Faculty Bibliography

Both advanced-stage lung cancer and malignant pleural mesothelioma are associated with a poor prognosis. Advances in treatment regimens for both diseases have had only a modest effect on their progressive course. Gene therapy for thoracic malignancies represents a novel therapeutic approach and has been evaluated in several clinical trials. Strategies have included induction of apoptosis, tumor suppressor gene replacement, suicide gene expression, cytokine-based therapy, various vaccination approaches, and adoptive transfer of modified immune cells. This review considers the clinical results, limitations, and future directions of gene therapy trials for thoracic malignancies.

There are 6 major types of airway complications following lung transplantation: necrosis and dehiscence, infection, granulation tissue formation, malacia, fistulae, and stenosis. This article reviews the risk factors for developing airway complications after lung transplantation, the clinical features of the complications, and treatment options for these problems.

The authors report the case of a 14-year-old girl with a residual malignant peripheral nerve sheath tumor after thoracotomy, chemotherapy, and radiation therapy. The residual tumor, which involved the intercostal muscles, aorta, and neural foramina of T4-10, was completely resected through a costotransversectomy and multiple hemilaminotomies with the patient in the prone position and was stabilized using a T1-12 pedicle screw fusion. Postoperatively, the patient developed several infections requiring multiple washouts and prolonged antibiotics. Thirty months after surgery, she developed a bronchocutaneous fistula. The hardware was removed, and a vascularized latissimus dorsi free flap was placed over the lung. She continued to have an air leak and presented 3 weeks later with a 40 degrees left thoracic curve. She returned to the operating room for a T2-L2 fusion with a vascularized fibular graft. On postoperative Day 1, she underwent a bronchoscopy and had her left lower lobe airways occluded with multiple novel one-way endobronchial valves. She is now 5 years out from her tumor resection and 3 years out from her definitive fusion. She has no evidence of residual tumor, infection, or pseudarthrosis and continues to remain asymptomatic.

PURPOSE: An endobronchial valve developed for treatment of severe emphysema has characteristics favorable for bronchoscopic treatment of air leaks. We present the results of a consecutive case series treating complex alveolopleural fistula with valves. DESCRIPTION: Patients with air leaks that persisted after treatment gave consent and compassionate use approval was obtained. Bronchoscopy with balloon occlusion was used to identify the airways to be treated. IBV Valves (Spiration, Redmond, WA) were placed after airway measurement. EVALUATION: During a 15-month period, 8 valve placement procedures were performed in 7 patients and all had improvement in the air leak. The median duration of air leakage was 4 weeks before and 1 day after treatment, with a mean of 4.5 days. Discharge within 2 to 3 days of the procedure occurred in 57% of the patients. A median of 3.5 valves (mode, 2.4) were used, and all valve removals were successful. There were no procedural or valve-related complications. CONCLUSIONS: Removable endobronchial valves appear to be a safe and effective intervention for prolonged air leaks.

BACKGROUND AND OBJECTIVE: This study evaluates two different techniques for topically anaesthetizing the airway with lidocaine during curvilinear probe endobronchial ultrasound bronchoscopy (CP-EBUS): standard injection through the working channel and spray catheter application. METHODS: This was a randomized, non-blinded, single-centre pilot study. Patients with plans for CP-EBUS under moderate sedation were enrolled. All patients received nebulized lidocaine followed by posterior oropharyngeal lidocaine via atomizer and a cotton ball swab using McGill forceps. Patients were then randomly assigned to lidocaine administration using spray catheter instillation or direct application through the working channel. Lidocaine was administered in a uniform fashion by a single investigator throughout the study. The primary end-point was the number of significant coughing episodes in the first 30 min of bronchoscopy. Other end-points included lidocaine and intravenous sedation medication dosage; severe coughing session; and number of transbronchial needle aspirations. RESULTS: Forty patients were included in the study: 20 patients in each group. The median numbers of coughing episodes in the first 30 min were 1 (spray catheter group) and 2 (standard injection group) (P < 0.004). Six patients in the standard installation group experienced severe coughing sessions, while there was none in the spray catheter group (P = 0.02). There were no statistical differences between the groups in the dosage of lidocaine or intravenous sedation medications used. There were a greater number of transbronchial needle aspirations performed in the spray catheter group (P = 0.008). CONCLUSIONS: Lidocaine delivery via the spray catheter reduced the number of significant coughing episodes compared with standard working channel injection during CP-EBUS. Larger studies are needed to confirm these exploratory findings.

Diagnostic bronchoscopy has undergone two major paradigm shifts in the last 40 years. First, the advent of flexible bronchoscopy gave chest physicians improved access to the tracheobronchial tree with a rapid learning curve and greater patient comfort compared with rigid bronchoscopy. The second paradigm shift has evolved over the last 5 years with the proliferation of new technologies that have significantly enhanced the diagnostic capabilities of flexible bronchoscopy compared with traditional methods. At the forefront of these new technologies is endobronchial ultrasound. In its various forms, endobronchial ultrasound has improved diagnostic yield for pulmonary masses, nodules, intrathoracic adenopathy, and disease extent, thereby reducing the need for more invasive surgical interventions. Various navigational bronchoscopy systems have become available to increase flexible bronchoscope access to small peripheral pulmonary lesions. Furthermore, various modalities of airway assessment, including optical microscopic imaging technologies, may play significant roles in the diagnosis of a variety of pulmonary diseases in the future. Finally, the combination of new diagnostic bronchoscopy technologies and novel approaches in molecular analysis and biomarker assessment hold promise for enhanced diagnosis and personalized management of many pulmonary disorders. In this review, we provide a contemporary review of diagnostic bronchoscopy developments over the past decade.

In the current era of organ shortages and long wait times for life-saving transplants, marginal or extended donors are increasingly being considered; one such category of marginal organs is from donors with a previous history of malignancy. Melanoma in particular has been associated with increased risk of developing late recurrence. In this report, we describe a case of fatal donor melanoma transmission to a 64-year-old lung transplant recipient 32 years after surgical excision of the melanoma. Based on this report and review of the available literature, we conclude that a history of donor melanoma, regardless of the stage and time interval from 'curative' surgical resection, should remain a strong relative contraindication to transplantation.

We previously showed that a single intrapleural dose of an adenoviral vector expressing interferon-beta (Ad.IFN-beta) in patients with malignant pleural mesothelioma (MPM) or malignant pleural effusions (MPE) resulted in gene transfer, humoral antitumor immune responses, and anecdotal clinical responses manifested by modified Response Evaluation Criteria in Solid Tumors (RECIST) disease stability in 3 of 10 patients at 2 months and an additional patient with significant metabolic response on positron emission tomography (PET) imaging. This phase I trial was conducted to determine whether using two doses of Ad.IFN-beta vector would be superior. Ten patients with MPM and seven with MPE received two doses of Ad.IFN-beta through an indwelling pleural catheter. Repeated doses were generally well tolerated. High levels of IFN-beta were detected in pleural fluid after the first dose; however, only minimal levels were seen after the second dose of vector. Lack of expression correlated with the rapid induction of neutralizing Ad antibodies (Nabs). Antibody responses against tumor antigens were induced in most patients. At 2 months, modified RECIST responses were as follows: one partial response, two stable disease, nine progressive disease, and two nonmeasurable disease. One patient died after 1 month. By PET scanning, 2 patients had mixed responses and 11 had stable disease. There were seven patients with survival times longer than 18 months. This approach was safe, induced immune responses and disease stability. However, rapid development of Nabs prevented effective gene transfer after the second dose, even with a dose interval as short as 7 days.