Daniel M. Libby

Early Lung Cancer Action Project: overall design and findings from baseline screening

BACKGROUND The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low-radiation-dose computed tomography (low-dose CT) in people at high risk of lung cancer. We report the baseline experience. METHODS ELCAP has enrolled 1000 symptom-free volunteers, aged 60 years or older, with at least 10 pack-years of cigarette smoking and no previous cancer, who were medically fit to undergo thoracic surgery. After a structured interview and informed consent, chest radiographs and low-dose CT were done for each participant. The diagnostic investigation of screen-detected non-calcified pulmonary nodules was guided by ELCAP recommendations, which included short-term high-resolution CT follow-up for the smallest non-calcified nodules. FINDINGS Non-calcified nodules were detected in 233 (23% [95% CI 21-26]) participants by low-dose CT at baseline, compared with 68 (7% [5-9]) by chest radiography. Malignant disease was detected in 27 (2.7% [1.8-3.8]) by CT and seven (0.7% [0.3-1.3]) by chest radiography, and stage I malignant disease in 23 (2.3% [1.5-3.3]) and four (0.4% [0.1-0.9]), respectively. Of the 27 CT-detected cancers, 26 were resectable. Biopsies were done on 28 of the 233 participants with non-calcified nodules; 27 had malignant non-calcified nodules and one had a benign nodule. Another three individuals underwent biopsy against the ELCAP recommendations; all had benign non-calcified nodules. No participant had thoracotomy for a benign nodule. INTERPRETATION Low-dose CT can greatly improve the likelihood of detection of small non-calcified nodules, and thus of lung cancer at an earlier and potentially more curable stage. Although false-positive CT results are common, they can be managed with little use of invasive diagnostic procedures.

Ordinal Scoring of Coronary Artery Calcifications on Low-Dose CT Scans of the Chest is Predictive of Death from Cardiovascular Disease

PURPOSE To assess the usefulness of ordinal scoring of the visual assessment of coronary artery calcification (CAC) on low-dose computed tomographic (CT) scans of the chest in the prediction of cardiovascular death. MATERIALS AND METHODS All participants consented to low-dose CT screening according to an institutional review board-approved protocol. The amount of CAC was assessed on ungated low-dose CT scans of the chest obtained between June 2000 and December 2005 in a cohort of 8782 smokers aged 40-85 years. The four main coronary arteries were visually scored, and each participant received a CAC score of 0-12. The date and cause of death was obtained by using the National Death Index. Follow-up time (median, 72.3 months; range, 0.3-91.9 months) was calculated as the time between CT and death, loss to follow-up, or December 31, 2007, whichever came first. Logistic regression analysis was used to determine the risk of mortality according to CAC category adjusted for age, pack-years of cigarette smoking, and sex. The same analysis to determine the hazard ratio for survival from cardiac death was performed by using Cox regression analysis. RESULTS The rate of cardiovascular deaths increased with an increasing CAC score and was 1.2% (43 of 3573 subjects) for a score of 0, 1.8% (66 of 3569 subjects) for a score of 1-3, 5.0% (51 of 1015 subjects) for a score of 4-6, and 5.3% (33 of 625 subjects) for a score of 7-12. With use of subjects with a CAC score of 0 as the reference group, a CAC score of at least 4 was a significant predictor of cardiovascular death (odds ratio [OR], 4.7; 95% confidence interval: 3.3, 6.8; P < .0001); when adjusted for sex, age, and pack-years of smoking, the CAC score remained significant (OR, 2.1; 95% confidence interval: 1.4, 3.1; P = .0002). CONCLUSION Visual assessment of CAC on low-dose CT scans provides clinically relevant quantitative information as to cardiovascular death.

Lung Cancers Diagnosed at Annual CT Screening: Volume Doubling Times

PURPOSE To empirically address the distribution of the volume doubling time (VDT) of lung cancers diagnosed in repeat annual rounds of computed tomographic (CT) screening in the International Early Lung Cancer Action Program (I-ELCAP), first and foremost with respect to rates of tumor growth but also in terms of cell types. MATERIALS AND METHODS All CT screenings in I-ELCAP from 1993 to 2009 were performed according to HIPAA-compliant protocols approved by the institutional review boards of the collaborating institutions. All instances of first diagnosis of primary lung cancer after a negative screening result 7-18 months earlier were identified, with symptom-prompted diagnoses included. Lesion diameter was calculated by using the measured length and width of each cancer at the time when the nodule was first identified for further work-up and at the time of the most recent prior screening, 7-18 months earlier. The length and width were measured a second time for each cancer, and the geometric mean of the two calculated diameters was used to calculate the VDT. The χ(2) statistic was used to compare the VDT distributions. RESULTS The median VDT for 111 cancers was 98 days (interquartile range, 108). For 56 (50%) cancers it was less than 100 days, and for three (3%) cancers it was more than 400 days. Adenocarcinoma was the most frequent cell type (50%), followed by squamous cell carcinoma (19%), small cell carcinoma (19%), and others (12%). Lung cancers manifesting as subsolid nodules had significantly longer VDTs than those manifesting as solid nodules (P < .0001). CONCLUSION Lung cancers diagnosed in annual repeat rounds of CT screening, as manifest by the VDT and cell-type distributions, are similar to those diagnosed in the absence of screening.

CT-guided transthoracic needle biopsy of small solitary pulmonary nodules

The use of CT guidance in performing transthoracic needle biopsy is well established. We evaluated its accuracy in the diagnosis of small solitary nodules and found it to be highly accurate regardless of size or location. While specific benign diagnoses were uncommon, additional confidence in a benign diagnosis can be gained by careful analysis of needle tip location using strict CT criteria.

The Solitary Pulmonary Nodule: Update 1995

PURPOSE This study analyzed the clinical characteristics, diagnostic evaluation, prevalence of malignancy, and outcome of patients with a solitary pulmonary nodule (SPN) encountered in the outpatient practice of a pulmonologist in an urban university hospital from 1990 to 1993. PATIENTS AND METHODS SPN was defined as a round or ovoid density < or = 3 cm in diameter within the lung parenchyma. Patients with and without lung cancer in SPNs were compared. RESULTS Forty patients had a mean age of 65 years, an almost equal sex distribution, high prevalences of cardiovascular disease (53%) and chronic obstructive pulmonary disease (COPD) (33%), but a low incidence of tuberculosis. The mean size of SPNs was 1.8 cm. The prevalence of malignancy was 53%. In SPNs < or = 2 cm in diameter, the prevalence of malignancy was 43%. Nonsurgical biopsy techniques made a diagnosis in 78% of patients. In 94% of patients with lung cancer in SPNs, the tumor was resectable (stage 1, 2, or 3A), emphasizing the need for early detection. Despite the small size of the SPNs, the prevalence of malignancy was high. CONCLUSION Despite the advanced age and high prevalence of cardiovascular disease and COPD in patients with SPNs, lung cancer that occurs in these lesions appears to have a favorable prognosis if detected promptly.

Acute respiratory failure in scoliosis or kyphosis: Prolonged survival and treatment

Acute respiratory failure (ARF) in adults with severe thoracic spinal deformity is said to be a preterminal event with a median survival of one year. Twenty patients with ARF (mean +/- S.D., arterial oxygen tension [PaO2] 35 +/- 7 mm Hg, arterial carbon dioxide tension [PaCO2] 63 +/- 9 mm Hg, pH 7.34 +/- 0.08) due to severe scoliosis or kyphosis (spinal curve 113 +/- 28 degrees ) were seen between 1965 and 1980. All 20 survived the initial episode of ARF and during the follow-up period (median, six years) experienced 2.4 additional episodes of ARF. The age at presentation was 52 years (mean, range 13 to 78), and the cause of spinal deformity was idiopathic (seven patients), poliomyelitis (seven), tuberculosis (five), and arthrogryposis multiplex congenita (one). ARF was treated with controlled low dose oxygen by Venturi mask and intensive general measures in 13 patients and by mechanical ventilation in seven. Of the latter seven patients, ventilatory failure was treated in two with a tank respirator and a cuirass, avoiding endotracheal intubation. Outpatient management was similar to conventional therapy for chronic obstructive pulmonary disease (COPD). Severe restrictive ventilatory impairment characterized the group after recovery from the first episode of ARF: vital capacity (VC) 906 +/- 362 ml (31 percent predicted) and FEV1 589 +/- 197 ml (23 percent). During follow-up, the VC decreased by 1.5 ml/year and the FEV1 by 13.9 ml/year. The PaO2 increased by 2.6 mm Hg/year and the PaCO2 increased by 1.7 mm Hg/year. Successful management of ARF due to severe scoliosis or kyphosis is possible in the great majority of patients, and long-term survival may be expected. Unlike COPD, pulmonary function following ARF in kyphosis or scoliosis deteriorates at a slower than expected rate and, in fact, may improve with treatment over many years.

Lung Cancer Associated With Cystic Airspaces

OBJECTIVE The objectives of this study were to determine the frequency of lung cancers associated with a discrete cystic airspace and to characterize the morphologic and pathologic features of the cancer and the cystic airspace. MATERIALS AND METHODS We reviewed all diagnosed cases of lung cancer resulting from baseline screening (n=595) and annual screening (n=111) in the International Early Lung Cancer Action Program to identify those abutting or in the wall of a cystic airspace. We also reviewed the pathologic specimens. RESULTS A total of 26 lung cancers were identified abutting or in the wall of a cystic airspace. Of these, 13 were identified at baseline (13/595, 2%) and 13 at annual screening (13/111, 12%), which was significant (p<0.0001). The median circumferential portion of wall involved was less for the annual cancers than for the baseline ones, but this difference did not reach significance (90° vs 240°, p=0.07). The diagnosis was adenocarcinoma in all but three cases. Histologic analysis showed that the cystic space was a bulla, a fibrous walled cyst without a defined lining, or a pleural bleb and that in all but one case, the tumor was eccentric relative to the airspace and the wall of the airspace was unevenly thickened. CONCLUSION At annual repeat CT screening, the finding of an isolated cystic airspace with increased wall thickness should raise the suspicion of lung cancer.

Clinical utility of computed tomography in the diagnosis of pulmonary embolism

This prospective clinical pilot study describes the clinical utility and cost effectiveness of computed tomography (CT) with contrast in the diagnosis and management of pulmonary embolism. The setting is a university teaching hospital, and the 20 patients, 26 to 81 years old, were found to have CT findings consistent with pulmonary embolism. Intraluminal pulmonary artery clots were observed on CT and contributed to clinical management, often obviating pulmonary arteriography. CT, particularly spiral CT, may demonstrate pulmonary embolism and offers advantages over ventilation-perfusion lung scanning and pulmonary arteriography in making the diagnosis of pulmonary embolism in high-risk patients or patients with preexisting parenchymal lung disease.

Aspiration of the Nasal Septum: A New Complication of Cocaine Abuse

Excerpt Altered mental status ranging from psychosis to coma occurs in over a quarter of patients presenting to emergency departments after use of cocaine and is second in frequency only to cardiop...

Ct-guided transthoracic needle biopsy following indeterminate fiberoptic bronchoscopy in solitary pulmonary nodules

We evaluated the role of computed tomography (CT)-guided transthoracic needle biopsy (TNB) in patients with solitary pulmonary nodule and indeterminate flexible fiberoptic bronchoscopy (FOB). A review of 112 patients with solitary nodules under 3 cm in size who underwent TNB was carried out. A total of 48 patients had prior FOB with negative or indeterminate results. We reviewed the results of CT-guided TNB of these 48 patients with respect to the cytology results, nodule size and location, and complications of the procedure. Among the 48 patients who had FOB with indeterminate cytology, 32 were found to have malignant cytology on subsequent TNB. Among the remaining 16 patients, eight had diagnostic thoracotomy, which showed that six of the nodules were benign and two were malignant. The remaining eight patients who did not undergo surgery have been followed for more than 2 years, without evidence of growth. Results were not influenced by size or location. TNB offers a high yield for diagnosis in this patient population.