Purpose
The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).

Patients and Methods
In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs).

Results
A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain.

Conclusion
Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America

List of Boxes. List of Tables and Figure. Preface. Abbreviations. Introduction. 1. Capitalism and the Capitalist Type of State. 2. The Keynesian Welfare National State. 3. The Schumpeterian Competition State. 4. Social Reproduction and the Workfare State. 5. The Political Economy of State Rescaling. 6. From Mixed Economy to Metagovernance. 7. Towards Schumpeterian Workfare Postnational Regimes?. Notes. References. Index.

The Future of the Capitalist State.

El articulo ofreece una presentacion comentada del Informe presentado a la
UNESCO por la Comision lnternacional sobre la Educacion para el siglo XXI,
presidida por Jacques Delors. Se trata de una obra de obligada lrctura para aquellos
que ejercen su labor docente o se preparan para ella a las puertas del proximo
milenio.

La educación encierra un tesoro

This guideline is based on a comprehensive review of the literature on pulmonary nodules and expert opinion. Although the management pathway for the majority of nodules detected is straightforward it is sometimes more complex and this is helped by the inclusion of detailed and specific recommendations and the 4 management algorithms below. The Guideline Development Group (GDG) wanted to highlight the new research evidence which has led to significant changes in management recommendations from previously published guidelines. These include the use of two malignancy prediction calculators (section ‘Initial assessment of the probability of malignancy in pulmonary nodules’, algorithm 1) to better characterise risk of malignancy. There are recommendations for a higher nodule size threshold for follow-up (≥5 mm or ≥80 mm3) and a reduction of the follow-up period to 1 year for solid pulmonary nodules; both of these will reduce the number of follow-up CT scans (sections ‘Initial assessment of the probability of malignancy in pulmonary nodules’ and ‘Imaging follow-up’, algorithms 1 and 2). Volumetry is recommended as the preferred measurement method and there are recommendations for the management of nodules with extended volume doubling times (section ‘Imaging follow-up’, algorithm 2). Acknowledging the good prognosis of sub-solid nodules (SSNs), there are recommendations for less aggressive options for their management (section ‘Management of SSNs’, algorithm 3).

The guidelines provide more clarity in the use of further imaging, with ordinal scale reporting for PET-CT recommended to facilitate incorporation into risk models (section ‘Further imaging in management of pulmonary nodules’) and more clarity about the place of biopsy (section ‘Non-imaging tests and non-surgical biopsy’, algorithm 4). There are recommendations for the threshold for treatment without histological confirmation (sections ‘Surgical excision biopsy’ and ‘Non-surgical treatment without pathological confirmation of malignancy’, algorithm 4).

Finally, and possibly most importantly, there are evidence-based recommendations about the information that people …

https://thorax.bmj.com/content/thoraxjnl/70/Suppl_2/ii1.full.pdf

British Thoracic Society guidelines for the investigation and management of pulmonary nodules: accredited by NICE

https://www.annalsthoracicsurgery.org/article/S0003-4975(13)01111-9/pdf

Efficacy and complications of computed tomography-guided hook wire localization.

Purpose: We retrospectively investigated the pathological diagnoses of pulmonary lesions presenting as pure ground-glass opacities (GGOs) to evaluate the risk of invasive malignancy. Methods: We examined 191 GGO lesions, including 114 pure GGO and 77 mixed lesions, in 160 patients who underwent resection between January 2008 and December 2010. Results: Of the 114 pure GGO lesions, 14 (12%) were diagnosed as invasive lung cancer and 16 (14%) as minimally invasive adenocarcinoma. Twenty-one lesions exhibited pleural indentation on high-resolution computed tomography (HRCT), and 5 of these were diagnosed as invasive cancer, indicating an invasive tendency of pure GGO lesions with pleural indentation (odds ratio, 2.64). Of 14 pure GGO lesions positive on positron emission tomography (PET), 8 were diagnosed as invasive lung cancer, indicating an invasive tendency of pure GGO lesions with PET positivity (odds ratio, 16.0; p <0.001; sensitivity, 67%; specificity, 89%). Conclusion: Invasive lung cancer accounted for 12% of the pure GGO lesions. Pure GGO lesions should be carefully monitored by periodic chest computed tomography, and surgical resection is recommended when they exhibit pleural indentation on HRCT or positivity on PET.

https://www.jstage.jst.go.jp/article/atcs/20/5/20_oa.13-00005/_pdf

Invasiveness and Malignant Potential of Pulmonary Lesions Presenting as Pure Ground-Glass Opacities

To diagnose small cell lung carcinoma (SCLC), neuroendocrine (NE) phenotype markers such as chromogranin A, synaptophysin, and CD56 are helpful. However, because they are dispensable, SCLCs occur without apparent NE phenotypes. Insulinoma-associated protein 1 (INSM1) is a transcription factor for NE differentiation and has emerged as a single practical marker for SCLC. Using the surgical samples of 141 pulmonary NE tumors (78 SCLCs, 44 large cell NE carcinomas, and 19 carcinoids), and 246 non-NE carcinomas, we examined the immunohistochemical expression and prognostic relevance of INSM1 in association with NE phenotype markers. We evaluated its sensitivity and specificity for SCLC diagnosis, as well as its usefulness to diagnose SCLC without NE marker expression and to estimate the prognosis. INSM1 was expressed in SCLCs (92%, 72/78), large cell NE carcinomas (68%, 30/44), and carcinoids (95%, 18/19). In addition, among SCLCs with no expression of NE phenotype markers (n=12), 9 (75%) were positive for INSM1. These data suggest the superiority of INSM1 to the phenotype markers. Only 7% of adenocarcinomas (9/134) and 4% of squamous cell carcinomas (4/112) were positive for INSM1. SCLC with low-INSM1 expression (n=28) had a significantly better prognosis (P=0.040) than the high-INSM1 group (n=50). Our study revealed that INSM1 is highly sensitive and specific to detect SCLC and can estimate prognosis. INSM1 will be a promising marker for SCLC.

Insulinoma-associated Protein 1 (INSM1) Is a Better Marker for the Diagnosis and Prognosis Estimation of Small Cell Lung Carcinoma Than Neuroendocrine Phenotype Markers Such as Chromogranin A, Synaptophysin, and CD56.

The purpose of this retrospective study was to review our experience with video-assisted thoracic surgery (VATS) for pulmonary aspergilloma. The patients (n=20) were aged 62+/-12 years, and eight (40%) were aged 70 years or more. The disease types were simple aspergilloma (SA) in six patients and complex aspergilloma (CA) in 14. The surgical procedures performed were lobectomy in 14 patients, segmentectomy in two, and wedge resection in four. The operation time was shorter (143+/-69 min vs. 216+/-85 min; P=0.08) and the blood loss was less (10+/-17 ml vs. 307+/-346 ml; P<0.01) for patients with SA than those with CA. Postoperative death occurred in one patient with CA who developed a bronchial stump fistula (30-day mortality; 5.0%). During follow-up, three patients died from other non-disease-related causes, and the remaining 17 patients survived without recurrence. The 5-year survival rate was 89%. In suitable cases, VATS for pulmonary aspergilloma may not be inferior to open surgery with regard to safety and efficacy. In particular, SA is considered to be a good indication for VATS.

Junji Ichinose

Papers

Efficacy and complications of computed tomography-guided hook wire localization.

Invasiveness and Malignant Potential of Pulmonary Lesions Presenting as Pure Ground-Glass Opacities

Insulinoma-associated Protein 1 (INSM1) Is a Better Marker for the Diagnosis and Prognosis Estimation of Small Cell Lung Carcinoma Than Neuroendocrine Phenotype Markers Such as Chromogranin A, Synaptophysin, and CD56.

Video-assisted thoracic surgery for pulmonary aspergilloma

Locoregional Control of Thoracoscopic Lobectomy With Selective Lymphadenectomy for Lung Cancer