Aortotracheal fistula secondary to bacterial aortitis.
Abstract: * Fistulas between the aorta and tracheobronchial tree are rare fatal complications that occur in patients treated with external and endobronchial radiation for carcinomas of the upper and lower respiratory tract. The etiopathogenesis can be multifactorial. We report the case of a patient with irradiated tracheal carcinoma who died of massive hemoptysis 25 months after completing therapy. Autopsy revealed a fistula between the trachea and arch of the aorta. Multiple colonies of cocci and bacilli were demonstrated within the media at the site of rupture and were absent in other areas of the aorta. The development of an aortotracheal fistula in this patient was most probably related to infection in an area of tracheal and vascular wall previously damaged by exposure to high doses of radiation.
Article Type: Case study
Subject: Fistula (Risk factors)
Fistula (Development and progression)
Bacterial infections (Complications and side effects)
Radiotherapy (Usage)
Trachea (Diseases)
Trachea (Diagnosis)
Trachea (Care and treatment)
Trachea (Risk factors)
Authors: Allende, Daniela S.
Rodriguez, E. Rene
D. Tan, Carmela
Pub Date: 06/01/2009
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 College of American Pathologists ISSN: 1543-2165
Issue: Date: June, 2009 Source Volume: 133 Source Issue: 6
Accession Number: 230152030
Full Text: Fistulas between the aorta and the tracheobronchial tree often arise as a complication in the setting of aortic atherosclerotic aneurysms or previous thoracic vascular surgery. (1,2) While the pathology in most cases originates from the aorta, a minority of cases are due to diseases of the tracheobronchial tree. The fistula occurs most frequently between the thoracic aorta and the left main bronchus. They often present as recurrent episodes of hemoptysis, but sometimes the sentinel event is an uncontrollable massive hemoptysis. When left untreated, the lesion is uniformly fatal. Among the reported cases in the English literature, few are well documented with histopathologic study demonstrating the fistula site. We present a case of aortotracheal fistula in a patient who developed postradiation tracheal necrosis after definitive management of a tracheal carcinoma.

REPORT OF A CASE

The patient was a 62-year-old man with a long-standing history of chronic obstructive pulmonary disease. A computed tomography scan of the chest done for workup of hemoptysis showed emphysema and a decrease in the coronal dimension of the intrathoracic trachea associated with widening of the sagittal diameter, a deformity known as a saber-sheath trachea. Bronchoscopy revealed a rounded submucosal mass, 3 cm in axial length, along the right lateral wall of the trachea, with the distal extension at 2 cm proximal to the carina. A biopsy showed non- keratinizing squamous cell carcinoma. The patient was then referred to our institution for definitive radiotherapeutic options, as he was not deemed to be a candidate for surgery. The result of a workup for possible metastases was negative. During the next 5 months, he received external beam radiation to a dose of 5000 rad followed by high-dose-rate brachytherapy boost of 3 endobronchial applications at 710 rad per fraction (Nucletron MicroSelectron Iridium 192, Nucleotron BV, Veenendaal, The Netherlands). Seven months after completion of treatment, he was found to have diffuse anterior tracheal necrosis that extended to the left lateral wall down to the carina and resulted in severe tracheomalacia and dynamic airway compromise. A permanent tracheostoma was created with tracheoplasty and airway reconstruction and insertion of an 18-French extended Silastic tracheostomy tube (T tube). Two years and one month after completion of radiotherapy, the patient suffered a massive hemoptysis. Emergency medical services found him pulseless and bleeding from the tracheostomy tube. Resuscitative measures were initiated and he was brought to the emergency room where he went into asystole. There was no history of previous episodes of hemoptysis. An autopsy was requested. The county coroner's office was notified and jurisdiction was released to our institution.

AUTOPSY FINDINGS

Dense fibrous adhesion on the lesser curvature of the aortic arch to the left side of the trachea and left main bronchus was noted. There was moderate atherosclerosis in the arch of the aorta, but this was not complicated by a penetrating ulcer, aneurysmal dilatation, or pseudoaneurysm formation. The innominate artery and bilateral carotid arteries were intact. The T tube was well-positioned and immediately distal to it was a stenotic portion of the trachea. Upon removal of the T tube, the underlying mucosa of the entire trachea was noted to be irregular with superficial erosions and focal deep ulcerations. Some areas were lined by white shiny hyperkeratotic epithelium. The anterior lower half of the trachea showed loss of the cartilaginous rings with fibrous replacement. A 0.8 X 0.5-cm deep ulcer was noted on the left lateral wall of the distal trachea, 1.0 cm proximal to the distal end of the T tube (Figure 1, A). Serial sectioning of this ulcerated area through the adherent aorta showed focal disruption of the wall in the lesser curvature of the aortic arch, thereby creating a fistulous tract with the tracheal ulcer (Figure 1, B). No mass lesion or tracheal or carinal lymphadenopathy was noted.

On histologic sections, a fistula was confirmed showing a deep ulcer in the tracheal wall that communicated with the aortic lumen (Figure 2). The fistula was lined by fibrinous exudate with neutrophilic infiltrates. The site of aortic rupture showed transmural necrosis and acute inflammation in the media (Figure 3, A). The intima showed atherosclerosis and the rest of the aortic wall showed a decreased number of smooth muscle cells and normal elastic lamellar architecture. Special stains for microorganisms revealed multiple bacterial colonies, consisting of Gram-positive cocci in clusters and small Gram-negative bacilli, in the area of the fistula. Grocott methenamine silver stain best demonstrated these organisms (Figure 3, B), in addition to larger bacillary microorganisms, which were not evident on Gram stain (Figure 3, C). The organisms were clearly spreading through the media, in between multiple layers of elastic lamellae, in the area adjacent to the fistula tract. These organisms were not found in other areas of the aorta, in the tracheobronchial tree, or lung parenchyma. The lungs showed severe emphysema and diffuse areas with blood-filled alveoli.

[FIGURE 1 OMITTED]

COMMENT

The most common site of aortotracheobronchial fistula formation is between the descending aorta and left main bronchus. This occurs at the point where both structures come in close proximity, as the aorta arches over the left main bronchus. Fistula between the aorta or its arch branch vessels and the trachea is much less common. The communication is usually formed at the level where the innominate artery obliquely crosses the anterior trachea in the ninth ring. (3)

In this case, we were presented with a patient who developed tracheal necrosis and stenosis after radiation therapy for a tracheal carcinoma. Cause of death was an aortotracheal fistula. The mechanism of death was attributed to aspiration of blood. Emergency medical services provided no adequate description of the scene to estimate the amount of blood loss by hemoptysis, although hemorrhage can also be a significant contributory factor to his death. Investigation of fistulas can be challenging to the pathologist because of their usually small size, making postmortem diagnosis and demonstration of the fistula often difficult. While tracheo-innominate fistula is a known complication of surgical tracheostomy, this rare complication is said to typically occur between 3 days to 6 weeks after tracheostomy and is secondary to mucosal ulceration and necrosis resulting from malpositioning of the tube cuff, elbow, or tip. (4) Careful examination of the arch branch vessels on both sides of the neck showed no evidence of rupture in these vessels.

Aortotracheobronchial fistula developing in the setting of upper and lower airway malignancy is commonly related to therapy, particularly with radiation. Direct tumor invasion through the media of large elastic arteries is rare but has been reported with esophageal carcinoma and not with tracheobronchial carcinomas. (5)

External beam irradiation is known to induce several changes in the tracheobronchial tree, including glandular atrophy, complete mucosal atrophy, and inflammation and fibrosis of the wall. (6,7) However, the more serious complications of stenosis and fatal hemoptysis were not observed with increasing frequency until the advent of high-dose-rate brachytherapy. (7) Brachytherapy is a method used to deliver localized radiation treatment to primary tracheobronchial tumors. This is performed through bronchoscopy with placement of the radiation source directly in contact with the tumor within the tracheobronchial tree. Prior or concurrent external radiation is believed to increase the risk of developing stenosis as a late complication.

The reported incidence of fatal hemoptysis associated with radiation therapy varies from 0% to 50%. (8-13) This wide range is not surprising as the patient population was diverse, with multiple variables pertaining to the tumor type and location, dose rate, and treatment protocol used. The risk of hemorrhage appears to be independent of dose or timing of brachytherapy. The concurrent use of external beam irradiation and endobronchial radiotherapy has been shown to increase the relative risk of death from massive hemoptysis. (12) In most of these studies, the cause of the fatal hemorrhage is rarely documented by autopsy. The etiology in most cases is hypothesized to be related to tumor erosion into an adjacent pulmonary artery because most of the patients had recurrent or residual tumor at the time of death. (14) A few patients showed no evidence of disease before death and the etiology could be treatment related.

[FIGURE 2 OMITTED]

The etiopathogenesis of aortotracheobronchial fistula formation is not entirely clear but seems to be multifactorial. In this case, it was not caused by tumor invasion, as there was no residual carcinoma after extensive sampling of the trachea. The ulceration was not due to the tracheostomy tube since the ulcer was found proximal to the tip of the tube and the tube was made of flexible silicone rubber. The fact that the patient developed tracheal necrosis was indicative of severe radiation reaction. The tracheal ulcer that eventually penetrated into the aorta appeared to be part of delayed radiation effects to the tracheal mucosa. Furthermore, the fibrosis around the trachea involved the surrounding soft tissue and adventitia of the aorta. This could compromise the vasa vasorum of the aorta, leading to laminar necrosis. Atherosclerosis can be accelerated by radiation and may also cause secondary damage to the media. We therefore hypothesize that radiation indirectly caused vascular wall fragility sufficient to weaken and predispose the aorta to rupture. More importantly, we consider a possible significant contributory role of infection in the development of fistula between the aorta and the trachea. The presence of acute inflammatory reaction in the media and mixed bacterial microorganisms within the aortic wall and fistula suggests that infection may have been the immediate trigger for the aortic rupture.

Mucosal and glandular atrophy of the tracheobronchial tree as a result of radiation injury leads to impaired clearance of secretions that, in turn, may increase the risk of secondary infections. The presence of bacterial colonies in bronchial biopsies taken from patients suffering from radiation reaction raises the potential role of infection for patients dying of massive hemoptysis. (12) Colonies of cocci and bacilli were also present in half of the cases in one series of radiation treatments complicated by arterial rupture. (15) Reports of aortic rupture secondary to bacterial aortitis, in the absence of an aneurysm, can be found in the literature. (16-17)

[FIGURE 3 OMITTED]

In conclusion, we have demonstrated a histologic documentation of a rare case of aortotracheal fistula. Late radiation effects to the tracheobronchial and vascular wall may predispose to the development of a fistula. Local infection in the compromised airway appears to be important in the pathogenesis of this process as the infection spreads to adjacent soft tissue and large vessels, leading to vascular rupture that can result in death from massive hemoptysis.

References

(1.) Macintosh EL, Parrott JC, Unruh HW. Fistulas between the aorta and tracheobronchial tree. Ann Thorac Surg. 1991;51:515-519.

(2.) Piciche M, De PR, Fabbri A, et al. Postoperative aortic fistulas into the airways: etiology, pathogenesis, presentation, diagnosis, and management. Ann Thorac Surg. 2003;75:1998-2006.

(3.) Oshinsky AE, Rubin JS, Gwozdz CS. The anatomical basis for post-tracheotomy innominate artery rupture. Laryngoscope. 1988;98:1061-1064.

(4.) Kapural L, Sprung J, Gluncic I, et al. Tracheo-innominate artery fistula after tracheostomy. Anesth Analg. 1999;88:777-780.

(5.) Cairols MA, Izquierdo LM, Barjau E, et al. Primary aorto-oesophageal fistula due to oesophageal carcinoma. Report of a successfully managed case. Int Angiol. 2000;19:290-293.

(6.) Cooper JS, Fu K, Marks J, et al. Late effects of radiation therapy in the head and neck region. Int J Radiat Oncol Biol Phys. 1995;31:1141-1164.

(7.) Speiser BL, Spratling L. Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation. Int J Radiat Oncol Biol Phys. 1993;25:589 597.

(8.) Khanavkar B, Stern P, Alberti W, et al. Complications associated with brachytherapy alone or with laser in lung cancer. Chest. 1991;99:1062-1065.

(9.) Roach M III, Leidholdt EM Jr, Tatera BS, et al. Endobronchial radiation therapy (EBRT)in the management of lung cancer. Int J Radiat Oncol Biol Phys.1990; 18:1449-1454.

(10.) Aygun C, Weiner S, Scariato A, et al. Treatment of non-small cell lung cancer with external beam radiotherapy and high dose rate brachytherapy. Int J Radiat Oncol Biol Phys. 1992;23:127-132.

(11.) Bedwinek J, Petty A, Bruton C, et al. The use of high dose rate endobronchial brachytherapy to palliate symptomatic endobronchial recurrence of previously irradiated bronchogenic carcinoma. Int J Radiat Oncol Biol Phys. 1992;22: 23-30.

(12.) Gollins SW, Ryder WD, Burt PA, et al. Massive haemoptysis death and other morbidity associated with high dose rate intraluminal radiotherapy for carcinoma of the bronchus. Radiother Oncol. 1996;39:105-116.

(13.) Escobar-Sacristan JA, Granda-Orive JI, Gutierrez JT, et al. Endobronchial brachytherapy in the treatment of malignant lung tumours. Eur Respir J. 2004;24: 348-352.

(14.) Mehta AC, Dweik RA. Necrosis of the bronchus. Role of radiation. Chest. 1995;108:1462-1466.

(15.) Fajardo LF, Lee A. Rupture of major vessels after radiation. Cancer. 1975; 36:904-913.

(16.) Stephens CT, Pounds LL, Killewich LA. Rupture of a nonaneurysmal aorta secondary to Staphylococcus aortitis. Angiology. 2006;57:506-512.

(17.) Mohamed HK, Elliott BM, Brothers TE, et al. Suprarenal Clostridium septicum aortitis with rupture and simultaneous colon cancer. Ann Vasc Surg. 2006; 20:825-829.

Daniela S. Allende, MD; E. Rene Rodriguez, MD; Carmela D. Tan, MD

Accepted for publication September 12, 2008.

From the Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Carmela D. Tan, MD, Department of Anatomic Pathology, Cleveland Clinic, 9500 Euclid Avenue/L25, Cleveland, OH 44195 (e-mail: tanc@ccf.org).
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