Matthew Evison

EBUS-TBNA in Elderly Patients with Lung Cancer: Safety and Performance Outcomes

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) enables minimally invasive lymph node sampling during bronchoscopy under conscious sedation. The primary purpose of this study was to investigate the safety profile of EBUS-TBNA in an elderly population. The secondary aim was to assess the efficacy of EBUS-TBNA for nodal staging and pathological diagnosis in elderly patients with primary lung cancer. Methods: This was a prospective cohort study of patients undergoing EBUS-TBNA, between March 2010 and August 2012, at a single U.K. hospital site. Procedure and outcome data including 6-month follow-up were collected prospectively. Patients were divided into less than 70 (<70yrs) or 70 and older (≥70yrs) age categories for analysis. Results: Four hundred and fifty-one patients underwent EBUS-TBNA during the study period. Mean age of the patients was 66.9 ± 11.9 years, 43.9% (n=198) of them were aged ≥70yrs. Older patients (≥70yrs) had a worse performance status (p=0.0001) and required significantly lower levels of sedation (p<0.000001) but had similar overall complication rates (<70yrs 8.7% versus ≥70yrs 5.1%; p=0.13) and tolerated the procedure better than younger patients (p=0.036). Sensitivity (92.9% versus 86.4%; p=0.12) was equivalent, but negative predictive value (91.8% versus 73.9%; p=0.001) and diagnostic accuracy (96.0% versus 90.2%; p=0.02) of nodal sampling in patients with confirmed or suspected lung cancer (n=273) was higher in the ≥70yrs cohort (n=131, 48.0%). However, the prevalence of nodal malignancy was significantly different between the two groups as was the proportion of patients subject to surgical lymph node sampling after negative EBUS-TBNA. EBUS-TBNA samples produced low non–small-cell lung cancer–not otherwise specified rates (6.9%) and high levels of successful epidermal growth factor receptor mutation analysis (97.5%) irrespective of age category. Conclusion: EBUS is a safe and well-tolerated procedure in elderly patients, which facilitates accurate pathological diagnosis and minimally invasive staging in patients with lung cancer.

Can Computed Tomography Characteristics Predict Outcomes in Patients Undergoing Radial Endobronchial Ultrasound-Guided Biopsy of Peripheral Lung Lesions?

Introduction: Percutaneous computed tomography (CT)-guided lung biopsy is a standard minimally invasive technique for sampling peripheral lung lesions. Radial endobronchial ultrasound (EBUS) offers an alternative approach but it has yet to be defined which patients are most suited to this procedure. The primary aim of this study was to investigate whether CT characteristics could predict the success of radial EBUS-guided sampling. Methods: The University Hospital South Manchester provides a radial EBUS service, under conscious sedation without fluoroscopy, double-hinged curettes, or guide sheaths, to a large cancer Network in the United Kingdom. This retrospective analysis of a prospectively maintained database included all patients undergoing radial EBUS from January 2011 to June 2013. Lesion size, structure, location, and presence of a bronchus sign on thoracic CT were analyzed against predefined outcomes using multivariate analysis. Results: One-hundred and seventeen patients underwent radial EBUS in the study period (mean age 69.5, mean lesion size 36.6 mm). The presence of a bronchus sign on CT was the only independent predictor of all predefined outcomes: (1) lesion identification with radial EBUS, (2) positioning of probe within the center of the lesion, and (3) accurate pathological diagnosis; odds ratio (OR) 31.1 (7.8–123.9, p < 0.0001), OR 44.8 (5.6–354.9, p < 0.0001) and OR 46.6 (11.1–195.3, p < 0.0001) respectively. The sensitivity and diagnostic accuracy for those patients with a bronchus sign on CT was 87.3% and 86.7% compared with 12.5% and 11.1% for those lacking the bronchus sign. Discussion: The patients most likely to benefit from radial EBUS, without the use of adjuncts, are those with a bronchus sign on CT.

Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion

BACKGROUND Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. METHODS Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single‐blind basis. Follow‐up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization. RESULTS The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between‐group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group. CONCLUSIONS Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012–000599–40.)

Nodal staging in lung cancer: a risk stratification model for lymph nodes classified as negative by EBUS-TBNA.

Background: Over the last 10 years, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become established as the first-line nodal staging procedure of choice for lung cancer patients. However, the pathway for patients following a negative EBUS-TBNA has not been clearly defined. The primary aim of this study was to develop and validate a risk stratification model to categorize lymph nodes deemed negative by EBUS-TBNA into “low-risk” and “high-risk” groups, where “risk” refers to the risk of false negative sampling. Methods: A retrospective analysis of a prospectively maintained database at a UK tertiary EBUS-TBNA centre was performed. Only patients with primary lung cancer and only negative lymph nodes by EBUS-TBNA were included in the analysis. A risk stratification model was built from a derivation set using independent predictors of malignancy and the validation set used to evaluate the constructed model. The study period was from March 2010 to August 2013. Results: Three hundred twenty-nine lymph nodes were included in the analysis (derivation set n = 196, validation set n = 133). Lymph node standardized uptake value, the standardized uptake value ratio between the lymph node and primary tumor, and heterogeneous echogenicity during sonographic assessment were the only independent predictors of malignancy. Using a simplified scoring system based on the natural logs of the odds ratios from the multivariable analysis on the derivation sample, lymph nodes can be stratified into low risk (score ⩽1) and high risk (score ≥2). One hundred forty-one of 142 and 94 of 96 lymph nodes classified as low risk in the derivation and validation set, respectively, were ultimately proven to be benign and 35 of 54 and 24 of 37 lymph nodes classified as high risk were proven malignant. The negative predictive value of the risk stratification model for the derivation set and validation set was 99.3% (95% confidence interval 96.1%–99.6%) and 97.9% (95% confidence interval 92%–99.6%), respectively. Conclusion: This risk stratification model may assist lung cancer multidisciplinary teams in deciding which patients need further staging procedures and which may proceed directly to treatment after a negative EBUS.

Resectable clinical N2 non-small cell lung cancer; what is the optimal treatment strategy? An update by the British Thoracic Society Lung Cancer Specialist Advisory Group

ABSTRACT Patients and clinicians are faced with uncertainty as to the optimal treatment strategy for potentially resectable NSCLC in which there is clinical evidence of involvement of the ipsilateral mediastinum. Randomized controlled trials and meta‐analyses have failed to demonstrate superiority of one bimodality strategy over another (chemotherapy plus surgery versus chemotherapy plus radiotherapy). One trial of trimodality treatment with chemotherapy, radiotherapy, and surgery demonstrated an improvement in progression‐free, but not overall, survival versus chemotherapy and radiotherapy. There are a number of limitations to the data in this complex and heterogenous patient group. No randomized controlled trial has specifically studied patients with single‐station N2 disease versus multistation N2 disease. When discussing treatment for fit patients with potentially resectable cN2 NSCLC, lung cancer teams should consider trimodality treatment with chemotherapy, radiotherapy, and surgery or bimodality treatment with chemotherapy and either surgery or radiotherapy. We advocate that all patients see both a thoracic surgeon and the oncology team to discuss these different approaches.

A study of patients with isolated mediastinal and hilar lymphadenopathy undergoing EBUS-TBNA

Background Isolated mediastinal and/or hilar lymphadenopathy (IMHL) may be caused by benign and malignant disorders or be ‘reactive’. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a reported low negative predictive value (NPV) in IMHL, necessitating mediastinoscopy in selected patients. The aim of this study was to examine the NPV of EBUS-TBNA in an IMHL population and determine whether clinical variables differentiate between pathological and reactive IMHL. Methods Analysis of a prospectively maintained database of consecutive patients with IMHL referred to a single UK centre for EBUS-TBNA. Results 100 patients with IMHL had EBUS-TBNA during the study (March 2010–February 2013), mean age 58.6±15.7 years, 63% men, 70% white British and mean follow-up 16.8±8.6 months. Pathological cause of IMHL established in 52 patients (sarcoidosis n=20, tuberculosis n=18, carcinoma n=7, lymphoma n=6, benign cyst n=1), 43 from EBUS-TBNA. 48/57 negative EBUS-TBNA samples were true negatives reflecting reactive lymphadenopathy in 48%. The diagnostic accuracy of EBUS-TBNA was 91% and NPV was 84.2% (95% CI 72.6% to 91.5%). Multivariate analysis of clinical covariates showed age (odds ratio (OR) 1.07, 95% CI 1.01 to 1.13; p=0.033), the presence of a relevant comorbidity (OR 9.49, 95% CI 2.20 to 41.04; p=0.003) and maximum lymph node size (OR 0.70, 95% CI 0.59 to 0.83; p=0.00004) to differentiate between reactive and pathological IMHL. Stratification of the study population according to comorbidity and maximum lymph node size (<20 mm) identified a low-risk cohort (n=32) where the NPV of EBUS-TBNA was 93.8% (95% CI 79.9% to 98.3%). Conclusions Reactive lymphadenopathy accounts for a significant proportion of patients with IMHL. In carefully selected patients with IMHL and a negative EBUS-TBNA, surveillance rather than further invasive sampling may be an appropriate strategy.

Implementing lung cancer screening: baseline results from a community-based ‘Lung Health Check’ pilot in deprived areas of Manchester

We report baseline results of a community-based, targeted, low-dose CT (LDCT) lung cancer screening pilot in deprived areas of Manchester. Ever smokers, aged 55–74 years, were invited to ‘lung health checks’ (LHCs) next to local shopping centres, with immediate access to LDCT for those at high risk (6-year risk ≥1.51%, PLCOM2012 calculator). 75% of attendees (n=1893/2541) were ranked in the lowest deprivation quintile; 56% were high risk and of 1384 individuals screened, 3% (95% CI 2.3% to 4.1%) had lung cancer (80% early stage) of whom 65% had surgical resection. Taking lung cancer screening into communities, with an LHC approach, is effective and engages populations in deprived areas.

Extracorporeal Membrane Oxygenation Assisted Segmentectomy for Metachronous Lung Cancer After Pneumonectomy

Advances in extracorporeal membrane oxygenation have enabled the facilitation of surgical intervention in patients who may otherwise be considered inoperable using conventional ventilation-for example, the resection of an early stage metachronous lung cancer in a patient who has previously undergone a pneumonectomy for a prior lung cancer. We present one such case: a 52-year-old man who underwent right lower lobe segmentectomy for a second primary lung cancer, 3 years after left pneumonectomy, using extracorporeal membrane oxygenation. To our knowledge, there are no published case reports describing the use of extracorporeal membrane oxygenation in resection of metachronous lung cancer after pneumonectomy.

Olanzapine-induced eosinophilic pleuritis

An elderly patient, with a history of depression with psychosis, presented with breathlessness, a right exudative pleural effusion and a peripheral eosinophilia. The pleural fluid was eosinophil-rich (10% of leucocytes). Olanzapine therapy had been commenced 12 months previously. There was a family history of TB and the patient was of African origin. A full diagnostic work-up ensued including computed tomography of the thorax and local anaesthetic thoracoscopy. The pleura was unremarkable on CT and displayed bland smooth thickening at visual inspection during thoracoscopy. Pleural biopsies demonstrated chronic inflammation with eosinophils but no evidence of granulomatous inflammation or malignancy. Pleural tissue culture did not yield mycobacteria. A diagnosis of olanzapine-induced eosinophilic pleuritis was suspected and the pleural disease resolved with withdrawal of olanzapine. Eosinophilic pleural fluid is not a marker of non-malignant aetiology and eosinophilic pleural effusions require a careful and systematic diagnostic work-up. This is the second case report to identify olanzapine as a causative agent in eosinophilic pleural effusion.

Cerebral air embolism following transbronchial lung biopsy during flexible bronchoscopy

During a diagnostic flexible bronchoscopy an 84 year old patient suffered a sudden reduction in conscious level following a transbronchial lung biopsy. A subsequent computed tomography brain scan confirmed cerebral air emboli. The patient survived following a period of supportive treatment in the critical care unit. Transbronchial lung biopsy may cause disruption of vessels walls within the lung parenchyma. Increased airway pressure, caused by the patient exhaling against a bronchoscope wedged within a segmental bronchi, may subsequently force air bubbles through the vessel wall defects. This may explain the occurrence of air emboli. This is a rare report of air embolism complicating transbronchial lung biopsy and all bronchoscopists should aware of this potentially fatal complication.