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Abstract Background It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be “stabilized” (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long‐term (2 years) following the endoscopic procedure. Results Sixty‐six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan–Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5–9.8], p = .01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p = .01). Conclusions Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3.

Purpose: Benign tracheal stenosis management is still controversial, and there is no international consensus on the best treatment option. Thus, we aimed to look into the history of PITS and the different strategies used in its treatment. The importance of bronchoscopic treatment was also defined, and its effectiveness and safety were assessed. Methods: Retrospective study of patients diagnosed with PITS, who were referred to the Bronchology Department between January 1996 and December 2016. Results: Of 115 patients enrolled (mean age 48.5 ± 17.6 years, 53% males), 66.1% had complex stenosis. The most common causes of intubation were respiratory (29.9%), neurological (26.8%) and surgical (19.6%). Complex stenosis was caused by longer intubation, and was more frequent among previously tracheostomized patients. The most common location was the upper third of trachea (60.9%). Most cases were initially treated by interventional bronchoscopy, and although serial dilations were effective in some complex PITS, a higher proportion of simple stenosis was successfully managed with this treatment option. Long-term recurrence after serial dilation was observed in 25.0% of cases. Stent placement was required (19.1%) only for complex PITS. Stent-related complications were frequent (61.9%) and linked to the stenting time (p

Objective: To explore the possible biological functions of the differentially expressed genes in patients with benign tracheal stenosis, and to provide a valuable molecular basis for investigating the pathogenesis of benign tracheal stenosis. Method: Whole transcriptome sequencing was performed on blood samples collected from patients with benign tracheal stenosis and normal controls. Differentially expressed mRNA, lncRNA, and circRNA were analyzed using the DESeq2 package. The protein interaction networks for differentially expressed mRNAs were constructed by STRING. The results of gene co-expression network analysis, Starbase database prediction, and differential gene expression were combined to construct a competing endogenous RNA network. The transcription factors of key genes were predicted using the Network Analyst database and a transcription factor-mRNA regulatory network was constructed. The classical pathways, intermolecular interaction networks, and upstream regulatory components of key genes were analyzed using Ingenuity Pathway Analysis (IPA). Finally, the DGIDB database was used to predict the potential therapeutic drugs to target the identified key genes. Result: Based on mRNA, lncRNA and circRNA expression data, we found that differentially expressed mRNAs were enriched in oxygen transport, neutrophil activation, immune response, and oxygen binding. Then the pearson correlation between mRNAs of 46 key genes and lncRNAs and cricRNAs were calculated, and the correlation greater than 0.9 were selected to construct the co-expression network of "mRNA-lncRA" and "mRNA-cricRNA." Moreover, a "lncRNA-miRNA-mRNA" network and a "circRNA-miRNA-mRNA" network were constructed. IPA analysis showed that the 46 key genes were significantly associated with inflammatory activation and acute respiratory distress syndrome. The constructed TF-mRNA regulatory network was composed of 274 nodes and 573 interacting pairs. 251 potential therapeutic drugs were identified from the DGIDB database. Conclusion: This study analyzed the differential genes associated with benign tracheal stenosis and explored the potential regulatory mechanisms, providing a scientific reference for further studies on the pathogenesis of benign tracheal stenosis. [ABSTRACT FROM AUTHOR]

Background: It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods: A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be "stabilized" (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long‐term (2 years) following the endoscopic procedure. Results: Sixty‐six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan–Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5–9.8], p =.01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p =.01). Conclusions: Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3. [ABSTRACT FROM AUTHOR]

Objective: To explore the possible biological functions of the differentially expressed genes in patients with benign tracheal stenosis, and to provide a valuable molecular basis for investigating the pathogenesis of benign tracheal stenosis.Method: Whole transcriptome sequencing was performed on blood samples collected from patients with benign tracheal stenosis and normal controls. Differentially expressed mRNA, lncRNA, and circRNA were analyzed using the DESeq2 package. The protein interaction networks for differentially expressed mRNAs were constructed by STRING. The results of gene co-expression network analysis, Starbase database prediction, and differential gene expression were combined to construct a competing endogenous RNA network. The transcription factors of key genes were predicted using the Network Analyst database and a transcription factor-mRNA regulatory network was constructed. The classical pathways, intermolecular interaction networks, and upstream regulatory components of key genes were analyzed using Ingenuity Pathway Analysis (IPA). Finally, the DGIDB database was used to predict the potential therapeutic drugs to target the identified key genes.Result: Based on mRNA, lncRNA and circRNA expression data, we found that differentially expressed mRNAs were enriched in oxygen transport, neutrophil activation, immune response, and oxygen binding. Then the pearson correlation between mRNAs of 46 key genes and lncRNAs and cricRNAs were calculated, and the correlation greater than 0.9 were selected to construct the co-expression network of “mRNA-lncRA” and “mRNA-cricRNA.” Moreover, a “lncRNA-miRNA-mRNA” network and a “circRNA-miRNA-mRNA” network were constructed. IPA analysis showed that the 46 key genes were significantly associated with inflammatory activation and acute respiratory distress syndrome. The constructed TF-mRNA regulatory network was composed of 274 nodes and 573 interacting pairs. 251 potential therapeutic drugs were identified from the DGIDB database.Conclusion: This study analyzed the differential genes associated with benign tracheal stenosis and explored the potential regulatory mechanisms, providing a scientific reference for further studies on the pathogenesis of benign tracheal stenosis.

Background: Benign tracheal stenosis may relapse after management. Objectives: This study aimed to assess the value of dyspnea and spirometry in detecting relapse of benign tracheal stenosis. Methods: Patients with benign tracheal stenosis were evaluated post-management, at regular follow-up and emergency visits, with the Medical Research Council (MRC) dyspnea scale, spirometry, and flexible bronchoscopy. Patient visits were categorized and compared, in terms of change in clinical and functional parameters, in 2 groups: visits with relapse (case group) and visits with no relapse (control group). The ability of the MRC dyspnea scale and spirometry to predict relapse was evaluated. Results: Thirty-five patients with benign tracheal stenosis were included. Mean follow-up duration was 3.2 years (standard deviation = 3.3). Spirometry data were analyzed from 43 relapse visits (23 patients) versus 90 nonrelapse visits. The MRC dyspnea score and most spirometric indices were associated with relapse. In the receiver operating characteristic analysis, forced expiratory volume in 1 s, forced expiratory flow when 25% of forced vital capacity has been expired, peak expiratory flow (PEF), and total peak flow were superior to the MRC dyspnea score in predicting relapse. Among spirometric indices, >10.8% of PEF reduction has been very sensitive and specific. Conclusions: This study supports the role of dyspnea and spirometry in monitoring benign tracheal stenosis, with spirometry predicting relapse even in clinically stable patients. PEF being a very sensitive index has the additional advantage of being assessed by peak flow meter and could potentially be used for remote monitoring. [ABSTRACT FROM AUTHOR]

Background: A limitation of bronchoscopic balloon dilatation (BBD) is that airflow must be completely blocked for as long as possible during the operation. However, the patient often cannot hold his or her breath for a long period affecting the efficacy of the procedure. In this study, we used an extra-small-diameter tube to provide assisted ventilation to patients undergoing BBD and assessed the efficacy and safety of this technique. Methods: Bronchoscopic balloon dilatation was performed in 26 patients with benign tracheal stenosis using an extra-small-diameter tube. The tracheal diameter, dyspnea index, blood gas analysis results, and complications were evaluated before and after BBD. Statistical analyses were performed by SPSS version 16.0 for Windows (SPSS, Inc., Chicago, IL, USA). Results: Sixty-three BBD procedures were performed in 26 patients. Dyspnea immediately improved in all patients after BBD. The tracheal diameter significantly increased from 5.5 ± 1.5 mm to 13.0 ± 1.3 mm (P < 0.001), and the dyspnea index significantly decreased from 3.4 ± 0.8 to 0.5 ± 0.6 (P < 0.001). There was no significant change in the partial pressure of oxygen during the operation (before, 102.5 ± 27.5 mmHg; during, 96.9 ± 30.4 mmHg; and after, 97.2 ± 21.5 mmHg; P = 0.364), but there was slight temporary retention of carbon dioxide during the operation (before, 43.5 ± 4.2 mmHg; during, 49.4 ± 6.8 mmHg; and after, 40.1 ± 3.9 mmHg; P < 0.001). Conclusion: Small-diameter tube-assisted BBD is an effective and safe method for the management of benign tracheal stenosis.

Abstract: Objective: To compare the safety and efficacy between using a small‐diameter tube‐assisted bronchoscopic balloon dilatation (BBD) and the traditional BBD in the treatment of benign tracheal stenosis. Methods: A retrospective study included 58 patients with benign tracheal stenosis from August 2009 to December 2014 was made. The patients who underwent traditional BBD were divided into group A, and who underwent a small‐diameter tube‐assisted BBD were divided into group B. The tracheal diameter, dyspnea index and blood gas analysis results were detected before and after BBD. Efficacy and complications were evaluated after BBD. Results: There were significant differences in oxygen saturation (PaO2) during the operations comparing with before and after operations in group A (P = .005), while there was no significant difference in group B (P = .079). The tracheal diameter obviously increased (in group A, from 4.16 ± 1.43 mm to 12.47 ± 1.41 mm, P = .000; in group B: from 4.94 ± 1.59 mm to 12.61 ± 1.41 mm, P = .000). Dyspnea index obviously decreased (group A: from 3.21 ± 0.93 to 0.50 ± 0.59, P = .000; group B: from 3.24 ± 0.89 to 0.65 ± 0.69, P = .000). The immediately cure rate in both groups was 100%. Long‐term effect was significantly better in group B than that in group A (85.3% vs 59.1%, P = .021), at the end of the follow‐up period. Conclusions: Small‐diameter tube‐assisted BBD obtains better safety and long‐term efficacy than the traditional BBD in the treatment of benign tracheal stenosis. However, close attention should be given to the risk of the adverse effects caused by carbon dioxide retention. [ABSTRACT FROM AUTHOR]

Background: Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis., Methods: An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks., Results: Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells., Conclusions: Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis., (© The Author(s) 2023. Published by Oxford University Press.)

We reported the role of endobronchial ultrasound as complement to standard diagnostic exams to better define the benign tracheal stenosis (i.e., thickness and tracheal cartilage integrity) and to plan the treatment with flexible instead of rigid bronchoscope. Under sedation and spontaneous ventilation, the flexible bronchoscope was inserted through the laryngeal mask airway that assured the ventilation. The stenosis was first resected with cold scissors and then dilated with balloon catheter. This strategy was successfully applied in five consecutive patients. Inclusion criteria for the procedure were stenosis < 1 cm in length, without tracheomalacia and with integrity of airway cartilage. [ABSTRACT FROM AUTHOR]

Background: Airway granulation tissue and scar formation pose a challenge because of the high incidence of recurrence after treatment. As an emerging treatment modality, topical application of mitomycin C has potential value in delaying the recurrence of airway obstruction. Several animal and clinical studies have already proven its feasibility and efficacy. However, the ideal dosage has still not been determined. Objectives: To establish a novel method for culturing primary fibroblasts isolated from human airway granulation tissue, and to investigate the dose-effect of mitomycin C on the fibroblast proliferation in vitro, so as to provide an experimental reference for clinical practitioners. Methods: Granulation tissues were collected during the routine bronchoscopy at our department. The primary fibroblasts were obtained by culturing the explanted tissues. The cells were treated with different concentrations of mitomycin C (0.1, 0.2, 0.4, 0.8 and 1.6 mg/ml) for 5 min followed by additional 48-hour culture before an MTT assay was performed to measure cell viability. Results: MTT assay showed that mitomycin C reduced cell viability at all tested concentrations. The inhibitory ratios were 10.26, 26.77, 32.88, 64.91 and 80.45% for cells treated with mitomycin C at 0.1, 0.2, 0.4, 0.8 and 1.6 mg/ml, respectively. Conclusions: Explant culture is a reliable method for culturing primary fibroblasts from human airway granulation tissue, and mitomycin C can inhibit proliferation of the fibroblasts in vitro. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We assessed the results of self-expanding metallic stent insertion into benign proximal tracheal stenosis in patients not appropriate or unfit for surgical repair. Proximal benign tracheal stenoses had occurred in 11 patients (7 men, 4 women, mean age 68.8 years) after long-time intubation (n = 6), tracheostomy (n = 4), or chondropathia (n = 1). Fourteen self-expanding nitinol stents were placed in the patients under general anesthesia with endoscopical and fluoroscopical guidance. Stent insertion was successful in all cases and led to immediate relief of the morphological and functional airway obstruction. No immediate complications were noted. During the mean follow-up period of 67.5 weeks we observed one recurrent dyspnea 3 months after implantation and granuloma formation at the stent insertion site in another patient. Both complications were successfully treated with additional stent insertion in one case and laser resection of granulomas in the other. Self-expanding nitinol stents should be considered for the treatment of benign proximal tracheal obstruction in selected patients for whom surgical repair is contraindicated. [ABSTRACT FROM AUTHOR]

Background: Endoluminal therapy either by dilatation, scar tissue resection or stent insertion is an established treatment for non-malignant airway stenosis although the surgical approach is still considered the "gold standard." No clear consensus exists on the structured role of each modality.Aims: We aimed to investigate the role of bronchoscopic management in non-operable tracheal stenosis cases, evaluating the effectiveness and safety of each procedure based on a structured algorithmic approach.Patients and Methods: This prospective study was carried out on (40) consecutive patients diagnosed between March 2017 and March 2020 with tracheal stenosis not amenable to surgery. All strictures were first evaluated by flexible bronchoscopy and classified as simple or complex. Patients were treated following a standardised therapeutic algorithm approach based on published evidence and our own expertise.Results: The mean age of the study population was 45.25 ± 18.79; lesions were classified as simple (14) and complex (24), while two patients had mixed type stenosis. Long term success rate was 100% in simple stenosis and 87.5% in the complex ones. Stents were deployed in 24 cases, most of which were of the complex type and only two of the simple type. Post-procedural mild to moderate complications were detected overall in 70% of the patients. All complications were non-life threatening, mostly stent-related and were effectively managed.Conclusion: We conclude that after accurate classification and a structured algorithmic approach, interventional bronchoscopic management may play a crucial role in the effective treatment of benign tracheal stenosis. [ABSTRACT FROM AUTHOR]

Benign tracheal stenosis is a life-threatening condition that needs a prompt treatment when the tracheal lumen is less than 5 mm. In patients unfit for surgery, endoscopic dilation with stent insertion (if indicated) remains the main alternative to restore airway patency and assure ventilation. Endoscopic management of tracheal stenosis may be a cumbersome procedure, that sometimes takes a long time, and may be complicated by stent dislocation especially in cases of complex stenosis, near to vocal folds. In recent years, the 3D printing industry has undergone rapid development, and 3D printing model has been increasingly applied to different medical fields where therapeutic interventions rely on defining complex anatomic structural relationships. Thus, in this review we aimed to evaluate whether the use of 3D printing model as tool for preoperative planning could facilitate the endoscopic treatment of tracheal stenosis and improve outcome. Three papers evaluated this issue: one paper reported a consecutive series of patients while the remaining single case report. All authors concluded that the 3D model aided the understanding of patient's anatomy and the stenosis's characteristic. The possibility of recreating the endoscopic procedure in the 3D model facilitated and shorted the procedural time in live patient. Furthermore, the 3D model was additionally useful to choose the length, diameter and shape of stent and to define the exact distance of the proximal end of stent from the vocal folds after its insertion. Finally, it represented an educational tool for patients and his/her family to understand the procedure, and for residents and fellows to improve endoscopic skills., Competing Interests: Conflicts of Interest: All authors have completed the ICJME disclosure form (available at http://dx.doi.org/10.21037/tcr.2020.01.22). The series “Recent Developments in Benign Tracheal Stenosis” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

The article describes an anesthetic management strategy for resection of the cervical trachea due to benign stenosis without using an endotracheal tube. The strategy includes: (1) insertion of an airway stent in the stenotic area, (2) insertion of a supraglottic airway device (SGAD), and (3) advancing a jet ventilation catheter through the SGAD. The stent is removed during surgery together with the resected part of the trachea. The technique of nonintubated tracheal resection allows the surgeon to work most comfortably and helps the anesthesiologist properly maintain the patient's vital functions in the operating room., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tracheal stenosis is a potentially life-threatening condition. Tracheostomy and endotracheal intubation remain the commonest causes of benign stenosis, despite improvements in design and management of tubes. Post-tracheostomy stenosis is more frequently encountered due to earlier performance of tracheostomy in the intensive care units, while the incidence of post-intubation stenosis has decreased with application of high-volume, low-pressure cuffs. In symptomatic benign tracheal stenosis the gold standard is surgical reconstruction (often after interventional bronchoscopy). Stenting is reserved for symptomatic tracheal narrowing deemed inoperable, due to local or general reasons: long strictures, inflammation, poor respiratory, cardiac or neurological status. When stenting is decided, silicone stent insertion is considered the treatment of choice in the presence of inflammation and/or when removal is desirable. We inserted tracheal silicone stents (Dumon) under general anaesthesia through rigid bronchoscopy in two patients with benign post-tracheostomy stenosis: a 39-year old woman with failed initial operation, and continuous relapses with proliferation after multiple bronchscopic interventions, and a 20-year old man in a poor neurological status, with a long tracheal stricture involving the subglottic larynx (lower posterior part), and inflamed tracheostomy site tissues (positive for methicillin resistant staphylococcus aureus). The airway was immediately re-establish, without complications. At 15- and 10-month follow-up (respectively) there was no stent migration, luminal patency was maintained without: adjacent structure erosion, secretion adherence inside the stents, granulation at the ends. Tracheostomy tissue inflammation was resolved (2(nd) patient), new infection was not noted. The patients maintain good respiratory function and will be evaluated for scheduled stent removal. Silicone stents are removable, resistant to microbial colonization and are associated with minimal granulation. In benign post-tracheostomy stenosis silicone stenting appeared safe and effective in re-stenosis after surgery and multiple bronchoscopic interventions, and in long stenosis, involving the lower posterior subglottic larynx in the presence on inflammation and poor neurological status.