Alban Lovis

Sleep-Disordered Breathing and Vascular Function in Patients With Chronic Mountain Sickness and Healthy High-Altitude Dwellers

BACKGROUND Chronic mountain sickness (CMS) is often associated with vascular dysfunction, but the underlying mechanism is unknown. Sleep-disordered breathing (SDB) frequently occurs at high altitude. At low altitude, SDB causes vascular dysfunction. Moreover, in SDB, transient elevations of right-sided cardiac pressure may cause right-to-left shunting in the presence of a patent foramen ovale (PFO) and, in turn, further aggravate hypoxemia and pulmonary hypertension. We speculated that SDB and nocturnal hypoxemia are more pronounced in patients with CMS compared with healthy high-altitude dwellers, and are related to vascular dysfunction. METHODS We performed overnight sleep recordings, and measured systemic and pulmonary artery pressure in 23 patients with CMS (mean ± SD age, 52.8 ± 9.8 y) and 12 healthy control subjects (47.8 ± 7.8 y) at 3,600 m. In a subgroup of 15 subjects with SDB, we assessed the presence of a PFO with transesophageal echocardiography. RESULTS The major new findings were that in patients with CMS, (1) SDB and nocturnal hypoxemia was more severe (P < .01) than in control subjects (apnea-hypopnea index [AHI], 38.9 ± 25.5 vs 14.3 ± 7.8 number of events per hour [nb/h]; arterial oxygen saturation, 80.2% ± 3.6% vs 86.8% ± 1.7%, CMS vs control group), and (2) AHI was directly correlated with systemic blood pressure (r = 0.5216; P = .001) and pulmonary artery pressure (r = 0.4497; P = .024). PFO was associated with more severe SDB (AHI, 48.8 ± 24.7 vs 14.8 ± 7.3 nb/h; P = .013, PFO vs no PFO) and hypoxemia. CONCLUSIONS SDB and nocturnal hypoxemia are more severe in patients with CMS than in control subjects and are associated with systemic and pulmonary vascular dysfunction. The presence of a PFO appeared to further aggravate SDB. Closure of the PFO may improve SDB, hypoxemia, and vascular dysfunction in patients with CMS. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Thoracoscopic resection of pulmonary metastasis: Current practice and results

Video-assisted thoracoscopic surgery (VATS) is currently a routinely performed procedure for the management of early non small cell lung cancer. The oncological results of VATS in terms of local recurrence and overall survival are equivalent or superior to those of conventional thoracotomy with lower morbidity and hospital stay. In the field of pulmonary metastasectomy, current guidelines support a thoracotomy approach in order to properly palpate the lung and detect nodules too small to be identified on standard radiological examinations (typically less than 5mm in diameter). However, the oncological and clinical significance of these millimetric nodules is not known. This has led some thoracic surgeons to rethink the approach of solitary pulmonary metastasectomy: because of improvements in thin slice helical CT-scans, some support a VATS approach for solitary pulmonary nodules without formal bimanual palpation and suggest this allows equivalent oncological results and decreased surgical morbidity.

Impact of induction therapy on airway complications after sleeve lobectomy for lung cancer.

BACKGROUND Sleeve lobectomy is a valid alternative to pneumonectomy for the treatment of centrally located operable non-small cell lung cancer (NSCLC), but concern has been evoked regarding a potentially increased risk of bronchial anastomosis complications after induction therapy. This study examined the impact of induction therapy on airway healing after sleeve lobectomy for NSCLC. METHODS Bronchial anastomosis complications were recorded with respect to the induction regimen applied (neoadjuvant chemotherapy vs chemoradiotherapy) in a consecutive series of patients with sleeve lobectomy for NSCLC. RESULTS Ninety-nine patients underwent sleeve resection, 28 of them after induction therapy. Twelve patients received chemotherapy alone, and 16 patients had radiochemotherapy. There were no significant differences in postoperative 90-day mortality (3.6% vs 2.8%) and morbidity (54% vs 49%) for patients with and without induction therapy. Bronchial anastomosis complications occurred in 3 patients (10.8%) with neoadjuvant therapy and in 2 (2.8%) without (p = 0.3). In the induction therapy group, two bronchial stenoses occurred after radiochemotherapy and one bronchopleural fistula after chemotherapy alone. In patients without induction therapy, one bronchial stenosis and one bronchopleural fistula were observed. All bronchial stenoses were successfully treated by dilatation, and both bronchopleural fistulas occurring after right lower lobectomy were successfully treated by reoperation and completion sleeve bilobectomy with preservation of the upper lobe. CONCLUSIONS Sleeve lobectomy for NSCLC can be safely performed after induction chemotherapy and radiochemotherapy with mortality and incidence of airway complications similar to that observed in nonpretreated patients. The treatment of airway complications does not differ for patients with and without induction therapy.

Impact of Lung Function Changes After Induction Radiochemotherapy on Resected T4 Non-Small Cell Lung Cancer Outcome

BACKGROUND Induction radiochemotherapy, followed by resection, for T4 non-small cell lung cancer, has shown promising long-term survival but may be associated with increased postoperative morbidity and death, depending on patient selection. Here, we determined the effect of induction radiochemotherapy on pulmonary function and whether postinduction pulmonary function changes predict hospital morbidity and death and long-term survival. METHODS A consecutive prospective cohort of 72 patients with T4 N0-2 M0 non-small cell lung cancer managed by radiochemotherapy, followed by resection, is reported. All patients underwent thoracoabdominal computed tomography or fusion positron emission tomography-computed tomography, brain imaging, mediastinoscopy, echocardiography, ventilation-perfusion scintigraphy, and pulmonary function testing before and after induction therapy. Resection was performed if the postoperative forced expiratory volume in 1 second and diffusion capacity of the lung for carbon monoxide exceeded 30% predicted and if the postoperative maximum oxygen consumption exceeded 10 mL/kg/min. RESULTS The postoperative 90-day mortality rate was 8% (lobectomy, 2%; pneumonectomy, 21%; p=0.01). All deaths after pneumonectomy occurred after right-sided procedures. The 3-year and 5-year survival was 50% (95% confidence interval, 36% to 62%) and 45% (95% confidence interval, 31% to 57%) and was significantly associated with completeness of resection (p=0.004) and resection type (pneumonectomy vs lobectomy, p=0.01). There was no correlation between postinduction pulmonary function changes and postoperative morbidity or death or long-term survival in patients managed by lobectomy or pneumonectomy. CONCLUSIONS In properly selected patients with T4 N0-2 M0 non-small cell lung cancer, resection after induction radiochemotherapy can be performed with a reasonable postoperative mortality rate and long-term survival, provided the resection is complete and a right-sided pneumonectomy is avoided. Postinduction pulmonary function changes did not correlate with postoperative morbidity or death or with long-term outcome.

Vacuum-assisted closure device for the management of infected postpneumonectomy chest cavities.

BACKGROUND Infected postpneumonectomy chest cavities may be related to chronic postpneumonectomy empyema or arise in rare situations of necrotizing pneumonia with complete lung destruction where pneumonectomy and pleural debridement are required. We evaluated the safety and efficacy of an intrathoracic vacuum-assisted closure device (VAC) for the treatment of infected postpneumonectomy chest cavities. METHOD A retrospective single institution review of all patients with infected postpneumonectomy chest cavities treated by VAC between 2005 and 2013. Patients underwent surgical debridement of the thoracic cavity, muscle flap closure of the bronchial stump when a fistula was present, and repeated intrathoracic VAC dressings until granulation tissue covered the entire chest cavity. After this, the cavity was obliterated by a Clagett procedure and closed. RESULTS Twenty-one patients (14 men and 7 women) underwent VAC treatment of their infected postpneumonectomy chest cavity. Twelve patients presented with a chronic postpneumonectomy empyema (10 of them with a bronchopleural fistula) and 9 patients with an empyema occurring in the context of necrotizing pneumonia treated by pneumonectomy. In-hospital mortality was 23%. The median duration of VAC therapy was 23 days (range, 4-61 days) and the median number of VAC changes per patient was 6 (range, 2-14 days). Infection control and successful chest cavity closure was achieved in all surviving patients. One adverse VAC treatment-related event was identified (5%). CONCLUSIONS The intrathoracic VAC application is a safe and efficient treatment of infected postpneumonectomy chest cavities and allows the preservation of chest wall integrity.

Use of Combined Suspension Laryngoscopy and Jet Ventilation for Y-Shaped Airway Stents Delivery

Airway stenting is a common endoscopic procedure that is used to treat a variety of central airway lesions. Obstructions or fistulas involving the carina or nearby tracheobronchial structures require the use of specially designed stents, commonly referred to as Y-stents. Conventional methods of endobronchial Y-stent delivery are all characterized by a blind and apneic period during the procedure that carries the risk of stent misplacement or ventilation/oxygenation problems or both. Using combined suspension laryngoscopy, flexible bronchoscopy, and jet ventilation, we describe a technique that makes challenging bronchoscopic interventions--such as self-expandable Y-shaped airway stent delivery--easy, precise, and safe.

Radial Ultrasound-Assisted Transbronchial Biopsy: A New Diagnostic Approach for Non-Resolving Pulmonary Infiltrates in Neutropenic Hemato-Oncological Patients

The role of radial-endobronchial ultrasound (R-EBUS) assisted transbronchial biopsy (TBB) for the diagnosis of peripheral pulmonary lesions is well established. However, no study has addressed its safety and value in hemato-oncological patients presenting with non-resolving infiltrates during persistent febrile neutropenia. To assess safety and feasibility of R-EBUS assisted TBB in severe thrombocytopenic and neutropenic patients. Over a period of 18 months, eight patients were assessed with R-EBUS assisted TBB after adequate platelet transfusion. This technique allowed precise localisation and sampling of the pulmonary lesions in seven of eight patients. In the seven patients, R-EBUS assisted TBB enabled treatment optimization. Invasive fungal infection was diagnosed in four patients, idiopathic acute fibrinous and organising pneumonia in three patients, and a granulomatous inflammation of undetermined origin in one patient. Importantly, no complications, such as bleeding, were observed. R-EBUS assisted TBB is a promising and safe procedure for the evaluation of nonresolving pulmonary infiltrates in febrile neutropenic hemato-oncological patients.

Human Bronchial Epithelial Cells Induce CD141/CD123/DC-SIGN/FLT3 Monocytes That Promote Allogeneic Th17 Differentiation

Little is known about monocyte differentiation in the lung mucosal environment and about how the epithelium shapes monocyte function. We studied the role of the soluble component of bronchial epithelial cells (BECs) obtained under basal culture conditions in innate and adaptive monocyte responses. Monocytes cultured in bronchial epithelial cell-conditioned media (BEC-CM) specifically upregulate CD141, CD123, and DC-SIGN surface levels and FLT3 expression, as well as the release of IL-1β, IL-6, and IL-10. BEC-conditioned monocytes stimulate naive T cells to produce IL-17 through IL-1β mechanism and also trigger IL-10 production by memory T cells. Furthermore, monocytes cultured in an inflammatory environment induced by the cytokines IL-6, IL-8, IL-1β, IL-15, TNF-α, and GM-CSF also upregulate CD123 and DC-SIGN expression. However, only inflammatory cytokines in the epithelial environment boost the expression of CD141. Interestingly, we identified a CD141/CD123/DC-SIGN triple positive population in the bronchoalveolar lavage fluid (BALF) from patients with different inflammatory conditions, demonstrating that this monocyte population exists in vivo. The frequency of this monocyte population was significantly increased in patients with sarcoidosis, suggesting a role in inflammatory mechanisms. Overall, these data highlight the specific role that the epithelium plays in shaping monocyte responses. Therefore, the unraveling of these mechanisms contributes to the understanding of the function that the epithelium may play in vivo.

Reduction of Respiratory Motion During PET/CT by Pulsatile-Flow Ventilation: A First Clinical Evaluation

Respiratory motion negatively affects PET/CT image quality and quantitation. A novel Pulsatile-Flow Ventilation (PFV) system reducing respiratory motion was applied in spontaneously breathing patients to induce sustained apnea during PET/CT. Methods: Four patients (aged 65 ± 14 y) underwent PET/CT for pulmonary nodule staging (mean, 11 ± 7 mm; range, 5–18 mm) at 63 ± 3 min after 18F-FDG injection and then at 47 ± 7 min afterward, during PFV-induced apnea (with imaging lasting ≥8.5 min). Anterior–posterior thoracic amplitude, SUVmax, and SUVpeak (SUVmean in a 1-cm-diameter sphere) were compared. Results: PFV PET/CT reduced thoracic amplitude (80%), increased mean lesion SUVmax (29%) and SUVpeak (11%), decreased lung background SUVpeak (25%), improved lesion detectability, and increased SUVpeak lesion-to-background ratio (54%). On linear regressions, SUVmax and SUVpeak significantly improved (by 35% and 23%, respectively; P ≤ 0.02). Conclusion: PFV-induced apnea reduces thoracic organ motion and increases lesion SUV, detectability, and delineation, thus potentially affecting patient management by improving diagnosis, prognostication, monitoring, and external-radiation therapy planning.

Linear-Endobronchial Ultrasound-guided Insertion of a Fiducial Marker: A New Tool for Tracking Central Lesions.

Stereotactic body radiotherapy (SBRT) is an effective method for the treatment of localized primary lung tumors. Cyberknife, a highly accurate SBRT technique, follows the target during respiratory cycles using a metallic fiducial marker (FM) previously inserted into the lesion. Various methods have been described for the placement of an FM in peripheral pulmonary lesions; however, none of these is appropriate for mediastinal or hilar tumors. The placement of FMs in central lesions to achieve accurate SBRT is particularly relevant due to their higher mobility during respiratory and cardiac cycles. Here, we describe the use of linear-endobronchial ultrasound for the insertion of an FM marker in a centrally located metastatic melanoma, thereby allowing subsequent treatment with Cyberknife.