Intramural injection with botulinum toxin significantly
elongates the pig esophagus
☆
Heidi Fhær Larsen
1
, Thorbjørn Søren Rønn Jensen
⁎
,1
, Lars Rasmussen,
Mark Ellebæk, Niels Qvist
Surgical Department A, Odense University Hospital, Denmark
Received 19 February 2013; accepted 6 March 2013
Key words:
Botulinum toxin type A;
Long gap esophageal
atresia;
Synaptophysin;
Pigs;
Acetylcholine
Abstract
Background/Purpose: Surgical treatment of long-gap esophageal atresia (LGEA) is challenging.
Methods which facilitate stretching of the esophageal pouches may allow primary anastomosis.
Botulinum toxin type A (BTX-A) blocks acetylcholine release in neuromuscular junctions, thereby
causing muscle relaxation. We hypothesized that intramural injections with BTX-A into the esophageal
wall of piglets would significantly elongate the tissue upon stretch.
Methods: Twenty-four piglets were randomized to receive BTX-A of placebo (saline). After one hour,
the esophagus was removed en bloc and tested in a stretch-tension device.
Results: The mean esophageal elongation was 84% (range 83–101) in the BTX-A-group and 65% (50–78) in
the control group. The mean difference between the two groups was 18%, which was significant (p b 0.001).
Conclusion: Intramural injections with botulinum toxin type A elongate the esophagus significantly.
Clinically, this could be a potential method to achieve primary anastomosis in LGEA. Additional clinical
studies are necessary to evaluate the method before it can be generally recommended.
© 2013 Elsevier Inc. All rights reserved.
In approximately 15% of children born with oesophageal
atresia a long-gap (LGEA) is present, where primary
anastomosis may be very difficult or even impossible.
Surgical treatment of LGEA includes primary gastric
transposition [1], different elongation techniques [2,3] or
secondary anastomosis after awaiting the spontaneous
growth of the upper and lower pouch [4]. Another option
may be colon interposition [1,5,6]. However, all procedures
are associated with severe side effects. Gastric transposition
may lead to significant swallowing dysfunction in one-third
of patients [7], and colonic interposition may result in long-
term functional problems including dysphagia and is
associated with a high frequency of early postoperative
complications [7]. The disadvantage of growth by traction is
long-term hospital stay with continuous suction on the upper
pouch and the placement of a gastrostomy tube for enteral
feeding [8]. Patients may also suffer from associated
gastroesophageal reflux [4], irrespective of which method
has been used. Therefore new treatment modalities facilitat-
ing primary anastomosis are highly warranted.
Intramural injection of botulinum toxin type A (BTX-A)
could be a potential treatment. BTX-A is derived from the
gram-positive bacterium Clostridium botulinum. It is well
known that BTX-A blocks the acetylcholine release in
☆
Conflicts of interest: The authors of this article reported no conflicts
of interest.
⁎
Corresponding author. Tel.: + 45 22334149.
E-mail address: tjens07@gmail.com (T.S.R. Jensen).
1
The two first authors contributed equally to the article.
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http://dx.doi.org/10.1016/j.jpedsurg.2013.03.062
Journal of Pediatric Surgery (2013) 48, 2032–2035