% CI 1.11-2.96; P = 0.017) on HRCT findings as independent prognostic factors for RFS. When patients were divided into high-risk (n = 331; solid component size of >2 cm or pure solid type) and low-risk (n = 236; solid component size of ≤2 cm and part solid type) groups, there was a significant difference in RFS (HR, 5.33; 95% CI 3.09-9.19; 5-year RFS, 69.8% vs. 92.9%, respectively; P < 0.001). This was confirmed in the validation set (HR, 5.32; 95% CI 3.61-7.85; 5-year RFS, 72.0% vs. 94.8%, respectively; P < 0.001). CONCLUSIONS: In clinical stage I NSCLC, patients with a solid component size of >2 cm or pure solid type on HRCT were at a high risk of recurrence.

15.
Sci Rep ; 11(1): 7830, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837261

RESUMO

PD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome's surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8+ TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I-III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p < 0.001) and the number of CD8+ TILs (p = 0.001). Patients with exosomal PD-L1 ≥ 166 pg/mL tended to have a worse RFS than those with < 166 pg/mL in all stage (p = 0.163) and stage I patients (p = 0.116). Seventeen patients exhibited postoperative recurrences and received anti-PD-1 treatment. The disease control rate of patients with exosomal PD-L1 ≥ 166 pg/mL was 100%. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and clinical outcomes in patients with NSCLC.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Exossomos/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/cirurgia , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão
16.
Transl Lung Cancer Res ; 10(3): 1484-1500, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33889524

RESUMO

BACKGROUND: Immune and stromal component evaluation is necessary to establish accurate prognostic markers for the prediction of clinical outcomes in lung adenocarcinoma (LUAD). We aimed to develop a gene signature based on the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE)-stromal-immune score in LUAD. METHODS: The transcriptomic profiles of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA), and the immune and stromal scores were derived using the ESTIMATE algorithm. The prognostic signature genes were selected from the differentially expressed genes (DEGs) using the robust partial likelihood-based cox proportional hazards regression method. The negative log-likelihood and the Akaike Information Criterion (AIC) were used to identify the optimal gene signature. The validation was carried out in 2 independent datasets from the Gene Expression Omnibus (GSE68571 and GSE72094). RESULTS: Patients with high ESTIMATE, stromal, and immune scores had better overall survivals (P=0.0035, P=0.066, and P=0.0077). The expression of thirty-seven genes was related to ESTIMATE-stromal-immune score. A risk stratification model was developed based on a gene signature containing CD74, JCHAIN, and PTGDS. The ESTIMATE-stromal-immune risk score was revealed to be a prognostic factor (P=0.009) after multivariate analysis. Four groups were classified based on this risk stratification model, yielding increasing survival outcomes (log-rank test, P=0.0051). This risk stratification model and other clinicopathological factors were combined to generate a nomogram. The calibration curves showed perfect agreement between the nomogram-predicted outcomes and those actually observed. Similar observations were made in 2 independent cohorts. CONCLUSIONS: The gene signature based on the ESTIMATE-stromal-immune score could predict the prognosis of patients with LUAD.

17.
PLoS One ; 16(3): e0248206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33668046

RESUMO

Distinguishing lung squamous cell carcinoma (LSQCC) from a solitary metastatic lung tumor (MSQCC) from head and neck squamous cell carcinoma (HNSQCC) presents a difficult diagnostic challenge even after detailed pathological assessment. Treatment options and estimated survival outcomes after pulmonary resection differ between patients with LSQCC and MSQCC. This study aimed to investigate whether microRNA (miRNA) profiling by RNA sequencing of HNSQCC, MSQCC, and LSQCC was useful for differential diagnosis of MSQCC and LSQCC. RNA sequencing was performed to identify bioinformatically significant miRNAs from a formalin-fixed paraffin-embedded (FFPE) block from a derivation set. MiRNA levels were confirmed by validation sets using FFPE samples and serum extracellular vesicles from patients. Step-wise discriminant analysis and canonical discriminant analysis identified 13 miRNAs by which the different expression patterns of LSQCC, MSQCC, and HNSQCC groups were demonstrated. Six miRNAs (miR-10a/28/141/320b/3120) were assessed in validation sets, and 4 miRNAs (miR-10a/28/141/3120) were significantly upregulated in LSQCCs compared with MSQCCs and HNSQCCs. Serum extracellular vesicles from LSQCC patients demonstrated significantly elevated miR-10a (p = .042), miR-28 (p = .041), and miR-3120 (p = .047) levels compared with those from MSQCC patients. RNA sequencing is useful for differential diagnosis of LSQCC and MSQCC, and the expression level of miR-10a, miR-28, and miR-3120 in serum extracellular vesicles are promising noninvasive tools for this purpose.


Assuntos
MicroRNA Circulante , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , RNA Neoplásico , RNA-Seq , Carcinoma de Células Escamosas de Cabeça e Pescoço , Idoso , Idoso de 80 Anos ou mais , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/classificação , Neoplasias de Cabeça e Pescoço/genética , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/genética , Masculino , RNA Neoplásico/sangue , RNA Neoplásico/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/classificação , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
18.
Surg Case Rep ; 7(1): 48, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591407

RESUMO

BACKGROUND: Mediastinal teratomas occasionally rupture into the thoracic cavity, which induces mediastinitis or various other severe complications. Surgical treatment is crucial for ruptured teratomas; however, few literature reviews to date have addressed the characteristics of ruptured mediastinal teratomas. CASE PRESENTATION: We report a 29-year-old woman with severe mediastinitis owing to a mediastinal mature teratoma that ruptured into the mediastinum and right pleural cavity. Surgical resection by median sternotomy was performed within 24 hours after emergency admission. Intraoperative findings demonstrated the ruptured wall of the tumor with exposure of its white contents, which appeared similar to skin and fat, and necrotic tissue in the anterior mediastinum. The tumor was adhered to the right upper lobe, the ascending aorta, and pericardium. Owing to the severe adhesion of the tumor caused by inflammation in the surrounding tissues, a small portion of the tumor could not be removed, and hence complete resection with a sufficient surgical margin was not achieved. Pathologically, the tumor consisted of a solid mass and a cystic mass with severe adhesion to the resected portion of the lung, which included skin and lipid tissue. The tumor was concluded to be a mature teratoma as neither an immature component nor malignant transformation was observed. The patient had an uneventful postoperative course. CONCLUSIONS: To our knowledge, this is the report of successful surgical resection of a ruptured mediastinal teratoma causing severe mediastinitis, with the first literature review of ruptured mediastinal teratomas. We also discuss relevant findings from reports in the literature.

19.
Clin Lung Cancer ; 22(2): 120-126.e3, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33485802

RESUMO

BACKGROUND: Despite the recent development of radiologic mediastinal staging modality, unexpected mediastinal lymph node metastasis still occurs. Preoperative accurate nodal staging is important to determine the optimal treatment. Therefore, this study aimed to identify predictors of unexpected N2 disease in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Data from a multicenter database of 2802 patients with clinical T1-2N0-1M0 NSCLC who underwent anatomical segmentectomy or lobectomy were retrospectively analyzed. Unexpected N2 disease was defined as pathologic N2 disease with clinical N0 or N1. The predictive criteria of unexpected N2 disease were established on the basis of the multivariable analysis results of a derivation cohort of 2019 patients, and the criteria were further tested in a validation cohort of 783 patients. RESULTS: In multivariable analyses, maximum standardized uptake value (SUVmax) of the primary tumor on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (odds ratio, 1.072; 95% confidence interval, 1.018-1.129; P = .008) and clinical N1 (vs. clinical N0) disease (odds ratio, 5.40; 95% confidence interval, 1.829-15.94; P = .002) were independent predictors of unexpected N2 disease. The predictive criteria of unexpected N2 disease was defined as tumors with SUVmax of ≥ 3.1, determined by receiver operating characteristic curves, and clinical N1 disease. This criterion showed diagnostic accuracy of 90.6% (sensitivity 32.0%, specificity 94.5%) in the derivation cohort and 91.3% (sensitivity 32.6%, specificity 94.7%) in the validation cohort. CONCLUSION: The predictive criteria of unexpected N2 disease (tumors with SUVmax of ≥ 3.1 and clinical N1) can be used to select candidates for preoperative invasive mediastinal staging in patients with clinical T1-2N0-1M0 NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Fluordesoxiglucose F18/uso terapêutico , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Linfonodos/patologia , Metástase Linfática , Masculino , Mediastino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Prognóstico , Curva ROC , Estudos Retrospectivos
20.
World J Surg ; 45(5): 1569-1574, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33469737

RESUMO

PURPOSE: We aimed to assess the clinical usefulness of the fissureless technique, which avoided dissection of the lung parenchyma over the pulmonary artery, in preventing prolonged air leak after video-assisted thoracic surgery right upper lobectomy (VATS RUL). METHODS: Perioperative outcomes, including the frequency of prolonged air leak after fissureless technique or traditional fissure dissection technique, which dissected the lung parenchyma through the fissure, were compared in patients who underwent VATS RUL (n = 213) between January 2016 and March 2020. We adopted our fissural grade to evaluate the degree of fused fissure ranging from II (light incomplete fissure) to IV (severe incomplete fissure), which covered all fissural grades in 213 patients. RESULTS: Fifty-four and 159 patients underwent fissureless and traditional techniques, respectively. Significant differences in the incidence of prolonged air leak (p = 0.037), time to air leak cessation (p = 0.047), and duration of chest tube placement (p = 0.017) were observed between fissureless and traditional technique groups. On multivariable analysis, traditional technique (p = 0.005), and greater fissural grade (III vs II, p = 0.020; IV vs II, p = 0.001) were significantly associated with prolonged air leak. CONCLUSIONS: Fissureless technique during VATS RUL can be a superior alternative to the traditional technique to prevent prolonged air leak in treating incomplete fissures.


Assuntos
Neoplasias Pulmonares , Pneumonectomia , Tubos Torácicos , Humanos , Pulmão , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Cirurgia Torácica Vídeoassistida
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