Application of Paclitaxel as Adjuvant Treatment for Benign Cicatricial Airway Stenosis

Benign cicatricial airway stenosis（BCAS） is a potentially life-threatening disease.Recurrence occurs frequently after endoscopic treatment.Paclitaxel is known to prevent restenosis,but its clinical efficacy and safety is undetermined.Therefore,in this study,we investigated the efficacy and associated complications of paclitaxel as adjuvant treatment for BCAS of different etiologies.The study cohort included 28 patients with BCAS resulting from tuberculosis,intubation,tracheotomy,and other etiologies.All patients were treated at the Department of Respiratory Diseases,Beijing Tian Tan Hospital,Capital Medical University,China,between January 2010 and August 2014.After primary treatment by balloon dilation,cryotherapy,and/or high-frequency needle-knife treatment,paclitaxel was applied to the airway mucosa at the site of stenosis using a newly developed local instillation catheter.The primary outcome measures were the therapeutic efficacy of paclitaxel as adjuvant treatment,and the incidence of complications was observed as well.According to our criteria for evaluating the clinical effects on BCAS,24 of the 28 cases achieved durable remission,three cases had remission,and one case showed no remission.Thus,the durable remission rate was 85.7%,and the combined effective rate was 96.4%.No differences in outcomes were observed among the different BCAS etiologies（P=0.144）,and few complications were observed.Our results indicated that paclitaxel as an adjuvant treatment has greater efficacy than previously reported BCAS treatment methods.

Scarring Airway Stenosis in Chinese Adults： Characteristics and Interventional Bronchoscopy Treatment

Background：Scarring airway stenosis is commonly seen in China as compared to other developed countries,due to the high prevalence of tuberculosis.Nowadays,interventional bronchoscopy treatment has been widely used to treat this disease in China.This study demonstrated the characteristics of scarring airway stenosis in Chinese adults and retrospectively evaluated the efficacy of interventional bronchoscopy treatment of this disease.Methods：Patients with scarring airway stenosis from 18 tertiary hospitals were enrolled between January 2013 and June 2016.The causes,site,and length of scarring airway stenosis were analyzed,and the efficacy of the interventional bronchoscopy treatment was evaluated.Results：The final study cohort consisted of 392 patients.Endotracheobronchial tuberculosis （EBTB） was the most common cause of scarring airway stenosis （305/392,77.8%） in Chinese adults with a high rate of incidence in young women.The left main bronchus was most susceptible to EBTB,and most posttuberculosis airway scarring stenosis length was 1.1-2.0 cm.The average clinical success rate of interventional bronchoscopy treatment for scarring airway stenosis in Chinese patients is 60.5%.The stent was inserted in 8.7% scarring airway stenosis in China.Conclusions：Scarring airway stenosis exhibits specific characteristics in Chinese patients.Interventional bronchoscopy is a useful and safe treatment method for the disease.

Comparison of clinical features and stent placement outcomes between airway stenosis caused by primary pulmonary malignancies and that caused by primary non-pulmonary malignancies

Background: Primary pulmonary malignancies (PPMs) and non-pulmonary malignancies (PNPMs) may result in airway stenosis requiring stenting. This study aimed to compare and evaluate the clinical features and stent placement outcomes of airway stenosis caused by PPMs and PNPMs. Methods: A total of 141 patients with malignant airway stenosis who underwent Micro-Tech stent placements between January 2004 and October 2017 at Department of Respiratory Medicine, Beijing Tian Tan Hospital, Capital Medical University were divided into PPM (n= 100) and PNPM groups (n = 41). Patients’ clinical features and stent placement outcomes were collected and analyzed. Chi-square test was used to compare the categorical variables, while independent- or paired-sample t test was used to compare the continuous variables. Results: There were no significant differences in age, sex, treatment history, respiratory symptoms, and incidence of obstructive pneumonia between groups. Multiple airway involvement (63.0% vs. 31.7%;χ^2=11.459, P= 0.001) and atelectasis (17.0% vs. 2.4%;χ^25.536, P= 0.019) were more common in the PPM group, while extraluminal obstruction (24.4% vs. 6.0%;χ^28.033, P= 0.005) was more common in the PNPM group. Before stenting, the American Thoracic Society Dyspnea Index (ADI) and Karnofsky Performance Scale (KPS) scores showed no significant differences between groups (all P > 0.05). After stenting, a satisfactory rate of symptom improvement was achieved in both groups (98.0% and 100.0% in the PPM and PNPM groups, respectively;χ^2 0.016, P= 0.898);ADI and KPS scores, which showed no significant differences between groups (all P > 0.05), were significantly improved in each group (all P < 0.001). Complications after stenting could be effectively managed using bronchoscopic procedures. Conclusions: Among cases of malignant airway stenosis requiring stenting, those caused by PPM are more likely to involve multiple airways and are associated with atelectasis, while those caused by PNPM are more likely to cause extraluminal obstruction. Micro- Tech stent placement has the same immediate effect in terms of improvement in respiratory symptoms and performance status for both malignant airway stenosis caused by PPM and that caused by PNPM.

Interventional Bronchoscopic Therapy in Adult Patients with Tracheobronchial Mucoepidermoid Carcinoma

Background： Tracheobronchial mucoepidermoid carcinoma （MEC） is a rare airway tumor in adults for which surgery is considered a first-line treatment. However, some patients already lost the best opportunity of a surgical intervention when diagnoses are confirmed, and surgery causes considerable trauma resulting in partial loss of pulmonary function. Moreover, the tumor is resistant to radiotherapy and chemotherapy. These factors make the treatment of tracheobronchial MEC challenging. This study aimed to evaluate the safety and et^cacy ofinterventional bronchoscopic therapy in adult patients with tracheobronchial MEC. Methods： We retrospectively analyzed the clinical manifestations, bronchoscopic interventions, complications, and outcomes of 11 adult patients with tracheobronchial MEC. Paired t-test was used to analyze the parameters of the American Thoracic Society Dyspnea Index and the Karnofsky Score before and after the first interventional bronchoscopic therapy. Results： All tumors occurred in the main bronchus and were easily visualized by bronchoscopy. After interventional bronchoscopic therapy, the symptoms of all patients showed significant improvement. The American Thoracic Society Dyspnea Index decreased from 1.91 ± 1.22 to 0.27 ± 0.47 （t = 6.708, P 〈 0.001） and the Kamofsky Score increased from 78.18 ±16.62 to 95.46 ± 8.20 （t =-5.190, P 〈 0.001 ）. Bronchoscopic intervention did not result in serious complications or mortality. During the follow-up period between 3 and 96 months after the first therapy, the following results were noted： （ 1 ） among the eight patients with low-grade tracheobronchial MEC, only one patient had a relapse and agreed to surgical treatment; （2） among the three patients with high-grade tracheobronchial MEC, one patient required repeated bronchoscopic interventions, one patient died of pulmonary infection, and one patient died of systemic failure owing to tumor metastasis. Conclusions： Interventional bronchoscopic therapy, as an alternative treatment, shows promise in some adult patients with low-grade tracheobronchial MEC confined to the bronchus. However, for adult patients with high-grade tracheobronchial MEC, early diagnosis and surgical treatment are still strongly recommended.

Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model

Background：Currently available silicone and metallic stents for tracheal stenosis are associated with many problems.Granulation proliferation is one of the main complications.The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model,as well as the pharmacokinetic features and safety profiles of the coated drug.Methods：Eight beagles were randomly divided into a control group （bare-metal stent group,n =4） and an experimental group （paclitaxel-eluting stent group,n =4）.The observation period was 5 months.One beagle in both groups was sacrificed at the end of the 1st and 3rd months,respectively.The last two beagles in both groups were sacrificed at the end of 5th month.The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups.Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent.The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent.Results：Compared with the control group,the proliferation of granulation tissue in the experimental group was significantly reduced.The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation （up to 70.9%）.Then,the release slowed down gradually.By the 54 month,the release reached up to 98.5%.During the observation period,a high concentration of the drug in the trachea （in the stented and adjacent unstented areas） and lung tissue was not noted,and the blood test showed no side effect.Conclusions：The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo,suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future.