Therapeutic bronchoscopy for malignant central airway obstructions caused by non-bronchogenic cancers: Results from the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: Little is known about malignant central airway obstruction (MCAO) complicating the metastatic spread of non-bronchogenic solid cancers (NBC) and their bronchoscopic management. This study aimed to describe the epidemiology of this population and determine prognostic factors before therapeutic bronchoscopy (TB). METHODS: In this multicenter study using the EpiGETIF registry, we analysed patients treated with TB for MCAO caused by NBC between January 2019 and December 2022. RESULTS: From a database of 2389 patients, 436 patients (18%) with MCAO and NBC were identified. After excluding patients with direct local invasion, 214 patients (8.9%) were analysed. The main primaries involved were kidney (17.8%), colon (16.4%), sarcoma (15.4%), thyroid (8.9%) and head and neck (7.9%) cancers. Most patients (63.8%) had already received one or more lines of systemic treatment. Obstructions were purely intrinsic in 58.2%, extrinsic in 11.1% and mixed in 30.8%. Mechanical debulking was used in 73.4% of cases, combined with thermal techniques in 25.6% of cases. Airway stenting was required in 38.4% of patients. Median survival after TB was 11.2 months, influenced by histology (p = 0.002), performance status (p = 0.019), initial hypoxia (HR 1.45 [1.01-2.18]), prior oncologic treatment received (HR 1.82 [1.28-2.56], p < 0.001) and assessment of success at the end of the procedure (HR 0.66 [0.44-0.99], p < 0.001). Complications rate was 8.8%, mostly mild, with no procedure-related mortality. CONCLUSION: TB for MCAO caused by a NBC metastasis provides rapid improvement of symptoms and prolonged survival. Patients should be promptly referred by medical oncologists for bronchoscopic management based on the prognostic factors identified.

Therapeutic bronchoscopy for malignant central airway obstruction: Introduction to the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: EpiGETIF is a web-based, multicentre clinical database created in 2019 aiming for prospective collection of data regarding therapeutic rigid bronchoscopy (TB) for malignant central airway obstruction (MCAO). METHODS: Patients were enrolled into the registry from January 2019 to November 2022. Data were prospectively entered through a web-interface, using standardized definitions for each item. The objective of this first extraction of data was to describe the population and the techniques used among the included centres to target, facilitate and encourage further studies in TB. RESULTS: Overall, 2118 patients from 36 centres were included. Patients were on average 63.7 years old, mostly male and smokers. Most patients had a WHO score ≤2 (70.2%) and 39.6% required preoperative oxygen support, including mechanical ventilation in 6.7%. 62.4% had an already known histologic diagnosis but only 46.3% had received any oncologic treatment. Most tumours were bronchogenic (60.6%), causing mainly intrinsic or mixed obstruction (43.3% and 41.5%, respectively). Mechanical debulking was the most frequent technique (67.3%), while laser (9.8%) and cryo-recanalization (2.7%) use depended on local expertise. Stenting was required in 54.7%, silicone being the main type of stent used (55.3%). 96.3% of procedure results were considered at least partially successful, resulting in a mean 4.1 points decrease on the Borg scale of dyspnoea. Complications were noted in 10.9%. CONCLUSION: This study exposes a high volume of TB that could represent a good source of future studies given the dismal amount of data about the effects of TB in certain populations and situations.

Preliminary results in tracheal replacement using stented aortic matrices for primary extensive tracheal cancer.

Objective: Recent studies have demonstrated the feasibility and favorable long-term results of tracheobronchial replacement using stented cryopreserved aortic allografts. We propose to investigate the outcomes of this emerging technique in the subgroup of patients with extensive tracheal cancer. Methods: This study was based on 13 patients with primary extensive tracheal cancer extracted from the prospective registry TRITON-01 (ClinicalTrials.gov Identifier: NCT04263129), which included 40 patients in total. We analyzed early and late outcomes in this subset of patients. Results: From March 2019 to September 2022, 13 patients were included in the study. There were 9 female and 4 male patients, with a mean age of 53.9 years [36-71 years]. They had tracheal replacement for extended adenoid cystic carcinoma (n = 11), squamous cell carcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). A venovenous extracorporeal membrane oxygenation was used in the 6 last cases. The mean length of resection was 81 mm [50-120 mm]. There was no 30-day postoperative mortality. A complete resection (R0) was achieved in 11 patients. The main late complications consisted of tracheal granulomas related to the stent and requiring repeated bronchoscopies (n = 9), pneumonia (n = 3), airway infection (n = 1), bronchoesophageal fistula (n = 1), mechanical stent obstruction requiring change (n = 2), and mediastinitis treated by antibiotics, drainage, and omentoplasty (n = 1). With a maximal follow-up of 3 years and 7 months, cancer recurrence was observed in 2 patients. All patients were alive at last follow-up except 2 (84.6%). Conclusions: Airway replacement using stented CAA represents a feasible and promising solution for extensive tracheal cancer.

Impact of Silicone Stent Placement in Symptomatic Airway Obstruction due to Non-Small Cell Lung Cancer - A French Multicenter Randomized Controlled Study: The SPOC Trial.

BACKGROUND: Therapeutic bronchoscopy (TB) is an accepted strategy for the symptomatic management of central airway malignant obstruction. Stent insertion is recommended in case of extrinsic compression, but its value in preventing airway re-obstruction after endobronchial treatment without extrinsic compression is unknown. OBJECTIVE: Silicone stent Placement in symptomatic airway Obstruction due to non-small cell lung Cancer (SPOC) is the first randomized controlled trial investigating the potential benefit of silicone stent insertion after successful TB in symptomatic malignant airway obstruction without extrinsic compression. METHOD: We planned an inclusion of 170 patients in each group (stent or no stent) over a period of 3 years with 1-year follow-up. The 1-year survival rate without symptomatic local recurrence was the main endpoint. Recurrence rate, survival, quality of life, and stent tolerance were secondary endpoints. During 1-year follow-up, clinical events were monitored by flexible bronchoscopies and were evaluated by an independent expert committee. RESULTS: Seventy-eight patients (mean age 65 years) were randomized into 2 arms: stents (n = 40) or no stents (n = 38) after IB. Consequently, our main endpoint could not be statistically answered. Improvement of dyspnea symptoms is noticeable in each group but lasts longer in the stent group. Stents do not change the survival curve but reduce unattended bronchoscopies. In the no stent group, 19 new TB were performed with 16 stents inserted contrasting with 10 rigid bronchoscopies and 3 stents placed in the stent group. In a subgroup analysis according to the oncologic management protocol following TB (first-line treatment and other lines or palliation), the beneficial effect of stenting on obstruction recurrence was highly significant (p < 0.002), but was not observed in the naïve group, free from first-line chemotherapy. CONCLUSION: Silicone stent placement maintains the benefit of TB after 1 year on dyspnea score, obstruction's recurrence, and the need for new TB. Stenting does not affect the quality of life and is suggested for patients after failure of first-line chemotherapy. It is not suggested in patients without previous oncologic treatment.

Clinical efficacy and cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration for preoperative staging of non-small-cell lung cancer: Results of a French prospective multicenter trial (EVIEPEB).

This two-step study evaluated the cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for presurgery staging of non-small cell lung cancer (NSCLC) in France (EVIEPEB; ClinicalTrial.gov identifier NCT00960271). Step 1 consisted of a high-benchmark EBUS-TBNA-training program in participating hospital centers. Step 2 was a prospective, national, multicenter study on patients with confirmed or suspected NSCLC and an indication for mediastinal staging with at least one lymph node > 1 cm in diameter. Patients with negative or uninformative EBUS-TBNA and positron-emission tomography-positive or -negative nodes, respectively, underwent either mediastinoscopy or surgery. Direct costs related to final diagnosis of node status were prospectively recorded. Sixteen of 22 participating centers were certified by the EBUS-TBNA-training program and enrolled 163 patients in Step 2. EBUS-TBNA was informative for 149 (91%) patients (75 malignant, 74 non-malignant) and uninformative for 14 (9%). Mediastinoscopy was avoided for 80% of the patients. With a 52% malignant-node rate, EBUS-TBNA positive- and negative-predictive values, respectively, were 100% and 90%. EBUS-TBNA was cost-effective, with expected savings of €1,450 per patient, and would have remained cost-effective even if all EBUS-TBNAs had been performed under general anesthesia or the cost of the procedure had been 30% higher (expected cost-saving of €994 and €1,427 per patient, respectively). After EBUS-TBNA training and certification of participating centers, the results of this prospective multicenter study confirmed EBUS-TBNA cost-effectiveness for NSCLC staging.

Performance of Endobronchial Ultrasound Elastography in the Differentiation of Malignant and Benign Mediastinal Lymph Nodes: Results in Real-life Practice.

BACKGROUND: Little data exists regarding the performance of elastography in EBUS-TBNA. The aim of the study was to evaluate the elastography score proposed and previously published by Izumo, in particular its capacity to perfectly identify benign lymph node, and to discriminate malignant ones. METHODS: This study included patients undergoing EBUS-TBNA for mediastinal lymph nodes (LN). Before LN needle aspiration, an elastography was performed which allowed a color elastogram to be superimposed on the ultrasound image. Three blinded assessors classified these elastograms into 3 types using the score published by Izumo: type 1 (predominantly not blue), type 2 (partially blue, partially not blue), or type 3 (predominantly blue). These types were then compared with pathology results. RESULTS: A total of 217 LN (114 patients) were analyzed: histologic findings identified 97 benign LN (44.7% of the lymph nodes) and 120 malignant LN (55.3%). There were 44 elastographies (20.2%) that were classified as type 1, 90 elastographies (41.5%) classified as type 2, and 83 elastographies (38.3%) classified as type 3. Considering type 1 as benign and type 3 as malignant, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 87.0%, 68.0% , 80.0% , and 77.0%. Ten (23%) of the 44 lymph nodes with a type 1 elastogram were malignant. CONCLUSION: Elastography does not preclude performing TBNA of the lymph nodes. It does not preclude EBUS-TBNA when a type 1 elastogram pattern is found. All lymph nodes visualized should be sampled by EBUS-TBNA, regardless of elastography pattern.

Pembrolizumab-induced pneumonitis.

Three cases of pembrolizumab-induced pneumonitis are described, two being consistent with organising pneumonia http://ow.ly/Dvhc308QI39.

Endobronchial metastases from melanoma: a survival analysis.

BACKGROUND: Metastatic spread to the tracheobronchial tree from other than bronchopulmonary tumors is a common clinical problem. However, malignant melanoma, a highly metastatic potential tumor, is rarely metastasing in the airways. Therefore little is known about survival of patients with endobronchial metastasis from melanoma. OBJECTIVES: The aim of our study was to assess survival of patients with endobronchial metastasis of melanomas according to clinical and radiological features, to determine any possible factor affecting survival. METHODS: This retrospective study included 19 patients who underwent a bronchoscopy from 11 different hospitals. Data about patients' demographics, symptoms, radiographic, endoscopic findings and treatment were investigated to evaluate any possible impact on survival. RESULTS: Endobronchial metastases occurred at a median of 48 months (range 0-120) following the diagnosis of the primary tumor. About 73.7% of patients had other proven metastases when the endobronchial involvement was diagnosed. Symptoms are not specific as well as radiological features. Median overall survival of the studied population was 6 months (range 1-46). Factors of poor survival were multiple metastatic sites (P = 0.019), pleural (P = 0.0014) and soft tissue metastasis (P = 0.024). Different treatment modalities applied in our patients showed no effect on survival. CONCLUSION: Patients with endobronchial metastasis have overall poor survival, affected by multiple organ involvement, the presence of pleural and soft tissue disease, while no impact on survival has been shown by any treatment applied.

Conservatively treated extended tracheal necrosis complicating pharyngolaryngectomy.

Tracheal necrosis is a rare life-threatening phenomenon that most often occurs after thyroid operations or prolonged intubation. Conservative treatment can be one choice in extensive tracheal necrosis. We report the case of a 59-year-old man, with tracheal necrosis that developed after pharyngolaryngectomy, that we treated conservatively using hyperbaric oxygen therapy and antibiotic therapy. The follow-up was assured by tracheobronchoscopy. A year after his discharge, the trachea was totally healed.

[Exercise-induced vocal cord dysfunction in asthma: a new diagnostic method]. / Diagnostic de la dysfonction des cordes vocales à l'exercice dans l'asthme sévère.

OBJECTIVE: Vocal cord dysfunction (VCD) is an under-recognized cause of dyspnea and is difficult to diagnose. The symptoms caused by exercise-induced VCD (IEVCD) often falsely suggest asthma, but there is sometimes a real association between the two diseases. The objective of this study was to evaluate a new, simple method for analyzing vocal cord behavior in the diagnosis of IEVCD, and to clarify the prevalence of IEVCD in an uncontrolled asthma population with unexplained exertional dyspnea. METHODS: This single-center study was conducted prospectively between April 2012 and March 2013. The main inclusion criterion was uncontrolled asthma with unexplained dyspnea. The assessment included cardiopulmonary exercise testing and supraglottal laryngoscopy during exercise with measurement of the vocal cord-opening angle (VCOA). Data from 15 asthmatic patients were compared with those from 10 non-asthmatic dyspneic patients (controls) to define specific criteria for the endoscopic diagnosis of IEVCD. RESULTS: Endoscopy during bicycle exercising was well tolerated. Normal value of inspiratory VCOA (itVCOA) was>49°. Values for the itVCOA were lower for asthmatics than for controls when exercising at 50% maximal power (52.8°±13.3° and 64.5°±8.3°, respectively). Four of the 15 asthmatics (26%) demonstrated IEVCD characterized with itVCOApeak of less than 49°. CONCLUSION: Measurement of VCOA represents a new, simple method for obtaining objective data in the exploration of VCD. The prevalence of IEVCD in uncontrolled asthmatic patients is important (26% in our small sample). IEVCD is probably an under-diagnosed aggravating factor in asthma, and its diagnosis and management could avoid the therapeutic climbing in asthma. This method of analysis may help to accurately and objectively assess vocal cord dysfunction.

Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside?

One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection.

Severely impaired health-related quality of life in chronic hyperventilation patients: exploratory data.

Patients with hyperventilation syndrome (HVS) report severe symptom-related suffering and often complain from insufficient medical attention. However, quality of life data in this context are scarce. We aimed at assessing the health-related quality of life (HRQoL) of HVS patients. Twenty-one HVS patients with extensive cardiorespiratory workup including cardiopulmonary exercise testing (CPET) filled in the generic SF-36 questionnaire and the results were compared to French normal values. Correlations between SF36 dimensions and clinical and functional data were established. All SF-36 scores were markedly decreased in HVS patients compared to healthy subjects: Physical Functioning: 44 ± 24, Social Functioning: 57 ± 27, Role Physical: 21 ± 32, Role Emotional: 48 ± 42, Mental Health: 51 ± 27, Vitality: 34 ± 20, Body Pain: 41 ± 21, General Health: 42 ± 21. These figures were all significantly lower in the HVS patients respective to the normal reference population. They were also lower than corresponding values published in patients with asthma or chronic obstructive pulmonary disease (COPD). "Vitality" and "Physical Functioning" scores were correlated with Nijmegen score (r = -0.594, p = 0.047) and peak respiratory frequency during CPET (r = -0.644, p = 0.019). The SF-36 Social Functioning score was correlated with the ventilatory threshold (r = 0.629, p = 0.034), peak V'E/V'CO2 (ventilation/CO2 production) (r = 0.650, p = 0.016) and peak PaCO2 (r = -0.664, p = 0.027). In conclusion, this study shows that HRQoL can be severely impaired in patients with HVS, which is one more reason to take this condition seriously.

Intubation-related tracheal ischemic lesions: incidence, risk factors, and outcome.

PURPOSE: To determine incidence, risk factors and outcome of tracheal ischemic lesions related to intubation. METHODS: Planned post hoc analysis using patients from a previous randomized controlled study. Fiberoptic tracheoscopy was performed during the 24 h following extubation. In patients with >2 ischemic lesions, ulcer or tracheal rupture, fiberoptic tracheoscopy was repeated 2 weeks after the last extubation. Tracheal ischemic lesions were predefined based on a quantitative score. RESULTS: Ninety-six adult patients were included in this study. Eighty (83 %) patients had at least one tracheal ischemic lesion. Thirty-seven (38 %) patients had a tracheal ischemia score > median score (5; IQ 1, 7). The most common tracheal ischemic lesion was ischemia (68 %), followed by hyperemia (54 %), ulcer (10 %), and tracheal rupture (1 %). Univariate analysis identified duration of neuromuscular-blocking agent use, overinflation of tracheal cuff (>30 cmH2O), percentage of P cuff determination >30 cmH2O, duration of assist-control ventilation, and plateau pressure as risk factors for having a tracheal ischemia score >5. Duration of assist-control mechanical ventilation was the only factor independently associated with tracheal ischemia score >5 [OR (95 % CI) 1.10 per hour (1.02-1.20)]. A fiberoptic tracheoscopy was performed 2 weeks after extubation in 22 patients. This examination was normal in all patients, except the one with tracheal rupture who had marked improvement. CONCLUSION: Tracheal ischemic lesions are common in intubated, critically ill patients. Duration of assist-control mechanical ventilation through a tracheal tube is the only independent risk factor. These lesions healed in the majority of patients 2 weeks after extubation.

Endoscopic ultrasound guided transbronchial fine needle aspiration: a French Department of Pathology's 4-year experience.

BACKGROUND: Endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA) is an accurate outpatient procedure used to explore mediastinal lymph nodes for lung cancer staging and unexplained mediastinal masses. AIMS AND METHODS: A retrospective study was conducted over four years on EBUS-TBNA sampled lymph nodes investigated for the staging of lung cancer or unexplained mediastinal lymphadenopathies, first using the conventional method (CM) and then a liquid based cytology (LBC). RESULTS: Of the 628 specimens (355 patients) collected, the overall rate of adequacy was 88% and the diagnosis of malignancy was achieved in 43% of cases. The inadequate rate was 6% with LBC and 21% with CM. A paraffin cytoblock was available in 80% with LBC and 62% with CM. Of the 628 aspirates, 270 (43%) were categorised as negative for malignancy including 26 cases consistent with sarcoidosis, 272 (43%) as malignant, 9 (1.4%) as suspicious for non-small-cell carcinoma and 77 as inadequate samples (12%). Of the 272 cases diagnosed as malignant, 87 (32%) were classified as non-small-cell carcinoma, 106 (39%) as adenocarcinoma, 48 (18%) as squamous cell carcinoma and 20 (7%) as small cell carcinoma. Five lymphomas, four metastatic melanomas and two carcinoids were also diagnosed. CONCLUSIONS: EBUS-TBNA is a reliable method for the staging of lung cancer and for unexplained mediastinal mass exploration. The LBC has a lower rate of inadequate samples, a better yield of cytoblock for immunohistochemistry and a dramatically reduced time requirement for interpretation as compared to CM.

Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.

RATIONALE: Underinflation of the tracheal cuff frequently occurs in critically ill patients and represents a risk factor for microaspiration of contaminated oropharyngeal secretions and gastric contents that plays a major role in the pathogenesis of ventilator-associated pneumonia (VAP). OBJECTIVES: To determine the impact of continuous control of tracheal cuff pressure (P(cuff)) on microaspiration of gastric contents. METHODS: Prospective randomized controlled trial performed in a single medical intensive care unit. A total of 122 patients expected to receive mechanical ventilation for at least 48 hours through a tracheal tube were randomized to receive continuous control of P(cuff) using a pneumatic device (intervention group, n = 61) or routine care of P(cuff) (control group, n = 61). MEASUREMENTS AND MAIN RESULTS: The primary outcome was microaspiration of gastric contents as defined by the presence of pepsin at a significant level in tracheal secretions collected during the 48 hours after randomization. Secondary outcomes included incidence of VAP, tracheobronchial bacterial concentration, and tracheal ischemic lesions. The pneumatic device was efficient in controlling P(cuff). Pepsin was measured in 1,205 tracheal aspirates. Percentage of patients with abundant microaspiration (18 vs. 46%; P = 0.002; OR [95% confidence interval], 0.25 [0.11-0.59]), bacterial concentration in tracheal aspirates (mean ± SD 1.6 ± 2.4 vs. 3.1 ± 3.7 log(10) cfu/ml, P = 0.014), and VAP rate (9.8 vs. 26.2%; P = 0.032; 0.30 [0.11-0.84]) were significantly lower in the intervention group compared with the control group. However, no significant difference was found in tracheal ischemia score between the two groups. CONCLUSIONS: Continuous control of P(cuff) is associated with significantly decreased microaspiration of gastric contents in critically ill patients.

Postoperative ischemic bronchitis after lymph node dissection and primary lung cancer resection.

BACKGROUND: The purpose of this study was to determine the incidence and symptoms of postoperative ischemic bronchitis (POIB) after systematic lymph node dissection (LND) and evaluate the effect of hyperbaric oxygen therapy in patients with primary lung cancer. METHODS: From January 2004 to December 2009, 1,071 patients underwent a standard resection for non-small cell lung cancer and radical systematic lymph node dissection. Fiberoptic bronchoscopy was performed systematically between days 7 and 12. We analyzed the clinical and biologic signs of POIB. Once the diagnosis established a treatment by hyperbaric oxygen, therapy was undertaken. RESULTS: A POIB was observed in 34 patients (3.21%) (2 women and 32 men). Mean age was 59 ± 10 years (range, 25 to 79 years). A POIB occurred within 8 ± 3 days; after right pulmonary resection (n = 21; 62%) and after left resection (n = 13; 38%). A POIB appeared asymptomatically for 27 patients (80%), whereas only 7 patients (20%) presented with fever and hyperleukocytosis. Their localization were bronchial stumps (n = 21; 62%), homolateral bronchial tree (n = 11; 32%), or extension toward the contralateral bronchial tree (n = 2; 6%). The mean number of hyperbaric oxygen therapy sessions was 14 (1 to 48). A POIB worsening was observed in 6 patients (18%), requiring a surgical rescue therapy. CONCLUSIONS: The clinical presentation of POIB is poor and systematic fiberoptic bronchoscopy should be performed, especially in patients with a high risk of bronchopleural fistula. Hyperbaric oxygen therapy in the management of ischemic bronchitis may be a promising adjunctive treatment.

In vivo intravital endoscopic confocal fluorescence microscopy of normal and acutely injured rat lungs.

We present a new lung imaging technique based on endoscopic confocal fluorescence microscopy (ECFM), which is a new method that is able to provide cellular and structural assessment of living tissue using a small confocal probe in direct contact with the visceral pleura. To observe distal airspace structure and cellular condition in normal and injured lungs (hyperoxic and bleomycin challenged), we used fluorescent-specific marker contrast and ECFM. Alveolar space ECFM with spectral analyses were performed at 488-nm excitation using FITC-labeled markers or naturally fluorescent dyes. The normal lung was compared with the sick lung, where our in vivo imaging experiments correlated well with results obtained with corresponding ex vivo conventional assays. Four main elements pertaining to the acute lung injury/acute respiratory distress syndrome (ALI/ARDS) pathophysiology and established early key events were specifically studied: alveolar epithelial membrane phenotype, lung cell apoptosis, neutrophil recruitment, and edema. ECFM allowed visualization of (i) fine-tuned ultrastructural lectin (RCA-1) and sialoglycoprotein (RTI40) epithelial cell membrane expression, (ii) YO-PRO-1-related DNA linking of lung cell apoptosis, (iii) PKH2 green fluorescent cell linker-labeled neutrophil tracking in lung microcirculatory network and airspaces, (iv) FITC-dextran plasma contrast and extravasation with edema formation. ECFM provides reliable results to corresponding ex vivo fluorescent methods. ECFM, using the minimally invasive Five-1(R) optical instrument and specific fluorescent markers, is able to provide real-time potentially useful imaging of live unfixed normal and injured lung tissue with promising developments for improving bedside diagnostic and decision-making therapeutic strategy in patients with ALI.

Bronchial fistula associated with sunitinib in a patient previously treated with radiation therapy.

OBJECTIVE: To report a case of bronchial fistula associated with sunitinib in a patient previously treated with radiation therapy. CASE SUMMARY: A 40-year-old man with renal cell cancer diagnosed in 2005 and initially treated by radical nephrectomy presented in March 2007 with a recurrence with cerebral, mediastinal, and lung metastases. A thoracic computed tomography (CT) scan showed a subcarinal tumor obstructing the bronchus intermedius. The patient was initially treated with cerebral and thoracic radiotherapy and then with sunitinib 50 mg/day (4 weeks on, 2 weeks off). Two months after the beginning of treatment, a CT scan revealed a dramatic reduction in the size of the tumor, associated with a bronchial fistula. This was confirmed by flexible bronchoscopy, which showed complete necrosis of the tumor and a large perforation of the bronchus intermedius. Sunitinib was immediately withdrawn and antibiotic prophylaxis was instituted. It was not possible to place an endobronchial stent. Two weeks later, flexible bronchoscopy revealed the reappearance of a yellowish mass protruding into the bronchus intermedius (40% obstruction). A few months later, the obstruction of the bronchus intermedius progressed to 90% and was associated with a contralateral obstruction of the left mainstem bronchus (20%). A rigid bronchoscopy was then performed to clear the obstruction and an endobronchial stent was placed, with satisfactory initial results. In February 2008, the patient presented with new bronchial obstruction under the endobronchial stent but refused a rigid bronchoscopy and died in March 2008. DISCUSSION: Sunitinib, a multitarget tyrosine kinase inhibitor with antiangiogenic and antitumoral activities, has been approved for the treatment of advanced renal cell carcinoma. This treatment is generally well tolerated. Serious complications may occur, however. According to the Naranjo probability scale, the bronchial fistula was possibly related to sunitinib treatment. CONCLUSIONS: This is a rare case of a bronchial perforation leading to a fistula associated with sunitinib treatment after mediastinal radiation therapy. Clinicians may consider strict follow-up of patients with proximal lung metastases treated with sunitinib (CT scan and, if appropriate, placement of an endobronchial stent).