Introduction
Esophagorespiratory fistulas (ERFs) can be congenital or acquired, either in the context
of prolonged mechanical ventilation, or mediastinal (esophageal or bronchopulmonary)
tumor after surgery of chemoradiation. They are associated with poor quality of life,
chronic respiratory symptoms, severe bronchopulmonary infections, and up to 27 % short-term
mortality[1]. Surgical management relies on soft tissue interposition or closure of the fistulous
tract, with 83 % efficacy, but up to 6 % perioperative mortality [2]
[3]. Endoscopic therapy using esophageal fully covered self expandable metal stents
(FCSEMS) aime at covering the esophageal defect, alone or combined with tracheal stents,
only yields a 46 % efficacy [1]. Indeed, stents neither completely seal the fistula, nor promote its healing. Other
endoscopic techniques, such as occlusion (by clips or glue), have not shown better
results [4].
A minimally invasive alternative using an Amplatzer cardiac or vascular plug septal
occluder (AGA Medical, Plymouth, Minnesota, United States), intended for percutaneous
vascular or septal defect closure or in cardiology, has been successfully used in
endoscopy for ERF closure in humans [5]
[6]. The Amplatzer consists of two to three biocompatible self-expanding discs made
of a nitinol mesh connected together by a thinner waist, ensuring the stability of
the device ([Fig. 1]). We describe a case series of six patients with ERF treated with endoscopically
placed Amplatzer occluders.
Fig. 1 Two types of Amplatzer occluders used in the series.
Patients and methods
Patients
Between June 2019 and September 2020, six patients had endoscopic closure attempts
for chronic acquired ERF using an Amplatzer occluder at our center. All patients were
selected after a multidisciplinary board discussion involving anesthesiologists, gastroenterologists,
a pulmonologist, and gastrointestinal surgeons. The patients’ written informed consent
was obtained after explaining the modalities, benefits, and risks of this procedure.
Endoscopic procedures
The endoscopic procedures were performed using a gastroscope (GIF-1TH190; Olympus,
Tokyo, Japan) and a bronchoscope (BFQ 180, Olympus, Tokyo, Japan), with patients under
general anesthesia with orotracheal intubation. Insufflation used air instead of CO2,
considering the esophagorespiratory fistula. The ERF was cannulated using the cap-fitted
gastroscope (12.4 mm, Model D-201-1104, Olympus, Tokyo, Japan) and a straight catheter
(Guide Catheter 6 Fr 220 cm, Cook Medical) in which a guidewire (JagWire straight,
450 cm 0.035 in, Boston Scientific, Natick, Massachusetts, United States) was inserted.
A bronchoscope placed in the trachea through the intubation canula allowed precise
localization of the fistula and visualization of the guidewire, and facilitated correct
positioning of the Amplatzer. The gastroscope was exchanged for a straight 7 Fr catheter
(Destination Guiding Sheath, RSC08, Terumo), which enabled positioning of a Vascular
Plug II Amplatzer (AGA Medical, Plymouth, Minnesota, United State), or a 9F catheter
(Torqvue Delivery System, Abbott, Plymouth, Minnesota, United States), which enabled
positioning of a Septal Occluder Amplatzer (Abbott, Plymouth, Minnesota, United States)
depending on the size and shape of the ERF, under double endoscopic control. Successively,
one disk was released in the trachea and one or two in the esophagus. Successful closure
of the ERF was confirmed by injection of contrast medium into the esophagus showing
the absence of passage in the tracheobronchial tree under fluoroscopy. The main steps
of the procedure are presented in [Fig. 2].
Fig. 2 Main steps in Amplatzer (vascular plug II) occluder placement in an esophagotracheal
fistula.
Patients were followed up clinically to ensure that cough resolved and no new episode
of pneumonia had occurred. Thoracic computed tomography (CT) with oral contrast ingestion
was performed before resuming food 1 to 2 days after the procedure. A double endoscopic
control 2 to 4 weeks after the procedure was performed to check the absence of migration
of the device.
Results
Case 1 was an 80-year-old patient followed for several episodes of aspiration pneumonia
and chronic cough after a prolonged intensive care admission for cardiac arrest. The
patint was diagnosed with an esophago-tracheal fistula on esophagogram. At 19 cm from
the dental arches, an 11-mm-wide esophago-tracheal fistula on the right side of the
esophagus was seen at esophagogastroduodenoscopy (EGD). A 14-mm Amplatzer vascular
plug was placed under double endoscopic control. The patient was discharged from the
hospital the next day and has not had any respiratory symptoms since then. Follow-up
endoscopy 4 months later showed the Amplatzer in place with no contrast medium leakage
towards the trachea.
Case 2 was a 67-year-old woman who was admitted to the Intensive Care Unit after an
Ivor Lewis esophagectomy following neoadjuvant chemoradiotherapy for treatment of
a squamous cell carcinoma of the esophagus. The diagnosis of ERF was suspected based
on recurrent aspiration with pneumonia. After confirmation of a 14-mm-wide esotracheal
fistula 25 cm from the dental arches on EGD, an esophageal FCSEMS was placed on the
12th postoperative day. The patient’s respiratory symptoms persisted despite two other
endoscopic procedures to replace the stent with larger (22-mm) stents, and we finally
placed an 18-mm Amplatzer vascular plug under double endoscopic control 3 months after
the surgery. Despite the technical success, the patient died from septic shock of
pulmonary origin 3 days after the procedure.
Case 3 was a 60-year-old man who was treated with repeat surgery and chemoradiotherapy
for medullary carcinoma of the thyroid and developed a 10-mm ERF, located 21 cm from
the dental arches. There was no evidence of local tumor recurrence. After failure
of conventional management using repeat placement of an esophageal FCSEMS, a 14-mm
Amplatzer vascular plug was deployed. Initially the procedure was clinically successful,
with resolution of respiratory symptoms. However, cough and pneumonia recurred 9 months
later and the patient reported new onset of dysphagia. EGD showed an esophageal stenosis
located in the cervical esophagus related to a local tumor recurrence. EGD with a
nasogastroscope permitted the stenosis to be passed and showed that the Amplatzer
was still in place, but only partially occluding an enlarged and tumor-invaded fistula,
with contrast leakage in the trachea. Repositioning of the Amplatzer was technically
impossible due to the stenosis, and the patient was switched to long-term enteral
nutrition.
Case 4 was a 71-year-old man in clinical remission from squamous cell carcinoma of
the upper third of the esophagus after intial chemoradiotherapy. He was diagnosed
with local and metastatic cancer recurrence 1 year later and an 8-mm ERF located 18 cm
from the dental arches, which caused cough during oral food intake. Placement of a
10-mm Amplatzer vascular plug allowed him to resume a well-tolerated normal diet by
mouth beginning on Day 3. However, the patient died 10 days later from massive aspiration
pneumonia.
Case 5 was a 56-year-old patient who was diagnosed with an ERF on a CT performed for
workup of a septic shock 12 days after an Ivor Lewis esophagectomy for esophageal
adenocarcinoma. EGD showed a 14-mm fistula located 29 cm from the dental arches and
bronchoscopy identified a fistula in the right primary bronchus. The fistula was initially
treated with three successive esophageal FCSEMS, without fistula closure. Six months
after the surgery, an 18-mm Amplatzer septal occluder was placed and allowed the patient
to resume oral food intake with no respiratory symptoms. Follow-up endoscopy 5 months
later found the Amplatzer in place with partial reepithelialization on the esophageal
side and no contrast leakage towards the respiratory tree.
Case 6 was a 57-year-old man who underwent an Ivor Lewis esophagectomy for an esophageal
adenocarcinoma and was diagnosed on the 9th postoperative day with an esophago-tracheal
fistula. Initial management consisted of repeated placement of esophageal FCSEMS over
a 2-year period. Given the absence of fistula closure, with a remaining 25-mm esophago-tracheal
fistula 24 cm from the dental arches, placement of a 24-mm Amplatzer septal occluder
was attempted. It did not provide a complete occlusion of the fistula, given the presence
of an irregular, nodular mucosa on the tracheal side, and was immediately retrieved
and replaced with another esophageal stent. The patient remained symptom-free at last
follow-up, 4 months after the last endoscopic procedure. Currently, an endotracheal
ablation procedure is scheduled to flatten the tracheal mucosa and correctly place
an Amplatzer.
Patient characteristics and outcomes data are summarized in [Table 1].
Table 1
Characteristics of the six patients with esophagorespiratory fistulas managed with
amplatzer occluders.
|
Case
|
Context of ERF
|
Location (cm from the DAs)
|
Size of the esophageal fistula (mm)
|
Amplatzer type
|
Technical success
|
Outcome
|
Follow-up (months)
|
|
1
|
Prolonged mechanical ventilation
|
19
|
11
|
Vascular Plug II,
14 mm
|
Yes
|
Clinical success
|
15
|
|
2
|
Ivor-Lewis esophagectomy
|
25
|
14
|
Vascular Plug II,
18 mm
|
Yes
|
Death 3 days after the procedure from pneumonia
|
–
|
|
3
|
Chemoradiotherapy, no residual tumor
|
21
|
10
|
Vascular Plug II,
14 mm
|
Yes
|
Cancer recurrence, recurrence of respiratory symptoms after 9 months
|
11
|
|
4
|
Chemoradiotherapy, residual tumor
|
18
|
8
|
Vascular Plug II,
10 mm
|
Yes
|
Death 8 days after the procedure from pneumonia
|
–
|
|
5
|
Ivor-Lewis esophagectomy
|
29
|
14
|
Septal occluder,
18 mm
|
Yes
|
Clinical success
|
5
|
|
6
|
Ivor-Lewis esophagectomy
|
24
|
20
|
Septal occluder,
24 mm
|
No
|
Technical failure
|
4
|
ERF, esophago-respiratory fistula; DA, dental arches.
Discussion
This case series found an 83 % (5/6) technical success rate and a 60 % (3/5) short-term
clinical success rate with ERF occlusion using endoscopically placed Amplatzers. Because
the recommended management of ERF relies on esophageal stents [7], we only included patients with chronic non-malignant ERF refractory to initial
management with conventional stents. Thus, we selected cases with well-organized,
fibrotic, large fistulas for which clipping, either directly during or after submucosal
dissection [8] was not possible. Indeed, the stability of the device requires a regular-shaped
and large fistula. Therefore, an Amplatzer is not likely to be an effective treatment
for malignant ERF, which is best managed with esophageal, tracheal, or combined stenting;
esophageal or tracheal stenoses often increase the stability of the stents [9]. Conversely, the long time between the onset of the ERF and the Amplatzer placement
led to the inclusion of an extremely frail patient population, explaining the 33 %
(2/6) mortality rate in our series.
The use of Amplatzer occluders, initially designed for cardial septal defect occlusion,
in the treatment of non-malignant refractory ERF has been reported in 10 case reports
(11 patients) since 2006 [5]
[6]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]. In four of 11 cases, the ERF occurred after esophagectomy, and in four of 11 patients
after prolonged mechanical ventilation. Clinical success was obtained in 45 % of the
cases (5/11), with heterogeneous follow-up duration, ranging from 1 month to 1 year.
The mortality was high in these 11 extremely frail and malnourished patients, reaching
40 % (4/11). In our case series, the mortality rate was 33 %, illustrating the severity
of the comorbid conditions of the patients, possibly accounting for the limited efficacy
of the Amplatzer occluders.
Although Amplatzer occluders can improve the quality of life of a proportion of patients
with refractory non-malignant ERF, the device suffers several limitations. First,
although long-term follow-up for cardiovascular indications shows an excellent safety
profile and endothelial regrowth [18], we only observed moderate epithelial growth on the esophageal side, and never on
the tracheal side. This indicates that tracheal obstruction due to granulation tissue
will not be an issue, but suggests that the device is only suspensive, and that ERF
might recur in case of Amplatzer migration. Second, the size of the intratracheal
flap, particularly with the vascular plug-type Amplatzer (for smaller-diameter fistulas),
might result in airway obstruction.
Erosion of the respiratory mucosa by the Amplatzer occluder might also constitute
a limitation of the use of this device, particularly in the bronchi, considering their
limited diameter, because a case of fatal hemoptysis after closure of a gastrobronchial
fistula was reported recently [19]. Use of novel occluders specifically designed for the endoscopic treatment of refractory
ERF has been reported in a recent animal study [20]. Finally, the outcomes of the patients in case studies 3 and 4 suggest that the
stability and the efficacy of the Amplatzer occluder can be compromised in cases of
active malignancy: therefore, the use of these devices is probably advisable in patients
with non-malignant ERF.
Conclusions
Endoscopic occlusion of chronic, refractory, non-malignant ERF is feasible, with clinical
success in half of such patients. Amplatzer occluders should be considered as a rescue
therapy in selected cases that can facilitate avoidance of highly morbid surgical
management.
