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1.
Artigo em Inglês | MEDLINE | ID: mdl-34647128

RESUMO

OBJECTIVES: Prognosis after segmentectomy for early-stage non-small cell lung cancer (NSCLC) with a high consolidation tumour ratio (CTR) and [18F]-fluoro-2-deoxy-D-glucose (FDG) accumulation on positron emission tomography/computed tomography is unclear. METHODS: Participants of this study were 465 patients who underwent lobectomy or segmentectomy for clinical N0 NSCLC presenting solid component predominant tumour (CTR >50%) with a whole size ≤3 cm. Accumulations of FDG on positron emission tomography/computed tomography scans were scored according to the Deauville criteria, a 5-point visual evaluating method (Deauville score). The correlations between Deauville score, prognosis, and procedures were analysed. RESULTS: Characteristics of pathological invasiveness, such as lymphatic invasion (P < 0.001), vascular invasion (P < 0.001) and pleural invasion (P < 0.001), and non-adenocarcinoma histologies (P < 0.001) were more common in patients with Deauville scores of 3-5. The cumulative incidence of recurrence (CIR) was higher in patients with Deauville scores of 3-5 (P < 0.001). The CIR after lobectomy and segmentectomy did not differ significantly among patients with Deauville scores of 1 or 2 (P = 0.598) or those with Deauville scores of 3-5 (P = 0.322). In the analysis of propensity score matched cohort, the CIR after lobectomy and segmentectomy did not differ significantly between patients with Deauville scores of 1 or 2 and Deauville scores of 3-5. CONCLUSIONS: Segmentectomy may be feasible for NSCLC with high CTR (>50%) and accumulation of FDG. This finding should be confirmed in larger prospective studies.

2.
Thorac Cancer ; 12(23): 3141-3149, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34643053

RESUMO

INTRODUCTION: Tumor size is an absolute recurrence risk in lung cancer. Although morphological features also reflect recurrence risk, its significance among lower-risk cases characterized by small size is unknown. We aimed to evaluate the relationship between pathological invasive tumor size and morphological features, and their prognostic impact by considering them simultaneously in lung adenocarcinoma. PATIENTS AND METHODS: We retrospectively reviewed 563 pN0M0 patients with pathological invasive size of ≤40 mm. The patients were classified by pathological invasive size and pathological malignant grading using the proportion of subhistological components. The prognostic impact was evaluated using recurrence-free survival (RFS) and overall survival (OS). The impact on prognosis was evaluated using uni- and multivariate analyses. RESULTS: The proportion of histological grade changed according to invasive tumor size. Patients with high malignant grade (G3) showed worse RFS than those with low and intermediate malignant grade (G1+2) with invasive size ≤20 mm. The 5-year RFS (G1+2 vs. G3) in 5-10 mm was 96.0% vs. 83.3% (HR = 5.505, 95% CI = 7.156-1850, p < 0.001) and in 10-20 mm was 87.8% vs. 67.1% (HR = 2.829, 95% CI = 4.160-43.14, p < 0.001). G3 patients were significantly bigger in invasive size and included more pleural/lymphatic/vascular invasion and recurrence. Multivariate analysis indicated pathological G3 status was significantly associated with worse RFS (HR = 2.097, 95% CI = 1.320-3.333, p = 0.002). CONCLUSIONS: Invasive tumor size and pathological malignant grade overlap in invasive adenocarcinoma. G3 patients are more likely to have pleural/lymphatic/vascular invasion and significantly worse RFS compared to G1/G2 cases, even with a small invasive size of ≤20 mm.

3.
JTO Clin Res Rep ; 2(2): 100126, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34589986

RESUMO

Introduction: The International Association for the Study of Lung Cancer proposed a new grading criteria for invasive adenocarcinoma. However, its utility has not been validated. Methods: Patients who underwent complete resection of lung adenocarcinoma were included in this study. Then, they were divided into the following three groups on the basis of the criteria recently proposed by the International Association for the Study of Lung Cancer: grade 1, lepidic predominant tumor, with less than 20% of high-grade patterns; grade 2, acinar or papillary predominant tumor, with less than 20% of high-grade patterns; and grade 3, any tumor with greater than or equal to 20% of high-grade patterns. Results: Recurrence-free survival (RFS) was significantly different among the proposed grades (p < 0.001). The RFS of patients upgrading from current grade 2 (papillary or acinar predominant tumor) to proposed grade 3 (5-y RFS, 65.2%) was significantly worse than that of patients with proposed grade 2 (77.1%, hazard ratio = 1.882, 95% confidence interval: 1.236-2.866) but not significantly different from that of patients with grade 3 in both the current (micropapillary or solid predominant tumor) and proposed criteria (53.2%, hazard ratio = 0.761, 95% confidence interval: 0.456-1.269). Among patients with pathologic stage 0 or I, RFS was well stratified by the new grading system (p < 0.001) but not among patients with stage II or III (p = 0.334). In the multivariable analysis, the new grading was not a predictive factor of RFS. Conclusions: Although the proposed grading system well stratified RFS in patients with pathologic stage 0 or I lung adenocarcinoma, there is room for improvement.

4.
Clin Lung Cancer ; 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34321190

RESUMO

BACKGROUND: The aim of this study was to investigate and compare the clinical behaviors of combined and pure high-grade neuroendocrine carcinoma (large-cell neuroendocrine carcinoma [LCNEC] and small-cell lung carcinoma [SCLC]). PATIENTS AND METHODS: Data of 132 patients who underwent complete resection for combined or pure high-grade neuroendocrine carcinoma (combined group, 67; pure group, 65) between January 2001 and December 2015 were retrospectively reviewed. The clinicopathological features were analyzed and compared, and the prognoses were assessed by performing the Kaplan-Meier method and Cox regression analysis. RESULTS: The combined and pure groups had nearly equivalent clinicopathological characteristics, specifically, older males with smoking history, almost the same percentage of pleural/lymphatic/vascular invasion, and nearly the same recurrence rates and relapse patterns. The combined group had prognosis equivalent to that of the pure group (5-year overall survival [OS] rates: 61.8% vs. 52.2%, respectively; P = .82 and 5-year recurrence-free survival [RFS] rates: 42.4% vs. 43.9%, respectively; P = .96), and this trend was identified in sub-analyses only for patients with LCNEC, SCLC, and the same pathological stage. Multivariable Cox regression analysis in patients with high-grade neuroendocrine carcinoma revealed that vascular invasion and pathological stage were independent prognostic factors for OS; more importantly, combined and pure histologies were proven to have nearly equivalent associations with prognosis (hazard ratio, 0.96; 95% confidence interval, 0.22to 1.66; P = .96). RESULTS: Combined high-grade neuroendocrine carcinoma had clinical behavior equivalent to those of pure high-grade neuroendocrine carcinoma, with similar clinicopathological characteristics.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34218331

RESUMO

PURPOSE: Liquid biopsy for early-stage lung cancer diagnosis is challenging, and optimal candidates' clinicopathological features are unknown. We investigated utility and clinicopathological features of optimal candidates in somatic mutation-targeted liquid biopsy using droplet digital polymerase chain reaction (ddPCR) in pN0M0 EGFR mutation-positive lung adenocarcinoma patients. METHODS: We performed EGFR mutation-targeted ddPCR liquid biopsy in 100 patients with resected pN0M0 invasive lung adenocarcinoma, whose tumor diameter in high-resolution computed tomography (HRCT) was ≤ 5 cm. Peripheral blood-derived serum was collected preoperatively. Two representative EGFR somatic variants (exon 19 [E746-A750 del (2235_2249 del)]; exon 21 (L858R)) were utilized as liquid biopsy targets. Clinicopathological features including radiological appearance, subhistology, and invasive status were compared between ddPCR-positive and ddPCR-negative patients. RESULTS: Among the 100 patients, 98 showed part-solid or pure-solid appearance in HRCT and 2 showed non-solid appearance; 98 were pathological stage IA1-IB. Of the 66 patients with EGFR mutation detection in ddPCR, 12 were significantly positive and 10 (83.3%, 10/12) exhibited pure-solid appearance in HRCT. Clinical invasive tumor ratio was significantly higher in ddPCR-positive than in ddPCR-negative patients (median: 100% vs. 85.4%, P = 0.0212), whereas other clinicopathological features were not significantly different. CONCLUSION: Mutation-targeted liquid biopsy using ddPCR detected lung cancer in 12.0% (12/100) of pN0M0 EGFR-mutant lung adenocarcinoma patients. In 83.3% of the ddPCR-positive patients, tumors showed pure-solid appearance in HRCT. The detection ratio increased to 21.3% (10/47) among patients with pure-solid appearance tumors. Tumor appearance might be useful for better selection of liquid biopsy candidates.

6.
Intern Med ; 60(13): 2047-2053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193774

RESUMO

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Piridinas , Sorafenibe/uso terapêutico
7.
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
8.
Jpn J Clin Oncol ; 51(10): 1561-1569, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34331062

RESUMO

OBJECTIVE: We aimed to determine the influences of surgical procedures on the postoperative death of octogenarians with clinical Stage IA non-small cell lung cancer excluding cT1mi. METHODS: We compared overall survival and the cumulative incidence of death due to all and other causes among 1 130 279, and 191 consecutive patients aged ≤79 and ≥80 years after lobectomy, segmentectomy and wedge resection at three institutions. Death due to other causes was defined as death due to any cause except non-small cell lung cancer. RESULTS: The median followup was 53 months. The 5-year overall survival rates for patients aged ≥ 80 and ≤ 79 years after lobectomy, segmentectomy and wedge resection were respectively, 78.0% (95% confidence interval, 63.8%-87.2%) versus 91.2% (95% confidence interval, 89.0%-92.9%), 68.1% (95% confidence interval, 45.2%-83.1%) versus 90.0% (95% confidence interval, 84.6%-93.5%), and 62.7% (95% confidence interval, 44.0-76.7%) versus 84.4% (95% confidence interval, 76.3%-89.9%) (P < 0.01 for all). The cumulative incidence of death due to other causes after wedge resection was similar between patients aged ≥ 80 and ≤ 79 years (P = 0.45), but significantly higher in those aged ≥ 80, than ≤ 79 years after lobectomy or segmentectomy (P = 0.00015 and 0.00091, respectively). CONCLUSIONS: The influence of wedge resection on death due to other causes was lower than that of lobectomy or segmentectomy in patients with non-small cell lung cancer aged ≥ 80 years. Wedge resection might be a useful option for octogenarians even if they can tolerate lobectomy/segmentectomy to avoid postoperative death due to causes other than non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia , Taxa de Sobrevida
9.
Ann Surg Oncol ; 28(13): 8347-8355, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34296359

RESUMO

BACKGROUND: Segmentectomy has been increasingly used for lung cancer treatment, however there are very limited data evaluating the postoperative pulmonary function of patients treated with complex segmentectomy. We evaluated the postoperative pulmonary function of patients who underwent complex segmentectomy compared with simple segmentectomy, wedge resection, and lobectomy. METHODS: We retrospectively analyzed data from 580 patients who underwent surgical resection. The patients were divided into four groups: complex segmentectomy (n = 135), simple segmentectomy (n = 83), wedge resection (n = 89), and lobectomy (n = 273). Functional testing included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and predicted diffusing capacity of the lung for carbon monoxide (%DLCO) measured preoperatively and at 12 months after surgery. RESULTS: During the postoperative course, the complex segmentectomy and simple segmentectomy groups showed a comparable course of pulmonary function. The complex segmentectomy group significantly preserved pulmonary function compared with the lobectomy group (FVC, p = 0.017; FEV1, p = 0.010; %DLCO, p = 0.0043). A similar trend was observed even when restricted to lung diseases in the right upper lobe. On the other hand, when comparing complex segmentectomy with wedge resection, complex segmentectomy showed a trend that was more disadvantageous than wedge resection, but this difference was not significant (FVC, p = 0.19; FEV1, p = 0.40; %DLCO, p = 0.96). CONCLUSIONS: Complex segmentectomy showed comparable postoperative pulmonary functions as simple segmentectomy. Complex segmentectomy could preserve pulmonary function significantly compared with lobectomy and did not result in significant loss compared with wedge resection.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Volume Expiratório Forçado , Humanos , Pulmão/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Estudos Retrospectivos
10.
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
11.
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.

12.
Ann Thorac Surg ; 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34186090

RESUMO

BACKGROUND: This study aimed to investigate the efficacy of adjuvant chemotherapy for pathologic stage I non-small cell lung cancer (NSCLC) with high risk for recurrence. METHODS: Prospectively collected data from 1278 patients with pathologic stage I NSCLC according to eighth edition staging guidelines who were undergoing lobectomy were retrospectively analyzed. Factors associated with high risk for recurrence were determined using the multivariable Cox proportional hazards model for recurrence-free survival (RFS). Survival was compared between patients who received adjuvant chemotherapy and those who did not. RESULTS: In multivariable analysis, age (>70 years), invasive component size (>2 cm), visceral pleural invasion, lymphatic invasion, and vascular invasion were identified as independent factors for RFS. In patients with high-risk factors for recurrence such as pathologic T1c or T2a or lymphovascular invasion (high-risk group; n = 641), adjuvant chemotherapy resulted in significantly longer RFS and overall survival (n = 222; 5-year RFS, 81.4%; 5-year overall survival, 92.7%) than in patients who did not receive adjuvant chemotherapy (n = 418; 5-year RFS, 73.8%; P = .023; 5-year overall survival, 81.7%; P < .0001). In patients without any high-risk factors for recurrence (low-risk group; n = 637), RFS was not significantly different between those who received adjuvant chemotherapy (n = 83; 5-yeat RFS, 98.1%) and those who did not (n = 554; 5-year RFS, 95.7%; P = .30). CONCLUSIONS: Adjuvant chemotherapy may improve survival in patients with pathologic stage I NSCLC who have factors associated with high risk for recurrence, such as pathologic T1c or T2a or lymphovascular invasion.

13.
BMC Pulm Med ; 21(1): 186, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078355

RESUMO

BACKGROUND: Acute exacerbation (AE) of interstitial pneumonia (IP) is the most fatal complication after lung resection for lung cancer. To improve the prognosis of lung cancer with IP, the risk factors of AE of IP after lung resection should be assessed. S100 calcium-binding protein A4 (S100A4) is a member of the S100 family of proteins and is a known marker of tissue fibrosis. We examined the usefulness of S100A4 in predicting AE of IP after lung resection for lung cancer. METHODS: This study included 162 patients with IP findings on preoperative high-resolution computed tomography scan who underwent curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum samples were collected preoperatively. Resected lung tissue from 76 patients exhibited usual IP (UIP) pattern in resected lung were performed immunohistochemistry (IHC). Relationship between S100A4 and the incidence of AE of IP and short-term mortality was analyzed. RESULTS: The receiver operating characteristic area under the curve for serum S100A4 to predict postoperative AE of IP was 0.871 (95% confidence interval [CI], 0.799-0.943; P < 0.001), with a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. Multivariable analysis revealed that a high serum S100A4 level (> 17.13 ng/mL) was a significant risk factor for AE of IP (odds ratio, 42.28; 95% CI, 3.98-449.29; P = 0.002). A 1-year overall survival (OS) was significantly shorter in patients with high serum levels of S100A4 (75.3%) than in those with low serum levels (92.3%; P = 0.003). IHC staining revealed that fibroblasts, lymphocytes, and macrophages expressed S100A4 in the UIP area, and the stroma and fibrosis in the primary tumor expressed S100A4, whereas tumor cells did not. CONCLUSIONS: Serum S100A4 had a high predictive value for postoperative AE of IP and short-term mortality after lung resection.


Assuntos
Doenças Pulmonares Intersticiais/sangue , Neoplasias Pulmonares/cirurgia , Pulmão/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Pulmão/cirurgia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/complicações , Masculino , Complicações Pós-Operatórias , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Taxa de Sobrevida
14.
Ann Thorac Surg ; 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34139190

RESUMO

BACKGROUND: In lung cancer patients with interstitial lung disease (ILD) postoperative acute exacerbation can be fatal. However the predictive biomarkers for postoperative exacerbation of ILD have not been fully elucidated. The soluble receptor for advanced glycation end products is a lung-derived antiinflammatory protein that can prevent acute lung injury. This study aimed to elucidate its role in this fatal complication, especially focusing on the predictive potential of serum levels of soluble receptor for advanced glycation end products. METHODS: We retrospectively enrolled 152 patients with lung cancer and ILD who underwent lung resection and had blood samples collected before surgery. Independent predictors of postoperative acute exacerbation were evaluated in all patients and in subgroups based on the surgical procedure. Additionally serial changes in soluble receptor levels in these subgroups were evaluated. RESULTS: Seventeen patients (11.2%) developed postoperative acute exacerbation. Receiver operating characteristic curve analysis revealed 547.4 pg/mL as the optimal soluble receptor level cutoff value. Univariate and multivariate logistic regression analyses revealed a significant association between soluble receptor serum levels (≤547.4 pg/mL) and postoperative acute exacerbation. In the subgroup analysis this independent association was observed only in the lobectomy group. Additionally lobectomy caused a significant reduction in postoperative soluble receptor levels. CONCLUSIONS: Decreased baseline levels of circulatory soluble receptor might be a potential risk factor for postoperative acute exacerbation in patients with lung cancer and ILD. Moreover additional reduction in the levels of this antiinflammatory protein occurs because of lung resection.

15.
Jpn J Clin Oncol ; 51(7): 1123-1131, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34002234

RESUMO

OBJECTIVES: The prognostic role of interstitial pneumonia with emphysema in lung cancer is not fully understood. This study aimed to examine the prognostic role of the presence of emphysema in patients with clinical stage I lung cancer and interstitial pneumonia. METHODS: The presence of interstitial pneumonia and emphysema was evaluated on preoperative high-resolution computed tomography. In total, 836 consecutive patients with clinical stage I lung cancer who underwent complete resection between April 2007 and March 2016 were retrospectively analyzed using the log-rank test and Cox proportional hazard model to examine survival differences. RESULTS: There was a significant difference in 5-year overall survival between patients with interstitial pneumonia and emphysema (n = 65) and those without (n = 771) (62.6% vs. 86.5%; P < 0.001). However, in patients with interstitial pneumonia on high-resolution computed tomography, there was no significant difference in 5-year overall survival between patients with emphysema (n = 65) and those without emphysema (n = 50) (62.6% vs. 59.4%, P = 0.84). Multivariable backward stepwise Cox proportional hazard analysis in patients with interstitial pneumonia showed that histology, %diffusing capacity of the lungs for carbon monoxide, radiologic interstitial pneumonia pattern and surgical procedure were independent prognostic factors for overall survival, but the presence of emphysema was not. CONCLUSIONS: The presence of emphysema was not an independent prognostic factor for overall survival in patients with clinical stage I lung cancer with interstitial pneumonia. Poor survival of patients with IP and emphysema may be due to the presence of interstitial pneumonia.


Assuntos
Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/mortalidade , Enfisema Pulmonar/mortalidade , Idoso , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/patologia , Tomografia Computadorizada por Raios X
16.
Sci Rep ; 11(1): 10105, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980944

RESUMO

Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29-11.70] ng/mL vs. 3.55 [2.07-5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.


Assuntos
Proteína HMGB1/sangue , Doenças Pulmonares Intersticiais/sangue , Neoplasias Pulmonares/cirurgia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos
17.
Ann Thorac Surg ; 2021 May 19.
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 [SUV max]) non-small cell lung cancer (NSCLC) remains controversial. This study compared the outcomes after complex segmentectomy and lobectomy in these patients. METHODS: We retrospectively reviewed 717 patients with radiologically hypermetabolic (SUV max ≥ 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 (CSS) rate, 89.9% vs. 91.1%, P = 0.98 and 5-year recurrence-free interval (RFI) rates, 83.0% vs. 77.5%, P = 0.62] in non-adjusted cohort. In 55 propensity score-matched pairs, oncologic outcomes were not significantly different between patients undergoing complex segmentectomy (5-year CSS, 89.9%; 5-year RFI, 83.0%) and lobectomy (5-year CSS, 83.6%; 5-year RFI, 82.5%). Multivariable Cox regression analysis for RFI revealed no significant differences between oncologic outcomes associated with complex segmentectomy and lobectomy (hazard ratio, 0.84; 95% confidence interval, 0.25-2.14; P = 0.74). CONCLUSIONS: Oncologic outcomes of complex segmentectomy and lobectomy were not significantly different in those with radiologically hypermetabolic, clinical Stage IA NSCLC patients. Complex segmentectomy can treat high SUV max, clinical Stage IA lung cancers without compromising oncologic results.

18.
Eur J Cancer ; 149: 14-22, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33813328

RESUMO

BACKGROUND: Osimertinib is now a standard treatment for patients with previously untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC). We here investigated whether the combination of osimertinib with cytotoxic chemotherapy might hold additive efficacy, as well as tolerability. PATIENTS AND METHODS: We conducted an open-label randomised phase 2 study to evaluate osimertinib and carboplatin-pemetrexed combination in comparison with osimertinib monotherapy in EGFR mutation-positive NSCLC patients who experienced disease progression associated with the emergence of the T790M resistance mutation of EGFR during first-line EGFR-TKI therapy. The primary endpoint was PFS, with secondary endpoints, including OS, response, and safety. Given that osimertinib was approved as a first-line treatment during the study, patient accrual was discontinued, and a final analysis was performed for the 62 enrolled patients. RESULTS: Median PFS was 15.8 months for the osimertinib monotherapy group and 14.6 months for the combination therapy group (hazard ratio of 1.09, with a 95% confidence interval of 0.51-2.32; P = .83). Median OS was not reached in either group. The overall response rate was 71.4% in the osimertinib monotherapy group and 53.6% in the combination group. The frequency or severity of known adverse events in the combination group was comparable to those with carboplatin and pemetrexed previously reported, and novel adverse events were not observed in this study. CONCLUSION: This is the first randomised study to investigate the efficacy and safety of the combination of osimertinib and cytotoxic chemotherapy for EGFR-mutated NSCLC. The addition of chemotherapy to osimertinib as a second-line treatment did not prolong survival, while it was found to be generally tolerable. This combination strategy will be further validated in the first-line setting. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCTs071180062.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Acrilamidas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Japão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Pemetrexede/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Fatores de Tempo
19.
J Cancer Res Clin Oncol ; 147(12): 3709-3718, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33796913

RESUMO

PURPOSE: The clinicopathological or genetic features related to the prognosis of mucinous adenocarcinoma are unknown because of its rarity. The clinicopathological or targetable features were investigated for better management of patients with mucinous adenocarcinoma of the lung. METHODS: We comprehensively evaluated the clinicopathological and genetic features of 60 completely resected mucinous lung adenocarcinomas. Targetable genetic variants were explored using nCounter and polymerase chain reaction, PD-L1 and TTF-1 expression were evaluated using immunohistochemistry. We analyzed the prognostic impact using the Kaplan-Meier method and log-rank test. RESULTS: Of the 60 enrolled patients, 13 (21.7%) had adenocarcinoma in situ/minimally invasive adenocarcinoma, and 47 (78.3%) had invasive mucinous adenocarcinoma (IMA). Fifteen patients (25%) showed a pneumonic appearance on computed tomography (CT). CD74-NRG1 fusion, EGFR mutations, and BRAF mutation were detected in three (5%), four (6.7%), and one (1.7%) patient(s), respectively. KRAS mutations were detected in 31 patients (51.7%). Two patients (3.5%) showed immunoreactivity for PD-L1. No in situ or minimally invasive cases recurred. IMA patients with pneumonic appearance had significantly worse recurrence-free survival (RFS) and overall survival (OS) (p < 0.001). Furthermore, IMA patients harboring KRAS mutations had worse RFS (p = 0.211). Multivariate analysis revealed that radiological pneumonic appearance was significantly associated with lower RFS (p < 0.003) and OS (p = 0.012). KRAS mutations served as an unfavorable status for RFS (p = 0.043). CONCLUSION: Mucinous adenocarcinoma had a low frequency of targetable genetic variants and PD-L1 immunoreactivity; however, KRAS mutations were frequent. Pneumonic appearance on CT imaging and KRAS mutations were clinicopathological features associated with a worse prognosis.


Assuntos
Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos
20.
Transl Lung Cancer Res ; 10(2): 766-775, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33718020

RESUMO

Background: The histological classification of non-small cell lung cancer (NSCLC) is essential in determining new cancer-specific targeted therapies. However, the accurate typing of poorly differentiated is difficult, particularly for poorly differentiated squamous cell carcinoma and adenocarcinoma of the lung with limited immunohistochemical markers. Thus, novel immunohistochemical markers are required. We assumed the possibility of the immunohistochemical expression of glypican-1 in lung squamous cell carcinoma. Methods: The microarray dataset GSE43580 from Gene Expression Omnibus database were analyzed for confirming the gene expression of glypican-1 in lung squamous cell carcinoma. We immunohistochemically investigated the use of glypican-1 as a novel positive diagnostic marker for lung squamous cell carcinoma. Glypican-1 expression in 63 cases of poorly differentiated lung squamous cell carcinoma and 60 cases of solid predominant lung adenocarcinoma was investigated by immunohistochemistry. Additionally, we compared glypican-1 expression with the expressions of p40, cytokeratin 5/6, thyroid transcription factor-1 (TTF-1), and napsin A. Results: All 63 cases of lung squamous cell carcinoma showed glypican-1 expression. In contrast, only 2 cases of lung adenocarcinoma showed glypican-1 expression. The sensitivity, specificity, and diagnostic accuracy of glypican-1 expression for differentiating lung squamous cell carcinoma from lung adenocarcinoma were 100%, 96.7%, and 98.4%, respectively. These were similar to those of p40 and significantly better than those of CK 5/6. Conclusions: We recommend the use of glypican-1 as an additional positive marker of lung squamous cell carcinoma.

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