Airway replacement using stented aortic matrices: Long-term follow-up and results of the TRITON-01 study in 35 adult patients.

Over the past 25 years, we have demonstrated the feasibility of airway bioengineering using stented aortic matrices experimentally then in a first-in-human trial (n = 13). The present TRITON-01 study analyzed all the patients who had airway replacement at our center to confirm that this innovative approach can be now used as usual care. For each patient, the following data were prospectively collected: postoperative mortality and morbidity, late airway complications, stent removal and status at last follow-up on November 2, 2021. From October 2009 to October 2021, 35 patients had airway replacement for malignant (n = 29) or benign (n = 6) lesions. The 30-day postoperative mortality and morbidity rates were 2.9% (n = 1/35) and 22.9% (n = 8/35) respectively. At a median follow-up of 29.5 months (range 1-133 months), 27 patients were alive. There have been no deaths directly related to the implanted bioprosthesis. Eighteen patients (52.9%) had stent-related granulomas requiring a bronchoscopic treatment. Ten among 35 patients (28.6%) achieved a stent free survival. The actuarial 2- and 5-year survival rates (Kaplan-Meier estimates) were respectively 88% and 75%. The TRITON-01 study confirmed that airway replacement using stented aortic matrices can be proposed as usual care at our center. Clinicaltrials.gov Identifier: NCT04263129.

Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices.

Importance: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. Objective: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. Design, Setting, and Participants: Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. Exposures: Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (-80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. Main Outcomes and Measures: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. Results: Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. Conclusions and Relevance: In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT01331863.

Human transplantation of a biologic airway substitute in conservative lung cancer surgery.

BACKGROUND: Pneumonectomies for lung cancer are associated with a high postoperative mortality, especially when right-sided, after neoadjuvant radiochemotherapy, and in patients over 70 years of age. Preliminary studies in our laboratory have shown that aortic grafts could be valuable airway substitutes. We report the first human bronchial transplantation of a cryopreserved aortic allograft used as a biologic airway substitute to prevent a pneumonectomy for lung cancer. METHODS: The procedure was performed in a high-risk 78-year old patient with an extensive right bronchopulmonary malignant tumor pretreated with chemotherapy. After a complete resection of the lung cancer using an upper bilobectomy with lymph node removal, mobilization procedures did not allow for a primary end-to-end bronchial anastomosis. A stent-supported cryopreserved aortic allograft from a certified tissue bank was interposed to restore the bronchial continuity with sparing of the lower lobe. RESULTS: The postoperative course was eventful for a supraventricular arrhythmia leading to mild pulmonary edema that resolved using standard medical therapy, and a right lower lobe atelectasis with bacterial colonization that required fiberoptic bronchoscopies in addition to antibiotic treatment. A 1-year postoperative evaluation found a well-functioning reimplanted lower lobe with no complications related to the cryopreserved aortic allograft or the stent. The patient recovered to his baseline activity with a satisfying health-related quality of life. CONCLUSIONS: We demonstrate the feasibility of this surgical innovation to prevent the high-risk procedure of pneumonectomy in a single case. If confirmed in larger series of selected patients, it could bring new perspectives in conservative lung cancer surgery.

Postoperative pneumonia after major pulmonary resections: an unsolved problem in thoracic surgery.

BACKGROUND: Antibiotics currently recommended for prophylaxis in thoracic surgery are first-generation and second-generation cephalosporins. Despite this prophylaxis, postoperative pneumonia after major pulmonary resections remains frequent and severe. However, in the medical literature, the origin of these infections is poorly documented. METHODS: To evaluate the efficiency of current prophylactic regimens, we retrospectively analyzed 312 consecutive cases of major pulmonary resection, performed between January 2000 and December 2004. For patients who experienced postoperative pulmonary infection, the microbiologic agents and their antibiotic susceptibility were studied. RESULTS: A postoperative pneumonia was diagnosed in 76 patients (24.4% +/- 0.43%). Sixty patients (78.9%) experienced the infection in the first 5 postoperative days. A microbiologic documentation was obtained in 44 cases (57.9%) with 56 microorganisms involved. Pathogens responsible for the infections were Staphylococcus aureus (n = 10), Streptococcus pneumoniae (n = 8), group B Streptococcus organisms (n = 1), nongroupable Streptococcus organisms (n = 2), Enterococcus faecalis (n = 1), Haemophilus spp. (n = 9), Branhamella catarrhalis (n = 2), Enterobacteriaceae (n = 15), Pseudomonas aeruginosa (n = 3), Acinetobacter baumannii (n = 1), and Candida spp. (n = 4). According to the antibiotic susceptibility testings, the prophylactic regimen by cefazolin proved ineffective for 84% of the microbiologically documented cases. CONCLUSIONS: This study confirmed the inefficiency of current prophylaxis against pathogens involved in postoperative pneumonia after major lung resections. Evaluation of new and more-adapted approaches of antibiotic prophylaxis should be the subject of prospective multicenter trials.

Cerebral ischemia during carotid artery cross-clamping: predictive value of phase-contrast magnetic resonance imaging.

The goal of this prospective study was to determine the utility of preoperative cerebral magnetic resonance imaging (MRI) in predicting cerebral ischemia during carotid artery cross-clamping for endarterectomy. Between January 2000 and December 2003, a total of 121 patients (95 men, 26 women) underwent three-dimensional phase-contrast MRI to assess collateral function prior to carotid endarterectomy. During regional anesthesia, patients were monitored to detect ischemic events and their timing in relation to cross-clamping and to determine mean intraoperative arterial pressure. These findings were then correlated with the collateral variations observed in the circle of Willis on preoperative MRI. Patients were classified into three groups according to neurological tolerance: normal tolerance (n = 106), immediate severe deficit (n = 9), and late deficit associated with arterial hypotension (n = 6). In the second group, a significant correlation was found between the absence of collateral circulation and neurological deficit (p < .0001). These results indicated that three-dimensional phase-contrast MRI is useful for predicting cerebral ischemia during carotid cross-clamping and selecting indications for shunting. Absence of visible collaterals of the circle of Willis on MRI is significantly predictive of early ischemia and an indication for systematic shunt placement.

Surgical resection of lung cancer in patients with underlying interstitial lung disease.

BACKGROUND: The association between interstitial lung disease (ILD) and an increased risk of developing lung cancer has been reported. The goal of this retrospective study was to determine the outcome of lung cancer resection among patients with ILD. METHODS: Between January 1979 and March 1999, 27 patients with both lung cancer and ILD were identified. Seven patients with poor pulmonary function tests or distant metastases underwent medical treatment and were excluded from this study. Twenty patients treated by surgical resection were analyzed. RESULTS: Various types of ILD such as sarcoidosis (n = 7), idiopathic interstitial pneumonia (n = 4), histiocytosis X (n = 4), pneumoconiosis (n = 4), and amiodarone-induced ILD (n = 1) were observed. Tumors were located in the peripheral part of the lung in 16 cases. The most frequent tumor cell types were squamous and adenocarcinoma. The resections consisted of lobectomy (n = 16), bilobectomy (n = 1), and pneumonectomy (n = 3). Most cancers were stage I (n = 10) or II (n = 6). There was no postoperative death. The postoperative course was uneventful in 16 cases. The majority of patients (70%) did not experience respiratory insufficiency during the follow-up period. The actuarial 2-year and 5-year survival rates were, respectively, 83.5% and 66.4%. CONCLUSIONS: In this series, the long-term survival of patients who had lung cancer resection appeared to be not affected by the association with ILD. This could be explained by an adequate preoperative selection based on pulmonary function tests and a preferential choice for lobectomies. Thus, surgical resection should be offered to properly selected patients with lung cancer and underlying ILD.