Anne V. Gonzalez

Methods for Staging Non-small Cell Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUNDnCorrectly staging lung cancer is important because the treatment options and prognosis differ significantly by stage. Several noninvasive imaging studies and invasive tests are available. Understanding the accuracy, advantages, and disadvantages of the available methods for staging non-small cell lung cancer is critical to decision-making.nnnMETHODSnTest accuracies for the available staging studies were updated from the second iteration of the American College of Chest Physicians Lung Cancer Guidelines. Systematic searches of the MEDLINE database were performed up to June 2012 with the inclusion of selected meta-analyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables.nnnRESULTSnThe sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were approximately 55% and 81%, respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For PET scanning, estimates of sensitivity and specificity for identifying mediastinal metastasis were approximately 77% and 86%, respectively. These findings demonstrate that PET scanning is more accurate than CT scanning, but tissue biopsy is still required to confirm PET scan findings. The needle techniques endobronchial ultrasound-needle aspiration, endoscopic ultrasound-needle aspiration, and combined endobronchial ultrasound/endoscopic ultrasound-needle aspiration have sensitivities of approximately 89%, 89%, and 91%, respectively. In direct comparison with surgical staging, needle techniques have emerged as the best first diagnostic tools to obtain tissue. Based on randomized controlled trials, PET or PET-CT scanning is recommended for staging and to detect unsuspected metastatic disease and avoid noncurative resections.nnnCONCLUSIONSnSince the last iteration of the staging guidelines, PET scanning has assumed a more prominent role both in its use prior to surgery and when evaluating for metastatic disease. Minimally invasive needle techniques to stage the mediastinum have become increasingly accepted and are the tests of first choice to confirm mediastinal disease in accessible lymph node stations. If negative, these needle techniques should be followed by surgical biopsy. All abnormal scans should be confirmed by tissue biopsy (by whatever method is available) to ensure accurate staging. Evidence suggests that more complete staging improves patient outcomes.

Lung injury following thoracoscopic talc insufflation: experience of a single North American center.

BACKGROUNDnThoracoscopic talc insufflation (TTI) has been used to obliterate the pleural space and prevent recurrent pleural effusions or pneumothorax. Reports of acute pneumonitis and ARDS after the use of talc raised concern about its safety. Differences in particle size of various talc preparations may explain the variable occurrence of pneumonitis. We sought to determine the incidence of lung injury after TTI over a 13-year period at our institution.nnnMETHODSnPatients who underwent TTI between January 1994 and July 2007 were identified from a prospectively maintained logbook. The talc used was commercially available sterile talc (Sclerosol). The hospital course was reviewed in detail, and all cases of respiratory insufficiency were examined with regard to onset, suspected cause, and outcome. Talc-related lung injury was defined as the presence of new infiltrates on chest radiograph and increased oxygen requirements, with no other identifiable trigger than talc exposure.nnnRESULTSnA total of 138 patients underwent 142 TTIs for recurrent pleural effusions or spontaneous pneumothorax. TTI was performed most frequently for malignant pleural effusions (75.5% of effusions). The median dose of talc was 6 g (range, 2-8 g). Dyspnea with increased oxygen requirements developed within 72 h postprocedure for 12 patients. Four patients (2.8%) had talc-related lung injury, and talc exposure may have contributed to the respiratory deterioration in four additional patients.nnnCONCLUSIONSnWe report the occurrence of lung injury after TTI using the only talc approved by the US Food and Drug Administration. These results reinforce previous concerns regarding the talc used for pleurodesis in North America.

The impact of tunneled pleural catheters on the quality of life of patients with malignant pleural effusions.

Background: Tunneled pleural catheters (TPC) are used in the management of malignant pleural effusions (MPE), but the impact of this palliative procedure on patient quality of life (QoL) has not been well described. Objectives: To ascertain the impact of TPCs on symptoms and QoL of patients with recurrent MPE. Methods: Patients with recurrent MPE completed the EORTC QLQ-C30 and LC13 QoL questionnaires at baseline, 2 and 14 weeks; FACIT-TS-G© treatment satisfaction surveys were completed at 14 weeks. Results: A total of 82 patients were recruited. Thirty-seven patients (37/82, 45%) died prior to their 14-week follow-up appointment. Significant improvements in dyspnea at 2 weeks were demonstrated with both dyspnea scores (LC13 baseline score 64.1, 2-week score 43.7, mean change –20.4, n = 56, p < 0.001; C30 baseline score 78.9, 2-week score 46.6, mean change –32.4, n = 68, p < 0.001), as well as with the MRC score (baseline median score 4, 2-week score 3, n = 70, p < 0.001). Global health status/QoL was also significantly improved at 2 weeks (baseline score 34.1, 2-week score 46.3, mean change 12.3, n = 68, p < 0.001). Improvements in cough, fatigue and all functional scales were noted at 2 weeks. The improvements in dyspnea and global health status/QoL were maintained to 14 weeks in surviving subjects and there was further improvement in the MRC score at 14 weeks. Patients who completed the FACIT-TS-G survey demonstrated overall satisfaction with TPC treatment. Conclusions: TPCs are associated with a significant improvement in global health status, QoL and dyspnea at the 2-week time point in patients with recurrent MPE.

Risk of glaucoma in elderly patients treated with inhaled corticosteroids for chronic airflow obstruction

BACKGROUNDnTopical and systemic corticosteroids are well known to raise intra-ocular pressure while the effect of inhaled corticosteroids (ICS) on the risk of glaucoma remains uncertain. We sought to determine the risk of new onset ocular hypertension or glaucoma requiring treatment, associated with the use of ICS in elderly patients treated for airways disease.nnnMETHODSnWe carried out a nested case-control study using the databases from the Québec provincial health insurance plan. A cohort of patients receiving respiratory medications was formed among all subjects 66 years of age and older. Cases were subjects in whom treatment for glaucoma was initiated between January 1, 1988 and December 31, 2003 after a first ever visit to an ophthalmologist within the preceding 90 days. Age-matched controls were selected among individuals who also visited an ophthalmologist for the first time within 90 days of the cases treatment date and did not receive a treatment for glaucoma.nnnRESULTSnA total of 2291 cases were identified. For comparison, a total of 13,445 age-matched controls were selected. The mean age was (75+/-4.2 years). The adjusted rate ratio for glaucoma was 1.05 (95% CI 0.91-1.20) with ICS use in the preceding 30 days. There was no dose-related effect of ICS on the risk of glaucoma or raised intra-ocular pressure requiring treatment. Continuous use of high-dose ICS for 3 of more months was not associated with an increased risk of glaucoma.nnnCONCLUSIONnIn a large cohort of elderly patients treated for airways disease, we found that current use and continuous use of high-dose ICS did not result in an increased risk of glaucoma or raised intra-ocular pressure requiring treatment.

Gender differences in survival following hospitalisation for COPD

Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Gender differences in the clinical expression of COPD are increasingly recognised, but outcome differences have not been systematically examined. Gender differences in survival and rate of rehospitalisation were investigated in a large cohort of elderly patients with chronic airflow obstruction hospitalised for COPD. Methods The databases from the Québec provincial health insurance plan were used. The study population included subjects aged >66u2005years who received ≥3 prescriptions for respiratory medications in any 1-year period between 1 January 1990 and 31 December 2001. The study cohort consisted of patients with a first hospitalisation for COPD, after selection into the study population. Patients were followed until death or 31 December 2003. The Kaplan–Meier method was used to estimate time to death and time to first hospitalisation for obstructive airways disease (COPD or asthma). The Cox proportional hazards model was used to determine the effect of male gender on all-cause mortality and rehospitalisation. Results The cohort consisted of 19u2008260 women and 23u2008893 men with a mean age of 77u2005years. 11u2008245 (58.4%) women and 16u2008754 (70.1%) men died after cohort entry. Male sex was associated with a significantly increased risk of death (adjusted HR 1.45, 95% CI 1.42 to 1.49) and with a significantly increased risk of rehospitalisation for obstructive airways disease (adjusted HR 1.12, 95% CI 1.09 to 1.15). Conclusion Mean survival and time to rehospitalisation for obstructive airways disease are significantly better for female patients.

Endobronchial ultrasound learning curve in interventional pulmonary fellows

Little published data exist regarding the learning curve for endobronchial ultrasound‐transbronchial needle aspiration (EBUS‐TBNA). We sought to assess the improvement in skill as trainees learned EBUS‐TBNA in a clinical setting.

Optimizing tissue sampling for the diagnosis, subtyping, and molecular analysis of lung cancer.

Lung cancer has entered the era of personalized therapy with histologic subclassification and the presence of molecular biomarkers becoming increasingly important in therapeutic algorithms. At the same time, biopsy specimens are becoming increasingly smaller as diagnostic algorithms seek to establish diagnosis and stage with the least invasive techniques. Here, we review techniques used in the diagnosis of lung cancer including bronchoscopy, ultrasound-guided bronchoscopy, transthoracic needle biopsy, and thoracoscopy. In addition to discussing indications and complications, we focus our discussion on diagnostic yields and the feasibility of testing for molecular biomarkers such as epidermal growth factor receptor and anaplastic lymphoma kinase, emphasizing the importance of a sufficient tumor biopsy.

Long-term Use of Inhaled Corticosteroids in COPD and the Risk of Fracture

Background It is uncertain whether long‐term use of inhaled corticosteroids (ICSs), widely used to treat COPD, increases the risk of fracture, particularly in women, in view of the postmenopausal risks. We assessed whether long‐term ICS use in patients with COPD increases the risk of hip or upper extremity fractures, and examined sex‐related differences. Methods The Quebec health‐care databases were used to form a cohort of patients with COPD over 1990 to 2005, followed until 2007 for the first hip or upper extremity fracture. In a nested case‐control analysis, each case of fracture was matched with 20 control subjects on age, sex, and follow‐up time. The adjusted rate ratio (RR) of fracture with ICS use, by duration and dose, was estimated using conditional logistic regression, with an interaction term to compare the risk in men and women. Results In the cohort of 240,110 subjects, 19,396 sustained a fracture during a mean 5.3 years (rate, 15.2 per 1,000 per year). Any use of ICSs was not associated with an increased rate of fracture (RR, 1.00; 95% CI, 0.97‐1.03). The fracture rate was increased with > 4 years of ICS use at daily doses ≥ 1,000 &mgr;g in fluticasone equivalents (RR, 1.10; 95% CI, 1.02‐1.19). This risk increase did not differ between men and women. Conclusions Long‐term ICS use at high doses is associated with a modest increase in the risk of hip and upper extremity fractures in patients with COPD. This dose‐duration risk increase does not appear to be higher for women.

Yield of EBUS-TBNA for the diagnosis of sarcoidosis: impact of operator and cytopathologist experience.

Background Studies have reported a high diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of sarcoidosis. We sought to review the yield of EBUS-TBNA for the diagnosis of sarcoidosis at our institution over time, and examine factors that may influence this yield. Methods Patients who underwent EBUS-TBNA for suspected sarcoidosis between December 2008 and November 2011 were identified. EBUS was performed without rapid on-site evaluation (ROSE) of samples. The final diagnosis was based on the results of all invasive diagnostic procedures and/or clinical follow-up. Logistic regression analysis was used to examine the effect of various factors on yield. Results 43 patients underwent 45 EBUS-TBNA procedures for suspected sarcoidosis. A total of 115 lymph nodes were sampled. The 21u2005G needle was used in 51% of procedures. The mean number of lymph node stations sampled was 2.6 (SD 0.7) and the mean number of needle passes per procedure was 7.8 (SD 2.0). Non-necrotising granulomatous inflammation was detected in EBUS-TBNA samples from 34/45 (76%) procedures. The overall diagnostic yield increased to 36/45 (80%) following a cytopathology review for this study. Needle gauge, number of lymph node stations sampled and number of needle passes were not associated with diagnostic yield. The yield of EBUS-TBNA increased significantly after the first 15 procedures performed for suspected sarcoidosis; the 2 additional cases diagnosed after the cytopathology review were part of this early experience. Conclusions EBUS-TBNA is a valuable technique for the diagnosis of sarcoidosis when performed without ROSE. The yield of the procedure improved significantly over time, based on operator and cytopathologist experience.

Evaluation of the patient with pleural effusion

KEY POINTSnEvaluation of the patient with pleural effusion is challenging, because the differential diagnosis is broad and includes both benign and life-threatening conditions. Moreover, the invasive and noninvasive tests required to make an etiological diagnosis may not be readily available in a