A multicenter pilot study of a bronchial valve for the treatment of severe emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects millions of people and has limited treatment options. Surgical treatments for severe COPD with emphysema are effective for highly selected patients. A minimally invasive method for treating emphysema could decrease morbidity and increase acceptance by patients. OBJECTIVE: To study the safety and effectiveness of the IBV(R) Valve for the treatment of severe emphysema. METHODS: A multicenter study treated 91 patients with severe obstruction, hyperinflation and upper lobe (UL)-predominant emphysema with 609 bronchial valves placed bilaterally into ULs. RESULTS: Valves were placed in desired airways with 99.7% technical success and no migration or erosion. There were no procedure-related deaths and 30-day morbidity and mortality were 5.5 and 1.1%, respectively. Pneumothorax was the most frequent serious device-related complication and primarily occurred when all segments of a lobe, especially the left UL, were occluded. Highly significant health-related quality of life (HRQL) improvement (-8.2 +/- 16.2, mean +/- SD change at 6 months) was observed. HRQL improvement was associated with a decreased volume (mean -294 +/- 427 ml, p = 0.007) in the treated lobes without visible atelectasis. FEV(1), exercise tests, and total lung volume were not changed but there was a proportional shift, a redirection of inspired volume to the untreated lobes. Combined with perfusion scan changes, this suggests that there is improved ventilation and perfusion matching in non-UL lung parenchyma. CONCLUSION: Bronchial valve treatment of emphysema has multiple mechanisms of action and acceptable safety, and significantly improves quality of life for the majority of patients.

Endoscopic treatment of early-stage lung cancer.

BACKGROUND: Disease-free survival after surgical resection of lung carcinoma in situ has been reported as over 90%. After resection of stage IA non-small cell lung cancer, survival at 5 years is approximately 60% to 70%. If endoscopic or bronchoscopic treatments of early-stage lung cancer can provide similar disease-free survival with less perioperative mortality, morbidity, and cost, then they may be alternative front-line therapies. METHODS: The authors review early-stage lung cancer detection by fluorescence bronchoscopy and the potential treatment of this disease by endoscopic techniques (photodynamic therapy, brachytherapy, Nd:YAG laser, electrocautery, and cryotherapy). RESULTS: Several reports have noted improved outcomes using endoscopic therapies for early-stage lung cancer, but insufficient data preclude firm conclusions regarding the role of fluorescence bronchoscopy, endobronchial brachytherapy, or electrocautery in early-stage lung cancer. Other than resection, photodynamic therapy may represent the best approach at this time. The principal indication for laser bronchoscopy is palliation of central airway obstruction. CONCLUSIONS: The identification of early-stage lung cancer provides no advantage if we have little to offer the patient short of traditional therapy. The value of newer treatment techniques and methods requires verification.

Cryotherapy, electrocautery, and brachytherapy.

Since it was first used 70 years ago, brachytherapy has become an effective tool in the treatment with tracheal bronchial malignancy including primary and recurrent bronchogenic carcinoma and metastatic carcinoma. The technique has evolved from interstitial implantation of radioactive sources directly to the tumor using rigid bronchoscopy to intraluminal placement of a radioactive source into a polyethylene afterloading catheter placed using FB. Intraluminal brachytherapy is effective in palliating complications caused by malignant endobronchial tumors such as dyspnea, hemoptysis, intractable cough, atelectasis, and postobstructive pneumonia. Brachytherapy may be combined with external beam radiation, Nd:YAG laser therapy, and chemotherapy to enhance the palliative treatments of patients. The risk of severe complications from brachytherapy may be caused more by location of tumor being treated rather than those fractionations scheme. When tumor involves the mainstem bronchi and upper lobes, it seems prudent to obtain CT to exclude tumor invasion of the pulmonary arteries or considerable destruction of the bronchial wall and mediastinal invasion of the tumor. Patients with findings such as these should not be treated with endobronchial brachytherapy or treated with LDR brachytherapy. Brachytherapy is proved to be effective and a safe palliative treatment for endobronchial malignancies, but further investigations are necessary to determine the optimal dose scheme and its efficiency in bronchogenic carcinoma and combined with external beam radiation therapy or surgery or other endobronchial procedures such as Nd:YAG laser or cryotherapy.

Tumor necrosis factor-alpha stimulates attachment of small cell lung carcinoma to endothelial cells.

Tumor cell attachment to endothelial cells (ECs) is an important step in the metastasis of small cell lung carcinoma (SCLC). Tumor necrosis factor-alpha (TNF-alpha) stimulation of ECs increases the attachment of some malignant cell types to ECs by affecting the expression of cell adhesion molecules (CAMs). Similarly, the inhibition of EC protein kinase C (PKC) and tyrosine kinase (TK) pathways modulates TNF-alpha-mediated effects on CAM expression. We hypothesized that TNF-alpha would increase SCLC attachment to ECs by affecting CAM expression through activation of PKC and TK pathways. To test this hypothesis, human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-alpha (0 to 500 U/mL) for variable time periods (1 to 24 hours), and the attachment of H82 cells (an SCLC cell line) to the HUVECs was quantified. TNF-alpha stimulation of the HUVECs increased H82 attachment from 28.1% +/- 1.6% to 48.8% +/- 1.7% (P < .05). Preincubation of HUVECs with the PKC inhibitors bis-indolylmaleimide (BIN) or calphostin C or the TK inhibitors genistein or herbimycin A (HMA) blocked the TNF-alpha-induced increase in H82 cell attachment. The addition of antibodies to vitronectin (Vn) or beta1-integrin to TNF-alpha-activated HUVECs before the addition of the H82 cells also significantly decreased H82 attachment, whereas the addition of antibodies to E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), neural cell adhesion molecule (NCAM), sialyl-Lewis(x), fibronectin (Fn), alpha(v)-integrin, alpha3-integrin, alpha4-integrin, or alpha5-integrin had no effect on SCLC attachment. In summary, the TNF-alpha-mediated increase in SCLC attachment to ECs appears to be mediated by the activation of EC PKC and TK pathways as well as through effects on the function or expression of EC Vn and beta1 integrin.

Long-term results of fiberoptic bronchoscopic balloon dilation in the management of benign tracheobronchial stenosis.

STUDY OBJECTIVES: To assess the short- and long-term effects of balloon dilatation using a fiberoptic bronchoscope in the management of benign tracheobronchial stenosis (TBS). Treatment strategies have included open surgical resection or endoscopic techniques. The endoscopic techniques have included Nd:Yag laser, cryotherapy, stent placement, rigid bronchoscopy, and balloon dilation (BD). DESIGN: Prospective sequentiality study. SETTING: Tertiary care academic hospital. PATIENTS: This study consisted of 14 patients, ages ranging from 35 to 72 years, whose symptoms of dyspnea, cough, or wheeze were attributable to a TBS. INTERVENTION: This study describes the use of flexible fiberoptic bronchoscopy (FFB) with a balloon catheter for airway dilation. Each patient underwent FFB, in which a balloon catheter was threaded over the guidewire and positioned across the stenosis. Under direct visualization, the balloon was inflated for 30 to 120 s. Repeat inflation-deflation cycles were done if airway narrowing remained after the initial attempt. RESULTS: Seven patients had TBS following lung transplantation, three after sleeve resection, two following irradiation therapy, and two due to fibrosing mediastinitis. All patients had initial success: increased airway dimensions and symptom relief. Ten patients had successful airway dilation after one session. Of the four patients who required multiple sessions, one had cryotherapy and in each of the others an airway stent was placed. CONCLUSIONS: BD offers immediate symptom relief and can be used in conjunction with Nd:Yag laser, cryotherapy, stent placement, or mechanical dilation with a rigid bronchoscope. The advantages of FFB with BD include operator familiarity, patient safety, and avoidance of general anesthesia.