Richard Harrison

Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non-small cell lung cancer: a multicenter study of 774 patients.

RATIONALE The current management of advanced non-small cell lung cancer (NSCLC) requires differentiation between squamous and nonsquamous subtypes as well as epidermal growth factor receptor (EGFR) mutation status. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasingly used for the diagnosis and staging of lung cancer. However, it is unclear whether cytology specimens obtained with EBUS-TBNA are suitable for the subclassification and genotyping of NSCLC. OBJECTIVES To determine whether cytology specimens obtained from EBUS-TBNA in routine practice are suitable for phenotyping and genotyping of NSCLC. METHODS Cytological diagnoses from EBUS-TBNA were recorded from 774 patients with known or suspected lung cancer across five centers in the United Kingdom between 2009 and 2011. MEASUREMENTS AND MAIN RESULTS The proportion of patients with a final diagnosis by EBUS-TBNA in whom subtype was classified was 77% (95% confidence interval [CI], 73-80). The rate of NSCLC not otherwise specified (NSCLC-NOS) was significantly reduced in patients who underwent immunohistochemistry (adjusted odds ratio, 0.50; 95% CI, 0.28-0.82; P = 0.016). EGFR mutation analysis was possible in 107 (90%) of the 119 patients in whom mutation analysis was requested. The sensitivity, negative predictive value, and diagnostic accuracy of EBUS-TBNA in patients with NSCLC were 88% (95% CI, 86-91), 72% (95% CI, 66-77), and 91% (95% CI, 89-93), respectively. CONCLUSIONS This large, multicenter, pragmatic study demonstrates that cytology samples obtained from EBUS-TBNA in routine practice are suitable for subtyping of NSCLC and EGFR mutation analysis and that the use of immunohistochemistry reduces the rate of NSCLC-NOS.

Suitability of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Specimens for Subtyping and Genotyping of Non–Small Cell Lung Cancer

RATIONALE The current management of advanced non-small cell lung cancer (NSCLC) requires differentiation between squamous and nonsquamous subtypes as well as epidermal growth factor receptor (EGFR) mutation status. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasingly used for the diagnosis and staging of lung cancer. However, it is unclear whether cytology specimens obtained with EBUS-TBNA are suitable for the subclassification and genotyping of NSCLC. OBJECTIVES To determine whether cytology specimens obtained from EBUS-TBNA in routine practice are suitable for phenotyping and genotyping of NSCLC. METHODS Cytological diagnoses from EBUS-TBNA were recorded from 774 patients with known or suspected lung cancer across five centers in the United Kingdom between 2009 and 2011. MEASUREMENTS AND MAIN RESULTS The proportion of patients with a final diagnosis by EBUS-TBNA in whom subtype was classified was 77% (95% confidence interval [CI], 73-80). The rate of NSCLC not otherwise specified (NSCLC-NOS) was significantly reduced in patients who underwent immunohistochemistry (adjusted odds ratio, 0.50; 95% CI, 0.28-0.82; P = 0.016). EGFR mutation analysis was possible in 107 (90%) of the 119 patients in whom mutation analysis was requested. The sensitivity, negative predictive value, and diagnostic accuracy of EBUS-TBNA in patients with NSCLC were 88% (95% CI, 86-91), 72% (95% CI, 66-77), and 91% (95% CI, 89-93), respectively. CONCLUSIONS This large, multicenter, pragmatic study demonstrates that cytology samples obtained from EBUS-TBNA in routine practice are suitable for subtyping of NSCLC and EGFR mutation analysis and that the use of immunohistochemistry reduces the rate of NSCLC-NOS.

Lung cancer in Teesside (UK) and Varese (Italy): a comparison of management and survival

Background: The survival of lung cancer patients in the UK is lower than in other similar European countries. The reasons for this are unclear. Methods: Two areas were selected with a similar incidence of lung cancer: Teesside in Northern England and Varese in Northern Italy. Data were collected prospectively on all new cases of lung cancer diagnosed in the year 2000. Comparisons were made of basic demographic characteristics, management, and survival. Results: There were 268 cases of lung cancer in Teesside and 243 in Varese. Patients in Teesside were older (p<0.05), were more likely to have smoked (p<0.001), had a higher occupational risk (p<0.001), higher co-morbidity (p<0.05), and poorer performance status (p<0.001). Fewer patients in Teesside presented as an incidental finding (p<0.001) and the histological confirmation rate was lower than in Varese (p<0.01). In Teesside there were more large cell carcinomas (p<0.001), more small cell carcinomas (p<0.05), and fewer early stage non-small cell lung cancers (p<0.05). The resection rate was lower in Teesside (7% v 24%; p<0.01) and more patients received no specific anti-cancer treatment (50% v 25%; p<0.001). Overall 3 year survival was lower in Teesside (7% v 14%; p<0.001). Surgical resection was the strongest multivariate survival predictor in Varese (HR = 0.46) and Teesside (HR = 0.31). Co-morbidity in Teesside resulted in a significantly lower resection rate (p<0.001). Conclusions: Patients with lung cancer in Teesside presented at a later stage, with more aggressive types of tumour, and had higher co-morbidity than patients in Varese. As a result, the resection rate was significantly lower and survival was worse.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for the Diagnosis of Intrathoracic Lymphadenopathy in Patients with Extrathoracic Malignancy: A Multicenter Study

Introduction: Mediastinal lymphadenopathy in patients with an extrathoracic malignancy is a common clinical scenario. Invasive sampling of intrathoracic lymph nodes may be performed by mediastinoscopy or endoscopic ultrasound-guided fine needle aspiration. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an alternative to mediastinoscopy and endoscopic ultrasound in patients with lung cancer and sarcoidosis. The utility of EBUS-TBNA in patients with extrathoracic malignancy was evaluated. Methods: Consecutive patients who were suspected to have intrathoracic lymph node metastases from an extrathoracic malignancy underwent EBUS-TBNA. When EBUS-TBNA did not provide a specific diagnosis, patients underwent mediastinoscopy or clinical follow-up of at least 6 months duration. Results: One hundred sixty-one patients meeting the inclusion criteria underwent EBUS-TBNA in five UK centers over a 3-year period. EBUS-TBNA diagnosed mediastinal or hilar metastases in 71 (44%) patients, new lung cancer in 20 (12%) patients, and sarcoidosis in 14 (9%) patients. The sensitivity, negative predictive value for malignancy, and overall accuracy for EBUS-TBNA were 87%, 73% and 88%, respectively. One hundred ten (68%) patients in the study had a final diagnosis of malignant intrathoracic lymphadenopathy. Conclusion: Because of the high prevalence of alternative diagnoses, pathological evaluation is important in patients with extrathoracic malignancy and suspected mediastinal or hilar lymph node metastases. EBUS-TBNA is a safe and sensitive technique and may be considered a first-line investigation in these patients.

Does living near heavy industry cause lung cancer in women? A case‐control study using life grid interviews

Background: The incidence of lung cancer among women is high in the highly industrialised area of Teesside in north-east England. Previous research has implicated industrial pollution as a possible cause. A study was undertaken to investigate whether prolonged residence close to heavy industry is associated with lung cancer among women in Teesside. Methods: Two hundred and four women aged <80 years with incident primary lung cancer and 339 age matched community controls were recruited to a population based case-control study. Life course residential, occupational, and active and passive smoking histories were obtained using an interviewer administered questionnaire. Results: The age adjusted odds ratio (OR) for lung cancer among people living >25 years v 0 years near (within 0–5 km) heavy industry in Teesside was 2.13 (95% CI 1.34 to 3.38). After adjustment for confounding factors the OR was 1.83 (95% CI 0.82 to 4.08) for >25 years or 1.10 (95% CI 0.96 to 1.26) for an additional 10 years living near industry. ORs were similar after residence near heavy industry outside Teesside was also included, and when latency was allowed for by disregarding residential exposures within the last 20 years. Adjustment for active smoking had the greatest effect on the OR. Conclusions: This population based study using life grid interviews for life course exposure assessment has addressed many deficiencies in the design of previous studies. The findings support those in most of the international literature of a modestly raised risk of lung cancer with prolonged residence close to heavy industry, although the confidence intervals were wide. The effect of air pollution on the incidence of lung cancer merits continued study.

Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD

Background Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high. The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care. We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools. Methods The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014. Consecutive admissions were identified by screening admissions and searching coding records. Admission clinical data, including DECAF indices, and mortality were recorded. The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve. Results In the internal and external validation cohorts, 880 and 845 patients were recruited. Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted. Overall mortality was 7.7%. The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality. Conclusions DECAF is a robust predictor of mortality, using indices routinely available on admission. Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0–1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3–6) for escalation planning or appropriate early palliation. Trial registration number UKCRN ID 14214.

Clinical management of older people with non-small cell lung cancer in England

Data for 25261 patients with non-small cell lung cancer whose details were submitted to the National Lung Cancer Audit in England were analysed to assess the effect of age at diagnosis on their clinical management, after accounting for sex, stage, performance status and comorbidity. Multivariate logistic regression showed the odds of having histocytological confirmation and anticancer treatment decreased progressively with age, and was also lower in women. It is likely that these results have a multifactorial explanation, and further research into the attitudes of patients, carers and healthcare professionals, and clinical trials of treatment in older populations, are necessary.

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.)

Resection rate of lung cancer in Teesside (UK) and Varese (Italy): a comparison after implementation of the National Cancer Plan

Background In a lung cancer survey in 2000 we showed significantly less favourable stage distribution and lower resection rate in Teesside (UK) than in the comparable industrialised area of Varese (Italy). Lung cancer services in Teesside were subsequently reorganised according to National Cancer Plan recommendations. Methods For all new lung cancer cases diagnosed in Teesside (n=324) and Varese (n=260) during the 12 months October 2010 to September 2011 (hereafter ‘the 2010 cohort’), demographic, clinico-pathological and disease management data were prospectively recorded using the same database and protocol as the 2000 survey. Findings were analysed focusing on resection rate. Results In the 2010 cohort compared with 2000, both in Teesside and Varese emergency referral decreased (p<0.001), performance status improved (p<0.001), but cancer stage shift was not seen; resection rate improved in Teesside, from 7% to 11% (p=0.054), and was unchanged in Varese (24%). Moreover, in Teesside compared with Varese the stage distribution remained less favourable, stage I–II non-small cell lung cancer (NSCLC) proportion being respectively 12% and 19% (p=0.040), and resection rate in all lung cancers remained lower (11% and 24%; p<0.001). On multivariate analysis, resection predictors in Teesside were as follows: stage I–II NSCLC (OR 86.14; 95% CI 31.80 to 233.37), performance status 0–1 (OR 5.02; 95% CI 1.48 to 17.07), belonging to 2010 cohort (OR 2.85; 95% CI 1.06 to 7.64). Conclusions In Teesside the main independent predictor of resection was disease stage; in 2010–2011 compared with 2000, lung cancer service improved but stage shift did not occur, and resection rate increased but remained significantly lower than in Varese.

Recurrent inflight chest pain due to a solitary bulla

Ms L is a 47-year-old lady who was referred with severe, left-sided pleuritic chest pain and painful left arm weakness that occurred predictably during consecutive commercial flights. Subsequent investigations diagnosed a large left-sided, isolated bulla. A VATS bullectomy was performed with no complications, and a symptomless flight followed. We discuss here the physiological explanation for her symptoms and the treatment of bulla in this unusual case.