Long-term Survival Results following Endobronchial RF Ablation in a Healthy-Porcine Model.

This paper presents results from long-term survival study where healthy swine were ablated with a novel technology designed for treating early-stage non-small cell lung cancer using an endobronchial flexible catheter.Methods - The radiofrequency ablation (RFA) system has been presented previously and consisted of an ablation catheter, radiofrequency generator, irrigation pump for infusion of hypertonic saline (HS) and a laptop. The catheter carried an occlusion balloon, a 5 mm long RF electrode, with irrigation holes, and a 1 mm long electrode for bipolar impedance measurements. The outer diameter (OD) was 1.4 mm for compatibility with current bronchoscopes, navigation systems and radial EBUS. Nine swine were treated in this study with survival times of 1, 4 and 12 weeks (N=3 at each time point). In all animals, the treatment sites consisted of one location in the upper right lung (RUL) and another one in the lower right lung (RLL). CTs were taken pre-op, immediately post-op and at every 2 weeks post treatment. Ablation times ranged from 6 to 8 min and average applied power was 68 W (range 63 - 72 W).Results - At 1-week survival, large zones of necrotic tissue were observed in all respective 6 ablations. Ablation volumes had an average diameter of 3.2 cm at RUL locations and 3.8 cm in RLLs (likely due to longer RLL ablation durations). As time progressed, the necrotic tissue was gradually replaced with fibrotic tissue. At 4-week survival, the replacement was almost complete in all respective 3 animals. As a result, ablation volumes decreased to an average diameter of 1.3 cm at RUL locations and 2.3 cm in RLLs (likely due to longer RLL ablation durations). At 12-week survival, as the replacement process continued, histopathology revealed zones of residual necrotic tissue that were further reduced in size. Ablation zones had been resorbed and contracted by fibrous scar tissue. The average volume of the treatment effect decreased to 1.1 cm (RUL) and to 1.6 cm (RLL) in equivalent diameter. There were no complications in any of the nine animals.Conclusion - In healthy swine lungs, RFA with a 1.4-mm OD, radial-EBUS-sheath-compatible, endobronchial catheter was effective and safe. This system and therapeutic approach may be considered for further evaluation in minimally invasive treatment of tumorous lung nodules.

Early Preclinical Experience with a Novel Endobronchial Radiofrequency Ablation System for Lung Cancer Treatment.

This paper introduces a novel technology for treating early-stage non-small cell lung cancer using an endobronchial approach via a flexible radiofrequency ablation (RFA) catheter. Methods - The RFA system consisted of an ablation catheter, radiofrequency generator, irrigation pump for infusion of hypertonic saline (HS) and a laptop. The catheter carried an occlusion balloon, a 5 mm long RF electrode, with irrigation holes, and a 1 mm long electrode for bipolar impedance measurements. The outer diameter was 1.4 mm for compatibility with current bronchoscopes, navigation systems and radial EBUS. The RFA system was extensively bench tested on fresh heart, liver and lung animal tissues using power levels of 30 - 60 W, RF energy delivery durations of 3 - 15 min and HS concentrations of 5% and 23.4%. Two swine were then treated at 60 W for 15 min per bronchus. Several bronchi were involved. For both animals and for all treatment sites, 20% HS was used. Animals were survived for six weeks. Results - Bench studies showed that 60 W, 7 - 15 min ablations can produce large ablation volumes, in excess of 3 - 4 cm diameter. In the chronic animal study, no clinically adverse events occurred. There was no evidence of hemorrhage. Animals vital signs, breathing patterns and their behavior were normal throughout the six-week period. Their appetite was normal and they gained weight according to expectations. The RF ablation created discrete volumes of thermal coagulative necrosis which were subsequently encapsulated ("walled off") by zones of organized fibrosis. The dimensions of coagulative necrotic sequestra met expectations, as at six weeks they exceeded volumes corresponding to 2 cm nodules, the size of tumors normally addressed in the peripheral lung by localized therapy. Conclusion - This therapy showed promise. Appropriate energy settings combined with suitable treatment locations safely produced large ablation volumes of uniform thermal coagulative necrosis. Further studies and optimization of treatment parameters can develop it into a mainstream therapy for treating early-stage lung tumors in humans.

Role of airway receptors in altitude-induced dyspnea.

PURPOSE: The purpose of this study was to examine the role of airway receptors in respiratory-related sensations after ascent to altitude. METHODS: Ratings of respiratory-related sensations, perceived exertion and acute mountain sickness, heart rate, and peripheral oxygen saturation were recorded at rest and exercise in male and female subjects who had inhaled either aerosolized saline or saline with tetracaine after acute ascent to an altitude of 3500 m and after prolonged acclimatization of 18 d at altitudes between 4000 and 5000 m. RESULTS: Tetracaine had no effect on respiratory-related sensations at altitude either at rest or during exercise, and male and female subjects experienced similar respiratory-related sensations. Sensations of rapid breathing were experienced at rest after acute exposure to 3500 m as compared with sea level, but not after acclimatization to 5000 m. Sensations of rapid breathing, air hunger, and heavy breathing were experienced during exercise after acute and prolonged altitude exposure as compared with sea level, with a sensation of chest tightness experienced at 3500 m and a sensation of gasping experienced at 5000 m. CONCLUSION: These results suggest that airway afferents play no role in the respiratory-related sensations experienced by male and female subjects either during acute ascent to altitude or after prolonged acclimatization at altitude.

Intrathoracic neoplasms other than bronchogenic carcinoma.

Intrathoracic neoplasms other than bronchogenic carcinoma comprise a disparate group of tumors that have in common an anatomic location within the thorax. For the purposes of this review, they are divided into three categories: pulmonary metastases from locations other than the thorax, mediastinal neoplasms, and unusual primary lung neoplasms. This article reviews the recent literature; discusses evolving strategies for imaging, diagnosis, and treatment; and presents promising research developments.

Sequential administration of cyclophosphamide and granulocyte-colony stimulating factor relieves impaired myeloid maturation in Felty's syndrome.

A patient with Felty's syndrome (FS) and persistent profound neutropenia developed recurrent infections and sepsis syndrome. No impairment of granulocyte-macrophage colony development was observed in vitro. Marrow morphology revealed an absence of mature neutrophil forms despite administration of granulocyte-colony stimulating factor (G-CSF). However, pretreatment with bolus cyclophosphamide (CY) permitted the growth factor to relieve this impairment of late myeloid maturation and resulted in a brisk, albeit short, burst of neutrophilia. This suggests that immune interference in myelopoiesis can be overcome by growth factor administration if immune activity is adequately dampened by immunosuppressive therapy.

Approach to pulmonary metastases.

The prognosis and response to therapy of metastases to the lungs are variable and highly dependent on the origin of the primary tumor and on the extent and pattern of spread. Due to the complex pathogenesis underlying the development of pulmonary metastases, specific tumor types often display characteristic clinical and radiographic patterns. Understanding these concepts is of paramount importance when planning a diagnostic work-up for patients with possible pulmonary metastases. This review presents state of the art strategies in imaging, medical therapy, and surgery. It should provide the busy pulmonologist with the information needed to devise safe and efficient diagnostic and treatment strategies for patients with pulmonary metastases of extrathoracic origin.

Mediastinal tumors.

Mediastinal tumors are comprised of various benign and malignant neoplasms that share the same anatomic location within the thorax. The mediastinum is traditionally divided into three compartments: the anterior, middle, and posterior mediastinum. This division, based on lateral chest radiographs, helps clinicians establish appropriate differential diagnoses and plan further imaging, diagnostic, and treatment strategies. With the continued and complex advances in imaging, medical treatment, and surgery, we recommend a multidisciplinary approach to the management of mediastinal tumors. This discussion is intended to guide the pulmonary specialist through this potentially complex approach.

Unusual primary lung neoplasms.

Bronchial carcinoids and hamartomas are, respectively, the most common malignant and benign unusual primary lung neoplasms. These tumors are often asymptomatic but can cause central airway obstruction. Helical computed tomographic and radionuclide scintigraphic advances in their detection and evolution, together with newer interventional bronchoscopy techniques such as neodymium:yttrium-aluminum-garnet laser phototherapy and cryotherapy, represent important improvements in the diagnosis and management of patients with such tumors.