Aortoesophageal fistula (AEF) usually results in fatal gastrointestinal bleeding and is associated with a high mortality rate, despite the use of advanced surgical and endovascular techniques [
The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A systematic search was undertaken in the PubMed, Embase, and Cochrane Library databases from 2000 to March 6, 2020. The search terms were “aortic aneurysm,” “aneurysm, dissecting,” “endovascular procedures,” “aortic surgery,” “endograft,” “stent graft,” and “esophageal fistula.” Only articles written in English were included. The references of retrieved articles were reviewed manually to identify missed studies.
Studies were included in accordance with the following eligibility criteria: (1) observational studies, case reports, or case series; (2) sufficient information for analysis including outcomes and management strategies; (3) AEF associated only with aortic aneurysm or dissection; and (4) full-text article or meeting abstract. Duplicate studies were excluded; only the latest version was included in the analysis when the information was inconsistent.
All articles were independently reviewed, and data were extracted by two reviewers (SL and FG); the final decision regarding inclusion was made by another reviewer (JZ). The following data were analyzed: age and sex; location and size of aortic aneurysm or dissection; a history of aortic surgery and/or endovascular treatment and the interval between the latest procedure and the occurrence of AEF; comorbidity and clinical symptoms (chest/abdominal/back pain, dysphagia, fever, and hemorrhage); elevated inflammatory markers and positive bacterial culture; diagnostic methods and related manifestations; location and size of fistula; treatments; and follow-up duration and prognosis.
Categorical variables are described as percentages and continuous variables as
The systematic review identified 184 eligible articles that included 219 patients with AEF. The mean patient age was
PRISMA flowchart.
The baseline characteristics of the survivors were similar to those of the nonsurvivors, except for age and hemorrhage shock (Table
Demographic, clinical, radiographic, and endoscopic findings of patients with AEF.
Total | Survivors | Nonsurvivors | ||
---|---|---|---|---|
Male sex | 63.1% (137/217) | 62.7% (64/102) | 63.5% (73/115) | 1.000 |
Mean age (years) | <0.001 | |||
Type of AEF | 0.077 | |||
Primary | 44.7% (98/219) | 51.5% (53/103) | 38.8% (45/116) | |
Secondary | 55.3% (121/219) | 48.5% (50/103) | 61.2% (71/116) | |
Comorbidity | ||||
Hypertension | 34.5% (48/139) | 28.8% (19/66) | 39.7% (29/73) | 0.212 |
Other arterial diseases | 24.5% (34/139) | 21.2% (14/66) | 27.4% (20/73) | 0.434 |
Coronary heart disease | 13.7% (19/139) | 16.7% (11/66) | 11.0% (8/73) | 0.459 |
COPD | 12.9% (18/139) | 12.1% (8/66) | 13.7% (10/73) | 0.806 |
Renal disease | 12.2% (17/139) | 9.1% (6/66) | 15.1% (11/73) | 0.312 |
Diabetes | 9.4% (13/139) | 4.5% (3/66) | 13.7% (10/73) | 0.082 |
Hyperlipidemia | 7.2% (10/139) | 3.0% (2/66) | 11.0% (8/73) | 0.101 |
Clinical presentation | ||||
Hemorrhage | 86.3% (183/212) | 86.0% (86/100) | 86.6% (97/112) | 1.000 |
Hemorrhagic shock | 50.5% (105/208) | 37.1% (36/97) | 62.2% (69/111) | <0.001 |
Chest/abdominal/back pain | 38.3% (79/206) | 39.6% (38/96) | 37.3% (41/110) | 0.775 |
Dysphagia | 11.7% (24/206) | 12.5% (12/96) | 10.9% (12/110) | 0.829 |
Fever | 25.2% (52/206) | 27.1% (26/96) | 23.6% (26/110) | 0.631 |
Chiari’s triad | 20.0% (41/205) | 15.8% (15/95) | 23.6% (26/110) | 0.220 |
Elevated inflammatory markers | 73.3% (63/86) | 77.1% (27/35) | 70.6% (36/51) | 0.622 |
Positive cultures | 27.9% (61/219) | 26.2% (27/103) | 29.3% (34/116) | 0.652 |
Mycotic AA | 7.8% (17/219) | 6.8% (7/103) | 8.6% (10/116) | 0.801 |
Imaging features | ||||
Mediastinal air bubbles in CT | 39.9% (71/178) | 35.2% (32/91) | 44.8% (39/87) | 0.221 |
Contrast leak in CT | 11.2% (20/178) | 8.8% (8/91) | 13.8% (12/87) | 0.346 |
Contrast leak in angiography | 36.7% (11/30) | 44.4% (8/18) | 25.0% (3/12) | 0.442 |
Contrast leak in esophagogram | 73.7% (14/19) | 60.0% (6/10) | 88.9% (8/9) | 0.303 |
Endoscopic features | ||||
Tumor-like submucosal mass | 21.9% (35/160) | 22.1% (17/77) | 21.7% (18/83) | 1.000 |
Blood clot | 40.0% (64/160) | 41.6% (32/77) | 38.6% (32/83) | 0.748 |
Mucosa necrosis | 42.5% (68/160) | 45.5% (35/77) | 39.8% (33/83) | 0.523 |
Pulsatile arterial bleeding | 7.5% (12/160) | 7.8% (6/77) | 7.2% (6/83) | 1.000 |
Visible aortic wall or graft | 23.1% (37/160) | 22.1% (17/77) | 24.1% (20/83) | 0.852 |
Type of aortic lesion | 1.000 | |||
Aneurysm | 84.5% (185/219) | 84.5% (87/103) | 84.5% (98/116) | |
Dissection | 15.5% (34/219) | 15.5% (16/103) | 15.5% (18/116) | |
Location of fistula | ||||
Descending aorta | 89.0% (195/219) | 90.3% (93/103) | 87.9% (102/116) | 0.667 |
Aortic arch | 17.4% (38/219) | 15.5% (16/103) | 19.0% (22/116) | 0.593 |
Ascending aorta | 2.7% (6/219) | 3.9% (4/103) | 1.7% (2/116) | 0.424 |
Upper esophagus | 19.4% (24/124) | 18.6% (11/59) | 20.0% (13/65) | 0.743 |
Middle esophagus | 66.1% (82/124) | 62.7% (37/59) | 69.2% (45/65) | 0.455 |
Lower esophagus | 16.1% (20/124) | 18.6% (11/59) | 13.8% (9/65) | 0.626 |
Fistula size (cm) | 0.391 | |||
Aneurysm size (cm) | 0.015 | |||
Complications | 38.4% (84/219) | 28.2% (29/103) | 47.4% (55/116) | 0.004 |
Sepsis | 23.3% (51/219) | 10.7% (11/103) | 34.5% (40/116) | <0.001 |
Multiorgan failure | 5.0% (11/219) | 0 | 9.5% (11/116) | 0.001 |
Pulmonary complications | 11.4% (25/219) | 13.6% (14/103) | 9.5% (11/116) | 0.397 |
Renal failure | 3.2% (7/219) | 1.9% (2/103) | 4.3% (5/116) | 0.451 |
Neural complications | 4.1% (9/219) | 2.9% (3/103) | 5.2% (6/116) | 0.506 |
Aortic rupture | 2.3% (5/219) | 0 | 4.3% (5/116) | 0.062 |
Fistula recurrence | 6.8% (15/219) | 6.8% (7/103) | 6.9% (8/116) | 1.000 |
Re-interventions within 30 d | 2.7% (6/219) | 2.9% (3/103) | 2.6% (3/116) | 1.000 |
Reinterventions unplanned after 30 d | 6.4% (14/219) | 7.8% (8/103) | 5.2% (6/116) | 0.582 |
AA: aortic aneurysm; AEF: aortoesophageal fistula; CT: computed tomography; SD: standard deviation.
Data are counts, percentages,
In our study, 7.8% (17/219) of total AEF patients were diagnosed as mycotic aortic aneurysms (AA). 47.1% (8/17) of which were primary AEFs, and 52.9% (9/17) were secondary AEFs which means AEF were confirmed after mycotic AA treated by graft replacement or TEVAR. For mycotic AA, the proportion of primary AEFs was significantly higher in survivors than in nonsurvivors while secondary AEFs took a larger proportion in nonsurvivors (85.7% vs.20.0%, 14.3% vs.80.0%,
Survival data for mycotic AA in AEF patients.
Total | Survivors | Nonsurvivors | ||
---|---|---|---|---|
Type of AEFs | 0.015 | |||
Primary AEFs | 47.1% (8/17) | 85.7% (6/7) | 20.0% (2/10) | |
Secondary AEFs | 52.9% (9/17) | 14.3% (1/7) | 80.0% (8/10) |
AA: aortic aneurysm; AEF: aortoesophageal fistula.
The treatments for aortic and esophageal lesions are shown in Table
Treatments and outcomes of patients with AEF.
Total | Survivors | Nonsurvivors | ||
---|---|---|---|---|
Treatment for aortic lesions | ||||
Aortic repair | 2.3% (5/219) | 1.9% (2/103) | 2.6% (3/116) | 1.000 |
Aortic graft | 32.9% (72/219) | 49.5% (51/103) | 18.1% (21/116) | <0.001 |
TEVAR | 21.5% (47/219) | 26.2% (27/103) | 17.2% (20/116) | 0.138 |
Aortic graft+TEVAR | 8.7% (19/219) | 12.6% (13/103) | 5.2% (6/116) | 0.057 |
No treatment | 34.7% (76/219) | 9.7% (10/103) | 56.9% (66/116) | <0.001 |
Treatment for esophageal lesions | ||||
Esophageal repair | 16.0% (35/219) | 19.4% (20/103) | 12.9% (15/116) | 0.202 |
Esophagectomy | 27.9% (61/219) | 45.6% (47/103) | 12.1% (14/116) | <0.001 |
Esophageal stents | 10.0% (22/219) | 9.7% (10/103) | 10.3% (12/116) | 1.000 |
Esophageal combination treatments | 5.0% (11/219) | 7.8% (8/103) | 2.6% (3/116) | 0.120 |
No treatment | 41.1% (90/219) | 17.5% (18/103) | 62.1% (72/116) | <0.001 |
Combination of therapy | ||||
Conservative treatment | 26.0% (57/219) | 1.9% (2/103) | 47.4% (55/116) | <0.001 |
Aortic repair±esophageal surgery | 2.3% (5/219) | 1.9% (2/103) | 2.6% (3/116) | 1.000 |
TEVAR | 11.9% (26/219) | 12.6% (13/103) | 11.2% (13/116) | 0.835 |
TEVAR+esophageal repair | 2.3% (5/219) | 2.9% (3/103) | 1.7% (2/116) | 0.668 |
TEVAR+esophagectomy | 1.8% (4/219) | 2.9% (3/103) | 0.9% (1/116) | 0.344 |
TEVAR+esophageal stent | 4.6% (10/219) | 6.8% (7/103) | 2.6% (3/116) | 0.196 |
Aortic graft | 2.3% (5/219) | 1.9% (2/103) | 2.6% (3/116) | 1.000 |
Aortic graft+esophageal repair | 10.0% (22/219) | 12.6% (13/103) | 7.8% (9/116) | 0.265 |
Aortic graft+esophagectomy | 17.4% (38/219) | 30.1% (31/103) | 6.0% (7/116) | <0.001 |
Aortic graft+esophageal stent | 0.9% (2/219) | 1.0% (1/103) | 0.9% (1/116) | 1.000 |
TEVAR+aortic graft±esophageal treatments | 8.7% (19/219) | 12.6% (13/103) | 5.2% (6/116) | 0.057 |
TEVAR/aortic graft+esophageal treatments | 3.2% (7/219) | 4.9% (5/103) | 1.7% (2/116) | 0.258 |
Esophageal repair | 1.8% (4/219) | 1.0% (1/103) | 2.6% (3/116) | 0.624 |
Esophagectomy | 3.2% (7/219) | 5.8% (6/103) | 0.9% (1/116) | 0.053 |
Esophageal stent | 3.7% (8/219) | 1.0% (1/103) | 6.0% (7/116) | 0.069 |
Antibiotics (>4 weeks) | 47.8% (65/136) | 53.3% (48/90) | 37.0% (17/46) | 0.102 |
AEF: aortoesophageal fistula; TEVAR: thoracic endovascular aortic repair.
Data are percentages. Numbers of patients with available data are shown in parentheses.
Summary of grafts used for aortic replacement.
Total | Survivors | Nonsurvivors | ||
---|---|---|---|---|
Prosthetic grafts | 27.6% (59/214) | 43.0% (43/100) | 14.0% (16/114) | <0.001 |
PTFE grafts | 1.0% (2/201) | 2.2% (2/92) | 0 | 0.208 |
Dacron grafts | 23.9% (48/201) | 39.1% (36/92) | 11.0% (12/109) | <0.001 |
Cryopreserved aortic allograft | 10.3% (22/214) | 15.0% (15/100) | 6.1% (7/114) | 0.042 |
Pericardial tube | 0.5% (1/214) | 1.0% (1/100) | 0 | 0.467 |
PTFE: polytetrafluoroethylene.
The overall in-hospital mortality rate was 42.0% (94/219). Complications were observed in 84 patients (38.4%, Table
The mean follow-up period was 8.6 months (interquartile range: 7 days–10.9 months). Kaplan–Meier survival analysis showed that the 1-year cumulative survival rate was
The overall survival rate of patients with AEF who underwent surgery for aortic or esophageal lesions was significantly higher than that of nonsurgical patients (
Overall survival of patients with aortoesophageal fistula (AEF). (a) Patients with AEF who underwent surgery for aortic or esophageal lesions had a significantly better prognosis compared to nonsurgical patients (
Univariable regression analysis showed that the odds of death increased with age and aortic rupture (
Cox regression analyses.
Univariable Cox regression | Multivariable Cox regression | |||||
---|---|---|---|---|---|---|
HR | 95% CI | HR | 95% CI | |||
Age | 1.027 | 1.011-1.043 | 0.001 | 1.004 | 0.988-1.021 | 0.587 |
Hemorrhagic shock | 2.124 | 1.444-3.123 | <0.001 | 1.824 | 1.217-2.735 | 0.004 |
Contrast leak in CT† | 2.102 | 1.134-3.897 | 0.018 | |||
Aneurysm size† | 1.155 | 1.044-1.279 | 0.005 | |||
Sepsis | 1.900 | 1.291-2.795 | 0.001 | 1.714 | 1.112-2.641 | 0.015 |
Multiorgan failure | 3.544 | 1.872-6.710 | <0.001 | 3.060 | 1.470-6.368 | 0.003 |
Aortic rupture | 3.186 | 1.289-7.786 | 0.012 | 2.410 | 0.949-6.117 | 0.064 |
Conservative treatment | 6.570 | 4.459-9.681 | <0.001 | 5.257 | 3.405-8.116 | <0.001 |
Aortic graft+esophagectomy | 0.214 | 0.099-0.460 | <0.001 | 0.319 | 0.125-0.813 | 0.017 |
TEVAR+aortic graft±esophageal treatments | 0.424 | 0.186-0.968 | 0.042 | 0.493 | 0.172-1.415 | 0.189 |
AEF: aortoesophageal fistula; TEVAR: thoracic endovascular aortic repair; CT: computed tomography; HR: hazard ratio; CI: confidence interval.
†Contrast leak in CT and aneurysm size were excluded from multivariate regression analysis due to the lack of information in more than 15% of patients with AEF.
AEF is a rare cause of upper gastrointestinal bleeding classically characterized by Chiari’s triad [
Although mycotic AA accounts for 7.8% of total AEF patients, positive blood or tissue cultures were reported in up to 27.9% of AEF patients, dominated by
The overall in-hospital mortality rate was 42.0%; complications were observed in 38.4% of patients with AEF. Sepsis was the most common complication and was significantly correlated with mortality rate (
Surgery for AEF is performed to repair the fistula and control bleeding and infection [
TEVAR for patients with AEF has the advantages of rapid control of bleeding and minimal invasiveness [
Endoscopic self-expanding esophageal stents are typically used for the palliation of malignant esophageal stricture; they can be helpful to control bleeding in esophageal fistula and prevent the entry of esophageal contents into the fistula [
This study had several limitations. First, the data were obtained from case reports and case series published by different researchers, and the lack of uniformity of reporting items could have affected the results. Second, publication bias might have existed because physicians are inclined to publish positive results and successful patient outcomes. A randomized prospective study was impossible because of the low incidence of AEF, so our findings can only be used for informational purposes.
In this study, we identified the risk factors for death in patients with AEF related to aortic aneurysm and dissection. Hemorrhagic shock, sepsis, and multiorgan failure were risk factors for death in patients with AEF. Additionally, conservative treatment was associated with a higher mortality rate, while combined aortic graft replacement and esophagectomy improved the prognosis. We hope that these findings can improve the prognosis of patients with AEF.
The authors declare no conflict of interest.
Shan Li and Feng Gao systematically searched the databases and reviewed and extracted data independently; Shan Li analyzed data and contributed to drafting of the manuscript; Haiou Hu and Jin Shi critically revised the manuscript; and Jie Zhang contributed to the concept and design of the study.
The authors thank Dr. Yong-chen Hao, Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, for instruction in statistical analysis.
Detailed information on the included articles is provided in the supplementary file.