Use of Mitomycin-C in Laryngotracheal Stenosis: A Focused Clinical Review.

BACKGROUND: Therapeutic options for managing laryngotracheal stenosis (LTS) are limited. Endoscopy is a minimally invasive approach to treating LTS, but carries a high risk of stenosis recurrence. Mitomycin C (MMC) is often used as an adjunct therapy to delay the time to symptomatic recurrence of LTS. This review synthesizes the current literature on the topic of MMC as an adjunct treatment strategy for LTS. METHODS: A focused literature search was carried out from PubMed on June 12, 2022 using the terms "mitomycin c AND stenosis" in all fields with no date limitations. Evidence-based recommendations relevant to the clinical application of MMC as an adjunct therapy for LTS were formulated. Three questions were addressed: 1) efficacy of MMC, 2) single versus multiple application(s) of MMC, and 3) safety of MMC. The evidence rating and recommendation strength were guided by the GRADE system. RESULTS: Twenty-nine studies were reviewed. The efficacy of MMC as an adjunct therapy for LTS varied across studies. Randomized controlled trials have not shown an outcome difference with MMC use, although methodologic flaws including underpowering were noted. A meta-analysis of observational studies with a comparator arm found the unadjusted probability of remaining symptom-free for > 1 year is greater with versus without MMC application (73% vs. 35%). Single versus multiple application(s) of MMC resulted in similar restenosis rates at long-term follow-up. Complications related to MMC use are rarely reported using conventional doses (0.4 mg/mL). Overall, the quality of evidence was low and the recommendation for intervention was weak. CONCLUSION: The role for MMC as an adjunct therapy in LTS is uncertain. While safe in its application, the efficacy of MMC in reducing stenosis recurrence remains a matter of debate. Large, prospective studies are needed to inform future recommendations.

Robotic Bronchoscopy for Peripheral Pulmonary Lesions: A Multicenter Pilot and Feasibility Study (BENEFIT).

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects. RESEARCH QUESTION: What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs? STUDY DESIGN AND METHODS: This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator. RESULTS: Fifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred. INTERPRETATION: This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov.

Accuracy of a Robotic Endoscopic System in Cadaver Models with Simulated Tumor Targets: ACCESS Study.

BACKGROUND: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear. OBJECTIVES: This study was performed to evaluate the performance of a robotic bronchoscopic system's ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs. METHODS: Artificial tumor targets sized 10-30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions. RESULTS: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21-30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura. CONCLUSIONS: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10-30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects.

3D printing for airway disease.

It has been 30 years since the first commercial three-dimensional (3D) printer was available on market. The technological advancement of 3D printing has far exceeded its implementation in medicine. The application of 3D printing technology has the potential of playing a major role within interventional pulmonology; specifically, in the management of complex airway disease. Tailoring management to the patient-specific anatomical malformation caused by benign or malignant disease is a major challenge faced by interventional pulmonologists. Such cases often require adjunctive therapeutic procedures with thermal therapies followed by dilation and airway stenting to maintain the patency of the airway. Airway-stent size matching is one key to reducing stent-related complications. A major barrier to matching is the expansion of the stent in two dimensions (fixed sizes in length and diameter) within the deformed airway. Additional challenges are created by the subjective oversizing of the stent to reduce the likelihood of migration. Improper sizing adversely affects the stability of the stent. The stent-airway mismatch can be complicated by airway erosion, perforation, or the formation of granulation tissue. Stents can migrate, fracture, obstruct, or become infected. The use of patient-specific 3D printed airway stents may be able to reduce the stent airway mismatch. These stents allow more precise stent-airway sizing and minimizes high-pressure points on distorted airway anatomy. In theory, this should reduce the incidence of the well-known complications of factory manufactured stents. In this article, the authors present the brief history of 3D printed stents, their consideration in select patients, processing steps for development, and future direction.

Intrabronchial Valves for Air Leaks After Lobectomy, Segmentectomy, and Lung Volume Reduction Surgery.

PURPOSE: Air leaks are common after lobectomy, segmentectomy, and lung volume reduction surgery (LVRS). This can increase post-operative morbidity, cost, and hospital length of stay. The management of post-pulmonary resection air leaks remains challenging. Minimally invasive effective interventions are necessary. The Spiration Valve System (SVS, Olympus/Spiration Inc., Redmond, WA, US) is approved by the FDA under humanitarian use exemption for management of prolonged air leaks. METHODS: This is a prospective multicenter registry of 39 patients with air leaks after lobectomy, segmentectomy, and LVRS managed with an intention to use bronchoscopic SVS to resolve air leaks. RESULTS: Bronchoscopic SVS placement was feasible in 82.1% of patients (32/39 patients) and 90 valves were placed with a median of 2 valves per patient (mean of 2.7 ± 1.5 valves, range of 1 to 7 valves). Positive response to SVS placement was documented in 76.9% of all patients (30/39 patients) and in 93.8% of patients when SVS placement was feasible (30/32 patients). Air leaks ultimately resolved when SVS placement was feasible in 87.5% of patients (28/32 patients), after a median of 2.5 days (mean ± SD of 8.9 ± 12.4 days). Considering all patients with an intention to treat analysis, bronchoscopic SVS procedure likely contributed to resolution of air leaks in 71.8% of patients (28/39 patients). The post-procedure median hospital stay was 4 days (mean 6.0 ± 6.1 days). CONCLUSIONS: This prospective registry adds to the growing body of literature supporting feasible and effective management of air leaks utilizing one-way valves.

Application of 3D Printing for Patient-Specific Silicone Stents: 1-Year Follow-Up on 2 Patients.

Managing complex benign airway disease is a major challenge in interventional pulmonology. Airway stent placement can result in complications due to a variety of factors, including poor fit of the stent in the airway. We report the 1-year outcome of 2 patients with airway disease caused by granulomatosis with polyangiitis (Wegener's) affecting the left main bronchus and secondary carina. These patients had not responded to systemic therapy or standard bronchoscopic techniques and had complications with commercially available airway stents. We describe a first-in-human, clinical experience to address these issues. Using computed tomography (CT) imaging and 3D printing technology, we generated and implanted patient-specific silicone airway stents to address airway disease. 3D patient-specific stent prescription was created using a CT scan of the patient's chest and a proprietary software package originally developed for orthopedic surgical planning. Silicone stents were manufactured and implanted. Observation for > 1 year after implantation compared to the 6 months prior to patient-specific stent implant were compared for the number, clinically required stent changes, procedure time, and general clinical improvement per usual standard of care after airway stenting. Patients showed improved durability, a shorter procedure time, and improvement of patient-reported symptoms leading to a reduced need for stent changes and modifications. The use of 3D printing technology to make patient-specific silicone stents is feasible with early clinical proof of concept noting a durable improvement over 1 year of follow-up.

Clinical Success Stenting Distal Bronchi for "Lobar Salvage" in Bronchial Stenosis.

BACKGROUND: Airway stents are traditionally used in central airway obstructions to maintain airway patency. Historically, distal bronchial stenting within lobar and segmental bronchi has not been amenable to stenting. In addition, there are questionable benefits to stenting small airways. The Atrium iCast stent is a polytetrafluoroethylene covered stainless steel balloon deployed stent which can be deployed through a flexible bronchoscope under direct visualization. The purpose of this study was to assess the feasibility, complications, and long-term impact of using this stent in patients with lobar bronchial stenosis either secondary to malignancy or benign etiologies. METHODS: All records of patients who had the placement of an iCast stent were reviewed over 3.5 years. For each patient the age, sex, location, histology, stent size, duration of stent placement, radiographic improvement, and complications were collected. RESULTS: A total of 122 iCast stents were deployed in 38 patients with lobar bronchial stenosis. The average age was 58 years with 50% male. The etiology included 45% malignant and 55% due to benign conditions. In total, 18.5% patients had stents placed in >1 segment. There was an average of 4 procedures per patient with a mean time to stent revision or removal of 85 days. All patients had symptomatic or radiographic improvement. Common complications included migration (10%), granulation tissue formation (5%), deployment malfunction (2%), stent dislodgement immediately after deployment (2%), mucous plugging (1%), and tumor occlusion (1%). CONCLUSION: Stenting small airways with lobar salvage is feasible and improves symptoms and radiographic outcomes.

Vanishing Bronchus After Lung Transplantation: The Role of Sequential Airway Dilatations.

BACKGROUND: Airway complications after lung transplant play an important role in patient survival. Early recognition and treatment of these complications are necessary to help ensure that patients who receive lung transplants have good outcomes. CASE REPORT: A 61-year-old female with a history of pulmonary venous occlusive disease presented to our hospital for a double-lung transplant. Her postoperative course was complicated by severe primary graft dysfunction. Airway examination showed significant mucosal ischemia distal to the anastomosis bilaterally with diffuse narrowing of all distal bronchial segments. Repeat bronchoscopies with debridement of necrotic material and balloon dilatation of stenotic airways were performed to maintain airway patency. CONCLUSION: Post-lung transplant airway necrosis and stenosis mandate early identification and treatment. Repetitive bronchoscopies with sequential balloon dilatations are mandatory to prevent future airway stenosis and airway vanishing.

The Feasibility of EBUS-Guided TBNA Through the Pulmonary Artery in Highly Selected Patients.

BACKGROUND: The use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis and staging of benign and malignant thoracic disease has rapidly evolved into the standard of care. The lymph node stations that can be reached by EBUS and EUS are substantially more than those that can be accessed by mediastinoscopy. In rare cases, the clinician is faced with extraordinary circumstances in which a minimally invasive approach to the lymph nodes in station 5 is required. We present our findings in 10 cases, at 7 different institutions, where EBUS was instrumental in reaching a diagnosis. METHODS: We retrospectively collected 10 cases where EBUS-TBNA was performed through the pulmonary artery in an attempt to reach the territory of lymph node station 5. All cases were performed by experienced interventional pulmonologists at 7 tertiary care centers in the United States and Canada. We describe the patients' demographics, comorbidities, complications, and cytopathology. RESULTS: A definitive diagnosis was reached in 9 of the 10 patients. One case showed atypical cells and required a confirmatory Chamberlain procedure. No complications occurred as a result of careful transpulmonary artery needle aspiration. CONCLUSIONS: This multicenter case series suggests that transpulmonary artery needle aspiration guided by EBUS is possible and safe in the hands of experienced interventional pulmonologists. It is important to recognize that this is not an alternative to left VATS or Chamberlain procedure, but a last resort procedure.

Endobronchial Ultrasound-guided Transvascular Needle Aspiration: A Single-Center Experience.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is well established for the staging and diagnosis of lung cancer and mediastinal lymphadenopathy. Central mediastinal vascular structures may preclude EBUS-TBNA access to lymph nodes in the aortopulmonary window and certain centrally located parenchymal lesions. Thus, a transvascular approach is necessitated. Few such reports exist in the literature. METHODS: We retrospectively analyzed the results of endobronchial ultrasound-guided transvascular needle aspiration (EBUS-TVNA) performed over 1 year to sample mediastinal lymph nodes (stations: 5) and lung lesions inaccessible by standard bronchoscopy or EBUS-TBNA. Data regarding the indication, location, size, and relationship to adjacent blood vessels, the number of transvascular passes, EBUS-TVNA diagnosis, the final diagnosis, procedural images, and complications were collected. Patients' charts were reviewed for 6 months after the procedure for evidence of late complications, including mediastinitis or mediastinal hemorrhage. RESULTS: Of 865 EBUS-TBNA procedures, 10 were performed by traversing the pulmonary artery or its branches. Nine were for left-sided lesions, 3 for hilar parenchymal nodules, 6 for hilar or mediastinal LN, and the remainder for a right-sided mass. Rapid-onsite evaluation was either diagnostic or positive for lymphoid cells in 9 patients and the final cytopathology was diagnostic in 9 patients: 5 non-small cell lung cancer, 1 small cell cancer, 1 metastatic colon cancer, and 2 normal lymphoid tissue. One patient had necrosis and required video assisted thoracoscopic surgery to diagnose histoplasmosis. Bleeding was insignificant, with no short-term/long-term complications. CONCLUSIONS: From our single-center experience, we conclude that in experienced hands, EBUS-TVNA is feasible, with a high yield, but without complications. Larger prospective trials are warranted to explore its diagnostic potential.

Malignant tracheal-mediastinal-parenchymal-pleural fistula after chemoradiation plus bevacizumab: management with a Y-silicone stent inside a metallic covered stent.

Tracheal or bronchial-mediastinal fistulas are a rare entity associated to high mortality. We report a case of a 58-year-old man with an unresectable non-small cell carcinoma of the lung, treated with chemoradiation followed by bevacizumab. Approximately, 6 weeks after starting bevacizumab he developed a severe cough with copious secretions He could not lie supine due to the feeling of drowning. Investigations revealed a large tracheo-mediastinal-parenchymal-pleural fistula. Palliative management was offered with interventional bronchoscopic techniques. He was found to have a large central airway defect that obliterated almost 40% of the trachea. Under general anesthesia and positive pressure ventilation, a unique approach was used to rebuild an eroded tracheal and right main stem bronchial wall. A self-expanding metallic stent (SEMS) was placed to provide a scaffold of support, whereas a Dumon Y-stent was placed inside the SEMS. This combination allowed for a patent, stable airway; recreating the normal anatomy in a minimally invasive manner walling off the fistula. The patient was discharged 2 days after the bronchoscopic intervention, with significant palliation of his symptomatology. Eighteen months later, the upper lobe cavity persists with a stable airway and stents perfectly positioned with clinically insignificant evidence of stent related granulation in the upper trachea.

Therapeutic bronchoscopy for malignant central airway obstruction: success rates and impact on dyspnea and quality of life.

BACKGROUND: There is significant variation between physicians in terms of how they perform therapeutic bronchoscopy, but there are few data on whether these differences impact effectiveness. METHODS: This was a multicenter registry study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was technical success, defined as reopening the airway lumen to > 50% of normal. Secondary outcomes were dyspnea as measured by the Borg score and health-related quality of life (HRQOL) as measured by the SF-6D. RESULTS: Fifteen centers performed 1,115 procedures on 947 patients. Technical success was achieved in 93% of procedures. Center success rates ranged from 90% to 98% (P = .02). Endobronchial obstruction and stent placement were associated with success, whereas American Society of Anesthesiology (ASA) score > 3, renal failure, primary lung cancer, left mainstem disease, and tracheoesophageal fistula were associated with failure. Clinically significant improvements in dyspnea occurred in 90 of 187 patients measured (48%). Greater baseline dyspnea was associated with greater improvements in dyspnea, whereas smoking, having multiple cancers, and lobar obstruction were associated with smaller improvements. Clinically significant improvements in HRQOL occurred in 76 of 183 patients measured (42%). Greater baseline dyspnea was associated with greater improvements in HRQOL, and lobar obstruction was associated with smaller improvements. CONCLUSIONS: Technical success rates were high overall, with the highest success rates associated with stent placement and endobronchial obstruction. Therapeutic bronchoscopy should not be withheld from patients based solely on an assessment of risk, since patients with the most dyspnea and lowest functional status benefitted the most.

Rigid bronchoscopy.

The purpose of this article is to provide an introduction to rigid bronchoscopy (RB). We will briefly discuss its history, evolution, and resurgence while we highlight its versatility and usefulness for today's interventional pulmonologist and thoracic surgeon. Despite being one of the earliest pulmonary procedures described, RB is still an important technique. Advances in thoracic medicine have made this skill critical for a fully functional interventional pulmonary program. If the interventional pulmonologist of this century is to be successful, he or she should be facile in this technique. Despite the availability of RB for decades, the invention of flexible bronchoscopy in 1966 led to a significant downturn in its usage. The growth of the interventional pulmonology field brought RB back into the spot light. Apart from the historic role of RB in treatment of central airway lesions and mechanical debulking of endobronchial lesions, RB is the key instrument that can adapt modern therapeutic tools such as laser, argon plasma coagulation, electrocautery, cryotherapy, and stent deployment. Performing RB requires proper preprocedure preparation, exceptional understanding of upper airway anatomy, specific hand-eye coordination, and open communication between the bronchoscopist and the anesthesiologist. These skills can be primarily learned and maintained with repetition. This article will review information relevant to this technique and lay a foundation to be built upon for years to come.

Complex metallic stent removal: decade after deployment.

Endobronchial involvement is a relatively uncommon but well-described presentation in Granulomatosis with polyangiitis (GPA). Self-expandable metallic stents (SEMs) should be reserved for the malignant airway disorder to maintain airway patency, but have been used for benign disease in specific cases. We present a case of longstanding endobronchial GPA with recurrent bronchial stenosis. Three SEMs were deployed in the distal left main bronchus 10 years prior. Two were removed in the standard manner, but the remaining stent SEM was completely embedded in the bronchial mucosa making its removal extraordinarily difficult. We placed an oversized silicone stent inside the stent leading to necrosis of the mucosa allowing for a less formidable removal of the embedded stent. Another silicone stent was temporarily placed. SEMs removal can be extremely complicated and should only be performed by experienced bronchoscopists in an institution with sufficient resources.

Impact of bedside bronchoscopy in critically ill lung transplant recipients.

BACKGROUND: Over 32,000 lung transplants have been performed worldwide for a variety of end-stage lung diseases (http://www.ishlt.org/). Flexible bronchoscopy (FB) is frequently used as a bedside-tool for diagnosis and management of respiratory failure among critically ill lung transplant recipients (LTRs). We study the indications, results, therapeutic impact, and complications of FB in LTRs admitted to medical intensive care unit (MICU). METHODS: Retrospective chart review was performed for all critically ill LTRs undergoing FB while admitted to MICU at the Cleveland Clinic Foundation between 2009 and 2011. ICD-9 codes for bronchoscopy were used to identify patients. The procedures were categorized as: (i) airway examination and interventions, (ii) microbiological, and (iii) histopathologic diagnosis. SAS version 9.2 was used for analysis. RESULTS: A cohort of 76 LTRs accounted for 93 hospital admissions, 101 MICU admissions, and 129 bronchoscopies. FB was helpful in evaluation and management of airway complications [secretion clearance (18% bronchoscopy procedures), stenosis/dehiscence (8% patients)] and optimizing management of lower respiratory tract infections. Isolation of resistant gram-negative organisms, community-acquired respiratory viruses, and fungi commonly led to modification in antimicrobial therapy (35% microbiological samples). Nonspecific finding of acute lung injury was the most commonly seen histopathology (70%) on transbronchial biopsy. Twenty percent (4/20) of transbronchial biopsies showed acute cellular rejection, with 1 episode contributing to respiratory failure. Occasional hypoxia and hypotension, but no deaths, were noted due to FB during the ICU admission. CONCLUSIONS: Use of FB modified clinical management in one third of airway evaluation and microbiological sampling procedures for critically ill LTRs. No fatalities were attributed to bronchoscopy in this critically ill population.

Intussusception technique of intrabronchial silicone stents: description of technique and a case report.

Respiratory tract infection with human papillomavirus has been associated with major airway complications, including tracheal stenosis. We report a case of recurrent respiratory papillomatosis infection complicated with iatrogenic airway fire injury causing airway stenosis. This was treated with reconstruction and a silicone Y stent placement. Three years after the stent placement, the patient presented with wheezing and shortness of breath. Bronchoscopy revealed tracheal narrowing proximal to the tracheal limb of the Y stent. The stenosis was treated with a stent intussusception technique with satisfactory results.

Newer modalities in the work-up of peripheral pulmonary nodules.

Technological advances in recent years have translated into the availability of newer modalities to establish the cause of peripheral pulmonary nodules (PPN). Even though the verdict is still out on the ideal diagnostic modality, there is no doubt that the bronchoscope is becoming a popular tool in the armamentarium of physicians who deal with PPN. This article focuses on newer bronchoscopic modalities being studied for the work-up of PPN. The authors also summarize the value of established diagnostic modalities to provide a balanced perspective.