7.0 ALTERNATIVE TREATMENTS
7.1 Growth factors
Four randomised placebo controlled studies have been
performed using growth hormone to stimulate mucosal
growth.130–133 In three studies there was no significant
increase in absorption but one showed a small improvement
in nutrient absorption.133 As plasma levels of GLP-2, which
causes villus growth, are low in patients with a jejunostomy,13
GLP-2 has been given as a subcutaneous injection and a
small increase in nutrient absorption occurred.134 An analogue
of GLP-2 that is resistant to degradation (teduglutide)
has shown a more pronounced effect in increasing intestinal
fluid absorption, and drug induced mucosal growth was
demonstrated for the first time in humans.135
7.2 Surgical treatments
Surgical treatments other than transplantation have tried to
slow intestinal transit or increase the surface area for
absorption. Favourable results have been reported from
reversal of a 10 cm segment of small intestine.136 137
7.3 Intestinal transplantation
Transplantation has now become a standard operation for
end stage liver, kidney, heart, or lung failure. Intestinal
transplantation is possible for patients with IF and over 1200
such operations have now been performed worldwide. In
many cases the patient may require a liver-small bowel graft
or a ‘‘multivisceral’’ graft, including other organs such as
the stomach and pancreas. Unlike renal failure, where
transplantation is preferable to long term extracorporeal
support, intestinal transplantation cannot yet be recommended
as an alternative therapy for patients stably
maintained on intravenous nutrition. This is due both to
the excellent outcomes reported overall for long term
parenteral nutrition138–145 and the challenges posed by
intestinal transplantation.146 The intestine is a difficult organ
to transplant due to its immunogenicity, large population of
donor immune cells present within the graft, and its nonsterile
contents. Rejection causes barrier failure and bacterial
translocation so that sepsis may occur at a time when
increased immunosuppression is required and the patient
may rapidly become too unwell to consider graft removal.
Significant recent advances have made intestinal transplantation
a more acceptable procedure. The development of
tacrolimus based immunosuppressive regimens in the 1990s
more than doubled the number of survivors following
intestinal transplantation compared with the use of ciclosporin
in the previous decade. The resulting increase in
lymphoproliferative disease resulting from heavy non-specific
immunosuppression has led to revision of immunosuppressive
regimens over the last few years, with further benefits in
patient outcome due to the use of antilymphocyte induction
therapy. Furthermore, while it was considered an option of
last resort, initially only the sickest patients were transplanted
with predictably poor results—identifying patients
likely to benefit from transplantation and offering the
operation at an earlier stage in the disease results in
improved survival.147
Intestinal transplantation is currently associated with
approximately 80% one year survival and approaching 50%
five year survival, with the majority of survivors being free of
parenteral nutrition.147 Studies indicate a considerable
increase in the quality of life following transplantation,
which has been found to be better than for patients on long
term parenteral nutrition with complications of therapy, and
equivalent to that of patients with uncomplicated IF.148 Direct
comparison of the results of intestinal transplantation with
long term survival rates on home parenteral nutrition are
invalid, as transplantation is only currently considered for
selected patients likely to experience a poor outcome on
intravenous feeding. Clearly, patients with IF comprise a
heterogeneous group and only recently have attempts been
made to identify those patients that have impaired survival
while receiving long term parenteral nutrition. Those most at
risk of poor outcomes on parenteral nutrition include patients
with very short residual small intestinal length (,50 cm),
those with an end jejunostomy, and patients with motility
disorders.149
Table 6 Summary of the problems of a short bowel
Jejunum-colon Jejunostomy
Presentation Gradual, diarrhoea and
undernutrition
Acute fluid losses
Water, sodium, and magnesium
depletion
Uncommon in the long-term Common
Nutrient malabsorption Common* Very common
D (2) lactic acidosis Occasionally None
Renal stones (calcium oxalate) 25% None
Gall stones (pigment) 45% 45%
Adaptation Functional adaptation No evidence
Social problems Diarrhoea High stomal output dehydration
dependency on treatment
*Bacterial fermentation of carbohydrate salvages some energy, but D (2) lactic acidosis can occur if the diet is high
in mono and oligosaccharides.
iv8 Nightingale, Woodward
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Most deaths of parenterally fed patients are attributable to
the underlying disease and with some exceptions (for
instance, liver and small bowel transplantation for mesenteric
infarction due to an inherited thrombophilic disorder),
the deaths preventable by transplantation are those caused
by complications of long term parenteral nutrition. These
include infection related to the indwelling venous feeding
catheter accounting for up to 70% of parenteral nutrition
related deaths,139 141 143 150 151 thrombosis precluding adequate
access for feeding,152–155 and liver complications.156–159 Certain
types of patients appear to be at increased risk of line related
sepsis, including those requiring high doses of opiates on a
regular basis and those with a stoma.150 160 161 Unfortunately,
life threatening infections occur stochastically, and while it
might be logical to consider that those with frequent line
related sepsis are at increased risk of such an event, current
data do not support a worse outcome for such patients.
Similarly, venous thromboses and occlusions preventing
adequate access occur infrequently154 and it is impossible to
predict the rate at which loss of vascular access may occur.
The extent to which serious liver complications occur as a
result of parenteral nutrition is controversial. Alterations in
biochemical liver function are common,156–158 162 163 but the
proportion of parenteral nutrition related deaths attributable
to liver disease varies in adults from 0%162 to 22%.163
Identification of those groups of patients at most risk of
major complications on parenteral nutrition and likely to
benefit from intestinal transplantation therefore remains a
high research priority.
Adult intestinal transplantation in the UK is carried out in
two national centres—at Addenbrooke’s Hospital in
Cambridge and in St James’ Hospital in Leeds, linked
respectively to the Intestinal Failure Units at St Mark’s and
the Hope Hospital for joint assessment of candidates.
Intestinal transplants in children are performed at the
Birmingham Children’s Hospital. Survival values are comparable
with those reported in international series164 but to date
only 14 adult patients have received intestinal grafts in this
country. Compared with other European and North American
transplant centres, fewer patients are referred for intestinal
transplantation in the UK and often too late to consider the
operation.165 As for all organ transplantation programmes,
early discussion with a view to referral for assessment is
essential. For instance, while lack of vascular access for
intravenous nutrition is an indication of intestinal transplantation,
it must be remembered that adequate central
venous access is still required for a successful operative
outcome. Furthermore, patients may have to wait a considerable
length of time for donor organs to become available.
As outcomes of intestinal transplantation continue to
improve, its indications will evolve, but the current major
criteria for referral for consideration of inte