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Intestine transplantation is now an established treatment for
irreversible intestinal failure, allowing affected children the
possibility to eat and drink normally while having an improved survival
with good growth, development, and quality of life.
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The first ventures into intestine transplantation were experiments
in animals, demonstrating the technical feasibility of this surgical innovation.1 Technical
achievements aside, clinical success remained elusive, primarily because
of the inability to control immunologic issues leading to rejection
and infection. Even during the 1980s, in which the use of cyclosporin
A was introduced, survival following intestinal transplantation
was extremely rare. The introduction of tacrolimus heralded in the
modern era for intestinal transplantation with improved long-term
graft and patient survival.
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To understand the challenges faced in achieving outcomes comparable
to other forms of solid organ transplantation, it is important to
recognize some fundamental differences between the gut and the more
familiar transplant organs: the kidney, heart, and liver. The gastrointestinal
tract is in direct and continual contact with billions of microbes
in an intensely immunologically complex environment. The mass of
intestinal tissue transplanted is large and carries a vast number
of lymphocytes both in the lamina propria and Peyer patches as part
of the gut’s mucosal immune system. The intestinal allograft
is not sterile and comes with it own sizable microbial populations. Immunosuppression
is critical to preventing cellular rejection and yet diminishes
immunoprotective mechanisms. In the face of mucosal injury as a
result of rejection, barrier functions is impaired allowing bacterial
translocation at a time when immunosuppressive medication is being
increased. The balancing act between too much and too little immunosuppression
is a common theme in transplant medicine but for intestinal transplantation
the margin for error is especially narrow.
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Over the past 20 years, as the success of the procedure has improved,
the number of intestine transplants has increased steadily to the
current figure of about 200 intestine transplants per year worldwide.
More widespread application is limited by: (1) the shortage of suitable
size-matched, deceased donor organs and (2) the continued high rates
of late graft and patient loss as a result of infection and rejection.2-6 The
first of these factors mean that even if listed the mortality on
the waiting list for intestine transplantation is the highest for
any group of patients awaiting solid organ transplantation and is
especially significant for the young children in need of composite
intestine and liver allografts where pretransplant mortality has
been reported as high as 60% of candidates. Competition
for organs, especially from the larger group of patients awaiting
isolated liver transplantation, as well as the size constraints
for intestine and liver donors because of the small peritoneal volume
in infant recipients with short gut syndrome, limits organ availability.
Although reducing intestinal length and removing the right hepatic
lobe can achieve reduction of allograft volume, outcome data for
this procedure are limited. There are no widely available living
related options but these have been successful at the ...