John F. Beamis

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 ∼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.

Endoscopic Treatment of Subglottic and Tracheal Stenosis by Radial Laser Incision and Dilation

Five patients with severe fibrous subglottic and tracheal stenosis were treated by endoscopic radial laser incision and dilation using both carbon dioxide and neodymium:yttrium aluminum garnet lasers. Good results were noted without complications in all patients in a follow-up period of at least 1 year. Careful selection of patients, excluding those with tracheal collapse or tracheomalacia, and preservation of tracheal epithelium with minimal heat and mechanical trauma are considered essential for good results.

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

BackgroundSevere 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.MethodsWe 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.ResultsThe 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.ConclusionWe 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.

Laser bronchoscopy in respiratory failure from malignant airway obstruction.

ObjectiveTo examine the value of laser bronchoscopy in patients with inoperable carcinoma of the lung who required ventilatory assistance for acute respiratory failure. DesignRetrospective review of the medical records of all patients undergoing laser bronchoscopy. SettingThe Lahey Clinic Medical Center, a tertiary referral center. PatientsThe medical records of 311 patients undergoing laser bronchoscopy at the Lahey Clinic Medical Center between 1982 and 1990 were reviewed. The 17 patients who required mechanical ventilation at the time of laser surgery formed the study group. InterventionsAll patients underwent neodymium:yttrium-aluminum-garnet laser bronchoscopy through a rigid bronchoscope in the operating room with use of jet ventilation and general anesthesia throughout the procedure. Postoperative care was directed by the same physician for all patients. Measurements and Main ResultsThe following data were extracted from medical records: age and sex of patient, cell type and location of tumor, length of time between diagnosis and laser therapy, treatment before and after laser therapy, number of days receiving mechanical ventilation before and after laser therapy, medical and operative complications, survival, and cause of death. The patients were divided into two groups on the basis of clinical improvement that permitted elective discontinuation of mechanical ventilation. Group 1 included patients who experienced clinical improvement permitting endotracheal extubation. Group 2 was composed of patients who died while still receiving mechanical ventilatory support or who were extubated before institution of comfort measures. The two groups were compared using nonparametric tests of significance, including the Mann-Whitney test.No significant differences were apparent between groups 1 and 2 regarding clinical characteristics before laser treatment. Patients in group 1 had significantly (p = .03) shorter requirements for mechanical ventilation after laser treatment than patients in group 2 (1 vs. 6 days). Similarly, patients in group 1 were more likely to receive additional treatment after laser therapy than patients in group 2 (seven of nine patients vs. two of eight patients; (p = .048). Patients in group 1 had significantly (p = .0038) longer survival than patients in group 2 (98 vs. 8.5 days). A greater endobronchial component to airway obstruction appeared to exist in patients in group 1 (nine of nine patients) vs. patients in group 2 (three of eight patients; p = .009). Extrinsic compression and submucosal tumor were more commonly seen in patients in group 2. In addition, patients in group 2 appeared to have a greater number of postoperative medical complications than patients in group 1. Operative complications were minor in both groups. ConclusionsIn nine of 17 patients, laser bronchoscopy appeared to improve the clinical status, permitting removal of mechanical ventilation and extubation and provided the opportunity for further treatment modalities in seven of the nine patients. Survival was improved in this subgroup, and requirement for mechanical ventilatory support was shortened. The improved outcome after laser therapy was related to the presence of obstructing endobronchial tumor as the cause of the respiratory insufficiency. Patients with inoperable carcinoma of the lung and respiratory failure should be evaluated for the presence of an endobronchial lesion that might

Efficacy of short term versus long term tube thoracostomy drainage before tetracycline pleurodesis in the treatment of malignant pleural effusions.

BACKGROUND--A study was undertaken to compare the efficacy of short term tube thoracostomy drainage with standard tube thoracostomy drainage before instillation of tetracycline for sclerotherapy of malignant pleural effusions. METHODS--The study consisted of a randomised clinical trial in a sequential sample of 25 patients with malignant pleural effusions documented cytopathologically. Fifteen patients were randomly assigned to group 1 (standard protocol) and 10 to group 2 (short term protocol). Patients in group 1 had tube thoracostomy suction drainage until radiological evidence of lung re-expansion was obtained and the amount of fluid drained was < 150 ml/day, before tetracycline (1.5 g) was instilled. The chest tube was removed when the amount of fluid drained after instillation was < 150 ml/day. Patients in group 2 also had suction drainage, but the tetracycline (1.5 g) was instilled when the chest radiograph showed the lung to be re-expanded and the effusion drained, which was usually within 24 hours. The chest tube was removed the next day. RESULTS--The response to tetracycline sclerotherapy in the two groups was the same (80%) but the duration of chest tube drainage was significantly shorter for patients in group 2 (median two days) than for those in group 1 (median seven days). CONCLUSIONS--The duration of chest tube drainage before sclerotherapy for malignant pleural effusions need not be influenced by the amount of fluid drained daily but by radiographic evidence of fluid evacuation and lung re-expansion. Shorter duration of drainage will reduce the length of hospital stay without sacrificing the efficacy of pleurodesis.

Endoscopic laser therapy for obstructing tracheobronchial lesions

The Lahey Clinic experience using laser bronchoscopy for relief of obstructive tracheobronchial lesions during a 7-year period from 1982 to 1989 involves 269 patients treated with 400 procedures. The carbon dioxide (CO2) laser was used for tracheal stenosis and granulation tissue. The neodymium:yttrium-aluminum-gamet (Nd:YAG) laser was used for all obstructing endobronchial neoplasms. Indications for therapy included severe dyspnea, hemoptysis, and postobstructive pneumonitis. All patients had relatively central lesions. A rigid bronchoscope was used to treat 88% of patients, and 12% of patients were treated with a flexible bronchoscope. One death occurred during the intraoperative period. Eleven deaths occurred within 1 week of therapy and were related to the presence of extensive malignant lesions or to coronary artery disease. Our experience indicates that bronchoscopic application of the CO2 or Nd: YAG laser affords effective palliation for patients with obstructive tracheobronchial lesions. The Nd:YAG laser is recommended for patients with bulky vascular endobronchial neoplasms, and the CO2 laser is best reserved for patients with benign tracheal stenosis and granulation tissue.

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.

Intraluminal low-dose rate brachytherapy for malignant endobronchial obstruction☆

From October 1985 through October 1989, 87 patients underwent 105 intraluminal brachytherapy treatments for endobronchial or endotracheal malignant tumors. Low-dose rate iridium-192 seeds were used. Of the 60 patients treated for primary lung carcinoma, 52 patients (87%) had previously received full-course external beam radiotherapy to the tumor sites. Ten patients were treated for symptomatic metastatic disease, and one patient had extension of tumor into the trachea from carcinoma of the cervical esophagus. Clinical or bronchoscopic improvement was noted in 42 patients (59%). No significant difference in the response rate was observed between various types of tumor. Patients who were treated with a radiation dose larger than 2500 cGy at a 2 cm radius had a significantly greater response rate (77%) than patients treated with a dose less than 2500 cGy (38%) (p = 0.001). A trend toward better results was apparent in patients who had undergone Nd:YAG laser bronchoscopy in the 2 weeks before brachytherapy. The treatments were well tolerated, and the incidence of serious complications was low and acceptable.

Lung cancer in women: Lahey clinic experience, 1957-1980

The incidence of lung cancer is increasing dramatically worldwide. Cancer of the lung, the number one cause of death from cancer in men in the United States, will soon surpass breast cancer to become the most frequent cause of cancer death in women. To detail the changing pattern of lung cancer, we reviewed the clinical features of all 1752 patients whose lung cancer was diagnosed at the Lahey Clinic from 1957 through 1980. Women comprised a constant proportion of the total number of clinic patients during this 24‐year period. Lung cancer in women increased markedly from 13% of all patients (1 to 6.8 ratio of women to men) in 1957 through 1960 to 35% (1 to 1.8 ratio) in 1977 through 1980. The authors reviewed pathologic specimens of 394 women with lung cancer. No significant change occurred in cell type distribution over the years: adenocarcinoma, 38%; epidermoid carcinoma, 20%; large cell carcinoma, 15%; small cell undifferentiated tumor, 13%; and other cell types, 14%. The incidence of all lung cancer cell types (Kreyberg Group 1 and Group 2) increased in women who smoked. Our study suggests that smoking is a major causal factor in the rising occurrence of all lung cancer cell types in women as contrasted to the preponderance of Kreyberg Group 1 tumors in men who smoke.

Safety Precautions for Bronchoscopic Nd-YAG Laser Surgery

The application of the neodymium-yttrium aluminum garnet (Nd-YAG) laser in bronchoscopy originated in Europe in 1981 and is now widespread in the United States. Transmissible through flexible fiberoptic quartz fibers and an efficient coagulator of tissue, the Nd-YAG laser deeply penetrates tissue not readily predictable by the endoscopist. Dangers associated with the Nd-YAG laser include complications secondary to inadvertent exposure to normal tissues or structures, tracheobronchial accidents (perforation, hemorrhage, fire), and complications related to anesthetic technique (respiratory depression). Hypoxemia related to persistent hemorrhage, accumulation of secretions or debris or both, or anesthesia-induced respiratory depression is the common denominator of most intraoperative and postoperative complications. Careful selection of patients, intraoperative monitoring of ventilation and blood gases, and techniques of rigid bronchoscopy are stressed to avoid complications.