Keywords
mitomycin C - esophageal stricture - tracheoesophageal fistula
Introduction
Tracheoesophageal fistulas (TEFs) are treated with operative ligation of the distal
fistula and anastomosis of the esophageal limbs. The development of an esophageal
stricture at the anastomosis is a well-described complication after repair, occurring
in approximately one-third of patients.[1] Endoscopic balloon dilatation is currently the preferred method of treatment for
both initial and recurrent esophageal strictures. Recently, the use of topical mitomycin
C (MMC) for the treatment of esophageal strictures after surgical repair and caustic
injury has been reported. In these studies, MMC treatment was largely successful in
the resolution of esophageal strictures with a minimal complication profile.[2]
[3] However, the vast majority of the reported cases of MMC use in esophageal strictures
have been secondary to caustic injury, with a paucity of reported cases after newborn
TEF repair. Herein, we report the successful use of topical MMC in combination with
balloon dilatation for the treatment of refractory esophageal strictures following
TEF repair in two neonates with complete resolution of the stricture without complications.
Case Reports
Case 1
A 39-week infant girl, born with VACTERL syndrome, was initially diagnosed with a
long-gap pure esophageal atresia due to inability to pass a nasogastric tube and a
gasless abdomen on abdominal radiograph. Shortly after birth, the patient underwent
a gastrostomy tube placement and end colostomy for imperforate anus. Two months later,
she underwent a right-sided thoracotomy, where a Type C TEF was encountered, as opposed
to a pure esophageal atresia. She underwent ligation of the distal fistula, resection
of a nonpatent fibrous cord of the distal esophageal limb with subsequent anastomosis
of the esophageal limbs under tension. A postoperative esophagram revealed an anastomotic
leak, which eventually resolved. Four months postoperatively, she underwent a follow-up
esophagram which revealed a tight stricture at the anastomosis ([Fig. 1a]). She underwent endoscopic balloon dilatation with fluoroscopic guidance every month
for four consecutive months with persistence of the stricture at the anastomosis and
no improvement.
Fig. 1 (a) Esophagram of a tight stricture (white arrow) at the anastomosis in a 39-week-old
infant girl, born with VACTERL syndrome. (b) Esophagram showing resolution (white arrow) of the esophageal stricture after balloon
dilatation and treatment with mitomycin C.
At 10 months of age, the patient underwent a fourth endoscopic and fluoroscopic guided
balloon dilatation of the stricture as before. After adequately dilating the stricture
and visualizing circumferential, superficial linear disruption of the strictured ring
at the anastomosis, we soaked 1/2-inch × 1/2-inch cottonoids in MMC solution (0.4
mg/mL). A rigid esophagoscope was utilized to apply the MMC-soaked cottonoid onto
the left side of the stricture for a 1-minute time period followed by the placement
of another MMC-soaked cottonoid on the right side of the stricture for 1 minute ([Fig. 2]). The cottonoids were removed, and the esophagus appeared intact. Follow-up surveillance
endoscopy was performed after MMC application, which showed no evidence of an anastomotic
stricture ([Fig. 1b]). No additional balloon dilatation was required thereafter, and no recurrence of
her stricture has since occurred. Now at 3 years of age, she remains asymptomatic,
eats regular food after gastrostomy tube removal, and has not required further treatment.
Fig. 2 Illustration of an endoscopic view of an esophageal stricture dilated by balloon
and treated with a cottonoid soaked in mitomycin C. (Illustration by Scott Holmes,
reprinted with permission from Baylor College of Medicine, Houston, Texas, United
States.)
Case 2
A 31-week twin infant girl underwent repair of a Type C TEF. Before thoracotomy, the
patient's clinical condition deteriorated with marked distention of her abdomen. An
open gastrostomy was first performed and placed to water seal, and a thoracotomy with
ligation of a distal TEF and esophagoesophagostomy was performed under moderate tension.
One month later, she developed symptoms of feeding intolerance, reflux, and tracheal
aspiration. A repeat esophagram demonstrated a near-obstructing stricture in the midesophagus.
The stricture was short, circumferential, and located at the site of the anastomosis.
She was taken to the operating room for endoscopic balloon dilatation with fluoroscopic
guidance, and subsequently underwent three more monthly balloon dilatations; however,
there was no interval improvement in the stricture.
At 5 months of age, MMC was applied during the fifth esophageal dilatation in the
same manner as described above. The patient underwent a follow-up surveillance endoscopy,
which demonstrated no evidence of residual stricture. Two and a half years after the
sole MMC application and dilatation, she remains asymptomatic.
Discussion
Esophageal stricture after TEF repair can develop when anastomoses are performed under
vascular compromise or when esophageal limbs are joined under tension.[4] Recurrent strictures may occur in patients with a predisposition for intense fibrinogenesis
during anastomotic healing or as a wound healing response after esophageal dilatation
treatment.[5] Based on this model, MMC may be an ideal treatment to break the cycle of fibrosis
and recurrent stricture formation.
MMC is an antineoplastic agent isolated from Streptomyces caespitosus, which can reduce scar formation by suppression of fibroblast proliferation and fibroblastic
collagen synthesis via inhibition of DNA-dependent RNA synthesis.[6] The antifibroblast properties of MMC have been applied to limit scar formation.[7]
[8] A review of 31 pediatric patients of refractory esophageal strictures due to a variety
of etiologies treated with MMC reports an 87.7% rate of improvement in symptoms.[2]
With regards to MMC use for esophageal strictures, there have been only five previously
reported cases following surgical repair in the neonatal period for variants of TEF
with esophageal atresia: three after Type C TEF repair and two after pure esophageal
atresia repair ([Table 1]).[9]
[10] Of these reported cases, the authors attributed the refractory esophageal stricture
to concomitant reflux in three cases and to a repair performed under tension in one
case. In four of the five cases reported, three to eight esophageal dilatations were
performed before the application of MMC. All had successful resolution of the strictures
without procedural complications. Similarly, our patients likely formed strictures
due to repair performed under tension. We recommend the prompt addition of MMC after
a moderate amount of dilatations with the rationale to break the proposed cycle of
fibrinogenesis and refractory stricture formation.
Table 1
Literature review of mitomycin C (MMC) used for esophageal strictures following surgical
repair in the neonatal period for variants of tracheoesophageal fistula (TEF) with
esophageal atresia
|
Author and year
|
TEF classification
|
Stricture description
|
Number of dilatations before MMC application
|
Number of MMC applications
|
Time of follow-up
|
Outcome
|
|
Uhlen et al (2006)
|
Type A
|
< 4 cm, short stenosis
|
7
|
1
|
19 mo
|
Asymptomatic
|
|
Uhlen et al (2006)
|
Type A
|
< 4 cm, short stenosis
|
4
|
1
|
21 mo
|
Asymptomatic
|
|
Rosseneu et al (2007)
|
Type C
|
10 mm stenosis
|
3
|
1
|
N/A
|
“Success”
|
|
Rosseneu et al (2007)
|
Type C
|
8–10 mm in length
|
102
|
2
|
N/A
|
“No success”
|
|
Heran et al (2011)
|
Type C
|
N/A
|
8
|
1
|
19 mo
|
Asymptomatic
|
|
Lakoma et al (present study)
|
Type C
|
Short, circumferential
|
3
|
1
|
2 y
|
Asymptomatic
|
|
Lakoma et al (present study)
|
Type C
|
Short, circumferential
|
4
|
1
|
2 y
|
Asymptomatic
|
Abbreviation: N/A, not available.
Initial reports of the use of MMC demonstrate a good safety profile. However, one
study of six pediatric patients with refractory esophageal stenosis discovered evidence
of de novo gastric metaplasia on follow-up esophageal biopsy in two patients.[11] Furthermore, MMC can be absorbed mucosally causing systemic side effects, which
include bone marrow suppression and hypersensitivity reactions.[12] The majority of the literature describes the procedure as being safe without adverse
effects.[2]
[9]
Conclusion
This case report supports the utility and safety of MMC treatment as an adjunct to
endoscopic balloon dilatation in managing refractory esophageal strictures following
TEF repair. Despite multiple failed esophageal dilatation attempts, our two patients
have remained asymptomatic and stricture-free over 2 years after a single application
of MMC, potentially saving these children from additional procedures.
