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Development of a Novel Prognostic Risk Classification System for Malignant Pleural Mesothelioma.


  • 影响因子:3.66
  • DOI:10.1016/j.cllc.2019.08.003
  • 作者列表:"Doi H","Kuribayashi K","Kitajima K","Yamakado K","Kijima T
  • 发表时间:2020-01-01

INTRODUCTION:This study aimed to assess prognostic factors to better understand malignant pleural mesothelioma (MPM) and to develop a new classification protocol beyond the standard tumor node metastasis (TNM) staging system. MATERIALS AND METHODS:We retrospectively reviewed the data of 188 patients with MPM who had not undergone surgical resection. For each patient, we calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis (TLG) on pretreatment 18F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography. Using the Cox proportional hazards model, we evaluated the relationships among potential MPM predictors, including age, gender, performance status, histologic type, stage, possible serum markers, and volume-based positron emission tomography parameters, as well as overall survival. RESULTS:The median survival was 461 days, and the 1- and 2-year overall survival rates were 60.70% and 31.10%, respectively. Univariate and multivariate analyses revealed that the significant independent predictors of poor survival outcomes were the non-epithelioid histologic type, elevated serum lactate dehydrogenase levels, a neutrophil-to-lymphocyte ratio of ≥ 5.0, and a TLG of ≥ 525 g. We then used these results to develop a prognostic risk classification system. From the resulting survival curve, we found a significant difference among the 3 risk groups of independent variables. Moreover, there were significant differences between all pairs of 2 separated risk groups. CONCLUSIONS:Pathologic subtypes, serum lactate dehydrogenase, neutrophil-to-lymphocyte ratio, and TLG in 18F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography were independent and significant prognostic factors of MPM. Using this model, we created a new risk classification system that supplants the standard TNM staging protocol.


简介: 本研究旨在评估预后因素,以更好地了解恶性胸膜间皮瘤 (MPM),并开发超出标准肿瘤淋巴结转移 (TNM) 分期系统的新分类方案。 材料和方法: 我们回顾性分析了 188 例未接受手术切除的 MPM 患者的资料。对于每位患者,我们计算了治疗前 18f-氟-2-脱氧葡萄糖-正电子发射断层扫描/计算机断层扫描的最大标准化摄取值 (SUVmax) 、代谢性肿瘤体积和总病变糖酵解 (TLG)。使用 Cox 比例风险模型,我们评估了潜在 MPM 预测因子之间的关系,包括年龄,性别,性能状态,组织学类型,分期,可能的血清标志物, 和基于体积的正电子发射断层扫描参数,以及总生存期。 结果: 中位生存期为 461 天,1 年和 2 年总生存率分别为 60.70% 和 31.10%。单因素和多因素分析显示,非上皮样组织学类型、血清乳酸脱氢酶水平升高、中性粒细胞与淋巴细胞比值 ≥ 5.0 是不良生存预后的显著独立预测因素, 和 ≥ 525g 的 TLG。然后我们用这些结果开发了一个预后风险分类系统。从得到的生存曲线中,我们发现独立变量的 3 个风险组之间存在显著差异。此外,所有 2 对分离的风险组之间存在显著差异。 结论: 18f-氟-2-脱氧葡萄糖正电子发射断层扫描/计算机断层扫描的病理亚型、血清乳酸脱氢酶、中性粒细胞与淋巴细胞比值和 TLG 是 MPM 的独立和显著的预后因素。使用该模型,我们创建了一个新的风险分类系统,取代了标准的 TNM 分期方案。



作者列表:["De Cunto G","Brancaleone V","Riemma MA","Cerqua I","Vellecco V","Spaziano G","Cavarra E","Bartalesi B","D'Agostino B","Lungarella G","Cirino G","Lucattelli M","Roviezzo F"]

METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.

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作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

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作者列表:["Zaragosi LE","Deprez M","Barbry P"]

METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

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