Randomized phase II trial of sulindac for lung cancer chemoprevention.

INTRODUCTION: Sulindac represents a promising candidate agent for lung cancer chemoprevention, but clinical trial data have not been previously reported. We conducted a randomized, phase II chemoprevention trial involving current or former cigarette smokers (≥30 pack-years) utilizing the multi-center, inter-disciplinary infrastructure of the Cancer Prevention Network (CPN). METHODS: At least 1 bronchial dysplastic lesion identified by fluorescence bronchoscopy was required for randomization. Intervention assignments were sulindac 150mg bid or an identical placebo bid for 6 months. Trial endpoints included changes in histologic grade of dysplasia (per-participant as primary endpoint and per lesion as secondary endpoint), number of dysplastic lesions (per-participant), and Ki67 labeling index. RESULTS: Slower than anticipated recruitment led to trial closure after randomizing participants (n=31 and n=30 in the sulindac and placebo arms, respectively). Pre- and post-intervention fluorescence bronchoscopy data were available for 53/61 (87%) randomized, eligible participants. The median (range) of dysplastic lesions at baseline was 2 (1-12) in the sulindac arm and 2 (1-7) in the placebo arm. Change in dysplasia was categorized as regression:stable:progression for 15:3:8 (58%:12%:31%) subjects in the sulindac arm and 15:2:10 (56%:7%:37%) subjects in the placebo arm; these distributions were not statistically different (p=0.85). Median Ki67 expression (% cells stained positive) was significantly reduced in both the placebo (30 versus 5; p=0.0005) and sulindac (30 versus 10; p=0.0003) arms, but the difference between arms was not statistically significant (p=0.92). CONCLUSIONS: Data from this multi-center, phase II squamous cell lung cancer chemoprevention trial do not demonstrate sufficient benefits from sulindac 150mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention.

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

BACKGROUND: Thoracoscopic 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. METHODS: Patients 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. RESULTS: A 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. CONCLUSIONS: We 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.

Changing patterns in interventional bronchoscopy.

BACKGROUND AND OBJECTIVE: Many interventional tools for airway disorders can now be delivered via flexible bronchoscopy (FB), including neodymium-yttrium aluminium garnet laser, electrocautery, argon plasma coagulation, cryotherapy, balloon dilatation and metal or hybrid stents. Comparison of outcomes for patients undergoing rigid bronchoscopy (RB) with those treated using FB highlights the usefulness of the FB approach. METHODS: A retrospective medical record review of all interventional bronchoscopy procedures performed at Lahey Clinic over the past 8 years was conducted. Patients were categorized into two groups according to the procedure used, that is, RB (251 patients), and FB (161 patients) groups. Patients with malignancies were included as a separate subgroup, comprising 178 RB and 117 FB patients. For every procedure, the location of the lesion, patient survival from the first interventional procedure performed, and in patients with malignancy, additional treatments received such as chemotherapy and radiation were recorded. RESULTS: Ninety per cent of RB procedures were performed in patients with tracheal or main stem lesions, while over half the patients undergoing FB had more distal lesions. A trend towards increasing use of FB for interventional procedures in recent years was noted. CONCLUSIONS: FB is a valuable alternative to RB for treating less advanced malignant disease or distal airway lesions.

Ease of use of watanabe spigot for alveolopleural fistulas.

Pulmonary fistulas are associated with a high risk of morbidity and mortality. We report 2 cases of alveolopleural fistulas, 1 in a patient with chronic hydropneumothorax and the other after wedge biopsy. In both cases, Watanabe spigot (Novatech, Grasse, France) was placed for bronchial occlusion with short-term success.

Molecular typing of Mycobacterium chelonae isolates from a pseudo-outbreak involving an automated bronchoscope washer.

We describe a pseudo-outbreak of Mycobacterium chelonae infection in bronchoalveolar lavage fluid from 9 patients that was traced to contamination of an automated bronchoscope washer. Molecular typing using repetitive extragenic palindromic polymerase chain reaction was helpful in confirming epidemiologic and clinical findings.

Post tracheostomy and post intubation tracheal stenosis: report of 31 cases and review of the literature.

BACKGROUND: Severe post tracheostomy (PT) and post intubation (PI) tracheal stenosis is an uncommon clinical entity that often requires interventional bronchoscopy before surgery is considered. We present our experience with severe PI and PT stenosis in regards to patient characteristics, possible risk factors, and therapy. METHODS: We conducted a retrospective chart review of 31 patients with PI and PT stenosis treated at Lahey Clinic over the past 8 years. Demographic characteristics, body mass index, co-morbidities, stenosis type and site, procedures performed and local treatments applied were recorded. RESULTS: The most common profile of a patient with tracheal stenosis in our series was a female (75%), obese (66%) patient with a history of diabetes mellitus (35.4%), hypertension (51.6%), and cardiovascular disease (45.1%), who was a current smoker (38.7%). Eleven patients (PI group) had only oro-tracheal intubation (5.2 days of intubation) and developed web-like stenosis at the cuff site. Twenty patients (PT group) had undergone tracheostomy (54.5 days of intubation) and in 17 (85%) of them the stenosis appeared around the tracheal stoma. There was an average of 2.4 procedures performed per patient. Rigid bronchoscopy with Nd:YAG laser and dilatation (mechanical or balloon) were the preferred methods used. Only 1(3.2%) patient was sent to surgery for re-stenosis after multiple interventional bronchoscopy treatments. CONCLUSION: We have identified putative risk factors for the development of PI and PT stenosis. Differences in lesions characteristics and stenosis site were noted in our two patient groups. All patients underwent interventional bronchoscopy procedures as the first-line, and frequently the only treatment approach.

Healthcare-associated pneumonia: principles and emerging concepts on management.

Healthcare-associated pneumonia (HCAP) is a relatively new entity that includes pneumonia occurring in healthcare settings other than acute-care hospitals. Many patients with HCAP are at greater risk for colonization and infection with multi-drug resistant (MDR) bacteria such as Pseudomonas aeruginosa, Gram-negative bacilli-producing extended-spectrum beta-lactamases and methicillin-resistant Staphylococcus aureus. Infections with these MDR pathogens require different empiric antibiotic therapy. To avoid initiation of inappropriate antibiotic therapy that may result in poorer patient outcomes, new principles for HCAP management were outlined in the 2005 American Thoracic Society and Infectious Diseases Society of America guidelines. These guidelines were suggested for patients assessed in acute-care hospitals and clinics, and may not be applicable for all patients with suspected HCAP in nursing homes and other long-term care settings. This review article addresses HCAP management strategies in both clinical settings.

Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.

Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80-85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine if gene expression in histologically normal large-airway epithelial cells obtained at bronchoscopy from smokers with suspicion of lung cancer could be used as a lung cancer biomarker. Using a training set (n = 77) and gene-expression profiles from Affymetrix HG-U133A microarrays, we identified an 80-gene biomarker that distinguishes smokers with and without lung cancer. We tested the biomarker on an independent test set (n = 52), with an accuracy of 83% (80% sensitive, 84% specific), and on an additional validation set independently obtained from five medical centers (n = 35). Our biomarker had approximately 90% sensitivity for stage 1 cancer across all subjects. Combining cytopathology of lower airway cells obtained at bronchoscopy with the biomarker yielded 95% sensitivity and a 95% negative predictive value. These findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke.

Interventional pulmonology techniques for treating malignant large airway obstruction: an update.

PURPOSE OF REVIEW: This paper reviews the recent literature on the management of malignant large airway obstruction using interventional pulmonology techniques. RECENT FINDINGS: A number of interventional techniques have been developed during the last 25 years. Recent papers expand on this work, reaffirming the utility of laser bronchoscopy; introducing newer, less expensive technologies with similar outcomes; and attesting to the benefit of airway stenting. Electrocautery is likely to replace laser as the preferred tool for coagulation of intrinsic airway tumors because it is readily available in most hospitals and is much less expensive to set up. Several large series have attested to the excellent results achieved with airway stents placed to relieve extrinsic large airway obstruction. Investigators are using new technologies in an attempt to predict the proper location of stent placement to achieve maximum palliation of symptoms. Published guidelines are available describing the application of interventional techniques. SUMMARY: A number of interventional pulmonology techniques are available to treat large airway obstruction from malignant tumor. Clinical studies and personal experience attest to their utility. More evidenced-based studies are needed to help determine the best technique for a particular type of obstruction.

A novel instrument for the evaluation of the pleural space: an experience in 34 patients.

STUDY OBJECTIVES: To test a novel semirigid pleuroscope to be used by pulmonologists for the diagnosis and treatment of pleural diseases. DESIGN: Prospective study. SETTING: Three tertiary referral centers for pulmonary diseases. PATIENTS: Thirty-four patients who were referred for medical thoracoscopy between September 2000 and April 2001. MEASUREMENTS AND RESULTS: Thirty-six procedures were performed. The most common indications were for pleurodesis of a malignant pleural effusion (53%) or for evaluation of an exudative effusion of unknown etiology (44%). All operators found the instrument easy to use. In all but one case, the images were thought to be adequate, despite the presence of adhesions in 12 patients and loculations in 8 patients. Pleural biopsies were performed in 13 patients, and talc pleurodesis procedures were performed in 25 patients. Mean (+/- SD) duration of chest tube drainage was 2.9 +/- 1.8 days postprocedure. There were no complications. CONCLUSIONS: The prototype semirigid pleuroscope is a useful instrument in the diagnosis and management of pleural diseases. It is similar in design to a standard flexible bronchoscope, so the skills involved in operating the instrument should already be familiar to the practicing pulmonologist. It is compatible with existing video processors and light sources, so little additional equipment must be added to the endoscopy suite. The semirigid pleuroscope may allow for an increase in the performance of medical thoracoscopy by pulmonologists.