Large airway obstruction occurs secondary to a variety

Medium-Term Follow-Up After Deployment of Ultraflex Expandable Metallic Stents to Manage Endobronchial Pathology Brendan P. Madden, MD, FRCP, John E. S. Park, MA, MRCP, and Abhijat Sheth, FRCS Department of Cardiothoracic Surgery, St. George s Hospital, London, England Background. Between March 1997 and March 2004 we deployed 80 Ultraflex metallic expandable stents (Boston Scientific, Waterson, MA) in 69 patients under direct vision using rigid bronchoscopy. We report our mediumto long-term experience in patients for whom these stents were deployed. Methods. To date 15 patients have been followed for more than 1 year (median 41 months, range 12 to 83 months) after stent deployment. Indications for stenting in these patients were neoplasia (5), stricture (5), airway malacia (1), iatrogenic tracheal tear (1), and compression from an aortic aneurysm (1), a right interrupted aortic arch (1), and a right brachiocephalic artery aneurysm with tracheomalacia (1). Ten tracheal stents (9 covered, 1 uncovered) and 10 bronchial stents (8 uncovered, 2 covered) were inserted, and 5 patients received two stents. Results. Five of these patients experienced no longterm problems. Complications included troublesome halitosis (5), which was difficult to treat despite various antibiotic regimes; granulation tissue formation above and below the stent that was successfully treated with low-power Nd:YAG laser therapy (7); and metal fatigue (1). We did not encounter stent migration. Conclusions. We conclude that Ultraflex expandable metallic stents have an important role in the management of selected patients with diverse endobronchial pathologies and are well tolerated in the long-term. Although associated granulation tissue can be successfully treated with Nd:YAG laser, halitosis can be a difficult problem to address. (Ann Thorac Surg 2004;78:1898 902) 2004 by The Society of Thoracic Surgeons Large airway obstruction occurs secondary to a variety of disease processes ranging from benign disorders to rapidly advancing malignant disease. Respiratory distress often ensues and requires urgent investigation and treatment. Surgical intervention is the mainstay of treatment, but many patients may be unsuitable for such intercession because of advanced malignancy or medical comorbidity. Interventional bronchoscopy has proved to be a valuable alternative to operation for selected patients, allowing the placement of tracheobronchial stents to restore airway patency or seal defects. Stenting can also be used alongside other bronchoscopic therapies, including laser ablation, and can be beneficial in stabilizing patients before receiving further treatment such as radiotherapy and chemotherapy, or for improving airway dynamics and facilitating weaning from mechanical ventilatory support. As experience with endobronchial stenting and availability of the procedure increases concerns have been expressed regarding the complications that might be experienced by longer-term survivors. We have deployed 80 expandable metallic stents in 69 patients. We wished to assess the long-term impact of these stents in Accepted for publication May 20, 2004. Address reprint requests to Dr Madden, Department of Cardiothoracic Surgery, St. George s Hospital, London SW17 0QT, UK; e-mail: brendan. madden@stgeorges.nhs.uk. our patients. From this population we report our experience of 15 patients who have now been followed up for more than 1 year after stent insertion. With increasing availability of this technique we believe it important to raise awareness of long-term tolerability and complications after metallic stent deployment. Material and Methods Covered and uncovered Ultraflex stents (Boston Scientific, Waterson, MA) were deployed. These consist of a flexible catheter delivery system with a compressed expandable metallic stent held in place by a crocheted nylon suture wrapped around it. The stent is composed of an open-ended cylindrical titanium mesh constructed from a single-stranded nitinol wire (SMA, Inc, San Jose, CA); the delivery catheter from which the stent is deployed has a flush taper tip at the distal end and a round hub handle at the proximal end. Covered stents have a single layer of translucent polyvinyl chloride enveloping the midsection of the metallic mesh. The crocheted release mechanism allows controlled stent deployment. The stents provide constant radial pressure maintaining patency while minimizing traumatic tissue compression and adapt to anatomic contours, thus enhancing patient comfort. Before stent placement all patients had rigid and flexible bronchoscopy under general anesthesia. The 2004 by The Society of Thoracic Surgeons 0003-4975/04/$30.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2004.05.062

Ann Thorac Surg MADDEN ET AL 2004;78:1898 902 MEDIUM-TERM METALLIC STENT FOLLOW-UP relevant airway portion was sized at this time and a stent was selected to bridge the lesion and overlap the normal mucosa by at least 10 mm at each end. The diameter of the stent was chosen to match the diameter of the normal proximal lumen. Stent placement was performed under direct vision by passing the delivery device through the rigid bronchoscope and retracting the nylon crotched suture when satisfied with appropriate placement, followed by removal of the delivery device. Correct positioning and deployment of the stent was then confirmed by bronchoscopy at the time of the procedure and by chest radiograph subsequently. Bronchoscopy was performed to check stent positioning at 14 days after deployment and subsequently as dictated by clinical indication. Details of the patients stented, the stents used, the indication for stenting, and the site of stenting were recorded at the time of discharge after stent placement. These data were analyzed retrospectively to determine patients who had stents placed for more than 1 year. Data concerning the status of these patients, complications, and follow-up period were retrieved from the hospital computerized patient information and results systems, medical notes, and clinic letters. In 1 patient the type and site of stent were recorded, but the indication for stenting had not been noted and the medical notes were unavailable. The computerized hospital results system did not aid in determining the diagnosis, but did list the patient as being deceased less than 12 months after stent deployment. Results Between March 1997 and February 2004 we deployed 80 stents in 69 patients (36 women, 33 men, median age 63 years, range 19 to 84 years). Thirty bronchial and 50 tracheal stents were sited. Indications for stenting are summarized in Table 1. We identified 15 patients who were followed up for more than 1 year after stent deployment (Table 2). Fourteen are still alive, but 1 died from a myocardial infarction 15 months after having a tracheal stent placed to relieve airway obstruction secondary to tracheomalacia and external compression from a right brachiocephalic artery aneurysm. Five of these patients experienced no long-term complications after stent deployment. Complications that occurred are summarized in Table 3. Granulation tissue formation was the most common, occurring in 7 patients. This complication was related to the uncovered tips of the stents in each patient, occurring proximally in 2 patients, distally in 4 patients, and at the upper and lower ends of the stent in 1 patient. In one case, one of our first stented patients, the patient declined to be followed up by us because of travel distance. He was subsequently re-referred with dyspnea due to extensive granulation tissue formation around the distal end of the stent. Complete clearance with Nd:YAG laser therapy was not possible. Granulation tissue developed in patient 4 but did not require treatment because it did not cause significant obstruction and had not progressed at serial bronchoscopy. The remaining 5 patients Table 1. Indications and Numbers of Patients for All Stents Inserted Diagnostic Category Specific Diagnosis No. of Patients Malignancy Primary lung carcinoma 22 Lung metastases or direct 14 invasion by nonlung primary Lymphomas 5 Myeloma 1 Malignant thymoma 1 Neuroendocrine tumor 1 Subtotal 44 Benign conditions Granulation tissue a 6 Tracheomalacia 5 Iatrogenic tracheal tear 2 Trachemalacia and 1 granulation tissue Bronchial stricture b 1 Benign multinodular goiter c 1 Tracheostomy subglottic web 1 Right brachiocephalic artery 1 aneurysm and tracheomalacia Inoperable aortic aneurysm 1 Right interrupted aortic arch 1 Bronchopleural pistula 1 Subtotal 21 Post lung transplant Anastomotic stricture 3 Unknown 1 TOTAL 69 1899 a Granulation tissue complicated prolonged intubation and mechanical ventilatory support (with tracheostomy) in 6 patients; b Following previously treated pulmonary tuberculosis; c This patient had congestive heart failure and end-stage chronic obstructive lung disease and was not considered suitable for thyroidectomy. were treated with low-power Nd:YAG laser. Of these, 1 (patient 7) required only one laser treatment and a second (patient 10) required two treatments. Both had subsequent bronchoscopies showing no further growth. One (patient 1) received one laser treatment and subsequent dilatations of the region with bougie dilators. The remaining 2 patients (patients 3 and 11) required three courses of laser therapy. Patient 3 required the three courses during the first 18 months after stent deployment and has not required any further treatment since that time. Patient 11 also required three courses of Nd:YAG laser treatment to date and continues to be followed up with regular bronchoscopic surveillance. Although we appreciate the potential risk of airway injury as a consequence of combustion to the stent with laser therapy applied locally, this complication did not occur in our series. We used low power (10 W) with a contact fiber and interrupted mechanical ventilatory support during treatment. All of the patients remain asymptomatic from an airway standpoint and had good airway patency. Halitosis is a troublesome complication, and was seen in 5 patients. Seven stents were placed in these 5 patients. GENERAL THORACIC

Table 2. Patients Followed-Up for More Than 12 Months After Endobronchial Stent Deployment Patient No. Age (years) Sex No. of Stents Site of Stents Type of Stents Diagnosis Reason for Stent Complications 1 44 F 1 B UNC Bilateral lung transplant Anastomotic stricture GT 83 2 65 M 1 B COV TB Fibrotic stricture Halitosis, GT 59 3 61 F 1 T COV Tracheostomy Stricture GT 42 Tracheal web repair 4 36 F 1 B UNC Single lung transplant Anastomotic stricture GT 52 5 59 F 1 B UNC Single lung transplant Anastomotic stricture None 52 6 62 M 2 B & T UNC & COV Adenocystic Ca Intrinsic compression None 12 7 52 F 2 B & T UNC & COV Adenocystic Ca Intrinsic compression GT, metal fatigue 51 8 77 F 1 T COV Rt brachiocephalic artery aneurysm Extrinsic compression Halitosis 15 9 70 F 2 T COV Post Op CABG & AVR Tracheomalacia Halitosis 42 10 57 F 1 T COV Rt aortic arch Extrinsic compression GT 39 11 59 M 1 T COV ITU ventilated Tracheal tear Halitosis, GT 36 12 21 F 2 B & T UNC & COV NHL Extrinsic compression Halitosis 19 13 29 F 2 B & T UNC Malignant thymoma Extrinsic compression None 18 14 69 F 1 B UNC Left upper lobectomy (for Ca lung) Extrinsic compression None 15 15 66 F 1 B COV Aortic aneurysm Extrinsic compression None 15 Follow-Up (months) AVR aortic valve replacement; B bronchial; Ca carcinoma; CABG coronary artery bypass grafting; COV covered; F female; GT granulation tissue; ITU intensive therapy unit; M male; NHL non-hodgkin s lymphoma; Op operation; Rt right; T tracheal; TB tuberculosis; UNC uncovered. 1900 MADDEN ET AL Ann Thorac Surg MEDIUM-TERM METALLIC STENT FOLLOW-UP 2004;78:1898 902

Ann Thorac Surg MADDEN ET AL 2004;78:1898 902 MEDIUM-TERM METALLIC STENT FOLLOW-UP Table 3. Number of Complications After Stent Deployment Complication All had covered stents (1 bronchial, 5 tracheal), with one having both covered (tracheal) and uncovered (bronchial) stents in place. Attempts were made to determine the cause of the halitosis. Barium swallow investigations in all did not show gastroesophageal reflux; highresolution computed tomography scanning did not reveal bronchiectasis. In addition all had microbiological samples (bronchoalveolar lavage) taken at subsequent bronchoscopies and sputum samples collected. Samples from 3 of the 5 patients did not grow any bacteria other than normal upper respiratory tract flora. The remaining 2 grew Pseudomonas aeruginosa. Treatment courses with intravenous and oral antibiotics, to which the species had proven sensitivity, were unsuccessful in eradicating the halitosis; nebulized antibiotic regimes were similarly unhelpful. Unfortunately halitosis continues to be a problem in these patients. Some patients receiving endobronchial stenting have episodes of recurrent respiratory tract infection (RTI) early after stent deployment. Recurrent RTI was not, however, a problem for any of the 15 patients 1 year after stent deployment. Bronchoscopy revealed evidence of epithelialization around uncovered ends of covered stents and through uncovered stents. Reassuringly we did not encounter stent migration. In one patient a stent did exhibit metal fatigue in which one of the metal struts was fragmented, but this condition did not cause any damage or compromise to the airway and has to date not required further intervention. One patient (patient 12) gave birth to a healthy child 16 months after stent deployment. Comment No. of Patients Granulation tissue 7 Halitosis 5 Metal fatigue 1 Interventional bronchoscopy techniques have developed progressively over the last decade. Large airway obstruction often presents as a medical emergency that requires prompt action to prevent suffocation. Surgical resection and reconstruction is the gold standard definitive treatment, but many patients are unsuitable for surgical intervention. It is for these patients that interventional bronchoscopy potentially has a useful role. For the majority with inoperable malignancy as a cause of airway obstruction, palliation is the aim of stent placement. The management of such situations with bronchoscopic strategies, including laser therapy and stenting, have been shown to be of benefit not only for symptomatic relief but also for physiologic respiratory measurements [1 6]. Furthermore an increase in availability of interventional bronchoscopy and improvements in technology and techniques has resulted in an increase in the number of 1901 individuals (particularly those who are poor surgical candidates) receiving intervention for airways obstruction as a result of more benign conditions. Concerns have, however, been raised regarding the complications in long-term survivors with expandable metal airway stents [7]. In our series granulation tissue formation was the most common complication, mirroring the experiences of other groups [8]. We have shown that this problem can be treated easily and effectively with Ng-YAG laser therapy. In addition we have found that granulation tissue may not require continued laser treatments, but instead only a discrete number of laser treatments in some patients. Such patients should continue to be followed up to monitor for recurrence. Halitosis proves to be a distressing and difficult complication to resolve. Previous studies have suggested that this condition is secondary to bacterial infection of the stent. All of our patients with halitosis had covered stents, which may provide a suitable environment for bacterial growth and prevent effective mucociliary clearance. Noppen and colleagues [9] showed that 78% of those receiving mainly silicone stents developed significant airways colonization with bacteria, of which 55% had potentially pathogenic organisms. Their study also found that the most common organisms found were P aeruginosa, the only potentially pathogenic organism we found to be present in our patients with halitosis. The polysaccharide glycocalyx material surrounding the outer cell wall of this organism may enhance its ability to bind to the polyvinyl chloride coating of covered stents and possibly explain our difficulty in eradicating the problem. Not only was antibiotic treatment guided by culture sensitivity ineffective, but so were empirical antibiotic regimes in patients with negative cultures. Similarly, nebulized antibiotics had no benefit in these patients. In light of the primary airway pathology and difficulty in removing the stents once deployed we did not believe that stent removal was an appropriate strategy. Only 40% of our patients with halitosis had positive microbiology from either sputum samples or bronchoalveolar lavage; therefore, bacterial growth does not appear to be the sole cause of halitosis, although this hypothesis is attractive. Halitosis can occur with prosthetic replacement of the trachea and it may be less of a problem for patients with removable stents deployed. However, these latter stents also have associated complications and furthermore it was our clinical assessment that metallic stents were appropriate for our patients. It is hoped that further research into this problem, including the structure of the covered stents themselves, will help resolve what can be a distressing issue for patients. Stent migration did not prove a problem in our series. We believe that this is due to accurate sizing of both airway diameter and distance to be stented at the time of stent insertion. Furthermore, the ability to directly visualize stent deployment under rigid bronchoscopy and make minor adjustments as required immediately after deployment provided additional accuracy [10, 11]. We GENERAL THORACIC

1902 MADDEN ET AL Ann Thorac Surg MEDIUM-TERM METALLIC STENT FOLLOW-UP 2004;78:1898 902 have not had any indication to remove the stents once they have been deployed. Metal fatigue was seen in only 1 of our patients, and this did not require any further intervention. Metal fatigue does present a potentially important complication and one that should continue to be monitored with patients having stents deployed who survive for longer periods. A previous long-term follow-up study [8] also reported metal fatigue in one stent (0.89%) at 48 months after stent deployment. No clinical sequelae were reported and the stent was successfully removed. We used covered stents to manage the airway in 3 patients who had extrinsic vascular compression of the airway. None of these patients was considered a candidate for formal vascular surgical intervention. Given the structure of the stents and the nature of the radial forces exerted by them on the airway, we did not believe that they would contribute to vascular erosion. These patients have been followed to date for 14, 15, and 39 months after stent deployment. All of our patients gained considerable benefit in terms of clinical and respiratory status after stent insertion. Five patients had no complications in the medium-term associated with their stent, and 1 subsequently gave birth to a healthy child 16 months after stent deployment. Our experience suggests that Ultraflex expandable metallic stents have a role to play in the management of a variety of endobronchial pathologies for carefully selected patients. Long-term complications do not necessitate stent removal and, with the exception of halitosis, can usually be managed effectively. References 1. Wood D, Liu Y, Vallieres E, Karmy-Jones R, Mulligan M. Airway stenting for malignant and benign tracheobronchial stenosis. Ann Thorac Surg 2003;76:167 74. 2. Chan K, Eng P, Hsu A, Huat G, Chow M. Rigid bronchoscopy and stenting for esophageal cancer causing airway obstruction. Chest 2002;122:1069 72. 3. Wilson G, Walshaw M, Hind C. Treatment of large airway obstruction in lung cancer using expandable metal stents under direct vision via the fiberoptic bronchoscope. Thorax 1996;51:248 52. 4. Monnier P, Mudry A, Stanzel F, et al. The use of the covered Wallstent for the palliative treatment of inoperable tracheobronchial cancers. A prospective, multicenter study. Chest 1996;110:1161 8. 5. Miyazawa T, Yamakido M, Ikeda S, et al. Implantation of Ultraflex nitinol stents in malignant tracheobronchial stenoses. Chest 2000;118:959 65. 6. Vonk-Noordegraaf A, Postmus P, Sutedja T. Tracheobronchial stenting in the terminal care of cancer airways obstruction. Chest 2001;120:1811 4. 7. Saad CP, Murthy S, Krizmanich G, Mehta AC. Selfexpandable metallic airway stents and flexible bronchoscopy: long-term outcomes analysis. Chest 2003;124:1993 9. 8. Gaissert H, Grillo H, Wright C, Donahue D, Wain J, Mathisen D. Complication of benign tracheobronchial strictures by self-expanding metal stents. J Thorac Cardiovasc Surg 2003;126:744 7. 9. Noppen M, Pierard D, Meysman M, Claes I, Vincken W. Bacterial colonization of central airways after stenting. Am J Respir Crit Care Med 1999;160:672 7. 10. Madden BP, Datta S, Charokopos N. Experience with Ultraflex expandable metallic stents in the management of endobronchial pathology. Ann Thorac Surg 2002;73:938 44. 11. Madden BP, Stamenkovics A, Mitchell P. Covered expandable tracheal stents in the management of benign tracheal granulation tissue formation. Ann Thorac Surg 2000;70: 1191 3.