Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.

https://www.bmj.com/content/bmj/340/bmj.c869.full.pdf

CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials

This document is an international evidence-based guideline on the diagnosis and management of idiopathic pulmonary fibrosis, and is a collaborative effort of the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. It represents the current state of knowledge regarding idiopathic pulmonary fibrosis (IPF), and contains sections on definition and epidemiology, risk factors, diagnosis, natural history, staging and prognosis, treatment, and monitoring disease course. For the diagnosis and treatment sections, pragmatic GRADE evidence-based methodology was applied in a question-based format. For each diagnosis and treatment question, the committee graded the quality of the evidence available (high, moderate, low, or very low), and made a recommendation (yes or no, strong or weak). Recommendations were based on majority vote. It is emphasized that clinicians must spend adequate time with patients to discuss patients' values and preferences and decide on the appropriate course of action.

An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-Based Guidelines for Diagnosis and Management

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

Summary Background Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. Methods We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m 2 on day 1 plus docetaxel (75 mg/m 2 on day 1) or gemcitabine (1250 mg/m 2 on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m 2 or AUC 5 with gemcitabine 1000 mg/m 2 ) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. Findings Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Interpretation Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Tematica de Investigacion Cooperativa en Cancer.

/pdf/erlotinib-versus-standard-chemotherapy-as-first-line-1hii4s3lek.pdf

Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.

The tumor, node and metastasis classification of malignant tumors is periodically revised. Its seventh edition includes the updated classification for lung cancer, based on the analyses of the International Association for the Study of Lung Cancer international database. It is the largest validation ever carried out to date: 100,869 patients registered in 46 databases from 20 countries. The analysis of this database allowed a detailed study of the impact of tumor size on prognosis, the reclassification of additional tumor nodules, the reclassification of pleural dissemination and the separation of two groups of metastatic disease. These changes led to modifications in stage grouping that better differentiate tumors with different prognosis. This updated classification is also recommended for small-cell lung cancer, and for broncho–pulmonary carcinoids. A new international nodal map with stations and zones, and a histological definition of visceral pleura invasion, have also been proposed.

Updated lung cancer staging system.

Review of blood transfusion practices in thoracic surgery.

Stage IIIA non–small-cell lung cancer with mediastinal node metastases (N2 non–small-cell lung cancer) is actually a spectrum of diseases with widely divergent prognoses. Each subset has been traditionally defined by the tests that are necessary to detect the N2 disease, which in itself is an indication of the extent and bulk of the nodal deposits. The subset with the worst prognosis has such gross N2 disease that it could be detected clinically as the patient enters the clinic. Survival in such patients is usually measured in months. The subset with the best prognosis has such subtle nodal disease that it eludes clinical examination, chest radiology, CT scanning, and even mediastinoscopy, and it is ultimately called unexpected N2 disease when found at thoracotomy. According to several authors, patients in this subset have a 20% survival at 5 years if, despite the mediastinal nodal disease, complete resection proves feasible. Even this subset is an amalgam of cases. Some unexpected N2 disease is not so much unexpected as unconfirmed; others might have small deposits, even widespread involvement, in nodes below the size threshold that would normally trigger a mediastinoscopy. Some cases are the result of a falsely negative mediastinoscopy, and others involve nodes beyond the reach of the mediastinoscope. The realization that N2 disease might elude even the most diligent preoperative evaluation led surgeons to undertake an increasingly detailed intrathoracic re-evaluation at thoracotomy. A central part of this has become the removal of apparently normal lymph nodes in the mediastinum and hilum for subsequent histologic examination. Such techniques have improved staging and have often discovered N2 disease that was not visualized by naked-eye assessment of the sliced nodal tissue but was discovered on subsequent histologic– even immunohistologic–examination after surgery. All of the component groups within the unexpected N2 subset had one unifying and comforting characteristic: in patients whose disease could not be confirmed before thoracotomy, complete resection was feasible in the majority of cases, and the survival rates justified the added risks of continuing with resection. The widespread use of positron emission tomography (PET) scanning with fluorodeoxyglucose has reshuffled the pack. The greater accuracy with which this technique detects N2 disease compared with computed tomography (CT) scanning and even with mediastinoscopy has resulted in some patients with “unexpected” N2 disease being identified before surgery. These patients, if their disease is confirmed histologically, now join the proven N2 cases, for which the current standard of care is induction therapy. Presumably, those cases of N2 disease that elude PET scanning and are discovered at thoracotomy will have even more subtle nodal disease. The principles of stage migration suggest that both groups should have an improved survival when compared with the older subsets. However, PET scanning has spawned two new problems. The specificity with which PET scanning identifies nodal disease is less than perfect, with around 10% false-positive rates in studies. How do we ensure that these patients proceed appropriately with surgical treatment? In those patients whose PET scan suggestion of N2 disease is confirmed histologically, how do we select patients who should then proceed with resection? The simple answer to the first question is to undertake mediastinoscopy in all PET-positive cases without extrathoracic disease. Studies have shown that the answer to the second question lies in selecting patients in whom induction therapy has downstaged the patients and eradicated the mediastinal nodal deposits. This favorable response in the mediastinal lymph nodes is presumably a surrogate for the eradication of occult distant metastases by induction therapy. Those with persistent N2 disease have low survival chances with surgery and are probably better served by consolidation therapy with chemoradiotherapy. The article by De Leyn et al from the Leuven Lung Cancer Group in Belgium seeks to answer the resulting dilemma. How, after induction chemotherapy, do we identify which patients have persistent N2 disease and should go on to chemoradiotherapy and which have been downstaged and should proceed with second-line surgery? Can further PET scanning undertake this reliably, or do we have to accept the problems inherent in repeat mediastinoscopy? They conclude that the sensitivity and accuracy of PET are sufficiently superior to those of repeat mediastinoscopy to justify its use as the technique of choice in these circumstances. This conclusion, and the magnitude of the difference between the results with these investigations, will surprise many. The sensitivity with which PET scanning after induction therapy identifies residual disease in the mediastinal lymph nodes, summarized in the De Leyn et al Table 6, is around 50% to 60%. This is considerably worse than the 83% sensitivity reported for PET scanning in the primary staging of lung cancer. However, the sensitivity of repeat PET in the study by De Leyn et al is 77%—within the range reported in the primary setting. Is this, as the authors claim, the result of coregistering PET and CT images in the newer generation of scanners? One study suggests that, in the primary setting, integrated PET-CT is superior to the visual correlation of images from separate PET and CT studies. However, in this study, the accuracy JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 24 NUMBER 21 JULY 2

Selection of Patients for Surgery After Induction Chemotherapy for N2 Non–Small-Cell Lung Cancer

Intrapleural tumor dissemination after video-assisted thoracoscopic surgery metastasectomy

https://www.annalsthoracicsurgery.org/article/S0003-4975(05)01574-2/pdf

Peter Goldstraw

Papers

Updated lung cancer staging system.

Review of blood transfusion practices in thoracic surgery.

Selection of Patients for Surgery After Induction Chemotherapy for N2 Non–Small-Cell Lung Cancer

Intrapleural tumor dissemination after video-assisted thoracoscopic surgery metastasectomy

Abdominal compartment syndrome: a rare complication of plication of the diaphragm.