Free Lung Cancer Screening Trends Toward a Twofold Increase in Lung Cancer Prevalence in the Underserved Southeastern United States.

OBJECTIVES: The National Lung Screening Trial (NLST) reported that the prevalence of lung cancer in individuals at high risk for the disease is 1%, and that screening these individuals using low-dose helical computed tomography of the chest saves lives. To increase screening accessibility in the underserved southeastern United States, we developed a free lung screening program, modeled after the Lahey Hospital & Medical Center Free Lung Screening Program, for individuals meeting National Comprehensive Cancer Network high-risk criteria. METHODS: This was a chart review of 264 participants screened in the first year of our program. Participants were divided into categories based on the Lung Imaging Reporting and Diagnostic System. Categories three and four were considered positive findings, with demographic and disease criteria collected on these patients. RESULTS: Of 264 participants screened, 28 (10.6%) were Lung Imaging Reporting and Diagnostic System category four, 23 (8.7%) were category three, 78 (29.5%) were category two, and 135 (51.1%) were category one. Eight of the 264 participants (3.0%) had lung cancer, with 75% detected in early stages. CONCLUSIONS: We found a lung cancer prevalence in our high-risk screened population of 3.0% (8 of 264). After adjusting for patients who were symptomatic on clinical evaluation, we report a prevalence of cancer at 2.2% compared with 1.1% in the first year of the National Lung Screening Trial and a prevalence of 1.9% versus 0.6% compared with the National Comprehensive Cancer Network criteria in the first 10 months at Lahey Hospital & Medical Center. This study justifies low-dose helical computed tomography screening in high-risk regions because lung cancer treatment before symptoms appear is more effective, and the prevalence of disease in the detectable preclinical phase is high.

Sleep apnea in end-stage renal disease patients: risk factors and mortality.

Sleep apnea (SA) is highly prevalent in the end-stage renal disease (ESRD) population. However, the impact of SA on mortality in ESRD is unclear. This study investigates the relationship between SA and mortality in ESRD. The United States Renal Data System was queried in a retrospective cohort study to identify ESRD patients aged 18-100 years who initiated hemodialysis between 2005 and 2013. Diagnoses of SA and comorbidities were determined from International Classification of Disease-9 codes and demographic variables from Centers for Medicare and Medicaid Services Form-2728. Cox proportional hazards models were used to examine the association of SA with mortality controlling for multiple variables. Of 858,131 subjects meeting inclusion criteria, 587 were found to have central SA (CSA) and 22,724 obstructive SA (OSA). The SA cohort was younger and more likely to be male and Caucasian compared to the non-SA cohort, with more diagnoses of tobacco and alcohol use, hypertension, heart failure, and diabetes. Both CSA (adjusted hazard ratio (aHR) = 1.42, 95% confidence interval (CI): 1.29-1.56) and OSA (aHR = 1.35, 95% CI: 1.32-1.37) were associated with increased mortality. Other variables associated with increased mortality included age, dialysis initiation with a catheter or graft, alcohol use, hypertension, and cardiovascular disease. Factors associated with decreased mortality included female sex, black race, Hispanic ethnicity, diagnosis of heart failure or diabetes, and an ESRD etiology of glomerulonephritis or polycystic kidney disease. Since a diagnosis of either OSA or CSA increases mortality risk, early identification of SA and therapy in this ESRD population may improve survival.

A 43-Year-Old Woman With Hoarseness of Voice and Chest Pressure.

CASE PRESENTATION: A 43-year-old woman with a medical history of cervical cancer treated with curative hysterectomy 12 years earlier developed progressive dyspnea, chest discomfort, and hoarse voice over a 7-month period. The patient never smoked and had no exposure history. Imaging at an outside hospital showed a mediastinal mass with hilar adenopathy (Fig 1A), which was biopsied via endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and revealed noncaseating granulomas with surrounding rims of lymphocytes (Fig 1B). The patient was given the diagnosis of sarcoidosis and started on prednisone 60 mg daily. She had no improvement in symptoms after 3 months of therapy and therefore presented for a second opinion.

Financial Analysis of Free Lung Cancer Screening Program Shows Profitability Using Broader NCCN Guidelines.

BACKGROUND: Lung cancer screening with low-dose computed tomography (LDCT) chest scans in high-risk populations has been established as an effective measure of preventive medicine by the National Lung Screening Trial. However, the sustainability of funding a program is still controversial. We present a 2.5-year profitability analysis of our screening program by using the broader National Comprehensive Cancer Network criteria. METHODS: Retrospective chart review was performed on the initial 2.5-year data set of a free LDCT chest scan program that targeted the underserved Southeastern United States. Patients were selected by the National Comprehensive Cancer Network high-risk criteria, screening twice as many patients compared with Centers for Medicare and Medicaid Services criteria. LDCT scans were performed during the off-service hours of our positron emission tomography CT scanner. Analysis of fiscal years 2015 to 2017 was done to evaluate indirect cost, direct cost, and adjusted net margin per case after factoring downstream revenue from positive scans and other findings. RESULTS: A total of 705 scans were performed with 418 patients referred for subsequent procedures or specialist evaluations. The mean overhead cost over total cost was 42.3%. The adjusted net margin per case was -$212 in the first year but turned positive to $177 in the third fiscal year. The total break-even point of adjusted net margin was between 6% and 7% of indirect cost as a function of charges. Of the 60 new patients introduced to the hospital system, a gross margin per case of $211 was found. CONCLUSIONS: Free lung cancer screening can demonstrate profitability from downstream revenue with a lag time of 2 years.

Malignancy in kaolin pneumoconiosis found with F-18 FDG positron emission tomography.

Kaolin pneumoconiosis may produce radiologic findings similar to those of malignancy. Current management includes serial radiologic examination and lung sampling of suspicious parenchymal opacities and nodules to exclude associated malignancy. This may result in unnecessary pulmonary resections in patients with already compromised lung function. In a patient with known kaolin pneumoconiosis and multiple nodules, we used positron emission tomography to identify suspicious areas for malignancy that were confirmed by open lung biopsy, leading to successful lung cancer treatment.

Using the Hybrid Operating Room in Thoracic Surgery: A Paradigm Shift.

We describe the integration of the hybrid operation room cone-beam computed tomography (CT) scan technology into the practice of general thoracic surgery. The combination of the following three techniques: (1) cone-beam CT scan augmented navigational bronchoscopy, (2) cone-beam CT-guided percutaneous biopsy and/or fiducial placement, and (3) fiducial or image-guided video-assisted thoracic surgery resection, into a single-stage, single-provider procedure allows for diagnosis and treatment in one setting. Rapid on-site evaluation of cytological or pathology specimens is key to this "all-in-one" approach. The time from diagnosis to curative treatment can significantly be reduced using the hybrid operation room technology, leading to decreased upstaging, increased survival and facilitating the otherwise difficult intraoperative detection and resection of small and deeper lesions. Not only does this benefit the overall thoracic healthcare of the community but also provides a cost-effective paradigm for the institution.

Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD.

BACKGROUND: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability. METHODS: Seventeen patients with COPD completed a randomized, double-blind, placebo (PLC)-controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow-mediated dilation (FMD), a bioassay of endothelial function, was completed prior to and 3 h following each treatment. Phospho- and total endothelial NO synthase (NOS3) protein was evaluated after incubating endothelial cells with plasma from the patients prior to and following treatment. Fifteen demographically matched control subjects were tested at baseline for case control comparisons. RESULTS: Treatment with BH4 significantly (P ≤ .004) increased FMD, improving endothelial function in patients compared to control values (P ≥ .327). BH4 increased (P = .013) the ratio of phospho-NOS3 to total NOS3 protein. No changes in FMD (P ≥ .776) or the protein ratio (P = .536) were observed following PLC. CONCLUSIONS: An acute dose of BH4 was able to improve endothelial function in patients with COPD to values similar to control subjects. The improvement in endothelial function was accompanied by an increase in NOS3 phosphorylation. BH4 may represent a potential novel therapy to improve endothelial function and reduce cardiovascular disease risk in patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01398943; URL: www.clinicaltrials.gov.

A comparison of polysomnography and the SleepStrip in the diagnosis of OSA.

OBJECTIVE: To investigate the role of a portable screening device (SleepStrip) in the diagnosis of obstructive sleep apnea (OSA). METHODS AND MATERIALS: Prospective, nonrandomized double-blinded single cohort study at an academic health center. Patients with suspected OSA scheduled for an attended overnight Level I polysomnogram (PSG) and who consented to participate in the study wore the SleepStrip device at home the night after the PSG. The apnea-hypopnea index (AHI) determined by PSG was compared with the results of the SleepStrip recording. RESULTS: Thirty-seven patients with a mean age of 52.1 +/- 12.2 years and mean body mass index of 35.7 +/- 5.2 participated in the study. The overall agreement between the AHI and the SleepStrip results using Cohen's Kappa value was 0.139 (P = 0.19). The sensitivity and specificity of the SleepStrip for diagnosing severe OSA when the AHI was >40 were 33.3% and 95% (P = 0.05). When the AHI was >25, the SleepStrip sensitivity and specificity were 43.8% and 81.3% (P = 0.26). The sensitivity and specificity of the SleepStrip for diagnosing OSA in patients with an AHI >15 were 54.6% and 70%, respectively (P = 0.26). CONCLUSION: The SleepStrip has a low correlation with the AHI as measured by PSG. Further studies are needed before this device can be recommended as a screening tool for the diagnosis of OSA. EBM RATING: B-2b.

Obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome is caused by upper airway collapse during inspiration, causing intermittent hypoxemia, hypercapnia, acidosis, sympathetic nervous system activation, and arousal from sleep. Nighttime blood pressure is higher, but unexpectedly, daytime hypertension occurs. The prevalence of hypertension is very high and the incidence of hypertension increases as the number of apneic and hypopneic events per hour rises. Obesity is a major predisposing factor for the development of obstructive sleep apnea. Daytime sleepiness, snoring, and breathing pauses are important symptoms to elicit from the patient or sleep partner. Resistant hypertension is an important clue. Overnight polysomnography is required for diagnosis. Weight loss, avoidance of nocturnal sedatives, cessation of evening alcohol ingestion, and avoidance of the supine position during sleep are initial therapeutic actions in mild obstructive sleep apnea syndrome. Continuous positive airway pressure is the treatment of choice for patients unable to find relief from lifestyle changes. Blood pressure modestly improves with treatment.

Pulmonary function testing and extreme environments.

Millions of people worldwide engage in leisure or occupational activities in extreme environments. These environments entail health risks even for normal subjects. The presence of lung disease, or other conditions, further predisposes to illness or injury. Patients who have lung conditions should, but often do not, consult with their pulmonary clinicians before traveling. Normal subjects, including elderly or deconditioned adults, may be referred to pulmonologists for evaluation of risk prior to exposure. Other patients may present for consultations after complications occur. Pulmonary function testing before or after exposure can assist physicians counseling patients about the likelihood of complications.

Uneven Distribution of Cancer Histology in the National Lung Screening Trial.

The National Lung Screening Trial reported a 20% lower mortality due to lung cancer in the patients screened with low-dose computed tomography (LDCT) compared with plain chest radiography (XRAY). A hypothesis was raised that LDCT should detect more cases of all tissue types or else the distribution of tissue types should be equal between groups. Data were extracted regarding the tissue types of lung cancer and presenting stages from the 2011 NSLT report. A total of 1,993 cases of tissue diagnosed lung cancer were reported, 1,054 for the LDCT group and 939 for the XRAY group. Two tissue types were more prevalent in the XRAY group: small cell carcinomas (16.9% versus 13%; P < 0.05) and other non-small cell (ONSC) carcinomas (16.8% versus 12.4%; P < 0.05). The ONSC category excluded the usual non-small cell tissue types: adenocarcinomas, squamous, and large cell carcinomas and did include other known biologically unfavorable tissue types. The XRAY group also had a disproportionately large number of stage IV small cell and ONSC tumors (P < 0.05 for ONSC). Bronchoalveolar cell carcinomas were more prevalent in the LDCT group (10.4% versus 3.7%, P < 0.05), likely reflecting greater sensitivity for detection. In summary, this review found uneven distribution of cases and higher preponderance of stage IV tumors for 2 adverse tissue types in the XRAY group. The results are consistent with greater severity of disease in the XRAY group with potential for length time bias and reduced mortality benefit from LDCT screening.

Metastasizing Bronchopulmonary Leiomyosarcoma.

An otherwise healthy 55-year-old female, nonsmoker, was seen in pulmonary consultation for progressively worsening shortness of breath. She had undergone a complete hysterectomy 7 years prior for bleeding leiomyomas. On presentation, her initial chest X-ray showed a large right-sided pleural effusion with multiple pulmonary nodules. Two thoracenteses failed to reveal any cytologic abnormalities. Bronchoscopy revealed smooth, round, endobronchial lesions. Histologic examination showed features consistent with leiomyosarcoma. We present a rare case of a patient that initially had possible leiomyomas of the uterus surgically removed and years later presented with bronchopulmonary leiomyosarcoma.

Assessments of endothelial function and arterial stiffness are reproducible in patients with COPD.

BACKGROUND: Elevated cardiovascular disease risk is observed in patients with COPD. Non-invasive assessments of endothelial dysfunction and arterial stiffness have recently emerged to provide mechanistic insight into cardiovascular disease risk in COPD; however, the reproducibility of endothelial function and arterial stiffness has yet to be investigated in this patient population. OBJECTIVES: This study sought to examine the within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD. METHODS: Baseline diameter, peak diameter, flow-mediated dilation, augmentation index, augmentation index at 75 beats per minute, and pulse wave velocity were assessed three times in 17 patients with COPD (six males, eleven females, age range 47-75 years old; forced expiratory volume in 1 second =51.5% predicted). Session A and B were separated by 3 hours (within-day), whereas session C was conducted at least 7 days following session B (between-day). Reproducibility was assessed by: 1) paired t-tests, 2) coefficients of variation, 3) coefficients of variation prime, 4) intra-class correlation coefficient, 5) Pearson's correlations (r), and 6) Bland-Altman plots. Five acceptable assessments were required to confirm reproducibility. RESULTS: Six out of six within-day criteria were met for endothelial function and arterial stiffness outcomes. Six out of six between-day criteria were met for baseline and peak diameter, augmentation index and pulse wave velocity, whereas five out of six criteria were met for flow-mediated dilation. CONCLUSION: The present study provides evidence for within-day and between-day reproducibility of endothelial function and arterial stiffness in patients with COPD.

Multiple endobronchial mycetomas with varied appearances and mixed fungal flora.

We present images of a patient with multiple endobronchial mycetomas visible by bronchoscopy with varying appearances and with mixed fungal flora on culture. A 44-year-old African American male previously treated for pulmonary tuberculosis 11 years earlier presented with moderate hemoptysis and infiltrates in the right upper lobe on chest radiograph. He received levofloxacin without improvement in the infiltrate. Computed tomography scan revealed bronchiectasis, multiple intrabronchial masses, and air crescents. Diagnostic evaluation was negative for acid fast bacilli. Bronchoscopy revealed 4 separate endobronchial masses with varied appearances within dilated bronchiectatic airways. Culture of washings revealed Cunninghamella species, Aspergillus fumigatus, and Penicillium species. The patient underwent a lobectomy and was discharged on an azole antifungal agent, which was discontinued after 6 weeks.

Suppression of respiratory papillomatosis with malignant transformation by erlotinib in a kidney transplant recipient.

A 52-year-old non-smoker and renal transplant recipient developed an incessant cough. A CT scan of the thorax revealed ill-defined hazy opacities in the right upper lung. He was diagnosed with non-tuberculosis Mycobacterium chelonae/abscessus infection based on sputum culture results. A trial of antibiotics initially resulted in some clinical improvement. A subsequent CT of the thorax documented worsening of the lesions in the right lung and new lesions on the left. An intratracheal growth was noted. Bronchoscopy with biopsy of the tracheal lesions documented respiratory papillomatosis with transformation to squamous cell cancer. Test for high-risk human papilloma virus was positive. Video-assisted thoracoscopic surgery biopsy with wedge resection of the left lower lobe revealed metastatic squamous cell lung cancer. He was treated with one ablation followed by four cycles of chemotherapy. He has been maintained on erlotinib ever since. There has been no recurrence of the cough or papillomas.

A failure of adaptive servo-ventilation to correct central apneas in Cheyne-Stokes breathing.

An 80-year-old man with severe central sleep apnea due to Cheyne-Stokes breathing (AHI 41.2) caused by severe cardiac failure underwent a trial of adaptive servo-ventilation (ASV) by full face mask after failure of a fixed CPAP trial. Recommended procedure was closely followed and the ASV device activated normally during central apneas. Initial settings were EEP 5, PSmin 3, PSmax 15 on room air. The device did not capture the thorax or abdomen, as shown by lack of change in respiratory inductive plethysmography, despite expected mask pressure waveforms. Snoring was also detected during apneas with device activation. Desaturation continued, followed by arousals during hyperpnea. On the device, the patient clearly slept for 1-3 epochs during the central apneas only to awaken during hyperpnea. We hypothesize that the failure to capture may have resulted from "reverse" obstructive apnea, possibly due to glottic closure during ASV activation. We suggest that earlier manual adjustments to ASV in cases such as ours, prior to waiting for the recommended 20 to 40 min of sleep, may be appropriate in selected patients. We also consider additional interventions that may increase the likelihood of a successful trial.

An unusual cause of massive pleural effusion.

Pleural effusions in ovarian hyperstimulation syndrome, whether transudative or exudative, can occur in up to 30% of cases. This disorder is always reversible but may have various clinical presentations and degrees of severity. Although assessing for risk factors to predict clinical severity is helpful, it is rare for ovarian hyperstimulation syndrome to present as a massive pleural effusion requiring emergent intervention. In this study, such a case is reported.

Fungal colonization of a pneumonectomy stump.

A 59-year-old woman developed mild recurring hemoptysis once a week for several months after a fall with trauma to the chest. Sixteen years earlier she had undergone a right pneumonectomy at a hospital elsewhere for sequelae of pulmonary tuberculosis. Bronchoscopy, performed because of the recent hemoptysis, showed material in the pneumonectomy stump. The material had a gelatinous appearance, green color with a pale margin, and oblique striations. The material was removed by grasping with forceps and withdrawing the bronchoscope. Grocott methanamine silver stain was positive for septate, nonpigmented fungal organisms. Anatomic pathology microscopy also showed mucous, acute inflammatory cells, and necrotic tissue. Cytopathology of washings from the bronchial stump showed rare degenerated benign bronchial epithelial cells and fungal hyphae. Acid fast bacilli smears and cultures were negative. Bacterial cultures showed 3+ Pseudomonas aeruginosa. The patient had no further hemoptysis.