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Utility of Nuclear Grading System in Epithelioid Malignant Pleural Mesothelioma in Biopsy-heavy Setting: An External Validation Study of 563 Cases.

核分级系统在活检重型上皮样恶性胸膜间皮瘤中的效用: 563例外部验证研究。

  • 影响因子:6.06
  • DOI:10.1097/PAS.0000000000001416
  • 作者列表:"Zhang YZ","Brambilla C","Molyneaux PL","Rice A","Robertus JL","Jordan S","Lim E","Lang-Lazdunski L","Begum S","Dusmet M","Anikin V","Beddow E","Finch J","Asadi N","Popat S","Cookson WOC","Moffatt MF","Nicholson AG
  • 发表时间:2020-03-01
Abstract

:Nuclear grading systems for epithelioid malignant pleural mesothelioma (MPM) have been proposed but it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies only. The median number of sites sampled was 1, with a median maximum tissue dimension of 17 mm (biopsy) and 150 mm (resection). The median overall survival (OS) was 14.7 months. The frequencies of grade I, II, and III tumors were 31% (132/563), 52% (292/563), and 17% (94/563). Grade I tumors were associated with the most favorable median OS (24.7 mo) followed by grades II (12.7 mo) and III (7.2 mo). The 2-tier nuclear grade separated tumors into low grade (19.3 mo) and high grade (8.9 mo). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear grade, and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant growth pattern, necrosis, and atypical mitosis (all P<0.001 except 2-tier nuclear grade, P=0.001). In the scenario of a single- site biopsy with tissue dimension ≤10 mm, none but age (P=0.002) were independently predictive. Our data also suggested sampling 3 sites or a maximum tissue dimension of at least 20 mm from a single site is optimal for nuclear grade assessment. In conclusion our study confirmed the utility of nuclear grade in epithelioid MPM using a biopsy-heavy cohort provided the tissue sample met minimum dimensional criteria.

摘要

: 已经提出了上皮样恶性胸膜间皮瘤 (MPM) 的核分级系统,但仍不确定它们是否可以应用于活检重的环境。使用所提出的系统,我们进行了一项独立的外部验证研究,使用了2003年至563年间在我们机构诊断的2017例连续上皮样MPM病例,其中87% 的患者仅接受活检。取样的中位位点数为1,中位最大组织尺寸为17mm mm (活检) 和150  mm (切除)。中位总生存期 (OS) 为14.7个月。I、II和III级肿瘤的频率分别为31% (132/563) 、52% (292/563) 和17% (94/563)。I级肿瘤与最有利的中位OS (24.7 mo mo) 相关,其次是II级 (12.7 mo mo) 和III级 (7.2 mo mo)。2级核分级将肿瘤分为低级别 (19.3 mo mo) 和高级别 (8.9  mo)。在多变量分析中,3层核级、2层核级和有丝分裂-坏死评分独立于年龄、手术类型、实体优势生长模式、坏死和非典型有丝分裂预测OS (除2层核级外,所有P<0.001,P = 0.001)。在组织尺寸 ≤ 10  mm的单部位活检的情况下,除年龄 (P = 0.002) 外,无其他独立预测因素。我们的数据还表明,从单个部位取样3个部位或最大组织尺寸至少为20  mm是核级评估的最佳选择。总之,如果组织样本符合最小尺寸标准,我们的研究证实了使用活检重队列在上皮样MPM中核级的效用。

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影响因子:3.60
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DOI:10.1245/s10434-019-07409-5
作者列表:["Letica-Kriegel AS","Leinwand JC","Sonett JR","Gorenstein LA","Taub RN","Chabot JA","Kluger MD"]

METHODS:BACKGROUND:The most common sites of malignant mesothelioma are the pleura and peritoneum, but little is known about the incidence, prognosis, or treatment of patients with disease in both cavities. Previous series suggest that multimodality treatment improves overall survival for pleural or peritoneal disease, but studies typically exclude patients with disease in both cavities. Despite limitations, this investigation is the only study to broadly examine outcomes for patients with malignant mesothelioma in both the pleural and peritoneal cavities. METHODS:This study retrospectively examined 50 patients with both pleural and peritoneal mesothelioma treated with the intent to prolong survival. The primary end point was overall survival from the initial operative intervention. RESULTS:The median overall survival was 33.9 months from the initial intervention. Female gender and intraperitoneal dwell chemotherapy were independent predictors of overall survival. Within 1 year after the initial diagnosis, second-cavity disease was diagnosed in 52% of the patients. The median time to the second-cavity diagnosis for those with a diagnosis 1 year after the initial diagnosis was 30 months. CONCLUSIONS:Well-selected patients with both pleural and peritoneal mesothelioma have a survival benefit over palliative treatment that is comparable with that seen in single-cavity disease. The presence of disease in both cavities is not a contraindication to multimodality treatment aimed at prolonging survival, whether the disease is diagnosed synchronously or metachronously. Patients with an initial diagnosis of single cavity disease are at the highest risk for identification of second-cavity disease within the first year after diagnosis.

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影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32419
作者列表:["Milosevic V","Kopecka J","Salaroglio IC","Libener R","Napoli F","Izzo S","Orecchia S","Ananthanarayanan P","Bironzo P","Grosso F","Tabbò F","Comunanza V","Alexa-Stratulat T","Bussolino F","Righi L","Novello S","Scagliotti GV","Riganti C"]

METHODS::Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness-related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo-sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5-knocked-out (KO) IC clones were resensitized to the drugs in vitro and in patient-derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β-catenin/c-myc axis that also increased IL-8 and IL-1β production. IL-8 and IL-1β-KO IC clones reduced the c-myc-driven transcription of ABCB5 and reacquired chemosensitivity. ABCB5-KO clones had lower IL-8 and IL-1β secretion, and c-myc transcriptional activity, suggesting that either Wnt/GSK3β/β-catenin and IL-8/IL-1β signaling drive c-myc-mediated transcription of ABCB5. ABCB5 correlated with lower time-to-progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first-line chemotherapy in MPM patients.

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影响因子:2.09
发表时间:2020-01-01
DOI:10.1016/j.jiph.2019.05.013
作者列表:["Nishimura A","Yamaguchi H","Ito Y","Tokumoto S","Toyoshima D","Kasai M","Maruyama A"]

METHODS::Empyema necessitatis (EN) is a rare complication of empyema in which the pleural infection spreads outside the pleural space. Lower airway infections are common among children with cerebral palsy (CP). Although harmless to healthy individuals, Pseudomonas aeruginosa can cause invasive infections, including CP, in immunocompromised hosts. Mycobacterium tuberculosis and Actinomyces spp. have been reported as common causative organisms of EN. However, EN caused by P. aeruginosa has never been reported. We report the case of an 8-year-old girl with CP without tracheotomy who was admitted to our hospital with complaints of fever and increased epileptic seizures. First, she was diagnosed with pneumonia and treated with antibiotics. However, seven days after admission, a palpable mobile mass overlying the lower part of the shoulder blade was noticed. Enhanced magnetic resonance imaging revealed broad high signal area on T2-weighted and diffusion-weighted images, indicating empyema of the left lower lung that had penetrated the pleural wall and spread to the subcutaneous area of the left back. Thus, she was diagnosed with EN. Twelve days after admission, P. aeruginosa was detected from the pus culture. Patients with CP who have chronic lung diseases, such as pneumonia, atelectasis, or empyema, may need careful follow up.

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胸膜疾病方向

胸膜疾病包括原发于胸膜的疾病,主要指胸膜间皮瘤,也包括胸膜腔内的异常情况,如脓胸、 血胸、胸腔积液等。

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