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PURPOSE: We elucidated the effects of planned resection volume on postoperative pulmonary function and changes in residual lung volume during segmentectomy. METHODS: This study included patients who underwent thoracoscopic segmentectomy between January 2017 and December 2022 and met eligibility criteria. Pre- and post-resection spirometry and computed tomography were performed. Three-dimensional reconstructions were performed by using computed tomography images to calculate the volumes of the resected, remaining, and nonoperative side regions. Based on the resected region volume, patients were divided into the higher and lower volume segmentectomy groups. Changes in lung volume and pulmonary function before and after the surgery were comparatively analyzed. RESULTS: The median percentage of resected lung volume was 10.9%, forming the basis for categorizing patients into the two groups. Postoperative forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) ratios to preoperative measurements in both groups did not differ significantly (FEV1, p = 0.254; FVC, p = 0.777). Postoperative FEV1 and FVC ratios to their predicted postoperative values were significantly higher in the higher volume segmentectomy group than in the lower volume segmentectomy group (FEV1, p = 0003; FVC, p < 0.001). The higher volume segmentectomy group showed significantly greater post-to-preoperative lung volume ratio in overall, contralateral, ipsilateral, residual lobe and residual segment than the lower volume segmentectomy group. CONCLUSIONS: Postoperative respiratory function did not differ significantly between the higher- and lower-volume segmentectomy groups, indicating improved respiratory function because of substantial postoperative residual lung expansion. Our findings would aid in determining the extent of resection during segmentectomy.
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Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.
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Carcinoma Adenoide Cístico , Carcinoma Mucoepidermoide , Neoplasias Pulmonares , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Neoplasias Pulmonares/patologia , Glândulas Salivares/patologia , Pulmão/patologia , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/cirurgiaRESUMO
The Lung Cancer Surgical Study Group (LCSSG) of the Japan Clinical Oncology Group (JCOG) was organized in 1986 and initially included 26 collaborative institutions, which has increased to 52 institutions currently. JCOG-LCSSG includes thoracic surgeons, medical oncologists, pathologists, and radiotherapists. In the early period, the JCOG-LCSSG mainly focused on combined modality therapies for lung cancer. Since the 2000s, the JCOG-LCSSG has investigated adequate modes of surgical resection for small-sized and peripheral non-small cell lung cancer and based on the radiological findings of whole tumor size and ground-glass opacity. Trials, such as JCOG0802, JCOG0804, and JCOG1211, have shown the appropriateness of sublobar resection, which has significantly influenced routine clinical practice. With the introduction of targeted therapy and immunotherapy, treatment strategies for lung cancer have changed significantly. Additionally, with the increasing aging population and medical costs, tailored medicine is strongly recommended to address medical issues. To ensure comprehensive treatment, strategies, including surgical and nonsurgical approaches, should be developed. Currently, the JCOG-LCSSG has conducted numerous clinical trials to adjust the diversity of lung cancer treatment strategies. This review highlights recent advancements in the surgical field, current status, and future direction of the JCOG-LCSSG.
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The perioperative treatments for non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the survival of patients with NSCLC who underwent surgical resection alone has been dismal except in stage IA patients. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant cisplatin-based chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy has been considered to be an appropriate treatment approach for locally advanced NSCLC patients. When nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy has conferred an overall survival benefit. More recently, neoadjuvant and/or adjuvant use of immunotherapy adding to the cisplatin-based chemotherapy has been revealed to improve survival of the patients with locally advanced NSCLC in many large-scale clinical trials; although, optimal treatment strategies are still evolving.
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BACKGROUND: The JCOG0804/WJOG4507L single-arm confirmatory trial indicated a satisfactory 10-year prognosis for patients who underwent limited resection for radiologically less-invasive lung cancer. However, only one prospective trial has reported a 10-year prognosis. METHODS: We conducted a multicenter prospective study coordinated by the National Cancer Center Hospital East and Kanagawa Cancer Center. We analyzed the long-term prognosis of 100 patients who underwent limited resection of a radiologically less-invasive lung cancer in the peripheral lung field. We defined radiologically less-invasive lung cancer as lung adenocarcinoma with a maximum tumor diameter of ≤2 cm, tumor disappearance ratio of ≥0.5 and cN0. The primary endpoint was the 10-year local recurrence-free survival. RESULTS: Our patients, with a median age of 62 years, included 39 males. A total of 58 patients were non-smokers; 87 had undergone wide wedge resection and 9 underwent segmentectomy. A total of four cases were converted to lobectomy because of the presence of poorly differentiated components in the frozen specimen or insufficient margin with segmentectomy. The median follow-up duration was 120.9 months. The 10-year recurrence-free survival and overall survival rates of patients with lung cancer were both 96.0%. Following the 10-year long-term follow-up, two patients experienced recurrences at resection ends after wedge resection. CONCLUSIONS: Limited resection imparted a satisfactory prognosis for patients with radiologically less-invasive lung cancer, except two cases of local recurrence >5 years after surgery. These findings suggest that patients with this condition who underwent limited resection may require continued follow-up >5 years after surgery.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Prospectivos , Seguimentos , Pneumonectomia , Pulmão/patologia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: The developments of perioperative treatments for patients with high-risk early-stage lung cancer are ongoing, however, real-world data and evidence of clinical significance of genetic aberration are lacking in this population. This study aimed to identify patients with early-stage lung adenocarcinoma at high risk for recurrence based on pathological indicators of poor prognosis, including the International Association for the Study of Lung Cancer (IASLC) grade, and elucidate the prognostic impact of epidermal growth factor receptor mutation (EGFRm) status. METHODS: This retrospective study included 494 consecutive patients who underwent complete resection for pathological stage I lung adenocarcinoma between 2011 and 2016. The patients were evaluated for EGFRm and IASLC grade. Multivariable analysis was used to identify pathological factors for poor prognosis associated with recurrence-free survival (RFS) and overall survival (OS). Patients with any one of these factors were classified into the high-risk group. The prognostic impact of EGFRm was evaluated using RFS, OS, and cumulative recurrence proportion. RESULTS: Multivariable analysis for RFS and OS revealed that IASLC grade 3, pathological invasion size>2 cm, and presence of lymphovascular invasion were indicators of poor prognosis. EGFRm-positive patients had a higher incidence of all types of recurrence, including central nervous system (CNS) metastasis and distant metastasis in high-risk group, but not in low-risk group. CONCLUSIONS: This study provides evidence that patients with EGFRm-positive stage I lung adenocarcinoma in the high-risk group have an increased risk of recurrence, including CNS metastasis. These findings highlight the need for development of adjuvant treatment in this population.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Prognóstico , Mutação , Receptores ErbB/genéticaRESUMO
PURPOSE: Among non-small cell lung cancers (NSCLC), 5 years is a benchmark in cancer control and treatment, but a certain percentage of cases recur after 5 years. The long-term post-recurrence outcomes remain controversial. To examine the accurate prognostic factors associated with survival and cancer recurrence among 5-year survivors, a landmark analysis that considered competing risks was performed. METHODS: Complete resection of NSCLC was performed in 2482 patients between January 2003 and December 2015. A total of 1431 patients were 5-year survivors without recurrence. A landmark time analysis was applied to the overall survival (OS) and recurrence-free survival (RFS) from 5 years after surgery, and the findings were calculated using the Kaplan-Meier method. The cumulative incidence of cause-specific death and recurrence was estimated using the cumulative incidence function, while carefully considering the competing risks. RESULTS: Postoperative recurrence was detected in 732 patients, of whom 68 (9.3%) had recurrence after 5 years. The median follow-up period was 8.2 years. In the competing risk analysis, the independent poor prognostic factors associated with cause-specific death were age ≥ 75 years, lymph node metastasis and pleural invasion. CONCLUSIONS: Patients requiring a follow-up for > 5 years were aged ≥ 75 years and had either lymph node metastasis or pleural invasion.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Recidiva Local de Neoplasia , Pneumonectomia , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Idoso , Pneumonectomia/métodos , Masculino , Feminino , Fatores de Tempo , Recidiva Local de Neoplasia/epidemiologia , Pessoa de Meia-Idade , Seguimentos , Fatores Etários , Metástase Linfática , Resultado do Tratamento , Prognóstico , Risco , Taxa de Sobrevida , Sobreviventes , Idoso de 80 Anos ou mais , Invasividade Neoplásica , Fatores de Risco , Pleura/cirurgia , Pleura/patologia , AdultoRESUMO
Dirty necrosis (DN) is a form of tumor necrosis (TN) with prominent neutrophil infiltration and cell detritus in the necrotic foci. This study aimed to characterize the clinicopathological features of DN in metastatic lung cancers of the colon and rectum (MLCRs). A total of 227 patients who underwent pulmonary metastasectomy and complete resection for MLCR were included in this study. TN was evaluated using digitally scanned resection specimens. These slides were immunostained for biomarkers of NETosis (citrullinated histone H3 [citH3] and myeloperoxidase [MPO]), and the area positive for citH3 and MPO was further quantified. TN was observed in 216 cases (95.2%), and 54 (25.0%) of these cases had DN. The presence of TN was not associated with a worse prognosis; however, patients with DN had a significantly shorter overall survival than those without DN (p < 0.01). Furthermore, the presence of DN was a poor prognostic factor in both the univariate and multivariate analyses. Immunohistochemical analysis revealed that the percentage of citH3-positive and MPO-positive areas in the DN-positive cases was significantly higher than that in the DN-negative cases (p < 0.01 and p < 0.01, respectively). In surgically resected MLCR, DN is the characteristic TN subtype associated with poor prognosis and neutrophil extracellular traps (NETs).
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Neoplasias Pulmonares , Reto , Humanos , Prognóstico , Reto/patologia , Histonas , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Colo/patologia , Necrose , Neutrófilos/patologiaRESUMO
A novel histologic grading system for invasive lung adenocarcinomas (LUAD) has been newly proposed and adopted by the World Health Organization (WHO) classification. We aimed to evaluate the concordance of newly established grades between preoperative biopsy and surgically resected LUAD samples. Additionally, factors affecting the concordance rate and its prognostic impact were also analyzed. In this study, surgically resected specimens of 222 patients with invasive LUAD and their preoperative biopsies collected between January 2013 and December 2020 were used. We determined the histologic subtypes of preoperative biopsy and surgically resected specimens and classified them separately according to the novel WHO grading system. The overall concordance rate of the novel WHO grades between preoperative biopsy and surgically resected samples was 81.5%, which was higher than that of the predominant subtype. When stratified by grades, the concordance rate of grades 1 (well-differentiated, 84.2%) and 3 (poorly differentiated, 89.1%) was found to be superior compared to grade 2 (moderately differentiated, 66.2%). Overall, the concordance rate was not significantly different from biopsy characteristics, including the number of biopsy samples, biopsy sample size, and tumor area size. On the other hand, the concordance rate of grades 1 and 2 was significantly higher in tumors with smaller invasive diameters, and that of grade 3 was significantly higher in tumors with larger invasive diameters. Preoperative biopsy specimens can predict the novel WHO grades, especially grades 1 and 3 of surgically resected specimens, more accurately than the former grading system, regardless of preoperative biopsy or clinicopathologic characteristics.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Biópsia , Prognóstico , Neoplasias Pulmonares/cirurgiaRESUMO
Alveolar macrophages (AMs) are resident macrophages in the lungs; however, whether the number of AMs plays a role in the lung neuroendocrine tumor (NET) prognosis remains unclear. We counted the number of AMs located around the tumor (peritumoral alveolar macrophages [pAMs]) and the number of AMs located apart from the tumor (distant macrophages; dAMs). In 73 cases of neuroendocrine carcinoma (NEC: small cell lung carcinoma and large cell neuroendocrine carcinoma), the group that contained higher pAMs (≥86/µm2 ) revealed shorter recurrent-free survival (RFS) than those with lower pAMs (<86/µm2 ) (p = 0.005). Bivariate analysis showed that the number of pAMs was an independent predictor of a poor RFS. In contrast, in the carcinoid tumor cohort (n = 29), there was no statistically significant correlation between the two groups with high and low numbers of pAMs in RFS (p = 0.113). Furthermore, we examined the correlation between genomic alterations and the number of pAMs in NEC, but no significant correlation was observed. In conclusion, the number of pAMs is a prognostic factor for NEC in the lung and pAMs may contribute to tumor progression within the peritumoral microenvironment.
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PURPOSE: This study investigated the prognostic factors of thymic epithelial tumors (TETs) to identify patients who require multidisciplinary treatment and improve the TET prognosis. METHODS: We retrospectively reviewed the data of 268 TET patients. Prognostic variables for the overall survival (OS) were analyzed in all TET stages (n = 268), and the recurrence-free survival (RFS) was analyzed in patients who achieved complete resection (n = 164). RESULTS: The median follow-up period was 7 years; thymic carcinomas (TCs) and advanced stages of tumor, node, and metastasis (TNM) classification had the worse prognosis according to a Kaplan-Meier analysis. The cut-off value of the tumor size to predict the OS and RFS was determined using modified Harrell's c-index calculated by a Cox regression analysis of the OS. Regarding the OS, a multivariate analysis revealed that age > 70 years old (p = 0.011), tumor size > 5 cm (p < 0.001), and TCs (p = 0.002) were significant prognostic factors aside from the TNM stage (p < 0.001). Regarding the RFS, tumor size > 5 cm was the only significant prognostic factor in the multivariate analysis (p = 0.002) aside from the TNM stage (p = 0.008). CONCLUSIONS: Tumor size > 5 cm was shown to be a prognostic predictor in addition to the WHO and TNM classifications. Therefore, multidisciplinary treatment should be developed for TET patients with poor prognostic factors, specifically tumor size.
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Neoplasias Epiteliais e Glandulares , Timoma , Neoplasias do Timo , Humanos , Idoso , Prognóstico , Estudos Retrospectivos , Timoma/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Epiteliais e Glandulares/patologia , Estadiamento de NeoplasiasRESUMO
Positron emission tomography is a useful technique for diagnosing lymph node (LN) metastasis. This study aimed to elucidate the association between fluorodeoxyglucose accumulation and the microenvironment in metastatic LNs in lung adenocarcinoma. We retrospectively analyzed 62 patients with surgically resected pathological N2 lung adenocarcinoma who underwent preoperative PET. The maximum standardized uptake value (SUVmax ) in the metastatic LNs was measured. Lymph node specimens were immunohistochemically analyzed for CD8+ , FoxP3+ , and CD79a+ lymphocytes, CD204+ tumor-associated macrophages (TAMs), and alpha-smooth muscle actin-positive cancer-associated fibroblasts (αSMA+ CAFs). We compared the clinicopathologic and immunohistochemical characteristics between two groups with high and low LN SUVmax . Using novel 3D hybrid spheroid models, we investigated the change in invasiveness of cancer cells in the presence of CAFs. In the multivariate analyses, LN SUVmax was an independent prognostic factor. The overall survival in the LN SUVmax high group was significantly worse than in the low group (P = .034). In the LN SUVmax high group, metastatic cancer cell invasion of extranodal tissue was more frequent (P = .005) and the number of CD204+ TAMs and αSMA+ CAFs in metastatic LNs was significantly higher than in the low group (P < .001 and P = .002, respectively). Hybrid spheroid models revealed that cancer cells coexisting with CAFs were more invasive than those without CAFs. Our results indicated a strong association between LN SUVmax and poor prognosis in patients with N2 lung adenocarcinoma. Moreover, LN SUVmax was suggested to be associated with the presence of tumor-promoting stromal cells in metastatic LNs.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Estudos Retrospectivos , Microambiente TumoralRESUMO
Extratumoral lymphatic permeation (ly-ext) has been reported as an independent poor prognostic factor for lung adenocarcinoma, but whether or not the number of ly-ext foci is associated with prognosis and its relationship to the immune microenvironment is unclear. We counted the number of ly-ext foci on pathological slides from patients with completely resected lung adenocarcinoma with ly-ext, and divided them into two groups: a group with a high number of ly-ext foci (ly-ext high) and one with a low number of ly-ext foci (ly-ext low). Among the patients with ly-ext, only a high number of ly-ext foci was an independent poor prognostic factor. The 3-year recurrence-free survival (RFS) rate of the ly-ext high group was significantly lower than that of the ly-ext low group (14.7% vs. 50.0%, P < 0.01). Then, we analyzed the immune microenvironment of pT1 lung adenocarcinoma with ly-ext (13 cases of ly-ext high and 11 cases of ly-ext low tumor) by immunohistochemistry using antibodies for stem cell markers (aldehyde dehydrogenase 1 A1 and CD44), tumor-promoting mucin (MUC1), tumor-infiltrating lymphocytes (CD4, CD8, FOXP3, and CD79a), and tumor-associated macrophages (CD204). The number of CD8+ TILs within the primary lesion was significantly lower and the number of FOXP3+ TILs within the primary lesion was significantly higher in the ly-ext high group (P < 0.05 and P < 0.01, respectively). Our results indicated that a high number of ly-ext foci was an independent poor prognostic factor. Moreover, tumors with high numbers of ly-ext foci had a more immunosuppressive microenvironment.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Fatores de Transcrição Forkhead , Humanos , Linfócitos do Interstício Tumoral , Prognóstico , Microambiente TumoralRESUMO
A cyclic hexapeptide, RA-VII isolated from the Rubiaceae family of plants, has high cytotoxic activity. Although RA-VII has been shown to inhibit protein synthesis in eukaryotic cells, the molecular mode of its action is not clear. Here we investigate the mechanism of the RAVII action on the translation apparatus. Biochemical functional assays showed that RA-VII inhibits poly(U)-dependent polyphenylalanine synthesis in the presence of animal elongation factors eEF1A and eEF2. Furthermore, RAVII prevented eEF2/ribosome-dependent GTPase activity, but not eEF-1A/ribosome-dependent activity. A filter binding assay demonstrated that RA-VII markedly enhances the binding affinity of eEF2 for GTP, but not for GDP, and prevents exchange of GTP in the eEF2-GTP complex, even after addition of a large excess of GTP/GDP. Limited proteolysis experiments indicated that RA-VII prevents the digestion of eEF2 in the presence of either GTP or GMPPCP, but not with GDP. Further footprint analysis and a translocation assay showed that the eEF2â¢GMPPNPâ¢RA-VII complex binds to the conserved rRNA regions at the factor-binding center of the ribosome and retains the ability to translocate the A site-bound tRNA to the P-site. These results suggest that RA-VII tightly stabilizes the GTPâ¢eEF2 complex structure, which is able to bind to the ribosomal functional site, but seems to suppress normal turnover of eEF2 after translocation. The properties of RA-VII make it a novel ligand for probing the action of eEF2 in the process of translocation on the ribosome.
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Eucariotos , Células Eucarióticas , Animais , Eucariotos/metabolismo , Células Eucarióticas/metabolismo , Guanosina Trifosfato/metabolismo , Fator 2 de Elongação de Peptídeos/metabolismo , Peptídeos CíclicosRESUMO
Among early-stage lung cancers that show ground-glass nodules on chest computed tomography, the lung cancer surgical study group of the Japan Clinical Oncology Group previously reported that nodules of ≤2 cm with a consolidation/tumor ratio of ≤0.25 were considered radiologically non-invasive cancers with a low risk of metastasis. However, there is no consensus based on high-quality evidence about the optimal timing of surgical intervention for radiologically non-invasive cancers. In June 2020, we launched a multi-institutional, single-arm confirmatory trial to evaluate the efficacy and safety of watchful waiting for patients with radiologically non-invasive lung cancer. It is planned that a total of 720 patients will be enrolled from 49 institutes over a 5-year period. The primary endpoint is 10-year overall survival (OS). The secondary endpoints are 5-year OS, operation-free survival, proportion of extensive lung resection, proportion of unresectable progression, lung cancer-specific survival and adverse events.
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Neoplasias Pulmonares , Conduta Expectante , Humanos , Japão , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Estadiamento de NeoplasiasRESUMO
Endogenous small interfering RNAs (endo-siRNAs) in Drosophila are processed by Dicer-2 (Dcr-2) and loaded onto Ago2 by the Dcr-2/R2D2 heterodimer. In r2d2 mutants, the level of endo-siRNAs is unchanged, but endo-siRNAs are misloaded onto Ago1. However, the mechanism underlying the control of endo-siRNA sorting by R2D2 remains unknown. Here, we show that R2D2 controls endo-siRNA sorting by localizing Dcr-2, and presumably endo-siRNA duplexes, to cytoplasmic foci, D2 bodies. Ago2, but not Ago1, localized to D2 bodies. dsRNA-binding-deficient mutant, but not wild-type, R2D2 failed to localize D2 bodies and caused endo-siRNA misdirection to Ago1 in R2D2-depleted cells. However, R2D2 was dispensable for sorting miRNAs and exogenous siRNAs onto Ago1 and Ago2, respectively, in vivo. Endo- and exo-siRNA guide selection also occurred R2D2 independently. The functions of R2D2 are required to avoid endo-siRNA misdirection to Ago1, because Ago1 is capable of loading incompletely complementary miRNA duplexes and endo-siRNA duplexes.
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Grânulos Citoplasmáticos/metabolismo , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/fisiologia , Animais , Proteínas Argonautas/metabolismo , Linhagem Celular , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Feminino , Oócitos/metabolismo , Domínios e Motivos de Interação entre Proteínas , Transporte Proteico , RNA Helicases/química , RNA Helicases/metabolismo , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Ribonuclease III/química , Ribonuclease III/metabolismoRESUMO
This study aims to determine the correlation between the percent viable tumor cells (%VTC) and the tumor microenvironment in resected non-small cell lung cancer after induction therapy. We enrolled 72 patients with non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT) or chemotherapy (CT) prior to surgery. The ratio of the area of viable tumor cells to the total tumor area was calculated to obtain the %VTC. We also examined the number of CD4 (+), CD8 (+), CD20 (+) and FOXP3 (+) tumor-infiltrating lymphocytes (TILs), podoplanin (PDPN) (+) cancer-associated fibroblasts (CAFs), and CD204 (+) tumor-associated macrophages (TAMs) by immunohistochemistry (IHC). In the CRT group (n = 37), the tumors had significantly lower %VTC than the CT group (n = 35) (P < 0.001). In both of the CT group and CRT group, the %VTC showed a significant positive correlation with the number of CD204 (+)-TAMs (P = 0.014 and 0.005, respectively). Only in the CRT group, a higher number of CD204 (+) TAMs was associated with a shorter overall survival (OS) (P = 0.007) and recurrence-free survival (RFS) (P = 0.015). In the CRT group, the number of CD204 (+) TAMs is associated with %VTC and prognosis, suggesting that these cells may have tumor-promoting effects on the residual lung cancer in specific microenvironments after CRT.
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Carcinoma Pulmonar de Células não Pequenas , Quimioterapia de Indução , Microambiente Tumoral , Biomarcadores Tumorais/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pulmão/patologia , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptores Depuradores Classe A/metabolismo , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologiaRESUMO
PURPOSE: To clarify the safety and effectiveness of continuing aspirin during the perioperative period of lung resection. METHODS: We analyzed, retrospectively, consecutive patients who underwent lung resection between 2008 and 2017. To investigate the safety of aspirin continuation, patients who continued taking aspirin perioperatively (Group C) were matched to other patients (Group O), using a propensity score, and bleeding outcomes were compared. To assess the effect of aspirin interruption, Group C was matched to a group of patients whose aspirin regimen was interrupted (Group I), and the postoperative complications related to thromboembolism were compared. RESULTS: Among 3393 patients, 52 continued on aspirin (Group C) perioperatively, whereas 184 had their aspirin discontinued (Group I). Comparing the matched cohorts extracted from Group C and Group O (n = 45), there were no significant differences in bleeding outcomes. Comparing the matched cohorts extracted from Group C and Group I (n = 40), group C had fewer postoperative complications related to thromboembolism (0% vs. 7.5%, p = 0.039). CONCLUSION: Bleeding complications did not increase by continuing aspirin, but thromboembolic complications increased when the aspirin regimen was interrupted during the perioperative period of lung resection. Thus, in the absence of a prohibitive bleeding risk, the continuation of aspirin during the perioperative period of lung resection appears to be desirable.
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Aspirina/administração & dosagem , Pulmão/cirurgia , Pneumonectomia , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Criança , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Segurança , Tromboembolia/epidemiologia , Resultado do Tratamento , Suspensão de Tratamento , Adulto JovemRESUMO
PURPOSE: Non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) have a poor prognosis. The present study evaluated the prognostic impact of home oxygen therapy (HOT) in NSCLC patients with ILD. METHODS: Overall, 3099 consecutive patients underwent complete resection of stage IA to IIIA NSCLC at our institution between 2002 and 2016. ILD was diagnosed and categorized based on high-resolution computed tomography. The criteria for HOT included less than 90% resting oxygen saturation in the peripheral arteries and severe exertional dyspnea. We retrospectively compared the overall survival between ILD patients with and without HOT. RESULTS: ILD was observed in 150 (5%) patients. Seventeen (11%) patients needed HOT at discharge. The incidences of usual interstitial pneumonia (UIP) pattern (p = 0.03) and blood loss (p < 0.01) were significantly higher in the patients requiring HOT than in those without HOT. Significantly more patients developed complications (p = 0.04) in the HOT group than in the non-HOT group, with three (18%) having acute exacerbations. The 3-year overall survival rate was significantly lower in the HOT patients than in those without HOT (28% vs. 63%, p = 0.03). CONCLUSIONS: Patients requiring postoperative HOT showed a significantly poorer prognosis after complete resection than those without HOT. Therefore, the indication for surgery should be investigated cautiously in order to prevent the need for postoperative HOT.
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Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/terapia , Oxigenoterapia Hiperbárica/mortalidade , Doenças Pulmonares Intersticiais/etiologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/terapia , Pneumonectomia , Cuidados Pós-Operatórios , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/complicações , Feminino , Humanos , Oxigenoterapia Hiperbárica/efeitos adversos , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: To investigate the prognostic implications and pathological features of clinical stage I lung adenocarcinoma with ground-glass opacity (GGO) on computed tomography (CT). METHODS: The subjects of this retrospective study were 1228 patients with lung adenocarcinoma classified as clinical stage I, who underwent complete resection by lobectomy. The patients were divided into four groups based on the presence and proportion of GGO according to the consolidation-to-tumor ratio (CTR); A, CTR ≤ 0.5; B, 0.5 < CTR ≤ 0.75; C, 0.75 < CTR ≤ 1.0 with GGO; D, without GGO (pure-solid). We compared overall survival, pathological findings (N/ly/v/STAS), and histological subtypes within each clinical stage among the four groups. RESULTS: We found no significant differences among tumors with GGO (groups A, B and C) for prognosis or pathological findings in all the clinical stages. The prognoses of groups A, B and C were significantly better than that of group D for patients with clinical stages IA2-IB disease. Tumors without GGO on CT had a significantly larger number of positive N, ly, v and STAS in almost all stages than tumors with GGO on CT. Tumors without GGO on CT had significantly more solid predominant and less lepidic predominant adenocarcinoma. CONCLUSION: Not the proportion of GGO, but its presence on CT, as well as the size of the solid component, were correlated significantly with pathological characteristics and survival.