Radiation-induced aortoesophageal fistula: an unusual case of massive upper gastrointestinal bleeding

The Journal of Emergency Medicine, Vol. 23, No. 2, pp. 175–178, 2002 Copyright © 2002 Elsevier Science Inc. Printed in the USA. All rights reserved 0736-4679/02 $–see front matter

PII S0736-4679(02)00488-2

Clinical Communications

RADIATION-INDUCED AORTOESOPHAGEAL FISTULA: AN UNUSUAL CASE OF MASSIVE UPPER GASTROINTESTINAL BLEEDING Sujith K. Sivaraman,

MDCM

and Robert Drummond,

MDCM

Department of Emergency Medicine, McGill University, Montreal, Quebec, Canada Reprint Address: Robert Drummond, MDCM, Department of Emergency Medicine, St. Mary’s Hospital Center, 3830 Lacombe, Montreal, Quebec, Canada H3T 1M5

e Abstract—Aortoesophageal fistula (AEF) is an unusual cause of massive upper gastrointestinal bleeding. Thoracic aortic aneurysm is the most common etiology of primary AEF followed by, respectively, foreign body ingestion, esophageal malignancy, and postsurgical fistulization. Radiation-induced damage to the great vessels is well recognized and some authors in the past have suggested that AEF may be caused by radiotherapy. However, previous case reports of radiation-induced AEF involved patients who received radiotherapy for esophageal carcinoma, and precise histopathologic differentiation between AEF secondary to esophageal malignancy and that induced by radiation was difficult. We present here the unique case of a patient with a non-esophageal carcinoma who received radiotherapy before the development of an AEF, thus providing further evidence for the role of radiation injury in the development of this condition. As well, we discuss current opinion regarding etiology, clinical presentation, diagnosis, and management of this entity. © 2002 Elsevier Science Inc.

presented to our Emergency Department (ED), and review current opinion regarding etiology, clinical presentation, diagnosis, and management of this entity.

CASE REPORT A 62-year-old man with a history of squamous cell carcinoma of the right lung and esophageal stricture after chemo-irradiation therapy presented to the ED complaining of chest pain and syncope. His past medical history was significant for stage III squamous cell carcinoma of the right middle lobe diagnosed in May 1998. He was subsequently managed with navalbine and cisplatinum chemotherapy with concurrent radiotherapy that was completed in November 1998. He then developed dysphagia, for which he underwent endoscopy in February 1999, revealing a narrowed, scarred esophagus consistent with stricture. Biopsy showed acute inflammatory exudate with underlying radiation changes. There was no evidence of malignancy. The patient was subsequently referred for esophageal dilatation, which was completed in January 2000. In February 2000, 1 week before his last admission, the patient was seen in the ED with complaints of right chest pain. There were no worrisome features on the review of systems, the physical examination was unremarkable, and the chest X-ray study showed no acute process. The clinical impression was that of chest pain

e Keywords—aortoesophageal fistula; radiation; upper gastrointestinal bleeding

INTRODUCTION Aortoesophageal fistula (AEF) is a rare, but often catastrophic, cause of upper gastrointestinal bleeding. First described in 1818 by Dubrueil, this condition is nearly always fatal, with few reports of survivors in the literature (1,2). We present here a unique case of AEF that

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secondary to chronic radiation pneumonitis and the patient was subsequently discharged. On March 3, 2000, the day of admission, the patient presented with chest pain accompanied by syncope. He was unclear as to the presence of any prodromal symptoms but noted that he had been dyspneic upon regaining consciousness. On examination in the ED, the patient was noted to be diaphoretic with initial vital signs as follows: temperature 36.4°C; blood pressure 130/74 mm Hg; heart rate 120 beats/min; respiratory rate 18 breaths/min. The cardiorespiratory and abdominal examinations were unremarkable. Notably, the stool was negative for occult blood. The initial impression was that of either a cardiac event or pulmonary embolus. One hour after admission, the hemoglobin was noted to be 11.5 g/L, as compared to 14.5 1 week previously. Shortly thereafter, the patient transiently lost consciousness and vomited approximately 400 cc of bright red blood. Resuscitation was instituted with crystalloid, a nasogastric tube inserted, the airway secured, and urgent endoscopy arranged, which revealed massive bleeding into the esophagus. A soft tissue mass seen at 25 cm was thought to represent either a tumor or erosion into the esophagus. Over the next several hours, the patient lost approximately 3 liters of bright red blood per nasogastric tube and vomitus. He became progressively hypotensive and tachycardic despite crystalloid, packed red blood cells, and inotropic support. A surgical opinion was sought and the impression was that the patient had developed an aortoenteric fistula but that his clinical status precluded operative intervention. Some 8 h after admission, the patient expired. Autopsy revealed a large ulcer in the esophagus measuring 2.5 ⫻ 2 cm, which was seen to deeply penetrate and directly communicate with the aorta, which itself had a linear 0.5 cm tear (Figure 1). The adjacent aorta showed uncomplicated atherosclerotic plaque. The esophagus distal to the ulcer was narrowed and scarred. There was approximately 2.5 liters of blood and clot extending from the ulcer into the esophagus and the stomach, and approximately 1.5 liters of blood in the small and proximal large intestine. Histology revealed acute esophagitis with ulceration and radiation changes in the blood vessels and underlying atypical mesenchymal cells consistent with radiation exposure. The right lung was noted to have evidence of radiation pneumonitis. Of significance, no residual carcinoma was noted in either the lung or the esophagus.

DISCUSSION Chiari was the first to describe the aortoesophageal syndrome in 1914, consisting of a clinical triad of midtho-

Figure 1. Autopsy specimen of the aorta showing a probe passing through the aortoesophageal fistula.

racic chest pain, followed by a sentinel arterial hemorrhage, and fatal arterial exsanguination after a symptomfree interval of hours to days (1,3). The exact mechanism whereby the sentinel hemorrhage occurs in aortoesophageal fistulas, and stops shortly thereafter, remains to be elucidated. However, as described below, endoscopic visualization during the latent interval suggests that the sentinel hemorrhage is limited by clot formation over the site of fistula formation itself. Chiari’s triad still forms the basis of diagnosis, which despite the availability of various diagnostic and imaging procedures, is still largely clinical. One review of all cases of aortoesophageal fistulas reported in a 30-year period found that midthoracic pain was present in 59% of patients and a sentinel hemorrhage in 65% (4). Our patient demonstrated both chest pain and an episode of hematemesis shortly after presentation. As well, the syncopal episode for which he initially presented to the ED may have been because of blood loss into the gastrointestinal (GI) tract. AEF may be differentiated from other causes of massive

Aortoesophageal Fistula

hematemesis by the presence of bright arterial bleeding, in contrast to (1) hemorrhage from esophageal varices, which is venous in nature, and (2) gastric bleeding which, though arterial in origin, is typically smaller in volume and darker as a result of exposure to the acidic gastric environment (4). The diagnosis of aortoesophageal fistula is often elusive. Because of the catastrophic nature of AEF, once the diagnosis is entertained in an unstable patient, immediate surgical intervention is warranted, as it is the only successful form of treatment. However, if the patient is clinically stable, further diagnostic procedures may allow for confirmation of the diagnosis before surgery. These should be performed in a timely fashion as the latent period between sentinel hemorrhage and terminal exsanguination is highly variable (5–7). Most authors agree that endoscopy is the most sensitive and specific diagnostic technique for diagnosing AEF, but may carry the risk of inducing massive hemorrhage (5,6,8–11). Endoscopic biopsy has been suggested as a precipitating cause of severe esophageal bleeding in at least two patients and is therefore contraindicated in suspected AEF (9,12). The timing of the endoscopic examination has been shown to influence the appearance of AEF (5,9). After the prodromal bleed, endoscopy may reveal a pulsatile submucosal mass with overlying clot. The adjacent mucosa may have a bluish– gray appearance indicative of a submucosal hematoma. During the latent period, the pulsatile mass begins to bulge into the esophagus, eroding the mucosa above with the resulting ulcerated area eventually being covered by a fibrinous exudate. The overall appearance has been described as being similar to that of a fungating neoplasm, and it is this pseudotumor that is most likely to be biopsied by the inexperienced endoscopist (5,11). External compression of the esophagus, small midesophageal traction diverticula, and otherwise normal esophageal mucosa may suggest an extrinsic cause of AEF (9). However, even if the fistula is not directly visualized, endoscopy is a relatively safe procedure that enables the exclusion of the other more common causes of GI bleeding. The usefulness of chest radiography for identification of AEF is limited. Chest X-rays may reveal a widened mediastinum in cases of aneurysm, mediastinitis, or tumor (10). Aortography can demonstrate a thoracic aortic aneurysm and may reveal extravasation of contrast through the fistula. However, clot formation during the symptom-free period after the herald bleed may prevent leak of contrast through the fistula, and thus, may result in false negative results (5,11–13). Computed tomography (CT) scans may be useful in the diagnosis of AEF. Although the fistula itself may not be evident, CT scans will often demonstrate aortic or esophageal lesions associated with AEF and mediastinal gas collections in cases of AEF secondary to perigraft infection. (4 –7,14 –16).

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To date there have been no survivors of nonsurgically managed AEF, and other interventions should be viewed as stabilizing measures until surgery can be performed. Emergency management of a patient with an AEF should consist first and foremost of aggressive fluid and blood replacement. Concomitant correction of any existing coagulopathy and electrolyte abnormalities should be undertaken and prophylactic broad-spectrum antibiotic therapy instituted to prevent infection of mediastinal structures with esophageal contaminants. Tamponade of the bleeding site with Sengstaken-Blakemore tubes has been reported to be an effective temporizing measure, as has radiographic embolization (17–20). However, as stated above, surgery is the only definitive treatment option and should be instituted as soon as possible. Thoracic aortic aneurysm, either atherosclerotic or traumatic, is by far the most common etiology of primary AEF, accounting for approximately one-half of all cases. The next commonest etiologies are, respectively, foreign body ingestion, esophageal malignancy, and postsurgical fistulization after esophageal or aortic surgery. Together these four etiologies account for more than 90% of all cases reported in the literature (4). As noted above, malignant intrathoracic neoplasm clearly has been shown to be associated with the development of AEF, with one review of the literature showing esophageal malignancy to be the third leading cause of AEF (4). However, there has been only one report of AEF associated with bronchogenic carcinoma and in this case the fistula was thought to result from advanced disease with massive mediastinal extension (10). The case presented here is unique in that the patient had no evidence of residual carcinoma on autopsy with the AEF presumably resulting solely from radiotherapy. Radiation induced damage to the great vessels is well recognized and some authors in the past have suggested that AEF may be caused by radiotherapy either alone or in combination with chemotherapy (21–23). Poon et al. demonstrated both macroscopic and ultrastructural changes in a human aorta that ruptured subsequent to irradiation for esophageal carcinoma (24). Specifically, they noted endothelial proliferation, intimal thickening and thrombosis in the vasa vasorum, leading to hyaline necrosis and subsequent perforation of the aortic wall. Furthermore, in the acute stages of irradiation injury, fibrinoid necrosis of the arterial walls without cellular reaction also may be present (22). A review of the literature since 1960 reveals seven case reports of patients who received radiotherapy for esophageal malignancy before development of an AEF (21–23,25–27). In five of these cases, an etiologic distinction between radiation exposure and carcinoma as a proximal cause of AEF formation is difficult because residual esophageal tumor was noted at autopsy (21,25–27).

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In only two cases was no macroscopic or histologic evidence of tumor found at autopsy, and it was postulated that AEF formation may have been induced by radiation exposure (22,23). Etiologic differentiation is further complicated by evidence that the final common pathway in the development of AEF in patients with esophageal carcinoma, regardless of the presence or absence of radiotherapy, appears to involve occlusion of the vasa vasorum leading to aortic necrosis and fistula formation (17,22,28). Thus, precise histopathologic differentiation between AEF secondary to esophageal malignancy and that induced by radiation is difficult. Also, as Hollander points out, the long latency period between the initial insult and the development of AEF in cases of foreign body ingestion suggests that the absence of identifiable tumor at autopsy does not exclude carcinoma as the etiology in patients with a past history of esophageal malignancy (4). In the case presented here, we report for the first time a patient who developed AEF after receiving radiotherapy for a nonesophageal malignancy. Although there has been mention of a previous case of AEF associated with bronchogenic carcinoma, fistulization was found to be a result of advanced disease with massive direct mediastinal extension (10). This is in contrast to our patient, in whom no residual malignancy was noted in either the lung or the mediastinal structures. The history of previous esophageal radiation exposure and suggestive histologic findings at autopsy, combined with the notable absence of esophageal or pulmonary malignancy, in our opinion, makes the diagnosis of radiation induced AEF more definitive than in previous reports.

SUMMARY Aortoesophageal fistula is a rare but life-threatening cause of massive hematemesis. A favorable outcome requires urgent hemodynamic stabilization, diagnosis if time permits, and early surgical management. Fistulization between aorta and esophagus has been noted in patients with esophageal malignancy, and radiation damage has been postulated to be involved in a small subset of these cases, although conclusive distinction has not been possible. We present a case of AEF in a patient who received radiation therapy for nonesophageal malignancy, and in whom no evidence of residual tumor could be found, thus providing further evidence for the role of radiation injury in the development of this condition. Furthermore, we recommend considering the diagnosis of aortoesophageal fistula in any patient presenting to the ED with a history of significant radiation exposure and upper gastrointestinal bleeding.

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