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Ann Thorac Surg 2003;76:381-384
© 2003 The Society of Thoracic Surgeons

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Original article: general thoracic

High dose rate brachytherapy in the management of lung transplant airway stenosis

^a Division of Thoracic Surgery, Emory University Hospital and Emory Crawford W. Long Hospital, Emory University School of Medicine, Atlanta, Georgia, USA, Joseph Brown Whitehead Department of Surgery
^b Department of Radiation Oncology, Emory University Hospital and Emory Crawford W. Long Hospital, Emory University School of Medicine, Atlanta, Georgia, USA
^c Andrew J. McKelvey Lung Transplantation Center, Emory University Hospital and Emory Crawford W. Long Hospital, Emory University School of Medicine, Atlanta, Georgia, USA

Accepted for publication February 27, 2003.

^* Address reprint requests to Dr Miller, Section of General Thoracic Surgery, The Emory Clinic, 1365 Clifton Rd, Building A, Atlanta, GA 30322, USA.
e-mail: jmille6331{at}aol.com

	Abstract

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
BACKGROUND: Airway complications after lung transplantation remain a major cause of postoperative morbidity and mortality. Interventional bronchoscopic management continues to be the main modality in the management of these problems.

METHODS: Four patients with airway stenoses after lung transplantation received high dose rate brachytherapy for management of recurrent stenosis. All 4 patients had been treated with various bronchoscopic interventions, including dilation and stenting, electrocautery ablation, and neodymium:yttrium-aluminum-garnet laser therapy. High dose rate endobronchial brachytherapy was subsequently used in all 4 patients for management of recurrent airway obstruction. The radiation dose for all 4 patients was 3 Gy at a distance of 1 cm from the center of the catheter.

RESULTS: All four patients have had routine follow-up after endobronchial brachytherapy treatments. Of the 4 patients, 2 treated with this modality showed a significant response to therapy in that the bronchus remained free of obstruction after treatment; 1 patient had partial improvement, and 1 patient failed to show significant improvement and expired from the sequelae of persistent airway obstruction.

CONCLUSIONS: Endobronchial brachytherapy can be an effective modality for managing recurrent stenoses caused by hyperplastic granulation tissue at the bronchial anastomosis. The optimal timing and ideal candidate for intraluminal radiation therapy for this problem remains a challenge and warrants further investigation.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Airway complications remain a significant source of morbidity and mortality after lung transplantation, with stenosis at the anastomosis being the most common manifestation. Bronchial stenosis after transplantation has been reported to range from 1.6% to 24.4% [1–4]. During the evolution of lung transplant surgery, numerous endoscopic interventions have been used to manage these complications and to improve patient quality of life, including balloon dilation, electrocautery debridement, neodymium:yttrium-aluminum-garnet laser therapy, and stent placement [5].

Review of the literature reveals only limited experience in managing bronchial stenoses with high dose rate brachytherapy. Kennedy and colleagues [6] describe the use of brachytherapy in 2 patients with bronchial stenosis within 4 months of transplantation, with significant relief of obstruction and improved respiratory function. Kramer and coworkers [7] reported the use of brachytherapy to manage recurrent stenosis after repair of a traumatic bronchial disruption [7]. We report a similar experience with 4 lung transplant recipients treated with brachytherapy at different stages of their management.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Four patients were treated at our institution with high dose rate brachytherapy for recurrent bronchial obstruction. A single thoracic surgeon and radiation oncologist at Emory University and Crawford W. Long Hospitals performed all procedures. We reviewed patient records and clinic notes for information regarding the timing and efficacy of these interventions. Of the 4 patients, 3 are currently living and are maintaining follow-up with their transplant pulmonologist at Emory University Hospital.

All brachytherapy treatments were performed on an outpatient basis in the Radiation Therapy Oncology Center. Before catheter placement, all patients had fiberoptic bronchoscopy with either laser or electrocautery debridement in the bronchosopy suite. Subsequently, a 5F afterloading catheter was placed at the region of stenosis and confirmed under fluoroscopy. In all 4 patients, granulation tissue was present along the distal aspect of the stent and was growing through the stent struts in 1 patient. All lesions were biopsied before radiation treatment to confirm benign disease.

In the Radiation Oncology Center, treatment planning was performed using a Nucletron Planning System (Nucletron, Inc, Columbia). The Nucletron system is a multichannel, high dose rate, remote afterloading system that uses iridium-192 as the radiation source delivered through the afterloading catheter. Treatment time, number, and position of the source were programmed independently for each treatment to give the required dose distribution for a particular patient. The treatment length was the area at risk, with a proximal and distal margin of 5 mm. For all patients, a dose of 3 Gy was prescribed to a depth of 1 cm from the center of the brachytherapy catheter, which was then attached to the remote afterloader. Total treatment time varied depending on the source and strength of the radiation dose. After the procedure, patients were monitored for 1 hour and then discharged.

	Results

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Demographic and treatment information for our 4 patients are shown in Table 1. All patients underwent laser or electrocautery debridement before brachytherapy. All 4 patients treated with brachytherapy showed responses to treatment; these were graded as follows: excellent (substantial improvement with no subsequent interventions; patient 2); good (substantial improvement with occasional subsequent interventions required; patient 1); fair (some improvement with frequent subsequent interventions required; patient 3); and poor (no improvement; patient 4). None of the patients had any complications due to endobronchial brachytherapy treatments.

Patient 2 had a Dumon stent placed 4 months after transplantation for left mainstem obstruction at the anastomosis. He received endobronchial brachytherapy in March and May 2000 for recurrent obstruction. He had a complete response after two treatments. One month later, he underwent Nd:YAG laser therapy for a residual proximal rim of granulation tissue and had the stent removed 2 months later for an area of fixed stenosis within the stent. He has experienced excellent clinical function and has required no further interventions over the past 2 years.

Patient 3 had a metallic wall stent placed 1 year posttransplant for obstruction of the bronchus intermedius. He received brachytherapy treatment in December 2001 and January 2002 for recurrent stenosis at the distal portion of the stent. He also had a reduction in the amount of granulation tissue present as well as improvement in his symptoms, although he does continue to require further intervention to manage his bronchial disease. This is, however, believed to be unrelated to his initial presentation of bronchial obstruction at the anastomosis. He does have a small but fixed region of stenosis within the metallic stent, which may be accounting for some of his symptomatology. The small rim of granulation tissue that was present at the distal aspect of the stent after his last brachytherapy treatment has not progressed as of his last bronchoscopy in July 2002. The patient continues to do well through April 2003.

Patient 4 had no benefit from four courses of endobronchial brachytherapy and eventually underwent pericardial flap reconstruction of the right mainstem bronchus. Despite all interventions, airway stenosis progressed and he subsequently expired in July 2002 from respiratory failure and pneumonia resulting from progressive airway stricture.

	Comment

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Bronchial obstruction continues to plague the success rate of lung transplantation. Although early stenosis can be attributed to ischemia at the anastomosis, persistent obstruction is likely related to the interventions used to manage the initial stenosis [4], as well as to localized infections of the anastomosis and proximal donor bronchus [8].

Of the patients who present with airway obstruction at the anastomosis, a large majority receive endobronchial stent placement as part of their treatment strategy. This may be accomplished with silicone or metallic stents. Cooper and colleagues [9] reported a large series in which silicone stents were endoscopically placed for the management of complex airway stenoses. This strategy is now common practice for patients with malignant or benign airway obstruction. Silicone stents must be inserted under general anesthesia after bronchial dilation but are easy to adjust and remove if necessary. However, they are more likely to occlude and are prone to migration [3, 10]. Expandable wire stents are being used more frequently, especially in patients who present with persistent obstruction. They can be inserted under local anesthesia or conscious sedation, are less likely to migrate, and have been associated with improved mucociliary clearance [3]. However, they are difficult to manipulate and remove, and granulation tissue growing through the struts is a common problem. Nevertheless, the insertion of endobronchial stents is fairly effective in providing long-term patency [3–5, 9]. Why a small percentage of these patients develop restenosis after stent placement is unclear, but may be due to the repetitive injury, the associated inflammatory response, and the presence of a foreign body associated with stent placement. These patients often have repeated treatments directed at the stenotic airway using a variety of modalities, but this usually provides only temporary relief.

Surgical reconstruction of the complex stenotic airway remains an option for those patients who do not respond to endoscopic measures [11]. These techniques are usually reserved for patients with bronchial necrosis or stenoses extending into the lobar bronchi or for those who fail to respond to repeated endoscopic interventions. The associated high morbidity and mortality, along with the diminished life expectancy in the lung transplant patient population, limit the application of these techniques. Patient 4 in our series ultimately underwent pericardial flap reconstruction of the stenotic right mainstem bronchus after all previous interventions had failed.

Hyperplastic granulation tissue in response to injury has been clearly documented in the literature. Long-term patency of coronary arteries after angioplasty and intracoronary stent placement is limited by the ensuing intimal hyperplasia that occurs after the intervention. Similar mechanisms are likely responsible for the resultant stenosis after placement of endobronchial stents. Multiple interventions may account for part of this proliferative response.

Radiation therapy has been described to inhibit the proliferative response in patients with intracoronary stents [12]. We have used endoluminal radiation therapy to manage malignant airway obstruction due to exophytic lesions and extrinsic compression of the airway [13]. It would therefore seem intuitive to include brachytherapy in the management of airway stenosis in the lung transplant patient. With high dose rate brachytherapy, a high-dose beam can be delivered to a small target area while sparing nearby normal tissues. The radiation is delivered to the prescribed depth of 1 cm, after which the rapid dose falloff enhances normal tissue sparing and limits complications.

This report details the results of brachytherapy as an adjunct in treating the stenotic airway encountered in 4 lung transplant patients after numerous other interventions had failed. In the report by Kennedy and colleagues [6], both patients were treated early in the posttransplantation period, with excellent results in the short term (6 and 7 months). The 2 patients in our report who experienced excellent or good responses to brachytherapy received radiation therapy much later, at 5 and almost 2 years, respectively. The single patient who failed to respond to treatment received radiation relatively early in his course at 9 months. Although this is a limited study, there does not seem to be any correlation between the number of treatments received and the benefits provided. Whether these or other variables predict the success rate of endobronchial brachytherapy remains uncertain. We believe that patient 4 in our series failed to respond not only because of an anastomotic stricture but also because of a more diffuse idiopathic obliteration of his airway that remains unexplained.

Proved in application for the management of malignant airway obstruction and in a host of other benign applications, the role of high dose rate brachytherapy for treatment of lung transplant airway stenosis deserves further investigation. Although many transplant patients with bronchial obstruction respond solely to endobronchial stent placement, many others continue to have narrowing attributable to the proliferative granulation tissue response and subsequent restenosis within the airway lumen. Although future modifications may improve the long-term patency of endobronchial stents, brachytherapy treatment for management of restenosis in the transplanted bronchus should be an option for these patients.

	Acknowledgments

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
This work was supported in part by the McKelvey Fund of the Tides Foundation, and the Andrew J. McKelvey Lung Transplantation Center of Emory University School of Medicine.

	References

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Joseph I. Miller, Jr Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Halkos, M. E. Articles by Miller, J. I. Search for Related Content PubMed PubMed Citation Articles by Halkos, M. E. Articles by Miller, J. I., Jr Related Collections Lung - transplantation