Composite Tissue Transplantation
Vascularised
composite tissue allotransplantation (CTA) reflects the fact that the
vascularised graft includes many different tissues, such as bone, nerve,
muscle, tendons and skin. The most common example is hand transplantation, but
face, laryngeal and abdominal wall transplantation are other examples.
Abdominal wall transplants have been used in a few multivisceral transplant
recipients to gain abdominal domain – in other words to make room for the
bowel.
Hand
transplantation
Indications
Loss
of one hand causes significant disability and carries many psychological and
social stigmata, but loss of both upper limbs is a devastating handicap. While
prosthetics may provide a substitute that can be used to compensate for loss of
a single limb, none can substitute for the tactile sense that is required for
many activities of daily living. The benefits of such transplantation need to
be balanced against the need for immunosuppression. Possible indications
include:
·
bilateral hand amputation;
·
loss of a single upper limb but already
requiring immunosuppression;
·
loss of the dominant hand – this is a relative
indication and the benefits need to be balanced against the risks of
immunosuppression and the psychology of the recipient.
The
candidates are usually trauma victims, often as a result of anti-personnel
explosive devices. Transplantation is not usually considered for congenital
anomalies or loss of limb due to cancer.
Assessment
Defining
the requirements
It
is important to define what is required by assessing the length of residual
limb (hand, forearm, upper arm) and its functionality. Skin colour is also
noted to try to achieve a reasonable match.
Patient
evaluation
Although
the surgery is long it is not as physically stressful to the recipient as other
forms of transplantation. Never theless
evaluation of cardiovascular fitness is important, as with any transplant.
Psychological
assessment is very important, due to the body image issues involved. It is
important to counsel recipients to manage their expectations. The first
successful hand transplant was lost within 3 years due to non-compliance with
medication, a consequence of the recipient’s failure to come to terms with his
new limb.
While
functional recovery is superior to a prosthesis, and better following a single
limb than a double limb transplant, it is never theless
not perfect.
The
transplant procedure
The
patient is positioned with a tourniquet occluding the blood in the upper limb.
The operative procedure involves the following sequence: bone fixation to
existing limb bone; flexor and extensor tendon repair; nerve repair; finally
the arterial and venous anastomoses are fashioned, all using microsurgical
techniques. The tourniquet is then released, reperfusing the hand.
Following
surgery, rehabilitation is a long process involving extensive physiotherapy.
Motor and sensory recovery are good but take time as the nerves regenerate
slowly; the higher the level of amputation the poorer the recovery,
particularly motor recovery. Perceptive and discriminative sensation improve in
hand recipients, while discriminative sensation shows less recovery in forearm
recipients. The results are generally as good as can be achieved by
reimplantation of someone’s own hand after traumatic amputation.
Face
transplantation
Face
transplantation is uncommon (around 10 worldwide at the time of writing), and
the term belittles the extent of what is involved. Varying components of the
donor face, including lips, chin, nose, eyelids and eyebrows, may be
transplanted together with the underlying tissues, possibly including the bones
of the facial skeleton, such as the maxilla and mandible. The first face
transplant was performed in France in 2005, and to date there have been very
few such transplants, the activity being restricted as much by the lack of
consent as by the psychological impact on the recipient.
Potential
recipients are patients who have suffered traumatic disfigurement; the first
recipient had lost her nose, mouth and chin following a dog attack; one
recipient has had a transplant for plexiform neurofibromatosis; others have
been victims of insults such as shotgun injuries or electrical burns. Loss of
tissue due to malignancy is generally a contraindication on account of the
effects of immunosuppression on the likelihood of recurrence.
As
with hand transplantation the principle non-immunological issues are the
psychological assessment and continued support of the recipient.
Since
it is undesirable to perform repeated biopsies of the skin of the face to
monitor for rejection, a separate piece of donor skin is transplanted to the
arm to permit frequent biopsies; oral mucosa can also be biopsied easily if
required.
The
long-term outcomes of face and hand transplantation remain uncertain.
Immunosuppression
and rejection
One
of the principal reasons that transplantation of composite tissues has taken so
long to come to the clinic was the belief that rejection would represent an
insurmountable challenge. Immunosuppression for skin grafting in animals, for
example, is the biggest challenge of any new immunosuppressant or
tolerance-induction programme. It turns out that the immunological response to
composite tissues is not as aggressive as once thought, and that it can be
managed by a standard regimen of lymphocyte-depleting induction agent and
tacrolimus, mycophenolate and steroid maintenance.
Rejection
has been shown to occur in any of the tissues transplanted, and may be in
isolation (asynchronous) or occur at the same time as rejection of other
tissues (synchronous). Examples of this also exist in other organs, such that a
pancreas may reject while a kidney transplanted at the same time does not, or
the small bowel may reject while the colon does
not.
