Dana M. Radu

Tracheal Replacement With Cryopreserved, Decellularized, or Glutaraldehyde-Treated Aortic Allografts

BACKGROUND Seven years of experimental research provided a valuable tracheal substitute, the aortic allograft, which can promote the regeneration of epithelium and cartilage. In human application, both fresh and preserved aortic allografts could be used. The optimal method of aortic allograft preservation remains to be evaluated. This study assessed the use of cryopreserved, decellularized, or glutaraldehyde-treated aortic allografts as tracheal substitutes. METHODS Twenty-two sheep underwent tracheal replacement using cryopreserved (n = 10), decellularized (n = 7) or glutaraldehyde-treated (n = 5) allografts, supported by a temporary stent to prevent airway collapse. Aortic segments were retrieved at regular intervals up to 12 months after implantation to analyze the regenerative process. RESULTS All animals survived the operation. Major complications such as infection, stent migration, or obstruction were predominantly encountered in the decellularized group. The lack of major inflammatory response within the aortic graft observed in the glutaraldehyde group was associated with the absence of tracheal regeneration. Histologic examinations showed a progressive transformation of the aorta into a tracheal tissue comprising respiratory epithelium and cartilage only in the cryopreserved group. CONCLUSIONS This study demonstrated that regeneration of a functional tissue could be obtained after tracheal replacement with a cryopreserved aortic allograft. The regenerative process followed the same pattern as previously described for fresh allografts. Cryopreserved aortic allografts present major advantages: availability in tissue banks, permanent storage, and no need for immunosuppression. This offers a new field of perspectives for clinical application in patients with extensive tracheal cancer.

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.

Bronchial Replacement With Arterial Allografts

BACKGROUND Pneumonectomy is well known for a high risk of postoperative death. The alternative, sleeve lobectomy, is sometimes technically inaccessible, and is associated with locoregional recurrence. In certain situations, the use of a bronchial substitute would allow longer bronchial resections with better security margins. Previous experiments demonstrated that aortic grafts are valuable tracheal and carinal substitutes. The present study evaluated bronchial replacement with arterial allografts. METHODS Fifteen female sheep underwent a left bilobectomy with replacement of the bronchus intermedius with arterial allografts: 5 received a fresh graft (group 1) and 10 received cryopreserved (group 2). A bronchial silicone stent was used to confer rigidity. Evaluation was conducted on clinical and histologic criteria at regular intervals up to 18 months. RESULTS There were no perioperative deaths. Atelectasis, the only early postoperative complication (n = 2), was successfully treated by fiberscopic aspiration. The late postoperative period was uneventful in 12 sheep. Complications included 1 bronchopneumonia, 1 pulmonary abscess, and 1 distortion of the bronchial stent. Fiberscopic examination revealed 3 sheep with granuloma formation. The bronchial stent was removed in 3 sheep, 1 at 9 months and 2 at 12 months, without clinical complications or stenosis of the graft. Histologic analysis showed regeneration of new bronchial tissue, comprising epithelium and cartilage. CONCLUSIONS This study confirmed that an arterial allograft could be a valuable bronchial substitute. The use of a bronchial substitute offers new perspectives in surgical resection of lung cancer because it would avoid pneumonectomy in some patients.

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

Biopsie pulmonaire chirurgicale : indications et incidences thérapeutiques

Surgical biopsy of lung parenchyma can be used to establish a diagnosis in interstitial lung disease both of acute and chronic presentation. The present article summarizes the current indications, the therapeutic implications, the different surgical techniques and postoperative complications of the procedure. Common controversies and problems related to surgical lung biopsy are also presented.

Mise au pointBiopsie pulmonaire chirurgicale : indications et incidences thérapeutiquesSurgical lung biopsy: Indications and therapeutic implications

Surgical biopsy of lung parenchyma can be used to establish a diagnosis in interstitial lung disease both of acute and chronic presentation. The present article summarizes the current indications, the therapeutic implications, the different surgical techniques and postoperative complications of the procedure. Common controversies and problems related to surgical lung biopsy are also presented.

Tumeurs malignes de la trachée

Les tumeurs malignes de la trachee sont rares. Les lesions primitives sont principalement le carcinome epidermoide et le carcinome adenoide kystique. Le diagnostic est habituellement retarde du fait de la latence clinique. La bronchoscopie est un examen fondamental dans le bilan preoperatoire. Le traitement assurant la meilleure survie a long terme est la chirurgie (resection-anastomose tracheale). Au-dela de lesions etendues a plus de la moitie de la trachee (5–6 cm), un substitut tracheal doit etre utilise pour la reconstruction. La recherche d’un greffon tracheal ideal fait l’objet de nombreux travaux actuellement. Le traitement par bronchoscopie interventionnelle (electrocoagulation, mise en place d’endoprothese) peut etre utilise en cas d’obstruction tumorale aigue ou chronique, mais doit etre considere comme palliatif. La radiotherapie et/ou la chimiotherapie sont d’efficacite inconstante.