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Histologic patterns and molecular characteristics of lung adenocarcinoma associated with clinical outcome.

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Histologic patterns and molecular characteristics of lung adenocarcinoma associated with clinical outcome.

Cancer. 2012 Jun 1;118(11):2889-99

Authors: Solis LM, Behrens C, Raso MG, Lin HY, Kadara H, Yuan P, Galindo H, Tang X, Lee JJ, Kalhor N, Wistuba II, Moran CA

Abstract
BACKGROUND: Lung adenocarcinoma is histologically heterogeneous and has 5 distinct histologic growth patterns: lepidic, acinar, papillary, micropapillary, and solid. To date, there is no consensus regarding the clinical utility of these patterns.
METHODS: The authors performed a detailed semiquantitative assessment of histologic patterns of 240 lung adenocarcinomas and determined the association with patients' clinicopathologic features, including recurrence-free survival (RFS) and overall survival (OS) rates. In a subset of tumors, expression levels of 2 prognostic molecular markers were evaluated: thyroid transcription factor-1 (TTF-1) (n = 218) and a panel of 5 proteins (referred as the FILM signature index) (n = 185).
RESULTS: Four mutually exclusive tumor histology pattern groups were identified: 1) any solid (38%), 2) any papillary but no solid (14%), 3) lepidic and acinar but no solid or papillary (30%), and 4) acinar only (18%). Patients in group 3 had a higher RFS rate than patients in group 1 (hazard ratio [HR], 0.4510; P = .0165) and group 2 (HR, 0.4253; P = .0425). Solid pattern tumors (group 1) were associated with a lower OS rate than nonsolid pattern tumors (all stages: HR; 1.665; P = .0144; stages I and II: HR, 2.157; P = .008). In the patients who had tumors with a nonsolid pattern, high TTF-1 expression was associated significantly with higher RFS (HR, 0.994; P = .0017) and OS (HR, 0.996; P = .0276) rates in all stages, and a high FILM signature index score was associated with lower RFS and OS rates in all stages (RFS: HR, 1.343; P = .0192; OS: HR, 1.371; P = .0156) and in stages I and II (RFS: HR, 1.419; P = .0095; OS: HR, 1.315; P = .0422).
CONCLUSIONS: The presence of a solid histologic pattern was identified as a marker of unfavorable prognosis in patients with primary lung adenocarcinoma. High TTF-1 expression and low FILM signature index scores were associated with a better prognosis for patients who had tumors with a nonsolid pattern.

PMID: 22020674 [PubMed - indexed for MEDLINE]

Deposition of small particles in the developing lung.

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Deposition of small particles in the developing lung.

Paediatr Respir Rev. 2012 Jun;13(2):73-8

Authors: Amirav I, Newhouse MT

Abstract
Infancy is a time of marked and rapid changes in respiratory tract development. Infants (0-1 year of age) and young children (1- 3 years of age) are a unique subpopulation with regard to therapeutic aerosols. Anatomical, physiological and emotional factors, peculiar to these age groups, present significant challenges for aerosol delivery to the respiratory tract. Most studies with inhaled corticosteroids (ICS) have administered aerosols with relatively large particles, frequently > 3 μm in mass median aerodynamic diameter (MMAD). These drugs were designed for use in adults and older children and were administered with masks which were frequently rejected by children under age 3-4 years. We review the reasons that large-particle aerosols are likely to be less effective in infants and young children. We suggest that the benefit of inhaled medications in this age group requires further evaluation to determine if better therapeutic outcomes might be achieved using smaller particles and more patient-friendly delivery systems.

PMID: 22475251 [PubMed - indexed for MEDLINE]

Beyond the guidelines: fatal and near-fatal asthma.

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Beyond the guidelines: fatal and near-fatal asthma.

Paediatr Respir Rev. 2012 Jun;13(2):106-11

Authors: Rubin BK, Pohanka V

Abstract
While asthma is extremely common, fatal and near fatal asthma is rare and often preventable if there is early recognition of symptom progression and appropriate intervention. In the past decade, asthma mortality has progressively declined in association with the widespread use of inhaled corticosteroids and asthma care plans. Management of life threatening asthma requires patient education to ensure the proper use of medications and to enable the patient to recognize when additional therapy for poorly controlled asthma is required. There is some evidence that suggests that the overly aggressive use of asthma medications when treating a severe exacerbation may contribute to morbidity. Because of the risks of air trapping and barotrauma associated with partial airway obstruction, it is best to avoid mechanical ventilation if possible but when this is used, low tidal volumes, longer exhalation times, and permissive hypercarbia can minimize these risks. There is the promise that a better understanding of asthma immunology and severe asthma "phenotypes" will lead to better prevention and therapy.

PMID: 22475257 [PubMed - indexed for MEDLINE]

Nutritional support in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

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Nutritional support in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Am J Clin Nutr. 2012 Jun;95(6):1385-95

Authors: Collins PF, Stratton RJ, Elia M

Abstract
BACKGROUND: The efficacy of nutritional support in the management of malnutrition in chronic obstructive pulmonary disease (COPD) is controversial. Previous meta-analyses, based on only cross-sectional analysis at the end of intervention trials, found no evidence of improved outcomes.
OBJECTIVE: The objective was to conduct a meta-analysis of randomized controlled trials (RCTs) to clarify the efficacy of nutritional support in improving intake, anthropometric measures, and grip strength in stable COPD.
DESIGN: Literature databases were searched to identify RCTs comparing nutritional support with controls in stable COPD.
RESULTS: Thirteen RCTs (n = 439) of nutritional support [dietary advice (1 RCT), oral nutritional supplements (ONS; 11 RCTs), and enteral tube feeding (1 RCT)] with a control comparison were identified. An analysis of the changes induced by nutritional support and those obtained only at the end of the intervention showed significantly greater increases in mean total protein and energy intakes with nutritional support of 14.8 g and 236 kcal daily. Meta-analyses also showed greater mean (±SE) improvements in favor of nutritional support for body weight (1.94 ± 0.26 kg, P < 0.001; 11 studies, n = 308) and grip strength (5.3%, P < 0.050; 4 studies, n = 156), which was not shown by ANOVA at the end of the intervention, largely because of bias associated with baseline imbalance between groups.
CONCLUSION: This systematic review and meta-analysis showed that nutritional support, mainly in the form of ONS, improves total intake, anthropometric measures, and grip strength in COPD. These results contrast with the results of previous analyses that were based on only cross-sectional measures at the end of intervention trials.

PMID: 22513295 [PubMed - indexed for MEDLINE]

Prognostic predictors in non-small cell lung cancer patients undergoing intentional segmentectomy.

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Prognostic predictors in non-small cell lung cancer patients undergoing intentional segmentectomy.

Ann Thorac Surg. 2012 Jun;93(6):1788-94

Authors: Koike T, Koike T, Yamato Y, Yoshiya K, Toyabe S

Abstract
BACKGROUND: Despite recent studies reporting on the results of prospective intentional sublobar resection for patients with small non-small cell lung cancer (NSCLC), few studies have investigated predictors for prognosis or recurrence exclusively in patients undergoing intentional sublobar resection.
METHODS: We retrospectively reviewed 223 patients with small (2 cm or less) peripheral NSCLC who underwent intentional segmentectomy at the Niigata Cancer Center Hospital between 1992 and 2009. The significant demographic, clinical, and pathologic factors identified with the log rank test in univariate analyses were analyzed with the Cox proportional hazards regression model to examine independent predictors for prognosis and recurrence in multivariate analysis.
RESULTS: The 5-year and 10-year overall survival rates were 89.6% and 81.0%, respectively, and the 5-year and 10-year recurrence-free probabilities were 91.1% and 91.1%, respectively. Eight patients had locoregional recurrence, and 12 had distant recurrence. Multivariate analyses revealed that age more than 70 years (hazard ratio [HR] 2.389), male (HR 2.750), more than 75% consolidation/tumor ratio on high-resolution computed tomography (HR 2.750), and lymphatic permeation (HR 5.618) were independent poor prognostic factors, and lymphatic permeation (HR 16.257) was an independent predictor for recurrence.
CONCLUSIONS: The factors related to upstaging on pathologic diagnosis were not identified as independent predictors; therefore, the current patient selection criterion seems reasonable. If lymphatic permeation is present on pathologic findings, careful follow-up is recommended. The predictors identified in this study will support assessment and interpretation of the results of ongoing prospective randomized trials of lobar versus sublobar resection in patients with small peripheral NSCLC.

PMID: 22560265 [PubMed - indexed for MEDLINE]

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